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Q16665

- HIF1A_HUMAN

UniProt

Q16665 - HIF1A_HUMAN

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Protein

Hypoxia-inducible factor 1-alpha

Gene

HIF1A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.10 Publications

GO - Molecular functioni

  1. enzyme binding Source: UniProtKB
  2. histone acetyltransferase binding Source: UniProtKB
  3. Hsp90 protein binding Source: BHF-UCL
  4. nuclear hormone receptor binding Source: UniProtKB
  5. protein heterodimerization activity Source: UniProtKB
  6. protein kinase binding Source: UniProtKB
  7. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
  8. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  9. RNA polymerase II transcription factor binding transcription factor activity Source: Ensembl
  10. sequence-specific DNA binding Source: Ensembl
  11. sequence-specific DNA binding transcription factor activity Source: UniProtKB
  12. signal transducer activity Source: InterPro
  13. transcription factor binding Source: BHF-UCL
  14. transcription factor binding transcription factor activity Source: BHF-UCL
  15. ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  1. angiogenesis Source: Ensembl
  2. axon transport of mitochondrion Source: UniProtKB
  3. B-1 B cell homeostasis Source: Ensembl
  4. cardiac ventricle morphogenesis Source: Ensembl
  5. cartilage development Source: Ensembl
  6. cellular iron ion homeostasis Source: Ensembl
  7. cellular response to hypoxia Source: UniProtKB
  8. cellular response to interleukin-1 Source: BHF-UCL
  9. cerebral cortex development Source: Ensembl
  10. collagen metabolic process Source: BHF-UCL
  11. connective tissue replacement involved in inflammatory response wound healing Source: BHF-UCL
  12. digestive tract morphogenesis Source: Ensembl
  13. dopaminergic neuron differentiation Source: Ensembl
  14. elastin metabolic process Source: BHF-UCL
  15. embryonic hemopoiesis Source: Ensembl
  16. embryonic placenta development Source: Ensembl
  17. epithelial cell differentiation involved in mammary gland alveolus development Source: Ensembl
  18. epithelial to mesenchymal transition Source: BHF-UCL
  19. glucose homeostasis Source: Ensembl
  20. heart looping Source: Ensembl
  21. hemoglobin biosynthetic process Source: Ensembl
  22. intestinal epithelial cell maturation Source: Ensembl
  23. lactate metabolic process Source: Ensembl
  24. lactation Source: Ensembl
  25. mRNA transcription from RNA polymerase II promoter Source: BHF-UCL
  26. muscle cell cellular homeostasis Source: Ensembl
  27. negative regulation of bone mineralization Source: Ensembl
  28. negative regulation of growth Source: Ensembl
  29. negative regulation of mesenchymal cell apoptotic process Source: Ensembl
  30. negative regulation of neuron apoptotic process Source: Ensembl
  31. negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
  32. negative regulation of thymocyte apoptotic process Source: Ensembl
  33. negative regulation of TOR signaling Source: Ensembl
  34. neural crest cell migration Source: Ensembl
  35. neural fold elevation formation Source: Ensembl
  36. Notch signaling pathway Source: Reactome
  37. outflow tract morphogenesis Source: Ensembl
  38. oxygen homeostasis Source: HGNC
  39. positive regulation of angiogenesis Source: BHF-UCL
  40. positive regulation of chemokine-mediated signaling pathway Source: BHF-UCL
  41. positive regulation of chemokine production Source: BHF-UCL
  42. positive regulation of endothelial cell proliferation Source: BHF-UCL
  43. positive regulation of epithelial cell migration Source: BHF-UCL
  44. positive regulation of erythrocyte differentiation Source: BHF-UCL
  45. positive regulation of glycolytic process Source: BHF-UCL
  46. positive regulation of hormone biosynthetic process Source: BHF-UCL
  47. positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: Ensembl
  48. positive regulation of neuroblast proliferation Source: Ensembl
  49. positive regulation of nitric-oxide synthase activity Source: BHF-UCL
  50. positive regulation of receptor biosynthetic process Source: BHF-UCL
  51. positive regulation of transcription, DNA-templated Source: UniProtKB
  52. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  53. positive regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: UniProtKB
  54. positive regulation of vascular endothelial growth factor receptor signaling pathway Source: BHF-UCL
  55. positive regulation vascular endothelial growth factor production Source: UniProtKB
  56. regulation of gene expression Source: UniProtKB
  57. regulation of transcription, DNA-templated Source: UniProtKB
  58. regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: Reactome
  59. regulation of transcription from RNA polymerase II promoter in response to oxidative stress Source: BHF-UCL
  60. regulation of transforming growth factor beta2 production Source: BHF-UCL
  61. response to hypoxia Source: UniProtKB
  62. response to muscle activity Source: Ensembl
  63. retina vasculature development in camera-type eye Source: Ensembl
  64. signal transduction Source: BHF-UCL
  65. vascular endothelial growth factor production Source: BHF-UCL
  66. visual learning Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_118780. NOTCH1 Intracellular Domain Regulates Transcription.
REACT_120916. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
REACT_121092. Regulation of gene expression by Hypoxia-inducible Factor.
REACT_121226. Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha.
REACT_24941. Circadian Clock.
SignaLinkiQ16665.

Names & Taxonomyi

Protein namesi
Recommended name:
Hypoxia-inducible factor 1-alpha
Short name:
HIF-1-alpha
Short name:
HIF1-alpha
Alternative name(s):
ARNT-interacting protein
Basic-helix-loop-helix-PAS protein MOP1
Class E basic helix-loop-helix protein 78
Short name:
bHLHe78
Member of PAS protein 1
PAS domain-containing protein 8
Gene namesi
Name:HIF1A
Synonyms:BHLHE78, MOP1, PASD8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 14

Organism-specific databases

HGNCiHGNC:4910. HIF1A.

Subcellular locationi

Cytoplasm. Nucleus
Note: Cytoplasmic in normoxia, nuclear translocation in response to hypoxia. Colocalizes with SUMO1 in the nucleus, under hypoxia.

