ID RNF31_HUMAN Reviewed; 1072 AA. AC Q96EP0; A0A962; Q86VI2; Q8TEI0; Q96GB4; Q96NF1; Q9H5F1; Q9NWD2; DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 27-MAR-2024, entry version 206. DE RecName: Full=E3 ubiquitin-protein ligase RNF31; DE EC=2.3.2.31 {ECO:0000269|PubMed:17006537, ECO:0000269|PubMed:19136968, ECO:0000269|PubMed:20005846, ECO:0000269|PubMed:28481331}; DE AltName: Full=HOIL-1-interacting protein {ECO:0000303|PubMed:22863777}; DE Short=HOIP {ECO:0000303|PubMed:22863777}; DE AltName: Full=RING finger protein 31 {ECO:0000312|HGNC:HGNC:16031}; DE AltName: Full=RING-type E3 ubiquitin transferase RNF31 {ECO:0000305}; DE AltName: Full=Zinc in-between-RING-finger ubiquitin-associated domain protein {ECO:0000303|PubMed:15093743}; GN Name=RNF31 {ECO:0000312|HGNC:HGNC:16031}; GN Synonyms=ZIBRA {ECO:0000303|PubMed:15093743}; 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), ALTERNATIVE SPLICING, AND TISSUE RP SPECIFICITY. RC TISSUE=Mammary carcinoma; RX PubMed=15093743; DOI=10.1016/j.yexcr.2004.01.019; RA Thompson H.G.R., Harris J.W., Lin L., Brody J.P.; RT "Identification of the protein Zibra, its genomic organization, regulation, RT and expression in breast cancer cells."; RL Exp. Cell Res. 295:448-459(2004). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION IN THE LUBAC RP COMPLEX, FUNCTION OF THE LUBAC COMPLEX, CATALYTIC ACTIVITY, PATHWAY, AND RP MUTAGENESIS OF CYS-699; CYS-702; CYS-871 AND CYS-874. RX PubMed=17006537; DOI=10.1038/sj.emboj.7601360; RA Kirisako T., Kamei K., Murata S., Kato M., Fukumoto H., Kanie M., Sano S., RA Tokunaga F., Tanaka K., Iwai K.; RT "A ubiquitin ligase complex assembles linear polyubiquitin chains."; RL EMBO J. 25:4877-4887(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP ILE-1061. RC TISSUE=Embryo, and Hair follicle dermal papilla; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Ovary, and Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 526-1072 (ISOFORMS 1/3). RC TISSUE=Spleen; RX PubMed=12693554; DOI=10.1093/dnares/10.1.49; RA Jikuya H., Takano J., Kikuno R., Hirosawa M., Nagase T., Nomura N., RA Ohara O.; RT "Characterization of long cDNA clones from human adult spleen. II. The RT complete sequences of 81 cDNA clones."; RL DNA Res. 10:49-57(2003). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466, 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 POLYUBIQUITIN-BINDING, FUNCTION OF THE LUBAC COMPLEX, CATALYTIC ACTIVITY, RP PATHWAY, ASSOCIATION WITH TNF-RSC, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=20005846; DOI=10.1016/j.molcel.2009.10.013; RA Haas T.L., Emmerich C.H., Gerlach B., Schmukle A.C., Cordier S.M., RA Rieser E., Feltham R., Vince J., Warnken U., Wenger T., Koschny R., RA Komander D., Silke J., Walczak H.; RT "Recruitment of the linear ubiquitin chain assembly complex stabilizes the RT TNF-R1 signaling complex and is required for TNF-mediated gene induction."; RL Mol. Cell 36:831-844(2009). RN [11] RP FUNCTION OF THE LUBAC COMPLEX, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=19136968; DOI=10.1038/ncb1821; RA Tokunaga F., Sakata S., Saeki Y., Satomi Y., Kirisako T., Kamei K., RA Nakagawa T., Kato M., Murata S., Yamaoka S., Yamamoto M., Akira S., RA Takao T., Tanaka K., Iwai K.; RT "Involvement of linear polyubiquitylation of NEMO in NF-kappaB RT activation."; RL Nat. Cell Biol. 11:123-132(2009). RN [12] RP IDENTIFICATION IN THE LUBAC COMPLEX, AND FUNCTION. RX PubMed=21455173; DOI=10.1038/nature09816; RA Gerlach B., Cordier S.M., Schmukle A.C., Emmerich C.H., Rieser E., RA Haas T.L., Webb A.I., Rickard J.A., Anderton H., Wong W.W., Nachbur U., RA Gangoda L., Warnken U., Purcell A.W., Silke J., Walczak H.; RT "Linear ubiquitination prevents inflammation and regulates immune RT signalling."; RL Nature 471:591-596(2011). RN [13] RP IDENTIFICATION IN THE LUBAC COMPLEX, AND FUNCTION. RX PubMed=21455180; DOI=10.1038/nature09815; RA Tokunaga F., Nakagawa T., Nakahara M., Saeki Y., Taniguchi M., Sakata S., RA Tanaka K., Nakano H., Iwai K.; RT "SHARPIN is a component of the NF-kappaB-activating linear ubiquitin chain RT assembly complex."; RL Nature 471:633-636(2011). RN [14] RP IDENTIFICATION IN THE LUBAC COMPLEX, FUNCTION, DOMAIN RANBP2-TYPE, RP UBIQUITIN-BINDING, AND MUTAGENESIS OF CYS-699; CYS-702; CYS-871 AND RP CYS-874. RX PubMed=21455181; DOI=10.1038/nature09814; RA Ikeda F., Deribe Y.L., Skanland S.S., Stieglitz B., Grabbe C., RA Franz-Wachtel M., van Wijk S.J., Goswami P., Nagy V., Terzic J., RA Tokunaga F., Androulidaki A., Nakagawa T., Pasparakis M., Iwai K., RA Sundberg J.P., Schaefer L., Rittinger K., Macek B., Dikic I.; RT "SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB RT activity and apoptosis."; RL Nature 471:637-641(2011). RN [15] RP FUNCTION, DOMAIN RING, DOMAIN LDD, AND ENZYME MECHANISM. RX PubMed=22863777; DOI=10.1038/emboj.2012.217; RA Smit J.J., Monteferrario D., Noordermeer S.M., van Dijk W.J., RA van der Reijden B.A., Sixma T.K.; RT "The E3 ligase HOIP specifies linear ubiquitin chain assembly through its RT RING-IBR-RING domain and the unique LDD extension."; RL EMBO J. 31:3833-3844(2012). RN [16] RP INTERACTION WITH RBCK1/HOIL1. RX PubMed=22430200; DOI=10.1038/embor.2012.24; RA Yagi H., Ishimoto K., Hiromoto T., Fujita H., Mizushima T., Uekusa Y., RA Yagi-Utsumi M., Kurimoto E., Noda M., Uchiyama S., Tokunaga F., Iwai K., RA Kato K.; RT "A non-canonical UBA-UBL interaction forms the linear-ubiquitin-chain RT assembly complex."; RL EMBO Rep. 13:462-468(2012). