SYVN1_HUMAN
ID SYVN1_HUMAN Reviewed; 617 AA.
AC Q86TM6; Q8N3K3; Q8N6E8; Q96JL5; Q96PK3;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=E3 ubiquitin-protein ligase synoviolin;
DE EC=2.3.2.27 {ECO:0000269|PubMed:12646171, ECO:0000269|PubMed:12975321, ECO:0000269|PubMed:14593114, ECO:0000269|PubMed:17059562, ECO:0000269|PubMed:17141218, ECO:0000269|PubMed:17170702};
DE AltName: Full=RING-type E3 ubiquitin transferase synoviolin {ECO:0000303|PubMed:12975321};
DE AltName: Full=Synovial apoptosis inhibitor 1;
GN Name=SYVN1; Synonyms=HRD1, KIAA1810;
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), FUNCTION, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-329, INDUCTION BY ER STRESS,
RP AUTOUBIQUITINATION, AND PATHWAY.
RX PubMed=12459480; DOI=10.1016/s0014-5793(02)03660-8;
RA Kaneko M., Ishiguro M., Niinuma Y., Uesugi M., Nomura Y.;
RT "Human HRD1 protects against ER stress-induced apoptosis through ER-
RT associated degradation.";
RL FEBS Lett. 532:147-152(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, AUTOUBIQUITINATION, AND CATALYTIC ACTIVITY.
RX PubMed=12646171; DOI=10.1016/s0006-291x(03)00279-1;
RA Nadav E., Shmueli A., Barr H., Gonen H., Ciechanover A., Reiss Y.;
RT "A novel mammalian endoplasmic reticulum ubiquitin ligase homologous to the
RT yeast Hrd1.";
RL Biochem. Biophys. Res. Commun. 303:91-97(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP AUTOUBIQUITINATION, AND CATALYTIC ACTIVITY.
RC TISSUE=Articular cartilage;
RX PubMed=12975321; DOI=10.1101/gad.1096603;
RA Amano T., Yamasaki S., Yagishita N., Tsuchimochi K., Shin H., Kawahara K.,
RA Aratani S., Fujita H., Zhang L., Ikeda R., Fujii R., Miura N., Komiya S.,
RA Nishioka K., Maruyama I., Fukamizu A., Nakajima T.;
RT "Synoviolin/Hrd1, an E3 ubiquitin ligase, as a novel pathogenic factor for
RT arthropathy.";
RL Genes Dev. 17:2436-2449(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, INDUCTION BY ER STRESS,
RP LACK OF GLYCOSYLATION, SUBCELLULAR LOCATION, TOPOLOGY, AND CATALYTIC
RP ACTIVITY.
RX PubMed=14593114; DOI=10.1074/jbc.m307453200;
RA Kikkert M., Doolman R., Dai M., Avner R., Hassink G., van Voorden S.,
RA Thanedar S., Roitelman J., Chau V., Wiertz E.;
RT "Human HRD1 is an E3 ubiquitin ligase involved in degradation of proteins
RT from the endoplasmic reticulum.";
RL J. Biol. Chem. 279:3525-3534(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Blood;
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 [8]
RP FUNCTION, HOMODIMERIZATION, INTERACTION WITH VCP; HERPUD1 AND DERL1,
RP IDENTIFICATION IN A COMPLEX WITH HERPUD1; VIMP AND DERL1, AND PATHWAY.
RX PubMed=16289116; DOI=10.1016/j.jmb.2005.10.020;
RA Schulze A., Standera S., Buerger E., Kikkert M., van Voorden S., Wiertz E.,
RA Koning F., Kloetzel P.-M., Seeger M.;
RT "The ubiquitin-domain protein HERP forms a complex with components of the
RT endoplasmic reticulum associated degradation pathway.";
RL J. Mol. Biol. 354:1021-1027(2005).
RN [9]
RP INTERACTION WITH VCP, AND SUBCELLULAR LOCATION.
