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([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.") 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(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.") 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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.") 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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.") 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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.") 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Chemin des Boveressses 155
CH-1066 Epalinges
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(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.") 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(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.") 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(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.") 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(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.") 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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.") 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(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 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(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") (affiliation [GK_167908]) (DB_ID 167911) 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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.") 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(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.") (ecNumber "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.") 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(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.") 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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.") 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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.") 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May be incorporated in the enamel matrix at the end of mineralization process.MISCELLANEOUS ODAM protein is the unique constituent of calcifying epithelial odontogenic tumors (CEOTs), also known as Pindborg tumors. CEOTs are benign but locally aggressive pathologic entities arising mainly in the mandible and commonly associated with an unerupted or embedded tooth. They are characterized by the presence of squamous-cell proliferation, calcification, and, notably, amyloid deposits.SIMILARITY Belongs to the ODAM family.") 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(pages "863-75") (pubMedIdentifier 19656901) (title "Endotoxin tolerance dysregulates MyD88- and Toll/IL-1R domain-containing adapter inducing IFN-beta-dependent pathways and increases expression of negative regulators of TLR signaling") (volume 86) (year 2009)) ([GK_2423801] of Person (_displayName "Diaz, Marco A Quevedo") (DB_ID 2423801) (firstname "Marco A Quevedo") (initial "MA") (surname "Diaz")) ([GK_2423811] of Person (_displayName "Akashi, Sachiko") (DB_ID 2423811) (firstname "Sachiko") (initial "S") (surname "Akashi")) ([GK_2423812] of Person (_displayName "Wakabayashi, Yasutaka") (DB_ID 2423812) (firstname "Yasutaka") (initial "Y") (surname "Wakabayashi")) ([GK_2423813] of Person (_displayName "Kosugi, Atsushi") (DB_ID 2423813) (firstname "Atsushi") (initial "A") (surname "Kosugi")) ([GK_2423814] of Person (_displayName "Kikuchi, Takane") (DB_ID 2423814) (firstname "Takane") (initial "T") (surname "Kikuchi")) ([GK_2423816] of LiteratureReference (_displayName "Lipopolysaccharide interaction with cell surface Toll-like receptor 4-MD-2: higher affinity than that with MD-2 or CD14") (author [GK_2423811] [GK_1678992] [GK_2423812] [GK_2423814] [GK_2423817] [GK_2423818] [GK_1679557] [GK_2423821] [GK_2423819] [GK_2423820] [GK_2423813] [GK_1679060]) (DB_ID 2423816) (journal "J. 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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.") 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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.") 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(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 (_displayName "Jeffrey, Philip D") (DB_ID 2672164) (firstname "Philip D") (initial "PD") (surname "Jeffrey")) ([GK_2672165] of LiteratureReference (_displayName "Target protease specificity of the viral serpin CrmA. Analysis of five caspases") (author [GK_2672211] [GK_2672179] [GK_2672202] [GK_2672176] [GK_2672188] [GK_2534135]) (DB_ID 2672165) (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)) ([GK_2672168] of Person (_displayName "Miura, M") (DB_ID 2672168) (firstname "M") (initial "M") (surname "Miura")) ([GK_2672170] of Person (_displayName "Burns, K") (DB_ID 2672170) (firstname "K") (initial "K") (surname "Burns")) ([GK_2672171] of Person (_displayName "Smith, G L") (DB_ID 2672171) (firstname "G L") (initial "GL") (surname "Smith")) ([GK_2672173] of LiteratureReference (_displayName "Tumor necrosis factor-induced apoptosis is mediated by a CrmA-sensitive cell death pathway") (author [GK_2672168] [GK_2672206] [GK_2672200]) (DB_ID 2672173) (journal "Proc. Natl. Acad. Sci. U.S.A.") (pages "8318-22") (pubMedIdentifier 7667287) (title "Tumor necrosis factor-induced apoptosis is mediated by a CrmA-sensitive cell death pathway") (volume 92) (year 1995)) ([GK_2672174] of Person (_displayName "Thome, M") (DB_ID 2672174) (firstname "M") (initial "M") (surname "Thome")) ([GK_2672175] of Person (_displayName "Tschopp, J") (DB_ID 2672175) (firstname "J") (initial "J") (surname "Tschopp")) ([GK_2672176] of Person (_displayName "Muzio, M") (DB_ID 2672176) (firstname "M") (initial "M") (surname "Muzio")) ([GK_2672179] of Person (_displayName "Snipas, S") (DB_ID 2672179) (firstname "S") (initial "S") (surname "Snipas")) ([GK_2672185] of LiteratureReference (_displayName "Fas- and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product") (author [GK_2672222] [GK_2672188]) (DB_ID 2672185) (journal "J. Biol. Chem.") (pages "3255-60") (pubMedIdentifier 7531702) (title "Fas- and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product") (volume 270) (year 1995)) ([GK_2672186] of Person (_displayName "Ehret, R") (DB_ID 2672186) (firstname "R") (initial "R") (surname "Ehret")) ([GK_2672188] of Person (_displayName "Dixit, V M") (DB_ID 2672188) (firstname "V M") (initial "VM") (surname "Dixit")) ([GK_2672191] of Summation (_displayName "SPI-2/CrmA (cytokine response modifier A) is a poxvirus gen...") (DB_ID 2672191) (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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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).")) 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(pages "27345-55") (pubMedIdentifier 15886205) (title "Rapid turnover of c-FLIPshort is determined by its unique C-terminal tail") (volume 280) (year 2005)) ([GK_3465369] of Person (_displayName "Litwack, G") (DB_ID 3465369) (firstname "G") (initial "G") (surname "Litwack")) ([GK_3465370] of Person (_displayName "Siegmund, Daniela") (DB_ID 3465370) (firstname "Daniela") (initial "D") (surname "Siegmund")) ([GK_3465371] of Person (_displayName "Kracht, Michael") (DB_ID 3465371) (firstname "Michael") (initial "M") (surname "Kracht")) ([GK_3465372] of Person (_displayName "Hsia, C") (DB_ID 3465372) (firstname "C") (initial "C") (surname "Hsia")) ([GK_3465373] of Person (_displayName "Eriksson, John E") (DB_ID 3465373) (firstname "John E") (initial "JE") (surname "Eriksson")) ([GK_3465374] of Person (_displayName "Westerlund, Mia") (DB_ID 3465374) (firstname "Mia") (initial "M") (surname "Westerlund")) ([GK_3465375] of Person (_displayName "Taylor, Alison") (DB_ID 3465375) (firstname "Alison") (initial "A") (surname "Taylor")) ([GK_3465376] of Person (_displayName "Kataoka, T") (DB_ID 3465376) (firstname "T") (initial "T") (surname "Kataoka")) ([GK_3465377] of Person (_displayName "Inoue, Hidekazu") (DB_ID 3465377) (firstname "Hidekazu") (initial "H") (surname "Inoue")) ([GK_3465378] of Person (_displayName "Asaoka, Tomoko") (DB_ID 3465378) (firstname "Tomoko") (initial "T") (surname "Asaoka")) ([GK_3465379] of Person (_displayName "Srinivasula, S M") (DB_ID 3465379) (firstname "S M") (initial "SM") (surname "Srinivasula")) ([GK_3465380] of LiteratureReference (_displayName "Modeling reveals that dynamic regulation of c-FLIP levels determines cell-to-cell distribution of CD95-mediated apoptosis") (author [GK_3465384] [GK_3465342] [GK_3465378] [GK_3465374] [GK_3465433] [GK_3465416] [GK_3465373] [GK_3465450]) (DB_ID 3465380) (journal "J. 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(pages "32585-90") (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") (DB_ID 3465383) (firstname "Jürg") (initial "J") (surname "Tschopp")) ([GK_3465384] of Person (_displayName "Toivonen, Hannu T") (DB_ID 3465384) (firstname "Hannu T") (initial "HT") (surname "Toivonen")) ([GK_3465385] of LiteratureReference (_displayName "The role of c-FLIP in modulation of CD95-induced apoptosis") (author [GK_2672219] [GK_3465496] [GK_2672214] [GK_2672197]) (DB_ID 3465385) (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") (author [GK_2672201] [GK_2672164] [GK_141951]) (DB_ID 3465386) (journal "Proc. Natl. Acad. Sci. U.S.A.") (pages "8169-74") (pubMedIdentifier 19416807) (title "Mechanism of procaspase-8 activation by c-FLIPL") (volume 106) (year 2009)) ([GK_3465387] of Person (_displayName "Sharp, Darcie A") (DB_ID 3465387) (firstname "Darcie A") (initial "DA") (surname "Sharp")) ([GK_3465388] of Person (_displayName "Kaunisto, A") (DB_ID 3465388) (firstname "A") (initial "A") (surname "Kaunisto")) ([GK_3465389] of Person (_displayName "Nesse, Alcira") (DB_ID 3465389) (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") (DB_ID 3465392) (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") (author [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) (literatureReference [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") (author [GK_3465370] [GK_3465507] [GK_429711] [GK_3465358] [GK_3465486]) (DB_ID 3465396) (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") (author [GK_3465406] [GK_3465475] [GK_3465427] [GK_3465348] [GK_3465474]) (DB_ID 3465397) (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") (DB_ID 3465398) (firstname "N") (initial "N") (surname "Holler")) ([GK_3465399] of Person (_displayName "Ye, H") (DB_ID 3465399) (firstname "H") (initial "H") (surname "Ye")) ([GK_3465400] of Person (_displayName "Ohmori, Shigeru") (DB_ID 3465400) (firstname "Shigeru") (initial "S") (surname "Ohmori")) ([GK_3465401] of Person (_displayName "Dittrich-Breiholz, Oliver") (DB_ID 3465401) (firstname "Oliver") (initial "O") (surname "Dittrich-Breiholz")) ([GK_3465402] of Summation (_displayName "Following recruitment to the DISC, FLIP(L) forms a heterodim...") (DB_ID 3465402) (literatureReference [GK_1267757] [GK_3465405] [GK_3465422] [GK_3465503] [GK_3465393]) (text "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 TNF-R1 signaling via interaction with the DED of FADD. The regulatory function of FLIP(L) has been found to differ depending on its expression levels. c-FLIP 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 (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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Cell Biol.") (pages "369-80") (pubMedIdentifier 15289496) (title "NFkappaB activation by Fas is mediated through FADD, caspase-8, and RIP and is inhibited by FLIP") (volume 166) (year 2004)) ([GK_3465477] of Person (_displayName "Fujikawa, Katsuhiko") (DB_ID 3465477) (firstname "Katsuhiko") (initial "K") (surname "Fujikawa")) ([GK_3465478] of LiteratureReference (_displayName "c-FLIP(L) is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis") (author [GK_2984183] [GK_1267808] [GK_3465470] [GK_3465482] [GK_3465364] [GK_3465435] [GK_2984181] [GK_1267777]) (DB_ID 3465478) (journal "EMBO J.") 