GO - Cellular componenti

  1. cytoplasm Source: BHF-UCL
  2. cytosol Source: UniProtKB
  3. motile cilium Source: Ensembl
  4. nucleolus Source: HPA
  5. nucleoplasm Source: Reactome
  6. nucleus Source: UniProtKB
  7. transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi247 – 2471S → A: Constitutive kinase activity. 1 Publication
Mutagenesisi247 – 2471S → D: Impaired kinase activity. 1 Publication
Mutagenesisi377 – 3771K → R: No change in HIF1A protein turnover rate but increased transcriptional activity; when associated with R-391; R-477 and R-532. 1 Publication
Mutagenesisi389 – 3891K → R: No change in sumoylation. 1 Publication
Mutagenesisi391 – 3911K → R: Abolishes 1 sumoylation. Abolishes 1 sumoylation; when associated with R-532. Abolishes 2 sumoylations; when associated with R-477. No change in HIF1A protein turnover rate but increased transcriptional activity; when associated with R-377; R-477 and R-532. 2 Publications
Mutagenesisi392 – 3921K → R: No change in sumoylation. 1 Publication
Mutagenesisi394 – 3941P → A: No change in VHLE3-dependent ubiquitination. 1 Publication
Mutagenesisi397 – 3971L → A: Abolishes VHLE3-dependent ubiquitination; when associated with A-400. 1 Publication
Mutagenesisi400 – 4001L → A: Abolishes VHLE3-dependent ubiquitination; when associated with A-397. 1 Publication
Mutagenesisi402 – 4021P → A: Abolishes in VHLE3-dependent ubiquitination, abolishes oxygen-dependent regulation of VP16, partially reduced VHLE target site ubiquitination and no interaction with VHL. No VHLE target site ubiquitination; when associated with G-564. Increases HIF1A instability and reduces HIF1A-induced target gene transcriptional activation; when associated with A-564. 3 Publications
Mutagenesisi442 – 4421K → R: No change in sumoylation. 1 Publication
Mutagenesisi460 – 4601K → R: No change in sumoylation nor in ARD1-mediated acetylation. 1 Publication
Mutagenesisi477 – 4771K → R: Abolishes 1 sumoylation. Abolishes 2 sumoylations; when associated with R-391. No change in HIF1A protein turnover rate but increased transcriptional activity; when associated with R-377; R-391 and R-532. 2 Publications
Mutagenesisi532 – 5321K → R: Reduced ubiquitination. No change in sumoylation nor on interaction with ARD1A. No change in HIF1A protein turnover rate but increased transcriptional activity; when associated with R-377; R-391 and R-477. Complete loss of ubiquitination, but no change in VHL binding; when associated with K-538 and K-547. 5 Publications
Mutagenesisi538 – 5381K → R: No change in sumoylation, but reduced ubiquitination. Complete loss of ubiquitination, but no change in VHL binding; when associated with K-532 and K-547. 3 Publications
Mutagenesisi547 – 5471K → R: No change in sumoylation, but reduced ubiquitination. Complete loss of ubiquitination, but no change in VHL binding; when associated with K-532 and K-538. 3 Publications
Mutagenesisi551 – 5511S → G: Constitutive expression under nonhypoxic conditions by decreasing ubiquitination. 1 Publication
Mutagenesisi552 – 5521T → A: Constitutive expression under nonhypoxic conditions by decreasing ubiquitination. 1 Publication
Mutagenesisi564 – 5641P → A: Increases HIF1A instability and reduces HIF1A-induced target gene transcriptional activation; when associated with A-402. 3 Publications
Mutagenesisi564 – 5641P → G: No change in VHL-dependent ubiquitination. Partially reduced VHLE target site ubiquitination. No VHLE target site ubiquitination; when associated with A-402. 3 Publications
Mutagenesisi576 – 5761S → A: Induces stabilization of the protein. 1 Publication
Mutagenesisi657 – 6571S → A: Induces stabilization of the protein. 1 Publication
Mutagenesisi709 – 7091K → R: Abolishes SIRT2-mediated deacetylation, increases HIF1A instability and reduces HIF1A-induced target gene transcriptional activation. Increases interaction with EGLN1. 1 Publication
Mutagenesisi719 – 7191K → T: Dramatic reduction of accumulation in the nucleus in response to hypoxia. 2 Publications
Mutagenesisi795 – 7951L → A: Inhibits interaction with EP300 and transactivation activity. 1 Publication
Mutagenesisi800 – 8001C → A: Blocks increase in transcriptional activation caused by nitrosylation. 2 Publications
Mutagenesisi800 – 8001C → S: Abolishes hypoxia-inducible transcriptional activation of ctaD. 2 Publications
Mutagenesisi803 – 8031N → A: Recruits CREBBP. No enhancement of CREBBP by Clioquinol in the presence of FIH1. No change in nuclear location nor on repression of transcriptional activity in the presence of histone deacetylase inhibitor. 2 Publications

Organism-specific databases

PharmGKBiPA29283.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 826826Hypoxia-inducible factor 1-alphaPRO_0000127220Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei247 – 2471Phosphoserine; by CK11 Publication
Cross-linki391 – 391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Modified residuei402 – 40214-hydroxyproline1 Publication
Cross-linki477 – 477Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Modified residuei532 – 5321N6-acetyllysine1 Publication
Cross-linki532 – 532Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki538 – 538Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki547 – 547Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei551 – 5511Phosphoserine; by GSK3-beta1 Publication
Modified residuei555 – 5551Phosphothreonine; by GSK3-beta1 Publication
Modified residuei564 – 56414-hydroxyproline3 Publications
Modified residuei576 – 5761Phosphoserine; by PLK31 Publication
Modified residuei589 – 5891Phosphoserine; by GSK3-beta1 Publication
Modified residuei657 – 6571Phosphoserine; by PLK31 Publication
Modified residuei709 – 7091N6-acetyllysine1 Publication
Modified residuei800 – 8001S-nitrosocysteine1 Publication
Modified residuei803 – 8031(3S)-3-hydroxyasparagine1 Publication

Post-translational modificationi

In normoxia, is hydroxylated on Pro-402 and Pro-564 in the oxygen-dependent degradation domain (ODD) by EGLN1/PHD1 and EGLN2/PHD2. EGLN3/PHD3 has also been shown to hydroxylate Pro-564. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Deubiquitinated by USP20. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization.4 Publications
In normoxia, is hydroxylated on Asn-803 by HIF1AN, thus abrogating interaction with CREBBP and EP300 and preventing transcriptional activation. This hydroxylation is inhibited by the Cu/Zn-chelator, Clioquinol.1 Publication
S-nitrosylation of Cys-800 may be responsible for increased recruitment of p300 coactivator necessary for transcriptional activity of HIF-1 complex.2 Publications
Requires phosphorylation for DNA-binding. Phosphorylation at Ser-247 by CSNK1D/CK1 represses kinase activity and impairs ARNT binding. Phosphorylation by GSK3-beta and PLK3 promote degradation by the proteasome.2 Publications
Sumoylated; with SUMO1 under hypoxia. Sumoylation is enhanced through interaction with RWDD3. Both sumoylation and desumoylation seem to be involved in the regulation of its stability during hypoxia. Sumoylation can promote either its stabilization or its VHL-dependent degradation by promoting hydroxyproline-independent HIF1A-VHL complex binding, thus leading to HIF1A ubiquitination and proteasomal degradation. Desumoylation by SENP1 increases its stability amd transcriptional activity. There is a disaccord between various publications on the effect of sumoylation and desumoylation on its stability and transcriptional activity.4 Publications
Acetylation of Lys-532 by ARD1 increases interaction with VHL and stimulates subsequent proteasomal degradation. Deacetylation of Lys-709 by SIRT2 increases its interaction with and hydroxylation by EGLN1 thereby inactivating HIF1A activity by inducing its proteasomal degradation.1 Publication
Ubiquitinated; in normoxia, following hydroxylation and interaction with VHL. Lys-532 appears to be the principal site of ubiquitination. Clioquinol, the Cu/Zn-chelator, inhibits ubiquitination through preventing hydroxylation at Asn-803.3 Publications
The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains.

Keywords - PTMi

Acetylation, Hydroxylation, Isopeptide bond, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

MaxQBiQ16665.
PaxDbiQ16665.
PRIDEiQ16665.

PTM databases

PhosphoSiteiQ16665.

Expressioni

Tissue specificityi

Expressed in most tissues with highest levels in kidney and heart. Overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors. A higher level expression seen in pituitary tumors as compared to the pituitary gland.1 Publication

Inductioni

Under reduced oxygen tension. Induced also by various receptor-mediated factors such as growth factors, cytokines, and circulatory factors such as PDGF, EGF, FGF2, IGF2, TGFB1, HGF, TNF, IL1B/interleukin-1 beta, angiotensin-2 and thrombin. However, this induction is less intense than that stimulated by hypoxia. Repressed by HIPK2 and LIMD1.3 Publications

Gene expression databases

BgeeiQ16665.
CleanExiHS_HIF1A.
ExpressionAtlasiQ16665. baseline and differential.
GenevestigatoriQ16665.

Organism-specific databases

HPAiCAB017442.
HPA001275.

Interactioni

Subunit structurei

Interacts with the HIF1A beta/ARNT subunit; heterodimerization is required for DNA binding. Interacts with COPS5; the interaction increases the transcriptional activity of HIF1A through increased stability (By similarity). Interacts with EP300 (via TAZ-type 1 domains); the interaction is stimulated in response to hypoxia and inhibited by CITED2. Interacts with CREBBP (via TAZ-type 1 domains). Interacts with NCOA1, NCOA2, APEX and HSP90. Interacts (hydroxylated within the ODD domain) with VHLL (via beta domain); the interaction, leads to polyubiquitination and subsequent HIF1A proteasomal degradation. During hypoxia, sumoylated HIF1A also binds VHL; the interaction promotes the ubiquitination of HIF1A. Interacts with SENP1; the interaction desumoylates HIF1A resulting in stabilization and activation of transcription. Interacts (Via the ODD domain) with ARD1A; the interaction appears not to acetylate HIF1A nor have any affect on protein stability, during hypoxia. Interacts with RWDD3; the interaction enhances HIF1A sumoylation. Interacts with TSGA10 (By similarity). Interacts with RORA (via the DNA binding domain); the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Interaction with PSMA7 inhibits the transactivation activity of HIF1A under both normoxic and hypoxia-mimicking conditions. Interacts with USP20. Interacts with GNB2L1/RACK1; promotes HIF1A ubiquitination and proteasome-mediated degradation. Interacts (via N-terminus) with USP19. Interacts with SIRT2. Interacts (deacetylated form) with EGLN1.By similarity28 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARP102752EBI-447269,EBI-608057
ARNTP275409EBI-447269,EBI-80809
ARRB1P494073EBI-447269,EBI-743313
CBX4O0025715EBI-447269,EBI-722425
CREBBPQ927932EBI-447269,EBI-81215
E2f7Q6S7F23EBI-447269,EBI-8030813From a different organism.
e2f7Q5RIX92EBI-447269,EBI-8030618From a different organism.
EGLN1Q9GZT94EBI-447269,EBI-1174818
EGLN2Q96KS02EBI-447269,EBI-726614
EGLN3Q9H6Z93EBI-447269,EBI-1175354
EP300Q0947215EBI-447269,EBI-447295
HIF1ANQ9NWT64EBI-447269,EBI-745632
KAT2BQ928312EBI-447269,EBI-477430
MTA1Q133306EBI-447269,EBI-714236
OS9Q134389EBI-447269,EBI-725454
PIAS4Q8N2W93EBI-447269,EBI-473160
PKMP14618-17EBI-447269,EBI-4304679
Rbfox3Q8BIF22EBI-447269,EBI-4567146From a different organism.
RorcP51450-22EBI-447269,EBI-4422078From a different organism.
SEPT9Q9UHD8-14EBI-447269,EBI-851558
SP1P080473EBI-447269,EBI-298336
SUMO1P631654EBI-447269,EBI-80140
UBXN7O948883EBI-447269,EBI-1993627
USP8P408182EBI-447269,EBI-1050865
VHLP4033717EBI-447269,EBI-301246

Protein-protein interaction databases

BioGridi109338. 115 interactions.
DIPiDIP-29722N.
IntActiQ16665. 60 interactions.
MINTiMINT-133270.
STRINGi9606.ENSP00000338018.

