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(DB_ID 1358429)
(identifier "REACT_76697")
(identifierVersion "1"))
([GK_1358435] of StableIdentifier
(_displayName "REACT_76703.1")
(DB_ID 1358435)
(identifier "REACT_76703")
(identifierVersion "1"))
([GK_1358465] of StableIdentifier
(_displayName "REACT_76733.1")
(DB_ID 1358465)
(identifier "REACT_76733")
(identifierVersion "1"))
([GK_1358509] of StableIdentifier
(_displayName "REACT_76777.1")
(DB_ID 1358509)
(identifier "REACT_76777")
(identifierVersion "1"))
([GK_1358519] of StableIdentifier
(_displayName "REACT_76787.1")
(DB_ID 1358519)
(identifier "REACT_76787")
(identifierVersion "1"))
([GK_1358524] of StableIdentifier
(_displayName "REACT_76792.1")
(DB_ID 1358524)
(identifier "REACT_76792")
(identifierVersion "1"))
([GK_1358546] of StableIdentifier
(_displayName "REACT_76814.1")
(DB_ID 1358546)
(identifier "REACT_76814")
(identifierVersion "1"))
([GK_1358552] of StableIdentifier
(_displayName "REACT_76820.1")
(DB_ID 1358552)
(identifier "REACT_76820")
(identifierVersion "1"))
([GK_1358566] of StableIdentifier
(_displayName "REACT_76834.1")
(DB_ID 1358566)
(identifier "REACT_76834")
(identifierVersion "1"))
([GK_1358567] of StableIdentifier
(_displayName "REACT_76835.1")
(DB_ID 1358567)
(identifier "REACT_76835")
(identifierVersion "1"))
([GK_1358575] of StableIdentifier
(_displayName "REACT_76843.1")
(DB_ID 1358575)
(identifier "REACT_76843")
(identifierVersion "1"))
([GK_1358579] of StableIdentifier
(_displayName "REACT_76847.1")
(DB_ID 1358579)
(identifier "REACT_76847")
(identifierVersion "1"))
([GK_1358592] of StableIdentifier
(_displayName "REACT_76860.1")
(DB_ID 1358592)
(identifier "REACT_76860")
(identifierVersion "1"))
([GK_1358602] of StableIdentifier
(_displayName "REACT_76870.1")
(DB_ID 1358602)
(identifier "REACT_76870")
(identifierVersion "1"))
([GK_1358620] of StableIdentifier
(_displayName "REACT_76888.1")
(DB_ID 1358620)
(identifier "REACT_76888")
(identifierVersion "1"))
([GK_1358637] of StableIdentifier
(_displayName "REACT_76905.1")
(DB_ID 1358637)
(identifier "REACT_76905")
(identifierVersion "1"))
([GK_1358639] of StableIdentifier
(_displayName "REACT_76907.1")
(DB_ID 1358639)
(identifier "REACT_76907")
(identifierVersion "1"))
([GK_139809] of GO_BiologicalProcess
(_displayName "regulation of cellular process")
(accession "0050794")
(DB_ID 139809)
(definition "Any process that modulates the frequency, rate or extent of a cellular process, any of those that are carried out at the cellular level, but are not necessarily restricted to a single cell. For example, cell communication occurs among more than one cell, but occurs at the cellular level.")
(name "regulation of cellular process")
(referenceDatabase [GK_1]))
([GK_139810] of GO_BiologicalProcess
(_displayName "regulation of biological process")
(accession "0050789")
(DB_ID 139810)
(definition "Any process that modulates the frequency, rate or extent of a biological process. Biological processes are regulated by many means; examples include the control of gene expression, protein modification or interaction with a protein or substrate molecule.")
(name "regulation of biological process")
(referenceDatabase [GK_1]))
([GK_139812] of GO_BiologicalProcess
(_displayName "regulation of apoptotic process")
(accession "0042981")
(DB_ID 139812)
(definition "Any process that modulates the occurrence or rate of cell death by apoptotic process.")
(name "regulation of apoptotic process")
(referenceDatabase [GK_1]))
([GK_139813] of GO_BiologicalProcess
(_displayName "regulation of programmed cell death")
(accession "0043067")
(DB_ID 139813)
(definition "Any process that modulates the frequency, rate or extent of programmed cell death, cell death resulting from activation of endogenous cellular processes.")
(name "regulation of programmed cell death")
(referenceDatabase [GK_1]))
([GK_139950] of Complex
(_displayName "[Hsa] Caspase-8 dimer [cytosol]")
(DB_ID 139950)
(hasComponent
[GK_75975]
[GK_76158])
(name "Caspase-8 dimer")
(species [GK_48887])
(stableIdentifier [GK_366061]))
([GK_139951] of CatalystActivity
(_displayName "[Hsa] cysteine-type endopeptidase activity of active caspase-8 [cytosol]")
(activity [GK_4344])
(DB_ID 139951)
(physicalEntity [GK_2562550]))
([GK_139952] of BlackBoxEvent
(_displayName "[Hsa] Caspase-8 processing in the DISC")
(_doRelease TRUE)
(catalystActivity [GK_139951])
(DB_ID 139952)
(edited [GK_3508822])
(input [GK_2671813])
(literatureReference
[GK_1267800]
[GK_2584573]
[GK_1267836])
(name "Caspase-8 processing in the DISC")
(output
[GK_2671814]
[GK_2562550]
[GK_2562550]
[GK_2562550])
(precedingEvent
[GK_141156]
[GK_141159]
[GK_73945])
(relatedSpecies
[GK_2671795]
[GK_2671781])
(reviewed
[GK_2594924]
[GK_3597630])
(species [GK_48887])
(stableIdentifier [GK_358238])
(summation [GK_178769]))
([GK_139957] of InstanceEdit
(_displayName "Gillespie, ME, 2004-08-10 16:59:18")
(author [GK_73681])
(dateTime "2004-08-10 16:59:18")
(DB_ID 139957))
([GK_139958] of Summation
(_displayName "The death receptors, all cell-surface receptors, begin the p...")
(DB_ID 139958)
(text "The death receptors, all cell-surface receptors, begin the process of caspase activation. The common feature of these type 1 transmembrane proteins is the \"death-domain\" a conserved cytoplasmic motif found on all of the three receptors (FAS/CD95, TNF-receptor, and TRAIL-receptor) that binds the Fas-associated protein with death domain (FADD). Ligand binding to death receptors (DR) results in receptor oligomerization and recruitment of adaptor proteins via homophilic interaction of death domains. This project describes an assembly of the death-inducing signaling complex (DISC) and shows protein composition and stoichiometry within the DISC. It also provides the appropriate literature references if available. However, the DISC signaling complex may vary in its components stoichiometry. DR signaling may trigger formation of higher order receptor structures or signaling through rearrangement of receptor chains, which is not reflected here."))
([GK_139959] of Summation
(_displayName "Known as the \"death receptor pathway\" the extrinsic or caspa...")
(DB_ID 139959)
(text "Known as the \"death receptor pathway\" the extrinsic or caspase 8/10 dependent pathway is activated by ligand binding. The \"death receptors\" are specialized cell-surface receptors including Fas/CD95, tumor necrosis factor-alpha (TNF-alpha) receptor 1, and two receptors, DR4 and DR5, that bind to the TNF-alpha related apoptosis-inducing ligand (TRAIL). The extrinsic and intrinsic pathways unite in the activation of Caspase-3, though the two pathways communicate through the pro-apoptotic Bcl-2 family member Bid before uniting at the shared activation of Caspase-3."))
([GK_139960] of LiteratureReference
(_displayName "The biochemistry of apoptosis.")
(author [GK_140492])
(DB_ID 139960)
(journal "Nature")
(pages "770-6")
(pubMedIdentifier 11048727)
(title "The biochemistry of apoptosis.")
(volume 407)
(year 2000))
([GK_140] of GO_BiologicalProcess
(_displayName "cell surface receptor signaling pathway")
(accession "0007166")
(DB_ID 140)
(definition "A series of molecular signals initiated by activation of a receptor on the surface of a cell. The pathway begins with binding of an extracellular ligand to a cell surface receptor, or for receptors that signal in the absence of a ligand, by ligand-withdrawal or the activity of a constitutively active receptor. The pathway ends with regulation of a downstream cellular process, e.g. transcription.")
(name "cell surface receptor signaling pathway")
(referenceDatabase [GK_1]))
([GK_140480] of InstanceEdit
(_displayName "Gillespie, ME, 2004-08-18 21:05:31")
(author [GK_73681])
(dateTime "2004-08-18 21:05:31")
(DB_ID 140480))
([GK_140481] of Summation
(_displayName "The Fas family of cell surface receptors initiate the apotot...")
(DB_ID 140481)
(literatureReference
[GK_140482]
[GK_140484]
[GK_140483])
(text "The Fas family of cell surface receptors initiate the apototic pathway through interaction with the external ligand, FasL. The cytoplasmic domain of Fas interacts with a number of molecules in the transduction of the external signal to the cytoplasmic side of the cell membrane. The most notable cytoplasmic domain is the Death Domain (DD) that is involved in recruiting the FAS-associating death domain-containing protein (FADD). This interaction drives downstream events."))
([GK_140482] of LiteratureReference
(_displayName "The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis")
(author
[GK_141169]
[GK_141174]
[GK_141175]
[GK_141172]
[GK_141170]
[GK_141171]
[GK_141166]
[GK_76786]
[GK_141176])
(DB_ID 140482)
(journal "Cell")
(pages "233-43")
(pubMedIdentifier 1713127)
(title "The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis")
(volume 66)
(year 1991))
([GK_140483] of LiteratureReference
(_displayName "FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis")
(author
[GK_141168]
[GK_141167]
[GK_141165]
[GK_141149])
(DB_ID 140483)
(journal "Cell")
(pages "505-12")
(pubMedIdentifier 7538907)
(title "FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis")
(volume 81)
(year 1995))
([GK_140484] of LiteratureReference
(_displayName "A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor")
(author
[GK_141174]
[GK_141175]
[GK_141172])
(DB_ID 140484)
(journal "J Exp Med")
(pages "1747-56")
(pubMedIdentifier 2469768)
(title "A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor")
(volume 169)
(year 1989))
([GK_140492] of Person
(_displayName "Hengartner, MO")
(DB_ID 140492)
(initial "MO")
(surname "Hengartner"))
([GK_140494] of Person
(_displayName "Wallach, D")
(DB_ID 140494)
(initial "D")
(surname "Wallach"))
([GK_140495] of LiteratureReference
(_displayName "A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain")
(author
[GK_140497]
[GK_140520]
[GK_140518]
[GK_140511]
[GK_111029]
[GK_140494])
(DB_ID 140495)
(journal "J Biol Chem")
(pages "7795-8")
(pubMedIdentifier 7536190)
(title "A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain")
(volume 270)
(year 1995))
([GK_140496] of Person
(_displayName "Hellbardt, S")
(DB_ID 140496)
(initial "S")
(surname "Hellbardt"))
([GK_140497] of Person
(_displayName "Boldin, MP")
(DB_ID 140497)
(initial "MP")
(surname "Boldin"))
([GK_140498] of Person
(_displayName "Krammer, PH")
(DB_ID 140498)
(initial "PH")
(surname "Krammer"))
([GK_140499] of Person
(_displayName "Lynch, DH")
(DB_ID 140499)
(initial "DH")
(surname "Lynch"))
([GK_140500] of Person
(_displayName "Echeverri, F")
(DB_ID 140500)
(initial "F")
(surname "Echeverri"))
([GK_140501] of Person
(_displayName "Yoo, NJ")
(DB_ID 140501)
(initial "NJ")
(surname "Yoo"))
([GK_140502] of Person
(_displayName "Peter, ME")
(DB_ID 140502)
(initial "ME")
(surname "Peter"))
([GK_140504] of Person
(_displayName "Pawlita, M")
(DB_ID 140504)
(initial "M")
(surname "Pawlita"))
([GK_140505] of LiteratureReference
(_displayName "Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor")
(author
[GK_140512]
[GK_140496]
[GK_140507]
[GK_140517]
[GK_140504]
[GK_140498]
[GK_140502])
(DB_ID 140505)
(journal "EMBO J")
(pages "5579-88")
(pubMedIdentifier 8521815)
(title "Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor")
(volume 14)
(year 1995))
([GK_140506] of Person
(_displayName "Brunner, T")
(DB_ID 140506)
(initial "T")
(surname "Brunner"))
([GK_140507] of Person
(_displayName "Behrmann, I")
(DB_ID 140507)
(initial "I")
(surname "Behrmann"))
([GK_140509] of Person
(_displayName "Mahboubi, A")
(DB_ID 140509)
(initial "A")
(surname "Mahboubi"))
([GK_140510] of Person
(_displayName "LaFace, D")
(DB_ID 140510)
(initial "D")
(surname "LaFace"))
([GK_140511] of Person
(_displayName "Mett, IL")
(DB_ID 140511)
(initial "IL")
(surname "Mett"))
([GK_140512] of Person
(_displayName "Kischkel, FC")
(DB_ID 140512)
(initial "FC")
(surname "Kischkel"))
([GK_140513] of LiteratureReference
(_displayName "Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas")
(author
[GK_140506]
[GK_140515]
[GK_140510]
[GK_140501]
[GK_140509]
[GK_140500]
[GK_140516]
[GK_140514]
[GK_140499]
[GK_140519])
(DB_ID 140513)
(journal "Nature")
(pages "441-4")
(pubMedIdentifier 7530336)
(title "Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas")
(volume 373)
(year 1995))
([GK_140514] of Person
(_displayName "Force, WR")
(DB_ID 140514)
(initial "WR")
(surname "Force"))
([GK_140515] of Person
(_displayName "Mogil, RJ")
(DB_ID 140515)
(initial "RJ")
(surname "Mogil"))
([GK_140516] of Person
(_displayName "Martin, SJ")
(DB_ID 140516)
(initial "SJ")
(surname "Martin"))
([GK_140517] of Person
(_displayName "Germer, M")
(DB_ID 140517)
(initial "M")
(surname "Germer"))
([GK_140518] of Person
(_displayName "Pancer, Z")
(DB_ID 140518)
(initial "Z")
(surname "Pancer"))
([GK_140519] of Person
(_displayName "Ware, CF")
(DB_ID 140519)
(initial "CF")
(surname "Ware"))
([GK_140520] of Person
(_displayName "Varfolomeev, EE")
(DB_ID 140520)
(initial "EE")
(surname "Varfolomeev"))
([GK_140534] of Pathway
(_displayName "[Hsa] Ligand-dependent caspase activation")
(_doRelease TRUE)
(DB_ID 140534)
(doi "10.3180/REACT_1503.7")
(edited [GK_3508822])
(goBiologicalProcess [GK_2266695])
(hasEvent
[GK_69416]
[GK_139952]
[GK_2562564]
[GK_3371378]
[GK_5357966])
(literatureReference
[GK_141160]
[GK_1267800]
[GK_879193]
[GK_2671825]
[GK_2584573])
(name "Ligand-dependent caspase activation")
(reviewed
[GK_2594924]
[GK_3597630])
(revised [GK_5661322])
(species [GK_48887])
(stableIdentifier [GK_362011])
(summation [GK_213088]))
([GK_140935] of Complex
(_displayName "[Hsa] TRAF2:TRADD:RIPK1 [cytosol]")
(DB_ID 140935)
(goCellularComponent [GK_161217])
(hasComponent
[GK_66370]
[GK_66370]
[GK_66370]
[GK_66376]
[GK_66376]
[GK_66376]
[GK_168651])
(name "TRAF2:TRADD:RIPK1")
(species [GK_48887])
(stableIdentifier [GK_363774]))
([GK_140936] of InstanceEdit
(_displayName "Gillespie, ME, 2004-08-24 21:32:45")
(author [GK_73681])
(dateTime "2004-08-24 21:32:45")
(DB_ID 140936))
([GK_140937] of Person
(_displayName "Hsu, H")
(DB_ID 140937)
(initial "H")
(surname "Hsu"))
([GK_140938] of Person
(_displayName "Aggarwal, BB")
(DB_ID 140938)
(initial "BB")
(surname "Aggarwal"))
([GK_140939] of LiteratureReference
(_displayName "TNF-R1 signaling: a beautiful pathway")
(author
[GK_140944]
[GK_75697])
(DB_ID 140939)
(journal "Science")
(pages "1634-5")
(pubMedIdentifier 12040173)
(title "TNF-R1 signaling: a beautiful pathway")
(volume 296)
(year 2002))
([GK_140940] of Person
(_displayName "Aiyer, RA")
(DB_ID 140940)
(initial "RA")
(surname "Aiyer"))
([GK_140941] of LiteratureReference
(_displayName "Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death")
(author
[GK_140497]
[GK_140949]
[GK_140947]
[GK_140494])
(DB_ID 140941)
(journal "Cell")
(pages "803-15")
(pubMedIdentifier 8681376)
(title "Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death")
(volume 85)
(year 1996))
([GK_140942] of Summation
(_displayName "The Tumor Necrosis Factor alpha (TNF-alpha) mediated apoptos...")
(DB_ID 140942)
(text "The Tumor Necrosis Factor alpha (TNF-alpha) mediated apoptosis pathway has been implicated in the pathogenesis of a number of diseases including sepsis, diabetes, cancer, osteoporosis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel diseases. The TNF signaling network provides extensive cross talk between the apoptotic pathway, and the other NF-B, and JNK pathways that also emanate from TNF-R."))
([GK_140943] of Person
(_displayName "Stauber, GB")
(DB_ID 140943)
(initial "GB")
(surname "Stauber"))
([GK_140944] of Person
(_displayName "Chen, G")
(DB_ID 140944)
(initial "G")
(surname "Chen"))
([GK_140945] of LiteratureReference
(_displayName "Human tumor necrosis factor-alpha receptor. Purification by immunoaffinity chromatography and initial characterization.")
(author
[GK_140943]
[GK_140940]
[GK_140938])
(DB_ID 140945)
(journal "J Biol Chem")
(pages "19098-104")
(pubMedIdentifier 2848815)
(title "Human tumor necrosis factor-alpha receptor. Purification by immunoaffinity chromatography and initial characterization.")
(volume 263)
(year 1988))
([GK_140946] of Complex
(_displayName "[Hsa] TNF-alpha:TNFR1:TRADD:RIPK1:TRAF2 [plasma membrane]")
(DB_ID 140946)
(goCellularComponent [GK_161217])
(hasComponent
[GK_66376]
[GK_66376]
[GK_66376]
[GK_66370]
[GK_66370]
[GK_66370]
[GK_168651]
[GK_3371401])
(literatureReference
[GK_3465353]
[GK_3465415]
[GK_140979]
[GK_3465531])
(name "TNF-alpha:TNFR1:TRADD:RIPK1:TRAF2")
(species [GK_48887])
(stableIdentifier [GK_371402]))
([GK_140947] of Person
(_displayName "Goltsev, YV")
(DB_ID 140947)
(initial "YV")
(surname "Goltsev"))
([GK_140948] of LiteratureReference
(_displayName "The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation")
(author
[GK_140937]
[GK_140950]
[GK_75697])
(DB_ID 140948)
(journal "Cell")
(pages "495-504")
(pubMedIdentifier 7758105)
(title "The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation")
(volume 81)
(year 1995))
([GK_140949] of Person
(_displayName "Goncharov, TM")
(DB_ID 140949)
(initial "TM")
(surname "Goncharov"))
([GK_140950] of Person
(_displayName "Xiong, J")
(DB_ID 140950)
(initial "J")
(surname "Xiong"))
([GK_140952] of InstanceEdit
(_displayName "Gillespie, ME, 2004-08-24 21:33:15")
(author [GK_73681])
(dateTime "2004-08-24 21:33:15")
(DB_ID 140952))
([GK_140975] of Person
(_displayName "Micheau, O")
(DB_ID 140975)
(initial "O")
(surname "Micheau"))
([GK_140976] of Complex
(_displayName "[Hsa] TRADD:TRAF2:RIP1:FADD:CASP8(1-479) [cytosol]")
(DB_ID 140976)
(goCellularComponent [GK_161217])
(hasComponent
[GK_57031]
[GK_5357793])
(literatureReference [GK_2984174])
(name "TRADD:TRAF2:RIP1:FADD:CASP8(1-479)")
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(stableIdentifier [GK_362216]))
([GK_140977] of Complex
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[GK_140935]
[GK_54639]
[GK_54639])
(literatureReference
[GK_140979]
[GK_3465531])
(name "TRADD:TRAF2:RIP1:FADD")
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(stableIdentifier [GK_367733]))
([GK_140978] of Reaction
(_displayName "[Hsa] TRADD:TRAF2:RIP1 complex binds FADD")
(_doRelease TRUE)
(DB_ID 140978)
(edited [GK_165085])
(input
[GK_140935]
[GK_54639]
[GK_54639])
(literatureReference [GK_140979])
(name "TRADD:TRAF2:RIP1 complex binds FADD")
(output [GK_140977])
(precedingEvent [GK_83582])
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[GK_165094]
[GK_3597630])
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(species [GK_48887])
(stableIdentifier [GK_358269])
(summation [GK_74353]))
([GK_140979] of LiteratureReference
(_displayName "Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes")
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[GK_140975]
[GK_77293])
(DB_ID 140979)
(journal "Cell")
(pages "181-90")
(pubMedIdentifier 12887920)
(title "Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes")
(volume 114)
(year 2003))
([GK_140991] of Person
(_displayName "Wang, S")
(DB_ID 140991)
(initial "S")
(surname "Wang"))
([GK_140992] of LiteratureReference
(_displayName "TRAIL and apoptosis induction by TNF-family death receptors")
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[GK_140991]
[GK_77151])
(DB_ID 140992)
(journal "Oncogene")
(pages "8628-33")
(pubMedIdentifier 14634624)
(title "TRAIL and apoptosis induction by TNF-family death receptors")
(volume 22)
(year 2003))
([GK_141] of GO_BiologicalProcess
(_displayName "signal transduction")
(accession "0007165")
(DB_ID 141)
(definition "The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.")
(name "signal transduction")
(referenceDatabase [GK_1]))
([GK_141075] of Person
(_displayName "Ashkenazi, A")
(DB_ID 141075)
(initial "A")
(surname "Ashkenazi"))
([GK_141083] of Summation
(_displayName "Tumor necrosis factor-related apoptosis-inducing ligand or A...")
(DB_ID 141083)
(literatureReference
[GK_140992]
[GK_3371373]
[GK_141314])
(text "Tumor necrosis factor-related apoptosis-inducing ligand or Apo 2 ligand (TRAIL/Apo2L) is a member of the tumor necrosis factor (TNF) family. This group of apoptosis induction pathways all work through protein interactions mediated by the intracellular death domain (DD), encoded within the cytoplasmic domain of the receptor. TRAIL selectively induces apoptosis through its interaction with the Fas-associated death domain protein (FADD) and caspase-8/10 (Wang S & el-Deiry WS 2003; Sprick MR et al. 2002). TRAIL and its receptors, TRAIL-R1 and TRAIL-R2, were shown to be rapidly endocytosed via clathrin-dependent and -independent manner in human Burkitt's lymphoma B cells (BJAB) (Kohlhaas SL et al. 2007). However, FADD and caspase-8 were able to bind TRAIL-R1/R2 in TRAIL-stimulated BJAB cells at 4oC (at which membrane trafficking is inhibited), suggesting that the endocytosis was not required for an assembly of the functional TRAIL DISC complex. Moreover, blocking of clathrin-dependent endocytosis did not interfere with the capacity of TRAIL to promote apoptosis (Kohlhaas SL et al. 2007).
"))
([GK_141084] of InstanceEdit
(_displayName "Gillespie, ME, 2004-08-31 03:31:31")
(author [GK_73681])
(dateTime "2004-08-31 03:31:31")
(DB_ID 141084))
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[GK_65505]
[GK_66186])
(name "TRAIL receptor-2:TRAIL complex")
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(stableIdentifier [GK_368665]))
([GK_141126] of Complex
(_displayName "[Hsa] TRAIL receptor-2:TRAIL Trimer [plasma membrane]")
(DB_ID 141126)
(hasComponent
[GK_141118]
[GK_141118]
[GK_141118])
(name "TRAIL receptor-2:TRAIL Trimer")
(species [GK_48887])
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([GK_141128] of LiteratureReference
(_displayName "FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2")
(author
[GK_141131]
[GK_141129]
[GK_141136]
[GK_141130]
[GK_141135]
[GK_141134]
[GK_140498]
[GK_141138])
(DB_ID 141128)
(journal "Immunity")
(pages "599-609")
(pubMedIdentifier 10894160)
(title "FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2")
(volume 12)
(year 2000))
([GK_141129] of Person
(_displayName "Weigand, MA")
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(initial "MA")
(surname "Weigand"))
([GK_141130] of Person
(_displayName "Rauch, CT")
(DB_ID 141130)
(initial "CT")
(surname "Rauch"))
([GK_141131] of Person
(_displayName "Sprick, MR")
(DB_ID 141131)
(initial "MR")
(surname "Sprick"))
([GK_141133] of Complex
(_displayName "[Hsa] TRAIL:TRAIL receptor-2 Trimer:FADD:procaspase-8 [plasma membrane]")
(DB_ID 141133)
(hasComponent
[GK_57031]
[GK_141137])
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[GK_141128]
[GK_3371373])
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([GK_141134] of Person
(_displayName "Blenis, J")
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([GK_141135] of Person
(_displayName "Juo, P")
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(surname "Juo"))
([GK_141136] of Person
(_displayName "Rieser, E")
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(initial "E")
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(_displayName "[Hsa] TRAIL:TRAIL receptor-2:FADD [plasma membrane]")
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[GK_141126]
[GK_54639]
[GK_54639])
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[GK_3465531]
[GK_141128])
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(DB_ID 141138)
(firstname "Henning")
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([GK_141139] of Reaction
(_displayName "[Hsa] Trimerization of TRAIL: TRAIL receptor-2 complex")
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[GK_141118]
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[GK_141118])
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([GK_141140] of Person
(_displayName "Salvesen, Guy S.")
(affiliation [GK_3597631])
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(firstname "Guy S.")
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(surname "Salvesen"))
([GK_141141] of Person
(_displayName "Sutherland, GR")
(DB_ID 141141)
(initial "GR")
(surname "Sutherland"))
([GK_141142] of Person
(_displayName "Wiley, SR")
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(surname "Wiley"))
([GK_141143] of Person
(_displayName "Boatright, KM")
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(_displayName "Identification and characterization of a new member of the TNF family that induces apoptosis")
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[GK_141153]
[GK_141148]
[GK_141154]
[GK_141157]
[GK_141155]
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[GK_141152]
[GK_141151]
[GK_111168])
(DB_ID 141147)
(journal "Immunity")
(pages "673-82")
(pubMedIdentifier 8777713)
(title "Identification and characterization of a new member of the TNF family that induces apoptosis")
(volume 3)
(year 1995))
([GK_141148] of Person
(_displayName "Smolak, PJ")
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([GK_141149] of Person
(_displayName "Dixit, VM")
(crossReference [GK_5625820])
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(_displayName "Smith, TD")
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([GK_141153] of Person
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([GK_141154] of Person
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(initial "JK")
(surname "Nicholl"))
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(_displayName "[Hsa] TRAIL-mediated dimerization of procaspase-8")
(_doRelease TRUE)
(DB_ID 141156)
(edited [GK_3508822])
(input
[GK_57031]
[GK_5637468])
(literatureReference
[GK_141128]
[GK_879193])
(name "TRAIL-mediated dimerization of procaspase-8")
(output [GK_2671816])
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([GK_141157] of Person
(_displayName "Huang, CP")
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(initial "CP")
(surname "Huang"))
([GK_141158] of LiteratureReference
(_displayName "Death receptors: signaling and modulation")
(author
[GK_141075]
[GK_141149])
(DB_ID 141158)
(journal "Science")
(pages "1305-8")
(pubMedIdentifier 9721089)
(title "Death receptors: signaling and modulation")
(volume 281)
(year 1998))
([GK_141159] of Reaction
(_displayName "[Hsa] TNF-mediated dimerization of procaspase-8")
(_doRelease TRUE)
(DB_ID 141159)
(edited [GK_3508822])
(input
[GK_140976]
[GK_57031])
(literatureReference
[GK_2984174]
[GK_140979]
[GK_2584573])
(name "TNF-mediated dimerization of procaspase-8")
(output [GK_2671812])
(precedingEvent [GK_75240])
(reviewed
[GK_2594924]
[GK_3597630])
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([GK_141160] of LiteratureReference
(_displayName "Mechanisms of caspase activation")
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[GK_141143]
[GK_141140])
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(journal "Curr Opin Cell Biol")
(pages "725-31")
(pubMedIdentifier 14644197)
(title "Mechanisms of caspase activation")
(volume 15)
(year 2003))
([GK_141165] of Person
(_displayName "Tewari, M")
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(initial "M")
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([GK_141166] of Person
(_displayName "Hase, A")
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(initial "A")
(surname "Hase"))
([GK_141167] of Person
(_displayName "O'Rourke, K")
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(surname "O'Rourke"))
([GK_141168] of Person
(_displayName "Chinnaiyan, AM")
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(_displayName "Mizushima, S")
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([GK_141171] of Person
(_displayName "Sameshima, M")
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([GK_141172] of Person
(_displayName "Yonehara, M")
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(initial "M")
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([GK_141174] of Person
(_displayName "Yonehara, S")
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([GK_141175] of Person
(_displayName "Ishii, A")
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([GK_141176] of Person
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(initial "S")
(surname "Nagata"))
([GK_141226] of Figure
(_displayName "/figures/FasL_Fas_FADD.jpg")
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(url "/figures/FasL_Fas_FADD.jpg"))
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(_displayName "/figures/FasL_Fas_FADD_Caspase8.jpg")
(DB_ID 141227)
(url "/figures/FasL_Fas_FADD_Caspase8.jpg"))
([GK_141228] of Figure
(_displayName "/figures/FasL_Fas_FADD_ProCaspase8.jpg")
(DB_ID 141228)
(url "/figures/FasL_Fas_FADD_ProCaspase8.jpg"))
([GK_141234] of Figure
(_displayName "/figures/FAS_Top.jpg")
(DB_ID 141234)
(url "/figures/FAS_Top.jpg"))
([GK_141237] of Figure
(_displayName "/figures/FasL_Fas.jpg")
(DB_ID 141237)
(url "/figures/FasL_Fas.jpg"))
([GK_141240] of Figure
(_displayName "/figures/FasL_Fas_FADD_ProCaspase10.jpg")
(DB_ID 141240)
(url "/figures/FasL_Fas_FADD_ProCaspase10.jpg"))
([GK_141277] of Figure
(_displayName "/figures/extrinsic_overview.jpeg")
(DB_ID 141277)
(url "/figures/extrinsic_overview.jpeg"))
([GK_141304] of Complex
(_displayName "[Hsa] TRAIL:TRAIL receptor-2 Trimer:FADD:Caspase-10 precursor complex [plasma membrane]")
(DB_ID 141304)
(hasComponent
[GK_57035]
[GK_141137])
(name "TRAIL:TRAIL receptor-2 Trimer:FADD:Caspase-10 precursor complex")
(species [GK_48887])
(stableIdentifier [GK_366444]))
([GK_141305] of Person
(_displayName "Grosse-Wilde, A")
(DB_ID 141305)
(initial "A")
(surname "Grosse-Wilde"))
([GK_141306] of LiteratureReference
(_displayName "Caspase-10 is an initiator caspase in death receptor signaling")
(author
[GK_84039]
[GK_141307]
[GK_141309]
[GK_141311]
[GK_141313])
(DB_ID 141306)
(journal "Proc Natl Acad Sci U S A")
(pages "13884-8")
(pubMedIdentifier 11717445)
(title "Caspase-10 is an initiator caspase in death receptor signaling")
(volume 98)
(year 2001))
([GK_141307] of Person
(_displayName "Chun, HJ")
(DB_ID 141307)
(initial "HJ")
(surname "Chun"))
([GK_141308] of Person
(_displayName "Stahl, H")
(DB_ID 141308)
(initial "H")
(surname "Stahl"))
([GK_141309] of Person
(_displayName "Wong, W")
(DB_ID 141309)
(initial "W")
(surname "Wong"))
([GK_141310] of Reaction
(_displayName "[Hsa] FASL:FAS Receptor Trimer:FADD complex binds procaspase-10")
(_doRelease TRUE)
(DB_ID 141310)
(figure [GK_141240])
(input
[GK_43124]
[GK_933453])
(literatureReference
[GK_141306]
[GK_141314])
(name "FASL:FAS Receptor Trimer:FADD complex binds procaspase-10")
(output [GK_141315])
(precedingEvent [GK_83650])
(reviewed [GK_3597630])
(species [GK_48887])
(stableIdentifier [GK_359435])
(summation [GK_178763]))
([GK_141311] of Person
(_displayName "Spencer, DM")
(DB_ID 141311)
(initial "DM")
(surname "Spencer"))
([GK_141313] of Person
(_displayName "Lenardo, MJ")
(DB_ID 141313)
(initial "MJ")
(surname "Lenardo"))
([GK_141314] of LiteratureReference
(_displayName "Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signalling complexes in a FADD-dependent manner but can not functionally substitute caspase-8")
(author
[GK_141131]
[GK_141136]
[GK_141308]
[GK_141305]
[GK_141129]
[GK_141138])
(DB_ID 141314)
(journal "EMBO J")
(pages "4520-30")
(pubMedIdentifier 12198154)
(title "Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signalling complexes in a FADD-dependent manner but can not functionally substitute caspase-8")
(volume 21)
(year 2002))
([GK_141315] of Complex
(_displayName "[Hsa] FASL:FAS Receptor Trimer:FADD:pro-Caspase-10 [plasma membrane]")
(DB_ID 141315)
(hasComponent
[GK_43124]
[GK_57035])
(name "FASL:FAS Receptor Trimer:FADD:pro-Caspase-10")
(species [GK_48887])
(stableIdentifier [GK_370192]))
([GK_141316] of Reaction
(_displayName "[Hsa] TRAIL:TRAIL-Receptor2 Trimer:FADD complex binds Caspase-10")
(_doRelease TRUE)
(DB_ID 141316)
(input
[GK_141137]
[GK_57035])
(literatureReference
[GK_141306]
[GK_141314])
(name "TRAIL:TRAIL-Receptor2 Trimer:FADD complex binds Caspase-10")
(output [GK_141304])
(precedingEvent [GK_75187])
(reviewed [GK_3597630])
(species [GK_48887])
(stableIdentifier [GK_358282])
(summation [GK_179246]))
([GK_141456] of Person
(_displayName "Vaux, David L")
(affiliation [GK_1247556])
(crossReference [GK_5626739])
(DB_ID 141456)
(firstname "David L")
(initial "DL")
(surname "Vaux"))
([GK_141644] of EntityWithAccessionedSequence
(_displayName "[Hsa] CASP3(29-175) [cytosol]")
(DB_ID 141644)
(endCoordinate 175)
(literatureReference [GK_141645])
(name
"CASP3(29-175)"
"CASP3"
"Caspase-3 (large subunit)")
(referenceEntity [GK_57022])
(species [GK_48887])
(stableIdentifier [GK_367891])
(startCoordinate 29))
([GK_141645] of LiteratureReference
(_displayName "Mechanisms of caspase activation and inhibition during apoptosis")
(author [GK_141951])
(DB_ID 141645)
(journal "Mol Cell")
(pages "459-70")
(pubMedIdentifier 11931755)
(title "Mechanisms of caspase activation and inhibition during apoptosis")
(volume 9)
(year 2002))
([GK_141646] of EntityWithAccessionedSequence
(_displayName "[Hsa] CASP3(176-277) [cytosol]")
(DB_ID 141646)
(endCoordinate 277)
(literatureReference [GK_141645])
(name
"CASP3(176-277)"
"Caspase-3 (small subunit)")
(referenceEntity [GK_57022])
(species [GK_48887])
(stableIdentifier [GK_370305])
(startCoordinate 176))
([GK_141853] of Person
(_displayName "Stennicke, HR")
(DB_ID 141853)
(firstname "H R")
(initial "HR")
(surname "Stennicke"))
([GK_141860] of Person
(_displayName "Park, YC")
(DB_ID 141860)
(firstname "Y C")
(initial "YC")
(surname "Park"))
([GK_141861] of Person
(_displayName "Rich, RL")
(DB_ID 141861)
(firstname "R L")
(initial "RL")
(surname "Rich"))
([GK_141862] of Person
(_displayName "Segal, D")
(DB_ID 141862)
(firstname "D")
(initial "D")
(surname "Segal"))
([GK_141863] of Person
(_displayName "Myszka, DG")
(DB_ID 141863)
(firstname "D G")
(initial "DG")
(surname "Myszka"))
([GK_141864] of Person
(_displayName "Wu, H")
(DB_ID 141864)
(firstname "H")
(initial "H")
(surname "Wu"))
([GK_141902] of Person
(_displayName "Vandenabeele, P")
(DB_ID 141902)
(firstname "Peter")
(initial "P")
(surname "Vandenabeele"))
([GK_141933] of Person
(_displayName "Wolf, BB")
(DB_ID 141933)
(firstname "B B")
(initial "BB")
(surname "Wolf"))
([GK_141937] of Person
(_displayName "Green, DR")
(DB_ID 141937)
(firstname "D R")
(initial "DR")
(surname "Green"))
([GK_141939] of Person
(_displayName "Silke, J")
(DB_ID 141939)
(firstname "John")
(initial "J")
(surname "Silke"))
([GK_141951] of Person
(_displayName "Shi, Y")
(DB_ID 141951)
(firstname "Yigong")
(initial "Y")
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([GK_142] of GO_BiologicalProcess
(_displayName "cell communication")
(accession "0007154")
(DB_ID 142)
(definition "Any process that mediates interactions between a cell and its surroundings. Encompasses interactions such as signaling or attachment between one cell and another cell, between a cell and an extracellular matrix, or between a cell and any other aspect of its environment.")
