Hif1a
entrez
29560
canonical
uniprot
O35800
canonical
ensembl
ENSRNOG00000008292
resolver
ensp
ENSRNOP00000042230
resolver
ensp
ENSRNOP00000112230
resolver
enst
ENSRNOT00000049725
resolver
genesymbol
Hif1a
resolver
uniprot
D4A8P8
resolver
uniprot
Q9WTU9
resolver
uniprot_entry
D4A8P8_RAT
resolver
uniprot_entry
HIF1A_RAT
resolver
uniprot_sec
Q9WTU9
resolver
activity_regulation
ACTIVITY REGULATION: Induced by reactive oxygen species (ROS). {ECO:0000250|UniProtKB:Q16665}.
uniprot
proteins
amino_acid_sequence
MEGAGGENEKKKMSSERRKEKSRDAARSRRSKESEVFYELAHQLPLPHNVSSHLDKASVMRLTISYLRVRKLLDAGDLDIEDEMKAQMNCFYLKAPDGFVMVLTDDGDMIYISDNVNKYMGLTQFELTGHSVFDFTHPCDHEEMREMLTHRNGPVRKGKEQNTQRSFFLRMKCTLTSRGRTMNIKSATWKVLHCTGHIHVYDTSSNQPQCGYKKPPMTCLVLICEPIPHPSNIEIPLDSKTFLSRHSLDMKFSYCDERITELMGYEPEELLGRSIYEYYHALDSDHLTKTHHDMFTKGQVTTGQYRMLAKRGGYVWVETQATVIYNTKDSQPQCIVCVNYVVSGIIQHDLIFSLQQTESVLKPVESSDMKMTQLFTKVESEDTSCLFDKLKKEPDALTLLAPAAGDTIISLDFGSDDTETEDQQLEDVPLYNDVMFPSSNEKLNINLAMSPLPASETPKPLRSSADPALNQEVALKLESSPESLGLSFTMPQIQDQPASPSDGSTRQSSPEPNSPSEYCFDVDSDMVNVFKLELVEKLFAEDTEAKNPFSAQDTDLDLEMLAPYIPMDDDFQLRSFDQLSPLESNSPSPPSVSTVTGFQQTQLQKPTITVTAATATTATTTDESKAVTKDNIEDIKILIASPPSTQVPQEMTTAKASAYSGTHSRTASPDRAGKRVIEKTDKAHPRSLNLSVTLNQRNTVPEEELNPRTIALQNAQRKRKMEHDGSLFQAAGIGTLLQQPGDRAPTMSLSWKRVKGYISSEQDGMEQKTIFLIPSDLACRLLGQSMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN
uniprot
proteins
function
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 (By similarity). 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 NCOA1 and/or NCOA2. Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia (By similarity). {ECO:0000250|UniProtKB:Q16665, ECO:0000250|UniProtKB:Q61221}.
uniprot
proteins
mass_dalton
92319
uniprot
proteins
post_translational_modification
PTM: S-nitrosylation of Cys-799 may be responsible for increased recruitment of p300 coactivator necessary for transcriptional activity of HIF-1 complex. {ECO:0000250|UniProtKB:Q16665}.; PTM: Acetylation of Lys-531 by ARD1 increases interaction with VHL and stimulates subsequent proteasomal degradation. Deacetylated by SIRT2 increases its interaction with and hydroxylation by EGLN1 thereby inactivating HIF1A activity by inducing its proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:Q16665}.; PTM: Ubiquitinated; in normoxia, following hydroxylation and interaction with VHL. Lys-531 appears to be the principal site of ubiquitination. Clioquinol, the Cu/Zn-chelator, inhibits ubiquitination through preventing hydroxylation at Asn-802. Ubiquitinated by E3 ligase VHL. Deubiquitinated by UCHL1 (By similarity). {ECO:0000250|UniProtKB:Q16665}.; PTM: 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 (By similarity). {ECO:0000250|UniProtKB:Q16665, ECO:0000250|UniProtKB:Q61221}.; PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains. {ECO:0000250|UniProtKB:Q16665}.; PTM: 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 (By similarity). {ECO:0000250|UniProtKB:Q16665, ECO:0000250|UniProtKB:Q61221}.; PTM: In normoxia, is hydroxylated on Pro-402 and Pro-563 in the oxygen-dependent degradation domain (ODD) by EGLN1/PHD2 and EGLN2/PHD1. EGLN3/PHD3 has also been shown to hydroxylate Pro-563. 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 (By similarity). In normoxia, is hydroxylated on Asn-802 by HIF1AN, thus abrogating interaction with CREBBP and EP300 and preventing transcriptional activation. Repressed by iron ion, via Fe(2+) prolyl hydroxylase (PHD) enzymes-mediated hydroxylation and subsequent proteasomal degradation. {ECO:0000250|UniProtKB:Q16665}.
uniprot
proteins
pubmed
11237857
uniprot
proteins
pubmed
11526200
uniprot
proteins
sequence_length
825
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q16665}. Nucleus. Nucleus speckle {ECO:0000250|UniProtKB:Q61221}. Note=Colocalizes with HIF3A in the nucleus and speckles (By similarity). Cytoplasmic in normoxia, nuclear translocation in response to hypoxia (By similarity). {ECO:0000250|UniProtKB:Q16665, ECO:0000250|UniProtKB:Q61221}.
uniprot
proteins