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Aliases for SIAH1 Gene

Aliases for SIAH1 Gene

  • Siah E3 Ubiquitin Protein Ligase 1 2 3
  • Seven In Absentia Homolog 1 3 4
  • Siah-1a 3 4
  • Seven In Absentia Homolog 1 (Drosophila) 2
  • E3 Ubiquitin-Protein Ligase SIAH1 3
  • EC 6.3.2.- 4
  • EC 6.3.2 63
  • HUMSIAH 4
  • SIAH1A 3
  • Siah-1 4

External Ids for SIAH1 Gene

Previous GeneCards Identifiers for SIAH1 Gene

  • GC16M038809
  • GC16M048443
  • GC16M048131
  • GC16M048172
  • GC16M046951
  • GC16M034285

Summaries for SIAH1 Gene

Entrez Gene Summary for SIAH1 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 the development of certain forms of Parkinson's disease, the regulation of the cellular response to hypoxia and induction of apoptosis. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]

GeneCards Summary for SIAH1 Gene

SIAH1 (Siah E3 Ubiquitin Protein Ligase 1) is a Protein Coding gene. Diseases associated with SIAH1 include hypoxia. Among its related pathways are L1CAM interactions and L1CAM interactions. GO annotations related to this gene include ubiquitin-protein transferase activity and protein C-terminus binding. An important paralog of this gene is SIAH3.

UniProtKB/Swiss-Prot for SIAH1 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 (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 regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. 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.

Gene Wiki entry for SIAH1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SIAH1 Gene

Genomics for SIAH1 Gene

Regulatory Elements for SIAH1 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for SIAH1 Gene

Start:
48,356,364 bp from pter
End:
48,448,402 bp from pter
Size:
92,039 bases
Orientation:
Minus strand

Genomic View for SIAH1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for SIAH1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SIAH1 Gene

Proteins for SIAH1 Gene

  • Protein details for SIAH1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8IUQ4-SIAH1_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase SIAH1
    Protein Accession:
    Q8IUQ4
    Secondary Accessions:
    • A0FKF3
    • O43269
    • Q49A58
    • Q92880

    Protein attributes for SIAH1 Gene

    Size:
    282 amino acids
    Molecular mass:
    31123 Da
    Quaternary structure:
    • Homodimer. Interacts with group 1 glutamate receptors GRM1 and GRM5. Interacts with DAB1, which may inhibit its activity. Interacts with UBE2E2. Interacts with PEG3. Interacts with GAPDH; leading to stabilize SIAH1 (By similarity). 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 KHDRBS3. Interacts with SNCAIP and HIPK2.

    Three dimensional structures from OCA and Proteopedia for SIAH1 Gene

    Alternative splice isoforms for SIAH1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SIAH1 Gene

Proteomics data for SIAH1 Gene at MOPED

Post-translational modifications for SIAH1 Gene

  • Phosphorylated on Ser-19 by ATM and ATR. This phosphorylation disrupts SIAH1 interaction with HIPK2, and subsequent proteasomal degradation of HIPK2.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SIAH1 Gene

Domains for SIAH1 Gene

Suggested Antigen Peptide Sequences for SIAH1 Gene

Graphical View of Domain Structure for InterPro Entry

Q8IUQ4

UniProtKB/Swiss-Prot:

SIAH1_HUMAN :
  • Q8IUQ4
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 (By similarity).
Family:
  • Belongs to the SINA (Seven in absentia) family.
Similarity:
  • Contains 1 RING-type zinc finger.
  • Contains 1 SIAH-type zinc finger.
genes like me logo Genes that share domains with SIAH1: view

No data available for Gene Families for SIAH1 Gene

Function for SIAH1 Gene

Molecular function for SIAH1 Gene

GENATLAS Biochemistry: Drosophila seven in absentia (sina) homolog 1,putatively involved in apoptosis and tumor suppression,also mediating through RING finger ubiquitin-conjugating enzyme (E2)-dependent ubiquitination
UniProtKB/Swiss-Prot EnzymeRegulation: Inhibited by interaction with SNCAIP (isoform 2, but not isoform 1). May be inhibited by interaction with PEG10.
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 (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 regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. 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.
UniProtKB/Swiss-Prot 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