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Biol. Chem.") (pages "18542-5") (pubMedIdentifier 9228018) (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") (DB_ID 3465489) (firstname "Ottmar") (initial "O") (surname "Janssen")) ([GK_3465490] of Person (_displayName "Beaudouin, Joel") (DB_ID 3465490) (firstname "Joel") (initial "J") (surname "Beaudouin")) ([GK_3465491] of Person (_displayName "Oh, Bermseok") (DB_ID 3465491) (firstname "Bermseok") (initial "B") (surname "Oh")) ([GK_3465492] of Person (_displayName "Micheau, Olivier") (DB_ID 3465492) (firstname "Olivier") (initial "O") (surname "Micheau")) ([GK_3465493] of Person (_displayName "Hockenbery, David M") (DB_ID 3465493) (firstname "David M") (initial "DM") (surname "Hockenbery")) ([GK_3465494] of LiteratureReference (_displayName "Differential responses of FLIPLong and FLIPShort-overexpressing human myeloid leukemia cells to TNF-alpha and TRAIL-initiated apoptotic signals") (author [GK_3465510] [GK_3465493] [GK_3465424] [GK_3465381] [GK_3465506] [GK_3465495]) (DB_ID 3465494) (journal "Exp. 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(pages "1660-72") (pubMedIdentifier 18838202) (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 (_displayName "Deeg, H Joachim") (DB_ID 3465495) (firstname "H Joachim") (initial "HJ") (surname "Deeg")) ([GK_3465496] of Person (_displayName "Schmitz, I") (DB_ID 3465496) (firstname "I") (initial "I") (surname "Schmitz")) ([GK_3465498] of Person (_displayName "Meinander, A") (DB_ID 3465498) (firstname "A") (initial "A") (surname "Meinander")) ([GK_3465499] of Complex (_displayName "[Hsa] FASL:FAS Receptor Trimer:FADD:pro-Caspase-8:FLIP(L) [plasma membrane]") (DB_ID 3465499) (hasComponent [GK_43124] [GK_57031] [GK_3371356]) (name "FASL:FAS Receptor Trimer:FADD:pro-Caspase-8:FLIP(L)") (species [GK_48887]) (stableIdentifier [GK_3655991])) ([GK_3465500] of Person (_displayName "Asaoka, T") (DB_ID 3465500) (firstname "T") (initial "T") (surname "Asaoka")) ([GK_3465502] of Person (_displayName "Nicholson, Donald W") (DB_ID 3465502) (firstname "Donald W") (initial "DW") (surname "Nicholson")) ([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. 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(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 (_displayName "Seal, Sudeshna") (DB_ID 3465510) (firstname "Sudeshna") (initial "S") (surname "Seal")) ([GK_3465511] of Person (_displayName "Rumpf, Jost-Julian") (DB_ID 3465511) (firstname "Jost-Julian") (initial "JJ") (surname "Rumpf")) ([GK_3465518] of InstanceEdit (_displayName "Shamovsky, V, 2013-05-17") (author [GK_429259]) (dateTime "2013-05-17 01:54:44") (DB_ID 3465518)) ([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) (goCellularComponent [GK_161217]) (hasComponent [GK_140977] [GK_57031] [GK_3371356]) (literatureReference [GK_3465412]) (name "TRADD:TRAF2:RIP1:FADD:procaspase-8:FLIP(L)") (species [GK_48887]) (stableIdentifier [GK_3655914])) ([GK_3465558] of Person (_displayName "Brennan, F M") (DB_ID 3465558) (firstname "F M") (initial "FM") (surname "Brennan")) ([GK_3465559] of LiteratureReference (_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") (DB_ID 3465561) (firstname "H J") (initial "HJ") (surname "Robertshaw")) ([GK_3465562] of Summation (_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.")) 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(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" "" "" "HIST1H3B" "H3FL" "" "" "HIST1H3C" "H3FC" "" "" "HIST1H3D" "H3FB" "" "" "HIST1H3E" "H3FD" "" "" "HIST1H3F" "H3FI" "" "" "HIST1H3G" "H3FH" "" "" "HIST1H3H" "H3FK" "" "" "HIST1H3I" "H3FF" "" "" "HIST1H3J" "H3FJ") (identifier "P68431") (isSequenceChanged TRUE) (keyword "3D-structure" "Acetylation" "Chromosome" "Citrullination" "Complete proteome" "Direct protein sequencing" "DNA-binding" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Ubl conjugation") (name "HIST1H3A") (referenceDatabase [GK_2]) (secondaryIdentifier "H31_HUMAN" "A0PJT7" "A5PLR1" "P02295" "P02296" "P16106" "Q6ISV8" "Q6NWP8" "Q6NWP9" "Q6NXU4" "Q71DJ3" "Q93081") (sequenceLength 136) (species [GK_48887])) ([GK_355447] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:Q71DI3 HIST2H3A recommendedName: Histone H3.2 alternativeName: Histone H3/m alternativeName: Histone H3/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. During nucleosome assembly the chaperone ASF1A interacts with the histone H3-H4 heterodimer.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.SIMILARITY Belongs to the histone H3 family.") (DB_ID 355447) (description "recommendedName: Histone H3.2 alternativeName: Histone H3/m alternativeName: Histone H3/o ") (geneName "HIST2H3A" "" "" "HIST2H3C" "H3F2" "H3FM" "" "" "HIST2H3D") (identifier "Q71DI3") (isSequenceChanged TRUE) (keyword "3D-structure" "Acetylation" "Chromosome" "Citrullination" "Complete proteome" "Direct protein sequencing" "DNA-binding" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Polymorphism" "Ubl conjugation") (name "HIST2H3A") (referenceDatabase [GK_2]) (secondaryIdentifier "H32_HUMAN" "A2BDF6" "A6NFS4" "Q6B053") (sequenceLength 136) (species [GK_48887])) ([GK_355448] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:P84243 H3F3A recommendedName: Histone H3.3 ") (checksum "1") (comment "DEVELOPMENTAL STAGE Expressed throughout the cell cycle independently of DNA synthesis.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 Specifically enriched in modifications associated with active chromatin such as methylation at Lys-5 (H3K4me), Lys-37 and Lys-80. 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), which are linked to gene repression, are underrepresented. 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.SIMILARITY Belongs to the histone H3 family.") (DB_ID 355448) (description "recommendedName: Histone H3.3 ") (geneName "H3F3A" "H3.3A" "H3F3" "PP781" "" "" "H3F3B" "H3.3B") (identifier "P84243") (isSequenceChanged TRUE) (keyword "3D-structure" "Acetylation" "Chromosome" "Citrullination" "Complete proteome" "Direct protein sequencing" "DNA-binding" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Ubl conjugation") (name "H3F3A") (referenceDatabase [GK_2]) (secondaryIdentifier "H33_HUMAN" "P06351" "P33155" "Q5VV55" "Q5VV56" "Q66I33" "Q9V3W4") (sequenceLength 136) (species [GK_48887])) ([GK_355449] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:P62805 HIST1H4A recommendedName: Histone H4 ") (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 Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.PTM Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.PTM Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.SIMILARITY Belongs to the histone H4 family.") 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Includes the plasma membrane and any external encapsulating structures such as the cell wall and cell envelope.") (instanceOf [GK_357]) (name "cell") (referenceDatabase [GK_1])) ([GK_357] of GO_CellularComponent (_displayName "cellular_component") (accession "0005575") (DB_ID 357) (definition "The part of a cell or its extracellular environment in which a gene product is located. A gene product may be located in one or more parts of a cell and its location may be as specific as a particular macromolecular complex, that is, a stable, persistent association of macromolecules that function together.") 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(DB_ID 433801) (literatureReference [GK_434101]) (text "Viral dsRNA triggers an antiviral pathway mediated by toll like receptor 3. TLR3 dimerization occurs upon ligand binding to positivly charged residues on the ectodomain termini of TLR3 wich are responsible for the interaction with sugar-phosphate groups of dsRNA.")) ([GK_433806] of Person (_displayName "Liu, L") (DB_ID 433806) (firstname "Lin") (initial "L") (surname "Liu")) ([GK_433833] of Person (_displayName "Leonard, JN") (DB_ID 433833) (firstname "Joshua N") (initial "JN") (surname "Leonard")) ([GK_433849] of LiteratureReference (_displayName "Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-{kappa}B activation but does not contribute to interferon regulatory factor 3 activation") (author [GK_433800] [GK_433888] [GK_378996] [GK_165916] [GK_434069]) (DB_ID 433849) (journal "J Biol Chem") (pages "36560-6") (pubMedIdentifier 16115877) (title "Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-{kappa}B activation but does not contribute to interferon regulatory factor 3 activation") (volume 280) (year 2005)) ([GK_433875] of Person (_displayName "Akazawa, T") (DB_ID 433875) (initial "T") (surname "Akazawa")) ([GK_433888] of Person (_displayName "Khurana, S") (DB_ID 433888) (initial "S") (surname "Khurana")) ([GK_433905] of GenomeEncodedEntity (_displayName "Viral dsRNA (-) Stranded [endosome membrane]") (crossReference [GK_5578725]) (DB_ID 433905) (name "Viral dsRNA (-) Stranded") (stableIdentifier [GK_1110342])) ([GK_433913] of Person (_displayName "Davies, DR") (DB_ID 433913) (firstname "David R") (initial "DR") (surname "Davies")) ([GK_433930] of Summation (_displayName "RIP1 is recruited to the activated TLR receptor by binding t...") (DB_ID 433930) (literatureReference [GK_433849] [GK_937071] [GK_936978] [GK_2569072] [GK_165954]) (text "RIP1 is recruited to the activated TLR receptor by binding to TICAM1(TRIF) via its RHIM motif, followed by its polyubiquitination. Polyubiquitination is possibly mediated by TRAF6 that is also recruited to the TICAM1 [Cusson-Hermance N et al 2005]. Other E3-ubiquitin ligases - cIAP1 and cIAP2 - have been reported to promote polyubiquitination of RIP proteins [Bertrand MJM et al 2011].

