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Aliases for HIF3A Gene

Aliases for HIF3A Gene

  • Hypoxia Inducible Factor 3 Alpha Subunit 2 3
  • Class E Basic Helix-Loop-Helix Protein 17 3 4
  • Hypoxia Inducible Factor 3, Alpha Subunit 3 5
  • Basic-Helix-Loop-Helix-PAS Protein MOP7 3 4
  • PAS Domain-Containing Protein 7 3 4
  • Inhibitory PAS Domain Protein 3 4
  • Member Of PAS Protein 7 3 4
  • HIF3-Alpha-1 3 4
  • BHLHe17 3 4
  • PASD7 3 4
  • IPAS 3 4
  • MOP7 3 4
  • HIF-3-Alpha 4
  • HIF3-Alpha 4
  • HIF-3A 3

External Ids for HIF3A Gene

Previous GeneCards Identifiers for HIF3A Gene

  • GC19P047444
  • GC19P047191
  • GC19P051476
  • GC19P051492
  • GC19P046800
  • GC19P043228

Summaries for HIF3A Gene

Entrez Gene Summary for HIF3A Gene

  • 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]

GeneCards Summary for HIF3A Gene

HIF3A (Hypoxia Inducible Factor 3 Alpha Subunit) is a Protein Coding gene. Diseases associated with HIF3A include hypoxia and renal cell carcinoma. Among its related pathways are Cellular response to hypoxia and Cellular Senescence. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and transcription coactivator activity. An important paralog of this gene is SIM2.

UniProtKB/Swiss-Prot for HIF3A Gene

  • Acts as a transcriptional regulator in adaptive response to low oxygen tension. Acts as a regulator of hypoxia-inducible gene expression (PubMed:11573933, PubMed:16126907, PubMed:19694616, PubMed:20416395, PubMed:21069422). Functions as an inhibitor of angiogenesis in hypoxic cells of the cornea. Plays a role in the development of the cardiorespiratory system. May also be involved in apoptosis (By similarity).

  • Isoform 2: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation. Also inhibits hypoxia-inducible ARNT-mediated gene expression.

  • Isoform 3: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.

  • isoform 4: Attenuates the ability of transcription factor HIF1A and EPAS1/HIF2A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation (PubMed:16126907, PubMed:17998805, PubMed:19694616, PubMed:20416395). May act as a tumor suppressor and inhibits malignant cell transformation (PubMed:17998805).

  • Isoform 5: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.

Gene Wiki entry for HIF3A Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HIF3A Gene

Genomics for HIF3A Gene

Regulatory Elements for HIF3A Gene

Enhancers for HIF3A Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around HIF3A on UCSC Golden Path with GeneCards custom track

Genomic Location for HIF3A Gene

Chromosome:
19
Start:
46,297,046 bp from pter
End:
46,343,433 bp from pter
Size:
46,388 bases
Orientation:
Plus strand

Genomic View for HIF3A Gene

Genes around HIF3A on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HIF3A Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HIF3A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HIF3A Gene

Proteins for HIF3A Gene

  • Protein details for HIF3A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y2N7-HIF3A_HUMAN
    Recommended name:
    Hypoxia-inducible factor 3-alpha
    Protein Accession:
    Q9Y2N7
    Secondary Accessions:
    • B0M185
    • B4DNA2
    • I6L988
    • Q58A43
    • Q66K72
    • Q8WXA1
    • Q96K34
    • Q9H7Z9
    • Q9HAI2

    Protein attributes for HIF3A Gene

    Size:
    669 amino acids
    Molecular mass:
    72433 Da
    Quaternary structure:
    • Isoform 2 interacts (via ODD domain) with VHL (via beta domain) (PubMed:12538644). Isoform 4 interacts with HIF1A; the interaction inhibits the binding of HIF1A to hypoxia-responsive element (HRE) and HIF1A/ARNT-dependent transcriptional activation (PubMed:16126907). Isoform 4 interacts with ARNT; the interaction occurs in a HIF1A- and DNA-binding-independent manner and does not induce HIF1A/ARNT-dependent transcriptional activation (PubMed:16126907). Isoform 4 interacts with EPAS1 (PubMed:17998805). Interacts with BAD, BCL2L2 and MCL1 (By similarity).
    SequenceCaution:
    • Sequence=AAL69947.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=BAB13865.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing site.; Evidence={ECO:0000305}; Sequence=BAB14824.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Aberrant splice sites.; Evidence={ECO:0000305}; Sequence=BAB55324.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=BAD93355.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=BAG07185.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for HIF3A Gene

