RNF25_HUMAN
ID RNF25_HUMAN Reviewed; 459 AA.
AC Q96BH1; A8K0D6; Q53HQ5; Q9H874;
DT 06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=E3 ubiquitin-protein ligase RNF25;
DE EC=2.3.2.27;
DE AltName: Full=RING finger protein 25;
DE AltName: Full=RING-type E3 ubiquitin transferase RNF25 {ECO:0000305};
GN Name=RNF25;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adipose tissue;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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, SUBCELLULAR LOCATION, INTERACTION WITH RELA, AND MUTAGENESIS OF
RP CYS-159 AND CYS-161.
RX PubMed=12748188; DOI=10.1074/jbc.m211831200;
RA Asamitsu K., Tetsuka T., Kanazawa S., Okamoto T.;
RT "RING finger protein AO7 supports NF-kappaB-mediated transcription by
RT interacting with the transactivation domain of the p65 subunit.";
RL J. Biol. Chem. 278:26879-26887(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450, AND IDENTIFICATION BY
RP 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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [10]
RP STRUCTURE BY NMR OF 10-134.
RG RIKEN structural genomics initiative (RSGI);
RT "An extended conformation of the RWD domain of human RING finger protein
RT 25.";
RL Submitted (OCT-2006) to the PDB data bank.
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and
CC subsequent proteasomal degradation of NKD2 (By similarity). Stimulates
CC transcription mediated by NF-kappa-B. {ECO:0000250,
CC ECO:0000269|PubMed:12748188}.
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 with UBE2D2, and may also interact with UBE2E1 and
CC UBE2E3. Interacts with NKD2 (By similarity). Interacts with RELA.
CC {ECO:0000250, ECO:0000269|PubMed:12748188}.
CC -!- INTERACTION:
CC Q96BH1; Q4G0X4: KCTD21; NbExp=3; IntAct=EBI-2129220, EBI-11976683;
CC Q96BH1; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-2129220, EBI-16439278;
CC Q96BH1; Q969F2: NKD2; NbExp=2; IntAct=EBI-2129220, EBI-1538629;
CC Q96BH1; O60260-5: PRKN; NbExp=3; IntAct=EBI-2129220, EBI-21251460;
CC Q96BH1; P51668: UBE2D1; NbExp=5; IntAct=EBI-2129220, EBI-743540;
CC Q96BH1; P62837: UBE2D2; NbExp=3; IntAct=EBI-2129220, EBI-347677;
CC Q96BH1; P61077: UBE2D3; NbExp=5; IntAct=EBI-2129220, EBI-348268;
CC Q96BH1; Q9Y2X8: UBE2D4; NbExp=3; IntAct=EBI-2129220, EBI-745527;
CC Q96BH1; P51965: UBE2E1; NbExp=3; IntAct=EBI-2129220, EBI-348546;
CC Q96BH1; Q969T4: UBE2E3; NbExp=3; IntAct=EBI-2129220, EBI-348496;
CC -!- DOMAIN: The RING-type zinc finger domain interacts with an ubiquitin-
CC conjugating enzyme (E2) and facilitates ubiquitination.
CC -!- PTM: Ubiquitinated. {ECO:0000250}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK023968; BAB14743.1; -; mRNA.
DR EMBL; AK289501; BAF82190.1; -; mRNA.
DR EMBL; AK222525; BAD96245.1; -; mRNA.
DR EMBL; AC009974; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471063; EAW70645.1; -; Genomic_DNA.
DR EMBL; BC015612; AAH15612.1; -; mRNA.
DR CCDS; CCDS2420.1; -.
DR RefSeq; NP_071898.2; NM_022453.2.
DR PDB; 2DAY; NMR; -; A=11-125.
DR PDB; 2DMF; NMR; -; A=11-134.
DR PDB; 5D1K; X-ray; 1.78 A; B=126-258.
DR PDB; 5D1L; X-ray; 1.62 A; B=126-258.
DR PDB; 5D1M; X-ray; 1.58 A; B=126-258.
DR PDBsum; 2DAY; -.
DR PDBsum; 2DMF; -.
DR PDBsum; 5D1K; -.
DR PDBsum; 5D1L; -.
DR PDBsum; 5D1M; -.
DR AlphaFoldDB; Q96BH1; -.
DR BMRB; Q96BH1; -.
DR SMR; Q96BH1; -.
DR BioGRID; 122133; 35.
DR DIP; DIP-29063N; -.
DR IntAct; Q96BH1; 24.
DR STRING; 9606.ENSP00000295704; -.
DR GlyGen; Q96BH1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96BH1; -.
DR PhosphoSitePlus; Q96BH1; -.
DR BioMuta; RNF25; -.
DR DMDM; 21362899; -.
DR EPD; Q96BH1; -.
DR jPOST; Q96BH1; -.
DR MassIVE; Q96BH1; -.
DR MaxQB; Q96BH1; -.
DR PaxDb; Q96BH1; -.
DR PeptideAtlas; Q96BH1; -.
DR PRIDE; Q96BH1; -.
DR ProteomicsDB; 76075; -.
DR Antibodypedia; 34282; 156 antibodies from 28 providers.
DR DNASU; 64320; -.
DR Ensembl; ENST00000295704.7; ENSP00000295704.2; ENSG00000163481.8.