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") (checksum "1") (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") (geneName "FGA") (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])) ([GK_5578725] of DatabaseIdentifier (_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" "" "" "HIST1H2AE" "H2AFA") (identifier "P04908") (isSequenceChanged TRUE) (keyword "3D-structure" "Acetylation" "Chromosome" "Citrullination" "Complete proteome" "DNA-binding" "Isopeptide bond" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Ubl conjugation") (name "HIST1H2AB") (referenceDatabase [GK_2]) (secondaryIdentifier "H2A1B_HUMAN" "P28001" "Q76P63") (sequenceLength 130) (species [GK_48887])) ([GK_56148] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:Q16777 HIST2H2AC recommendedName: Histone H2A type 2-C alternativeName: Histone H2A-GL101 alternativeName: Histone H2A/q ") (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 56148) (description "recommendedName: Histone H2A type 2-C alternativeName: Histone H2A-GL101 alternativeName: Histone H2A/q ") (geneName "HIST2H2AC" "H2AFQ") (identifier "Q16777") (isSequenceChanged TRUE) (keyword "Acetylation" "Chromosome" "Citrullination" "Complete proteome" "DNA-binding" "Isopeptide bond" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Ubl conjugation") (name "HIST2H2AC") (referenceDatabase [GK_2]) (secondaryIdentifier "H2A2C_HUMAN" "Q6DRA7" "Q8IUE5") (sequenceLength 129) (species [GK_48887])) ([GK_56152] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:P16104 H2AFX recommendedName: Histone H2A.x shortName:H2a/x ") (checksum "1") (comment "DEVELOPMENTAL STAGE Synthesized in G1 as well as in S-phase.DOMAIN The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family.PTM Monoubiquitination of Lys-120 (H2AXK119ub) by RING1 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Monoubiquitination and ionizing radiation-induced 'Lys-63'-linked ubiquitination are distinct events.SIMILARITY Belongs to the histone H2A family.") (DB_ID 56152) (description "recommendedName: Histone H2A.x shortName:H2a/x ") (geneName "H2AFX" "H2AX") (identifier "P16104") (isSequenceChanged TRUE) (keyword "3D-structure" "Acetylation" "Cell cycle" "Chromosome" "Complete proteome" "DNA damage" "DNA recombination" "DNA repair" "DNA-binding" "Isopeptide bond" "Meiosis" "Nucleosome core" "Nucleus" "Phosphoprotein" "Ubl conjugation") (name "H2AFX") (referenceDatabase [GK_2]) (secondaryIdentifier "H2AX_HUMAN" "Q4ZGJ7" "Q6IAS5") (sequenceLength 143) (species [GK_48887])) ([GK_56164] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:P62807 HIST1H2BC recommendedName: Histone H2B type 1-C/E/F/G/I alternativeName: Histone H2B.1 A alternativeName: Histone H2B.a shortName:H2B/a alternativeName: Histone H2B.a shortName:H2B/a alternativeName: Histone H2B.g shortName:H2B/g alternativeName: Histone H2B.g shortName:H2B/g alternativeName: Histone H2B.h shortName:H2B/h alternativeName: Histone H2B.h shortName:H2B/h alternativeName: Histone H2B.k shortName:H2B/k alternativeName: Histone H2B.k shortName:H2B/k alternativeName: Histone H2B.l shortName:H2B/l alternativeName: Histone H2B.l shortName:H2B/l ") (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 56164) (description "recommendedName: Histone H2B type 1-C/E/F/G/I alternativeName: Histone H2B.1 A alternativeName: Histone H2B.a shortName:H2B/a alternativeName: Histone H2B.a shortName:H2B/a alternativeName: Histone H2B.g shortName:H2B/g alternativeName: Histone H2B.g shortName:H2B/g alternativeName: Histone H2B.h shortName:H2B/h alternativeName: Histone H2B.h shortName:H2B/h alternativeName: Histone H2B.k shortName:H2B/k alternativeName: Histone H2B.k shortName:H2B/k alternativeName: Histone H2B.l shortName:H2B/l alternativeName: Histone H2B.l shortName:H2B/l ") (geneName "HIST1H2BC" "H2BFL" "" "" "HIST1H2BE" "H2BFH" "" "" "HIST1H2BF" "H2BFG" "" "" "HIST1H2BG" "H2BFA" "" "" "HIST1H2BI" "H2BFK") (identifier "P62807") (isSequenceChanged TRUE) (keyword "Acetylation" "Antibiotic" "Antimicrobial" "Chromosome" "Complete proteome" "Direct protein sequencing" "DNA-binding" "Isopeptide bond" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Polymorphism" "Ubl conjugation") (name "HIST1H2BC") (referenceDatabase [GK_2]) (secondaryIdentifier "H2B1C_HUMAN" "P02278" "Q3B872" "Q4VB69" "Q93078" "Q93080") (sequenceLength 126) (species [GK_48887])) ([GK_56168] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:P58876 HIST1H2BD recommendedName: Histone H2B type 1-D alternativeName: HIRA-interacting protein 2 alternativeName: Histone H2B.1 B alternativeName: Histone H2B.b shortName:H2B/b alternativeName: Histone H2B.b shortName:H2B/b ") (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.MISCELLANEOUS The mouse orthologous protein seems not to exist.SIMILARITY Belongs to the histone H2B family.") (DB_ID 56168) (description "recommendedName: Histone H2B type 1-D alternativeName: HIRA-interacting protein 2 alternativeName: Histone H2B.1 B alternativeName: Histone H2B.b shortName:H2B/b alternativeName: Histone H2B.b shortName:H2B/b ") (geneName "HIST1H2BD" "H2BFB" "HIRIP2") (identifier "P58876") (isSequenceChanged TRUE) (keyword "Acetylation" "Chromosome" "Complete proteome" "Direct protein sequencing" "DNA-binding" "Isopeptide bond" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Ubl conjugation") (name "HIST1H2BD") (referenceDatabase [GK_2]) (secondaryIdentifier "H2B1D_HUMAN") (sequenceLength 126) (species [GK_48887])) ([GK_56170] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:Q99880 HIST1H2BL recommendedName: Histone H2B type 1-L alternativeName: Histone H2B.c shortName:H2B/c alternativeName: Histone H2B.c shortName:H2B/c ") (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 56170) (description "recommendedName: Histone H2B type 1-L alternativeName: Histone H2B.c shortName:H2B/c alternativeName: Histone H2B.c shortName:H2B/c ") (geneName "HIST1H2BL" "H2BFC") (identifier "Q99880") (isSequenceChanged TRUE) (keyword "Acetylation" "Chromosome" "Complete proteome" "Direct protein sequencing" "DNA-binding" "Isopeptide bond" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Polymorphism" "Ubl conjugation") (name "HIST1H2BL") (referenceDatabase [GK_2]) (secondaryIdentifier "H2B1L_HUMAN" "B2R5A3" "Q52LW9") (sequenceLength 126) (species [GK_48887])) ([GK_56172] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:Q99877 HIST1H2BN recommendedName: Histone H2B type 1-N alternativeName: Histone H2B.d shortName:H2B/d alternativeName: Histone H2B.d shortName:H2B/d ") (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 56172) (description "recommendedName: Histone H2B type 1-N alternativeName: Histone H2B.d shortName:H2B/d alternativeName: Histone H2B.d shortName:H2B/d ") (geneName "HIST1H2BN" "H2BFD") (identifier "Q99877") (isSequenceChanged TRUE) (keyword "Acetylation" "Chromosome" "Complete proteome" "Direct protein sequencing" "DNA-binding" "Isopeptide bond" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Ubl conjugation") (name "HIST1H2BN") (referenceDatabase [GK_2]) (secondaryIdentifier "H2B1N_HUMAN" "B2R5L4" "Q494S8" "Q96FB7") (sequenceLength 126) (species [GK_48887])) ([GK_56174] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:Q99879 HIST1H2BM recommendedName: Histone H2B type 1-M alternativeName: Histone H2B.e shortName:H2B/e alternativeName: Histone H2B.e shortName:H2B/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 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 56174) (description "recommendedName: Histone H2B type 1-M alternativeName: Histone H2B.e shortName:H2B/e alternativeName: Histone H2B.e shortName:H2B/e ") (geneName "HIST1H2BM" "H2BFE") (identifier "Q99879") (isSequenceChanged TRUE) (keyword "Acetylation" "Chromosome" "Complete proteome" "Direct protein sequencing" "DNA-binding" "Isopeptide bond" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Polymorphism" "Ubl conjugation") (name "HIST1H2BM") (referenceDatabase [GK_2]) (secondaryIdentifier "H2B1M_HUMAN" "Q6NWQ3") (sequenceLength 126) (species [GK_48887])) ([GK_5617433] of Species (_displayName "Rotavirus") (crossReference [GK_5617434]) (DB_ID 5617433) (name "Rotavirus") (superTaxon [GK_5643913])) ([GK_5617434] of DatabaseIdentifier (_displayName "NCBI Taxonomy:10912") (DB_ID 5617434) (identifier "10912") (referenceDatabase [GK_72810])) ([GK_56176] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:P33778 HIST1H2BB recommendedName: Histone H2B type 1-B alternativeName: Histone H2B.1 alternativeName: Histone H2B.f shortName:H2B/f alternativeName: Histone H2B.f shortName:H2B/f ") (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 56176) (description "recommendedName: Histone H2B type 1-B alternativeName: Histone H2B.1 alternativeName: Histone H2B.f shortName:H2B/f alternativeName: Histone H2B.f shortName:H2B/f ") (geneName "HIST1H2BB" "H2BFF") (identifier "P33778") (isSequenceChanged TRUE) (keyword "Acetylation" "Chromosome" "Complete proteome" "DNA-binding" "Isopeptide bond" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Ubl conjugation") (name "HIST1H2BB") (referenceDatabase [GK_2]) (secondaryIdentifier "H2B1B_HUMAN" "Q4KN36") (sequenceLength 126) (species [GK_48887])) ([GK_56180] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:Q93079 HIST1H2BH recommendedName: Histone H2B type 1-H alternativeName: Histone H2B.j shortName:H2B/j alternativeName: Histone H2B.j shortName:H2B/j ") (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 56180) (description "recommendedName: Histone H2B type 1-H alternativeName: Histone H2B.j shortName:H2B/j alternativeName: Histone H2B.j shortName:H2B/j ") (geneName "HIST1H2BH" "H2BFJ") (identifier "Q93079") (isSequenceChanged TRUE) (keyword "Acetylation" "Chromosome" "Complete proteome" "Direct protein sequencing" "DNA-binding" "Isopeptide bond" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Ubl conjugation") (name "HIST1H2BH") (referenceDatabase [GK_2]) (secondaryIdentifier "H2B1H_HUMAN" "B2R541" "Q4VB74") (sequenceLength 126) (species [GK_48887])) ([GK_56184] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:P23527 HIST1H2BO recommendedName: Histone H2B type 1-O alternativeName: Histone H2B.2 alternativeName: Histone H2B.n shortName:H2B/n alternativeName: Histone H2B.n shortName:H2B/n ") (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.MISCELLANEOUS The mouse orthologous protein seems not to exist.SIMILARITY Belongs to the histone H2B family.") (DB_ID 56184) (description "recommendedName: Histone H2B type 1-O alternativeName: Histone H2B.2 alternativeName: Histone H2B.n shortName:H2B/n alternativeName: Histone H2B.n shortName:H2B/n ") (geneName "HIST1H2BO" "H2BFH" "H2BFN") (identifier "P23527") (isSequenceChanged TRUE) (keyword "Acetylation" "Chromosome" "Complete proteome" "Direct protein sequencing" "DNA-binding" "Isopeptide bond" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Ubl conjugation") (name "HIST1H2BO") (referenceDatabase [GK_2]) (secondaryIdentifier "H2B1O_HUMAN" "Q3KPI7" "Q8TCV6") (sequenceLength 126) (species [GK_48887])) ([GK_56186] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:Q16778 HIST2H2BE recommendedName: Histone H2B type 2-E alternativeName: Histone H2B-GL105 alternativeName: Histone H2B.q shortName:H2B/q alternativeName: Histone H2B.q shortName:H2B/q ") (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 56186) (description "recommendedName: Histone H2B type 2-E alternativeName: Histone H2B-GL105 alternativeName: Histone H2B.q shortName:H2B/q alternativeName: Histone H2B.q shortName:H2B/q ") (geneName "HIST2H2BE" "H2BFQ") (identifier "Q16778") (isSequenceChanged TRUE) (keyword "Acetylation" "Antibiotic" "Antimicrobial" "Chromosome" "Complete proteome" "Direct protein sequencing" "DNA-binding" "Isopeptide bond" "Methylation" "Nucleosome core" "Nucleus" "Phosphoprotein" "Ubl conjugation") (name "HIST2H2BE") (referenceDatabase [GK_2]) (secondaryIdentifier "H2B2E_HUMAN" "A3KMC7" "A8K110" "Q4KMY1" "Q5QNX0" "Q9UE88") (sequenceLength 126) (species [GK_48887])) ([GK_56188] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:P06899 HIST1H2BJ recommendedName: Histone H2B type 1-J alternativeName: Histone H2B.1 alternativeName: Histone H2B.r shortName:H2B/r alternativeName: Histone H2B.r shortName:H2B/r ") (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.") 