Q9NWT6 (HIF1N_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hypoxia-inducible factor 1-alpha inhibitor
EC=1.14.11.30
EC=1.14.11.n4

Alternative name(s):
Factor inhibiting HIF-1
Short name=FIH-1
Hypoxia-inducible factor asparagine hydroxylase

Gene names

Name:	HIF1AN
Synonyms:	FIH1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	349 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation. Ref.7 Ref.8 Ref.12 Ref.13 Ref.14 Ref.23 Ref.28 Ref.29
Catalytic activity	Hypoxia-inducible factor-L-asparagine + 2-oxoglutarate + O2 = hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + succinate + CO2. Ref.7 Ref.8 Ref.10 Ankyrin-repeat-L-histidine + 2-oxoglutarate + O2 = ankyrin-repeat-(3S)-3-hydroxy-L-histidine + succinate + CO2. Ref.7 Ref.8 Ref.10
Cofactor	Fe2+ ion.
Subunit structure	Homodimer; homodimerization is essential for catalytic activity. Interacts with VHL and HIF1A. Part of a complex with VHL, HIF1A and HDAC1 or HDAC2 or HDAC3. Interacts with NFKB1 and NFKBIA. Interacts with NOTCH1, NOTCH2 and NOTCH3 but not with NOTCH4. Interacts with APBA3; binding inhibits HIF1AN binding to HIF1A. Interacts with TNKS2. Interacts with PPP1R12A. Interacts with ASB4 By similarity. Interacts with UBE3A. Ref.1 Ref.9 Ref.10 Ref.12 Ref.14 Ref.15 Ref.17 Ref.18 Ref.20 Ref.23 Ref.29
Subcellular location	Nucleus. Cytoplasm. Cytoplasm › perinuclear region. Note: Mainly cytoplasmic localization, but interaction with NOTCH1 results in nuclear localization and interaction with ABPA3 results in perinuclear localization in macrophages. Ref.11 Ref.13 Ref.15
Sequence similarities	Contains 1 JmjC domain.
Biophysicochemical properties	Kinetic parameters: The kinetic constants are determined for the recombinant FLAG-His-tagged protein. KM=100 µM for HIF1A (788-822) peptide Ref.10 KM=160 µM for HIF2A (832-866) peptide KM=0.5 µM for Fe2+ KM=25 µM for 2-oxoglutarate KM=260 µM for ascorbate KM=90 µM for O2
Mass spectrometry	Molecular mass is 40566 Da from positions 1 - 349. Determined by ESI. Ref.9

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	Iron Metal-binding Zinc
Molecular function	Dioxygenase Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of Notch signaling pathway Inferred from direct assay Ref.13. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter in response to hypoxia Inferred from direct assay Ref.1. Source: UniProtKB peptidyl-asparagine hydroxylation Inferred from direct assay Ref.7PubMed 12215170Ref.11Ref.29. Source: UniProtKB peptidyl-aspartic acid hydroxylation Inferred from direct assay Ref.29. Source: UniProtKB peptidyl-histidine hydroxylation Inferred from direct assay Ref.28. Source: UniProtKB positive regulation of myoblast differentiation Inferred from direct assay Ref.13. Source: UniProtKB positive regulation of vasculogenesis Non-traceable author statement PubMed 17636018. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from direct assay Ref.15. Source: UniProtKB
Molecular_function	carboxylic acid binding Inferred from direct assay Ref.22. Source: UniProtKB cofactor binding Inferred from direct assay Ref.19. Source: UniProtKB iron ion binding Inferred from direct assay Ref.19. Source: UniProtKB oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW oxygen sensor activity Non-traceable author statement Ref.7. Source: UniProtKB peptidyl-asparagine 3-dioxygenase activity Inferred from direct assay PubMed 12215170Ref.11. Source: UniProtKB peptidyl-histidine dioxygenase activity Inferred from direct assay Ref.28. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.19. Source: UniProtKB zinc ion binding Inferred from direct assay Ref.19. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ASB9	Q96DX5	3	EBI-745632,EBI-745641
HIF1A	Q16665	3	EBI-745632,EBI-447269

