RNF12_MOUSE
ID RNF12_MOUSE Reviewed; 600 AA.
AC Q9WTV7; Q8CE02; Q91X19; Q9CYY2;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=E3 ubiquitin-protein ligase RLIM;
DE EC=2.3.2.27;
DE AltName: Full=LIM domain-interacting RING finger protein;
DE AltName: Full=RING finger LIM domain-binding protein;
DE Short=R-LIM;
DE AltName: Full=RING finger protein 12;
DE AltName: Full=RING-type E3 ubiquitin transferase RLIM {ECO:0000305};
GN Name=Rlim; Synonyms=Rnf12;
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]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Pituitary;
RX PubMed=10431247; DOI=10.1038/11970;
RA Bach I., Rodriguez-Esteban C., Carriere C., Bhushan A., Krones A.,
RA Rose D.W., Glass C.K., Andersen B., Izpisua-Belmonte J.-C., Rosenfeld M.G.;
RT "RLIM inhibits functional activity of LIM homeodomain transcription factors
RT via recruitment of the histone deacetylase complex.";
RL Nat. Genet. 22:394-399(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Head;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
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 [6]
RP FUNCTION, AND INTERACTION WITH LHX3; LDB1; LDB2 AND SIN3A.
RX PubMed=11882901; DOI=10.1038/416099a;
RA Ostendorff H.P., Peirano R.I., Peters M.A., Schluter A., Bossenz M.,
RA Scheffner M., Bach I.;
RT "Ubiquitination-dependent cofactor exchange on LIM homeodomain
RT transcription factors.";
RL Nature 416:99-103(2002).
RN [7]
RP INTERACTION WITH LIMK1.
RX PubMed=16204183; DOI=10.1101/gad.1340605;
RA Tursun B., Schlueter A., Peters M.A., Viehweger B., Ostendorff H.P.,
RA Soosairajah J., Drung A., Bossenz M., Johnsen S.A., Schweizer M.,
RA Bernard O., Bach I.;
RT "The ubiquitin ligase Rnf6 regulates local LIM kinase 1 levels in axonal
RT growth cones.";
RL Genes Dev. 19:2307-2319(2005).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=19945382; DOI=10.1016/j.cell.2009.10.034;
RA Jonkers I., Barakat T.S., Achame E.M., Monkhorst K., Kenter A.,
RA Rentmeester E., Grosveld F., Grootegoed J.A., Gribnau J.;
RT "RNF12 is an X-encoded dose-dependent activator of X chromosome
RT inactivation.";
RL Cell 139:999-1011(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163; SER-227 AND SER-229, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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).
RN [10]
RP FUNCTION.
RX PubMed=22596162; DOI=10.1038/nature11070;
RA Gontan C., Achame E.M., Demmers J., Barakat T.S., Rentmeester E.,
RA van Ijcken W., Grootegoed J.A., Gribnau J.;
RT "RNF12 initiates X-chromosome inactivation by targeting REX1 for
RT degradation.";
RL Nature 485:386-390(2012).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that acts as a negative
CC coregulator for LIM homeodomain transcription factors by mediating the
CC ubiquitination and subsequent degradation of LIM cofactors LDB1 and
CC LDB2 and by mediating the recruitment the SIN3a/histone deacetylase
CC corepressor complex. Ubiquitination and degradation of LIM cofactors
CC LDB1 and LDB2 allows DNA-bound LIM homeodomain transcription factors to
CC interact with other protein partners such as RLIM. Plays a role in
CC telomere length-mediated growth suppression by mediating the
CC ubiquitination and degradation of TERF1. By targeting ZFP42 for
CC degradation, acts as an activator of random inactivation of X
CC chromosome in the embryo, a stochastic process in which one X
CC chromosome is inactivated to minimize sex-related dosage differences of
CC X-encoded genes in somatic cells of female placental mammals.
CC {ECO:0000269|PubMed:10431247, ECO:0000269|PubMed:11882901,
CC ECO:0000269|PubMed:19945382, ECO:0000269|PubMed:22596162}.
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;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts (via N-terminus) with TERF1. Interacts (via C-
CC terminus) with ESR1 (By similarity). Interacts with LIM/homeobox
CC factors such as LHX3. Interacts with LDB1, LDB2 and SIN3A. Interacts
CC with LIMK1. {ECO:0000250, ECO:0000269|PubMed:11882901,
CC ECO:0000269|PubMed:16204183}.
CC -!- INTERACTION:
CC Q9WTV7; O55203: Ldb2; NbExp=2; IntAct=EBI-15657872, EBI-15657830;
CC Q9WTV7; P22227: Zfp42; NbExp=8; IntAct=EBI-15657872, EBI-2313372;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19945382}.
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed in early development.
CC Expressed in the time window of embryonic stem (ES) cell
CC differentiation. {ECO:0000269|PubMed:19945382}.
CC -!- INDUCTION: Expressed at higher level in female compared to males cells
CC (at protein level). {ECO:0000269|PubMed:19945382}.
CC -!- SIMILARITY: Belongs to the RNF12 family. {ECO:0000305}.
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DR EMBL; AF069992; AAD34209.1; -; mRNA.
DR EMBL; AK013207; BAB28712.1; -; mRNA.
DR EMBL; AK029295; BAC26379.1; -; mRNA.
DR EMBL; AL805911; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466564; EDL14089.1; -; Genomic_DNA.
DR EMBL; CH466564; EDL14090.1; -; Genomic_DNA.
DR EMBL; BC012960; AAH12960.1; -; mRNA.
DR CCDS; CCDS30331.1; -.
DR RefSeq; NP_035406.3; NM_011276.3.
DR RefSeq; XP_006527981.1; XM_006527918.3.