Enzyme Numbers (IUBMB) for SIAH1 Gene

Gene Ontology (GO) - Molecular Function for SIAH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity ISS --
GO:0005515 protein binding IPI 11483518
GO:0008022 protein C-terminus binding IPI 11389840
GO:0008270 zinc ion binding ISS --
GO:0016874 ligase activity IEA --
genes like me logo Genes that share ontologies with SIAH1: view
genes like me logo Genes that share phenotypes with SIAH1: view

Animal Models for SIAH1 Gene

MGI Knock Outs for SIAH1:

Animal Model Products

CRISPR Products

miRNA for SIAH1 Gene

miRTarBase miRNAs that target SIAH1

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for SIAH1

In Situ Assay Products

Flow Cytometry Products

No data available for Transcription Factor Targeting and HOMER Transcription for SIAH1 Gene

Localization for SIAH1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SIAH1 Gene

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

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for SIAH1 Gene COMPARTMENTS Subcellular localization image for SIAH1 gene
Compartment Confidence
nucleus 5
cytosol 4
endosome 2
mitochondrion 2
plasma membrane 2

Gene Ontology (GO) - Cellular Components for SIAH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus ISS --
GO:0005737 cytoplasm TAS 9334332
GO:0005769 early endosome IEA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IEA --
genes like me logo Genes that share ontologies with SIAH1: view

Pathways for SIAH1 Gene

genes like me logo Genes that share pathways with SIAH1: view

Pathways by source for SIAH1 Gene

1 BioSystems pathway for SIAH1 Gene
3 Reactome pathways for SIAH1 Gene

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

UniProtKB/Swiss-Prot Q8IUQ4-SIAH1_HUMAN

  • Pathway: Protein modification; protein ubiquitination

Gene Ontology (GO) - Biological Process for SIAH1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis --
GO:0006511 ubiquitin-dependent protein catabolic process IDA 23001567
GO:0006915 apoptotic process TAS 9403064
GO:0007049 cell cycle IEA --
GO:0007275 multicellular organismal development --
genes like me logo Genes that share ontologies with SIAH1: view

Compounds for SIAH1 Gene

(4) HMDB Compounds for SIAH1 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine monophosphate
  • 5'-AMP
61-19-8
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
Phosphoric acid
  • acide phosphorique (FRENCH)
7664-38-2
Pyrophosphate
  • (4-)Diphosphoric acid ion
14000-31-8

(1) Novoseek inferred chemical compound relationships for SIAH1 Gene

Compound -log(P) Hits PubMed IDs
nitric oxide 0 2
genes like me logo Genes that share compounds with SIAH1: view

Transcripts for SIAH1 Gene

Unigene Clusters for SIAH1 Gene

Siah E3 ubiquitin protein ligase 1:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for SIAH1

Primer Products

  • QuantiTect SYBR Green Assays in human,mouse,rat
  • Pre-validated RT² qPCR Primer Assay in human,mouse,rat
  • QuantiFast Probe-based Assays in human,mouse,rat

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for SIAH1 Gene

No ASD Table

Relevant External Links for SIAH1 Gene

GeneLoc Exon Structure for
SIAH1
ECgene alternative splicing isoforms for
SIAH1

Expression for SIAH1 Gene

mRNA expression in normal human tissues for SIAH1 Gene

mRNA differential expression in normal tissues according to GTEx for SIAH1 Gene

This gene is overexpressed in Testis (4.5).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for SIAH1 Gene

SOURCE GeneReport for Unigene cluster for SIAH1 Gene Hs.706828

mRNA Expression by UniProt/SwissProt for SIAH1 Gene

Q8IUQ4-SIAH1_HUMAN
Tissue specificity: Widely expressed at a low level. Down-regulated in advanced hepatocellular carcinomas.
genes like me logo Genes that share expressions with SIAH1: view

