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P61092 (SIA1A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase SIAH1A

EC=6.3.2.-
Alternative name(s):
Seven in absentia homolog 1a
Short name=Siah-1a
Short name=Siah1a
Short name=mSiah-1a
Gene names
Name:Siah1a
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length282 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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), the cell-surface receptor-type tyrosine kinase FLT3, the 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. Required for completion of meiosis I in males. Induces apoptosis in cooperation with PEG3. 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. Ref.3 Ref.5 Ref.8

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Homodimer. Interacts with group 1 glutamate receptors GRM1 and GRM5. Interacts with SNCAIP and HIPK2. Interacts with GAPDH; leading to stabilize SIAH1 By similarity. Interacts with UBE2E2. 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 By similarity. Interacts with DAB1, which may inhibit its activity. Interacts with PEG3 and KLF10. Ref.3 Ref.4 Ref.7 Ref.8

Subcellular location

Cytoplasm. Nucleus. Note: Predominantly cytoplasmic. Partially nuclear.

Tissue specificity

Widely expressed at low level in embryos and adults. Expressed at higher level in testis. Due to the high similarity between SIAH1A and SIAH1B, it is difficult to distinguish its own tissue specificity. Ref.1

Induction

May be induced by p53/TP53, suggesting that it may be required to modulate p53/TP53 response. The relevance of such activity in vivo is however unclear and may not exist. Ref.6

Domain

The RING-type zinc finger domain is essential for ubiquitin ligase activity.

The SBD domain (substrate-binding domain) mediates the homodimerization and the interaction with substrate proteins. It is related to the TRAF family.

Post-translational modification

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

Sequence similarities

Belongs to the SINA (Seven in absentia) family.

Contains 1 RING-type zinc finger.

Contains 1 SIAH-type zinc finger.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
Differentiation
Spermatogenesis
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   DomainZinc-finger
   LigandMetal-binding
Zinc
   Molecular functionDevelopmental protein
Ligase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

male meiosis I

Inferred from mutant phenotype Ref.5. Source: MGI

neuron apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

post-embryonic development

Inferred from mutant phenotype Ref.5. Source: MGI

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from direct assay Ref.8. Source: UniProtKB

protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from direct assay Ref.8. Source: UniProtKB

regulation of multicellular organism growth

Inferred from mutant phenotype Ref.5. Source: MGI

spermatogenesis

Inferred from mutant phenotype Ref.5. Source: MGI

   Cellular_componentcytosol

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionprotein binding

Inferred from physical interaction Ref.4. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction Ref.8. Source: UniProtKB

ubiquitin-protein transferase activity

Inferred from direct assay Ref.8. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.8. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Dab1P973183EBI-446761,EBI-81680

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 282282E3 ubiquitin-protein ligase SIAH1A
PRO_0000056164

Regions

Zinc finger41 – 7636RING-type
Zinc finger93 – 15361SIAH-type
Region90 – 282193SBD

Sites

Metal binding981Zinc 1
Metal binding1051Zinc 1
Metal binding1171Zinc 1
Metal binding1211Zinc 1
Metal binding1281Zinc 2
Metal binding1351Zinc 2
Metal binding1471Zinc 2
Metal binding1521Zinc 2

Amino acid modifications

Modified residue191Phosphoserine; by ATM and ATR By similarity

Experimental info

Mutagenesis1561T → E: Strongly reduced binding and degradation of target proteins; when associated with D-158. Ref.8
Mutagenesis1581L → D or K: Strongly reduced binding of target proteins. Strongly reduced degradation of target proteins. Ref.8
Mutagenesis1661L → K: Minor effect on binding and degradation of target proteins. Ref.8
Mutagenesis1801M → K: Strongly reduced binding of target proteins. Strongly reduced degradation of target proteins. Ref.8

Secondary structure

.................................. 282
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P61092 [UniParc].

Last modified April 26, 2004. Version 1.
Checksum: 852EADC5DD4A4FFA

FASTA28231,137
        10         20         30         40         50         60 
MSRQTATALP TGTSKCPPSQ RVPALTGTTA SNNDLASLFE CPVCFDYVLP PILQCQSGHL 

        70         80         90        100        110        120 
VCSNCRPKLT CCPTCRGPLG SIRNLAMEKV ANSVLFPCKY ASSGCEITLP HTEKAEHEEL 

       130        140        150        160        170        180 
CEFRPYSCPC PGASCKWQGS LDAVMPHLMH QHKSITTLQG EDIVFLATDI NLPGAVDWVM 

