SIAH1_HUMAN
ID SIAH1_HUMAN Reviewed; 282 AA.
AC Q8IUQ4; A0FKF3; O43269; Q49A58; Q92880;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=E3 ubiquitin-protein ligase SIAH1;
DE EC=2.3.2.27 {ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:28546513};
DE AltName: Full=RING-type E3 ubiquitin transferase SIAH1 {ECO:0000305};
DE AltName: Full=Seven in absentia homolog 1;
DE Short=Siah-1;
DE AltName: Full=Siah-1a;
GN Name=SIAH1; Synonyms=HUMSIAH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Intestinal epithelium;
RX PubMed=8799150; DOI=10.1073/pnas.93.17.9039;
RA Nemani M., Linares-Cruz G., Bruzzoni-Giovanelli H., Roperch J.-P.,
RA Tuynder M., Bougueleret L., Cherif D., Medhioub M., Pasturaud P.,
RA Alvaro V., Der Sarkissan H., Cazes L., Le Paslier D., Le Gall I.,
RA Israeli D., Dausset J., Sigaux F., Chumakov I., Oren M., Calvo F.,
RA Amson R.B., Cohen D., Telerman A.;
RT "Activation of the human homologue of the Drosophila sina gene in apoptosis
RT and tumor suppression.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:9039-9042(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=9403064; DOI=10.1006/geno.1997.4997;
RA Hu G., Chung Y.-L., Glover T., Valentine V., Look A.T., Fearon E.R.;
RT "Characterization of human homologs of the Drosophila seven in absentia
RT (sina) gene.";
RL Genomics 46:103-111(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10956387;
RX DOI=10.1002/1097-0215(20000915)87:6<794::aid-ijc5>3.0.co;2-b;
RA Medhioub M., Vaury C., Hamelin R., Thomas G.;
RT "Lack of somatic mutation in the coding sequence of SIAH1 in tumors
RT hemizygous for this candidate tumor suppressor gene.";
RL Int. J. Cancer 87:794-797(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=17420721; DOI=10.1038/sj.onc.1210449;
RA Mei Y., Xie C., Xie W., Wu Z., Wu M.;
RT "Siah-1S, a novel splice variant of Siah-1 (seven in absentia homolog),
RT counteracts Siah-1-mediated downregulation of beta-catenin.";
RL Oncogene 26:6319-6331(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Retina;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, Pancreas, and Testis;
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 FUNCTION IN DEGRADATION OF DCC, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP UBE2I AND DCC.
RX PubMed=9334332; DOI=10.1101/gad.11.20.2701;
RA Hu G., Zhang S., Vidal M., Baer J.L., Xu T., Fearon E.R.;
RT "Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-
RT proteasome pathway.";
RL Genes Dev. 11:2701-2714(1997).
RN [8]
RP INTERACTION WITH BAG1, AND SUBCELLULAR LOCATION.
RX PubMed=9582267; DOI=10.1093/emboj/17.10.2736;
RA Matsuzawa S., Takayama S., Froesch B.A., Zapata J.M., Reed J.C.;
RT "p53-inducible human homologue of Drosophila seven in absentia (Siah)
RT inhibits cell growth: suppression by BAG-1.";
RL EMBO J. 17:2736-2747(1998).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-40; CYS-41; CYS-44;
RP CYS-55; HIS-59; ARG-66; LYS-68; ARG-76; HIS-152; HIS-202 AND LEU-211.
RX PubMed=9858595; DOI=10.1128/mcb.19.1.724;
RA Hu G., Fearon E.R.;
RT "Siah-1 N-terminal RING domain is required for proteolysis function, and C-
RT terminal sequences regulate oligomerization and binding to target
RT proteins.";
RL Mol. Cell. Biol. 19:724-732(1999).
RN [10]
RP FUNCTION IN DEGRADATION OF KIF22, AND INTERACTION WITH ALPHA-TUBULIN.
RX PubMed=11146551; DOI=10.1038/sj.onc.1204002;
RA Germani A., Bruzzoni-Giovanelli H., Fellous A., Gisselbrecht S.,
RA Varin-Blank N., Calvo F.;
RT "SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the
RT proteasome pathway during mitosis.";
RL Oncogene 19:5997-6006(2000).
RN [11]
RP FUNCTION IN DEGRADATION OF MYB.
RX PubMed=10747903; DOI=10.1074/jbc.m000372200;
RA Tanikawa J., Ichikawa-Iwata E., Kanei-Ishii C., Nakai A., Matsuzawa S.,
RA Reed J.C., Ishii S.;
RT "p53 suppresses the c-Myb-induced activation of heat shock transcription
RT factor 3.";
RL J. Biol. Chem. 275:15578-15585(2000).
RN [12]
RP FUNCTION IN DEGRADATION OF CTNNB1, AND SUBUNIT OF A COMPLEX WITH UBE2D1;
RP CACYBP; SKP1; APC AND TBL1X.
RX PubMed=11389839; DOI=10.1016/s1097-2765(01)00242-8;
RA Matsuzawa S., Reed J.C.;
RT "Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin
RT degradation linked to p53 responses.";
RL Mol. Cell 7:915-926(2001).
RN [13]
RP FUNCTION IN DEGRADATION OF CTNNB1.
RX PubMed=11389840; DOI=10.1016/s1097-2765(01)00241-6;
RA Liu J., Stevens J., Rote C.A., Yost H.J., Hu Y., Neufeld K.L., White R.L.,
RA Matsunami N.;
RT "Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to
RT the adenomatous polyposis coli protein.";
RL Mol. Cell 7:927-936(2001).
RN [14]
RP FUNCTION IN DEGRADATION OF POU2AF1, AND SUBCELLULAR LOCATION.
RX PubMed=11483517; DOI=10.1093/emboj/20.15.4143;
RA Tiedt R., Bartholdy B.A., Matthias G., Newell J.W., Matthias P.;
RT "The RING finger protein Siah-1 regulates the level of the transcriptional
RT coactivator OBF-1.";
RL EMBO J. 20:4143-4152(2001).
RN [15]
RP FUNCTION IN DEGRADATION OF POU2AF1.
RX PubMed=11483518; DOI=10.1093/emboj/20.15.4153;
RA Boehm J., He Y., Greiner A., Staudt L., Wirth T.;
RT "Regulation of BOB.1/OBF.1 stability by SIAH.";
RL EMBO J. 20:4153-4162(2001).
RN [16]
RP FUNCTION IN DEGRADATION OF NUMB.
RX PubMed=11752454; DOI=10.1073/pnas.261571998;
RA Susini L., Passer B.J., Amzallag-Elbaz N., Juven-Gershon T., Prieur S.,
RA Privat N., Tuynder M., Gendron M.-C., Israeel A., Amson R., Oren M.,
RA Telerman A.;
RT "Siah-1 binds and regulates the function of Numb.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:15067-15072(2001).
RN [17]
RP FUNCTION IN DEGRADATION OF KLF10.
