RN139_MOUSE
ID RN139_MOUSE Reviewed; 668 AA.
AC Q7TMV1; Q8BZU9;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 25-MAY-2022, entry version 143.
DE RecName: Full=E3 ubiquitin-protein ligase RNF139;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q8WU17};
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|MGI:MGI:1923091};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000312|EMBL:BAC28327.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC28327.1};
RC TISSUE=Colon {ECO:0000312|EMBL:BAC28327.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2] {ECO:0000312|EMBL:AAH52901.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6NCr {ECO:0000312|EMBL:AAH52901.1};
RC TISSUE=Hematopoietic stem cell;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-667, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-667, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: E3-ubiquitin ligase; acts as a negative regulator of cell
CC proliferation through mechanisms involving G2/M arrest and cell death.
CC Required for MHC class I ubiquitination in cells expressing the
CC cytomegalovirus protein US2 before dislocation from the endoplasmic
CC reticulum (ER). Affects SREBP processing by hindering the SREBP-SCAP
CC complex translocation from the ER to the Golgi, thereby reducing SREBF2
CC target gene expression. Involved in the sterol-accelerated degradation
CC of HMGCR. This is achieved through binding to INSIG1 and/or INSIG2 at
CC the ER membrane. In addition, interaction of RNF139 with AUP1
CC facilitates interaction of RNF139 with ubiquitin-conjugating enzyme
CC UBE2G2 and ubiquitin ligase AMFR, leading to ubiquitination of HMGCR.
CC The ubiquitinated HMGCR is then released from the ER by the complex
CC into the cytosol for subsequent destruction. Required for INSIG1
CC ubiquitination. May be required for EIF3 complex ubiquitination.
CC {ECO:0000250|UniProtKB:Q8WU17}.
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:0000250|UniProtKB:Q8WU17};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q8WU17}.
CC -!- SUBUNIT: Interacts with VHL. Interacts with MHC class I and HM13.
CC Component of SCAP-SREBP complex composed of SREBF2, SCAP and RNF139;
CC the complex hampers the interaction between SCAP and SEC24B, thereby
CC reducing SREBF2 proteolytic processing. Interacts with SREBF2 (via C-
CC terminal domain). Interacts with SCAP; the interaction inhibits the
CC interaction of SCAP with SEC24B and hampering the ER to Golgi transport
CC of the SCAP-SREBP complex. Interacts with SEC24B. Interacts with INSIG1
CC and INSIG2. Interacts with EIF3F and EIF3H; the interaction leads to
CC protein translation inhibitions in a ubiquitination-dependent manner.
CC Interacts with XBP1 isoform 1; the interaction induces ubiquitination
CC and degradation of XBP1 isoform 1. Interacts with AUP1, AMFR and
CC UBE2G2; interaction with AUP1 facilitates interaction of RNF139 with
CC ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase AMFR/gp78,
CC leading to sterol-induced ubiquitination of HMGCR and its subsequent
CC proteasomal degradation. {ECO:0000250|UniProtKB:Q8WU17}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8WU17}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8WU17}.
CC -!- DOMAIN: The RING-type zinc finger domain may be essential for ubiquitin
CC ligase activity. {ECO:0000250|UniProtKB:O75485}.
CC -!- PTM: Autoubiquitinated. Ubiquitination is induced by sterol and leads
CC to ist degradation via the ubiquitin-proteasome pathway.
CC {ECO:0000250|UniProtKB:Q8WU17}.
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DR EMBL; AK033506; BAC28327.1; -; mRNA.
DR EMBL; BC052901; AAH52901.1; -; mRNA.
DR CCDS; CCDS27494.1; -.
DR RefSeq; NP_780435.1; NM_175226.4.
DR AlphaFoldDB; Q7TMV1; -.
DR SMR; Q7TMV1; -.
DR BioGRID; 217784; 1.
DR STRING; 10090.ENSMUSP00000046467; -.
DR iPTMnet; Q7TMV1; -.
DR PhosphoSitePlus; Q7TMV1; -.
DR MaxQB; Q7TMV1; -.
DR PaxDb; Q7TMV1; -.
DR PeptideAtlas; Q7TMV1; -.
DR PRIDE; Q7TMV1; -.
DR ProteomicsDB; 300489; -.
DR DNASU; 75841; -.
DR GeneID; 75841; -.
DR KEGG; mmu:75841; -.
DR UCSC; uc007vtq.2; mouse.
DR CTD; 11236; -.
DR MGI; MGI:1923091; Rnf139.
DR eggNOG; KOG0802; Eukaryota.
DR InParanoid; Q7TMV1; -.
DR OrthoDB; 897451at2759; -.
DR PhylomeDB; Q7TMV1; -.
DR TreeFam; TF318635; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 75841; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Rnf139; mouse.
DR PRO; PR:Q7TMV1; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q7TMV1; protein.
DR GO; GO:0036513; C:Derlin-1 retrotranslocation complex; ISO:MGI.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0019787; F:ubiquitin-like protein transferase activity; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0036503; P:ERAD pathway; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0017148; P:negative regulation of translation; ISO:MGI.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0060628; P:regulation of ER to Golgi vesicle-mediated transport; ISO:MGI.
DR GO; GO:0070613; P:regulation of protein processing; ISO:MGI.
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; Endoplasmic reticulum; Membrane; Metal-binding;
KW Phosphoprotein; Receptor; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8WU17"
FT CHAIN 2..668
FT /note="E3 ubiquitin-protein ligase RNF139"
FT /id="PRO_0000056099"
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 470..490
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 602..668
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 616..632
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q8WU17"
FT MOD_RES 636
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8WU17"
FT MOD_RES 637
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8WU17"
FT MOD_RES 667
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT CONFLICT 248
FT /note="T -> A (in Ref. 1; BAC28327)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 668 AA; 76185 MW; 6DA76DFC64C6374D CRC64;
MAAVGPPQQQ VRMAQQQVWA ALEVALRVPC LYIIDAIFNS YYDSSQSRFC IGLQIFLRLL
GIVVSSIVLI LSQRSLFKFY MYSSAFLLAA TSVLVNYYAA LHIDFYGAYN TSAFGIELLP
RKGPSLWMAL IVLQLTFGIG YVTLLQIQSI YSQLMILNIL VPIIGLITEL PLHIRETVVL
MSSLILIFNT VLVLAVKLKW FYYSTRYVYL LVRHMYRIYG LQLLMEDTWK RIRFPDILRV
FWLTRITTQA TVLMYILRMA NETESFFISW DDFWDVICNL IISGCDSTLT VLGMSAVISS
IAHYLGLGIL AFIGSTEEDD RRLGFVAPVL FFILALQTGL SGLRPEERLI RLSRNMCLLL
TAVLHFIHGM TDPVLMSLSA SHVSSFHRHF PVLFVSACLF ILPVLLSYVL WHHYALNTWL
FAVTAFCVEL CLKVIVSLTV YTLFMIDGYY NVLWEKLDDY VYFVRSTGNI IEFIFGVVMF
GNGAYTMMFE SGSKIRACMM CLHAYFNIYL QVKNGWKTFM NRRTAVKKIN SLPEIKGSHL
QEIDDVCAIC YHEFTTSARI TPCNHYFHAL CLRKWLYIQD TCPMCHQKVY IEDEIKDNSN
ASNNNGFIAP NENPNPEEAL REDAAGSDRE LNEDDSTDCD DDAQRERNGG IQHTGAAAAA
AEFNDDTD
