ID RN139_HUMAN Reviewed; 664 AA. AC Q8WU17; B3KMD5; O75485; Q7LDL3; DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2002, sequence version 1. DT 27-MAR-2024, entry version 183. DE RecName: Full=E3 ubiquitin-protein ligase RNF139; DE EC=2.3.2.27 {ECO:0000269|PubMed:17016439}; DE AltName: Full=RING finger protein 139; DE AltName: Full=RING-type E3 ubiquitin transferase RNF139 {ECO:0000305}; DE AltName: Full=Translocation in renal carcinoma on chromosome 8 protein; GN Name=RNF139 {ECO:0000312|HGNC:HGNC:17023}; GN Synonyms=TRC8 {ECO:0000303|PubMed:22143767}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] {ECO:0000305, ECO:0000312|EMBL:AAC39930.1} RP NUCLEOTIDE SEQUENCE [MRNA], NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-60, RP TISSUE SPECIFICITY, AND CHROMOSOMAL TRANSLOCATION WITH FHIT. RX PubMed=9689122; DOI=10.1073/pnas.95.16.9572; RA Gemmill R.M., West J.D., Boldog F., Tanaka N., Robinson L.J., Smith D.I., RA Li F., Drabkin H.A.; RT "The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a RT patched-related gene, TRC8."; RL Proc. Natl. Acad. Sci. U.S.A. 95:9572-9577(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] {ECO:0000312|EMBL:AAH21571.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung {ECO:0000312|EMBL:AAH21571.1}, and Pancreas RC {ECO:0000312|EMBL:AAH64636.1}; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] {ECO:0000305} RP FUNCTION. RX PubMed=10500182; DOI=10.1073/pnas.96.20.11364; RA Lorick K.L., Jensen J.P., Fang S., Ong A.M., Hatakeyama S., Weissman A.M.; RT "RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent RT ubiquitination."; RL Proc. Natl. Acad. Sci. U.S.A. 96:11364-11369(1999). RN [6] {ECO:0000305} RP FUNCTION, INTERACTION WITH VHL, AND SUBCELLULAR LOCATION. RX PubMed=12032852; DOI=10.1038/sj.onc.1205437; RA Gemmill R.M., Bemis L.T., Lee J.P., Sozen M.A., Baron A., Zeng C., RA Erickson P.F., Hooper J.E., Drabkin H.A.; RT "The TRC8 hereditary kidney cancer gene suppresses growth and functions RT with VHL in a common pathway."; RL Oncogene 21:3507-3516(2002). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-663, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 547-CYS--CYS-550; RP 547-CYS--HIS-586; 557-SER--ARG-559; 572-LEU--LYS-574 AND 582-CYS--CYS-585. RX PubMed=17016439; DOI=10.1038/sj.onc.1210017; RA Brauweiler A., Lorick K.L., Lee J.P., Tsai Y.C., Chan D., Weissman A.M., RA Drabkin H.A., Gemmill R.M.; RT "RING-dependent tumor suppression and G2/M arrest induced by the TRC8 RT hereditary kidney cancer gene."; RL Oncogene 26:2263-2271(2007). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-663, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-663, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [12] RP FUNCTION, INTERACTION WITH SREBF2; SCAP AND SEC24B, UBIQUITINATION, AND RP MUTAGENESIS OF 547-CYS--CYS-550 AND 547-CYS--HIS-586. RX PubMed=19706601; DOI=10.1074/jbc.m109.041376; RA Irisawa M., Inoue J., Ozawa N., Mori K., Sato R.; RT "The sterol-sensing endoplasmic reticulum (ER) membrane protein TRC8 RT hampers ER to Golgi transport of sterol regulatory element-binding protein- RT 2 (SREBP-2)/SREBP cleavage-activated protein and reduces SREBP-2 RT cleavage."; RL J. Biol. Chem. 284:28995-29004(2009). RN [13] RP FUNCTION, INTERACTION WITH MHC CLASS I AND HM13, AND MUTAGENESIS OF RP 547-CYS--CYS-550 AND 547-CYS--HIS-586. RX PubMed=19720873; DOI=10.1083/jcb.200906110; RA Stagg H.R., Thomas M., van den Boomen D., Wiertz E.J., Drabkin H.A., RA Gemmill R.M., Lehner P.J.; RT "The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation RT from the ER."; RL J. Cell Biol. 186:685-692(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-663, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP FUNCTION, INTERACTION WITH INSIG1; INSIG2; EIF3F AND EIF3H, INDUCTION, AND RP MUTAGENESIS OF 547-CYS--CYS-550 AND 547-CYS--HIS-586. RX PubMed=20068067; DOI=10.1158/1541-7786.mcr-08-0491; RA Lee J.P., Brauweiler A., Rudolph M., Hooper J.E., Drabkin H.A., RA Gemmill R.M.; RT "The TRC8 ubiquitin ligase is sterol regulated and interacts with lipid and RT protein biosynthetic pathways."; RL Mol. Cancer Res. 8:93-106(2010). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-663, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [17] RP FUNCTION, AND INTERACTION WITH INSIG1 AND INSIG2. RX PubMed=22143767; DOI=10.1073/pnas.1112831108; RA Jo Y., Lee P.C., Sguigna P.V., DeBose-Boyd R.A.; RT "Sterol-induced degradation of HMG CoA reductase depends on interplay of RT two Insigs and two ubiquitin ligases, gp78 and Trc8."; RL Proc. Natl. Acad. Sci. U.S.A. 108:20503-20508(2011). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-663, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-663, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [21] RP FUNCTION, AND INTERACTION WITH AUP1; AMFR AND UBE2G2. RX PubMed=23223569; DOI=10.1091/mbc.e12-07-0564; RA Jo Y., Hartman I.Z., DeBose-Boyd R.A.; RT "Ancient ubiquitous protein-1 mediates sterol-induced ubiquitination of 3- RT hydroxy-3-methylglutaryl CoA reductase in lipid droplet-associated RT endoplasmic reticulum membranes."; RL Mol. Biol. Cell 24:169-183(2013). RN [22] RP INTERACTION WITH HM13 AND XBP1. RX PubMed=25239945; DOI=10.15252/embj.201488208; RA Chen C.Y., Malchus N.S., Hehn B., Stelzer W., Avci D., Langosch D., RA Lemberg M.K.; RT "Signal peptide peptidase functions in ERAD to cleave the unfolded protein RT response regulator XBP1u."; RL EMBO J. 33:2492-2506(2014). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-634 AND THR-635, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: E3-ubiquitin ligase; acts as a negative regulator of cell CC proliferation through mechanisms involving G2/M arrest and cell death CC (PubMed:10500182, PubMed:12032852, PubMed:17016439). Required for MHC CC class I ubiquitination in cells expressing the cytomegalovirus protein CC US2 before dislocation from the endoplasmic reticulum (ER) CC (PubMed:19720873). Affects SREBP processing by hindering the SREBP-SCAP CC complex translocation from the ER to the Golgi, thereby reducing SREBF2 CC target gene expression (PubMed:19706601, PubMed:20068067). Involved in CC the sterol-accelerated degradation of HMGCR (PubMed:22143767, CC PubMed:23223569). This is achieved through binding of RNF139 to INSIG1 CC and/or INSIG2 at the ER membrane (PubMed:22143767). In addition, CC interaction of RNF139 with AUP1 facilitates interaction of RNF139 with CC ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase AMFR, leading CC to ubiquitination of HMGCR (PubMed:23223569). The ubiquitinated HMGCR CC is then released from the ER into the cytosol for subsequent CC destruction (PubMed:22143767, PubMed:23223569). Required for INSIG1 CC ubiquitination (PubMed:20068067). May be required for EIF3 complex CC ubiquitination (PubMed:20068067). {ECO:0000269|PubMed:10500182, CC ECO:0000269|PubMed:12032852, ECO:0000269|PubMed:17016439, CC ECO:0000269|PubMed:19706601, ECO:0000269|PubMed:19720873, CC ECO:0000269|PubMed:20068067, ECO:0000269|PubMed:22143767, CC ECO:0000269|PubMed:23223569}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:17016439}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:17016439, ECO:0000269|PubMed:22143767}. CC -!