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Q16665 (HIF1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 170. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:HIF1A
Synonyms:BHLHE78, MOP1, PASD8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length826 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.16 Ref.21 Ref.23 Ref.30 Ref.34 Ref.35 Ref.36 Ref.42 Ref.43

Subunit structure

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. Ref.11 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.22 Ref.24 Ref.29 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.37 Ref.38 Ref.39 Ref.40 Ref.45 Ref.46

Subcellular location

Cytoplasm. Nucleus. Note: Cytoplasmic in normoxia, nuclear translocation in response to hypoxia. Colocalizes with SUMO1 in the nucleus, under hypoxia. Ref.13

Tissue specificity

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.

Induction

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. Ref.41 Ref.47

Domain

Contains two independent C-terminal transactivation domains, NTAD and CTAD, which function synergistically. Their transcriptional activity is repressed by an intervening inhibitory domain (ID). Ref.12 Ref.14 Ref.15

Post-translational modification

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.

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.

S-nitrosylation of Cys-800 may be responsible for increased recruitment of p300 coactivator necessary for transcriptional activity of HIF-1 complex.

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.

Sumoylated; with SUMO1 under hypoxia. Sumoylation is enhanced through interaction with RWDD3. Desumoylation by SENP1 leads to increased HIF1A stability and transriptional activity By similarity. Ref.30 Ref.36 Ref.37

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. Ref.14 Ref.20 Ref.21 Ref.23 Ref.32 Ref.35 Ref.39

The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains.

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Contains 1 PAC (PAS-associated C-terminal) domain.

Contains 2 PAS (PER-ARNT-SIM) domains.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandDNA-binding
   Molecular functionActivator
   PTMHydroxylation
Isopeptide bond
Phosphoprotein
S-nitrosylation
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processB-1 B cell homeostasis

Inferred from electronic annotation. Source: Ensembl

Notch signaling pathway

Traceable author statement. Source: Reactome

angiogenesis

Inferred from electronic annotation. Source: Ensembl

axon transport of mitochondrion

Inferred from mutant phenotype Ref.42. Source: UniProtKB

cardiac ventricle morphogenesis

Inferred from electronic annotation. Source: Ensembl

cartilage development

Inferred from electronic annotation. Source: Ensembl

cellular iron ion homeostasis

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Inferred from direct assay PubMed 11573933Ref.42Ref.44. Source: UniProtKB

cellular response to interleukin-1

Inferred from expression pattern PubMed 12958148. Source: BHF-UCL

cerebral cortex development

Inferred from electronic annotation. Source: Ensembl

collagen metabolic process

Inferred from sequence or structural similarity PubMed 18037992. Source: BHF-UCL

connective tissue replacement involved in inflammatory response wound healing

Inferred from sequence or structural similarity PubMed 18037992. Source: BHF-UCL

digestive tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

dopaminergic neuron differentiation

Inferred from electronic annotation. Source: Ensembl

elastin metabolic process

Inferred from sequence or structural similarity PubMed 18037992. Source: BHF-UCL

embryonic hemopoiesis

Inferred from electronic annotation. Source: Ensembl

embryonic placenta development

Inferred from electronic annotation. Source: Ensembl

epithelial cell differentiation involved in mammary gland alveolus development

Inferred from electronic annotation. Source: Ensembl

epithelial to mesenchymal transition

Inferred from sequence or structural similarity PubMed 18037992. Source: BHF-UCL

glucose homeostasis

Inferred from electronic annotation. Source: Ensembl

heart looping

Inferred from electronic annotation. Source: Ensembl

hemoglobin biosynthetic process

Inferred from electronic annotation. Source: Ensembl

intestinal epithelial cell maturation

Inferred from electronic annotation. Source: Ensembl

lactate metabolic process

Inferred from electronic annotation. Source: Ensembl

lactation

Inferred from electronic annotation. Source: Ensembl

mRNA transcription from RNA polymerase II promoter

Inferred by curator Ref.1. Source: BHF-UCL

muscle cell cellular homeostasis

Inferred from electronic annotation. Source: Ensembl

negative regulation of TOR signaling

Inferred from electronic annotation. Source: Ensembl

negative regulation of bone mineralization

Inferred from electronic annotation. Source: Ensembl

negative regulation of growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of mesenchymal cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of thymocyte apoptotic process