(name "cell communication")
(referenceDatabase [GK_1]))
([GK_143] of GO_BiologicalProcess
(_displayName "cellular process")
(accession "0009987")
(DB_ID 143)
(definition "Any process that is carried out at the cellular level, but not necessarily restricted to a single cell. For example, cell communication occurs among more than one cell, but occurs at the cellular level.")
(name "cellular process")
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(_displayName "[Hsa] UniProt:P01258 CALCA recommendedName: Calcitonin component recommendedName: Calcitonin /component component recommendedName: Katacalcin alternativeName: Calcitonin carboxyl-terminal peptide shortName:CCP alternativeName: PDN-21 /component")
(checksum "1")
(comment "FUNCTION Calcitonin causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones.FUNCTION Katacalcin is a potent plasma calcium-lowering peptide.SIMILARITY Belongs to the calcitonin family.")
(DB_ID 144921)
(description "recommendedName: Calcitonin component recommendedName: Calcitonin /component component recommendedName: Katacalcin alternativeName: Calcitonin carboxyl-terminal peptide shortName:CCP alternativeName: PDN-21 /component")
(geneName
"CALCA"
"CALC1")
(identifier "P01258")
(isSequenceChanged TRUE)
(keyword
"3D-structure"
"Alternative splicing"
"Amidation"
"Cleavage on pair of basic residues"
"Complete proteome"
"Direct protein sequencing"
"Disulfide bond"
"Hormone"
"Polymorphism"
"Secreted"
"Signal")
(name "CALCA")
(referenceDatabase [GK_2])
(secondaryIdentifier
"CALC_HUMAN"
"B7ZL39"
"Q13935"
"Q13937"
"Q52LX7")
(sequenceLength 141)
(species [GK_48887]))
([GK_145326] of ReferenceIsoform
(_displayName "[Hsa] UniProt:O15519-2 CFLAR recommendedName: CASP8 and FADD-like apoptosis regulator alternativeName: Caspase homolog shortName:CASH alternativeName: Caspase-eight-related protein shortName:Casper alternativeName: Caspase-like apoptosis regulatory protein shortName:CLARP alternativeName: Cellular FLICE-like inhibitory protein shortName:c-FLIP alternativeName: FADD-like antiapoptotic molecule 1 shortName:FLAME-1 alternativeName: Inhibitor of FLICE shortName:I-FLICE alternativeName: MACH-related inducer of toxicity shortName:MRIT alternativeName: Usurpin component recommendedName: CASP8 and FADD-like apoptosis regulator subunit p43 /component component recommendedName: CASP8 and FADD-like apoptosis regulator subunit p12 /component")
(checksum "8C6D7E92AE1EB672")
(comment "FUNCTION Apoptosis regulator protein which may function as a crucial link between cell survival and cell death pathways in mammalian cells. Acts as an inhibitor of TNFRSF6 mediated apoptosis. A proteolytic fragment (p43) is likely retained in the death-inducing signaling complex (DISC) thereby blocking further recruitment and processing of caspase-8 at the complex. Full length and shorter isoforms have been shown either to induce apoptosis or to reduce TNFRSF-triggered apoptosis. Lacks enzymatic (caspase) activity.SUBUNIT TNFRSF6 stimulation triggers recruitment to the death-inducing signaling complex (DISC) formed by TNFRSF6, FADD and caspase-8. A proteolytic fragment (p43) stays associated with the DISC. Also interacts with caspase-10, caspase-3, TRAF1, TRAF2 and Bcl-X(L) (in vitro). Interacts with HBV protein X.TISSUE SPECIFICITY Widely expressed. Higher expression in skeletal muscle, pancreas, heart, kidney, placenta, and peripheral blood leukocytes. Also detected in diverse cell lines. Isoform 8 is predominantly expressed in testis and skeletal muscle.INDUCTION Repressed by IL2/interleukin-2 after TCR stimulation, during progression to the S phase of the cell cycle.DOMAIN The caspase domain lacks the active sites residues involved in catalysis.PTM Proteolytically processed; probably by caspase-8. Processing likely occurs at the DISC and generates subunit p43 and p12.SIMILARITY Belongs to the peptidase C14A family.SIMILARITY Contains 2 DED (death effector) domains.")
(DB_ID 145326)
(description "recommendedName: CASP8 and FADD-like apoptosis regulator alternativeName: Caspase homolog shortName:CASH alternativeName: Caspase-eight-related protein shortName:Casper alternativeName: Caspase-like apoptosis regulatory protein shortName:CLARP alternativeName: Cellular FLICE-like inhibitory protein shortName:c-FLIP alternativeName: FADD-like antiapoptotic molecule 1 shortName:FLAME-1 alternativeName: Inhibitor of FLICE shortName:I-FLICE alternativeName: MACH-related inducer of toxicity shortName:MRIT alternativeName: Usurpin component recommendedName: CASP8 and FADD-like apoptosis regulator subunit p43 /component component recommendedName: CASP8 and FADD-like apoptosis regulator subunit p12 /component")
(geneName
"CFLAR"
"CASH"
"CASP8AP1"
"CLARP"
"MRIT")
(identifier "O15519")
(isoformParent [GK_51926])
(isSequenceChanged FALSE)
(keyword
"3D-structure"
"Alternative splicing"
"Apoptosis"
"Complete proteome"
"Host-virus interaction"
"Polymorphism"
"Reference proteome"
"Repeat")
(name "CFLAR")
(referenceDatabase [GK_2])
(secondaryIdentifier
"CFLAR_HUMAN"
"B4DJE0"
"B7Z9F9"
"O14673"
"O14674"
"O14675"
"O15137"
"O15138"
"O15356"
"O15510"
"O43618"
"O43619"
"O43620"
"O60458"
"O60459"
"Q53TS6"
"Q54AF1"
"Q96TE4"
"Q9UEW1")
(sequenceLength 480)
(species [GK_48887])
(variantIdentifier "O15519-2"))
([GK_1474059] of Person
(_displayName "Li, L")
(affiliation [GK_1474061])
(DB_ID 1474059)
(firstname "Liwu")
(initial "L")
(surname "Li"))
([GK_1474061] of Affiliation
(_displayName "Virginia Polytechnic Institute, Department of Biological Sciences")
(address "Blacksburg, VA")
(DB_ID 1474061)
(name "Virginia Polytechnic Institute, Department of Biological Sciences"))
([GK_148293] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:O60814 HIST1H2BK recommendedName: Histone H2B type 1-K shortName:H2B K alternativeName: HIRA-interacting protein 1 ")
(checksum "1")
(comment "SUBUNIT The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.PTM Monoubiquitination of Lys-121 by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II.SIMILARITY Belongs to the histone H2B family.")
(DB_ID 148293)
(description "recommendedName: Histone H2B type 1-K shortName:H2B K alternativeName: HIRA-interacting protein 1 ")
(geneName
"HIST1H2BK"
"H2BFT"
"HIRIP1")
(identifier "O60814")
(isSequenceChanged TRUE)
(keyword
"3D-structure"
"Acetylation"
"Antibiotic"
"Antimicrobial"
"Chromosome"
"Complete proteome"
"Direct protein sequencing"
"DNA-binding"
"Isopeptide bond"
"Methylation"
"Nucleosome core"
"Nucleus"
"Phosphoprotein"
"Ubl conjugation")
(name "HIST1H2BK")
(referenceDatabase [GK_2])
(secondaryIdentifier
"H2B1K_HUMAN"
"A8K7P7"
"Q2VPI7")
(sequenceLength 126)
(species [GK_48887]))
([GK_148294] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:Q96A08 HIST1H2BA recommendedName: Histone H2B type 1-A alternativeName: Histone H2B, testis alternativeName: Testis-specific histone H2B ")
(checksum "1")
(comment "FUNCTION Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.SUBUNIT The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.PTM Monoubiquitination of Lys-122 by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II.SIMILARITY Belongs to the histone H2B family.")
(DB_ID 148294)
(description "recommendedName: Histone H2B type 1-A alternativeName: Histone H2B, testis alternativeName: Testis-specific histone H2B ")
(geneName
"HIST1H2BA"
"TSH2B")
(identifier "Q96A08")
(isSequenceChanged TRUE)
(keyword
"Acetylation"
"Chromosome"
"Complete proteome"
"DNA-binding"
"Isopeptide bond"
"Methylation"
"Nucleosome core"
"Nucleus"
"Ubl conjugation")
(name "HIST1H2BA")
(referenceDatabase [GK_2])
(secondaryIdentifier
"H2B1A_HUMAN"
"B2R544"
"Q6NZ98"
"Q6NZA0"
"Q6NZA1")
(sequenceLength 127)
(species [GK_48887]))
([GK_148296] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:Q8N257 HIST3H2BB recommendedName: Histone H2B type 3-B alternativeName: H2B type 12 ")
(checksum "1")
(comment "FUNCTION Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.SUBUNIT The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.PTM Monoubiquitination of Lys-121 by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II.SIMILARITY Belongs to the histone H2B family.")
(DB_ID 148296)
(description "recommendedName: Histone H2B type 3-B alternativeName: H2B type 12 ")
(geneName "HIST3H2BB")
(identifier "Q8N257")
(isSequenceChanged TRUE)
(keyword
"Acetylation"
"Chromosome"
"Complete proteome"
"Direct protein sequencing"
"DNA-binding"
"Isopeptide bond"
"Methylation"
"Nucleosome core"
"Nucleus"
"Phosphoprotein"
"Ubl conjugation")
(name "HIST3H2BB")
(referenceDatabase [GK_2])
(secondaryIdentifier
"H2B3B_HUMAN"
"A4FU05"
"Q3ZCP6"
"Q5TA30")
(sequenceLength 126)
(species [GK_48887]))
([GK_1485578] of InstanceEdit
(_displayName "Shamovsky, V, 2011-08-12")
(author [GK_429259])
(dateTime "2011-08-12 16:09:37")
(DB_ID 1485578))
([GK_157508] of Affiliation
(_displayName "University of Lausanne")
(address "Department of Biochemistry
Chemin des Boveressses 155
CH-1066 Epalinges
Switzerland")
(DB_ID 157508)
(name "University of Lausanne"))
([GK_157517] of Affiliation
(_displayName "Johns Hopkins University")
(address "Professor\nMolecular Microbiology and Immunology\n615 North Wolfe Street\nSuite E5132\nBaltimore, MD 21205")
(DB_ID 157517)
(name "Johns Hopkins University"))
([GK_158007] of Affiliation
(_displayName "Cold Spring Harbor Laboratory")
(address "1 Bungtown Road, Cold Spring Harbor, NY 11724")
(DB_ID 158007)
(name
"Cold Spring Harbor Laboratory"
"CSHL"))
([GK_158417] of SimpleEntity
(_displayName "Zn2+ [extracellular region]")
(crossReference [GK_29427])
(DB_ID 158417)
(name
"Zn2+"
"Zn++"
"zinc(2+)"
"Zinc ion"
"Zn(II)")
(referenceEntity [GK_114751])
(stableIdentifier [GK_366839]))
([GK_159955] of GO_CellularComponent
(_displayName "organelle")
(accession "0043226")
(DB_ID 159955)
(definition "Organized structure of distinctive morphology and function. Includes the nucleus, mitochondria, plastids, vacuoles, vesicles, ribosomes and the cytoskeleton, and prokaryotic structures such as anammoxosomes and pirellulosomes. Excludes the plasma membrane.")
(instanceOf [GK_357])
(name "organelle")
(referenceDatabase [GK_1]))
([GK_159957] of GO_CellularComponent
(_displayName "intracellular organelle")
(accession "0043229")
(DB_ID 159957)
(definition "Organized structure of distinctive morphology and function, occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, vesicles, ribosomes and the cytoskeleton. Excludes the plasma membrane.")
(instanceOf
[GK_159955]
[GK_258148])
(name "intracellular organelle")
(referenceDatabase [GK_1]))
([GK_159959] of GO_CellularComponent
(_displayName "membrane-bounded organelle")
(accession "0043227")
(DB_ID 159959)
(definition "Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane.")
(instanceOf [GK_159955])
(name "membrane-bounded organelle")
(referenceDatabase [GK_1]))
([GK_159960] of GO_CellularComponent
(_displayName "intracellular membrane-bounded organelle")
(accession "0043231")
(DB_ID 159960)
(definition "Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane and occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane.")
(instanceOf
[GK_159959]
[GK_159957])
(name "intracellular membrane-bounded organelle")
(referenceDatabase [GK_1]))
([GK_159961] of GO_BiologicalProcess
(_displayName "cellular metabolic process")
(accession "0044237")
(DB_ID 159961)
(definition "The chemical reactions and pathways by which individual cells transform chemical substances.")
(name "cellular metabolic process")
(referenceDatabase [GK_1]))
([GK_159962] of GO_BiologicalProcess
(_displayName "primary metabolic process")
(accession "0044238")
(DB_ID 159962)
(definition "The chemical reactions and pathways involving those compounds which are formed as a part of the normal anabolic and catabolic processes. These processes take place in most, if not all, cells of the organism.")
(name "primary metabolic process")
(referenceDatabase [GK_1]))
([GK_159968] of GO_BiologicalProcess
(_displayName "response to stimulus")
(accession "0050896")
(DB_ID 159968)
(definition "Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus. The process begins with detection of the stimulus and ends with a change in state or activity or the cell or organism.")
(name "response to stimulus")
(referenceDatabase [GK_1]))
([GK_159972] of GO_BiologicalProcess
(_displayName "macromolecule metabolic process")
(accession "0043170")
(DB_ID 159972)
(definition "The chemical reactions and pathways involving macromolecules, any molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass.")
(name "macromolecule metabolic process")
(referenceDatabase [GK_1]))
([GK_159974] of GO_BiologicalProcess
(_displayName "cellular macromolecule metabolic process")
(accession "0044260")
(DB_ID 159974)
(definition "The chemical reactions and pathways involving macromolecules, any molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass, as carried out by individual cells.")
(name "cellular macromolecule metabolic process")
(referenceDatabase [GK_1]))
([GK_159975] of GO_BiologicalProcess
(_displayName "cellular protein metabolic process")
(accession "0044267")
(DB_ID 159975)
(definition "The chemical reactions and pathways involving a specific protein, rather than of proteins in general, occurring at the level of an individual cell. Includes cellular protein modification.")
(name "cellular protein metabolic process")
(referenceDatabase [GK_1]))
([GK_159979] of GO_CellularComponent
(_displayName "protein complex")
(accession "0043234")
(DB_ID 159979)
(definition "A stable macromolecular complex composed (only) of two or more polypeptide subunits along with any covalently attached molecules (such as lipid anchors or oligosaccharide) or non-protein prosthetic groups (such as nucleotides or metal ions). Prosthetic group in this context refers to a tightly bound cofactor. The component polypeptide subunits may be identical.")
(instanceOf [GK_258170])
(name "protein complex")
(referenceDatabase [GK_1]))
([GK_159990] of GO_BiologicalProcess
(_displayName "positive regulation of biological process")
(accession "0048518")
(DB_ID 159990)
(definition "Any process that activates or increases the frequency, rate or extent of a biological process. Biological processes are regulated by many means; examples include the control of gene expression, protein modification or interaction with a protein or substrate molecule.")
(name "positive regulation of biological process")
(referenceDatabase [GK_1]))
([GK_160005] of GO_BiologicalProcess
(_displayName "negative regulation of biological process")
(accession "0048519")
(DB_ID 160005)
(definition "Any process that stops, prevents, or reduces the frequency, rate or extent of a biological process. Biological processes are regulated by many means; examples include the control of gene expression, protein modification or interaction with a protein or substrate molecule.")
(name "negative regulation of biological process")
(referenceDatabase [GK_1]))
([GK_160044] of GO_BiologicalProcess
(_displayName "regulation of protein metabolic process")
(accession "0051246")
(DB_ID 160044)
(definition "Any process that modulates the frequency, rate or extent of the chemical reactions and pathways involving a protein.")
(name "regulation of protein metabolic process")
(referenceDatabase [GK_1]))
([GK_160045] of GO_BiologicalProcess
(_displayName "positive regulation of protein metabolic process")
(accession "0051247")
(DB_ID 160045)
(definition "Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways involving a protein.")
(name "positive regulation of protein metabolic process")
(referenceDatabase [GK_1]))
([GK_160064] of GO_BiologicalProcess
(_displayName "positive regulation of cellular process")
(accession "0048522")
(DB_ID 160064)
(definition "Any process that activates or increases the frequency, rate or extent of a cellular process, any of those that are carried out at the cellular level, but are not necessarily restricted to a single cell. For example, cell communication occurs among more than one cell, but occurs at the cellular level.")
(name "positive regulation of cellular process")
(referenceDatabase [GK_1]))
([GK_160114] of GO_BiologicalProcess
(_displayName "regulation of catalytic activity")
(accession "0050790")
(DB_ID 160114)
(definition "Any process that modulates the activity of an enzyme.")
(name "regulation of catalytic activity")
(referenceDatabase [GK_1]))
([GK_160116] of GO_BiologicalProcess
(_displayName "positive regulation of catalytic activity")
(accession "0043085")
(DB_ID 160116)
(definition "Any process that activates or increases the activity of an enzyme.")
(name "positive regulation of catalytic activity")
(referenceDatabase [GK_1]))
([GK_160129] of GO_CellularComponent
(_displayName "organelle membrane")
(accession "0031090")
(componentOf [GK_159959])
(DB_ID 160129)
(definition "A membrane that is one of the two lipid bilayers of an organelle envelope or the outermost membrane of single membrane bound organelle.")
(instanceOf
[GK_383187]
[GK_258146])
(name "organelle membrane")
(referenceDatabase [GK_1]))
([GK_160200] of GO_BiologicalProcess
(_displayName "negative regulation of cellular process")
(accession "0048523")
(DB_ID 160200)
(definition "Any process that stops, prevents, or reduces the frequency, rate or extent of a cellular process, any of those that are carried out at the cellular level, but are not necessarily restricted to a single cell. For example, cell communication occurs among more than one cell, but occurs at the cellular level.")
(name "negative regulation of cellular process")
(referenceDatabase [GK_1]))
([GK_160227] of GO_BiologicalProcess
(_displayName "positive regulation of programmed cell death")
(accession "0043068")
(DB_ID 160227)
(definition "Any process that activates or increases the frequency, rate or extent of programmed cell death, cell death resulting from activation of endogenous cellular processes.")
(name "positive regulation of programmed cell death")
(referenceDatabase [GK_1]))
([GK_160291] of GO_BiologicalProcess
(_displayName "regulation of hydrolase activity")
(accession "0051336")
(DB_ID 160291)
(definition "Any process that modulates the frequency, rate or extent of hydrolase activity, the catalysis of the hydrolysis of various bonds, e.g. C-O, C-N, C-C, phosphoric anhydride bonds, etc. Hydrolase is the systematic name for any enzyme of EC class 3.")
(name "regulation of hydrolase activity")
(referenceDatabase [GK_1]))
([GK_160292] of GO_BiologicalProcess
(_displayName "regulation of cysteine-type endopeptidase activity involved in apoptotic process")
(accession "0043281")
(DB_ID 160292)
(definition "Any process that modulates the activity of a cysteine-type endopeptidase involved in apoptosis.")
(name "regulation of cysteine-type endopeptidase activity involved in apoptotic process")
(referenceDatabase [GK_1]))
([GK_160293] of GO_BiologicalProcess
(_displayName "positive regulation of hydrolase activity")
(accession "0051345")
(DB_ID 160293)
(definition "Any process that activates or increases the frequency, rate or extent of hydrolase activity, the catalysis of the hydrolysis of various bonds.")
(name "positive regulation of hydrolase activity")
(referenceDatabase [GK_1]))
([GK_160294] of GO_BiologicalProcess
(_displayName "positive regulation of cysteine-type endopeptidase activity involved in apoptotic process")
(accession "0043280")
(DB_ID 160294)
(definition "Any process that activates or increases the activity of a cysteine-type endopeptidase involved in the apoptotic process.")
(name "positive regulation of cysteine-type endopeptidase activity involved in apoptotic process")
(referenceDatabase [GK_1]))
([GK_160483] of GO_CellularComponent
(_displayName "extraorganismal space")
(accession "0043245")
(DB_ID 160483)
(definition "The environmental space outside of an organism; this may be a host organism in the case of parasitic and symbiotic organisms.")
(instanceOf [GK_258201])
(name "extraorganismal space")
(referenceDatabase [GK_1]))
([GK_160565] of GO_BiologicalProcess
(_displayName "positive regulation of apoptotic process")
(accession "0043065")
(DB_ID 160565)
(definition "Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process.")
(name "positive regulation of apoptotic process")
(referenceDatabase [GK_1]))
([GK_161217] of GO_CellularComponent
(_displayName "death-inducing signaling complex")
(accession "0031264")
(DB_ID 161217)
(definition "A protein complex formed by the association of signaling proteins with a death receptor upon ligand binding. The complex includes procaspases and death domain-containing proteins in addition to the ligand-bound receptor, and may control the activation of caspases 8 and 10.")
(instanceOf
[GK_159979]
[GK_258155])
(name "death-inducing signaling complex")
(referenceDatabase [GK_1]))
([GK_163570] of Person
(_displayName "Wernstedt, C")
(DB_ID 163570)
(firstname "Christier")
(initial "C")
(surname "Wernstedt"))
([GK_164487] of Taxon
(_displayName "root")
(DB_ID 164487)
(name "root"))
([GK_165085] of InstanceEdit
(_displayName "Gillespie, ME, 0000-00-00 00:00:00")
(author [GK_73681])
(dateTime "0000-00-00 00:00:00")
(DB_ID 165085))
([GK_165094] of InstanceEdit
(_displayName "Vaux, D, 0000-00-00 00:00:00")
(author [GK_141456])
(dateTime "0000-00-00 00:00:00")
(DB_ID 165094))
([GK_165789] of ReferenceGeneProduct
(_chainChangeLog "initiator methionine:1 added on Fri February 6 2015;chain:2-235 added on Fri February 6 2015")
(_displayName "[Hsa] UniProt:Q86XR7 TICAM2 recommendedName: TIR domain-containing adapter molecule 2 shortName:TICAM-2 alternativeName: Putative NF-kappa-B-activating protein 502 alternativeName: TRIF-related adapter molecule alternativeName: Toll-like receptor adaptor protein 3 alternativeName: Toll/interleukin-1 receptor domain-containing protein shortName:MyD88-4 ")
(chain
"initiator methionine:1"
"chain:2-235")
(checksum "2D1171F9B04D9C4C")
(comment "FUNCTION Functions as sorting adapter in LPS-TLR4 signaling to regulate the MYD88-independent pathway during the innate immune response to LPS. Physically bridges TLR4 and TICAM1 and functionally transmits LPS-TRL4 signal to TICAM1; signaling is proposed to occur in early endosomes after endocytosis of TLR4. May also be involved in IL1-triggered NF-kappa-B activation, functioning upstream of IRAK1, IRAK2, TRAF6, and IKBKB; however, reports are controversial. Involved in IL-18 signaling and is proposed to function as a sorting adaptor for MYD88 in IL-18 signaling during adaptive immune response.FUNCTION Isoform 2: Proposed to inhibit LPS-TLR4 signaling at the late endosome by interaction with isoform 1 thereby disrupting the association of isoform 1 with TICAM1. May be involved in TLR4 degradation in late endosomes.")
(DB_ID 165789)
(description "recommendedName: TIR domain-containing adapter molecule 2 shortName:TICAM-2 alternativeName: Putative NF-kappa-B-activating protein 502 alternativeName: TRIF-related adapter molecule alternativeName: Toll-like receptor adaptor protein 3 alternativeName: Toll/interleukin-1 receptor domain-containing protein shortName:MyD88-4 ")
(geneName
"TICAM2"
"TIRAP3"
"TIRP"
"TRAM")
(identifier "Q86XR7")
(isSequenceChanged FALSE)
(keyword
"3D-structure"
"Alternative splicing"
"Cell membrane"
"Complete proteome"
"Cytoplasm"
"Endoplasmic reticulum"
"Endosome"
"Golgi apparatus"
"Immunity"
"Inflammatory response"
"Innate immunity"
"Lipoprotein"
"Membrane"
"Myristate"
"Phosphoprotein"
"Reference proteome")
(name "TICAM2")
(referenceDatabase [GK_2])
(secondaryIdentifier
"TCAM2_HUMAN"
"B3Y698"
"Q6JUT2")
(sequenceLength 235)
(species [GK_48887]))
([GK_165792] of ReferenceGeneProduct
(_chainChangeLog "chain:1-712 added on Sat February 7 2015")
(_displayName "[Hsa] UniProt:Q8IUC6 TICAM1 recommendedName: TIR domain-containing adapter molecule 1 shortName:TICAM-1 alternativeName: Proline-rich, vinculin and TIR domain-containing protein B alternativeName: Putative NF-kappa-B-activating protein 502H alternativeName: Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta shortName:MyD88-3 shortName:TIR domain-containing adapter protein inducing IFN-beta ")
(chain "chain:1-712")
(checksum "5D071E3BE9240D9A")
(comment "SIMILARITY Contains 1 TIR domain.")
(DB_ID 165792)
(description "recommendedName: TIR domain-containing adapter molecule 1 shortName:TICAM-1 alternativeName: Proline-rich, vinculin and TIR domain-containing protein B alternativeName: Putative NF-kappa-B-activating protein 502H alternativeName: Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta shortName:MyD88-3 shortName:TIR domain-containing adapter protein inducing IFN-beta ")
(geneName
"TICAM1"
"PRVTIRB"
"TRIF")
(identifier "Q8IUC6")
(isSequenceChanged FALSE)
(keyword
"3D-structure"
"Antiviral defense"
"Apoptosis"
"Complete proteome"
"Disease mutation"
"Immunity"
"Inflammatory response"
"Innate immunity"
"Phosphoprotein"
"Polymorphism"
"Reference proteome"
"Ubl conjugation")
(name "TICAM1")
(referenceDatabase [GK_2])
(secondaryIdentifier
"TCAM1_HUMAN"
"B3Y691"
"O75532"
"Q86XP8"
"Q96GA0")
(sequenceLength 712)
(species [GK_48887]))
([GK_165828] of Person
(_displayName "Golenbock, DT")
(DB_ID 165828)
(initial "DT")
(surname "Golenbock"))
([GK_165841] of Person
(_displayName "Gay, NJ")
(affiliation [GK_1237412])
(DB_ID 165841)
(firstname "Nicholas J")
(initial "NJ")
(surname "Gay"))
([GK_165849] of Person
(_displayName "Takeda, K")
(DB_ID 165849)
(initial "K")
(surname "Takeda"))
([GK_165851] of Person
(_displayName "Sato, S")
(DB_ID 165851)
(initial "S")
(surname "Sato"))
([GK_165854] of Person
(_displayName "Hoshino, K")
(DB_ID 165854)
(initial "K")
(surname "Hoshino"))
([GK_165855] of Person
(_displayName "Takeuchi, O")
(DB_ID 165855)
(firstname "Osamu")
(initial "O")
(surname "Takeuchi"))
([GK_165858] of Person
(_displayName "Hemmi, H")
(DB_ID 165858)
(initial "H")
(surname "Hemmi"))
([GK_165859] of Person
(_displayName "Uematsu, S")
(DB_ID 165859)
(firstname "Satoshi")
(initial "S")
(surname "Uematsu"))
([GK_165860] of Person
(_displayName "Kaisho, T")
(DB_ID 165860)
(initial "T")
(surname "Kaisho"))
([GK_165861] of LiteratureReference
(_displayName "TRAM is specifically involved in the Toll-like receptor 4-mediated")
(author
[GK_75497]
[GK_165851]
[GK_165858]
[GK_165859]
[GK_165854]
[GK_165860]
[GK_165855]
[GK_165849])
(DB_ID 165861)
(journal "Nat Immunol")
(pages "1144-50")
(pubMedIdentifier 14556004)
(title "TRAM is specifically involved in the Toll-like receptor 4-mediated")
(volume 4)
(year 2003))
([GK_165872] of Person
(_displayName "Flavell, RA")
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(initial "RA")
(surname "Flavell"))
([GK_165873] of Person
(_displayName "Medzhitov, R")
(DB_ID 165873)
(firstname "Ruslan")
(initial "R")
(surname "Medzhitov"))
([GK_165908] of Person
(_displayName "Pitha-Rowe, PM")
(affiliation [GK_157517])
(DB_ID 165908)
(firstname "Paula M")
(initial "PM")
(surname "Pitha-Rowe"))
([GK_165909] of LiteratureReference
(_displayName "LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters")
(author
[GK_165916]
[GK_165913]
[GK_165914]
[GK_165910]
[GK_1679130]
[GK_165912]
[GK_1679119]
[GK_165908]
[GK_165828])
(DB_ID 165909)
(journal "J Exp Med")
(pages "1043-55")
(pubMedIdentifier 14517278)
(title "LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters")
(volume 198)
(year 2003))
([GK_165910] of Person
(_displayName "Caffrey, DR")
(DB_ID 165910)
(initial "DR")
(surname "Caffrey"))
([GK_165912] of Person
(_displayName "Latz, E")
(DB_ID 165912)
(initial "E")
(surname "Latz"))
([GK_165913] of Person
(_displayName "Rowe, DC")
(DB_ID 165913)
(initial "DC")
(surname "Rowe"))
([GK_165914] of Person
(_displayName "Barnes, BJ")
(DB_ID 165914)
(initial "BJ")
(surname "Barnes"))
([GK_165916] of Person
(_displayName "Fitzgerald, Katherine A")
(affiliation [GK_638653])
(DB_ID 165916)
(firstname "Katherine A")
(initial "KA")
(surname "Fitzgerald"))
([GK_165918] of Person
(_displayName "Sanjo, H")
(DB_ID 165918)
(initial "H")
(surname "Sanjo"))
([GK_165953] of Person
(_displayName "Martinon, F")
(DB_ID 165953)
(initial "F")
(surname "Martinon"))
([GK_165954] of LiteratureReference
(_displayName "RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B")
(author
[GK_165956]
[GK_165959]
[GK_165955]
[GK_165957]
[GK_165953]
[GK_165958]
[GK_77293])
(DB_ID 165954)
(journal "Nat Immunol")
(pages "503-7")
(pubMedIdentifier 15064760)
(title "RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B")
(volume 5)
(year 2004))
([GK_165955] of Person
(_displayName "Hofmann, K")
(DB_ID 165955)
(initial "K")
(surname "Hofmann"))
([GK_165956] of Person
(_displayName "Meylan, E")
(DB_ID 165956)
(initial "E")
(surname "Meylan"))
([GK_165957] of Person
(_displayName "Blancheteau, V")
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(initial "V")
(surname "Blancheteau"))
([GK_165958] of Person
(_displayName "Kelliher, M")
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([GK_165959] of Person
(_displayName "Burns, K")
(DB_ID 165959)
(initial "K")
(surname "Burns"))
([GK_166017] of InstanceEdit
(_displayName "de Bono, B, 2005-08-16 10:54:15")
(author [GK_114499])
(dateTime "2005-08-16 10:54:15")
(DB_ID 166017))
([GK_166032] of ModifiedResidue
(_displayName "N-asparaginyl-glycosylphosphatidylinositolethanolamine at 345")
(coordinate 345)
(DB_ID 166032)
(psiMod [GK_445675])
(referenceSequence [GK_51618]))
([GK_166158] of LiteratureReference
(_displayName "Endotoxin recognition and signal transduction by the TLR4/MD2-complex")
(author
[GK_165916]
[GK_165913]
[GK_165828])
(DB_ID 166158)
(journal "Microbes Infect")
(pages "1361-7")
(pubMedIdentifier 15596121)
(title "Endotoxin recognition and signal transduction by the TLR4/MD2-complex")
(volume 6)
(year 2004))
([GK_166162] of ModifiedResidue
(_displayName "N-myristoylglycine at 2")
(coordinate 2)
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(psiMod [GK_445679])
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[GK_2201299]
[GK_2201336]
[GK_2201336])
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[GK_936981]
[GK_166158])
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(species [GK_48887])
(stableIdentifier [GK_363539]))
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(name
"TICAM1"
"TRIF")
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(stableIdentifier [GK_369652])
(startCoordinate 1))
([GK_166172] of Complex
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(DB_ID 166172)
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[GK_166163]
[GK_166170]
[GK_166170])
(literatureReference
[GK_2423800]
[GK_165909])
(name "TRIF:TRAM:TLR4:LY96:LPS:CD14")
(species [GK_48887])
(stableIdentifier [GK_367817]))
([GK_166175] of Reaction
(_displayName "[Hsa] TRAM:TLR4:LY96:LPS:CD14 recruits TRIF (TICAM1)")
(_doRelease TRUE)
(authored [GK_166017])
(DB_ID 166175)
(edited [GK_1485578])
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[GK_166170]
[GK_166163]
[GK_166170])
(literatureReference
[GK_177881]
[GK_165861]
[GK_165909])
(name "TRAM:TLR4:LY96:LPS:CD14 recruits TRIF (TICAM1)")
(output [GK_166172])
(releaseDate "2010-12-14")
(reviewed
[GK_188961]
[GK_1095192]
[GK_2582977])
(species [GK_48887])
(stableIdentifier [GK_361230])
(summation [GK_169810]))
([GK_167743] of EntityWithAccessionedSequence
(_displayName "[Hsa] Beta-2-microglobulin [plasma membrane]")
(DB_ID 167743)
(endCoordinate 119)
(name "Beta-2-microglobulin")
(referenceEntity [GK_50591])
(species [GK_48887])
(stableIdentifier [GK_368685])
(startCoordinate 21))
([GK_1678992] of Person
(_displayName "Saitoh, S")
(DB_ID 1678992)
(firstname "Shin-Ichiroh")
(initial "S")
(surname "Saitoh"))
([GK_1679060] of Person
(_displayName "Miyake, K")
(DB_ID 1679060)
(firstname "Kensuke")
(initial "K")
(surname "Miyake"))
([GK_167907] of InstanceEdit
(_displayName "Luo, F, 2005-11-10 11:23:18")
(author [GK_167911])
(dateTime "2005-11-10 11:23:18")
(DB_ID 167907))
([GK_167908] of Affiliation
(_displayName "University of Texas Southwestern Medical Center at Dallas")
(DB_ID 167908)
(name "University of Texas Southwestern Medical Center at Dallas"))
([GK_167911] of Person
(_displayName "Luo, F")
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(DB_ID 167911)
(firstname "Feng")
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([GK_1679119] of Person
(_displayName "Monks, BG")
(DB_ID 1679119)
(firstname "Brian G")
(initial "BG")
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([GK_1679130] of Person
(_displayName "Visintin, A")
(DB_ID 1679130)
(firstname "Alberto")
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([GK_1679557] of Person
(_displayName "Kusumoto, Y")
(DB_ID 1679557)
(firstname "Yutaka")
(initial "Y")
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([GK_167985] of Complex
(_displayName "[Hsa] viral dsRNA :TLR3 [endosome membrane]")
(authored [GK_167907])
(DB_ID 167985)
(hasComponent
[GK_433905]
[GK_2000341]
[GK_2000341])
(literatureReference
[GK_2445220]
[GK_2445239])
(name "viral dsRNA :TLR3")
(species [GK_48887])
(stableIdentifier [GK_368892]))
([GK_168092] of Reaction
(_displayName "[Hsa] Viral dsRNA binds the Toll-Like Receptor 3 (TLR3)")
(_doRelease TRUE)
(authored [GK_167907])
(DB_ID 168092)
(edited [GK_2129343])
(input
[GK_434118]
[GK_2000341]
[GK_2000341])
(literatureReference
[GK_177856]
[GK_434101])
(name "Viral dsRNA binds the Toll-Like Receptor 3 (TLR3)")
(output [GK_167985])
(relatedSpecies [GK_5617433])
(releaseDate "2010-12-14")
(reviewed [GK_188961])
(revised [GK_442879])
(species [GK_48887])
(stableIdentifier [GK_359837])
(summation [GK_433801]))
([GK_168344] of InstanceEdit
(_displayName "Luo, F, 2005-11-16 12:05:41")
(author [GK_167911])
(dateTime "2005-11-16 12:05:41")
(DB_ID 168344))
([GK_168651] of EntityWithAccessionedSequence
(_displayName "[Hsa] RIPK1 [cytosol]")
(authored [GK_168344])
(DB_ID 168651)
(endCoordinate 671)
(name
"RIPK1"
"Receptor-interacting serine/threonine-protein kinase 1"
"receptor interacting protein 1 kinase"
"RIP1")
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(species [GK_48887])
(stableIdentifier [GK_364408])
(startCoordinate 1))
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"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4"
"3.4")
(name "peptidase activity")
(referenceDatabase [GK_1]))
([GK_168907] of Complex
(_displayName "[Hsa] viral dsRNA:TLR3:TRIF [endosome membrane]")
(authored [GK_167907])
(DB_ID 168907)
(hasComponent
[GK_167985]
[GK_450316]
[GK_450316])
(literatureReference [GK_2428862])
(name "viral dsRNA:TLR3:TRIF ")
(species [GK_48887])
(stableIdentifier [GK_371234]))
([GK_168912] of Complex
(_displayName "[Hsa] RIP1:TRIF:activated TLR3/TLR4 [endosome membrane]")
(authored [GK_168344])
(DB_ID 168912)
(hasComponent
[GK_2201340]
[GK_168651]
[GK_168651])
(literatureReference
[GK_433849]
[GK_165954]
[GK_936978])
(name "RIP1:TRIF:activated TLR3/TLR4")
(species [GK_48887])
(stableIdentifier [GK_364813]))
([GK_168921] of Reaction
(_displayName "[Hsa] TRIF:activated TLR3/TLR4 complex recruits RIP1")
(_doRelease TRUE)
(authored [GK_166017])
(DB_ID 168921)
(edited [GK_1485578])
(input
[GK_168651]
[GK_168651]
[GK_2201340])
(literatureReference
[GK_433849]
[GK_936978])
(name "TRIF:activated TLR3/TLR4 complex recruits RIP1")
(output [GK_168912])
(precedingEvent
[GK_166175]
[GK_168929])
(releaseDate "2010-12-14")
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[GK_188961]
[GK_1095192]
[GK_2582977])
(species [GK_48887])
(stableIdentifier [GK_359745])
(summation [GK_433930]))
([GK_168929] of Reaction
(_displayName "[Hsa] Viral dsRNA:TLR3 recruits TRIF (TICAM1)")
(_doRelease TRUE)
(authored [GK_167907])
(DB_ID 168929)
(edited [GK_450360])
(input
[GK_166170]
[GK_166170]
[GK_167985])
(literatureReference
[GK_434112]
[GK_177881]
[GK_165909])
(name "Viral dsRNA:TLR3 recruits TRIF (TICAM1)")
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(releaseDate "2010-12-14")
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[GK_188961]
[GK_2582977])
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(species [GK_48887])
(stableIdentifier [GK_361340])
(summation [GK_450288]))
([GK_169810] of Summation
(_displayName "TRIF (TICAM1) mediates the MyD88-independent pathway from TL...")
