RNF31_HUMAN
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 03-AUG-2022, entry version 197.
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).
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}.
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};
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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; 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; 7V8F; -.
DR PDBsum; 7V8G; -.
DR AlphaFoldDB; Q96EP0; -.
DR BMRB; Q96EP0; -.
DR SMR; Q96EP0; -.
DR BioGRID; 120389; 418.
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; Q96EP0; -.
DR PeptideAtlas; Q96EP0; -.
DR PRIDE; Q96EP0; -.
DR ProteomicsDB; 76429; -. [Q96EP0-1]
DR ProteomicsDB; 76430; -. [Q96EP0-2]
DR ProteomicsDB; 76431; -. [Q96EP0-3]
DR ABCD; Q96EP0; 10 sequenced antibodies.
DR Antibodypedia; 22671; 264 antibodies from 36 providers.
DR DNASU; 55072; -.
DR Ensembl; ENST00000324103.11; ENSP00000315112.6; ENSG00000092098.17. [Q96EP0-1]
DR Ensembl; ENST00000559275.5; ENSP00000453574.1; ENSG00000092098.17. [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 CTD; 55072; -.
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; RNNDPEY; -.
DR OrthoDB; 1188714at2759; -.
DR PhylomeDB; Q96EP0; -.
DR TreeFam; TF350529; -.
DR BRENDA; 2.3.2.31; 2681.
DR PathwayCommons; Q96EP0; -.
DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-HSA-5357956; TNFR1-induced NFkappaB signaling pathway.
DR SignaLink; Q96EP0; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 55072; 83 hits in 1120 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 97 other tissues.
DR ExpressionAtlas; Q96EP0; baseline and differential.
DR Genevisible; Q96EP0; HS.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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: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 I-kappaB kinase/NF-kappaB signaling; 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 Gene3D; 3.30.40.10; -; 1.
DR IDEAL; IID00576; -.
DR InterPro; IPR002867; IBR_dom.
DR InterPro; IPR036339; PUB-like_dom_sf.
DR InterPro; IPR018997; PUB_domain.
DR InterPro; IPR026254; RNF31-like.
DR InterPro; IPR032065; RNF31-UBA.
DR InterPro; IPR041031; RNF31_C.
DR InterPro; IPR040641; RNF31_PUB.
DR InterPro; IPR044066; TRIAD_supradom.
DR InterPro; IPR015940; UBA.
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; PTHR16004; 2.
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; SSF143503; 1.
DR SUPFAM; SSF90209; SSF90209; 1.
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.
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 BINDING 702
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
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 BINDING 725
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 799
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 802
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 817
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 820
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 825
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 828
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 836
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 841
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 871
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 874
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 890
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 893
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 898
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 901
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 916
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 925
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
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 483..493
FT /evidence="ECO:0007829|PDB:4DBG"
FT HELIX 505..515
FT /evidence="ECO:0007829|PDB:4DBG"
FT HELIX 521..527
FT /evidence="ECO:0007829|PDB:4DBG"
FT HELIX 531..542
FT /evidence="ECO:0007829|PDB:4DBG"
FT HELIX 544..546
FT /evidence="ECO:0007829|PDB:4DBG"
FT HELIX 551..560
FT /evidence="ECO:0007829|PDB:4DBG"
FT TURN 561..563
FT /evidence="ECO:0007829|PDB:4DBG"
FT HELIX 565..585
FT /evidence="ECO:0007829|PDB:4DBG"
FT HELIX 590..592
FT /evidence="ECO:0007829|PDB:4DBG"
FT HELIX 594..600
FT /evidence="ECO:0007829|PDB:4DBG"
FT TURN 601..603
FT /evidence="ECO:0007829|PDB:4DBG"
FT HELIX 605..616
FT /evidence="ECO:0007829|PDB:4DBG"
FT HELIX 618..625
FT /evidence="ECO:0007829|PDB:4DBG"
FT TURN 700..702
FT /evidence="ECO:0007829|PDB:6SC5"
FT HELIX 708..710
FT /evidence="ECO:0007829|PDB:6SC5"
FT STRAND 711..713
FT /evidence="ECO:0007829|PDB:6SC5"
FT TURN 715..717
FT /evidence="ECO:0007829|PDB:6SC5"
FT HELIX 723..735
FT /evidence="ECO:0007829|PDB:6SC5"
FT HELIX 739..741
FT /evidence="ECO:0007829|PDB:6SC5"
FT STRAND 745..747
FT /evidence="ECO:0007829|PDB:6SC5"
FT TURN 755..757
FT /evidence="ECO:0007829|PDB:6SC6"
FT HELIX 759..772
FT /evidence="ECO:0007829|PDB:6SC5"
FT HELIX 775..788
FT /evidence="ECO:0007829|PDB:6SC5"
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
