HIF1A_RAT
ID HIF1A_RAT Reviewed; 825 AA.
AC O35800; Q9WTU9;
DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Hypoxia-inducible factor 1-alpha;
DE Short=HIF-1-alpha;
DE Short=HIF1-alpha;
GN Name=Hif1a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Hepatocyte;
RX PubMed=11237857; DOI=10.1042/0264-6021:3540531;
RA Kietzmann T., Cornesse Y., Brechtel K., Modaressi S., Jungermann K.;
RT "Perivenous expression of the mRNA of the three hypoxia-inducible factor a-
RT subunits HIF-1a, HIF2a and HIF3a in rat liver.";
RL Biochem. J. 354:531-537(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=11526200; DOI=10.1152/physiolgenomics.2001.6.3.159;
RA Zou A.-P., Yang Z.-Z., Li P.-L., Cowley A.W. Jr.;
RT "Oxygen-dependent expression of hypoxia-inducible factor-1alpha in renal
RT medullary cells of rats.";
RL Physiol. Genomics 6:159-168(2001).
CC -!- FUNCTION: Functions as a master transcriptional regulator of the
CC adaptive response to hypoxia. Under hypoxic conditions, activates the
CC transcription of over 40 genes, including erythropoietin, glucose
CC transporters, glycolytic enzymes, vascular endothelial growth factor,
CC HILPDA, and other genes whose protein products increase oxygen delivery
CC or facilitate metabolic adaptation to hypoxia. Plays an essential role
CC in embryonic vascularization, tumor angiogenesis and pathophysiology of
CC ischemic disease (By similarity). Heterodimerizes with ARNT;
CC heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia
CC response element (HRE) of target gene promoters (By similarity).
CC Activation requires recruitment of transcriptional coactivators such as
CC CREBBP and EP300. Activity is enhanced by interaction with NCOA1 and/or
CC NCOA2. Interaction with redox regulatory protein APEX1 seems to
CC activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved
CC in the axonal distribution and transport of mitochondria in neurons
CC during hypoxia (By similarity). {ECO:0000250|UniProtKB:Q16665,
CC ECO:0000250|UniProtKB:Q61221}.
CC -!- ACTIVITY REGULATION: Induced by reactive oxygen species (ROS).
CC {ECO:0000250|UniProtKB:Q16665}.
CC -!- SUBUNIT: Interacts with the ARNT; forms a heterodimer that binds core
CC DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of
CC target gene promoters (By similarity). Interacts with COPS5; the
CC interaction increases the transcriptional activity of HIF1A through
CC increased stability (By similarity). Interacts with EP300 (via TAZ-type
CC 1 domains); the interaction is stimulated in response to hypoxia and
CC inhibited by CITED2. Interacts with CREBBP (via TAZ-type 1 domains).
CC Interacts with NCOA1, NCOA2, APEX1 and HSP90. Interacts (hydroxylated
CC within the ODD domain) with VHLL (via beta domain); the interaction,
CC leads to polyubiquitination and subsequent HIF1A proteasomal
CC degradation. During hypoxia, sumoylated HIF1A also binds VHL; the
CC interaction promotes the ubiquitination of HIF1A (By similarity).
CC Interacts with SENP1; the interaction desumoylates HIF1A resulting in
CC stabilization and activation of transcription (By similarity).
CC Interacts (via the ODD domain) with NAA10; the interaction appears not
CC to acetylate HIF1A nor have any affect on protein stability, during
CC hypoxia. Interacts with RWDD3; the interaction enhances HIF1A
CC sumoylation (By similarity). Interacts with TSGA10. Interacts with
CC HIF3A (By similarity). Interacts with RORA (via the DNA binding
CC domain); the interaction enhances HIF1A transcription under hypoxia
CC through increasing protein stability. Interaction with PSMA7 inhibits
CC the transactivation activity of HIF1A under both normoxic and hypoxia-
CC mimicking conditions. Interacts with USP20. Interacts with RACK1;
CC promotes HIF1A ubiquitination and proteasome-mediated degradation.