RX PubMed=12072443; DOI=10.1074/jbc.m204812200;
RA Johnsen S.A., Subramaniam M., Monroe D.G., Janknecht R., Spelsberg T.C.;
RT "Modulation of transforming growth factor beta (TGFbeta)/Smad
RT transcriptional responses through targeted degradation of TGFbeta-inducible
RT early gene-1 by human seven in absentia homologue.";
RL J. Biol. Chem. 277:30754-30759(2002).
RN [18]
RP FUNCTION IN DEGRADATION OF SNCAIP, AND SUBCELLULAR LOCATION.
RX PubMed=14506261; DOI=10.1074/jbc.m306347200;
RA Nagano Y., Yamashita H., Takahashi T., Kishida S., Nakamura T., Iseki E.,
RA Hattori N., Mizuno Y., Kikuchi A., Matsumoto M.;
RT "Siah-1 facilitates ubiquitination and degradation of synphilin-1.";
RL J. Biol. Chem. 278:51504-51514(2003).
RN [19]
RP INTERACTION WITH PEG10.
RX PubMed=12810624;
RA Okabe H., Satoh S., Furukawa Y., Kato T., Hasegawa S., Nakajima Y.,
RA Yamaoka Y., Nakamura Y.;
RT "Involvement of PEG10 in human hepatocellular carcinogenesis through
RT interaction with SIAH1.";
RL Cancer Res. 63:3043-3048(2003).
RN [20]
RP TISSUE SPECIFICITY.
RX PubMed=12557228; DOI=10.1002/gcc.10170;
RA Matsuo K., Satoh S., Okabe H., Nomura A., Maeda T., Yamaoka Y., Ikai I.;
RT "SIAH1 inactivation correlates with tumor progression in hepatocellular
RT carcinomas.";
RL Genes Chromosomes Cancer 36:283-291(2003).
RN [21]
RP FUNCTION IN DEGRADATION OF RBBP8.
RX PubMed=14654780; DOI=10.1038/sj.onc.1206994;
RA Germani A., Prabel A., Mourah S., Podgorniak M.-P., Di Carlo A.,
RA Ehrlich R., Gisselbrecht S., Varin-Blank N., Calvo F.,
RA Bruzzoni-Giovanelli H.;
RT "SIAH-1 interacts with CtIP and promotes its degradation by the proteasome
RT pathway.";
RL Oncogene 22:8845-8851(2003).
RN [22]
RP INTERACTION WITH CACYBP, MUTANTS A; B; C; D AND E, AND MUTAGENESIS OF
RP ARG-124; ASP-142; GLN-151; ARG-224; GLU-226; ARG-233; GLU-237; ASN-253 AND
RP GLN-265.
RX PubMed=12421809; DOI=10.1074/jbc.m210263200;
RA Matsuzawa S., Li C., Ni C.-Z., Takayama S., Reed J.C., Ely K.R.;
RT "Structural analysis of Siah1 and its interactions with Siah-interacting
RT protein (SIP).";
RL J. Biol. Chem. 278:1837-1840(2003).
RN [23]
RP INTERACTION WITH KHDRBS3.
RX PubMed=15163637; DOI=10.1093/hmg/ddh165;
RA Venables J.P., Dalgliesh C., Paronetto M.P., Skitt L., Thornton J.K.,
RA Saunders P.T., Sette C., Jones K.T., Elliott D.J.;
RT "SIAH1 targets the alternative splicing factor T-STAR for degradation by
RT the proteasome.";
RL Hum. Mol. Genet. 13:1525-1534(2004).
RN [24]
RP FUNCTION IN DEGRADATION OF PML, AND MUTANTS A AND D.
RX PubMed=14645235; DOI=10.1074/jbc.m306407200;
RA Fanelli M., Fantozzi A., De Luca P., Caprodossi S., Matsuzawa S.,
RA Lazar M.A., Pelicci P.G., Minucci S.;
RT "The coiled-coil domain is the structural determinant for mammalian
RT homologues of Drosophila Sina-mediated degradation of promyelocytic
RT leukemia protein and other tripartite motif proteins by the proteasome.";
RL J. Biol. Chem. 279:5374-5379(2004).
RN [25]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SNCAIP AND SNCA, AND
RP MUTAGENESIS OF CYS-55; HIS-59 AND CYS-72.
RX PubMed=15064394; DOI=10.1073/pnas.0401081101;
RA Liani E., Eyal A., Avraham E., Shemer R., Szargel R., Berg D.,
RA Bornemann A., Riess O., Ross C.A., Rott R., Engelender S.;
RT "Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence
RT in cellular inclusions and Lewy bodies imply a role in Parkinson's
RT disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:5500-5505(2004).
RN [26]
RP FUNCTION, MUTAGENESIS OF SER-19 AND CYS-44, INTERACTION WITH HIPK2, AND
RP PHOSPHORYLATION AT SER-19 BY ATM AND ATR.
RX PubMed=18536714; DOI=10.1038/ncb1743;
RA Winter M., Sombroek D., Dauth I., Moehlenbrink J., Scheuermann K.,
RA Crone J., Hofmann T.G.;
RT "Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint
RT kinases ATM and ATR.";
RL Nat. Cell Biol. 10:812-824(2008).
RN [27]
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 [28]
RP INTERACTION WITH SNCAIP, CATALYTIC ACTIVITY, ACTIVITY REGULATION, FUNCTION,
RP AND PATHWAY.
RX PubMed=19224863; DOI=10.1074/jbc.m805990200;
RA Szargel R., Rott R., Eyal A., Haskin J., Shani V., Balan L., Wolosker H.,
RA Engelender S.;
RT "Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates
RT alpha-synuclein monoubiquitylation and inclusion formation.";
RL J. Biol. Chem. 284:11706-11716(2009).
RN [29]
RP FUNCTION IN UBIQUITINATION OF FLT3.
RX PubMed=20508617; DOI=10.1038/leu.2010.114;
RA Buchwald M., Pietschmann K., Muller J.P., Bohmer F.D., Heinzel T.,
RA Kramer O.H.;
RT "Ubiquitin conjugase UBCH8 targets active FMS-like tyrosine kinase 3 for
RT proteasomal degradation.";
RL Leukemia 24:1412-1421(2010).
RN [30]
RP FUNCTION.
RX PubMed=22483617; DOI=10.1016/j.molcel.2012.03.007;
RA Liu M., Hsu J., Chan C., Li Z., Zhou Q.;
RT "The ubiquitin ligase Siah1 controls ELL2 stability and formation of super
RT elongation complexes to modulate gene transcription.";
RL Mol. Cell 46:325-334(2012).
RN [31] {ECO:0007744|PDB:2A25}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 90-282 IN COMPLEX WITH ZINC IONS
RP AND CACYBP, FUNCTION, MUTAGENESIS OF 198-LYS--ASP-200 AND MET-252, AND
RP INTERACTION WITH CACYBP.
RX PubMed=16085652; DOI=10.1074/jbc.m506707200;
RA Santelli E., Leone M., Li C., Fukushima T., Preece N.E., Olson A.J.,
RA Ely K.R., Reed J.C., Pellecchia M., Liddington R.C., Matsuzawa S.;
RT "Structural analysis of Siah1-Siah-interacting protein interactions and
RT insights into the assembly of an E3 ligase multiprotein complex.";
RL J. Biol. Chem. 280:34278-34287(2005).