Inferred from electronic annotation. Source: Ensembl

neural crest cell migration

Inferred from electronic annotation. Source: Ensembl

neural fold elevation formation

Inferred from electronic annotation. Source: Ensembl

outflow tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

oxygen homeostasis

Inferred from direct assay PubMed 16956324. Source: HGNC

positive regulation of angiogenesis

Inferred by curator PubMed 8756616. Source: BHF-UCL

positive regulation of chemokine production

Traceable author statement PubMed 18370914. Source: BHF-UCL

positive regulation of chemokine-mediated signaling pathway

Inferred by curator PubMed 17178876. Source: BHF-UCL

positive regulation of endothelial cell proliferation

Inferred by curator PubMed 8756616. Source: BHF-UCL

positive regulation of epithelial cell migration

Inferred from sequence or structural similarity PubMed 18037992. Source: BHF-UCL

positive regulation of erythrocyte differentiation

Inferred by curator PubMed 1448077. Source: BHF-UCL

positive regulation of glycolysis

Inferred by curator PubMed 8089148. Source: BHF-UCL

positive regulation of hormone biosynthetic process

Inferred from direct assay PubMed 1448077. Source: BHF-UCL

positive regulation of insulin secretion involved in cellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuroblast proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of nitric-oxide synthase activity

Traceable author statement PubMed 18254728. Source: BHF-UCL

positive regulation of receptor biosynthetic process

Inferred from mutant phenotype PubMed 17178876. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 11573933. Source: UniProtKB

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

Inferred from direct assay PubMed 22735262. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.16PubMed 99104162. Source: UniProtKB

positive regulation of vascular endothelial growth factor receptor signaling pathway

Inferred by curator PubMed 12958148PubMed 8756616. Source: BHF-UCL

positive regulation vascular endothelial growth factor production

Inferred from direct assay. Source: BHF-UCL

regulation of gene expression

Inferred from direct assay PubMed 18419598. Source: UniProtKB

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

Traceable author statement. Source: Reactome

regulation of transcription from RNA polymerase II promoter in response to oxidative stress

Inferred from direct assay PubMed 8089148PubMed 8387214. Source: BHF-UCL

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 15261140. Source: UniProtKB

regulation of transforming growth factor beta2 production

Inferred from mutant phenotype PubMed 12411310. Source: BHF-UCL

response to hypoxia

Inferred from direct assay PubMed 15261140PubMed 18419598Ref.16PubMed 99104162. Source: UniProtKB

response to muscle activity

Inferred from electronic annotation. Source: Ensembl

retina vasculature development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

signal transduction

Inferred from mutant phenotype PubMed 12411310. Source: BHF-UCL

vascular endothelial growth factor production

Inferred from direct assay PubMed 12958148. Source: BHF-UCL

visual learning

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 19651758. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

motile cilium

Inferred from electronic annotation. Source: Ensembl

nucleolus

Inferred from direct assay. Source: HPA

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 15261140Ref.40PubMed 20810912. Source: UniProtKB

transcription factor complex

Inferred from physical interaction PubMed 9576906. Source: MGI

   Molecular_functionHsp90 protein binding

Inferred from direct assay Ref.2. Source: BHF-UCL

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 8387214Ref.2. Source: BHF-UCL

RNA polymerase II transcription factor binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

enzyme binding

Inferred from physical interaction PubMed 11641274. Source: UniProtKB

histone acetyltransferase binding

Inferred from physical interaction PubMed 15261140. Source: UniProtKB

protein heterodimerization activity

Inferred from physical interaction PubMed 12239177. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.44. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Traceable author statement. Source: UniProtKB

signal transducer activity

Inferred from electronic annotation. Source: InterPro

transcription factor binding

Inferred from physical interaction Ref.1. Source: BHF-UCL

transcription factor binding transcription factor activity

Inferred from direct assay PubMed 22735262. Source: BHF-UCL

transcription regulatory region DNA binding

Inferred from direct assay PubMed 99104162. Source: UniProtKB

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 11641274. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q16665-1)

