RNF4_MOUSE
ID RNF4_MOUSE Reviewed; 194 AA.
AC Q9QZS2; O35941; Q541Z6;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=E3 ubiquitin-protein ligase RNF4;
DE EC=2.3.2.27;
DE AltName: Full=RING finger protein 4;
DE AltName: Full=RING-type E3 ubiquitin transferase RNF4 {ECO:0000305};
GN Name=Rnf4;
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 INTERACTION WITH GSC2.
RC STRAIN=CD-1; TISSUE=Embryo;
RX PubMed=10822263;
RX DOI=10.1002/(sici)1097-0177(200005)218:1<102::aid-dvdy9>3.0.co;2-a;
RA Galili N., Nayak S., Epstein J.A., Buck C.A.;
RT "Rnf4, a RING protein expressed in the developing nervous and reproductive
RT systems, interacts with Gscl, a gene within the DiGeorge critical region.";
RL Dev. Dyn. 218:102-111(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RC TISSUE=Bone marrow, Embryo, Kidney, Lymph node, and Visual cortex;
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 MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-178.
RC TISSUE=Embryo;
RX PubMed=9479498; DOI=10.1006/geno.1997.5105;
RA Chiariotti L., Benvenuto G., Fedele M., Santoro M., Simeone A., Fusco A.,
RA Bruni C.B.;
RT "Identification and characterization of a novel RING-finger gene (RNF4)
RT mapping at 4p16.3.";
RL Genomics 47:258-265(1998).
RN [5]
RP INTERACTION WITH TCF20.
RX PubMed=10849425; DOI=10.1074/jbc.m003405200;
RA Lyngsoe C., Bouteiller G., Damgaard C.K., Ryom D., Sanchez-Munoz S.,
RA Noerby P.L., Bonven B.J., Joergensen P.;
RT "Interaction between the transcription factor SPBP and the positive
RT cofactor RNF4. An interplay between protein binding zinc fingers.";
RL J. Biol. Chem. 275:26144-26149(2000).
RN [6]
RP INTERACTION WITH TRPS1.
RX PubMed=12885770; DOI=10.1074/jbc.m306259200;
RA Kaiser F.J., Moeroey T., Chang G.T., Horsthemke B., Luedecke H.J.;
RT "The RING finger protein RNF4, a co-regulator of transcription, interacts
RT with the TRPS1 transcription factor.";
RL J. Biol. Chem. 278:38780-38785(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98, 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 [8]
RP INTERACTION WITH PARP1.
RX PubMed=19779455; DOI=10.1038/emboj.2009.279;
RA Martin N., Schwamborn K., Schreiber V., Werner A., Guillier C., Zhang X.D.,
RA Bischof O., Seeler J.S., Dejean A.;
RT "PARP-1 transcriptional activity is regulated by sumoylation upon heat
RT shock.";
RL EMBO J. 28:3534-3548(2009).
RN [9]
RP FUNCTION, AUTOUBIQUITINATION, MUTAGENESIS OF VAL-134; SER-155; VAL-161 AND
RP TYR-193, AND SUBUNIT.
RX PubMed=20681948; DOI=10.1042/bj20100957;
RA Liew C.W., Sun H., Hunter T., Day C.L.;
RT "RING domain dimerization is essential for RNF4 function.";
RL Biochem. J. 431:23-29(2010).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98 AND SER-99, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, and Spleen;
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-protein ligase which binds polysumoylated chains
CC covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-
CC 48'- and 'Lys-63'-linked polyubiquitination of those substrates and
CC their subsequent targeting to the proteasome for degradation. Regulates
CC the degradation of several proteins including PML and the
CC transcriptional activator PEA3. Involved in chromosome alignment and
CC spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK
CC complex by targeting polysumoylated CENPI to proteasomal degradation.
CC Regulates the cellular responses to hypoxia and heat shock through
CC degradation of respectively EPAS1 and PARP1. Alternatively, it may also
CC bind DNA/nucleosomes and have a more direct role in the regulation of
CC transcription for instance enhancing basal transcription and steroid
CC receptor-mediated transcriptional activation.
CC {ECO:0000269|PubMed:20681948}.
