RN216_HUMAN
ID RN216_HUMAN Reviewed; 866 AA.
AC Q9NWF9; Q6Y691; Q75ML7; Q7Z2H7; Q7Z7C1; Q8NHW7; Q9NYT1;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 3.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=E3 ubiquitin-protein ligase RNF216;
DE EC=2.3.2.27;
DE AltName: Full=RING finger protein 216;
DE AltName: Full=RING-type E3 ubiquitin transferase RNF216 {ECO:0000305};
DE AltName: Full=Triad domain-containing protein 3;
DE AltName: Full=Ubiquitin-conjugating enzyme 7-interacting protein 1;
DE AltName: Full=Zinc finger protein inhibiting NF-kappa-B;
GN Name=RNF216; Synonyms=TRIAD3, UBCE7IP1, ZIN;
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 [MRNA] (ISOFORM 3), AND INTERACTION WITH RIPK1.
RX PubMed=11854271; DOI=10.1074/jbc.m108675200;
RA Chen D., Li X., Zhai Z., Shu H.-B.;
RT "A novel zinc finger protein interacts with receptor-interacting protein
RT (RIP) and inhibits tumor necrosis factor (TNF)- and IL1-induced NF-kappa B
RT activation.";
RL J. Biol. Chem. 277:15985-15991(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, AND INTERACTION
RP WITH TLR3; TLR4; TLR5 AND TLR9.
RC TISSUE=Placenta;
RX PubMed=15107846; DOI=10.1038/ni1066;
RA Chuang T.-H., Ulevitch R.J.;
RT "Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors.";
RL Nat. Immunol. 5:495-502(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Endometrium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney, and Uterus;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 450-866 (ISOFORMS 1/2/3).
RC TISSUE=Embryo;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 509-866 (ISOFORMS 1/2/3).
RA van der Reijden B.A., Jansen J.H.;
RT "Identification of a novel TRIAD protein, TRIAD3.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP INTERACTION WITH HIV VIF PROTEIN (ISOFORM 3) (MICROBIAL INFECTION).
RX PubMed=15367624; DOI=10.1128/jvi.78.19.10574-10581.2004;
RA Feng F., Davis A., Lake J.A., Carr J., Xia W., Burrell C., Li P.;
RT "Ring finger protein ZIN interacts with human immunodeficiency virus type 1
RT Vif.";
RL J. Virol. 78:10574-10581(2004).
RN [9]
RP FUNCTION, AND INTERACTION WITH TRAF3.
RX PubMed=19893624; DOI=10.1371/journal.ppat.1000650;
RA Nakhaei P., Mesplede T., Solis M., Sun Q., Zhao T., Yang L., Chuang T.H.,
RA Ware C.F., Lin R., Hiscott J.;
RT "The E3 ubiquitin ligase Triad3A negatively regulates the RIG-I/MAVS
RT signaling pathway by targeting TRAF3 for degradation.";
RL PLoS Pathog. 5:E1000650-E1000650(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
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 [11]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-448 AND LYS-658, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [12]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-351, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [13]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-351 AND LYS-658, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [14]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-100; LYS-351; LYS-354; LYS-425;
RP LYS-430; LYS-448; LYS-459; LYS-485; LYS-619; LYS-658; LYS-666; LYS-765 AND
RP LYS-773, SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-80 AND LYS-89 (ISOFORM
RP 2), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [15]
RP VARIANTS GDHS CYS-660 AND CYS-694.
RX PubMed=23656588; DOI=10.1056/nejmoa1215993;
RA Margolin D.H., Kousi M., Chan Y.M., Lim E.T., Schmahmann J.D.,
RA Hadjivassiliou M., Hall J.E., Adam I., Dwyer A., Plummer L., Aldrin S.V.,
RA O'Rourke J., Kirby A., Lage K., Milunsky A., Milunsky J.M., Chan J.,
RA Hedley-Whyte E.T., Daly M.J., Katsanis N., Seminara S.B.;
RT "Ataxia, dementia, and hypogonadotropism caused by disordered
RT ubiquitination.";
RL N. Engl. J. Med. 368:1992-2003(2013).
CC -!- FUNCTION: Isoform 1 acts as an E3 ubiquitin ligase, which accepts
CC ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then
CC transfers it to substrates promoting their degradation by the
CC proteasome. Promotes degradation of TRAF3, TLR4 and TLR9. Contributes
CC to the regulation of antiviral responses. Down-regulates activation of
CC NF-kappa-B, IRF3 activation and IFNB production. Isoform 3 inhibits TNF
CC and IL-1 mediated activation of NF-kappa-B. Promotes TNF and RIP
CC mediated apoptosis. {ECO:0000269|PubMed:15107846,
CC ECO:0000269|PubMed:19893624}.
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 UBE2L3 and to some extent with UBE2L6.
CC Interacts with TRAF3, TLR3, TLR4, TLR5 and TLR9. Isoform 3/ZIN binds
CC RIPK1. {ECO:0000269|PubMed:11854271, ECO:0000269|PubMed:15107846,
CC ECO:0000269|PubMed:19893624}.
CC -!- SUBUNIT: (Microbial infection) Isoform 3/ZIN binds RIPK1 and HIV Vif.
CC {ECO:0000269|PubMed:15367624}.
CC -!- INTERACTION:
CC Q9NWF9; O75808: CAPN15; NbExp=3; IntAct=EBI-723313, EBI-6149008;
CC Q9NWF9; Q92567-2: FAM168A; NbExp=3; IntAct=EBI-723313, EBI-11978259;
CC Q9NWF9; O15037: KHNYN; NbExp=3; IntAct=EBI-723313, EBI-6148525;
CC Q9NWF9; Q14149: MORC3; NbExp=3; IntAct=EBI-723313, EBI-2556145;
CC Q9NWF9; Q8N3F0: MTURN; NbExp=3; IntAct=EBI-723313, EBI-11980301;
CC Q9NWF9; Q96CV9: OPTN; NbExp=3; IntAct=EBI-723313, EBI-748974;
CC Q9NWF9; P21580: TNFAIP3; NbExp=3; IntAct=EBI-723313, EBI-527670;
CC Q9NWF9; Q9BSL1: UBAC1; NbExp=3; IntAct=EBI-723313, EBI-749370;
CC Q9NWF9; P57075-2: UBASH3A; NbExp=3; IntAct=EBI-723313, EBI-7353612;
CC Q9NWF9; Q8TF42: UBASH3B; NbExp=3; IntAct=EBI-723313, EBI-1380492;
CC Q9NWF9; P68036: UBE2L3; NbExp=3; IntAct=EBI-723313, EBI-711173;
CC Q9NWF9; O14933: UBE2L6; NbExp=3; IntAct=EBI-723313, EBI-2129974;
CC Q9NWF9; P45974-2: USP5; NbExp=3; IntAct=EBI-723313, EBI-12072186;
CC Q9NWF9; Q5VVQ6: YOD1; NbExp=3; IntAct=EBI-723313, EBI-2510804;
CC Q9NWF9; Q8N6M9: ZFAND2A; NbExp=3; IntAct=EBI-723313, EBI-3921109;
CC Q9NWF9-3; P12504: vif; Xeno; NbExp=4; IntAct=EBI-723337, EBI-779991;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=TRIAD3A;
CC IsoId=Q9NWF9-2; Sequence=Displayed;
CC Name=2; Synonyms=TRIAD3B;
CC IsoId=Q9NWF9-1; Sequence=VSP_012444;
CC Name=3; Synonyms=ZIN, TRIAD3;
CC IsoId=Q9NWF9-3; Sequence=VSP_012443;
CC -!- TISSUE SPECIFICITY: Ubiquitous, with the highest levels of expression
CC in testis and peripheral blood leukocytes.
CC -!- DOMAIN: The RING-type zinc finger domain mediates binding to an E2
CC ubiquitin-conjugating enzyme. {ECO:0000250}.
CC -!- PTM: Auto-ubiquitinated.
CC -!- DISEASE: Gordon Holmes syndrome (GDHS) [MIM:212840]: A disease
CC characterized by cerebellar symptoms and signs of sex steroid
CC deficiency. Clinical features include cerebellar and brain stem
CC atrophy, cerebellar ataxia, hypothalamic LHRH deficiency,
CC hypogonadotrophic hypogonadism, lack of secondary sexual
CC characteristics, and infertility. {ECO:0000269|PubMed:23656588}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: 4 different alternatively spliced mRNAs
CC code for this protein isoform. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91422.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY062174; AAL38043.1; -; mRNA.
DR EMBL; AF513717; AAP47174.1; -; mRNA.
DR EMBL; AF513718; AAP47175.1; -; mRNA.
DR EMBL; AY177396; AAO60361.1; -; mRNA.
DR EMBL; AY177397; AAO60362.1; -; mRNA.
DR EMBL; AY177398; AAO60363.1; -; mRNA.
DR EMBL; BX537406; CAD97648.1; -; mRNA.
DR EMBL; AC008167; AAS07532.1; -; Genomic_DNA.
DR EMBL; BC000787; AAH00787.2; -; mRNA.
DR EMBL; BC063825; AAH63825.1; -; mRNA.
DR EMBL; AK000916; BAA91422.1; ALT_INIT; mRNA.
DR EMBL; AF228527; AAF36723.1; -; mRNA.
DR CCDS; CCDS34594.1; -. [Q9NWF9-1]
DR CCDS; CCDS34595.1; -. [Q9NWF9-2]
DR RefSeq; NP_996994.1; NM_207111.3. [Q9NWF9-1]
DR RefSeq; NP_996999.1; NM_207116.2. [Q9NWF9-2]
DR RefSeq; XP_005249842.1; XM_005249785.2. [Q9NWF9-1]
DR RefSeq; XP_011513738.1; XM_011515436.1. [Q9NWF9-3]
DR RefSeq; XP_016867852.1; XM_017012363.1.
DR RefSeq; XP_016867854.1; XM_017012365.1.
DR PDB; 7M4M; X-ray; 2.39 A; A/B=510-784.
DR PDB; 7M4N; X-ray; 2.52 A; A/B=649-784.
DR PDB; 7M4O; X-ray; 2.21 A; A=649-784.
DR PDBsum; 7M4M; -.
DR PDBsum; 7M4N; -.
DR PDBsum; 7M4O; -.
DR AlphaFoldDB; Q9NWF9; -.
DR SMR; Q9NWF9; -.
DR BioGRID; 119981; 47.
DR IntAct; Q9NWF9; 22.
DR MINT; Q9NWF9; -.
DR STRING; 9606.ENSP00000374552; -.
DR iPTMnet; Q9NWF9; -.
DR PhosphoSitePlus; Q9NWF9; -.
DR BioMuta; RNF216; -.
DR DMDM; 57015417; -.
DR EPD; Q9NWF9; -.
DR jPOST; Q9NWF9; -.
DR MassIVE; Q9NWF9; -.
DR MaxQB; Q9NWF9; -.
DR PeptideAtlas; Q9NWF9; -.
DR PRIDE; Q9NWF9; -.
DR ProteomicsDB; 82933; -. [Q9NWF9-2]
DR ProteomicsDB; 82934; -. [Q9NWF9-1]
DR ProteomicsDB; 82935; -. [Q9NWF9-3]
DR Antibodypedia; 11455; 215 antibodies from 28 providers.
DR DNASU; 54476; -.
DR Ensembl; ENST00000389902.8; ENSP00000374552.3; ENSG00000011275.19. [Q9NWF9-1]
DR Ensembl; ENST00000425013.6; ENSP00000404602.2; ENSG00000011275.19. [Q9NWF9-2]
DR GeneID; 54476; -.
DR KEGG; hsa:54476; -.
DR MANE-Select; ENST00000389902.8; ENSP00000374552.3; NM_207111.4; NP_996994.1. [Q9NWF9-1]
DR UCSC; uc003sox.3; human. [Q9NWF9-2]
DR CTD; 54476; -.
DR DisGeNET; 54476; -.
DR GeneCards; RNF216; -.
DR HGNC; HGNC:21698; RNF216.
DR HPA; ENSG00000011275; Low tissue specificity.
DR MalaCards; RNF216; -.
DR MIM; 212840; phenotype.
DR MIM; 609948; gene.
DR neXtProt; NX_Q9NWF9; -.
DR OpenTargets; ENSG00000011275; -.
DR Orphanet; 1173; Cerebellar ataxia-hypogonadism syndrome.
DR PharmGKB; PA162401829; -.
DR VEuPathDB; HostDB:ENSG00000011275; -.
DR eggNOG; KOG1812; Eukaryota.
DR GeneTree; ENSGT00510000048032; -.
DR HOGENOM; CLU_011576_1_0_1; -.
DR InParanoid; Q9NWF9; -.
DR OMA; MDGNCTC; -.
DR OrthoDB; 1486032at2759; -.
DR PhylomeDB; Q9NWF9; -.
DR TreeFam; TF330852; -.
DR PathwayCommons; Q9NWF9; -.
DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling.
DR SignaLink; Q9NWF9; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 54476; 18 hits in 1122 CRISPR screens.
DR ChiTaRS; RNF216; human.
DR GeneWiki; RNF216; -.
DR GenomeRNAi; 54476; -.
DR Pharos; Q9NWF9; Tbio.
DR PRO; PR:Q9NWF9; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9NWF9; protein.
DR Bgee; ENSG00000011275; Expressed in right testis and 197 other tissues.
DR ExpressionAtlas; Q9NWF9; baseline and differential.
DR Genevisible; Q9NWF9; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:LIFEdb.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; EXP:Reactome.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0032480; P:negative regulation of type I interferon production; TAS:Reactome.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0050691; P:regulation of defense response to virus by host; IDA:UniProtKB.
DR GO; GO:0032648; P:regulation of interferon-beta production; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR002867; IBR_dom.
DR InterPro; IPR044066; TRIAD_supradom.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR SMART; SM00647; IBR; 2.
DR PROSITE; PS51873; TRIAD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Coiled coil; Cytoplasm;
KW Disease variant; Host-virus interaction; Hypogonadotropic hypogonadism;
KW Isopeptide bond; Metal-binding; Phosphoprotein; Reference proteome; Repeat;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..866
FT /note="E3 ubiquitin-protein ligase RNF216"
FT /id="PRO_0000056293"
FT ZN_FING 515..564
FT /note="RING-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 583..648
FT /note="IBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 675..703
FT /note="RING-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 46..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..161
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 211..240
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 511..728
FT /note="TRIAD supradomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT COILED 475..491
FT /evidence="ECO:0000255"
FT COILED 737..763
FT /evidence="ECO:0000255"
FT COMPBIAS 55..76
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 133..154
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 688
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 515
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 518
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 537
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 540
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 605
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 608
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 623
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 628
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 633
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 636
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 643
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 648
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 675
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 678
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 693
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 695
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 700
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 703
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 716
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 724
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT MOD_RES 419
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 100
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 351
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT CROSSLNK 354
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 425
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 430
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 448
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 459
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 485
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 619
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 658
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733"
FT CROSSLNK 666
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 765
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 773
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..378
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11854271,
FT ECO:0000303|PubMed:15107846"
FT /id="VSP_012443"
FT VAR_SEQ 67
FT /note="E -> ETNKPQRSRPNLIKPAAQWQDLKRLGEERPKKSRAAFESDKSSYFSV
FT CNNPLFDSGAQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15107846"
FT /id="VSP_012444"
FT VARIANT 660
FT /note="R -> C (in GDHS; dbSNP:rs1335215379)"
FT /evidence="ECO:0000269|PubMed:23656588"
FT /id="VAR_070048"
FT VARIANT 694
FT /note="R -> C (in GDHS; dbSNP:rs387907368)"
FT /evidence="ECO:0000269|PubMed:23656588"
FT /id="VAR_070049"
FT CONFLICT 408
FT /note="L -> F (in Ref. 1; AAL38043)"
FT /evidence="ECO:0000305"
FT STRAND 601..604
FT /evidence="ECO:0007829|PDB:7M4M"
FT TURN 606..608
FT /evidence="ECO:0007829|PDB:7M4M"
FT STRAND 611..614
FT /evidence="ECO:0007829|PDB:7M4M"
FT STRAND 620..622
FT /evidence="ECO:0007829|PDB:7M4M"
FT TURN 626..628
FT /evidence="ECO:0007829|PDB:7M4M"
FT STRAND 631..636
FT /evidence="ECO:0007829|PDB:7M4M"
FT HELIX 641..643
FT /evidence="ECO:0007829|PDB:7M4M"
FT HELIX 653..671
FT /evidence="ECO:0007829|PDB:7M4O"
FT TURN 676..678
FT /evidence="ECO:0007829|PDB:7M4O"
FT STRAND 681..687
FT /evidence="ECO:0007829|PDB:7M4O"
FT STRAND 689..692
FT /evidence="ECO:0007829|PDB:7M4O"
FT STRAND 698..700
FT /evidence="ECO:0007829|PDB:7M4O"
FT TURN 701..703
FT /evidence="ECO:0007829|PDB:7M4O"
FT STRAND 706..709
FT /evidence="ECO:0007829|PDB:7M4O"
FT HELIX 710..712
FT /evidence="ECO:0007829|PDB:7M4O"
FT STRAND 730..733
FT /evidence="ECO:0007829|PDB:7M4O"
FT HELIX 737..758
FT /evidence="ECO:0007829|PDB:7M4O"
FT STRAND 760..762
FT /evidence="ECO:0007829|PDB:7M4M"
FT CROSSLNK Q9NWF9-1:80
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK Q9NWF9-1:89
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
SQ SEQUENCE 866 AA; 99406 MW; 6A46B66A6569DE74 CRC64;
MEEGNNNEEV IHLNNFHCHR GQEWINLRDG PITISDSSDE ERIPMLVTPA PQQHEEEDLD
DDVILTEDDS EDDYGEFLDL GPPGISEFTK PSGQTEREPK PGPSHNQAAN DIVNPRSEQK
VIILEEGSLL YTESDPLETQ NQSSEDSETE LLSNLGESAA LADDQAIEED CWLDHPYFQS
LNQQPREITN QVVPQERQPE AELGRLLFQH EFPGPAFPRP EPQQGGISGP SSPQPAHPLG
EFEDQQLASD DEEPGPAFPM QESQEPNLEN IWGQEAAEVD QELVELLVKE TEARFPDVAN
GFIEEIIHFK NYYDLNVLCN FLLENPDYPK REDRIIINPS SSLLASQDET KLPKIDFFDY
SKLTPLDQRC FIQAADLLMA DFKVLSSQDI KWALHELKGH YAITRKALSD AIKKWQELSP
ETSGKRKKRK QMNQYSYIDF KFEQGDIKIE KRMFFLENKR RHCRSYDRRA LLPAVQQEQE
FYEQKIKEMA EHEDFLLALQ MNEEQYQKDG QLIECRCCYG EFPFEELTQC ADAHLFCKEC
LIRYAQEAVF GSGKLELSCM EGSCTCSFPT SELEKVLPQT ILYKYYERKA EEEVAAAYAD
ELVRCPSCSF PALLDSDVKR FSCPNPHCRK ETCRKCQGLW KEHNGLTCEE LAEKDDIKYR
TSIEEKMTAA RIRKCHKCGT GLIKSEGCNR MSCRCGAQMC YLCRVSINGY DHFCQHPRSP
GAPCQECSRC SLWTDPTEDD EKLIEEIQKE AEEEQKRKNG ENTFKRIGPP LEKPVEKVQR
VEALPRPVPQ NLPQPQMPPY AFAHPPFPLP PVRPVFNNFP LNMGPIPAPY VPPLPNVRVN
YDFGPIHMPL EHNLPMHFGP QPRHRF