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.
Isoform 2 (identifier: Q16665-2)

The sequence of this isoform differs from the canonical sequence as follows:
     735-735: G → I
     736-826: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q16665-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 826826Hypoxia-inducible factor 1-alpha
PRO_0000127220

Regions

Domain17 – 7054bHLH
Domain85 – 15874PAS 1
Domain228 – 29871PAS 2
Domain302 – 34544PAC
Region1 – 401401Interaction with TSGA10 By similarity
Region380 – 41738N-terminal VHL recognition site
Region401 – 603203ODD
Region531 – 57545NTAD
Region556 – 57217C-terminal VHL recognition site
Region576 – 785210ID
Region786 – 82641CTAD
Motif718 – 7214Nuclear localization signal Potential
Compositional bias615 – 6217Poly-Thr

Amino acid modifications

Modified residue2471Phosphoserine; by CK1 Ref.45
Modified residue40214-hydroxyproline Ref.21
Modified residue5511Phosphoserine; by GSK3-beta Ref.44
Modified residue5551Phosphothreonine; by GSK3-beta Ref.44
Modified residue56414-hydroxyproline Ref.21 Ref.23 Ref.26
Modified residue5761Phosphoserine; by PLK3 Ref.44
Modified residue5891Phosphoserine; by GSK3-beta Ref.44
Modified residue6571Phosphoserine; by PLK3 Ref.44
Modified residue8001S-nitrosocysteine Probable
Modified residue8031(3S)-3-hydroxyasparagine Ref.25
Cross-link391Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.30 Ref.36
Cross-link477Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.30 Ref.36
Cross-link532Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable
Cross-link538Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable
Cross-link547Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable

Natural variations

Alternative sequence1 – 1212MEGAG…NDKKK → MSSQCRSLENKFVFLKEGLG NSKPEELEEIRIENGR in isoform 3.
VSP_044942
Alternative sequence7351G → I in isoform 2.
VSP_047335
Alternative sequence736 – 82691Missing in isoform 2.
VSP_007738
Natural variant5821P → S.
Corresponds to variant rs11549465 [ dbSNP | Ensembl ].
VAR_049541
Natural variant5881A → T.
Corresponds to variant rs11549467 [ dbSNP | Ensembl ].
VAR_049542
Natural variant7961T → A.
Corresponds to variant rs1802821 [ dbSNP | Ensembl ].
VAR_015854

Experimental info

Mutagenesis2471S → A: Constitutive kinase activity. Ref.45
Mutagenesis2471S → D: Impaired kinase activity. Ref.45
Mutagenesis3771K → R: No change in HIF1A protein turnover rate but increased transcriptional activity; when associated with R-391; R-477 and R-532. Ref.30 Ref.36
Mutagenesis3891K → R: No change in sumoylation. Ref.30
Mutagenesis3911K → 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. Ref.30 Ref.36
Mutagenesis3921K → R: No change in sumoylation. Ref.30
Mutagenesis3941P → A: No change in VHLE3-dependent ubiquitination. Ref.21
Mutagenesis3971L → A: Abolishes VHLE3-dependent ubiquitination; when associated with A-400. Ref.21
Mutagenesis4001L → A: Abolishes VHLE3-dependent ubiquitination; when associated with A-397. Ref.21
Mutagenesis4021P → 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. Ref.21 Ref.39
Mutagenesis4421K → R: No change in sumoylation. Ref.30
Mutagenesis4601K → R: No change in sumoylation nor in ARD1-mediated acetylation. Ref.30
Mutagenesis4771K → 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. Ref.30 Ref.36
Mutagenesis5321K → 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. Ref.18 Ref.30 Ref.33 Ref.36 Ref.39
Mutagenesis5381K → 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. Ref.18 Ref.30 Ref.39
Mutagenesis5471K → 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. Ref.18 Ref.30 Ref.39
Mutagenesis5511S → G: Constitutive expression under nonhypoxic conditions by decreasing ubiquitination. Ref.20
Mutagenesis5521T → A: Constitutive expression under nonhypoxic conditions by decreasing ubiquitination. Ref.20
Mutagenesis5641P → G: No change in VHL-dependent ubiquitination. Partially reduced VHLE target site ubiquitination. No VHLE target site ubiquitination; when associated with A-402. Ref.21 Ref.39
Mutagenesis5761S → A: Induces stabilization of the protein. Ref.44
Mutagenesis6571S → A: Induces stabilization of the protein. Ref.44
Mutagenesis7191K → T: Dramatic reduction of accumulation in the nucleus in response to hypoxia. Ref.13 Ref.18
Mutagenesis7951L → A: Inhibits interaction with EP300 and transactivation activity. Ref.29
Mutagenesis8001C → A: Blocks increase in transcriptional activation caused by nitrosylation. Ref.15 Ref.27
Mutagenesis8001C → S: Abolishes hypoxia-inducible transcriptional activation of ctaD. Ref.15 Ref.27
Mutagenesis8031N → 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. Ref.34 Ref.35
Sequence conflict5721F → L in AAC68568. Ref.3