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(pages "101-6") (pubMedIdentifier 14759524) (title "The solution structure of the SODD BAG domain reveals additional electrostatic interactions in the HSP70 complexes of SODD subfamily BAG domains") (volume 558) (year 2004)) ([GK_5657694] of Summation (_displayName "BAG4, also known as silencer of death domain (SODD), belongs...") (DB_ID 5657694) (literatureReference [GK_5657708] [GK_5657695] [GK_5657697] [GK_5657711] [GK_5657693] [GK_5657681] [GK_5657731] [GK_5657729] [GK_5657704] [GK_5692356] [GK_5692336]) (text "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: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.") 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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.") 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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" "" "" "SAA2") (identifier "P02735") (isSequenceChanged TRUE) (keyword "Acute phase" "Amyloid" "Amyloidosis" "Complete proteome" "Direct protein sequencing" "HDL" "Methylation" "Polymorphism" "Secreted" "Signal") (name "SAA1") (referenceDatabase [GK_2]) (secondaryIdentifier "SAA_HUMAN" "P02736" "P02737" "Q16730" "Q16834" "Q16835" "Q16879" "Q3KRB3" "Q6FG67" "Q96QN0" "Q9UCK9" "Q9UCL0") (sequenceLength 122) (species [GK_48887])) ([GK_64128] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:P02743 APCS recommendedName: Serum amyloid P-component shortName:SAP alternativeName: 9.5S alpha-1-glycoprotein component recommendedName: Serum amyloid P-component(1-203) /component") (checksum "1") (comment "FUNCTION Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells. May also function as a calcium-dependent lectin.COFACTOR Binds 2 calcium ions per subunit.SUBUNIT Homopentamer. Pentaxin (or pentraxin) have a discoid arrangement of 5 non-covalently bound subunits.DISEASE Note=SAP is a precursor of amyloid component P which is found in basement membrane and associated with amyloid deposits.SIMILARITY Belongs to the pentaxin family.SIMILARITY Contains 1 pentaxin domain.") (DB_ID 64128) (description "recommendedName: Serum amyloid P-component shortName:SAP alternativeName: 9.5S alpha-1-glycoprotein component recommendedName: Serum amyloid P-component(1-203) /component") (geneName "APCS" "PTX2") (identifier "P02743") (isSequenceChanged TRUE) (keyword "3D-structure" "Acetylation" "Amyloid" "Calcium" "Complete proteome" "Direct protein sequencing" "Disulfide bond" "Glycoprotein" "Lectin" "Metal-binding" "Phosphoprotein" "Polymorphism" "Secreted" "Signal") (name "APCS") (referenceDatabase [GK_2]) (secondaryIdentifier "SAMP_HUMAN") (sequenceLength 223) (species [GK_48887])) ([GK_64296] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:P04279 SEMG1 recommendedName: Semenogelin-1 alternativeName: Semenogelin I shortName:SGI alternativeName: Semenogelin I shortName:SGI component recommendedName: Alpha-inhibin-92 /component component recommendedName: Alpha-inhibin-31 /component component recommendedName: Seminal basic protein /component") (checksum "1") (comment "FUNCTION Predominant protein in semen. It participates in the formation of a gel matrix entrapping the accessory gland secretions and ejaculated spermatozoa. Fragments of semenogelin and/or fragments of the related proteins may contribute to the activation of progressive sperm movements as the gel-forming proteins are fragmented by KLK3/PSA.FUNCTION Alpha-inhibin-92 and alpha-inhibin-31, derived from the proteolytic degradation of semenogelin, inhibit the secretion of pituitary follicle-stimulating hormone.SUBUNIT Occurs in disulfide-linked complexes which may also contain two less abundant 71- and 76-kDa semenogelin-related polypeptides.TISSUE SPECIFICITY Seminal vesicle.PTM Transglutaminase substrate.PTM Rapidly cleaved after ejaculation by KLK3/PSA, resulting in liquefaction of the semen coagulum and the progressive release of motile spermatozoa.SIMILARITY Belongs to the semenogelin family.") (DB_ID 64296) (description "recommendedName: Semenogelin-1 alternativeName: Semenogelin I shortName:SGI alternativeName: Semenogelin I shortName:SGI component recommendedName: Alpha-inhibin-92 /component component recommendedName: Alpha-inhibin-31 /component component recommendedName: Seminal basic protein /component") (geneName "SEMG1" "SEMG") (identifier "P04279") (isSequenceChanged TRUE) (keyword "Alternative splicing" "Complete proteome" "Direct protein sequencing" "Disulfide bond" "Polymorphism" "Pyrrolidone carboxylic acid" "Repeat" "Secreted" "Signal") (name "SEMG1") (referenceDatabase [GK_2]) (secondaryIdentifier "SEMG1_HUMAN" "Q53ZV0" "Q53ZV1" "Q53ZV2" "Q6X4I9" "Q6Y809" "Q6Y822" "Q6Y823" "Q86U64" "Q96QM3") (sequenceLength 462) (species [GK_48887])) ([GK_6486] of GO_CellularComponent (_displayName "host") (accession "0018995") (DB_ID 6486) (definition "Any organism in which another organism, especially a parasite or symbiont, spends part or all of its life cycle and from which it obtains nourishment and/or protection.") (instanceOf [GK_447576]) (name "host") (referenceDatabase [GK_1])) ([GK_6542] of GO_BiologicalProcess (_displayName "induction of apoptosis") (accession "0006917") (DB_ID 6542) (definition "A process that directly activates any of the steps required for cell death by apoptosis.") (name "induction of apoptosis") (referenceDatabase [GK_1])) ([GK_6543] of GO_BiologicalProcess (_displayName "induction of programmed cell death") (accession "0012502") (DB_ID 6543) (definition "A process which directly activates any of the steps required for programmed cell death.") (name "induction of programmed cell death") (referenceDatabase [GK_1])) ([GK_65462] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:P37840 SNCA recommendedName: Alpha-synuclein alternativeName: Non-A beta component of AD amyloid alternativeName: Non-A4 component of amyloid precursor shortName:NACP alternativeName: Non-A4 component of amyloid precursor shortName:NACP ") (checksum "1") (comment "FUNCTION May be involved in the regulation of dopamine release and transport. Induces fibrillization of microtubule-associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase-3 activation.TISSUE SPECIFICITY Expressed principally in brain but is also expressed in low concentrations in all tissues examined except in liver. Concentrated in presynaptic nerve terminals.PTM Hallmark lesions of neurodegenerative synucleinopathies contain alpha-synuclein that is modified by nitration of tyrosine residues and possibly by dityrosine cross-linking to generated stable oligomers.DISEASE Note=Genetic alterations of SNCA resulting in aberrant polymerization into fibrils, are associated with several neurodegenerative diseases (synucleinopathies). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimer disease amyloid plaque, and a major component of Lewy body inclusions. They are also found within Lewy body (LB)-like intraneuronal inclusions, glial inclusions and axonal spheroids in neurodegeneration with brain iron accumulation type 1.DISEASE Defects in SNCA are the cause of Parkinson disease type 4 (PARK4) [MIM:605543]. A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia.DISEASE Defects in SNCA are the cause of dementia Lewy body (DLB) [MIM:127750]. A neurodegenerative disorder clinically characterized by mental impairment leading to dementia, parkinsonism, often with fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease.SIMILARITY Belongs to the synuclein family.") (DB_ID 65462) (description "recommendedName: Alpha-synuclein alternativeName: Non-A beta component of AD amyloid alternativeName: Non-A4 component of amyloid precursor shortName:NACP alternativeName: Non-A4 component of amyloid precursor shortName:NACP ") (geneName "SNCA" "NACP" "PARK1") (identifier "P37840") (isSequenceChanged TRUE) (keyword "3D-structure" "Alternative splicing" "Alzheimer disease" "Amyloid" "Cell junction" "Complete proteome" "Cytoplasm" "Direct protein sequencing" "Disease mutation" "Membrane" "Neurodegeneration" "Nucleus" "Parkinson disease" "Parkinsonism" "Phosphoprotein" "Repeat" "Synapse" "Ubl conjugation") (name "SNCA") (referenceDatabase [GK_2]) (secondaryIdentifier "SYUA_HUMAN" "A8K2A4" "Q13701" "Q4JHI3" "Q6IAU6") (sequenceLength 140) (species [GK_48887])) ([GK_65504] of ReferenceGeneProduct (_chainChangeLog "signal peptide:1-23 added on Fri February 6 2015;chain:24-468 added on Fri February 6 2015") (_displayName "[Hsa] UniProt:O00220 TNFRSF10A recommendedName: Tumor necrosis factor receptor superfamily member 10A alternativeName: Death receptor 4 alternativeName: TNF-related apoptosis-inducing ligand receptor 1 shortName:TRAIL receptor 1 shortName:TRAIL-R1 cdAntigenNameCD261/cdAntigenName") (chain "signal peptide:1-23" "chain:24-468") (checksum "7E96619D0BDC0CD4") (comment "TISSUE SPECIFICITY Widely expressed. High levels are found in spleen, peripheral blood leukocytes, small intestine and thymus, but also in K-562 erythroleukemia cells, MCF-7 breast carcinoma cells and activated T-cells.") (DB_ID 65504) (description "recommendedName: Tumor necrosis factor receptor superfamily member 10A alternativeName: Death receptor 4 alternativeName: TNF-related apoptosis-inducing ligand receptor 1 shortName:TRAIL receptor 1 