RN [32] {ECO:0007744|PDB:5WZZ}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 93-282 IN COMPLEX WITH ZINC IONS
RP AND AXIN1, INTERACTION WITH AXIN1, FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=28546513; DOI=10.1101/gad.300053.117;
RA Ji L., Jiang B., Jiang X., Charlat O., Chen A., Mickanin C., Bauer A.,
RA Xu W., Yan X., Cong F.;
RT "The SIAH E3 ubiquitin ligases promote Wnt/beta-catenin signaling through
RT mediating Wnt-induced Axin degradation.";
RL Genes Dev. 31:904-915(2017).
RN [33]
RP VARIANTS BURHAS GLY-41; LEU-50; PHE-128; ALA-168 AND ARG-174,
RP CHARACTERIZATION OF VARIANTS BURHAS GLY-41; LEU-50; PHE-128; ALA-168 AND
RP ARG-174, AND FUNCTION.
RX PubMed=32430360; DOI=10.1136/jmedgenet-2019-106335;
RA Buratti J., Ji L., Keren B., Lee Y., Booke S., Erdin S., Kim S.Y.,
RA Palculict T.B., Meiner V., Chae J.H., Woods C.G., Tam A., Heron D.,
RA Cong F., Harel T.;
RT "De novo variants in SIAH1, encoding an E3 ubiquitin ligase, are associated
RT with developmental delay, hypotonia and dysmorphic features.";
RL J. Med. Genet. 58:205-212(2021).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and
CC subsequent proteasomal degradation of target proteins (PubMed:14506261,
CC PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652,
CC PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332,
CC PubMed:9858595, PubMed:28546513, PubMed:32430360). E3 ubiquitin ligases
CC accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of
CC a thioester and then directly transfers the ubiquitin to targeted
CC substrates (PubMed:14506261, PubMed:14645235, PubMed:14654780,
CC PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617,
CC PubMed:22483617, PubMed:9334332, PubMed:9858595). Mediates E3 ubiquitin
CC ligase activity either through direct binding to substrates or by
CC functioning as the essential RING domain subunit of larger E3 complexes
CC (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394,
CC PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617,
CC PubMed:9334332, PubMed:9858595). Triggers the ubiquitin-mediated
CC degradation of many substrates, including proteins involved in
CC transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell
CC surface receptor (DCC), the cell-surface receptor-type tyrosine kinase
CC FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and
CC NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein
CC (KIF22), a protein involved in synaptic vesicle function in neurons
CC (SYP), a structural protein (CTNNB1) and SNCAIP (PubMed:10747903,
CC PubMed:11146551, PubMed:11389839, PubMed:11389840, PubMed:11483517,
CC PubMed:11483518, PubMed:11752454, PubMed:12072443). Confers
CC constitutive instability to HIPK2 through proteasomal degradation
CC (PubMed:18536714). It is thereby involved in many cellular processes
CC such as apoptosis, tumor suppression, cell cycle, axon guidance,
CC transcription regulation, spermatogenesis and TNF-alpha signaling
CC (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394,
CC PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617,
CC PubMed:9334332, PubMed:9858595). Has some overlapping function with
CC SIAH2 (PubMed:14506261, PubMed:14645235, PubMed:14654780,
CC PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617,
CC PubMed:22483617, PubMed:9334332, PubMed:9858595). Induces apoptosis in
CC cooperation with PEG3 (By similarity). Upon nitric oxid (NO) generation
CC that follows apoptotic stimulation, interacts with S-nitrosylated
CC GAPDH, mediating the translocation of GAPDH to the nucleus (By
CC similarity). GAPDH acts as a stabilizer of SIAH1, facilitating the
CC degradation of nuclear proteins (By similarity). Mediates
CC ubiquitination and degradation of EGLN2 and EGLN3 in response to the
CC unfolded protein response (UPR), leading to their degradation and
CC subsequent stabilization of ATF4 (By similarity). Also part of the Wnt
CC signaling pathway in which it mediates the Wnt-induced ubiquitin-
CC mediated proteasomal degradation of AXIN1 (PubMed:28546513,
CC PubMed:32430360). {ECO:0000250|UniProtKB:P61092,
CC ECO:0000250|UniProtKB:Q920M9, ECO:0000269|PubMed:10747903,
CC ECO:0000269|PubMed:11146551, ECO:0000269|PubMed:11389839,
CC ECO:0000269|PubMed:11389840, ECO:0000269|PubMed:11483517,
CC ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:11752454,
CC ECO:0000269|PubMed:12072443, ECO:0000269|PubMed:14506261,
CC ECO:0000269|PubMed:14645235, ECO:0000269|PubMed:14654780,
CC ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:16085652,
CC ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:19224863,
CC ECO:0000269|PubMed:20508617, ECO:0000269|PubMed:22483617,
CC ECO:0000269|PubMed:28546513, ECO:0000269|PubMed:32430360,
CC ECO:0000269|PubMed:9334332, ECO:0000269|PubMed:9858595}.
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:19224863,
CC ECO:0000269|PubMed:28546513};
CC -!- ACTIVITY REGULATION: Inhibited by interaction with SNCAIP (isoform 2,
CC but not isoform 1). May be inhibited by interaction with PEG10.
CC {ECO:0000269|PubMed:19224863}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:28546513}.
CC -!- SUBUNIT: Homodimer. Interacts with group 1 glutamate receptors GRM1 and
CC GRM5. Interacts with DAB1, which may inhibit its activity. Interacts
CC with UBE2E2. Interacts with PEG3. Interacts with GAPDH; leading to
CC stabilize SIAH1 (By similarity). Component of some large E3 complex
CC composed of UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts
CC with UBE2I. Interacts with alpha-tubulin. Interacts with PEG10, which
CC may inhibit its activity. Interacts with KHDRBS3. Interacts with SNCAIP
CC and HIPK2. Interacts with Bassoon/BSN and Piccolo/PLCO; these
CC interactions negatively regulate SIAH1 E3 ligase activity (By
CC similarity). Interacts with DCC (PubMed:9334332). Interacts with AXIN1;
CC catalyzes AXIN1 ubiquitination and subsequent proteasome-mediated
CC ubiquitin-dependent degradation (PubMed:28546513).
CC {ECO:0000250|UniProtKB:P61092, ECO:0000250|UniProtKB:Q920M9,
CC ECO:0000269|PubMed:11146551, ECO:0000269|PubMed:11389839,
CC ECO:0000269|PubMed:12421809, ECO:0000269|PubMed:12810624,
CC ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:15163637,
CC ECO:0000269|PubMed:16085652, ECO:0000269|PubMed:18536714,
CC ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:9334332,
CC ECO:0000269|PubMed:9582267}.