CC Interacts (via N-terminus) with USP19. Interacts with SIRT2. Interacts
CC (deacetylated form) with EGLN1. Interacts with CBFA2T3. Interacts with
CC HSP90AA1 and HSP90AB1. Interacts with DCUN1D1; this interaction
CC increases the interaction between VHL and DCUN1D1. Interacts with
CC HIF1AN (By similarity). {ECO:0000250|UniProtKB:Q16665,
CC ECO:0000250|UniProtKB:Q61221}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q16665}.
CC Nucleus. Nucleus speckle {ECO:0000250|UniProtKB:Q61221}.
CC Note=Colocalizes with HIF3A in the nucleus and speckles (By
CC similarity). Cytoplasmic in normoxia, nuclear translocation in response
CC to hypoxia (By similarity). {ECO:0000250|UniProtKB:Q16665,
CC ECO:0000250|UniProtKB:Q61221}.
CC -!- TISSUE SPECIFICITY: Expressed in the kidney, higher expression is seen
CC in the renal medulla than in the cortex. Expressed also in the
CC perivenous zone of the liver.
CC -!- DOMAIN: Contains two independent C-terminal transactivation domains,
CC NTAD and CTAD, which function synergistically. Their transcriptional
CC activity is repressed by an intervening inhibitory domain (ID) (By
CC similarity). {ECO:0000250|UniProtKB:Q16665}.
CC -!- PTM: S-nitrosylation of Cys-799 may be responsible for increased
CC recruitment of p300 coactivator necessary for transcriptional activity
CC of HIF-1 complex. {ECO:0000250|UniProtKB:Q16665}.
CC -!- PTM: Acetylation of Lys-531 by ARD1 increases interaction with VHL and
CC stimulates subsequent proteasomal degradation. Deacetylated by SIRT2
CC increases its interaction with and hydroxylation by EGLN1 thereby
CC inactivating HIF1A activity by inducing its proteasomal degradation (By
CC similarity). {ECO:0000250|UniProtKB:Q16665}.
CC -!- PTM: Requires phosphorylation for DNA-binding. Phosphorylation at Ser-
CC 247 by CSNK1D/CK1 represses kinase activity and impairs ARNT binding.
CC Phosphorylation by GSK3-beta and PLK3 promote degradation by the
CC proteasome (By similarity). {ECO:0000250|UniProtKB:Q16665,
CC ECO:0000250|UniProtKB:Q61221}.
CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of
CC asparagine is (S) stereospecific within HIF CTAD domains.
CC {ECO:0000250|UniProtKB:Q16665}.
CC -!- PTM: Sumoylated; with SUMO1 under hypoxia. Sumoylation is enhanced
CC through interaction with RWDD3. Both sumoylation and desumoylation seem
CC to be involved in the regulation of its stability during hypoxia.
CC Sumoylation can promote either its stabilization or its VHL-dependent
CC degradation by promoting hydroxyproline-independent HIF1A-VHL complex
CC binding, thus leading to HIF1A ubiquitination and proteasomal
CC degradation. Desumoylation by SENP1 increases its stability amd
CC transcriptional activity. There is a disaccord between various
CC publications on the effect of sumoylation and desumoylation on its
CC stability and transcriptional activity (By similarity).
CC {ECO:0000250|UniProtKB:Q16665, ECO:0000250|UniProtKB:Q61221}.
CC -!- PTM: In normoxia, is hydroxylated on Pro-402 and Pro-563 in the oxygen-
CC dependent degradation domain (ODD) by EGLN1/PHD2 and EGLN2/PHD1.
CC EGLN3/PHD3 has also been shown to hydroxylate Pro-563. The hydroxylated
CC prolines promote interaction with VHL, initiating rapid ubiquitination
CC and subsequent proteasomal degradation. Deubiquitinated by USP20. Under
CC hypoxia, proline hydroxylation is impaired and ubiquitination is
CC attenuated, resulting in stabilization (By similarity). In normoxia, is
CC hydroxylated on Asn-802 by HIF1AN, thus abrogating interaction with
CC CREBBP and EP300 and preventing transcriptional activation. Repressed
CC by iron ion, via Fe(2+) prolyl hydroxylase (PHD) enzymes-mediated
CC hydroxylation and subsequent proteasomal degradation.
CC {ECO:0000250|UniProtKB:Q16665}.