(DB_ID 169810)
(literatureReference [GK_165861])
(text "TRIF (TICAM1) mediates the MyD88-independent pathway from TLR4."))
([GK_171090] of Person
(_displayName "Soutar, AK")
(DB_ID 171090)
(firstname "Anne K")
(initial "AK")
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([GK_171324] of GO_BiologicalProcess
(_displayName "regulation of cellular metabolic process")
(accession "0031323")
(DB_ID 171324)
(definition "Any process that modulates the frequency, rate or extent of the chemical reactions and pathways by which individual cells transform chemical substances.")
(name "regulation of cellular metabolic process")
(referenceDatabase [GK_1]))
([GK_171336] of GO_BiologicalProcess
(_displayName "positive regulation of cellular metabolic process")
(accession "0031325")
(DB_ID 171336)
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(name "positive regulation of cellular metabolic process")
(referenceDatabase [GK_1]))
([GK_171348] of GO_BiologicalProcess
(_displayName "regulation of response to stimulus")
(accession "0048583")
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(name "regulation of response to stimulus")
(referenceDatabase [GK_1]))
([GK_171349] of GO_BiologicalProcess
(_displayName "positive regulation of response to stimulus")
(accession "0048584")
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(name "positive regulation of response to stimulus")
(referenceDatabase [GK_1]))
([GK_171391] of GO_CellularComponent
(_displayName "membrane-enclosed lumen")
(accession "0031974")
(DB_ID 171391)
(definition "The enclosed volume within a sealed membrane or between two sealed membranes. Encompasses the volume enclosed by the membranes of a particular organelle, e.g. endoplasmic reticulum lumen, or the space between the two lipid bilayers of a double membrane surrounding an organelle, e.g. nuclear envelope lumen.")
(instanceOf [GK_357])
(name "membrane-enclosed lumen")
(referenceDatabase [GK_1]))
([GK_171449] of GO_BiologicalProcess
(_displayName "negative regulation of response to stimulus")
(accession "0048585")
(DB_ID 171449)
(definition "Any process that stops, prevents, or reduces the frequency, rate or extent of a response to a stimulus. Response to stimulus is a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus.")
(name "negative regulation of response to stimulus")
(referenceDatabase [GK_1]))
([GK_171571] of GO_BiologicalProcess
(_displayName "cellular response to stimulus")
(accession "0051716")
(DB_ID 171571)
(definition "Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus. The process begins with detection of the stimulus by a cell and ends with a change in state or activity or the cell.")
(name "cellular response to stimulus")
(referenceDatabase [GK_1]))
([GK_172054] of GO_BiologicalProcess
(_displayName "protein maturation")
(accession "0051604")
(DB_ID 172054)
(definition "Any process leading to the attainment of the full functional capacity of a protein.")
(name "protein maturation")
(referenceDatabase [GK_1]))
([GK_172710] of GO_BiologicalProcess
(_displayName "zymogen activation")
(accession "0031638")
(DB_ID 172710)
(definition "The proteolytic processing of an inactive enzyme to an active form.")
(name "zymogen activation")
(referenceDatabase [GK_1]))
([GK_174719] of EntityWithAccessionedSequence
(_displayName "[Hsa] perlecan [plasma membrane]")
(DB_ID 174719)
(endCoordinate 4391)
(name
"perlecan"
"HSPG2")
(referenceEntity [GK_61584])
(species [GK_48887])
(stableIdentifier [GK_366563])
(startCoordinate 22))
([GK_177846] of Person
(_displayName "Alexopoulou, L")
(DB_ID 177846)
(initial "L")
(surname "Alexopoulou"))
([GK_177849] of Person
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(DB_ID 177849)
(firstname "Kenji")
(initial "K")
(surname "Funami"))
([GK_177851] of Person
(_displayName "Okabe, M")
(DB_ID 177851)
(initial "M")
(surname "Okabe"))
([GK_177853] of Person
(_displayName "Holt, AC")
(DB_ID 177853)
(initial "AC")
(surname "Holt"))
([GK_177854] of Person
(_displayName "Oshiumi, H")
(DB_ID 177854)
(firstname "Hiroyuki")
(initial "H")
(surname "Oshiumi"))
([GK_177856] of LiteratureReference
(_displayName "Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3")
(author
[GK_177846]
[GK_177853]
[GK_165873]
[GK_165872])
(DB_ID 177856)
(journal "Nature")
(pages "732-8")
(pubMedIdentifier 11607032)
(title "Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3")
(volume 413)
(year 2001))
([GK_177869] of Person
(_displayName "Matsumoto, M")
(DB_ID 177869)
(firstname "Misako")
(initial "M")
(surname "Matsumoto"))
([GK_177871] of Person
(_displayName "Sugiyama, M")
(DB_ID 177871)
(initial "M")
(surname "Sugiyama"))
([GK_177878] of Person
(_displayName "Seya, T")
(DB_ID 177878)
(firstname "Tsukasa")
(initial "T")
(surname "Seya"))
([GK_177881] of LiteratureReference
(_displayName "Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway")
(author
[GK_75497]
[GK_165851]
[GK_165858]
[GK_165854]
[GK_165860]
[GK_165918]
[GK_165855]
[GK_177871]
[GK_177851]
[GK_165849])
(DB_ID 177881)
(journal "Science")
(pages "640-3")
(pubMedIdentifier 12855817)
(title "Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway")
(volume 301)
(year 2003))
([GK_178760] of Summation
(_displayName "Monomeric caspase-8 zymogens undergo dimerization and subseq...")
(DB_ID 178760)
(text "Monomeric caspase-8 zymogens undergo dimerization and subsequent conformational changes at the FASL:FAS Receptor Trimer:FADD:procaspase-8 receptor complex leading to the formation of the catalytically active form of procaspase-8."))
([GK_178761] of Summation
(_displayName "FASL (FAS antigen ligand) binds FAS receptor (CD95) (Brunner...")
(DB_ID 178761)
(literatureReference [GK_140513])
(text "FASL (FAS antigen ligand) binds FAS receptor (CD95) (Brunner et al. 1995). "))
([GK_178762] of Summation
(_displayName "FADD (FAS-associating death domain-containing) protein binds...")
(DB_ID 178762)
(literatureReference [GK_140495])
(text "FADD (FAS-associating death domain-containing) protein binds FASL:FAS receptor trimer through interaction of death domains of FADD and FAS (Boldin et al. 1995)."))
([GK_178763] of Summation
(_displayName "FADD recruits caspase-10 precursor (pro-caspase-10) to FASL:...")
(DB_ID 178763)
(literatureReference
[GK_141306]
[GK_141314])
(text "FADD recruits caspase-10 precursor (pro-caspase-10) to FASL:FAS receptor trimer (Wang et al. 2001, Sprick et al. 2002). "))
([GK_178764] of Summation
(_displayName "Caspase-8 precursor (Pro-Caspase-8, also known as MACH) bind...")
(DB_ID 178764)
(literatureReference [GK_140941])
(text "Caspase-8 precursor (Pro-Caspase-8, also known as MACH) binds the complex of FADD and FASL:FAS receptor trimer (Boldin et al. 1996). "))
([GK_178769] of Summation
(_displayName "Caspase-8 zymogens are present in the cells as inactive mono...")
(DB_ID 178769)
(text "Caspase-8 zymogens are present in the cells as inactive monomers, containing a large N-terminal prodomain with two death effector domains (DED), and a C-terminal catalytic subunit composed of small and a large domains separated by a smaller linker region [Donepudi M et al 2003; Keller N et al 2009]. Dimerization is required for the caspase-8 activation [Donepudi M et al 2003]. Once dimerized, caspase-8 zymogen undergoes a series of autoproteolytic cleavage events at aspartic acid residues in their interdomain linker regions. A second cleavage event between the the N-terminal prodomain and the catalytic domain releases the active caspase from the activation complex into the cytosol. The resulting fully active enzyme is a homodimer of catalytic domains, where each domain is composed of a large p18 and a small p10 subunit [Keller N et al 2009; Oberst A et al 2010]."))
([GK_1791] of GO_MolecularFunction
(_displayName "metalloendopeptidase activity")
(accession "0004222")
(DB_ID 1791)
(definition "Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a mechanism in which water acts as a nucleophile, one or two metal ions hold the water molecule in place, and charged amino acid side chains are ligands for the metal ions.")
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"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24"
"3.4.24")
(name "metalloendopeptidase activity")
(referenceDatabase [GK_1]))
([GK_179238] of Summation
(_displayName "TNF-alpha (tumor necrosis factor-alpha, TNF) binds TNF-RI (t...")
(DB_ID 179238)
(literatureReference [GK_140945])
(text "TNF-alpha (tumor necrosis factor-alpha, TNF) binds TNF-RI (tumor necrosis factor receptor superfamily member 1A, TNFRSF1A) (Stauber et al. 1988)."))
([GK_179239] of Summation
(_displayName "Monomeric caspase-8 zymogens undergo dimerization and subseq...")
(DB_ID 179239)
(text "Monomeric caspase-8 zymogens undergo dimerization and subsequent conformational changes at the TRADD:TRAF2:RIP1:FADD:Capase-8 receptor complex leading to the formation of the catalytically active form of procaspase-8."))
([GK_179240] of Summation
(_displayName "Caspase-8-precursor (pro-caspase-8) binds TRAF2:TRADD:RIP1:F...")
(DB_ID 179240)
(literatureReference [GK_140979])
(text "Caspase-8-precursor (pro-caspase-8) binds TRAF2:TRADD:RIP1:FADD complex (Micheau and Tschopp, 2003). "))
([GK_179243] of Summation
(_displayName "TRAIL (TNF-related apoptosis-inducing ligand) binds TRAIL re...")
(DB_ID 179243)
(literatureReference [GK_141147])
(text "TRAIL (TNF-related apoptosis-inducing ligand) binds TRAIL receptor-1 (TNFRSF10A) or TRAIL receptor-2 (TNFRSF10B) (Wiley et al. 1995, Pan et al. 1997, Walczak et al. 1997). "))
([GK_179244] of Summation
(_displayName "Monomeric caspase-8 zymogens undergo dimerization and subseq...")
(DB_ID 179244)
(text "Monomeric caspase-8 zymogens undergo dimerization and subsequent conformational changes at the TRAIL:TRAIL receptor-2:FADD receptor complex leading to the formation of the catalytically active form of procaspase-8."))
([GK_179245] of Summation
(_displayName "The trimeric complex of TRAIL and TRAIL receptor-1 (TNFSF10:...")
(DB_ID 179245)
(literatureReference [GK_141128])
(text "The trimeric complex of TRAIL and TRAIL receptor-1 (TNFSF10:TNFRSF10A) or TRAIL receptor-2 (TNFSF10:TNFRSF10B) binds FADD (Sprick et al. 2000)."))
([GK_179246] of Summation
(_displayName "Caspase-10 precursor is recruited to the TRAIL:TRAIL recepto...")
(DB_ID 179246)
(literatureReference
[GK_141306]
[GK_141314])
(text "Caspase-10 precursor is recruited to the TRAIL:TRAIL receptor-2:FADD complex (Sprick et al. 2002) through interaction of death effector domains of caspase-10 and FADD (Wang et al. 2001). "))
([GK_179247] of Summation
(_displayName "FADD recruits caspase-8 precursor to trimeric complex of TRA...")
(DB_ID 179247)
(literatureReference [GK_141128])
(text "FADD recruits caspase-8 precursor to trimeric complex of TRAIL (TNFSF10) and TRAIL receptors (TNFRSF10A or TNFRSF10B) (Sprick et al. 2000)."))
([GK_179272] of Summation
(_displayName "The complex of FASL (FAS antigen ligand) and FAS receptor (C...")
(DB_ID 179272)
(literatureReference [GK_140505])
(text "The complex of FASL (FAS antigen ligand) and FAS receptor (CD95) trimerizes (Kischkel et al. 1995)."))
([GK_179273] of Summation
(_displayName "The complex of TRAIL and TRAIL receptor-2 trimerizes (Sprick...")
(DB_ID 179273)
(literatureReference [GK_141128])
(text "The complex of TRAIL and TRAIL receptor-2 trimerizes (Sprick et al. 2000). "))
([GK_1793] of GO_MolecularFunction
(_displayName "endopeptidase activity")
(accession "0004175")
(DB_ID 1793)
(definition "Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain.")
(name "endopeptidase activity")
(referenceDatabase [GK_1]))
([GK_1795] of GO_MolecularFunction
(_displayName "metallopeptidase activity")
(accession "0008237")
(DB_ID 1795)
(definition "Catalysis of the hydrolysis of peptide bonds by a mechanism in which water acts as a nucleophile, one or two metal ions hold the water molecule in place, and charged amino acid side chains are ligands for the metal ions.")
(name "metallopeptidase activity")
(referenceDatabase [GK_1]))
([GK_179878] of EntityWithAccessionedSequence
(_displayName "[Hsa] ADAM17 [plasma membrane]")
(DB_ID 179878)
(endCoordinate 824)
(name
"ADAM17"
"ADAM 17 metalloprotease"
"ADAM 17 sheddase"
"TACE")
(referenceEntity [GK_49678])
(species [GK_48887])
(stableIdentifier [GK_363923])
(startCoordinate 215))
([GK_181090] of Person
(_displayName "Segal, DM")
(DB_ID 181090)
(firstname "David M")
(initial "DM")
(surname "Segal"))
([GK_183154] of ReferenceDatabase
(_displayName "PubChem Substance")
(accessUrl "http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=###ID###")
(DB_ID 183154)
(name "PubChem Substance")
(url "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pcsubstance"))
([GK_183308] of DatabaseIdentifier
(_displayName "PubChem Substance:11533263")
(DB_ID 183308)
(identifier "11533263")
(referenceDatabase [GK_183154]))
([GK_183728] of DatabaseIdentifier
(_displayName "PubChem Substance:8145461")
(DB_ID 183728)
(identifier "8145461")
(referenceDatabase [GK_183154]))
([GK_186930] of Person
(_displayName "Yamaguchi, I")
(DB_ID 186930)
(firstname "Isomaro")
(initial "I")
(surname "Yamaguchi"))
([GK_188072] of Person
(_displayName "O'Neill, LA")
(DB_ID 188072)
(initial "LA")
(surname "O'Neill"))
([GK_188961] of InstanceEdit
(_displayName "Gay, NJ, 2006-04-24 16:48:17")
(author [GK_165841])
(dateTime "2006-04-24 16:48:17")
(DB_ID 188961))
([GK_189563] of Person
(_displayName "Hasegawa, K")
(DB_ID 189563)
(initial "K")
(surname "Hasegawa"))
([GK_193525] of Person
(_displayName "Suzuki, Y")
(DB_ID 193525)
(firstname "Yasuyuki")
(initial "Y")
(surname "Suzuki"))
([GK_193908] of Person
(_displayName "Schneider, P")
(DB_ID 193908)
(initial "P")
(surname "Schneider"))
([GK_194488] of Person
(_displayName "Yamashita, T")
(DB_ID 194488)
(initial "T")
(surname "Yamashita"))
([GK_1996045] of GO_BiologicalProcess
(_displayName "positive regulation of cysteine-type endopeptidase activity")
(accession "2001056")
(DB_ID 1996045)
(definition "Any process that activates or increases the frequency, rate or extent of cysteine-type endopeptidase activity.")
(name "positive regulation of cysteine-type endopeptidase activity")
(referenceDatabase [GK_1]))
([GK_2] of ReferenceDatabase
(_displayName "UniProt")
(accessUrl "http://www.uniprot.org/entry/###ID###")
(DB_ID 2)
(name
"UniProt"
"SWALL"
"SPTR"
"SwissProt"
"SPTREMBL")
(url "http://www.uniprot.org"))
([GK_2000341] of EntityWithAccessionedSequence
(_displayName "[Hsa] TLR3 [endosome membrane]")
(DB_ID 2000341)
(endCoordinate 904)
(name
"TLR3"
"Toll-like Receptor 3")
(referenceEntity [GK_66105])
(species [GK_48887])
(stableIdentifier [GK_2017983])
(startCoordinate 24))
([GK_200479] of Person
(_displayName "Marquez, VE")
(DB_ID 200479)
(firstname "Victor E")
(initial "VE")
(surname "Marquez"))
([GK_2016988] of StableIdentifier
(_displayName "REACT_116419.2")
(DB_ID 2016988)
(identifier "REACT_116419")
(identifierVersion "2"))
([GK_2017983] of StableIdentifier
(_displayName "REACT_117413.1")
(DB_ID 2017983)
(identifier "REACT_117413")
(identifierVersion "1"))
([GK_2023025] of DatabaseIdentifier
(_displayName "COMPOUND:C00338")
(DB_ID 2023025)
(identifier "C00338")
(referenceDatabase [GK_6]))
([GK_2023030] of ReferenceMolecule
(_displayName "lipopolysaccharide [ChEBI:16412]")
(crossReference [GK_2023025])
(DB_ID 2023030)
(identifier "16412")
(name
"lipopolysaccharide"
"lipopolysaccharides"
"LPS")
(referenceDatabase [GK_114984]))
([GK_202465] of Person
(_displayName "Thome, M")
(DB_ID 202465)
(initial "M")
(surname "Thome"))
([GK_202881] of Person
(_displayName "Wang, S")
(DB_ID 202881)
(initial "S")
(surname "Wang"))
([GK_203163] of Person
(_displayName "Yang, W")
(DB_ID 203163)
(initial "W")
(surname "Yang"))
([GK_204598] of Person
(_displayName "Yamamoto, S")
(DB_ID 204598)
(initial "S")
(surname "Yamamoto"))
([GK_204605] of EntityWithAccessionedSequence
(_displayName "[Hsa] Kerato-epithelin [plasma membrane]")
(DB_ID 204605)
(endCoordinate 683)
(name
"Kerato-epithelin"
"Transforming growth factor-beta induced protein IG-H3 precursor"
"BGH3_HUMAN"
"TGFBI")
(referenceEntity [GK_50810])
(species [GK_48887])
(stableIdentifier [GK_1358063])
(startCoordinate 24))
([GK_204663] of Person
(_displayName "Bell, JK")
(DB_ID 204663)
(firstname "Jessica K")
(initial "JK")
(surname "Bell"))
([GK_205591] of Person
(_displayName "Williams, MG")
(DB_ID 205591)
(initial "MG")
(project "FlyBase")
(surname "Williams"))
([GK_20676] of GO_BiologicalProcess
(_displayName "regulation of proteolysis")
(accession "0030162")
(DB_ID 20676)
(definition "Any process that modulates the frequency, rate or extent of the hydrolysis of a peptide bond or bonds within a protein.")
(name "regulation of proteolysis")
(referenceDatabase [GK_1]))
([GK_207144] of Person
(_displayName "Lemaitre, B")
(DB_ID 207144)
(initial "B")
(surname "Lemaitre"))
([GK_207287] of Person
(_displayName "Eulitz, M")
(DB_ID 207287)
(initial "M")
(surname "Eulitz"))
([GK_207482] of Person
(_displayName "Ikeda, S")
(DB_ID 207482)
(initial "S")
(surname "Ikeda"))
([GK_207489] of Person
(_displayName "Kim, SE")
(DB_ID 207489)
(initial "SE")
(surname "Kim"))
([GK_207642] of Person
(_displayName "Sawaya, MR")
(DB_ID 207642)
(initial "MR")
(surname "Sawaya"))
([GK_207774] of Person
(_displayName "Silverman, N")
(crossReference [GK_5662807])
(DB_ID 207774)
(initial "N")
(surname "Silverman"))
([GK_212111] of Person
(_displayName "Wong, J")
(DB_ID 212111)
(initial "J")
(surname "Wong"))
([GK_212143] of Person
(_displayName "Szyf, M")
(DB_ID 212143)
(initial "M")
(surname "Szyf"))
([GK_2129343] of InstanceEdit
(_displayName "Shamovsky, V, 2012-02-19")
(author [GK_429259])
(dateTime "2012-02-19 18:37:51")
(DB_ID 2129343))
([GK_213088] of Summation
(_displayName "Caspase-8 is synthesized as zymogen (procaspase-8) and is fo...")
(DB_ID 213088)
(text "Caspase-8 is synthesized as zymogen (procaspase-8) and is formed from procaspase-8 as a cleavage product. However, the cleavage itself appears not to be sufficient for the formation of an active caspase-8. Only the coordinated dimerization and cleavage of the zymogen produce efficient activation in vitro and apoptosis in cellular systems [Boatright KM and Salvesen GS 2003; Keller N et al 2010; Oberst A et al 2010].
The caspase-8 zymogens are present in the cells as inactive monomers, which are recruited to the death-inducing signaling complex (DISC) by homophilic interactions with the DED domain of FADD. The monomeric zymogens undergo dimerization and the subsequent conformational changes at the receptor complex, which results in the formation of catalytically active form of procaspase-8.[Boatright KM et al 2003; Donepudi M et al 2003; Keller N et al 2010; Oberst A et al 2010]."))
([GK_213104] of Summation
(_displayName "Procaspase-8 monomers undergo dimerization. The dimerization...")
(DB_ID 213104)
(text "Procaspase-8 monomers undergo dimerization. The dimerization event occurs at death-inducing signaling complex (DISC) and results in a reposition of the procaspase-8 inter-subunit linker to become accessible for intermolecular processing by the associated procaspase-8 molecule [Keller N et al 2010; Oberst A et al 2010]."))
([GK_2132740] of GO_BiologicalProcess
(_displayName "signal transduction in absence of ligand")
(accession "0038034")
(DB_ID 2132740)
(definition "A series of molecular signals initiated by the absence of a ligand or the withdrawal of a ligand from a receptor.")
(name "signal transduction in absence of ligand")
(referenceDatabase [GK_1]))
([GK_2133460] of GO_MolecularFunction
(_displayName "cysteine-type endopeptidase activity involved in apoptotic process")
(accession "0097153")
(DB_ID 2133460)
(definition "Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a mechanism in which the sulfhydryl group of a cysteine residue at the active center acts as a nucleophile, and contributing to the apoptotic process.")
(name "cysteine-type endopeptidase activity involved in apoptotic process")
(referenceDatabase [GK_1]))
([GK_2133497] of GO_BiologicalProcess
(_displayName "apoptotic signaling pathway")
(accession "0097190")
(DB_ID 2133497)
(definition "A series of molecular signals which triggers the apoptotic death of a cell. The pathway starts with reception of a signal, and ends when the execution phase of apoptosis is triggered.")
(name "apoptotic signaling pathway")
(referenceDatabase [GK_1]))
([GK_2133498] of GO_BiologicalProcess
(_displayName "extrinsic apoptotic signaling pathway")
(accession "0097191")
(DB_ID 2133498)
(definition "A series of molecular signals in which a signal is conveyed from the cell surface to trigger the apoptotic death of a cell. The pathway starts with either a ligand binding to a cell surface receptor, or a ligand being withdrawn from a cell surface receptor (e.g. in the case of signaling by dependence receptors), and ends when the execution phase of apoptosis is triggered.")
(name "extrinsic apoptotic signaling pathway")
(referenceDatabase [GK_1]))
([GK_2133499] of GO_BiologicalProcess
(_displayName "extrinsic apoptotic signaling pathway in absence of ligand")
(accession "0097192")
(DB_ID 2133499)
(definition "A series of molecular signals in which a signal is conveyed from the cell surface to trigger the apoptotic death of a cell. The pathway starts with withdrawal of a ligand from a cell surface receptor, and ends when the execution phase of apoptosis is triggered.")
(name "extrinsic apoptotic signaling pathway in absence of ligand")
(referenceDatabase [GK_1]))
([GK_2133501] of GO_BiologicalProcess
(_displayName "execution phase of apoptosis")
(accession "0097194")
(DB_ID 2133501)
(definition "A stage of the apoptotic process that starts with the controlled breakdown of the cell through the action of effector caspases or other effector molecules (e.g. cathepsins, calpains etc.). Key steps of the execution phase are rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.")
(name "execution phase of apoptosis")
(referenceDatabase [GK_1]))
([GK_2133506] of GO_MolecularFunction
(_displayName "cysteine-type endopeptidase activity involved in apoptotic signaling pathway")
(accession "0097199")
(DB_ID 2133506)
(definition "Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a mechanism in which the sulfhydryl group of a cysteine residue at the active center acts as a nucleophile, and contributing to the apoptotic signaling pathway.")
(name "cysteine-type endopeptidase activity involved in apoptotic signaling pathway")
(referenceDatabase [GK_1]))
([GK_2133509] of GO_BiologicalProcess
(_displayName "activation of cysteine-type endopeptidase activity")
(accession "0097202")
(DB_ID 2133509)
(definition "Any process that initiates the activity of the inactive enzyme cysteine-type endopeptidase.")
(name "activation of cysteine-type endopeptidase activity")
(referenceDatabase [GK_1]))
([GK_2133692] of GO_BiologicalProcess
(_displayName "regulation of apoptotic signaling pathway")
(accession "2001233")
(DB_ID 2133692)
(definition "Any process that modulates the frequency, rate or extent of apoptotic signaling pathway.")
(name "regulation of apoptotic signaling pathway")
(referenceDatabase [GK_1]))
([GK_2133693] of GO_BiologicalProcess
(_displayName "negative regulation of apoptotic signaling pathway")
(accession "2001234")
(DB_ID 2133693)
(definition "Any process that stops, prevents or reduces the frequency, rate or extent of apoptotic signaling pathway.")
(name "negative regulation of apoptotic signaling pathway")
(referenceDatabase [GK_1]))
([GK_2133694] of GO_BiologicalProcess
(_displayName "positive regulation of apoptotic signaling pathway")
(accession "2001235")
(DB_ID 2133694)
(definition "Any process that activates or increases the frequency, rate or extent of apoptotic signaling pathway.")
(name "positive regulation of apoptotic signaling pathway")
(referenceDatabase [GK_1]))
([GK_2133695] of GO_BiologicalProcess
(_displayName "regulation of extrinsic apoptotic signaling pathway")
(accession "2001236")
(DB_ID 2133695)
(definition "Any process that modulates the frequency, rate or extent of extrinsic apoptotic signaling pathway.")
(name "regulation of extrinsic apoptotic signaling pathway")
(referenceDatabase [GK_1]))
([GK_2133696] of GO_BiologicalProcess
(_displayName "negative regulation of extrinsic apoptotic signaling pathway")
(accession "2001237")
(DB_ID 2133696)
(definition "Any process that stops, prevents or reduces the frequency, rate or extent of extrinsic apoptotic signaling pathway.")
(name "negative regulation of extrinsic apoptotic signaling pathway")
(referenceDatabase [GK_1]))
([GK_2133698] of GO_BiologicalProcess
(_displayName "regulation of extrinsic apoptotic signaling pathway in absence of ligand")
(accession "2001239")
(DB_ID 2133698)
(definition "Any process that modulates the frequency, rate or extent of extrinsic apoptotic signaling pathway in absence of ligand.")
(name "regulation of extrinsic apoptotic signaling pathway in absence of ligand")
(referenceDatabase [GK_1]))
([GK_2133726] of GO_BiologicalProcess
(_displayName "regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway")
(accession "2001267")
(DB_ID 2133726)
(definition "Any process that modulates the frequency, rate or extent of cysteine-type endopeptidase activity involved in apoptotic signaling pathway.")
(name "regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway")
(referenceDatabase [GK_1]))
([GK_2133728] of GO_BiologicalProcess
(_displayName "positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway")
(accession "2001269")
(DB_ID 2133728)
(definition "Any process that activates or increases the frequency, rate or extent of cysteine-type endopeptidase activity involved in apoptotic signaling pathway.")
(name "positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway")
(referenceDatabase [GK_1]))
([GK_216603] of Person
(_displayName "Munier, FL")
(DB_ID 216603)
(initial "FL")
(surname "Munier"))
([GK_216645] of Person
(_displayName "Schorderet, DF")
(DB_ID 216645)
(initial "DF")
(surname "Schorderet"))
([GK_217036] of Person
(_displayName "Lee, M")
(DB_ID 217036)
(initial "M")
(surname "Lee"))
([GK_217173] of Person
(_displayName "Seki, M")
(DB_ID 217173)
(initial "M")
(surname "Seki"))
([GK_2201284] of EntityWithAccessionedSequence
(_displayName "[Hsa] GPIN-CD14(20-345) [endosome membrane]")
(DB_ID 2201284)
(endCoordinate 345)
(hasModifiedResidue [GK_166032])
(name
"GPIN-CD14(20-345)"
"GPI-N345-CD14"
"GPI-anchored form of CD14")
(referenceEntity [GK_51618])
(species [GK_48887])
(stableIdentifier [GK_2297267])
(startCoordinate 20))
([GK_2201285] of EntityWithAccessionedSequence
(_displayName "[Hsa] TLR4 [endosome membrane]")
(DB_ID 2201285)
(endCoordinate 839)
(name "TLR4")
(referenceEntity [GK_66107])
(species [GK_48887])
(stableIdentifier [GK_2296779])
(startCoordinate 24))
([GK_2201291] of Complex
(_displayName "[Hsa] TLR4:LY96 [endosome membrane]")
(DB_ID 2201291)
(hasComponent
[GK_2201307]
[GK_2201285])
(literatureReference [GK_936996])
(name "TLR4:LY96")
(species [GK_48887])
(stableIdentifier [GK_2299421]))
([GK_2201294] of Person
(_displayName "Chen, H")
(DB_ID 2201294)
(firstname "Haiyan")
(initial "H")
(surname "Chen"))
([GK_2201299] of Complex
(_displayName "[Hsa] TLR4:LY96:LPS:CD14 [endosome membrane]")
(DB_ID 2201299)
(hasComponent
[GK_2201311]
[GK_2201311]
[GK_2201284]
[GK_2201284]
[GK_2201291]
[GK_2201291])
(literatureReference [GK_2423816])
(name "TLR4:LY96:LPS:CD14")
(species [GK_48887])
(stableIdentifier [GK_2298671]))
([GK_2201307] of EntityWithAccessionedSequence
(_displayName "[Hsa] LY96 [endosome membrane]")
(DB_ID 2201307)
(endCoordinate 160)
(name
"LY96"
"MD2")
(referenceEntity [GK_59097])
(species [GK_48887])
(stableIdentifier [GK_2298211])
(startCoordinate 19))
([GK_2201311] of SimpleEntity
(_displayName "LPS [endosome lumen]")
(DB_ID 2201311)
(name
"LPS"
"Gram Negative Bacterial Lipopolysaccharide"
"lipopolysaccharide")
(referenceEntity [GK_2023030])
(stableIdentifier [GK_2296629]))
([GK_2201326] of Person
(_displayName "Piao, W")
(DB_ID 2201326)
(firstname "Wenji")
(initial "W")
(surname "Piao"))
([GK_2201329] of Person
(_displayName "Song, C")
(DB_ID 2201329)
(firstname "Chang")
(initial "C")
(surname "Song"))
([GK_2201335] of ModifiedResidue
(_displayName "O-phospho-L-serine at 16")
(coordinate 16)
(DB_ID 2201335)
(psiMod [GK_445687])
(referenceSequence [GK_165789]))
([GK_2201336] of EntityWithAccessionedSequence
(_displayName "[Hsa] MyrG-p-S16-TICAM2 [endosome membrane]")
(DB_ID 2201336)
(endCoordinate 235)
(hasModifiedResidue
[GK_166162]
[GK_2201335])
(name
"MyrG-p-S16-TICAM2"
"TRAM")
(referenceEntity [GK_165789])
(species [GK_48887])
(stableIdentifier [GK_2299512])
(startCoordinate 2))
([GK_2201340] of DefinedSet
(_displayName "[Hsa] TRIF:activated TLR3/TLR4 [endosome membrane]")
(DB_ID 2201340)
(hasMember
[GK_166172]
[GK_168907])
(name "TRIF:activated TLR3/TLR4")
(species [GK_48887])
(stableIdentifier [GK_2297995]))
([GK_2248861] of InstanceEdit
(_displayName "Shamovsky, V, 2012-05-15")
(author [GK_429259])
(dateTime "2012-05-15 06:42:04")
(DB_ID 2248861))
([GK_2266695] of GO_BiologicalProcess
(_displayName "activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway")
(accession "0097296")
(DB_ID 2266695)
(definition "Any process that initiates the activity of an inactive cysteine-type endopeptidase involved in the apoptotic signaling pathway.")
(name "activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway")
(referenceDatabase [GK_1]))
([GK_2266716] of GO_BiologicalProcess
(_displayName "regulation of execution phase of apoptosis")
(accession "1900117")
(DB_ID 2266716)
(definition "Any process that modulates the frequency, rate or extent of execution phase of apoptosis.")
(name "regulation of execution phase of apoptosis")
(referenceDatabase [GK_1]))
([GK_2273] of GO_BiologicalProcess
(_displayName "apoptotic process")
(accession "0006915")
(DB_ID 2273)
(definition "A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.")
(name "apoptotic process")
(referenceDatabase [GK_1]))
([GK_2274] of GO_BiologicalProcess
(_displayName "programmed cell death")
(accession "0012501")
(DB_ID 2274)
(definition "A process which begins when a cell receives an internal or external signal and activates a series of biochemical events (signaling pathway). The process ends with the death of the cell.")
(name "programmed cell death")
(referenceDatabase [GK_1]))
([GK_2275] of GO_BiologicalProcess
(_displayName "cell death")
(accession "0008219")
(DB_ID 2275)
(definition "Any biological process that results in permanent cessation of all vital functions of a cell. A cell should be considered dead when any one of the following molecular or morphological criteria is met: (1) the cell has lost the integrity of its plasma membrane; (2) the cell, including its nucleus, has undergone complete fragmentation into discrete bodies (frequently referred to as \"apoptotic bodies\"); and/or (3) its corpse (or its fragments) have been engulfed by an adjacent cell in vivo.")
(name "cell death")
(referenceDatabase [GK_1]))
([GK_2276] of GO_BiologicalProcess
(_displayName "death")
(accession "0016265")
(DB_ID 2276)
(definition "A permanent cessation of all vital functions: the end of life; can be applied to a whole organism or to a part of an organism.")
