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 27-MAR-2024, entry version 179. DE RecName: Full=E3 ubiquitin-protein ligase RNF25 {ECO:0000305}; DE EC=2.3.2.27 {ECO:0000269|PubMed:26475854, ECO:0000269|PubMed:36638793, ECO:0000269|PubMed:37651229}; DE AltName: Full=RING finger protein 25 {ECO:0000305}; DE AltName: Full=RING finger protein AO7 {ECO:0000303|PubMed:26475854}; GN Name=RNF25 {ECO:0000303|PubMed:36638793, ECO:0000312|HGNC:HGNC:14662}; 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. RN [11] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=36638793; DOI=10.1016/j.cell.2022.12.025; RA Oltion K., Carelli J.D., Yang T., See S.K., Wang H.Y., Kampmann M., RA Taunton J.; RT "An E3 ligase network engages GCN1 to promote the degradation of RT translation factors on stalled ribosomes."; RL Cell 0:0-0(2023). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF 135-CYS--CYS-138. RX PubMed=37651229; DOI=10.1016/j.celrep.2023.113056; RA Gurzeler L.A., Link M., Ibig Y., Schmidt I., Galuba O., Schoenbett J., RA Gasser-Didierlaurant C., Parker C.N., Mao X., Bitsch F., Schirle M., RA Couttet P., Sigoillot F., Ziegelmueller J., Uldry A.C., Teodorowicz W., RA Schmiedeberg N., Muehlemann O., Reinhardt J.; RT "Drug-induced eRF1 degradation promotes readthrough and reveals a new RT branch of ribosome quality control."; RL Cell Rep. 42:113056-113056(2023). RN [13] RP FUNCTION. RX PubMed=37951216; DOI=10.1016/j.molcel.2023.10.012; RA Zhao S., Cordes J., Caban K.M., Goetz M.J., Mackens-Kiani T., Veltri A.J., RA Sinha N.K., Weickert P., Kaya S., Hewitt G., Nedialkova D.D., Froehlich T., RA Beckmann R., Buskirk A.R., Green R., Stingele J.; RT "RNF14-dependent atypical ubiquitylation promotes translation-coupled RT resolution of RNA-protein crosslinks."; RL Mol. Cell 0:0-0(2023). RN [14] {ECO:0007744|PDB:5D1K, ECO:0007744|PDB:5D1L, ECO:0007744|PDB:5D1M} RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 126-258 IN COMPLEX WITH ZN(2+) RP AND UBE2D2, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH UBE2D2, RP AUTOUBIQUITINATION, AND MUTAGENESIS OF ILE-137; TYR-165; PRO-199; TYR-242 RP AND GLN-245. RX PubMed=26475854; DOI=10.1074/jbc.m115.685867; RA Li S., Liang Y.H., Mariano J., Metzger M.B., Stringer D.K., Hristova V.A., RA Li J., Randazzo P.A., Tsai Y.C., Ji X., Weissman A.M.; RT "Insights into ubiquitination from the unique clamp-like binding of the RT RING E3 AO7 to the E2 UbcH5B."; RL J. Biol. Chem. 290:30225-30239(2015). CC -!- FUNCTION: E3 ubiquitin-protein ligase that plays a key role in the CC RNF14-RNF25 translation quality control pathway, a pathway that takes CC place when a ribosome has stalled during translation, and which CC promotes ubiquitination and degradation of translation factors on CC stalled ribosomes (PubMed:36638793, PubMed:37651229, PubMed:37951216). CC Catalyzes ubiquitination of RPS27A in response to ribosome collisions, CC promoting activation of RNF14 (PubMed:36638793). RNF25 catalyzes CC ubiquitination of other ribosomal proteins on stalled ribosomes, such CC as RPL0, RPL1, RPL12, RPS13 and RPS17 (PubMed:36638793). Also involved CC in ubiquitination and degradation of stalled ETF1/eRF1 CC (PubMed:36638793, PubMed:37651229). Independently of its function in CC the response to stalled ribosomes, mediates ubiquitination and CC subsequent proteasomal degradation of NKD2 (By similarity). May also CC stimulate transcription mediated by NF-kappa-B via its interaction with CC RELA/p65 (PubMed:12748188). {ECO:0000250|UniProtKB:Q9QZR0, CC ECO:0000269|PubMed:12748188, ECO:0000269|PubMed:36638793, CC ECO:0000269|PubMed:37651229, ECO:0000269|PubMed:37951216}. 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:0000269|PubMed:26475854, CC ECO:0000269|PubMed:36638793, ECO:0000269|PubMed:37651229}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:26475854, ECO:0000269|PubMed:36638793, CC ECO:0000269|PubMed:37651229}. CC -!- SUBUNIT: Interacts with UBE2D2, and may also interact with UBE2E1 and CC UBE2E3 (PubMed:26475854). Interacts with RELA/p65 (PubMed:12748188). CC {ECO:0000269|PubMed:12748188, ECO:0000269|PubMed:26475854}. 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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q7SXJ6}. CC -!- PTM: Ubiquitinated; autoubiquitinated. {ECO:0000269|PubMed:26475854}. CC -!- SIMILARITY: Belongs to the RNF25 family. {ECO:0000305}. 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; 48. 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; 9606-ENSP00000295704; -. DR PeptideAtlas; Q96BH1; -. DR ProteomicsDB; 76075; -. DR Pumba; Q96BH1; -. DR Antibodypedia; 34282; 176 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 AGR; HGNC:14662; -. 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; PWEISIT; -. DR OrthoDB; 5405601at2759; -. 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 SIGNOR; Q96BH1; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 64320; 73 hits in 1200 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 149 other cell types or tissues. DR ExpressionAtlas; Q96BH1; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0022626; C:cytosolic ribosome; IDA:UniProt. 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; IDA:UniProtKB. 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:0085020; P:protein K6-linked ubiquitination; IDA:UniProt. DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB. DR GO; GO:0072344; P:rescue of stalled ribosome; IDA:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProt. DR CDD; cd16470; RING-H2_RNF25; 1. DR Gene3D; 3.10.110.10; Ubiquitin Conjugating Enzyme; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR039133; RNF25. DR InterPro; IPR006575; RWD_dom. DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR13198:SF4; E3 UBIQUITIN-PROTEIN LIGASE RNF25; 1. DR PANTHER; PTHR13198; RING FINGER PROTEIN 25; 1. DR Pfam; PF05773; RWD; 1. DR Pfam; PF13639; zf-RING_2; 1. DR SMART; SM00184; RING; 1. DR SMART; SM00591; RWD; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF54495; UBC-like; 1. DR PROSITE; PS50908; RWD; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR Genevisible; Q96BH1; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; 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 BINDING 135 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:26475854, FT ECO:0007744|PDB:5D1K, ECO:0007744|PDB:5D1L, FT ECO:0007744|PDB:5D1M" FT BINDING 138 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:26475854, FT ECO:0007744|PDB:5D1K, ECO:0007744|PDB:5D1L, FT ECO:0007744|PDB:5D1M" FT BINDING 153 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:26475854, FT ECO:0007744|PDB:5D1K, ECO:0007744|PDB:5D1L, FT ECO:0007744|PDB:5D1M" FT BINDING 155 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:26475854, FT ECO:0007744|PDB:5D1K, ECO:0007744|PDB:5D1L, FT ECO:0007744|PDB:5D1M" FT BINDING 158 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:26475854, FT ECO:0007744|PDB:5D1K, ECO:0007744|PDB:5D1L, FT ECO:0007744|PDB:5D1M" FT BINDING 161 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:26475854, FT ECO:0007744|PDB:5D1K, ECO:0007744|PDB:5D1L, FT ECO:0007744|PDB:5D1M" FT BINDING 198 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:26475854, FT ECO:0007744|PDB:5D1K, ECO:0007744|PDB:5D1L, FT ECO:0007744|PDB:5D1M" FT BINDING 201 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:26475854, FT ECO:0007744|PDB:5D1K, ECO:0007744|PDB:5D1L, FT ECO:0007744|PDB:5D1M" FT MOD_RES 450 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MUTAGEN 135..138 FT /note="CVIC->SVIS: Abolished E3 ubiquitin-protein ligase FT activity." FT /evidence="ECO:0000269|PubMed:37651229" FT MUTAGEN 137 FT /note="I->A: Strongly reduced E3 ubiquitin-protein ligase FT activity, slightly reduced binding to UBE2D2." FT /evidence="ECO:0000269|PubMed:26475854" 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 MUTAGEN 165 FT /note="Y->A: Decreased E3 ubiquitin-protein ligase FT activity, increased binding to UBE2D2." FT /evidence="ECO:0000269|PubMed:26475854" FT MUTAGEN 199 FT /note="P->A: Decreased E3 ubiquitin-protein ligase activity FT without affecting binding to UBE2D2." FT /evidence="ECO:0000269|PubMed:26475854" FT MUTAGEN 242 FT /note="Y->A: Decreased binding to UBE2D2." FT /evidence="ECO:0000269|PubMed:26475854" FT MUTAGEN 245 FT /note="Q->A: Decreased binding to UBE2D2." FT /evidence="ECO:0000269|PubMed:26475854" 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 //