Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha

Gene Expr. 1998;7(3):205-13.


Hypoxia inducible factors (HIFs) are heterodimeric transcription factors that regulate a number of adaptive responses to low oxygen tension. They are composed of alpha- and beta-subunits that belong to the basic helix-loop-helix-PAS (bHLH-PAS) superfamily. In our efforts to identify new bHLH-PAS proteins, we cloned a cDNA encoding a novel alpha-class hypoxia inducible factor, HIF3alpha. The HIF3alpha open reading frame encodes a 662-amino acid protein with a predicted molecular weight of 73 kDa and is expressed in adult thymus, lung, brain, heart, and kidney. The N-terminal bHLH-PAS domain of this protein shares amino acid sequence identity with that of HIF1alpha and HIF2alpha (57% and 53% identity, respectively). The C-terminus of HIF3alpha contains a 36-amino acid sequence that shares 61% identity with the hypoxia responsive domain-1 (HRD1) of HIF1alpha. In transient transfections, this domain confers hypoxia responsiveness when linked to a heterologous transactivation domain. In vitro studies reveal that HIF3alpha dimerizes with a prototype beta-class subunit, ARNT, and that the resultant heterodimer recognizes the hypoxia responsive element (HRE) core sequence, TACGTG. Transient transfection experiments demonstrate that the HIF3alpha-ARNT interaction can occur in vivo, and that the activity of HIF3alpha is upregulated in response to cobalt chloride or low oxygen tension.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • Chromosomes, Human, Pair 9*
  • Cloning, Molecular
  • Conserved Sequence
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Databases, Factual
  • Enhancer Elements, Genetic
  • Helix-Loop-Helix Motifs
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Molecular Sequence Data
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Repressor Proteins
  • Transcription Factors / genetics*
  • Transfection
  • Up-Regulation


  • Apoptosis Regulatory Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • HIF1A protein, human
  • HIF3A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • Transcription Factors

Associated data

  • GENBANK/AF060194
  • GENBANK/AF079140
  • GENBANK/AF079141
  • GENBANK/AF079142
  • GENBANK/AF079143
  • GENBANK/AF079144
  • GENBANK/AF079145
  • GENBANK/AF079146
  • GENBANK/AF079147
  • GENBANK/AF079148
  • GENBANK/AF079149
  • GENBANK/AF079150
  • GENBANK/AF079151
  • GENBANK/AF079152
  • GENBANK/AF079153