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Protein

E3 ubiquitin-protein ligase SIAH1

Gene

Siah1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3 (By similarity). Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins.By similarity2 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi98 – 981Zinc 1By similarity
Metal bindingi105 – 1051Zinc 1By similarity
Metal bindingi117 – 1171Zinc 1By similarity
Metal bindingi121 – 1211Zinc 1By similarity
Metal bindingi128 – 1281Zinc 2By similarity
Metal bindingi135 – 1351Zinc 2By similarity
Metal bindingi147 – 1471Zinc 2By similarity
Metal bindingi152 – 1521Zinc 2By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri41 – 7636RING-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri93 – 15361SIAH-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Ligase

Keywords - Biological processi

Apoptosis, Cell cycle, Differentiation, Spermatogenesis, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-373752. Netrin-1 signaling.
R-RNO-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase SIAH1 (EC:6.3.2.-)
Alternative name(s):
Seven in absentia homolog 1
Short name:
Siah-1
Siah-1a
Gene namesi
Name:Siah1
Synonyms:Siah1a
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 19

Organism-specific databases

RGDi620449. Siah1.

Subcellular locationi

GO - Cellular componenti

  • beta-catenin destruction complex Source: UniProtKB
  • cytosol Source: UniProtKB
  • early endosome Source: RGD
  • nucleus Source: UniProtKB
  • plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 282282E3 ubiquitin-protein ligase SIAH1PRO_0000056166Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei19 – 191Phosphoserine; by ATM and ATRBy similarity

Post-translational modificationi

Phosphorylated on Ser-19 by ATM and ATR. This phosphorylation disrupts SIAH1 interaction with HIPK2, and subsequent proteasomal degradation of HIPK2 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ920M9.
PRIDEiQ920M9.

Expressioni

Gene expression databases

ExpressionAtlasiQ920M9. baseline and differential.
GenevisibleiQ920M9. RN.

Interactioni

Subunit structurei

Homodimer. Component of some large E3 complex composed of UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with UBE2I. Interacts with alpha-tubulin. Interacts with PEG10, which may inhibit its activity. Interacts with PEG3 and HIPK2 (By similarity). Interacts with group 1 glutamate receptors GRM1 and GRM5. Interacts with DAB1, which may inhibit its activity. Interacts with UBE2E2. Interacts with SNCAIP. Interacts with GAPDH; leading to stabilize SIAH1.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BsnO887783EBI-957514,EBI-2271660
PcloQ9JKS62EBI-957514,EBI-2271602
Sh3rf1Q71F542EBI-957514,EBI-957526

GO - Molecular functioni

  • protein C-terminus binding Source: RGD

Protein-protein interaction databases

BioGridi250875. 7 interactions.
DIPiDIP-35686N.
IntActiQ920M9. 3 interactions.
STRINGi10116.ENSRNOP00000020329.

Structurei

3D structure databases

ProteinModelPortaliQ920M9.
SMRiQ920M9. Positions 30-282.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni90 – 282193SBDAdd
BLAST

Domaini

The RING-type zinc finger domain is essential for ubiquitin ligase activity.By similarity
The SBD domain (substrate-binding domain) mediates the homodimerization and the interaction with substrate proteins. It is related to the TRAF family (By similarity).By similarity

Sequence similaritiesi

Belongs to the SINA (Seven in absentia) family.Curated
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 1 SIAH-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri41 – 7636RING-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri93 – 15361SIAH-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3002. Eukaryota.
ENOG410XVP0. LUCA.
GeneTreeiENSGT00390000005434.
HOGENOMiHOG000231487.
HOVERGENiHBG055701.
InParanoidiQ920M9.
KOiK04506.
OMAiPKANVAG.
OrthoDBiEOG7JT6XC.
PhylomeDBiQ920M9.
TreeFamiTF312976.

Family and domain databases

Gene3Di2.60.210.10. 1 hit.
3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProiIPR018121. 7-in-absentia-prot_TRAF-dom.
IPR013323. SIAH-type.
IPR004162. SINA-like.
IPR008974. TRAF-like.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR013010. Znf_SIAH.
[Graphical view]
PANTHERiPTHR10315. PTHR10315. 1 hit.
PfamiPF03145. Sina. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 1 hit.
PROSITEiPS50089. ZF_RING_2. 1 hit.
PS51081. ZF_SIAH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q920M9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRQTATALP TGTSKCPPSQ RVPALTGTTA SNNDLASLFE CPVCFDYVLP
60 70 80 90 100
PILQCQSGHL VCSNCRPKLT CCPTCRGPLG SIRNLAMEKV ANSVLFPCKY
110 120 130 140 150
ASSGCEITLP HTEKAEHEEL CEFRPYSCPC PGASCKWQGS LDAVMPHLMH
160 170 180 190 200
QHKSITTLQG EDIVFLATDI NLPGAVDWVM MQSCFGFHFM LVLEKQEKYD
210 220 230 240 250
GHQQFFAIVQ LIGTRKQAEN FAYRLELNGH RRRLTWEATP RSIHEGIATA
260 270 280
IMNSDCLVFD TSIAQLFAEN GNLGINVTIS MC
Length:282
Mass (Da):31,137
Last modified:April 26, 2004 - v2
Checksum:i852EADC5DD4A4FFA
GO

Sequence cautioni

The sequence BAB70753.1 differs from that shown. Reason: Erroneous initiation. Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF389476 mRNA. Translation: AAL91362.1.
AB067814 mRNA. Translation: BAB70753.1. Different initiation.
RefSeqiNP_543181.2. NM_080905.2.
XP_006255275.1. XM_006255213.2.
XP_008770567.1. XM_008772345.1.
UniGeneiRn.73937.

Genome annotation databases

EnsembliENSRNOT00000020329; ENSRNOP00000020329; ENSRNOG00000015143.
GeneIDi140941.
KEGGirno:140941.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF389476 mRNA. Translation: AAL91362.1.
AB067814 mRNA. Translation: BAB70753.1. Different initiation.
RefSeqiNP_543181.2. NM_080905.2.
XP_006255275.1. XM_006255213.2.
XP_008770567.1. XM_008772345.1.
UniGeneiRn.73937.

3D structure databases

ProteinModelPortaliQ920M9.
SMRiQ920M9. Positions 30-282.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250875. 7 interactions.
DIPiDIP-35686N.
IntActiQ920M9. 3 interactions.
STRINGi10116.ENSRNOP00000020329.

Proteomic databases

PaxDbiQ920M9.
PRIDEiQ920M9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000020329; ENSRNOP00000020329; ENSRNOG00000015143.
GeneIDi140941.
KEGGirno:140941.

Organism-specific databases

CTDi6477.
RGDi620449. Siah1.

Phylogenomic databases

eggNOGiKOG3002. Eukaryota.
ENOG410XVP0. LUCA.
GeneTreeiENSGT00390000005434.
HOGENOMiHOG000231487.
HOVERGENiHBG055701.
InParanoidiQ920M9.
KOiK04506.
OMAiPKANVAG.
OrthoDBiEOG7JT6XC.
PhylomeDBiQ920M9.
TreeFamiTF312976.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-RNO-373752. Netrin-1 signaling.
R-RNO-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

PROiQ920M9.

Gene expression databases

ExpressionAtlasiQ920M9. baseline and differential.
GenevisibleiQ920M9. RN.

Family and domain databases

Gene3Di2.60.210.10. 1 hit.
3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProiIPR018121. 7-in-absentia-prot_TRAF-dom.
IPR013323. SIAH-type.
IPR004162. SINA-like.
IPR008974. TRAF-like.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR013010. Znf_SIAH.
[Graphical view]
PANTHERiPTHR10315. PTHR10315. 1 hit.
PfamiPF03145. Sina. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 1 hit.
PROSITEiPS50089. ZF_RING_2. 1 hit.
PS51081. ZF_SIAH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Regulation of synaptophysin degradation by mammalian homologues of Seven in Absentia."
    Wheeler T.C., Chin L.-S., Li Y., Roudabush F.L., Li L.
    J. Biol. Chem. 277:10273-10282(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN DEGRADATION OF SYP, SUBCELLULAR LOCATION, INTERACTION WITH UBE2E2.
    Strain: Sprague-Dawley.
  2. "Rat Siah1A."
    Yamaguchi A., Hori O., Tohyama M.
    Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Competitive interaction of seven in absentia homolog-1A and Ca2+/calmodulin with the cytoplasmic tail of group 1 metabotropic glutamate receptors."
    Ishikawa K., Nash S.R., Nishimune A., Neki A., Kaneko S., Nakanishi S.
    Genes Cells 4:381-390(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GRM1 AND GRM5.
  4. "Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease."
    Liani E., Eyal A., Avraham E., Shemer R., Szargel R., Berg D., Bornemann A., Riess O., Ross C.A., Rott R., Engelender S.
    Proc. Natl. Acad. Sci. U.S.A. 101:5500-5505(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SNCAIP.
  5. "S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding."
    Hara M.R., Agrawal N., Kim S.F., Cascio M.B., Fujimuro M., Ozeki Y., Takahashi M., Cheah J.H., Tankou S.K., Hester L.D., Ferris C.D., Hayward S.D., Snyder S.H., Sawa A.
    Nat. Cell Biol. 7:665-674(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH GAPDH.
  6. "Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates alpha-synuclein monoubiquitylation and inclusion formation."
    Szargel R., Rott R., Eyal A., Haskin J., Shani V., Balan L., Wolosker H., Engelender S.
    J. Biol. Chem. 284:11706-11716(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SNCAIP, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiSIAH1_RAT
AccessioniPrimary (citable) accession number: Q920M9
Secondary accession number(s): Q06984
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: July 6, 2016
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.