CC -!- INTERACTION:
CC Q8IUQ4; Q9NRN7: AASDHPPT; NbExp=3; IntAct=EBI-747107, EBI-740884;
CC Q8IUQ4; Q9UHB7: AFF4; NbExp=5; IntAct=EBI-747107, EBI-395282;
CC Q8IUQ4; Q9UHB7-2: AFF4; NbExp=5; IntAct=EBI-747107, EBI-10261324;
CC Q8IUQ4; P29972: AQP1; NbExp=3; IntAct=EBI-747107, EBI-745213;
CC Q8IUQ4; Q7Z3E5-2: ARMC9; NbExp=3; IntAct=EBI-747107, EBI-10256990;
CC Q8IUQ4; O15265: ATXN7; NbExp=2; IntAct=EBI-747107, EBI-708350;
CC Q8IUQ4; P41182: BCL6; NbExp=3; IntAct=EBI-747107, EBI-765407;
CC Q8IUQ4; P40121: CAPG; NbExp=3; IntAct=EBI-747107, EBI-4291044;
CC Q8IUQ4; Q9NVL8: CCDC198; NbExp=3; IntAct=EBI-747107, EBI-10238351;
CC Q8IUQ4; Q9UJX2: CDC23; NbExp=3; IntAct=EBI-747107, EBI-396137;
CC Q8IUQ4; P49427: CDC34; NbExp=3; IntAct=EBI-747107, EBI-975634;
CC Q8IUQ4; Q8N619: CDK5R1; NbExp=3; IntAct=EBI-747107, EBI-10266998;
CC Q8IUQ4; Q8TAM4: CDK5R1; NbExp=3; IntAct=EBI-747107, EBI-10271838;
CC Q8IUQ4; Q9UJV9: DDX41; NbExp=3; IntAct=EBI-747107, EBI-1046350;
CC Q8IUQ4; Q9Y5T4: DNAJC15; NbExp=3; IntAct=EBI-747107, EBI-10329228;
CC Q8IUQ4; O14645: DNALI1; NbExp=3; IntAct=EBI-747107, EBI-395638;
CC Q8IUQ4; P29692: EEF1D; NbExp=4; IntAct=EBI-747107, EBI-358607;
CC Q8IUQ4; Q8N2X6: EXOC3-AS1; NbExp=3; IntAct=EBI-747107, EBI-749333;
CC Q8IUQ4; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-747107, EBI-6658203;
CC Q8IUQ4; Q01543: FLI1; NbExp=3; IntAct=EBI-747107, EBI-2271018;
CC Q8IUQ4; Q8TAN2: FZD9; NbExp=3; IntAct=EBI-747107, EBI-741016;
CC Q8IUQ4; Q8WTR4: GDPD5; NbExp=3; IntAct=EBI-747107, EBI-2833203;
CC Q8IUQ4; P62805: H4C9; NbExp=3; IntAct=EBI-747107, EBI-302023;
CC Q8IUQ4; P05111: INHA; NbExp=3; IntAct=EBI-747107, EBI-10194422;
CC Q8IUQ4; Q9H0B3: IQCN; NbExp=3; IntAct=EBI-747107, EBI-745878;
CC Q8IUQ4; Q9BW62: KATNAL1; NbExp=3; IntAct=EBI-747107, EBI-743591;
CC Q8IUQ4; P78508: KCNJ10; NbExp=3; IntAct=EBI-747107, EBI-9117877;
CC Q8IUQ4; Q8IZA0: KIAA0319L; NbExp=3; IntAct=EBI-747107, EBI-5240269;
CC Q8IUQ4; Q5T5P2-6: KIAA1217; NbExp=3; IntAct=EBI-747107, EBI-10188326;
CC Q8IUQ4; O60333: KIF1B; NbExp=3; IntAct=EBI-747107, EBI-465633;
CC Q8IUQ4; Q9BVG8: KIFC3; NbExp=3; IntAct=EBI-747107, EBI-2125614;
CC Q8IUQ4; Q53H82: LACTB2; NbExp=3; IntAct=EBI-747107, EBI-3943430;
CC Q8IUQ4; Q13394: MAB21L1; NbExp=3; IntAct=EBI-747107, EBI-10229059;
CC Q8IUQ4; P53778: MAPK12; NbExp=3; IntAct=EBI-747107, EBI-602406;
CC Q8IUQ4; O60336: MAPKBP1; NbExp=3; IntAct=EBI-747107, EBI-947402;
CC Q8IUQ4; Q70IA8: MOB3C; NbExp=3; IntAct=EBI-747107, EBI-9679267;
CC Q8IUQ4; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-747107, EBI-3923617;
CC Q8IUQ4; P20591: MX1; NbExp=3; IntAct=EBI-747107, EBI-929476;
CC Q8IUQ4; Q99836: MYD88; NbExp=3; IntAct=EBI-747107, EBI-447677;
CC Q8IUQ4; Q92692: NECTIN2; NbExp=3; IntAct=EBI-747107, EBI-718419;
CC Q8IUQ4; Q9H3P2: NELFA; NbExp=3; IntAct=EBI-747107, EBI-5461341;
CC Q8IUQ4; Q9H6R4-4: NOL6; NbExp=3; IntAct=EBI-747107, EBI-10307896;
CC Q8IUQ4; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-747107, EBI-741158;
CC Q8IUQ4; P35372: OPRM1; NbExp=4; IntAct=EBI-747107, EBI-2624570;
CC Q8IUQ4; Q96DC9: OTUB2; NbExp=3; IntAct=EBI-747107, EBI-746259;
CC Q8IUQ4; Q86TG7: PEG10; NbExp=3; IntAct=EBI-747107, EBI-2858265;
CC Q8IUQ4; P08237: PFKM; NbExp=3; IntAct=EBI-747107, EBI-514788;
CC Q8IUQ4; Q8IXK0: PHC2; NbExp=5; IntAct=EBI-747107, EBI-713786;
CC Q8IUQ4; Q16633: POU2AF1; NbExp=2; IntAct=EBI-747107, EBI-943588;
CC Q8IUQ4; Q8WWY3: PRPF31; NbExp=3; IntAct=EBI-747107, EBI-1567797;
CC Q8IUQ4; P86479: PRR20C; NbExp=5; IntAct=EBI-747107, EBI-10172814;
CC Q8IUQ4; Q8WUK0: PTPMT1; NbExp=3; IntAct=EBI-747107, EBI-7199479;
CC Q8IUQ4; Q9UHX1: PUF60; NbExp=7; IntAct=EBI-747107, EBI-1053259;
CC Q8IUQ4; P11216: PYGB; NbExp=3; IntAct=EBI-747107, EBI-1047231;
CC Q8IUQ4; Q2TAL8: QRICH1; NbExp=3; IntAct=EBI-747107, EBI-2798044;
CC Q8IUQ4; Q14088: RAB33A; NbExp=3; IntAct=EBI-747107, EBI-744685;
CC Q8IUQ4; Q96B01: RAD51AP1; NbExp=3; IntAct=EBI-747107, EBI-1178724;
CC Q8IUQ4; Q96B01-2: RAD51AP1; NbExp=3; IntAct=EBI-747107, EBI-1178743;
CC Q8IUQ4; Q9Y4B4: RAD54L2; NbExp=3; IntAct=EBI-747107, EBI-948156;
CC Q8IUQ4; Q86WX3: RPS19BP1; NbExp=3; IntAct=EBI-747107, EBI-4479407;
CC Q8IUQ4; O00560: SDCBP; NbExp=3; IntAct=EBI-747107, EBI-727004;
CC Q8IUQ4; O43236-6: SEPTIN4; NbExp=2; IntAct=EBI-747107, EBI-4372019;
CC Q8IUQ4; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-747107, EBI-747107;
