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SIAH2 siah E3 ubiquitin protein ligase 2 [ Homo sapiens (human) ]

Gene ID: 6478, updated on 5-Mar-2024

Summary

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Official Symbol
SIAH2provided by HGNC
Official Full Name
siah E3 ubiquitin protein ligase 2provided by HGNC
Primary source
HGNC:HGNC:10858
See related
Ensembl:ENSG00000181788 MIM:602213; AllianceGenome:HGNC:10858
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
hSiah2
Summary
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]
Expression
Ubiquitous expression in adrenal (RPKM 42.6), placenta (RPKM 22.5) and 24 other tissues See more
Orthologs
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Genomic context

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See SIAH2 in Genome Data Viewer
Location:
3q25.1
Exon count:
2
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (150741125..150763169, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (153492334..153514363, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (150458912..150480956, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ERICH6 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:150442941-150443442 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:150443443-150443942 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:150445187-150445686 Neighboring gene CRISPRi-validated cis-regulatory element chr3.4443 Neighboring gene CRISPRi-validated cis-regulatory element chr3.4444 Neighboring gene small nuclear ribonucleoprotein polypeptide C pseudogene 3 Neighboring gene uncharacterized LOC101928105 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14817 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20697 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20698 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:150480427-150481373 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20699 Neighboring gene uncharacterized LOC124909447 Neighboring gene SIAH2 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14819 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr3:150523844-150524366 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr3:150524367-150524888 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:150539149-150539823 Neighboring gene NANOG hESC enhancer GRCh37_chr3:150566660-150567161 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14820 Neighboring gene MINDY family member 4B Neighboring gene uncharacterized LOC124909446

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The role of Siah2 in tumorigenesis and cancer therapy. Li K, et al. Gene, 2022 Jan 30. PMID 34687788
  2. Inhibition of Siah2 Ubiquitin Ligase by Vitamin K3 Attenuates Chronic Myeloid Leukemia Chemo-Resistance in Hypoxic Microenvironment. Huang J, et al. Med Sci Monit, 2018 Feb 5. PMID 29400343, Free PMC Article
  3. Overexpression of seven in absentia homolog 2 protein in human breast cancer tissues is associated with the promotion of tumor cell malignant behavior in in vitro. Sun J, et al. Oncol Rep, 2016 Sep. PMID 27459914
  4. The expression and function of E3 ligase SIAH2 in acute T lymphoblastic leukemia. Chen H, et al. Leuk Res, 2016 Mar. PMID 26859780
  5. The Expression of the Ubiquitin Ligase SIAH2 (Seven In Absentia Homolog 2) Is Increased in Human Lung Cancer. Moreno P, et al. PLoS One, 2015. PMID 26580787, Free PMC Article

See all (125) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. SIAH2 regulates DNA end resection and replication fork recovery by promoting CtIP ubiquitination.
    Title: SIAH2 regulates DNA end resection and replication fork recovery by promoting CtIP ubiquitination.
  2. Decreased Expression of Programmed Death Ligand-L1 by Seven in Absentia Homolog 2 in Cholangiocarcinoma Enhances T-Cell-Mediated Antitumor Activity.
    Title: Decreased Expression of Programmed Death Ligand-L1 by Seven in Absentia Homolog 2 in Cholangiocarcinoma Enhances T-Cell-Mediated Antitumor Activity.
  3. The role of Siah2 in tumorigenesis and cancer therapy.
    Title: The role of Siah2 in tumorigenesis and cancer therapy.
  4. Helicobacter pylori-induced gastric cancer is orchestrated by MRCKbeta-mediated Siah2 phosphorylation.
    Title: Helicobacter pylori-induced gastric cancer is orchestrated by MRCKβ-mediated Siah2 phosphorylation.
  5. Siah2 integrates mitogenic and extracellular matrix signals linking neuronal progenitor ciliogenesis with germinal zone occupancy.
    Title: Siah2 integrates mitogenic and extracellular matrix signals linking neuronal progenitor ciliogenesis with germinal zone occupancy.
  6. SIAH2-mediated and organ-specific restriction of HO-1 expression by a dual mechanism.
    Title: SIAH2-mediated and organ-specific restriction of HO-1 expression by a dual mechanism.
  7. Low SIAH2 and FOXP3 expression is identified in immune responsive human melanoma tumors.
    Title: Siah2 control of T-regulatory cells limits anti-tumor immunity.
  8. Testin and filamin-C downregulation by acetylated Siah2 increases invasiveness of Helicobacter pylori-infected gastric cancer cells
    Title: Testin and filamin-C downregulation by acetylated Siah2 increases invasiveness of Helicobacter pylori-infected gastric cancer cells.
  9. Acetylation-mediated Siah2 stabilization enhances PHD3 degradation in Helicobacter pylori-infected gastric epithelial cancer cells.
    Title: Acetylation-mediated Siah2 stabilization enhances PHD3 degradation in Helicobacter pylori-infected gastric epithelial cancer cells.
  10. DHX15 regulates androgen receptor (AR) activity by modulating E3 ligase Siah2-mediated AR ubiquitination independent of its ATPase activity promoting prostate cancer progression.
    Title: DHX15 promotes prostate cancer progression by stimulating Siah2-mediated ubiquitination of androgen receptor.
Submit: New GeneRIF Correction See all GeneRIFs (64)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study identifies a genetic variant in the SIAH2 locus associated with hormonal receptor-positive breast cancer in Japanese.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables transcription corepressor activity TAS
Traceable Author Statement
more info
 PubMed 
enables ubiquitin conjugating enzyme binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ubiquitin protein ligase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables ubiquitin-protein transferase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables ubiquitin-protein transferase activity TAS
Traceable Author Statement
more info
  
enables zinc ion binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in amyloid fibril formation TAS
Traceable Author Statement
more info
  
involved_in apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in canonical Wnt signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cell cycle IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of DNA-templated transcription IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_or_within negative regulation of canonical Wnt signaling pathway IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in negative regulation of cysteine-type endopeptidase activity involved in apoptotic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of extrinsic apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein ubiquitination IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of circadian rhythm IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of protein ubiquitination IEA
Inferred from Electronic Annotation
more info
  
involved_in rhythmic process IEA
Inferred from Electronic Annotation
more info
  
involved_in small GTPase-mediated signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in ubiquitin-dependent protein catabolic process ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in early endosome IEA
Inferred from Electronic Annotation
more info
  
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
located_in neuronal cell body IEA
Inferred from Electronic Annotation
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
E3 ubiquitin-protein ligase SIAH2
Names
RING-type E3 ubiquitin transferase SIAH2
seven in absentia homolog 2
siah-2
NP_005058.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_005067.7 → NP_005058.3  E3 ubiquitin-protein ligase SIAH2

    See identical proteins and their annotated locations for NP_005058.3

    Status: VALIDATED

    Source sequence(s)
    AC011317, AK223565, BC013082, BX110898, CK823254
    Consensus CDS
    CCDS3152.1
    UniProtKB/Swiss-Prot
    O43255, O43270
    UniProtKB/TrEMBL
    Q53ES4
    Related
    ENSP00000322457.3, ENST00000312960.4
    Conserved Domains (2) summary
    cd16752
    Location:78 → 115
    RING-HC_SIAH2; RING finger, HC subclass, found in seven in absentia homolog 2 (SIAH2) and similar proteins
    pfam03145
    Location:122 → 318
    Sina; Seven in absentia protein family

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    150741125..150763169 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    153492334..153514363 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O43255.1 GenPept UniProtKB/Swiss-Prot:O43255

Gene LinkOut

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