Candidate Genes Diabetic Retinopathy

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

Official Symbol
HIF1A
Alternative Names
OTTHUMP00000179063
member of PAS protein 1
ARNT interacting protein
ARNT-interacting protein
member of PAS superfamily 1
PAS domain-containing protein 8
basic-helix-loop-helix-PAS protein MOP1
class E basic helix-loop-helix protein 78
hypoxia-inducible factor 1 alpha isoform I.3
HIF1; MOP1; PASD8; bHLHe78; HIF-1alpha; HIF1-ALPHA
Description
This gene encodes the alpha subunit of transcription factor hypoxia-inducible factor-1 (HIF-1), which is a heterodimer composed of an alpha and a beta subunit. HIF-1 functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes, including those involved in energy metabolism, angiogenesis, apoptosis, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. HIF-1 thus plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene
Location
14q23.2
Map
Chr 17
Start: 62,162,119 bp from pter
End: 62,214,977 bp from pter
Size: 52,859 bases
Orientation: plus strand
Exons and Introns
15 exons and 31 distinct introns (30 gt-ag, 1 gc-ag)
Nucleotide Sequence
Aminoacid Sequence
Variation
rs962962 A/G
Motif
Pfam: PAS_3 HIF-1a_CTAD HIF-1 PAS PAS_4 HLH
PROSITE: PAS HLH
Induction
Under reduced oxygen tension. Induced also by various receptor-mediated factors such as growth factors, cytokines, and circulatory factors such as PDGF, EGF, FGF2, IGF2, TGFB1, HGF, TNF, IL1B/interleukin-1 beta, angiotensin-2 and thrombin. However, this induction is less intense than that stimulated by hypoxia. Repressed by HIPK2
Pathway
mTOR signaling pathway
Pathway
Pathways in cancer
Pathway
Renal cell carcinoma
Interactors
Protein Interactors
c Jun
CREBBP
Death associated protein 3
ERK1
HSP90A
MAX protein
MDM2
p53
Post Translational Modification
Hydroxylation Isopeptide bond
Phosphorylation
S-nitrosylation
Ubl conjugation
Sumoylated; by SUMO1 under hypoxia. Sumoylation is enhanced through interaction with RWDD3. Desumoylation by SENP1 leads to increased HIF1A stability and transriptional activity
Molecular Weight
92670 da
Molecular Class
Transcription factor
Molecular 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, 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
3D Structure