CC Q8IUQ4; Q8NEY3: SPATA4; NbExp=3; IntAct=EBI-747107, EBI-7067221;
CC Q8IUQ4; Q9H0A9: SPATC1L; NbExp=3; IntAct=EBI-747107, EBI-372911;
CC Q8IUQ4; O43581: SYT7; NbExp=3; IntAct=EBI-747107, EBI-10184345;
CC Q8IUQ4; Q9NU19: TBC1D22B; NbExp=3; IntAct=EBI-747107, EBI-8787464;
CC Q8IUQ4; Q9BTV4: TMEM43; NbExp=3; IntAct=EBI-747107, EBI-721293;
CC Q8IUQ4; Q6FIE9: TOLLIP; NbExp=3; IntAct=EBI-747107, EBI-10249783;
CC Q8IUQ4; Q13625-3: TP53BP2; NbExp=3; IntAct=EBI-747107, EBI-10175039;
CC Q8IUQ4; P36406: TRIM23; NbExp=3; IntAct=EBI-747107, EBI-740098;
CC Q8IUQ4; P14373: TRIM27; NbExp=3; IntAct=EBI-747107, EBI-719493;
CC Q8IUQ4; Q9C029: TRIM7; NbExp=3; IntAct=EBI-747107, EBI-2813981;
CC Q8IUQ4; P61086: UBE2K; NbExp=4; IntAct=EBI-747107, EBI-473850;
CC Q8IUQ4; O95045: UPP2; NbExp=3; IntAct=EBI-747107, EBI-10191025;
CC Q8IUQ4; Q9UBK9: UXT; NbExp=3; IntAct=EBI-747107, EBI-357355;
CC Q8IUQ4; P98170: XIAP; NbExp=3; IntAct=EBI-747107, EBI-517127;
CC Q8IUQ4; A2RRL9: ZBP1; NbExp=3; IntAct=EBI-747107, EBI-10173066;
CC Q8IUQ4; Q8TBK6: ZCCHC10; NbExp=3; IntAct=EBI-747107, EBI-597063;
CC Q8IUQ4; Q8WW36: ZCCHC13; NbExp=3; IntAct=EBI-747107, EBI-954111;
CC Q8IUQ4; Q9BQ24: ZFYVE21; NbExp=3; IntAct=EBI-747107, EBI-2849569;
CC Q8IUQ4; Q9HA38: ZMAT3; NbExp=3; IntAct=EBI-747107, EBI-2548480;
CC Q8IUQ4; Q9UQR1: ZNF148; NbExp=3; IntAct=EBI-747107, EBI-2688184;
CC Q8IUQ4; Q96KM6: ZNF512B; NbExp=3; IntAct=EBI-747107, EBI-1049952;
CC Q8IUQ4; Q59GP6; NbExp=3; IntAct=EBI-747107, EBI-10243413;
CC Q8IUQ4; Q64693: Pou2af1; Xeno; NbExp=5; IntAct=EBI-747107, EBI-943530;
CC Q8IUQ4; Q69ZI1: Sh3rf1; Xeno; NbExp=5; IntAct=EBI-747107, EBI-957380;
CC Q8IUQ4; P69713: X; Xeno; NbExp=4; IntAct=EBI-747107, EBI-7088789;
CC Q8IUQ4-2; Q06481-5: APLP2; NbExp=3; IntAct=EBI-11522811, EBI-25646567;
CC Q8IUQ4-2; P05067: APP; NbExp=3; IntAct=EBI-11522811, EBI-77613;
CC Q8IUQ4-2; P05067-2: APP; NbExp=3; IntAct=EBI-11522811, EBI-17264467;
CC Q8IUQ4-2; Q86V38: ATN1; NbExp=3; IntAct=EBI-11522811, EBI-11954292;
CC Q8IUQ4-2; P54253: ATXN1; NbExp=3; IntAct=EBI-11522811, EBI-930964;
CC Q8IUQ4-2; A0A0S2Z4M1: AXIN1; NbExp=3; IntAct=EBI-11522811, EBI-16429430;
CC Q8IUQ4-2; O95817: BAG3; NbExp=3; IntAct=EBI-11522811, EBI-747185;
CC Q8IUQ4-2; O95429: BAG4; NbExp=3; IntAct=EBI-11522811, EBI-2949658;
CC Q8IUQ4-2; Q96A83-2: COL26A1; NbExp=3; IntAct=EBI-11522811, EBI-21553822;
CC Q8IUQ4-2; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-11522811, EBI-9087876;
CC Q8IUQ4-2; P05111: INHA; NbExp=3; IntAct=EBI-11522811, EBI-10194422;
CC Q8IUQ4-2; Q92876: KLK6; NbExp=3; IntAct=EBI-11522811, EBI-2432309;
CC Q8IUQ4-2; Q9NS86: LANCL2; NbExp=3; IntAct=EBI-11522811, EBI-2510837;
CC Q8IUQ4-2; Q8TC57: M1AP; NbExp=3; IntAct=EBI-11522811, EBI-748182;
CC Q8IUQ4-2; Q9UPY8: MAPRE3; NbExp=3; IntAct=EBI-11522811, EBI-726739;
CC Q8IUQ4-2; O75376: NCOR1; NbExp=3; IntAct=EBI-11522811, EBI-347233;
CC Q8IUQ4-2; Q9BSJ6: PIMREG; NbExp=3; IntAct=EBI-11522811, EBI-2568609;
CC Q8IUQ4-2; Q8WWY3: PRPF31; NbExp=3; IntAct=EBI-11522811, EBI-1567797;
CC Q8IUQ4-2; P86480: PRR20D; NbExp=3; IntAct=EBI-11522811, EBI-12754095;
CC Q8IUQ4-2; Q9H082: RAB33B; NbExp=3; IntAct=EBI-11522811, EBI-3048549;
CC Q8IUQ4-2; Q96B01: RAD51AP1; NbExp=3; IntAct=EBI-11522811, EBI-1178724;
CC Q8IUQ4-2; P28702-3: RXRB; NbExp=3; IntAct=EBI-11522811, EBI-16429492;
CC Q8IUQ4-2; Q5VUG0: SFMBT2; NbExp=3; IntAct=EBI-11522811, EBI-12025260;
CC Q8IUQ4-2; Q13148: TARDBP; NbExp=3; IntAct=EBI-11522811, EBI-372899;
CC Q8IUQ4-2; Q9BTV4: TMEM43; NbExp=3; IntAct=EBI-11522811, EBI-721293;
CC Q8IUQ4-2; P61086: UBE2K; NbExp=6; IntAct=EBI-11522811, EBI-473850;
CC Q8IUQ4-2; A0A0S2Z639: UPP2; NbExp=3; IntAct=EBI-11522811, EBI-16440814;
CC Q8IUQ4-2; A0A0S2Z6U5: UPP2; NbExp=3; IntAct=EBI-11522811, EBI-16432858;
CC Q8IUQ4-2; O95045-2: UPP2; NbExp=6; IntAct=EBI-11522811, EBI-11528386;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Predominantly
CC cytoplasmic. Partially nuclear.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8IUQ4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IUQ4-2; Sequence=VSP_010166;
CC Name=3; Synonyms=Siah-1S;
CC IsoId=Q8IUQ4-3; Sequence=VSP_029210, VSP_029211;
CC -!- TISSUE SPECIFICITY: Widely expressed at a low level. Down-regulated in
CC advanced hepatocellular carcinomas. {ECO:0000269|PubMed:12557228,
CC ECO:0000269|PubMed:9403064}.
CC -!- INDUCTION: May be induced by p53/TP53, suggesting that it may be
CC required to modulate p53/TP53 response. The relevance of such activity
CC in vivo is however unclear and may not exist.
CC -!- DOMAIN: The RING-type zinc finger domain is essential for ubiquitin
CC ligase activity.
CC -!- DOMAIN: The SBD domain (substrate-binding domain) mediates the
CC homodimerization and the interaction with substrate proteins. It is
CC related to the TRAF family. {ECO:0000250|UniProtKB:P61092}.
CC -!- PTM: Phosphorylated on Ser-19 by ATM and ATR. This phosphorylation
CC disrupts SIAH1 interaction with HIPK2, and subsequent proteasomal
CC degradation of HIPK2. {ECO:0000269|PubMed:18536714}.
CC -!- DISEASE: Buratti-Harel syndrome (BURHAS) [MIM:619314]: An autosomal
CC dominant neurodevelopmental disorder characterized by hypotonia
CC apparent in early infancy, global developmental delay, delayed walking,
CC language and speech delay, impaired intellectual development, and
CC dysmorphic facial features. {ECO:0000269|PubMed:32430360}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the SINA (Seven in absentia) family.
CC {ECO:0000305}.
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DR EMBL; U63295; AAC12950.1; -; mRNA.
DR EMBL; U76247; AAC51907.1; -; mRNA.
DR EMBL; AJ400626; CAC35542.1; -; Genomic_DNA.
DR EMBL; EF026094; ABK15529.1; -; mRNA.
DR EMBL; BX647064; CAE46191.1; -; mRNA.
DR EMBL; BC035562; AAH35562.1; -; mRNA.
DR EMBL; BC042550; AAH42550.1; -; mRNA.
DR EMBL; BC044920; AAH44920.1; -; mRNA.
DR CCDS; CCDS10735.1; -. [Q8IUQ4-1]
DR CCDS; CCDS32444.1; -. [Q8IUQ4-2]
DR RefSeq; NP_001006611.1; NM_001006610.1. [Q8IUQ4-2]
DR RefSeq; NP_003022.3; NM_003031.3. [Q8IUQ4-1]
DR RefSeq; XP_006721309.1; XM_006721246.1. [Q8IUQ4-1]
DR RefSeq; XP_011521581.1; XM_011523279.1. [Q8IUQ4-1]
DR PDB; 2A25; X-ray; 2.20 A; A=90-282.
DR PDB; 4C9Z; X-ray; 1.95 A; A/B=91-282.
DR PDB; 4CA1; X-ray; 1.58 A; A/B=91-282.
DR PDB; 4I7B; X-ray; 3.00 A; A/C=90-282.
DR PDB; 4I7C; X-ray; 2.80 A; A/C=90-282.
DR PDB; 4I7D; X-ray; 2.40 A; A/C=90-282.
DR PDB; 4X3G; X-ray; 2.34 A; A/B=91-282.
DR PDB; 5WZZ; X-ray; 2.10 A; A/B/C/D=93-282.
DR PDBsum; 2A25; -.
DR PDBsum; 4C9Z; -.
DR PDBsum; 4CA1; -.
DR PDBsum; 4I7B; -.
DR PDBsum; 4I7C; -.
DR PDBsum; 4I7D; -.
DR PDBsum; 4X3G; -.
DR PDBsum; 5WZZ; -.
DR AlphaFoldDB; Q8IUQ4; -.
DR SMR; Q8IUQ4; -.
DR BioGRID; 112372; 211.
DR CORUM; Q8IUQ4; -.
DR DIP; DIP-35684N; -.
DR IntAct; Q8IUQ4; 150.
DR MINT; Q8IUQ4; -.
DR STRING; 9606.ENSP00000349156; -.
DR MoonDB; Q8IUQ4; Predicted.
DR TCDB; 8.A.133.1.1; the siah1 e3 ubiquitin-protein ligase (siah1) family.
DR iPTMnet; Q8IUQ4; -.
DR PhosphoSitePlus; Q8IUQ4; -.
DR BioMuta; SIAH1; -.
DR DMDM; 46577493; -.
DR EPD; Q8IUQ4; -.
DR jPOST; Q8IUQ4; -.
DR MassIVE; Q8IUQ4; -.
DR MaxQB; Q8IUQ4; -.
DR PaxDb; Q8IUQ4; -.
DR PeptideAtlas; Q8IUQ4; -.
DR PRIDE; Q8IUQ4; -.
DR ProteomicsDB; 70593; -. [Q8IUQ4-1]
DR ProteomicsDB; 70594; -. [Q8IUQ4-2]
DR ProteomicsDB; 70595; -. [Q8IUQ4-3]
DR Antibodypedia; 14482; 421 antibodies from 36 providers.
DR DNASU; 6477; -.
DR Ensembl; ENST00000356721.3; ENSP00000349156.3; ENSG00000196470.12. [Q8IUQ4-2]
DR Ensembl; ENST00000380006.2; ENSP00000369343.2; ENSG00000196470.12. [Q8IUQ4-1]
DR Ensembl; ENST00000394725.3; ENSP00000378214.2; ENSG00000196470.12. [Q8IUQ4-1]
DR Ensembl; ENST00000568007.5; ENSP00000456421.1; ENSG00000196470.12. [Q8IUQ4-1]
DR GeneID; 6477; -.
DR KEGG; hsa:6477; -.
DR MANE-Select; ENST00000394725.3; ENSP00000378214.2; NM_003031.4; NP_003022.3.
DR UCSC; uc002efl.4; human. [Q8IUQ4-1]
DR CTD; 6477; -.
DR DisGeNET; 6477; -.
DR GeneCards; SIAH1; -.
DR HGNC; HGNC:10857; SIAH1.
DR HPA; ENSG00000196470; Low tissue specificity.
DR MIM; 602212; gene.
DR MIM; 619314; phenotype.
DR neXtProt; NX_Q8IUQ4; -.
DR OpenTargets; ENSG00000196470; -.
DR PharmGKB; PA35759; -.