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383 AND SER-466, AND RP 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 FUNCTION, AND INTERACTION WITH OTULIN. RX PubMed=23708998; DOI=10.1038/nature12296; RA Rivkin E., Almeida S.M., Ceccarelli D.F., Juang Y.C., Maclean T.A., RA Srikumar T., Huang H., Dunham W.H., Fukumura R., Xie G., Gondo Y., RA Raught B., Gingras A.C., Sicheri F., Cordes S.P.; RT "The linear ubiquitin-specific deubiquitinase gumby regulates RT angiogenesis."; RL Nature 498:318-324(2013). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383 AND SER-466, AND RP 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 [20] RP FUNCTION, INTERACTION WITH SPATA2, AND MUTAGENESIS OF ASN-102. RX PubMed=27458237; DOI=10.15252/embr.201642592; RA Schlicher L., Wissler M., Preiss F., Brauns-Schubert P., Jakob C., RA Dumit V., Borner C., Dengjel J., Maurer U.; RT "SPATA2 promotes CYLD activity and regulates TNF-induced NF-kappaB RT signaling and cell death."; RL EMBO Rep. 17:1485-1497(2016). RN [21] RP INTERACTION WITH SPATA2. RX PubMed=27545878; DOI=10.1016/j.celrep.2016.07.086; RA Kupka S., De Miguel D., Draber P., Martino L., Surinova S., Rittinger K., RA Walczak H.; RT "SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to RT Signaling Complexes."; RL Cell Rep. 16:2271-2280(2016). RN [22] RP INTERACTION WITH CYLD. RX PubMed=26997266; DOI=10.1016/j.celrep.2016.02.062; RA Hrdinka M., Fiil B.K., Zucca M., Leske D., Bagola K., Yabal M., RA Elliott P.R., Damgaard R.B., Komander D., Jost P.J., Gyrd-Hansen M.; RT "CYLD limits Lys63- and Met1-linked ubiquitin at receptor complexes to RT regulate innate immune signaling."; RL Cell Rep. 14:2846-2858(2016). RN [23] RP FUNCTION, AND INTERACTION WITH CARD11. RX PubMed=27777308; DOI=10.1074/jbc.m116.754028; RA Yang Y.K., Yang C., Chan W., Wang Z., Deibel K.E., Pomerantz J.L.; RT "Molecular determinants of scaffold-induced linear ubiquitinylation of B RT Cell Lymphoma/Leukemia 10 (Bcl10) during T cell receptor and oncogenic RT caspase recruitment domain-containing protein 11 (CARD11) signaling."; RL J. Biol. Chem. 291:25921-25936(2016). RN [24] RP INTERACTION WITH S.FLEXNERI IPAH1.4 AND IPAH2.5 (MICROBIAL INFECTION), RP UBIQUITINATION AT LYS-735; LYS-783 AND LYS-875 (MICROBIAL INFECTION), AND RP MUTAGENESIS OF LYS-735; LYS-783 AND LYS-875. RX PubMed=27572974; DOI=10.1038/nmicrobiol.2016.84; RA de Jong M.F., Liu Z., Chen D., Alto N.M.; RT "Shigella flexneri suppresses NF-kappaB activation by inhibiting linear RT ubiquitin chain ligation."; RL Nat. Microbiol. 1:16084-16084(2016). RN [25] RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN THE LUBAC COMPLEX, PATHWAY, RP UBIQUITINATION (MICROBIAL INFECTION), AND MUTAGENESIS OF THR-360; CYS-885; RP ARG-935 AND ASP-983. RX PubMed=28481331; DOI=10.1038/nmicrobiol.2017.63; RA Noad J., von der Malsburg A., Pathe C., Michel M.A., Komander D., RA Randow F.; RT "LUBAC-synthesized linear ubiquitin chains restrict cytosol-invading RT bacteria by activating autophagy and NF-kappaB."; RL Nat. Microbiol. 2:17063-17063(2017). RN [26] RP FUNCTION, INTERACTION WITH SPATA2, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF RP ASP-390. RX PubMed=28189684; DOI=10.1016/j.bbrc.2017.02.040; RA Goto E., Tokunaga F.; RT "Decreased linear ubiquitination of NEMO and FADD on apoptosis with RT caspase-mediated cleavage of HOIP."; RL Biochem. Biophys. Res. Commun. 485:152-159(2017). RN [27] RP FUNCTION. 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 [28] RP STRUCTURE BY NMR OF 779-851. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the IBR domain of the RING finger protein 31."; RL Submitted (NOV-2005) to the PDB data bank. RN [29] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-184 IN COMPLEX WITH OTULIN, RP UBIQUITINATION, DOMAIN, INTERACTION WITH OTULIN, IDENTIFICATION IN THE RP LUBAC COMPLEX, AND MUTAGENESIS OF TYR-82; ASN-85; LYS-99; ASN-101; ASN-102 RP AND VAL-104. RX PubMed=24726323; DOI=10.1016/j.molcel.2014.03.018; RA Elliott P.R., Nielsen S.V., Marco-Casanova P., Fiil B.K., Keusekotten K., RA Mailand N., Freund S.M., Gyrd-Hansen M., Komander D.; RT "Molecular basis and regulation of OTULIN-LUBAC interaction."; RL Mol. Cell 54:335-348(2014). RN [30] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-179 IN COMPLEX WITH OTULIN, AND RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-179 IN COMPLEX WITH VCP. RX PubMed=24726327; DOI=10.1016/j.molcel.2014.03.016; RA Schaeffer V., Akutsu M., Olma M.H., Gomes L.C., Kawasaki M., Dikic I.; RT "Binding of OTULIN to the PUB domain of HOIP controls NF-kappaB RT signaling."; RL Mol. Cell 54:349-361(2014). RN [31] {ECO:0007744|PDB:5LJN} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 5-176 IN COMPLEX WITH SPATA2, AND RP INTERACTION WITH SPATA2. RX PubMed=27591049; DOI=10.1016/j.molcel.2016.08.001; RA Elliott P.R., Leske D., Hrdinka