RNF4_RAT
ID RNF4_RAT Reviewed; 194 AA.
AC O88846;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 166.
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};
DE AltName: Full=Small nuclear ring finger protein;
DE Short=Protein SNURF;
GN Name=Rnf4; Synonyms=Snurf;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH AR AND TBP, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Testis;
RX PubMed=9710597; DOI=10.1128/mcb.18.9.5128;
RA Moilanen A.-M., Poukka H., Karvonen U., Hakli M., Janne O.A., Palvimo J.J.;
RT "Identification of a novel RING finger protein as a coregulator in steroid
RT receptor-mediated gene transcription.";
RL Mol. Cell. Biol. 18:5128-5139(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Yan W., Hirvonen S.J., Moilanen A.-M., Janne O.A., Palvimo J.J.,
RA Toppari J.;
RT "Analysis of androgen receptor coregulator SNURF/RNF4 expression in rat
RT testis.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 FUNCTION, MUTAGENESIS OF 8-ARG--ARG-11, AND SUBCELLULAR LOCATION.
RX PubMed=11319220; DOI=10.1074/jbc.m009891200;
RA Haekli M., Karvonen U., Jaenne O.A., Palvimo J.J.;
RT "The RING finger protein SNURF is a bifunctional protein possessing DNA
RT binding activity.";
RL J. Biol. Chem. 276:23653-23660(2001).
RN [5]
RP FUNCTION, AUTOUBIQUITINATION, AND MUTAGENESIS OF CYS-136; CYS-139; CYS-177
RP AND CYS-180.
RX PubMed=14987998; DOI=10.1016/s0014-5793(04)00070-5;
RA Haekli M., Lorick K.L., Weissman A.M., Jaenne O.A., Palvimo J.J.;
RT "Transcriptional coregulator SNURF (RNF4) possesses ubiquitin E3 ligase
RT activity.";
RL FEBS Lett. 560:56-62(2004).
RN [6]
RP FUNCTION, SUMOYLATION, AND INTERACTION WITH PML.
RX PubMed=15707587; DOI=10.1016/j.yexcr.2004.10.029;
RA Haekli M., Karvonen U., Jaenne O.A., Palvimo J.J.;
RT "SUMO-1 promotes association of SNURF (RNF4) with PML nuclear bodies.";
RL Exp. Cell Res. 304:224-233(2005).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF 40-ILE--VAL-43; 50-ILE--ASP-53; 61-VAL--VAL-63
RP AND 71-VAL--VAL-74.
RX PubMed=18408734; DOI=10.1038/ncb1716;
RA Tatham M.H., Geoffroy M.C., Shen L., Plechanovova A., Hattersley N.,
RA Jaffray E.G., Palvimo J.J., Hay R.T.;
RT "RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-
RT induced PML degradation.";
RL Nat. Cell Biol. 10:538-546(2008).
RN [8]
RP FUNCTION, INTERACTION WITH SUMOYLATED PML, AND SUBCELLULAR LOCATION.
RX PubMed=20943951; DOI=10.1091/mbc.e10-05-0449;
RA Geoffroy M.C., Jaffray E.G., Walker K.J., Hay R.T.;
RT "Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear
RT bodies.";
RL Mol. Biol. Cell 21:4227-4239(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98 AND SER-99, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 124-194 IN COMPLEX WITH ZINC IONS,
RP DOMAIN, 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).
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:11319220, ECO:0000269|PubMed:14987998,
CC ECO:0000269|PubMed:15707587, ECO:0000269|PubMed:18408734,
CC ECO:0000269|PubMed:20943951, ECO:0000269|PubMed:9710597}.
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 PATZ1 (By similarity). Interacts with TRPS1; negatively regulates the
CC TRPS1 transcriptional repressor activity (By similarity). Interacts
CC with GSC2 (By similarity). Interacts with TCF20 (By similarity).
CC Interacts with PARP1 (By similarity). Interacts with AR/the androgen
CC receptor and TBP. Interacts with PML; SUMO1-dependent. Interacts with
CC PML; SUMO2-dependent. Interacts with PML (By similarity). Interacts
CC with PRDM1 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P78317}.
CC -!- INTERACTION:
CC O88846; O88846: Rnf4; NbExp=4; IntAct=EBI-7258907, EBI-7258907;
CC O88846; P27695: APEX1; Xeno; NbExp=2; IntAct=EBI-7258907, EBI-1048805;
CC O88846; P61956: SUMO2; Xeno; NbExp=2; IntAct=EBI-7258907, EBI-473220;
CC O88846; Q13569: TDG; Xeno; NbExp=2; IntAct=EBI-7258907, EBI-348333;
CC O88846; P51668: UBE2D1; Xeno; NbExp=4; IntAct=EBI-7258907, EBI-743540;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus, PML body. Nucleus,
CC nucleoplasm.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in testis.
CC -!- DOMAIN: The RING-type zinc finger domain is required for the
CC ubiquitination of polysumoylated substrates.
CC {ECO:0000269|PubMed:20681948}.
CC -!- DOMAIN: The SUMO interaction motifs (SIMs) mediates the binding to
CC polysumoylated substrate. {ECO:0000269|PubMed:18408734}.
CC -!- PTM: Sumoylated; conjugated by one or two SUMO1 moieties.
CC {ECO:0000269|PubMed:15707587}.
CC -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:14987998}.
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DR EMBL; AF022081; AAC35248.1; -; mRNA.
DR EMBL; AY050655; AAL06715.1; -; mRNA.
DR EMBL; BC062024; AAH62024.1; -; mRNA.
DR RefSeq; NP_062055.1; NM_019182.2.
DR RefSeq; XP_008768493.1; XM_008770271.2.
DR RefSeq; XP_008768494.1; XM_008770272.2.
DR RefSeq; XP_008768495.1; XM_008770273.2.
DR RefSeq; XP_017454634.1; XM_017599145.1.
DR RefSeq; XP_017454635.1; XM_017599146.1.
DR PDB; 3NG2; X-ray; 1.80 A; A/B=124-194.
DR PDB; 4AP4; X-ray; 2.21 A; A=131-194.
DR PDB; 5AIT; X-ray; 3.40 A; A=131-194.
DR PDB; 5AIU; X-ray; 2.21 A; A=131-194.
DR PDBsum; 3NG2; -.
DR PDBsum; 4AP4; -.
DR PDBsum; 5AIT; -.
DR PDBsum; 5AIU; -.
DR AlphaFoldDB; O88846; -.
DR BMRB; O88846; -.
DR SMR; O88846; -.
DR BioGRID; 247945; 13.
DR IntAct; O88846; 12.
DR MINT; O88846; -.
DR STRING; 10116.ENSRNOP00000019555; -.
DR iPTMnet; O88846; -.
DR PhosphoSitePlus; O88846; -.
DR PaxDb; O88846; -.
DR Ensembl; ENSRNOT00000095762; ENSRNOP00000096496; ENSRNOG00000013930.
DR GeneID; 29274; -.
DR KEGG; rno:29274; -.
DR CTD; 6047; -.
DR RGD; 3583; Rnf4.
DR eggNOG; KOG0320; Eukaryota.
DR GeneTree; ENSGT00390000010318; -.
DR HOGENOM; CLU_106856_0_0_1; -.
DR InParanoid; O88846; -.
DR OrthoDB; 1431236at2759; -.
DR PhylomeDB; O88846; -.
DR TreeFam; TF328387; -.
DR BRENDA; 2.3.2.27; 5301.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR EvolutionaryTrace; O88846; -.
DR PRO; PR:O88846; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000013930; Expressed in testis and 19 other tissues.
DR ExpressionAtlas; O88846; baseline and differential.
DR Genevisible; O88846; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050681; F:nuclear androgen receptor binding; IPI:RGD.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:RGD.
DR GO; GO:0033142; F:nuclear progesterone receptor binding; IPI:RGD.
DR GO; GO:0031491; F:nucleosome binding; IDA:UniProtKB.
DR GO; GO:0032184; F:SUMO polymer binding; IDA:RGD.
DR GO; GO:0017025; F:TBP-class protein binding; IDA:RGD.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IPI:RGD.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:RGD.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:RGD.
DR GO; GO:0071243; P:cellular response to arsenic-containing substance; IEP:RGD.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IEP:RGD.
DR GO; GO:0071480; P:cellular response to gamma radiation; IMP:RGD.
DR GO; GO:0072711; P:cellular response to hydroxyurea; IMP:RGD.
