Entry sw:RN139_HUMAN

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   02-NOV-2016, entry version 142.
DE   RecName: Full=E3 ubiquitin-protein ligase RNF139;
DE            EC=6.3.2.-;
DE   AltName: Full=RING finger protein 139;
DE   AltName: Full=Translocation in renal carcinoma on chromosome 8 protein;
GN   Name=RNF139 {ECO:0000312|HGNC:HGNC:17023};
GN   Synonyms=TRC8 {ECO:0000312|EMBL:AAC39930.1};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Smith D.I., 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: 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.,
RA   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
RT   functions with VHL in a common pathway.";
RL   Oncogene 21:3507-3516(2002).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-663, AND IDENTIFICATION
RP   BY 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.,
RA   Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in
RT   signaling networks.";
RL   Cell 127:635-648(2006).
RN   [8]
RP   FUNCTION, AND MUTAGENESIS OF 547-CYS--CYS-550; 547-CYS--HIS-586;
RP   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.,
RA   Weissman A.M., 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
RP   BY 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
RT   the kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-663, AND IDENTIFICATION
RP   BY 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.,
RA   Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT   a refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [12]
RP   FUNCTION, INTERACTION WITH SREBF2; SCAP AND SEC24B, UBIQUITINATION,
RP   AND 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
RT   protein-2 (SREBP-2)/SREBP cleavage-activated protein and reduces
RT   SREBP-2 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
RT   dislocation from the ER.";
RL   J. Cell Biol. 186:685-692(2009).
RN   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-663, AND IDENTIFICATION
RP   BY 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,
RP   AND 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
RT   lipid and protein biosynthetic pathways.";
RL   Mol. Cancer Res. 8:93-106(2010).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-663, AND IDENTIFICATION
RP   BY 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.,
RA   Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full
RT   phosphorylation site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [17]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-663, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA   Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA   Blagoev B.;
RT   "System-wide temporal characterization of the proteome and
RT   phosphoproteome of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [18]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [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.,
RA   Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA   Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-
RT   terminal acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [19]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-663, AND IDENTIFICATION
RP   BY 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   [20]
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
RT   protein response regulator XBP1u.";
RL   EMBO J. 33:2492-2506(2014).
RN   [21]
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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- FUNCTION: E3-ubiquitin ligase; acts as a negative regulator of the
CC       cell proliferation through mechanisms involving G2/M arrest and
CC       cell death. Required for MHC class I ubiquitination in cells
CC       expressing the cytomegalovirus protein US2 before dislocation from
CC       the endoplasmic reticulum (ER). Affects SREBP processing by
CC       hindering the SREBP/SCAP complex translocation from the ER to the
CC       Golgi, thereby reducing SREBF2 target gene expression. Required
CC       for INSIG1 ubiquitination. May be required for EIF3 complex
CC       ubiquitination. May function as a signaling receptor.
CC       {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:12032852,
CC       ECO:0000269|PubMed:17016439, ECO:0000269|PubMed:19706601,
CC       ECO:0000269|PubMed:19720873, ECO:0000269|PubMed:20068067}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Interacts with MHC class I and HM13 (PubMed:19720873,
CC       PubMed:25239945). Interacts with VHL. Component of SCAP/SREBP
CC       complex composed of SREBF2, SCAP and RNF139; the complex hampers
CC       the interaction between SCAP and SEC24B, thereby reducing SREBF2
CC       proteolytic processing. Interacts with SREBF2 (via C-terminal
CC       domain). Interacts with SCAP; the interaction inhibits the
CC       interaction of SCAP with SEC24B and hampering the ER to Golgi
CC       transport of the SCAP/SREBP complex. Interacts with SEC24B.
CC       Interacts with INSIG1 and INSIG2. Interacts with EIF3F and EIF3H;
CC       the interaction leads to protein translation inhibitions in a
CC       ubiquitination-dependent manner (PubMed:12032852, PubMed:19706601,
CC       PubMed:20068067). Interacts with XBP1 isoform 1; the interaction
CC       induces ubiquitination and degradation of XBP1 isoform 1
CC       (PubMed:25239945). {ECO:0000269|PubMed:12032852,
CC       ECO:0000269|PubMed:19706601, ECO:0000269|PubMed:19720873,
CC       ECO:0000269|PubMed:20068067, ECO:0000269|PubMed:25239945}.
CC   -!- INTERACTION:
CC       Q8TCT9:HM13; NbExp=2; IntAct=EBI-1551681, EBI-347472;
CC       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
CC       adrenal gland. Moderate expression in heart, brain, liver,
CC       skeletal muscle and pancreas, and low expression in lung and
CC       kidney. {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
CC       leads to ist degradation via the ubiquitin-proteasome pathway.