Structurei

Secondary structure

1
826
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi241 – 2466
Beta strandi251 – 2555
Helixi258 – 2636
Helixi267 – 2704
Helixi275 – 2773
Turni281 – 2833
Helixi284 – 29714
Beta strandi298 – 3014
Beta strandi305 – 3084
Beta strandi310 – 32516
Turni327 – 3293
Beta strandi332 – 34110
Helixi559 – 5613
Turni779 – 7835
Helixi784 – 7874
Beta strandi789 – 7924
Helixi797 – 8037
Beta strandi807 – 8093
Helixi815 – 8228

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1D7Gmodel-D15-73[»]
1H2KX-ray2.15S786-826[»]
1H2LX-ray2.25S786-826[»]
1H2MX-ray2.50S775-826[»]
1L3ENMR-A786-826[»]
1L8CNMR-B776-826[»]
1LM8X-ray1.85H556-575[»]
1LQBX-ray2.00D549-582[»]
2ILMX-ray2.30S786-826[»]
3HQRX-ray2.00S558-574[»]
3HQUX-ray2.30S558-574[»]
4AJYX-ray1.73H559-577[»]
4H6JX-ray1.52A238-348[»]
DisProtiDP00262.
ProteinModelPortaliQ16665.
SMRiQ16665. Positions 220-374, 776-826.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16665.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini17 – 7054bHLHPROSITE-ProRule annotationAdd
BLAST
Domaini85 – 15874PAS 1PROSITE-ProRule annotationAdd
BLAST
Domaini228 – 29871PAS 2PROSITE-ProRule annotationAdd
BLAST
Domaini302 – 34544PACAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 401401Interaction with TSGA10By similarityAdd
BLAST
Regioni380 – 41738N-terminal VHL recognition siteAdd
BLAST
Regioni401 – 603203ODDAdd
BLAST
Regioni531 – 57545NTADAdd
BLAST
Regioni556 – 57217C-terminal VHL recognition siteAdd
BLAST
Regioni576 – 785210IDAdd
BLAST
Regioni786 – 82641CTADAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi718 – 7214Nuclear localization signalSequence Analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi615 – 6217Poly-Thr

Domaini

Contains two independent C-terminal transactivation domains, NTAD and CTAD, which function synergistically. Their transcriptional activity is repressed by an intervening inhibitory domain (ID).

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation
Contains 2 PAS (PER-ARNT-SIM) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG289264.
GeneTreeiENSGT00760000118788.
HOGENOMiHOG000234306.
HOVERGENiHBG060456.
InParanoidiQ16665.
KOiK08268.
OMAiQNAQRKR.
OrthoDBiEOG7JDQX8.
PhylomeDBiQ16665.
TreeFamiTF317772.

Family and domain databases

InterProiIPR011598. bHLH_dom.
IPR001321. HIF-1_alpha.
IPR014887. HIF-1_TAD_C.
IPR021537. HIF_alpha_subunit.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
[Graphical view]
PfamiPF11413. HIF-1. 1 hit.
PF08778. HIF-1a_CTAD. 1 hit.
PF00989. PAS. 1 hit.
[Graphical view]
PRINTSiPR01080. HYPOXIAIF1A.
SMARTiSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
TIGRFAMsiTIGR00229. sensory_box. 2 hits.
PROSITEiPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q16665) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEGAGGANDK KKISSERRKE KSRDAARSRR SKESEVFYEL AHQLPLPHNV
60 70 80 90 100
SSHLDKASVM RLTISYLRVR KLLDAGDLDI EDDMKAQMNC FYLKALDGFV
110 120 130 140 150
MVLTDDGDMI YISDNVNKYM GLTQFELTGH SVFDFTHPCD HEEMREMLTH
160 170 180 190 200
RNGLVKKGKE QNTQRSFFLR MKCTLTSRGR TMNIKSATWK VLHCTGHIHV
210 220 230 240 250
YDTNSNQPQC GYKKPPMTCL VLICEPIPHP SNIEIPLDSK TFLSRHSLDM
260 270 280 290 300
KFSYCDERIT ELMGYEPEEL LGRSIYEYYH ALDSDHLTKT HHDMFTKGQV
310 320 330 340 350
TTGQYRMLAK RGGYVWVETQ ATVIYNTKNS QPQCIVCVNY VVSGIIQHDL
360 370 380 390 400
IFSLQQTECV LKPVESSDMK MTQLFTKVES EDTSSLFDKL KKEPDALTLL
410 420 430 440 450
APAAGDTIIS LDFGSNDTET DDQQLEEVPL YNDVMLPSPN EKLQNINLAM
460 470 480 490 500
SPLPTAETPK PLRSSADPAL NQEVALKLEP NPESLELSFT MPQIQDQTPS
510 520 530 540 550
PSDGSTRQSS PEPNSPSEYC FYVDSDMVNE FKLELVEKLF AEDTEAKNPF
560 570 580 590 600
STQDTDLDLE MLAPYIPMDD DFQLRSFDQL SPLESSSASP ESASPQSTVT
610 620 630 640 650
VFQQTQIQEP TANATTTTAT TDELKTVTKD RMEDIKILIA SPSPTHIHKE
660 670 680 690 700
TTSATSSPYR DTQSRTASPN RAGKGVIEQT EKSHPRSPNV LSVALSQRTT
710 720 730 740 750
VPEEELNPKI LALQNAQRKR KMEHDGSLFQ AVGIGTLLQQ PDDHAATTSL
760 770 780 790 800
SWKRVKGCKS SEQNGMEQKT IILIPSDLAC RLLGQSMDES GLPQLTSYDC
810 820
EVNAPIQGSR NLLQGEELLR ALDQVN
Length:826
Mass (Da):92,670
Last modified:November 1, 1996 - v1
Checksum:iABD4F7DAA135BE2D
GO
Isoform 2 (identifier: Q16665-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     735-735: G → I
     736-826: Missing.

Note: No experimental confirmation available.

