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HUMAN:HIF1N

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Species (Taxon ID) Homo sapiens (Human). (9606)
Gene Name(s) HIF1AN (synonyms: FIH1)
Protein Name(s) Hypoxia-inducible factor 1-alpha inhibitor

Factor inhibiting HIF-1 FIH-1 Hypoxia-inducible factor asparagine hydroxylase

External Links
UniProt Q9NWT6
EMBL AF395830
AK000622
AL133352
CH471066
CH471066
BC007719
AL359615
CCDS CCDS7498.1
PIR T50633
RefSeq NP_060372.2
UniGene Hs.500788
PDB 1H2K
1H2L
1H2M
1H2N
1IZ3
1MZE
1MZF
1YCI
2CGN
2CGO
2ILM
2W0X
2WA3
2WA4
2XUM
2Y0I
2YC0
2YDE
3D8C
3KCX
3KCY
3OD4
3P3N
3P3P
4AI8
4B7E
4B7K
4BIO
4JAA
PDBsum 1H2K
1H2L
1H2M
1H2N
1IZ3
1MZE
1MZF
1YCI
2CGN
2CGO
2ILM
2W0X
2WA3
2WA4
2XUM
2Y0I
2YC0
2YDE
3D8C
3KCX
3KCY
3OD4
3P3N
3P3P
4AI8
4B7E
4B7K
4BIO
4JAA
ProteinModelPortal Q9NWT6
SMR Q9NWT6
BioGrid 120794
IntAct Q9NWT6
MINT MINT-1465958
STRING 9606.ENSP00000299163
BindingDB Q9NWT6
ChEMBL CHEMBL5909
PhosphoSite Q9NWT6
DMDM 32129605
MaxQB Q9NWT6
PaxDb Q9NWT6
PRIDE Q9NWT6
DNASU 55662
Ensembl ENST00000299163
GeneID 55662
KEGG hsa:55662
UCSC uc001krj.4
CTD 55662
GeneCards GC10P102285
HGNC HGNC:17113
HPA HPA048742
MIM 606615
neXtProt NX_Q9NWT6
PharmGKB PA29284
eggNOG NOG71927
GeneTree ENSGT00530000062914
HOGENOM HOG000008146
HOVERGEN HBG051903
InParanoid Q9NWT6
KO K18055
OMA MIKGRYD
PhylomeDB Q9NWT6
TreeFam TF329609
BioCyc MetaCyc:HS15407-MONOMER
Reactome REACT_121226
ChiTaRS HIF1AN
EvolutionaryTrace Q9NWT6
GeneWiki HIF1AN
GenomeRNAi 55662
NextBio 60403
PRO PR:Q9NWT6
Proteomes UP000005640
Bgee Q9NWT6
CleanEx HS_HIF1AN
ExpressionAtlas Q9NWT6
Genevestigator Q9NWT6
GO GO:0005737
GO:0005829
GO:0005634
GO:0048471
GO:0071532
GO:0031406
GO:0048037
GO:0005506
GO:0051059
GO:0005112
GO:0016706
GO:0019826
GO:0036140
GO:0036139
GO:0042803
GO:0008270
GO:0071456
GO:0045746
GO:0061428
GO:0055114
GO:0042265
GO:0042264
GO:0036138
GO:0045663
GO:2001214
GO:0061418
GO:0006351
Gene3D 1.10.287.1010
InterPro IPR027445
IPR027452
IPR003347
PANTHER PTHR12461:SF19
SMART SM00558
PROSITE PS51184

Annotations

Qualifier GO ID GO term name Reference ECO ID ECO term name with/from Aspect Extension Notes Status
GO:0018126

protein hydroxylation

PMID:16585195[1]

ECO:0000314

P

Figure 1 shows the effect of overexpression of FIH. This results in the hydroxylation of Asn.

complete

GO:0043433

negative regulation of sequence-specific DNA binding transcription factor activity

PMID:11641274[2]

ECO:0000315

P

Figure 3

complete

GO:0008593

regulation of Notch signaling pathway

PMID:18299578[3]

ECO:0000315

P

Figure 1: To control the Notch downstream response, FIH-1 hydroxylates N1945 and N2012 of Notch 1 ICD, thereby regulating Notch activity.