DR RefSeq; XP_006527982.1; XM_006527919.3.
DR RefSeq; XP_006527983.1; XM_006527920.3.
DR RefSeq; XP_006527984.1; XM_006527921.3.
DR RefSeq; XP_011245853.1; XM_011247551.2.
DR RefSeq; XP_011245854.1; XM_011247552.2.
DR AlphaFoldDB; Q9WTV7; -.
DR SMR; Q9WTV7; -.
DR BioGRID; 202918; 13.
DR DIP; DIP-46445N; -.
DR IntAct; Q9WTV7; 11.
DR MINT; Q9WTV7; -.
DR STRING; 10090.ENSMUSP00000112820; -.
DR iPTMnet; Q9WTV7; -.
DR PhosphoSitePlus; Q9WTV7; -.
DR EPD; Q9WTV7; -.
DR jPOST; Q9WTV7; -.
DR MaxQB; Q9WTV7; -.
DR PaxDb; Q9WTV7; -.
DR PeptideAtlas; Q9WTV7; -.
DR PRIDE; Q9WTV7; -.
DR ProteomicsDB; 300552; -.
DR Antibodypedia; 13786; 194 antibodies from 24 providers.
DR DNASU; 19820; -.
DR Ensembl; ENSMUST00000070705; ENSMUSP00000070662; ENSMUSG00000056537.
DR Ensembl; ENSMUST00000121153; ENSMUSP00000112820; ENSMUSG00000056537.
DR GeneID; 19820; -.
DR KEGG; mmu:19820; -.
DR UCSC; uc009tzz.1; mouse.
DR CTD; 51132; -.
DR MGI; MGI:1342291; Rlim.
DR VEuPathDB; HostDB:ENSMUSG00000056537; -.
DR eggNOG; KOG0800; Eukaryota.
DR eggNOG; KOG4628; Eukaryota.
DR GeneTree; ENSGT00940000155753; -.
DR HOGENOM; CLU_025933_1_0_1; -.
DR InParanoid; Q9WTV7; -.
DR OMA; HHNISSQ; -.
DR OrthoDB; 1487241at2759; -.
DR PhylomeDB; Q9WTV7; -.
DR TreeFam; TF325756; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 19820; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Rlim; mouse.
DR PRO; PR:Q9WTV7; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q9WTV7; protein.
DR Bgee; ENSMUSG00000056537; Expressed in ectoplacental cone and 264 other tissues.
DR Genevisible; Q9WTV7; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IGI:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0060816; P:random inactivation of X chromosome; IDA:UniProtKB.
DR GO; GO:1900095; P:regulation of dosage compensation by inactivation of X chromosome; IMP:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..600
FT /note="E3 ubiquitin-protein ligase RLIM"
FT /id="PRO_0000056053"
FT ZN_FING 546..587
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 49..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 417..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 597..600
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 89..189
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 227..251
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 282..310
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 320..334
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 335..352
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 417..431
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 439..482
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9NVW2"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NVW2"
FT MOD_RES 227
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 229
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NVW2"
FT CONFLICT 114
FT /note="G -> R (in Ref. 1; AAD34209)"
FT /evidence="ECO:0000305"
FT CONFLICT 146
FT /note="N -> S (in Ref. 2; BAC26379)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="A -> T (in Ref. 1; AAD34209)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="R -> M (in Ref. 1; AAD34209)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="R -> G (in Ref. 2; BAC26379)"
FT /evidence="ECO:0000305"
FT CONFLICT 362
FT /note="R -> S (in Ref. 2; BAB28712)"
FT /evidence="ECO:0000305"
FT CONFLICT 470
FT /note="E -> K (in Ref. 1; AAD34209)"
FT /evidence="ECO:0000305"
FT CONFLICT 486
FT /note="R -> K (in Ref. 1; AAD34209)"
FT /evidence="ECO:0000305"
FT CONFLICT 505
FT /note="L -> F (in Ref. 1; AAD34209)"
FT /evidence="ECO:0000305"
FT CONFLICT 557
FT /note="N -> D (in Ref. 1; AAD34209)"
FT /evidence="ECO:0000305"
FT CONFLICT 568
FT /note="Y -> F (in Ref. 1; AAD34209)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 600 AA; 66377 MW; 6BFB9958502FDAED CRC64;
MENSDSNDKG SDQSAAQRRS QMDRLDREEA FYQFVNNLSE EDYRLMRDNN LLGTPGESTE
EELLRRLQQI KEGPPPQSPD ENRAGESSDD VTNSDSIIDW LNSVRQTGNT TRSGQRGNQS
WRAVSRTNPN SGDFRFSLEI NVNRNNGSQT SENESEPSTR RLSVENMESS SQRQMENSAS
ESASARPSRA ERNSAEAVTE VPTTRAQRRA RSRSPEHRRT RARAERSRSP LQPTSEIPRR
APTLEQSSEN EPEGSSRTRH HVTLRQQISG PELLGRGLFA ASGSRNPSQG TSSSDTGSNS
ESSGSGQRPP TIVLDLQVRR VRPGEYRQRD SIASRTRSRS QAPNNTVTYE SERGGFRRTF
SRSERAGVRT YVSTIRIPIR RILNTGLSET TSVAIQTMLR QIMTGFGELS YFMYSDSDSE
PSASVSSRNV ERVESRNGRG SSGGGNSSGS SSSSSPSPSS SGESSESSSE MFEGSSEGGS
SGPSRRDGRH RAPVTFDESG SLPFLSLAQF FLLNEDDEDQ PRGLTKEQID NLAMRSFGEN
DALKTCSVCI TEYTEGNKLR KLPCSHEYHV HCIDRWLSEN STCPICRRAV LSSGNRESVV
