Hypoxia Inducible Factor 1 Alpha Subunit Inhibitor (HIF1aN)

FIH1; Peptide-Aspartate Beta-Dioxygenase; Hypoxia-inducible factor asparagine hydroxylase

SPN	Q489
HGNC	17113
MGI	2442345
PubMed	23793029
RGD	1308281
UniProt	Q9NWT6
Wiki	HIF1AN

The deduced 349-amino acid HIF1AN protein is homologous to rat Pass1 and to fly and worm sequences, indicating evolutionary conservation of this protein family. Binding analyses of truncated HIF1AN peptides showed that the inhibitory domain rather than the transactivating domains of HIF1A interacts with HIF1AN, although the presence of TAD-C optimizes binding.

Functional analysis indicated that HIAF1AN inhibits HIF1A transcriptional activity in hypoxic and nonhypoxic cells. Further binding analysis determined that the N terminus of HIF1AN interacts with the N terminus of VHL, and that both interact with HIF1A at distinct sites (VHL with TAD-N of HIF1A), allowing the formation of ternary complexes of the 3 proteins.

Reference

"FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity."
Genes Dev. 15:2675-2686(2001) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and comparative analysis of human chromosome 10."
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"The full-ORF clone resource of the German cDNA consortium."
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]

"FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor."
Genes Dev. 16:1466-1471(2002) [PubMed] [Europe PMC] [Abstract]

"Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family."
J. Biol. Chem. 277:26351-26355(2002) [PubMed] [Europe PMC] [Abstract]

"Disruption of dimerization and substrate phosphorylation inhibit factor inhibiting hypoxia-inducible factor (FIH) activity."
Biochem. J. 383:429-437(2004) [PubMed] [Europe PMC] [Abstract]

"Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases."
J. Biol. Chem. 279:9899-9904(2004) [PubMed] [Europe PMC] [Abstract]

"Substrate requirements of the oxygen-sensing asparaginyl hydroxylase factor-inhibiting hypoxia-inducible factor."
J. Biol. Chem. 279:14391-14397(2004) [PubMed] [Europe PMC] [Abstract]

"Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH)."
Proc. Natl. Acad. Sci. U.S.A. 103:14767-14772(2006) [PubMed] [Europe PMC] [Abstract]

"Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways."
Proc. Natl. Acad. Sci. U.S.A. 105:3368-3373(2008) [PubMed] [Europe PMC] [Abstract]

"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH)."
Biochem. J. 420:327-333(2009) [PubMed] [Europe PMC] [Abstract]

"Mint3 enhances the activity of hypoxia-inducible factor-1 (HIF-1) in macrophages by suppressing the activity of factor inhibiting HIF-1."
J. Biol. Chem. 284:30350-30359(2009) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes."
Mol. Cell. Biol. 32:3095-3106(2012) [PubMed] [Europe PMC] [Abstract]

"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]

"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]

"Structure of factor-inhibiting hypoxia-inducible factor 1: an asparaginyl hydroxylase involved in the hypoxic response pathway."
Proc. Natl. Acad. Sci. U.S.A. 99:15351-15356(2002) [PubMed] [Europe PMC] [Abstract]

"Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha."
J. Biol. Chem. 278:1802-1806(2003) [PubMed] [Europe PMC] [Abstract]

"Structure of human FIH-1 reveals a unique active site pocket and interaction sites for HIF-1 and von Hippel-Lindau."
J. Biol. Chem. 278:7558-7563(2003) [PubMed] [Europe PMC] [Abstract]

"Selective inhibition of factor inhibiting hypoxia-inducible factor."
J. Am. Chem. Soc. 127:7680-7681(2005) [PubMed] [Europe PMC] [Abstract]

"Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates."
J. Biol. Chem. 282:3293-3301(2007) [PubMed] [Europe PMC] [Abstract]

"Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor."
J. Biol. Chem. 282:24027-24038(2007) [PubMed] [Europe PMC] [Abstract]

"Evidence that two enzyme-derived histidine ligands are sufficient for iron binding and catalysis by factor inhibiting HIF (FIH)."
J. Biol. Chem. 283:25971-25978(2008) [PubMed] [Europe PMC] [Abstract]

"Structural basis for binding of cyclic 2-oxoglutarate analogues to factor-inhibiting hypoxia-inducible factor."
Bioorg. Med. Chem. Lett. 20:6125-6128(2010) [PubMed] [Europe PMC] [Abstract]

"Crystal structures of human FIH-1 in complex with quinol family inhibitors."
Mol. Cells 29:471-474(2010) [PubMed] [Europe PMC] [Abstract]

"The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases."
EMBO Rep. 12:463-469(2011) [PubMed] [Europe PMC] [Abstract]

"Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains."
FEBS J. 278:1086-1097(2011) [PubMed] [Europe PMC] [Abstract]

"Asparagine and aspartate hydroxylation of the cytoskeletal ankyrin family is catalyzed by factor-inhibiting hypoxia-inducible factor."
J. Biol. Chem. 286:7648-7660(2011) [PubMed] [Europe PMC] [Abstract]