SIAH1_RAT
ID SIAH1_RAT Reviewed; 282 AA.
AC Q920M9; Q06984;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=E3 ubiquitin-protein ligase SIAH1;
DE EC=2.3.2.27 {ECO:0000269|PubMed:11786535, ECO:0000269|PubMed:15951807};
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=Siah1a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN DEGRADATION OF SYP, CATALYTIC
RP ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND INTERACTION WITH UBE2E2.
RC STRAIN=Sprague-Dawley;
RX PubMed=11786535; DOI=10.1074/jbc.m107857200;
RA Wheeler T.C., Chin L.-S., Li Y., Roudabush F.L., Li L.;
RT "Regulation of synaptophysin degradation by mammalian homologues of Seven
RT in Absentia.";
RL J. Biol. Chem. 277:10273-10282(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yamaguchi A., Hori O., Tohyama M.;
RT "Rat Siah1A.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH GRM1 AND GRM5.
RX PubMed=10469171; DOI=10.1046/j.1365-2443.1999.00269.x;
RA Ishikawa K., Nash S.R., Nishimune A., Neki A., Kaneko S., Nakanishi S.;
RT "Competitive interaction of seven in absentia homolog-1A and
RT Ca2+/calmodulin with the cytoplasmic tail of group 1 metabotropic glutamate
RT receptors.";
RL Genes Cells 4:381-390(1999).
RN [4]
RP INTERACTION WITH SNCAIP.
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH GAPDH.
RX PubMed=15951807; DOI=10.1038/ncb1268;
RA Hara M.R., Agrawal N., Kim S.F., Cascio M.B., Fujimuro M., Ozeki Y.,
RA Takahashi M., Cheah J.H., Tankou S.K., Hester L.D., Ferris C.D.,
RA Hayward S.D., Snyder S.H., Sawa A.;
RT "S-nitrosylated GAPDH initiates apoptotic cell death by nuclear
RT translocation following Siah1 binding.";
RL Nat. Cell Biol. 7:665-674(2005).
RN [6]
RP INTERACTION WITH SNCAIP, AND SUBCELLULAR LOCATION.
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 [7]
RP INTERACTION WITH BSN AND PCLO.
RX PubMed=23403927; DOI=10.1038/emboj.2013.27;
RA Waites C.L., Leal-Ortiz S.A., Okerlund N., Dalke H., Fejtova A.,
RA Altrock W.D., Gundelfinger E.D., Garner C.C.;
RT "Bassoon and Piccolo maintain synapse integrity by regulating protein
RT ubiquitination and degradation.";
RL EMBO J. 32:954-969(2013).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and
CC subsequent proteasomal degradation of target proteins (PubMed:11786535,
CC PubMed:15951807). E3 ubiquitin ligases accept ubiquitin from an E2
CC ubiquitin-conjugating enzyme in the form of a thioester and then
CC directly transfers the ubiquitin to targeted substrates
CC (PubMed:11786535, PubMed:15951807). Mediates E3 ubiquitin ligase
CC activity either through direct binding to substrates or by functioning
CC as the essential RING domain subunit of larger E3 complexes
CC (PubMed:11786535, PubMed:15951807). 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), cytoplasmic signal transduction molecules
CC (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule
CC motor protein (KIF22), a protein involved in synaptic vesicle function
CC in neurons (SYP), a structural protein (CTNNB1) and SNCAIP
CC (PubMed:11786535). Confers constitutive instability to HIPK2 through
CC proteasomal degradation (By similarity). It is thereby involved in many
CC cellular processes such as apoptosis, tumor suppression, cell cycle,
CC axon guidance, transcription, spermatogenesis and TNF-alpha signaling
CC (By similarity). Has some overlapping function with SIAH2 (By
CC similarity). Induces apoptosis in cooperation with PEG3 (By
CC similarity). Upon nitric oxid (NO) generation that follows apoptotic
CC stimulation, interacts with S-nitrosylated GAPDH, mediating the
CC translocation of GAPDH to the nucleus (PubMed:15951807). GAPDH acts as
CC a stabilizer of SIAH1, facilitating the degradation of nuclear proteins
CC (PubMed:15951807). Mediates ubiquitination and degradation of EGLN2 and
CC EGLN3 in response to the unfolded protein response (UPR), leading to
CC their degradation and subsequent stabilization of ATF4 (By similarity).
CC Also part of the Wnt signaling pathway in which it mediates the Wnt-
CC induced ubiquitin-mediated proteasomal degradation of AXIN1.
CC {ECO:0000250|UniProtKB:P61092, ECO:0000250|UniProtKB:Q8IUQ4,
CC ECO:0000269|PubMed:11786535, ECO:0000269|PubMed:15951807}.
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:11786535,
CC ECO:0000269|PubMed:15951807};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:11786535, ECO:0000269|PubMed:15951807}.
CC -!- SUBUNIT: Homodimer. Component of some large E3 complex composed of
CC UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with UBE2I.
CC Interacts with alpha-tubulin. Interacts with PEG10, which may inhibit
CC its activity. Interacts with PEG3 and HIPK2 (By similarity). Interacts
CC with group 1 glutamate receptors GRM1 and GRM5. Interacts with DAB1,
CC which may inhibit its activity. Interacts with UBE2E2. Interacts with
CC SNCAIP. Interacts with GAPDH; leading to stabilize SIAH1. Interacts
CC with Bassoon/BSN and Piccolo/PLCO; these interactions negatively
CC regulate SIAH1 E3 ligase activity. Interacts with DCC (By similarity).
CC Interacts with AXIN1; catalyzes AXIN1 ubiquitination and subsequent
CC proteasome-mediated ubiquitin-dependent degradation.
CC {ECO:0000250|UniProtKB:P61092, ECO:0000250|UniProtKB:Q8IUQ4,
CC ECO:0000269|PubMed:10469171, ECO:0000269|PubMed:11786535,
CC ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:15951807,
CC ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:23403927}.
CC -!- INTERACTION:
CC Q920M9; O88778: Bsn; NbExp=3; IntAct=EBI-957514, EBI-2271660;
CC Q920M9; Q9JKS6: Pclo; NbExp=2; IntAct=EBI-957514, EBI-2271602;
CC Q920M9; Q71F54: Sh3rf1; NbExp=2; IntAct=EBI-957514, EBI-957526;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Predominantly
CC cytoplasmic. Partially nuclear.
CC -!- DOMAIN: The RING-type zinc finger domain is essential for ubiquitin
CC ligase activity. {ECO:0000250}.
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 (By similarity). {ECO:0000250|UniProtKB:Q8IUQ4}.
CC -!- SIMILARITY: Belongs to the SINA (Seven in absentia) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB70753.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF389476; AAL91362.1; -; mRNA.
DR EMBL; AB067814; BAB70753.1; ALT_INIT; mRNA.
DR RefSeq; NP_543181.2; NM_080905.2.
DR RefSeq; XP_008770567.1; XM_008772345.2.
DR AlphaFoldDB; Q920M9; -.
DR SMR; Q920M9; -.
DR BioGRID; 250875; 7.
DR DIP; DIP-35686N; -.
DR IntAct; Q920M9; 4.
DR MINT; Q920M9; -.
DR STRING; 10116.ENSRNOP00000020329; -.
DR PaxDb; Q920M9; -.
DR Ensembl; ENSRNOT00000020329; ENSRNOP00000020329; ENSRNOG00000015143.
DR Ensembl; ENSRNOT00000097354; ENSRNOP00000092754; ENSRNOG00000015143.
DR Ensembl; ENSRNOT00000111812; ENSRNOP00000089183; ENSRNOG00000015143.
DR Ensembl; ENSRNOT00000112896; ENSRNOP00000092688; ENSRNOG00000015143.
DR Ensembl; ENSRNOT00000117078; ENSRNOP00000088384; ENSRNOG00000015143.
DR GeneID; 140941; -.
DR KEGG; rno:140941; -.
DR CTD; 6477; -.
DR RGD; 620449; Siah1.
DR eggNOG; KOG3002; Eukaryota.
DR GeneTree; ENSGT00940000154837; -.
DR HOGENOM; CLU_028215_0_0_1; -.
DR InParanoid; Q920M9; -.
DR OMA; ADHEDAC; -.
DR OrthoDB; 780610at2759; -.
DR PhylomeDB; Q920M9; -.
DR TreeFam; TF312976; -.
DR Reactome; R-RNO-373752; Netrin-1 signaling.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q920M9; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000015143; Expressed in cerebellum and 20 other tissues.
DR ExpressionAtlas; Q920M9; baseline and differential.
DR Genevisible; Q920M9; RN.
DR GO; GO:0030877; C:beta-catenin destruction complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; ISO:RGD.
DR GO; GO:0097718; F:disordered domain specific binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:RGD.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007141; P:male meiosis I; ISO:RGD.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0009791; P:post-embryonic development; ISO:RGD.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; ISO:RGD.
DR GO; GO:0031648; P:protein destabilization; IMP:RGD.
DR GO; GO:0040014; P:regulation of multicellular organism growth; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; ISO:RGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 2.60.210.10; -; 1.
DR Gene3D; 3.30.40.10; -; 2.
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 Apoptosis; Cell cycle; Cytoplasm; Developmental protein; Differentiation;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Spermatogenesis; Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..282
FT /note="E3 ubiquitin-protein ligase SIAH1"
FT /id="PRO_0000056166"
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:0000250|UniProtKB:Q8IUQ4"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8IUQ4"
FT BINDING 117
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8IUQ4"
FT BINDING 121
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q8IUQ4"
FT BINDING 128
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8IUQ4"
FT BINDING 135
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8IUQ4"
FT BINDING 147
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8IUQ4"
FT BINDING 152
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q8IUQ4"
FT MOD_RES 19
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000250|UniProtKB:Q8IUQ4"
SQ SEQUENCE 282 AA; 31137 MW; 852EADC5DD4A4FFA CRC64;
MSRQTATALP TGTSKCPPSQ RVPALTGTTA SNNDLASLFE CPVCFDYVLP PILQCQSGHL
VCSNCRPKLT CCPTCRGPLG SIRNLAMEKV ANSVLFPCKY ASSGCEITLP HTEKAEHEEL
CEFRPYSCPC PGASCKWQGS LDAVMPHLMH QHKSITTLQG EDIVFLATDI NLPGAVDWVM
MQSCFGFHFM LVLEKQEKYD GHQQFFAIVQ LIGTRKQAEN FAYRLELNGH RRRLTWEATP
RSIHEGIATA IMNSDCLVFD TSIAQLFAEN GNLGINVTIS MC
