This gene encodes a protein that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligase and is involved in ubiquitination and proteasome-mediated degradation of specific proteins. The activity of this ubiquitin ligase has been implicated in regulating cellular response to hypoxia. [provided by RefSeq, Jul 2008] See more...

Aliases for SIAH2 Gene

Aliases for SIAH2 Gene

  • Siah E3 Ubiquitin Protein Ligase 2 2 3 5
  • RING-Type E3 Ubiquitin Transferase SIAH2 3 4
  • E3 Ubiquitin-Protein Ligase SIAH2 3 4
  • Seven In Absentia Homolog 2 3 4
  • Siah-2 3 4
  • HSiah2 3 4
  • Seven In Absentia (Drosophila) Homolog 2 2
  • Seven In Absentia Homolog 2 (Drosophila) 2
  • EC 2.3.2.27 4
  • EC 6.3.2 52

External Ids for SIAH2 Gene

Previous GeneCards Identifiers for SIAH2 Gene

  • GC03M147291
  • GC03M151291
  • GC03M151740
  • GC03M151779
  • GC03M151941
  • GC03M150458
  • GC03M147832

Summaries for SIAH2 Gene

Entrez Gene Summary for SIAH2 Gene

  • This gene encodes a protein that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligase and is involved in ubiquitination and proteasome-mediated degradation of specific proteins. The activity of this ubiquitin ligase has been implicated in regulating cellular response to hypoxia. [provided by RefSeq, Jul 2008]

GeneCards Summary for SIAH2 Gene

SIAH2 (Siah E3 Ubiquitin Protein Ligase 2) is a Protein Coding gene. Diseases associated with SIAH2 include Usher Syndrome. Among its related pathways are Metabolism of proteins and Class I MHC mediated antigen processing and presentation. Gene Ontology (GO) annotations related to this gene include ligase activity and transcription corepressor activity. An important paralog of this gene is SIAH1.

UniProtKB/Swiss-Prot Summary for SIAH2 Gene

  • 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 (GPS2, POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP). Mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia. It is thereby involved in apoptosis, tumor suppression, cell cycle, transcription and signaling processes. Has some overlapping function with SIAH1. Triggers the ubiquitin-mediated degradation of TRAF2, whereas SIAH1 does not. Promotes monoubiquitination of SNCA. Regulates cellular clock function via ubiquitination of the circadian transcriptional repressors NR1D1 and NR1D2 leading to their proteasomal degradation. Plays an important role in mediating the rhythmic degradation/clearance of NR1D1 and NR1D2 contributing to their circadian profile of protein abundance (PubMed:26392558).

Gene Wiki entry for SIAH2 Gene

Additional gene information for SIAH2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SIAH2 Gene

Genomics for SIAH2 Gene

GeneHancer (GH) Regulatory Elements for SIAH2 Gene

Promoters and enhancers for SIAH2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SIAH2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SIAH2

Top Transcription factor binding sites by QIAGEN in the SIAH2 gene promoter:
  • AML1a
  • ATF
  • c-Myc
  • CP2
  • E47
  • IRF-2
  • Max1
  • SEF-1 (1)
  • USF-1
  • USF1

Genomic Locations for SIAH2 Gene

Genomic Locations for SIAH2 Gene
chr3:150,741,123-150,763,477
(GRCh38/hg38)
Size:
22,355 bases
Orientation:
Minus strand
chr3:150,458,910-150,481,264
(GRCh37/hg19)
Size:
22,355 bases
Orientation:
Minus strand

Genomic View for SIAH2 Gene

Genes around SIAH2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SIAH2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SIAH2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIAH2 Gene

Proteins for SIAH2 Gene

  • Protein details for SIAH2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43255-SIAH2_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase SIAH2
    Protein Accession:
    O43255
    Secondary Accessions:
    • O43270

    Protein attributes for SIAH2 Gene

    Size:
    324 amino acids
    Molecular mass:
    34615 Da
    Quaternary structure:
    • Homodimer. Interacts with UBE2E2. Interacts with PEG3 (By similarity). Interacts with VAV1, without mediating its ubiquitin-mediated degradation. Interacts with CACYBP/SIP. Probable component of some large E3 complex possibly composed of UBE2D1, SIAH2, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with PEG10, which may inhibit its activity. Interacts with EGLN2 and SNCAIP. Interacts with DYRK2. Interacts with NR1D1 and NR1D2 (PubMed:26392558).

    Three dimensional structures from OCA and Proteopedia for SIAH2 Gene

neXtProt entry for SIAH2 Gene

Selected DME Specific Peptides for SIAH2 Gene

O43255:
  • RRRLTWEA
  • FMLVLEKQE
  • PRSIHDGV
  • HKSITTLQGEDIVFLATDI
  • YRLELNG
  • IRNLAME
  • WEATPRSIH
  • CPCPGASCKW
  • LIGTRKQA
  • VLFPCKYA
  • SDCLVFD
  • NGNLGINVTIS

Post-translational modifications for SIAH2 Gene

  • Phosphorylated at Ser-28 by MAPK14, which mediates the degradation by the proteasome of EGLN3 (By similarity). Phosphorylated at Ser-28 by DYRK2; this increases the ubiquitin ligase activity and promotes degradation of EGLN3.
  • Ubiquitination at Lys13 and Lys107
  • Modification sites at PhosphoSitePlus

Other Protein References for SIAH2 Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for SIAH2 Gene

Gene Families for SIAH2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for SIAH2 Gene

Suggested Antigen Peptide Sequences for SIAH2 Gene

GenScript: Design optimal peptide antigens:
  • Seven in absentia homolog 2 (SIAH2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O43255

UniProtKB/Swiss-Prot:

SIAH2_HUMAN :
  • The RING-type zinc finger domain is essential for ubiquitin ligase activity.
  • Belongs to the SINA (Seven in absentia) family.
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.
Family:
  • Belongs to the SINA (Seven in absentia) family.
genes like me logo Genes that share domains with SIAH2: view

Function for SIAH2 Gene

Molecular function for SIAH2 Gene

UniProtKB/Swiss-Prot 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 (GPS2, POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP). Mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia. It is thereby involved in apoptosis, tumor suppression, cell cycle, transcription and signaling processes. Has some overlapping function with SIAH1. Triggers the ubiquitin-mediated degradation of TRAF2, whereas SIAH1 does not. Promotes monoubiquitination of SNCA. Regulates cellular clock function via ubiquitination of the circadian transcriptional repressors NR1D1 and NR1D2 leading to their proteasomal degradation. Plays an important role in mediating the rhythmic degradation/clearance of NR1D1 and NR1D2 contributing to their circadian profile of protein abundance (PubMed:26392558).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by interaction with SNCAIP (isoform 2, but not isoform 1). May be inhibited by interaction with PEG10.
GENATLAS Biochemistry:
Drosophila seven in absentia (sina) homolog 2,involved in vertebrate (? photoreceptor) development,widely expressed,also mediating through RING finger,ubiquitin-conjugating enzyme (E2)-dependent ubiquitination

Enzyme Numbers (IUBMB) for SIAH2 Gene

Phenotypes From GWAS Catalog for SIAH2 Gene

Gene Ontology (GO) - Molecular Function for SIAH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003714 transcription corepressor activity TAS 10207103
GO:0004842 ubiquitin-protein transferase activity TAS --
GO:0005515 protein binding IPI,IEA 21586138
GO:0008270 zinc ion binding IEA --
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with SIAH2: view
genes like me logo Genes that share phenotypes with SIAH2: view

Animal Models for SIAH2 Gene

MGI Knock Outs for SIAH2:

Animal Model Products

  • Taconic Biosciences Mouse Models for SIAH2

CRISPR Products

Clone Products

  • Addgene plasmids for SIAH2

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SIAH2 Gene

Localization for SIAH2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIAH2 Gene

Cytoplasm. Nucleus. Note=Predominantly cytoplasmic. Partially nuclear. {ECO:0000269 PubMed:22878263}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SIAH2 gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
endosome 2
peroxisome 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SIAH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm TAS 10207103
GO:0005769 early endosome IEA --
GO:0005829 cytosol IEA,TAS --
genes like me logo Genes that share ontologies with SIAH2: view

Pathways & Interactions for SIAH2 Gene

genes like me logo Genes that share pathways with SIAH2: view

Pathways by source for SIAH2 Gene

1 GeneGo (Thomson Reuters) pathway for SIAH2 Gene
  • Proteolysis Role of Parkin in the Ubiquitin-Proteasomal Pathway

UniProtKB/Swiss-Prot O43255-SIAH2_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for SIAH2 Gene

Activates:
Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for SIAH2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination TAS --
GO:0006511 ubiquitin-dependent protein catabolic process IEA,ISS --
GO:0006915 apoptotic process IEA --
GO:0007049 cell cycle IEA --
GO:0007264 small GTPase mediated signal transduction TAS 10207103
genes like me logo Genes that share ontologies with SIAH2: view

Drugs & Compounds for SIAH2 Gene

(3) Drugs for SIAH2 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phosphoric acid Approved Pharma 0
Adenosine monophosphate Approved, Investigational Nutra 0
ATP Investigational Nutra Agonist, Activator, Full agonist, Antagonist, Pore Blocker, Potentiation 0

(1) Additional Compounds for SIAH2 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
pyrophosphate
  • [(ho)2P(O)OP(O)(OH)2]
  • Acide diphosphorique
  • Diphosphorsaeure
  • H4P2O7
  • PYROphosphATE
14000-31-8
genes like me logo Genes that share compounds with SIAH2: view

Transcripts for SIAH2 Gene

mRNA/cDNA for SIAH2 Gene

1 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for SIAH2

Alternative Splicing Database (ASD) splice patterns (SP) for SIAH2 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b · 2c ^ 3a · 3b
SP1: - -
SP2: -
SP3:

Relevant External Links for SIAH2 Gene

GeneLoc Exon Structure for
SIAH2

Expression for SIAH2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SIAH2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SIAH2 Gene

This gene is overexpressed in Whole Blood (x5.7).