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for SIAH1 Gene

Orthologs for SIAH1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for SIAH1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SIAH1 35
  • 99.65 (n)
  • 100 (a)
SIAH1 36
  • 95 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SIAH1 35
  • 93.61 (n)
  • 97.44 (a)
SIAH1 36
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia SIAH1 35
  • 93.72 (n)
  • 97.44 (a)
SIAH1 36
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Siah1a 35
  • 92.67 (n)
  • 99.65 (a)
Siah1a 16
Siah1a 36
  • 100 (a)
OneToMany
Siah1b 36
  • 98 (a)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia SIAH1 36
  • 87 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Siah1a 35
  • 91.84 (n)
  • 99.65 (a)
chicken
(Gallus gallus)
Aves SIAH1 35
  • 90.31 (n)
  • 99.65 (a)
SIAH1 36
  • 100 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SIAH1 36
  • 95 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.2090 35
tropical clawed frog
(Silurana tropicalis)
Amphibia siah1 35
  • 84.75 (n)
  • 99.29 (a)
Str.642 35
zebrafish
(Danio rerio)
Actinopterygii idibd2635 35
siah1 35
  • 76.76 (n)
  • 97.18 (a)
siah1 36
  • 97 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP006127 35
  • 66.67 (n)
  • 77.85 (a)
fruit fly
(Drosophila melanogaster)
Insecta CG2681 36
  • 11 (a)
OneToMany
sina 35
  • 64.56 (n)
  • 79.18 (a)
sinah 36
  • 37 (a)
OneToMany
sina 37
  • 83 (a)
CG13030 37
  • 40 (a)
worm
(Caenorhabditis elegans)
Secernentea siah-1 35
  • 58.5 (n)
  • 63.4 (a)
Y37E11AR.2 37
  • 67 (a)
rice
(Oryza sativa)
Liliopsida Os07g0659800 35
  • 46.27 (n)
  • 36.47 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.9219 35
Species with no ortholog for SIAH1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • 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 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 SIAH1 Gene

ENSEMBL:
Gene Tree for SIAH1 (if available)
TreeFam:
Gene Tree for SIAH1 (if available)

Paralogs for SIAH1 Gene

Paralogs for SIAH1 Gene

Selected SIMAP similar genes for SIAH1 Gene using alignment to 3 proteins:

Pseudogenes.org Pseudogenes for SIAH1 Gene

genes like me logo Genes that share paralogs with SIAH1: view

Variants for SIAH1 Gene

Sequence variations from dbSNP and Humsavar for SIAH1 Gene

SNP ID Clin Chr 16 pos Sequence Context AA Info Type MAF
rs1545942 -- 48,393,395(+) actca(C/G)tggct intron-variant
rs3809684 -- 48,387,400(-) AAATT(A/T)ATAAT intron-variant
rs3809685 -- 48,386,682(-) CTTCC(C/T)GTGTA upstream-variant-2KB, intron-variant
rs4785516 -- 48,366,006(+) GGGCG(A/G)TGCCC upstream-variant-2KB, intron-variant
rs4785517 -- 48,381,951(+) cgtgt(A/C/G)ggggc intron-variant

Structural Variations from Database of Genomic Variants (DGV) for SIAH1 Gene

Variant ID Type Subtype PubMed ID
nsv833219 CNV Gain 17160897
dgv888e1 CNV Complex 17122850
esv26254 CNV Loss 19812545

Relevant External Links for SIAH1 Gene

HapMap Linkage Disequilibrium report
SIAH1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SIAH1 Gene

Disorders for SIAH1 Gene

MalaCards: The human disease database

MalaCards: The human disease database. (1) Diseases for SIAH1 Gene including...

Search for SIAH1 Gene in MalaCards »

(2) Novoseek inferred disease relationships for SIAH1 Gene

Disease -log(P) Hits PubMed IDs
parkinson disease 45.8 2
tumors 0 3

Relevant External Links for SIAH1

Genetic Association Database (GAD)
SIAH1
Human Genome Epidemiology (HuGE) Navigator
SIAH1
genes like me logo Genes that share disorders with SIAH1: view

No data available for UniProtKB/Swiss-Prot for SIAH1 Gene

Publications for SIAH1 Gene

  1. Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein. (PMID: 11389840) Liu J. … Matsunami N. (Mol. Cell 2001) 3 4 23
  2. Modulation of transforming growth factor beta (TGFbeta)/Smad transcriptional responses through targeted degradation of TGFbeta- inducible early gene-1 by human seven in absentia homologue. (PMID: 12072443) Johnsen S.A. … Spelsberg T.C. (J. Biol. Chem. 2002) 3 4 23
  3. Structural analysis of Siah1 and its interactions with Siah- interacting protein (SIP). (PMID: 12421809) Matsuzawa S. … Ely K.R. (J. Biol. Chem. 2003) 3 4 23
  4. Siah-1 facilitates ubiquitination and degradation of synphilin-1. (PMID: 14506261) Nagano Y. … Matsumoto M. (J. Biol. Chem. 2003) 3 4 23
  5. SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome. (PMID: 15163637) Venables J.P. … Elliott D.J. (Hum. Mol. Genet. 2004) 3 4 23

Products for SIAH1 Gene

Sources for SIAH1 Gene

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