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 349

349

Hypoxia-inducible factor 1-alpha inhibitor

PRO_0000083974

Regions

Domain

142 – 312

171

JmjC

Region

1 – 125

125

Interaction with VHL

Region

181 – 183

3

Substrate binding

Region

201 – 203

3

Substrate binding

Region

238 – 239

2

Substrate binding

Sites

Metal binding

199

1

Iron; via tele nitrogen; catalytic

Metal binding

199

1

Zinc; via tele nitrogen

Metal binding

201

1

Iron; via tele nitrogen; catalytic

Metal binding

201

1

Zinc; via tele nitrogen

Metal binding

279

1

Iron; via tele nitrogen; catalytic

Metal binding

279

1

Zinc; via tele nitrogen

Binding site

145

1

2-oxoglutarate

Binding site

152

1

Substrate

Binding site

196

1

2-oxoglutarate

Binding site

205

1

2-oxoglutarate

Binding site

214

1

2-oxoglutarate

Binding site

294

1

2-oxoglutarate

Binding site

300

1

Substrate; via amide nitrogen

Binding site

321

1

Substrate

Site

340

1

Important for dimer formation

Natural variations

Natural variant

41

1

P → A. Ref.4
Corresponds to variant rs2295778 [ dbSNP | Ensembl ].

VAR_051028

Experimental info

Mutagenesis

199

1

H → A: Prevents suppression of HIF CAD activity. Strongly stimulates 2-oxoglutarate turnover. No stimulation of 2-oxoglutarate turnover; when associated with R-340. Ref.7

Mutagenesis

201

1

D → A: Prevents suppression of HIF CAD activity. Ref.7 Ref.24 Ref.29

Mutagenesis

201

1

D → E: Loss of HIF1A Asn hydroxylation activity. Slightly stimulates 2-oxoglutarate turnover. Ref.7 Ref.24 Ref.29

Mutagenesis

201

1

D → G: No impact on HIF1A Asn hydroxylation activity. Loss of Asp hydroxylation ability. Strongly stimulates 2-oxoglutarate turnover. Loss of HIF1A Asn hydroxylation activity and slight stimulation of 2-oxoglutarate turnover; when associated with R-296. Ref.7 Ref.24 Ref.29

Mutagenesis

239

1

Q → H: No effect on Asp hydroxylation ability. Ref.29

Mutagenesis

296

1

W → R: Loss of HIF1A Asn hydroxylation activity and slight stimulation of 2-oxoglutarate turnover; when associated with G-201. Ref.24

Mutagenesis

340

1

L → R: Impairs dimer formation, leading to loss of HIF1A Asn hydroxylation activity. No stimulation of 2-oxoglutarate turnover; when associated with A-201. Ref.9 Ref.24

Mutagenesis

344

1

I → R: No effect on dimer formation and HIF1A Asn hydroxylation activity. Ref.9

Sequence conflict

10

1

A → T in BAA91291. Ref.2

Sequence conflict

28

1

D → H in BAA91291. Ref.2

Sequence conflict

156

1

R → G in BAA91291. Ref.2

Secondary structure

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349

Helix Strand Turn

Details...

