BioPAX pathway converted from "Golgi Associated Vesicle Biogenesis" in the Reactome database.Golgi Associated Vesicle BiogenesisProteins that have been synthesized, processed and sorted eventually reach the final steps of the secretory pathway. This pathway is responsible not only for proteins that are secreted from the cell but also enzymes and other resident proteins in the lumen of the ER, Golgi, and lysosomes as well as integral proteins transported in the vesicle membranes.Authored: Gillespie, ME, 2009-08-27Reviewed: Simpson, Jeremy C, 2009-08-27Edited: Gillespie, ME, 2009-08-14LEFT-TO-RIGHTFormation Of Bloc-1 ComplexThe ubiquitously expressed protein complexes, named biogenesis of lysosome-related organelles complex or BLOC are required for normal biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense granules.Authored: Gillespie, ME, 2009-08-27Reviewed: Simpson, Jeremy C, 2009-08-27Edited: Gillespie, ME, 2009-09-09TXNDC5Thioredoxin domain-containing protein 5TXND5_HUMANReactome DB_ID: 429813lysosomal lumenGENE ONTOLOGYGO:0043202UniProt:Q8NBS9 TXNDC5TXNDC5TLP46UNQ364/PRO700FUNCTION Possesses thioredoxin activity. Has been shown to reduce insulin disulfide bonds. Also complements protein disulfide-isomerase deficiency in yeast (By similarity).SIMILARITY Belongs to the protein disulfide isomerase family.Homo sapiensNCBI Taxonomy9606UniProtQ8NBS933EQUAL432EQUALReactome Database ID Release 75429813Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429813ReactomeR-HSA-4298131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429813.1Reactomehttp://www.reactome.orgNAPAAlpha-soluble NSF attachment proteinSNAA_HUMANReactome DB_ID: 264469cytosolGENE ONTOLOGYGO:0005829UniProt:P54920 NAPANAPASNAPAFUNCTION Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus (Probable). Together with GNA12 promotes CDH5 localization to plasma membrane (PubMed:15980433).SUBUNIT Interacts with PRKCABP, and disrupts the interaction between GRIA2 and PRKCABP, leading to the internalization of GRIA2 (By similarity). Found in a complex with VAMP8 (By similarity). Component of a SNARE-like complex that contains at least ZW10, USE1L, RINT1, STX18 and NAPA/SNAP-alpha (PubMed:15029241). Interacts with VTI1A (By similarity). Interacts with STX12 (By similarity). Interacts with GNA12 (via N-terminus); the interaction promotes CDH5 localization to plasma membrane (PubMed:15980433).SIMILARITY Belongs to the SNAP family.UniProtP549201EQUAL295EQUALReactome Database ID Release 75264469Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=264469ReactomeR-HSA-2644691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-264469.1BLOC1S1Biogenesis of lysosome-related organelles complex 1 subunit 1BL1S1_HUMANReactome DB_ID: 429821lysosomal membraneGENE ONTOLOGYGO:0005765UniProt:P78537 BLOC1S1BLOC1S1BLOS1GCN5L1RT14FUNCTION Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension (PubMed:17182842). As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor (PubMed:25898167).FUNCTION May negatively regulate aerobic respiration through mitochondrial protein lysine-acetylation. May counteract the action of the deacetylase SIRT3 by acetylating and regulating proteins of the mitochondrial respiratory chain including ATP5F1A and NDUFA9.SUBUNIT Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8 (PubMed:15102850, PubMed:22203680). The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos (By similarity). Component of the BLOC-one-related complex (BORC) which is composed of BLOC1S1, BLOC1S2, BORCS5, BORCS6, BORCS7, BORCS8, KXD1 and SNAPIN (PubMed:25898167). Interacts with ATP5F1A and NDUFA9; involved in their acetylation on lysine residues (PubMed:22309213). Interacts with KXD1 (By similarity).SIMILARITY Belongs to the BLOC1S1 family.UniProtP785371EQUAL153EQUALReactome Database ID Release 75429821Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429821ReactomeR-HSA-4298211Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429821.1CNOBLOC1S4Protein cappuccino homologCNO_HUMANReactome DB_ID: 429817UniProt:Q9NUP1 BLOC1S4BLOC1S4CNOFUNCTION Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking.SUBUNIT Interacts with BLOC1S5 and BLOC1S6 (By similarity). Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos.SIMILARITY Belongs to the BLOC1S4 family.UniProtQ9NUP11EQUAL217EQUALReactome Database ID Release 75429817Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429817ReactomeR-HSA-4298171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429817.1BLOC1S3Biogenesis of lysosome-related organelles complex 1 subunit 3BL1S3_HUMANReactome DB_ID: 429820UniProt:Q6QNY0 BLOC1S3BLOC1S3BLOS3FUNCTION Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking.SUBUNIT Interacts with BLOC1S4, BLOC1S5 and BLOC1S6 (By similarity). Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos. Interacts directly with BLOC1S2.SIMILARITY Belongs to the BLOC1S3 family.UniProtQ6QNY01EQUAL202EQUALReactome Database ID Release 75429820Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429820ReactomeR-HSA-4298201Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429820.1DTNBP1DysbindinDTBP1_HUMANReactome DB_ID: 429819UniProt:Q96EV8 DTNBP1DTNBP1BLOC1S8My031FUNCTION Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Associates with the BLOC-2 complex to facilitate the transport of TYRP1 independent of AP-3 function. Plays a role in synaptic vesicle trafficking and in neurotransmitter release. Plays a role in the regulation of cell surface exposure of DRD2. May play a role in actin cytoskeleton reorganization and neurite outgrowth. May modulate MAPK8 phosphorylation. Appears to promote neuronal transmission and viability through regulating the expression of SNAP25 and SYN1, modulating PI3-kinase-Akt signaling and influencing glutamatergic release. Regulates the expression of SYN1 through binding to its promoter. Modulates prefrontal cortical activity via the dopamine/D2 pathway.SUBUNIT Interacts (via its coiled coil domain) with KXD1. Interacts with CMYA5, PI4K2 and RNF151 (By similarity). Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of at least BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Interacts directly in the complex with BLOC1S5, BLOC1S6 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos. This BLOC-1 complex also associates with the BLOC-2 complex in endosomes. Binds to DTNA and DTNB but may not be a physiological binding partner (PubMed:16980328). Interacts (isoform 1 and isoform 2 only) with the DNA-dependent protein kinase complex DNA-PK; the interaction phosphorylates DTNBP1 in vitro. Interacts directly in this complex with XRCC5 and XRCC6. Interacts with AP3M1, AP3B2 and TRIM32. Interacts with XPO1; the interaction exports DTNBP1 out of the nucleus.TISSUE SPECIFICITY Detected in brain, in neurons and in neuropil. Isoform 1 is expressed in the cerebral cortex, and hippocampal frontal (HF). Specific expression in the posterior half of the superior temporal gyrus (pSTG). Higher expression of isoform 2 and 3 in the HF than in the pSTG while isoform 1 shows no difference in expression in these areas. In the HF, detected in dentate gyrus (DG) and in pyramidal cells of hippocampus CA2 and CA3 (at protein level). Expressed in all principal neuronal populations of the HF, namely pyramidal neurons in the subiculum and CA1-3, granule cells in the dense cell layer of the DG (DGg), and polymorph cells in the hilus of the DG (DGh). Maximal levels in CA2, CA3, and DGh. Isoform 2 not expressed in the cerebral cortex.PTM Ubiquitinated by TRIM32. Ubiquitination leads to DTNBP1 degradation.PTM Isoforms 1 and 2 highly phosphorylated by PRKDC in vitro. Isoform 3 only weakly phosphorylated by PRKDC in vitro.DISEASE Defects in DTNBP1 are associated with susceptibility to schizophrenia, a mental disorder characterized by a breakdown of thought processes and by poor emotional responsiveness. Genetic mutations lead to alterations in the glutamatergic transmission in the brain and modified Akt signaling (PubMed:15345706). Protein levels and expression are reduced in nerve terminals of the hippocampus and there is an increased release of glutamate in schizophrenic patients (PubMed:15124027). Levels of isoform 1 are reduced in the pSTG, but not in HF, by about 48% in 92% of schizophrenic patients. In the HF, there is an average of 33% reduction in synaptic expression of isoform 2 in 67% of cases, and of isoform 3, an average reduction of 35% in 80% of cases. In the dorsolateral prefrontal cortex (DLPFC), significant reductions in levels of isoform 3 are observed about 71% of schizophrenic patients showed an average reduction of this isoform of about 60% (PubMed:19617633).SIMILARITY Belongs to the dysbindin family.UniProtQ96EV81EQUAL351EQUALReactome Database ID Release 75429819Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429819ReactomeR-HSA-4298191Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429819.1PLDNBLOC1S6PallidinPLDN_HUMANReactome DB_ID: 429816UniProt:Q9UL45 BLOC1S6BLOC1S6PAPLDNFUNCTION Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. May play a role in intracellular vesicle trafficking, particularly in the vesicle-docking and fusion process.SUBUNIT Interacts with BLOC1S4 and DTNBP1/BLOC1S7 (By similarity). Homodimer. Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos. Interacts with BLOC1S5, F-actin, SNAP25 isoform 1 and isoform 2, SNAP47 and STX12.TISSUE SPECIFICITY Widely expressed.PTM Phosphorylated.SIMILARITY Belongs to the BLOC1S6 family.CAUTION A paper showing involvement in Hermansky-Pudlak syndrome 9 was retracted due to image duplication.UniProtQ9UL451EQUAL172EQUALReactome Database ID Release 75429816Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429816ReactomeR-HSA-4298161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429816.1BLOC-1 ComplexReactome DB_ID: 4298251111111Reactome Database ID Release 75429825Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429825ReactomeR-HSA-4298251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429825.1ComplexPortalCPX-1910additional informationMIMI:0361Reactome Database ID Release 75429815Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429815ReactomeR-HSA-4298152Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429815.217116749Pubmed2006Comparative proteomics of clathrin-coated vesiclesBorner, GHHarbour, MHester, SLilley, KSRobinson, MSJ Cell Biol 175:571-815102850Pubmed2004Identification of snapin and three novel proteins (BLOS1, BLOS2, and BLOS3/reduced pigmentation) as subunits of biogenesis of lysosome-related organelles complex-1 (BLOC-1)Starcevic, MDell'Angelica, ECJ Biol Chem 279:28393-401LEFT-TO-RIGHTRecruitment Of Cytoplasmic Proteins To VesiclesCytosolic proteins are also recruited to the cytoplasmic face of newly formed vesicles.Authored: Gillespie, ME, 2009-08-12Reviewed: Simpson, Jeremy C, 2009-08-27Edited: Gillespie, ME, 2008-09-08 03:19:22SH3D19SH3 domain-containing protein 19SH319_HUMANReactome DB_ID: 434202UniProt:Q5HYK7 SH3D19SH3D19FUNCTION May play a role in regulating A disintegrin and metalloproteases (ADAMs) in the signaling of EGFR-ligand shedding. May be involved in suppression of Ras-induced cellular transformation and Ras-mediated activation of ELK1. Plays a role in the regulation of cell morphology and cytoskeletal organization.SUBUNIT Interacts with ADAM12. Isoform 4 and isoform 5 (but not isoform 1 and isoform 2) interact with ADAM9, ADAM10, ADAM15 and ADAM17. Interacts with SH3GL1 SH3 domain. Interacts via SH3 3 and SH3 4 or SH3 4 and SH3 5 domains with SOS2. Probably forms a trimeric complex with SH3GL1 and SOS2. Interacts with SH3YL1 (By similarity).TISSUE SPECIFICITY Widely expressed with highest levels in heart, skeletal muscle, kidney, liver, placenta, small intestine and lung. Expressed at low levels in colon, thymus, spleen and leukocytes.CAUTION It is uncertain whether Met-1 or Met-4 is the initiator.UniProtQ5HYK71EQUAL790EQUALReactome Database ID Release 75434202Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434202ReactomeR-HSA-4342021Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434202.1Ferritin ComplexReactome DB_ID: 434350Converted from EntitySet in ReactomeFTH1:FTLReactome DB_ID: 434356FTH1Ferritin heavy chainFRIH_HUMANReactome DB_ID: 434212UniProt:P02794 FTH1FTH1FTHFTHL6OK/SW-cl.84PIG15FUNCTION Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity).SUBUNIT Oligomer of 24 subunits. There are two types of subunits: L (light) chain and H (heavy) chain. The major chain can be light or heavy, depending on the species and tissue type. In the human liver, the heavy chain is predominant. The functional molecule forms a roughly spherical shell with a diameter of 12 nm and contains a central cavity into which the insoluble mineral iron core is deposited.TISSUE SPECIFICITY Expressed in the liver.SIMILARITY Belongs to the ferritin family.UniProtP027941EQUAL183EQUALReactome Database ID Release 75434212Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434212ReactomeR-HSA-4342121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434212.1FTLFerritin light chainFRIL_HUMANReactome DB_ID: 434215UniProt:P02792 FTLFTLFUNCTION Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity).SUBUNIT Oligomer of 24 subunits. There are two types of subunits: L (light) chain and H (heavy) chain. The major chain can be light or heavy, depending on the species and tissue type. The functional molecule forms a roughly spherical shell with a diameter of 12 nm and contains a central cavity into which the insoluble mineral iron core is deposited. Iron enters the spherical protein shell through pores that are formed between subunits. Mutations leading to truncation or the addition of extra residues at the C-terminus interfere with normal pore formation and with iron accumulation.SIMILARITY Belongs to the ferritin family.UniProtP027922EQUAL175EQUALReactome Database ID Release 75434215Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434215ReactomeR-HSA-4342151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434215.1Reactome Database ID Release 75434356Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434356ReactomeR-HSA-4343561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434356.124Reactome Database ID Release 75434350Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434350ReactomeR-HSA-4343501Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434350.1CLINT1Clathrin interactor 1EPN4_HUMANReactome DB_ID: 429811UniProt:Q14677 CLINT1CLINT1ENTHEPN4EPNRKIAA0171FUNCTION Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May have a role in transport via clathrin-coated vesicles from the trans-Golgi network to endosomes. Stimulates clathrin assembly.SUBUNIT Binds clathrin heavy chain, GGA2, AP-2 and AP1G1 (PubMed:12213833, PubMed:12429846, PubMed:12538641). Interacts with VTI1B (PubMed:18033301).TISSUE SPECIFICITY Ubiquitously expressed at low to intermediate levels.POLYMORPHISM Genetic variations in CLINT1 may contribute to susceptibility to schizophrenia (SCZD1) and psychotic disorders in some populations.SIMILARITY Belongs to the epsin family.UniProtQ146771EQUAL625EQUALReactome Database ID Release 75429811Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429811ReactomeR-HSA-4298111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429811.1PUM1Pumilio homolog 1PUM1_HUMANReactome DB_ID: 434211UniProt:Q14671 PUM1PUM1KIAA0099PUMH1FUNCTION Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-UGUANAUA-3', that is related to the Nanos Response Element (NRE) (PubMed:21572425, PubMed:18328718, PubMed:21653694, PubMed:21397187). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation (PubMed:22955276). Also mediates deadenylation-independent repression by promoting accessibility of miRNAs (PubMed:18776931, PubMed:20818387, PubMed:20860814, PubMed:22345517). Following growth factor stimulation, phosphorylated and binds to the 3'-UTR of CDKN1B/p27 mRNA, inducing a local conformational change that exposes miRNA-binding sites, promoting association of miR-221 and miR-222, efficient suppression of CDKN1B/p27 expression, and rapid entry to the cell cycle (PubMed:20818387). Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation (PubMed:22345517, PubMed:29474920). Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm (PubMed:26724866). Involved in neuronal functions by regulating ATXN1 mRNA levels: acts by binding to the 3'-UTR of ATXN1 transcripts, leading to their down-regulation independently of the miRNA machinery (PubMed:25768905, PubMed:29474920). Plays a role in cytoplasmic sensing of viral infection (PubMed:25340845). In testis, acts as a post-transcriptional regulator of spermatogenesis by binding to the 3'-UTR of mRNAs coding for regulators of p53/TP53. Involved in embryonic stem cell renewal by facilitating the exit from the ground state: acts by targeting mRNAs coding for naive pluripotency transcription factors and accelerates their down-regulation at the onset of differentiation (By similarity). Binds specifically to miRNA MIR199A precursor, with PUM2, regulates miRNA MIR199A expression at a postranscriptional level (PubMed:28431233).SUBUNIT Recruits the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation (PubMed:22955276). In case of viral infection, interacts with DHX58 (PubMed:25340845). Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner (PubMed:23125361).TISSUE SPECIFICITY Expressed in brain, heart, kidney, muscle, intestine and stomach. Not expressed in cerebellum, corpus callosum, caudate nucleus, hippocampus, medulla oblongata and putamen. Expressed in all fetal tissues tested.INDUCTION Strongly down-regulated in keratinocytes upon UVB irradiation.DOMAIN The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. RNA-binding occurs on the concave side of the surface (PubMed:21397187). PUM1 is composed of 8 pumilio repeats of 36 residues; each repeat binds a single nucleotide in its RNA target. Residues at positions 12 and 16 of the pumilio repeat bind each RNA base via hydrogen bonding or van der Waals contacts with the Watson-Crick edge, while the amino acid at position 13 makes a stacking interaction. The recognition of RNA by pumilio repeats is base specific: cysteine and glutamine at position 12 and 16, respectively, bind adenine; asparagine and glutamine bind uracil; and serine and glutamate bind guanine (PubMed:21572425. PubMed:18328718, PubMed:21653694).PTM Phosphorylation at Ser-714 promotes RNA-binding activity. Following growth factor stimulation phosphorylated at Ser-714, promoting binding to the 3'-UTR of CDKN1B/p27 mRNA.UniProtQ146711EQUAL1186EQUALReactome Database ID Release 75434211Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434211ReactomeR-HSA-4342111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434211.1Converted from EntitySet in ReactomeVampReactome DB_ID: 432673VAMP2Reactome DB_ID: 375436cytoplasmic vesicle membraneGENE ONTOLOGYGO:0030659UniProt:P63027 VAMP2VAMP2SYB2FUNCTION Involved in the targeting and/or fusion of transport vesicles to their target membrane (By similarity). Major SNARE protein of synaptic vesicles which mediates fusion of synaptic vesicles to release neurotransmitters. Essential for fast vesicular exocytosis and activity-dependent neurotransmitter release as well as fast endocytosis that mediates rapid reuse of synaptic vesicles (By similarity) (PubMed:30929742). Modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1.SUBUNIT Part of the SNARE core complex containing SNAP25, VAMP2 and STX1A. This complex binds to CPLX1. Interacts with BVES and STX4 (By similarity). Interacts with VAPA and VAPB. Interacts with WDFY2, PRKCZ and PRKCI (PubMed:17313651). Forms a complex with WDFY2 and PRKCZ (PubMed:17313651). Interacts (via N-terminus) with KCNB1 (via N-terminus and C-terminus); stimulates the channel inactivation rate of KCNB1 (By similarity). Interacts with SEPT8; the interaction inhibits interaction of VAMP2 with SYP. Interacts with SYP; the interaction is inhibited by interaction with SEPT8 (By similarity). Interacts with PICALM (PubMed:22118466, PubMed:21808019). Interacts with alpha-synuclein/SNCA (PubMed:20798282). Interacts with STX3 (By similarity).TISSUE SPECIFICITY Nervous system and skeletal muscle.PTM Phosphorylated by PRKCZ in vitro and this phosphorylation is increased in the presence of WDFY2.PTM (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type B (BoNT/B, botB) which hydrolyzes the 76-Gln-|-Phe-77 bond and probably inhibits neurotransmitter release (PubMed:7803399).PTM (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type D (BoNT/D, botD) which probably hydrolyzes the 59-Lys-|-Leu-60 bond and inhibits neurotransmitter release (PubMed:22289120). Note that humans are not known to be infected by C.botulinum type D.PTM (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type F (BoNT/F, botF) which hydrolyzes the 58-Gln-|-Lys-59 bond and probably inhibits neurotransmitter release (PubMed:19543288).PTM (Microbial infection) Targeted and hydrolyzed by C.tetani tetanus toxin (tetX) which hydrolyzes the 76-Gln-|-Phe-77 bond and probably inhibits neurotransmitter release (PubMed:7803399).SIMILARITY Belongs to the synaptobrevin family.CAUTION A structure of a fragment of this protein in complex with the catalytic domain of C.botulinum neurotoxin type B (BoNT/B, botB) was reported; because of the lack of clear and continuous electron density for the VAMP2 peptide in the complex structure, the paper was retracted (PubMed:10932255, PubMed:19578378). However this protein is a substrate for BoNT/B (PubMed:7803399, PubMed:22289120).UniProtP630272EQUAL116EQUALReactome Database ID Release 75375436Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=375436ReactomeR-HSA-3754361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-375436.1VAMP7Vesicle-associated membrane protein 7VAMP7_HUMANReactome DB_ID: 376336UniProt:P51809 VAMP7VAMP7SYBL1FUNCTION Involved in the targeting and/or fusion of transport vesicles to their target membrane during transport of proteins from the early endosome to the lysosome. Required for heterotypic fusion of late endosomes with lysosomes and homotypic lysosomal fusion. Required for calcium regulated lysosomal exocytosis. Involved in the export of chylomicrons from the endoplasmic reticulum to the cis Golgi. Required for exocytosis of mediators during eosinophil and neutrophil degranulation, and target cell killing by natural killer cells. Required for focal exocytosis of late endocytic vesicles during phagosome formation.SUBUNIT Component of the SNARE complex composed of STX4, SNAP23 and VAMP7 that binds SYT7 during lysosomal exocytosis. Component of the SNARE complex composed of STX7, STX8, VAMP7 and VTI1B that is required for heterotypic fusion of late endosomes with lysosomes. May interact with STX17 (By similarity). Interacts with PICALM (PubMed:23741335). Interacts with RAB21 (PubMed:25648148).TISSUE SPECIFICITY Detected in all tissues tested.MISCELLANEOUS The gene coding for this protein is located in the pseudoautosomal region 2 (PAR2) of X and Y chromosomes.MISCELLANEOUS Loss-of-function mutant (antisense inhibition) displays impaired granzyme B release and target cell killing by natural killer cells.SIMILARITY Belongs to the synaptobrevin family.UniProtP518092EQUAL220EQUALReactome Database ID Release 75376336Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=376336ReactomeR-HSA-3763361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-376336.1VAMP8Vesicle-associated membrane protein 8VAMP8_HUMANReactome DB_ID: 376373UniProt:Q9BV40 VAMP8VAMP8FUNCTION SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. VAMP8 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane via its interaction with the STX17-SNAP29 binary t-SNARE complex (PubMed:23217709, PubMed:25686604). Also required for dense-granule secretion in platelets (PubMed:12130530). Plays also a role in regulated enzyme secretion in pancreatic acinar cells (By similarity). Involved in the abscission of the midbody during cell division, which leads to completely separate daughter cells (By similarity). Involved in the homotypic fusion of early and late endosomes (By similarity). Participates also in the activation of type I interferon antiviral response through a TRIM6-dependent mechanism (PubMed:31694946).SUBUNIT Forms a SNARE complex composed of VAMP8, SNAP29 and STX17 involved in fusion of autophagosome with lysosome (PubMed:25686604). Found in a number of SNARE complexes with NAPA, SNAP23, SNAP25, STX1A, STX4, STX7, STX8 and VTI1B (PubMed:12130530). Interacts with PICALM (By similarity). SNARE complex formation and binding by PICALM are mutually exclusive processes for VAMP8 (By similarity). Interacts with SBF2/MTMR13 (PubMed:25648148). Interacts with RAB21 (in GTP-bound form) in response to starvation; the interaction probably regulates VAMP8 endolysosomal trafficking (PubMed:25648148). Interacts with STX17; this interaction is increased in the absence of TMEM39A (PubMed:31806350). Interacts with TRIM6 (PubMed:31694946).TISSUE SPECIFICITY Platelets.SIMILARITY Belongs to the synaptobrevin family.UniProtQ9BV401EQUAL100EQUALReactome Database ID Release 75376373Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=376373ReactomeR-HSA-3763731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-376373.1Reactome Database ID Release 75432673Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=432673ReactomeR-HSA-4326731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-432673.1Golgi-associated vesicle interacting proteinsReactome DB_ID: 4343511111Reactome Database ID Release 75434351Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434351ReactomeR-HSA-4343511Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434351.1Reactome Database ID Release 75434362Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434362ReactomeR-HSA-4343622Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434362.2LEFT-TO-RIGHTVamp And trans-Golgi Network AP-1 Binding Coupled With Cargo CaptureOnce AP-1 is recruited to the trans-Golgi Network membrane the complex of functional vesicle building proteins is joined by the cargo that will be within that vesicle. As with other types of vesicles the cargo itself is part of the vesicle development. Here the cargo is destined for the Golgi-associated vesicle membrane. It is at this stage that a specific Synaptobrevin (Vamp) molecule also joins the complex. It should be noted that only certain Vamp molecules will be found with specific cargo molecules on the newly forming vesicles. However here we represent this reaction in bulk, without specific Vamp and cargo molecule pairings.Authored: Gillespie, ME, 2009-08-27Reviewed: Simpson, Jeremy C, 2009-08-27Edited: Gillespie, ME, 2008-05-21 20:31:35AP-1 ComplexReactome DB_ID: 167717Converted from EntitySet in ReactomeAP-1 muReactome DB_ID: 167716AP1M1AP-1 mu 1Reactome DB_ID: 167700UniProt:Q9BXS5 AP1M1AP1M1CLTNMFUNCTION Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.SUBUNIT Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3). Interacts with MARCHF11 (By similarity). Associates with the AP1(MU)-Nef-MHC-I complex; this complex is required for MHC-I internalization.SUBUNIT (Microbial infection) Interacts with HIV-1 Nef.PTM Phosphorylation of membrane-bound AP1M1/AP1M2 increases its affinity for sorting signals.SIMILARITY Belongs to the adaptor complexes medium subunit family.UniProtQ9BXS52EQUAL423EQUALReactome Database ID Release 75167700Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167700ReactomeR-HSA-1677001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-167700.1AP1M2AP-1 mu 2Reactome DB_ID: 167699UniProt:Q9Y6Q5 AP1M2AP1M2FUNCTION Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.SUBUNIT Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3).PTM Phosphorylation of membrane-bound AP1M1/AP1M2 increases its affinity for sorting signals.SIMILARITY Belongs to the adaptor complexes medium subunit family.UniProtQ9Y6Q51EQUAL423EQUALReactome Database ID Release 75167699Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167699ReactomeR-HSA-1676991Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-167699.1Reactome Database ID Release 75167716Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167716ReactomeR-HSA-1677161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-167716.11AP1B1AP-1 beta subunitReactome DB_ID: 167705UniProt:Q10567 AP1B1AP1B1ADTB1BAM22CLAPB2FUNCTION Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes (PubMed:31630791). The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.SUBUNIT Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3).TISSUE SPECIFICITY Widely expressed.SIMILARITY Belongs to the adaptor complexes large subunit family.UniProtQ105671EQUAL949EQUALReactome Database ID Release 75167705Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167705ReactomeR-HSA-1677051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-167705.11Converted from EntitySet in ReactomeAP-1 sigmaReactome DB_ID: 167713AP1S1AP-1 sigma 1AReactome DB_ID: 167696UniProt:P61966 AP1S1AP1S1AP19CLAPS1FUNCTION Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.SUBUNIT Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3).TISSUE SPECIFICITY Widely expressed.INDUCTION Up-regulated in response to enterovirus 71 (EV71) infection.SIMILARITY Belongs to the adaptor complexes small subunit family.UniProtP619661EQUAL158EQUALReactome Database ID Release 75167696Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167696ReactomeR-HSA-1676961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-167696.1AP1S2AP-1 sigma 1BReactome DB_ID: 167695UniProt:P56377 AP1S2AP1S2DC22FUNCTION Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.SUBUNIT Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3). Binds to MUC1.TISSUE SPECIFICITY Widely expressed.SIMILARITY Belongs to the adaptor complexes small subunit family.UniProtP563771EQUAL157EQUALReactome Database ID Release 75167695Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167695ReactomeR-HSA-1676951Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-167695.1AP1S3AP-1 sigma 1CReactome DB_ID: 167692UniProt:Q96PC3 AP1S3AP1S3FUNCTION Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. Involved in TLR3 trafficking (PubMed:24791904).SUBUNIT Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3).TISSUE SPECIFICITY Widely expressed.SIMILARITY Belongs to the adaptor complexes small subunit family.UniProtQ96PC31EQUAL154EQUALReactome Database ID Release 75167692Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167692ReactomeR-HSA-1676921Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-167692.1Reactome Database ID Release 75167713Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167713ReactomeR-HSA-1677131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-167713.11AP1G1AP-1 gamma subunitReactome DB_ID: 167703UniProt:O43747 AP1G1AP1G1ADTGCLAPG1FUNCTION Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.SUBUNIT Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3). Binds RABEP1 and SYNRG. Interacts (via GAE domain) with AP1AR (via coiled-coil domain). Interacts with CLN3 (via dileucine motif); this interaction facilitates lysosomal targeting (PubMed:15598649).TISSUE SPECIFICITY Widely expressed.SIMILARITY Belongs to the adaptor complexes large subunit family.UniProtO437472EQUAL822EQUALReactome Database ID Release 75167703Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167703ReactomeR-HSA-1677031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-167703.11Reactome Database ID Release 75167717Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167717ReactomeR-HSA-1677171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-167717.1ComplexPortalCPX-5050ComplexPortalCPX-5049ComplexPortalCPX-5047ComplexPortalCPX-5048Converted from EntitySet in ReactomeGolgi-associated Vesicle Destined CargoReactome DB_ID: 432674CPDCarboxypeptidase DCBPD_HUMANReactome DB_ID: 432675Golgi membraneGENE ONTOLOGYGO:0000139UniProt:O75976 CPDCPDTISSUE SPECIFICITY Highly expressed in placenta, pancreas and hepatoma cells. Lower levels found in skeletal muscle, heart and colon carcinoma and melanoma cell lines.DOMAIN There are 3 carboxypeptidase-like domains. Only the first two domains seem to have kept a catalytic activity.SIMILARITY Belongs to the peptidase M14 family.UniProtO7597632EQUAL1380EQUALReactome Database ID Release 75432675Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=432675ReactomeR-HSA-4326751Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-432675.1PIK3C2APhosphatidylinositol-4-phosphate 3-kinase C2 domain-containing alpha polypeptideP3C2A_HUMANReactome DB_ID: 432679UniProt:O00443 PIK3C2APIK3C2AFUNCTION Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. Involved in the regulation of ciliogenesis and trafficking of ciliary components (PubMed:31034465).ACTIVITY REGULATION Activated by insulin (By similarity). Only slightly inhibited by wortmannin and LY294002. Activated by clathrin.SUBUNIT Part of a complex with ERBB2 and EGFR (PubMed:10805725). Interacts with clathrin trimers (PubMed:11239472, PubMed:16215232). Interacts with SBF2/MTMR13 (By similarity).TISSUE SPECIFICITY Expressed in columnar and transitional epithelia, mononuclear cells, smooth muscle cells, and endothelial cells lining capillaries and small venules (at protein level). Ubiquitously expressed, with highest levels in heart, placenta and ovary, and lowest levels in the kidney. Detected at low levels in islets of Langerhans from type 2 diabetes mellitus individuals.PTM Phosphorylated upon insulin stimulation; which may lead to enzyme activation (By similarity). Phosphorylated on Ser-259 during mitosis and upon UV irradiation; which does not change enzymatic activity but leads to proteasomal degradation. Ser-259 phosphorylation may be mediated by CDK1 or JNK, depending on the physiological state of the cell.SIMILARITY Belongs to the PI3/PI4-kinase family.UniProtO004432EQUAL1686EQUALReactome Database ID Release 75432679Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=432679ReactomeR-HSA-4326791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-432679.1SNX9Sorting nexin-9SNX9_HUMANReactome DB_ID: 432988UniProt:Q9Y5X1 SNX9SNX9SH3PX1SH3PXD3AFUNCTION Involved in endocytosis and intracellular vesicle trafficking, both during interphase and at the end of mitosis. Required for efficient progress through mitosis and cytokinesis. Required for normal formation of the cleavage furrow at the end of mitosis. Plays a role in endocytosis via clathrin-coated pits, but also clathrin-independent, actin-dependent fluid-phase endocytosis. Plays a role in macropinocytosis. Promotes internalization of TNFR. Promotes degradation of EGFR after EGF signaling. Stimulates the GTPase activity of DNM1. Promotes DNM1 oligomerization. Promotes activation of the Arp2/3 complex by WASL, and thereby plays a role in the reorganization of the F-actin cytoskeleton. Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate and promotes membrane tubulation. Has lower affinity for membranes enriched in phosphatidylinositol 3-phosphate.SUBUNIT Homodimer, and homooligomer. Heterodimer with SNX18. Interacts with ITCH. Interacts (via SH3 domain) with TNK2, WASL and ARP3. Identified in a complex with TNK2 and clathrin heavy chains. Identified in a complex with the AP-2 complex, clathrin and DNM2. Interacts (via SH3 domain) with DNM1 and DNM2. Identified in an oligomeric complex containing DNM1 and SNX9. Interacts with FCHSD1 (By similarity). Interacts with ADAM9 and ADAM15 cytoplasmic tails.TISSUE SPECIFICITY Widely expressed, with highest levels in heart and placenta, and lowest levels in thymus and peripheral blood leukocytes.DOMAIN The PX domain mediates interaction with membranes enriched in phosphatidylinositol phosphate. Has high affinity for phosphatidylinositol 4,5-bisphosphate, but can also bind to membranes enriched in other phosphatidylinositol phosphates.PTM Ubiquitinated by ITCH.PTM Phosphorylated on tyrosine residues by TNK2. Phosphorylation promotes its activity in the degradation of EGFR.SIMILARITY Belongs to the sorting nexin family.UniProtQ9Y5X11EQUAL595EQUALReactome Database ID Release 75432988Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=432988ReactomeR-HSA-4329881Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-432988.1AP3B1AP-3 complex subunit beta-1AP3B1_HUMANReactome DB_ID: 434335UniProt:O00203 AP3B1AP3B1ADTB3AFUNCTION Subunit of non-clathrin- and clathrin-associated adaptor protein complex 3 (AP-3) that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. AP-3 appears to be involved in the sorting of a subset of transmembrane proteins targeted to lysosomes and lysosome-related organelles. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.SUBUNIT Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2) (Probable). AP-3 associates with the BLOC-1 complex (By similarity). Interacts with KIF3A; interaction is direct; interaction is impaired by pyrophosphorylation of AP3B1 (PubMed:19934039).TISSUE SPECIFICITY Ubiquitously expressed.PTM Phosphorylated on serine residues.PTM Pyrophosphorylation by 5-diphosphoinositol pentakisphosphate (5-IP7) impairs interaction with KIF3A (PubMed:19934039). Serine pyrophosphorylation is achieved by Mg(2+)-dependent, but enzyme independent transfer of a beta-phosphate from a inositol pyrophosphate to a pre-phosphorylated serine residue (PubMed:19934039).SIMILARITY Belongs to the adaptor complexes large subunit family.UniProtO002031EQUAL1094EQUALReactome Database ID Release 75434335Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434335ReactomeR-HSA-4343351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434335.1AP3S1AP-3 complex subunit sigma-1AP3S1_HUMANReactome DB_ID: 434343UniProt:Q92572 AP3S1AP3S1CLAPS3FUNCTION Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.SUBUNIT Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2). Interacts with AGAP1. AP-3 associates with the BLOC-1 complex (By similarity).TISSUE SPECIFICITY Present in all adult tissues examined.SIMILARITY Belongs to the adaptor complexes small subunit family.UniProtQ925721EQUAL193EQUALReactome Database ID Release 75434343Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434343ReactomeR-HSA-4343431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434343.1AP4B1AP-4 complex subunit beta-1AP4B1_HUMANReactome DB_ID: 434337UniProt:Q9Y6B7 AP4B1AP4B1FUNCTION Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable).SUBUNIT Adaptor protein complex 4 (AP-4) is a heterotetramer composed of two large adaptins (epsilon-type subunit AP4E1 and beta-type subunit AP4B1), a medium adaptin (mu-type subunit AP4M1) and a small adaptin (sigma-type AP4S1) (PubMed:10066790, PubMed:10436028). Interacts with TEPSIN; this interaction requires the presence of a functional AP-4 complex (PubMed:22472443, PubMed:26542808, PubMed:26756312). Interacts with GRIA2; probably indirect it mediates the somatodendritic localization of GRIA2 in neurons (By similarity).TISSUE SPECIFICITY Widely expressed.SIMILARITY Belongs to the adaptor complexes large subunit family.UniProtQ9Y6B71EQUAL739EQUALReactome Database ID Release 75434337Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434337ReactomeR-HSA-4343371Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434337.1AP4E1AP-4 complex subunit epsilon-1AP4E1_HUMANReactome DB_ID: 434338UniProt:Q9UPM8 AP4E1AP4E1FUNCTION Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable).SUBUNIT Adaptor protein complex 4 (AP-4) is a heterotetramer composed of two large adaptins (epsilon-type subunit AP4E1 and beta-type subunit AP4B1), a medium adaptin (mu-type subunit AP4M1) and a small adaptin (sigma-type AP4S1) (PubMed:10436028, PubMed:10066790). Interacts with TEPSIN (PubMed:26542808). Interacts with GRIA2; probably indirect it mediates the somatodendritic localization of GRIA2 in neurons (By similarity).TISSUE SPECIFICITY Widely expressed.SIMILARITY Belongs to the adaptor complexes large subunit family.UniProtQ9UPM81EQUAL1137EQUALReactome Database ID Release 75434338Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434338ReactomeR-HSA-4343381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434338.1NECAP1Adaptin ear-binding coat-associated protein 1NECP1_HUMANReactome DB_ID: 434327UniProt:Q8NC96 NECAP1NECAP1FUNCTION Involved in endocytosis.SUBUNIT Interacts with AP1G1 and AP2A1 components of the adapter protein complexes AP-1 and AP-2. Interacts with the GAE domain proteins GGA1, GGA2 and GGA3 (By similarity).DOMAIN The WXXF motifs mediate binding of accessory proteins to the ear-domain of AP-1, GGAs and AP-2 through hydrophobic interactions. Selective binding to the GAE domains of AP-1 or to the alpha-ear domain of AP-2 is tuned by the acidic context surrounding the motif and the properties of the second residue of the motif itself. The WXXF motif 1, which is preceded by an acidic residue and has a glycine in second position mediates specific interaction with AP-1. The WXXF motif 2, which is followed by the C-terminal carboxyl group negative charge, allows specific interaction with AP-2 (By similarity).SIMILARITY Belongs to the NECAP family.UniProtQ8NC961EQUAL275EQUALReactome Database ID Release 75434327Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434327ReactomeR-HSA-4343271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434327.1GAKCyclin G-associated kinaseGAK_HUMANReactome DB_ID: 434340UniProt:O14976 GAKGAKFUNCTION Associates with cyclin G and CDK5. Seems to act as an auxilin homolog that is involved in the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells. Expression oscillates slightly during the cell cycle, peaking at G1.TISSUE SPECIFICITY Ubiquitous. Highest in testis.SIMILARITY Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.UniProtO149762EQUAL1311EQUALReactome Database ID Release 75434340Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434340ReactomeR-HSA-4343401Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434340.1HIP1RHuntingtin-interacting protein 1-related proteinHIP1R_HUMANReactome DB_ID: 434348UniProt:O75146 HIP1RHIP1RHIP12KIAA0655FUNCTION Component of clathrin-coated pits and vesicles, that may link the endocytic machinery to the actin cytoskeleton. Binds 3-phosphoinositides (via ENTH domain). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis.SUBUNIT Interacts with actin. Does not interact with huntingtin (By similarity). Interacts with CLTB and HIP1. Homodimer. Homodimerization promotes actin binding.TISSUE SPECIFICITY Brain, heart, kidney, pancreas, and liver, but not in lung or placenta.DOMAIN Binds F-actin via the talin-like I/LWEQ domain.SIMILARITY Belongs to the SLA2 family.UniProtO751461EQUAL1068EQUALReactome Database ID Release 75434348Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434348ReactomeR-HSA-4343481Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434348.1OCRLInositol polyphosphate 5-phosphatase OCRL-1OCRL_HUMANReactome DB_ID: 434339UniProt:Q01968 OCRLOCRLOCRL1FUNCTION Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3,4,5-bisphosphate (PtdIns(3,4,5)P3), with the greatest catalytic activity towards PtdIns(4,5)P2 (PubMed:7761412, PubMed:15474001, PubMed:9430698, PubMed:10764818). Able also to hydrolyzes the 4-phosphate of inositol 1,4,5-trisphosphate and of inositol 1,3,4,5-tetrakisphosphate (PubMed:7761412, PubMed:25869668). Regulates traffic in the endosomal pathway by regulating the specific pool of phosphatidylinositol 4,5-bisphosphate that is associated with endosomes (PubMed:21971085). Involved in primary cilia assembly (PubMed:22228094, PubMed:22543976). Acts as a regulator of phagocytosis, hydrolyzing PtdIns(4,5)P2 to promote phagosome closure, through attenuation of PI3K signaling (PubMed:22072788).SUBUNIT Interacts with APPL1, FAM109A/SES1 and FAM109B/SES2; APPL1-binding and FAM109A-binding are mutually exclusive. Interacts with clathrin heavy chain. Interacts with several Rab GTPases, at least RAB1B, RAB5A, RAB6A, RAB8A and RAB31; these interactions may play a dual role in targeting OCRL to the specific membranes and stimulating the phosphatase activity. Interaction with RAB8A modulates OCRL recruitment to cilia. Interacts with INPP5F (PubMed:25869668).TISSUE SPECIFICITY Brain, skeletal muscle, heart, kidney, lung, placenta and fibroblasts. Expressed in the retina and the retinal pigment epithelium.DOMAIN The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating) domains form a single folding module. The ASH domain has an immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic arginine and is catalytically inactive. The ASH-RhoGAP module regulates the majority of the protein-protein interactions currently described. The ASH domain mediates association with membrane-targeting Rab GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1, which is then displaced by FAM109A and FAM109B as endosomes mature.SIMILARITY Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.CAUTION It is uncertain whether Met-1, Met-18 or Met-20 is the initiator.UniProtQ019681EQUAL901EQUALReactome Database ID Release 75434339Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434339ReactomeR-HSA-4343391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434339.1PICALMPhosphatidylinositol-binding clathrin assembly proteinPICAL_HUMANReactome DB_ID: 434341UniProt:Q13492 PICALMPICALMCALMFUNCTION Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalization of cell receptors, synaptic transmission or removal of apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of plasma membrane leading to clathrin-coated vesicles (CCVs) assembly (PubMed:10436022, PubMed:16262731, PubMed:27574975). Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature (PubMed:25898166). In addition to binding to clathrin, mediates the endocytosis of small R-SNARES (Soluble NSF Attachment Protein REceptors) between plasma membranes and endosomes including VAMP2, VAMP3, VAMP4, VAMP7 or VAMP8 (PubMed:22118466, PubMed:21808019, PubMed:23741335). In turn, PICALM-dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors (PubMed:25241929). Modulates thereby autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP-CTF) (PubMed:25241929, PubMed:24067654).SUBUNIT Binds to clathrin; involves primarily the C-terminal sequences, but the full-length protein is required for full binding capacity. Binds phosphatidylinositol 4,5- bisphosphate. Interacts with PIMREG; this interaction may change the subcellular location into the nucleus (PubMed:16491119). Interacts with AP2A1 (via its alpha-appendage domain) (PubMed:16262731). Interacts (via N-terminus) with VAMP2; VAMP3; VAMP7 and VAMP8 (Via N-terminus) (PubMed:22118466, PubMed:21808019, PubMed:23741335). Interacts with LC3/MAP1LC3A (PubMed:24067654).TISSUE SPECIFICITY Expressed in all tissues examined.DISEASE A chromosomal aberration involving PICALM is found in diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with MLLT10.SIMILARITY Belongs to the PICALM/SNAP91 family.UniProtQ134922EQUAL652EQUALReactome Database ID Release 75434341Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434341ReactomeR-HSA-4343411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434341.1YIPF6Protein YIPF6YIPF6_HUMANReactome DB_ID: 434346UniProt:Q96EC8 YIPF6YIPF6FUNCTION May be required for stable YIPF1 and YIPF2 protein expression.SUBUNIT Predominantly interacts with YIPF1 or YIPF2, but may also form a ternary complex with YIPF1 and YIPF2. This interaction may stabilize YIPF1 and YIPF2.SIMILARITY Belongs to the YIP1 family.UniProtQ96EC81EQUAL236EQUALReactome Database ID Release 75434346Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434346ReactomeR-HSA-4343461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434346.1RAB5CRas-related protein Rab-5CRAB5C_HUMANReactome DB_ID: 434334UniProt:P51148 RAB5CRAB5CRABLFUNCTION Protein transport. Probably involved in vesicular traffic (By similarity).SUBUNIT Interacts with EEA1 (PubMed:12493736). Interacts with INCA1 (PubMed:21750715). Interacts with GDI1, GDI2, CHML and CHM; phosphorylation at Ser-85 disrupts this interaction (PubMed:29125462).PTM Phosphorylation of Ser-85 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.SIMILARITY Belongs to the small GTPase superfamily. Rab family.UniProtP511481EQUAL216EQUALReactome Database ID Release 75434334Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434334ReactomeR-HSA-4343341Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434334.1SNAPINSNARE-associated protein SnapinSNAPN_HUMANReactome DB_ID: 434344UniProt:O95295 SNAPINSNAPINBLOC1S7SNAP25BPSNAPAPFUNCTION Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking and synaptic vesicle recycling. May modulate a step between vesicle priming, fusion and calcium-dependent neurotransmitter release through its ability to potentiate the interaction of synaptotagmin with the SNAREs and the plasma-membrane-associated protein SNAP25. Its phosphorylation state influences exocytotic protein interactions and may regulate synaptic vesicle exocytosis. May also have a role in the mechanisms of SNARE-mediated membrane fusion in non-neuronal cells (PubMed:17182842, PubMed:18167355). As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor (PubMed:25898167).SUBUNIT Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos (PubMed:15102850, PubMed:22203680). Component of the BLOC-one-related complex (BORC) which is composed of BLOC1S1, BLOC1S2, BORCS5, BORCS6, BORCS7, BORCS8, KXD1 and SNAPIN (PubMed:25898167). Associates with the SNARE complex. Interacts with CSNK1D, SNAP23 and STX4A but not with STX1A, VAMP2 and SYT1. Interacts with SNAP25; the interaction with SNAP25 is increased by its phosphorylation. Interacts with CNTRL, NANOS1, PUM2 and RGS7 (PubMed:12659861, PubMed:16213214, PubMed:19168546). Interacts with TOR1A; the interaction is direct and associates SNAPIN with the CSN complex (PubMed:18167355, PubMed:21102408).SUBUNIT (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL70.TISSUE SPECIFICITY Expressed in male germ cells of adult testis (at protein level).DEVELOPMENTAL STAGE Expressed in germ cells of 22-week prenatal testis.PTM Phosphorylated by CSNK1D/CK1 (By similarity). Phosphorylated by PKD, phosphorylation controls SNAPIN protein stability.SIMILARITY Belongs to the SNAPIN family.UniProtO952952EQUAL136EQUALReactome Database ID Release 75434344Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434344ReactomeR-HSA-4343441Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434344.1SORT1SortilinSORT_HUMANReactome DB_ID: 434332UniProt:Q99523 SORT1SORT1FUNCTION Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Lysosomal proteins bind specifically to the receptor in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex. The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer. Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi.SUBUNIT Interacts with LPL and SLC2A4 (By similarity). Interacts with the cytosolic adapter proteins GGA1 and GGA2 (PubMed:20015111). Interacts with numerous ligands including the receptor-associated protein LRPAP1/RAP, GM2A and NTS. Forms a complex with NGFR which binds specifically to the precursor forms of NGFB (proNGFB) and BDNF (proBDNF). Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; may regulate their anterograde axonal transport and signaling. Interacts with CLN5 (PubMed:22431521). Interacts with PSAP (PubMed:22431521, PubMed:14657016). Interacts with GRN; this interaction mediates endocytosis and lysosome delivery of progranulin; interaction occurs at the neuronal cell surface in a stressed nervous system (PubMed:21092856). Interacts with the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35; which is involved in retrograde trafficking of the receptor from endosomes to the Golgi apparatus (PubMed:18817523).TISSUE SPECIFICITY Expressed in brain and prostate (at protein level). Expressed at high levels in brain, spinal cord, heart, skeletal muscle, thyroid, placenta and testis. Expressed at lower levels in lymphoid organs, kidney, colon and liver.INDUCTION During osteoblast differentiation.DOMAIN The N-terminal propeptide may facilitate precursor transport within the Golgi stack. Intrachain binding of the N-terminal propeptide and the extracellular domain may also inhibit premature ligand binding.DOMAIN The extracellular domain may be shed following protease cleavage in some cell types.PTM The N-terminal propeptide is cleaved by furin and possibly other homologous proteases.PTM Palmitoylated (PubMed:18817523). Undergoes cysteine S-palmitoylation which promotes the partitioning of the receptor into an endosomal membrane subdomain where it can interact with the retromer cargo-selective complex which mediates its retrograde trafficking to the Golgi apparatus (PubMed:18817523).PTM Phosphorylation at Ser-825 facilitates the interaction with GGA1.POLYMORPHISM Genetic variations in SORT1 influence low density lipoprotein cholesterol (LDL-C) variability and contribute to the low density lipoprotein cholesterol level quantitative trait locus 6 (LDLCQ6) [MIM:613589].DISEASE A common polymorphism located in a non-coding region between CELSR2 and PSRC1 alters a CEBP transcription factor binding site and is responsible for changes in hepatic expression of SORT1. Altered SORT1 expression in liver affects low density lipoprotein cholesterol levels in plasma and is associated with susceptibility to myocardial infarction.SIMILARITY Belongs to the VPS10-related sortilin family. SORT1 subfamily.UniProtQ9952378EQUAL831EQUALReactome Database ID Release 75434332Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434332ReactomeR-HSA-4343321Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434332.1SNX2Sorting nexin-2SNX2_HUMANReactome DB_ID: 434333UniProt:O60749 SNX2SNX2TRG9FUNCTION Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:16179610). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex (PubMed:17101778). The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC) (Probable). Can sense membrane curvature and has in vitro vesicle-to-membrane remodeling activity (PubMed:23085988). Required for retrograde endosome-to-TGN transport of TGN38 (PubMed:20138391). Promotes KALRN- and RHOG-dependent but retromer-independent membrane remodeling such as lamellipodium formation; the function is dependent on GEF activity of KALRN (PubMed:20604901).SUBUNIT Predominantly forms heterodimers with BAR domain-containing sorting nexins SNX5, SNX6 and SNX32; can self-associate to form homodimers (PubMed:23085988). The heterodimers are proposed to self-assemble into helical arrays on the membrane to stabilize and expand local membrane curvature underlying endosomal tubule formation. Thought to be a component of the originally described retromer complex (also called SNX-BAR retromer) which is a pentamer containing the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity (Probable). Interacts with SNX5, SNX6, SNX32, VPS26A, VPS29, VPS35, FNBP1, KALRN, RHOG (GDP-bound form) (PubMed:11438682, PubMed:14596906, PubMed:17101778, PubMed:19935774., PubMed:19619496, PubMed:20604901, PubMed:23085988).DOMAIN The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of a N-terminal amphipatric helix (AH) in the membrane (Probable).SIMILARITY Belongs to the sorting nexin family.UniProtO607491EQUAL519EQUALReactome Database ID Release 75434333Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434333ReactomeR-HSA-4343331Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434333.1SNX5Sorting nexin-5SNX5_HUMANReactome DB_ID: 434336UniProt:Q9Y5X3 SNX5SNX5FUNCTION Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) (PubMed:15561769). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC) (Probable). Does not have in vitro vesicle-to-membrane remodeling activity (PubMed:23085988). Involved in retrograde transport of lysosomal enzyme receptor IGF2R (PubMed:17148574, PubMed:18596235). May function as link between endosomal transport vesicles and dynactin (Probable). Plays a role in the internalization of EGFR after EGF stimulation (Probable). Involved in EGFR endosomal sorting and degradation; the function involves PIP5K1C isoform 3 and is retromer-independent (PubMed:23602387). Together with PIP5K1C isoform 3 facilitates HGS interaction with ubiquitinated EGFR, which initiates EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body for subsequent lysosomal degradation (Probable). Involved in E-cadherin sorting and degradation; inhibits PIP5K1C isoform 3-mediated E-cadherin degradation (PubMed:24610942). Plays a role in macropinocytosis (PubMed:18854019, PubMed:21048941).SUBUNIT Forms heterodimers with BAR domain-containing sorting nexins SNX1 and SNX2; does not homodimerize (PubMed:23085988). The heterodimers are proposed to self-assemble into helical arrays on the membrane to stabilize and expand local membrane curvature underlying endosomal tubule formation. Thought to be a component of the originally described retromer complex (also called SNX-BAR retromer) which is a pentamer containing the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity (Probable). Interacts with SNX1, SNX2, VPS26A, VPS29, VPS35, DCTN1, DOCK1, MIB1, PIP5K1C isoform 3. Interacts with HGS; increased by PIP5K1C isoform 3 kinase activity and by PtdIns(3P) and/or PtdIns(3,4)P2 (PubMed:16857196, PubMed:16968745, PubMed:19619496, PubMed:23085988, PubMed:18596235, PubMed:23602387, PubMed:24610942).DOMAIN The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate.DOMAIN The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of an amphipatric helix (AH) in the membrane (Probable).SIMILARITY Belongs to the sorting nexin family.CAUTION The selectivity for particular phosphatidylinositol lipids is under debate. According to one report (PubMed:19553671), the rat protein binds exclusively to phosphatidylinositol 4,5-bisphosphate, while the human protein has been reported (PubMed:15561769) to bind to phosphatidylinositol 3,4-bisphosphate and also to phosphatidylinositol 3-phosphate.UniProtQ9Y5X32EQUAL404EQUALReactome Database ID Release 75434336Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434336ReactomeR-HSA-4343361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434336.1TGOLN2Trans-Golgi network integral membrane protein 2TGON2_HUMANReactome DB_ID: 434342UniProt:O43493 TGOLN2TGOLN2TGN46TGN51FUNCTION May be involved in regulating membrane traffic to and from trans-Golgi network.TISSUE SPECIFICITY Isoform TGN46 is widely expressed. Isoform TGN51 is more abundant in fetal lung and kidney. Isoform TGN48 is barely expressed in embryonic kidney and promyelocytic cells.UniProtO4349322EQUAL480EQUALReactome Database ID Release 75434342Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434342ReactomeR-HSA-4343421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434342.1TFRCTFRC(1-760)Transferrin receptor protein 1TFR1_HUMANReactome DB_ID: 434330UniProt:P02786 TFRCTFRCFUNCTION Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the heditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site. Positively regulates T and B cell proliferation through iron uptake (PubMed:26642240). Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway (PubMed:26214738). When dietary levels of stearate (C18:0) are low, promotes activation of the JNK pathway, resulting in HUWE1-mediated ubiquitination and subsequent degradation of the mitofusin MFN2 and inhibition of mitochondrial fusion (PubMed:26214738). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (PubMed:26214738).FUNCTION (Microbial infection) Acts as a receptor for new-world arenaviruses: Guanarito, Junin and Machupo virus.SUBUNIT Homodimer; disulfide-linked. Binds one transferrin or HFE molecule per subunit. Binds the HLA class II histocompatibility antigen, DR1. Interacts with SH3BP3. Interacts with STEAP3; facilitates TFRC endocytosis in erythroid precursor cells (PubMed:26642240).SUBUNIT (Microbial infection) Interacts with Guanarito, Junin and Machupo arenavirus glycoprotein complex (PubMed:17287727, PubMed:18268337).INDUCTION Regulated by cellular iron levels through binding of the iron regulatory proteins, IRP1 and IRP2, to iron-responsive elements in the 3'-UTR. Up-regulated upon mitogenic stimulation.PTM Stearoylated by ZDHHC6 which inhibits TFRC-mediated activation of the JNK pathway and promotes mitochondrial fragmentation (PubMed:26214738). Stearoylation does not affect iron uptake (PubMed:26214738).PTM N- and O-glycosylated, phosphorylated and palmitoylated. The serum form is only glycosylated.PTM Proteolytically cleaved on Arg-100 to produce the soluble serum form (sTfR).PTM Palmitoylated on both Cys-62 and Cys-67. Cys-62 seems to be the major site of palmitoylation.MISCELLANEOUS Serum transferrin receptor (sTfR) is used as a means of detecting erythropoietin (EPO) misuse by athletes and as a diagnostic test for anemia resulting from a number of conditions including rheumatoid arthritis, pregnancy, irritable bowel syndrome and in HIV patients.MISCELLANEOUS Canine and feline parvoviruses bind human and feline transferrin receptors and use these receptors to enter and infect cells.SIMILARITY Belongs to the peptidase M28 family. M28B subfamily.UniProtP027861EQUAL760EQUALReactome Database ID Release 75434330Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434330ReactomeR-HSA-4343301Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434330.1IGF2RCation-independent mannose-6-phosphate receptorMPRI_HUMANReactome DB_ID: 434345UniProt:P11717 IGF2RIGF2RMPRIFUNCTION Mediates the transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes (PubMed:2963003, PubMed:18817523). Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex (PubMed:2963003, PubMed:18817523). The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer (PubMed:18817523). This receptor also binds IGF2 (PubMed:18046459). Acts as a positive regulator of T-cell coactivation by binding DPP4 (PubMed:10900005).SUBUNIT Binds HA-I and HA-II plasma membrane adapters (By similarity). Interacts with DPP4; the interaction is direct. Binds GGA1, GGA2 and GGA3. Interacts with the heterotrimeric retromer cargo-selective complex (CSC), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35; which is involved in retrograde trafficking of the receptor from endosomes to the Golgi apparatus (Probable).DOMAIN Contains 15 repeating units of approximately 147 AA harboring four disulfide bonds each. The most highly conserved region within the repeat consists of a stretch of 13 AA that contains cysteines at both ends.PTM Palmitoylated (PubMed:18817523). Undergoes cysteine S-palmitoylation which promotes interaction with the retromer cargo-selective complex which mediates its retrograde trafficking to the Golgi apparatus (PubMed:18817523).SIMILARITY Belongs to the MRL1/IGF2R family.UniProtP1171741EQUAL2491EQUALReactome Database ID Release 75434345Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434345ReactomeR-HSA-4343451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434345.1Reactome Database ID Release 75432674Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=432674ReactomeR-HSA-4326741Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-432674.1Arf1-GTPReactome DB_ID: 199981ARF1Arf1Reactome DB_ID: 199971UniProt:P84077 ARF1ARF1FUNCTION GTP-binding protein involved in protein trafficking among different compartments. Modulates vesicle budding and uncoating within the Golgi complex. Deactivation induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, suggesting a crucial role in protein trafficking. In its GTP-bound form, its triggers the association with coat proteins with the Golgi membrane. The hydrolysis of ARF1-bound GTP, which is mediated by ARFGAPs proteins, is required for dissociation of coat proteins from Golgi membranes and vesicles. The GTP-bound form interacts with PICK1 to limit PICK1-mediated inhibition of Arp2/3 complex activity; the function is linked to AMPA receptor (AMPAR) trafficking, regulation of synaptic plasicity of excitatory synapses and spine shrinkage during long-term depression (LTD).FUNCTION (Microbial infection) Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase.SUBUNIT Interacts (when activated) with GGA1, GGA2 and GGA3; the interaction is required for proper subcellular location of GGA1, GGA2 and GGA3 (PubMed:11950392, PubMed:28868155). Interacts with ARHGAP21, ASAP2, HERC1, PRKCABP, PIP5K1B, TMED2, PSCD2, TMED10 and GRIA2 (PubMed:10022920, PubMed:17347647, PubMed:23889934, PubMed:8861955). Interacts with ARFGAP1, which hydrolyzes GTP and thus, regulates its function (PubMed:10102276). Interacts with PI4KB in the Golgi complex (PubMed:17555535). Interacts with NCS1/FREQ in the Golgi and at the plasma membrane (PubMed:17555535). Interacts with PLEKHA3 (PubMed:21454700). Interacts with PLEKHA8; the interaction, together with phosphatidylinositol 4-phosphate binding, is required for FAPP2-mediated glucosylceramide transfer activity (PubMed:15107860). Interacts (activated) with PICK1 (via PDZ domain); the interaction blocks Arp2/3 complex inhibition (PubMed:23889934). Interacts with IQSEC1 (PubMed:24058294). Interacts with C9orf72 (By similarity) (PubMed:24058294).PTM Demyristoylated by S.flexneri cysteine protease IpaJ which cleaves the peptide bond between N-myristoylated Gly-2 and Asn-3.SIMILARITY Belongs to the small GTPase superfamily. Arf family.UniProtP840772EQUAL181EQUALReactome Database ID Release 75199971Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=199971ReactomeR-HSA-1999711Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-199971.11GTPGuanosine 5'-triphosphateReactome DB_ID: 29438GTP [ChEBI:15996]GTPGuanosine 5'-triphosphateChEBICHEBI:15996Reactome Database ID Release 7529438Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29438ReactomeR-ALL-294383Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29438.3COMPOUNDC000441Reactome Database ID Release 75199981Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=199981ReactomeR-HSA-1999811Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-199981.1Converted from EntitySet in ReactomeVampReactome DB_ID: 432668VAMP2Reactome DB_ID: 3754252EQUAL116EQUALReactome Database ID Release 75375425Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=375425ReactomeR-HSA-3754251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-375425.1VAMP7Vesicle-associated membrane protein 7VAMP7_HUMANReactome DB_ID: 2661972EQUAL220EQUALReactome Database ID Release 75266197Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=266197ReactomeR-HSA-2661971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-266197.1VAMP8Vesicle-associated membrane protein 8VAMP8_HUMANReactome DB_ID: 2662011EQUAL100EQUALReactome Database ID Release 75266201Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=266201ReactomeR-HSA-2662011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-266201.1Reactome Database ID Release 75432668Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=432668ReactomeR-HSA-4326681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-432668.1Converted from EntitySet in ReactomeGolgi-associated Vesicle Destined CargoReactome DB_ID: 435032TPD52Tumor protein D52TPD52_HUMANReactome DB_ID: 434329Golgi lumenGENE ONTOLOGYGO:0005796UniProt:P55327 TPD52TPD52SUBUNIT Forms a homodimer or heterodimer with other members of the family. All isoforms interact with several 14-3-3 proteins.TISSUE SPECIFICITY Isoform 2 is expressed in colon, breast, prostate, pancreas and kidney tumor cell lines. Isoform 2 is expressed at high levels in kidney, prostate, brain, small intestine and pancreas, at moderate levels in placenta and colon, at low levels in lung, liver and heart, and at very low levels in spleen, thymus, peripheral mononuclear blood cells, testis and ovary.DEVELOPMENTAL STAGE Isoform 2 is expressed at lower levels in fetal brain and kidney than in adult brain and kidney.SIMILARITY Belongs to the TPD52 family.UniProtP553271EQUAL224EQUALReactome Database ID Release 75434329Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434329ReactomeR-HSA-4343291Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434329.1TPD52L1Tumor protein D53TPD53_HUMANReactome DB_ID: 434331UniProt:Q16890 TPD52L1TPD52L1SUBUNIT Forms a homodimer or heterodimer with other members of the family.SIMILARITY Belongs to the TPD52 family.UniProtQ168901EQUAL204EQUALReactome Database ID Release 75434331Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434331ReactomeR-HSA-4343311Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434331.1TBC1D8BTBC1 domain family member 8BTBC8B_HUMANReactome DB_ID: 434328UniProt:Q0IIM8 TBC1D8BTBC1D8BFUNCTION Involved in vesicular recycling, probably as a RAB11B GTPase-activating protein.SUBUNIT Interacts (via domain Rab-GAP TBC) with RAB11B (in GTP-bound form).TISSUE SPECIFICITY Kidney (at protein level).DEVELOPMENTAL STAGE Expressed in glomerular podocytes and tubules in the fetal kidney (gestational age 25 weeks)(at protein level).DOMAIN The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site.UniProtQ0IIM81EQUAL1120EQUALReactome Database ID Release 75434328Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434328ReactomeR-HSA-4343281Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434328.1Reactome Database ID Release 75435032Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=435032ReactomeR-HSA-4350321Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-435032.1ARRB1Beta-arrestin-1ARRB1_HUMANReactome DB_ID: 264470UniProt:P49407 ARRB1ARRB1ARR1FUNCTION Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Involved in internalization of P2RY4 and UTP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 ands subsequent recycling. Involved in the degradation of cAMP by recruiting cAMP phosphodiesterases to ligand-activated receptors. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2). ERK1/2 activated by the beta-arrestin scaffold is largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Recruits c-Src/SRC to ADRB2 resulting in ERK activation. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Inhibits ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Is required for SP-stimulated endocytosis of NK1R and recruits c-Src/SRC to internalized NK1R resulting in ERK1/2 activation, which is required for the antiapoptotic effects of SP. Is involved in proteinase-activated F2RL1-mediated ERK activity. Acts as signaling scaffold for the AKT1 pathway. Is involved in alpha-thrombin-stimulated AKT1 signaling. Is involved in IGF1-stimulated AKT1 signaling leading to increased protection from apoptosis. Involved in activation of the p38 MAPK signaling pathway and in actin bundle formation. Involved in F2RL1-mediated cytoskeletal rearrangement and chemotaxis. Involved in AGTR1-mediated stress fiber formation by acting together with GNAQ to activate RHOA. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. May serve as nuclear messenger for GPCRs. Involved in OPRD1-stimulated transcriptional regulation by translocating to CDKN1B and FOS promoter regions and recruiting EP300 resulting in acetylation of histone H4. Involved in regulation of LEF1 transcriptional activity via interaction with DVL1 and/or DVL2 Also involved in regulation of receptors other than GPCRs. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Binds phosphoinositides. Binds inositolhexakisphosphate (InsP6) (By similarity). Involved in IL8-mediated granule release in neutrophils. Required for atypical chemokine receptor ACKR2-induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. Involved in the internalization of the atypical chemokine receptor ACKR3. Negatively regulates the NOTCH signaling pathway by mediating the ubiquitination and degradation of NOTCH1 by ITCH. Participates in the recruitment of the ubiquitin-protein ligase to the receptor (PubMed:23886940).SUBUNIT Monomer. Homodimer. Homooligomer; the self-association is mediated by InsP6-binding. Heterooligomer with ARRB2; the association is mediated by InsP6-binding. Interacts with GPR143. Interacts with ADRB2 (phosphorylated). Interacts with CHRM2 (phosphorylated). Interacts with LHCGR. Interacts with CYTH2 and CASR. Interacts with AP2B1 (dephosphorylated at 'Tyr-737'); phosphorylation of AP2B1 at 'Tyr-737' disrupts the interaction. Interacts (dephosphorylated at Ser-412) with CLTC. Interacts with CCR2 and GRK2. Interacts with CRR5. Interacts with PTAFR (phosphorylated on serine residues). Interacts with CLTC and MAP2K3. Interacts with CREB1. Interacts with TRAF6. Interacts with IGF1R and MDM2. Interacts with C5AR1. Interacts with PDE4D. Interacts with SRC (via the SH3 domain and the protein kinase domain); the interaction is independent of the phosphorylation state of SRC C-terminus. Interacts with TACR1. Interacts with RAF1. Interacts with CHUK, IKBKB and MAP3K14. Interacts with DVL1; the interaction is enhanced by phosphorylation of DVL1. Interacts with DVL2; the interaction is enhanced by phosphorylation of DVL2. Interacts with IGF1R. Associates with MAP kinase p38. Part of a MAPK signaling complex consisting of TACR1, ARRB1, SRC, MAPK1 (activated) and MAPK3 (activated). Part of a MAPK signaling complex consisting of F2RL1, ARRB1, RAF1, MAPK1 (activated) and MAPK3 (activated) (By similarity). Interacts with MAP2K4/MKK4. Interacts with HCK and CXCR1 (phosphorylated). Interacts with ACKR3 and ACKR4. Interacts with ARRDC1; the interaction is direct (PubMed:23886940). Interacts with GPR61, GPR62 and GPR135 (PubMed:28827538).DOMAIN The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1 (By similarity). Binding to phosphorylated GPCRs induces a conformationanl change that exposes the motif to the surface.DOMAIN The N-terminus binds InsP6 with low affinity.DOMAIN The C-terminus binds InsP6 with high affinity.PTM Constitutively phosphorylated at Ser-412 in the cytoplasm. At the plasma membrane, is rapidly dephosphorylated, a process that is required for clathrin binding and ADRB2 endocytosis but not for ADRB2 binding and desensitization. Once internalized, is rephosphorylated.PTM The ubiquitination status appears to regulate the formation and trafficking of beta-arrestin-GPCR complexes and signaling. Ubiquitination appears to occur GPCR-specific. Ubiquitinated by MDM2; the ubiquitination is required for rapid internalization of ADRB2. Deubiquitinated by USP33; the deubiquitination leads to a dissociation of the beta-arrestin-GPCR complex. Stimulation of a class A GPCR, such as ADRB2, induces transient ubiquitination and subsequently promotes association with USP33.SIMILARITY Belongs to the arrestin family.UniProtP494071EQUAL418EQUALReactome Database ID Release 75264470Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=264470ReactomeR-HSA-2644701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-264470.1Cargo:AP-1:Arf1-GTP:beta-Arrestin-1:Vamp ComplexReactome DB_ID: 432669AP-1 ComplexReactome DB_ID: 350811Converted from EntitySet in ReactomeAP-1 sigmaReactome DB_ID: 350807AP1S1AP-1 sigma 1AReactome DB_ID: 3508041EQUAL158EQUALReactome Database ID Release 75350804Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350804ReactomeR-HSA-3508041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350804.1AP1S2AP-1 sigma 1BReactome DB_ID: 3508121EQUAL157EQUALReactome Database ID Release 75350812Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350812ReactomeR-HSA-3508121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350812.1AP1S3AP-1 sigma 1CReactome DB_ID: 3508061EQUAL154EQUALReactome Database ID Release 75350806Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350806ReactomeR-HSA-3508061Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350806.1Reactome Database ID Release 75350807Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350807ReactomeR-HSA-3508071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350807.11AP1B1AP-1 beta subunitReactome DB_ID: 3508091EQUAL949EQUALReactome Database ID Release 75350809Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350809ReactomeR-HSA-3508091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350809.11AP1G1AP-1 gamma subunitReactome DB_ID: 3508082EQUAL822EQUALReactome Database ID Release 75350808Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350808ReactomeR-HSA-3508081Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350808.11Converted from EntitySet in ReactomeAP-1 muReactome DB_ID: 350815AP1M1AP-1 mu 1Reactome DB_ID: 3508052EQUAL423EQUALReactome Database ID Release 75350805Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350805ReactomeR-HSA-3508051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350805.1AP1M2AP-1 mu 2Reactome DB_ID: 3508131EQUAL423EQUALReactome Database ID Release 75350813Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350813ReactomeR-HSA-3508131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350813.1Reactome Database ID Release 75350815Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350815ReactomeR-HSA-3508151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350815.11Reactome Database ID Release 75350811Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350811ReactomeR-HSA-3508111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350811.1ComplexPortalCPX-5050ComplexPortalCPX-5049ComplexPortalCPX-5047ComplexPortalCPX-50481ARRB1Beta-arrestin-1ARRB1_HUMANReactome DB_ID: 3508311EQUAL418EQUALReactome Database ID Release 75350831Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350831ReactomeR-HSA-3508311Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350831.111111Reactome Database ID Release 75432669Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=432669ReactomeR-HSA-4326691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-432669.1Reactome Database ID Release 75421833Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=421833ReactomeR-HSA-4218331Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-421833.111994746Pubmed2002Regulated transport of the glucose transporter GLUT4.Bryant, NJGovers, RJames, DENat Rev Mol Cell Biol 3:267-7711694590Pubmed2001GGAs: roles of the different domains and comparison with AP-1 and clathrinHirst, JLindsay, MRRobinson, MSMol Biol Cell 12:3573-88LEFT-TO-RIGHTtrans-Golgi Network Coat AssemblyOnce the basic components of the docking complex are assembled with one end of AP-1 bound to cargo molecules, the other end binds to clathrin. Clathrin triskelions polymerize into hexagons and pentagons, forming a cage, which leads to membrane deformation. This polymerization step drives the sculpting of the vesicle. The number of clathrin triskelions required to sculpt a vesicle appears to be variable, but has been estimated to require 36 - 60 triskelions assocaited with 30 - 66 AP-1 complexes. Here a ~380 angstroms vesicle is represented with 48 clathrin triskelions and 52 AP-1 complexes.Authored: Gillespie, ME, 2009-08-27Reviewed: Simpson, Jeremy C, 2009-08-27Edited: Gillespie, ME, 2008-05-21 20:31:35SH3GL2EndophilinReactome DB_ID: 182958UniProt:Q99962 SH3GL2SH3GL2CNSA2SH3D2AFUNCTION Implicated in synaptic vesicle endocytosis. May recruit other proteins to membranes with high curvature. Required for BDNF-dependent dendrite outgrowth. Cooperates with SH3GL2 to mediate BDNF-NTRK2 early endocytic trafficking and signaling from early endosomes.SUBUNIT Monomer; in cytoplasm. Homodimer; when associated with membranes (By similarity). Interacts with OPHN1 (By similarity). Interacts with SYNJ1 (PubMed:10542231). Interacts with DNM1 (By similarity). Interacts with MAP4K3; the interaction appears to regulate MAP4K3-mediated JNK activation (By similarity). Interacts with PDCD6IP (PubMed:17350572). Interacts with ATX2 (PubMed:18602463). Interacts with ADAM9 and ADAM15 cytoplasmic tails (PubMed:10531379). Interacts with BIN2 (PubMed:23285027). Interacts with TMEM108 (By similarity). Interacts with ADGRB2 (PubMed:28891236).TISSUE SPECIFICITY Brain, mostly in frontal cortex. Expressed at high level in fetal cerebellum.DOMAIN An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes. The BAR domain dimer forms a rigid crescent shaped bundle of helices with the pair of second amphipathic helices protruding towards the membrane-binding surface.MISCELLANEOUS HeLa cells expressing the N-BAR domain of SH3GL2 show tubulation of the plasma membrane. The N-BAR domain binds liposomes and induces formation of tubules from liposomes. The N-terminal amphipathic helix is required for liposome binding. The second amphipathic helix enhances liposome tubulation.SIMILARITY Belongs to the endophilin family.UniProtQ999621EQUAL352EQUALReactome Database ID Release 75182958Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=182958ReactomeR-HSA-1829581Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-182958.1DNM2Dynamin-2Reactome DB_ID: 2213180UniProt:P50570 DNM2DNM2DYN2FUNCTION Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Plays an important role in vesicular trafficking processes, in particular endocytosis. Involved in cytokinesis (PubMed:12498685). Regulates maturation of apoptotic cell corpse-containing phagosomes by recruiting PIK3C3 to the phagosome membrane (By similarity).SUBUNIT Interacts with MYOF (By similarity). Interacts with CTTN and ACTN1 (By similarity). Interacts with SHANK1, SHANK2, SH3BP4 and NOSTRIN. Interacts with SNX9. Interacts with SNX33 (via SH3 domain). Interacts with MYO1E (via SH3 domain). Interacts with PSTPIP1. Interacts with CTNND2 (PubMed:22022388). May interact with PIK3C3 (By similarity). May be a component of a complex composed of RAB5A (in GDP-bound form), DYN2 and PIK3C3 (By similarity). Interacts with BIN1 (PubMed:17676042).TISSUE SPECIFICITY Ubiquitously expressed.PTM Phosphorylation at Ser-764 by CDK1 is greatly increased upon mitotic entry. It regulates cytokinesis downstream of calcineurin, and does not affect clathrin-mediated endocytosis. Dephosphorylated by calcineurin/PP2 (By similarity). Phosphorylated on tyrosine residues after activation of SRC (By similarity).MISCELLANEOUS Overexpression of CNM- and CMT-related DNM2 mutants in COS7 cells, whatever the mutated domain, led to a reduction in clathrin-mediated receptor endocytosis associated with MAPK ERK-1 and ERK-2 impairment. The membrane trafficking impairment process may represent a common pathophysiological pathway in the autosomal forms of CNM DNM2-CMT neuropathy.SIMILARITY Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.UniProtP505701EQUAL870EQUALReactome Database ID Release 752213180Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2213180ReactomeR-HSA-22131801Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2213180.1Clathrin TriskelionReactome DB_ID: 350827CLTC-1Clathrin heavy chain isoform 1Reactome DB_ID: 350824UniProt:Q00610-1 CLTCCLTCCLH17CLTCL2KIAA0034FUNCTION Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:16968737, PubMed:21297582). The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Plays a role in early autophagosome formation (PubMed:20639872).SUBUNIT Clathrin triskelions, composed of 3 heavy chains and 3 light chains, are the basic subunits of the clathrin coat (PubMed:16968737). In the presence of light chains, hub assembly is influenced by both the pH and the concentration of calcium. Interacts with HIP1 (PubMed:11532990). Interacts with DENND1A, DENND1B and DENND1C (By similarity). May interact with OCRL (By similarity). Interacts with ERBB2 (PubMed:16314522). Interacts with FKBP6 (PubMed:18529014). Interacts with CKAP5 and TACC3 forming the TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules bridges; the complex implicates clathrin triskelions; TACC3 and CLTC are proposed to form a composite microtubule interaction surface (PubMed:21297582). Interacts with ATG16L1 (via N-terminus) (PubMed:20639872). Interacts with RFTN1; the interaction occurs in response to pathogens (PubMed:27022195, PubMed:21266579). Interacts with USP2 isoform 4 (PubMed:26756164).DOMAIN The N-terminal seven-bladed beta-propeller is formed by WD40-like repeats, and projects inward from the polyhedral outer clathrin coat. It constitutes a major protein-protein interaction node.SIMILARITY Belongs to the clathrin heavy chain family.UniProt IsoformQ00610-12EQUAL1675EQUALReactome Database ID Release 75350824Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350824ReactomeR-HSA-3508241Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350824.13CLTA-1Clathrin light chainCLTA isoform 1Reactome DB_ID: 350828UniProt:P09496-1 CLTACLTAFUNCTION Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:21297582).SUBUNIT Clathrin coats are formed from molecules containing 3 heavy chains and 3 light chains. Interacts with CALY; the interaction stimulates clathrin self-assembly and clathrin-mediated endocytosis. Interacts with CKAP5 and TACC3 forming the TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules bridges; the complex implicates clathrin triskelions.SIMILARITY Belongs to the clathrin light chain family.UniProt IsoformP09496-11EQUAL248EQUALReactome Database ID Release 75350828Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350828ReactomeR-HSA-3508281Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350828.13Reactome Database ID Release 75350827Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350827ReactomeR-HSA-3508271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350827.14852Arf1-GDPReactome DB_ID: 201340ARF1Arf1Reactome DB_ID: 2008262EQUAL181EQUALReactome Database ID Release 75200826Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=200826ReactomeR-HSA-2008261Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-200826.11GDPGuanosine 5'-diphosphateGuanosine diphosphateReactome DB_ID: 29420GDP [ChEBI:17552]GDPGuanosine 5'-diphosphateGuanosine diphosphateChEBICHEBI:17552Reactome Database ID Release 7529420Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29420ReactomeR-ALL-294202Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29420.2COMPOUNDC000351Reactome Database ID Release 75201340Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=201340ReactomeR-HSA-2013401Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-201340.152Cargo:AP-1:Beta-arrestin:Vamp:Clathrin Triskelion:Dynamin:Endophilin ComplexReactome DB_ID: 350825SH3GL2EndophilinReactome DB_ID: 3511891EQUAL352EQUALReactome Database ID Release 75351189Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351189ReactomeR-HSA-3511891Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351189.11Cargo:AP-1:beta-Arrestin-1:Vamp ComplexReactome DB_ID: 43267711111Reactome Database ID Release 75432677Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=432677ReactomeR-HSA-4326771Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-432677.152DNM2Dynamin-2DYN2_HUMANReactome DB_ID: 29808421EQUAL870EQUALReactome Database ID Release 752980842Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2980842ReactomeR-HSA-29808421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2980842.1148Reactome Database ID Release 75350825Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350825ReactomeR-HSA-3508251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350825.1PiOrthophosphatehydrogenphosphatePhosphateInorganic PhosphateReactome DB_ID: 29372hydrogenphosphate [ChEBI:43474]hydrogenphosphatehydrogen phosphatephosphate[PO3(OH)](2-)INORGANIC PHOSPHATE GROUPHYDROGENPHOSPHATE IONHPO4(2-)[P(OH)O3](2-)ChEBICHEBI:43474Reactome Database ID Release 7529372Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29372ReactomeR-ALL-293724Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29372.4COMPOUNDC0000952Reactome Database ID Release 75421831Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=421831ReactomeR-HSA-4218311Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-421831.110394364Pubmed1999Functional organization of clathrin in coats: combining electron cryomicroscopy and X-ray crystallographyMusacchio, ASmith, CJRoseman, AMHarrison, SCKirchhausen, TomasPearse, BMMol Cell 3:761-7017095010Pubmed2007Cryo-electron tomography of clathrin-coated vesicles: structural implications for coat assemblyCheng, YBoll, WKirchhausen, THarrison, SCWalz, TJ Mol Biol 365:892-9LEFT-TO-RIGHTtrans-Golgi Network Derived Vesicle UncoatingThe heat shock protein Hsc70 and auxilin, a J-domain containing protein, are responsible for clathrin disassembly through an ATP-dependent reaction. This uncoating step may be a point in the pathway subject to regulation. This final step releases the vesicle from the clathrin cage. The vesicle still contatins a specific Vamp molecule, part of the targeting and fusion mechanism that delivers the vesicle to its ultimate destination. This vesicle also contains its cargo, membrane proteins embeded in the Golgi-associated vesicle membrane.Authored: Gillespie, ME, 2009-08-27Reviewed: Simpson, Jeremy C, 2009-08-27Edited: Gillespie, ME, 2008-05-21 20:31:41HSC70:Auxillin ComplexReactome DB_ID: 351175DNAJC6Putative tyrosine-protein phosphatase auxilinAUXI_HUMANReactome DB_ID: 264472UniProt:O75061 DNAJC6DNAJC6KIAA0473FUNCTION Recruits HSPA8/HSC70 to clathrin-coated vesicles and promotes uncoating of clathrin-coated vesicles. Plays a role in clathrin-mediated endocytosis in neurons (By similarity).SUBUNIT Interacts with HSPA8/HSC70. Interacts with CLTC. Interacts with AP2A2 (By similarity).TISSUE SPECIFICITY Expressed in various brain regions, including cerebellum, corpus callosum, cortex, striatum, brainstem, pons, putamen, spinal cord and substantia nigra. Very low expression in non-neural tissues such as leukocytes, liver, adipose tissue, skeletal muscle and bone marrow.UniProtO750611EQUAL913EQUALReactome Database ID Release 75264472Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=264472ReactomeR-HSA-2644721Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-264472.11HSPA8Heat shock cognate 71 kDa proteinHSP7C_HUMANHSC70Reactome DB_ID: 264476UniProt:P11142 HSPA8HSPA8HSC70HSP73HSPA10FUNCTION Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24318877, PubMed:27474739, PubMed:24121476, PubMed:26865365). Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:10722728, PubMed:11276205). Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). Interacts with VGF-derived peptide TLQP-21 (PubMed:28934328).SUBUNIT Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with PACRG. Interacts with HSPH1/HSP105. Interacts with IRAK1BP1 and BAG1. Interacts with DNAJC7. Interacts with DNAJB12 (via J domain) (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661). Interacts with DNAJB14 (via J domain) (PubMed:23018488, PubMed:24732912, PubMed:27916661). Interacts (via C-terminus) with the E3 ligase CHIP forming a 210 kDa complex of one CHIP and two HSPA8 molecules. Interacts with CITED1 (via N-terminus); the interaction suppresses the association of CITED1 to p300/CBP and Smad-mediated transcription transactivation. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts with TRIM5. Part of a complex composed at least of ASCL2, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. Interacts with METTL21A. Following LPS binding, may form a complex with CXCR4, GDF5 and HSP90AA1. Interacts with PRKN. Interacts with FOXP3. Interacts with DNAJC9 (via J domain) (PubMed:17182002). Interacts with MLLT11 (PubMed:24880125). Interacts with RNF207 (PubMed:25281747). Interacts with DNAJC21 (PubMed:27346687). Interacts with DNAJB2 (PubMed:15936278). Interacts with TTC1 (via TPR repeats) (PubMed:15708368). Interacts with SGTA (via TPR repeats) (By similarity). Interacts with HSF1 (via transactivation domain) (PubMed:9499401). Interacts with HOPX, HSP40 and HSP90 (PubMed:27708256). Interacts with STUB1 (PubMed:27708256). Interacts with BAG2 (PubMed:24318877). Interacts with BAG3 (PubMed:27474739, PubMed:24318877). Interacts with DNAJC12 (PubMed:24122553). Interacts with ZMYND10 (PubMed:29601588). Interacts with HSPC138 (PubMed:25760597). Interacts with BCL2L1, GIMAP5 and MCL1; the interaction with BCL2L1 or MCL1 is impaired in the absence of GIMAP5 (By similarity). Interacts with NLPR12 (PubMed:17947705). Interacts with TTC4 (PubMed:18320024).SUBUNIT (Microbial infection) Interacts with SV40 VP1.TISSUE SPECIFICITY Ubiquitous.INDUCTION Constitutively synthesized.DOMAIN The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.PTM Acetylated.PTM ISGylated.PTM Trimethylation at Lys-561 reduces fibrillar SNCA binding.SIMILARITY Belongs to the heat shock protein 70 family.UniProtP111422EQUAL646EQUALReactome Database ID Release 75264476Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=264476ReactomeR-HSA-2644761Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-264476.11Reactome Database ID Release 75351175Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351175ReactomeR-HSA-3511751Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351175.1Cargo:AP-1:Beta-arrestin:Clathrin Triskelion:Vamp ComplexReactome DB_ID: 351198Converted from EntitySet in ReactomeGolgi-associated Vesicle CargoReactome DB_ID: 432672CPDCarboxypeptidase DCBPD_HUMANReactome DB_ID: 43267132EQUAL1380EQUALReactome Database ID Release 75432671Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=432671ReactomeR-HSA-4326711Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-432671.1PIK3C2APhosphatidylinositol-4-phosphate 3-kinase C2 domain-containing alpha polypeptideP3C2A_HUMANReactome DB_ID: 4326832EQUAL1686EQUALReactome Database ID Release 75432683Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=432683ReactomeR-HSA-4326831Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-432683.1SNX9Sorting nexin-9SNX9_HUMANReactome DB_ID: 4329901EQUAL595EQUALReactome Database ID Release 75432990Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=432990ReactomeR-HSA-4329901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-432990.1PICALMPhosphatidylinositol-binding clathrin assembly proteinPICAL_HUMANReactome DB_ID: 4298122EQUAL652EQUALReactome Database ID Release 75429812Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429812ReactomeR-HSA-4298121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429812.1TGOLN2Trans-Golgi network integral membrane protein 2TGON2_HUMANReactome DB_ID: 42981822EQUAL480EQUALReactome Database ID Release 75429818Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429818ReactomeR-HSA-4298181Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429818.1OCRLInositol polyphosphate 5-phosphatase OCRL-1OCRL_HUMANReactome DB_ID: 4342141EQUAL901EQUALReactome Database ID Release 75434214Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434214ReactomeR-HSA-4342141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434214.1IGF2RCation-independent mannose-6-phosphate receptorMPRI_HUMANReactome DB_ID: 43421341EQUAL2491EQUALReactome Database ID Release 75434213Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434213ReactomeR-HSA-4342131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434213.1NECAP1Adaptin ear-binding coat-associated protein 1NECP1_HUMANReactome DB_ID: 4342181EQUAL275EQUALReactome Database ID Release 75434218Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434218ReactomeR-HSA-4342181Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434218.1SNX2Sorting nexin-2SNX2_HUMANReactome DB_ID: 4342161EQUAL519EQUALReactome Database ID Release 75434216Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434216ReactomeR-HSA-4342161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434216.1SORT1SortilinSORT_HUMANReactome DB_ID: 43422178EQUAL831EQUALReactome Database ID Release 75434221Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434221ReactomeR-HSA-4342211Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434221.1YIPF6Protein YIPF6YIPF6_HUMANReactome DB_ID: 4341991EQUAL236EQUALReactome Database ID Release 75434199Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434199ReactomeR-HSA-4341991Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434199.1RAB5CRas-related protein Rab-5CRAB5C_HUMANReactome DB_ID: 4341981EQUAL216EQUALReactome Database ID Release 75434198Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434198ReactomeR-HSA-4341981Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434198.1SNX5Sorting nexin-5SNX5_HUMANReactome DB_ID: 4342072EQUAL404EQUALReactome Database ID Release 75434207Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434207ReactomeR-HSA-4342071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434207.1GAKCyclin G-associated kinaseGAK_HUMANReactome DB_ID: 4342032EQUAL1311EQUALReactome Database ID Release 75434203Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434203ReactomeR-HSA-4342031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434203.1HIP1RHuntingtin-interacting protein 1-related proteinHIP1R_HUMANReactome DB_ID: 4342011EQUAL1068EQUALReactome Database ID Release 75434201Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434201ReactomeR-HSA-4342011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434201.1SNAPINSNARE-associated protein SnapinSNAPN_HUMANReactome DB_ID: 4342042EQUAL136EQUALReactome Database ID Release 75434204Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434204ReactomeR-HSA-4342041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434204.1AP3B1AP-3 complex subunit beta-1AP3B1_HUMANReactome DB_ID: 4341971EQUAL1094EQUALReactome Database ID Release 75434197Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434197ReactomeR-HSA-4341971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434197.1TFRCTFRC(1-760)Transferrin receptor protein 1TFR1_HUMANReactome DB_ID: 4341961EQUAL760EQUALReactome Database ID Release 75434196Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434196ReactomeR-HSA-4341961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434196.1AP3S1AP-3 complex subunit sigma-1AP3S1_HUMANReactome DB_ID: 4342051EQUAL193EQUALReactome Database ID Release 75434205Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434205ReactomeR-HSA-4342051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434205.1AP4E1AP-4 complex subunit epsilon-1AP4E1_HUMANReactome DB_ID: 4342091EQUAL1137EQUALReactome Database ID Release 75434209Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434209ReactomeR-HSA-4342091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434209.1AP4B1AP-4 complex subunit beta-1AP4B1_HUMANReactome DB_ID: 4342001EQUAL739EQUALReactome Database ID Release 75434200Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434200ReactomeR-HSA-4342001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434200.1Reactome Database ID Release 75432672Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=432672ReactomeR-HSA-4326721Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-432672.152AP-1 ComplexReactome DB_ID: 351186Converted from EntitySet in ReactomeAP-1 muReactome DB_ID: 351192AP1M1AP-1 mu 1Reactome DB_ID: 3511962EQUAL423EQUALReactome Database ID Release 75351196Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351196ReactomeR-HSA-3511961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351196.1AP1M2AP-1 mu 2Reactome DB_ID: 3511911EQUAL423EQUALReactome Database ID Release 75351191Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351191ReactomeR-HSA-3511911Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351191.1Reactome Database ID Release 75351192Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351192ReactomeR-HSA-3511921Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351192.11AP1G1AP-1 gamma subunitReactome DB_ID: 3511942EQUAL822EQUALReactome Database ID Release 75351194Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351194ReactomeR-HSA-3511941Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351194.11AP1B1AP-1 beta subunitReactome DB_ID: 3511811EQUAL949EQUALReactome Database ID Release 75351181Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351181ReactomeR-HSA-3511811Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351181.11Converted from EntitySet in ReactomeAP-1 sigmaReactome DB_ID: 351180AP1S1AP-1 sigma 1AReactome DB_ID: 3511971EQUAL158EQUALReactome Database ID Release 75351197Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351197ReactomeR-HSA-3511971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351197.1AP1S2AP-1 sigma 1BReactome DB_ID: 3511881EQUAL157EQUALReactome Database ID Release 75351188Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351188ReactomeR-HSA-3511881Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351188.1AP1S3AP-1 sigma 1CReactome DB_ID: 3511901EQUAL154EQUALReactome Database ID Release 75351190Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351190ReactomeR-HSA-3511901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351190.1Reactome Database ID Release 75351180Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351180ReactomeR-HSA-3511801Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351180.11Reactome Database ID Release 75351186Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351186ReactomeR-HSA-3511861Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351186.152Converted from EntitySet in ReactomeGolgi-associated Vesicle CargoReactome DB_ID: 435029TBC1D8BTBC1 domain family member 8BTBC8B_HUMANReactome DB_ID: 434219cytoplasmic vesicle lumenGENE ONTOLOGYGO:00602051EQUAL1120EQUALReactome Database ID Release 75434219Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434219ReactomeR-HSA-4342192Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434219.2TPD52Tumor protein D52TPD52_HUMANReactome DB_ID: 4342101EQUAL224EQUALReactome Database ID Release 75434210Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434210ReactomeR-HSA-4342102Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434210.2TPD52L1Tumor protein D53TPD53_HUMANReactome DB_ID: 4342201EQUAL204EQUALReactome Database ID Release 75434220Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=434220ReactomeR-HSA-4342202Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-434220.2Reactome Database ID Release 75435029Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=435029ReactomeR-HSA-4350292Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-435029.25248ARRB1Beta-arrestin-1ARRB1_HUMANReactome DB_ID: 3511871EQUAL418EQUALReactome Database ID Release 75351187Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351187ReactomeR-HSA-3511871Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351187.15252Reactome Database ID Release 75351198Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351198ReactomeR-HSA-3511981Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-351198.1ATPAdenosine 5'-triphosphateATP(4-)Reactome DB_ID: 113592ATP(4-) [ChEBI:30616]ATP(4-)ATPatpAdenosine 5'-triphosphateChEBICHEBI:30616Reactome Database ID Release 75113592Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113592ReactomeR-ALL-1135924Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113592.4COMPOUNDC00002525252ADPAdenosine 5'-diphosphateADP(3-)Reactome DB_ID: 29370ADP(3-) [ChEBI:456216]ADP(3-)ADP5'-O-[(phosphonatooxy)phosphinato]adenosineADP trianionChEBICHEBI:456216Reactome Database ID Release 7529370Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29370ReactomeR-ALL-293704Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29370.4COMPOUNDC00008485252Reactome Database ID Release 75421836Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=421836ReactomeR-HSA-4218361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-421836.18524399Pubmed1995Role of auxilin in uncoating clathrin-coated vesiclesUngewickell, EUngewickell, HHolstein, SELindner, RPrasad, KBarouch, WMartin, BGreene, LEEisenberg, ENature 378:632-516155256Pubmed2005Depletion of GAK/auxilin 2 inhibits receptor-mediated endocytosis and recruitment of both clathrin and clathrin adaptorsLee, DWZhao, XiaodongZhang, FEisenberg, EGreene, LEJ Cell Sci 118:4311-218374173Pubmed1993Alteration of clathrin light chain expression by transfection and gene disruptionActon, SLWong, DHParham, PBrodsky, FMJackson, APMol Biol Cell 4:647-60LEFT-TO-RIGHT3.6.5.43.6.5.33.6.5.23.6.5.1trans-Golgi Network Vesicle ScissionDynamin is recruited to the growing vesicle and, under conditions that interfere with its GTPase activity, dynamin forms a collar or ring around the neck of the budding vesicle. It is unclear whether dynamin acts as a mechanochemical transducer to generate fission or as a recruiter to attach other proteins that are directly responsible for the fission step. Lipid-modifying enzymes such as endophilin are also involved in vesicle formation. Endophilin is an acyltransferase that interacts with dynamin and that generates lysophosphatidic acid. The current view is that this reaction produces a negative curvature at the neck of the vesicle.Authored: Gillespie, ME, 2009-08-27Reviewed: Simpson, Jeremy C, 2009-08-27Edited: Gillespie, ME, 2008-05-21 20:31:41ACTIVATIONactiveUnit: #Protein75GENE ONTOLOGYGO:0003924gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 75351174Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351174Reactome Database ID Release 75421835Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=421835ReactomeR-HSA-4218351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-421835.18670264Pubmed1996Dynamin II binds to the trans-Golgi networkMaier, OKnoblich, MWestermann, PBiochem Biophys Res Commun 223:229-3311604418Pubmed2001Generation of high curvature membranes mediated by direct endophilin bilayer interactionsFarsad, KRingstad, NTakei, KFloyd, SRRose, KDe Camilli, PietroJ Cell Biol 155:193-200LEFT-TO-RIGHTACBD3 binds GOLGB1Golgi resident protein GCP60 (ACBD3) is a Golgi membrane-associated protein thought to be involved in the maintenance of the Golgi structure by interacting with Golgin subfamily B member 1 (GOLGB1, giantin), which may mediate protein transport between the endoplasmic reticulum and the Golgi (Sohda et al. 2001).Authored: Jassal, Bijay, 2016-05-31Reviewed: D'Eustachio, Peter, 2016-07-15Edited: Jassal, Bijay, 2016-05-31GOLGB1 homodimerReactome DB_ID: 6810505GOLGB1Golgin subfamily B member 1372 kDa Golgi complex-associated proteinGCP372GiantinMacrogolginReactome DB_ID: 6810004UniProt:Q14789 GOLGB1GOLGB1FUNCTION May participate in forming intercisternal cross-bridges of the Golgi complex.SUBUNIT Homodimer; disulfide-linked. Interacts with PLK3.MISCELLANEOUS Antigen in chronic rheumatoid arthritis and in the autoimmune disease Sjoegren syndrome.UniProtQ147891EQUAL3259EQUALReactome Database ID Release 756810004Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=6810004ReactomeR-HSA-68100041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-6810004.12Reactome Database ID Release 756810505Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=6810505ReactomeR-HSA-68105051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-6810505.1ACBD3Golgi resident protein GCP60GCP60_HUMANReactome DB_ID: 8874981UniProt:Q9H3P7 ACBD3ACBD3GCP60GOCAP1GOLPH1FUNCTION Involved in the maintenance of Golgi structure by interacting with giantin, affecting protein transport between the endoplasmic reticulum and Golgi (PubMed:11590181). Involved in hormone-induced steroid biosynthesis in testicular Leydig cells (By similarity). Recruits PI4KB to the Golgi apparatus membrane; enhances the enzyme activity of PI4KB activity via its membrane recruitment thereby increasing the local concentration of the substrate in the vicinity of the kinase (PubMed:27009356).FUNCTION (Microbial infection) Plays an essential role in Aichi virus RNA replication by recruiting PI4KB at the viral replication sites.SUBUNIT Homodimer (PubMed:23572552). Interacts with the C-terminal cytoplasmic domain of giantin/GOLGB1 (PubMed:11590181). Interacts with PBR and PKA regulatory subunit RI-alpha. Does not interact with PKA regulatory subunit RI-beta nor PKA regulatory subunit RII-alpha (By similarity). Interacts (via Q domain) with PI4KB (via N-terminus) (PubMed:23572552, PubMed:27009356, PubMed:27989622, PubMed:22124328, PubMed:22258260). Interacts (via Q domain) with TBC1D22A AND TBC1D22B; interactions with PI4KB and with TBC1D22A and TBC1D22B are mutually exclusive (PubMed:23572552, PubMed:27009356, PubMed:27989622, PubMed:22124328). Interacts with C10ORF76 and RAB11B (PubMed:23572552).SUBUNIT (Microbial infection) Interacts (via GOLD domain) with 3A proteins from various picornaviruses, including poliovirus, enterovirus A71, enterovirus D68, hepatitis A virus, human parechovirus 1, poliovirus, Human rhinovirus-14 (Hrv-14), coysackievirus B2, coysackievirus B3, coysackievirus B5, Aichi virus and human klassevirus (PubMed:23572552, PubMed:22258260, PubMed:31381608). Interacts (via GOLD domain) with Aichi virus protein 3A; this interaction allows the formation of a 3A/ACBD3/PI4KB complex in order to synthesize PI4P at the viral RNA replication sites (PubMed:23572552, PubMed:22124328, PubMed:27989622, PubMed:30755512) (Probable). Interacts with Aichi virus protein 2B (PubMed:22124328). Interacts with Aichi virus protein 2C (PubMed:22124328).TISSUE SPECIFICITY Ubiquitous, with highest expression in testis and ovary.DOMAIN The central Gln-rich region (Q domain) is involved in binding to PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). The C-terminal GOLD domain is essential for giantin binding. The GOLD domain is also involved in homodimerization (PubMed:23572552).DOMAIN (Microbial infection) The GOLD domain is involved in binding to the picornaviral protein 3A.UniProtQ9H3P72EQUAL528EQUALReactome Database ID Release 758874981Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8874981ReactomeR-HSA-88749811Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8874981.1ACBD3:GOLGB1 dimerReactome DB_ID: 887497511Reactome Database ID Release 758874975Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8874975ReactomeR-HSA-88749751Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8874975.1Reactome Database ID Release 758874979Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8874979ReactomeR-HSA-88749791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8874979.111590181Pubmed2001Identification and characterization of a novel Golgi protein, GCP60, that interacts with the integral membrane protein giantinSohda, MMisumi, YYamamoto, AYano, ANakamura, NIkehara, YJ. Biol. Chem. 276:45298-306Reactome Database ID Release 75432722Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=432722ReactomeR-HSA-4327223Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-432722.3