Secondary structure

.................................... 826
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: ABD4F7DAA135BE2D

FASTA82692,670
        10         20         30         40         50         60 
MEGAGGANDK KKISSERRKE KSRDAARSRR SKESEVFYEL AHQLPLPHNV SSHLDKASVM 

        70         80         90        100        110        120 
RLTISYLRVR KLLDAGDLDI EDDMKAQMNC FYLKALDGFV MVLTDDGDMI YISDNVNKYM 

       130        140        150        160        170        180 
GLTQFELTGH SVFDFTHPCD HEEMREMLTH RNGLVKKGKE QNTQRSFFLR MKCTLTSRGR 

       190        200        210        220        230        240 
TMNIKSATWK VLHCTGHIHV YDTNSNQPQC GYKKPPMTCL VLICEPIPHP SNIEIPLDSK 

       250        260        270        280        290        300 
TFLSRHSLDM KFSYCDERIT ELMGYEPEEL LGRSIYEYYH ALDSDHLTKT HHDMFTKGQV 

       310        320        330        340        350        360 
TTGQYRMLAK RGGYVWVETQ ATVIYNTKNS QPQCIVCVNY VVSGIIQHDL IFSLQQTECV 

       370        380        390        400        410        420 
LKPVESSDMK MTQLFTKVES EDTSSLFDKL KKEPDALTLL APAAGDTIIS LDFGSNDTET 

       430        440        450        460        470        480 
DDQQLEEVPL YNDVMLPSPN EKLQNINLAM SPLPTAETPK PLRSSADPAL NQEVALKLEP 

       490        500        510        520        530        540 
NPESLELSFT MPQIQDQTPS PSDGSTRQSS PEPNSPSEYC FYVDSDMVNE FKLELVEKLF 

       550        560        570        580        590        600 
AEDTEAKNPF STQDTDLDLE MLAPYIPMDD DFQLRSFDQL SPLESSSASP ESASPQSTVT 

       610        620        630        640        650        660 
VFQQTQIQEP TANATTTTAT TDELKTVTKD RMEDIKILIA SPSPTHIHKE TTSATSSPYR 

       670        680        690        700        710        720 
DTQSRTASPN RAGKGVIEQT EKSHPRSPNV LSVALSQRTT VPEEELNPKI LALQNAQRKR 

       730        740        750        760        770        780 
KMEHDGSLFQ AVGIGTLLQQ PDDHAATTSL SWKRVKGCKS SEQNGMEQKT IILIPSDLAC 

       790        800        810        820 
RLLGQSMDES GLPQLTSYDC EVNAPIQGSR NLLQGEELLR ALDQVN 

« Hide

Isoform 2 [UniParc].

Checksum: 34DD604FB4E4418E
Show »

FASTA73582,746
Isoform 3 (I.3) [UniParc].