Show »
Length:735
Mass (Da):82,746
Checksum:i34DD604FB4E4418E
GO
Isoform 3 (identifier: Q16665-3) [UniParc]FASTAAdd to Basket

Also known as: I.3

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MEGAGGANDKKK → MSSQCRSLENKFVFLKEGLGNSKPEELEEIRIENGR

Note: Up-regulated in peripheral T-lymphocytes after T-cell receptor stimulation. Highest expression in peripheral blood leukocytes and thymus.

Show »
Length:850
Mass (Da):95,634
Checksum:i272C9EFAFD7A1E48
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti572 – 5721F → L in AAC68568. (PubMed:9782081)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti582 – 5821P → S.
Corresponds to variant rs11549465 [ dbSNP | Ensembl ].
VAR_049541
Natural varianti588 – 5881A → T.
Corresponds to variant rs11549467 [ dbSNP | Ensembl ].
VAR_049542
Natural varianti796 – 7961T → A.
Corresponds to variant rs1802821 [ dbSNP | Ensembl ].
VAR_015854

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1212MEGAG…NDKKK → MSSQCRSLENKFVFLKEGLG NSKPEELEEIRIENGR in isoform 3. 1 PublicationVSP_044942Add
BLAST
Alternative sequencei735 – 7351G → I in isoform 2. 1 PublicationVSP_047335
Alternative sequencei736 – 82691Missing in isoform 2. 1 PublicationVSP_007738Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U22431 mRNA. Translation: AAC50152.1.
U29165 mRNA. Translation: AAC51210.1.
AF050127
, AF050115, AF050116, AF050117, AF050118, AF050119, AF050120, AF050121, AF050122, AF050123, AF050124, AF050125, AF050126 Genomic DNA. Translation: AAC68568.1.
FJ790247 mRNA. Translation: ACN88547.1.
AF207601 mRNA. Translation: AAF20139.1.
AF207602 mRNA. Translation: AAF20140.1.
AF208487 Genomic DNA. Translation: AAF20149.1.
AF304431 mRNA. Translation: AAG43026.1.
AB073325 mRNA. Translation: BAB70608.1.
BT009776 mRNA. Translation: AAP88778.1.
AL137129 Genomic DNA. No translation available.
BC012527 mRNA. Translation: AAH12527.1.
CCDSiCCDS58324.1. [Q16665-3]
CCDS9753.1. [Q16665-1]
CCDS9754.1. [Q16665-2]
PIRiI38972.
RefSeqiNP_001230013.1. NM_001243084.1. [Q16665-3]
NP_001521.1. NM_001530.3. [Q16665-1]
NP_851397.1. NM_181054.2. [Q16665-2]
UniGeneiHs.597216.
Hs.719495.

Genome annotation databases

EnsembliENST00000323441; ENSP00000323326; ENSG00000100644. [Q16665-2]
ENST00000337138; ENSP00000338018; ENSG00000100644. [Q16665-1]
ENST00000539097; ENSP00000437955; ENSG00000100644. [Q16665-3]
GeneIDi3091.
KEGGihsa:3091.
UCSCiuc001xfq.2. human. [Q16665-1]
uc021rua.1. human.

Polymorphism databases

DMDMi2498017.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Hypoxia inducible factor entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U22431 mRNA. Translation: AAC50152.1 .
U29165 mRNA. Translation: AAC51210.1 .
AF050127
, AF050115 , AF050116 , AF050117 , AF050118 , AF050119 , AF050120 , AF050121 , AF050122 , AF050123 , AF050124 , AF050125 , AF050126 Genomic DNA. Translation: AAC68568.1 .
FJ790247 mRNA. Translation: ACN88547.1 .
AF207601 mRNA. Translation: AAF20139.1 .
AF207602 mRNA. Translation: AAF20140.1 .
AF208487 Genomic DNA. Translation: AAF20149.1 .
AF304431 mRNA. Translation: AAG43026.1 .
AB073325 mRNA. Translation: BAB70608.1 .
BT009776 mRNA. Translation: AAP88778.1 .
AL137129 Genomic DNA. No translation available.
BC012527 mRNA. Translation: AAH12527.1 .
CCDSi CCDS58324.1. [Q16665-3 ]
CCDS9753.1. [Q16665-1 ]
CCDS9754.1. [Q16665-2 ]
PIRi I38972.
RefSeqi NP_001230013.1. NM_001243084.1. [Q16665-3 ]
NP_001521.1. NM_001530.3. [Q16665-1 ]
NP_851397.1. NM_181054.2. [Q16665-2 ]
UniGenei Hs.597216.
Hs.719495.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1D7G model - D 15-73 [» ]
1H2K X-ray 2.15 S 786-826 [» ]
1H2L X-ray 2.25 S 786-826 [» ]
1H2M X-ray 2.50 S 775-826 [» ]
1L3E NMR - A 786-826 [» ]
1L8C NMR - B 776-826 [» ]
1LM8 X-ray 1.85 H 556-575 [» ]
1LQB X-ray 2.00 D 549-582 [» ]
2ILM X-ray 2.30 S 786-826 [» ]
3HQR X-ray 2.00 S 558-574 [» ]
3HQU X-ray 2.30 S 558-574 [» ]
4AJY X-ray 1.73 H 559-577 [» ]
4H6J X-ray 1.52 A 238-348 [» ]
DisProti DP00262.
ProteinModelPortali Q16665.
SMRi Q16665. Positions 220-374, 776-826.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109338. 115 interactions.
DIPi DIP-29722N.
IntActi Q16665. 60 interactions.
MINTi MINT-133270.
STRINGi 9606.ENSP00000338018.

Chemistry

BindingDBi Q16665.
ChEMBLi CHEMBL2221345.
DrugBanki DB01136. Carvedilol.

PTM databases

PhosphoSitei Q16665.

Polymorphism databases

DMDMi 2498017.

Proteomic databases

MaxQBi Q16665.
PaxDbi Q16665.
PRIDEi Q16665.