(name "death")
(referenceDatabase [GK_1]))
([GK_2296629] of StableIdentifier
(_displayName "REACT_122729.1")
(DB_ID 2296629)
(identifier "REACT_122729")
(identifierVersion "1"))
([GK_2296779] of StableIdentifier
(_displayName "REACT_122879.1")
(DB_ID 2296779)
(identifier "REACT_122879")
(identifierVersion "1"))
([GK_2297267] of StableIdentifier
(_displayName "REACT_123367.2")
(DB_ID 2297267)
(identifier "REACT_123367")
(identifierVersion "2"))
([GK_2297995] of StableIdentifier
(_displayName "REACT_124095.2")
(DB_ID 2297995)
(identifier "REACT_124095")
(identifierVersion "2"))
([GK_2298211] of StableIdentifier
(_displayName "REACT_124311.2")
(DB_ID 2298211)
(identifier "REACT_124311")
(identifierVersion "2"))
([GK_2298671] of StableIdentifier
(_displayName "REACT_124771.2")
(DB_ID 2298671)
(identifier "REACT_124771")
(identifierVersion "3"))
([GK_2299421] of StableIdentifier
(_displayName "REACT_125521.2")
(DB_ID 2299421)
(identifier "REACT_125521")
(identifierVersion "3"))
([GK_2299512] of StableIdentifier
(_displayName "REACT_125612.3")
(DB_ID 2299512)
(identifier "REACT_125612")
(identifierVersion "3"))
([GK_231418] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:Q6FI13 HIST2H2AA3 recommendedName: Histone H2A type 2-A alternativeName: Histone H2A.2 alternativeName: Histone H2A/o ")
(checksum "1")
(comment "FUNCTION Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.SUBUNIT The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.PTM Deiminated on Arg-4 in granulocytes upon calcium entry.PTM Phosphorylation on Ser-2 is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1.SIMILARITY Belongs to the histone H2A family.")
(DB_ID 231418)
(description "recommendedName: Histone H2A type 2-A alternativeName: Histone H2A.2 alternativeName: Histone H2A/o ")
(geneName
"HIST2H2AA3"
"H2AFO"
"HIST2H2AA"
""
" Prevention of RIP1 ubiquitination leads to a strong association of RIP1 and caspase-8 [Feoktistova M et al 2011, Tenev et al 2011]."))
([GK_2584545] of Summation
(_displayName "TLR3/4 signaling component were shown to mediate apoptosis i...")
(DB_ID 2584545)
(text "TLR3/4 signaling component were shown to mediate apoptosis in various human cell lines in the FADD:caspasse-8-dependent manner [Kalai M et al 2002; Kaiser WJ and Offermann MK 2005; Estornes Y et al 2012]. Caspase-8 zymogens (procaspase-8) are present in the cells as inactive monomers, containing a large N-terminal prodomain with two death effector domains (DED), and a C-terminal catalytic subunit composed of small and a large domains separated by a smaller linker region [Donepudi M et al 2003; Keller N et al 2009]. Dimerization is required for caspase-8 activation [Donepudi M et al 2003]. The dimerization event occurs at the receptor signaling complex. Once dimerized, caspase-8 zymogen undergoes a series of autoproteolytic cleavage events at aspartic acid residues in their interdomain linker regions. A second cleavage event between the the N-terminal prodomain and the catalytic domain releases the active caspase from the activation complex into the cytosol. The resulting fully active enzyme is a homodimer of catalytic domains, where each domain is compsed of a large p18 and a small p10 subunit [Keller N et al 2009; Oberst A et al 2010]."))
([GK_2584548] of LiteratureReference
(_displayName "Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA")
(author
[GK_2584536]
[GK_2584569]
[GK_2584549]
[GK_2584561]
[GK_2584560]
[GK_2584567]
[GK_2584558])
(DB_ID 2584548)
(journal "Cell Death Differ.")
(pages "981-94")
(pubMedIdentifier 12181749)
(title "Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA")
(volume 9)
(year 2002))
([GK_2584549] of Person
(_displayName "Vanden Berghe, T")
(DB_ID 2584549)
(firstname "T")
(initial "T")
(surname "Vanden Berghe"))
([GK_2584550] of Person
(_displayName "Broemer, Meike")
(DB_ID 2584550)
(firstname "Meike")
(initial "M")
(surname "Broemer"))
([GK_2584551] of Person
(_displayName "Wallberg, Fredrik")
(DB_ID 2584551)
(firstname "Fredrik")
(initial "F")
(surname "Wallberg"))
([GK_2584552] of Person
(_displayName "Wang, Xiaodong")
(DB_ID 2584552)
(firstname "Xiaodong")
(initial "X")
(surname "Wang"))
([GK_2584553] of Person
(_displayName "Zachariou, Anna")
(DB_ID 2584553)
(firstname "Anna")
(initial "A")
(surname "Zachariou"))
([GK_2584555] of Person
(_displayName "Darding, Maurice")
(DB_ID 2584555)
(firstname "Maurice")
(initial "M")
(surname "Darding"))
([GK_2584556] of Person
(_displayName "Tenev, Tencho")
(DB_ID 2584556)
(firstname "Tencho")
(initial "T")
(surname "Tenev"))
([GK_2584558] of Person
(_displayName "Vandenabeele, P")
(DB_ID 2584558)
(firstname "P")
(initial "P")
(surname "Vandenabeele"))
([GK_2584560] of Person
(_displayName "Burm, W")
(DB_ID 2584560)
(firstname "W")
(initial "W")
(surname "Burm"))
([GK_2584561] of Person
(_displayName "Meeus, A")
(DB_ID 2584561)
(firstname "A")
(initial "A")
(surname "Meeus"))
([GK_2584562] of LiteratureReference
(_displayName "The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs")
(author
[GK_2584556]
[GK_2584563]
[GK_2584555]
[GK_2584550]
[GK_2562553]
[GK_2584551]
[GK_2584553]
[GK_2584564]
[GK_2562548]
[GK_2562560]
[GK_2584565])
(DB_ID 2584562)
(journal "Mol. Cell")
(pages "432-48")
(pubMedIdentifier 21737329)
(title "The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs")
(volume 43)
(year 2011))
([GK_2584563] of Person
(_displayName "Bianchi, Katiuscia")
(DB_ID 2584563)
(firstname "Katiuscia")
(initial "K")
(surname "Bianchi"))
([GK_2584564] of Person
(_displayName "Lopez, Juanita")
(DB_ID 2584564)
(firstname "Juanita")
(initial "J")
(surname "Lopez"))
([GK_2584565] of Person
(_displayName "Meier, Pascal")
(DB_ID 2584565)
(firstname "Pascal")
(initial "P")
(surname "Meier"))
([GK_2584567] of Person
(_displayName "Saelens, X")
(DB_ID 2584567)
(firstname "X")
(initial "X")
(surname "Saelens"))
([GK_2584569] of Person
(_displayName "Van Loo, G")
(DB_ID 2584569)
(firstname "G")
(initial "G")
(surname "Van Loo"))
([GK_2584570] of Person
(_displayName "Grütter, Markus G")
(DB_ID 2584570)
(firstname "Markus G")
(initial "MG")
(surname "Grütter"))
([GK_2584571] of Person
(_displayName "Briand, Christophe")
(DB_ID 2584571)
(firstname "Christophe")
(initial "C")
(surname "Briand"))
([GK_2584573] of LiteratureReference
(_displayName "Insights into the regulatory mechanism for caspase-8 activation")
(author
[GK_2584575]
[GK_2584574]
[GK_2584571]
[GK_2584570])
(DB_ID 2584573)
(journal "Mol. Cell")
(pages "543-9")
(pubMedIdentifier 12620240)
(title "Insights into the regulatory mechanism for caspase-8 activation")
(volume 11)
(year 2003))
([GK_2584574] of Person
(_displayName "Mac Sweeney, Aengus")
(DB_ID 2584574)
(firstname "Aengus")
(initial "A")
(surname "Mac Sweeney"))
([GK_2584575] of Person
(_displayName "Donepudi, Mrudula")
(DB_ID 2584575)
(firstname "Mrudula")
(initial "M")
(surname "Donepudi"))
([GK_2587987] of GO_BiologicalProcess
(_displayName "single-organism process")
(accession "0044699")
(DB_ID 2587987)
(definition "A biological process that involves only one organism.")
(name "single-organism process")
(referenceDatabase [GK_1]))
([GK_2587988] of GO_BiologicalProcess
(_displayName "single organism signaling")
(accession "0044700")
(DB_ID 2587988)
(definition "A signaling process occurring within a single organism.")
(name "single organism signaling")
(referenceDatabase [GK_1]))
([GK_258858] of GO_BiologicalProcess
(_displayName "regulation of peptidase activity")
(accession "0052547")
(DB_ID 258858)
(definition "Any process that modulates the frequency, rate or extent of peptidase activity, the hydrolysis of peptide bonds within proteins.")
(name "regulation of peptidase activity")
(referenceDatabase [GK_1]))
([GK_258859] of GO_BiologicalProcess
(_displayName "regulation of endopeptidase activity")
(accession "0052548")
(DB_ID 258859)
(definition "Any process that modulates the frequency, rate or extent of endopeptidase activity, the endohydrolysis of peptide bonds within proteins.")
(name "regulation of endopeptidase activity")
(referenceDatabase [GK_1]))
([GK_258867] of GO_BiologicalProcess
(_displayName "positive regulation of cellular protein metabolic process")
(accession "0032270")
(DB_ID 258867)
(definition "Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways involving a protein, occurring at the level of an individual cell.")
(name "positive regulation of cellular protein metabolic process")
(referenceDatabase [GK_1]))
([GK_259431] of GO_CellularComponent
(_displayName "host cell")
(accession "0043657")
(componentOf [GK_6486])
(DB_ID 259431)
(definition "A cell within a host organism. Includes the host plasma membrane and any external encapsulating structures such as the host cell wall and cell envelope.")
(name "host cell")
(referenceDatabase [GK_1]))
([GK_259432] of GO_CellularComponent
(_displayName "host cell part")
(accession "0033643")
(componentOf [GK_259431])
(DB_ID 259432)
(definition "Any constituent part of a host cell. The host is defined as the larger of the organisms involved in a symbiotic interaction.")
(instanceOf [GK_447577])
(name "host cell part")
(referenceDatabase [GK_1]))
([GK_259433] of GO_CellularComponent
(_displayName "intracellular region of host")
(accession "0043656")
(DB_ID 259433)
(definition "That space within the plasma membrane of a host cell.")
(instanceOf [GK_259432])
(name "intracellular region of host")
(referenceDatabase [GK_1]))
([GK_259434] of GO_CellularComponent
(_displayName "host intracellular part")
(accession "0033646")
(componentOf [GK_259433])
(DB_ID 259434)
(definition "Any constituent part of the living contents of a host cell; the matter contained within (but not including) the plasma membrane, usually taken to exclude large vacuoles and masses of secretory or ingested material. In eukaryotes it includes the nucleus and cytoplasm. The host is defined as the larger of the organisms involved in a symbiotic interaction.")
(instanceOf [GK_259432])
(name "host intracellular part")
(referenceDatabase [GK_1]))
([GK_259437] of GO_CellularComponent
(_displayName "host cell cytoplasm part")
(accession "0033655")
(componentOf [GK_80155])
(DB_ID 259437)
(definition "Any constituent part of the host cell cytoplasm, all of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. The host is defined as the larger of the organisms involved in a symbiotic interaction.")
(instanceOf [GK_259434])
(name "host cell cytoplasm part")
(referenceDatabase [GK_1]))
([GK_2594924] of InstanceEdit
(_displayName "Gillespie, ME, 2012-11-19")
(author [GK_73681])
(dateTime "2012-11-19 14:31:40")
(DB_ID 2594924))
([GK_2603274] of InstanceEdit
(_displayName "Shamovsky, V, 2012-11-19")
(author [GK_429259])
(dateTime "2012-11-19 17:29:17")
(DB_ID 2603274))
([GK_264078] of GO_BiologicalProcess
(_displayName "bleb assembly")
(accession "0032060")
(DB_ID 264078)
(definition "The assembly of a bleb, a cell extension caused by localized decoupling of the cytoskeleton from the plasma membrane and characterized by rapid formation, rounded shape, and scarcity of organelles within the protrusion. Plasma membrane blebbing occurs during apoptosis and other cellular processes, including cell locomotion, cell division, and as a result of physical or chemical stresses.")
(name "bleb assembly")
(referenceDatabase [GK_1]))
([GK_264348] of Person
(_displayName "Steiner, DF")
(DB_ID 264348)
(initial "DF")
(surname "Steiner"))
([GK_264874] of ModifiedResidue
(_displayName "half cystine at 109")
(coordinate 109)
(DB_ID 264874)
(psiMod [GK_448182])
(referenceSequence [GK_57415]))
([GK_264928] of ModifiedResidue
(_displayName "half cystine at 95")
(coordinate 95)
(DB_ID 264928)
(psiMod [GK_448182])
(referenceSequence [GK_57415]))
([GK_264936] of ModifiedResidue
(_displayName "half cystine at 96")
(coordinate 96)
(DB_ID 264936)
(psiMod [GK_448182])
(referenceSequence [GK_57415]))
([GK_265017] of ModifiedResidue
(_displayName "half cystine at 43")
(coordinate 43)
(DB_ID 265017)
(psiMod [GK_448182])
(referenceSequence [GK_57415]))
([GK_265035] of ModifiedResidue
(_displayName "half cystine at 100")
(coordinate 100)
(DB_ID 265035)
(psiMod [GK_448182])
(referenceSequence [GK_57415]))
([GK_265094] of ModifiedResidue
(_displayName "half cystine at 31")
(coordinate 31)
(DB_ID 265094)
(psiMod [GK_448182])
(referenceSequence [GK_57415]))
([GK_265170] of EntityWithAccessionedSequence
(_displayName "[Hsa] Insulin A Chain [extracellular region]")
(DB_ID 265170)
(endCoordinate 110)
(hasModifiedResidue
[GK_265035]
[GK_264874]
[GK_264928]
[GK_264936])
(name "Insulin A Chain")
(referenceEntity [GK_57415])
(species [GK_48887])
(stableIdentifier [GK_387943])
(startCoordinate 90))
([GK_265516] of Person
(_displayName "Ma, Y")
(DB_ID 265516)
(firstname "Yongming")
(initial "Y")
(surname "Ma"))
([GK_2671781] of Species
(_displayName "Human herpesvirus 8")
(crossReference [GK_3159236])
(DB_ID 2671781)
(name
"Human herpesvirus 8"
"Kaposi's sarcoma-associated herpesvirus"
"Human herpesvirus 8 type P"
"Kaposi's sarcoma-associated herpesvirus - Human herpesvirus 8"
"Kaposi's sarcoma-associated herpes-like virus"
"KSHV"
"HHV8")
(superTaxon [GK_3162934]))
([GK_2671784] of EntityWithAccessionedSequence
(_displayName "[Vvi] SPI-2 [cytosol]")
(DB_ID 2671784)
(endCoordinate 345)
(name
"SPI-2"
"Serine proteinase inhibitor 2"
"B13R")
(referenceEntity [GK_2671799])
(species [GK_2671785])
(startCoordinate 1))
([GK_2671785] of Species
(_displayName "Vaccinia virus")
(crossReference [GK_3159243])
(DB_ID 2671785)
(name
"Vaccinia virus"
"vaccinia virus VV")
(superTaxon [GK_3162966]))
([GK_2671786] of EntityWithAccessionedSequence
(_displayName "[Cvi] CRMA [cytosol]")
(DB_ID 2671786)
(endCoordinate 341)
(name
"CRMA"
"Serine proteinase inhibitor 2"
"Serpin-2")
(referenceEntity [GK_2671797])
(species [GK_2671792])
(startCoordinate 1))
([GK_2671791] of Species
(_displayName "Human cytomegalovirus")
(crossReference [GK_3159246])
(DB_ID 2671791)
(name
"Human cytomegalovirus"
"human herpesvirus type 5"
"HHV-5"
"Human cytomegalovirus HCMV"
"human cytomegalovirus CMV")
(superTaxon [GK_3162945]))
([GK_2671792] of Species
(_displayName "Cowpox virus")
(crossReference [GK_3159247])
(DB_ID 2671792)
(name
"Cowpox virus"
"CPXV")
(superTaxon [GK_3162966]))
([GK_2671795] of Species
(_displayName "Molluscum contagiosum virus subtype 1")
(crossReference [GK_3159240])
(DB_ID 2671795)
(name
"Molluscum contagiosum virus subtype 1"
"Molluscum contagiosum virus type 1"
"Molluscum contagiosum virus subtype I MCV I"
"Molluscum contagiosum virus 1"
"McVI")
(superTaxon [GK_3162958]))
([GK_2671797] of ReferenceGeneProduct
(_displayName "[Cvi] UniProt:P07385 CRMA recommendedName: Serine proteinase inhibitor 2 shortName:Serp-2 shortName:Serpin-2 alternativeName: Cytokine response modifier protein A alternativeName: Hemorrhage-inducing 38 kDa protein alternativeName: ICE inhibitor ")
(checksum "25AE4E0CB123E172")
(comment "FUNCTION Specific and potent inhibitor of the interleukin-1-beta converting enzyme (ICE) thereby suppressing an interleukin-1 beta response to infection. The inhibition of ICE by crmA is an example of a \"cross-class\" interaction, in which a serpin inhibits a non-serine proteinase. Also inhibits granzyme B.SIMILARITY Belongs to the serpin family. Poxviruses subfamily.")
(DB_ID 2671797)
(description "recommendedName: Serine proteinase inhibitor 2 shortName:Serp-2 shortName:Serpin-2 alternativeName: Cytokine response modifier protein A alternativeName: Hemorrhage-inducing 38 kDa protein alternativeName: ICE inhibitor ")
(geneName
"CRMA"
"SPI-2"
"CPXV207")
(identifier "P07385")
(isSequenceChanged FALSE)
(keyword
"3D-structure"
"Host cytoplasm"
"Host-virus interaction"
"Inhibition of host caspases by virus"
"Modulation of host cell apoptosis by virus"
"Protease inhibitor"
"Thiol protease inhibitor")
(name "CRMA")
(referenceDatabase [GK_2])
(secondaryIdentifier "SPI2_CWPXB")
(sequenceLength 341)
(species [GK_2671792]))
([GK_2671799] of ReferenceGeneProduct
(_displayName "[Vvi] UniProt:P15059 SPI-2 recommendedName: Serine proteinase inhibitor 2 shortName:Serp-2 shortName:Serpin-2 ")
(checksum "8A067A10B803F5EF")
(comment "FUNCTION Inhibits the proteolytic activity of interleukin 1-beta converting enzyme (ICE) and ICE-like enzymes. Can also block apoptosis through host tumor necrosis factor (TNF) receptor.INDUCTION Expressed in the early phase of the viral replicative cycle.SIMILARITY Belongs to the serpin family. Poxviruses subfamily.")
(DB_ID 2671799)
(description "recommendedName: Serine proteinase inhibitor 2 shortName:Serp-2 shortName:Serpin-2 ")
(geneName
"SPI-2"
"VACWR195"
"B13R")
(identifier "P15059")
(isSequenceChanged FALSE)
(keyword
"Complete proteome"
"Early protein"
"Host cytoplasm"
"Host-virus interaction"
"Inhibition of host caspases by virus"
"Modulation of host cell apoptosis by virus"
"Protease inhibitor"
"Reference proteome"
"Serine protease inhibitor")
(name "SPI-2")
(referenceDatabase [GK_2])
(secondaryIdentifier
"SPI2_VACCW"
"Q76ZL0")
(sequenceLength 345)
(species [GK_2671785]))
([GK_2671811] of Complex
(_displayName "[Hsa] FASL:FAS receptor trimer:FADD:procaspase-8-dimer [plasma membrane]")
(DB_ID 2671811)
(hasComponent
[GK_43124]
[GK_2671817])
(literatureReference [GK_2562554])
(name "FASL:FAS receptor trimer:FADD:procaspase-8-dimer ")
(species [GK_48887])
(stableIdentifier [GK_3203544]))
([GK_2671812] of Complex
(_displayName "[Hsa] TRAF2:TRADD:RIP1:FADD:2xCASP8(1-479) [cytosol]")
(DB_ID 2671812)
(goCellularComponent [GK_161217])
(hasComponent
[GK_140977]
[GK_2671817])
(isChimeric FALSE)
(name "TRAF2:TRADD:RIP1:FADD:2xCASP8(1-479)")
(species [GK_48887])
(stableIdentifier [GK_3203706]))
([GK_2671813] of DefinedSet
(_displayName "[Hsa] DISC:procaspase-8-dimer [plasma membrane, cytosol]")
(DB_ID 2671813)
(hasMember
[GK_2671811]
[GK_2671812]
[GK_2671816])
(name
"DISC:procaspase-8-dimer"
"death-inducing signaling complex:procaspase-8-dimer")
(species [GK_48887])
(stableIdentifier [GK_3202731]))
([GK_2671814] of DefinedSet
(_displayName "[Hsa] DISC [plasma membrane, cytosol]")
(DB_ID 2671814)
(hasMember
[GK_43124]
[GK_140977]
[GK_5637464])
(name
"DISC"
"death-inducing signaling complex")
(species [GK_48887])
(stableIdentifier [GK_3202937]))
([GK_2671816] of Complex
(_displayName "[Hsa] TNFSF10:TNFRSF10A,B:FADD:2xCASP8(1-479) [plasma membrane]")
(DB_ID 2671816)
(hasComponent
[GK_2671817]
[GK_5637464])
(isChimeric FALSE)
(name "TNFSF10:TNFRSF10A,B:FADD:2xCASP8(1-479)")
(species [GK_48887])
(stableIdentifier [GK_3201394]))
([GK_2671817] of Complex
(_displayName "[Hsa] procaspase-8 dimer [cytosol]")
(DB_ID 2671817)
(hasComponent
[GK_57031]
[GK_57031])
(isChimeric FALSE)
(name "procaspase-8 dimer")
(species [GK_48887])
(stableIdentifier [GK_3200756]))
([GK_2671823] of Person
(_displayName "Zerbe, O")
(DB_ID 2671823)
(firstname "O")
(initial "O")
(surname "Zerbe"))
([GK_2671824] of Person
(_displayName "Keller, N")
(DB_ID 2671824)
(firstname "N")
(initial "N")
(surname "Keller"))
([GK_2671825] of LiteratureReference
(_displayName "Studies of the molecular mechanism of caspase-8 activation by solution NMR")
(author
[GK_2671824]
[GK_2562587]
[GK_2671823])
(DB_ID 2671825)
(journal "Cell Death Differ.")
(pages "710-8")
(pubMedIdentifier 19851329)
(title "Studies of the molecular mechanism of caspase-8 activation by solution NMR")
(volume 17)
(year 2010))
([GK_2671826] of InstanceEdit
(_displayName "Shamovsky, V, 2012-11-26")
(author [GK_429259])
(dateTime "2012-11-26 04:21:07")
(DB_ID 2671826))
([GK_2672034] of Person
(_displayName "Liu, W")
(DB_ID 2672034)
(firstname "W")
(initial "W")
(surname "Liu"))
([GK_2672161] of Person
(_displayName "Jassoy, C")
(DB_ID 2672161)
(firstname "C")
(initial "C")
(surname "Jassoy"))
([GK_2672164] of Person
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[GK_2672179]
[GK_2672202]
[GK_2672176]
[GK_2672188]
[GK_2534135])
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(journal "J. Biol. Chem.")
(pages "7797-800")
(pubMedIdentifier 9065443)
(title "Target protease specificity of the viral serpin CrmA. Analysis of five caspases")
(volume 272)
(year 1997))
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[GK_2672168]
[GK_2672206]
[GK_2672200])
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(title "Tumor necrosis factor-induced apoptosis is mediated by a CrmA-sensitive cell death pathway")
(volume 92)
(year 1995))
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(_displayName "Fas- and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product")
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[GK_2672222]
[GK_2672188])
(DB_ID 2672185)
(journal "J. Biol. Chem.")
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(title "Fas- and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product")
(volume 270)
(year 1995))
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(text "SPI-2/CrmA (cytokine response modifier A) is a poxvirus gene product with homology to members of the serpin (serine protease inhibitor) superfamily. Cowpox virus-derived and vaccinia virus-derived CrmA cDNAs transfected into cells can inhibit apoptosis induced by Fas-ligation and activation of the tumor necrosis factor receptor [Tewari M and Dixit VM 1995; Miura M et al 1995; Kettle S et al 1997]. Cowpox virus-derived CrmA was shown to selectively inhibit caspases in Fas-mediated apoptosis, showing the highest affinity for interleukin-1 beta-converting enzyme (ICE) and the second highest for the caspase-8 with Ki = 0.95 nM [Zhou Q et al 1997]."))
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[GK_3465422]
[GK_3465385]
[GK_3465382]
[GK_3465460])
(name "FLIP(L) and procaspase-8 form heterodimer in TRAIL signaling")
(output [GK_3371390])
(precedingEvent [GK_75146])
(releaseDate "2013-06-11")
(reviewed [GK_3597630])
(species [GK_48887])
(stableIdentifier [GK_3654456])
(summation [GK_3465446]))
([GK_3371360] of Reaction
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(_doRelease TRUE)
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(DB_ID 3371360)
(edited [GK_3508822])
(input
[GK_3371356]
[GK_140976])
(literatureReference
[GK_140979]
[GK_2584573]
[GK_3465454]
[GK_3465455]
[GK_3465494])
(name "FLIP(L) and procaspase-8 form heterodimer in TNF signaling")
(output [GK_3465532])
(precedingEvent [GK_75240])
(releaseDate "2013-06-11")
(reviewed [GK_3597630])
(species [GK_48887])
(stableIdentifier [GK_3654502])
(summation [GK_3465402]))
([GK_3371361] of Person
(_displayName "Sun, Xiao-Ming")
(DB_ID 3371361)
(firstname "Xiao-Ming")
(initial "XM")
(surname "Sun"))
([GK_3371362] of Person
(_displayName "Hung MC, MC")
(DB_ID 3371362)
(initial "MC")
(surname "Hung MC"))
([GK_3371363] of Person
(_displayName "Hayakawa, Takao")
(DB_ID 3371363)
(firstname "Takao")
(initial "T")
(surname "Hayakawa"))
([GK_3371364] of Person
(_displayName "Ohkawa, Akiko")
(DB_ID 3371364)
(firstname "Akiko")
(initial "A")
(surname "Ohkawa"))
([GK_3371365] of Person
(_displayName "Minowa, Kyoko")
(DB_ID 3371365)
(firstname "Kyoko")
(initial "K")
(surname "Minowa"))
([GK_3371366] of Person
(_displayName "Shibata, Hiroko")
(DB_ID 3371366)
(firstname "Hiroko")
(initial "H")
(surname "Shibata"))
([GK_3371367] of Person
(_displayName "Nomura, Tetsuya")
(DB_ID 3371367)
(firstname "Tetsuya")
(initial "T")
(surname "Nomura"))
([GK_3371368] of Person
(_displayName "Tsunoda, Shin-ichi")
(DB_ID 3371368)
(firstname "Shin-ichi")
(initial "S")
(surname "Tsunoda"))
([GK_3371369] of Person
(_displayName "Ohta, Tsunetaka")
(DB_ID 3371369)
(firstname "Tsunetaka")
(initial "T")
(surname "Ohta"))
([GK_3371370] of Complex
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(DB_ID 3371370)
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[GK_976821]
[GK_976821]
[GK_976821])
(isChimeric FALSE)
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(name
"TNF-alpha trimer"
"TNF-alpha trimer, soluble form")
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(stableIdentifier [GK_3655921]))
([GK_3371371] of Person
(_displayName "Sugita, Toshiki")
(DB_ID 3371371)
(firstname "Toshiki")
(initial "T")
(surname "Sugita"))
([GK_3371372] of Person
(_displayName "Abe, Yasuhiro")
(DB_ID 3371372)
(firstname "Yasuhiro")
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(_displayName "Receptor-mediated endocytosis is not required for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis")
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[GK_3371375]
[GK_3371394]
[GK_3371361]
[GK_3371358]
[GK_2984178])
(DB_ID 3371373)
(journal "J. Biol. Chem.")
(pages "12831-41")
(pubMedIdentifier 17327223)
(title "Receptor-mediated endocytosis is not required for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis")
(volume 282)
(year 2007))
([GK_3371374] of Person
(_displayName "Yoshikawa, Tomoaki")
(DB_ID 3371374)
(firstname "Tomoaki")
(initial "T")
(surname "Yoshikawa"))
([GK_3371375] of Person
(_displayName "Kohlhaas, Susan L")
(DB_ID 3371375)
(firstname "Susan L")
(initial "SL")
(surname "Kohlhaas"))
([GK_3371376] of Person
(_displayName "Aggarwal, Bharat B")
(DB_ID 3371376)
(firstname "Bharat B")
(initial "BB")
(surname "Aggarwal"))
([GK_3371377] of Person
(_displayName "Yoshioka, Yasuo")
(DB_ID 3371377)
(firstname "Yasuo")
(initial "Y")
(surname "Yoshioka"))
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(_displayName "[Hsa] Regulation by c-FLIP")
(_doRelease TRUE)
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(DB_ID 3371378)
(edited [GK_3508822])
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[GK_3371360]
[GK_3371359]
[GK_3465459]
[GK_3465448])
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[GK_1250231]
[GK_1267786]
[GK_3465386])
(name "Regulation by c-FLIP")
(releaseDate "2013-06-11")
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(species [GK_48887])
(stableIdentifier [GK_3654555])
(summation [GK_3465346]))
([GK_3371379] of Person
(_displayName "Taniai, Madoka")
(DB_ID 3371379)
(firstname "Madoka")
(initial "M")
(surname "Taniai"))
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(_displayName "Creation and X-ray structure analysis of the tumor necrosis factor receptor-1-selective mutant of a tumor necrosis factor-alpha antagonist")
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[GK_3371366]
[GK_3371377]
[GK_3371364]
[GK_3371365]
[GK_3371395]
[GK_3371372]
[GK_3371379]
[GK_3371367]
[GK_3371355]
[GK_3371398]
[GK_3371371]
[GK_3371382]
[GK_3371389]
[GK_3371374]
[GK_3371399]
[GK_3371391]
[GK_3371396]
[GK_3371369]
[GK_3371363]
[GK_3371357]
[GK_141902]
[GK_3371376]
[GK_3371393]
[GK_2393943]
[GK_3371368]
[GK_3371349]
[GK_3371350])
(DB_ID 3371380)
(journal "J. Biol. Chem.")
(pages "998-1007")
(pubMedIdentifier 18003610)
(title "Creation and X-ray structure analysis of the tumor necrosis factor receptor-1-selective mutant of a tumor necrosis factor-alpha antagonist")
(volume 283)
(year 2008))
([GK_3371381] of Complex
(_displayName "[Hsa] DISC:procaspase-8:FLIP(L) [plasma membrane]")
(DB_ID 3371381)
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[GK_3371356]
[GK_3465443])
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(name "DISC:procaspase-8:FLIP(L)")
(species [GK_48887])
(stableIdentifier [GK_3655002]))
([GK_3371382] of Person
(_displayName "Imai, Sunao")
(DB_ID 3371382)
(firstname "Sunao")
(initial "S")
(surname "Imai"))
([GK_3371384] of Person
(_displayName "Reis, Carlos R")
(DB_ID 3371384)
(firstname "Carlos R")
(initial "CR")
(surname "Reis"))
([GK_3371385] of Reaction
(_displayName "[Hsa] TNF-alpha is cleaved by ADAM17 (TACE)")
(_doRelease TRUE)
(authored [GK_3371406])
(catalystActivity [GK_1251983])
(DB_ID 3371385)
(edited [GK_3632865])
(input [GK_3371351])
(isChimeric FALSE)
(literatureReference
[GK_3465559]
[GK_3465568])
(name "TNF-alpha is cleaved by ADAM17 (TACE)")
(output [GK_3371370])
(releaseDate "2013-06-11")
(reviewed [GK_3597630])
(species [GK_48887])
(stableIdentifier [GK_3654338])
(summation [GK_3465572]))
([GK_3371386] of Person
(_displayName "Eck, M J")
(DB_ID 3371386)
(firstname "M J")
(initial "MJ")
(surname "Eck"))
([GK_3371387] of Person
(_displayName "Cool, Robbert H")
(DB_ID 3371387)
(firstname "Robbert H")
(initial "RH")
(surname "Cool"))
([GK_3371388] of Person
(_displayName "Klostergaard, J")
(DB_ID 3371388)
(firstname "J")
(initial "J")
(surname "Klostergaard"))
([GK_3371389] of Person
(_displayName "Nagano, Kazuya")
(DB_ID 3371389)
(firstname "Kazuya")
(initial "K")
(surname "Nagano"))
([GK_3371390] of Complex
(_displayName "[Hsa] TNFSF10:TNFRSF10A,B:FADD:CASP8(1-479):CFLAR [plasma membrane]")
(DB_ID 3371390)
(hasComponent
[GK_57031]
[GK_3371356]
[GK_5637464])
(name "TNFSF10:TNFRSF10A,B:FADD:CASP8(1-479):CFLAR")
(species [GK_48887])
(stableIdentifier [GK_3655740]))
([GK_3371391] of Person
(_displayName "Nakagawa, Shinsaku")
(DB_ID 3371391)
(firstname "Shinsaku")
(initial "S")
(surname "Nakagawa"))
([GK_3371392] of Person
(_displayName "Sprang, S R")
(DB_ID 3371392)
(firstname "S R")
(initial "SR")
(surname "Sprang"))
([GK_3371393] of Person
(_displayName "Nakamura, Teruya")
(DB_ID 3371393)
(firstname "Teruya")
(initial "T")
(surname "Nakamura"))
([GK_3371394] of Person
(_displayName "Craxton, Andrew")
(DB_ID 3371394)
(firstname "Andrew")
(initial "A")
(surname "Craxton"))
([GK_3371395] of Person
(_displayName "Mukai, Yohei")
(DB_ID 3371395)
(firstname "Yohei")
(initial "Y")
(surname "Mukai"))
([GK_3371396] of Person
(_displayName "Yamamoto, Akira")
(DB_ID 3371396)
(firstname "Akira")
(initial "A")
(surname "Yamamoto"))
([GK_3371397] of Complex
(_displayName "[Hsa] soluble TNF-alpha:TNFR1 [plasma membrane]")
(DB_ID 3371397)
(hasComponent
[GK_66344]
[GK_66344]
[GK_66344]
[GK_3371370])
(literatureReference [GK_3371380])
(name "soluble TNF-alpha:TNFR1")
(species [GK_48887])
(stableIdentifier [GK_3655101]))
([GK_3371398] of Person
(_displayName "Nabeshi, Hiromi")
(DB_ID 3371398)
(firstname "Hiromi")
(initial "H")
(surname "Nabeshi"))
([GK_3371399] of Person
(_displayName "Fujita, Takuya")
(DB_ID 3371399)
(firstname "Takuya")
(initial "T")
(surname "Fujita"))
([GK_3371400] of Person
(_displayName "Tang, P")
(DB_ID 3371400)
(firstname "P")
(initial "P")
(surname "Tang"))
([GK_3371401] of DefinedSet
(_displayName "[Hsa] TNF-alpha trimer:TNF-R1 trimer [plasma membrane]")
(DB_ID 3371401)
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[GK_74277]
[GK_3371397])
(name "TNF-alpha trimer:TNF-R1 trimer")
(species [GK_48887])
(stableIdentifier [GK_3655775]))
([GK_3371402] of LiteratureReference
(_displayName "The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding")
(author
[GK_3371386]
[GK_3371392])
(DB_ID 3371402)
(journal "J. Biol. Chem.")
(pages "17595-605")
(pubMedIdentifier 2551905)
(title "The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding")
(volume 264)
(year 1989))
([GK_3371403] of Person
(_displayName "Quax, Wim J")
(DB_ID 3371403)
(firstname "Wim J")
(initial "WJ")
(surname "Quax"))
([GK_3371404] of InstanceEdit
(_displayName "Shamovsky, V, 2013-05-13")
(author [GK_429259])
(dateTime "2013-05-13 13:54:08")
(DB_ID 3371404))
([GK_3371406] of InstanceEdit
(_displayName "Shamovsky, V, 2013-05-13")
(author [GK_429259])
(dateTime "2013-05-13 13:56:05")
(DB_ID 3371406))
([GK_3446165] of GO_BiologicalProcess
(_displayName "regulation of extrinsic apoptotic signaling pathway via death domain receptors")
(accession "1902041")
(DB_ID 3446165)
(definition "Any process that modulates the frequency, rate or extent of extrinsic apoptotic signaling pathway via death domain receptors.")