Protein differential expression in normal tissues from HIPED for SIAH2 Gene

This gene is overexpressed in Platelet (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for SIAH2 Gene



Protein tissue co-expression partners for SIAH2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SIAH2

SOURCE GeneReport for Unigene cluster for SIAH2 Gene:

Hs.477959

mRNA Expression by UniProt/SwissProt for SIAH2 Gene:

O43255-SIAH2_HUMAN
Tissue specificity: Widely expressed at low level.

Evidence on tissue expression from TISSUES for SIAH2 Gene

  • Nervous system(4.4)
genes like me logo Genes that share expression patterns with SIAH2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for SIAH2 Gene

Orthologs for SIAH2 Gene

This gene was present in the common ancestor of animals.

Orthologs for SIAH2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SIAH2 31 30
  • 99.9 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SIAH2 31
  • 96 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SIAH2 31 30
  • 93.21 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Siah2 30
  • 92.98 (n)
mouse
(Mus musculus)
Mammalia Siah2 17 31 30
  • 92.57 (n)
dog
(Canis familiaris)
Mammalia SIAH2 30
  • 88.89 (n)
chicken
(Gallus gallus)
Aves SIAH2 31 30
  • 83.91 (n)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia siah2 30
  • 78.2 (n)
African clawed frog
(Xenopus laevis)
Amphibia siah2-A 30
zebrafish
(Danio rerio)
Actinopterygii siah2l 31 30
  • 78.92 (n)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta sina 31 32
  • 67 (a)
OneToMany
CG13030 32
  • 37 (a)
worm
(Caenorhabditis elegans)
Secernentea Y37E11AR.2 32
  • 67 (a)
siah-1 31
  • 44 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.8769 31
  • 81 (a)
OneToMany
Species where no ortholog for SIAH2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for SIAH2 Gene

ENSEMBL:
Gene Tree for SIAH2 (if available)
TreeFam:
Gene Tree for SIAH2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SIAH2: view image

Paralogs for SIAH2 Gene

Paralogs for SIAH2 Gene

(2) SIMAP similar genes for SIAH2 Gene using alignment to 2 proteins:

  • SIAH2_HUMAN
  • C9J9D7_HUMAN
genes like me logo Genes that share paralogs with SIAH2: view

Variants for SIAH2 Gene

Additional dbSNP identifiers (rs#s) for SIAH2 Gene

Structural Variations from Database of Genomic Variants (DGV) for SIAH2 Gene

Variant ID Type Subtype PubMed ID
dgv8650n54 CNV gain 21841781
dgv8651n54 CNV gain 21841781
esv25944 CNV loss 19812545
esv3342752 CNV insertion 20981092
nsv1074633 CNV deletion 25765185
nsv4061 CNV insertion 18451855
nsv592037 CNV loss 21841781
nsv592041 CNV loss 21841781
nsv592043 CNV gain+loss 21841781

Variation tolerance for SIAH2 Gene

Residual Variation Intolerance Score: 25.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.46; 54.94% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SIAH2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SIAH2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SIAH2 Gene

Disorders for SIAH2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for SIAH2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
usher syndrome
  • retinitis pigmentosa-deafness syndrome
- elite association - COSMIC cancer census association via MalaCards
Search SIAH2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for SIAH2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with SIAH2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SIAH2 Gene

Publications for SIAH2 Gene

  1. Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway. (PMID: 9334332) Hu G … Fearon ER (Genes & development 1997) 2 3 4 54
  2. Ubiquitin ligase Siah2 regulates RevErbα degradation and the mammalian circadian clock. (PMID: 26392558) DeBruyne JP … Hogenesch JB (Proceedings of the National Academy of Sciences of the United States of America 2015) 3 4 54
  3. Mutual regulation between SIAH2 and DYRK2 controls hypoxic and genotoxic signaling pathways. (PMID: 22878263) Pérez M … Calzado MA (Journal of molecular cell biology 2012) 3 4 54
  4. The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors. (PMID: 19730683) Landa I … Robledo M (PLoS genetics 2009) 3 41 54
  5. Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates alpha-synuclein monoubiquitylation and inclusion formation. (PMID: 19224863) Szargel R … Engelender S (The Journal of biological chemistry 2009) 3 4 54

Products for SIAH2 Gene

Sources for SIAH2 Gene