RX PubMed=16186510; DOI=10.1073/pnas.0505006102;
RA Ye Y., Shibata Y., Kikkert M., van Voorden S., Wiertz E., Rapoport T.A.;
RT "Recruitment of the p97 ATPase and ubiquitin ligases to the site of
RT retrotranslocation at the endoplasmic reticulum membrane.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:14132-14138(2005).
RN [10]
RP IDENTIFICATION IN A COMPLEX WITH DERL2 AND SEL1L, AND INTERACTION WITH
RP SEL1L.
RX PubMed=16186509; DOI=10.1073/pnas.0505014102;
RA Lilley B.N., Ploegh H.L.;
RT "Multiprotein complexes that link dislocation, ubiquitination, and
RT extraction of misfolded proteins from the endoplasmic reticulum membrane.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:14296-14301(2005).
RN [11]
RP FUNCTION, PATHWAY, AND CATALYTIC ACTIVITY.
RX PubMed=17059562; DOI=10.1111/j.1471-4159.2006.04155.x;
RA Omura T., Kaneko M., Okuma Y., Orba Y., Nagashima K., Takahashi R.,
RA Fujitani N., Matsumura S., Hata A., Kubota K., Murahashi K., Uehara T.,
RA Nomura Y.;
RT "A ubiquitin ligase HRD1 promotes the degradation of Pael receptor, a
RT substrate of Parkin.";
RL J. Neurochem. 99:1456-1469(2006).
RN [12]
RP FUNCTION, AND PATHWAY.
RX PubMed=16847254; DOI=10.1073/pnas.0604816103;
RA Arteaga M.F., Wang L., Ravid T., Hochstrasser M., Canessa C.M.;
RT "An amphipathic helix targets serum and glucocorticoid-induced kinase 1 to
RT the endoplasmic reticulum-associated ubiquitin-conjugation machinery.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11178-11183(2006).
RN [13]
RP FUNCTION, INTERACTION WITH TP53, AND CATALYTIC ACTIVITY.
RX PubMed=17170702; DOI=10.1038/sj.emboj.7601490;
RA Yamasaki S., Yagishita N., Sasaki T., Nakazawa M., Kato Y., Yamadera T.,
RA Bae E., Toriyama S., Ikeda R., Zhang L., Fujitani K., Yoo E.,
RA Tsuchimochi K., Ohta T., Araya N., Fujita H., Aratani S., Eguchi K.,
RA Komiya S., Maruyama I., Higashi N., Sato M., Senoo H., Ochi T.,
RA Yokoyama S., Amano T., Kim J., Gay S., Fukamizu A., Nishioka K., Tanaka K.,
RA Nakajima T.;
RT "Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident
RT ubiquitin ligase 'Synoviolin'.";
RL EMBO J. 26:113-122(2007).
RN [14]
RP FUNCTION, INTERACTION WITH HTT, AND CATALYTIC ACTIVITY.
RX PubMed=17141218; DOI=10.1016/j.yexcr.2006.10.031;
RA Yang H., Zhong X., Ballar P., Luo S., Shen Y., Rubinsztein D.C.,
RA Monteiro M.J., Fang S.;
RT "Ubiquitin ligase Hrd1 enhances the degradation and suppresses the toxicity
RT of polyglutamine-expanded huntingtin.";
RL Exp. Cell Res. 313:538-550(2007).
RN [15]
RP INTERACTION WITH UBXN6.
RX PubMed=18656546; DOI=10.1016/j.biocel.2008.06.008;
RA Madsen L., Andersen K.M., Prag S., Moos T., Semple C.A., Seeger M.,
RA Hartmann-Petersen R.;
RT "Ubxd1 is a novel co-factor of the human p97 ATPase.";
RL Int. J. Biochem. Cell Biol. 40:2927-2942(2008).
RN [16]
RP INTERACTION WITH ERLEC1; HSPA5; OS9 AND SEL1L.