(name "regulation of extrinsic apoptotic signaling pathway via death domain receptors")
(referenceDatabase [GK_1]))
([GK_3446166] of GO_BiologicalProcess
(_displayName "negative regulation of extrinsic apoptotic signaling pathway via death domain receptors")
(accession "1902042")
(DB_ID 3446166)
(definition "Any process that stops, prevents or reduces the frequency, rate or extent of extrinsic apoptotic signaling pathway via death domain receptors.")
(name "negative regulation of extrinsic apoptotic signaling pathway via death domain receptors")
(referenceDatabase [GK_1]))
([GK_3465328] of Summation
(_displayName "In the presence of FLIP(L), both caspase-8 and FLIP(L) are r...")
(DB_ID 3465328)
(literatureReference
[GK_1250231]
[GK_3465478]
[GK_3465386]
[GK_1267786])
(text "In the presence of FLIP(L), both caspase-8 and FLIP(L) are recruited and partially processed at the death-inducing signaling complex (DISC). The partially processed proteins stay bound to the DISC. The long cellular FLIP (FLIP(L) or c-FLIPL) has two death effector domains (DED) and a caspase-like domain that lacks catalytic activity due to absence of a cysteine residue. Processing of FLIP(L) occurs at the DISC and depends on caspase-8 activity (zymogen and mature form). Upon activation FLIP(L) is cleaved to generate N-terminal FLIP(p43) and C-terminal FLIP(p12)(Irmler M et al. 1997; Jong WY et al. 2009). Processed FLIP(L) can enhance the proteolytic activity of procaspase-8 (Chang DW et al. 2002; Jong WY et al. 2009; Pop C et al. 2011). However, the increased FLIP(L) protein levels in cells have been found to limit caspase-8 activity and inhibit apoptotic signaling pathway,"))
([GK_3465329] of Person
(_displayName "Kovacsovics, M")
(DB_ID 3465329)
(firstname "M")
(initial "M")
(surname "Kovacsovics"))
([GK_3465330] of LiteratureReference
(_displayName "PKC-mediated phosphorylation regulates c-FLIP ubiquitylation and stability")
(author
[GK_3465388]
[GK_3465434]
[GK_3465500]
[GK_3465458]
[GK_3465344]
[GK_3465498]
[GK_3465331])
(DB_ID 3465330)
(journal "Cell Death Differ.")
(pages "1215-26")
(pubMedIdentifier 19343040)
(title "PKC-mediated phosphorylation regulates c-FLIP ubiquitylation and stability")
(volume 16)
(year 2009))
([GK_3465331] of Person
(_displayName "Eriksson, J E")
(DB_ID 3465331)
(firstname "J E")
(initial "JE")
(surname "Eriksson"))
([GK_3465333] of Person
(_displayName "Kennedy, N")
(DB_ID 3465333)
(firstname "N")
(initial "N")
(surname "Kennedy"))
([GK_3465334] of LiteratureReference
(_displayName "The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways")
(author
[GK_3465376]
[GK_3465485]
[GK_3465398]
[GK_2672174]
[GK_3465452]
[GK_3465449]
[GK_2672170]
[GK_3465481]
[GK_3465333]
[GK_3465329]
[GK_2672175])
(DB_ID 3465334)
(journal "Curr. Biol.")
(pages "640-8")
(pubMedIdentifier 10837247)
(title "The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways")
(volume 10)
(year 2000))
([GK_3465335] of Person
(_displayName "Eils, Roland")
(DB_ID 3465335)
(firstname "Roland")
(initial "R")
(surname "Eils"))
([GK_3465336] of Person
(_displayName "Vittori, Daniela")
(DB_ID 3465336)
(firstname "Daniela")
(initial "D")
(surname "Vittori"))
([GK_3465337] of Person
(_displayName "Langa, Susana")
(DB_ID 3465337)
(firstname "Susana")
(initial "S")
(surname "Langa"))
([GK_3465338] of Person
(_displayName "Haag, Christian")
(DB_ID 3465338)
(firstname "Christian")
(initial "C")
(surname "Haag"))
([GK_3465339] of Person
(_displayName "Poukkula, Minna")
(DB_ID 3465339)
(firstname "Minna")
(initial "M")
(surname "Poukkula"))
([GK_3465340] of Person
(_displayName "Richter, Petra")
(DB_ID 3465340)
(firstname "Petra")
(initial "P")
(surname "Richter"))
([GK_3465342] of Person
(_displayName "Meinander, Annika")
(DB_ID 3465342)
(firstname "Annika")
(initial "A")
(surname "Meinander"))
([GK_3465343] of Person
(_displayName "Schneider, Pascal")
(DB_ID 3465343)
(firstname "Pascal")
(initial "P")
(surname "Schneider"))
([GK_3465344] of Person
(_displayName "Poukkula, M")
(DB_ID 3465344)
(firstname "M")
(initial "M")
(surname "Poukkula"))
([GK_3465345] of Person
(_displayName "Kreuz, Sebastian")
(DB_ID 3465345)
(firstname "Sebastian")
(initial "S")
(surname "Kreuz"))
([GK_3465346] of Summation
(_displayName "c-FLIP proteins (CASP8 and FADD-like apoptosis regulators or...")
(DB_ID 3465346)
(literatureReference
[GK_1250231]
[GK_3465444]
[GK_3465488]
[GK_3465397]
[GK_3465385]
[GK_3465361]
[GK_3465380]
[GK_3465456])
(text "c-FLIP proteins (CASP8 and FADD-like apoptosis regulators or c-FLICE inhibitory proteins) are death effector domain (DED)-containing proteins that are recruited to the death-inducing signaling complex (DISC) to regulate activation of caspases-8. Three out of 13 distinct spliced variants of c-FLIP had been found to be expressed at the protein level, the 26 kDa short form FLIP(S), the 24 kDa form FLIP(R), and the 55 kDa long form FLIP(L) (Irmler M et al. 1997; Shu HB et al. 1997; Srinivasula SM et al. 1997; Scaffidi C et al. 1999; Golks A et al. 2005; Haag C et al. 2011) All c-FLIP proteins carry two DEDs at their N termini, which can bind FADD and procaspase-8. In addition to two DEDs, FLIP(L) contains a large (p20) and a small (p12) caspase-like domain without catalytic activity. FLIP(S) and FLIP(R) consist of two DEDs and a small C terminus. Depending on its level of expression FLIP(L) may function as an anti-apoptotic or pro-apoptotic factor, while FLIP(S) and FLIP(R) protect cells from apoptosis by blocking the processing of caspase-8 at the receptor level (Scaffidi C et al. 1999; Golks A et al. 2005; Toivonen HT et al. 2011; Fricker N et al. 2010)."))
([GK_3465347] of Person
(_displayName "Siegmund, D")
(DB_ID 3465347)
(firstname "D")
(initial "D")
(surname "Siegmund"))
([GK_3465348] of Person
(_displayName "Krammer, Peter H")
(DB_ID 3465348)
(firstname "Peter H")
(initial "PH")
(surname "Krammer"))
([GK_3465349] of Person
(_displayName "Chung, Jee Y")
(DB_ID 3465349)
(firstname "Jee Y")
(initial "JY")
(surname "Chung"))
([GK_3465350] of Person
(_displayName "Callero, Mariana")
(DB_ID 3465350)
(firstname "Mariana")
(initial "M")
(surname "Callero"))
([GK_3465351] of Person
(_displayName "Johnson, Mark S")
(DB_ID 3465351)
(firstname "Mark S")
(initial "MS")
(surname "Johnson"))
([GK_3465352] of Complex
(_displayName "[Hsa] DISC:procaspase-8:FLIP(S) [plasma membrane]")
(DB_ID 3465352)
(hasComponent
[GK_3465443]
[GK_3465357])
(isChimeric FALSE)
(name "DISC:procaspase-8:FLIP(S)")
(species [GK_48887])
(stableIdentifier [GK_3654708]))
([GK_3465353] of LiteratureReference
(_displayName "A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction")
(author
[GK_141860]
[GK_3465399]
[GK_3465372]
[GK_141862]
[GK_141861]
[GK_3465419]
[GK_141863]
[GK_141864])
(DB_ID 3465353)
(journal "Cell")
(pages "777-87")
(pubMedIdentifier 10892748)
(title "A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction")
(volume 101)
(year 2000))
([GK_3465354] of Person
(_displayName "Chamorro, María E")
(DB_ID 3465354)
(firstname "María E")
(initial "ME")
(surname "Chamorro"))
([GK_3465355] of Person
(_displayName "Alnemri, E S")
(DB_ID 3465355)
(firstname "E S")
(initial "ES")
(surname "Alnemri"))
([GK_3465356] of Person
(_displayName "Katajamäki, Tuire")
(DB_ID 3465356)
(firstname "Tuire")
(initial "T")
(surname "Katajamäki"))
([GK_3465357] of EntityWithAccessionedSequence
(_displayName "[Hsa] FLIP(S) [cytosol]")
(DB_ID 3465357)
(endCoordinate 221)
(name
"FLIP(S)"
"CASP8 and FADD-like apoptosis regulator Isoform 2"
"CLARP2"
"MRIT beta-1"
"CASH beta")
(referenceEntity [GK_145326])
(species [GK_48887])
(stableIdentifier [GK_3656025])
(startCoordinate 1))
([GK_3465358] of Person
(_displayName "Vornlocher, Hans-Peter")
(DB_ID 3465358)
(firstname "Hans-Peter")
(initial "HP")
(surname "Vornlocher"))
([GK_3465359] of Person
(_displayName "Kim, Young-Youl")
(DB_ID 3465359)
(firstname "Young-Youl")
(initial "YY")
(surname "Kim"))
([GK_3465360] of Person
(_displayName "Vota, Daiana")
(DB_ID 3465360)
(firstname "Daiana")
(initial "D")
(surname "Vota"))
([GK_3465361] of LiteratureReference
(_displayName "Identification of c-FLIP(L) and c-FLIP(S) as critical regulators of death receptor-induced apoptosis in pancreatic cancer cells")
(author
[GK_3465338]
[GK_3465447]
[GK_3465417]
[GK_3465439]
[GK_3465418]
[GK_3465421]
[GK_3465457])
(DB_ID 3465361)
(journal "Gut")
(pages "225-37")
(pubMedIdentifier 20876774)
(title "Identification of c-FLIP(L) and c-FLIP(S) as critical regulators of death receptor-induced apoptosis in pancreatic cancer cells")
(volume 60)
(year 2011))
([GK_3465362] of Person
(_displayName "Palacios, Carmen")
(DB_ID 3465362)
(firstname "Carmen")
(initial "C")
(surname "Palacios"))
([GK_3465363] of Person
(_displayName "Reichwein, M")
(DB_ID 3465363)
(firstname "M")
(initial "M")
(surname "Reichwein"))
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(_displayName "Banks, S")
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([GK_3465366] of Person
(_displayName "Halpin, D R")
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([GK_3465367] of Person
(_displayName "Lens, S")
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(_displayName "Rapid turnover of c-FLIPshort is determined by its unique C-terminal tail")
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[GK_3465339]
[GK_3465462]
[GK_3214933]
[GK_3465487]
[GK_3465356]
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[GK_3214959]
[GK_3465373])
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(journal "J. Biol. Chem.")
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(pubMedIdentifier 15886205)
(title "Rapid turnover of c-FLIPshort is determined by its unique C-terminal tail")
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(year 2005))
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([GK_3465372] of Person
(_displayName "Hsia, C")
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([GK_3465373] of Person
(_displayName "Eriksson, John E")
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([GK_3465374] of Person
(_displayName "Westerlund, Mia")
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([GK_3465375] of Person
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([GK_3465376] of Person
(_displayName "Kataoka, T")
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([GK_3465377] of Person
(_displayName "Inoue, Hidekazu")
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([GK_3465378] of Person
(_displayName "Asaoka, Tomoko")
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([GK_3465379] of Person
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[GK_3465384]
[GK_3465342]
[GK_3465378]
[GK_3465374]
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[GK_3465450])
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(journal "J. Biol. Chem.")
(pages "18375-82")
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(title "Modeling reveals that dynamic regulation of c-FLIP levels determines cell-to-cell distribution of CD95-mediated apoptosis")
(volume 286)
(year 2011))
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(_displayName "Kiem, Hans-Peter")
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(_displayName "Fas-associated death domain protein (FADD) and caspase-8 mediate up-regulation of c-Fos by Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) via a FLICE inhibitory protein (FLIP)-regulated pathway")
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[GK_3465347]
[GK_3465414]
[GK_3465428]
[GK_3465469]
[GK_2672174]
[GK_3465363]
[GK_3465436]
[GK_3465420]
[GK_2672175]
[GK_3465508])
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(journal "J. Biol. Chem.")
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(pubMedIdentifier 11384965)
(title "Fas-associated death domain protein (FADD) and caspase-8 mediate up-regulation of c-Fos by Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) via a FLICE inhibitory protein (FLIP)-regulated pathway")
(volume 276)
(year 2001))
([GK_3465383] of Person
(_displayName "Tschopp, Jürg")
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([GK_3465384] of Person
(_displayName "Toivonen, Hannu T")
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(firstname "Hannu T")
(initial "HT")
(surname "Toivonen"))
([GK_3465385] of LiteratureReference
(_displayName "The role of c-FLIP in modulation of CD95-induced apoptosis")
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[GK_2672219]
[GK_3465496]
[GK_2672214]
[GK_2672197])
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(journal "J. Biol. Chem.")
(pages "1541-8")
(pubMedIdentifier 9880531)
(title "The role of c-FLIP in modulation of CD95-induced apoptosis")
(volume 274)
(year 1999))
([GK_3465386] of LiteratureReference
(_displayName "Mechanism of procaspase-8 activation by c-FLIPL")
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[GK_2672201]
[GK_2672164]
[GK_141951])
(DB_ID 3465386)
(journal "Proc. Natl. Acad. Sci. U.S.A.")
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(pubMedIdentifier 19416807)
(title "Mechanism of procaspase-8 activation by c-FLIPL")
(volume 106)
(year 2009))
([GK_3465387] of Person
(_displayName "Sharp, Darcie A")
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([GK_3465388] of Person
(_displayName "Kaunisto, A")
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(initial "A")
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([GK_3465389] of Person
(_displayName "Nesse, Alcira")
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(firstname "Alcira")
(initial "A")
(surname "Nesse"))
([GK_3465391] of Person
(_displayName "Scheurich, Peter")
(DB_ID 3465391)
(firstname "Peter")
(initial "P")
(surname "Scheurich"))
([GK_3465392] of Person
(_displayName "Lawrence, David A")
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(firstname "David A")
(initial "DA")
(surname "Lawrence"))
([GK_3465393] of LiteratureReference
(_displayName "NF-kappaB inducers upregulate cFLIP, a cycloheximide-sensitive inhibitor of death receptor signaling")
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[GK_3465445]
[GK_3465347]
[GK_3465420]
[GK_3465508])
(DB_ID 3465393)
(journal "Mol. Cell. Biol.")
(pages "3964-73")
(pubMedIdentifier 11359904)
(title "NF-kappaB inducers upregulate cFLIP, a cycloheximide-sensitive inhibitor of death receptor signaling")
(volume 21)
(year 2001))
([GK_3465394] of Person
(_displayName "Holler, Nils")
(DB_ID 3465394)
(firstname "Nils")
(initial "N")
(surname "Holler"))
([GK_3465395] of Summation
(_displayName "The short form of cellular FLIP (FLIP(S) or c-FLIPS) has two...")
(DB_ID 3465395)
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[GK_3465385]
[GK_3465368]
[GK_3465330]
[GK_3465503])
(text "The short form of cellular FLIP (FLIP(S) or c-FLIPS) has two death effector domain DEDs, which can bind to FADD and caspase-8. FLIP(S) protects the cells from apoptosis by inhibiting the processing of caspase-8 at the receptor level (Scaffidi C et al. 1999; Micheau O et al 2001) FLIP(S) is a short-lived protein which is sensitive to ubiquitination and proteasomal degradation (Poukkula M et al. 2005;) Protein kinase C (PKC)- mediated phosphorylation of FLIP(S) at Ser193 was shown to prolongs the half-lives of FLIP-S by inhibiting its polyubiquitination (Kaunisto A et al. 2009)"))
([GK_3465396] of LiteratureReference
(_displayName "Selective inhibition of FLICE-like inhibitory protein expression with small interfering RNA oligonucleotides is sufficient to sensitize tumor cells for TRAIL-induced apoptosis")
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[GK_3465370]
[GK_3465507]
[GK_429711]
[GK_3465358]
[GK_3465486])
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(journal "Mol. Med.")
(pages "725-32")
(pubMedIdentifier 12520089)
(title "Selective inhibition of FLICE-like inhibitory protein expression with small interfering RNA oligonucleotides is sufficient to sensitize tumor cells for TRAIL-induced apoptosis")
(volume 8)
(year 2002))
([GK_3465397] of LiteratureReference
(_displayName "c-FLIPR, a new regulator of death receptor-induced apoptosis")
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[GK_3465406]
[GK_3465475]
[GK_3465427]
[GK_3465348]
[GK_3465474])
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(journal "J. Biol. Chem.")
(pages "14507-13")
(pubMedIdentifier 15701649)
(title "c-FLIPR, a new regulator of death receptor-induced apoptosis")
(volume 280)
(year 2005))
([GK_3465398] of Person
(_displayName "Holler, N")
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(initial "N")
(surname "Holler"))
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(_displayName "Ye, H")
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(surname "Ye"))
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(_displayName "Following recruitment to the DISC, FLIP(L) forms a heterodim...")
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[GK_1267757]
[GK_3465405]
[GK_3465422]
[GK_3465503]
[GK_3465393])
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"CASP8(1-374)"
"caspase-8 p43/41 fragment"
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[GK_3465479]
[GK_3465377]
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[GK_3465407]
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[GK_3465426]
[GK_3465400]
[GK_3465477]
[GK_3465403]
[GK_3465465])
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(journal "Lab. Invest.")
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(volume 83)
(year 2003))
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"CASP8 and FADD-like apoptosis regulator Isoform 1 subunit p43"
"CLARP1"
"MRIT alpha-1"
"CASH alpha"
"I-FLICE 1"
"FLAME-1 gamma"
"CASP8 and FADD-like apoptosis regulator")
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[GK_1267838]
[GK_3465383])
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(year 2004))
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[GK_3465349]
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(year 2007))
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[GK_3465442]
[GK_3465411]
[GK_3465491]
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(year 2008))
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[GK_3465343]
[GK_3465394]
[GK_3465383]
[GK_3465502]
[GK_2584571]
[GK_2584570])
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(volume 277)
(year 2002))
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(_displayName "Pro-caspase-8 and FLIP(L) are recruited to FAS/CD95 receptor...")
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[GK_3465456]
[GK_3465380]
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[GK_3465405]
[GK_3465503]
[GK_3465393]
[GK_3465478])
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(initial "SA")
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([GK_3465439] of Person
(_displayName "Bachem, Max G")
(DB_ID 3465439)
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([GK_3465440] of Person
(_displayName "Sugimoto, Kazushi")
(DB_ID 3465440)
(firstname "Kazushi")
(initial "K")
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([GK_3465441] of Person
(_displayName "Fernandes-Alnemri, T")
(DB_ID 3465441)
(firstname "T")
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([GK_3465442] of Person
(_displayName "Kim, Dong-Joon")
(DB_ID 3465442)
(firstname "Dong-Joon")
(initial "DJ")
(surname "Kim"))
([GK_3465443] of Complex
(_displayName "[Hsa] DISC:procaspase-8 [plasma membrane]")
(DB_ID 3465443)
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[GK_57031]
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"DISC:procaspase-8"
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([GK_3465444] of LiteratureReference
(_displayName "Casper is a FADD- and caspase-related inducer of apoptosis")
(author
[GK_3465505]
[GK_3465366]
[GK_75697])
(DB_ID 3465444)
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(pages "751-63")
(pubMedIdentifier 9208847)
(title "Casper is a FADD- and caspase-related inducer of apoptosis")
(volume 6)
(year 1997))
([GK_3465445] of Person
(_displayName "Kreuz, S")
(DB_ID 3465445)
(firstname "S")
(initial "S")
(surname "Kreuz"))
([GK_3465446] of Summation
(_displayName "Pro-caspase-8 and FLIP(L) are recruited to the DISC. Followi...")
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(text "Pro-caspase-8 and FLIP(L) are recruited to the DISC. Following recruitment to the DISC, FLIP-L forms a heterodimer with caspase-8 through both death effector domain (DED) and caspase-like domain (CLD). In addition, FLIP(L) can also regulate signaling via interaction with the DED of FADD. The regulatory function of FLIP(L) has been found to differ depending on its expression levels. FLIP(L) was shown to inhibit death receptor (DR)-mediated apoptosis only when expressed at high levels, while low cell levels of FLIP(L) enhanced DR signaling to apoptosis (Sharp DA et al. 2005; Siegmund D et al. 2002; Boatright KM et al. 2004; Okano H et al. 2003; Yerbes R et al. 2011). The expression levels of c-FLIP proteins were shown to be regulated by NFkappaB signaling pathway (Micheau O et a. 2001; Kreuz S et al 2001)."))
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[GK_3465336]
[GK_3465360]
[GK_3465350]
[GK_3465354]
[GK_3465389])
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(pubMedIdentifier 20218968)
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(volume 34)
(year 2010))
([GK_3465455] of LiteratureReference
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[GK_3465437]
[GK_3465375]
[GK_3465337]
[GK_3465468])
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(pubMedIdentifier 18256533)
(title "TNF signaling gets FLIPped off: TNF-induced regulation of FLIP")
(volume 7)
(year 2008))
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(volume 190)
(year 2010))
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[GK_3465387]
[GK_3465392]
[GK_1250148])
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(journal "J. Biol. Chem.")
(pages "19401-9")
(pubMedIdentifier 15760909)
(title "Selective knockdown of the long variant of cellular FLICE inhibitory protein augments death receptor-mediated caspase-8 activation and apoptosis")
(volume 280)
(year 2005))
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(journal "J. Cell Biol.")
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(pubMedIdentifier 15289496)
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(volume 166)
(year 2004))
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[GK_2984183]
[GK_1267808]
[GK_3465470]
[GK_3465482]
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[GK_3465435]
[GK_2984181]
[GK_1267777])
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(journal "EMBO J.")
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(pubMedIdentifier 12110583)
(title "c-FLIP(L) is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis")
(volume 21)
(year 2002))
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"FLIP(L)(377-480)"
"FLIP(L) subunit p12"
"CASP8 and FADD-like apoptosis regulator Isoform 1 subunit p12"
"CLARP1"
"MRIT alpha-1"
"CASH alpha"
"I-FLICE 1"
"FLAME-1 gamma"
"CASP8 and FADD-like apoptosis regulator")
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([GK_3465486] of Person
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(DB_ID 3465487)
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[GK_3465473]
[GK_3465464]
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(pages "18542-5")
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(title "FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis")
(volume 272)
(year 1997))
([GK_3465489] of Person
(_displayName "Janssen, Ottmar")
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(initial "O")
(surname "Janssen"))
([GK_3465490] of Person
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(firstname "Joel")
(initial "J")
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[GK_3465493]
[GK_3465424]
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(title "Differential responses of FLIPLong and FLIPShort-overexpressing human myeloid leukemia cells to TNF-alpha and TRAIL-initiated apoptotic signals")
(volume 36)
(year 2008))
([GK_3465495] of Person
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(initial "HJ")
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(_displayName "Schmitz, I")
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(initial "I")
(surname "Schmitz"))
([GK_3465498] of Person
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(initial "A")
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(_displayName "[Hsa] FASL:FAS Receptor Trimer:FADD:pro-Caspase-8:FLIP(L) [plasma membrane]")
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[GK_43124]
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([GK_3465500] of Person
(_displayName "Asaoka, T")
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(firstname "T")
(initial "T")
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([GK_3465502] of Person
(_displayName "Nicholson, Donald W")
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(firstname "Donald W")
(initial "DW")
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([GK_3465503] of LiteratureReference
(_displayName "NF-kappaB signals induce the expression of c-FLIP")
(author
[GK_2562544]
[GK_3465367]
[GK_3465467]
[GK_3465430]
[GK_2672175])
(DB_ID 3465503)
(journal "Mol. Cell. Biol.")
(pages "5299-305")
(pubMedIdentifier 11463813)
(title "NF-kappaB signals induce the expression of c-FLIP")
(volume 21)
(year 2001))
([GK_3465505] of Person
(_displayName "Shu, H B")
(DB_ID 3465505)
(firstname "H B")
(initial "HB")
(surname "Shu"))
([GK_3465506] of Person
(_displayName "Abbassi, Nissa")
(DB_ID 3465506)
(firstname "Nissa")
(initial "N")
(surname "Abbassi"))
([GK_3465507] of Person
(_displayName "Hadwiger, Philipp")
(DB_ID 3465507)
(firstname "Philipp")
(initial "P")
(surname "Hadwiger"))
([GK_3465508] of Person
(_displayName "Wajant, H")
(DB_ID 3465508)
(firstname "H")
(initial "H")
(surname "Wajant"))
([GK_3465509] of Person
(_displayName "Okano, Hiroshi")
(DB_ID 3465509)
(firstname "Hiroshi")
(initial "H")
(surname "Okano"))
([GK_3465510] of Person
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(firstname "Sudeshna")
(initial "S")
(surname "Seal"))
([GK_3465511] of Person
(_displayName "Rumpf, Jost-Julian")
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(firstname "Jost-Julian")
(initial "JJ")
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([GK_3465518] of InstanceEdit
(_displayName "Shamovsky, V, 2013-05-17")
(author [GK_429259])
(dateTime "2013-05-17 01:54:44")
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([GK_3465522] of LiteratureReference
(_displayName "Ebselen sensitizes glioblastoma cells to Tumor Necrosis Factor (TNFalpha)-induced apoptosis through two distinct pathways involving NF-kappaB downregulation and Fas-mediated formation of death inducing signaling complex")
(author
[GK_3465527]
[GK_3465523]
[GK_3465524]
[GK_3465526]
[GK_3465528])
(DB_ID 3465522)
(journal "Int. J. Cancer")
(pages "2204-12")
(pubMedIdentifier 18709644)
(title "Ebselen sensitizes glioblastoma cells to Tumor Necrosis Factor (TNFalpha)-induced apoptosis through two distinct pathways involving NF-kappaB downregulation and Fas-mediated formation of death inducing signaling complex")
(volume 123)
(year 2008))
([GK_3465523] of Person
(_displayName "Tewari, Richa")
(DB_ID 3465523)
(firstname "Richa")
(initial "R")
(surname "Tewari"))
([GK_3465524] of Person
(_displayName "Sk, Ugir Hossain")
(DB_ID 3465524)
(firstname "Ugir Hossain")
(initial "UH")
(surname "Sk"))
([GK_3465526] of Person
(_displayName "Joseph, Christy")
(DB_ID 3465526)
(firstname "Christy")
(initial "C")
(surname "Joseph"))
([GK_3465527] of Person
(_displayName "Sharma, Vivek")
(DB_ID 3465527)
(firstname "Vivek")
(initial "V")
(surname "Sharma"))
([GK_3465528] of Person
(_displayName "Sen, Ellora")
(DB_ID 3465528)
(firstname "Ellora")
(initial "E")
(surname "Sen"))
([GK_3465529] of Person
(_displayName "Hughes, Michelle")
(DB_ID 3465529)
(firstname "Michelle")
(initial "M")
(surname "Hughes"))
([GK_3465531] of LiteratureReference
(_displayName "Fas-associated death domain protein and caspase-8 are not recruited to the tumor necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced apoptosis")
(author
[GK_2984182]
[GK_3465529]
[GK_2562548]
[GK_2984178])
(DB_ID 3465531)
(journal "J. Biol. Chem.")
(pages "25534-41")
(pubMedIdentifier 12721308)
(title "Fas-associated death domain protein and caspase-8 are not recruited to the tumor necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced apoptosis")
(volume 278)
(year 2003))
([GK_3465532] of Complex
(_displayName "[Hsa] TRADD:TRAF2:RIP1:FADD:procaspase-8:FLIP(L) [cytosol]")
(DB_ID 3465532)
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[GK_57031]
[GK_3371356])
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([GK_3465558] of Person
(_displayName "Brennan, F M")
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(firstname "F M")
(initial "FM")
(surname "Brennan"))
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(_displayName "Release of tumour necrosis factor alpha (TNFalpha) by TNFalpha cleaving enzyme (TACE) in response to septic stimuli in vitro")
(author
[GK_3465561]
[GK_3465558])
(DB_ID 3465559)
(journal "Br J Anaesth")
(pages "222-8")
(pubMedIdentifier 15556967)
(title "Release of tumour necrosis factor alpha (TNFalpha) by TNFalpha cleaving enzyme (TACE) in response to septic stimuli in vitro")
(volume 94)
(year 2005))
([GK_3465561] of Person
(_displayName "Robertshaw, H J")
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(surname "Robertshaw"))
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(_displayName "The soluble form of TNF-alpha is cleaved from membrane-ancho...")
(DB_ID 3465562)
(literatureReference
[GK_140945]
[GK_5657708]
[GK_5657695]
[GK_5657697]
[GK_5657711]
[GK_5657693]
[GK_5657681]
[GK_5657731]
[GK_5657729]
[GK_5657704]
[GK_5692352]
[GK_5692341]
[GK_5692342]
[GK_5692339]
[GK_5692356]
[GK_5692336])
(text "The soluble form of TNF-alpha is cleaved from membrane-anchored TNF-alpha and retains the ability to bind to TNF receptor 1(TNFR1) and TNFR2. BAG4, also known as silencer of death domain (SODD), belongs to the BAG family of anti-apoptotic proteins. Mammalian BAG4 was found to associate with TNFR1 preventing receptor signaling in the absence of ligand (Jiang Y et al. 1999; Miki K and Eddy EM 2002). Furthermore, crystallographic data and biochemical analysis showed that TNFR1 forms inactive homodimers or homotrimers in the absence of TNF by the N-terminal domain, the pre ligand assembly domain (PLAD) (Chan FK et al. 2000; Wang YL et al. 2011). Upon TNF-alpha binding BAG4 is quickly released from TNFR1 and three receptor molecules form a complex with the TNF trimer. The TNF-alpha homologue ligand, lymphotoxin-alpha (LTA, also known as TNF-beta), which as homotrimer only occurs as a soluble ligand, also interacts with TNFR1. LTA binds three receptor molecules and triggers the same effects as soluble TNF-alpha (Banner DW et al. 1993; Etemadi N et al. 2013). The TNF-alpha:TNFR1 receptor complex then transmits the signal leading to cell death or survival. However, it remains unclear whether BAG4 binds to death domain of monomeric TNFR1 to prevent receptor oligomerization or recognizes receptor trimers to facilitate ATP-dependent TNFR1 trimer disassembly (Jiang Y et al. 1999; Miki K and Eddy EM 2002). Additionally, BAG4 is known to interact with HSP70, death receptor 3, and the anti-apoptotic protein Bcl-2 (Antoku et al. 2001; Brockmann et al. 2004; Jiang et al. 1999). BAG4-overexpressing HeLa cells showed reduced cellular sensitivity to treatment with extracellular TNFalpha and CD95 ligand (Eichholtz-Wirth H et al. 2003). In addition, increased expression level of BAG4 in tumor cells leads to resistance of TNFalpha-induced cell death and is associated with pancreatic cancer, some types of melanoma, acute lymphoblastic leukemia etc.(Ozawa et al. 2000; Tao H et ql. 2007; Reuland SN et al. 2013). The physiological relevance of BAG4 for TNFR1 signaling, however, is difficult to judge because BAG4 knockout mice have no or only a mild effect on pro-inflammatory TNF signaling and give no evidence for an inhibitory role of BAG4 in TNFR1-induced cell death (Takada H et al. 2003; Endres R et al. 2003)."))
([GK_3465563] of InstanceEdit
(_displayName "Shamovsky, V, 2013-05-17")
(author [GK_429259])
(dateTime "2013-05-17 04:50:56")
(DB_ID 3465563))
([GK_3465564] of Person
(_displayName "Dumont, Serge")
(DB_ID 3465564)
(firstname "Serge")
(initial "S")
(surname "Dumont"))
([GK_3465565] of Person
(_displayName "Peluso, Jean")
(DB_ID 3465565)
(firstname "Jean")
(initial "J")
(surname "Peluso"))
([GK_3465566] of Person
(_displayName "Moreira-Tabaka, Helena")
(DB_ID 3465566)
(firstname "Helena")
(initial "H")
(surname "Moreira-Tabaka"))
([GK_3465567] of Person
(_displayName "Kessler, Pascal")
(DB_ID 3465567)
(firstname "Pascal")
(initial "P")
(surname "Kessler"))
([GK_3465568] of LiteratureReference
(_displayName "Unlike for human monocytes after LPS activation, release of TNF-? by THP-1 cells is produced by a TACE catalytically different from constitutive TACE")
(author
[GK_3465566]
[GK_3465565]
[GK_3465573]
[GK_3465570]
[GK_3465567]
[GK_3465571]
[GK_3465564]
[GK_3465574])
(DB_ID 3465568)
(journal "PLoS ONE")
(pages "e34184")
(pubMedIdentifier 22479555)
(title "Unlike for human monocytes after LPS activation, release of TNF-? by THP-1 cells is produced by a TACE catalytically different from constitutive TACE")
(volume 7)
(year 2012))
([GK_3465570] of Person
(_displayName "Hentsch, Didier")
(DB_ID 3465570)
(firstname "Didier")
(initial "D")
(surname "Hentsch"))
([GK_3465571] of Person
(_displayName "Reimund, Jean-Marie")
(DB_ID 3465571)
(firstname "Jean-Marie")
(initial "JM")
(surname "Reimund"))
([GK_3465572] of Summation
(_displayName "TNF-alpha is initially synthesized as a 26kDa transmembrane ...")
(DB_ID 3465572)
(literatureReference
[GK_3371352]
[GK_3465559]
[GK_3465568]
[GK_5692301]
[GK_5668480])
(text "TNF-alpha is initially synthesized as a 26kDa transmembrane protein (membrane TNF-alpha), which is processed by proteolytic cleavage known as ectodomain shedding (Tang P et al. 1996). TNF-alpha-converting enzyme (TACE or ADAM17) mediates the cleavage of TNF-alpha generating the soluble 17kDa form (Robertshaw HJ & Brennan FM 2005). Inhibition of TACE activity resulted in an accumulation of unprocessed TNF-alpha on the cell surface of human monocytic cells (THP1) (Tabaka HN et al. 2012). Both membrane-bound and secreted forms of TNF-alpha are biologically active and may trigger different activities due to their differential capacities to stimulate TNFR1 and TNFR2. TNFR1 is efficiently activated by soluble and membrane TNF-alpha, TNFR2 signaling, however, is preferentially stimulated by membrane TNF-alpha while the soluble form has limited activity on this receptor despite efficient binding (Grell M et al. 1995; Grell M et al. 1998)."))
([GK_3465573] of Person
(_displayName "Vonesch, Jean-Luc")
(DB_ID 3465573)
(firstname "Jean-Luc")
(initial "JL")
(surname "Vonesch"))
([GK_3465574] of Person
(_displayName "Muller, Christian D")
(DB_ID 3465574)
(firstname "Christian D")
(initial "CD")
(surname "Muller"))
([GK_3465576] of Summation
(_displayName "The inflammatory cytokine tumor necrosis factor (TNF) alpha ...")
(DB_ID 3465576)
(literatureReference
[GK_5657948]
[GK_5657952]
[GK_5657955])
(text "The inflammatory cytokine tumor necrosis factor (TNF) alpha exerts its biological activity through the membrane bound (tmTNF-alpha) or soluble (sTNF-alpha) forms. Both sTNF-alpha and tmTNF-alpha ligands interact with either TNFR1 (p55, CD120a) or TNFR2 (p75, CD120b) on a variety of immune and nonimmune cell types. Transmembrane TNF-alpha functions as a bipolar molecule that can transmit signals both as a ligand and as a receptor in a cell-to-cell contact fashion (Eissner G et al. 2004; Zhang H et al. 2008; Juhász K et al. 2013). As a ligand tmTNF-alpha binds to receptors TNFR1 or -R2 on TNF-responsive cells to initiate signaling pathways that lead among other things to cell death or NFkB-mediated expression of inflammatory genes. Binding of tmTNF-alpha by TNFRs can simultaneously induce a reverse signals transmiting back to the tmTNF-bearing cell. The molecular basis of TNF reverse signaling remains largely unexplored."))
([GK_350870] of Complex
(_displayName "[Hsa] Active Caspase-3 heterotetramer [cytosol]")
(DB_ID 350870)
(hasComponent
[GK_350888]
[GK_350888])
(name "Active Caspase-3 heterotetramer")
(species [GK_48887])
(stableIdentifier [GK_369067]))
([GK_3508822] of InstanceEdit
(_displayName "Shamovsky, V, 2013-05-17")
(author [GK_429259])
(dateTime "2013-05-17 21:57:50")
(DB_ID 3508822))
([GK_350888] of Complex
(_displayName "[Hsa] Caspase-3 heterodimer [cytosol]")
(DB_ID 350888)
(hasComponent
[GK_141646]
[GK_141644])
(name "Caspase-3 heterodimer")
(species [GK_48887])
(stableIdentifier [GK_371035]))
([GK_354] of GO_CellularComponent
(_displayName "intracellular")
(accession "0005622")
(DB_ID 354)
(definition "The living contents of a cell; the matter contained within (but not including) the plasma membrane, usually taken to exclude large vacuoles and masses of secretory or ingested material. In eukaryotes it includes the nucleus and cytoplasm.")