shortName:TRAIL-R1 cdAntigenNameCD261/cdAntigenName") (geneName "TNFRSF10A" "APO2" "DR4" "TRAILR1") (identifier "O00220") (isSequenceChanged FALSE) (keyword "Apoptosis" "Complete proteome" "Disulfide bond" "Glycoprotein" "Membrane" "Phosphoprotein" "Polymorphism" "Receptor" "Reference proteome" "Repeat" "Signal" "Transmembrane" "Transmembrane helix") (name "TNFRSF10A") (referenceDatabase [GK_2]) (secondaryIdentifier "TR10A_HUMAN" "A8K5I4" "Q53Y72" "Q96E62") (sequenceLength 468) (species [GK_48887])) ([GK_65505] of EntityWithAccessionedSequence (_displayName "[Hsa] TNFRSF10B [plasma membrane]") (DB_ID 65505) (endCoordinate 440) (name "TNFRSF10B" "TRAIL receptor-2" "Tumor necrosis factor receptor superfamily member 10B precursor (Death receptor 5) (TNF-related apoptosis-inducing ligand receptor 2) (TRAIL receptor-2) (TRAIL-R2)" "Tumor necrosis factor receptor superfamily member 10B precursor" "Death receptor 5" "TNF-related apoptosis-inducing ligand receptor 2" "TRAIL-R2") (referenceEntity [GK_65506]) (species [GK_48887]) (stableIdentifier [GK_371450]) (startCoordinate 56)) ([GK_65506] of ReferenceGeneProduct (_chainChangeLog "signal peptide:1-55 added on Fri February 6 2015;chain:56-440 added on Fri February 6 2015") (_displayName "[Hsa] UniProt:O14763 TNFRSF10B recommendedName: Tumor necrosis factor receptor superfamily member 10B alternativeName: Death receptor 5 alternativeName: TNF-related apoptosis-inducing ligand receptor 2 shortName:TRAIL receptor 2 shortName:TRAIL-R2 cdAntigenNameCD262/cdAntigenName") (chain "signal peptide:1-55" "chain:56-440") (checksum "60358EAF2A835870") (comment "TISSUE SPECIFICITY Widely expressed in adult and fetal tissues; very highly expressed in tumor cell lines such as HeLaS3, K-562, HL-60, SW480, A-549 and G-361; highly expressed in heart, peripheral blood lymphocytes, liver, pancreas, spleen, thymus, prostate, ovary, uterus, placenta, testis, esophagus, stomach and throughout the intestinal tract; not detectable in brain.") (DB_ID 65506) (description "recommendedName: Tumor necrosis factor receptor superfamily member 10B alternativeName: Death receptor 5 alternativeName: TNF-related apoptosis-inducing ligand receptor 2 shortName:TRAIL receptor 2 shortName:TRAIL-R2 cdAntigenNameCD262/cdAntigenName") (geneName "TNFRSF10B" "DR5" "KILLER" "TRAILR2" "TRICK2" "ZTNFR9" "UNQ160/PRO186") (identifier "O14763") (isSequenceChanged FALSE) (keyword "3D-structure" "Alternative splicing" "Apoptosis" "Complete proteome" "Direct protein sequencing" "Disulfide bond" "Membrane" "Polymorphism" "Receptor" "Reference proteome" "Repeat" "Signal" "Transmembrane" "Transmembrane helix") (name "TNFRSF10B") (referenceDatabase [GK_2]) (secondaryIdentifier "TR10B_HUMAN" "O14720" "O15508" "O15517" "O15531" "Q6UXM8" "Q7Z360" "Q9BVE0") (sequenceLength 440) (species [GK_48887])) ([GK_66105] of ReferenceGeneProduct (_chainChangeLog "signal peptide:1-23 added on Fri February 6 2015;chain:24-904 added on Fri February 6 2015") (_displayName "[Hsa] UniProt:O15455 TLR3 recommendedName: Toll-like receptor 3 cdAntigenNameCD283/cdAntigenName") (chain "signal peptide:1-23" "chain:24-904") (checksum "034E05ECA7A4D2F7") (comment "DOMAIN ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18.POLYMORPHISM The Phe-412 allele (dbSNP:rs3775291) occurs with a frequency of 30% in populations with European and Asian ancestry, and confers some natural resistance to HIV-1 infection.") (DB_ID 66105) (description "recommendedName: Toll-like receptor 3 cdAntigenNameCD283/cdAntigenName") (geneName "TLR3") (identifier "O15455") (isSequenceChanged FALSE) (keyword "3D-structure" "Alternative splicing" "Complete proteome" "Direct protein sequencing" "Disease mutation" "Disulfide bond" "Endoplasmic reticulum" "Endosome" "Glycoprotein" "Immunity" "Inflammatory response" "Innate immunity" "Leucine-rich repeat" "Membrane" "Phosphoprotein" "Polymorphism" "Receptor" "Reference proteome" "Repeat" "RNA-binding" "Signal" "Transmembrane" "Transmembrane helix") (name "TLR3") (referenceDatabase [GK_2]) (secondaryIdentifier "TLR3_HUMAN" "B2RAI7" "B7Z7K0" "E6Y0F0" "E6Y0F1" "E9PGH4" "Q4VAL2" "Q504W0") (sequenceLength 904) (species [GK_48887])) ([GK_66107] of ReferenceGeneProduct (_chainChangeLog "signal peptide:1-23 added on Sat February 7 2015;chain:24-839 added on Sat February 7 2015") (_displayName "[Hsa] UniProt:O00206 TLR4 recommendedName: Toll-like receptor 4 alternativeName: hToll cdAntigenNameCD284/cdAntigenName") (chain "signal peptide:1-23" "chain:24-839") (checksum "92C48F55821133E8") (comment "TISSUE SPECIFICITY Highly expressed in placenta, spleen and peripheral blood leukocytes. Detected in monocytes, macrophages, dendritic cells and several types of T-cells.DOMAIN The TIR domain mediates interaction with NOX4.POLYMORPHISM Allele TLR4*B (Gly-299, Ile-399) is associated with a blunted response to inhaled LPS.MISCELLANEOUS His-456 and His-458 are found in TLR4 of human and several other primate species and may be responsible for inflammatory responses triggered by nickel (Ni(2+)). Ni(2+) may cross-link the two receptor monomers through specific histidines, triggering the formation of a dimer that structurally resembles that induced by LPS. This process may be the basis for the development of contact allergy to Ni(2+). A mouse model of contact allergy to Ni(2+) in which TLR4-deficient mice expresses human TLR4 has been proposed.") (DB_ID 66107) (description "recommendedName: Toll-like receptor 4 alternativeName: hToll cdAntigenNameCD284/cdAntigenName") (geneName "TLR4") (identifier "O00206") (isSequenceChanged FALSE) (keyword "3D-structure" "Age-related macular degeneration" "Alternative splicing" "Cell membrane" "Complete proteome" "Direct protein sequencing" "Disulfide bond" "Glycoprotein" "Immunity" "Inflammatory response" "Innate immunity" "Leucine-rich repeat" "Membrane" "Polymorphism" "Receptor" "Reference proteome" "Repeat" "Signal" "Transmembrane" "Transmembrane helix") (name "TLR4") (referenceDatabase [GK_2]) (secondaryIdentifier "TLR4_HUMAN" "A8K1Y8" "A9XLP9" "A9XLQ0" "A9XLQ1" "B4E194" "D1CS52" "D1CS53" "Q5VZI8" "Q5VZI9" "Q9UK78" "Q9UM57") (sequenceLength 839) (species [GK_48887])) ([GK_66186] of EntityWithAccessionedSequence (_displayName "[Hsa] TNFSF10 [extracellular region]") (DB_ID 66186) (endCoordinate 281) (name "TNFSF10" "TRAIL" "Tumor necrosis factor ligand superfamily member 10 (TNF-related apoptosis inducing ligand) (TRAIL protein) (Apo-2 ligand) (Apo-2L)" "Tumor necrosis factor ligand superfamily member 10" "TNF-related apoptosis inducing ligand" "TRAIL protein" "Apo-2 ligand" "Apo-2L") (referenceEntity [GK_66187]) (species [GK_48887]) (stableIdentifier [GK_366902]) (startCoordinate 1)) ([GK_66187] of ReferenceGeneProduct (_chainChangeLog "chain:1-281 added on Sat February 7 2015") (_displayName "[Hsa] UniProt:P50591 TNFSF10 recommendedName: Tumor necrosis factor ligand superfamily member 10 alternativeName: Apo-2 ligand shortName:Apo-2L alternativeName: TNF-related apoptosis-inducing ligand shortName:Protein TRAIL cdAntigenNameCD253/cdAntigenName") (chain "chain:1-281") (checksum "DDAAAF78DAAB2F6D") (comment "FUNCTION Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG. Induces apoptosis. Its activity may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and TNFRSF11B/OPG that cannot induce apoptosis.SUBUNIT Homotrimer.TISSUE SPECIFICITY Widespread; most predominant in spleen, lung and prostate.") (DB_ID 66187) (description "recommendedName: Tumor necrosis factor ligand superfamily member 10 alternativeName: Apo-2 ligand shortName:Apo-2L alternativeName: TNF-related apoptosis-inducing ligand shortName:Protein TRAIL cdAntigenNameCD253/cdAntigenName") (geneName "TNFSF10" "APO2L" "TRAIL") (identifier "P50591") (isSequenceChanged FALSE) (keyword "3D-structure" "Alternative splicing" "Apoptosis" "Complete proteome" "Cytokine" "Membrane" "Metal-binding" "Phosphoprotein" "Polymorphism" "Reference proteome" "Signal-anchor" "Transmembrane" "Transmembrane helix" "Zinc") (name "TNFSF10") (referenceDatabase [GK_2]) (secondaryIdentifier "TNF10_HUMAN" "A1Y9B3") (sequenceLength 281) (species [GK_48887])) ([GK_66212] of EntityWithAccessionedSequence (_displayName "[Hsa] FASLG(1-281) [extracellular region]") (DB_ID 66212) (endCoordinate 281) (name "FASLG(1-281)" "FASL" "Tumor necrosis factor ligand superfamily member 6 (FAS antigen ligand) (Apoptosis antigen ligand) (APTL) (CD178 antigen)" "Tumor necrosis factor ligand superfamily member 6" "FAS antigen ligand" "Apoptosis antigen ligand" "APTL" "CD178 antigen") (referenceEntity [GK_66213]) (species [GK_48887]) (stableIdentifier [GK_364838]) (startCoordinate 1)) ([GK_66213] of ReferenceGeneProduct (_chainChangeLog "chain:1-281 added on Sat February 7 2015;chain:1-129 added on Sat February 7 2015;chain:1-81 added on Sat February 7 2015;chain:130-281 added on Sat February 7 2015") (_displayName "[Hsa] UniProt:P48023 FASLG recommendedName: Tumor necrosis factor ligand superfamily member 6 alternativeName: Apoptosis antigen ligand shortName:APTL alternativeName: CD95 ligand shortName:CD95-L alternativeName: Fas antigen ligand shortName:Fas ligand shortName:FasL cdAntigenNameCD178/cdAntigenName component recommendedName: Tumor necrosis factor ligand superfamily member 6, membrane form /component component recommendedName: Tumor necrosis factor ligand superfamily member 6, soluble form alternativeName: Receptor-binding FasL ectodomain alternativeName: Soluble Fas ligand shortName:sFasL /component component recommendedName: ADAM10-processed FasL form shortName:APL /component component recommendedName: FasL intracellular domain shortName:FasL ICD alternativeName: SPPL2A-processed FasL form shortName:SPA /component") (chain "chain:1-281" "chain:1-129" "chain:1-81" "chain:130-281") (checksum "A8A6EB358246E9BB") (comment "PTM N-glycosylated.PTM Monoubiquitinated.") (DB_ID 66213) (description "recommendedName: Tumor necrosis factor ligand superfamily member 6 alternativeName: Apoptosis antigen ligand shortName:APTL alternativeName: CD95 ligand shortName:CD95-L alternativeName: Fas antigen ligand shortName:Fas ligand shortName:FasL cdAntigenNameCD178/cdAntigenName component recommendedName: Tumor necrosis factor ligand superfamily member 6, membrane form /component component recommendedName: Tumor necrosis factor ligand superfamily member 6, soluble form alternativeName: Receptor-binding FasL ectodomain alternativeName: Soluble Fas ligand shortName:sFasL /component component recommendedName: ADAM10-processed FasL form shortName:APL /component component recommendedName: FasL intracellular domain shortName:FasL ICD alternativeName: SPPL2A-processed FasL form shortName:SPA /component") (geneName "FASLG" "APT1LG1" "CD95L" "FASL" "TNFSF6") (identifier "P48023") (isSequenceChanged FALSE) (keyword "3D-structure" "Alternative