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hypoxia-inducible factor 1 alpha; ARNT interacting protein; member of PAS protein 1 (HIF1A, MOP1)
Function:
- in hypoxia, complexes with aryl hydrocarbon receptor nuclear translocation factor
- translocates to nucleus & binds to HRE elements in promoter regions of genes
- in normal conditions, HIF1-alpha is bound to VHL protein in the presence of oxygen resulting in HIF1-alpha becoming ubiquitinated & targeted to proteasomes
- HIF1-alpha is regulated by
a) prolyl hydroxylase
b) 2-oxoglutarate
Compartment: nucleus, cytoplasm
Pathology:
- histologically, increased levels of HIF1-alpha was associated with poorer prognosis & resistance to therapy in head & neck cancers
- overexpression of HIF1-alpha was seen in
a) colon carcinoma
b) breast cancer
c) gastric cancer
d) esophageal cancer
e) lung carcinoma
f) skin cancer
g) ovarian cancer
h) pancreatic cancer
i) prostate cancer
j) renal carcinomas
- associated with cell proliferation
Interactions
molecular events
General
basic helix loop helix (bHLH) family transcription factor
Properties
SIZE: MW = 93 kD
entity length = 826 aa
COMPARTMENT: cell nucleus
MOTIF: DNA-binding motif
SITE: 17-30
PAS domain {85-158}
PAS domain {228-298}
basic helix-loop-helix
MOTIF: basic DNA-binding motif
helix-loop-helix
NAME: helix-loop-helix
FOR-BINDING-VIA: helix-loop-helix
FOR-BINDING-OF: DNA motif
FOR-BINDING-VIA: helix-loop-helix
References
- Harris AL.
Hypoxia-a key regulatory factor in tumour growth.
Nat Rev Cancer. 2002 Jan;2(1):38-47. Review.
PMID: 11902584
- UniProt :accession Q16665
Component-of
molecular complex
Databases & Figures
OMIM 603348
UniProt Q16665
Entrez Gene 3091
HIF-1 pathway