    Alternative splice isoforms for HIF3A Gene

neXtProt entry for HIF3A Gene

Proteomics data for HIF3A Gene at MOPED

Post-translational modifications for HIF3A Gene

  • In normoxia, hydroxylated on Pro-492 in the oxygen-dependent degradation domain (ODD) by prolyl hydroxylase(s) (PHD). The hydroxylated proline promotes interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation.
  • Ubiquitinated; ubiquitination occurs in a VHL- and oxygen-dependent pathway and subsequently targeted for proteasomal degradation.
  • Ubiquitination at Lys 467 and Lys 570
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for HIF3A Gene

Domains & Families for HIF3A Gene

Gene Families for HIF3A Gene

Graphical View of Domain Structure for InterPro Entry

Q9Y2N7

UniProtKB/Swiss-Prot:

HIF3A_HUMAN :
  • Contains 1 bHLH (basic helix-loop-helix) domain.
Domain:
  • Contains 1 bHLH (basic helix-loop-helix) domain.
  • Contains 2 PAS (PER-ARNT-SIM) domains.
genes like me logo Genes that share domains with HIF3A: view

Function for HIF3A Gene

Molecular function for HIF3A Gene

UniProtKB/Swiss-Prot Function:
Acts as a transcriptional regulator in adaptive response to low oxygen tension. Acts as a regulator of hypoxia-inducible gene expression (PubMed:11573933, PubMed:16126907, PubMed:19694616, PubMed:20416395, PubMed:21069422). Functions as an inhibitor of angiogenesis in hypoxic cells of the cornea. Plays a role in the development of the cardiorespiratory system. May also be involved in apoptosis (By similarity).
UniProtKB/Swiss-Prot Function:
Isoform 2: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation. Also inhibits hypoxia-inducible ARNT-mediated gene expression.
UniProtKB/Swiss-Prot Function:
Isoform 3: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.
UniProtKB/Swiss-Prot Function:
isoform 4: Attenuates the ability of transcription factor HIF1A and EPAS1/HIF2A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation (PubMed:16126907, PubMed:17998805, PubMed:19694616, PubMed:20416395). May act as a tumor suppressor and inhibits malignant cell transformation (PubMed:17998805).
UniProtKB/Swiss-Prot Function:
Isoform 5: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.
UniProtKB/Swiss-Prot Induction:
Up-regulated by hypoxia (at protein level) (PubMed:16775626). Induced by hypoxia (PubMed:16775626). Isoform 2, isoform 3, isoform 4 and isoform 5 are up-regulated by hypoxia in a HIF1A- and EPAS1/HIF2A-dependent manner (PubMed:19694616, PubMed:20416395, PubMed:21069422). Isoform 4 is down-regulated by hypoxia and up-regulated upon restoring normoxia in embryonic kidney cells (PubMed:16126907).

Gene Ontology (GO) - Molecular Function for HIF3A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding IBA --
GO:0005515 protein binding IEA --
genes like me logo Genes that share ontologies with HIF3A: view
genes like me logo Genes that share phenotypes with HIF3A: view

Animal Models for HIF3A Gene

MGI Knock Outs for HIF3A:

Animal Model Products

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HIF3A Gene

Localization for HIF3A Gene

Subcellular locations from UniProtKB/Swiss-Prot for HIF3A Gene

Nucleus. Cytoplasm. Nucleus speckle. Mitochondrion. Note=In the nuclei of all periportal and perivenous hepatocytes. In the distal perivenous zone, detected in the cytoplasm of the hepatocytes. Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner. Colocalizes with BAD in the cytoplasm. Colocalizes with EPAS1 and HIF1A in the nucleus and speckles (By similarity). Localized in the cytoplasm and nuclei under normoxia, but increased in the nucleus under hypoxic conditions (PubMed:19694616). Colocalized with HIF1A in kidney tumors (PubMed:19694616). {ECO:0000250 UniProtKB:Q0VBL6, ECO:0000250 UniProtKB:Q9JHS2, ECO:0000269 PubMed:19694616}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for HIF3A Gene COMPARTMENTS Subcellular localization image for HIF3A gene
Compartment Confidence
cytosol 5
nucleus 5
mitochondrion 4

Gene Ontology (GO) - Cellular Components for HIF3A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with HIF3A: view

Pathways & Interactions for HIF3A Gene

genes like me logo Genes that share pathways with HIF3A: view

Gene Ontology (GO) - Biological Process for HIF3A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001666 response to hypoxia IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription from RNA polymerase II promoter IDA 11573933
GO:0006915 apoptotic process IEA --
GO:0045944 positive regulation of transcription from RNA polymerase II promoter IBA --
genes like me logo Genes that share ontologies with HIF3A: view

No data available for SIGNOR curated interactions for HIF3A Gene

Drugs & Compounds for HIF3A Gene

(1) Drugs for HIF3A Gene - From: ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
FG-4592 (ASP1517) Pharma HIF prolyl-hydroxylase inhibitor 0

(1) ApexBio Compounds for HIF3A Gene

Compound Action Cas Number
FG-4592 (ASP1517) HIF prolyl-hydroxylase inhibitor 808118-40-3
genes like me logo Genes that share compounds with HIF3A: view

Transcripts for HIF3A Gene

Unigene Clusters for HIF3A Gene

Hypoxia inducible factor 3, alpha subunit:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for HIF3A Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6 ^ 7a · 7b ^ 8 ^ 9a · 9b · 9c · 9d ^ 10a · 10b ^ 11a · 11b ^ 12 ^ 13 ^ 14 ^ 15 ^ 16a · 16b ^
SP1: - - - - - -
SP2: - - - - -
SP3: - - - - - -
SP4: - - - - - - - - -
SP5: - - - - -
SP6: - - -
SP7:
SP8: - - - - - -
SP9: - - -
SP10: - - - - - -
SP11:

ExUns: 17a · 17b · 17c ^ 18 ^ 19
SP1:
SP2: -
SP3:
SP4: -
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:

Relevant External Links for HIF3A Gene

GeneLoc Exon Structure for
HIF3A
ECgene alternative splicing isoforms for
HIF3A

Expression for HIF3A Gene

mRNA expression in normal human tissues for HIF3A Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for HIF3A Gene

This gene is overexpressed in Plasma (66.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for HIF3A Gene



SOURCE GeneReport for Unigene cluster for HIF3A Gene Hs.420830

mRNA Expression by UniProt/SwissProt for HIF3A Gene

Q9Y2N7-HIF3A_HUMAN
Tissue specificity: Expressed in vascular cells (at protein level) (PubMed:21069422). Expressed in kidney (PubMed:11573933, PubMed:19694616). Expressed in lung epithelial cells (PubMed:16775626). Expressed in endothelial cells (venous and arterial cells from umbilical cord and aortic endothelial cells) and in vascular smooth muscle cells (aorta) (PubMed:21069422). Strongly expressed in the heart, placenta, and skeletal muscle, whereas a weak expression profile was found in the lung, liver, and kidney (PubMed:12538644). Expressed weakly in cell renal cell carcinoma (CC-RCC) compared to normal renal cells (PubMed:16126907). Expression is down-regulated in numerous kidney tumor cells compared to non tumor kidney tissues (PubMed:16126907). Isoform 2 is expressed in heart, placenta, lung, liver, skeletal muscle and pancreas and in numerous cancer cell lines (PubMed:20416395). Isoform 3 and isoform 4 are weakly expressed in heart, placenta, lung, liver, skeletal muscle and pancreas (PubMed:20416395). Isoform 4 is expressed in fetal tissues, such as heart, brain, thymus, lung, liver, skeletal kidney and spleen (PubMed:20416395). Isoform 3 is weakly expressed in fetal tissues, such as liver and kidney (PubMed:20416395).
genes like me logo Genes that share expression patterns with HIF3A: view

Protein tissue co-expression partners for HIF3A Gene

- Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for HIF3A Gene

Orthologs for HIF3A Gene

This gene was present in the common ancestor of animals.

Orthologs for HIF3A Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia HIF3A 35
  • 88.31 (n)
  • 87.86 (a)
HIF3A 36
  • 89 (a)
OneToOne
dog
(Canis familiaris)
Mammalia HIF3A 35
  • 89.19 (n)
  • 90.08 (a)
mouse
(Mus musculus)
Mammalia Hif3a 35
  • 83.94 (n)
  • 82.58 (a)
Hif3a 16
Hif3a 36
  • 83 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia HIF3A 35
  • 99.1 (n)
  • 99.1 (a)
HIF3A 36
  • 98 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hif3a 35
  • 83.13 (n)
  • 80.91 (a)
platypus
(Ornithorhynchus anatinus)
Mammalia HIF3A 36
  • 55 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia HIF3A 36
  • 55 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii hif1al 35
  • 57.89 (n)
  • 51.44 (a)
hif1al 36
  • 40 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta sima 36
  • 13 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea hif-1 36
  • 19 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 22 (a)
OneToMany
Species with no ortholog for HIF3A:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • chicken (Gallus gallus)
  • 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)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for HIF3A Gene

ENSEMBL:
Gene Tree for HIF3A (if available)
TreeFam:
Gene Tree for HIF3A (if available)

Paralogs for HIF3A Gene

Paralogs for HIF3A Gene

genes like me logo Genes that share paralogs with HIF3A: view

Variants for HIF3A Gene

Sequence variations from dbSNP and Humsavar for HIF3A Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
rs3764609 - 46,320,445(+) CAGCC(A/G)GGTGG nc-transcript-variant, reference, missense
rs7253301 - 46,325,586(+) GACTC(C/T)TCACC nc-transcript-variant, reference, missense
rs757638 -- 46,308,869(+) CTCCT(A/G)GGCTG intron-variant
rs759296 -- 46,307,859(+) AGGTT(A/G)AGGCT intron-variant
rs759298 -- 46,308,509(+) GGTCC(A/G)AGGGG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for HIF3A Gene

Variant ID Type Subtype PubMed ID
esv2573837 CNV Deletion 19546169
esv2661691 CNV Deletion 23128226
esv2718653 CNV Deletion 23290073

Variation tolerance for HIF3A Gene

Residual Variation Intolerance Score: 87.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.96; 83.99% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HIF3A Gene

HapMap Linkage Disequilibrium report
HIF3A

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HIF3A Gene

Disorders for HIF3A Gene

MalaCards: The human disease database

(3) MalaCards diseases for HIF3A Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
hypoxia
renal cell carcinoma
  • renal cell carcinoma, clear cell, somatic
extratemporal epilepsy
- elite association - COSMIC cancer census association via MalaCards
Search HIF3A in MalaCards View complete list of genes associated with diseases

Relevant External Links for HIF3A

Human Genome Epidemiology (HuGE) Navigator
HIF3A
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HIF3A
genes like me logo Genes that share disorders with HIF3A: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HIF3A Gene

Publications for HIF3A Gene

  1. Expression and characterization of hypoxia-inducible factor (HIF)- 3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha. (PMID: 11573933) Hara S. … Imura N. (Biochem. Biophys. Res. Commun. 2001) 2 3 4 67
  2. Dominant-negative HIF-3 alpha 4 suppresses VHL-null renal cell carcinoma progression. (PMID: 17998805) Maynard M.A. … Ohh M. (Cell Cycle 2007) 3 23
  3. Binding and regulation of hypoxia-inducible factor-1 by the inhibitory PAS proteins. (PMID: 16182248) Jang M.S. … Cho S. (Biochem. Biophys. Res. Commun. 2005) 3 23
  4. Multiple splice variants of the human HIF-3 alpha locus are targets of the von Hippel-Lindau E3 ubiquitin ligase complex. (PMID: 12538644) Maynard M.A. … Ohh M. (J. Biol. Chem. 2003) 3 23
  5. Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. (PMID: 11734856) Makino Y. … Poellinger L. (Nature 2001) 2 3

Products for HIF3A Gene

Sources for HIF3A Gene

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