UniProt functional annotation for Q99816



	UniProt functional annotation for Q99816

UniProt code: Q99816.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). It may also play a role in the extracellular release of microvesicles that differ from the exosomes (PubMed:22315426). {ECO:0000269|PubMed:11916981, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:21070952, ECO:0000269|PubMed:21757351, ECO:0000269|PubMed:22315426, ECO:0000269|PubMed:22660413}.

Subunit: Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry (PubMed:18005716). Interacts with VPS37A, VPS37B and VPS37C (PubMed:15218037, PubMed:15509564). Interacts with DMAP1 (PubMed:10888872). Interacts with ubiquitin (PubMed:11595185). Interacts with stathmin, GMCL and AATF (By similarity). Component of an ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, VPS37A and UBAP1 in a 1:1:1:1 stoichiometry (PubMed:21757351). Interacts with HGS; the interaction mediates the association with the ESCRT-0 complex. Interacts with GGA1 and GGA3 (PubMed:15143060, PubMed:15039775). Interacts (via UEV domain) with PDCD6IP/AIP1 (PubMed:14505570, PubMed:14519844). Interacts with VPS28, SNF8 and VPS36 (PubMed:14505570). Self-associates (PubMed:14505570, PubMed:14519844). Interacts with MVB12A; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS37D. Interacts with LRSAM1. Interacts with CEP55; the interaction is required for cytokinesis but not for viral budding (PubMed:17853893). Interacts with PDCD6 (PubMed:18256029). Interacts with LITAF (PubMed:23166352). Interacts with MGRN1 (PubMed:17229889). Interacts with ARRDC1; recruits TSG101 to the plasma membrane (PubMed:21191027, PubMed:22315426). {ECO:0000250, ECO:0000250|UniProtKB:Q6IRE4, ECO:0000269|PubMed:10888872, ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:15039775, ECO:0000269|PubMed:15053872, ECO:0000269|PubMed:15143060, ECO:0000269|PubMed:15218037, ECO:0000269|PubMed:15509564, ECO:0000269|PubMed:15858022, ECO:0000269|PubMed:17229889, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18005716, ECO:0000269|PubMed:18256029, ECO:0000269|PubMed:19520058, ECO:0000269|PubMed:19703557, ECO:0000269|PubMed:21191027, ECO:0000269|PubMed:21757351, ECO:0000269|PubMed:22315426, ECO:0000269|PubMed:23166352}.

Subunit: (Microbial infection) Interacts with HIV-1 p6. {ECO:0000269|PubMed:11427703, ECO:0000269|PubMed:11595185, ECO:0000269|PubMed:12900394, ECO:0000269|PubMed:21070952, ECO:0000269|PubMed:21643473}.

Subunit: (Microbial infection) Interacts with human spumavirus Gag. {ECO:0000269|PubMed:15858022}.

Subunit: (Microbial infection) Interacts with HTLV-1 Gag. {ECO:0000269|PubMed:14581525}.

Subunit: (Microbial infection) Interacts with Ebola virus VP40. {ECO:0000269|PubMed:12559917}.

Subunit: (Microbial infection) Interacts with EIAV p9; the interaction has been shown in vitro. {ECO:0000269|PubMed:14519844}.

Subunit: (Microbial infection) Interacts with Lassa virus protein Z. {ECO:0000269|PubMed:16571837}.

Subunit: (Microbial infection) Interacts with hepatitis E virus protein ORF3. {ECO:0000269|PubMed:21068219}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:17853893}. Early endosome membrane {ECO:0000269|PubMed:23166352}; Peripheral membrane protein {ECO:0000305|PubMed:23166352}; Cytoplasmic side {ECO:0000305|PubMed:23166352}. Late endosome membrane {ECO:0000269|PubMed:11916981, ECO:0000269|PubMed:17229889}; Peripheral membrane protein. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:17853893}. Midbody, Midbody ring {ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893}. Nucleus {ECO:0000269|PubMed:17229889}. Note=Mainly cytoplasmic. Membrane- associated when active and soluble when inactive. Nuclear localization is cell cycle-dependent. Interaction with CEP55 is required for localization to the midbody during cytokinesis. {ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893}.

Tissue specificity: Heart, brain, placenta, lung, liver, skeletal, kidney and pancreas.

Domain: The UEV domain is required for the interaction of the complex with ubiquitin. It also mediates the interaction with PTAP/PSAP motifs of HIV-1 P6 protein and human spumaretrovirus Gag protein.

Domain: The coiled coil domain may interact with stathmin.

Domain: The UEV domain binds ubiquitin and P-[ST]-A-P peptide motif independently.

Ptm: Monoubiquitinated at multiple sites by LRSAM1 and by MGRN1. Ubiquitination inactivates it, possibly by regulating its shuttling between an active membrane-bound protein and an inactive soluble form. Ubiquitination by MGRN1 requires the presence of UBE2D1. {ECO:0000269|PubMed:15256501, ECO:0000269|PubMed:17229889, ECO:0000269|PubMed:19703557}.

Miscellaneous: [Isoform 2]: Detected in normal as well as cancer tissues. {ECO:0000305}.

Similarity: Belongs to the ubiquitin-conjugating enzyme family. UEV subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). It may also play a role in the extracellular release of microvesicles that differ from the exosomes (PubMed:22315426). {ECO:0000269\|PubMed:11916981, ECO:0000269\|PubMed:17556548, ECO:0000269\|PubMed:17853893, ECO:0000269\|PubMed:21070952, ECO:0000269\|PubMed:21757351, ECO:0000269\|PubMed:22315426, ECO:0000269\|PubMed:22660413}.