DR GeneID; 64320; -.
DR KEGG; hsa:64320; -.
DR MANE-Select; ENST00000295704.7; ENSP00000295704.2; NM_022453.3; NP_071898.2.
DR UCSC; uc002vit.4; human.
DR CTD; 64320; -.
DR DisGeNET; 64320; -.
DR GeneCards; RNF25; -.
DR HGNC; HGNC:14662; RNF25.
DR HPA; ENSG00000163481; Low tissue specificity.
DR MIM; 616014; gene.
DR neXtProt; NX_Q96BH1; -.
DR OpenTargets; ENSG00000163481; -.
DR PharmGKB; PA34429; -.
DR VEuPathDB; HostDB:ENSG00000163481; -.
DR eggNOG; KOG4445; Eukaryota.
DR GeneTree; ENSGT00390000001557; -.
DR HOGENOM; CLU_051859_0_0_1; -.
DR InParanoid; Q96BH1; -.
DR OMA; HHRPWDC; -.
DR OrthoDB; 968943at2759; -.
DR PhylomeDB; Q96BH1; -.
DR TreeFam; TF324097; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; Q96BH1; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q96BH1; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 64320; 72 hits in 1123 CRISPR screens.
DR ChiTaRS; RNF25; human.
DR EvolutionaryTrace; Q96BH1; -.
DR GeneWiki; RNF25; -.
DR GenomeRNAi; 64320; -.
DR Pharos; Q96BH1; Tbio.
DR PRO; PR:Q96BH1; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q96BH1; protein.
DR Bgee; ENSG00000163481; Expressed in adenohypophysis and 147 other tissues.
DR ExpressionAtlas; Q96BH1; baseline and differential.
DR Genevisible; Q96BH1; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051059; F:NF-kappaB binding; IPI:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR Gene3D; 3.10.110.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR039133; RNF25.
DR InterPro; IPR006575; RWD-domain.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR13198; PTHR13198; 1.
DR Pfam; PF05773; RWD; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00591; RWD; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS50908; RWD; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Metal-binding; Phosphoprotein; Reference proteome;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..459
FT /note="E3 ubiquitin-protein ligase RNF25"
FT /id="PRO_0000056066"
FT DOMAIN 18..128
FT /note="RWD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00179"
FT ZN_FING 135..202
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 268..309
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 322..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 281..301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 345..366
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MUTAGEN 159
FT /note="C->S: Reduced activation of NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:12748188"
FT MUTAGEN 161
FT /note="C->S: Strongly reduced activation of NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:12748188"
FT CONFLICT 186
FT /note="H -> R (in Ref. 2; BAD96245)"
FT /evidence="ECO:0000305"
FT CONFLICT 346
FT /note="P -> S (in Ref. 2; BAD96245)"
FT /evidence="ECO:0000305"
FT HELIX 15..26
FT /evidence="ECO:0007829|PDB:2DAY"
FT TURN 28..30
FT /evidence="ECO:0007829|PDB:2DAY"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:2DAY"
FT TURN 38..40
FT /evidence="ECO:0007829|PDB:2DMF"
FT STRAND 43..49
FT /evidence="ECO:0007829|PDB:2DAY"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:2DAY"
FT STRAND 63..70
FT /evidence="ECO:0007829|PDB:2DAY"
FT STRAND 80..89
FT /evidence="ECO:0007829|PDB:2DAY"
FT HELIX 91..107
FT /evidence="ECO:0007829|PDB:2DAY"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:2DAY"
FT HELIX 114..125
FT /evidence="ECO:0007829|PDB:2DAY"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:5D1M"
FT TURN 136..138
FT /evidence="ECO:0007829|PDB:5D1M"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:5D1M"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:5D1M"
FT HELIX 159..176
FT /evidence="ECO:0007829|PDB:5D1M"
FT TURN 199..201
FT /evidence="ECO:0007829|PDB:5D1M"
FT HELIX 209..214
FT /evidence="ECO:0007829|PDB:5D1M"
FT HELIX 229..247
FT /evidence="ECO:0007829|PDB:5D1M"
SQ SEQUENCE 459 AA; 51219 MW; CE7C66EF2E988917 CRC64;
MAASASAAAG EEDWVLPSEV EVLESIYLDE LQVIKGNGRT SPWEIYITLH PATAEDQDSQ
YVCFTLVLQV PAEYPHEVPQ ISIRNPRGLS DEQIHTILQV LGHVAKAGLG TAMLYELIEK
GKEILTDNNI PHGQCVICLY GFQEKEAFTK TPCYHYFHCH CLARYIQHME QELKAQGQEQ
EQERQHATTK QKAVGVQCPV CREPLVYDLA SLKAAPEPQQ PMELYQPSAE SLRQQEERKR
LYQRQQERGG IIDLEAERNR YFISLQQPPA PAEPESAVDV SKGSQPPSTL AAELSTSPAV
QSTLPPPLPV ATQHICEKIP GTRSNQQRLG ETQKAMLDPP KPSRGPWRQP ERRHPKGGEC
HAPKGTRDTQ ELPPPEGPLK EPMDLKPEPH SQGVEGPPQE KGPGSWQGPP PRRTRDCVRW
ERSKGRTPGS SYPRLPRGQG AYRPGTRRES LGLESKDGS