       190        200        210        220        230        240 
MQSCFGFHFM LVLEKQEKYD GHQQFFAIVQ LIGTRKQAEN FAYRLELNGH RRRLTWEATP 

       250        260        270        280 
RSIHEGIATA IMNSDCLVFD TSIAQLFAEN GNLGINVTIS MC 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and characterisation of murine homologues of the Drosophila seven in absentia gene (sina)."
Della N.G., Senior P.V., Bowtell D.D.L.
Development 117:1333-1343(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Strain: Swiss.
Tissue: Eye.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Olfactory epithelium.
[3]"Pw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis."
Relaix F., Wei X., Li W., Pan J., Lin Y., Bowtell D.D., Sassoon D.A., Wu X.
Proc. Natl. Acad. Sci. U.S.A. 97:2105-2110(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PEG3.
[4]"Inhibition of ubiquitin ligase Siah-1A by disabled-1."
Park T.-J., Hamanaka H., Ohshima T., Watanabe N., Mikoshiba K., Nukina N.
Biochem. Biophys. Res. Commun. 302:671-678(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB1.
[5]"The ubiquitin ligase component Siah1a is required for completion of meiosis I in male mice."
Dickins R.A., Frew I.J., House C.M., O'Bryan M.K., Holloway A.J., Haviv I., Traficante N., de Kretser D.M., Bowtell D.D.L.
Mol. Cell. Biol. 22:2294-2303(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Normal p53 function in primary cells deficient for Siah genes."
Frew I.J., Dickins R.A., Cuddihy A.R., Del Rosario M., Reinhard C., O'Connell M.J., Bowtell D.D.L.
Mol. Cell. Biol. 22:8155-8164(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[7]"Siah ubiquitin ligase is structurally related to TRAF and modulates TNF-alpha signaling."
Polekhina G., House C.M., Traficante N., Mackay J.P., Relaix F., Sassoon D.A., Parker M.W., Bowtell D.D.L.
Nat. Struct. Biol. 9:68-75(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 93-282 IN COMPLEX WITH ZINC, HOMODIMERIZATION.
[8]"Elucidation of the substrate binding site of Siah ubiquitin ligase."
House C.M., Hancock N.C., Moller A., Cromer B.A., Fedorov V., Bowtell D.D., Parker M.W., Polekhina G.
Structure 14:695-701(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 92-282 IN COMPLEX WITH ZINC AND PEPTIDE SUBSTRATE, FUNCTION, INTERACTION WITH KLF10, MUTAGENESIS OF THR-156; LEU-158; LEU-166 AND MET-180.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z19579 mRNA. Translation: CAA79630.1.
BC046317 mRNA. Translation: AAH46317.1.
CCDSCCDS22504.1.
PIRI48763.
RefSeqNP_033198.1. NM_009172.2.
UniGeneMm.324553.
Mm.474080.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1K2FX-ray2.60A/B93-282[»]
2AN6X-ray3.00A/B/C/D92-282[»]
ProteinModelPortalP61092.
SMRP61092. Positions 35-81, 93-282.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid203231. 7 interactions.
DIPDIP-29100N.
IntActP61092. 3 interactions.
STRING10090.ENSMUSP00000044123.

PTM databases

PhosphoSiteP61092.

Proteomic databases

PRIDEP61092.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000045296; ENSMUSP00000044123; ENSMUSG00000036840.
GeneID20437.
KEGGmmu:20437.
UCSCuc009mqn.2. mouse.

Organism-specific databases

CTD20437.
MGIMGI:108064. Siah1a.

Phylogenomic databases

eggNOGNOG264215.
GeneTreeENSGT00390000005434.
HOGENOMHOG000231487.
HOVERGENHBG055701.
InParanoidP61092.
KOK04506.
OMAHEETCEF.
OrthoDBEOG7JT6XC.
PhylomeDBP61092.
TreeFamTF312976.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

BgeeP61092.
CleanExMM_SIAH1A.
GenevestigatorP61092.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProIPR018121. 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]
PANTHERPTHR10315. PTHR10315. 1 hit.
PfamPF03145. Sina. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
[Graphical view]
SUPFAMSSF49599. SSF49599. 1 hit.
PROSITEPS50089. ZF_RING_2. 1 hit.
PS51081. ZF_SIAH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSiah1a. mouse.
EvolutionaryTraceP61092.
NextBio298464.
PROP61092.
SOURCESearch...

Entry information

Entry nameSIA1A_MOUSE
AccessionPrimary (citable) accession number: P61092
Secondary accession number(s): Q06984
Entry history
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: July 9, 2014
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot