HIF1AN explained

Hypoxia-inducible factor 1-alpha inhibitor is a protein that in humans is encoded by the HIF1AN gene.^{[1] [2]}

Interactions

HIF1AN has been shown to interact with HIF1A and Von Hippel-Lindau tumor suppressor.^[1] Additionally, asparaginyl hydroxylation of HIF1α by FIH-1 (HIF1AN) at N803 impairs its interaction with CBP/P300.^[3]

Further reading

• Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML . Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch . Science . 295 . 5556 . 858–61 . 2002 . 11823643 . 10.1126/science.1068592 . 2002Sci...295..858L . 24045310 .
• Freedman SJ, Sun ZY, Poy F, Kung AL, Livingston DM, Wagner G, Eck MJ . Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1α . Proc. Natl. Acad. Sci. U.S.A. . 99 . 8 . 5367–72 . 2002 . 11959990 . 122775 . 10.1073/pnas.082117899 . free . 2002PNAS...99.5367F .
• Hewitson KS, McNeill LA, Riordan MV, Tian YM, Bullock AN, Welford RW, Elkins JM, Oldham NJ, Bhattacharya S, Gleadle JM, Ratcliffe PJ, Pugh CW, Schofield CJ . 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 . 29 . 26351–5 . 2002 . 12042299 . 10.1074/jbc.C200273200 . free .
• Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML, Bruick RK . FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor . Genes Dev. . 16 . 12 . 1466–71 . 2002 . 12080085 . 186346 . 10.1101/gad.991402 .
• Dann CE, Bruick RK, Deisenhofer J . 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 . 24 . 15351–6 . 2003 . 12432100 . 137720 . 10.1073/pnas.202614999 . free .
• Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ . Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha . J. Biol. Chem. . 278 . 3 . 1802–6 . 2003 . 12446723 . 10.1074/jbc.C200644200 . free .
• Lee C, Kim SJ, Jeong DG, Lee SM, Ryu SE . 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 . 9 . 7558–63 . 2003 . 12482756 . 10.1074/jbc.M210385200 . free .
• Koivunen P, Hirsilä M, Günzler V, Kivirikko KI, Myllyharju J . 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 . 11 . 9899–904 . 2004 . 14701857 . 10.1074/jbc.M312254200 . free .
• Linke S, Stojkoski C, Kewley RJ, Booker GW, Whitelaw ML, Peet DJ . Substrate requirements of the oxygen-sensing asparaginyl hydroxylase factor-inhibiting hypoxia-inducible factor . J. Biol. Chem. . 279 . 14 . 14391–7 . 2004 . 14734545 . 10.1074/jbc.M313614200 . free .
• Kato H, Tamamizu-Kato S, Shibasaki F . Histone deacetylase 7 associates with hypoxia-inducible factor 1alpha and increases transcriptional activity . J. Biol. Chem. . 279 . 40 . 41966–74 . 2004 . 15280364 . 10.1074/jbc.M406320200 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Cockman ME, Lancaster DE, Stolze IP, Hewitson KS, McDonough MA, Coleman ML, Coles CH, Yu X, Hay RT, Ley SC, Pugh CW, Oldham NJ, Masson N, Schofield CJ, Ratcliffe PJ . Posttranslational hydroxylation of ankyrin repeats in IκB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH) . Proc. Natl. Acad. Sci. U.S.A. . 103 . 40 . 14767–72 . 2006 . 17003112 . 1578504 . 10.1073/pnas.0606877103 . free . 2006PNAS..10314767C .
• Coleman ML, McDonough MA, Hewitson KS, Coles C, Mecinovic J, Edelmann M, Cook KM, Cockman ME, Lancaster DE, Kessler BM, Oldham NJ, Ratcliffe PJ, Schofield CJ . Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor . J. Biol. Chem. . 282 . 33 . 24027–38 . 2007 . 17573339 . 10.1074/jbc.M704102200 . free .
• Chen C, Lou T . Hypoxia inducible factors in hepatocellular carcinoma . Oncotarget . 8 . 28 . 46691–703 . 2017 . 28493839 . 10.18632/oncotarget.17358 . 5542303 . free .

Notes and References

1. Mahon PC, Hirota K, Semenza GL . FIH-1: a novel protein that interacts with HIF-1α and VHL to mediate repression of HIF-1 transcriptional activity . Genes Dev . 15 . 20 . 2675–86 . Oct 2001 . 11641274 . 312814 . 10.1101/gad.924501 .
2. Web site: Entrez Gene: HIF1AN hypoxia-inducible factor 1, alpha subunit inhibitor.
3. Chen C, Lou T . Hypoxia inducible factors in hepatocellular carcinoma . Oncotarget . 8 . 28 . 46691–703 . 2017 . 28493839 . 10.18632/oncotarget.17358 . 5542303 .