DR GO; GO:0071394; P:cellular response to testosterone stimulus; IDA:RGD.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:RGD.
DR GO; GO:0070979; P:protein K11-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0044752; P:response to human chorionic gonadotropin; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
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_0000056045"
FT ZN_FING 136..181
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..20
FT /note="Required for ubiquitination activity"
FT /evidence="ECO:0000250"
FT REGION 6..65
FT /note="Mediates interaction with TRPS1"
FT /evidence="ECO:0000250"
FT MOTIF 40..43
FT /note="SUMO interaction motif 1"
FT /evidence="ECO:0000269|PubMed:18408734"
FT MOTIF 50..53
FT /note="SUMO interaction motif 2"
FT /evidence="ECO:0000269|PubMed:18408734"
FT MOTIF 61..63
FT /note="SUMO interaction motif 3"
FT /evidence="ECO:0000269|PubMed:18408734"
FT MOTIF 71..74
FT /note="SUMO interaction motif 4"
FT /evidence="ECO:0000269|PubMed:18408734"
FT COMPBIAS 1..34
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 8..11
FT /note="RKRR->AAAA: Altered DNA-binding activity."
FT /evidence="ECO:0000269|PubMed:11319220"
FT MUTAGEN 40..43
FT /note="IELV->AEAA: No effect. Loss of binding and
FT ubiquitination of poly-SUMO chains; when associated with
FT 50-A--A-53; 61-A--A-63 and 71-A--A-74."
FT /evidence="ECO:0000269|PubMed:18408734"
FT MUTAGEN 50..53
FT /note="IVDL->AADA: Alters binding to poly-SUMO chains. Loss
FT of binding and ubiquitination of poly-SUMO chains; when
FT associated with 40-A--A-43; 61-A--A-63 and 71-A--A-74."
FT /evidence="ECO:0000269|PubMed:18408734"
FT MUTAGEN 61..63
FT /note="VVV->AAA: No effect. Loss of binding and
FT ubiquitination of poly-SUMO chains; when associated with
FT 40-A--A-43; 50-A--A-53 and 71-A--A-74."
FT /evidence="ECO:0000269|PubMed:18408734"
FT MUTAGEN 71..74
FT /note="VVIV->AAAA: No effect. Loss of binding and
FT ubiquitination of poly-SUMO chains; when associated with
FT 40-A--A-43; 50-A--A-53 and 61-A--A-63."
FT /evidence="ECO:0000269|PubMed:18408734"
FT MUTAGEN 136
FT /note="C->S: Loss of ubiquitination activity; when
FT associated with S-139."
FT /evidence="ECO:0000269|PubMed:14987998"
FT MUTAGEN 139
FT /note="C->S: Loss of ubiquitination activity; when
FT associated with S-136."
FT /evidence="ECO:0000269|PubMed:14987998"
FT MUTAGEN 177
FT /note="C->S: Loss of ubiquitination activity; when
FT associated with S-180."
FT /evidence="ECO:0000269|PubMed:14987998"
FT MUTAGEN 180
FT /note="C->S: Loss of ubiquitination activity; when
FT associated with S-177."
FT /evidence="ECO:0000269|PubMed:14987998"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:4AP4"
FT TURN 137..139
FT /evidence="ECO:0007829|PDB:3NG2"
FT HELIX 143..147
FT /evidence="ECO:0007829|PDB:3NG2"
FT TURN 148..150
FT /evidence="ECO:0007829|PDB:3NG2"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:3NG2"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:3NG2"
FT HELIX 164..173
FT /evidence="ECO:0007829|PDB:3NG2"
FT TURN 178..180
FT /evidence="ECO:0007829|PDB:3NG2"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:4AP4"
FT STRAND 189..192
FT /evidence="ECO:0007829|PDB:4AP4"
SQ SEQUENCE 194 AA; 21897 MW; 40C13970FC11DFF2 CRC64;
MSTRNPQRKR RGGAVNSRQT QKRTRETTST PEISLEAEPI ELVETVGDEI VDLTCESLEP
VVVDLTHNDS VVIVEERRRP RRNGRRLRQD HADSCVVSSD DEELSKDKDV YVTTHTPRST
KDEGTTGLRP SGTVSCPICM DGYSEIVQNG RLIVSTECGH VFCSQCLRDS LKNANTCPTC
RKKINHKRYH PIYI