M., Bagola K., Fiil B.K., McLaughlin S.H., RA Wagstaff J., Volkmar N., Christianson J.C., Kessler B.M., Freund S.M., RA Komander D., Gyrd-Hansen M.; RT "SPATA2 links CYLD to LUBAC, activates CYLD, and controls LUBAC RT signaling."; RL Mol. Cell 63:990-1005(2016). RN [32] {ECO:0007744|PDB:7V8F, ECO:0007744|PDB:7V8G} RP X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF 697-793 IN COMPLEX WITH RP S.FLEXNERI IPAH1.4; UBE2L3 AND ZINC, AND UBIQUITINATION (MICROBIAL RP INFECTION). RX PubMed=35294289; DOI=10.1073/pnas.2116776119; RA Liu J., Wang Y., Wang D., Wang Y., Xu X., Zhang Y., Li Y., Zhang M., RA Gong X., Tang Y., Shen L., Li M., Pan L.; RT "Mechanistic insights into the subversion of the linear ubiquitin chain RT assembly complex by the E3 ligase IpaH1.4 of Shigella flexneri."; RL Proc. Natl. Acad. Sci. U.S.A. 119:e2116776119-e2116776119(2022). CC -!- FUNCTION: E3 ubiquitin-protein ligase component of the LUBAC complex CC which conjugates linear ('Met-1'-linked) polyubiquitin chains to CC substrates and plays a key role in NF-kappa-B activation and regulation CC of inflammation (PubMed:17006537, PubMed:19136968, PubMed:20005846, CC PubMed:21455173, PubMed:21455180, PubMed:21455181, PubMed:22863777, CC PubMed:28481331, PubMed:28189684). LUBAC conjugates linear CC polyubiquitin to IKBKG and RIPK1 and is involved in activation of the CC canonical NF-kappa-B and the JNK signaling pathways (PubMed:17006537, CC PubMed:19136968, PubMed:20005846, PubMed:21455173, PubMed:21455180, CC PubMed:21455181, PubMed:22863777, PubMed:28189684). Linear CC ubiquitination mediated by the LUBAC complex interferes with TNF- CC induced cell death and thereby prevents inflammation (PubMed:21455173, CC PubMed:28189684). LUBAC is recruited to the TNF-R1 signaling complex CC (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 CC and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and CC possibly other components contributing to the stability of the complex CC (PubMed:20005846, PubMed:27458237). The LUBAC complex is also involved CC in innate immunity by conjugating linear polyubiquitin chains at the CC surface of bacteria invading the cytosol to form the ubiquitin coat CC surrounding bacteria (PubMed:28481331, PubMed:34012115). LUBAC is not CC able to initiate formation of the bacterial ubiquitin coat, and can CC only promote formation of linear polyubiquitins on pre-existing CC ubiquitin (PubMed:28481331). Recruited to the surface of bacteria by CC RNF213, which initiates the bacterial ubiquitin coat (PubMed:34012115). CC The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy CC and promotes NF-kappa-B activation (PubMed:28481331, PubMed:34012115). CC Together with OTULIN, the LUBAC complex regulates the canonical Wnt CC signaling during angiogenesis (PubMed:23708998). RNF31 is required for CC linear ubiquitination of BCL10, thereby promoting TCR-induced NF-kappa- CC B activation (PubMed:27777308). Binds polyubiquitin of different CC linkage types (PubMed:23708998). {ECO:0000269|PubMed:17006537, CC ECO:0000269|PubMed:19136968, ECO:0000269|PubMed:20005846, CC ECO:0000269|PubMed:21455173, ECO:0000269|PubMed:21455180, CC ECO:0000269|PubMed:21455181, ECO:0000269|PubMed:22863777, CC ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:27458237, CC ECO:0000269|PubMed:27777308, ECO:0000269|PubMed:28189684, CC ECO:0000269|PubMed:28481331, ECO:0000269|PubMed:34012115}. CC -!- CATALYTIC ACTIVITY: CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.; CC EC=2.3.2.31; Evidence={ECO:0000269|PubMed:17006537, CC ECO:0000269|PubMed:19136968, ECO:0000269|PubMed:20005846, CC ECO:0000269|PubMed:28481331}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:17006537, ECO:0000269|PubMed:19136968, CC ECO:0000269|PubMed:20005846, ECO:0000269|PubMed:28481331}. CC -!- SUBUNIT: Component of the LUBAC complex (linear ubiquitin chain CC assembly complex) which consists of SHARPIN, RBCK1 and RNF31 CC (PubMed:17006537, PubMed:21455173, PubMed:21455180, PubMed:21455181, CC PubMed:28481331). LUBAC has a MW of approximately 600 kDa suggesting a CC heteromultimeric assembly of its subunits (PubMed:17006537, CC PubMed:21455173, PubMed:21455180, PubMed:21455181). Associates with the CC TNF-R1 signaling complex (TNF-RSC) in a stimulation-dependent manner CC (PubMed:20005846). Interacts (via the PUB domain) with OTULIN (via the CC PIM motif); the interaction is direct (PubMed:23708998, CC PubMed:24726323, PubMed:24726327). Interacts (via the PUB domain) with CC VCP (via the PIM motif) (PubMed:24726327). Interacts (via the PUB CC domain) with SPATA2 (via the PIM motif); interaction is direct and CC bridges RNF31 and CYLD (PubMed:27458237, PubMed:27545878, CC PubMed:28189684, PubMed:27591049). Interacts with CYLD; the interaction CC is indirect and is mediated via SPATA2 (PubMed:27458237, CC PubMed:27545878, PubMed:26997266). Interacts with MUSK (By similarity). CC Interacts with CARD11, promoting linear ubiquitination of BCL10 CC (PubMed:27777308). {ECO:0000250|UniProtKB:Q924T7, CC ECO:0000269|PubMed:17006537, ECO:0000269|PubMed:20005846, CC ECO:0000269|PubMed:21455173, ECO:0000269|PubMed:21455180, CC ECO:0000269|PubMed:21455181, ECO:0000269|PubMed:22430200, CC ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:24726323, CC ECO:0000269|PubMed:24726327, ECO:0000269|PubMed:26997266, CC ECO:0000269|PubMed:27458237, ECO:0000269|PubMed:27545878, CC ECO:0000269|PubMed:27591049, ECO:0000269|PubMed:27777308, CC ECO:0000269|PubMed:28189684, ECO:0000269|PubMed:28481331}. CC -!