tumor susceptibility gene 101 protein (TSG101)

Function: 1) regulator of vesicular trafficking process 2) required for sorting of endocytic (EGF receptors) cargos 3) role in cell growth & differentiation (putative) 4) negative growth regulator 5) role in budding of many viruses 6) interacts with ubiquitin, stathmin, GMCL, DMAP1, HGS & AATF 7) interacts with GGA1 & GGA3 8) interacts with PDCD6IP/AIP1 9) monoubiquitinated at multiple sites by LRSAM1 - ubiquitination inactivates it, possibly by regulating its shuttling between an active membrane-bound protein & an inactive soluble form Structure: - belongs to the ubiquitin-conjugating enzyme family, UEV subfamily. - contains 1 UEV domain (ubiquitin E2 variant domain) - UEV domain is required for interaction with ubiquitin - also mediates interaction with PTAP/PSAP motifs of HIV-1 P6 protein & human spumaretrovirus Gag protein - contains 1 SB domain (steadiness box domain) - coiled coil domain may interact with stathmin Compartment: - cytoplasm, peripheral membrane, nucleus - mainly cytoplasmic - membrane-associated when active & soluble when inactive - depending on stage of cell cycle, detected in nucleus Alternative splicing: - named isoforms=2 - additional isoforms seem to exist Expression: - heart, brain, placenta, lung, liver, skeletal, kidney, pancreas Pathology: - role in budding of many viruses - interacts with viral proteins that contain a late-budding motif P-[ST]-A-P, essential for viral particle budding of numerous retroviruses - these viral proteins include: HIV-1 p6, human spumavirus Gag, HTLV-1 Gag, Ebolavirus VP40 - several shorter isoforms are detected in primary breast cancers & other tumors

Properties

SIZE: MW = 44 kD entity length = 390 aa COMPARTMENT: cytoplasm cell nucleus MOTIF: UEV {1-133} coiled coil {235-316} PTAP {320-323} SB {346-390}

Database Correlations

OMIM 601387 UniProt Q99816 Pfam PF05743

References

UniProt :accession Q99816