splicing" "Apoptosis" "Cell membrane" "Complete proteome" "Cytokine" "Cytoplasmic vesicle" "Disulfide bond" "Glycoprotein" "Lysosome" "Membrane" "Nucleus" "Polymorphism" "Reference proteome" "Repressor" "Secreted" "Signal-anchor" "Transcription" "Transcription regulation" "Transmembrane" "Transmembrane helix" "Ubl conjugation") (name "FASLG") (referenceDatabase [GK_2]) (secondaryIdentifier "TNFL6_HUMAN" "Q9BZP9") (sequenceLength 281) (species [GK_48887])) ([GK_66220] of EntityWithAccessionedSequence (_displayName "[Hsa] TNF(1-233) [plasma membrane]") (DB_ID 66220) (endCoordinate 233) (name "TNF(1-233)" "TNF-alpha" "Tumor necrosis factor precursor (TNF-alpha) (Tumor necrosis factor ligand superfamily member 2) (Cachectin)" "Tumor necrosis factor precursor" "Tumor necrosis factor ligand superfamily member 2" "TNF-a" "Cachectin") (referenceEntity [GK_66221]) (species [GK_48887]) (stableIdentifier [GK_370748]) (startCoordinate 1)) ([GK_66221] of ReferenceGeneProduct (_chainChangeLog "chain:1-233 added on Fri February 6 2015;chain:1-39 added on Fri February 6 2015;chain:1-35 added on Fri February 6 2015;chain:50- added on Fri February 6 2015;chain:52- added on Fri February 6 2015;chain:77-233 added on Fri February 6 2015") (_displayName "[Hsa] UniProt:P01375 TNF recommendedName: Tumor necrosis factor alternativeName: Cachectin alternativeName: TNF-alpha alternativeName: Tumor necrosis factor ligand superfamily member 2 shortName:TNF-a component recommendedName: Tumor necrosis factor, membrane form alternativeName: N-terminal fragment shortName:NTF /component component recommendedName: Intracellular domain 1 shortName:ICD1 /component component recommendedName: Intracellular domain 2 shortName:ICD2 /component component recommendedName: C-domain 1 /component component recommendedName: C-domain 2 /component component recommendedName: Tumor necrosis factor, soluble form /component") (chain "chain:1-233" "chain:1-39" "chain:1-35" "chain:50-" "chain:52-" "chain:77-233") (checksum "3DF90F96C9031FFE") (comment "POLYMORPHISM Genetic variations in TNF influence susceptibility to hepatitis B virus (HBV) infection [MIM:610424].POLYMORPHISM Genetic variations in TNF are involved in susceptibility to malaria [MIM:611162].") (DB_ID 66221) (description "recommendedName: Tumor necrosis factor alternativeName: Cachectin alternativeName: TNF-alpha alternativeName: Tumor necrosis factor ligand superfamily member 2 shortName:TNF-a component recommendedName: Tumor necrosis factor, membrane form alternativeName: N-terminal fragment shortName:NTF /component component recommendedName: Intracellular domain 1 shortName:ICD1 /component component recommendedName: Intracellular domain 2 shortName:ICD2 /component component recommendedName: C-domain 1 /component component recommendedName: C-domain 2 /component component recommendedName: Tumor necrosis factor, soluble form /component") (geneName "TNF" "TNFA" "TNFSF2") (identifier "P01375") (isSequenceChanged FALSE) (keyword "3D-structure" "Cell membrane" "Complete proteome" "Cytokine" "Direct protein sequencing" "Disulfide bond" "Glycoprotein" "Lipoprotein" "Membrane" "Myristate" "Phosphoprotein" "Polymorphism" "Reference proteome" "Secreted" "Signal-anchor" "Transmembrane" "Transmembrane helix") (name "TNF") (referenceDatabase [GK_2]) (secondaryIdentifier "TNFA_HUMAN" "O43647" "Q9P1Q2" "Q9UIV3") (sequenceLength 233) (species [GK_48887])) ([GK_66248] of EntityWithAccessionedSequence (_displayName "[Hsa] FAS [plasma membrane]") (DB_ID 66248) (endCoordinate 335) (name "FAS" "FAS Receptor" "Tumor necrosis factor receptor superfamily member 6 precursor (FASL receptor) (Apoptosis-mediating surface antigen FAS) (Apo-1 antigen) (CD95)" "Tumor necrosis factor receptor superfamily member 6 precursor" "FASL receptor" "Apoptosis-mediating surface antigen FAS" "Apo-1 antigen" "CD95") (referenceEntity [GK_66249]) (species [GK_48887]) (stableIdentifier [GK_364006]) (startCoordinate 26)) ([GK_66249] of ReferenceGeneProduct (_chainChangeLog "signal peptide:1-25 added on Fri February 6 2015;chain:26-335 added on Fri February 6 2015") (_displayName "[Hsa] UniProt:P25445 FAS recommendedName: Tumor necrosis factor receptor superfamily member 6 alternativeName: Apo-1 antigen alternativeName: Apoptosis-mediating surface antigen FAS alternativeName: FASLG receptor cdAntigenNameCD95/cdAntigenName") (chain "signal peptide:1-25" "chain:26-335") (checksum "0139942535111410") (comment "DOMAIN Contains a death domain involved in the binding of FADD, and maybe to other cytosolic adapter proteins.") (DB_ID 66249) (description "recommendedName: Tumor necrosis factor receptor superfamily member 6 alternativeName: Apo-1 antigen alternativeName: Apoptosis-mediating surface antigen FAS alternativeName: FASLG receptor cdAntigenNameCD95/cdAntigenName") (geneName "FAS" "APT1" "FAS1" "TNFRSF6") (identifier "P25445") (isSequenceChanged FALSE) (keyword "3D-structure" "Alternative splicing" "Apoptosis" "Cell membrane" "Complete proteome" "Direct protein sequencing" "Disease mutation" "Disulfide bond" "Glycoprotein" "Membrane" "Phosphoprotein" "Polymorphism" "Receptor" "Reference proteome" "Repeat" "Secreted" "Signal" "Transmembrane" "Transmembrane helix") (name "FAS") (referenceDatabase [GK_2]) (secondaryIdentifier "TNR6_HUMAN" "A9UJX4" "B6VNV4" "Q14292" "Q14293" "Q14294" "Q14295" "Q16652" "Q5T9P1" "Q5T9P2" "Q5T9P3" "Q6SSE9") (sequenceLength 335) (species [GK_48887])) ([GK_66344] of EntityWithAccessionedSequence (_displayName "[Hsa] TNFRSF1A(22-455) [plasma membrane]") (DB_ID 66344) (endCoordinate 455) (name "TNFRSF1A(22-455)" "TNF-RI" "Tumor necrosis factor receptor superfamily member 1A precursor (p60) (TNF-R1) (TNF-RI) (p55) (CD120a) (Contains: Tumor necrosis factor binding protein 1 (TBPI))" "Tumor necrosis factor receptor superfamily member 1A precursor" "p60" "TNF-R1" "p55" "CD120a" "Tumor necrosis factor binding protein 1" "TBPI") (referenceEntity [GK_66345]) (species [GK_48887]) (stableIdentifier [GK_368490]) (startCoordinate 22)) ([GK_66345] of ReferenceGeneProduct (_chainChangeLog "signal peptide:1-21 added on Fri February 6 2015;chain:22-455 added on Fri February 6 2015;chain:41-201 added on Fri February 6 2015") (_displayName "[Hsa] UniProt:P19438 TNFRSF1A recommendedName: Tumor necrosis factor receptor superfamily member 1A alternativeName: Tumor necrosis factor receptor 1 shortName:TNF-R1 alternativeName: Tumor necrosis factor receptor type I shortName:TNF-RI shortName:TNFR-I alternativeName: p55 alternativeName: p60 cdAntigenNameCD120a/cdAntigenName component recommendedName: Tumor necrosis factor receptor superfamily member 1A, membrane form /component component recommendedName: Tumor necrosis factor-binding protein 1 shortName:TBPI /component") (chain "signal peptide:1-21" "chain:22-455" "chain:41-201") (checksum "4CEFBA96D03B8225") (comment "FUNCTION Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.DOMAIN The domain that induces A-SMASE is probably identical to the death domain. The N-SMASE activation domain (NSD) is both necessary and sufficient for activation of N-SMASE.PTM The soluble form is produced from the membrane form by proteolytic processing.") (DB_ID 66345) (description "recommendedName: Tumor necrosis factor receptor superfamily member 1A alternativeName: Tumor necrosis factor receptor 1 shortName:TNF-R1 alternativeName: Tumor necrosis factor receptor type I shortName:TNF-RI shortName:TNFR-I alternativeName: p55 alternativeName: p60 cdAntigenNameCD120a/cdAntigenName component recommendedName: Tumor necrosis factor receptor superfamily member 1A, membrane form /component component recommendedName: Tumor necrosis factor-binding protein 1 shortName:TBPI /component") (geneName "TNFRSF1A" "TNFAR" "TNFR1") (identifier "P19438") (isSequenceChanged FALSE) (keyword "3D-structure" "Alternative splicing" "Amyloidosis" "Apoptosis" "Cell membrane" "Cleavage on pair of basic residues" "Complete proteome" "Direct protein sequencing" "Disease mutation" "Disulfide bond" "Glycoprotein" "Golgi apparatus" "Host-virus interaction" "Membrane" "Polymorphism" "Receptor" "Reference proteome" "Repeat" "Secreted" "Signal" "Transmembrane" "Transmembrane helix") (name "TNFRSF1A") (referenceDatabase [GK_2]) (secondaryIdentifier "TNR1A_HUMAN" "A8K4X3" "B2RDE4" "B3KPQ1" "B4DQB7" "B4E309" "B5M0B5" "D3DUR1" "Q9UCA4") (sequenceLength 455) (species [GK_48887])) ([GK_66370] of EntityWithAccessionedSequence (_displayName "[Hsa] TRAF2 [cytosol]") (DB_ID 66370) (endCoordinate 501) (name "TRAF2" "TNF receptor associated factor 2" "Tumor necrosis factor type 2 receptor associated protein 3") (referenceEntity [GK_66371]) (species [GK_48887]) (stableIdentifier [GK_369343]) (startCoordinate 2)) ([GK_66371] of ReferenceGeneProduct (_chainChangeLog "initiator methionine:1 added on Fri February 6 2015;chain:2-501 added on Fri February 6 2015") (_displayName "[Hsa] UniProt:Q12933 TRAF2 recommendedName: TNF receptor-associated factor 2 ecNumber6.3.2.-/ecNumber alternativeName: E3 ubiquitin-protein ligase TRAF2 alternativeName: Tumor necrosis factor type 2 receptor-associated protein 3 ") (chain "initiator methionine:1" "chain:2-501") (checksum "C508BE185B783B20") (comment "PATHWAY Protein modification; protein ubiquitination.") (DB_ID 66371) (description "recommendedName: TNF receptor-associated factor 2 ecNumber6.3.2.