tumor susceptibility gene 101 protein (TSG101)

Function

• regulator of vesicular trafficking process
• required for sorting of endocytic (EGF receptors) cargos
• role in cell growth & differentiation (putative)
• negative growth regulator
• role in budding of many viruses
• interacts with ubiquitin, stathmin, GMCL, DMAP1, HGS & AATF
• interacts with GGA1 & GGA3
• interacts with PDCD6IP/AIP1
• 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

More general terms

• carrier protein (transporter)

Database

• OMIM: https://mirror.omim.org/entry/601387
• UniProt: http://www.uniprot.org/uniprot/Q99816.html