(instanceOf [GK_258147])
(name "intracellular")
(referenceDatabase [GK_1]))
([GK_355446] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P68431 HIST1H3A recommendedName: Histone H3.1 alternativeName: Histone H3/a alternativeName: Histone H3/b alternativeName: Histone H3/c alternativeName: Histone H3/d alternativeName: Histone H3/f alternativeName: Histone H3/h alternativeName: Histone H3/i alternativeName: Histone H3/j alternativeName: Histone H3/k alternativeName: Histone H3/l ")
(checksum "1")
(comment "FUNCTION Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.SUBUNIT The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.DEVELOPMENTAL STAGE Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.PTM Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me).PTM Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.PTM Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.PTM Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin.MISCELLANEOUS This histone is only present in mammals and is enriched in acetylation of Lys-15 and dimethylation of Lys-10 (H3K9me2).SIMILARITY Belongs to the histone H3 family.")
(DB_ID 355446)
(description "recommendedName: Histone H3.1 alternativeName: Histone H3/a alternativeName: Histone H3/b alternativeName: Histone H3/c alternativeName: Histone H3/d alternativeName: Histone H3/f alternativeName: Histone H3/h alternativeName: Histone H3/i alternativeName: Histone H3/j alternativeName: Histone H3/k alternativeName: Histone H3/l ")
(geneName
"HIST1H3A"
"H3FA"
" RIP3 was shown to inhibit TRIF-induced NF-kB activation in dose-dependent manner when overexpressed in HEK293T cells by competing with TRIF to bind RIP1 [Meylan E et al 2004]. "))
([GK_433999] of Person
(_displayName "Burns, K")
(DB_ID 433999)
(initial "K")
(surname "Burns"))
([GK_434026] of Person
(_displayName "Botos, I")
(DB_ID 434026)
(firstname "Istvan")
(initial "I")
(surname "Botos"))
([GK_434069] of Person
(_displayName "Kelliher, MA")
(DB_ID 434069)
(initial "MA")
(surname "Kelliher"))
([GK_434074] of Person
(_displayName "Shiloach, J")
(DB_ID 434074)
(firstname "Joseph")
(initial "J")
(surname "Shiloach"))
([GK_434101] of LiteratureReference
(_displayName "Structural basis of toll-like receptor 3 signaling with double-stranded RNA")
(author
[GK_433806]
[GK_434026]
[GK_110823]
[GK_433833]
[GK_434074]
[GK_181090]
[GK_433913])
(DB_ID 434101)
(journal "Science")
(pages "379-81")
(pubMedIdentifier 18420935)
(title "Structural basis of toll-like receptor 3 signaling with double-stranded RNA")
(volume 320)
(year 2008))
([GK_434112] of LiteratureReference
(_displayName "TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction")
(author
[GK_177854]
[GK_177869]
[GK_177849]
[GK_433875]
[GK_177878])
(DB_ID 434112)
(journal "Nat Immunol")
(pages "161-7")
(pubMedIdentifier 12539043)
(title "TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction")
(volume 4)
(year 2003))
([GK_434118] of GenomeEncodedEntity
(_displayName "Viral dsRNA (-) stranded [endosome]")
(crossReference [GK_5578725])
(DB_ID 434118)
(name "Viral dsRNA (-) stranded")
(stableIdentifier [GK_1110356]))
([GK_4344] of GO_MolecularFunction
(_displayName "cysteine-type endopeptidase activity")
(accession "0004197")
(DB_ID 4344)
(definition "Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a mechanism in which the sulfhydryl group of a cysteine residue at the active center acts as a nucleophile.")
(ecNumber
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22"
"3.4.22")
(name "cysteine-type endopeptidase activity")
(referenceDatabase [GK_1]))
([GK_437238] of Person
(_displayName "Aigner, S")
(DB_ID 437238)
(initial "S")
(surname "Aigner"))
([GK_437354] of ReferenceDatabase
(_displayName "MOD")
(accessUrl "http://www.ebi.ac.uk/ontology-lookup/?termId=MOD:###ID###")
(DB_ID 437354)
(name
"MOD"
"PSI-MOD")
(url "http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=MOD"))
([GK_442879] of InstanceEdit
(_displayName "Shamovsky, V, 2009-09-29")
(author [GK_429259])
(dateTime "2009-09-29 16:39:25")
(DB_ID 442879))
([GK_445564] of Person
(_displayName "Takahashi, N")
(DB_ID 445564)
(initial "N")
(surname "Takahashi"))
([GK_445675] of PsiMod
(_displayName "N-asparaginyl-glycosylphosphatidylinositolethanolamine [MOD:00167]")
(DB_ID 445675)
(definition "A protein modification that effectively converts an L-asparagine residue to N-asparaginyl-glycosylphosphatidylinositolethanolamine.")
(identifier "00167")
(name "N-asparaginyl-glycosylphosphatidylinositolethanolamine")
(referenceDatabase [GK_437354])
(synonym
"GPI-anchor amidated asparagine"
"GPIAsn"))
([GK_445679] of PsiMod
(_displayName "N-myristoylglycine [MOD:00068]")
(DB_ID 445679)
(definition "A protein modification that effectively converts a glycine residue to N-myristoylglycine.")
(identifier "00068")
(name "N-myristoylglycine")
(referenceDatabase [GK_437354])
(synonym
"(tetradecanoylamino)ethanoic acid"
"N-myristoyl glycine"
"NMyrGly"
"N-myristoylated glycine"
"Myristoylation"
"Myristoyl"))
([GK_445687] of PsiMod
(_displayName "O-phospho-L-serine [MOD:00046]")
(DB_ID 445687)
(definition "A protein modification that effectively converts an L-serine residue to O-phospho-L-serine.")
(identifier "00046")
(name "O-phospho-L-serine")
(referenceDatabase [GK_437354])
(synonym
"Phospho Seryl"
"(S)-2-amino-3-(phosphonooxy)propanoic acid"
"Phosphoserine"
"OPhosSer"
"O-phosphorylated L-serine"
"Phosphorylation"
"Phospho"))
([GK_447576] of GO_CellularComponent
(_displayName "other organism")
(accession "0044215")
(DB_ID 447576)
(definition "A secondary organism with which the first organism is interacting.")
(instanceOf [GK_160483])
(name "other organism")
(referenceDatabase [GK_1]))
([GK_447577] of GO_CellularComponent
(_displayName "other organism part")
(accession "0044217")
(componentOf [GK_447576])
(DB_ID 447577)
(definition "Any constituent part of a secondary organism with which the first organism is interacting.")
(instanceOf [GK_258201])
(name "other organism part")
(referenceDatabase [GK_1]))
([GK_448179] of PsiMod
(_displayName "N6-myristoyl-L-lysine [MOD:00087]")
(DB_ID 448179)
(definition "A protein modification that effectively converts an L-lysine residue to N6-myristoyl-L-lysine.")
(identifier "00087")
(name "N6-myristoyl-L-lysine")
(referenceDatabase [GK_437354])
(synonym
"(S)-2-amino-6-(tetradecanoylamino)hexanoic acid"
"N6-myristoyl lysine"
"N6MyrLys"
"N6-myristoylated L-lysine"
"Myristoylation"
"Myristoyl"))
([GK_448182] of PsiMod
(_displayName "half cystine [MOD:00798]")
(DB_ID 448182)
(definition "A protein modification that can be regarded as effectively either one half of a cystine cross-link, or a cysteine residue with one hydrogen atom or proton removed.")
(identifier "00798")
(name "half cystine")
(referenceDatabase [GK_437354])
(synonym
"Half of a disulfide bridge"
"Dehydro"))
([GK_448675] of Person
(_displayName "Creagh, EM")
(DB_ID 448675)
(initial "EM")
(surname "Creagh"))
([GK_448684] of LiteratureReference
(_displayName "Caspase-activation pathways in apoptosis and immunity")
(author
[GK_448675]
[GK_448700]
[GK_140516])
(DB_ID 448684)
(journal "Immunol Rev")
(pages "10-21")
(pubMedIdentifier 12752666)
(title "Caspase-activation pathways in apoptosis and immunity")
(volume 193)
(year 2003))
([GK_448700] of Person
(_displayName "Conroy, H")
(DB_ID 448700)
(initial "H")
(surname "Conroy"))
([GK_450] of GO_MolecularFunction
(_displayName "hydrolase activity")
(accession "0016787")
(DB_ID 450)
(definition "Catalysis of the hydrolysis of various bonds, e.g. C-O, C-N, C-C, phosphoric anhydride bonds, etc. Hydrolase is the systematic name for any enzyme of EC class 3.")
(ecNumber
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3"
"3")
(name "hydrolase activity")
(referenceDatabase [GK_1]))
([GK_450288] of Summation
(_displayName "TIR-domain-containing adaptor inducing interferon-beta (TRIF...")
(DB_ID 450288)
(text "TIR-domain-containing adaptor inducing interferon-beta (TRIF or TICAM1) was shown to play an essential role in TLR3 signaling. All poly(I:C)-induced pathways leading to NFkB and IRF3 activation were abolished in TRIF-/- mice [Yamamoto et al. 2003]."))
([GK_450316] of EntityWithAccessionedSequence
(_displayName "[Hsa] TICAM1 [endosome membrane]")
(DB_ID 450316)
(endCoordinate 712)
(name
"TICAM1"
"TRIF")
(referenceEntity [GK_165792])
(species [GK_48887])
(stableIdentifier [GK_1111152])
(startCoordinate 1))
([GK_450360] of InstanceEdit
(_displayName "Shamovsky, V, 2009-12-16")
(author [GK_429259])
(dateTime "2009-12-16 18:32:27")
(DB_ID 450360))
([GK_450629] of Person
(_displayName "Lee, J")
(DB_ID 450629)
(firstname "Jungwoon")
(initial "J")
(surname "Lee"))
([GK_452043] of Person
(_displayName "Shin, H")
(DB_ID 452043)
(firstname "Hyunshun")
(initial "H")
(surname "Shin"))
([GK_452587] of Person
(_displayName "Betsholtz, C")
(DB_ID 452587)
(initial "C")
(surname "Betsholtz"))
([GK_457] of GO_CellularComponent
(_displayName "vacuole")
(accession "0005773")
(DB_ID 457)
(definition "A closed structure, found only in eukaryotic cells, that is completely surrounded by unit membrane and contains liquid material. Cells contain one or several vacuoles, that may have different functions from each other. Vacuoles have a diverse array of functions. They can act as a storage organelle for nutrients or waste products, as a degradative compartment, as a cost-effective way of increasing cell size, and as a homeostatic regulator controlling both turgor pressure and pH of the cytosol.")
(instanceOf
[GK_159960]
[GK_258163])
(name "vacuole")
(referenceDatabase [GK_1]))
([GK_469669] of Person
(_displayName "Gilbey, SG")
(DB_ID 469669)
(initial "SG")
(surname "Gilbey"))
([GK_480491] of Person
(_displayName "Heinzmann, C")
(DB_ID 480491)
(initial "C")
(surname "Heinzmann"))
([GK_48887] of Species
(_displayName "Homo sapiens")
(crossReference [GK_72938])
(DB_ID 48887)
(name
"Homo sapiens"
"H. sapiens"
"Hs"
"human"
"man")
(superTaxon [GK_72939]))
([GK_49678] of ReferenceGeneProduct
(_chainChangeLog "signal peptide:1-17 added on Fri February 6 2015;propeptide:18-214 added on Fri February 6 2015;chain:215-824 added on Fri February 6 2015")
(_displayName "[Hsa] UniProt:P78536 ADAM17 recommendedName: Disintegrin and metalloproteinase domain-containing protein 17 shortName:ADAM 17 ecNumber3.4.24.86/ecNumber alternativeName: Snake venom-like protease alternativeName: TNF-alpha convertase alternativeName: TNF-alpha-converting enzyme cdAntigenNameCD156b/cdAntigenName")
(chain
"signal peptide:1-17"
"propeptide:18-214"
"chain:215-824")
(checksum "5B1032F6B88A837F")
(comment "CATALYTIC ACTIVITY Narrow endopeptidase specificity. Cleaves Pro-Leu-Ala-Gln-Ala-|-Val-Arg-Ser-Ser-Ser in the membrane-bound, 26-kDa form of tumor necrosis factor alpha (TNF-alpha). Similarly cleaves other membrane-anchored, cell-surface proteins to 'shed' the extracellular domains.TISSUE SPECIFICITY Ubiquitously expressed. Expressed at highest levels in adult heart, placenta, skeletal muscle, pancreas, spleen, thymus, prostate, testes, ovary and small intestine, and in fetal brain, lung, liver and kidney.INDUCTION In arthritis-affected cartilage.DOMAIN The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.")
(DB_ID 49678)
(description "recommendedName: Disintegrin and metalloproteinase domain-containing protein 17 shortName:ADAM 17 ecNumber3.4.24.86/ecNumber alternativeName: Snake venom-like protease alternativeName: TNF-alpha convertase alternativeName: TNF-alpha-converting enzyme cdAntigenNameCD156b/cdAntigenName")
(geneName
"ADAM17"
"CSVP"
"TACE")
(identifier "P78536")
(isSequenceChanged FALSE)
(keyword
"3D-structure"
"Alternative splicing"
"Cleavage on pair of basic residues"
"Complete proteome"
"Direct protein sequencing"
"Disulfide bond"
"Glycoprotein"
"Hydrolase"
"Membrane"
"Metal-binding"
"Metalloprotease"
"Notch signaling pathway"
"Phosphoprotein"
"Polymorphism"
"Protease"
"Reference proteome"
"SH3-binding"
"Signal"
"Transmembrane"
"Transmembrane helix"
"Zinc"
"Zymogen")
(name "ADAM17")
(referenceDatabase [GK_2])
(secondaryIdentifier
"ADA17_HUMAN"
"O60226")
(sequenceLength 824)
(species [GK_48887]))
([GK_49984] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P01160 NPPA recommendedName: Natriuretic peptides A alternativeName: CDD-ANF alternativeName: Prepronatriodilatin component recommendedName: Cardiodilatin-related peptide shortName:CDP /component component recommendedName: Atrial natriuretic factor shortName:ANF alternativeName: Atrial natriuretic peptide shortName:ANP /component")
(checksum "1")
(comment "PTM Cleaved by CORIN upon secretion to produce the functional hormone.POLYMORPHISM There are two different prepronatriodilatin alleles. One codes for 2 Arg residues at the C-terminus that are cleaved to form the mature peptide, while the other ends in a termination codon immediately after the last codon of the mature peptide.SIMILARITY Belongs to the natriuretic peptide family.")
(DB_ID 49984)
(description "recommendedName: Natriuretic peptides A alternativeName: CDD-ANF alternativeName: Prepronatriodilatin component recommendedName: Cardiodilatin-related peptide shortName:CDP /component component recommendedName: Atrial natriuretic factor shortName:ANF alternativeName: Atrial natriuretic peptide shortName:ANP /component")
(geneName
"NPPA"
"ANP"
"PND")
(identifier "P01160")
(isSequenceChanged TRUE)
(keyword
"3D-structure"
"Atrial fibrillation"
"Complete proteome"
"Direct protein sequencing"
"Disulfide bond"
"Hormone"
"Polymorphism"
"Secreted"
"Signal"
"Vasoactive")
(name "NPPA")
(referenceDatabase [GK_2])
(secondaryIdentifier
"ANF_HUMAN"
"Q13766"
"Q5JZE1")
(sequenceLength 153)
(species [GK_48887]))
([GK_500144] of Person
(_displayName "Baker, D")
(DB_ID 500144)
(firstname "David")
(initial "D")
(surname "Baker"))
([GK_500361] of Person
(_displayName "Peng, S")
(DB_ID 500361)
(initial "S")
(surname "Peng"))
([GK_50094] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P02647 APOA1 recommendedName: Apolipoprotein A-I shortName:Apo-AI shortName:ApoA-I alternativeName: Apolipoprotein A1 component recommendedName: Apolipoprotein A-I(1-242) /component")
(checksum "1")
(comment "PTM Phosphorylation sites are present in the extracelllular medium.SIMILARITY Belongs to the apolipoprotein A1/A4/E family.")
(DB_ID 50094)
(description "recommendedName: Apolipoprotein A-I shortName:Apo-AI shortName:ApoA-I alternativeName: Apolipoprotein A1 component recommendedName: Apolipoprotein A-I(1-242) /component")
(geneName "APOA1")
(identifier "P02647")
(isSequenceChanged TRUE)
(keyword
"3D-structure"
"Amyloid"
"Amyloidosis"
"Atherosclerosis"
"Cholesterol metabolism"
"Complete proteome"
"Direct protein sequencing"
"Disease mutation"
"Glycation"
"Glycoprotein"
"HDL"
"Lipid metabolism"
"Lipid transport"
"Lipoprotein"
"Neuropathy"
"Palmitate"
"Phosphoprotein"
"Polymorphism"
"Repeat"
"Secreted"
"Signal"
"Steroid metabolism"
"Transport")
(name "APOA1")
(referenceDatabase [GK_2])
(secondaryIdentifier
"APOA1_HUMAN"
"A8K866"
"Q6LDN9"
"Q6Q785"
"Q9UCS8"
"Q9UCT8")
(sequenceLength 267)
(species [GK_48887]))
([GK_50098] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P06727 APOA4 recommendedName: Apolipoprotein A-IV shortName:Apo-AIV shortName:ApoA-IV alternativeName: Apolipoprotein A4 ")
(checksum "1")
(comment "FUNCTION May have a role in chylomicrons and VLDL secretion and catabolism. Required for efficient activation of lipoprotein lipase by ApoC-II; potent activator of LCAT. Apoa-IV is a major component of HDL and chylomicrons.DOMAIN Nine of the thirteen 22-amino acid tandem repeats (each 22-mer is actually a tandem array of two, A and B, related 11-mers) occurring in this sequence are predicted to be highly alpha-helical, and many of these helices are amphipathic. They may therefore serve as lipid-binding domains with lecithin:cholesterol acyltransferase (LCAT) activating abilities.PTM Phosphorylation sites are present in the extracelllular medium.POLYMORPHISM Eight alleles have been characterized (APOA-IV*0 to APOA-IV*7). APOA-IV*1 is the major allele (90%), APOA-IV*2 is also common (8%), the others are rare alleles. The sequence shown represents allele APOA-IV*1.SIMILARITY Belongs to the apolipoprotein A1/A4/E family.")
(DB_ID 50098)
(description "recommendedName: Apolipoprotein A-IV shortName:Apo-AIV shortName:ApoA-IV alternativeName: Apolipoprotein A4 ")
(geneName "APOA4")
(identifier "P06727")
(isSequenceChanged TRUE)
(keyword
"Chylomicron"
"Complete proteome"
"HDL"
"Lipid transport"
"Phosphoprotein"
"Polymorphism"
"Repeat"
"Secreted"
"Signal"
"Transport")
(name "APOA4")
(referenceDatabase [GK_2])
(secondaryIdentifier
"APOA4_HUMAN"
"A8MSL6"
"Q14CW8"
"Q6Q787")
(sequenceLength 396)
(species [GK_48887]))
([GK_504] of GO_BiologicalProcess
(_displayName "metabolic process")
(accession "0008152")
(DB_ID 504)
(definition "The chemical reactions and pathways, including anabolism and catabolism, by which living organisms transform chemical substances. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation.")
(name "metabolic process")
(referenceDatabase [GK_1]))
([GK_50591] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P61769 B2M recommendedName: Beta-2-microglobulin component recommendedName: Beta-2-microglobulin form pI 5.3 /component")
(checksum "1")
(comment "FUNCTION Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.PTM Glycation of Ile-21 is observed in long-term hemodialysis patients.SIMILARITY Belongs to the beta-2-microglobulin family.SIMILARITY Contains 1 Ig-like C1-type (immunoglobulin-like) domain.")
(DB_ID 50591)
(description "recommendedName: Beta-2-microglobulin component recommendedName: Beta-2-microglobulin form pI 5.3 /component")
(geneName
"B2M"
"CDABP0092"
"HDCMA22P")
(identifier "P61769")
(isSequenceChanged TRUE)
(keyword
"3D-structure"
"Amyloid"
"Amyloidosis"
"Complete proteome"
"Direct protein sequencing"
"Disease mutation"
"Disulfide bond"
"Glycation"
"Glycoprotein"
"Immunity"
"Immunoglobulin domain"
"MHC I"
"Pyrrolidone carboxylic acid"
"Secreted"
"Signal")
(name "B2M")
(referenceDatabase [GK_2])
(secondaryIdentifier
"B2MG_HUMAN"
"P01884"
"Q540F8"
"Q6IAT8"
"Q9UCK0"
"Q9UD48"
"Q9UDF4")
(sequenceLength 119)
(species [GK_48887]))
([GK_50677] of ReferenceGeneProduct
(_chainChangeLog "chain:1-457 added on Fri February 6 2015")
(_displayName "[Hsa] UniProt:O95429 BAG4 recommendedName: BAG family molecular chaperone regulator 4 shortName:BAG-4 alternativeName: Bcl-2-associated athanogene 4 alternativeName: Silencer of death domains ")
(chain "chain:1-457")
(checksum "B89D59E8118684A3")
(comment "TISSUE SPECIFICITY Ubiquitous.")
(DB_ID 50677)
(description "recommendedName: BAG family molecular chaperone regulator 4 shortName:BAG-4 alternativeName: Bcl-2-associated athanogene 4 alternativeName: Silencer of death domains ")
(geneName
"BAG4"
"SODD")
(identifier "O95429")
(isSequenceChanged FALSE)
(keyword
"3D-structure"
"Alternative splicing"
"Chaperone"
"Complete proteome"
"Cytoplasm"
"Reference proteome")
(name "BAG4")
(referenceDatabase [GK_2])
(secondaryIdentifier
"BAG4_HUMAN"
"B4E217"
"O95818")
(sequenceLength 457)
(species [GK_48887]))
([GK_508059] of Person
(_displayName "Lee, H")
(DB_ID 508059)
(firstname "Hane")
(initial "H")
(surname "Lee"))
([GK_50810] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:Q15582 TGFBI recommendedName: Transforming growth factor-beta-induced protein ig-h3 shortName:Beta ig-h3 alternativeName: Kerato-epithelin alternativeName: RGD-containing collagen-associated protein shortName:RGD-CAP alternativeName: RGD-containing collagen-associated protein shortName:RGD-CAP ")
(checksum "1")
(comment "FUNCTION Binds to type I, II, and IV collagens. This adhesion protein may play an important role in cell-collagen interactions. In cartilage, may be involved in endochondral bone formation.INDUCTION By TGFB1.DISEASE Defects in TGFBI are the cause of corneal dystrophy lattice type 1 (CDL1) [MIM:122200]. Inheritance is autosomal dominant.DISEASE Defects in TGFBI are a cause of corneal dystrophy Thiel-Behnke type (CDTB) [MIM:602082]; also known as corneal dystrophy of Bowman layer type 2 (CDB2).DISEASE Defects in TGFBI are the cause of Avellino corneal dystrophy (ACD) [MIM:607541]. ACD could be considered a variant of granular dystrophy with a significant amyloidogenic tendency. Inheritance is autosomal dominant.SIMILARITY Contains 1 EMI domain.SIMILARITY Contains 4 FAS1 domains.")
(DB_ID 50810)
(description "recommendedName: Transforming growth factor-beta-induced protein ig-h3 shortName:Beta ig-h3 alternativeName: Kerato-epithelin alternativeName: RGD-containing collagen-associated protein shortName:RGD-CAP alternativeName: RGD-containing collagen-associated protein shortName:RGD-CAP ")
(geneName
"TGFBI"
"BIGH3")
(identifier "Q15582")
(isSequenceChanged TRUE)
(keyword
"3D-structure"
"Amyloid"
"Cell adhesion"
"Complete proteome"
"Disease mutation"
"Disulfide bond"
"Extracellular matrix"
"Gamma-carboxyglutamic acid"
"Polymorphism"
"Repeat"
"Secreted"
"Sensory transduction"
"Signal"
"Vision")
(name "TGFBI")
(referenceDatabase [GK_2])
(secondaryIdentifier
"BGH3_HUMAN"
"D3DQB1"
"O14471"
"O14472"
"O14476"
"O43216"
"O43217"
"O43218"
"O43219"
"Q53XM1")
(sequenceLength 683)
(species [GK_48887]))
([GK_511] of GO_BiologicalProcess
(_displayName "cellular component organization")
(accession "0016043")
(DB_ID 511)
(definition "A process that results in the assembly, arrangement of constituent parts, or disassembly of a cellular component.")
(name "cellular component organization")
(referenceDatabase [GK_1]))
([GK_51618] of ReferenceGeneProduct
(_chainChangeLog "signal peptide:1-19 added on Sat February 7 2015;chain:20-367 added on Sat February 7 2015;chain:20-345 added on Sat February 7 2015;propeptide:346-375 added on Sat February 7 2015")
(_displayName "[Hsa] UniProt:P08571 CD14 recommendedName: Monocyte differentiation antigen CD14 alternativeName: Myeloid cell-specific leucine-rich glycoprotein cdAntigenNameCD14/cdAntigenName component recommendedName: Monocyte differentiation antigen CD14, urinary form /component component recommendedName: Monocyte differentiation antigen CD14, membrane-bound form /component")
(chain
"signal peptide:1-19"
"chain:20-367"
"chain:20-345"
"propeptide:346-375")
(checksum "1746CDB41F394F8D")
(comment "SUBUNIT Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, MD-2 and TLR4.TISSUE SPECIFICITY Expressed strongly on the surface of monocytes and weakly on the surface of granulocytes; also expressed by most tissue macrophages.")
(DB_ID 51618)
(description "recommendedName: Monocyte differentiation antigen CD14 alternativeName: Myeloid cell-specific leucine-rich glycoprotein cdAntigenNameCD14/cdAntigenName component recommendedName: Monocyte differentiation antigen CD14, urinary form /component component recommendedName: Monocyte differentiation antigen CD14, membrane-bound form /component")
(geneName "CD14")
(identifier "P08571")
(isSequenceChanged FALSE)
(keyword
"3D-structure"
"Cell membrane"
"Complete proteome"
"Direct protein sequencing"
"Disulfide bond"
"Glycoprotein"
"GPI-anchor"
"Immunity"
"Inflammatory response"
"Innate immunity"
"Leucine-rich repeat"
"Lipoprotein"
"Membrane"
"Polymorphism"
"Reference proteome"
"Repeat"
"Signal")
(name "CD14")
(referenceDatabase [GK_2])
(secondaryIdentifier
"CD14_HUMAN"
"Q53XT5"
"Q96FR6"
"Q96L99"
"Q9UNS3")
(sequenceLength 375)
(species [GK_48887]))
([GK_517749] of Person
(_displayName "Hudson, J")
(DB_ID 517749)
(initial "J")
(surname "Hudson"))
([GK_51926] of ReferenceGeneProduct
(_chainChangeLog "chain:1-376 added on Fri February 6 2015;chain:377-480 added on Fri February 6 2015")
(_displayName "[Hsa] UniProt:O15519 CFLAR recommendedName: CASP8 and FADD-like apoptosis regulator alternativeName: Caspase homolog shortName:CASH alternativeName: Caspase-eight-related protein shortName:Casper alternativeName: Caspase-like apoptosis regulatory protein shortName:CLARP alternativeName: Cellular FLICE-like inhibitory protein shortName:c-FLIP alternativeName: FADD-like antiapoptotic molecule 1 shortName:FLAME-1 alternativeName: Inhibitor of FLICE shortName:I-FLICE alternativeName: MACH-related inducer of toxicity shortName:MRIT alternativeName: Usurpin component recommendedName: CASP8 and FADD-like apoptosis regulator subunit p43 /component component recommendedName: CASP8 and FADD-like apoptosis regulator subunit p12 /component")
(chain
"chain:1-376"
"chain:377-480")
(checksum "8C6D7E92AE1EB672")
(comment "TISSUE SPECIFICITY Widely expressed. Higher expression in skeletal muscle, pancreas, heart, kidney, placenta, and peripheral blood leukocytes. Also detected in diverse cell lines. Isoform 8 is predominantly expressed in testis and skeletal muscle.DOMAIN The caspase domain lacks the active sites residues involved in catalysis.PTM Proteolytically processed; probably by caspase-8. Processing likely occurs at the DISC and generates subunit p43 and p12.")
(DB_ID 51926)
(description "recommendedName: CASP8 and FADD-like apoptosis regulator alternativeName: Caspase homolog shortName:CASH alternativeName: Caspase-eight-related protein shortName:Casper alternativeName: Caspase-like apoptosis regulatory protein shortName:CLARP alternativeName: Cellular FLICE-like inhibitory protein shortName:c-FLIP alternativeName: FADD-like antiapoptotic molecule 1 shortName:FLAME-1 alternativeName: Inhibitor of FLICE shortName:I-FLICE alternativeName: MACH-related inducer of toxicity shortName:MRIT alternativeName: Usurpin component recommendedName: CASP8 and FADD-like apoptosis regulator subunit p43 /component component recommendedName: CASP8 and FADD-like apoptosis regulator subunit p12 /component")
(geneName
"CFLAR"
"CASH"
"CASP8AP1"
"CLARP"
"MRIT")
(identifier "O15519")
(isSequenceChanged FALSE)
(keyword
"3D-structure"
"Alternative splicing"
"Apoptosis"
"Complete proteome"
"Host-virus interaction"
"Polymorphism"
"Reference proteome"
"Repeat")
(name "CFLAR")
(referenceDatabase [GK_2])
(secondaryIdentifier
"CFLAR_HUMAN"
"B4DJE0"
"B7Z9F9"
"O14673"
"O14674"
"O14675"
"O15137"
"O15138"
"O15356"
"O15510"
"O43618"
"O43619"
"O43620"
"O60458"
"O60459"
"Q53TS6"
"Q54AF1"
"Q96TE4"
"Q9UEW1")
(sequenceLength 480)
(species [GK_48887]))
([GK_5212670] of EntityWithAccessionedSequence
(_displayName "[Hsa] BAG4 [cytosol]")
(DB_ID 5212670)
(endCoordinate 457)
(name
"BAG4"
"SODD"
"BAG family molecular chaperone regulator 4")
(referenceEntity [GK_50677])
(species [GK_48887])
(stableIdentifier [GK_5680828])
(startCoordinate 1))
([GK_5212671] of EntityWithAccessionedSequence
(_displayName "[Hsa] RIPK1(325-671) [cytosol]")
(authored [GK_168344])
(DB_ID 5212671)
(endCoordinate 671)
(name
"RIPK1(325-671)"
"receptor interacting protein 1")
(referenceEntity [GK_63119])
(species [GK_48887])
(stableIdentifier [GK_5645972])
(startCoordinate 325))
([GK_528243] of GO_BiologicalProcess
(_displayName "regulation of signaling")
(accession "0023051")
(DB_ID 528243)
(definition "Any process that modulates the frequency, rate or extent of a signaling process.")
(name "regulation of signaling")
(referenceDatabase [GK_1]))
([GK_528244] of GO_BiologicalProcess
(_displayName "signaling")
(accession "0023052")
(DB_ID 528244)
(definition "The entirety of a process in which information is transmitted within a biological system. This process begins with an active signal and ends when a cellular response has been triggered.")
(name "signaling")
(referenceDatabase [GK_1]))
([GK_528248] of GO_BiologicalProcess
(_displayName "positive regulation of signaling")
(accession "0023056")
(DB_ID 528248)
(definition "Any process that activates, maintains or increases the frequency, rate or extent of a signaling process.")
(name "positive regulation of signaling")
(referenceDatabase [GK_1]))
([GK_528249] of GO_BiologicalProcess
(_displayName "negative regulation of signaling")
(accession "0023057")
(DB_ID 528249)
(definition "Any process that stops, prevents, or reduces the frequency, rate or extent of a signaling process.")
(name "negative regulation of signaling")
(referenceDatabase [GK_1]))
([GK_5321754] of Person
(_displayName "Zheng, L")
(DB_ID 5321754)
(firstname "L")
(initial "L")
(surname "Zheng"))
([GK_53331] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P01034 CST3 recommendedName: Cystatin-C alternativeName: Cystatin-3 alternativeName: Gamma-trace alternativeName: Neuroendocrine basic polypeptide alternativeName: Post-gamma-globulin ")
(checksum "1")
(comment "FUNCTION As an inhibitor of cysteine proteinases, this protein is thought to serve an important physiological role as a local regulator of this enzyme activity.SUBUNIT Homodimer.MISCELLANEOUS Potential cerebrospinal fluid marker for the diagnosis of Creutzfeldt-Jakob disease.SIMILARITY Belongs to the cystatin family.")
(DB_ID 53331)
(description "recommendedName: Cystatin-C alternativeName: Cystatin-3 alternativeName: Gamma-trace alternativeName: Neuroendocrine basic polypeptide alternativeName: Post-gamma-globulin ")
(geneName "CST3")
(identifier "P01034")
(isSequenceChanged TRUE)
(keyword
"3D-structure"
"Age-related macular degeneration"
"Amyloid"
"Amyloidosis"
"Complete proteome"
"Direct protein sequencing"
"Disease mutation"
"Disulfide bond"
"Glycoprotein"
"Polymorphism"
"Protease inhibitor"
"Secreted"
"Signal"
"Thiol protease inhibitor")
(name "CST3")
(referenceDatabase [GK_2])
(secondaryIdentifier
"CYTC_HUMAN"
"B2R5J9"
"D3DW42"
"Q6FGW9")
(sequenceLength 146)
(species [GK_48887]))
([GK_5334734] of ReferenceDatabase
(_displayName "ORCID")
(accessUrl "http://orcid.org/###ID###")
(DB_ID 5334734)
(name "ORCID")
(url "http://orcid.org/"))
([GK_5357622] of DatabaseIdentifier
(_displayName "ORCID:0000-0002-2187-2241")
(DB_ID 5357622)
(identifier "0000-0002-2187-2241")
(referenceDatabase [GK_5334734]))
([GK_5357623] of DatabaseIdentifier
(_displayName "ORCID:0000-0002-5766-1702")
(DB_ID 5357623)
(identifier "0000-0002-5766-1702")
(referenceDatabase [GK_5334734]))
([GK_5357748] of Person
(_displayName "Froelich, C J")
(DB_ID 5357748)
(firstname "C J")
(initial "CJ")
(surname "Froelich"))
([GK_5357777] of Person
(_displayName "Ellerby, L M")
(DB_ID 5357777)
(firstname "L M")
(initial "LM")
(surname "Ellerby"))
([GK_5357784] of Person
(_displayName "Jürgensmeier, J M")
(DB_ID 5357784)
(firstname "J M")
(initial "JM")
(surname "Jürgensmeier"))
([GK_5357793] of Complex
(_displayName "[Hsa] TRADD:TRAF2:RIP1(325-671):FADD [cytosol]")
(DB_ID 5357793)
(goCellularComponent [GK_161217])
(hasComponent
[GK_54639]
[GK_54639]
[GK_5357809])
(name "TRADD:TRAF2:RIP1(325-671):FADD")
(species [GK_48887])
(stableIdentifier [GK_5649198]))
([GK_5357809] of Complex
(_displayName "[Hsa] TRAF2:TRADD:RIP1(325-671) [cytosol]")
(DB_ID 5357809)
(goCellularComponent [GK_161217])
(hasComponent
[GK_66370]
[GK_66370]
[GK_66370]
[GK_66376]
[GK_66376]
[GK_66376]
[GK_5212671])
(name "TRAF2:TRADD:RIP1(325-671)")
(species [GK_48887])
(stableIdentifier [GK_5647751]))
([GK_5357825] of Person
(_displayName "Ashktorab, Hassan")
(DB_ID 5357825)
(firstname "Hassan")
(initial "H")
(surname "Ashktorab"))
([GK_5357843] of LiteratureReference
(_displayName "In vivo and in vitro activation of caspase-8 and -3 associated with Helicobacter pylori infection")
(author
[GK_5357825]
[GK_5357854]
[GK_5357917]
[GK_5357879]
[GK_5357911]
[GK_5357926]
[GK_5357878]
[GK_5357882])
(DB_ID 5357843)
(journal "Microbes Infect.")