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DR EMBL; Y09507; CAA70701.1; -; mRNA.
DR EMBL; AF057308; AAD24413.1; -; mRNA.
DR PIR; JC5809; JC5809.
DR RefSeq; NP_077335.1; NM_024359.1.
DR AlphaFoldDB; O35800; -.
DR SMR; O35800; -.
DR BioGRID; 248194; 10.
DR IntAct; O35800; 1.
DR MINT; O35800; -.
DR STRING; 10116.ENSRNOP00000042230; -.
DR PhosphoSitePlus; O35800; -.
DR PaxDb; O35800; -.
DR PRIDE; O35800; -.
DR GeneID; 29560; -.
DR KEGG; rno:29560; -.
DR UCSC; RGD:61928; rat.
DR CTD; 3091; -.
DR RGD; 61928; Hif1a.
DR eggNOG; KOG3558; Eukaryota.
DR InParanoid; O35800; -.
DR OrthoDB; 547545at2759; -.
DR Reactome; R-RNO-1234158; Regulation of gene expression by Hypoxia-inducible Factor.
DR Reactome; R-RNO-1234174; Cellular response to hypoxia.
DR Reactome; R-RNO-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR Reactome; R-RNO-8857538; PTK6 promotes HIF1A stabilization.
DR Reactome; R-RNO-8951664; Neddylation.
DR PRO; PR:O35800; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0000791; C:euchromatin; ISO:RGD.
DR GO; GO:0031514; C:motile cilium; ISO:RGD.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0005667; C:transcription regulator complex; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0070888; F:E-box binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:RGD.
DR GO; GO:0051879; F:Hsp90 protein binding; ISO:RGD.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:RGD.
DR GO; GO:0002039; F:p53 binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0001223; F:transcription coactivator binding; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:RGD.
DR GO; GO:0006953; P:acute-phase response; IEP:RGD.
DR GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR GO; GO:0019896; P:axonal transport of mitochondrion; ISS:UniProtKB.
DR GO; GO:0001922; P:B-1 B cell homeostasis; ISO:RGD.
DR GO; GO:0001568; P:blood vessel development; ISO:RGD.
DR GO; GO:0048514; P:blood vessel morphogenesis; ISO:RGD.
DR GO; GO:0048593; P:camera-type eye morphogenesis; ISO:RGD.
DR GO; GO:0003208; P:cardiac ventricle morphogenesis; ISO:RGD.
DR GO; GO:0051216; P:cartilage development; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; ISO:RGD.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISO:RGD.
DR GO; GO:0071245; P:cellular response to carbon monoxide; IEP:RGD.
DR GO; GO:0071279; P:cellular response to cobalt ion; IEP:RGD.
DR GO; GO:1903928; P:cellular response to cyanide; IEP:RGD.
DR GO; GO:0071257; P:cellular response to electrical stimulus; IEP:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IMP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
DR GO; GO:0071482; P:cellular response to light stimulus; IEP:RGD.
DR GO; GO:0071396; P:cellular response to lipid; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0071250; P:cellular response to nitrite; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:0097237; P:cellular response to toxic substance; IEP:RGD.
DR GO; GO:0098586; P:cellular response to virus; ISO:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0021987; P:cerebral cortex development; ISO:RGD.
DR GO; GO:0032963; P:collagen metabolic process; ISO:RGD.
DR GO; GO:0002248; P:connective tissue replacement involved in inflammatory response wound healing; ISO:RGD.
DR GO; GO:0048546; P:digestive tract morphogenesis; ISO:RGD.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; ISO:RGD.
DR GO; GO:0051541; P:elastin metabolic process; ISO:RGD.
DR GO; GO:0035162; P:embryonic hemopoiesis; ISO:RGD.
DR GO; GO:0001892; P:embryonic placenta development; ISO:RGD.
DR GO; GO:0061030; P:epithelial cell differentiation involved in mammary gland alveolus development; ISO:RGD.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0001947; P:heart looping; ISO:RGD.
DR GO; GO:0042541; P:hemoglobin biosynthetic process; ISO:RGD.
DR GO; GO:0097411; P:hypoxia-inducible factor-1alpha signaling pathway; ISO:RGD.