complete

GO:0030528

transcription regulator activity

PMID:11641274[2]

ECO:0000314

F

Figure 3: FIH-1 inhibits the transcriptional activity of HIF-1alpha.

complete

involved_in

GO:2001214

positive regulation of vasculogenesis

PMID:17636018[4]

ECO:0000303

author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

enables

GO:0071532

ankyrin repeat binding

PMID:21251231[5]

ECO:0000353

physical interaction evidence used in manual assertion

UniProtKB:Q9H2K2

F

Seeded From UniProt

complete

enables

GO:0071532

ankyrin repeat binding

PMID:21177872[6]

ECO:0000353

physical interaction evidence used in manual assertion

UniProtKB:P16157

F

Seeded From UniProt

complete

enables

GO:0071532

ankyrin repeat binding

PMID:21177872[6]

ECO:0000353

physical interaction evidence used in manual assertion

UniProtKB:Q01484

F

Seeded From UniProt

complete

enables

GO:0071532

ankyrin repeat binding

PMID:17636018[4]

ECO:0000353

physical interaction evidence used in manual assertion

UniProtKB:Q9WV71

F

Seeded From UniProt

complete

enables

GO:0071532

ankyrin repeat binding

PMID:17003112[7]

ECO:0000353

physical interaction evidence used in manual assertion

UniProtKB:P25963

F

Seeded From UniProt

complete

enables

GO:0071532

ankyrin repeat binding

PMID:17003112[7]

ECO:0000353

physical interaction evidence used in manual assertion

UniProtKB:Q9UK73

F

Seeded From UniProt

complete

enables

GO:0071532

ankyrin repeat binding

PMID:17003112[7]

ECO:0000353

physical interaction evidence used in manual assertion

UniProtKB:Q9BZF9

F

Seeded From UniProt

complete

involved_in

GO:0061428

negative regulation of transcription from RNA polymerase II promoter in response to hypoxia

PMID:11641274[2]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0055114

oxidation-reduction process

PMID:12215170[8]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0055114

oxidation-reduction process

PMID:12080085[9]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

enables

GO:0051059

NF-kappaB binding

PMID:17003112[7]

ECO:0000353

physical interaction evidence used in manual assertion

UniProtKB:P19838

F

Seeded From UniProt

complete

part_of

GO:0048471

perinuclear region of cytoplasm

PMID:19726677[10]

ECO:0000314

direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

enables

GO:0048037

cofactor binding

PMID:12446723[11]

ECO:0000314

direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

involved_in

GO:0045746

negative regulation of Notch signaling pathway

PMID:18299578[3]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0045663

positive regulation of myoblast differentiation

PMID:18299578[3]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

enables

GO:0042803

protein homodimerization activity

PMID:12446723[11]

ECO:0000314

direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

involved_in

GO:0042265

peptidyl-asparagine hydroxylation

PMID:19245366[12]

ECO:0000315

mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0042265

peptidyl-asparagine hydroxylation

PMID:21177872[6]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0042265

peptidyl-asparagine hydroxylation

PMID:12215170[8]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0042265

peptidyl-asparagine hydroxylation

PMID:14734545[13]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0042265

peptidyl-asparagine hydroxylation

PMID:12080085[9]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

involved_in

GO:0042264

peptidyl-aspartic acid hydroxylation

PMID:21177872[6]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

enables

GO:0036140

peptidyl-asparagine 3-dioxygenase activity

PMID:19245366[12]

ECO:0000315

mutant phenotype evidence used in manual assertion

F

has_direct_input:(UniProtKB:O14974)

Seeded From UniProt

complete

enables

GO:0036140

peptidyl-asparagine 3-dioxygenase activity

PMID:12215170[8]

ECO:0000314

direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

enables

GO:0036140

peptidyl-asparagine 3-dioxygenase activity

PMID:14734545[13]

ECO:0000314

direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

enables

GO:0036139

peptidyl-histidine dioxygenase activity

PMID:21251231[5]

ECO:0000314

direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

involved_in

GO:0036138

peptidyl-histidine hydroxylation

PMID:21251231[5]

ECO:0000314

direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

enables

GO:0031406

carboxylic acid binding

PMID:17135241[14]

ECO:0000314

direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

enables

GO:0019826

oxygen sensor activity

PMID:12080085[9]

ECO:0000303

author statement without traceable support used in manual assertion

F

Seeded From UniProt

complete

enables

GO:0008270

zinc ion binding

PMID:12446723[11]

ECO:0000314

direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

part_of

GO:0005737

cytoplasm

PMID:14734545[13]

ECO:0000314

direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

colocalizes_with

GO:0005634

nucleus

PMID:18299578[3]

ECO:0000314

direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

enables

GO:0005506

iron ion binding

PMID:12446723[11]

ECO:0000314

direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

enables

GO:0005112

Notch binding

PMID:18299578[3]

ECO:0000353

physical interaction evidence used in manual assertion

UniProtKB:Q01705

F

Seeded From UniProt

complete

enables

GO:0005112

Notch binding

PMID:17573339[15]

ECO:0000353

physical interaction evidence used in manual assertion

UniProtKB:Q61982

F

Seeded From UniProt

complete

enables

GO:0005112

Notch binding

PMID:17573339[15]

ECO:0000353

physical interaction evidence used in manual assertion

UniProtKB:O35516

F

Seeded From UniProt

complete

enables

GO:0071532

ankyrin repeat binding

PMID:21873635[16]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN000967060
UniProtKB:Q9NWT6

F

Seeded From UniProt

complete

involved_in

GO:0061428

negative regulation of transcription from RNA polymerase II promoter in response to hypoxia

PMID:21873635[16]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN000967060
UniProtKB:Q9NWT6

P

Seeded From UniProt

complete

involved_in

GO:0045746

negative regulation of Notch signaling pathway

PMID:21873635[16]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN000967060
UniProtKB:Q9NWT6

P

Seeded From UniProt

complete

involved_in

GO:0042265

peptidyl-asparagine hydroxylation

PMID:21873635[16]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN000967060
UniProtKB:Q9NWT6

P

Seeded From UniProt

complete

involved_in

GO:0042264

peptidyl-aspartic acid hydroxylation

PMID:21873635[16]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN000967060
UniProtKB:Q9NWT6

P

Seeded From UniProt

complete

enables

GO:0036140

peptidyl-asparagine 3-dioxygenase activity

PMID:21873635[16]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN000967060
UniProtKB:Q9NWT6

F

Seeded From UniProt

complete

enables

GO:0036139

peptidyl-histidine dioxygenase activity

PMID:21873635[16]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN000967060
UniProtKB:Q9NWT6

F

Seeded From UniProt

complete

involved_in

GO:0036138

peptidyl-histidine hydroxylation

PMID:21873635[16]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN000967060
UniProtKB:Q9NWT6

P

Seeded From UniProt

complete

enables

GO:0016706

2-oxoglutarate-dependent dioxygenase activity

PMID:21873635[16]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN002488274
UniProtKB:A2RUC4
UniProtKB:Q8N371
UniProtKB:Q9NWT6

F

Seeded From UniProt

complete

part_of

GO:0005737

cytoplasm

PMID:21873635[16]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN000967060
UniProtKB:Q9NWT6

C

Seeded From UniProt

complete

part_of

GO:0005634

nucleus

PMID:21873635[16]

ECO:0000318

biological aspect of ancestor evidence used in manual assertion

PANTHER:PTN000967060
UniProtKB:Q9NWT6

C

Seeded From UniProt

complete

part_of

GO:0005829

cytosol

GO_REF:0000052

ECO:0000314

direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

part_of

GO:0005654

nucleoplasm

GO_REF:0000052

ECO:0000314

direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

enables

GO:0102113

hypoxia-inducible factor-asparagine oxygenase activity

GO_REF:0000003

ECO:0000501

evidence used in automatic assertion

EC:1.14.11.30

F

Seeded From UniProt

complete

involved_in

GO:0061418

regulation of transcription from RNA polymerase II promoter in response to hypoxia