(pages "713-22")
(pubMedIdentifier 12067831)
(title "In vivo and in vitro activation of caspase-8 and -3 associated with Helicobacter pylori infection")
(volume 4)
(year 2002))
([GK_5357854] of Person
(_displayName "Neapolitano, Mattew")
(DB_ID 5357854)
(firstname "Mattew")
(initial "M")
(surname "Neapolitano"))
([GK_5357862] of Person
(_displayName "Ellerby, H M")
(DB_ID 5357862)
(firstname "H M")
(initial "HM")
(surname "Ellerby"))
([GK_5357867] of Person
(_displayName "Bredesen, D")
(DB_ID 5357867)
(firstname "D")
(initial "D")
(surname "Bredesen"))
([GK_5357878] of Person
(_displayName "Naab, Tammy")
(DB_ID 5357878)
(firstname "Tammy")
(initial "T")
(surname "Naab"))
([GK_5357879] of Person
(_displayName "Allen, Cornel")
(DB_ID 5357879)
(firstname "Cornel")
(initial "C")
(surname "Allen"))
([GK_5357882] of Person
(_displayName "Smoot, Duane T")
(DB_ID 5357882)
(firstname "Duane T")
(initial "DT")
(surname "Smoot"))
([GK_5357893] of Person
(_displayName "Deveraux, Q")
(DB_ID 5357893)
(firstname "Q")
(initial "Q")
(surname "Deveraux"))
([GK_5357895] of Person
(_displayName "Shin, H")
(DB_ID 5357895)
(firstname "H")
(initial "H")
(surname "Shin"))
([GK_5357911] of Person
(_displayName "Ahmed, Amel")
(DB_ID 5357911)
(firstname "Amel")
(initial "A")
(surname "Ahmed"))
([GK_5357917] of Person
(_displayName "Bomma, Chandara")
(DB_ID 5357917)
(firstname "Chandara")
(initial "C")
(surname "Bomma"))
([GK_5357926] of Person
(_displayName "Dubois, Andre")
(DB_ID 5357926)
(firstname "Andre")
(initial "A")
(surname "Dubois"))
([GK_5357965] of LiteratureReference
(_displayName "Pro-caspase-3 is a major physiologic target of caspase-8")
(author
[GK_141853]
[GK_5357784]
[GK_5357895]
[GK_5357893]
[GK_141933]
[GK_2685097]
[GK_2672211]
[GK_5357862]
[GK_5357777]
[GK_5357867]
[GK_141937]
[GK_3700976]
[GK_5357748]
[GK_2534135])
(DB_ID 5357965)
(journal "J. Biol. Chem.")
(pages "27084-90")
(pubMedIdentifier 9765224)
(title "Pro-caspase-3 is a major physiologic target of caspase-8")
(volume 273)
(year 1998))
([GK_5357966] of BlackBoxEvent
(_displayName "[Hsa] CASP3 is cleaved by CASP8")
(_doRelease FALSE)
(catalystActivity [GK_139951])
(DB_ID 5357966)
(input
[GK_57021]
[GK_57021])
(isChimeric FALSE)
(literatureReference
[GK_5357965]
[GK_5357843])
(name "CASP3 is cleaved by CASP8")
(output [GK_350870])
(precedingEvent
[GK_139952]
[GK_2562564])
(species [GK_48887])
(summation [GK_5364138]))
([GK_5357984] of DatabaseIdentifier
(_displayName "ORCID:0000-0002-3218-5631")
(DB_ID 5357984)
(identifier "0000-0002-3218-5631")
(referenceDatabase [GK_5334734]))
([GK_5364059] of Person
(_displayName "Murphy, James M")
(DB_ID 5364059)
(firstname "James M")
(initial "JM")
(surname "Murphy"))
([GK_5364090] of Person
(_displayName "Alexander, Warren S")
(DB_ID 5364090)
(firstname "Warren S")
(initial "WS")
(surname "Alexander"))
([GK_5364138] of Summation
(_displayName "Caspase-3 is activated through cleavage of the 32 kDa precur...")
(DB_ID 5364138)
(text "Caspase-3 is activated through cleavage of the 32 kDa precursor molecule into a 20 kDa and a 10 kDa heterodimeric fragment. In some cell types including lymphocytes active caspase-8 directly catalyzes the proteolytic maturation of caspase-3, thereby triggering the executioner phase of caspase-dependent apoptosis in a mitochondrion-independent manner."))
([GK_538696] of Person
(_displayName "Enghild, JJ")
(DB_ID 538696)
(initial "JJ")
(surname "Enghild"))
([GK_5433258] of GO_CellularComponent
(_displayName "bounding membrane of organelle")
(accession "0098588")
(DB_ID 5433258)
(definition "The lipid bilayer that forms the outer-most layer of an organelle.")
(instanceOf [GK_160129])
(name "bounding membrane of organelle")
(referenceDatabase [GK_1]))
([GK_54639] of EntityWithAccessionedSequence
(_displayName "[Hsa] FADD [cytosol]")
(DB_ID 54639)
(endCoordinate 208)
(literatureReference [GK_140483])
(name
"FADD"
"FADD protein (FAS-associating death domain-containing protein) (Mediator of receptor induced toxicity)"
"FADD protein"
"FAS-associating death domain-containing protein"
"Mediator of receptor induced toxicity")
(referenceEntity [GK_54640])
(species [GK_48887])
(stableIdentifier [GK_365546])
(startCoordinate 1))
([GK_54640] of ReferenceGeneProduct
(_chainChangeLog "chain:1-208 added on Sat February 7 2015")
(_displayName "[Hsa] UniProt:Q13158 FADD recommendedName: FAS-associated death domain protein alternativeName: FAS-associating death domain-containing protein alternativeName: Growth-inhibiting gene 3 protein alternativeName: Mediator of receptor induced toxicity alternativeName: Protein FADD ")
(chain "chain:1-208")
(checksum "0E65E2F852E83507")
(comment "TISSUE SPECIFICITY Expressed in a wide variety of tissues, except for peripheral blood mononuclear leukocytes.")
(DB_ID 54640)
(description "recommendedName: FAS-associated death domain protein alternativeName: FAS-associating death domain-containing protein alternativeName: Growth-inhibiting gene 3 protein alternativeName: Mediator of receptor induced toxicity alternativeName: Protein FADD ")
(geneName
"FADD"
"MORT1"
"GIG3")
(identifier "Q13158")
(isSequenceChanged FALSE)
(keyword
"3D-structure"
"Apoptosis"
"Complete proteome"
"Disease mutation"
"Host-virus interaction"
"Immunity"
"Innate immunity"
"Phosphoprotein"
"Reference proteome")
(name "FADD")
(referenceDatabase [GK_2])
(secondaryIdentifier
"FADD_HUMAN"
"Q14866"
"Q6IBR4")
(sequenceLength 208)
(species [GK_48887]))
([GK_54840] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P02671 FGA recommendedName: Fibrinogen alpha chain component recommendedName: Fibrinopeptide A /component component recommendedName: Fibrinogen alpha chain /component")
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(comment "FUNCTION Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation.DOMAIN A long coiled coil structure formed by 3 polypeptide chains connects the central nodule to the C-terminal domains (distal nodules). The long C-terminal ends of the alpha chains fold back, contributing a fourth strand to the coiled coil structure.PTM Forms F13A-mediated cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming fibronectin-fibrinogen heteropolymers.PTM Conversion of fibrinogen to fibrin is triggered by thrombin, which cleaves fibrinopeptides A and B from alpha and beta chains, and thus exposes the N-terminal polymerization sites responsible for the formation of the soft clot. The soft clot is converted into the hard clot by factor XIIIA which catalyzes the epsilon-(gamma-glutamyl)lysine cross-linking between gamma chains (stronger) and between alpha chains (weaker) of different monomers.PTM Phosphorylation sites are present in the extracelllular medium.DISEASE Defects in FGA are a cause of congenital afibrinogenemia (CAFBN) [MIM:202400]. This is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=The majority of cases of afibrinogenemia are due to truncating mutations. Variations in position Arg-35 (the site of cleavage of fibrinopeptide a by thrombin) leads to alpha-dysfibrinogenemias.SIMILARITY Contains 1 fibrinogen C-terminal domain.")
(DB_ID 54840)
(description "recommendedName: Fibrinogen alpha chain component recommendedName: Fibrinopeptide A /component component recommendedName: Fibrinogen alpha chain /component")
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(identifier "P02671")
(isSequenceChanged TRUE)
(keyword
"3D-structure"
"Alternative splicing"
"Amyloid"
"Amyloidosis"
"Blood coagulation"
"Coiled coil"
"Complete proteome"
"Direct protein sequencing"
"Disease mutation"
"Disulfide bond"
"Glycoprotein"
"Isopeptide bond"
"Phosphoprotein"
"Polymorphism"
"Secreted"
"Signal")
(name "FGA")
(referenceDatabase [GK_2])
(secondaryIdentifier
"FIBA_HUMAN"
"D3DP14"
"D3DP15"
"Q4QQH7"
"Q9BX62"
"Q9UCH2")
(sequenceLength 866)
(species [GK_48887]))
([GK_549516] of Person
(_displayName "Yoo, OJ")
(DB_ID 549516)
(initial "OJ")
(surname "Yoo"))
([GK_552] of GO_BiologicalProcess
(_displayName "protein metabolic process")
(accession "0019538")
(DB_ID 552)
(definition "The chemical reactions and pathways involving a specific protein, rather than of proteins in general. Includes protein modification.")
(name "protein metabolic process")
(referenceDatabase [GK_1]))
([GK_55564] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P06396 GSN recommendedName: Gelsolin alternativeName: AGEL alternativeName: Actin-depolymerizing factor shortName:ADF alternativeName: Actin-depolymerizing factor shortName:ADF alternativeName: Brevin ")
(checksum "1")
(comment "TISSUE SPECIFICITY Phagocytic cells, platelets, fibroblasts, nonmuscle cells, smooth and skeletal muscle cells.PTM Phosphorylation on Tyr-86, Tyr-409, Tyr-465, Tyr-603 and Tyr-651 in vitro is induced in presence of phospholipids.SIMILARITY Belongs to the villin/gelsolin family.SIMILARITY Contains 6 gelsolin-like repeats.")
(DB_ID 55564)
(description "recommendedName: Gelsolin alternativeName: AGEL alternativeName: Actin-depolymerizing factor shortName:ADF alternativeName: Actin-depolymerizing factor shortName:ADF alternativeName: Brevin ")
(geneName "GSN")
(identifier "P06396")
(isSequenceChanged TRUE)
(keyword
"3D-structure"
"Actin capping"
"Actin-binding"
"Alternative initiation"
"Amyloid"
"Amyloidosis"
"Calcium"
"Cilium biogenesis/degradation"
"Complete proteome"
"Cytoplasm"
"Cytoskeleton"
"Direct protein sequencing"
"Disease mutation"
"Disulfide bond"
"Phosphoprotein"
"Polymorphism"
"Repeat"
"Secreted"
"Signal")
(name "GSN")
(referenceDatabase [GK_2])
(secondaryIdentifier
"GELS_HUMAN"
"Q8WVV7")
(sequenceLength 782)
(species [GK_48887]))
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(_displayName "ChEBI:67208")
(DB_ID 5578725)
(identifier "67208")
(referenceDatabase [GK_114984]))
([GK_5602560] of Person
(_displayName "Takada, Hidetoshi")
(DB_ID 5602560)
(firstname "Hidetoshi")
(initial "H")
(surname "Takada"))
([GK_56134] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:Q99878 HIST1H2AJ recommendedName: Histone H2A type 1-J alternativeName: Histone H2A/e ")
(checksum "1")
(comment "FUNCTION Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.SUBUNIT The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.PTM Deiminated on Arg-4 in granulocytes upon calcium entry.PTM Phosphorylation on Ser-2 is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1.SIMILARITY Belongs to the histone H2A family.")
(DB_ID 56134)
(description "recommendedName: Histone H2A type 1-J alternativeName: Histone H2A/e ")
(geneName
"HIST1H2AJ"
"H2AFE")
(identifier "Q99878")
(isSequenceChanged TRUE)
(keyword
"Acetylation"
"Chromosome"
"Citrullination"
"Complete proteome"
"DNA-binding"
"Isopeptide bond"
"Methylation"
"Nucleosome core"
"Nucleus"
"Phosphoprotein"
"Ubl conjugation")
(name "HIST1H2AJ")
(referenceDatabase [GK_2])
(secondaryIdentifier
"H2A1J_HUMAN"
"A2RUU6"
"Q5JXQ5")
(sequenceLength 128)
(species [GK_48887]))
([GK_56136] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P20671 HIST1H2AD recommendedName: Histone H2A type 1-D alternativeName: Histone H2A.3 alternativeName: Histone H2A/g ")
(checksum "1")
(comment "FUNCTION Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.SUBUNIT The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.PTM Deiminated on Arg-4 in granulocytes upon calcium entry.PTM Phosphorylation on Ser-2 is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1.SIMILARITY Belongs to the histone H2A family.CAUTION Was originally (PubMed:2587222) thought to originate from mouse.")
(DB_ID 56136)
(description "recommendedName: Histone H2A type 1-D alternativeName: Histone H2A.3 alternativeName: Histone H2A/g ")
(geneName
"HIST1H2AD"
"H2AFG")
(identifier "P20671")
(isSequenceChanged TRUE)
(keyword
"Acetylation"
"Chromosome"
"Citrullination"
"Complete proteome"
"DNA-binding"
"Isopeptide bond"
"Methylation"
"Nucleosome core"
"Nucleus"
"Phosphoprotein"
"Ubl conjugation")
(name "HIST1H2AD")
(referenceDatabase [GK_2])
(secondaryIdentifier
"H2A1D_HUMAN"
"A0PK91"
"P57754"
"Q6FGY6")
(sequenceLength 130)
(species [GK_48887]))
([GK_56140] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:Q93077 HIST1H2AC recommendedName: Histone H2A type 1-C alternativeName: Histone H2A/l ")
(checksum "1")
(comment "FUNCTION Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.SUBUNIT The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.PTM Deiminated on Arg-4 in granulocytes upon calcium entry.PTM Phosphorylation on Ser-2 is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1.SIMILARITY Belongs to the histone H2A family.")
(DB_ID 56140)
(description "recommendedName: Histone H2A type 1-C alternativeName: Histone H2A/l ")
(geneName
"HIST1H2AC"
"H2AFL")
(identifier "Q93077")
(isSequenceChanged TRUE)
(keyword
"Acetylation"
"Chromosome"
"Citrullination"
"Complete proteome"
"DNA-binding"
"Isopeptide bond"
"Methylation"
"Nucleosome core"
"Nucleus"
"Phosphoprotein"
"Ubl conjugation")
(name "HIST1H2AC")
(referenceDatabase [GK_2])
(secondaryIdentifier
"H2A1C_HUMAN"
"B2R4F7"
"O00775"
"O00776"
"O00777"
"O00778"
"Q540R1")
(sequenceLength 130)
(species [GK_48887]))
([GK_56142] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P04908 HIST1H2AB recommendedName: Histone H2A type 1-B/E alternativeName: Histone H2A.2 alternativeName: Histone H2A/a alternativeName: Histone H2A/m ")
(checksum "1")
(comment "FUNCTION Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.SUBUNIT The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.PTM Deiminated on Arg-4 in granulocytes upon calcium entry.PTM Phosphorylation on Ser-2 is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1.SIMILARITY Belongs to the histone H2A family.")
(DB_ID 56142)
(description "recommendedName: Histone H2A type 1-B/E alternativeName: Histone H2A.2 alternativeName: Histone H2A/a alternativeName: Histone H2A/m ")
(geneName
"HIST1H2AB"
"H2AFM"
" The TNF-alpha:TNFR1 receptor complex then transmits the signal leading to cell death or survival. However, it remains unclear whether BAG4 binds to death domain of monomeric TNFR1 to prevent receptor oligomerization or recognizes receptor trimers to facilitate ATP-dependent TNFR1 trimer disassembly (Jiang Y et al. 1999; Miki K and Eddy EM 2002). Additionally, BAG4 is known to interact with HSP70, death receptor 3, and the anti-apoptotic protein Bcl-2 (Antoku et al. 2001; Brockmann et al. 2004; Jiang et al. 1999). BAG4-overexpressing HeLa cells showed reduced cellular sensitivity to treatment with extracellular TNFalpha and CD95 ligand (Eichholtz-Wirth H et al. 2003). In addition, increased expression level of BAG4 in tumor cells leads to resistance of TNFalpha-induced cell death and is associated with pancreatic cancer, some types of melanoma, acute lymphoblastic leukemia etc.(Ozawa et al. 2000; Tao H et ql. 2007; Reuland SN et al. 2013). The physiological relevance of BAG4 for TNFR1 signaling, however, is difficult to judge because BAG4 knockout mice have no or only a mild effect on pro-inflammatory TNF signaling and give no evidence for an inhibitory role of BAG4 in TNFR1-induced cell death (Takada H et al. 2003; Endres R et al. 2003)."))
([GK_5657695] of LiteratureReference
(_displayName "Tumor necrosis factor receptor 1 is an ATPase regulated by silencer of death domain")
(author
[GK_3595145]
[GK_70446])
(DB_ID 5657695)
(journal "Mol. Cell. Biol.")
(pages "2536-43")
(pubMedIdentifier 11909948)
(title "Tumor necrosis factor receptor 1 is an ATPase regulated by silencer of death domain")
(volume 22)
(year 2002))
([GK_5657696] of Person
(_displayName "Wolz, Lucie")
(DB_ID 5657696)
(firstname "Lucie")
(initial "L")
(surname "Wolz"))
([GK_5657697] of LiteratureReference
(_displayName "Overexpression of the 'silencer of death domain', SODD/BAG-4, modulates both TNFR1- and CD95-dependent cell death pathways")
(author
[GK_5657719]
[GK_5657732]
[GK_5657696])
(DB_ID 5657697)
(journal "Cancer Lett.")
(pages "81-9")
(pubMedIdentifier 12706861)
(title "Overexpression of the 'silencer of death domain', SODD/BAG-4, modulates both TNFR1- and CD95-dependent cell death pathways")
(volume 194)
(year 2003))
([GK_5657698] of Person
(_displayName "Zhou, L Y")
(DB_ID 5657698)
(firstname "L Y")
(initial "LY")
(surname "Zhou"))
([GK_5657699] of Person
(_displayName "Kleeff, J")
(DB_ID 5657699)
(firstname "J")
(initial "J")
(surname "Kleeff"))
([GK_5657700] of Person
(_displayName "Zhang, Qinghong")
(DB_ID 5657700)
(firstname "Qinghong")
(initial "Q")
(surname "Zhang"))
([GK_5657701] of Person
(_displayName "Diehl, Annette")
(DB_ID 5657701)
(firstname "Annette")
(initial "A")
(surname "Diehl"))
([GK_5657702] of Person
(_displayName "Scully, W J")
(DB_ID 5657702)
(firstname "W J")
(initial "WJ")
(surname "Scully"))
([GK_5657703] of Person
(_displayName "Oschkinat, Hartmut")
(DB_ID 5657703)
(firstname "Hartmut")
(initial "H")
(surname "Oschkinat"))
([GK_5657704] of LiteratureReference
(_displayName "Significance of SODD expression in childhood acute lymphoblastic leukemia and its influence on chemotherapy")
(author
[GK_5657720]
[GK_5657718]
[GK_5657680]
[GK_5657726]
[GK_5657688]
[GK_5657698]
[GK_5657724])
(DB_ID 5657704)
(journal "Genet. Mol. Res.")
(pages "2020-31")
(pubMedIdentifier 24737427)
(title "Significance of SODD expression in childhood acute lymphoblastic leukemia and its influence on chemotherapy")
(volume 13)
(year 2014))
([GK_5657705] of Person
(_displayName "Goldstein, Nathaniel B")
(DB_ID 5657705)
(firstname "Nathaniel B")
(initial "NB")
(surname "Goldstein"))
([GK_5657707] of Person
(_displayName "Friess, H")
(DB_ID 5657707)
(firstname "H")
(initial "H")
(surname "Friess"))
([GK_5657708] of LiteratureReference
(_displayName "Prevention of constitutive TNF receptor 1 signaling by silencer of death domains")
(author
[GK_2425399]
[GK_5657687]
[GK_2672034]
[GK_75697])
(DB_ID 5657708)
(journal "Science")
(pages "543-6")
(pubMedIdentifier 9915703)
(title "Prevention of constitutive TNF receptor 1 signaling by silencer of death domains")
(volume 283)
(year 1999))
([GK_5657709] of Person
(_displayName "Shellman, Yiqun G")
(DB_ID 5657709)
(firstname "Yiqun G")
(initial "YG")
(surname "Shellman"))
([GK_5657710] of Person
(_displayName "Fang, Jianlin")
(DB_ID 5657710)
(firstname "Jianlin")
(initial "J")
(surname "Fang"))
([GK_5657711] of LiteratureReference
(_displayName "Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein")
(author
[GK_5657690]
[GK_110819]
[GK_5657702]
[GK_5657691]
[GK_5657686])
(DB_ID 5657711)
(journal "Biochem. Biophys. Res. Commun.")
(pages "1003-10")
(pubMedIdentifier 11527400)
(title "Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein")
(volume 286)
(year 2001))
([GK_5657712] of Person
(_displayName "Kühne, Ronald")
(DB_ID 5657712)
(firstname "Ronald")
(initial "R")
(surname "Kühne"))
([GK_5657713] of Person
(_displayName "Liu, Shuangyou")
(DB_ID 5657713)
(firstname "Shuangyou")
(initial "S")
(surname "Liu"))
([GK_5657714] of Person
(_displayName "Büssow, Konrad")
(DB_ID 5657714)
(firstname "Konrad")
(initial "K")
(surname "Büssow"))
([GK_5657715] of Person
(_displayName "Brockmann, Christoph")
(DB_ID 5657715)
(firstname "Christoph")
(initial "C")
(surname "Brockmann"))
([GK_5657716] of Person
(_displayName "Partyka, Katie A")
(DB_ID 5657716)
(firstname "Katie A")
(initial "KA")
(surname "Partyka"))
([GK_5657717] of Person
(_displayName "Labudde, Dirk")
(DB_ID 5657717)
(firstname "Dirk")
(initial "D")
(surname "Labudde"))
([GK_5657718] of Person
(_displayName "Liu, Y S")
(DB_ID 5657718)
(firstname "Y S")
(initial "YS")
(surname "Liu"))
([GK_5657719] of Person
(_displayName "Eichholtz-Wirth, Hedda")
(DB_ID 5657719)
(firstname "Hedda")
(initial "H")
(surname "Eichholtz-Wirth"))
([GK_5657720] of Person
(_displayName "Tao, H F")
(DB_ID 5657720)
(firstname "H F")
(initial "HF")
(surname "Tao"))
([GK_5657721] of Person
(_displayName "Zimmermann, A")
(DB_ID 5657721)
(firstname "A")
(initial "A")
(surname "Zimmermann"))
([GK_5657722] of Person
(_displayName "Hu, Ying")
(DB_ID 5657722)
(firstname "Ying")
(initial "Y")
(surname "Hu"))
([GK_5657723] of Person
(_displayName "Sievert, Volker")
(DB_ID 5657723)
(firstname "Volker")
(initial "V")
(surname "Sievert"))
([GK_5657724] of Person
(_displayName "Zhu, Y S")
(DB_ID 5657724)
(firstname "Y S")
(initial "YS")
(surname "Zhu"))
([GK_5657725] of Person
(_displayName "Hu, Qun")
(DB_ID 5657725)
(firstname "Qun")
(initial "Q")
(surname "Hu"))
([GK_5657726] of Person
(_displayName "Su, Y Z")
(DB_ID 5657726)
(firstname "Y Z")
(initial "YZ")
(surname "Su"))
([GK_5657727] of Person
(_displayName "Bemis, Lynne T")
(DB_ID 5657727)
(firstname "Lynne T")
(initial "LT")
(surname "Bemis"))
([GK_5657728] of Person
(_displayName "Smith, Shilo M")
(DB_ID 5657728)
(firstname "Shilo M")
(initial "SM")
(surname "Smith"))
([GK_5657729] of LiteratureReference
(_displayName "MicroRNA-26a is strongly downregulated in melanoma and induces cell death through repression of silencer of death domains (SODD)")
(author
[GK_5657733]
[GK_5657728]
[GK_5657727]
[GK_5657705]
[GK_5657679]
[GK_5657716]
[GK_200479]
[GK_5657700]
[GK_5657683]
[GK_5657709])
(DB_ID 5657729)
(journal "J. Invest. Dermatol.")
(pages "1286-93")
(pubMedIdentifier 23190898)
(title "MicroRNA-26a is strongly downregulated in melanoma and induces cell death through repression of silencer of death domains (SODD)")
(volume 133)
(year 2013))
([GK_5657730] of Person
(_displayName "Büchler, M W")
(DB_ID 5657730)
(firstname "M W")
(initial "MW")
(surname "Büchler"))
([GK_5657731] of LiteratureReference
(_displayName "Expression of SODD and P65 in ALL of children and its relationship with chemotherapeutic drugs")
(author
[GK_5657682]
[GK_5657725]
[GK_5657710]
[GK_5657689]
[GK_5657713]
[GK_5657685]
[GK_5657722])
(DB_ID 5657731)
(journal "J. Huazhong Univ. Sci. Technol. Med. Sci.")
(pages "326-9")
(pubMedIdentifier 17641854)
(title "Expression of SODD and P65 in ALL of children and its relationship with chemotherapeutic drugs")
(volume 27)
(year 2007))
([GK_5657732] of Person
(_displayName "Fritz, Eberhard")
(DB_ID 5657732)
(firstname "Eberhard")
(initial "E")
(surname "Fritz"))
([GK_5657733] of Person
(_displayName "Reuland, Steven N")
(DB_ID 5657733)
(firstname "Steven N")
(initial "SN")
(surname "Reuland"))
([GK_5657944] of Person
(_displayName "Feng, Wei")
(DB_ID 5657944)
(firstname "Wei")
(initial "W")
(surname "Feng"))
([GK_5657946] of Person
(_displayName "Pang, Yan")
(DB_ID 5657946)
(firstname "Yan")
(initial "Y")
(surname "Pang"))
([GK_5657947] of Person
(_displayName "Yan, Dan")
(DB_ID 5657947)
(firstname "Dan")
(initial "D")
(surname "Yan"))
([GK_5657948] of LiteratureReference
(_displayName "Importance of reverse signaling of the TNF superfamily in immune regulation")
(author
[GK_5657962]
[GK_5657957]
[GK_5657956])
(DB_ID 5657948)
(journal "Expert Rev Clin Immunol")
(pages "335-48")
(pubMedIdentifier 23557269)
(title "Importance of reverse signaling of the TNF superfamily in immune regulation")
(volume 9)
(year 2013))
([GK_5657949] of Person
(_displayName "Yin, Bingjiao")
(DB_ID 5657949)
(firstname "Bingjiao")
(initial "B")
(surname "Yin"))
([GK_5657950] of Person
(_displayName "Zhou, Muxiang")
(DB_ID 5657950)
(firstname "Muxiang")
(initial "M")
(surname "Zhou"))
([GK_5657951] of Person
(_displayName "Jiang, Xiaodan")
(DB_ID 5657951)
(firstname "Xiaodan")
(initial "X")
(surname "Jiang"))
([GK_5657952] of LiteratureReference
(_displayName "Ligands working as receptors: reverse signaling by members of the TNF superfamily enhance the plasticity of the immune system")
(author
[GK_5657963]
[GK_5657959]
[GK_3465391])
(DB_ID 5657952)
(journal "Cytokine Growth Factor Rev.")
(pages "353-66")
(pubMedIdentifier 15450251)
(title "Ligands working as receptors: reverse signaling by members of the TNF superfamily enhance the plasticity of the immune system")
(volume 15)
(year 2004))
([GK_5657953] of Person
(_displayName "Li, Zhuoya")
(DB_ID 5657953)
(firstname "Zhuoya")
(initial "Z")
(surname "Li"))
([GK_5657954] of Person
(_displayName "Liang, Huifang")
(DB_ID 5657954)
(firstname "Huifang")
(initial "H")
(surname "Liang"))
([GK_5657955] of LiteratureReference
(_displayName "Transmembrane TNF-alpha mediates \"forward\" and \"reverse\" signaling, inducing cell death or survival via the NF-kappaB pathway in Raji Burkitt lymphoma cells")
(author
[GK_5657961]
[GK_5657947]
[GK_5657958]
[GK_5657954]
[GK_5657946]
[GK_5657960]
[GK_3900183]
[GK_3642160]
[GK_5657949]
[GK_5657951]
[GK_5657944]
[GK_5657964]
[GK_5657950]
[GK_5657953])
(DB_ID 5657955)
(journal "J. Leukoc. Biol.")
(pages "789-97")
(pubMedIdentifier 18550789)
(title "Transmembrane TNF-alpha mediates \"forward\" and \"reverse\" signaling, inducing cell death or survival via the NF-kappaB pathway in Raji Burkitt lymphoma cells")
(volume 84)
(year 2008))
([GK_5657956] of Person
(_displayName "Duda, Ern?")
(DB_ID 5657956)
(firstname "Ern?")
(initial "E")
(surname "Duda"))
([GK_5657957] of Person
(_displayName "Buzás, Krisztina")
(DB_ID 5657957)
(firstname "Krisztina")
(initial "K")
(surname "Buzás"))
([GK_5657958] of Person
(_displayName "Shi, Xu")
(DB_ID 5657958)
(firstname "Xu")
(initial "X")
(surname "Shi"))
([GK_5657959] of Person
(_displayName "Kolch, Walter")
(DB_ID 5657959)
(firstname "Walter")
(initial "W")
(surname "Kolch"))
([GK_5657960] of Person
(_displayName "Qin, Nalin")
(DB_ID 5657960)
(firstname "Nalin")
(initial "N")
(surname "Qin"))
([GK_5657961] of Person
(_displayName "Zhang, Hailong")
(DB_ID 5657961)
(firstname "Hailong")
(initial "H")
(surname "Zhang"))
([GK_5657962] of Person
(_displayName "Juhász, Kata")
(DB_ID 5657962)
(firstname "Kata")
(initial "K")
(surname "Juhász"))
([GK_5657963] of Person
(_displayName "Eissner, Günther")
(DB_ID 5657963)
(firstname "Günther")
(initial "G")
(surname "Eissner"))
([GK_5657964] of Person
(_displayName "Zhang, Wenjie")
(DB_ID 5657964)
(firstname "Wenjie")
(initial "W")
(surname "Zhang"))
([GK_5661322] of InstanceEdit
(_displayName "Shamovsky, V, 2015-01-12")
(author [GK_429259])
(dateTime "2015-01-12 00:01:01")
(DB_ID 5661322))
([GK_5662807] of DatabaseIdentifier
(_displayName "ORCID:0000-0002-4259-456X")
(DB_ID 5662807)
(identifier "0000-0002-4259-456X")
(referenceDatabase [GK_5334734]))
([GK_5668416] of Person
(_displayName "Maxeiner, B")
(DB_ID 5668416)
(firstname "B")
(initial "B")
(surname "Maxeiner"))
([GK_5668446] of Person
(_displayName "Löhden, M")
(DB_ID 5668446)
(firstname "M")
(initial "M")
(surname "Löhden"))
([GK_5668448] of Person
(_displayName "Clauss, M")
(DB_ID 5668448)
(firstname "M")
(initial "M")
(surname "Clauss"))
([GK_5668457] of Person
(_displayName "Lesslauer, W")
(DB_ID 5668457)
(firstname "W")
(initial "W")
(surname "Lesslauer"))
([GK_5668466] of Person
(_displayName "Georgopoulos, S")
(DB_ID 5668466)
(firstname "S")
(initial "S")
(surname "Georgopoulos"))
([GK_5668480] of LiteratureReference
(_displayName "The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor")
(author
[GK_5668509]
[GK_5668490]
[GK_3465508]
[GK_5668446]
[GK_5668448]
[GK_5668416]
[GK_5668466]
[GK_5668457]
[GK_5668505]
[GK_5668494]
[GK_3465420])
(DB_ID 5668480)
(journal "Cell")
(pages "793-802")
(pubMedIdentifier 8521496)
(title "The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor")
(volume 83)
(year 1995))
([GK_5668490] of Person
(_displayName "Douni, E")
(DB_ID 5668490)
(firstname "E")
(initial "E")
(surname "Douni"))
([GK_5668494] of Person
(_displayName "Pfizenmaier, K")
(DB_ID 5668494)
(firstname "K")
(initial "K")
(surname "Pfizenmaier"))
([GK_5668505] of Person
(_displayName "Kollias, G")
(DB_ID 5668505)
(firstname "G")
(initial "G")
(surname "Kollias"))
([GK_5668509] of Person
(_displayName "Grell, M")
(DB_ID 5668509)
(firstname "M")
(initial "M")
(surname "Grell"))
([GK_5675041] of InstanceEdit
(_displayName "Shamovsky, V, 2015-02-15")
(author [GK_429259])
(dateTime "2015-02-15 05:08:58")
(DB_ID 5675041))
([GK_5675580] of Person
(_displayName "Chan, F K")
(DB_ID 5675580)
(firstname "F K")
(initial "FK")
(surname "Chan"))
([GK_5676311] of Person
(_displayName "Chau, Diep")
(DB_ID 5676311)
(firstname "Diep")
(initial "D")
(surname "Chau"))
([GK_5680828] of StableIdentifier
(_displayName "REACT_356045.1")
(DB_ID 5680828)
(identifier "REACT_356045")
(identifierVersion "1"))
([GK_5681003] of StableIdentifier
(_displayName "REACT_356202.1")
(DB_ID 5681003)
(identifier "REACT_356202")
(identifierVersion "1"))
([GK_5686148] of Person
(_displayName "Nachbur, Ueli")
(DB_ID 5686148)
(firstname "Ueli")
(initial "U")
(surname "Nachbur"))
([GK_5692299] of Person
(_displayName "Zimmermann, G")
(DB_ID 5692299)
(firstname "G")
(initial "G")
(surname "Zimmermann"))
([GK_5692301] of LiteratureReference
(_displayName "The type 1 receptor (CD120a) is the high-affinity receptor for soluble tumor necrosis factor")
(author
[GK_5668509]
[GK_3465508]
[GK_5692299]
[GK_3465420])
(DB_ID 5692301)
(journal "Proc. Natl. Acad. Sci. U.S.A.")
(pages "570-5")
(pubMedIdentifier 9435233)
(title "The type 1 receptor (CD120a) is the high-affinity receptor for soluble tumor necrosis factor")
(volume 95)
(year 1998))
([GK_5692335] of Person
(_displayName "Siegel, R M")
(DB_ID 5692335)
(firstname "R M")
(initial "RM")
(surname "Siegel"))
([GK_5692336] of LiteratureReference
(_displayName "Apparently normal tumor necrosis factor receptor 1 signaling in the absence of the silencer of death domains")
(author
[GK_5692360]
[GK_2562574]
[GK_5692348]
[GK_5692354])
(DB_ID 5692336)
(journal "Mol. Cell. Biol.")
(pages "6609-17")
(pubMedIdentifier 12944486)
(title "Apparently normal tumor necrosis factor receptor 1 signaling in the absence of the silencer of death domains")
(volume 23)
(year 2003))
([GK_5692337] of Person
(_displayName "Chang, Deh-Ming")
(DB_ID 5692337)
(firstname "Deh-Ming")
(initial "DM")
(surname "Chang"))
([GK_5692338] of Person
(_displayName "Mirtsos, Christine")
(DB_ID 5692338)
(firstname "Christine")
(initial "C")
(surname "Mirtsos"))
([GK_5692339] of LiteratureReference
(_displayName "Lymphotoxin α induces apoptosis, necroptosis and inflammatory signals with the same potency as tumour necrosis factor")
(author
[GK_5692344]
[GK_5692362]
[GK_5676311]
[GK_5692343]
[GK_5364059]
[GK_5364090]
[GK_71171]
[GK_141939]
[GK_5686148])
(DB_ID 5692339)
(journal "FEBS J.")
(pages "5283-97")
(pubMedIdentifier 23815148)
(title "Lymphotoxin α induces apoptosis, necroptosis and inflammatory signals with the same potency as tumour necrosis factor")
(volume 280)
(year 2013))
([GK_5692340] of Person
(_displayName "Bui, K L")
(DB_ID 5692340)
(firstname "K L")
(initial "KL")
(surname "Bui"))
([GK_5692341] of LiteratureReference
(_displayName "Targeting pre-ligand assembly domain of TNFR1 ameliorates autoimmune diseases - an unrevealed role in downregulation of Th17 cells")
(author
[GK_5692347]
[GK_5692346]
[GK_5692349]
[GK_5623718]
[GK_5692337]
[GK_5623746])
(DB_ID 5692341)
(journal "J. Autoimmun.")