- SUBUNIT: (Microbial infection) Interacts with S.flexneri E3 ubiquitin- CC protein ligases IpaH1.4 and IpaH2.5, leading to its ubiquitination. CC {ECO:0000269|PubMed:27572974}. CC -!- INTERACTION: CC Q96EP0; P54253: ATXN1; NbExp=4; IntAct=EBI-948111, EBI-930964; CC Q96EP0; P54252: ATXN3; NbExp=3; IntAct=EBI-948111, EBI-946046; CC Q96EP0; O14645: DNALI1; NbExp=3; IntAct=EBI-948111, EBI-395638; CC Q96EP0; Q9UMF0: ICAM5; NbExp=3; IntAct=EBI-948111, EBI-6398041; CC Q96EP0; Q9Y6K9: IKBKG; NbExp=10; IntAct=EBI-948111, EBI-81279; CC Q96EP0; O14901: KLF11; NbExp=3; IntAct=EBI-948111, EBI-948266; CC Q96EP0; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-948111, EBI-2811583; CC Q96EP0; Q9BYM8: RBCK1; NbExp=48; IntAct=EBI-948111, EBI-2340624; CC Q96EP0; Q96EP0: RNF31; NbExp=3; IntAct=EBI-948111, EBI-948111; CC Q96EP0; Q9H0F6: SHARPIN; NbExp=32; IntAct=EBI-948111, EBI-3942966; CC Q96EP0; P84022: SMAD3; NbExp=2; IntAct=EBI-948111, EBI-347161; CC Q96EP0; P62837: UBE2D2; NbExp=3; IntAct=EBI-948111, EBI-347677; CC Q96EP0; Q9QYP6: Azi2; Xeno; NbExp=2; IntAct=EBI-948111, EBI-6115874; CC Q96EP0; Q4VA12: Traf1; Xeno; NbExp=2; IntAct=EBI-948111, EBI-6116765; CC Q96EP0-3; Q8N4L8: CCDC24; NbExp=3; IntAct=EBI-10225152, EBI-1104933; CC Q96EP0-3; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-10225152, EBI-1044640; CC Q96EP0-3; Q5TAL4: SNRPC; NbExp=3; IntAct=EBI-10225152, EBI-10246938; CC Q96EP0-3; Q08117: TLE5; NbExp=3; IntAct=EBI-10225152, EBI-717810; CC Q96EP0-3; Q9Y5U2: TSSC4; NbExp=3; IntAct=EBI-10225152, EBI-717229; CC Q96EP0-3; Q6EMK4: VASN; NbExp=3; IntAct=EBI-10225152, EBI-10249550; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q924T7}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q96EP0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96EP0-2; Sequence=VSP_009647, VSP_009648; CC Name=3; CC IsoId=Q96EP0-3; Sequence=VSP_014006, VSP_014007; CC -!- TISSUE SPECIFICITY: Expressed in both normal and transformed breast CC epithelial cell lines. {ECO:0000269|PubMed:15093743}. CC -!- DOMAIN: The PUB domain mediates interaction with the PIM motifs of VCP CC and RNF31, with a strong preference for RNF31. CC {ECO:0000269|PubMed:24726323, ECO:0000269|PubMed:24726327}. CC -!- DOMAIN: The RanBP2-type zinc fingers mediate the specific interaction CC with ubiquitin. {ECO:0000269|PubMed:21455181}. CC -!- DOMAIN: The UBA domain mediates association with RBCK1/HOIL1 via CC interaction with its UBL domain. CC -!- DOMAIN: RING 1 and IBR zinc-fingers catalyze the first step transfer of CC ubiquitin from the E2 onto RING 2, to transiently form a HECT-like CC covalent thioester intermediate. {ECO:0000269|PubMed:22863777}. CC -!- DOMAIN: The linear ubiquitin chain determining domain (LDD) mediates CC the final transfer of ubiquitin from RING 2 onto the N-terminus of a CC target ubiquitin. {ECO:0000269|PubMed:22863777}. CC -!- PTM: Autoubiquitinated (PubMed:24726323). Interaction with OTULIN is CC required to suppress formation of 'Met-1'-linked polyubiquitin chains CC and prevent subsequent inactivation of the LUBAC complex CC (PubMed:24726323). {ECO:0000269|PubMed:24726323}. CC -!- PTM: Cleaved by caspase during apoptosis. CC {ECO:0000269|PubMed:28189684}. CC -!- PTM: (Microbial infection) Ubiquitinated by S.flexneri E3 ubiquitin- CC protein ligases IpaH1.4 and IpaH2.5, leading to its degradation by the CC proteasome, thereby preventing formation of the bacterial ubiquitin CC coat and activation of innate immunity. {ECO:0000269|PubMed:27572974, CC ECO:0000269|PubMed:28481331, ECO:0000269|PubMed:35294289}. CC -!- SIMILARITY: Belongs to the RBR family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB15675.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB15675.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAB15675.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; CC Sequence=BAB70948.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY256461; AAP12522.1; -; mRNA. DR EMBL; AB265810; BAF35583.1; -; mRNA. DR EMBL; AK000973; BAA91450.1; -; mRNA. DR EMBL; AK027154; BAB15675.1; ALT_FRAME; mRNA. DR EMBL; AK055542; BAB70948.1; ALT_INIT; mRNA. DR EMBL; AK291247; BAF83936.1; -; mRNA. DR EMBL; AL136295; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471078; EAW66098.1; -; Genomic_DNA. DR EMBL; BC009821; AAH09821.3; -; mRNA. DR EMBL; BC012077; AAH12077.1; -; mRNA. DR EMBL; BC017376; AAH17376.3; -; mRNA. DR EMBL; AK074144; BAB84970.1; -; mRNA. DR CCDS; CCDS41931.1; -. [Q96EP0-1] DR CCDS; CCDS81792.1; -. [Q96EP0-3] DR RefSeq; NP_001297261.1; NM_001310332.1. [Q96EP0-3] DR RefSeq; NP_060469.4; NM_017999.4. [Q96EP0-1] DR PDB; 2CT7; NMR; -; A=779-851. DR PDB; 4DBG; X-ray; 2.71 A; B=480-636. DR PDB; 4JUY; X-ray; 2.40 A; A/B=1-180. DR PDB; 4LJO; X-ray; 1.56 A; A=853-1072. DR PDB; 4LJP; X-ray; 2.15 A; A=853-1072. DR PDB; 4LJQ; X-ray; 2.45 A; A/B/C/D=853-1072. DR PDB; 4OWF; X-ray; 2.00 A; G=350-379. DR PDB; 4OYJ; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J/K/L/M=1-184. DR PDB; 4OYK; X-ray; 2.00 A; A/B=3-179. DR PDB; 4P09; X-ray; 1.70 A; A=1-179. DR PDB; 4P0A; X-ray; 2.30 A; A/C=1-179. DR PDB; 4P0B; X-ray; 2.70 A; A/C=1-179. DR PDB; 5EDV; X-ray; 3.48 A; A/B=696-1072. DR PDB; 5LJN; X-ray; 2.70 A; A/B=5-176. DR PDB; 5X0W; X-ray; 3.00 A; A/C/E/G=480-639. DR PDB; 6GZY; X-ray; 2.15 A; A/B=853-1072. DR PDB; 6KC5; X-ray; 1.54 A; B=853-1072. DR PDB; 6KC6; X-ray; 2.12 A; A/C/E/G/I/K=853-1072. DR PDB; 6SC5; X-ray; 2.10 A; A=697-1072. DR PDB; 6SC6; X-ray; 2.25 A; A=697-1072. DR PDB; 6SC7; X-ray; 2.56 A; A=697-1072. DR PDB; 6SC8; X-ray; 2.11 A; A=697-1072. DR PDB; 6SC9; X-ray; 2.47 A; A=697-1072. DR PDB; 7TV4; X-ray; 4.20 A; K=350-379. DR PDB; 7UY2; X-ray; 2.51 A; A/B=1-179. DR PDB; 7UYJ; X-ray; 2.32 A; A/B=1-179. DR PDB; 7UYK; X-ray; 2.70 A; A/B=480-639. DR PDB; 7V8F; X-ray; 1.66 A; B=697-793. DR PDB; 7V8G; X-ray; 2.75 A; C/D=697-793. DR PDBsum; 2CT7; -. DR PDBsum; 4DBG; -. DR PDBsum; 4JUY; -. DR PDBsum; 4LJO; -. DR PDBsum; 4LJP; -. DR PDBsum; 4LJQ; -. DR PDBsum; 4OWF; -. DR PDBsum; 4OYJ; -. DR PDBsum; 4OYK; -. DR PDBsum; 4P09; -. DR PDBsum; 4P0A; -. DR PDBsum; 4P0B; -. DR PDBsum; 5EDV; -. DR PDBsum; 5LJN; -. DR PDBsum; 5X0W; -. DR PDBsum; 6GZY; -. DR PDBsum; 6KC5; -. DR PDBsum; 6KC6; -. DR PDBsum; 6SC5; -. DR PDBsum; 6SC6; -. DR PDBsum; 6SC7; -. DR PDBsum; 6SC8; -. DR PDBsum; 6SC9; -. DR PDBsum; 7TV4; -. DR PDBsum; 7UY2; -. DR PDBsum; 7UYJ; -. DR PDBsum; 7UYK; -. DR PDBsum; 7V8F; -. DR PDBsum; 7V8G; -. DR AlphaFoldDB; Q96EP0; -. DR BMRB; Q96EP0; -. DR EMDB; EMD-11054; -. DR SMR; Q96EP0; -. DR BioGRID; 120389; 432. DR ComplexPortal; CPX-1877; LUBAC ubiquitin ligase complex. DR CORUM; Q96EP0; -. DR DIP; DIP-44034N; -. DR IntAct; Q96EP0; 70. DR MINT; Q96EP0; -. DR STRING; 9606.ENSP00000315112; -. DR BindingDB; Q96EP0; -. DR ChEMBL; CHEMBL4296109; -. DR iPTMnet; Q96EP0; -. DR MetOSite; Q96EP0; -. DR PhosphoSitePlus; Q96EP0; -. DR BioMuta; RNF31; -. DR DMDM; 45477216; -. DR EPD; Q96EP0; -. DR jPOST; Q96EP0; -. DR MassIVE; Q96EP0; -. DR MaxQB; Q96EP0; -. DR PaxDb; 9606-ENSP00000315112; -. DR PeptideAtlas; Q96EP0; -. DR ProteomicsDB; 76429; -. [Q96EP0-1] DR ProteomicsDB; 76430; -. [Q96EP0-2] DR ProteomicsDB; 76431; -. [Q96EP0-3] DR Pumba; Q96EP0; -. DR ABCD; Q96EP0; 10 sequenced antibodies. DR Antibodypedia; 22671; 281 antibodies from 36 providers. DR DNASU; 55072; -. DR Ensembl; ENST00000324103.11; ENSP00000315112.6; ENSG00000092098.18. [Q96EP0-1] DR Ensembl; ENST00000559275.5; ENSP00000453574.1; ENSG00000092098.18. [Q96EP0-3] DR Ensembl; ENST00000642631.1; ENSP00000494011.1; ENSG00000285152.2. [Q96EP0-3] DR Ensembl; ENST00000647495.2; ENSP00000496609.1; ENSG00000285152.2. [Q96EP0-1] DR GeneID; 55072; -. DR KEGG; hsa:55072; -. DR MANE-Select; ENST00000324103.11; ENSP00000315112.6; NM_017999.5; NP_060469.4. DR UCSC; uc001wml.2; human. [Q96EP0-1] DR AGR; HGNC:16031; -. DR DisGeNET; 55072; -. DR GeneCards; RNF31; -. DR HGNC; HGNC:16031; RNF31. DR HPA; ENSG00000092098; Low tissue specificity. DR MalaCards; RNF31; -. DR MIM; 612487; gene. DR neXtProt; NX_Q96EP0; -. DR OpenTargets; ENSG00000092098; -. DR OpenTargets; ENSG00000259529; -. DR Orphanet; 329173; Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis. DR PharmGKB; PA134906471; -. DR VEuPathDB; HostDB:ENSG00000092098; -. DR eggNOG; KOG1812; Eukaryota. DR GeneTree; ENSGT00530000064112; -. DR InParanoid; Q96EP0; -. DR OMA; YNTFYAK; -. DR OrthoDB; 2909614at2759; -. DR PhylomeDB; Q96EP0; -. DR TreeFam; TF350529; -. DR BRENDA; 2.3.2.31; 2681. DR PathwayCommons; Q96EP0; -. DR Reactome; R-HSA-5357786; TNFR1-induced proapoptotic signaling. DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. DR Reactome; R-HSA-5357956; TNFR1-induced NF-kappa-B signaling pathway. DR SignaLink; Q96EP0; -. DR SIGNOR; Q96EP0; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 55072; 92 hits in 1199 CRISPR screens. DR ChiTaRS; RNF31; human. DR EvolutionaryTrace; Q96EP0; -. DR GeneWiki; RNF31; -. DR GenomeRNAi; 55072; -. DR Pharos; Q96EP0; Tbio. DR PRO; PR:Q96EP0; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q96EP0; Protein. DR Bgee; ENSG00000092098; Expressed in spleen and 99 other cell types or tissues. DR ExpressionAtlas; Q96EP0; baseline and differential. DR GO; GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISS:BHF-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0071797; C:LUBAC complex; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0036435; F:K48-linked polyubiquitin modification-dependent protein binding; IBA:GO_Central. DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IBA:GO_Central. DR GO; GO:1990450; F:linear polyubiquitin binding; IBA:GO_Central. DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0023035; P:CD40 signaling pathway; ISS:BHF-UCL. DR GO; GO:0042742; P:defense response to bacterium; IDA:UniProtKB. DR GO; GO:0060546; P:negative regulation of necroptotic process; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; HMP:ParkinsonsUK-UCL. DR GO; GO:1904417; P:positive regulation of xenophagy; IDA:UniProtKB. DR GO; GO:0097039; P:protein linear polyubiquitination; IDA:UniProtKB. DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB. DR GO; GO:0050852; P:T cell receptor signaling pathway; IDA:UniProtKB. DR CDD; cd19815; Bbox1_HOIP; 1. DR CDD; cd20337; BRcat_RBR_HOIP; 1. DR CDD; cd16631; mRING-HC-C4C4_RBR_HOIP; 1. DR CDD; cd10464; PUB_RNF31; 1. DR CDD; cd20351; Rcat_RBR_HOIP; 1. DR CDD; cd14325; UBA_RNF31; 1. DR Gene3D; 1.20.120.1750; -; 1. DR Gene3D; 1.20.58.2190; -; 1. DR Gene3D; 6.10.140.1100; -; 1. DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1. DR Gene3D; 4.10.1060.10; Zinc finger, RanBP2-type; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR IDEAL; IID00576; -. DR InterPro; IPR047543; Bbox1_RNF31-like. DR InterPro; IPR047540; BRcat_RBR_RNF31-like. DR InterPro; IPR002867; IBR_dom. DR InterPro; IPR036339; PUB-like_dom_sf. DR InterPro; IPR018997; PUB_domain. DR InterPro; IPR047542; Rcat_RBR_RNF31-like. DR InterPro; IPR026254; RNF31-like. DR InterPro; IPR032065; RNF31-UBA. DR InterPro; IPR041031; RNF31_C. DR InterPro; IPR040641; RNF31_PUB. DR InterPro; IPR047541; RNF31_RBR_mRING-HC-like. DR InterPro; IPR044066; TRIAD_supradom. DR InterPro; IPR015940; UBA. DR InterPro; IPR047539; UBA_RNF31. DR InterPro; IPR001876; Znf_RanBP2. DR InterPro; IPR036443; Znf_RanBP2_sf. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR16004:SF2; E3 UBIQUITIN-PROTEIN LIGASE RNF31; 1. DR PANTHER; PTHR16004; RING FINGER PROTEIN 31-RELATED; 1. DR Pfam; PF18091; E3_UbLigase_RBR; 1. DR Pfam; PF16678; HOIP-UBA; 1. DR Pfam; PF01485; IBR; 1. DR Pfam; PF09409; PUB; 1. DR Pfam; PF18486; PUB_1; 1. DR SMART; SM00647; IBR; 2. DR SMART; SM00547; ZnF_RBZ; 3. DR SUPFAM; SSF143503; PUG domain-like; 1. DR SUPFAM; SSF90209; Ran binding protein zinc finger-like; 1. DR SUPFAM; SSF57850; RING/U-box; 3. DR PROSITE; PS51873; TRIAD; 1. DR PROSITE; PS50030; UBA; 1. DR PROSITE; PS01358; ZF_RANBP2_1; 3. DR PROSITE; PS50199; ZF_RANBP2_2; 2. DR PROSITE; PS00518; ZF_RING_1; 1. DR Genevisible; Q96EP0; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Isopeptide bond; KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Transferase; KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..1072 FT /note="E3 ubiquitin-protein ligase RNF31" FT /id="PRO_0000056069" FT DOMAIN 71..142 FT /note="PUB" FT /evidence="ECO:0000255" FT DOMAIN 564..615 FT /note="UBA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212" FT ZN_FING 299..329 FT /note="RanBP2-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322" FT ZN_FING 350..379 FT /note="RanBP2-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322" FT ZN_FING 409..438 FT /note="RanBP2-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322" FT ZN_FING 699..749 FT /note="RING-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT ZN_FING 779..841 FT /note="IBR-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT ZN_FING 871..901 FT /note="RING-type 2; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT REGION 1..485 FT /note="Polyubiquitin-binding" FT REGION 263..290 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 443..484 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 563..616 FT /note="Interaction with RBCK1" FT REGION 695..929 FT /note="TRIAD supradomain" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT REGION 910..1072 FT /note="LDD domain" FT COMPBIAS 452..466 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 885 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 699 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221, FT ECO:0000269|PubMed:35294289, ECO:0007744|PDB:7V8F, FT ECO:0007744|PDB:7V8G" FT BINDING 702 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221, FT ECO:0000269|PubMed:35294289, ECO:0007744|PDB:7V8F, FT ECO:0007744|PDB:7V8G" FT BINDING 717 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:35294289, FT ECO:0007744|PDB:7V8F, ECO:0007744|PDB:7V8G" FT BINDING 719 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:35294289, FT ECO:0007744|PDB:7V8F, ECO:0007744|PDB:7V8G" FT BINDING 722 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221, FT ECO:0000269|PubMed:35294289, ECO:0007744|PDB:7V8F, FT ECO:0007744|PDB:7V8G" FT BINDING 725 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221, FT ECO:0000269|PubMed:35294289, ECO:0007744|PDB:7V8F, FT ECO:0007744|PDB:7V8G" FT BINDING 744 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:35294289, FT ECO:0007744|PDB:7V8F, ECO:0007744|PDB:7V8G" FT BINDING 747 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:35294289, FT ECO:0007744|PDB:7V8F, ECO:0007744|PDB:7V8G" FT BINDING 799 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 802 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 817 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 820 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 825 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 828 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 836 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 841 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 871 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 874 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 890 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 893 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 