-/ecNumber alternativeName: E3 ubiquitin-protein ligase TRAF2 alternativeName: Tumor necrosis factor type 2 receptor-associated protein 3 ") (geneName "TRAF2" "TRAP3") (identifier "Q12933") (isSequenceChanged FALSE) (keyword "3D-structure" "Acetylation" "Alternative splicing" "Apoptosis" "Coiled coil" "Complete proteome" "Cytoplasm" "Isopeptide bond" "Ligase" "Lipid-binding" "Metal-binding" "Phosphoprotein" "Reference proteome" "Repeat" "Ubl conjugation" "Ubl conjugation pathway" "Zinc" "Zinc-finger") (name "TRAF2") (referenceDatabase [GK_2]) (secondaryIdentifier "TRAF2_HUMAN" "A8K107" "B4DPJ7" "Q7Z337" "Q96NT2") (sequenceLength 501) (species [GK_48887])) ([GK_66376] of EntityWithAccessionedSequence (_displayName "[Hsa] TRADD [cytosol]") (DB_ID 66376) (endCoordinate 312) (name "TRADD" "TNFR1-associated DEATH domain protein" "Tumor necrosis factor receptor type 1 associated DEATH domain protein" "TNFRSF1A-associated via death domain") (referenceEntity [GK_66377]) (species [GK_48887]) (stableIdentifier [GK_365494]) (startCoordinate 1)) ([GK_66377] of ReferenceGeneProduct (_chainChangeLog "chain:1-312 added on Sat February 7 2015") (_displayName "[Hsa] UniProt:Q15628 TRADD recommendedName: Tumor necrosis factor receptor type 1-associated DEATH domain protein shortName:TNFR1-associated DEATH domain protein alternativeName: TNFRSF1A-associated via death domain ") (chain "chain:1-312") (checksum "5645D7E63E5FF05A") (comment "TISSUE SPECIFICITY Found in all examined tissues.DOMAIN Requires the intact death domain to associate with TNFRSF1A/TNFR1.") (DB_ID 66377) (description "recommendedName: Tumor necrosis factor receptor type 1-associated DEATH domain protein shortName:TNFR1-associated DEATH domain protein alternativeName: TNFRSF1A-associated via death domain ") (geneName "TRADD") (identifier "Q15628") (isSequenceChanged FALSE) (keyword "3D-structure" "Alternative splicing" "Apoptosis" "Complete proteome" "Cytoplasm" "Cytoskeleton" "Nucleus" "Reference proteome") (name "TRADD") (referenceDatabase [GK_2]) (secondaryIdentifier "TRADD_HUMAN" "B2RDS3" "B3KQZ9" "Q52NZ1") (sequenceLength 312) (species [GK_48887])) ([GK_66401] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:P02788 LTF Lactotransferrin shortName:Lactoferrin alternativeName: Talalactoferrin component recommendedName: Kaliocin-1 /component component recommendedName: Lactoferroxin-A /component component recommendedName: Lactoferroxin-B /component component recommendedName: Lactoferroxin-C /component") (checksum "1") (comment "CATALYTIC ACTIVITY Preferential at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-aminomethylcoumarin.SUBUNIT Monomer.SIMILARITY Belongs to the transferrin family.SIMILARITY Contains 2 transferrin-like domains.") (DB_ID 66401) (description " Lactotransferrin shortName:Lactoferrin alternativeName: Talalactoferrin component recommendedName: Kaliocin-1 /component component recommendedName: Lactoferroxin-A /component component recommendedName: Lactoferroxin-B /component component recommendedName: Lactoferroxin-C /component") (geneName "LTF" "LF") (identifier "P02788") (isSequenceChanged TRUE) (keyword "3D-structure" "Antibiotic" "Antimicrobial" "Complete proteome" "Direct protein sequencing" "Disulfide bond" "Glycoprotein" "Hydrolase" "Ion transport" "Iron" "Iron transport" "Metal-binding" "Phosphoprotein" "Polymorphism" "Protease" "Repeat" "Secreted" "Serine protease" "Signal" "Transport") (name "LTF") (referenceDatabase [GK_2]) (secondaryIdentifier "TRFL_HUMAN" "O00756" "Q16780" "Q16785" "Q16786" "Q16789" "Q8IU92" "Q8IZH6" "Q8TCD2" "Q96KZ4" "Q96KZ5" "Q9H1Z3" "Q9UCY5") (sequenceLength 710) (species [GK_48887])) ([GK_66545] of ReferenceGeneProduct (_displayName "[Hsa] UniProt:P02766 TTR recommendedName: Transthyretin alternativeName: ATTR alternativeName: Prealbumin alternativeName: TBPA ") (checksum "1") (comment "DOMAIN Each monomer has two 4-stranded beta sheets and the shape of a prolate ellipsoid. Antiparallel beta-sheet interactions link monomers into dimers. A short loop from each monomer forms the main dimer-dimer interaction. These two pairs of loops separate the opposed, convex beta-sheets of the dimers to form an internal channel.MISCELLANEOUS Tetramer dissociation and partial unfolding leads to the formation of aggregates and amyloid fibrils. Small molecules that occupy at least one of the thyroid hormone binding sites stabilize the tetramer, and thereby stabilize the native state and protect against misfolding and the formation of amyloid fibrils.MISCELLANEOUS Two binding sites for thyroxine are located in the channel. Less than 1% of plasma prealbumin molecules are normally involved in thyroxine transport. L-thyroxine binds to the transthyretin by an order of magnitude stronger than does the triiodo-L-thyronine. Thyroxine-binding globulin is the major carrier protein for thyroid hormones in man.MISCELLANEOUS About 40% of plasma transthyretin circulates in a tight protein-protein complex with the plasma retinol-binding protein (RBP). The formation of the complex with RBP stabilizes the binding of retinol to RBP and decreases the glomerular filtration and renal catabolism of the relatively small RBP molecule. There is evidence for 2 binding sites for RBP, one possibly being a region that includes Ile-104, located on the outer surface of the transthyretin molecule.SIMILARITY Belongs to the transthyretin family.") 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Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent processing of C80 and C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid beta proteins, amyloid-beta 40 (Abeta40) and amyloid-beta 42 (Abeta42), major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59).PTM Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond. In vitro, the APP-Cu(+) complex in the presence of hydrogen peroxide results in an increased production of beta-amyloid-containing peptides.PTM Beta-amyloid peptides are degraded by IDE.MISCELLANEOUS Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between beta-amyloid molecules resulting in beta-amyloid-metal aggregates. The affinity for copper is much higher than for other transient metals and is increased under acidic conditions. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding.SIMILARITY Belongs to the APP family.SIMILARITY Contains 1 BPTI/Kunitz inhibitor domain.") 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[GK_3371351]) (literatureReference [GK_3371380]) (name "TNF-alpha:TNFR1") (species [GK_48887]) (stableIdentifier [GK_367488])) ([GK_74302] of Summation (_displayName "Once the TNF-alpha:TNFR1:TRADD:RIPK1 complex has been formed...") (DB_ID 74302) (literatureReference [GK_140979]) (text "Once the TNF-alpha:TNFR1:TRADD:RIPK1 complex has been formed there is concomitant recruitment of TRAF2:cIAP1/2 complex and then of the TAB2:TAK1 and the IKK complex. RIPK1 and the TRAF2:cIAP1/2 can be released from TNFR1 receptor complex in a poorly understood process associated with internalization and after that there is the formation of a so called complex II containing the adapter protein FADD, caspase-8 and RIPK1. Complex II has the potential to activate caspase-8 (Micheau O & Tschopp J 2003). The steps leading to the JUN, NF kappaB or apoptotic pathways are rife with opportunities for modulation.")) ([GK_74353] of Summation (_displayName "Once formed in context of the TNFR1 signaling complex the TR...") (DB_ID 74353) (text "Once formed in context of the TNFR1 signaling complex the TRADD:TRAF2:RIPK1 complex may dissociate from the TNF:TNFR1 platform. With the recruitment of FADD and caspase-8 to the TRADD:TRAF2:RIPK1 complex the cell is pushed along the apoptotic pathway provided that the protective FLIP protein and TRAF2-associated BIRC (cIAPs) do not inhibit caspase-8 activation by RIPK1 and RIPK3-mediated activation of the necroptotic pathway.")) ([GK_75114] of Complex (_displayName "[Hsa] FASL:FAS trimer:FADD:CASP8(1-479) [plasma membrane]") (DB_ID 75114) (hasComponent [GK_43124] [GK_57031]) (literatureReference [GK_3465531] [GK_3465522]) (name "FASL:FAS trimer:FADD:CASP8(1-479)") (species [GK_48887]) (stableIdentifier [GK_362769])) ([GK_75146] of Reaction (_displayName "[Hsa] TRAIL:TRAIL Receptor Trimer:FADD complex binds procaspase-8") (_doRelease TRUE) (authored [GK_140952]) (DB_ID 75146) (edited [GK_5633134]) (input [GK_57031] [GK_5637464]) (literatureReference [GK_141128]) (name "TRAIL:TRAIL Receptor Trimer:FADD complex binds procaspase-8") (output [GK_5637468]) (precedingEvent [GK_75187]) (reviewed [GK_3597630]) (revised [GK_5634834]) (species [GK_48887]) (stableIdentifier [GK_359034]) (summation [GK_179247])) ([GK_75157] of Pathway (_displayName "[Hsa] FasL/ CD95L signaling") (_doRelease TRUE) (authored [GK_140480]) (DB_ID 75157) (edited [GK_165085]) (figure [GK_141234]) (goBiologicalProcess [GK_2133497]) (hasEvent 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(stableIdentifier [GK_360371]) (summation [GK_179240])) ([GK_75244] of Reaction (_displayName "[Hsa] FASL binds FAS Receptor") (_doRelease TRUE) (DB_ID 75244) (figure [GK_141237]) (goBiologicalProcess [GK_2133497]) (input [GK_66212] [GK_66248]) (literatureReference [GK_140513]) (name "FASL binds FAS Receptor") (output [GK_76564]) (reviewed [GK_3597630]) (species [GK_48887]) (stableIdentifier [GK_361795]) (summation [GK_178761])) ([GK_75497] of Person (_displayName "Yamamoto, M") (DB_ID 75497) (firstname "M") (initial "M") (surname "Yamamoto")) ([GK_75542] of Person (_displayName "Teplow, DB") (DB_ID 75542) (firstname "D B") (initial "DB") (surname "Teplow")) ([GK_75579] of Person (_displayName "Klisak, I") (DB_ID 75579) (firstname "I") (initial "I") (surname "Klisak")) ([GK_75582] of Person (_displayName "Mohandas, T") (DB_ID 75582) (firstname "T") (initial "T") (surname "Mohandas")) ([GK_75583] of Person (_displayName "Sparkes, RS") (DB_ID 75583) (firstname "R S") (initial "RS") 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"553-7") (pubMedIdentifier 8464497) (title "Human lysozyme gene mutations cause hereditary systemic amyloidosis") (volume 362) (year 1993)) ([GK_976878] of EntityWithAccessionedSequence (_displayName "[Hsa] ABri/ADan amyloid peptide [extracellular region]") (DB_ID 976878) (endCoordinate 266) (name "ABri/ADan amyloid peptide" "Integral membrane protein 2B" "ITM2B_HUMAN" "ITM2B") (referenceEntity [GK_57627]) (species [GK_48887]) (stableIdentifier [GK_1358324]) (startCoordinate 244) (summation [GK_976914])) ([GK_976879] of LiteratureReference (_displayName "Mutation in cystatin C gene causes hereditary brain haemorrhage") (author [GK_976933] [GK_976855] [GK_976909] [GK_976943] [GK_976888] [GK_976938] [GK_976887]) (DB_ID 976879) (journal "Lancet") (pages "603-4") (pubMedIdentifier 2900981) (title "Mutation in cystatin C gene causes hereditary brain haemorrhage") (volume 2) (year 1988)) ([GK_976880] of Person (_displayName "Goto, Y") (DB_ID 976880) (initial "Y") (surname "Goto")) 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(DB_ID 976914) (text "The ABri and ADan peptides are extensions of the normal C terminus of ITM2B (BRI). The sequence of ABri results from mutatin of the normal stop codon to R, resulting in an additional 11 residues. The ABri peptide is the last 34 residues of this mutated peptide - EASNCFAIRHFENKFAVETLICSRTVKKNIIEEN.\nThe ADan peptide is the result of a 10 nucleotide insertion between the codons for residue 265 and 266, introducing a frameshift that adds a different extension to the normal peptide. The ADan peptide is the last 34 residues of this mutated peptide, identical to ABri for the first 22 residues.