(pages "160-70")
(pubMedIdentifier 21689905)
(title "Targeting pre-ligand assembly domain of TNFR1 ameliorates autoimmune diseases - an unrevealed role in downregulation of Th17 cells")
(volume 37)
(year 2011))
([GK_5692342] of LiteratureReference
(_displayName "Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation")
(author
[GK_5692353]
[GK_5692363]
[GK_5692361]
[GK_5634823]
[GK_5692355]
[GK_5692350]
[GK_5692357]
[GK_5668457])
(DB_ID 5692342)
(journal "Cell")
(pages "431-45")
(pubMedIdentifier 8387891)
(title "Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation")
(volume 73)
(year 1993))
([GK_5692343] of Person
(_displayName "Dewson, Grant")
(DB_ID 5692343)
(firstname "Grant")
(initial "G")
(surname "Dewson"))
([GK_5692344] of Person
(_displayName "Etemadi, Nima")
(DB_ID 5692344)
(firstname "Nima")
(initial "N")
(surname "Etemadi"))
([GK_5692345] of Person
(_displayName "Chun, H J")
(DB_ID 5692345)
(firstname "H J")
(initial "HJ")
(surname "Chun"))
([GK_5692346] of Person
(_displayName "Chou, Feng-Cheng")
(DB_ID 5692346)
(firstname "Feng-Cheng")
(initial "FC")
(surname "Chou"))
([GK_5692347] of Person
(_displayName "Wang, Yen-Ling")
(DB_ID 5692347)
(firstname "Yen-Ling")
(initial "YL")
(surname "Wang"))
([GK_5692348] of Person
(_displayName "Brosch, Inge")
(DB_ID 5692348)
(firstname "Inge")
(initial "I")
(surname "Brosch"))
([GK_5692349] of Person
(_displayName "Chen, Shyi-Jou")
(DB_ID 5692349)
(firstname "Shyi-Jou")
(initial "SJ")
(surname "Chen"))
([GK_5692350] of Person
(_displayName "Broger, C")
(DB_ID 5692350)
(firstname "C")
(initial "C")
(surname "Broger"))
([GK_5692351] of Person
(_displayName "Lenardo, M J")
(DB_ID 5692351)
(firstname "M J")
(initial "MJ")
(surname "Lenardo"))
([GK_5692352] of LiteratureReference
(_displayName "A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling")
(author
[GK_5675580]
[GK_5692345]
[GK_5321754]
[GK_5692335]
[GK_5692340]
[GK_5692351])
(DB_ID 5692352)
(journal "Science")
(pages "2351-4")
(pubMedIdentifier 10875917)
(title "A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling")
(volume 288)
(year 2000))
([GK_5692353] of Person
(_displayName "Banner, D W")
(DB_ID 5692353)
(firstname "D W")
(initial "DW")
(surname "Banner"))
([GK_5692354] of Person
(_displayName "Pfeffer, Klaus")
(DB_ID 5692354)
(firstname "Klaus")
(initial "K")
(surname "Pfeffer"))
([GK_5692355] of Person
(_displayName "Schoenfeld, H J")
(DB_ID 5692355)
(firstname "H J")
(initial "HJ")
(surname "Schoenfeld"))
([GK_5692356] of LiteratureReference
(_displayName "Role of SODD in regulation of tumor necrosis factor responses")
(author
[GK_5602560]
[GK_5692358]
[GK_5692338]
[GK_571202]
[GK_571208]
[GK_3215264]
[GK_2428863]
[GK_571219])
(DB_ID 5692356)
(journal "Mol. Cell. Biol.")
(pages "4026-33")
(pubMedIdentifier 12748303)
(title "Role of SODD in regulation of tumor necrosis factor responses")
(volume 23)
(year 2003))
([GK_5692357] of Person
(_displayName "Loetscher, H")
(DB_ID 5692357)
(firstname "H")
(initial "H")
(surname "Loetscher"))
([GK_5692358] of Person
(_displayName "Chen, Nien-Jung")
(DB_ID 5692358)
(firstname "Nien-Jung")
(initial "NJ")
(surname "Chen"))
([GK_5692360] of Person
(_displayName "Endres, Robert")
(DB_ID 5692360)
(firstname "Robert")
(initial "R")
(surname "Endres"))
([GK_5692361] of Person
(_displayName "Janes, W")
(DB_ID 5692361)
(firstname "W")
(initial "W")
(surname "Janes"))
([GK_5692362] of Person
(_displayName "Holien, Jessica K")
(DB_ID 5692362)
(firstname "Jessica K")
(initial "JK")
(surname "Holien"))
([GK_5692363] of Person
(_displayName "D'Arcy, A")
(DB_ID 5692363)
(firstname "A")
(initial "A")
(surname "D'Arcy"))
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(_displayName "[Hsa] UniProt:P10997 IAPP recommendedName: Islet amyloid polypeptide alternativeName: Amylin alternativeName: Diabetes-associated peptide shortName:DAP alternativeName: Diabetes-associated peptide shortName:DAP alternativeName: Insulinoma amyloid peptide ")
(checksum "1")
(comment "FUNCTION Selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism.PTM Amyloid fibrils are degraded by IDE.MISCELLANEOUS IAPP is the peptide subunit of amyloid found in pancreatic islets of type 2 diabetic patients and in insulinomas.SIMILARITY Belongs to the calcitonin family.")
(DB_ID 56978)
(description "recommendedName: Islet amyloid polypeptide alternativeName: Amylin alternativeName: Diabetes-associated peptide shortName:DAP alternativeName: Diabetes-associated peptide shortName:DAP alternativeName: Insulinoma amyloid peptide ")
(geneName "IAPP")
(identifier "P10997")
(isSequenceChanged TRUE)
(keyword
"3D-structure"
"Amidation"
"Amyloid"
"Cleavage on pair of basic residues"
"Complete proteome"
"Direct protein sequencing"
"Disulfide bond"
"Hormone"
"Polymorphism"
"Secreted"
"Signal")
(name "IAPP")
(referenceDatabase [GK_2])
(secondaryIdentifier
"IAPP_HUMAN"
"Q0ZD87"
"Q14598")
(sequenceLength 89)
(species [GK_48887]))
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(_displayName "[Hsa] CASP3(1-277) [cytosol]")
(DB_ID 57021)
(endCoordinate 277)
(name
"CASP3(1-277)"
"Caspase-3 precursor"
"Apopain precursor "
"Cysteine protease CPP32"
"Yama protein"
"CPP-32"
"CASP-3"
"SREBP cleavage activity 1"
"SCA-1")
(referenceEntity [GK_57022])
(species [GK_48887])
(stableIdentifier [GK_370468])
(startCoordinate 1))
([GK_57022] of ReferenceGeneProduct
(_chainChangeLog "propeptide:1-9 added on Fri February 6 2015;propeptide:10-28 added on Fri February 6 2015;chain:29-175 added on Fri February 6 2015;chain:176-277 added on Fri February 6 2015")
(_displayName "[Hsa] UniProt:P42574 CASP3 recommendedName: Caspase-3 shortName:CASP-3 ecNumber3.4.22.56/ecNumber alternativeName: Apopain alternativeName: Cysteine protease CPP32 shortName:CPP-32 alternativeName: Protein Yama alternativeName: SREBP cleavage activity 1 shortName:SCA-1 component recommendedName: Caspase-3 subunit p17 /component component recommendedName: Caspase-3 subunit p12 /component")
(chain
"propeptide:1-9"
"propeptide:10-28"
"chain:29-175"
"chain:176-277")
(checksum "2F35CD3BCF7FF64A")
(comment "CATALYTIC ACTIVITY Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp-|- with a hydrophobic amino-acid residue at P2 and a hydrophilic amino-acid residue at P3, although Val or Ala are also accepted at this position.ENZYME REGULATION Inhibited by isatin sulfonamides.TISSUE SPECIFICITY Highly expressed in lung, spleen, heart, liver and kidney. Moderate levels in brain and skeletal muscle, and low in testis. Also found in many cell lines, highest expression in cells of the immune system.PTM Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the propeptides is likely due to the autocatalytic activity of the activated protease. Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice versa.")
(DB_ID 57022)
(description "recommendedName: Caspase-3 shortName:CASP-3 ecNumber3.4.22.56/ecNumber alternativeName: Apopain alternativeName: Cysteine protease CPP32 shortName:CPP-32 alternativeName: Protein Yama alternativeName: SREBP cleavage activity 1 shortName:SCA-1 component recommendedName: Caspase-3 subunit p17 /component component recommendedName: Caspase-3 subunit p12 /component")
(geneName
"CASP3"
"CPP32")
(identifier "P42574")
(isSequenceChanged FALSE)
(keyword
"3D-structure"
"Acetylation"
"Apoptosis"
"Complete proteome"
"Cytoplasm"
"Direct protein sequencing"
"Hydrolase"
"Phosphoprotein"
"Polymorphism"
"Protease"
"Reference proteome"
"S-nitrosylation"
"Thiol protease"
"Zymogen")
(name "CASP3")
(referenceDatabase [GK_2])
(secondaryIdentifier
"CASP3_HUMAN"
"A8K5M2"
"D3DP53"
"Q96AN1"
"Q96KP2")
(sequenceLength 277)
(species [GK_48887]))
([GK_57031] of EntityWithAccessionedSequence
(_displayName "[Hsa] CASP8(1-479) [cytosol]")
(DB_ID 57031)
(endCoordinate 479)
(name
"CASP8(1-479)"
"Caspase-8 precursor "
"ICE-like apoptotic protease 5"
"MORT1-associated CED-3 homolog"
"MACH"
"FADD-homologous ICE/CED-3- like protease"
"FADD-like ICE"
"FLICE"
"Apoptotic cysteine protease"
"Apoptotic protease Mch-5"
"CAP4")
(referenceEntity [GK_57032])
(species [GK_48887])
(stableIdentifier [GK_362980])
(startCoordinate 1))
([GK_57032] of ReferenceGeneProduct
(_chainChangeLog "propeptide:1-216 added on Fri February 6 2015;chain:217-374 added on Fri February 6 2015;propeptide:375-384 added on Fri February 6 2015;chain:385-479 added on Fri February 6 2015")
(_displayName "[Hsa] UniProt:Q14790 CASP8 recommendedName: Caspase-8 shortName:CASP-8 ecNumber3.4.22.61/ecNumber alternativeName: Apoptotic cysteine protease alternativeName: Apoptotic protease Mch-5 alternativeName: CAP4 alternativeName: FADD-homologous ICE/ced-3-like protease alternativeName: FADD-like ICE shortName:FLICE alternativeName: ICE-like apoptotic protease 5 alternativeName: MORT1-associated ced-3 homolog shortName:MACH component recommendedName: Caspase-8 subunit p18 /component component recommendedName: Caspase-8 subunit p10 /component")
(chain
"propeptide:1-216"
"chain:217-374"
"propeptide:375-384"
"chain:385-479")
(checksum "7A5FEAA6B39B582F")
(comment "TISSUE SPECIFICITY Isoform 1, isoform 5 and isoform 7 are expressed in a wide variety of tissues. Highest expression in peripheral blood leukocytes, spleen, thymus and liver. Barely detectable in brain, testis and skeletal muscle.DOMAIN Isoform 9 contains a N-terminal extension that is required for interaction with the BCAP31 complex.POLYMORPHISM Genetic variations in CASP8 are associated with reduced risk of lung cancer [MIM:211980] in a population of Han Chinese subjects. Genetic variations are also associated with decreased risk of cancer of various other forms including esophageal, gastric, colorectal, cervical, and breast, acting in an allele dose-dependent manner.")
(DB_ID 57032)
(description "recommendedName: Caspase-8 shortName:CASP-8 ecNumber3.4.22.61/ecNumber alternativeName: Apoptotic cysteine protease alternativeName: Apoptotic protease Mch-5 alternativeName: CAP4 alternativeName: FADD-homologous ICE/ced-3-like protease alternativeName: FADD-like ICE shortName:FLICE alternativeName: ICE-like apoptotic protease 5 alternativeName: MORT1-associated ced-3 homolog shortName:MACH component recommendedName: Caspase-8 subunit p18 /component component recommendedName: Caspase-8 subunit p10 /component")
(geneName
"CASP8"
"MCH5")
(identifier "Q14790")
(isSequenceChanged FALSE)
(keyword
"3D-structure"
"Acetylation"
"Alternative splicing"
"Apoptosis"
"Complete proteome"
"Cytoplasm"
"Direct protein sequencing"
"Disease mutation"
"Host-virus interaction"
"Hydrolase"
"Phosphoprotein"
"Polymorphism"
"Protease"
"Reference proteome"
"Repeat"
"Thiol protease"
"Zymogen")
(name "CASP8")
(referenceDatabase [GK_2])
(secondaryIdentifier
"CASP8_HUMAN"
"O14676"
"Q14791"
"Q14792"
"Q14793"
"Q14794"
"Q14795"
"Q14796"
"Q15780"
"Q15806"
"Q53TT5"
"Q8TDI1"
"Q8TDI2"
"Q8TDI3"
"Q8TDI4"
"Q8TDI5"
"Q96T22"
"Q9C0K4"
"Q9UQ81")
(sequenceLength 479)
(species [GK_48887]))
([GK_57035] of EntityWithAccessionedSequence
(_displayName "[Hsa] CASP10(220-415) [plasma membrane]")
(DB_ID 57035)
(endCoordinate 415)
(name
"CASP10(220-415)"
"Caspase-10 precursor "
"ICE-like apoptotic protease 4"
"Apoptotic protease Mch-4"
"FAS-associated death domain protein interleukin-1B-converting enzyme 2"
"FLICE2")
(referenceEntity [GK_57036])
(species [GK_48887])
(stableIdentifier [GK_370163])
(startCoordinate 220))
([GK_57036] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:Q92851 CASP10 recommendedName: Caspase-10 shortName:CASP-10 ecNumber3.4.22.63/ecNumber alternativeName: Apoptotic protease Mch-4 alternativeName: FAS-associated death domain protein interleukin-1B-converting enzyme 2 shortName:FLICE2 alternativeName: ICE-like apoptotic protease 4 component recommendedName: Caspase-10 subunit p23/17 /component component recommendedName: Caspase-10 subunit p12 /component")
(checksum "840348AE602B8243")
(comment "CATALYTIC ACTIVITY Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Leu-Gln-Thr-Asp-|-Gly.TISSUE SPECIFICITY Detectable in most tissues. Lowest expression is seen in brain, kidney, prostate, testis and colon.PTM Cleavage by granzyme B and autocatalytic activity generate the two active subunits.")
(DB_ID 57036)
(description "recommendedName: Caspase-10 shortName:CASP-10 ecNumber3.4.22.63/ecNumber alternativeName: Apoptotic protease Mch-4 alternativeName: FAS-associated death domain protein interleukin-1B-converting enzyme 2 shortName:FLICE2 alternativeName: ICE-like apoptotic protease 4 component recommendedName: Caspase-10 subunit p23/17 /component component recommendedName: Caspase-10 subunit p12 /component")
(geneName
"CASP10"
"MCH4")
(identifier "Q92851")
(isSequenceChanged FALSE)
(keyword
"Alternative splicing"
"Apoptosis"
"Complete proteome"
"Direct protein sequencing"
"Disease mutation"
"Hydrolase"
"Polymorphism"
"Protease"
"Reference proteome"
"Repeat"
"Thiol protease"
"Zymogen")
(name "CASP10")
(referenceDatabase [GK_2])
(secondaryIdentifier
"CASPA_HUMAN"
"Q68HC0"
"Q6KF62"
"Q6KF63"
"Q8IUP5"
"Q8WYQ8"
"Q99845"
"Q9Y2U6"
"Q9Y2U7")
(sequenceLength 521)
(species [GK_48887]))
([GK_571202] of Person
(_displayName "Suzuki, S")
(DB_ID 571202)
(firstname "Shinobu")
(initial "S")
(surname "Suzuki"))
([GK_571208] of Person
(_displayName "Suzuki, N")
(DB_ID 571208)
(firstname "Nobutaka")
(initial "N")
(surname "Suzuki"))
([GK_571213] of Person
(_displayName "Zhou, H")
(DB_ID 571213)
(firstname "Huaijun")
(initial "H")
(surname "Zhou"))
([GK_571219] of Person
(_displayName "Yeh, WC")
(DB_ID 571219)
(firstname "Wen-Chen")
(initial "WC")
(surname "Yeh"))
([GK_57415] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P01308 INS recommendedName: Insulin component recommendedName: Insulin B chain /component component recommendedName: Insulin A chain /component")
(checksum "1")
(comment "FUNCTION Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.SUBUNIT Heterodimer of a B chain and an A chain linked by two disulfide bonds.PHARMACEUTICAL Available under the names Humulin or Humalog (Eli Lilly) and Novolin (Novo Nordisk). Used in the treatment of diabetes. Humalog is an insulin analog with 52-Lys-Pro-53 instead of 52-Pro-Lys-53.SIMILARITY Belongs to the insulin family.")
(DB_ID 57415)
(description "recommendedName: Insulin component recommendedName: Insulin B chain /component component recommendedName: Insulin A chain /component")
(geneName "INS")
(identifier "P01308")
(isSequenceChanged TRUE)
(keyword
"3D-structure"
"Carbohydrate metabolism"
"Cleavage on pair of basic residues"
"Complete proteome"
"Diabetes mellitus"
"Direct protein sequencing"
"Disease mutation"
"Disulfide bond"
"Glucose metabolism"
"Hormone"
"Pharmaceutical"
"Polymorphism"
"Secreted"
"Signal")
(name "INS")
(referenceDatabase [GK_2])
(secondaryIdentifier
"INS_HUMAN"
"Q5EEX2")
(sequenceLength 110)
(species [GK_48887]))
([GK_57627] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:Q9Y287 ITM2B recommendedName: Integral membrane protein 2B alternativeName: Protein E25B alternativeName: Transmembrane protein BRI component recommendedName: ABri/ADan amyloid peptide /component")
(checksum "1")
(comment "TISSUE SPECIFICITY Expressed in brain and in other tissues.DISEASE Defects in ITM2B are a cause of cerebral amyloid angiopathy ITM2B-related type 2 (CAA-ITM2B2) [MIM:117300]; also known as heredopathia ophthalmo-oto-encephalica. A disorder characterized by amyloid deposition in the walls of the blood vessels of the cerebrum, choroid plexus, cerebellum, spinal cord and retina. Plaques and neurofibrillary tangles are observed in the hippocampus. Clinical features include progressive ataxia, dementia, cataracts and deafness.SIMILARITY Belongs to the ITM2 family.SIMILARITY Contains 1 BRICHOS domain.")
(DB_ID 57627)
(description "recommendedName: Integral membrane protein 2B alternativeName: Protein E25B alternativeName: Transmembrane protein BRI component recommendedName: ABri/ADan amyloid peptide /component")
(geneName
"ITM2B"
"BRI"
"BRI2")
(identifier "Q9Y287")
(isSequenceChanged TRUE)
(keyword
"Amyloid"
"Amyloidosis"
"Cell membrane"
"Cleavage on pair of basic residues"
"Complete proteome"
"Deafness"
"Disease mutation"
"Disulfide bond"
"Glycoprotein"
"Golgi apparatus"
"Membrane"
"Signal-anchor"
"Transmembrane"
"Transmembrane helix")
(name "ITM2B")
(referenceDatabase [GK_2])
(secondaryIdentifier
"ITM2B_HUMAN"
"Q9NYH1")
(sequenceLength 266)
(species [GK_48887]))
([GK_58841] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P61626 LYZ Lysozyme C alternativeName: 1,4-beta-N-acetylmuramidase C ")
(checksum "1")
(comment "FUNCTION Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents.CATALYTIC ACTIVITY Hydrolysis of (1->4)-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrins.SUBUNIT Monomer.MISCELLANEOUS Lysozyme C is capable of both hydrolysis and transglycosylation; it shows also a slight esterase activity. It acts rapidly on both peptide-substituted and unsubstituted peptidoglycan, and slowly on chitin oligosaccharides.SIMILARITY Belongs to the glycosyl hydrolase 22 family.")
(DB_ID 58841)
(description " Lysozyme C alternativeName: 1,4-beta-N-acetylmuramidase C ")
(geneName
"LYZ"
"LZM")
(identifier "P61626")
(isSequenceChanged TRUE)
(keyword
"3D-structure"
"Amyloid"
"Amyloidosis"
"Antimicrobial"
"Bacteriolytic enzyme"
"Complete proteome"
"Direct protein sequencing"
"Disease mutation"
"Disulfide bond"
"Glycosidase"
"Hydrolase"
"Polymorphism"
"Secreted"
"Signal")
(name "LYZ")
(referenceDatabase [GK_2])
(secondaryIdentifier
"LYSC_HUMAN"
"P00695"
"Q13170"
"Q9UCF8")
(sequenceLength 148)
(species [GK_48887]))
([GK_59097] of ReferenceGeneProduct
(_chainChangeLog "signal peptide:1-18 added on Sat February 7 2015;chain:19-160 added on Sat February 7 2015")
(_displayName "[Hsa] UniProt:Q9Y6Y9 LY96 recommendedName: Lymphocyte antigen 96 shortName:Ly-96 alternativeName: ESOP-1 alternativeName: Protein MD-2 ")
(chain
"signal peptide:1-18"
"chain:19-160")
(checksum "0F92AFF583637C6B")
(comment "FUNCTION Cooperates with TLR4 in the innate immune response to bacterial lipopolysaccharide (LPS), and with TLR2 in the response to cell wall components from Gram-positive and Gram-negative bacteria. Enhances TLR4-dependent activation of NF-kappa-B. Cells expressing both MD2 and TLR4, but not TLR4 alone, respond to LPS.")
(DB_ID 59097)
(description "recommendedName: Lymphocyte antigen 96 shortName:Ly-96 alternativeName: ESOP-1 alternativeName: Protein MD-2 ")
(geneName
"LY96"
"ESOP1"
"MD2")
(identifier "Q9Y6Y9")
(isSequenceChanged FALSE)
(keyword
"3D-structure"
"Alternative splicing"
"Complete proteome"
"Disulfide bond"
"Glycoprotein"
"Immunity"
"Inflammatory response"
"Innate immunity"
"Polymorphism"
"Reference proteome"
"Secreted"
"Signal")
(name "LY96")
(referenceDatabase [GK_2])
(secondaryIdentifier
"LY96_HUMAN"
"B3Y6A5"
"E5RJJ7")
(sequenceLength 160)
(species [GK_48887]))
([GK_59185] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:Q08431 MFGE8 recommendedName: Lactadherin alternativeName: Breast epithelial antigen BA46 alternativeName: HMFG alternativeName: MFGM alternativeName: Milk fat globule-EGF factor 8 shortName:MFG-E8 alternativeName: Milk fat globule-EGF factor 8 shortName:MFG-E8 alternativeName: SED1 component recommendedName: Lactadherin short form /component component recommendedName: Medin /component")
(checksum "1")
(comment "TISSUE SPECIFICITY Mammary epithelial cell surfaces and aortic media. Overexpressed in several carcinomas.PTM Medin has a ragged N-terminus with minor species starting at Pro-264 and Gly-273.SIMILARITY Contains 1 EGF-like domain.SIMILARITY Contains 2 F5/8 type C domains.")
(DB_ID 59185)
(description "recommendedName: Lactadherin alternativeName: Breast epithelial antigen BA46 alternativeName: HMFG alternativeName: MFGM alternativeName: Milk fat globule-EGF factor 8 shortName:MFG-E8 alternativeName: Milk fat globule-EGF factor 8 shortName:MFG-E8 alternativeName: SED1 component recommendedName: Lactadherin short form /component component recommendedName: Medin /component")
(geneName "MFGE8")
(identifier "Q08431")
(isSequenceChanged TRUE)
(keyword
"Alternative splicing"
"Amyloid"
"Angiogenesis"
"Cell adhesion"
"Complete proteome"
"Direct protein sequencing"
"Disulfide bond"
"EGF-like domain"
"Fertilization"
"Glycoprotein"
"Host-virus interaction"
"Membrane"
"Polymorphism"
"Repeat"
"Secreted"
"Signal")
(name "MFGE8")
(referenceDatabase [GK_2])
(secondaryIdentifier
"MFGM_HUMAN"
"B2R6M7"
"Q53FU9"
"Q7Z3D2"
"Q9BTL9")
(sequenceLength 387)
(species [GK_48887]))
([GK_6] of ReferenceDatabase
(_displayName "COMPOUND")
(accessUrl "http://www.genome.ad.jp/dbget-bin/www_bget?cpd:###ID###")
(DB_ID 6)
(name "COMPOUND")
(url "http://www.genome.ad.jp/kegg/"))
([GK_611062] of PsiMod
(_displayName "L-lysine residue [MOD:00021]")
(DB_ID 611062)
(definition "A protein modification that effectively converts a source amino acid residue to L-lysine.")
(identifier "00021")
(name "L-lysine residue")
(referenceDatabase [GK_437354])
(synonym
"(S)-2,6-diaminohexanoic acid"
"Lys"
"alpha,epsilon-diaminocaproic acid"))
([GK_611064] of PsiMod
(_displayName "L-asparagine removal [MOD:01633]")
(DB_ID 611064)
(definition "A protein modification that effectively removes or replaces an L-asparagine.")
(identifier "01633")
(name "L-asparagine removal")
(referenceDatabase [GK_437354]))
([GK_611065] of PsiMod
(_displayName "L-lysine removal [MOD:01642]")
(DB_ID 611065)
(definition "A protein modification that effectively removes or replaces an L-lysine.")
(identifier "01642")
(name "L-lysine removal")
(referenceDatabase [GK_437354]))
([GK_611066] of PsiMod
(_displayName "L-arginine residue [MOD:00011]")
(DB_ID 611066)
(definition "A protein modification that effectively converts a source amino acid residue to an L-arginine.")
(identifier "00011")
(name "L-arginine residue")
(referenceDatabase [GK_437354])
(synonym
"(S)-2-amino-5-(carbamimidamido)pentanoic acid"
"Arg"))
([GK_611067] of PsiMod
(_displayName "L-glutamic acid residue [MOD:00015]")
(DB_ID 611067)
(definition "A protein modification that effectively converts a source amino acid residue to an L-glutamic acid.")
(identifier "00015")
(name "L-glutamic acid residue")
(referenceDatabase [GK_437354])
(synonym
"(S)-2-aminopentanedioic acid"
"Glu"))
([GK_611068] of PsiMod
(_displayName "glycine residue [MOD:00017]")
(DB_ID 611068)
(definition "A protein modification that effectively converts a source amino acid residue to a glycine.")
(identifier "00017")
(name "glycine residue")
(referenceDatabase [GK_437354])
(synonym
"aminoethanoic acid"
"Gly"))
([GK_611069] of PsiMod
(_displayName "L-proline residue [MOD:00024]")
(DB_ID 611069)
(definition "A protein modification that effectively converts a source amino acid residue to L-proline.")
(identifier "00024")
(name "L-proline residue")
(referenceDatabase [GK_437354])
(synonym
"(S)-2-pyrrolidinecarboxylic acid"
"Pro"
"pyrrolidine-2-carboxylic acid"))
([GK_611070] of PsiMod
(_displayName "L-aspartic acid residue [MOD:00013]")
(DB_ID 611070)
(definition "A protein modification that effectively converts a source amino acid residue to an L-aspartic acid.")
(identifier "00013")
(name "L-aspartic acid residue")
(referenceDatabase [GK_437354])
(synonym
"(S)-2-aminobutanedioic acid"
"Asp"
"aminosuccinic acid"))
([GK_611072] of PsiMod
(_displayName "L-proline removal [MOD:01645]")
(DB_ID 611072)
(definition "A protein modification that effectively removes or replaces an L-proline.")
(identifier "01645")
(name "L-proline removal")
(referenceDatabase [GK_437354]))
([GK_611082] of PsiMod
(_displayName "L-threonine residue [MOD:00026]")
(DB_ID 611082)
(definition "A protein modification that effectively converts a source amino acid residue to L-threonine.")
(identifier "00026")
(name "L-threonine residue")
(referenceDatabase [GK_437354])
(synonym
"(2S,3R)-2-amino-3-hydroxybutanoic acid"
"Thr"))
([GK_611087] of PsiMod
(_displayName "L-threonine removal [MOD:01647]")
(DB_ID 611087)
(definition "A protein modification that effectively removes or replaces an L-threonine.")
(identifier "01647")
(name "L-threonine removal")
(referenceDatabase [GK_437354]))
([GK_611088] of PsiMod
(_displayName "L-glutamine residue [MOD:00016]")
(DB_ID 611088)
(definition "A protein modification that effectively converts a source amino acid residue to an L-glutamine.")
(identifier "00016")
(name "L-glutamine residue")
(referenceDatabase [GK_437354])
(synonym
"(S)-2-amino-5-pentanediamic acid"
"Gln"))
([GK_611093] of PsiMod
(_displayName "L-leucine residue [MOD:00020]")
(DB_ID 611093)
(definition "A protein modification that effectively converts a source amino acid residue to an L-leucine.")
(identifier "00020")
(name "L-leucine residue")
(referenceDatabase [GK_437354])
(synonym
"(S)-2-amino-4-methylpentanoic acid"
"Leu"))
([GK_61584] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P98160 HSPG2 recommendedName: Basement membrane-specific heparan sulfate proteoglycan core protein shortName:HSPG alternativeName: Perlecan shortName:PLC alternativeName: Perlecan shortName:PLC component recommendedName: Endorepellin /component component recommendedName: LG3 peptide /component")
(checksum "1")
(comment "TISSUE SPECIFICITY Found in the basement membranes.PTM Proteolytic processing produces the C-terminal angiogenic peptide, endorepellin. This peptide can be further processed to produce the LG3 peptide.MISCELLANEOUS The LG3 peptide has been found in the urine of patients with end-stage renal disease and in the amniotic fluid of pregnant women with premature rupture of fetal membranes.SIMILARITY Contains 4 EGF-like domains.SIMILARITY Contains 22 Ig-like C2-type (immunoglobulin-like) domains.SIMILARITY Contains 11 laminin EGF-like domains.SIMILARITY Contains 3 laminin G-like domains.SIMILARITY Contains 3 laminin IV type A domains.SIMILARITY Contains 4 LDL-receptor class A domains.SIMILARITY Contains 1 SEA domain.")
(DB_ID 61584)
(description "recommendedName: Basement membrane-specific heparan sulfate proteoglycan core protein shortName:HSPG alternativeName: Perlecan shortName:PLC alternativeName: Perlecan shortName:PLC component recommendedName: Endorepellin /component component recommendedName: LG3 peptide /component")
(geneName "HSPG2")
(identifier "P98160")
(isSequenceChanged TRUE)
(keyword
"Angiogenesis"
"Basement membrane"
"Complete proteome"
"Direct protein sequencing"
"Disease mutation"
"Disulfide bond"
"EGF-like domain"
"Extracellular matrix"
"Glycoprotein"
"Heparan sulfate"
"Immunoglobulin domain"
"Laminin EGF-like domain"
"Polymorphism"
"Proteoglycan"
"Repeat"
"Secreted"
"Signal")
(name "HSPG2")
(referenceDatabase [GK_2])
(secondaryIdentifier
"PGBM_HUMAN"
"Q16287"
"Q5SZI3"
"Q9H3V5")
(sequenceLength 4391)
(species [GK_48887]))
([GK_6192] of GO_BiologicalProcess
(_displayName "regulation of signal transduction")
(accession "0009966")
(DB_ID 6192)
(definition "Any process that modulates the frequency, rate or extent of signal transduction.")
(name "regulation of signal transduction")
(referenceDatabase [GK_1]))
([GK_6194] of GO_BiologicalProcess
(_displayName "positive regulation of signal transduction")
(accession "0009967")
(DB_ID 6194)
(definition "Any process that activates or increases the frequency, rate or extent of signal transduction.")
(name "positive regulation of signal transduction")
(referenceDatabase [GK_1]))
([GK_6196] of GO_BiologicalProcess
(_displayName "negative regulation of signal transduction")
(accession "0009968")
(DB_ID 6196)
(definition "Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction.")
(name "negative regulation of signal transduction")
(referenceDatabase [GK_1]))
([GK_62178] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P01236 PRL recommendedName: Prolactin shortName:PRL ")
(checksum "1")
(comment "FUNCTION Prolactin acts primarily on the mammary gland by promoting lactation.SIMILARITY Belongs to the somatotropin/prolactin family.")
(DB_ID 62178)
(description "recommendedName: Prolactin shortName:PRL ")
(geneName "PRL")
(identifier "P01236")
(isSequenceChanged TRUE)
(keyword
"3D-structure"
"Complete proteome"
"Direct protein sequencing"
"Disulfide bond"
"Glycoprotein"
"Hormone"
"Lactation"
"Secreted"
"Signal")
(name "PRL")
(referenceDatabase [GK_2])
(secondaryIdentifier
"PRL_HUMAN"
"Q15199"
"Q92996")
(sequenceLength 227)
(species [GK_48887]))
([GK_63118] of EntityWithAccessionedSequence
(_displayName "[Hsa] RIP [cytosol]")
(DB_ID 63118)
(endCoordinate -1)
(name
"RIP"
"Receptor-interacting serine/threonine protein kinase 2 (EC 2.7.1.-) (Serine/threonine protein kinase RIP) (Cell death protein RIP) (Receptor interacting protein)"
"Receptor-interacting serine/threonine protein kinase 2 "
"Serine/threonine protein kinase RIP"
"Cell death protein RIP"
"Receptor interacting protein")
(referenceEntity [GK_63119])
(species [GK_48887])
(stableIdentifier [GK_367393])
(startCoordinate 1))
([GK_63119] of ReferenceGeneProduct
(_chainChangeLog "chain:1-671 added on Fri February 6 2015")
(_displayName "[Hsa] UniProt:Q13546 RIPK1 recommendedName: Receptor-interacting serine/threonine-protein kinase 1 ecNumber2.7.11.1/ecNumber alternativeName: Cell death protein RIP alternativeName: Receptor-interacting protein 1 shortName:RIP-1 alternativeName: Serine/threonine-protein kinase RIP ")
(chain "chain:1-671")
(checksum "976E2428D525A9B2")
(comment "PTM RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Phosphorylation of Ser-161 by RIPK3 is necessary for the formation of the necroptosis-inducing complex.SIMILARITY Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.SIMILARITY Contains 1 death domain.SIMILARITY Contains 1 protein kinase domain.")
(DB_ID 63119)
(description "recommendedName: Receptor-interacting serine/threonine-protein kinase 1 ecNumber2.7.11.1/ecNumber alternativeName: Cell death protein RIP alternativeName: Receptor-interacting protein 1 shortName:RIP-1 alternativeName: Serine/threonine-protein kinase RIP ")
(geneName
"RIPK1"
"RIP"
"RIP1")
(identifier "Q13546")
(isSequenceChanged FALSE)
(keyword
"3D-structure"
"Alternative splicing"
"ATP-binding"
"Cell membrane"
"Complete proteome"
"Cytoplasm"
"Isopeptide bond"
"Kinase"
"Membrane"
"Necrosis"
"Nucleotide-binding"
"Phosphoprotein"
"Polymorphism"
"Reference proteome"
"Serine/threonine-protein kinase"
"Transferase"
"Ubl conjugation")
(name "RIPK1")
(referenceDatabase [GK_2])
(secondaryIdentifier
"RIPK1_HUMAN"
"A0AV89"
"B2RAG1"
"B4E3F9"
"Q13180"
"Q59H33")
(sequenceLength 671)
(species [GK_48887]))
([GK_638653] of Affiliation
(_displayName "University of Massachusetts Medical School")
(address "Worcester, MA, USA")
(DB_ID 638653)
(name "University of Massachusetts Medical School"))
([GK_64108] of ReferenceGeneProduct
(_displayName "[Hsa] UniProt:P02735 SAA1 recommendedName: Serum amyloid A protein shortName:SAA component recommendedName: Amyloid protein A alternativeName: Amyloid fibril protein AA /component component recommendedName: Serum amyloid protein A(2-104) /component component recommendedName: Serum amyloid protein A(3-104) /component component recommendedName: Serum amyloid protein A(2-103) /component component recommendedName: Serum amyloid protein A(2-102) /component component recommendedName: Serum amyloid protein A(4-101) /component")
(checksum "1")
(comment "FUNCTION Major acute phase reactant. Apolipoprotein of the HDL complex.INDUCTION Upon cytokine stimulation.PTM This protein is the precursor of amyloid protein A, which is formed by the removal of approximately 24 residues from the C-terminal end.POLYMORPHISM Both SAA1 and SAA2 have a number of alleles. We use here the nomenclature of PubMed:1546977. The sequence shown is that of 1-alpha.DISEASE Note=Reactive, secondary amyloidosis is characterized by the extracellular accumulation in various tissues of the SAA protein. These deposits are highly insoluble and resistant to proteolysis; they disrupt tissue structure and compromise function.DISEASE Note=Elevated serum SSA protein levels may be associated with lung cancer.SIMILARITY Belongs to the SAA family.")
(DB_ID 64108)
(description "recommendedName: Serum amyloid A protein shortName:SAA component recommendedName: Amyloid protein A alternativeName: Amyloid fibril protein AA /component component recommendedName: Serum amyloid protein A(2-104) /component component recommendedName: Serum amyloid protein A(3-104) /component component recommendedName: Serum amyloid protein A(2-103) /component component recommendedName: Serum amyloid protein A(2-102) /component component recommendedName: Serum amyloid protein A(4-101) /component")
(geneName
"SAA1"
"