898 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 901 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 916 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT BINDING 925 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221" FT SITE 390..391 FT /note="Cleavage; by caspase" FT /evidence="ECO:0000269|PubMed:28189684" FT MOD_RES 383 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 466 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT CROSSLNK 735 FT /note="(Microbial infection) Glycyl lysine isopeptide (Lys- FT Gly) (interchain with G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:27572974" FT CROSSLNK 783 FT /note="(Microbial infection) Glycyl lysine isopeptide (Lys- FT Gly) (interchain with G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:27572974" FT CROSSLNK 875 FT /note="(Microbial infection) Glycyl lysine isopeptide (Lys- FT Gly) (interchain with G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:27572974" FT VAR_SEQ 1..151 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15093743" FT /id="VSP_014006" FT VAR_SEQ 73..630 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_009647" FT VAR_SEQ 152..164 FT /note="EVLLLRTELSLLL -> MDLCTRAGEPSLT (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15093743" FT /id="VSP_014007" FT VAR_SEQ 833..841 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_009648" FT VARIANT 1061 FT /note="V -> I (in dbSNP:rs2277484)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_052102" FT MUTAGEN 82 FT /note="Y->A: Abolished interaction with OTULIN." FT /evidence="ECO:0000269|PubMed:24726323" FT MUTAGEN 82 FT /note="Y->F: Reduced interaction with OTULIN." FT /evidence="ECO:0000269|PubMed:24726323" FT MUTAGEN 85 FT /note="N->A: Reduced interaction with OTULIN." FT /evidence="ECO:0000269|PubMed:24726323" FT MUTAGEN 99 FT /note="K->E: Reduced interaction with OTULIN." FT /evidence="ECO:0000269|PubMed:24726323" FT MUTAGEN 101 FT /note="N->R: Does not affect interaction with OTULIN." FT /evidence="ECO:0000269|PubMed:24726323" FT MUTAGEN 102 FT /note="N->A: Abolished interaction with SPATA2." FT /evidence="ECO:0000269|PubMed:27458237" FT MUTAGEN 102 FT /note="N->D: Abolished interaction with OTULIN." FT /evidence="ECO:0000269|PubMed:24726323" FT MUTAGEN 104 FT /note="V->A: Reduced interaction with OTULIN." FT /evidence="ECO:0000269|PubMed:24726323" FT MUTAGEN 360 FT /note="T->A: Decreased ubiquitin-binding and ability to FT promote formation of the bacterial ubiquitin coat." FT /evidence="ECO:0000269|PubMed:28481331" FT MUTAGEN 390 FT /note="D->A: Abolishes cleavage by caspase." FT /evidence="ECO:0000269|PubMed:28189684" FT MUTAGEN 699 FT /note="C->S: Abolishes polyubiquitination activity of FT LUBAC; when associated with S-702." FT /evidence="ECO:0000269|PubMed:17006537, FT ECO:0000269|PubMed:21455181" FT MUTAGEN 702 FT /note="C->S: Abolishes polyubiquitination activity of FT LUBAC; when associated with S-699." FT /evidence="ECO:0000269|PubMed:17006537, FT ECO:0000269|PubMed:21455181" FT MUTAGEN 735 FT /note="K->R: Reduced ubiquitination; when associated with FT R-783 and R-875." FT /evidence="ECO:0000269|PubMed:27572974" FT MUTAGEN 783 FT /note="K->R: Reduced ubiquitination; when associated with FT R-735 and R-875." FT /evidence="ECO:0000269|PubMed:27572974" FT MUTAGEN 871 FT /note="C->S: Abolishes polyubiquitination activity of FT LUBAC; when associated with S-874." FT /evidence="ECO:0000269|PubMed:17006537, FT ECO:0000269|PubMed:21455181" FT MUTAGEN 874 FT /note="C->S: Abolishes polyubiquitination activity of FT LUBAC; when associated with S-871." FT /evidence="ECO:0000269|PubMed:17006537, FT ECO:0000269|PubMed:21455181" FT MUTAGEN 875 FT /note="K->R: Reduced ubiquitination; when associated with FT R-735 and R-783." FT /evidence="ECO:0000269|PubMed:27572974" FT MUTAGEN 885 FT /note="C->A: Abolished E3 ubiquitin-protein ligase activity FT and ability to promote formation of the bacterial ubiquitin FT coat; when associated with A-935 and A-983." FT /evidence="ECO:0000269|PubMed:28481331" FT MUTAGEN 935 FT /note="R->A: Abolished E3 ubiquitin-protein ligase activity FT and ability to promote formation of the bacterial ubiquitin FT coat; when associated with A-885 and A-983." FT /evidence="ECO:0000269|PubMed:28481331" FT MUTAGEN 983 FT /note="D->A: Abolished E3 ubiquitin-protein ligase activity FT and ability to promote formation of the bacterial ubiquitin FT coat; when associated with A-885 and A-935." FT /evidence="ECO:0000269|PubMed:28481331" FT CONFLICT 529 FT /note="P -> S (in Ref. 1; AAP12522)" FT /evidence="ECO:0000305" FT CONFLICT 800 FT /note="A -> V (in Ref. 3; BAA91450)" FT /evidence="ECO:0000305" FT CONFLICT 925 FT /note="H -> R (in Ref. 3; BAB15675)" FT /evidence="ECO:0000305" FT CONFLICT 1005 FT /note="Y -> N (in Ref. 3; BAB15675)" FT /evidence="ECO:0000305" FT CONFLICT 1018 FT /note="A -> S (in Ref. 3; BAB15675)" FT /evidence="ECO:0000305" FT CONFLICT 1021 FT /note="Y -> D (in Ref. 3; BAB15675)" FT /evidence="ECO:0000305" FT HELIX 4..23 FT /evidence="ECO:0007829|PDB:4P09" FT HELIX 31..38 FT /evidence="ECO:0007829|PDB:4P09" FT HELIX 44..47 FT /evidence="ECO:0007829|PDB:4P09" FT