HIF3A hypoxia inducible factor 3, alpha subunit [Homo sapiens] - Gene

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Summary

Official Symbol: HIF3Aprovided by HGNC
Official Full Name: hypoxia inducible factor 3, alpha subunitprovided by HGNC
Primary source: HGNC:15825
See related: Ensembl:ENSG00000124440; HPRD:17104; MIM:609976; Vega:OTTHUMG00000141296
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: IPAS; MOP7; PASD7; HIF-3A; bHLHe17
Summary: The protein encoded by this gene is the alpha-3 subunit of one of several alpha/beta-subunit heterodimeric transcription factors that regulate many adaptive responses to low oxygen tension (hypoxia). The alpha-3 subunit lacks the transactivation domain found in factors containing either the alpha-1 or alpha-2 subunits. It is thought that factors containing the alpha-3 subunit are negative regulators of hypoxia-inducible gene expression. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2011]

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Genomic context

Location :: 19q13.32

Sequence :: Chromosome: 19; NC_000019.9 (46800303..46846690)

See HIF3A in Epigenomics, MapViewer

Chromosome 19 - NC_000019.9 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?

data indicate that the HIF-3alpha variants may have more versatile and specific roles in the regulation of the hypoxia response than previously anticipated
Title: Roles of the human hypoxia-inducible factor (HIF)-3α variants in the hypoxia response.
Cell-specific and hypoxia-dependent regulation of human HIF-3alpha.
Title: Cell-specific and hypoxia-dependent regulation of human HIF-3α: inhibition of the expression of HIF target genes in vascular cells.
It is a negative regulator of tumorigenesis. (review)
Title: [Hypoxia-inducible factor-3alpha as a negative regulator of tumorigenesis].
HIF3A is regulated by hypoxia in the developing human lung.
Title: Effect of oxygen on the expression of hypoxia-inducible factors in human fetal lung explants.
Hypoxia upregulated transcription from all three alternative HIF-3alpha promoters. siRNA experiments showed that this induction is mediated specifically by HIF-1 and not by HIF-2.
Title: Hypoxia-inducible factor (HIF)-3alpha is subject to extensive alternative splicing in human tissues and cancer cells and is regulated by HIF-1 but not HIF-2.
The findings shed light on a novel aspect of HIF-3alpha as a HIF-1 target gene and point to a possible role as a modulator of hypoxic gene induction.
Title: The human HIF (hypoxia-inducible factor)-3alpha gene is a HIF-1 target gene and may modulate hypoxic gene induction.
The expression of HIF-3alpha4 suppresses the growth of tumor xenografts in SCID mice.
Title: Dominant-negative HIF-3 alpha 4 suppresses VHL-null renal cell carcinoma progression.
The splice isoform HIF-3alpha4 inhibits transcription of VEGF and GLUT1 by binding to and inhibiting HIF-1alpha and HIF-1beta.
Title: Human HIF-3alpha4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma.
findings suggest that HIF-3alpha, as a member of the HIF system, is complementary rather than redundant to HIF-1alpha induction in protection against hypoxic damage in alveolar epithelial cells.
Title: Hypoxia upregulates hypoxia inducible factor (HIF)-3alpha expression in lung epithelial cells: characterization and comparison with HIF-1alpha.
multiple splice variants of locus are targets of the von Hippel-Lindau E3 ubiquitin ligase complex
Title: Multiple splice variants of the human HIF-3 alpha locus are targets of the von Hippel-Lindau E3 ubiquitin ligase complex.

Submit: New GeneRIF Correction See all (11)

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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
Hypoxia inducible factor 3 alpha subunit	Q9GZT9	EGLN1	HPRD	PubMed
Hypoxia inducible factor 3 alpha subunit	Q96KS0	EGLN2	HPRD	PubMed
Hypoxia inducible factor 3 alpha subunit	Q9H6Z9	EGLN3	HPRD	PubMed
Hypoxia inducible factor 3 alpha subunit	Q16665	HIF1A	HPRD	PubMed
Hypoxia inducible factor 3 alpha subunit	P40337	VHL	HPRD	PubMed
BioGRID:122143	BioGRID:113269	VHL	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex

Function	Evidence Code	Pubs
DNA binding	IEA Inferred from Electronic Annotation more info
sequence-specific DNA binding transcription factor activity	IEA Inferred from Electronic Annotation more info
signal transducer activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
positive regulation of transcription from RNA polymerase II promoter	IEA Inferred from Electronic Annotation more info
response to hypoxia	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

Preferred Names: hypoxia-inducible factor 3-alpha

Names: hypoxia-inducible factor 3-alpha; HIF3-alpha-1; member of PAS protein 7; inhibitory PAS domain protein; PAS domain-containing protein 7; basic-helix-loop-helix-PAS protein MOP7; class E basic helix-loop-helix protein 17

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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.

Genomic

NG_029679.1 RefSeqGene

Range

4999..51386

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_022462.4 → NP_071907.4 hypoxia-inducible factor 3-alpha isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and 5' coding region, and uses an alternate start codon, compared to variant 3. The resulting isoform (b) has a distinct and shorter N-terminus, compared to isoform c.

Source sequence(s)

AC007193, AK297828, BM971722, DC423791

Consensus CDS

CCDS42580.2

Related

ENSP00000244303, OTTHUMP00000230128, ENST00000244303, OTTHUMT00000384749

Conserved Domains (3) summary

cd00130
Location:172 – 269
Blast Score: 169

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam08447
Location:182 – 269
Blast Score: 164

PAS_3; PAS fold

pfam11413
Location:419 – 441
Blast Score: 114

HIF-1; Hypoxia-inducible factor-1
NM_152794.3 → NP_690007.1 hypoxia-inducible factor 3-alpha isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 5' UTR and 5' coding region, compared to variant 3. The resulting isoform (a) has a distinct and shorter N-terminus, compared to isoform c.

Source sequence(s)

AB054067, AC007193, AK314680, BM971722

Consensus CDS

CCDS12682.1

UniProtKB/TrEMBL

B2RBI6

UniProtKB/Swiss-Prot

Q9Y2N7

Related

ENSP00000300862, OTTHUMP00000180610, ENST00000300862, OTTHUMT00000280559

Conserved Domains (4) summary

cd00083
Location:11 – 66
Blast Score: 104

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

cd00130
Location:239 – 336
Blast Score: 167

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam08447
Location:249 – 336
Blast Score: 161

PAS_3; PAS fold

pfam11413
Location:486 – 508
Blast Score: 116

HIF-1; Hypoxia-inducible factor-1
NM_152795.3 → NP_690008.2 hypoxia-inducible factor 3-alpha isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) encodes the longest isoform (c).

Source sequence(s)

AC007193, BC080551, BM971722, DR001068

Consensus CDS

CCDS12681.2

UniProtKB/Swiss-Prot

Q9Y2N7

Related

ENSP00000366898, OTTHUMP00000180608, ENST00000377670, OTTHUMT00000280556

Conserved Domains (4) summary

cd00083
Location:13 – 68
Blast Score: 104

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

cd00130
Location:241 – 338
Blast Score: 167

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam08447
Location:251 – 338
Blast Score: 162

PAS_3; PAS fold

pfam11413
Location:488 – 510
Blast Score: 117

HIF-1; Hypoxia-inducible factor-1
NM_152796.2 → NP_690009.1 hypoxia-inducible factor 3-alpha isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and 5' coding region, uses an alternate start codon, and differs in the 3' coding region and 3' UTR, compared to variant 3. The resulting isoform (d) has distinct N- and C-termini, and is shorter than isoform c.

Source sequence(s)

AC007193, AU143858, BE250295, CA437428, CF593418, DA559979, DC423791

Related

ENSP00000434653, OTTHUMP00000230131, ENST00000472815, OTTHUMT00000280557

Conserved Domains (3) summary

cd00130
Location:172 – 269
Blast Score: 169

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam08447
Location:182 – 269
Blast Score: 166

PAS_3; PAS fold

pfam13900
Location:426 – 450
Blast Score: 99

GVQW; Putative binding domain

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_000019.9 Reference GRCh37.p5 Primary Assembly

Range

46800303..46846690

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000151.1 Alternate HuRef

Range

43228311..43274715

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC007193.1	AAD22667.1
		AAD22668.1
genomic	CH471126.1	EAW57408.1
		EAW57409.1
		EAW57410.1
		EAW57411.1
		EAW57412.1
		EAW57413.1
		EAW57414.1
mRNA	AB054067.1	BAB69689.1
mRNA	AB118749.1	BAD93355.1
mRNA	AB295039.1	BAG07185.1
mRNA	AF079154.1	AAC99397.1
mRNA	AF463492.1	AAL69947.1
mRNA	AK021421.1	BAB13819.1
mRNA	AK021653.1	BAB13865.1
mRNA	AK021881.1	None
mRNA	AK024095.1	BAB14824.1
mRNA	AK027725.1	BAB55324.1
mRNA	AK297828.1	BAG60164.1
mRNA	AK299699.1	BAG61601.1
mRNA	AK304747.1	BAG65505.1
mRNA	AK314680.1	BAG37233.1
mRNA	AL541807.3	None
mRNA	AU143858.2	None
mRNA	BC026308.1	AAH26308.1
mRNA	BC080551.1	AAH80551.1
mRNA	BE250295.1	None
mRNA	BE250712.1	None
mRNA	BI772109.1	None
mRNA	BM971722.1	None
mRNA	BQ706970.1	None
mRNA	CA437428.1	None
mRNA	CF593418.1	None
mRNA	DA559979.1	None
mRNA	DA562618.1	None
mRNA	DB176660.1	None
mRNA	DC423791.1	None
mRNA	DN989983.1	None
mRNA	DR001068.1	None

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
O95262	GenPept	UniProtKB/TrEMBL:O95262
Q9HAM5	GenPept	UniProtKB/TrEMBL:Q9HAM5
Q9UPH7	GenPept	UniProtKB/TrEMBL:Q9UPH7
Q9Y2N7.2	GenPept	UniProtKB/Swiss-Prot:Q9Y2N7