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: Homodimer (via RING-type zinc finger domain). Interacts with
CC AR/the androgen receptor and TBP (By similarity). Interacts with PATZ1
CC (By similarity). Interacts with PML; SUMO1-dependent. Interacts with
CC PML; SUMO2-dependent (By similarity). Interacts with TRPS1; negatively
CC regulates the TRPS1 transcriptional repressor activity. Interacts with
CC GSC2. Interacts with TCF20. Interacts with PARP1. Interacts with PML
CC (By similarity). Interacts with PRDM1 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P78317}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus, PML body
CC {ECO:0000250}. Nucleus, nucleoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: In the embryo, expressed primarily in the
CC developing nervous system with strong expression in the dorsal root
CC ganglia and gonads. Ubiquitously expressed in the adult.
CC -!- DEVELOPMENTAL STAGE: Expression is detected from embryonic day 7 and
CC continues throughout development and into adulthood.
CC -!- DOMAIN: The SUMO interaction motifs (SIMs) mediates the binding to
CC polysumoylated substrate. {ECO:0000250|UniProtKB:P78317}.
CC -!- DOMAIN: The RING-type zinc finger domain is required for the
CC ubiquitination of polysumoylated substrates.
CC {ECO:0000250|UniProtKB:O88846}.
CC -!- PTM: Sumoylated; conjugated by one or two SUMO1 moieties.
CC {ECO:0000250}.
CC -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:20681948}.
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DR EMBL; AF169300; AAF00620.1; -; mRNA.
DR EMBL; AK019171; BAB31585.1; -; mRNA.
DR EMBL; AK090162; BAC41119.1; -; mRNA.
DR EMBL; AK147057; BAE27641.1; -; mRNA.
DR EMBL; AK151116; BAE30125.1; -; mRNA.
DR EMBL; AK158987; BAE34757.1; -; mRNA.
DR EMBL; AK159778; BAE35362.1; -; mRNA.
DR EMBL; AK159949; BAE35505.1; -; mRNA.
DR EMBL; BC003282; AAH03282.1; -; mRNA.
DR EMBL; U95141; AAC53539.1; -; mRNA.
DR CCDS; CCDS57336.1; -.
DR RefSeq; NP_001291198.1; NM_001304269.1.
DR RefSeq; NP_001291199.1; NM_001304270.1.
DR RefSeq; NP_035408.1; NM_011278.5.
DR PDB; 2MP2; NMR; -; C=45-69.
DR PDBsum; 2MP2; -.
DR AlphaFoldDB; Q9QZS2; -.
DR BMRB; Q9QZS2; -.
DR SMR; Q9QZS2; -.
DR BioGRID; 202920; 5.
DR IntAct; Q9QZS2; 1.
DR MINT; Q9QZS2; -.
DR STRING; 10090.ENSMUSP00000138555; -.
DR iPTMnet; Q9QZS2; -.
DR PhosphoSitePlus; Q9QZS2; -.
DR EPD; Q9QZS2; -.
DR jPOST; Q9QZS2; -.
DR MaxQB; Q9QZS2; -.
DR PaxDb; Q9QZS2; -.
DR PRIDE; Q9QZS2; -.
DR ProteomicsDB; 260989; -.
DR Antibodypedia; 22369; 139 antibodies from 24 providers.
DR DNASU; 19822; -.
DR Ensembl; ENSMUST00000030992; ENSMUSP00000030992; ENSMUSG00000029110.
DR Ensembl; ENSMUST00000182047; ENSMUSP00000138411; ENSMUSG00000029110.
DR Ensembl; ENSMUST00000182709; ENSMUSP00000138555; ENSMUSG00000029110.
DR GeneID; 19822; -.
DR KEGG; mmu:19822; -.
DR UCSC; uc008xcc.2; mouse.
DR CTD; 6047; -.
DR MGI; MGI:1201691; Rnf4.
DR VEuPathDB; HostDB:ENSMUSG00000029110; -.
DR eggNOG; KOG0320; Eukaryota.
DR GeneTree; ENSGT00390000010318; -.
DR HOGENOM; CLU_106856_0_0_1; -.
DR InParanoid; Q9QZS2; -.
DR OMA; LRNANSC; -.
DR OrthoDB; 1431236at2759; -.
DR PhylomeDB; Q9QZS2; -.
DR TreeFam; TF328387; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 19822; 17 hits in 73 CRISPR screens.
DR ChiTaRS; Rnf4; mouse.
DR PRO; PR:Q9QZS2; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9QZS2; protein.
DR Bgee; ENSMUSG00000029110; Expressed in seminiferous tubule of testis and 263 other tissues.
DR ExpressionAtlas; Q9QZS2; baseline and differential.
DR Genevisible; Q9QZS2; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:1990752; C:microtubule end; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0016605; C:PML body; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0050681; F:nuclear androgen receptor binding; ISO:MGI.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; ISO:MGI.
DR GO; GO:0033142; F:nuclear progesterone receptor binding; ISO:MGI.
DR GO; GO:0031491; F:nucleosome binding; ISS:UniProtKB.
DR GO; GO:0032184; F:SUMO polymer binding; ISS:UniProtKB.
DR GO; GO:0017025; F:TBP-class protein binding; ISO:MGI.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0071480; P:cellular response to gamma radiation; ISO:MGI.
DR GO; GO:0072711; P:cellular response to hydroxyurea; ISO:MGI.
DR GO; GO:0071394; P:cellular response to testosterone stimulus; ISO:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0070979; P:protein K11-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISO:MGI.
DR GO; GO:0090234; P:regulation of kinetochore assembly; ISS:UniProtKB.
DR GO; GO:0090169; P:regulation of spindle assembly; ISS:UniProtKB.
DR GO; GO:0046685; P:response to arsenic-containing substance; ISO:MGI.
DR CDD; cd16533; RING-HC_RNF4; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR043295; RING-HC_RNF4.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cytoplasm; DNA-binding; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..194
FT /note="E3 ubiquitin-protein ligase RNF4"
FT /id="PRO_0000056044"
FT ZN_FING 136..181
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..20
FT /note="Required for ubiquitination activity"
FT REGION 6..65
FT /note="Mediates interaction with TRPS1"
FT /evidence="ECO:0000269|PubMed:12885770"
FT REGION 110..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 40..43
FT /note="SUMO interaction motif 1; mediates the binding to
FT polysumoylated substrates"
FT /evidence="ECO:0000250|UniProtKB:P78317"
FT MOTIF 50..53
FT /note="SUMO interaction motif 2; mediates the binding to
FT polysumoylated substrates"
FT /evidence="ECO:0000250|UniProtKB:P78317"
FT MOTIF 61..63
FT /note="SUMO interaction motif 3; mediates the binding to
FT polysumoylated substrates"
FT /evidence="ECO:0000250|UniProtKB:P78317"
FT MOTIF 71..74
FT /note="SUMO interaction motif 4; mediates the binding to
FT polysumoylated substrates"
FT /evidence="ECO:0000250|UniProtKB:P78317"
FT COMPBIAS 1..35
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 134
FT /note="V->E: Abolishes homodimerization. Strongly reduced
FT E3 ubiquitin ligase activity."
FT /evidence="ECO:0000269|PubMed:20681948"
FT MUTAGEN 155
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:20681948"
FT MUTAGEN 155
FT /note="S->E: Abolishes homodimerization. Strongly reduced
FT E3 ubiquitin ligase activity."
FT /evidence="ECO:0000269|PubMed:20681948"
FT MUTAGEN 161
FT /note="V->A: Abolishes homodimerization. Strongly reduced
FT E3 ubiquitin ligase activity."
FT /evidence="ECO:0000269|PubMed:20681948"
FT MUTAGEN 193
FT /note="Y->A: Abolishes homodimerization. Loss of E3
FT ubiquitin ligase activity."
FT /evidence="ECO:0000269|PubMed:20681948"
SQ SEQUENCE 194 AA; 21911 MW; 9A0A4277725C62E5 CRC64;
MSTRNPQRKR RGGTVNSRQT QKRTRETTST PEVSLETEPI ELVETVGDEI VDLTCESLEP
VVVDLTHNDS VVIVEERRRP RRNGRRLRQD HADSCVVSSD DEELSRDKDV YVTTHTPRST
KDDGATGPRP SGTVSCPICM DGYSEIVQNG RLIVSTECGH VFCSQCLRDS LKNANTCPTC
RKKINHKRYH PIYI