Checksum: 272C9EFAFD7A1E48
Show »

FASTA85095,634

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"An essential role for p300/CBP in the cellular response to hypoxia."
Arany Z., Huang L.E., Eckner R., Bhattacharya S., Jiang C., Goldberg M.A., Bunn H.F., Livingston D.M.
Proc. Natl. Acad. Sci. U.S.A. 93:12969-12973(1996) [PubMed] [Europe PMC] [Abstract]
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]"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.
[42]"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.
[43]"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.
[44]"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.
[45]"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.
[46]"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.
[47]"The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity."
Foxler D.E., Bridge K.S., James V., Webb T.M., Mee M., Wong S.C., Feng Y., Constantin-Teodosiu D., Petursdottir T.E., Bjornsson J., Ingvarsson S., Ratcliffe P.J., Longmore G.D., Sharp T.V.
Nat. Cell Biol. 14:201-208(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[48]"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.
[49]"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.
[50]"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.
[51]"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.
[52]"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.
[53]"Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL."
Hon W.-C., Wilson M.I., Harlos K., Claridge T.D.W., Schofield C.J., Pugh C.W., Maxwell P.H., Ratcliffe P.J., Stuart D.I., Jones E.Y.
Nature 417:975-978(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 549-582 IN COMPLEX WITH 17-112 OF TCEB1; TCEB2 AND 52-213 OF VHL.
+Additional computationally mapped references.

Web resources

Wikipedia

Hypoxia inducible factor entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U22431 mRNA. Translation: AAC50152.1.
U29165 mRNA. Translation: AAC51210.1.
AF050127 expand/collapse EMBL AC list , 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.
PIRI38972.
RefSeqNP_001230013.1. NM_001243084.1.
NP_001521.1. NM_001530.3.
NP_851397.1. NM_181054.2.
UniGeneHs.597216.
Hs.719495.

3D structure databases

PDBe
RCSB PDB
PDBj
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-ray1.73H562-577[»]
4H6JX-ray1.52A238-348[»]
DisProtDP00262.
ProteinModelPortalQ16665.
SMRQ16665. Positions 19-374, 776-826.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109338. 110 interactions.
DIPDIP-29722N.
IntActQ16665. 51 interactions.
MINTMINT-133270.
STRING9606.ENSP00000338018.

Chemistry

BindingDBQ16665.
ChEMBLCHEMBL4261.

PTM databases

PhosphoSiteQ16665.

Polymorphism databases

DMDM2498017.

Proteomic databases

PaxDbQ16665.
PRIDEQ16665.

Protocols and materials databases

DNASU3091.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000323441; ENSP00000323326; ENSG00000100644. [Q16665-2]
ENST00000337138; ENSP00000338018; ENSG00000100644. [Q16665-1]
ENST00000539097; ENSP00000437955; ENSG00000100644. [Q16665-3]
GeneID3091.
KEGGhsa:3091.
UCSCuc001xfq.2. human. [Q16665-1]
uc021rua.1. human.

Organism-specific databases

CTD3091.
GeneCardsGC14P062162.
HGNCHGNC:4910. HIF1A.
HPACAB017442.
HPA001275.
MIM603348. gene.
neXtProtNX_Q16665.
PharmGKBPA29283.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG289264.
HOGENOMHOG000234306.
HOVERGENHBG060456.
KOK08268.
OMAQNAQRKR.
OrthoDBEOG7JDQX8.
PhylomeDBQ16665.
TreeFamTF317772.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_120956. Cellular responses to stress.
SignaLinkQ16665.

Gene expression databases

ArrayExpressQ16665.
BgeeQ16665.
CleanExHS_HIF1A.
GenevestigatorQ16665.

Family and domain databases

InterProIPR011598. bHLH_dom.
IPR001321. HIF-1_alpha.
IPR014887. HIF-1_TAD_C.
IPR021537. HIF_alpha_subunit.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
[Graphical view]
PfamPF11413. HIF-1. 1 hit.
PF08778. HIF-1a_CTAD. 1 hit.
PF00989. PAS. 1 hit.
[Graphical view]
PRINTSPR01080. HYPOXIAIF1A.
SMARTSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
TIGRFAMsTIGR00229. sensory_box. 2 hits.
PROSITEPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHIF1A. human.
EvolutionaryTraceQ16665.
GeneWikiHIF1A.
GenomeRNAi3091.
NextBio12265.
PROQ16665.
SOURCESearch...

Entry information

Entry nameHIF1A_HUMAN
AccessionPrimary (citable) accession number: Q16665
Secondary accession number(s): C0LZJ3 expand/collapse secondary AC list , Q53XP6, Q96PT9, Q9UPB1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 170 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM