ID RN213_HUMAN Reviewed; 5207 AA. AC Q63HN8; C9JCP4; D6RI12; F8WKS1; Q658P6; Q69YK7; Q6MZR1; Q8IWF4; Q8IZX1; AC Q8IZX2; Q8N406; Q8TEU0; Q9H6C9; Q9H6H9; Q9H6P3; Q9H8A9; Q9HCF4; Q9HCL8; DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot. DT 21-MAR-2012, sequence version 3. DT 27-MAR-2024, entry version 174. DE RecName: Full=E3 ubiquitin-protein ligase RNF213 {ECO:0000305}; DE EC=2.3.2.27 {ECO:0000269|PubMed:21799892, ECO:0000269|PubMed:32139119, ECO:0000269|PubMed:33842849}; DE EC=3.6.4.- {ECO:0000269|PubMed:21799892, ECO:0000305|PubMed:24658080, ECO:0000305|PubMed:26126547}; DE AltName: Full=ALK lymphoma oligomerization partner on chromosome 17 {ECO:0000303|PubMed:12112524}; DE AltName: Full=E3 ubiquitin-lipopolysaccharide ligase RNF213 {ECO:0000305}; DE EC=2.3.2.- {ECO:0000269|PubMed:34012115}; DE AltName: Full=Mysterin {ECO:0000303|PubMed:26126547}; DE AltName: Full=RING finger protein 213 {ECO:0000305}; GN Name=RNF213 {ECO:0000312|HGNC:HGNC:14539}; GN Synonyms=ALO17 {ECO:0000303|PubMed:12112524}, C17orf27 GN {ECO:0000312|HGNC:HGNC:14539}, KIAA1554 {ECO:0000303|PubMed:10997877}, GN KIAA1618 {ECO:0000303|PubMed:10997877}, MYSTR GN {ECO:0000303|PubMed:26126547}; 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 1), FUNCTION, CATALYTIC ACTIVITY, RP AUTOUBIQUITINATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS RP ASP-3962; GLN-4062; SER-4608; ASN-4863; ASP-4950; VAL-5021; GLU-5160 AND RP GLY-5176, AND VARIANTS MYMY2 ASN-4013 AND LYS-4810. RX PubMed=21799892; DOI=10.1371/journal.pone.0022542; RA Liu W., Morito D., Takashima S., Mineharu Y., Kobayashi H., Hitomi T., RA Hashikata H., Matsuura N., Yamazaki S., Toyoda A., Kikuta K., Takagi Y., RA Harada K.H., Fujiyama A., Herzig R., Krischek B., Zou L., Kim J.E., RA Kitakaze M., Miyamoto S., Nagata K., Hashimoto N., Koizumi A.; RT "Identification of RNF213 as a susceptibility gene for moyamoya disease and RT its possible role in vascular development."; RL PLoS ONE 6:E22542-E22542(2011). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 3021-5207 (ISOFORMS 1/2). RC TISSUE=Endometrium, Lymph node, Melanoma, and Uterus; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4). RC TISSUE=Eye, and Lung; 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-163 (ISOFORMS 1 AND 2/3), AND CHROMOSOMAL RP TRANSLOCATION WITH ALK. RX PubMed=12112524; DOI=10.1002/gcc.10033; RA Cools J., Wlodarska I., Somers R., Mentens N., Pedeutour F., Maes B., RA De Wolf-Peeters C., Pauwels P., Hagemeijer A., Marynen P.; RT "Identification of novel fusion partners of ALK, the anaplastic lymphoma RT kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic RT tumor."; RL Genes Chromosomes Cancer 34:354-362(2002). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 136-1509 AND 3888-5207 (ISOFORMS RP 1/2). RC TISSUE=Brain; RX PubMed=10997877; DOI=10.1093/dnares/7.4.271; RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVIII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:273-281(2000). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3770-5207 (ISOFORMS 1/2). RC TISSUE=Spleen, and Thyroid; 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 [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1258, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1258, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1258, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1258, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1258, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [13] RP INTERACTION WITH M.TUBERCULOSIS RV3655C (MICROBIAL INFECTION), AND RP INDUCTION (MICROBIAL INFECTION). RX PubMed=20454556; DOI=10.1371/journal.pone.0010474; RA Danelishvili L., Yamazaki Y., Selker J., Bermudez L.E.; RT "Secreted Mycobacterium tuberculosis Rv3654c and Rv3655c proteins RT participate in the suppression of macrophage apoptosis."; RL PLoS ONE 5:E10474-E10474(2010). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-217 AND SER-1258, AND RP IDENTIFICATION BY 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 [15] 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1258, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-217; SER-1258 AND SER-2273, RP AND IDENTIFICATION BY 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-208; SER-217 AND SER-1258, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [19] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1151, AND IDENTIFICATION BY MASS RP 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 [20] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-2426; GLU-2488; RP LYS-2775 AND GLU-2845. RX PubMed=24658080; DOI=10.1038/srep04442; RA Morito D., Nishikawa K., Hoseki J., Kitamura A., Kotani Y., Kiso K., RA Kinjo M., Fujiyoshi Y., Nagata K.; RT "Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ RT ATPase, which dynamically changes its oligomeric state."; RL Sci. Rep. 4:4442-4442(2014). RN [21] RP INDUCTION. RX PubMed=26070522; DOI=10.1016/j.jstrokecerebrovasdis.2015.01.041; RA Zhao S., Gong Z., Zhang J., Xu X., Liu P., Guan W., Jing L., Peng T., RA Teng J., Jia Y.; RT "Elevated serum microRNA Let-7c in Moyamoya disease."; RL J. Stroke Cerebrovasc. Dis. 24:1709-1714(2015). RN [22] RP FUNCTION, AND INDUCTION. RX PubMed=26278786; DOI=10.1038/srep13191; RA Ohkubo K., Sakai Y., Inoue H., Akamine S., Ishizaki Y., Matsushita Y., RA Sanefuji M., Torisu H., Ihara K., Sardiello M., Hara T.; RT "Moyamoya disease susceptibility gene RNF213 links inflammatory and RT angiogenic signals in endothelial cells."; RL Sci. Rep. 5:13191-13191(2015). RN [23] RP FUNCTION. RX PubMed=26766444; DOI=10.1016/j.devcel.2015.12.015; RA Scholz B., Korn C., Wojtarowicz J., Mogler C., Augustin I., Boutros M., RA Niehrs C., Augustin H.G.; RT "Endothelial RSPO3 controls vascular stability and pruning through non- RT canonical WNT/Ca(2+)/NFAT signaling."; RL Dev. Cell 36:79-93(2016). RN [24] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-2426; GLU-2488; RP LYS-2775 AND GLU-2845. RX PubMed=30705059; DOI=10.1083/jcb.201712120; RA Sugihara M., Morito D., Ainuki S., Hirano Y., Ogino K., Kitamura A., RA Hirata H., Nagata K.; RT "The AAA+ ATPase/ubiquitin ligase mysterin stabilizes cytoplasmic lipid RT droplets."; RL J. Cell Biol. 218:949-960(2019). RN [25] RP FUNCTION. RX PubMed=30846318; DOI=10.1016/j.molcel.2019.01.036; RA Piccolis M., Bond L.M., Kampmann M., Pulimeno P., Chitraju C., RA Jayson C.B.K., Vaites L.P., Boland S., Lai Z.W., Gabriel K.R., RA Elliott S.D., Paulo J.A., Harper J.W., Weissman J.S., Walther T.C., RA Farese R.V. Jr.; RT "Probing the global cellular responses to lipotoxicity caused by saturated RT fatty acids."; RL Mol. Cell 74:32-44(2019). RN [26] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH UBE2N, RP CHARACTERIZATION OF VARIANTS TYR-3997; ARG-4007; ASN-4014; SER-4017; RP CYS-4019; ARG-4024; ARG-4032 AND LEU-4033, AND VARIANT MYMY2 ASN-4013. RX PubMed=32139119; DOI=10.1016/j.bbrc.2020.02.024; RA Takeda M., Tezuka T., Kim M., Choi J., Oichi Y., Kobayashi H., Harada K.H., RA Mizushima T., Taketani S., Koizumi A., Youssefian S.; RT "Moyamoya disease patient mutations in the RING domain of RNF213 reduce its RT ubiquitin ligase activity and enhance NFkappaB activation and apoptosis in RT an AAA+ domain-dependent manner."; RL Biochem. Biophys. Res. Commun. 525:668-674(2020). RN [27] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND INTERACTION WITH UBE2N. RX PubMed=33842849; DOI=10.1096/fba.2019-00092; RA Habu T., Harada K.H.; RT "UBC13 is an RNF213-associated E2 ubiquitin-conjugating enzyme, and Lysine RT 63-linked ubiquitination by the RNF213-UBC13 axis is responsible for RT angiogenic activity."; RL FASEB Bioadv. 3:243-258(2021). RN [28] RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, CHARACTERIZATION OF VARIANTS RP ILE-4638; ASP-4950 AND VAL-5021, CHARACTERIZATION OF VARIANT MYMY2 RP LYS-4810, AND MUTAGENESIS OF LYS-2426; GLU-2488; LYS-2775; GLU-2845; RP HIS-4014; TRP-4024 AND HIS-4509. RX PubMed=34012115; DOI=10.1038/s41586-021-03566-4; RA Otten E.G., Werner E., Crespillo-Casado A., Boyle K.B., Dharamdasani V., RA Pathe C., Santhanam B., Randow F.; RT "Ubiquitylation of lipopolysaccharide by RNF213 during bacterial RT infection."; RL Nature 594:111-116(2021). RN [29] RP VARIANTS GLU-2554; VAL-3891; GLY-3915; MET-4567 AND MET-4765, AND VARIANTS RP MYMY2 THR-4399 AND LYS-4810. RX PubMed=21048783; DOI=10.1038/jhg.2010.132; RA Kamada F., Aoki Y., Narisawa A., Abe Y., Komatsuzaki S., Kikuchi A., RA Kanno J., Niihori T., Ono M., Ishii N., Owada Y., Fujimura M., Mashimo Y., RA Suzuki Y., Hata A., Tsuchiya S., Tominaga T., Matsubara Y., Kure S.; RT "A genome-wide association study identifies RNF213 as the first Moyamoya RT disease gene."; RL J. Hum. Genet. 56:34-40(2011). RN [30] RP VARIANT MYMY2 LYS-4810. RX PubMed=22931863; DOI=10.1038/jhg.2012.105; RA Miyatake S., Touho H., Miyake N., Ohba C., Doi H., Saitsu H., Taguri M., RA Morita S., Matsumoto N.; RT "Sibling cases of moyamoya disease having homozygous and heterozygous RT c.14576G>A variant in RNF213 showed varying clinical course and severity."; RL J. Hum. Genet. 57:804-806(2012). RN [31] RP VARIANT MYMY2 LYS-4810. RX PubMed=22688072; DOI=10.2176/nmc.52.339; RA Shimoda Y., Fujimura M., Inoue T., Shimizu H., Tominaga T.; RT "Temporal profile of de novo development of moyamoya vasculopathy in an RT adult: case report."; RL Neurol. Med. Chir. 52:339-342(2012). RN [32] RP VARIANT MYMY2 LYS-4810. RX PubMed=22377813; DOI=10.1212/wnl.0b013e318249f71f; RA Miyatake S., Miyake N., Touho H., Nishimura-Tadaki A., Kondo Y., Okada I., RA Tsurusaki Y., Doi H., Sakai H., Saitsu H., Shimojima K., Yamamoto T., RA Higurashi M., Kawahara N., Kawauchi H., Nagasaka K., Okamoto N., Mori T., RA Koyano S., Kuroiwa Y., Taguri M., Morita S., Matsubara Y., Kure S., RA Matsumoto N.; RT "Homozygous c.14576G>A variant of RNF213 predicts early-onset and severe RT form of moyamoya disease."; RL Neurology 78:803-810(2012). RN [33] RP VARIANTS MYMY2 THR-4399 AND LYS-4810, AND VARIANTS ARG-4007; LEU-4367; RP PRO-4586; VAL-4631; ASP-4950; VAL-5021 AND ILE-5136. RX PubMed=23110205; DOI=10.1371/journal.pone.0048179; RA Wu Z., Jiang H., Zhang L., Xu X., Zhang X., Kang Z., Song D., Zhang J., RA Guan M., Gu Y.; RT "Molecular analysis of RNF213 gene for moyamoya disease in the Chinese Han RT population."; RL PLoS ONE 7:E48179-E48179(2012). RN [34] RP CHARACTERIZATION OF VARIANT MYMY2 LYS-4810. RX PubMed=23994138; DOI=10.1016/j.bbrc.2013.08.067; RA Hitomi T., Habu T., Kobayashi H., Okuda H., Harada K.H., Osafune K., RA Taura D., Sone M., Asaka I., Ameku T., Watanabe A., Kasahara T., Sudo T., RA Shiota F., Hashikata H., Takagi Y., Morito D., Miyamoto S., Nakao K., RA Koizumi A.; RT "The moyamoya disease susceptibility variant RNF213 R4810K (rs112735431) RT induces genomic instability by mitotic abnormality."; RL Biochem. Biophys. Res. Commun. 439:419-426(2013). RN [35] RP VARIANT THR-4185. RX PubMed=25043520; DOI=10.1111/ijs.12306; RA Smith K.R., Leventer R.J., Mackay M.T., Pope K., Gillies G., RA Delatycki M.B., Amor D.J., Bahlo M., Lockhart P.J.; RT "Identification of a novel RNF213 variant in a family with heterogeneous RT intracerebral vasculopathy."; RL Int. J. Stroke 9:E26-E27(2014). RN [36] RP VARIANTS MYMY2 ASN-4013 AND LYS-4810, AND VARIANTS ALA-529 DEL; GLN-3922; RP TYR-3997; CYS-4019; VAL-4076; LYS-4115 DEL; GLU-4237; THR-4732 AND RP ILE-5163. RX PubMed=25278557; DOI=10.1161/strokeaha.114.006244; RG University of Washington Center for Mendelian Genomics; RA Cecchi A.C., Guo D., Ren Z., Flynn K., Santos-Cortez R.L., Leal S.M., RA Wang G.T., Regalado E.S., Steinberg G.K., Shendure J., Bamshad M.J., RA Grotta J.C., Nickerson D.A., Pannu H., Milewicz D.M.; RT "RNF213 rare variants in an ethnically diverse population with Moyamoya RT disease."; RL Stroke 45:3200-3207(2014). RN [37] RP VARIANT PHE-4118, AND INVOLVEMENT IN MYMY2. RX PubMed=26198278; DOI=10.1002/ajmg.a.37230; RA Harel T., Posey J.E., Graham B.H., Walkiewicz M., Yang Y., Lalani S.R., RA Belmont J.W.; RT "Atypical presentation of moyamoya disease in an infant with a de novo RT RNF213 variant."; RL Am. J. Med. Genet. A 167A:2742-2747(2015). RN [38] RP CHARACTERIZATION OF VARIANT MYMY2 LYS-4810, FUNCTION, CATALYTIC ACTIVITY, RP AND MUTAGENESIS OF GLU-2488. RX PubMed=26126547; DOI=10.1161/jaha.115.002146; RA Kobayashi H., Matsuda Y., Hitomi T., Okuda H., Shioi H., Matsuda T., RA Imai H., Sone M., Taura D., Harada K.H., Habu T., Takagi Y., Miyamoto S., RA Koizumi A.; RT "Biochemical and functional characterization of RNF213 (Mysterin) R4810K, a RT susceptibility mutation of Moyamoya disease, in angiogenesis in vitro and RT in vivo."; RL J. Am. Heart Assoc. 4:0-0(2015). RN [39] RP VARIANTS VAL-1622; MET-3933 AND CYS-4131, AND VARIANT MYMY2 LYS-4810. RX PubMed=25956231; DOI=10.1016/j.jns.2015.04.019; RA Lee M.J., Chen Y.F., Fan P.C., Wang K.C., Wang K., Wang J., Kuo M.F.; RT "Mutation genotypes of RNF213 gene from moyamoya patients in Taiwan."; RL J. Neurol. Sci. 353:161-165(2015). RN [40] RP VARIANTS CYS-4019; LYS-4042; ALA-4146 AND LEU-4677, CHARACTERIZATION OF RP VARIANT MYMY2 ASN-4013, AND CHARACTERIZATION OF VARIANTS CYS-4019 AND RP ALA-4146. RX PubMed=27736983; DOI=10.1371/journal.pone.0164759; RA Kobayashi H., Brozman M., Kyselova K., Viszlayova D., Morimoto T., RA Roubec M., Skoloudik D., Petrovicova A., Juskanic D., Strauss J., Halaj M., RA Kurray P., Hranai M., Harada K.H., Inoue S., Yoshida Y., Habu T., RA Herzig R., Youssefian S., Koizumi A.; RT "RNF213 rare variants in Slovakian and Czech moyamoya disease patients."; RL PLoS ONE 11:E0164759-E0164759(2016). RN [41] RP VARIANTS ARG-118; MET-133; ASN-209; LEU-395; VAL-1135; LYS-1705; LEU-1721; RP THR-1844; HIS-3846; THR-3927; MET-3933; ASN-4014; CYS-4019; ARG-4032; RP LEU-4033; LYS-4042; PRO-4051; GLN-4062; VAL-4122; SER-4608 AND SER-4640, RP AND VARIANTS MYMY2 ASN-4013 AND THR-4399. RX PubMed=28635953; DOI=10.1038/ejhg.2017.92; RG FREX consortium; RA Guey S., Kraemer M., Herve D., Ludwig T., Kossorotoff M., Bergametti F., RA Schwitalla J.C., Choi S., Broseus L., Callebaut I., Genin E., RA Tournier-Lasserve E.; RT "Rare RNF213 variants in the C-terminal region encompassing the RING-finger RT domain are associated with moyamoya angiopathy in Caucasians."; RL Eur. J. Hum. Genet. 