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Protein

E3 ubiquitin-protein ligase SIAH1A

Gene

Siah1a

Organism
Mus musculus (Mouse)
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), 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.3 Publications

Pathway:iprotein 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 12 Publications
Metal bindingi105 – 1051Zinc 12 Publications
Metal bindingi117 – 1171Zinc 12 Publications
Metal bindingi121 – 1211Zinc 12 Publications
Metal bindingi128 – 1281Zinc 22 Publications
Metal bindingi135 – 1351Zinc 22 Publications
Metal bindingi147 – 1471Zinc 22 Publications
Metal bindingi152 – 1521Zinc 22 Publications

Regions

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

GO - Molecular functioni

  • identical protein binding Source: MGI
  • ligase activity Source: UniProtKB-KW
  • protein C-terminus binding Source: MGI
  • protein homodimerization activity Source: UniProtKB
  • ubiquitin protein ligase activity Source: MGI
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • male meiosis I Source: MGI
  • neuron apoptotic process Source: UniProtKB
  • positive regulation of apoptotic process Source: MGI
  • positive regulation of intrinsic apoptotic signaling pathway Source: MGI
  • post-embryonic development Source: MGI
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein catabolic process Source: MGI
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: UniProtKB
  • regulation of multicellular organism growth Source: MGI
  • spermatogenesis Source: MGI
  • ubiquitin-dependent protein catabolic process Source: MGI
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

BRENDAi6.3.2.19. 3474.
ReactomeiREACT_293956. Netrin-1 signaling.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Siah1a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:108064. Siah1a.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi156 – 1561T → E: Strongly reduced binding and degradation of target proteins; when associated with D-158. 1 Publication
Mutagenesisi158 – 1581L → D or K: Strongly reduced binding of target proteins. Strongly reduced degradation of target proteins. 1 Publication
Mutagenesisi166 – 1661L → K: Minor effect on binding and degradation of target proteins. 1 Publication
Mutagenesisi180 – 1801M → K: Strongly reduced binding of target proteins. Strongly reduced degradation of target proteins. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 282282E3 ubiquitin-protein ligase SIAH1APRO_0000056164Add
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

PRIDEiP61092.

PTM databases

PhosphoSiteiP61092.

Expressioni

Tissue specificityi

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.1 Publication

Inductioni

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.1 Publication

Gene expression databases

BgeeiP61092.
CleanExiMM_SIAH1A.
GenevisibleiP61092. MM.

Interactioni

Subunit structurei

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.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Dab1P973183EBI-446761,EBI-81680

Protein-protein interaction databases

BioGridi203231. 8 interactions.
DIPiDIP-29100N.
IntActiP61092. 3 interactions.
STRINGi10090.ENSMUSP00000044123.

Structurei

Secondary structure

1
282
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi101 – 1033Combined sources
Helixi111 – 1133Combined sources
Helixi114 – 1196Combined sources
Beta strandi130 – 1323Combined sources
Helixi141 – 1433Combined sources
Helixi144 – 1507Combined sources
Beta strandi156 – 16712Combined sources
Beta strandi177 – 1848Combined sources
Beta strandi187 – 19812Combined sources
Turni199 – 2013Combined sources
Beta strandi202 – 21312Combined sources
Helixi215 – 2184Combined sources
Beta strandi221 – 2299Combined sources
Beta strandi232 – 2387Combined sources
Turni243 – 2453Combined sources
Helixi248 – 2525Combined sources
Beta strandi256 – 2605Combined sources
Helixi261 – 2677Combined sources
Beta strandi272 – 28110Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1K2FX-ray2.60A/B93-282[»]
2AN6X-ray3.00A/B/C/D92-282[»]
ProteinModelPortaliP61092.
SMRiP61092. Positions 30-282.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP61092.

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

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

eggNOGiNOG264215.
GeneTreeiENSGT00390000005434.
HOGENOMiHOG000231487.
HOVERGENiHBG055701.
InParanoidiP61092.
KOiK04506.
OMAiPKANVAG.
OrthoDBiEOG7JT6XC.
PhylomeDBiP61092.
TreeFamiTF312976.

Family and domain databases

Gene3Di3.30.40.10. 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]
SMARTiSM00184. RING. 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.

P61092-1 [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 - v1
Checksum:i852EADC5DD4A4FFA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z19579 mRNA. Translation: CAA79630.1.
BC046317 mRNA. Translation: AAH46317.1.
CCDSiCCDS22504.1.
PIRiI48763.
RefSeqiNP_033198.1. NM_009172.2.
UniGeneiMm.324553.
Mm.474080.

Genome annotation databases

EnsembliENSMUST00000045296; ENSMUSP00000044123; ENSMUSG00000036840.
GeneIDi20437.
KEGGimmu:20437.
UCSCiuc009mqn.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z19579 mRNA. Translation: CAA79630.1.
BC046317 mRNA. Translation: AAH46317.1.
CCDSiCCDS22504.1.
PIRiI48763.
RefSeqiNP_033198.1. NM_009172.2.
UniGeneiMm.324553.
Mm.474080.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1K2FX-ray2.60A/B93-282[»]
2AN6X-ray3.00A/B/C/D92-282[»]
ProteinModelPortaliP61092.
SMRiP61092. Positions 30-282.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203231. 8 interactions.
DIPiDIP-29100N.
IntActiP61092. 3 interactions.
STRINGi10090.ENSMUSP00000044123.

PTM databases

PhosphoSiteiP61092.

Proteomic databases

PRIDEiP61092.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000045296; ENSMUSP00000044123; ENSMUSG00000036840.
GeneIDi20437.
KEGGimmu:20437.
UCSCiuc009mqn.2. mouse.

Organism-specific databases

CTDi20437.
MGIiMGI:108064. Siah1a.

Phylogenomic databases

eggNOGiNOG264215.
GeneTreeiENSGT00390000005434.
HOGENOMiHOG000231487.
HOVERGENiHBG055701.
InParanoidiP61092.
KOiK04506.
OMAiPKANVAG.
OrthoDBiEOG7JT6XC.
PhylomeDBiP61092.
TreeFamiTF312976.

Enzyme and pathway databases

UniPathwayiUPA00143.
BRENDAi6.3.2.19. 3474.
ReactomeiREACT_293956. Netrin-1 signaling.

Miscellaneous databases

ChiTaRSiSiah1a. mouse.
EvolutionaryTraceiP61092.
NextBioi298464.
PROiP61092.
SOURCEiSearch...

Gene expression databases

BgeeiP61092.
CleanExiMM_SIAH1A.
GenevisibleiP61092. MM.

Family and domain databases

Gene3Di3.30.40.10. 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]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 1 hit.
PROSITEiPS50089. ZF_RING_2. 1 hit.
PS51081. ZF_SIAH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiSIA1A_MOUSE
AccessioniPrimary (citable) accession number: P61092
Secondary accession number(s): Q06984
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: July 22, 2015
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.