InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: HIF1A

Summary

InnateDB Protein

IDBP-8512.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

HIF1A

Protein Name

hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)

Synonyms

bHLHe78; HIF-1A; HIF-1alpha; HIF1; HIF1-ALPHA; MOP1; PASD8;

Species

Homo sapiens

Ensembl Protein

ENSP00000338018

InnateDB Gene

IDBG-8510 (HIF1A)

Protein Structure

UniProt Annotation

Function

Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia. {ECO:0000269PubMed:11292861, ECO:0000269PubMed:11566883, ECO:0000269PubMed:15465032, ECO:0000269PubMed:16543236, ECO:0000269PubMed:16973622, ECO:0000269PubMed:17610843, ECO:0000269PubMed:19528298, ECO:0000269PubMed:20624928, ECO:0000269PubMed:22009797, ECO:0000269PubMed:9887100}.

Subcellular Localization

Cytoplasm. Nucleus. Note=Cytoplasmic in normoxia, nuclear translocation in response to hypoxia. Colocalizes with SUMO1 in the nucleus, under hypoxia.

Disease Associations

Tissue Specificity

Expressed in most tissues with highest levels in kidney and heart. Overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors. A higher level expression seen in pituitary tumors as compared to the pituitary gland. {ECO:0000269PubMed:22009797}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 258 experimentally validated interaction(s) in this database.
They are also associated with 21 interaction(s) predicted by orthology.

Experimentally validated
Total	262 [view]
Protein-Protein	220 [view]
Protein-DNA	38 [view]
Protein-RNA	1 [view]
DNA-DNA	3 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	21 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000989	transcription factor binding transcription factor activity
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003705	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity
GO:0004871	signal transducer activity
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0019899	enzyme binding
GO:0019901	protein kinase binding
GO:0031625	ubiquitin protein ligase binding
GO:0035035	histone acetyltransferase binding
GO:0035257	nuclear hormone receptor binding
GO:0043565	sequence-specific DNA binding
GO:0044212	transcription regulatory region DNA binding
GO:0046982	protein heterodimerization activity
GO:0046983	protein dimerization activity
GO:0051879	Hsp90 protein binding

Biological Process

GO:0001666	response to hypoxia
GO:0001837	epithelial to mesenchymal transition
GO:0001938	positive regulation of endothelial cell proliferation
GO:0002248	connective tissue replacement involved in inflammatory response wound healing
GO:0006355	regulation of transcription, DNA-templated
GO:0007165	signal transduction
GO:0007219	Notch signaling pathway
GO:0010468	regulation of gene expression
GO:0010573	vascular endothelial growth factor production
GO:0010575	positive regulation vascular endothelial growth factor production
GO:0010634	positive regulation of epithelial cell migration
GO:0010870	positive regulation of receptor biosynthetic process
GO:0019896	axon transport of mitochondrion
GO:0030949	positive regulation of vascular endothelial growth factor receptor signaling pathway
GO:0032364	oxygen homeostasis
GO:0032722	positive regulation of chemokine production
GO:0032909	regulation of transforming growth factor beta2 production
GO:0032963	collagen metabolic process
GO:0042789	mRNA transcription from RNA polymerase II promoter
GO:0043619	regulation of transcription from RNA polymerase II promoter in response to oxidative stress
GO:0045087	innate immune response (InnateDB)
GO:0045648	positive regulation of erythrocyte differentiation
GO:0045766	positive regulation of angiogenesis
GO:0045821	positive regulation of glycolytic process
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046886	positive regulation of hormone biosynthetic process
GO:0051000	positive regulation of nitric-oxide synthase activity
GO:0051541	elastin metabolic process
GO:0061418	regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0061419	positive regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0070101	positive regulation of chemokine-mediated signaling pathway
GO:0071347	cellular response to interleukin-1
GO:0071456	cellular response to hypoxia

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005667	transcription factor complex
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005829	cytosol

Protein Structure and Domains

PDB ID

InterPro

IPR000014 PAS domain
IPR001321 Hypoxia-inducible factor-1 alpha
IPR001610 PAC motif
IPR011598 Myc-type, basic helix-loop-helix (bHLH) domain
IPR013655 PAS fold-3
IPR013767 PAS fold
IPR014887 HIF-1 alpha, transactivation domain, C-terminal
IPR021537 Hypoxia-inducible factor, alpha subunit

PFAM