RX PubMed=18502753; DOI=10.1074/jbc.m709336200;
RA Hosokawa N., Wada I., Nagasawa K., Moriyama T., Okawa K., Nagata K.;
RT "Human XTP3-B forms an endoplasmic reticulum quality control scaffold with
RT the HRD1-SEL1L ubiquitin ligase complex and BiP.";
RL J. Biol. Chem. 283:20914-20924(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-613, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [18]
RP INTERACTION WITH ERLEC1; OS9 AND SEL1L.
RX PubMed=18264092; DOI=10.1038/ncb1689;
RA Christianson J.C., Shaler T.A., Tyler R.E., Kopito R.R.;
RT "OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L
RT ubiquitin ligase complex for ERAD.";
RL Nat. Cell Biol. 10:272-282(2008).
RN [19]
RP IDENTIFICATION BY 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-613, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP INTERACTION WITH BAG6.
RX PubMed=21636303; DOI=10.1016/j.molcel.2011.05.010;
RA Wang Q., Liu Y., Soetandyo N., Baek K., Hegde R., Ye Y.;
RT "A ubiquitin ligase-associated chaperone holdase maintains polypeptides in
RT soluble states for proteasome degradation.";
RL Mol. Cell 42:758-770(2011).
RN [23]
RP FUNCTION IN ERAD PATHWAY, AND PATHWAY.
RX PubMed=22607976; DOI=10.1016/j.molcel.2012.04.015;
RA Sato T., Sako Y., Sho M., Momohara M., Suico M.A., Shuto T., Nishitoh H.,
RA Okiyoneda T., Kokame K., Kaneko M., Taura M., Miyata M., Chosa K., Koga T.,
RA Morino-Koga S., Wada I., Kai H.;
RT "STT3B-dependent posttranslational N-glycosylation as a surveillance system
RT for secretory protein.";
RL Mol. Cell 47:99-110(2012).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-613, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
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 [26]
RP FUNCTION, INTERACTION WITH SEL1L, SUBCELLULAR LOCATION, AND PATHWAY.
RX PubMed=26471130; DOI=10.1111/febs.13564;
RA Hosokawa N., Wada I.;
RT "Association of the SEL1L protein transmembrane domain with HRD1 ubiquitin
RT ligase regulates ERAD-L.";
RL FEBS J. 283:157-172(2016).
RN [27]
RP FUNCTION, IDENTIFICATION IN THE HRD1 COMPLEX, AND MUTAGENESIS OF CYS-294
RP AND ARG-503.
RX PubMed=28827405; DOI=10.1242/jcs.206847;
RA Schulz J., Avci D., Queisser M.A., Gutschmidt A., Dreher L.S., Fenech E.J.,
RA Volkmar N., Hayashi Y., Hoppe T., Christianson J.C.;
RT "Conserved cytoplasmic domains promote Hrd1 ubiquitin ligase complex
RT formation for ER-associated degradation (ERAD).";
RL J. Cell Sci. 130:3322-3335(2017).
RN [28]
RP FUNCTION, AND INVOLVEMENT IN ABC-DLBCL.
RX PubMed=28842558; DOI=10.1038/s41467-017-00476-w;
RA Wang W.F., Yan L., Liu Z., Liu L.X., Lin J., Liu Z.Y., Chen X.P., Zhang W.,
RA Xu Z.Z., Shi T., Li J.M., Zhao Y.L., Meng G., Xia Y., Li J.Y., Zhu J.;
RT "HSP70-Hrd1 axis precludes the oncorepressor potential of N-terminal
RT misfolded Blimp-1s in lymphoma cells.";
RL Nat. Commun. 8:363-363(2017).
RN [29] {ECO:0007744|PDB:6A3Z}
RP STRUCTURE BY NMR OF 279-334 IN COMPLEX WITH ZINC.
