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Protein Page:
HIF1A (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
HIF1A 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. 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. 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. 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 RACK1; promotes HIF1A ubiquitination and proteasome- mediated degradation. Interacts (via N-terminus) with USP19. 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, angiotensin-2 and thrombin. However, this induction is less intense than that stimulated by hypoxia. Repressed by HIPK2 and LIMD1. 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. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Transcription factor; DNA binding protein; Autophagy
Cellular Component: nucleoplasm; transcription factor complex; cytoplasm; nucleolus; cytosol; nucleus
Molecular Function: RNA polymerase II transcription factor activity, enhancer binding; histone deacetylase binding; Hsp90 protein binding; transcription factor binding; protein kinase binding; histone acetyltransferase binding; signal transducer activity; protein binding; enzyme binding; protein heterodimerization activity; sequence-specific DNA binding; ubiquitin protein ligase binding; transcription factor activity; nuclear hormone receptor binding
Biological Process: lactation; oxygen homeostasis; response to muscle activity; embryonic placenta development; cellular iron ion homeostasis; positive regulation of transcription, DNA-dependent; signal transduction; glucose homeostasis; positive regulation of vascular endothelial growth factor receptor signaling pathway; muscle maintenance; negative regulation of bone mineralization; elastin metabolic process; connective tissue replacement during inflammatory response; axon transport of mitochondrion; regulation of transcription, DNA-dependent; visual learning; angiogenesis; negative regulation of neuron apoptosis; heart looping; regulation of transcription from RNA polymerase II promoter in response to oxidative stress; neural crest cell migration; negative regulation of growth; hemoglobin biosynthetic process; positive regulation of neuroblast proliferation; negative regulation of TOR signaling pathway; regulation of transforming growth factor-beta2 production; Notch signaling pathway; collagen metabolic process; embryonic hemopoiesis; positive regulation of nitric-oxide synthase activity; positive regulation of erythrocyte differentiation; B-1 B cell homeostasis; digestive tract morphogenesis; mRNA transcription from RNA polymerase II promoter; positive regulation of chemokine production; positive regulation of angiogenesis; neural fold elevation formation; regulation of gene expression; positive regulation of hormone biosynthetic process; cartilage development; lactate metabolic process; positive regulation of glycolysis; response to hypoxia; epithelial to mesenchymal transition; positive regulation of endothelial cell proliferation; positive regulation of transcription from RNA polymerase II promoter; cerebral cortex development
Reference #:  Q16665 (UniProtKB)
Alt. Names/Synonyms: ARNT interacting protein; ARNT-interacting protein; Basic-helix-loop-helix-PAS protein MOP1; BHLHE78; Class E basic helix-loop-helix protein 78; HIF-1-alpha; HIF-1alpha; HIF1; HIF1-alpha; HIF1A; hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor); hypoxia-inducible factor 1 alpha isoform I.3; hypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor); Hypoxia-inducible factor 1-alpha; Member of PAS protein 1; member of PAS superfamily 1; MOP1; PAS domain-containing protein 8; PASD8
Gene Symbols: HIF1A
Molecular weight: 92,670 Da
Basal Isoelectric point: 5.17  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis  |  mTOR Signaling  |  Warburg Effect
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

HIF1A

Protein Structure Not Found.


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Sites Implicated In
carcinogenesis, altered: S247‑p
cell cycle regulation: S247‑p
cell growth, induced: S668‑p
cell motility, induced: S668‑p
transcription, altered: S641‑p, S643‑p, S696‑p
transcription, induced: S641‑p, S643‑p, T796‑p
transcription, inhibited: S247‑p
activity, induced: S641‑p, S643‑p
activity, inhibited: S247‑p
intracellular localization: S641‑p, S643‑p
molecular association, regulation: S247‑p
protein degradation: S576‑p, S657‑p
protein stabilization: S668‑p, S696‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
1 0 K10-ac GAGGANDkkkISSER
1 0 K11-ac AGGANDkkkISSERR
1 0 K12-ac GGANDkkkISSERRk
1 0 K19-ac kISSERRkEkSRDAA
1 0 K21-ac SSERRkEkSRDAARS
0 1 K32-ub AARSRRSkESEVFYE
0 1 Y66-p VMRLTISyLRVRkLL
0 1 K71-ub ISyLRVRkLLDAGDL
0 1 I80 LDAGDLDIEDDMKAQ
0 1 S113-p DGDMIYIsDNVNKYM
0 1 K185-ub RGRTMNIkSATWKVL
1 0 S247-p KTFLSRHsLDMKFSY
0 1 K289-ub LDSDHLTkTHHDMFT
0 1 K297-ub THHDMFTkGQVTTGQ
0 1 T357 LIFSLQQTECVLKPV
0 1 S366 CVLKPVESSDMKMTQ
0 1 K377-ub KMTQLFTkVESEDTS
1 0 K389-ac DTSSLFDkLkKEPDA
0 1 K389-ub DTSSLFDkLkKEPDA
0 1 K391-ub SSLFDkLkKEPDALT
1 1 K391-sm SSLFDkLkKEPDALT
0 2 S451-p QNINLAMsPLPtAEt
0 1 T455-p LAMsPLPtAEtPKPL
0 1 T458-p sPLPtAEtPKPLRSS
0 1 K477-ub LNQEVALkLEPNPES
1 0 K477-sm LNQEVALkLEPNPES
5 0 K532-ac SDMVNEFkLELVEkL
3 0 K532-ub SDMVNEFkLELVEkL
1 3 K538-ub FkLELVEkLFAEDTE
1 0 K547-ub FAEDTEAkNPFSTQD
0 1 T555-p NPFSTQDtDLDLEML
0 1 Y565-p DLEMLAPyIPMDDDF
1 0 S576-p DDDFQLRsFDQLSPL
2 2 S641-p DIKILIAsPsPTHIH
2 2 S643-p KILIAsPsPTHIHKE
0 1 T645 LIAsPsPTHIHKEtt
0 1 T651-p PTHIHKEttsATssP
0 1 T652-p THIHKEttsATssPY
0 3 S653-p HIHKEttsATssPYR
0 1 S656-p KEttsATssPYRDTQ
1 1 S657-p EttsATssPYRDTQS
1 1 S668-p DTQSRTAsPNRAGkG
2 0 K674-ac AsPNRAGkGVIEQTE
0 1 K674-ub AsPNRAGkGVIEQTE
0 2 S687-p TEKSHPRsPNVLSVA
1 1 S696-p NVLSVALsQRTTVPE
1 0 K709-ac PEEELNPkILALQNA
0 1 K709-ub PEEELNPkILALQNA
1 0 T796-p ESGLPQLtSYDCEVN
  mouse