CC       {ECO:0000269|PubMed:19706601}.
CC   -!- DISEASE: Renal cell carcinoma (RCC) [MIM:144700]: Renal cell
CC       carcinoma is a heterogeneous group of sporadic or hereditary
CC       carcinoma derived from cells of the proximal renal tubular
CC       epithelium. It is subclassified into clear cell renal carcinoma
CC       (non-papillary carcinoma), papillary renal cell carcinoma,
CC       chromophobe renal cell carcinoma, collecting duct carcinoma with
CC       medullary carcinoma of the kidney, and unclassified renal cell
CC       carcinoma. Clear cell renal cell carcinoma is the most common
CC       subtype. Note=The disease may be caused by mutations affecting the
CC       gene represented in this entry. A chromosomal aberration involving
CC       RNF139 has been found in a lymphoblastoid cell line established
CC       from a family with renal cell carcinoma and thyroid carcinoma.
CC       Translocation (3;8)(q14.2;q24.1) with FHIT. RNF139 is found to be
CC       fused to FHIT and disrupted within the sterol-sensing domain. In
CC       contrast, the FHIT coding region is maintained and expressed.
CC       Sporadic cases of renal carcinoma, where an acquired mutation in
CC       RNF139 results in the duplication of 12 nucleotides in the 5'-UTR,
CC       has also been identified.
CC   -!- SIMILARITY: Contains 1 RING-type zinc finger.
CC       {ECO:0000255|PROSITE-ProRule:PRU00175}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/TRC8ID500.html";
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   UniGene; Hs.744151; -.
DR   ProteinModelPortal; Q8WU17; -.
DR   SMR; Q8WU17; -.
DR   BioGrid; 116401; 17.
DR   IntAct; Q8WU17; 8.
DR   STRING; 9606.ENSP00000304051; -.
DR   iPTMnet; Q8WU17; -.
DR   PhosphoSitePlus; Q8WU17; -.
DR   BioMuta; RNF139; -.
DR   DMDM; 74760542; -.
DR   EPD; Q8WU17; -.
DR   MaxQB; Q8WU17; -.
DR   PaxDb; Q8WU17; -.
DR   PeptideAtlas; Q8WU17; -.
DR   PRIDE; Q8WU17; -.
DR   Ensembl; ENST00000303545; ENSP00000304051; ENSG00000170881.
DR   GeneID; 11236; -.
DR   KEGG; hsa:11236; -.
DR   UCSC; uc003yrc.4; human.
DR   CTD; 11236; -.
DR   DisGeNET; 11236; -.
DR   GeneCards; RNF139; -.
DR   HGNC; HGNC:17023; RNF139.
DR   HPA; HPA001202; -.
DR   MalaCards; RNF139; -.
DR   MIM; 144700; phenotype.
DR   MIM; 603046; gene.
DR   neXtProt; NX_Q8WU17; -.
DR   OpenTargets; ENSG00000170881; -.
DR   Orphanet; 151; Familial renal cell carcinoma.
DR   PharmGKB; PA134945850; -.
DR   eggNOG; KOG0802; Eukaryota.
DR   eggNOG; COG5243; LUCA.
DR   GeneTree; ENSGT00530000062938; -.
DR   HOGENOM; HOG000267029; -.
DR   HOVERGEN; HBG053146; -.
DR   InParanoid; Q8WU17; -.
DR   KO; K15703; -.
DR   OMA; RIRFPDI; -.
DR   OrthoDB; EOG091G020N; -.
DR   PhylomeDB; Q8WU17; -.
DR   TreeFam; TF318635; -.
DR   BioCyc; ZFISH:ENSG00000170881-MONOMER; -.
DR   Reactome; R-HSA-901032; ER Quality Control Compartment (ERQC).
DR   UniPathway; UPA00143; -.
DR   GeneWiki; RNF139; -.
DR   GenomeRNAi; 11236; -.
DR   PRO; PR:Q8WU17; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   Bgee; ENSG00000170881; -.
DR   CleanEx; HS_RNF139; -.
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:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; TAS:UniProtKB.
DR   GO; GO:0016874; F:ligase activity; TAS:UniProtKB.
DR   GO; GO:0002020; F:protease binding; IPI:UniProtKB.
DR   GO; GO:0004872; F:receptor activity; TAS:UniProtKB.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
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 proliferation; IDA:UniProtKB.
DR   GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR   GO; GO:2000060; P:positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR   GO; GO:0031648; P:protein destabilization; IMP:UniProtKB.
DR   GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
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   GO; GO:0031396; P:regulation of protein ubiquitination; IDA:UniProtKB.
DR   Gene3D; 3.30.40.10; -; 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   Pfam; PF13705; TRC8_N; 1.
DR   Pfam; PF13639; zf-RING_2; 1.
DR   SMART; SM00184; RING; 1.
DR   SMART; SM00744; RINGv; 1.
DR   PROSITE; PS50089; ZF_RING_2; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Chromosomal rearrangement; Complete proteome;
KW   Endoplasmic reticulum; Ligase; Membrane; Metal-binding;
KW   Phosphoprotein; Receptor; Reference proteome; Transmembrane;
KW   Transmembrane helix; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW   Zinc-finger.
FT   INIT_MET      1      1       Removed. {ECO:0000244|PubMed:22814378}.
FT   CHAIN         2    664       E3 ubiquitin-protein ligase RNF139.
FT                                /FTId=PRO_0000056098.
FT   TRANSMEM     51     71       Helical. {ECO:0000255}.
FT   TRANSMEM     85    105       Helical. {ECO:0000255}.
FT   TRANSMEM    125    145       Helical. {ECO:0000255}.
FT   TRANSMEM    154    174       Helical. {ECO:0000255}.
FT   TRANSMEM    178    198       Helical. {ECO:0000255}.
FT   TRANSMEM    293    313       Helical. {ECO:0000255}.
FT   TRANSMEM    323    343       Helical. {ECO:0000255}.
FT   TRANSMEM    356    376       Helical. {ECO:0000255}.
FT   TRANSMEM    390    410       Helical. {ECO:0000255}.
FT   TRANSMEM    420    440       Helical. {ECO:0000255}.
FT   TRANSMEM    469    489       Helical. {ECO:0000255}.
FT   TRANSMEM    495    512       Helical. {ECO:0000255}.
FT   ZN_FING     547    586       RING-type; atypical.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00175}.
FT   MOD_RES       2      2       N-acetylalanine.
FT                                {ECO:0000244|PubMed:22814378}.
FT   MOD_RES     634    634       Phosphoserine.
FT                                {ECO:0000244|PubMed:24275569}.
FT   MOD_RES     635    635       Phosphothreonine.
FT                                {ECO:0000244|PubMed:24275569}.
FT   MOD_RES     663    663       Phosphothreonine.
FT                                {ECO:0000244|PubMed:17081983,
FT                                ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:18691976,
FT                                ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:20068231,
FT                                ECO:0000244|PubMed:21406692,
FT                                ECO:0000244|PubMed:23186163}.
FT   MUTAGEN     547    586       Missing: Increases proliferation. Rescues
FT                                MHC class I to the cell surface. Fails to
FT                                down-regulate SREBF1 and SREBF2.
FT                                {ECO:0000269|PubMed:17016439,
FT                                ECO:0000269|PubMed:19706601,
FT                                ECO:0000269|PubMed:19720873,
FT                                ECO:0000269|PubMed:20068067}.
FT   MUTAGEN     547    550       CAIC->SAIS: Abolishes ubiquitination
FT                                activity. Increases proliferation. Does
FT                                not phosphorylates CHEK2 on T-68. Does
FT                                not phosphorylates ATM on S-1981. Rescues
FT                                MHC class I to the cell surface.
FT                                Suppresses SREBF2 processing in the
FT                                presence or absence of sterols. Fails to
FT                                down-regulate SREBF1 and SREBF2.
FT                                Decreases INSIG1 ubiquitination.
FT                                {ECO:0000269|PubMed:17016439,
FT                                ECO:0000269|PubMed:19706601,
FT                                ECO:0000269|PubMed:19720873,
FT                                ECO:0000269|PubMed:20068067}.
FT   MUTAGEN     557    559       SAR->AAA: Retaines about 30% of
FT                                ubiquitination activity.
FT                                {ECO:0000269|PubMed:17016439}.
FT   MUTAGEN     572    574       LRK->AAA: Abolishes ubiquitination
FT                                activity. Increases proliferation.
FT                                {ECO:0000269|PubMed:17016439}.
FT   MUTAGEN     582    585       CPMC->APMA: Abolishes ubiquitination
FT                                activity. Increases proliferation.
FT                                {ECO:0000269|PubMed:17016439}.
FT   CONFLICT     18     18       V -> I (in Ref. 1; AAC39930/AAC39931).
FT                                {ECO:0000305}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT       547    586       iprf:ZF_RING_2 [T]
FT   MYHIT       547    585       ismart:RING [T]
FT   MYHIT       546    585       ipfam:zf-RING_2 [T]
FT   MYHIT       546    586       ismart:RINGv [T]
FT   MYHIT        20    516       ipfam:TRC8_N [T]
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
//