Helix

2 – 9

8

Turn

20 – 22

3

Beta strand

24 – 26

3

Helix

29 – 31

3

Beta strand

39 – 41

3

Helix

50 – 57

8

Beta strand

62 – 65

4

Helix

71 – 75

5

Helix

78 – 84

7

Beta strand

85 – 88

4

Beta strand

90 – 99

10

Helix

105 – 107

3

Turn

108 – 110

3

Beta strand

111 – 113

3

Beta strand

117 – 123

7

Helix

125 – 138

14

Beta strand

143 – 149

7

Beta strand

151 – 154

4

Helix

156 – 163

8

Helix

167 – 176

10

Beta strand

182 – 184

3

Beta strand

186 – 190

5

Beta strand

195 – 199

5

Beta strand

202 – 212

11

Beta strand

214 – 219

6

Helix

221 – 223

3

Helix

224 – 227

4

Turn

235 – 238

4

Beta strand

239 – 242

4

Beta strand

244 – 246

3

Turn

249 – 251

3

Helix

253 – 257

5

Beta strand

260 – 265

6

Beta strand

270 – 273

4

Beta strand

278 – 283

6

Beta strand

290 – 298

9

Helix

312 – 329

18

Beta strand

330 – 332

3

Helix

333 – 335

3

Helix

336 – 344

9

Turn

345 – 347

3

Sequences

	Sequence		Length	Mass (Da)
	Q9NWT6 [UniParc]. Last modified June 16, 2003. Version 2. Checksum: 96A033BA7B3BD8C7	FASTA	349	40,285
	10 20 30 40 50 60 MAATAAEAVA SGSGEPREEA GALGPAWDES QLRSYSFPTR PIPRLSQSDP RAEELIENEE 70 80 90 100 110 120 PVVLTDTNLV YPALKWDLEY LQENIGNGDF SVYSASTHKF LYYDEKKMAN FQNFKPRSNR 130 140 150 160 170 180 EEMKFHEFVE KLQDIQQRGG EERLYLQQTL NDTVGRKIVM DFLGFNWNWI NKQQGKRGWG 190 200 210 220 230 240 QLTSNLLLIG MEGNVTPAHY DEQQNFFAQI KGYKRCILFP PDQFECLYPY PVHHPCDRQS 250 260 270 280 290 300 QVDFDNPDYE RFPNFQNVVG YETVVGPGDV LYIPMYWWHH IESLLNGGIT ITVNFWYKGA 310 320 330 340 PTPKRIEYPL KAHQKVAIMR NIEKMLGEAL GNPQEVGPLL NTMIKGRYN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity." Mahon P.C., Hirota K., Semenza G.L. Genes Dev. 15:2675-2686(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH HIF1A; VHL AND HISTONE DEACETYLASES. Tissue: Brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Signet-ring cell carcinoma.
[3]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-41.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle.
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 89-349. Tissue: Melanoma.
[7]	"FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor." Lando D., Peet D.J., Gorman J.J., Whelan D.A., Whitelaw M.L., Bruick R.K. Genes Dev. 16:1466-1471(2002) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF HIS-199 AND ASP-201.
[8]	"Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family." Hewitson K.S., McNeill L.A., Riordan M.V., Tian Y.-M., Bullock A.N., Welford R.W., Elkins J.M., Oldham N.J., Bhattacharya S., Gleadle J.M., Ratcliffe P.J., Pugh C.W., Schofield C.J. J. Biol. Chem. 277:26351-26355(2002) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, FUNCTION.
[9]	"Disruption of dimerization and substrate phosphorylation inhibit factor inhibiting hypoxia-inducible factor (FIH) activity." Lancaster D.E., McNeill L.A., McDonough M.A., Aplin R.T., Hewitson K.S., Pugh C.W., Ratcliffe P.J., Schofield C.J. Biochem. J. 383:429-437(2004) [PubMed] [Europe PMC] [Abstract] Cited for: DIMERIZATION, MASS SPECTROMETRY, MUTAGENESIS OF LEU-340 AND ILE-344.
[10]	"Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases." Koivunen P., Hirsila M., Gunzler V., Kivirikko K.I., Myllyharju J. J. Biol. Chem. 279:9899-9904(2004) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES.
[11]	"Substrate requirements of the oxygen-sensing asparaginyl hydroxylase factor-inhibiting hypoxia-inducible factor." Linke S., Stojkoski C., Kewley R.J., Booker G.W., Whitelaw M.L., Peet D.J. J. Biol. Chem. 279:14391-14397(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH)." Cockman M.E., Lancaster D.E., Stolze I.P., Hewitson K.S., McDonough M.A., Coleman M.L., Coles C.H., Yu X., Hay R.T., Ley S.C., Pugh C.W., Oldham N.J., Masson N., Schofield C.J., Ratcliffe P.J. Proc. Natl. Acad. Sci. U.S.A. 103:14767-14772(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH NFKB1 AND NFKBIA.
[13]	"Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways." Zheng X., Linke S., Dias J.M., Zheng X., Gradin K., Wallis T.P., Hamilton B.R., Gustafsson M., Ruas J.L., Wilkins S., Bilton R.L., Brismar K., Whitelaw M.L., Pereira T., Gorman J.J., Ericson J., Peet D.J., Lendahl U., Poellinger L. Proc. Natl. Acad. Sci. U.S.A. 105:3368-3373(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[14]	"MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH)." Webb J.D., Muranyi A., Pugh C.W., Ratcliffe P.J., Coleman M.L. Biochem. J. 420:327-333(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PPP1R12A.
[15]	"Mint3 enhances the activity of hypoxia-inducible factor-1 (HIF-1) in macrophages by suppressing the activity of factor inhibiting HIF-1." Sakamoto T., Seiki M. J. Biol. Chem. 284:30350-30359(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH APBA3, SUBCELLULAR LOCATION.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes." Martinez-Noel G., Galligan J.T., Sowa M.E., Arndt V., Overton T.M., Harper J.W., Howley P.M. Mol. Cell. Biol. 32:3095-3106(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBE3A.
[18]	"Structure of factor-inhibiting hypoxia-inducible factor 1: an asparaginyl hydroxylase involved in the hypoxic response pathway." Dann C.E. III, Bruick R.K., Deisenhofer J. Proc. Natl. Acad. Sci. U.S.A. 99:15351-15356(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH IRON AND 2-OXOGLUTARATE, SUBUNIT.
[19]	"Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha." Elkins J.M., Hewitson K.S., McNeill L.A., Seibel J.F., Schlemminger I., Pugh C.W., Ratcliffe P.J., Schofield C.J. J. Biol. Chem. 278:1802-1806(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH 786-826 OF HIF1A; IRON; ZINC AND 2-OXOGLUTARATE.
[20]	"Structure of human FIH-1 reveals a unique active site pocket and interaction sites for HIF-1 and von Hippel-Lindau." Lee C., Kim S.J., Jeong D.G., Lee S.M., Ryu S.E. J. Biol. Chem. 278:7558-7563(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS), SUBUNIT.
[21]	"Selective inhibition of factor inhibiting hypoxia-inducible factor." McDonough M.A., McNeill L.A., Tilliet M., Papamicael C.A., Chen Q.Y., Banerji B., Hewitson K.S., Schofield C.J. J. Am. Chem. Soc. 127:7680-7681(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) IN COMPLEX WITH IRON AND INHIBITOR.
[22]	"Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates." Hewitson K.S., Lienard B.M., McDonough M.A., Clifton I.J., Butler D., Soares A.S., Oldham N.J., McNeill L.A., Schofield C.J. J. Biol. Chem. 282:3293-3301(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH IRON; SUCCINATE AND FUMARATE.
[23]	"Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor." Coleman M.L., McDonough M.A., Hewitson K.S., Coles C., Mecinovic J., Edelmann M., Cook K.M., Cockman M.E., Lancaster D.E., Kessler B.M., Oldham N.J., Ratcliffe P.J., Schofield C.J. J. Biol. Chem. 282:24027-24038(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEXES WITH 1930-1949 OR 1997-2016 OF MOUSE NOTCH1; IRON AND 2-OXOGLUTARATE, FUNCTION, SUBUNIT.
[24]	"Evidence that two enzyme-derived histidine ligands are sufficient for iron binding and catalysis by factor inhibiting HIF (FIH)." Hewitson K.S., Holmes S.L., Ehrismann D., Hardy A.P., Chowdhury R., Schofield C.J., McDonough M.A. J. Biol. Chem. 283:25971-25978(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 11-349 OF MUTANTS ALA-201 AND GLY-201 IN COMPLEXES WITH 786-826 OR 788-806 OF HIF1A; IRON OR ZINC AND 2-OXOGLUTARATE, MUTAGENESIS OF ASP-201; TRP-296 AND LEU-340.
[25]	"Structural basis for binding of cyclic 2-oxoglutarate analogues to factor-inhibiting hypoxia-inducible factor." Conejo-Garcia A., McDonough M.A., Loenarz C., McNeill L.A., Hewitson K.S., Ge W., Lienard B.M., Schofield C.J., Clifton I.J. Bioorg. Med. Chem. Lett. 20:6125-6128(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.12 ANGSTROMS) IN COMPLEX WITH IRON AND 2-OXOGLUTARATE ANALOGS.
[26]	"Crystal structures of human FIH-1 in complex with quinol family inhibitors." Moon H., Han S., Park H., Choe J. Mol. Cells 29:471-474(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 15-349 IN COMPLEX WITH IRON AND QUINOL FAMILY INHIBITORS.
[27]	"The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases." Chowdhury R., Yeoh K.K., Tian Y.M., Hillringhaus L., Bagg E.A., Rose N.R., Leung I.K., Li X.S., Woon E.C., Yang M., McDonough M.A., King O.N., Clifton I.J., Klose R.J., Claridge T.D., Ratcliffe P.J., Schofield C.J., Kawamura A. EMBO Rep. 12:463-469(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH IRON AND INHIBITORS.
[28]	"Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains." Yang M., Chowdhury R., Ge W., Hamed R.B., McDonough M.A., Claridge T.D., Kessler B.M., Cockman M.E., Ratcliffe P.J., Schofield C.J. FEBS J. 278:1086-1097(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) IN COMPLEX WITH IRON; 2-OXOGLUTARATE AND 538-558 OF TNKS2, FUNCTION.
[29]	"Asparagine and aspartate hydroxylation of the cytoskeletal ankyrin family is catalyzed by factor-inhibiting hypoxia-inducible factor." Yang M., Ge W., Chowdhury R., Claridge T.D., Kramer H.B., Schmierer B., McDonough M.A., Gong L., Kessler B.M., Ratcliffe P.J., Coleman M.L., Schofield C.J. J. Biol. Chem. 286:7648-7660(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF MUTANT HIS-239 IN COMPLEX WITH ZINC; N-OXALYLGLYCINE AND PEPTIDE SUBSTRATE, FUNCTION, INTERACTION WITH ANK1, MUTAGENESIS OF ASP-201 AND GLN-239.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF395830 mRNA. Translation: AAL27308.1.
AK000622 mRNA. Translation: BAA91291.1.
AL133352 Genomic DNA. Translation: CAH73566.1.
CH471066 Genomic DNA. Translation: EAW49817.1.
CH471066 Genomic DNA. Translation: EAW49818.1.
BC007719 mRNA. Translation: AAH07719.1.
AL359615 mRNA. Translation: CAB94885.1.