DR VEuPathDB; HostDB:ENSG00000196470; -.
DR eggNOG; KOG3002; Eukaryota.
DR GeneTree; ENSGT00940000154837; -.
DR HOGENOM; CLU_028215_0_0_1; -.
DR InParanoid; Q8IUQ4; -.
DR OMA; ADHEDAC; -.
DR OrthoDB; 780610at2759; -.
DR PhylomeDB; Q8IUQ4; -.
DR TreeFam; TF312976; -.
DR PathwayCommons; Q8IUQ4; -.
DR Reactome; R-HSA-373752; Netrin-1 signaling.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q8IUQ4; -.
DR SIGNOR; Q8IUQ4; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 6477; 35 hits in 1137 CRISPR screens.
DR ChiTaRS; SIAH1; human.
DR EvolutionaryTrace; Q8IUQ4; -.
DR GeneWiki; SIAH1; -.
DR GenomeRNAi; 6477; -.
DR Pharos; Q8IUQ4; Tbio.
DR PRO; PR:Q8IUQ4; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q8IUQ4; protein.
DR Bgee; ENSG00000196470; Expressed in secondary oocyte and 202 other tissues.
DR ExpressionAtlas; Q8IUQ4; baseline and differential.
DR Genevisible; Q8IUQ4; HS.
DR GO; GO:0030877; C:beta-catenin destruction complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IMP:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:1990000; P:amyloid fibril formation; TAS:Reactome.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0007411; P:axon guidance; TAS:ProtInc.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0051402; P:neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; IDA:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:MGI.
DR DisProt; DP02608; -.
DR Gene3D; 2.60.210.10; -; 1.
DR Gene3D; 3.30.40.10; -; 2.
DR IDEAL; IID00120; -.
DR InterPro; IPR018121; 7-in-absentia-prot_TRAF-dom.
DR InterPro; IPR004162; SINA-like_animal.
DR InterPro; IPR008974; TRAF-like.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR013010; Znf_SIAH.
DR PANTHER; PTHR45877; PTHR45877; 1.
DR Pfam; PF03145; Sina; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
DR PROSITE; PS51081; ZF_SIAH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cell cycle; Cytoplasm;
KW Developmental protein; Differentiation; Disease variant;
KW Intellectual disability; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Spermatogenesis; Transferase; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..282
FT /note="E3 ubiquitin-protein ligase SIAH1"
FT /id="PRO_0000056163"
FT ZN_FING 41..76
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 93..153
FT /note="SIAH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00455"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 90..282
FT /note="SBD"
FT /evidence="ECO:0000250|UniProtKB:P61092"
FT BINDING 98
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:28546513,
FT ECO:0007744|PDB:5WZZ"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:28546513,
FT ECO:0007744|PDB:5WZZ"
FT BINDING 117
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:28546513,
FT ECO:0007744|PDB:5WZZ"
FT BINDING 121
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:28546513,
FT ECO:0007744|PDB:5WZZ"
FT BINDING 128
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:16085652,
FT ECO:0000269|PubMed:28546513, ECO:0007744|PDB:2A25,
FT ECO:0007744|PDB:5WZZ"
FT BINDING 135
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:16085652,
FT ECO:0000269|PubMed:28546513, ECO:0007744|PDB:2A25,
FT ECO:0007744|PDB:5WZZ"
FT BINDING 147
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:16085652,
FT ECO:0000269|PubMed:28546513, ECO:0007744|PDB:2A25,
FT ECO:0007744|PDB:5WZZ"
FT BINDING 152
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:16085652,
FT ECO:0000269|PubMed:28546513, ECO:0007744|PDB:2A25,
FT ECO:0007744|PDB:5WZZ"
FT MOD_RES 19
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000269|PubMed:18536714"
FT VAR_SEQ 1
FT /note="M -> MTGKATPPSLYSWRGVLFTCLPAARTRKRKEM (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_010166"
FT VAR_SEQ 193..195
FT /note="LEK -> DLS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17420721"
FT /id="VSP_029210"
FT VAR_SEQ 196..282
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17420721"
FT /id="VSP_029211"
FT VARIANT 41
FT /note="C -> G (in BURHAS; loss of function in Wnt signaling
FT pathway)"
FT /evidence="ECO:0000269|PubMed:32430360"
FT /id="VAR_085780"
FT VARIANT 50
FT /note="P -> L (in BURHAS)"
FT /evidence="ECO:0000269|PubMed:32430360"
FT /id="VAR_085781"
FT VARIANT 128
FT /note="C -> F (in BURHAS; loss of function in Wnt signaling
FT pathway)"
FT /evidence="ECO:0000269|PubMed:32430360"
FT /id="VAR_085782"
FT VARIANT 168
FT /note="T -> A (in BURHAS; loss of function in Wnt signaling
FT pathway)"
FT /evidence="ECO:0000269|PubMed:32430360"
FT /id="VAR_085783"
FT VARIANT 174
FT /note="G -> R (in BURHAS; loss of function in Wnt signaling
FT pathway)"
FT /evidence="ECO:0000269|PubMed:32430360"
FT /id="VAR_085784"
FT MUTAGEN 19
FT /note="S->A: Impaired ATM mediated phosphorylation, but
FT normal interaction with HIPK2 and HIPK2 subsequent
FT proteasomal degradation."
FT /evidence="ECO:0000269|PubMed:18536714"
FT MUTAGEN 19
FT /note="S->D: Reduced interaction with HIPK2 and HIPK2
FT subsequent proteasomal degradation."
FT /evidence="ECO:0000269|PubMed:18536714"
FT MUTAGEN 40
FT /note="E->R: Loss of function."
FT /evidence="ECO:0000269|PubMed:9858595"
FT MUTAGEN 41
FT /note="C->S: Loss of function; when associated with S-44."
FT /evidence="ECO:0000269|PubMed:9858595"
FT MUTAGEN 44
FT /note="C->S: Loss of function."
FT /evidence="ECO:0000269|PubMed:18536714,
FT ECO:0000269|PubMed:9858595"
FT MUTAGEN 55
FT /note="C->A: Loss of function; when associated with A-59
FT and S-72."
FT /evidence="ECO:0000269|PubMed:15064394,
FT ECO:0000269|PubMed:9858595"
FT MUTAGEN 55
FT /note="C->S: Loss of function; when associated with Y-59."
FT /evidence="ECO:0000269|PubMed:15064394,
FT ECO:0000269|PubMed:9858595"
FT MUTAGEN 59
FT /note="H->A: Loss of function; when associated with A-55
FT and S-72."
FT /evidence="ECO:0000269|PubMed:15064394,
FT ECO:0000269|PubMed:9858595"
FT MUTAGEN 59
FT /note="H->Y: Loss of function."
FT /evidence="ECO:0000269|PubMed:15064394,
FT ECO:0000269|PubMed:9858595"
FT MUTAGEN 66
FT /note="R->L: Decreased activity; when associated with T-
FT 68."
FT /evidence="ECO:0000269|PubMed:9858595"
FT MUTAGEN 68
FT /note="K->T: Decreased activity; when associated with L-
FT 66."
FT /evidence="ECO:0000269|PubMed:9858595"
FT MUTAGEN 72
FT /note="C->S: Loss of function; when associated with A-55
FT and A-59."
FT /evidence="ECO:0000269|PubMed:15064394"
FT MUTAGEN 76
FT /note="R->E: Decreased activity."
FT /evidence="ECO:0000269|PubMed:9858595"
FT MUTAGEN 124
FT /note="R->A: In D; does not impair its ability to interact
FT with CACYBP and degrade CTNNB1 and PML; when associated
FT with A-214; A-215; A-231 and A-232."
FT /evidence="ECO:0000269|PubMed:12421809,
FT ECO:0000269|PubMed:14645235"
FT MUTAGEN 142
FT /note="D->A: In E; does not impair its ability to interact
FT with CACYBP and degrade CTNNB1; when associated with A-
FT 151."
FT /evidence="ECO:0000269|PubMed:12421809"
FT MUTAGEN 151
FT /note="Q->A: In E; does not impair its ability to interact
FT with CACYBP and degrade CTNNB1; when associated with A-
FT 142."
FT /evidence="ECO:0000269|PubMed:12421809"
FT MUTAGEN 152
FT /note="H->Y: Abolishes ability to degrade DCC."
FT /evidence="ECO:0000269|PubMed:9858595"
FT MUTAGEN 161..162
FT /note="ED->AA: In A; does not impair its ability to degrade
FT PML while it abolishes its ability to interact with CACYBP
FT and degrade CTNNB1; when associated with A-226 and A-237."
FT /evidence="ECO:0000269|PubMed:12421809,
FT ECO:0000269|PubMed:14645235"
FT MUTAGEN 198..200
FT /note="KYD->GDG: Impairs CTNNB1 degradation."
FT /evidence="ECO:0000269|PubMed:16085652"
FT MUTAGEN 202
FT /note="H->Y: No effect."
FT /evidence="ECO:0000269|PubMed:9858595"
FT MUTAGEN 211
FT /note="L->R: Abolishes ability to degrade DCC."
FT /evidence="ECO:0000269|PubMed:9858595"
FT MUTAGEN 214..215
FT /note="TR->AA: In D; does not impair its ability to
FT interact with CACYBP and degrade CTNNB1 and PML; when
FT associated with A-124; A-231 and A-232."
FT /evidence="ECO:0000269|PubMed:12421809,
FT ECO:0000269|PubMed:14645235"
FT MUTAGEN 224
FT /note="R->A: In C; does not impair its ability to interact
FT with CACYBP and degrade CTNNB1; when associated with A-
FT 233."
FT /evidence="ECO:0000269|PubMed:12421809"
FT MUTAGEN 226
FT /note="E->A: In A; does not impair its ability to degrade
FT PML while it abolishes its ability to interact with CACYBP
FT and degrade CTNNB1; when associated with A-161; A-162 and
FT A-237."
FT /evidence="ECO:0000269|PubMed:12421809,
FT ECO:0000269|PubMed:14645235"
FT MUTAGEN 231..232
FT /note="RR->AA: In D; does not impair its ability to
FT interact with CACYBP and degrade CTNNB1 and PML; when
FT associated with A-124; A-214 and A-215."
FT /evidence="ECO:0000269|PubMed:12421809,
FT ECO:0000269|PubMed:14645235"
FT MUTAGEN 233
FT /note="R->A: In C; does not impair its ability to interact
FT with CACYBP and degrade CTNNB1; when associated with A-
FT 233."
FT /evidence="ECO:0000269|PubMed:12421809"
FT MUTAGEN 237
FT /note="E->A: In A; does not impair its ability to degrade
FT PML while it abolishes its ability to interact with CACYBP
FT and degrade CTNNB1; when associated with A-161; A-162 and
FT A-226."
FT /evidence="ECO:0000269|PubMed:12421809,
FT ECO:0000269|PubMed:14645235"
FT MUTAGEN 252
FT /note="M->D,K: Impairs CTNNB1 degradation."
FT /evidence="ECO:0000269|PubMed:16085652"
FT MUTAGEN 253
FT /note="N->A: In B; does not impair its ability to interact
FT with CACYBP and degrade CTNNB1; when associated with A-
FT 265."
FT /evidence="ECO:0000269|PubMed:12421809"
FT MUTAGEN 265
FT /note="Q->A: In B; does not impair its ability to interact
FT with CACYBP and degrade CTNNB1; when associated with A-
FT 253."
FT /evidence="ECO:0000269|PubMed:12421809"
FT CONFLICT 173
FT /note="P -> S (in Ref. 5; CAE46191)"
FT /evidence="ECO:0000305"
FT CONFLICT 245
FT /note="E -> G (in Ref. 5; CAE46191)"
FT /evidence="ECO:0000305"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:4X3G"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:4CA1"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:4X3G"
FT HELIX 111..120
FT /evidence="ECO:0007829|PDB:4CA1"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:4I7B"
FT STRAND 130..134
FT /evidence="ECO:0007829|PDB:4CA1"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:4CA1"
FT HELIX 144..151
FT /evidence="ECO:0007829|PDB:4CA1"
FT STRAND 156..167
FT /evidence="ECO:0007829|PDB:4CA1"
FT STRAND 172..184
FT /evidence="ECO:0007829|PDB:4CA1"
FT STRAND 187..197
FT /evidence="ECO:0007829|PDB:4CA1"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:5WZZ"
FT STRAND 203..213
FT /evidence="ECO:0007829|PDB:4CA1"
FT HELIX 215..218
FT /evidence="ECO:0007829|PDB:4CA1"
FT STRAND 221..229
FT /evidence="ECO:0007829|PDB:4CA1"
FT STRAND 232..238
FT /evidence="ECO:0007829|PDB:4CA1"
FT TURN 243..245
FT /evidence="ECO:0007829|PDB:4CA1"
FT HELIX 248..252
FT /evidence="ECO:0007829|PDB:4CA1"
FT STRAND 256..260
FT /evidence="ECO:0007829|PDB:4CA1"
FT HELIX 261..267
FT /evidence="ECO:0007829|PDB:4CA1"
FT STRAND 272..281
FT /evidence="ECO:0007829|PDB:4CA1"
SQ SEQUENCE 282 AA; 31123 MW; FA0698D0DC1B0A15 CRC64;
MSRQTATALP TGTSKCPPSQ RVPALTGTTA SNNDLASLFE CPVCFDYVLP PILQCQSGHL
VCSNCRPKLT CCPTCRGPLG SIRNLAMEKV ANSVLFPCKY ASSGCEITLP HTEKADHEEL
CEFRPYSCPC PGASCKWQGS LDAVMPHLMH QHKSITTLQG EDIVFLATDI NLPGAVDWVM
MQSCFGFHFM LVLEKQEKYD GHQQFFAIVQ LIGTRKQAEN FAYRLELNGH RRRLTWEATP
RSIHEGIATA IMNSDCLVFD TSIAQLFAEN GNLGINVTIS MC