Protocols and materials databases

DNASUi 3091.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000323441 ; ENSP00000323326 ; ENSG00000100644 . [Q16665-2 ]
ENST00000337138 ; ENSP00000338018 ; ENSG00000100644 . [Q16665-1 ]
ENST00000539097 ; ENSP00000437955 ; ENSG00000100644 . [Q16665-3 ]
GeneIDi 3091.
KEGGi hsa:3091.
UCSCi uc001xfq.2. human. [Q16665-1 ]
uc021rua.1. human.

Organism-specific databases

CTDi 3091.
GeneCardsi GC14P062162.
HGNCi HGNC:4910. HIF1A.
HPAi CAB017442.
HPA001275.
MIMi 603348. gene.
neXtProti NX_Q16665.
PharmGKBi PA29283.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG289264.
GeneTreei ENSGT00760000118788.
HOGENOMi HOG000234306.
HOVERGENi HBG060456.
InParanoidi Q16665.
KOi K08268.
OMAi QNAQRKR.
OrthoDBi EOG7JDQX8.
PhylomeDBi Q16665.
TreeFami TF317772.

Enzyme and pathway databases

Reactomei REACT_118780. NOTCH1 Intracellular Domain Regulates Transcription.
REACT_120916. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
REACT_121092. Regulation of gene expression by Hypoxia-inducible Factor.
REACT_121226. Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha.
REACT_24941. Circadian Clock.
SignaLinki Q16665.

Miscellaneous databases

ChiTaRSi HIF1A. human.
EvolutionaryTracei Q16665.
GeneWikii HIF1A.
GenomeRNAii 3091.
NextBioi 12265.
PROi Q16665.
SOURCEi Search...

Gene expression databases

Bgeei Q16665.
CleanExi HS_HIF1A.
ExpressionAtlasi Q16665. baseline and differential.
Genevestigatori Q16665.

