Protein: Vacuolar protein sorting-associated protein 33A (hVPS33A) (Q96AX1)
Organism: Homo sapiens (Human)
Function: Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations. Required for fusion of endosomes and autophagosomes with lysosomes; the function is dependent on its association with VPS16 but not VIPAS39. The function in autophagosome-lysosome fusion implicates STX17 but not UVRAG.
Subcellular location: Cytoplasmic vesicle {ECO:0000250|UniProtKB:Q63615}. Late endosome membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Lysosome membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Early endosome {ECO:0000305}. Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:24554770}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000305}.
Sequence: MAAHLSYGRVNLNVLREAVRRELREFLDKCAGSKAIVWDEYLTGPFGLIAQYSLLKEHEVEKMFTLKGNRLPAADVKNIIFFVRPRLELMDIIAENVLSEDRRGPTRDFHILFVPRRSLLCEQRLKDLGVLGSFIHREEYSLDLIPFDGDLLSMESEGAFKECYLEGDQTSLYHAAKGLMTLQALYGTIPQIFGKGECARQVANMMIRMKREFTGSQNSIFPVFDNLLLLDRNVDLLTPLATQLTYEGLIDEIYGIQNSYVKLPPEKFAPKKQGDGGKDLPTEAKKLQLNSAEELYAEIRDKNFNAVGSVLSKKAKIISAAFEERHNAKTVGEIKQFVSQLPHMQAARGSLANHTSIAELIKDVTTSEDFFDKLTVEQEFMSGIDTDKVNNYIEDCIAQKHSLIKVLRLVCLQSVCNSGLKQKVLDYYKREILQTYGYEHILTLHNLEKAGLLKPQTGGRNNYPTIRKTLRLWMDDVNEQNPTDISYVYSGYAPLSVRLAQLLSRPGWRSIEEVLRILPGPHFEERQPLPTGLQKKRQPGENRVTLIFFLGGVTFAEIAALRFLSQLEDGGTEYVIATTKLMNGTSWIEALMEKPF
InterPro domains: - IPR043155: Vacuolar protein sorting-associated protein 33, domain 3b (homologous_superfamily) [368-459]
- IPR001619: Sec1-like protein (family) [26-591]
- IPR036045: Sec1-like superfamily (homologous_superfamily) [10-593]
- IPR043154: Sec1-like, domain 1 (homologous_superfamily) [1-143]
- IPR043127: Sec1-like, domain 3a (homologous_superfamily) [243-367]
- IPR027482: Sec1-like, domain 2 (homologous_superfamily) [502-596]
Interaction partners: - Vacuolar protein sorting-associated protein 16 homolog
- Vacuolar protein sorting-associated protein 41 homolog
- Vacuolar protein sorting-associated protein 11 homolog
- Vam6/Vps39-like protein
- Vacuolar protein sorting-associated protein 18 homolog
- Transforming growth factor-beta receptor-associated protein 1
- Vacuolar protein sorting-associated protein 8 homolog
- Spermatogenesis-defective protein 39 homolog
- Syntaxin-7
- Syntaxin-12
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0044877 (protein-containing complex binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0051179 (localization), GO:0050789 (regulation of biological process), GO:0002376 (immune system process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0051641 (cellular localization), GO:0001775 (cell activation), GO:0051051 (negative regulation of transport), GO:0045321 (leukocyte activation), GO:0006955 (immune response), GO:0032879 (regulation of localization), GO:0006807 (nitrogen compound metabolic process), GO:0051234 (establishment of localization), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0033036 (macromolecule localization), GO:0044237 (cellular metabolic process), GO:0050794 (regulation of cellular process), GO:0002252 (immune effector process), GO:0140352 (export from cell), GO:0048523 (negative regulation of cellular process), GO:0044238 (primary metabolic process), GO:0051049 (regulation of transport), GO:1901564 (organonitrogen compound metabolic process), GO:1903828 (negative regulation of protein localization), GO:0044248 (cellular catabolic process), GO:0060341 (regulation of cellular localization), GO:0019538 (protein metabolic process), GO:0051224 (negative regulation of protein transport), GO:0051649 (establishment of localization in cell), GO:0060627 (regulation of vesicle-mediated