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
RC Pancreas {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";
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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 Genevisible; Q8WU17; HS.
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.
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 T-
FT 68. Does not phosphorylate ATM on S-1981. Rescues MHC class
FT I to the cell surface. Suppresses SREBF2 processing in the
FT presence or absence of sterols. Fails to down-regulate
FT SREBF1 and SREBF2. Decreases INSIG1 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
//