\n\nEASNCFAIRHFENKFAVETLICFNLFLNSQEKHY ")) ([GK_976915] of Person (_displayName "Plant, G") (DB_ID 976915) (initial "G") (surname "Plant")) ([GK_976916] of Polymer (_displayName "[Hsa] Variant apolipoprotein AII fibril [extracellular region]") (DB_ID 976916) (literatureReference [GK_976913]) (name "Variant apolipoprotein AII fibril") (repeatedUnit [GK_976870]) (species [GK_48887]) (stableIdentifier [GK_1358575])) ([GK_976917] of Person (_displayName "Wetzel, R") (DB_ID 976917) (initial "R") (surname "Wetzel")) ([GK_976918] of Person (_displayName "Hong, DP") (DB_ID 976918) (initial "DP") (surname "Hong")) ([GK_976919] of Polymer (_displayName "[Hsa] Gelsolin amyloid fibril [extracellular region]") (DB_ID 976919) (literatureReference [GK_976852]) (name "Gelsolin amyloid fibril") (repeatedUnit [GK_976940]) (species [GK_48887]) (stableIdentifier [GK_1358387])) ([GK_976920] of Summation (_displayName "Amyloid is a term used to describe typically extracellular d...") (DB_ID 976920) (literatureReference [GK_977172] [GK_1247722] [GK_1247762] [GK_1247745] [GK_1247696] [GK_1247719] [GK_1247704] [GK_1247703] [GK_1247812] [GK_1247715] [GK_1247805]) (text "Amyloid is a term used to describe typically extracellular deposits of aggregated proteins, sometimes known as plaques. Abnormal accumulation of amyloid is amyloidosis, a term associated with diseased organs and tissues, particularly neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntingdon's. Amyloid deposits consist predominantly of amyloid fibrils, rigid, non-branching structures that form ordered assemblies, characteristically with a cross beta-sheet structure where the sheets run parallel to the direction of the fibril (Sawaya et al. 2007). Often the fibril has a left-handed twist (Nelson & Eisenberg 2006). At least 27 human proteins form amyloid fibrils (Sipe et al. 2010). Many of these proteins have non-pathological functions; the trigger that leads to abnormal aggregations differs between proteins and is not well understood but in many cases the peptides are abnormal fragments or mutant forms arising from polymorphisms, suggesting that the initial event may be aggregation of misfolded or unfolded peptides. Early studies of Amyloid-Beta assembly led to a widely accepted model that assembly was a nucleation-dependent polymerization reaction (Teplow 1998) but it is now understood to be more complex, with multiple 'off-pathway' events leading to a variety of oligomeric structures in addition to fibrils (Roychaudhuri et al. 2008). An increasing body of evidence suggests that these oligomeric forms are primarily responsible for the neurotoxic effects of Amyloid-beta (Roychaudhuri et al. 2008), alpha-synuclein (Winner et al. 2011) and tau (Dance & Strobel 2009, Meraz-Rios et al. 2010). Amyloid oligomers are believed to have a common structural motif that is independent of the protein involved and not present in fibrils (Kayed et al. 2003). Conformation dependent, aggregation specific antibodies suggest that there are 3 general classes of amyloid oligomer structures (Glabe 2009) including annular structures which may be responsible for the widely reported membrane permeabilization effect of amyloid oligomers. Toxicity of amyloid oligomers preceeds the appearance of plaques in mouse models (Ferretti et al. 2011). \nFibrils are often associated with other molecules, notably heparan sulfate proteoglycans and Serum Amyloid P-component, which are universally associated and seem to stabilize fibrils, possibly by protecting them from degradation.")) 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apolipoprotein AI as a major constituent of a human hereditary amyloid") (volume 156) (year 1988)) ([GK_976942] of LiteratureReference (_displayName "A new human hereditary amyloidosis: the result of a stop-codon mutation in the apolipoprotein AII gene") (author [GK_976904] [GK_976874] [GK_976886] [GK_194488] [GK_976931] [GK_976861] [GK_976932]) (DB_ID 976942) (journal "Genomics") (pages "272-7") (pubMedIdentifier 11401442) (title "A new human hereditary amyloidosis: the result of a stop-codon mutation in the apolipoprotein AII gene") (volume 72) (year 2001)) ([GK_976943] of Person (_displayName "Arnason, A") (DB_ID 976943) (initial "A") (surname "Arnason")) ([GK_976944] of EntityWithAccessionedSequence (_displayName "[Hsa] Variant lysozyme C [extracellular region]") (DB_ID 976944) (endCoordinate 148) (hasModifiedResidue [GK_976926]) (literatureReference [GK_976877]) (name "Variant lysozyme C" "LYZ" "LYSC_HUMAN" "LYZ") (referenceEntity [GK_58841]) (species [GK_48887]) (stableIdentifier [GK_1357692]) (startCoordinate 19)) ([GK_976945] of Polymer (_displayName "[Hsa] Beta2-microglobulin fibril [extracellular region]") (DB_ID 976945) (literatureReference [GK_976896] [GK_976937]) (name "Beta2-microglobulin fibril") (repeatedUnit [GK_167743]) (species [GK_48887]) (stableIdentifier [GK_1358224])) ([GK_976946] of Person (_displayName "Bergström, J") (DB_ID 976946) (initial "J") (surname "Bergström")) ([GK_976947] of Person (_displayName "Tennent, GA") (DB_ID 976947) (initial "GA") (surname "Tennent")) ([GK_976948] of Person (_displayName "Lelyveld, V") (DB_ID 976948) (initial "V") (surname "Lelyveld")) ([GK_976949] of LiteratureReference (_displayName "Codeposition of apolipoprotein A-IV and transthyretin in senile systemic (ATTR) amyloidosis") (author [GK_976946] [GK_976953] [GK_207287] [GK_976922] [GK_374884] [GK_976858] [GK_976884]) (DB_ID 976949) (journal "Biochem Biophys Res Commun") (pages "903-8") (pubMedIdentifier 11467836) (title "Codeposition of apolipoprotein 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[GK_1358509]) (startCoordinate 1)) ([GK_977561] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2B.b [extracellular region]") (DB_ID 977561) (endCoordinate -1) (name "Histone H2B.b") (referenceEntity [GK_56168]) (species [GK_48887]) (stableIdentifier [GK_1358546]) (startCoordinate 1)) ([GK_977562] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2B.e [extracellular region]") (DB_ID 977562) (endCoordinate -1) (name "Histone H2B.e") (referenceEntity [GK_56174]) (species [GK_48887]) (stableIdentifier [GK_1358096]) (startCoordinate 1)) ([GK_977563] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2A.q [extracellular region]") (DB_ID 977563) (endCoordinate -1) (name "Histone H2A.q") (referenceEntity [GK_56148]) (species [GK_48887]) (stableIdentifier [GK_1358143]) (startCoordinate 1)) ([GK_977564] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2B.a/g/h/k/l [extracellular region]") (DB_ID 977564) (endCoordinate -1) (name "Histone 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([GK_977573] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2A.e [extracellular region]") (DB_ID 977573) (endCoordinate -1) (name "Histone H2A.e") (referenceEntity [GK_56134]) (species [GK_48887]) (stableIdentifier [GK_1358008]) (startCoordinate 1)) ([GK_977574] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2B K [extracellular region]") (DB_ID 977574) (endCoordinate -1) (name "Histone H2B K") (referenceEntity [GK_148293]) (species [GK_48887]) (stableIdentifier [GK_1358155]) (startCoordinate 1)) ([GK_977575] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2A.z [extracellular region]") (DB_ID 977575) (endCoordinate -1) (name "Histone H2A.z") (referenceEntity [GK_231437]) (species [GK_48887]) (stableIdentifier [GK_1358027]) (startCoordinate 1)) ([GK_977576] of CandidateSet (_displayName "[Hsa] Histone H2B [extracellular region]") (DB_ID 977576) (hasCandidate [GK_977574] [GK_977572] [GK_977582] [GK_977564] [GK_977561] [GK_977579] [GK_977559] [GK_977562] [GK_977566] [GK_977580] [GK_977557] [GK_977571] [GK_977565] [GK_977588]) (name "Histone H2B") (species [GK_48887]) (stableIdentifier [GK_1358114])) ([GK_977577] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2A.m [extracellular region]") (DB_ID 977577) (endCoordinate -1) (name "Histone H2A.m") (referenceEntity [GK_56142]) (species [GK_48887]) (stableIdentifier [GK_1357757]) (startCoordinate 1)) ([GK_977578] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H3.2 [extracellular region]") (DB_ID 977578) (endCoordinate 136) (name "Histone H3.2") (referenceEntity [GK_355447]) (species [GK_48887]) (stableIdentifier [GK_1358248]) (startCoordinate 2)) ([GK_977579] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2B.c [extracellular region]") (DB_ID 977579) (endCoordinate -1) (name "Histone H2B.c") (referenceEntity [GK_56170]) (species [GK_48887]) (stableIdentifier [GK_1357703]) (startCoordinate 1)) ([GK_977580] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2B.j [extracellular region]") (DB_ID 977580) (endCoordinate -1) (name "Histone H2B.j") (referenceEntity [GK_56180]) (species [GK_48887]) (stableIdentifier [GK_1358076]) (startCoordinate 1)) ([GK_977582] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2B, testis [extracellular region]") (DB_ID 977582) (endCoordinate -1) (name "Histone H2B, testis") (referenceEntity [GK_148294]) (species [GK_48887]) (stableIdentifier [GK_1358072]) (startCoordinate 1)) ([GK_977583] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2A.x [extracellular region]") (DB_ID 977583) (endCoordinate -1) (name "Histone H2A.x" "H2a/x") (referenceEntity [GK_56152]) (species [GK_48887]) (stableIdentifier [GK_1357805]) (startCoordinate 1)) ([GK_977584] of Complex (_displayName "[Hsa] Chromatin [extracellular region]") (DB_ID 977584) (hasComponent [GK_977585]) (isChimeric FALSE) (name "Chromatin") (species [GK_48887]) (stableIdentifier [GK_1358067])) ([GK_977585] of Complex (_displayName "[Hsa] Nucleosome (Deacetylated) [extracellular region]") (DB_ID 977585) (hasComponent [GK_977576] [GK_977586] [GK_977586] [GK_977558] [GK_977558] [GK_977576] [GK_977569] [GK_977569]) (name "Nucleosome (Deacetylated)") (species [GK_48887]) (stableIdentifier [GK_1357767])) ([GK_977586] of DefinedSet (_displayName "[Hsa] Histone H3 [extracellular region]") (DB_ID 977586) (hasMember [GK_977570] [GK_977578] [GK_977567]) (name "Histone H3") (species [GK_48887]) (stableIdentifier [GK_1358465])) ([GK_977587] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2A.o [extracellular region]") (DB_ID 977587) (endCoordinate -1) (name "Histone H2A.o") (referenceEntity [GK_231418]) (species [GK_48887]) (stableIdentifier [GK_1357848]) (startCoordinate 1)) ([GK_977588] of EntityWithAccessionedSequence (_displayName "[Hsa] Histone H2B.s [extracellular region]") (DB_ID 977588) (endCoordinate -1) (name "Histone H2B.s") (referenceEntity [GK_56190]) (species [GK_48887]) (stableIdentifier [GK_1358620]) (startCoordinate 1)) ([GK_977589] of DefinedSet (_displayName "[Hsa] Double-stranded DNA and chromatin [extracellular region]") (DB_ID 977589) (hasMember [GK_977584]) (name "Double-stranded DNA and chromatin") (species [GK_48887]) (stableIdentifier [GK_1358102])) ([GK_981768] of Person (_displayName "Wiltzius, JJ") (DB_ID 981768) (initial "JJ") (surname "Wiltzius")) ([GKB_core_00388] of %3ASTANDARD-FACET ) ([GO_BiologicalProcess] of %3AEXTENDED-CLASS ) ([GO_CellularComponent] of %3AEXTENDED-CLASS ) ([GO_MolecularFunction] of %3AEXTENDED-CLASS ) ([goBiologicalProcess] of %3AEXTENDED-SLOT ) ([goCellularComponent] of %3AEXTENDED-SLOT ) ([GroupModifiedResidue] of %3AEXTENDED-CLASS ) ([hasCandidate] of %3AEXTENDED-SLOT ) ([hasComponent] of %3AEXTENDED-SLOT ) ([hasEHLD] of %3AEXTENDED-SLOT (attributeCategory OPTIONAL)) ([hasEvent] of %3AEXTENDED-SLOT ) ([hasFunctionalVariants] of %3AEXTENDED-SLOT 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