25:995-1003(2017). RN [42] RP VARIANTS LYS-996; PRO-4058 AND GLN-4062, AND INVOLVEMENT IN MYMY2. RX PubMed=29387438; DOI=10.1038/hgv.2017.60; RA Akagawa H., Mukawa M., Nariai T., Nomura S., Aihara Y., Onda H., RA Yoneyama T., Kudo T., Sumita K., Maehara T., Kawamata T., Kasuya H.; RT "Novel and recurrent RNF213 variants in Japanese pediatric patients with RT moyamoya disease."; RL Hum. Genome Var. 5:17060-17060(2018). RN [43] RP VARIANTS GLU-4185 AND THR-4188, AND INVOLVEMENT IN MYMY2. RX PubMed=31645973; DOI=10.1038/s41439-019-0066-6; RA Gagunashvili A.N., Ocaka L., Kelberman D., Munot P., Bacchelli C., RA Beales P.L., Ganesan V.; RT "Novel missense variants in the RNF213 gene from a European family with RT Moyamoya disease."; RL Hum. Genome Var. 6:35-35(2019). RN [44] RP VARIANTS SER-4017 AND LEU-4677, AND INVOLVEMENT IN MYMY2. RX PubMed=27787485; DOI=10.23736/s0390-5616.16.03900-x; RA Raso A., Biassoni R., Mascelli S., Nozza P., Ugolotti E., Di Marco E., RA De Marco P., Merello E., Cama A., Pavanello M., Capra V.; RT "Moyamoya vasculopathy shows a genetic mutational gradient decreasing from RT East to West."; RL J. Neurosurg. Sci. 64:165-172(2020). RN [45] RP VARIANTS 3996-PRO-CYS-3997 DELINS GLY-LEU-GLY; ARG-4114 AND LEU-4120, AND RP INVOLVEMENT IN MYMY2. RX PubMed=33568546; DOI=10.1212/wnl.0000000000011653; RA Pinard A., Fiander M.D.J., Cecchi A.C., Rideout A.L., Azouz M., RA Fraser S.M., McNeely P.D., Walling S., Novara S.C., Hurst A.C.E., Guo D., RA Parkash S., Bamshad M.J., Nickerson D.A., Vandersteen A.M., Milewicz D.M.; RT "Association of de novo RNF213 variants with childhood onset Moyamoya RT disease and diffuse occlusive vasculopathy."; RL Neurology 96:e1783-e1791(2021). CC -!- FUNCTION: Atypical E3 ubiquitin ligase that can catalyze ubiquitination CC of both proteins and lipids, and which is involved in various CC processes, such as lipid metabolism, angiogenesis and cell-autonomous CC immunity (PubMed:21799892, PubMed:26126547, PubMed:26278786, CC PubMed:26766444, PubMed:30705059, PubMed:32139119, PubMed:34012115). CC Acts as a key immune sensor by catalyzing ubiquitination of the lipid A CC moiety of bacterial lipopolysaccharide (LPS) via its RZ-type zinc- CC finger: restricts the proliferation of cytosolic bacteria, such as CC Salmonella, by generating the bacterial ubiquitin coat through the CC ubiquitination of LPS (PubMed:34012115). Also acts indirectly by CC mediating the recruitment of the LUBAC complex, which conjugates linear CC polyubiquitin chains (PubMed:34012115). Ubiquitination of LPS triggers CC cell-autonomous immunity, such as antibacterial autophagy, leading to CC degradation of the microbial invader (PubMed:34012115). Involved in CC lipid metabolism by regulating fat storage and lipid droplet formation; CC act by inhibiting the lipolytic process (PubMed:30705059). Also CC regulates lipotoxicity by inhibiting desaturation of fatty acids CC (PubMed:30846318). Also acts as an E3 ubiquitin-protein ligase via its CC RING-type zinc finger: mediates 'Lys-63'-linked ubiquitination of CC target proteins (PubMed:32139119, PubMed:33842849). Involved in the CC non-canonical Wnt signaling pathway in vascular development: acts by CC mediating ubiquitination and degradation of FLNA and NFATC2 downstream CC of RSPO3, leading to inhibit the non-canonical Wnt signaling pathway CC and promoting vessel regression (PubMed:26766444). Also has ATPase CC activity; ATPase activity is required for ubiquitination of LPS CC (PubMed:34012115). {ECO:0000269|PubMed:21799892, CC ECO:0000269|PubMed:26126547, ECO:0000269|PubMed:26278786, CC ECO:0000269|PubMed:26766444, ECO:0000269|PubMed:30705059, CC ECO:0000269|PubMed:30846318, ECO:0000269|PubMed:32139119, CC ECO:0000269|PubMed:33842849, ECO:0000269|PubMed:34012115}. 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:21799892, CC ECO:0000269|PubMed:32139119, ECO:0000269|PubMed:33842849}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; CC Evidence={ECO:0000269|PubMed:21799892, ECO:0000305|PubMed:24658080, CC ECO:0000305|PubMed:26126547}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000269|PubMed:21799892, ECO:0000305|PubMed:24658080, CC ECO:0000305|PubMed:26126547}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:32139119, ECO:0000269|PubMed:33842849, CC ECO:0000305|PubMed:21799892}. CC -!- SUBUNIT: Monomer (By similarity). Interacts with UBE2L3/UBCH7; CC UBE2L3/UBCH7 is the most efficient ubiquitin-conjugating enzyme E2 for CC the ubiquitin ligase activity (By similarity). Interacts with CC UBE2N/UBC13; promoting 'Lys-63'-linked ubiquitination of target CC proteins (PubMed:32139119, PubMed:33842849). CC {ECO:0000250|UniProtKB:E9Q555, ECO:0000269|PubMed:32139119, CC ECO:0000269|PubMed:33842849}. CC -!- SUBUNIT: (Microbial infection) Interacts with M.tuberculosis protein CC Rv3655c, which impairs caspase-8 activation and suppresses macrophage CC apoptosis by blocking the extrinsic pathway. CC {ECO:0000269|PubMed:20454556}. CC -!- INTERACTION: CC Q63HN8-6; Q08379: GOLGA2; NbExp=3; IntAct=EBI-10248548, EBI-618309; CC Q63HN8-6; Q6A162: KRT40; NbExp=3; IntAct=EBI-10248548, EBI-10171697; CC Q63HN8-6; Q04864: REL; NbExp=3; IntAct=EBI-10248548, EBI-307352; CC Q63HN8-6; P36406: TRIM23; NbExp=3; IntAct=EBI-10248548, EBI-740098; CC Q63HN8-6; P14373: TRIM27; NbExp=3; IntAct=EBI-10248548, EBI-719493; CC Q63HN8-6; Q15654: TRIP6; NbExp=3; IntAct=EBI-10248548, EBI-742327; CC Q63HN8-6; Q5T124: UBXN11; NbExp=3; IntAct=EBI-10248548, EBI-746004; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:21799892, CC ECO:0000269|PubMed:30705059, ECO:0000269|PubMed:34012115}. Lipid CC droplet {ECO:0000269|PubMed:30705059}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q63HN8-3; Sequence=Displayed; CC Name=2; CC IsoId=Q63HN8-4; Sequence=VSP_042417; CC Name=3; CC IsoId=Q63HN8-5; Sequence=VSP_042418, VSP_042419; CC Name=4; CC IsoId=Q63HN8-6; Sequence=VSP_042416, VSP_042420; CC -!- TISSUE SPECIFICITY: Widely expressed (at protein level). CC {ECO:0000269|PubMed:21799892}. CC -!