- SUBUNIT: Interacts with MHC class I and HM13 (PubMed:19720873, CC PubMed:25239945). Interacts with VHL (PubMed:12032852). Component of CC SCAP-SREBP complex composed of SREBF2, SCAP and RNF139; the complex CC hampers the interaction between SCAP and SEC24B, thereby reducing CC SREBF2 proteolytic processing (PubMed:19706601). Interacts with SREBF2 CC (via C-terminal domain) (PubMed:19706601). Interacts with SCAP; the CC interaction inhibits the interaction of SCAP with SEC24B and hampering CC the ER to Golgi transport of the SCAP-SREBP complex (PubMed:19706601). CC Interacts with SEC24B (PubMed:19706601). Interacts with INSIG1 and CC INSIG2 (PubMed:20068067, PubMed:22143767). Interacts with EIF3F and CC EIF3H; the interaction leads to protein translation inhibitions in a CC ubiquitination-dependent manner (PubMed:20068067). Interacts with XBP1 CC isoform 1; the interaction induces ubiquitination and degradation of CC XBP1 isoform 1 (PubMed:25239945). Interacts with AUP1, AMFR and UBE2G2; CC interaction with AUP1 facilitates interaction of RNF139 with ubiquitin- CC conjugating enzyme UBE2G2 and ubiquitin ligase AMFR/gp78, leading to CC sterol-induced ubiquitination of HMGCR and its subsequent proteasomal CC degradation (PubMed:23223569). {ECO:0000269|PubMed:12032852, CC ECO:0000269|PubMed:19706601, ECO:0000269|PubMed:19720873, CC ECO:0000269|PubMed:20068067, ECO:0000269|PubMed:22143767, CC ECO:0000269|PubMed:23223569, ECO:0000269|PubMed:25239945}. CC -!- INTERACTION: CC Q8WU17; P54253: ATXN1; NbExp=6; IntAct=EBI-1551681, EBI-930964; CC Q8WU17; Q8TCT9: HM13; NbExp=2; IntAct=EBI-1551681, EBI-347472; CC Q8WU17; P40337: VHL; NbExp=2; IntAct=EBI-1551681, EBI-301246; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:12032852}; Multi-pass membrane protein CC {ECO:0000269|PubMed:12032852}. CC -!- TISSUE SPECIFICITY: Highly expressed in testis, placenta and adrenal CC gland. Moderate expression in heart, brain, liver, skeletal muscle and CC pancreas, and low expression in lung and kidney. CC {ECO:0000269|PubMed:9689122}. CC -!- INDUCTION: Down-regulated by sterols (at protein level). CC {ECO:0000269|PubMed:20068067}. CC -!- DOMAIN: The RING-type zinc finger domain mediates ubiquitin ligase CC activity. CC -!- PTM: Autoubiquitinated. Ubiquitination is induced by sterol and leads CC to ist degradation via the ubiquitin-proteasome pathway. CC {ECO:0000269|PubMed:19706601}. CC -!- DISEASE: Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma CC is a heterogeneous group of sporadic or hereditary carcinoma derived CC from cells of the proximal renal tubular epithelium. It is CC subclassified into clear cell renal carcinoma (non-papillary CC carcinoma), papillary renal cell carcinoma, chromophobe renal cell CC carcinoma, collecting duct carcinoma with medullary carcinoma of the CC kidney, and unclassified renal cell carcinoma. Clear cell renal cell CC carcinoma is the most common subtype. Note=The disease may be caused by CC variants affecting the gene represented in this entry. A chromosomal CC aberration involving RNF139 has been found in a lymphoblastoid cell CC line established from a family with renal cell carcinoma and thyroid CC carcinoma. Translocation (3;8)(q14.2;q24.1) with FHIT. RNF139 is found CC to be fused to FHIT and disrupted within the sterol-sensing domain. In CC contrast, the FHIT coding region is maintained and expressed. Sporadic CC cases of renal carcinoma, where an acquired mutation in RNF139 results CC in the duplication of 12 nucleotides in the 5'-UTR, has also been CC identified. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/500/TRC8"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF064800; AAC39931.1; -; Genomic_DNA. DR EMBL; AF064801; AAC39930.1; -; mRNA. DR EMBL; AK001602; BAG50947.1; -; mRNA. DR EMBL; CH471060; EAW92064.1; -; Genomic_DNA. DR EMBL; BC021571; AAH21571.1; -; mRNA. DR EMBL; BC064636; AAH64636.1; -; mRNA. DR CCDS; CCDS6350.1; -. DR RefSeq; NP_009149.2; NM_007218.3. DR AlphaFoldDB; Q8WU17; -. DR SMR; Q8WU17; -. DR BioGRID; 116401; 45. DR IntAct; Q8WU17; 10. DR MINT; Q8WU17; -. DR STRING; 9606.ENSP00000304051; -. DR iPTMnet; Q8WU17; -. DR PhosphoSitePlus; Q8WU17; -. DR BioMuta; RNF139; -. DR DMDM; 74760542; -. DR EPD; Q8WU17; -. DR jPOST; Q8WU17; -. DR MassIVE; Q8WU17; -. DR MaxQB; Q8WU17; -. DR PaxDb; 9606-ENSP00000304051; -. DR PeptideAtlas; Q8WU17; -. DR ProteomicsDB; 74623; -. DR Antibodypedia; 747; 210 antibodies from 28 providers. DR DNASU; 11236; -. DR Ensembl; ENST00000303545.4; ENSP00000304051.4; ENSG00000170881.5. DR Ensembl; ENST00000708475.1; ENSP00000517238.1; ENSG00000291729.1. DR GeneID; 11236; -. DR KEGG; hsa:11236; -. DR MANE-Select; ENST00000303545.4; ENSP00000304051.4; NM_007218.4; NP_009149.2. DR UCSC; uc003yrc.4; human. DR AGR; HGNC:17023; -. DR CTD; 11236; -. DR DisGeNET; 11236; -. DR GeneCards; RNF139; -. DR HGNC; HGNC:17023; RNF139. DR HPA; ENSG00000170881; Tissue enhanced (bone). DR MalaCards; RNF139; -. DR MIM; 144700; phenotype. DR MIM; 603046; gene. DR neXtProt; NX_Q8WU17; -. DR OpenTargets; ENSG00000170881; -. DR Orphanet; 422526; Hereditary clear cell renal cell carcinoma. DR PharmGKB; PA134945850; -. DR VEuPathDB; HostDB:ENSG00000170881; -. DR eggNOG; KOG0802; Eukaryota. DR GeneTree; ENSGT00940000158932; -. DR HOGENOM; CLU_016467_0_1_1; -. DR InParanoid; Q8WU17; -. DR OMA; NGAYTMV; -. DR OrthoDB; 2912447at2759; -. DR PhylomeDB; Q8WU17; -. DR TreeFam; TF318635; -. DR PathwayCommons; Q8WU17; -. DR Reactome; R-HSA-901032; ER Quality Control Compartment (ERQC). DR SignaLink; Q8WU17; -. DR SIGNOR; Q8WU17; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 11236; 29 hits in 1192 CRISPR screens. DR ChiTaRS; RNF139; human. DR GeneWiki; RNF139; -. DR GenomeRNAi; 11236; -. DR Pharos; Q8WU17; Tbio. DR PRO; PR:Q8WU17; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q8WU17; Protein. DR Bgee; ENSG00000170881; Expressed in sperm and 213 other cell types or tissues. DR ExpressionAtlas; Q8WU17; baseline and differential. DR GO; GO:0036513; C:Derlin-1 retrotranslocation complex; IDA:ParkinsonsUK-UCL. DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; TAS:UniProtKB. DR GO; GO:0002020; F:protease binding; IPI:UniProtKB. DR GO; GO:0038023; F:signaling receptor activity; TAS:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB. DR GO; GO:0019787; F:ubiquitin-like protein transferase activity; IDA:UniProtKB. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0036503; P:ERAD pathway; IMP:ParkinsonsUK-UCL. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB. DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0060628; P:regulation of ER to Golgi vesicle-mediated transport; IDA:UniProtKB. DR GO; GO:0070613; P:regulation of protein processing; IDA:UniProtKB. DR CDD; cd16683; RING-H2_RNF139; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR025754; TRC8_N_dom. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR011016; Znf_RING-CH. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR22763:SF163; E3 UBIQUITIN-PROTEIN LIGASE RNF139; 1. DR PANTHER; PTHR22763; RING ZINC FINGER PROTEIN; 1. DR Pfam; PF13705; TRC8_N; 1. DR Pfam; PF13639; zf-RING_2; 1. DR SMART; SM00184; RING; 1. DR SMART; SM00744; RINGv; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR Genevisible; Q8WU17; HS. PE 1: Evidence at protein level; KW Acetylation; Chromosomal rearrangement; Endoplasmic reticulum; Membrane; KW Metal-binding; Phosphoprotein; Receptor; Reference proteome; Transferase; KW Transmembrane; Transmembrane helix; Ubl conjugation; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT CHAIN 2..664 FT /note="E3 ubiquitin-protein ligase RNF139" FT /id="PRO_0000056098" FT TRANSMEM 51..71 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 85..105 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 125..145 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 154..174 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 178..198 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 293..313 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 323..343 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 356..376 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 390..410 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 420..440 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 469..489 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 495..512 FT /note="Helical" FT /evidence="ECO:0000255" FT ZN_FING 547..586 FT /note="RING-type; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT REGION 601..664 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 634 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 635 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 663 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MUTAGEN 547..586 FT /note="Missing: Increases proliferation. Rescues MHC class FT I to the cell surface. Fails to down-regulate SREBF1 and FT SREBF2." FT /evidence="ECO:0000269|PubMed:17016439, FT ECO:0000269|PubMed:19706601, ECO:0000269|PubMed:19720873, FT ECO:0000269|PubMed:20068067" FT MUTAGEN 547..550 FT /note="CAIC->SAIS: Abolishes ubiquitination activity. FT Increases proliferation. Does not phosphorylate CHEK2 on FT T-68. Does not phosphorylate ATM on S-1981. Rescues MHC FT class I to the cell surface. Suppresses SREBF2 processing FT in the presence or absence of sterols. Fails to FT down-regulate SREBF1 and SREBF2. Decreases INSIG1 FT ubiquitination." FT /evidence="ECO:0000269|PubMed:17016439, FT ECO:0000269|PubMed:19706601, ECO:0000269|PubMed:19720873, FT ECO:0000269|PubMed:20068067" FT MUTAGEN 557..559 FT /note="SAR->AAA: Retaines about 30% of ubiquitination FT activity." FT /evidence="ECO:0000269|PubMed:17016439" FT MUTAGEN 572..574 FT /note="LRK->AAA: Abolishes ubiquitination activity. FT Increases proliferation." FT /evidence="ECO:0000269|PubMed:17016439" FT MUTAGEN 582..585 FT /note="CPMC->APMA: Abolishes ubiquitination activity. FT Increases proliferation." FT /evidence="ECO:0000269|PubMed:17016439" FT CONFLICT 18 FT /note="V -> I (in Ref. 1; AAC39930/AAC39931)" FT /evidence="ECO:0000305" SQ SEQUENCE 664 AA; 75994 MW; 9885F5915F019EF5 CRC64; MAAVGPPQQQ VRMAHQQVWA ALEVALRVPC LYIIDAIFNS YPDSSQSRFC IVLQIFLRLF GVFASSIVLI LSQRSLFKFY TYSSAFLLAA TSVLVNYYAS LHIDFYGAYN TSAFGIELLP RKGPSLWMAL IVLQLTFGIG YVTLLQIHSI YSQLIILDLL VPVIGLITEL PLHIRETLLF TSSLILTLNT VFVLAVKLKW FYYSTRYVYL LVRHMYRIYG LQLLMEDTWK RIRFPDILRV FWLTRVTAQA TVLMYILRMA NETDSFFISW DDFWDLICNL IISGCDSTLT VLGMSAVISS VAHYLGLGIL AFIGSTEEDD RRLGFVAPVL FFILALQTGL SGLRPEERLI RLSRNMCLLL TAVLHFIHGM TDPVLMSLSA SHVSSFRRHF PVLFVSACLF ILPVLLSYVL WHHYALNTWL FAVTAFCVEL CLKVIVSLTV YTLFMIDGYY NVLWEKLDDY VYYVRSTGSI IEFIFGVVMF GNGAYTMMFE SGSKIRAFMM CLHAYFNIYL QAKNGWKTFM NRRTAVKKIN SLPEIKGSRL QEINDVCAIC YHEFTTSARI TPCNHYFHAL CLRKWLYIQD TCPMCHQKVY IEDDIKDNSN VSNNNGFIPP NETPEEAVRE AAAESDRELN EDDSTDCDDD VQRERNGVIQ HTGAAAEEFN DDTD //