IPI

IPI00941238.

PIR

T50633.

RefSeq

NP_060372.2. NM_017902.2.

UniGene

Hs.500788.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H2K	X-ray	2.15	A	1-349	[»]
1H2L	X-ray	2.25	A	1-349	[»]
1H2M	X-ray	2.50	A	1-349	[»]
1H2N	X-ray	2.84	A	1-349	[»]
1IZ3	X-ray	2.80	A	1-349	[»]
1MZE	X-ray	2.20	A	1-349	[»]
1MZF	X-ray	2.40	A	1-349	[»]
1YCI	X-ray	2.70	A	1-349	[»]
2CGN	X-ray	2.40	A	1-349	[»]
2CGO	X-ray	2.30	A	1-349	[»]
2ILM	X-ray	2.30	A	1-349	[»]
2W0X	X-ray	2.12	A	1-349	[»]
2WA3	X-ray	2.50	A	1-349	[»]
2WA4	X-ray	2.50	A	1-349	[»]
2XUM	X-ray	2.20	A	1-349	[»]
2Y0I	X-ray	2.28	A	1-349	[»]
2YC0	X-ray	2.15	A	1-349	[»]
2YDE	X-ray	2.28	A	1-349	[»]
3D8C	X-ray	2.10	A	11-349	[»]
3KCX	X-ray	2.60	A	15-349	[»]
3KCY	X-ray	2.59	A	15-349	[»]
3OD4	X-ray	2.20	A	1-349	[»]
3P3N	X-ray	2.40	A	1-349	[»]
3P3P	X-ray	2.60	A	1-349	[»]
4AI8	X-ray	2.40	A	1-349	[»]
4B7E	X-ray	2.50	A	1-349	[»]
4B7K	X-ray	2.39	A	1-349	[»]

ProteinModelPortal

Q9NWT6.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NWT6. 5 interactions.

MINT

MINT-1465958.

STRING

9606.ENSP00000299163.

PTM databases

PhosphoSite

Q9NWT6.

Polymorphism databases

DMDM

32129605.

Proteomic databases

PaxDb

Q9NWT6.

PRIDE

Q9NWT6.

Protocols and materials databases

DNASU

55662.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000299163; ENSP00000299163; ENSG00000166135.

GeneID

55662.

KEGG

hsa:55662.

UCSC

uc001krj.4. human.

Organism-specific databases

CTD

55662.

GeneCards

GC10P102285.

HGNC

HGNC:17113. HIF1AN.

MIM

606615. gene.

neXtProt

NX_Q9NWT6.

PharmGKB

PA29284.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG71927.

HOGENOM

HOG000008146.

HOVERGEN

HBG051903.

InParanoid

Q9NWT6.

KO

K00476.

OrthoDB

EOG4WSW9R.

PhylomeDB

Q9NWT6.

Enzyme and pathway databases

BioCyc

MetaCyc:HS15407-MONOMER.

Pathway_Interaction_DB

hif1apathway. Hypoxic and oxygen homeostasis regulation of HIF-1-alpha.

Reactome

REACT_120956. Cellular responses to stress.

Gene expression databases

ArrayExpress

Q9NWT6.

Bgee

Q9NWT6.

CleanEx

HS_HIF1AN.

Genevestigator

Q9NWT6.

GermOnline

ENSG00000166135. Homo sapiens.

Family and domain databases

InterPro

IPR003347. JmjC_dom.
[Graphical view]

SMART

SM00558. JmjC. 1 hit.
[Graphical view]

PROSITE

PS51184. JMJC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9NWT6.

ChEMBL

CHEMBL5909.

EvolutionaryTrace

Q9NWT6.

GenomeRNAi

55662.

NextBio

60403.

SOURCE

Search...

Entry information

Entry name

HIF1N_HUMAN

Accession

Primary (citable) accession number: Q9NWT6
Secondary accession number(s): D3DR69 , Q5W147, Q969Q7, Q9NPV5

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 16, 2003
Last sequence update:	June 16, 2003
Last modified:	May 1, 2013
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.