- TISSUE SPECIFICITY: [Isoform 1]: Major isoform detected in all tissues CC examined. {ECO:0000269|PubMed:21799892}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: Minor isoform with restricted CC expression. {ECO:0000269|PubMed:21799892}. CC -!- INDUCTION: Down-regulated by let-7c miRNA, which binds to the 3'-UTR CC transcript of RNF213 (PubMed:26070522). Induced by pro-inflammatory CC cytokines (PubMed:26278786). {ECO:0000269|PubMed:26070522, CC ECO:0000269|PubMed:26278786}. CC -!- INDUCTION: (Microbial infection) Up-regulated in macrophages infected CC by M.tuberculosis. {ECO:0000269|PubMed:20454556}. CC -!- DOMAIN: Composed of an N-terminal stalk, a dynein-like core comprised CC of two catalytically active and four inactive ATPase domains, and a C- CC terminal E3 module. The ATPase regions do not generate movement but CC rather act like an intricate molecular 'switch'. CC {ECO:0000250|UniProtKB:E9Q555}. CC -!- DOMAIN: The RING-type zinc finger domain is required for the ubiquitin- CC protein ligase activity. {ECO:0000269|PubMed:21799892}. CC -!- DOMAIN: The RZ-type (RNF213-ZNFX1) zinc-finger is required for the CC ubiquitination of the lipid A moiety of bacterial lipopolysaccharide CC (LPS). {ECO:0000269|PubMed:34012115}. CC -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:21799892}. CC -!- DISEASE: Moyamoya disease 2 (MYMY2) [MIM:607151]: A progressive CC cerebral angiopathy characterized by bilateral intracranial carotid CC artery stenosis and telangiectatic vessels in the region of the basal CC ganglia. The abnormal vessels resemble a 'puff of smoke' (moyamoya) on CC cerebral angiogram. Affected individuals can develop transient ischemic CC attacks and/or cerebral infarction, and rupture of the collateral CC vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset CC and epileptic seizures constitute the prevailing presentation in CC childhood, while subarachnoid bleeding occurs more frequently in CC adults. {ECO:0000269|PubMed:21048783, ECO:0000269|PubMed:21799892, CC ECO:0000269|PubMed:22377813, ECO:0000269|PubMed:22688072, CC ECO:0000269|PubMed:22931863, ECO:0000269|PubMed:23110205, CC ECO:0000269|PubMed:23994138, ECO:0000269|PubMed:25278557, CC ECO:0000269|PubMed:25956231, ECO:0000269|PubMed:26126547, CC ECO:0000269|PubMed:26198278, ECO:0000269|PubMed:27736983, CC ECO:0000269|PubMed:27787485, ECO:0000269|PubMed:28635953, CC ECO:0000269|PubMed:29387438, ECO:0000269|PubMed:31645973, CC ECO:0000269|PubMed:32139119, ECO:0000269|PubMed:33568546, CC ECO:0000269|PubMed:34012115}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- DISEASE: Note=A chromosomal aberration involving RNF213 is associated CC with anaplastic large-cell lymphoma (ALCL). Translocation CC t(2;17)(p23;q25) with ALK. {ECO:0000269|PubMed:12112524}. CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000305}. CC -!- CAUTION: The stoichiometry is unclear: was initially thought to form CC homohexamers (PubMed:24658080, PubMed:26126547). However, the electron CC microscopy structure showed that it is monomeric and is composed of six CC ATPase modules within a single polypeptide chain (By similarity). CC {ECO:0000250|UniProtKB:E9Q555, ECO:0000269|PubMed:24658080, CC ECO:0000269|PubMed:26126547}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH32220.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB13444.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC Sequence=BAB14708.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB15212.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB15280.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB15330.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAH10615.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=CAH56189.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/480/ALO17"; 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; AB537889; BAK53191.1; -; mRNA. DR EMBL; AL832920; CAH10615.1; ALT_FRAME; mRNA. DR EMBL; AL833201; CAH56308.1; -; mRNA. DR EMBL; BX640932; CAE45967.1; -; mRNA. DR EMBL; BX647946; CAH56189.1; ALT_INIT; mRNA. DR EMBL; AC123764; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC124319; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC032220; AAH32220.1; ALT_INIT; mRNA. DR EMBL; BC036891; AAH36891.1; -; mRNA. DR EMBL; BC040341; AAH40341.1; -; mRNA. DR EMBL; AF397204; AAN63520.1; -; mRNA. DR EMBL; AF397205; AAN63521.1; -; mRNA. DR EMBL; AB046774; BAB13380.1; -; mRNA. DR EMBL; AB046838; BAB13444.1; ALT_SEQ; mRNA. DR EMBL; AK023871; BAB14708.1; ALT_INIT; mRNA. DR EMBL; AK025676; BAB15212.1; ALT_INIT; mRNA. DR EMBL; AK025914; BAB15280.1; ALT_SEQ; mRNA. DR EMBL; AK026038; BAB15330.1; ALT_INIT; mRNA. DR EMBL; AK074030; BAB84856.1; -; mRNA. DR CCDS; CCDS11772.1; -. [Q63HN8-5] DR CCDS; CCDS32761.2; -. [Q63HN8-4] DR CCDS; CCDS58606.1; -. [Q63HN8-3] DR RefSeq; NP_001243000.2; NM_001256071.2. DR RefSeq; NP_066005.2; NM_020954.3. [Q63HN8-5] DR SMR; Q63HN8; -. DR BioGRID; 121705; 178. DR IntAct; Q63HN8; 50. DR MINT; Q63HN8; -. DR STRING; 9606.ENSP00000464087; -. DR GlyCosmos; Q63HN8; 5 sites, 2 glycans. DR GlyGen; Q63HN8; 5 sites, 2 O-linked glycans (5 sites). DR iPTMnet; Q63HN8; -. DR MetOSite; Q63HN8; -. DR PhosphoSitePlus; Q63HN8; -. DR SwissPalm; Q63HN8; -. DR BioMuta; RNF213; -. DR DMDM; 380865458; -. DR EPD; Q63HN8; -. DR jPOST; Q63HN8; -. DR MassIVE; Q63HN8; -. DR MaxQB; Q63HN8; -. DR PaxDb; 9606-ENSP00000464087; -. DR PeptideAtlas; Q63HN8; -. DR ProteomicsDB; 65884; -. [Q63HN8-3] DR ProteomicsDB; 65885; -. [Q63HN8-4] DR ProteomicsDB; 65886; -. [Q63HN8-5] DR ProteomicsDB; 65887; -. [Q63HN8-6] DR Pumba; Q63HN8; -. DR Antibodypedia; 46314; 210 antibodies from 27 providers. DR DNASU; 57674; -. DR Ensembl; ENST00000319921.4; ENSP00000324392.4; ENSG00000173821.20. [Q63HN8-5] DR GeneID; 57674; -. DR KEGG; hsa:57674; -. DR UCSC; uc002jyf.5; human. [Q63HN8-3] DR AGR; HGNC:14539; -. DR CTD; 57674; -. DR DisGeNET; 57674; -. DR GeneCards; RNF213; -. DR HGNC; HGNC:14539; RNF213. DR HPA; ENSG00000173821; Low tissue specificity. DR MalaCards; RNF213; -. DR MIM; 607151; phenotype. DR MIM; 613768; gene. DR neXtProt; NX_Q63HN8; -. DR OpenTargets; ENSG00000173821; -. DR Orphanet; 2573; Moyamoya disease. DR PharmGKB; PA162401681; -. DR VEuPathDB; HostDB:ENSG00000173821; -. DR eggNOG; ENOG502QQ65; Eukaryota. DR GeneTree; ENSGT00630000089884; -. DR HOGENOM; CLU_011233_0_0_1; -. DR InParanoid; Q63HN8; -. DR OrthoDB; 116673at2759; -. DR TreeFam; TF343131; -. DR PathwayCommons; Q63HN8; -. DR Reactome; R-HSA-9635465; Suppression of apoptosis. DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q63HN8; -. DR SIGNOR; Q63HN8; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 57674; 15 hits in 1195 CRISPR screens. DR ChiTaRS; RNF213; human. DR GeneWiki; RNF213; -. DR GenomeRNAi; 57674; -. DR Pharos; Q63HN8; Tbio. DR PRO; PR:Q63HN8; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q63HN8; Protein. DR Bgee; ENSG00000173821; Expressed in granulocyte and 176 other cell types or tissues. DR ExpressionAtlas; Q63HN8; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB. DR GO; GO:0042742; P:defense response to bacterium; IDA:UniProtKB. DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW. DR GO; GO:0140042; P:lipid droplet formation; IDA:UniProtKB. DR GO; GO:0120323; P:lipid ubiquitination; IDA:UniProtKB. DR GO; GO:2000051; P:negative regulation of non-canonical Wnt signaling pathway; IMP:UniProtKB. DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB. DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0019216; P:regulation of lipid metabolic process; IDA:UniProtKB. DR GO; GO:0002040; P:sprouting angiogenesis; IMP:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0098792; P:xenophagy; IDA:UniProtKB. DR CDD; cd16561; RING-HC_RNF213; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR031248; RNF213. DR InterPro; IPR046439; ZF_RZ_dom. DR InterPro; IPR018957; Znf_C3HC4_RING-type. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR22605:SF16; E3 UBIQUITIN-PROTEIN LIGASE RNF213; 1. DR PANTHER; PTHR22605; UNCHARACTERIZED; 1. DR Pfam; PF00097; zf-C3HC4; 1. DR Pfam; PF20173; ZnF_RZ-type; 1. DR SMART; SM00382; AAA; 2. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR PROSITE; PS51981; ZF_RZ; 1. DR Genevisible; Q63HN8; HS. PE 1: Evidence at protein level; KW Alternative splicing; Angiogenesis; ATP-binding; Chromosomal rearrangement; KW Coiled coil; Cytoplasm; Disease variant; Hydrolase; Immunity; KW Isopeptide bond; Lipid droplet; Lipid metabolism; Metal-binding; KW Multifunctional enzyme; Nucleotide-binding; Phosphoprotein; Proto-oncogene; KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway; KW Zinc; Zinc-finger. FT CHAIN 1..5207 FT /note="E3 ubiquitin-protein ligase RNF213" FT /id="PRO_0000415917" FT ZN_FING 3997..4036 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT ZN_FING 4483..4555 FT /note="RZ-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01325, FT ECO:0000269|PubMed:34012115" FT REGION 1..20 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 27..365 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 343..374 FT /evidence="ECO:0000255" FT COMPBIAS 32..46 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 118..155 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 211..228 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 251..267 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 296..310 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 311..364 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 4516 FT /note="Nucleophile; for E3 ubiquitin-lipopolysaccharide FT ligase activity" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01325" FT BINDING 1995..2000 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 2098 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 2155 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 2216 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 2499 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 2574 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 3997 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 4000 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 4012 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 4014 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 4017 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 4020 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 4032 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 4035 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:E9Q555" FT BINDING 4505 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01325" FT BINDING 4509 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01325" FT BINDING 4525 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01325" FT BINDING 4528 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01325" FT MOD_RES 208 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 217 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 1258 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18318008, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 2273 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 1151 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447" FT VAR_SEQ 1..4650 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_042416" FT VAR_SEQ 87 FT /note="E -> EGATSEVLVDAAVDLISDEWEAANAIPSKRRKQDAAPLEAASVPSAD FT CEQ (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_042417" FT VAR_SEQ 1009..1063 FT /note="SQTSILQGFSYSDLRKFGIVLSAVITKSWPRTADNFNDILKHLLTLADVKHV FT FRL -> VNNLSSWETDSGSQLCSAMTQLRAMKHPLGLSSSANSEIGKWAPSSLAKGNG FT AEI (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:17974005" FT /id="VSP_042418" FT VAR_SEQ 1064..5207 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:17974005" FT /id="VSP_042419" FT VAR_SEQ 4651..4660 FT /note="QEQHQLSSRR -> MTRKSAPTSG (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_042420" FT VARIANT 118 FT /note="C -> R (rare variant detected in a patient with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:28635953" FT /id="VAR_085287" FT VARIANT 133 FT /note="L -> M (rare variant detected in a patient with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:28635953" FT /id="VAR_085288" FT VARIANT 209 FT /note="I -> N (rare variant detected in a patient with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:28635953" FT /id="VAR_085289" FT VARIANT 395 FT /note="P -> L (rare variant detected in a patient with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:28635953" FT /id="VAR_085290" FT VARIANT 529 FT /note="Missing (rare variant detected in a sporadic case of FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:25278557" FT /id="VAR_075635" FT VARIANT 996 FT /note="E -> K (rare variant detected in cases of Moyamoya FT disease in East Asian populations)" FT /evidence="ECO:0000269|PubMed:29387438" FT /id="VAR_085291" FT VARIANT 1135 FT /note="A -> V (rare variant detected in a patient with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:28635953" FT /id="VAR_085292" FT VARIANT 1622 FT /note="A -> V (rare variant detected in a sporadic case of FT Moyamoya disease in East Asian population)" FT /evidence="ECO:0000269|PubMed:25956231" FT /id="VAR_075636" FT VARIANT 1705 FT /note="T -> K (rare variant detected in a patient with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:28635953" FT /id="VAR_085293" FT VARIANT 1721 FT /note="P -> L (rare variant detected in a patient with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:28635953" FT /id="VAR_085294" FT VARIANT 1844 FT /note="A -> T (rare variant detected in a patient with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:28635953" FT /id="VAR_085295" FT VARIANT 2554 FT /note="D -> E (in dbSNP:rs138516230)" FT /evidence="ECO:0000269|PubMed:21048783" FT /id="VAR_067020" FT VARIANT 3846 FT /note="R -> H (rare variant detected in a patient with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:28635953" FT /id="VAR_085296" FT VARIANT 3891 FT /note="M -> V (rare variant detected in a sporadic case of FT Moyamoya disease)" FT /evidence="ECO:0000269|PubMed:21048783" FT /id="VAR_067021" FT VARIANT 3915 FT /note="E -> G (in dbSNP:rs61740658)" FT /evidence="ECO:0000269|PubMed:21048783" FT /id="VAR_067022" FT VARIANT 3922 FT /note="R -> Q (rare variant detected in a sporadic case of FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:25278557" FT /id="VAR_075637" FT VARIANT 3927 FT /note="A -> T (rare variant detected in a patient with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:28635953" FT /id="VAR_085297" FT VARIANT 3933 FT /note="V -> M (rare variant detected in patients with FT Moyamoya disease in East Asian and Caucasian populations)" FT /evidence="ECO:0000269|PubMed:25956231, FT ECO:0000269|PubMed:28635953" FT /id="VAR_075638" FT VARIANT 3962 FT /note="N -> D (variant detected in cases of Moyamoya FT disease in Caucasian populations)" FT /evidence="ECO:0000269|PubMed:21799892" FT /id="VAR_067023" FT VARIANT 3996..3997 FT /note="PC -> GLG (rare variant detected in cases of FT Moyamoya disease)" FT /evidence="ECO:0000269|PubMed:33568546" FT /id="VAR_085298" FT VARIANT 3997 FT /note="C -> Y (rare variant detected in a sporadic case of FT Moyamoya disease in Caucasian population; abolished E3 FT ubiquitin-protein ligase activity)" FT /evidence="ECO:0000269|PubMed:25278557, FT ECO:0000269|PubMed:32139119" FT /id="VAR_075639" FT VARIANT 4007 FT /note="P -> R (rare variant detected in a sporadic case of FT Moyamoya disease in East Asian population; abolished E3 FT ubiquitin-protein ligase activity)" FT /evidence="ECO:0000269|PubMed:23110205, FT ECO:0000269|PubMed:32139119" FT /id="VAR_075640" FT VARIANT 4013 FT /note="D -> N (in MYMY2; variant detected in cases of FT Moyamoya disease in Caucasian and Asian populations; FT inhibitory effect on angiogenic activity of vascular FT endothelial cells; does not affect E3 ubiquitin-protein FT ligase activity)" FT /evidence="ECO:0000269|PubMed:21799892, FT ECO:0000269|PubMed:25278557, ECO:0000269|PubMed:27736983, FT ECO:0000269|PubMed:28635953, ECO:0000269|PubMed:32139119" FT /id="VAR_067024" FT VARIANT 4014 FT /note="H -> N (rare variant detected in a patient with FT Moyamoya disease in Caucasian population; abolished E3 FT ubiquitin-protein ligase activity)" FT /evidence="ECO:0000269|PubMed:28635953, FT ECO:0000269|PubMed:32139119" FT /id="VAR_085299" FT VARIANT 4017 FT /note="C -> S (rare variant detected in patients with FT Moyamoya disease; abolished E3 ubiquitin-protein ligase FT activity)" FT /evidence="ECO:0000269|PubMed:27787485, FT ECO:0000269|PubMed:32139119" FT /id="VAR_085300" FT VARIANT 4019 FT /note="R -> C (rare variant detected in patients with FT Moyamoya disease in Caucasian population; strongly FT decreased E3 ubiquitin-protein ligase activity)" FT /evidence="ECO:0000269|PubMed:25278557, FT ECO:0000269|PubMed:27736983, ECO:0000269|PubMed:28635953, FT ECO:0000269|PubMed:32139119" FT /id="VAR_075641" FT VARIANT 4024 FT /note="W -> R (variant detected in patients with Moyamoya FT disease; strongly decreased E3 ubiquitin-protein ligase FT activity)" FT /evidence="ECO:0000269|PubMed:32139119" FT /id="VAR_085301" FT VARIANT 4032 FT /note="C -> R (rare variant detected in a patient with FT Moyamoya disease in Caucasian population; abolished E3 FT ubiquitin-protein ligase activity)" FT /evidence="ECO:0000269|PubMed:28635953, FT ECO:0000269|PubMed:32139119" FT /id="VAR_085302" FT VARIANT 4033 FT /note="P -> L (rare variant detected in a patient with FT Moyamoya disease in Caucasian population; abolished E3 FT ubiquitin-protein ligase activity)" FT /evidence="ECO:0000269|PubMed:28635953, FT ECO:0000269|PubMed:32139119" FT /id="VAR_085303" FT VARIANT 4042 FT /note="E -> K (rare variant detected in patients with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:27736983, FT ECO:0000269|PubMed:28635953" FT /id="VAR_079573" FT VARIANT 4051 FT /note="H -> P (rare variant detected in a patient with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:28635953" FT /id="VAR_085304" FT VARIANT 4058 FT /note="H -> P (rare variant detected in cases of Moyamoya FT disease in East Asian populations)" FT /evidence="ECO:0000269|PubMed:29387438" FT /id="VAR_085305" FT VARIANT 4062 FT /note="R -> Q (variant detected in cases of Moyamoya FT disease in Caucasian and East Asian populations)" FT /evidence="ECO:0000269|PubMed:21799892, FT ECO:0000269|PubMed:28635953, ECO:0000269|PubMed:29387438" FT /id="VAR_067025" FT VARIANT 4076 FT /note="I -> V (rare variant detected in a sporadic case of FT Moyamoya disease in Asian population)" FT /evidence="ECO:0000269|PubMed:25278557" FT /id="VAR_075642" FT VARIANT 4114 FT /note="T -> R (rare variant detected in cases of Moyamoya FT disease)" FT /evidence="ECO:0000269|PubMed:33568546" FT /id="VAR_085306" FT VARIANT 4115 FT /note="Missing (rare variant detected in a sporadic case of FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:25278557" FT /id="VAR_075643" FT VARIANT 4118 FT /note="S -> F (rare variant detected in a sporadic case of FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:26198278" FT /id="VAR_075644" FT VARIANT 4120 FT /note="F -> L (rare variant detected in cases of Moyamoya FT disease)" FT /evidence="ECO:0000269|PubMed:33568546" FT /id="VAR_085307" FT VARIANT 4122 FT /note="D -> V (rare variant detected in a patient with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:28635953" FT /id="VAR_085308" FT VARIANT 4131 FT /note="R -> C (rare variant detected in a sporadic case of FT Moyamoya disease in East Asian population)" FT /evidence="ECO:0000269|PubMed:25956231" FT /id="VAR_075645" FT VARIANT 4146 FT /note="V -> A (rare variant detected in cases of Moyamoya FT disease in Slovakian and Czech populations; inhibitory FT effect on angiogenic activity of vascular endothelial FT cells)" FT /evidence="ECO:0000269|PubMed:27736983" FT /id="VAR_079574" FT VARIANT 4185 FT /note="K -> E (variant detected in cases of Moyamoya FT disease in a Caucasian family)" FT /evidence="ECO:0000269|PubMed:31645973" FT /id="VAR_085309" FT VARIANT 4185 FT /note="K -> T (found in a heterozygous family with FT heterogeneous intracerebral vasculopathy)" FT /evidence="ECO:0000269|PubMed:25043520" FT /id="VAR_075646" FT VARIANT 4188 FT /note="A -> T (variant detected in cases of Moyamoya FT disease in a Caucasian family)" FT /evidence="ECO:0000269|PubMed:31645973" FT /id="VAR_085310" FT VARIANT 4237 FT /note="D -> E (rare variant detected in a sporadic case of FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:25278557" FT /id="VAR_075647" FT VARIANT 4367 FT /note="Q -> L (rare variant detected in a sporadic case of FT Moyamoya disease in East Asian population)" FT /evidence="ECO:0000269|PubMed:23110205" FT /id="VAR_075648" FT VARIANT 4399 FT /note="A -> T (in MYMY2; dbSNP:rs148731719)" FT /evidence="ECO:0000269|PubMed:21048783, FT ECO:0000269|PubMed:23110205, ECO:0000269|PubMed:28635953" FT /id="VAR_067026" FT VARIANT 4567 FT /note="V -> M (rare variant detected in a sporadic case of FT Moyamoya disease; dbSNP:rs145282452)" FT /evidence="ECO:0000269|PubMed:21048783" FT /id="VAR_067027" FT VARIANT 4586 FT /note="T -> P (rare variant detected in a sporadic case of FT Moyamoya disease in East Asian population)" FT /evidence="ECO:0000269|PubMed:23110205" FT /id="VAR_075649" FT VARIANT 4608 FT /note="P -> S (variant detected in cases of Moyamoya FT disease in Caucasian populations)" FT /evidence="ECO:0000269|PubMed:21799892, FT ECO:0000269|PubMed:28635953" FT /id="VAR_067028" FT VARIANT 4631 FT /note="L -> V (rare variant detected in a sporadic case of FT Moyamoya disease in East Asian population)" FT /evidence="ECO:0000269|PubMed:23110205" FT /id="VAR_075650" FT VARIANT 4638 FT /note="T -> I (rare variant detected in a case of Moyamoya FT disease; does not affect ubiquitination of FT lipopolysaccharide)" FT /evidence="ECO:0000269|PubMed:34012115" FT /id="VAR_085311" FT VARIANT 4640 FT /note="G -> S (rare variant detected in a patient with FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:28635953" FT /id="VAR_085312" FT VARIANT 4677 FT /note="W -> L (rare variant detected in patients with FT Moyamoya disease)" FT /evidence="ECO:0000269|PubMed:27736983, FT ECO:0000269|PubMed:27787485" FT /id="VAR_079575" FT VARIANT 4732 FT /note="K -> T (rare variant detected in a sporadic case of FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:25278557" FT /id="VAR_075651" FT VARIANT 4765 FT /note="V -> M (rare variant detected in a sporadic case of FT Moyamoya disease)" FT /evidence="ECO:0000269|PubMed:21048783" FT /id="VAR_067029" FT VARIANT 4810 FT /note="R -> K (in MYMY2; very frequent in individuals FT affected by Moyamoya disease; strongly increases the risk FT of Moyamoya disease; induces genomic instability; shows FT decreased ATPase activity; does not affect ubiquitination FT of lipopolysaccharide)" FT /evidence="ECO:0000269|PubMed:21048783, FT ECO:0000269|PubMed:21799892, ECO:0000269|PubMed:22377813, FT ECO:0000269|PubMed:22688072, ECO:0000269|PubMed:22931863, FT ECO:0000269|PubMed:23110205, ECO:0000269|PubMed:23994138, FT ECO:0000269|PubMed:25278557, ECO:0000269|PubMed:25956231, FT ECO:0000269|PubMed:26126547, ECO:0000269|PubMed:34012115" FT /id="VAR_067030" FT VARIANT 4863 FT /note="D -> N (variant detected in cases of Moyamoya FT disease in East Asian populations)" FT /evidence="ECO:0000269|PubMed:21799892" FT /id="VAR_067031" FT VARIANT 4950 FT /note="E -> D (variant detected in cases of Moyamoya FT disease in East Asian populations and rare variant detected FT in a sporadic case of Moyamoya disease; does not affect FT ubiquitination of lipopolysaccharide)" FT /evidence="ECO:0000269|PubMed:21799892, FT ECO:0000269|PubMed:23110205, ECO:0000269|PubMed:34012115" FT /id="VAR_067032" FT VARIANT 5021 FT /note="A -> V (variant detected in cases of Moyamoya FT disease in East Asian populations and rare variant detected FT in a sporadic case of Moyamoya disease; does not affect FT ubiquitination of lipopolysaccharide; dbSNP:rs138130613)" FT /evidence="ECO:0000269|PubMed:21799892, FT ECO:0000269|PubMed:23110205, ECO:0000269|PubMed:34012115" FT /id="VAR_067033" FT VARIANT 5136 FT /note="M -> I (rare variant detected in a sporadic case of FT Moyamoya disease in East Asian population)" FT /evidence="ECO:0000269|PubMed:23110205" FT /id="VAR_075652" FT VARIANT 5160 FT /note="D -> E (variant detected in cases of Moyamoya FT disease in East Asian populations)" FT /evidence="ECO:0000269|PubMed:21799892" FT /id="VAR_067034" FT VARIANT 5163 FT /note="V -> I (rare variant detected in a sporadic case of FT Moyamoya disease in Caucasian population)" FT /evidence="ECO:0000269|PubMed:25278557" FT /id="VAR_075653" FT VARIANT 5176 FT /note="E -> G (variant detected in cases of Moyamoya FT disease in East Asian populations)" FT /evidence="ECO:0000269|PubMed:21799892" FT /id="VAR_067035" FT MUTAGEN 2426 FT /note="K->A: Impaired ATP-binding leading to decreased FT ATPase activity; abolished ubiquitination of FT lipopolysaccharide. In mutant A1A2; abolished ATP-binding FT and localization to lipid droplets; when associated with FT A-2775." FT /evidence="ECO:0000269|PubMed:24658080, FT ECO:0000269|PubMed:30705059, ECO:0000269|PubMed:34012115" FT MUTAGEN 2488 FT /note="E->A: Decreased ATPase activity; abolished FT ubiquitination of lipopolysaccharide. In mutant B1B2; FT abolished ATPase activity and localization to lipid FT droplets; when associated with A-2845." FT /evidence="ECO:0000269|PubMed:24658080, FT ECO:0000269|PubMed:30705059, ECO:0000269|PubMed:34012115" FT MUTAGEN 2488 FT /note="E->Q: Loss of ATPase hydrolysis." FT /evidence="ECO:0000269|PubMed:26126547" FT MUTAGEN 2775 FT /note="K->A: Impaired ATP-binding leading to decreased FT ATPase activity; abolished ubiquitination of FT lipopolysaccharide. In mutant A1A2; abolished ATP-binding FT and localization to lipid droplets; when associated with FT A-2426." FT /evidence="ECO:0000269|PubMed:24658080, FT ECO:0000269|PubMed:30705059, ECO:0000269|PubMed:34012115" FT MUTAGEN 2845 FT /note="E->A: Decreased ATPase activity; abolished FT ubiquitination of lipopolysaccharide. In mutant B1B2; FT abolished ATPase activity and localization to lipid FT droplets; when associated with A-2488." FT /evidence="ECO:0000269|PubMed:24658080, FT ECO:0000269|PubMed:30705059, ECO:0000269|PubMed:34012115" FT MUTAGEN 4014 FT /note="H->N: Abolished E3 ubiquitin-protein ligase FT activity; does not affect ubiquitination of FT lipopolysaccharide." FT /evidence="ECO:0000269|PubMed:34012115" FT MUTAGEN 4024 FT /note="W->R: Abolished E3 ubiquitin-protein ligase FT activity; does not affect ubiquitination of FT lipopolysaccharide." FT /evidence="ECO:0000269|PubMed:34012115" FT MUTAGEN 4509 FT /note="H->A: Abolished ability to ubiquitinate FT lipopolysaccharide." FT /evidence="ECO:0000269|PubMed:34012115" FT CONFLICT 270 FT /note="M -> T (in Ref. 4; AAH36891/AAH40341)" FT /evidence="ECO:0000305" FT CONFLICT 321 FT /note="M -> T (in Ref. 4; AAH36891/AAH40341)" FT /evidence="ECO:0000305" FT CONFLICT 369 FT /note="K -> N (in Ref. 4; AAH36891)" FT /evidence="ECO:0000305" FT CONFLICT 1045 FT /note="N -> D (in Ref. 1; BAK53191 and 6; BAB13444)" FT /evidence="ECO:0000305" FT CONFLICT 1133 FT /note="Q -> K (in Ref. 6; BAB13444)" FT /evidence="ECO:0000305" FT CONFLICT 1195 FT /note="V -> M (in Ref. 6; BAB13444)" FT /evidence="ECO:0000305" FT CONFLICT 1272 FT /note="E -> Q (in Ref. 6; BAB13444)" FT /evidence="ECO:0000305" FT CONFLICT 1331 FT /note="D -> G (in Ref. 6; BAB13444)" FT /evidence="ECO:0000305" FT CONFLICT 3323 FT /note="R -> G (in Ref. 2; CAH56189)" FT /evidence="ECO:0000305" FT CONFLICT 4220 FT /note="E -> G (in Ref. 7; BAB15212)" FT /evidence="ECO:0000305" FT CONFLICT 4571 FT /note="D -> G (in Ref. 7; BAB15280)" FT /evidence="ECO:0000305" FT CONFLICT 4853 FT /note="K -> R (in Ref. 7; BAB15212)" FT /evidence="ECO:0000305" FT CONFLICT 4892 FT /note="N -> S (in Ref. 7; BAB15212)" FT /evidence="ECO:0000305" FT CONFLICT 5139 FT /note="L -> S (in Ref. 7; BAB15280)" FT /evidence="ECO:0000305" FT CONFLICT 5187 FT /note="L -> P (in Ref. 7; BAB15330)" FT /evidence="ECO:0000305" SQ SEQUENCE 5207 AA; 591407 MW; 9BA6847099EE6E08 CRC64; MECPSCQHVS KEETPKFCSQ CGERLPPAAP IADSENNNST MASASEGEME CGQELKEEGG PCLFPGSDSW QENPEEPCSK ASWTVQESKK KKRKKKKKGN KSASSELASL PLSPASPCHL TLLSNPWPQD TALPHSQAQQ SGPTGQPSQP PGTATTPLEG DGLSAPTEVG DSPLQAQALG EAGVATGSEA QSSPQFQDHT EGEDQDASIP SGGRGLSQEG TGPPTSAGEG HSRTEDAAQE LLLPESKGGS SEPGTELQTT EQQAGASASM AVDAVAEPAN AVKGAGKEMK EKTQRMKQPP ATTPPFKTHC QEAETKTKDE MAAAEEKVGK NEQGEPEDLK KPEGKNRSAA AVKNEKEQKN QEADVQEVKA STLSPGGGVT VFFHAIISLH FPFNPDLHKV FIRGGEEFGE SKWDSNICEL HYTRDLGHDR VLVEGIVCIS KKHLDKYIPY KYVIYNGESF EYEFIYKHQQ KKGEYVNRCL FIKSSLLGSG DWHQYYDIVY MKPHGRLQKV MNHITDGPRK DLVKGKQIAA ALMLDSTFSI LQTWDTINLN SFFTQFEQFC FVLQQPMIYE GQAQLWTDLQ YREKEVKRYL WQHLKKHVVP LPDGKSTDFL PVDCPVRSKL KTGLIVLFVV EKIELLLEGS LDWLCHLLTS DASSPDEFHR DLSHILGIPQ SWRLYLVNLC QRCMDTRTYT WLGALPVLHC CMELAPRHKD AWRQPEDTWA ALEGLSFSPF REQMLDTSSL LQFMREKQHL LSIDEPLFRS WFSLLPLSHL VMYMENFIEH LGRFPAHILD CLSGIYYRLP GLEQVLNTQD VQDVQNVQNI LEMLLRLLDT YRDKIPEEAL SPSYLTVCLK LHEAICSSTK LLKFYELPAL SAEIVCRMIR LLSLVDSAGQ RDETGNNSVQ TVFQGTLAAT KRWLREVFTK NMLTSSGASF TYVKEIEVWR RLVEIQFPAE HGWKESLLGD MEWRLTKEEP LSQITAYCNS CWDTKGLEDS VAKTFEKCII EAVSSACQSQ TSILQGFSYS DLRKFGIVLS AVITKSWPRT ADNFNDILKH LLTLADVKHV FRLCGTDEKI LANVTEDAKR LIAVADSVLT KVVGDLLSGT ILVGQLELII KHKNQFLDIW QLREKSLSPQ DEQCAVEEAL DWRREELLLL KKEKRCVDSL LKMCGNVKHL IQVDFGVLAV RHSQDLSSKR LNDTVTVRLS TSSNSQRATH YHLSSQVQEM AGKIDLLRDS HIFQLFWREA AEPLSEPKED QEAAELLSEP EEESERHILE LEEVYDYLYQ PSYRKFIKLH QDLKSGEVTL AEIDVIFKDF VNKYTDLDSE LKIMCTVDHQ DQRDWIKDRV EQIKEYHHLH QAVHAAKVIL QVKESLGLNG DFSVLNTLLN FTDNFDDFRR ETLDQINQEL IQAKKLLQDI SEARCKGLQA LSLRKEFICW VREALGGINE LKVFVDLASI SAGENDIDVD RVACFHDAVQ GYASLLFKLD PSVDFSAFMK HLKKLWKALD KDQYLPRKLC DSARNLEWLK TVNESHGSVE RSSLTLATAI NQRGIYVIQA PKGGQKISPD TVLHLILPES PGSHEESREY SLEEVKELLN KLMLMSGKKD RNNTEVERFS EVFCSVQRLS QAFIDLHSAG NMLFRTWIAM AYCSPKQGVS LQMDFGLDLV TELKEGGDVT ELLAALCRQM EHFLDSWKRF VTQKRMEHFY LNFYTAEQLV YLSTELRKQP PSDAALTMLS FIKSNCTLRD VLRASVGCGS EAARYRMRRV MEELPLMLLS EFSLVDKLRI IMEQSMRCLP AFLPDCLDLE TLGHCLAHLA GMGGSPVERC LPRGLQVGQP NLVVCGHSEV LPAALAVYMQ TPSQPLPTYD EVLLCTPATT FEEVALLLRR CLTLGSLGHK VYSLLFADQL SYEVARQAEE LFHNLCTQQH REDYQLVMVC DGDWEHCYLP SAFSQHKVFV TPQAPLEAIQ AYLAGHYRVP KQTLSAAAVF NDRLCVGIVA SERAGVGKSL YVKRLHDKMK MQLNVKNVPL KTIRLIDPQV DESRVLGALL PFLDAQYQKV PVLFHLDVTS SVQTGIWVFL FKLLILQYLM DINGKMWLRN PCHLYIVEIL ERRTSVPSRS SSALRTRVPQ FSFLDIFPKV TCRPPKEVID MELSALRSDT EPGMDLWEFC SETFQRPYQY LRRFNQNQDL DTFQYQEGSV EGTPEECLQH FLFHCGVINP SWSELRNFAR FLNYQLRDCE ASLFCNPSFI GDTLRGFKKF VVTFMIFMAR DFATPSLHTS DQSPGKHMVT MDGVREEDLA PFSLRKRWES EPHPYVFFND DHTTMTFIGF HLQPNINGSV DAISHLTGKV IKRDVMTRDL YQGLLLQRVP FNVDFDKLPR HKKLERLCLT LGIPQATDPD KTYELTTDNM LKILAIEMRF RCGIPVIIMG ETGCGKTRLI KFLSDLRRGG TNADTIKLVK VHGGTTADMI YSRVREAENV AFANKDQHQL DTILFFDEAN TTEAISCIKE VLCDHMVDGQ PLAEDSGLHI IAACNPYRKH SEEMICRLES AGLGYRVSME ETADRLGSIP LRQLVYRVHA LPPSLIPLVW DFGQLSDVAE KLYIQQIVQR LVESISLDEN GTRVITEVLC ASQGFMRKTE DECSFVSLRD VERCVKVFRW FHEHSAMLLA QLNAFLSKSS VSKNHTERDP VLWSLMLAIG VCYHASLEKK DSYRKAIARF FPKPYDDSRL LLDEITRAQD LFLDGVPLRK TIAKNLALKE NVFMMVVCIE LKIPLFLVGK PGSSKSLAKT IVADAMQGPA AYSDLFRSLK QVHLVSFQCS PHSTPQGIIS TFRQCARFQQ GKDLQQYVSV VVLDEVGLAE DSPKMPLKTL HPLLEDGCIE DDPAPHKKVG FVGISNWALD PAKMNRGIFV SRGSPNETEL IESAKGICSS DILVQDRVQG YFASFAKAYE TVCKRQDKEF FGLRDYYSLI KMVFAAAKAS NRKPSPQDIA QAVLRNFSGK DDIQALDIFL ANLPEAKCSE EVSPMQLIKQ NIFGPSQKVP GGEQEDAESR YLLVLTKNYV ALQILQQTFF EGDQQPEIIF GSGFPKDQEY TQLCRNINRV KICMETGKMV LLLNLQNLYE SLYDALNQYY VHLGGQKYVD LGLGTHRVKC RVHPNFRLIV IEEKDVVYKH FPIPLINRLE KHYLDINTVL EKWQKSIVEE LCAWVEKFIN VKAHHFQKRH KYSPSDVFIG YHSDACASVV LQVIERQGPR ALTEELHQKV SEEAKSILLN CATPDAVVRL SAYSLGGFAA EWLSQEYFHR QRHNSFADFL QAHLHTADLE RHAIFTEITT FSRLLTSHDC EILESEVTGR APKPTLLWLQ QFDTEYSFLK EVRNCLTNTA KCKILIFQTD FEDGIRSAQL IASAKYSVIN EINKIRENED RIFVYFITKL SRVGRGTAYV GFHGGLWQSV HIDDLRRSTL MVSDVTRLQH VTISQLFAPG DLPELGLEHR AEDGHEEAME TEASTSGEVA EVAEEAMETE SSEKVGKETS ELGGSDVSIL DTTRLLRSCV QSAVGMLRDQ NESCTRNMRR VVLLLGLLNE DDACHASFLR VSKMRLSVFL KKQEESQFHP LEWLAREACN QDALQEAGTF RHTLWKRVQG AVTPLLASMI SFIDRDGNLE LLTRPDTPPW ARDLWMFIFS DTMLLNIPLV MNNERHKGEM AYIVVQNHMN LSENASNNVP FSWKIKDYLE ELWVQAQYIT DAEGLPKKFV DIFQQTPLGR FLAQLHGEPQ QELLQCYLKD FILLTMRVST EEELKFLQMA LWSCTRKLKA ASEAPEEEVS LPWVHLAYQR FRSRLQNFSR ILTIYPQVLH SLMEARWNHE LAGCEMTLDA FAAMACTEML TRNTLKPSPQ AWLQLVKNLS MPLELICSDE HMQGSGSLAQ AVIREVRAQW SRIFSTALFV EHVLLGTESR VPELQGLVTE HVFLLDKCLR ENSDVKTHGP FEAVMRTLCE CKETASKTLS RFGIQPCSIC LGDAKDPVCL PCDHVHCLRC LRAWFASEQM ICPYCLTALP DEFSPAVSQA HREAIEKHAR FRQMCNSFFV DLVSTICFKD NAPPEKEVIE SLLSLLFVQK GRLRDAAQRH CEHTKSLSPF NDVVDKTPVI RSVILKLLLK YSFHDVKDYI QEYLTLLKKK AFITEDKTEL YMLFINCLED SILEKTSAYS RNDELNHLEE EGRFLKAYSP ASRGREPANE ASVEYLQEVA RIRLCLDRAA DFLSEPEGGP EMAKEKQCYL QQVKQFCIRV ENDWHRVYLV RKLSSQRGME FVQGLSKPGR PHQWVFPKDV VKQQGLRQDH PGQMDRYLVY GDEYKALRDA VAKAVLECKP LGIKTALKAC KTPQSQQSAY FLLTLFREVA ILYRSHNASL HPTPEQCEAV SKFIGECKIL SPPDISRFAT SLVDNSVPLL RAGPSDSNLD GTVTEMAIHA AAVLLCGQNE LLEPLKNLAF SPATMAHAFL PTMPEDLLAQ ARRWKGLERV HWYTCPNGHP CSVGECGRPM EQSICIDCHA PIGGIDHKPR DGFHLVKDKA DRTQTGHVLG NPQRRDVVTC DRGLPPVVFL LIRLLTHLAL LLGASQSSQA LINIIKPPVR DPKGFLQQHI LKDLEQLAKM LGHSADETIG VVHLVLRRLL QEQHQLSSRR LLNFDTELST KEMRNNWEKE IAAVISPELE HLDKTLPTMN NLISQDKRIS SNPVAKIIYG DPVTFLPHLP RKSVVHCSKI WSCRKRITVE YLQHIVEQKN GKERVPILWH FLQKEAELRL VKFLPEILAL QRDLVKQFQN VQQVEYSSIR GFLSKHSSDG LRQLLHNRIT VFLSTWNKLR RSLETNGEIN LPKDYCSTDL DLDTEFEILL PRRRGLGLCA TALVSYLIRL HNEIVYAVEK LSKENNSYSV DAAEVTELHV ISYEVERDLT PLILSNCQYQ VEEGRETVQE FDLEKIQRQI VSRFLQGKPR LSLKGIPTLV YRHDWNYEHL FMDIKNKMAQ DSLPSSVISA ISGQLQSYSD ACEVLSVVEV TLGFLSTAGG DPNMQLNVYT QDILQMGDQT IHVLKALNRC QLKHTIALWQ FLSAHKSEQL LRLHKEPFGE ISSRYKADLS PENAKLLSTF LNQTGLDAFL LELHEMIILK LKNPQTQTEE RFRPQWSLRD TLVSYMQTKE SEILPEMASQ FPEEILLASC VSVWKTAAVL KWNREMR //