STRAND 49..51 FT /evidence="ECO:0007829|PDB:4P09" FT HELIX 53..58 FT /evidence="ECO:0007829|PDB:4P09" FT HELIX 65..86 FT /evidence="ECO:0007829|PDB:4P09" FT STRAND 88..90 FT /evidence="ECO:0007829|PDB:4P09" FT TURN 93..96 FT /evidence="ECO:0007829|PDB:4P09" FT STRAND 97..102 FT /evidence="ECO:0007829|PDB:4P09" FT HELIX 103..107 FT /evidence="ECO:0007829|PDB:4P09" FT HELIX 109..111 FT /evidence="ECO:0007829|PDB:4P09" FT HELIX 115..122 FT /evidence="ECO:0007829|PDB:4P09" FT STRAND 126..128 FT /evidence="ECO:0007829|PDB:4P09" FT STRAND 131..133 FT /evidence="ECO:0007829|PDB:4P09" FT HELIX 143..164 FT /evidence="ECO:0007829|PDB:4P09" FT HELIX 171..177 FT /evidence="ECO:0007829|PDB:4P09" FT TURN 357..359 FT /evidence="ECO:0007829|PDB:4OWF" FT TURN 371..373 FT /evidence="ECO:0007829|PDB:4OWF" FT HELIX 490..501 FT /evidence="ECO:0007829|PDB:7UYK" FT HELIX 505..514 FT /evidence="ECO:0007829|PDB:7UYK" FT HELIX 521..526 FT /evidence="ECO:0007829|PDB:7UYK" FT HELIX 528..542 FT /evidence="ECO:0007829|PDB:7UYK" FT HELIX 544..546 FT /evidence="ECO:0007829|PDB:4DBG" FT HELIX 551..560 FT /evidence="ECO:0007829|PDB:7UYK" FT TURN 561..563 FT /evidence="ECO:0007829|PDB:7UYK" FT HELIX 565..584 FT /evidence="ECO:0007829|PDB:7UYK" FT TURN 585..587 FT /evidence="ECO:0007829|PDB:7UYK" FT HELIX 590..592 FT /evidence="ECO:0007829|PDB:7UYK" FT HELIX 594..600 FT /evidence="ECO:0007829|PDB:7UYK" FT TURN 601..603 FT /evidence="ECO:0007829|PDB:7UYK" FT HELIX 605..625 FT /evidence="ECO:0007829|PDB:7UYK" FT TURN 700..702 FT /evidence="ECO:0007829|PDB:7V8F" FT STRAND 705..707 FT /evidence="ECO:0007829|PDB:7V8F" FT HELIX 708..710 FT /evidence="ECO:0007829|PDB:7V8F" FT STRAND 711..713 FT /evidence="ECO:0007829|PDB:7V8F" FT TURN 715..717 FT /evidence="ECO:0007829|PDB:6SC5" FT HELIX 723..736 FT /evidence="ECO:0007829|PDB:7V8F" FT HELIX 739..741 FT /evidence="ECO:0007829|PDB:7V8F" FT TURN 745..747 FT /evidence="ECO:0007829|PDB:7V8F" FT HELIX 755..757 FT /evidence="ECO:0007829|PDB:7V8F" FT HELIX 758..772 FT /evidence="ECO:0007829|PDB:7V8F" FT HELIX 775..787 FT /evidence="ECO:0007829|PDB:7V8F" FT STRAND 796..798 FT /evidence="ECO:0007829|PDB:6SC5" FT TURN 800..802 FT /evidence="ECO:0007829|PDB:6SC5" FT STRAND 805..807 FT /evidence="ECO:0007829|PDB:6SC5" FT STRAND 813..816 FT /evidence="ECO:0007829|PDB:6SC5" FT TURN 818..820 FT /evidence="ECO:0007829|PDB:6SC5" FT STRAND 823..825 FT /evidence="ECO:0007829|PDB:6SC5" FT TURN 826..828 FT /evidence="ECO:0007829|PDB:6SC5" FT HELIX 834..836 FT /evidence="ECO:0007829|PDB:6SC5" FT HELIX 841..849 FT /evidence="ECO:0007829|PDB:6SC5" FT HELIX 853..858 FT /evidence="ECO:0007829|PDB:6SC5" FT HELIX 859..864 FT /evidence="ECO:0007829|PDB:4LJO" FT STRAND 868..870 FT /evidence="ECO:0007829|PDB:4LJO" FT TURN 872..874 FT /evidence="ECO:0007829|PDB:6KC5" FT STRAND 877..879 FT /evidence="ECO:0007829|PDB:4LJO" FT STRAND 887..889 FT /evidence="ECO:0007829|PDB:6KC5" FT TURN 891..893 FT /evidence="ECO:0007829|PDB:6KC5" FT STRAND 896..898 FT /evidence="ECO:0007829|PDB:6KC5" FT TURN 899..901 FT /evidence="ECO:0007829|PDB:6KC5" FT STRAND 904..906 FT /evidence="ECO:0007829|PDB:6KC5" FT TURN 908..910 FT /evidence="ECO:0007829|PDB:6SC8" FT TURN 917..920 FT /evidence="ECO:0007829|PDB:4LJO" FT STRAND 921..924 FT /evidence="ECO:0007829|PDB:4LJO" FT STRAND 928..930 FT /evidence="ECO:0007829|PDB:5EDV" FT HELIX 931..934 FT /evidence="ECO:0007829|PDB:6KC5" FT HELIX 939..948 FT /evidence="ECO:0007829|PDB:6KC5" FT STRAND 965..968 FT /evidence="ECO:0007829|PDB:4LJP" FT STRAND 972..977 FT /evidence="ECO:0007829|PDB:4LJO" FT STRAND 980..985 FT /evidence="ECO:0007829|PDB:4LJO" FT TURN 992..996 FT /evidence="ECO:0007829|PDB:6KC5" FT HELIX 999..1012 FT /evidence="ECO:0007829|PDB:6KC5" FT HELIX 1017..1020 FT /evidence="ECO:0007829|PDB:6KC5" FT HELIX 1023..1034 FT /evidence="ECO:0007829|PDB:6KC5" FT HELIX 1046..1060 FT /evidence="ECO:0007829|PDB:6KC5" FT STRAND 1065..1067 FT /evidence="ECO:0007829|PDB:6KC5" SQ SEQUENCE 1072 AA; 119652 MW; CFAD183A14F764BA CRC64; MPGEEEERAF LVAREELASA LRRDSGQAFS LEQLRPLLAS SLPLAARYLQ LDAARLVRCN AHGEPRNYLN TLSTALNILE KYGRNLLSPQ RPRYWRGVKF NNPVFRSTVD AVQGGRDVLR LYGYTEEQPD GLSFPEGQEE PDEHQVATVT LEVLLLRTEL SLLLQNTHPR QQALEQLLED KVEDDMLQLS EFDPLLREIA PGPLTTPSVP GSTPGPCFLC GSAPGTLHCP SCKQALCPAC DHLFHGHPSR AHHLRQTLPG VLQGTHLSPS LPASAQPRPQ STSLLALGDS SLSSPNPASA HLPWHCAACA MLNEPWAVLC VACDRPRGCK GLGLGTEGPQ GTGGLEPDLA RGRWACQSCT FENEAAAVLC SICERPRLAQ PPSLVVDSRD AGICLQPLQQ GDALLASAQS QVWYCIHCTF CNSSPGWVCV MCNRTSSPIP AQHAPRPYAS SLEKGPPKPG PPRRLSAPLP SSCGDPEKQR QDKMREEGLQ LVSMIREGEA AGACPEEIFS ALQYSGTEVP LQWLRSELPY VLEMVAELAG QQDPGLGAFS CQEARRAWLD RHGNLDEAVE ECVRTRRRKV QELQSLGFGP EEGSLQALFQ HGGDVSRALT ELQRQRLEPF RQRLWDSGPE PTPSWDGPDK QSLVRRLLAV YALPSWGRAE LALSLLQETP RNYELGDVVE AVRHSQDRAF LRRLLAQECA VCGWALPHNR MQALTSCECT ICPDCFRQHF TIALKEKHIT DMVCPACGRP DLTDDTQLLS YFSTLDIQLR ESLEPDAYAL FHKKLTEGVL MRDPKFLWCA QCSFGFIYER EQLEATCPQC HQTFCVRCKR QWEEQHRGRS CEDFQNWKRM NDPEYQAQGL AMYLQENGID CPKCKFSYAL ARGGCMHFHC TQCRHQFCSG CYNAFYAKNK CPEPNCRVKK SLHGHHPRDC LFYLRDWTAL RLQKLLQDNN VMFNTEPPAG ARAVPGGGCR VIEQKEVPNG LRDEACGKET PAGYAGLCQA HYKEYLVSLI NAHSLDPATL YEVEELETAT ERYLHVRPQP LAGEDPPAYQ ARLLQKLTEE VPLGQSIPRR RK //