Subunit:		Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry (PubMed:18005716). Interacts with VPS37A, VPS37B and VPS37C (PubMed:15218037, PubMed:15509564). Interacts with DMAP1 (PubMed:10888872). Interacts with ubiquitin (PubMed:11595185). Interacts with stathmin, GMCL and AATF (By similarity). Component of an ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, VPS37A and UBAP1 in a 1:1:1:1 stoichiometry (PubMed:21757351). Interacts with HGS; the interaction mediates the association with the ESCRT-0 complex. Interacts with GGA1 and GGA3 (PubMed:15143060, PubMed:15039775). Interacts (via UEV domain) with PDCD6IP/AIP1 (PubMed:14505570, PubMed:14519844). Interacts with VPS28, SNF8 and VPS36 (PubMed:14505570). Self-associates (PubMed:14505570, PubMed:14519844). Interacts with MVB12A; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS37D. Interacts with LRSAM1. Interacts with CEP55; the interaction is required for cytokinesis but not for viral budding (PubMed:17853893). Interacts with PDCD6 (PubMed:18256029). Interacts with LITAF (PubMed:23166352). Interacts with MGRN1 (PubMed:17229889). Interacts with ARRDC1; recruits TSG101 to the plasma membrane (PubMed:21191027, PubMed:22315426). {ECO:0000250, ECO:0000250\|UniProtKB:Q6IRE4, ECO:0000269\|PubMed:10888872, ECO:0000269\|PubMed:14505570, ECO:0000269\|PubMed:15039775, ECO:0000269\|PubMed:15053872, ECO:0000269\|PubMed:15143060, ECO:0000269\|PubMed:15218037, ECO:0000269\|PubMed:15509564, ECO:0000269\|PubMed:15858022, ECO:0000269\|PubMed:17229889, ECO:0000269\|PubMed:17556548, ECO:0000269\|PubMed:17853893, ECO:0000269\|PubMed:18005716, ECO:0000269\|PubMed:18256029, ECO:0000269\|PubMed:19520058, ECO:0000269\|PubMed:19703557, ECO:0000269\|PubMed:21191027, ECO:0000269\|PubMed:21757351, ECO:0000269\|PubMed:22315426, ECO:0000269\|PubMed:23166352}.
Subunit:		(Microbial infection) Interacts with HIV-1 p6. {ECO:0000269\|PubMed:11427703, ECO:0000269\|PubMed:11595185, ECO:0000269\|PubMed:12900394, ECO:0000269\|PubMed:21070952, ECO:0000269\|PubMed:21643473}.
Subunit:		(Microbial infection) Interacts with human spumavirus Gag. {ECO:0000269\|PubMed:15858022}.
Subunit:		(Microbial infection) Interacts with HTLV-1 Gag. {ECO:0000269\|PubMed:14581525}.
Subunit:		(Microbial infection) Interacts with Ebola virus VP40. {ECO:0000269\|PubMed:12559917}.
Subunit:		(Microbial infection) Interacts with EIAV p9; the interaction has been shown in vitro. {ECO:0000269\|PubMed:14519844}.
Subunit:		(Microbial infection) Interacts with Lassa virus protein Z. {ECO:0000269\|PubMed:16571837}.
Subunit:		(Microbial infection) Interacts with hepatitis E virus protein ORF3. {ECO:0000269\|PubMed:21068219}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:17853893}. Early endosome membrane {ECO:0000269\|PubMed:23166352}; Peripheral membrane protein {ECO:0000305\|PubMed:23166352}; Cytoplasmic side {ECO:0000305\|PubMed:23166352}. Late endosome membrane {ECO:0000269\|PubMed:11916981, ECO:0000269\|PubMed:17229889}; Peripheral membrane protein. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269\|PubMed:17853893}. Midbody, Midbody ring {ECO:0000269\|PubMed:17556548, ECO:0000269\|PubMed:17853893}. Nucleus {ECO:0000269\|PubMed:17229889}. Note=Mainly cytoplasmic. Membrane- associated when active and soluble when inactive. Nuclear localization is cell cycle-dependent. Interaction with CEP55 is required for localization to the midbody during cytokinesis. {ECO:0000269\|PubMed:17556548, ECO:0000269\|PubMed:17853893}.
Tissue specificity:		Heart, brain, placenta, lung, liver, skeletal, kidney and pancreas.
Domain:		The UEV domain is required for the interaction of the complex with ubiquitin. It also mediates the interaction with PTAP/PSAP motifs of HIV-1 P6 protein and human spumaretrovirus Gag protein.
Domain:		The coiled coil domain may interact with stathmin.
Domain:		The UEV domain binds ubiquitin and P-[ST]-A-P peptide motif independently.
Ptm:		Monoubiquitinated at multiple sites by LRSAM1 and by MGRN1. Ubiquitination inactivates it, possibly by regulating its shuttling between an active membrane-bound protein and an inactive soluble form. Ubiquitination by MGRN1 requires the presence of UBE2D1. {ECO:0000269\|PubMed:15256501, ECO:0000269\|PubMed:17229889, ECO:0000269\|PubMed:19703557}.
Miscellaneous:		[Isoform 2]: Detected in normal as well as cancer tissues. {ECO:0000305}.
Similarity:		Belongs to the ubiquitin-conjugating enzyme family. UEV subfamily. {ECO:0000305}.