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hypoxia-inducible factor 3 alpha (HIF-3 alpha, HIF3 alpha 1, member of PAS protein 7, basic-helix-loop-helix-PAS protein MOP7, inhibitory PAS domain protein, IPAS, HIF3A, MOP7)

Function: - role in adaptive response to hypoxia - suppresses hypoxia-inducible expression of HIF1A & EPAS1 - binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters - the complex HIF3A-ARNT activates transcription of reporter genes driven by HRE - isoform 4 has a dominant-negative function of inactivating HIF1A-mediated transcription - isoform 4 attenuates the binding of HIF1A to hypoxia-responsive elements (HRE), thus inhibiting HRE- driven transcription - hypoxia induces down-regulation of isoform 4,leading to activation of HIF1A in hypoxia - conversely, upon restoring normoxia, expression of isoform 4 increases thus restoring inhibition of HIF1A activity - isoform 4 may be a negative regulator of hypoxia-inducible gene expression in kidney - functions as an inhibitor of angiogenesis in cornea - heterodimerizes with ARNT - interacts via the oxygen-dependent degradation domain (ODD) with the beta domain of VHL - in normoxia, hydroxylated on Pro-492 in the O2-dependent degradation domain (ODD) by PHD; the hydroxylated Pro promotes interaction with VHL, initiating rapid ubiquitination & subsequent proteasomal degradation Structure: - contains 1 basic helix-loop-helix (bHLH) domain - contains 2 PAS domains (PER-ARNT-SIM domains) Compartment: - nucleus, cytoplasm - in nuclei of all periportal & perivenous hepatocytes - in distal perivenous zone, detected in cytoplasm of hepatocytes Alternative splicing: named isoforms=6 Expression: - expressed in kidney - expressed abundantly in lung epithelial cells - expression is regulated in an oxygen-dependent manner - strongly induced by hypoxia (1% O2, both at mRNA & protein level due to transcriptional activation & an increase in protein stability Pathology: - isoform 4 may be involved in renal tumorigenesis

General

basic helix loop helix (bHLH) family transcription factor hypoxia inducible factor

Properties

SIZE: MW = 72 kD entity length = 669 aa COMPARTMENT: cytoplasm cell nucleus MOTIF: DNA-binding motif SITE: 12-27 helix-loop-helix NAME: helix-loop-helix SITE: 28-68 FOR-BINDING-VIA: helix-loop-helix PAS domain {82-154} PAS domain {227-297} LRRLL {414-418} ODD {452-581} MOTIF: NTAD {454-506} LAPYISMD {490-497}

Database Correlations

UniProt Q9Y2N7 PFAM correlations

References

  1. UniProt :accession Q9Y2N7
  2. Wikipedia hypoxia inducible factor entry http://en.wikipedia.org/wiki/Hypoxia_inducible_factor