RNF139
entrez
11236
canonical
uniprot
Q8WU17
canonical
ensembl
ENSG00000170881
resolver
ensembl
ENSG00000291729
resolver
ensp
ENSP00000304051
resolver
ensp
ENSP00000517238
resolver
ensp
ENSP00000520565
resolver
enst
ENST00000303545
resolver
enst
ENST00000708475
resolver
enst
ENST00000716592
resolver
genesymbol
RNF139
resolver
genesymbol_syn
TRC8
resolver
hgnc
HGNC:17023
resolver
uniprot
B3KMD5
resolver
uniprot
O75485
resolver
uniprot
Q7LDL3
resolver
uniprot_entry
RN139_HUMAN
resolver
uniprot_sec
B3KMD5
resolver
uniprot_sec
O75485
resolver
uniprot_sec
Q7LDL3
resolver
amino_acid_sequence
MAAVGPPQQQVRMAHQQVWAALEVALRVPCLYIIDAIFNSYPDSSQSRFCIVLQIFLRLFGVFASSIVLILSQRSLFKFYTYSSAFLLAATSVLVNYYASLHIDFYGAYNTSAFGIELLPRKGPSLWMALIVLQLTFGIGYVTLLQIHSIYSQLIILDLLVPVIGLITELPLHIRETLLFTSSLILTLNTVFVLAVKLKWFYYSTRYVYLLVRHMYRIYGLQLLMEDTWKRIRFPDILRVFWLTRVTAQATVLMYILRMANETDSFFISWDDFWDLICNLIISGCDSTLTVLGMSAVISSVAHYLGLGILAFIGSTEEDDRRLGFVAPVLFFILALQTGLSGLRPEERLIRLSRNMCLLLTAVLHFIHGMTDPVLMSLSASHVSSFRRHFPVLFVSACLFILPVLLSYVLWHHYALNTWLFAVTAFCVELCLKVIVSLTVYTLFMIDGYYNVLWEKLDDYVYYVRSTGSIIEFIFGVVMFGNGAYTMMFESGSKIRAFMMCLHAYFNIYLQAKNGWKTFMNRRTAVKKINSLPEIKGSRLQEINDVCAICYHEFTTSARITPCNHYFHALCLRKWLYIQDTCPMCHQKVYIEDDIKDNSNVSNNNGFIPPNETPEEAVREAAAESDRELNEDDSTDCDDDVQRERNGVIQHTGAAAEEFNDDTD
uniprot
proteins
disease_involvement
DISEASE: Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype. Note=The disease may be caused by variants affecting the gene represented in this entry. A chromosomal aberration involving RNF139 has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma and thyroid carcinoma. Translocation (3;8)(q14.2;q24.1) with FHIT. RNF139 is found to be fused to FHIT and disrupted within the sterol-sensing domain. In contrast, the FHIT coding region is maintained and expressed. Sporadic cases of renal carcinoma, where an acquired mutation in RNF139 results in the duplication of 12 nucleotides in the 5'-UTR, has also been identified.
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
FUNCTION: E3-ubiquitin ligase; acts as a negative regulator of cell proliferation through mechanisms involving G2/M arrest and cell death (PubMed:10500182, PubMed:12032852, PubMed:17016439). Required for MHC class I ubiquitination in cells expressing the cytomegalovirus protein US2 before dislocation from the endoplasmic reticulum (ER) (PubMed:19720873). Affects SREBP processing by hindering the SREBP-SCAP complex translocation from the ER to the Golgi, thereby reducing SREBF2 target gene expression (PubMed:19706601, PubMed:20068067). Involved in the sterol-accelerated degradation of HMGCR (PubMed:22143767, PubMed:23223569). This is achieved through binding of RNF139 to INSIG1 and/or INSIG2 at the ER membrane (PubMed:22143767). In addition, interaction of RNF139 with AUP1 facilitates interaction of RNF139 with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase AMFR, leading to ubiquitination of HMGCR (PubMed:23223569). The ubiquitinated HMGCR is then released from the ER into the cytosol for subsequent destruction (PubMed:22143767, PubMed:23223569). Required for INSIG1 ubiquitination (PubMed:20068067). May be required for EIF3 complex ubiquitination (PubMed:20068067). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:12032852, ECO:0000269|PubMed:17016439, ECO:0000269|PubMed:19706601, ECO:0000269|PubMed:19720873, ECO:0000269|PubMed:20068067, ECO:0000269|PubMed:22143767, ECO:0000269|PubMed:23223569}.
uniprot
proteins
mass_dalton
75994
uniprot
proteins
mutagenesis
MUTAGEN 547..586; /note="Missing: Increases proliferation. Rescues MHC class I to the cell surface. Fails to down-regulate SREBF1 and SREBF2."; /evidence="ECO:0000269|PubMed:17016439, ECO:0000269|PubMed:19706601, ECO:0000269|PubMed:19720873, ECO:0000269|PubMed:20068067"; MUTAGEN 547..550; /note="CAIC->SAIS: Abolishes ubiquitination activity. Increases proliferation. Does not phosphorylate CHEK2 on T-68. Does not phosphorylate ATM on S-1981. Rescues MHC class I to the cell surface. Suppresses SREBF2 processing in the presence or absence of sterols. Fails to down-regulate SREBF1 and SREBF2. Decreases INSIG1 ubiquitination."; /evidence="ECO:0000269|PubMed:17016439, ECO:0000269|PubMed:19706601, ECO:0000269|PubMed:19720873, ECO:0000269|PubMed:20068067"; MUTAGEN 557..559; /note="SAR->AAA: Retaines about 30% of ubiquitination activity."; /evidence="ECO:0000269|PubMed:17016439"; MUTAGEN 572..574; /note="LRK->AAA: Abolishes ubiquitination activity. Increases proliferation."; /evidence="ECO:0000269|PubMed:17016439"; MUTAGEN 582..585; /note="CPMC->APMA: Abolishes ubiquitination activity. Increases proliferation."; /evidence="ECO:0000269|PubMed:17016439
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:17016439, ECO:0000269|PubMed:22143767}.
uniprot
proteins
post_translational_modification
PTM: Autoubiquitinated. Ubiquitination is induced by sterol and leads to ist degradation via the ubiquitin-proteasome pathway. {ECO:0000269|PubMed:19706601}.
uniprot
proteins
pubmed
10500182
uniprot
proteins
pubmed
12032852
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17016439
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19706601
uniprot
proteins
pubmed
19720873
uniprot
proteins
pubmed
20068067
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22143767
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23223569
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25239945
uniprot
proteins
pubmed
9689122
uniprot
proteins
sequence_length
664
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:12032852}; Multi-pass membrane protein {ECO:0000269|PubMed:12032852}.
uniprot
proteins
transmembrane_region
TRANSMEM 51..71; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 85..105; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 125..145; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 154..174; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 178..198; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 293..313; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 323..343; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 356..376; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 390..410; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 420..440; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 469..489; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 495..512; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins