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Q16665 Proteins PAS domain Repeats
Uniprot ID:Q16665
Protein name: Hypoxia-inducible factor 1-alpha
Gene : HIF1A BHLHE78 MOP1 PASD8
Protein Family:
Squence Length : 826
Sequnce
>Q16665 827 MEGAGGANDKKKISSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAGDLDIEDDMKAQMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYMGLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKEQNTQRSFFLRMKCTLTSRGRTMNIKSATWKVLHCTGHIHVYDTNSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSKTFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQVTTGQYRMLAKRGGYVWVETQATVIYNTKNSQPQCIVCVNYVVSGIIQHDLIFSLQQTECVLKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPAAGDTIISLDFGSNDTETDDQQLEEVPLYNDVMLPSPNEKLQNINLAMSPLPTAETPKPLRSSADPALNQEVALKLEPNPESLELSFTMPQIQDQTPSPSDGSTRQSSPEPNSPSEYCFYVDSDMVNEFKLELVEKLFAEDTEAKNPFSTQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESSSASPESASPQSTVTVFQQTQIQEPTANATTTTATTDELKTVTKDRMEDIKILIASPSPTHIHKETTSATSSPYRDTQSRTASPNRAGKGVIEQTEKSHPRSPNVLSVALSQRTTVPEEELNPKILALQNAQRKRKMEHDGSLFQAVGIGTLLQQPDDHAATTSLSWKRVKGCKSSEQNGMEQKTIILIPSDLACRLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN
Domains
DOMAIN 17 70 bHLH DOMAIN 85 158 PAS 1 DOMAIN 228 298 PAS 2 DOMAIN 302 345 PAC
PAS sequence regions
85 - 158 QMNCFYLKALDGFVMVLTDDGDMIYISDNVNKYMGLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGLVKKGKE 228 - 298 PSNIEIPLDSKTFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQV
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. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP 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"
Motifs
MOTIF 718 721 Nuclear localization signal
Mutation
"247 247 S->A: Constitutive kinase activity 247 247 S->D: Impaired kinase activity 377 377 K->R: No change in HIF1A protein turnover rate but increased transcriptional activity when associated with R-391 R-477 and R-532 389 389 K->R: No change in sumoylation 391 391 K->R: Abolishes 1 sumoylation when associated with R-532 when associated with R-477 when associated with R-377 R-477 and R-532 392 392 K->R: No change in sumoylation 394 394 P->A: No change in VHLE3-dependent ubiquitination 397 397 L->A: Abolishes VHLE3-dependent ubiquitination when associated with A-400 400 400 L->A: Abolishes VHLE3-dependent ubiquitination when associated with A-397 402 402 P->A: Abolishes in VHLE3-dependent ubiquitination, abolishes oxygen-dependent regulation of VP16, partially reduced VHLE target site ubiquitination and no interaction with VHL when associated with G-564 when associated with A-564 442 442 K->R: No change in sumoylation 460 460 K->R: No change in sumoylation nor in ARD1-mediated acetylation 477 477 K->R: Abolishes 1 sumoylation when associated with R-391 when associated with R-377 R-391 and R-532 532 532 K->R: Reduced ubiquitination when associated with R-377 R-391 and R-477 when associated with K-538 and K-547 538 538 K->R: No change in sumoylation, but reduced ubiquitination when associated with K-532 and K-547 547 547 K->R: No change in sumoylation, but reduced ubiquitination when associated with K-532 and K-538 551 551 S->G: Constitutive expression under nonhypoxic conditions by decreasing ubiquitination 552 552 T->A: Constitutive expression under nonhypoxic conditions by decreasing ubiquitination 564 564 P->A: Increases HIF1A instability and reduces HIF1A-induced target gene transcriptional activation when associated with A-402 564 564 P->G: No change in VHL-dependent ubiquitination when associated with A-402 576 576 S->A: Induces stabilization of the protein 657 657 S->A: Induces stabilization of the protein 709 709 K->R: Abolishes SIRT2-mediated deacetylation, increases HIF1A instability and reduces HIF1A-induced target gene transcriptional activation 719 719 K->T: Dramatic reduction of accumulation in the nucleus in response to hypoxia 795 795 L->A: Inhibits interaction with EP300 and transactivation activity 800 800 C->A: Blocks increase in transcriptional activation caused by nitrosylation 800 800 C->S: Abolishes hypoxia-inducible transcriptional activation of ctaD 803 803 N->A: Recruits CREBBP"