Reactome:R-HSA-1234174

ECO:0000304

author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

part_of

GO:0005829

cytosol

Reactome:R-HSA-1234164

ECO:0000304

author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

enables

GO:0051213

dioxygenase activity

GO_REF:0000037

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0223

F

Seeded From UniProt

complete

involved_in

GO:0055114

oxidation-reduction process

GO_REF:0000037

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0560

P

Seeded From UniProt

complete

enables

GO:0016491

oxidoreductase activity

GO_REF:0000037

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0560

F

Seeded From UniProt

complete

part_of

GO:0005737

cytoplasm

GO_REF:0000037
GO_REF:0000039

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0963
UniProtKB-SubCell:SL-0086

C

Seeded From UniProt

complete

part_of

GO:0005634

nucleus

GO_REF:0000037
GO_REF:0000039

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0539
UniProtKB-SubCell:SL-0191

C

Seeded From UniProt

complete

enables

GO:0046872

metal ion binding

GO_REF:0000037

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-KW:KW-0479

F

Seeded From UniProt

complete

part_of

GO:0048471

perinuclear region of cytoplasm

GO_REF:0000039

ECO:0000322

imported manually asserted information used in automatic assertion

UniProtKB-SubCell:SL-0198

C

Seeded From UniProt

complete

Notes

References

See Help:References for how to manage references in GONUTS.

  1. Dayan, F et al. (2006) The oxygen sensor factor-inhibiting hypoxia-inducible factor-1 controls expression of distinct genes through the bifunctional transcriptional character of hypoxia-inducible factor-1alpha. Cancer Res. 66 3688-98 PubMed GONUTS page
  2. 2.0 2.1 2.2 Mahon, PC et al. (2001) FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev. 15 2675-86 PubMed GONUTS page
  3. 3.0 3.1 3.2 3.3 3.4 Zheng, X et al. (2008) 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 3368-73 PubMed GONUTS page
  4. 4.0 4.1 Ferguson, JE 3rd et al. (2007) ASB4 is a hydroxylation substrate of FIH and promotes vascular differentiation via an oxygen-dependent mechanism. Mol. Cell. Biol. 27 6407-19 PubMed GONUTS page
  5. 5.0 5.1 5.2 Yang, M et al. (2011) Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains. FEBS J. 278 1086-97 PubMed GONUTS page
  6. 6.0 6.1 6.2 6.3 Yang, M et al. (2011) Asparagine and aspartate hydroxylation of the cytoskeletal ankyrin family is catalyzed by factor-inhibiting hypoxia-inducible factor. J. Biol. Chem. 286 7648-60 PubMed GONUTS page
  7. 7.0 7.1 7.2 7.3 Cockman, ME et al. (2006) 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 14767-72 PubMed GONUTS page
  8. 8.0 8.1 8.2 McNeill, LA et al. (2002) Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the beta-carbon of asparagine-803. Biochem. J. 367 571-5 PubMed GONUTS page
  9. 9.0 9.1 9.2 Lando, D et al. (2002) FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev. 16 1466-71 PubMed GONUTS page
  10. Sakamoto, T & Seiki, M (2009) 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 30350-9 PubMed GONUTS page
  11. 11.0 11.1 11.2 11.3 Elkins, JM et al. (2003) Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1 alpha. J. Biol. Chem. 278 1802-6 PubMed GONUTS page
  12. 12.0 12.1 Webb, JD et al. (2009) MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH). Biochem. J. 420 327-33 PubMed GONUTS page
  13. 13.0 13.1 13.2 Linke, S et al. (2004) Substrate requirements of the oxygen-sensing asparaginyl hydroxylase factor-inhibiting hypoxia-inducible factor. J. Biol. Chem. 279 14391-7 PubMed GONUTS page
  14. Hewitson, KS et al. (2007) Structural and mechanistic studies on the inhibition of the hypoxia-inducible transcription factor hydroxylases by tricarboxylic acid cycle intermediates. J. Biol. Chem. 282 3293-301 PubMed GONUTS page
  15. 15.0 15.1 Coleman, ML et al. (2007) Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor. J. Biol. Chem. 282 24027-38 PubMed GONUTS page
  16. 16.00 16.01 16.02 16.03 16.04 16.05 16.06 16.07 16.08 16.09 16.10 Gaudet, P et al. (2011) Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Brief. Bioinformatics 12 449-62 PubMed GONUTS page