transport), GO:0043170 (macromolecule metabolic process), GO:0045184 (establishment of protein localization), GO:0042127 (regulation of cell population proliferation), GO:0046907 (intracellular transport), GO:0006810 (transport), GO:0002263 (cell activation involved in immune response), GO:0070727 (cellular macromolecule localization), GO:0032940 (secretion by cell), GO:0016043 (cellular component organization), GO:0002274 (myeloid leukocyte activation), GO:1901575 (organic substance catabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0023061 (signal release), GO:0035592 (establishment of protein localization to extracellular region), GO:0019730 (antimicrobial humoral response), GO:0071705 (nitrogen compound transport), GO:1901565 (organonitrogen compound catabolic process), GO:0006508 (proteolysis), GO:0009306 (protein secretion), GO:0010256 (endomembrane system organization), GO:0070201 (regulation of establishment of protein localization), GO:0030163 (protein catabolic process), GO:0071702 (organic substance transport), GO:0046903 (secretion), GO:0032880 (regulation of protein localization), GO:0036211 (protein modification process), GO:0009057 (macromolecule catabolic process), GO:0006886 (intracellular protein transport), GO:0043412 (macromolecule modification), GO:0051223 (regulation of protein transport), GO:0044265 (cellular macromolecule catabolic process), GO:0015031 (protein transport), GO:0030101 (natural killer cell activation), GO:0016192 (vesicle-mediated transport), GO:0008104 (protein localization), GO:0007034 (vacuolar transport), GO:0006996 (organelle organization), GO:1904950 (negative regulation of establishment of protein localization), GO:0022411 (cellular component disassembly), GO:0061024 (membrane organization), GO:0032386 (regulation of intracellular transport), GO:0072666 (establishment of protein localization to vacuole), GO:0016050 (vesicle organization), GO:0070647 (protein modification by small protein conjugation or removal), GO:0033157 (regulation of intracellular protein transport), GO:0008333 (endosome to lysosome transport), GO:0018193 (peptidyl-amino acid modification), GO:0048193 (Golgi vesicle transport), GO:0007030 (Golgi organization), GO:0071692 (protein localization to extracellular region), GO:0007041 (lysosomal transport), GO:0007009 (plasma membrane organization), GO:0032366 (intracellular sterol transport), GO:0045055 (regulated exocytosis), GO:0061025 (membrane fusion), GO:0006622 (protein targeting to lysosome), GO:0006892 (post-Golgi vesicle-mediated transport), GO:0090174 (organelle membrane fusion), GO:0072665 (protein localization to vacuole), GO:0061462 (protein localization to lysosome)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0099023 (vesicle tethering complex), GO:0005829 (cytosol), GO:0048471 (perinuclear region of cytoplasm), GO:0098796 (membrane protein complex), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031090 (organelle membrane), GO:0030141 (secretory granule), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0005794 (Golgi apparatus), GO:0005773 (vacuole), GO:0030897 (HOPS complex), GO:0043227 (membrane-bounded organelle), GO:0000323 (lytic vacuole), GO:0099503 (secretory vesicle), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0012506 (vesicle membrane), GO:0031091 (platelet alpha granule), GO:0005770 (late endosome), GO:0005769 (early endosome), GO:0030135 (coated vesicle), GO:0010008 (endosome membrane), GO:0031982 (vesicle), GO:0030659 (cytoplasmic vesicle membrane), GO:0005764 (lysosome), GO:0097708 (intracellular vesicle), GO:0031901 (early endosome membrane), GO:0030136 (clathrin-coated vesicle)