RX PubMed=30345569; DOI=10.1002/pro.3532;
RA Miyamoto K., Taguchi Y., Saito K.;
RT "Unique RING finger structure from the human HRD1 protein.";
RL Protein Sci. 28:448-453(2019).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin
CC specifically from endoplasmic reticulum-associated UBC7 E2 ligase and
CC transfers it to substrates, promoting their degradation
CC (PubMed:12459480, PubMed:12646171, PubMed:12975321, PubMed:14593114,
CC PubMed:16289116, PubMed:16847254, PubMed:17059562, PubMed:17141218,
CC PubMed:17170702, PubMed:22607976, PubMed:26471130, PubMed:28827405).
CC Component of the endoplasmic reticulum quality control (ERQC) system
CC also called ER-associated degradation (ERAD) involved in ubiquitin-
CC dependent degradation of misfolded endoplasmic reticulum proteins
CC (PubMed:12459480, PubMed:12646171, PubMed:12975321, PubMed:14593114,
CC PubMed:16289116, PubMed:16847254, PubMed:17059562, PubMed:17141218,
CC PubMed:17170702, PubMed:22607976, PubMed:26471130, PubMed:28842558).
CC Also promotes the degradation of normal but naturally short-lived
CC proteins such as SGK. Protects cells from ER stress-induced apoptosis.
CC Protects neurons from apoptosis induced by polyglutamine-expanded
CC huntingtin (HTT) or unfolded GPR37 by promoting their degradation
CC (PubMed:17141218). Sequesters p53/TP53 in the cytoplasm and promotes
CC its degradation, thereby negatively regulating its biological function
CC in transcription, cell cycle regulation and apoptosis
CC (PubMed:17170702). Mediates the ubiquitination and subsequent
CC degradation of cytoplasmic NFE2L1 (By similarity). During the early
CC stage of B cell development, required for degradation of the pre-B cell
CC receptor (pre-BCR) complex, hence supporting further differentiation
CC into mature B cells (By similarity). {ECO:0000250|UniProtKB:Q9DBY1,
CC ECO:0000269|PubMed:12459480, ECO:0000269|PubMed:12646171,
CC ECO:0000269|PubMed:12975321, ECO:0000269|PubMed:14593114,
CC ECO:0000269|PubMed:16289116, ECO:0000269|PubMed:16847254,
CC ECO:0000269|PubMed:17059562, ECO:0000269|PubMed:17141218,
CC ECO:0000269|PubMed:17170702, ECO:0000269|PubMed:22607976,
CC ECO:0000269|PubMed:26471130, ECO:0000269|PubMed:28827405,
CC ECO:0000269|PubMed:28842558}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:12646171,
CC ECO:0000269|PubMed:12975321, ECO:0000269|PubMed:14593114,
CC ECO:0000269|PubMed:17059562, ECO:0000269|PubMed:17141218,
CC ECO:0000269|PubMed:17170702};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:12459480, ECO:0000269|PubMed:16289116,
CC ECO:0000269|PubMed:16847254, ECO:0000269|PubMed:17059562,
CC ECO:0000269|PubMed:22607976, ECO:0000269|PubMed:26471130}.
CC -!- SUBUNIT: Homodimer (PubMed:16289116). Interacts with p53/TP53
CC (PubMed:17170702). Interacts with HTT (PubMed:17141218). Component of
CC the HRD1 complex, which comprises at least SYNV1/HRD1, DERL1/2, FAM8A1,
CC HERPUD1/HERP, OS9, SEL1L and UBE2J1 (PubMed:16289116, PubMed:16186509,
CC PubMed:18264092, PubMed:26471130, PubMed:28827405). FAM8A1 is
CC stabilized by interaction with SYNV1, which prevents its proteasomal
CC degradation. OS9 and UBE2J1 recruitment to the complex may be mediated
CC by SEL1L (PubMed:28827405). SYNV1 assembles with SEL1L and FAM8A1
CC through its transmembrane domains, but interaction with its cytoplasmic
CC domain is required to confer stability to FAM8A1 and enhance
CC recruitment of HERPUD1 (PubMed:28827405). The HRD1 complex also
CC associates with VIMP and may transfer misfolded proteins from the
CC endoplasmic reticulum to VCP (PubMed:16289116). May form a complex with
CC ERLEC1; HSPA5; OS9 AND SEL1L (PubMed:18502753, PubMed:18264092).
