SIAH2 siah E3 ubiquitin protein ligase 2 [Homo sapiens] - Gene

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Summary

Official Symbol: SIAH2provided by HGNC
Official Full Name: siah E3 ubiquitin protein ligase 2provided by HGNC
Primary source: HGNC:10858
See related: Ensembl:ENSG00000181788; HPRD:03737; MIM:602213; Vega:OTTHUMG00000159847
Gene type: protein coding
RefSeq status: REVIEWED
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]

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Genomic context

Location :: 3q25

Sequence :: Chromosome: 3; NC_000003.11 (150458910..150481263, complement)

See SIAH2 in Epigenomics, MapViewer

Chromosome 3 - NC_000003.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Siah2 acts as an E3 ligase to directly ubiquitylate TIN2 in vitro.
Title: TIN2 stability is regulated by the E3 ligase Siah2.
Src kinase activity downregulates C/EBP-delta protein but not mRNA levels through a SIAH2 E3 ligase-dependent mechanism.
Title: Identification of a Src tyrosine kinase/SIAH2 E3 ubiquitin ligase pathway that regulates C/EBPδ expression and contributes to transformation of breast tumor cells.
study identifies a new layer of Siah2 regulation mediated by USP13 binding to ubiquitinated Siah2 protein with a concomitant inhibitory effect on its activity under normoxia
Title: USP13 enzyme regulates Siah2 ligase stability and activity via noncatalytic ubiquitin-binding domains.
The data presented here define POSH and Siah2 as important mediators of death receptor mediated apoptosis and suggest targeting the interaction of these two E3 ligases is a promising novel cancer therapeutic strategy.
Title: Possible role of death receptor-mediated apoptosis by the E3 ubiquitin ligases Siah2 and POSH.
Review: Define the regulatory axis consisting of Siah2 and HIF-1alpha/FoxA2 cooperation and suggest novel therapeutic modalities to treat these most aggressive forms of prostate cancer.
Title: The Siah2-HIF-FoxA2 axis in prostate cancer – new markers and therapeutic opportunities.
The ability of myosin phosphatase to modulate myosin light chain might be regulated by the degradation of its targeting subunit MYPT1 through the SIAH2-ubiquitin-proteasomal pathway.
Title: Regulation of MYPT1 stability by the E3 ubiquitin ligase SIAH2.
Observational study of gene-disease association. (HuGE Navigator)
Title: The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors.
In primary breast tumor specimens as well as in vitro low SIAH2 levels associated with resistance to endocrine therapy.
Title: Downregulation of SIAH2, an ubiquitin E3 ligase, is associated with resistance to endocrine therapy in breast cancer.
Siah1 (human) reduced PHD3 protein levels similar to that observed with Siah2. PHDs may not interact directly with Siah2, but that the substrate-binding groove of Siah is nevertheless important.
Title: Inhibition of Siah ubiquitin ligase function.
Hypoxic conditions allow a markedly increased HIPK2/Siah2 interaction and result in efficient polyubiquitylation and proteasomal degradation of the kinase.
Title: An inducible autoregulatory loop between HIPK2 and Siah2 at the apex of the hypoxic response.

Submit: New GeneRIF Correction See all (22)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_005058.3	NP_005206.1	DCC	BIND	PubMed	DCC interacts with Siah-2.
NP_005058.3	NP_005206.1	DCC	BIND	PubMed	hSiah2 interacts with DCC.
NP_005058.3	NP_003336.1	UBE2I	BIND	PubMed	Ubc9 interacts with Siah-2.
NP_005058.3	NP_003336.1	UBE2I	BIND	PubMed	hSiah2 interacts with Ubc9.
O43255	P51825	AFF1	HPRD	PubMed
O43255	P54259	ATN1	HPRD	PubMed
O43255	Q9HB71	CACYBP	HPRD	PubMed
O43255	P43146	DCC	HPRD	PubMed
O43255	Q9H422	HIPK3	HPRD	PubMed
O43255	Paternally expressed 10	PEG10	HPRD	PubMed
O43255	Q9GZU2	PEG3	HPRD	PubMed
O43255	Q16633	POU2AF1	HPRD	PubMed
O43255	Q99708	RBBP8	HPRD	PubMed
O43255	P08247	SYP	HPRD	PubMed
O43255	Q12933	TRAF2	HPRD	PubMed
O43255	O14933	UBE2L6	HPRD	PubMed
O43255	P15498	VAV1	HPRD	PubMed
BioGRID:112373	BioGRID:113818	AKAP1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112373	BioGRID:198048	Akap1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112373	BioGRID:108087	DLST	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112373	BioGRID:120060	EGLN1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112373	BioGRID:125184	EGLN2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112373	BioGRID:125185	EGLN3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112373	BioGRID:114368	HDAC3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112373	BioGRID:118815	HIPK2	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:112373	BioGRID:116717	PEG10	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:112373	BioGRID:111204	PEG3	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:112373	BioGRID:114124	PIAS1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex; Two-hybrid
BioGRID:112373	BioGRID:114523	PIAS2	BioGRID	PubMed	Two-hybrid
BioGRID:112373	BioGRID:115673	PIAS3	BioGRID	PubMed	Reconstituted Complex
BioGRID:112373	BioGRID:119370	PLCE1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112373	BioGRID:111683	PSMD4	BioGRID	PubMed	Biochemical Activity
BioGRID:112373	BioGRID:111867	RBBP8	BioGRID	PubMed	Reconstituted Complex
BioGRID:112373	BioGRID:112388	SKI	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112373	BioGRID:112506	SNCA	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:112373	BioGRID:114986	SNCAIP	BioGRID	PubMed	Biochemical Activity
BioGRID:112373	BioGRID:115547	SPRY2	BioGRID	PubMed	Reconstituted Complex
BioGRID:112373	BioGRID:112721	SYP	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:112373	BioGRID:117660	TINF2	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Two-hybrid
BioGRID:112373	BioGRID:113038	TRAF2	BioGRID	PubMed	Reconstituted Complex
BioGRID:112373	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112373	BioGRID:113177	UBE2I	BioGRID	PubMed	Two-hybrid
BioGRID:112373	BioGRID:114672	UBE2L6	BioGRID	PubMed	Co-fractionation
BioGRID:112373	BioGRID:114465	USP13	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:112373	BioGRID:113252	VAV1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:112373	BioGRID:99646	spry2	BioGRID	PubMed	Two-hybrid

Function	Evidence Code	Pubs
ligase activity	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info
transcription corepressor activity	TAS Traceable Author Statement more info	PubMed
ubiquitin-protein ligase activity	IEA Inferred from Electronic Annotation more info
zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
axon guidance	TAS Traceable Author Statement more info
cell cycle	IEA Inferred from Electronic Annotation more info
cellular protein catabolic process	IGI Inferred from Genetic Interaction more info	PubMed
multicellular organismal development	IEA Inferred from Electronic Annotation more info
negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info
negative regulation of canonical Wnt receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	IMP Inferred from Mutant Phenotype more info
negative regulation of extrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info
small GTPase mediated signal transduction	TAS Traceable Author Statement more info	PubMed
ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
cytosol	IDA Inferred from Direct Assay more info
cytosol	TAS Traceable Author Statement more info
nucleus	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: E3 ubiquitin-protein ligase SIAH2

Names: E3 ubiquitin-protein ligase SIAH2; siah-2; seven in absentia homolog 2

NP_005058.3

EC 6.3.2.-

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NCBI Reference Sequences (RefSeq)

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)

NM_005067.5 → NP_005058.3 E3 ubiquitin-protein ligase SIAH2

Status: REVIEWED

Source sequence(s)

AC011317, AJ323446, BC013082, BF514387, BM970396

Consensus CDS

CCDS3152.1

UniProtKB/Swiss-Prot

O43255

Related

ENSP00000322457, OTTHUMP00000216722, ENST00000312960, OTTHUMT00000357697

Conserved Domains (3) summary

cd03829
Location:195 – 321
Blast Score: 603

Sina; Seven in absentia (Sina) protein family, C-terminal substrate binding domain; composed of the Drosophila Sina protein, the mammalian Sina homolog (Siah), the plant protein SINAT5, and similar proteins. Sina, Siah and SINAT5 are RING-containing proteins ...

pfam03145
Location:122 – 318
Blast Score: 705

Sina; Seven in absentia protein family

pfam13923
Location:78 – 115
Blast Score: 86

zf-C3HC4_2; Zinc finger, C3HC4 type (RING finger)

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000003.11 Reference GRCh37.p5 Primary Assembly

Range

150458910..150481263, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000135.1 Alternate HuRef

Range

147832386..147876859, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC011317.23 (83380..105733)	None
genomic	AJ323446.1	None
genomic	CH471052.2	EAW78821.1
mRNA	AK055290.1	None
mRNA	AK223565.1	BAD97285.1
mRNA	BC013082.2	AAH13082.1
mRNA	BF514387.1	None
mRNA	BM970396.1	None
mRNA	U76248.1	AAC51908.1
mRNA	Y15268.1	CAA75557.1