DR GO; GO:0060574; P:intestinal epithelial cell maturation; ISO:RGD.
DR GO; GO:0061072; P:iris morphogenesis; ISO:RGD.
DR GO; GO:0006089; P:lactate metabolic process; ISO:RGD.
DR GO; GO:0007595; P:lactation; ISO:RGD.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEP:RGD.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0030502; P:negative regulation of bone mineralization; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0045926; P:negative regulation of growth; ISO:RGD.
DR GO; GO:2001054; P:negative regulation of mesenchymal cell apoptotic process; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0030279; P:negative regulation of ossification; ISO:RGD.
DR GO; GO:1903377; P:negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; ISO:RGD.
DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; ISO:RGD.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:RGD.
DR GO; GO:0045906; P:negative regulation of vasoconstriction; IMP:RGD.
DR GO; GO:0001755; P:neural crest cell migration; ISO:RGD.
DR GO; GO:0021502; P:neural fold elevation formation; ISO:RGD.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISO:RGD.
DR GO; GO:0032364; P:oxygen homeostasis; ISO:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0010508; P:positive regulation of autophagy; ISO:RGD.
DR GO; GO:1903599; P:positive regulation of autophagy of mitochondrion; ISO:RGD.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0045793; P:positive regulation of cell size; IEP:RGD.
DR GO; GO:0070101; P:positive regulation of chemokine-mediated signaling pathway; ISO:RGD.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISO:RGD.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IMP:RGD.
DR GO; GO:0046886; P:positive regulation of hormone biosynthetic process; ISO:RGD.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:RGD.
DR GO; GO:0016239; P:positive regulation of macroautophagy; ISO:RGD.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:RGD.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; ISO:RGD.
DR GO; GO:2000273; P:positive regulation of signaling receptor activity; ISO:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0061419; P:positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISS:UniProtKB.
DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:1903715; P:regulation of aerobic respiration; ISO:RGD.
DR GO; GO:0050790; P:regulation of catalytic activity; ISO:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:1900037; P:regulation of cellular response to hypoxia; IEP:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0006110; P:regulation of glycolytic process; ISS:UniProtKB.
DR GO; GO:2000434; P:regulation of protein neddylation; ISS:UniProtKB.
DR GO; GO:0070243; P:regulation of thymocyte apoptotic process; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0043619; P:regulation of transcription from RNA polymerase II promoter in response to oxidative stress; IMP:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0032909; P:regulation of transforming growth factor beta2 production; ISO:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0043279; P:response to alkaloid; IEP:RGD.
DR GO; GO:0072347; P:response to anesthetic; IEP:RGD.
DR GO; GO:0010996; P:response to auditory stimulus; IEP:RGD.
DR GO; GO:0032025; P:response to cobalt ion; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0060992; P:response to fungicide; IMP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0009749; P:response to glucose; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IDA:RGD.
DR GO; GO:0010039; P:response to iron ion; ISO:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0014850; P:response to muscle activity; ISO:RGD.
DR GO; GO:0014074; P:response to purine-containing compound; IEP:RGD.
DR GO; GO:0000302; P:response to reactive oxygen species; ISS:UniProtKB.
DR GO; GO:0009651; P:response to salt stress; IEP:RGD.
DR GO; GO:0010165; P:response to X-ray; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0061298; P:retina vasculature development in camera-type eye; ISO:RGD.
DR GO; GO:0007165; P:signal transduction; ISO:RGD.
DR GO; GO:0010573; P:vascular endothelial growth factor production; ISO:RGD.
DR GO; GO:0001944; P:vasculature development; ISO:RGD.
DR GO; GO:0008542; P:visual learning; ISO:RGD.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR001321; HIF-1_alpha.
DR InterPro; IPR014887; HIF-1_TAD_C.
DR InterPro; IPR021537; HIF_alpha_subunit.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR001610; PAC.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013655; PAS_fold_3.
DR Pfam; PF11413; HIF-1; 1.
DR Pfam; PF08778; HIF-1a_CTAD; 1.
DR Pfam; PF08447; PAS_3; 1.
DR Pfam; PF13426; PAS_9; 1.
DR PRINTS; PR01080; HYPOXIAIF1A.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00086; PAC; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR TIGRFAMs; TIGR00229; sensory_box; 2.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 2: Evidence at transcript level;
KW Acetylation; Activator; Cytoplasm; DNA-binding; Hydroxylation;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW S-nitrosylation; Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..825
FT /note="Hypoxia-inducible factor 1-alpha"
FT /id="PRO_0000127222"
FT DOMAIN 17..70
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 85..158
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 228..298
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 302..345
FT /note="PAC"
FT REGION 1..401
FT /note="Interaction with TSGA10"
FT /evidence="ECO:0000250|UniProtKB:Q61221"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 21..30
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q61221"
FT REGION 170..191
FT /note="Required for heterodimer formation with ARNT"
FT /evidence="ECO:0000250|UniProtKB:Q61221"
FT REGION 401..602
FT /note="ODD"
FT REGION 492..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 530..574
FT /note="NTAD"
FT REGION 575..784
FT /note="ID"
FT REGION 579..602
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 654..674
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 785..825
FT /note="CTAD"
FT MOTIF 717..721
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 492..515
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 247
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 402
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 531
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 550
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 554
FT /note="Phosphothreonine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 563
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 575
FT /note="Phosphoserine; by PLK3"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 588
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 657
FT /note="Phosphoserine; by PLK3"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 799
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 802
FT /note="(3S)-3-hydroxyasparagine"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT CROSSLNK 531
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT CROSSLNK 537
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT CROSSLNK 546
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT CONFLICT 12
FT /note="K -> NR (in Ref. 2; AAD24413)"
FT /evidence="ECO:0000305"
FT CONFLICT 74
FT /note="D -> G (in Ref. 2; AAD24413)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="P -> L (in Ref. 2; AAD24413)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="D -> N (in Ref. 2; AAD24413)"
FT /evidence="ECO:0000305"
FT CONFLICT 613..619
FT /note="ATATTAT -> TATA (in Ref. 2; AAD24413)"
FT /evidence="ECO:0000305"
FT CONFLICT 708
FT /note="R -> K (in Ref. 2; AAD24413)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 825 AA; 92319 MW; C4109A57F38667E9 CRC64;
MEGAGGENEK KKMSSERRKE KSRDAARSRR SKESEVFYEL AHQLPLPHNV SSHLDKASVM
RLTISYLRVR KLLDAGDLDI EDEMKAQMNC FYLKAPDGFV MVLTDDGDMI YISDNVNKYM
GLTQFELTGH SVFDFTHPCD HEEMREMLTH RNGPVRKGKE QNTQRSFFLR MKCTLTSRGR
TMNIKSATWK VLHCTGHIHV YDTSSNQPQC GYKKPPMTCL VLICEPIPHP SNIEIPLDSK
TFLSRHSLDM KFSYCDERIT ELMGYEPEEL LGRSIYEYYH ALDSDHLTKT HHDMFTKGQV
TTGQYRMLAK RGGYVWVETQ ATVIYNTKDS QPQCIVCVNY VVSGIIQHDL IFSLQQTESV
LKPVESSDMK MTQLFTKVES EDTSCLFDKL KKEPDALTLL APAAGDTIIS LDFGSDDTET
EDQQLEDVPL YNDVMFPSSN EKLNINLAMS PLPASETPKP LRSSADPALN QEVALKLESS
PESLGLSFTM PQIQDQPASP SDGSTRQSSP EPNSPSEYCF DVDSDMVNVF KLELVEKLFA
EDTEAKNPFS AQDTDLDLEM LAPYIPMDDD FQLRSFDQLS PLESNSPSPP SVSTVTGFQQ
TQLQKPTITV TAATATTATT TDESKAVTKD NIEDIKILIA SPPSTQVPQE MTTAKASAYS
GTHSRTASPD RAGKRVIEKT DKAHPRSLNL SVTLNQRNTV PEEELNPRTI ALQNAQRKRK
MEHDGSLFQA AGIGTLLQQP GDRAPTMSLS WKRVKGYISS EQDGMEQKTI FLIPSDLACR
LLGQSMDESG LPQLTSYDCE VNAPIQGSRN LLQGEELLRA LDQVN