Family and domain databases

InterProi IPR011598. bHLH_dom.
IPR001321. HIF-1_alpha.
IPR014887. HIF-1_TAD_C.
IPR021537. HIF_alpha_subunit.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
[Graphical view ]
Pfami PF11413. HIF-1. 1 hit.
PF08778. HIF-1a_CTAD. 1 hit.
PF00989. PAS. 1 hit.
[Graphical view ]
PRINTSi PR01080. HYPOXIAIF1A.
SMARTi SM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view ]
SUPFAMi SSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
TIGRFAMsi TIGR00229. sensory_box. 2 hits.
PROSITEi PS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension."
    Wang G.L., Jiang B.-H., Rue E.A., Semenza G.L.
    Proc. Natl. Acad. Sci. U.S.A. 92:5510-5514(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 166-170; 259-289 AND 771-781.
  2. "Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway."
    Hogenesch J.B., Chan W.K., Jackiw V.H., Brown R.C., Gu Y.-Z., Pray-Grant M., Perdew G.H., Bradfield C.A.
    J. Biol. Chem. 272:8581-8593(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Hepatoma.
  3. "The human hypoxia-inducible factor 1alpha gene: HIF1A structure and evolutionary conservation."
    Iyer N.V., Leung S.W., Semenza G.L.
    Genomics 52:159-165(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
  4. "Preferential expression of the novel alternative isoform I.3 of hypoxia-inducible factor 1alpha in activated human T lymphocytes."
    Lukashev D., Sitkovsky M.
    Hum. Immunol. 69:421-425(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING.
  5. "HIF1a sequence in the Quechua, a high altitude population."
    Rupert J.L., Hochachka P.W.
    Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
  6. Sun B., Zhao H.R., Yu R.T., Ni M.S.H.
    Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Glial tumor.
  7. "Hypoxia-inducible factor-1 alpha variant isolated from human liver tissue."
    Tanaka S., Sugimachi K.
    Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Liver.
  8. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  9. "The DNA sequence and analysis of human chromosome 14."
    Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
    , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
    Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  10. "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] (ISOFORM 1).
    Tissue: Choriocarcinoma and Placenta.
  11. Cited for: IDENTIFICATION IN COMPLEX WITH EP300 AND CREBBP, INTERACTION WITH EP300.
  12. "Transactivation and inhibitory domains of hypoxia-inducible factor 1alpha. Modulation of transcriptional activity by oxygen tension."
    Jiang B.H., Zheng J.Z., Leung S.W., Roe R., Semenza G.L.
    J. Biol. Chem. 272:19253-19260(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: TRANSACTIVATION DOMAINS NTAD AND CTAD.
  13. "Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1alpha."
    Kallio P.J., Okamoto K., O'Brien S., Carrero P., Makino Y., Tanaka H., Poellinger L.
    EMBO J. 17:6573-6586(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-719.
  14. "Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway."
    Huang L.E., Gu J., Schau M., Bunn H.F.
    Proc. Natl. Acad. Sci. U.S.A. 95:7987-7992(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: OXYGEN-DEPENDENT DEGRADATION DOMAIN.
  15. "Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300."
    Ema M., Hirota K., Mimura J., Abe H., Yodoi J., Sogawa K., Poellinger L., Fujii-Kuriyama Y.
    EMBO J. 18:1905-1914(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: TRANSACTIVATION DOMAINS NTAD AND CTAD, INTERACTION WITH APEX, MUTAGENESIS OF CYS-800.
  16. "Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1."
    Bhattacharya S., Michels C.M., Leung M.K., Arany Z.P., Kung A.L., Livingston D.M.
    Genes Dev. 13:64-75(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DNA-BINDING, INTERACTION WITH EP300.
  17. "Drosophila von Hippel-Lindau tumor suppressor complex possesses E3 ubiquitin ligase activity."
    Aso T., Yamazaki K., Aigaki T., Kitajima S.
    Biochem. Biophys. Res. Commun. 276:355-361(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH VHL.
  18. "Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel-Lindau tumor suppressor protein."
    Tanimoto K., Makino Y., Pereira T., Poellinger L.
    EMBO J. 19:4298-4309(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH VHL AND ARNT, MUTAGENESIS OF LYS-532; LYS-538; LYS-547 AND LYS-719.
  19. "Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1alpha."
    Carrero P., Okamoto K., Coumailleau P., O'Brien S., Tanaka H., Poellinger L.
    Mol. Cell. Biol. 20:402-415(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NCOA1; NCOA2 AND APEX.
  20. "Hypoxia-inducible factor 1alpha protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations."
    Sutter C.H., Laughner E., Semenza G.L.
    Proc. Natl. Acad. Sci. U.S.A. 97:4748-4753(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF SER-551 AND THR-552, UBIQUITINATION.
  21. "Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation."
    Masson N., Willam C., Maxwell P.H., Pugh C.W., Ratcliffe P.J.
    EMBO J. 20:5197-5206(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: HYDROXYLATION AT PRO-402 AND PRO-564, UBIQUITINATION, INTERACTION WITH THE VHLE COMPLEX, FUNCTION, MUTAGENESIS OF PRO-394; LEU-397; LEU-400; PRO-402 AND PRO-564.
  22. "Binding and regulation of HIF-1alpha by a subunit of the proteasome complex, PSMA7."
    Cho S., Choi Y.J., Kim J.M., Jeong S.T., Kim J.H., Kim S.H., Ryu S.E.
    FEBS Lett. 498:62-66(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PSMA7.
  23. "Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation."
    Jaakkola P., Mole D.R., Tian Y.-M., Wilson M.I., Gielbert J., Gaskell S.J., von Kriegsheim A., Hebestreit H.F., Mukherji M., Schofield C.J., Maxwell P.H., Pugh C.W., Ratcliffe P.J.
    Science 292:468-472(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION, FUNCTION, HYDROXYLATION AT PRO-564.
  24. "Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation."
    Jeong J.-W., Bae M.-K., Ahn M.-Y., Kim S.-H., Sohn T.-K., Bae M.-H., Yoo M.-A., Song E.-J., Lee K.-J., Kim K.-W.
    Cell 111:709-720(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ARD1A.
  25. "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: HYDROXYLATION AT ASN-803, IDENTIFICATION BY MASS SPECTROMETRY.
  26. "Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor."
    Ivan M., Haberberger T., Gervasi D.C., Michelson K.S., Guenzler V., Kondo K., Yang H., Sorokina I., Conaway R.C., Conaway J.W., Kaelin W.G. Jr.
    Proc. Natl. Acad. Sci. U.S.A. 99:13459-13464(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: HYDROXYLATION AT PRO-564, IDENTIFICATION BY MASS SPECTROMETRY.
  27. "S-nitrosation of Cys-800 of HIF-1alpha protein activates its interaction with p300 and stimulates its transcriptional activity."
    Yasinska I.M., Sumbayev V.V.
    FEBS Lett. 549:105-109(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: S-NITROSYLATION AT CYS-800, MUTAGENESIS OF CYS-800.
  28. "HIF-1 alpha protein as a target for S-nitrosation."
    Sumbayev V.V., Budde A., Zhou J., Bruene B.
    FEBS Lett. 535:106-112(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: S-NITROSYLATION.
  29. "Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2."
    Freedman S.J., Sun Z.Y., Kung A.L., France D.S., Wagner G., Eck M.J.
    Nat. Struct. Biol. 10:504-512(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EP300, MUTAGENESIS OF LEU-795.
  30. "Sumoylation increases HIF-1alpha stability and its transcriptional activity."
    Bae S.-H., Jeong J.-W., Park J.A., Kim S.-H., Bae M.-K., Choi S.-J., Kim K.-W.
    Biochem. Biophys. Res. Commun. 324:394-400(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION AT LYS-391 AND LYS-477, FUNCTION, MUTAGENESIS OF LYS-389; LYS-391; LYS-392; LYS-442; LYS-460; LYS-477; LYS-532; LYS-538 AND LYS-547.
  31. "Molecular cloning and characterization of the von Hippel-Lindau-like protein."