 
K10 GAGGENEKKKMSSER
K11 AGGENEKKKMSSERR
K12 GGENEKKKMSSERRK
K19 KMSSERRKEKSRDAA
K21 SSERRKEKSRDAARS
K32 AARSRRSKESEVFYE
Y66 VMRLTISYLRVRKLL
K71 ISYLRVRKLLDAGGL
S80-p LDAGGLDsEDEMKAQ
S113 DGDMVYISDNVNKYM
K185 RGRTMNIKSATWKVL
S247 KTFLSRHSLDMKFSY
K289 LDSDHLTKTHHDMFT
K297 THHDMFTKGQVTTGQ
T357-p LIFSLQQtESVLKPV
S366-p SVLKPVEsSDMKMTQ
K377 KMTQLFTKVESEDTS
K389 DTSCLFDKLKKEPDA
K389 DTSCLFDKLKKEPDA
K391 SCLFDKLKKEPDALT
K391 SCLFDKLKKEPDALT
S450 LNINLAMSPLPSSET
S454 LAMSPLPSSETPKPL
T457 SPLPSSETPKPLRSS
K476 LNQEVALKLESSPES
K476 LNQEVALKLESSPES
K545 SDMVNVFKLELVEKL
K545 SDMVNVFKLELVEKL
K551 FKLELVEKLFAEDTE
K560 FAEDTEAKNPFSTQD
T568 NPFSTQDTDLDLEML
Y578 DLEMLAPYIPMDDDF
S589 DDDFQLRSFDQLSPL
S652 DIKILIASPsStQVP
S654-p KILIASPsStQVPQE
T656-p LIASPsStQVPQETT
T662 StQVPQETTTAKASA
T663 tQVPQETTTAKASAY
T664 QVPQETTTAKASAYS
A667 QETTTAKASAYSGTH
S668 ETTTAKASAYSGTHS
S679 GTHSRTASPDRAGKR
K685 ASPDRAGKRVIEQTD
K685 ASPDRAGKRVIEQTD
S698 TDKAHPRSLNLSATL
N706 LNLSATLNQRNTVPE
K719 PEEELNPKTIASQNA
K719 PEEELNPKTIASQNA
T806 ESGLPQLTSYDCEVN
  rat

 
K10 GAGGENEKKKMSSER
K11 AGGENEKKKMSSERR
K12 GGENEKKKMSSERRK
K19 KMSSERRKEKSRDAA
K21 SSERRKEKSRDAARS
K32 AARSRRSKESEVFYE
Y66 VMRLTISYLRVRKLL
K71 ISYLRVRKLLDAGDL
I80 LDAGDLDIEDEMKAQ
S113 DGDMIYISDNVNKYM
K185 RGRTMNIKSATWKVL
S247 KTFLSRHSLDMKFSY
K289 LDSDHLTKTHHDMFT
K297 THHDMFTKGQVTTGQ
T357 LIFSLQQTESVLKPV
S366 SVLKPVESSDMKMTQ
K377 KMTQLFTKVESEDTS
K389 DTSCLFDKLKKEPDA
K389 DTSCLFDKLKKEPDA
K391 SCLFDKLKKEPDALT
K391 SCLFDKLKKEPDALT
S450 LNINLAMSPLPASET
A454 LAMSPLPASETPKPL
T457 SPLPASETPKPLRSS
K476 LNQEVALKLESSPES
K476 LNQEVALKLESSPES
K531 SDMVNVFKLELVEKL
K531 SDMVNVFKLELVEKL
K537 FKLELVEKLFAEDTE
K546 FAEDTEAKNPFSAQD
T554 NPFSAQDTDLDLEML
Y564 DLEMLAPYIPMDDDF
S575 DDDFQLRSFDQLSPL
S641 DIKILIASPPSTQVP
P643 KILIASPPSTQVPQE
T645 LIASPPSTQVPQEMT
M651 STQVPQEMTTAKASA
T652 TQVPQEMTTAKASAY
T653 QVPQEMTTAKASAYS
A656 QEMTTAKASAYSGTH
S657 EMTTAKASAYSGTHS
S668 GTHSRTASPDRAGKR
K674 ASPDRAGKRVIEKTD
K674 ASPDRAGKRVIEKTD
S687 TDKAHPRSLNLSVTL
N696 under review
R708 PEEELNPRTIALQNA
R708 PEEELNPRTIALQNA
T795 ESGLPQLTSYDCEVN
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