CC Interacts with VCP (PubMed:16289116, PubMed:16186510). Interacts with
CC UBXN6 (PubMed:18656546). Interacts with BAG6 (PubMed:21636303).
CC Interacts with NFE2L1 (By similarity). Interacts (via N-terminus) with
CC components of the pre-B cell receptor, including IGLL1 and VPREB1 (By
CC similarity). Interacts with CREB3L3; this interaction leads to CREB3L3
CC ubiquitination and proteasomal degradation (By similarity).
CC {ECO:0000250|UniProtKB:Q9DBY1, ECO:0000269|PubMed:16186509,
CC ECO:0000269|PubMed:16186510, ECO:0000269|PubMed:16289116,
CC ECO:0000269|PubMed:17141218, ECO:0000269|PubMed:17170702,
CC ECO:0000269|PubMed:18264092, ECO:0000269|PubMed:18502753,
CC ECO:0000269|PubMed:18656546, ECO:0000269|PubMed:21636303,
CC ECO:0000269|PubMed:26471130, ECO:0000269|PubMed:28827405}.
CC -!- INTERACTION:
CC Q86TM6; O75477: ERLIN1; NbExp=2; IntAct=EBI-947849, EBI-359299;
CC Q86TM6; O94905: ERLIN2; NbExp=2; IntAct=EBI-947849, EBI-4400770;
CC Q86TM6; O75460: ERN1; NbExp=2; IntAct=EBI-947849, EBI-371750;
CC Q86TM6; O75460-1: ERN1; NbExp=3; IntAct=EBI-947849, EBI-15600828;
CC Q86TM6; Q9UBU6: FAM8A1; NbExp=20; IntAct=EBI-947849, EBI-6309101;
CC Q86TM6; Q9UBV2: SEL1L; NbExp=20; IntAct=EBI-947849, EBI-358766;
CC Q86TM6; P04637: TP53; NbExp=5; IntAct=EBI-947849, EBI-366083;
CC Q86TM6; Q9Y385: UBE2J1; NbExp=15; IntAct=EBI-947849, EBI-988826;
CC Q86TM6; Q9Y4E8: USP15; NbExp=8; IntAct=EBI-947849, EBI-1043104;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12459480, ECO:0000269|PubMed:12646171,
CC ECO:0000269|PubMed:14593114, ECO:0000269|PubMed:16186510,
CC ECO:0000269|PubMed:26471130}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:12459480, ECO:0000269|PubMed:12646171,
CC ECO:0000269|PubMed:14593114, ECO:0000269|PubMed:16186510}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=b, long;
CC IsoId=Q86TM6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86TM6-2; Sequence=VSP_023777, VSP_023778;
CC Name=3; Synonyms=a, short;
CC IsoId=Q86TM6-3; Sequence=VSP_023778;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in
CC liver and kidney (at protein level). Up-regulated in synovial tissues
CC from patients with rheumatoid arthritis (at protein level).
CC {ECO:0000269|PubMed:12459480, ECO:0000269|PubMed:12646171,
CC ECO:0000269|PubMed:12975321}.
CC -!- INDUCTION: By endoplasmic reticulum stress-inducing agents such as
CC thapsigargin, tunicamycin or brefeldin A, but not by heat shock.
CC {ECO:0000269|PubMed:12459480, ECO:0000269|PubMed:14593114}.
CC -!- DOMAIN: The RING-type zinc finger is required for E3 ligase activity.
CC -!- PTM: Not N-glycosylated.
CC -!- PTM: Auto-ubiquitinated. {ECO:0000269|PubMed:12459480,
CC ECO:0000269|PubMed:12646171, ECO:0000269|PubMed:12975321}.
CC -!- DISEASE: Note=In certain aggressive cases of activated B cell-like
CC diffuse large B-cell lymphoma (ABC-DLBCL), plays a role in the
CC degradation of misfolded N-terminal mutated PRDM1 proteins.
CC {ECO:0000269|PubMed:28842558}.
CC -!- SIMILARITY: Belongs to the HRD1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB47439.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB085847; BAC24801.1; -; mRNA.
DR EMBL; AB024690; BAC57449.1; -; mRNA.
DR EMBL; AF317634; AAL26903.1; -; mRNA.
DR EMBL; AB058713; BAB47439.1; ALT_INIT; mRNA.
DR EMBL; AL834262; CAD38937.1; -; mRNA.
DR EMBL; BC030530; AAH30530.1; -; mRNA.
DR CCDS; CCDS31605.1; -. [Q86TM6-1]
DR CCDS; CCDS8097.1; -. [Q86TM6-3]
DR RefSeq; NP_115807.1; NM_032431.2. [Q86TM6-3]
DR RefSeq; NP_757385.1; NM_172230.2. [Q86TM6-1]
DR RefSeq; XP_011543605.1; XM_011545303.2. [Q86TM6-1]
DR PDB; 6A3Z; NMR; -; A=279-334.
DR PDBsum; 6A3Z; -.
DR AlphaFoldDB; Q86TM6; -.
DR SMR; Q86TM6; -.
DR BioGRID; 124085; 334.
DR CORUM; Q86TM6; -.
DR DIP; DIP-43982N; -.
DR IntAct; Q86TM6; 57.
DR MINT; Q86TM6; -.
DR STRING; 9606.ENSP00000366395; -.
DR TCDB; 3.A.16.1.4; the endoplasmic reticular retrotranslocon (er-rt) family.
DR GlyGen; Q86TM6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86TM6; -.
DR PhosphoSitePlus; Q86TM6; -.
DR BioMuta; SYVN1; -.
DR DMDM; 134035039; -.
DR EPD; Q86TM6; -.
DR jPOST; Q86TM6; -.
DR MassIVE; Q86TM6; -.
DR MaxQB; Q86TM6; -.
DR PaxDb; Q86TM6; -.
DR PeptideAtlas; Q86TM6; -.
DR PRIDE; Q86TM6; -.
DR ProteomicsDB; 69713; -. [Q86TM6-1]
DR ProteomicsDB; 69714; -. [Q86TM6-2]
DR ProteomicsDB; 69715; -. [Q86TM6-3]
DR Antibodypedia; 1694; 395 antibodies from 37 providers.
DR DNASU; 84447; -.
DR Ensembl; ENST00000294256.12; ENSP00000294256.8; ENSG00000162298.19. [Q86TM6-3]
DR Ensembl; ENST00000307289.10; ENSP00000302035.6; ENSG00000162298.19. [Q86TM6-2]
DR Ensembl; ENST00000377190.8; ENSP00000366395.3; ENSG00000162298.19. [Q86TM6-1]
DR Ensembl; ENST00000526060.5; ENSP00000436984.1; ENSG00000162298.19. [Q86TM6-3]
DR GeneID; 84447; -.
DR KEGG; hsa:84447; -.
DR MANE-Select; ENST00000377190.8; ENSP00000366395.3; NM_172230.3; NP_757385.1.
DR UCSC; uc001odb.4; human. [Q86TM6-1]
DR CTD; 84447; -.
DR DisGeNET; 84447; -.
DR GeneCards; SYVN1; -.
DR HGNC; HGNC:20738; SYVN1.
DR HPA; ENSG00000162298; Low tissue specificity.
DR MIM; 608046; gene.
DR neXtProt; NX_Q86TM6; -.
DR OpenTargets; ENSG00000162298; -.
DR PharmGKB; PA128394735; -.
DR VEuPathDB; HostDB:ENSG00000162298; -.
DR eggNOG; KOG0802; Eukaryota.
DR GeneTree; ENSGT00940000157743; -.
DR HOGENOM; CLU_009169_3_0_1; -.
DR InParanoid; Q86TM6; -.
DR OMA; PGMGAPF; -.
DR OrthoDB; 897451at2759; -.
DR PhylomeDB; Q86TM6; -.
DR TreeFam; TF318635; -.
DR PathwayCommons; Q86TM6; -.
DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes.
DR Reactome; R-HSA-5358346; Hedgehog ligand biogenesis.
DR Reactome; R-HSA-5362768; Hh mutants are degraded by ERAD.
DR Reactome; R-HSA-901032; ER Quality Control Compartment (ERQC).
DR SignaLink; Q86TM6; -.
DR SIGNOR; Q86TM6; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 84447; 230 hits in 1137 CRISPR screens.
DR ChiTaRS; SYVN1; human.
DR GeneWiki; SYVN1; -.
DR GenomeRNAi; 84447; -.
DR Pharos; Q86TM6; Tbio.
DR PRO; PR:Q86TM6; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q86TM6; protein.
DR Bgee; ENSG00000162298; Expressed in ileal mucosa and 176 other tissues.
DR ExpressionAtlas; Q86TM6; baseline and differential.
DR Genevisible; Q86TM6; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0036513; C:Derlin-1 retrotranslocation complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IDA:UniProtKB.
DR GO; GO:0000836; C:Hrd1p ubiquitin ligase complex; TAS:ParkinsonsUK-UCL.
DR GO; GO:0000839; C:Hrd1p ubiquitin ligase ERAD-L complex; IDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; NAS:ParkinsonsUK-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051117; F:ATPase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0051087; F:chaperone binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:1990381; F:ubiquitin-specific protease binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0051082; F:unfolded protein binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:1904380; P:endoplasmic reticulum mannose trimming; TAS:Reactome.
DR GO; GO:0036503; P:ERAD pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:0002327; P:immature B cell differentiation; ISS:UniProtKB.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0050821; P:protein stabilization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0016567; P:protein ubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030970; P:retrograde protein transport, ER to cytosol; IMP:ParkinsonsUK-UCL.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:ParkinsonsUK-UCL.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR032832; E3_lig_synoviolin/Hrd1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR22763:SF169; PTHR22763:SF169; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Endoplasmic reticulum; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Stress response;
KW Transferase; Transmembrane; Transmembrane helix; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..617
FT /note="E3 ubiquitin-protein ligase synoviolin"
FT /id="PRO_0000280548"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 5..25
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 26..41
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 42..62
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 63..98
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 99..119
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 120..140
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 141..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 191..224
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 225..245
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 246..617
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT ZN_FING 291..330
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..251
FT /note="Involved in FAM8A1 interaction"
FT /evidence="ECO:0000269|PubMed:28827405"
FT REGION 1..84
FT /note="Necessary and sufficient for SEL1L interaction"
FT /evidence="ECO:0000269|PubMed:28827405"
FT REGION 236..270
FT /note="Interaction with p53/TP53"
FT /evidence="ECO:0000269|PubMed:17170702"
FT REGION 337..375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 393..453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 480..535
FT /note="HAF-H domain; necessary to form higher-order Hrd1
FT complexes"
FT /evidence="ECO:0000303|PubMed:28827405"
FT REGION 535..617
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 339..375
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 411..441
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 535..566
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 567..581
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 598..617
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 291
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:30345569,
FT ECO:0007744|PDB:6A3Z"
FT BINDING 294
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:30345569,
FT ECO:0007744|PDB:6A3Z"
FT BINDING 307
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:30345569,
FT ECO:0007744|PDB:6A3Z"
FT BINDING 309
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:30345569,
FT ECO:0007744|PDB:6A3Z"
FT BINDING 312
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:30345569,
FT ECO:0007744|PDB:6A3Z"
FT BINDING 315
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:30345569,
FT ECO:0007744|PDB:6A3Z"
FT BINDING 326
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:30345569,
FT ECO:0007744|PDB:6A3Z"
FT BINDING 329
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:30345569,
FT ECO:0007744|PDB:6A3Z"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 127..177
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11347906"
FT /id="VSP_023777"
FT VAR_SEQ 411
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11347906,
FT ECO:0000303|PubMed:12459480, ECO:0000303|PubMed:14593114,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_023778"
FT MUTAGEN 294
FT /note="C->A: No effect on interaction with FAM8A1, HERPUD1,
FT OS9, SEL1L and UBE2J1."
FT /evidence="ECO:0000269|PubMed:28827405"
FT MUTAGEN 329
FT /note="C->S: Abolishes E3 ligase activity."
FT /evidence="ECO:0000269|PubMed:12459480"
FT MUTAGEN 503
FT /note="R->L: Loss of interaction with FAM8A1, HERPUD1, OS9
FT and UBE2J1, impaired degradation of immature core-
FT glycosylated basigin/CD147."
FT /evidence="ECO:0000269|PubMed:28827405"
FT CONFLICT 145
FT /note="M -> I (in Ref. 1; BAC24801 and 4; AAL26903)"
FT /evidence="ECO:0000305"
FT CONFLICT 545
FT /note="E -> G (in Ref. 3; BAC57449)"
FT /evidence="ECO:0000305"
FT HELIX 281..285
FT /evidence="ECO:0007829|PDB:6A3Z"
FT TURN 286..289
FT /evidence="ECO:0007829|PDB:6A3Z"
FT TURN 292..295
FT /evidence="ECO:0007829|PDB:6A3Z"
FT STRAND 299..304
FT /evidence="ECO:0007829|PDB:6A3Z"
FT STRAND 310..312
FT /evidence="ECO:0007829|PDB:6A3Z"
FT HELIX 313..319
FT /evidence="ECO:0007829|PDB:6A3Z"
FT TURN 320..322
FT /evidence="ECO:0007829|PDB:6A3Z"
FT TURN 327..329
FT /evidence="ECO:0007829|PDB:6A3Z"
SQ SEQUENCE 617 AA; 67685 MW; B8A6BACBAF9673C1 CRC64;
MFRTAVMMAA SLALTGAVVA HAYYLKHQFY PTVVYLTKSS PSMAVLYIQA FVLVFLLGKV
MGKVFFGQLR AAEMEHLLER SWYAVTETCL AFTVFRDDFS PRFVALFTLL LFLKCFHWLA
EDRVDFMERS PNISWLFHCR IVSLMFLLGI LDFLFVSHAY HSILTRGASV QLVFGFEYAI
LMTMVLTIFI KYVLHSVDLQ SENPWDNKAV YMLYTELFTG FIKVLLYMAF MTIMIKVHTF
PLFAIRPMYL AMRQFKKAVT DAIMSRRAIR NMNTLYPDAT PEELQAMDNV CIICREEMVT
GAKRLPCNHI FHTSCLRSWF QRQQTCPTCR MDVLRASLPA QSPPPPEPAD QGPPPAPHPP
PLLPQPPNFP QGLLPPFPPG MFPLWPPMGP FPPVPPPPSS GEAVAPPSTS AAALSRPSGA
ATTTAAGTSA TAASATASGP GSGSAPEAGP APGFPFPPPW MGMPLPPPFA FPPMPVPPAG
FAGLTPEELR ALEGHERQHL EARLQSLRNI HTLLDAAMLQ INQYLTVLAS LGPPRPATSV
NSTEETATTV VAAASSTSIP SSEATTPTPG ASPPAPEMER PPAPESVGTE EMPEDGEPDA
AELRRRRLQK LESPVAH