    Qi H., Gervais M.L., Li W., DeCaprio J.A., Challis J.R.G., Ohh M.
    Mol. Cancer Res. 2:43-52(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH VHLL.
  32. "VHL protein-interacting deubiquitinating enzyme 2 deubiquitinates and stabilizes HIF-1alpha."
    Li Z., Wang D., Messing E.M., Wu G.
    EMBO Rep. 6:373-378(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP20, INTERACTION WITH USP20.
  33. "Interaction between HIF-1 alpha (ODD) and hARD1 does not induce acetylation and destabilization of HIF-1 alpha."
    Arnesen T., Kong X., Evjenth R., Gromyko D., Varhaug J.E., Lin Z., Sang N., Caro J., Lillehaug J.R.
    FEBS Lett. 579:6428-6432(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ARD1A, MUTAGENESIS OF LYS-532.
  34. "Histone deacetylase inhibitors repress the transactivation potential of hypoxia-inducible factors independently of direct acetylation of HIF-alpha."
    Fath D.M., Kong X., Liang D., Lin Z., Chou A., Jiang Y., Fang J., Caro J., Sang N.
    J. Biol. Chem. 281:13612-13619(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH EP300 IN THE HIF1A/EP300/CREBBP COMPLEX, MUTAGENESIS OF ASN-803.
  35. "Clioquinol, a Cu(II)/Zn(II) chelator, inhibits both ubiquitination and asparagine hydroxylation of hypoxia-inducible factor-1alpha, leading to expression of vascular endothelial growth factor and erythropoietin in normoxic cells."
    Choi S.M., Choi K.-O., Park Y.K., Cho H., Yang E.G., Park H.
    J. Biol. Chem. 281:34056-34063(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION, HYDROXYLATION, FUNCTION, INTERACTION WITH CBPP, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF ASN-803.
  36. "SUMOylation of hypoxia-inducible factor-1alpha reduces its transcriptional activity."
    Berta M.A., Mazure N., Hattab M., Pouyssegur J., Brahimi-Horn M.C.
    Biochem. Biophys. Res. Commun. 360:646-652(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION AT LYS-391 AND LYS-477, FUNCTION, MUTAGENESIS OF LYS-377; LYS-391; LYS-477 AND LYS-532.
  37. "RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia."
    Carbia-Nagashima A., Gerez J., Perez-Castro C., Paez-Pereda M., Silberstein S., Stalla G.K., Holsboer F., Arzt E.
    Cell 131:309-323(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION, INTERACTION WITH RWDD3.
  38. "RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF-1alpha."
    Liu Y.V., Baek J.H., Zhang H., Diez R., Cole R.N., Semenza G.L.
    Mol. Cell 25:207-217(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH GNB2L1.
  39. "HIF-1alpha and EPAS ubiquitination mediated by the VHL tumour suppressor involves flexibility in the ubiquitination mechanism, similar to other RING E3 ligases."
    Paltoglou S., Roberts B.J.
    Oncogene 26:604-609(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION AT LYS-532; LYS-538 AND LYS-547, INTERACTION WITH VHL, MUTAGENESIS OF PRO-402; LYS-532; LYS-538; LYS-547 AND PRO-564.
  40. "Transcriptional activation of HIF-1 by RORalpha and its role in hypoxia signaling."
    Kim E.J., Yoo Y.G., Yang W.K., Lim Y.S., Na T.Y., Lee I.K., Lee M.O.
    Arterioscler. Thromb. Vasc. Biol. 28:1796-1802(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RORA.
  41. Cited for: REVIEW ON REGULATION.
  42. "Transcriptional regulation of hypoxia-inducible factor 1alpha by HIPK2 suggests a novel mechanism to restrain tumor growth."
    Nardinocchi L., Puca R., Guidolin D., Belloni A.S., Bossi G., Michiels C., Sacchi A., Onisto M., D'Orazi G.
    Biochim. Biophys. Acta 1793:368-377(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY HIPK2.
  43. "HUMMR, a hypoxia- and HIF-1alpha-inducible protein, alters mitochondrial distribution and transport."
    Li Y., Lim S., Hoffman D., Aspenstrom P., Federoff H.J., Rempe D.A.
    J. Cell Biol. 185:1065-1081(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN MITOCHONDRIAL TRANSPORT.
  44. "Hypoxia-inducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1."
    Gimm T., Wiese M., Teschemacher B., Deggerich A., Schodel J., Knaup K.X., Hackenbeck T., Hellerbrand C., Amann K., Wiesener M.S., Honing S., Eckardt K.U., Warnecke C.
    FASEB J. 24:4443-4458(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  45. "Plk3 functions as an essential component of the hypoxia regulatory pathway by direct phosphorylation of HIF-1alpha."
    Xu D., Yao Y., Lu L., Costa M., Dai W.
    J. Biol. Chem. 285:38944-38950(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-551; THR-555; SER-576; SER-589 AND SER-657, MUTAGENESIS OF SER-576 AND SER-657.
  46. "Casein kinase 1 regulates human hypoxia-inducible factor HIF-1."
    Kalousi A., Mylonis I., Politou A.S., Chachami G., Paraskeva E., Simos G.
    J. Cell Sci. 123:2976-2986(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-247 BY CSNK1D/CK1, MUTAGENESIS OF SER-247, INTERACTION WITH ARNT.
  47. "RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour cells."
    Shan B., Gerez J., Haedo M., Fuertes M., Theodoropoulou M., Buchfelder M., Losa M., Stalla G.K., Arzt E., Renner U.
    Endocr. Relat. Cancer 19:13-27(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
  48. "Ubiquitin-specific protease 19 (USP19) regulates hypoxia-inducible factor 1alpha (HIF-1alpha) during hypoxia."
    Altun M., Zhao B., Velasco K., Liu H., Hassink G., Paschke J., Pereira T., Lindsten K.
    J. Biol. Chem. 287:1962-1969(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH USP19.
  49. Cited for: INDUCTION.
  50. "In silico structural and functional characterization of the RSUME splice variants."
    Gerez J., Fuertes M., Tedesco L., Silberstein S., Sevlever G., Paez-Pereda M., Holsboer F., Turjanski A.G., Arzt E.
    PLoS ONE 8:E57795-E57795(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RWDD3.
  51. "SIRT2 regulates tumour hypoxia response by promoting HIF-1alpha hydroxylation."
    Seo K.S., Park J.H., Heo J.Y., Jing K., Han J., Min K.N., Kim C., Koh G.Y., Lim K., Kang G.Y., Uee Lee J., Yim Y.H., Shong M., Kwak T.H., Kweon G.R.
    Oncogene 0:0-0(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION, DEACETYLATION AT LYS-709 BY SIRT2, HYDROXYLATION, INTERACTION WITH SIRT2 AND EGLN1, MUTAGENESIS OF PRO-402; PRO-564 AND LYS-709.
  52. "A model for the complex between the hypoxia-inducible factor-1 (HIF-1) and its consensus DNA sequence."
    Michel G., Minet E., Ernest I., Roland I., Durant F., Remacle J., Michiels C.
    J. Biomol. Struct. Dyn. 18:169-179(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: 3D-STRUCTURE MODELING.
  53. "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) OF 775-826 IN COMPLEX WITH HIF1AN.
  54. "Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha."
    Freedman S.J., Sun Z.-Y.J., Poy F., Kung A.L., Livingston D.M., Wagner G., Eck M.J.
    Proc. Natl. Acad. Sci. U.S.A. 99:5367-5372(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 786-826 IN COMPLEX WITH 302-418 OF EP300.
  55. "Structural basis for Hif-1 alpha /CBP recognition in the cellular hypoxic response."
    Dames S.A., Martinez-Yamout M., De Guzman R.N., Dyson H.J., Wright P.E.
    Proc. Natl. Acad. Sci. U.S.A. 99:5271-5276(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 776-826 IN COMPLEX WITH 345-439 OF CREBBP.
  56. "Structure of an HIF-1alpha-pVHL complex: hydroxyproline recognition in signaling."
    Min J.-H., Yang H., Ivan M., Gertler F., Kaelin W.G. Jr., Pavletich N.P.
    Science 296:1886-1889(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 556-575 IN COMPLEX WITH TCEB1; TCEB2 AND 54-213 OF VHL.
  57. Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 549-582 IN COMPLEX WITH 17-112 OF TCEB1; TCEB2 AND 52-213 OF VHL.

Entry informationi

Entry nameiHIF1A_HUMAN
AccessioniPrimary (citable) accession number: Q16665
Secondary accession number(s): C0LZJ3
, Q53XP6, Q96PT9, Q9UPB1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: October 29, 2014
This is version 176 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

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