ID HIF1A_CHICK Reviewed; 811 AA.
AC Q9YIB9;
DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 2.
DT 08-NOV-2023, entry version 145.
DE RecName: Full=Hypoxia-inducible factor 1-alpha;
DE Short=HIF-1-alpha;
DE Short=HIF1-alpha;
GN Name=HIF1A;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RA Takahashi T.;
RT "Molecular cloning and expression of an avian cDNA for hypoxia-inducible
RT factor-1 alpha in embryonic ventricular myocytes.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
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. {ECO:0000250|UniProtKB:Q16665}.
CC -!- ACTIVITY REGULATION: Induced by reactive oxygen species (ROS).
CC {ECO:0000250|UniProtKB:Q16665}.
CC -!- SUBUNIT: Efficient DNA binding requires heterodimerization of an alpha
CC and a beta/ARNT subunit. {ECO:0000250|UniProtKB:Q16665}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q16665}. Nucleus
CC {ECO:0000250|UniProtKB:Q16665}. Nucleus speckle
CC {ECO:0000250|UniProtKB:Q61221}. Note=Cytoplasmic in normoxia, nuclear
CC translocation in response to hypoxia. {ECO:0000250|UniProtKB:Q16665}.
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: In normoxia, is hydroxylated on Pro-402 and Pro-562. The
CC hydroxylated prolines promote interaction with VHL, initiating rapid
CC ubiquitination and subsequent proteasomal degradation. Under hypoxia,
CC proline hydroxylation is impaired and ubiquitination is attenuated,
CC resulting in stabilization (By similarity).
CC {ECO:0000250|UniProtKB:Q16665}.
CC -!- PTM: In normoxia, is hydroxylated on Asn-788, thus abrogating
CC interaction with CREBBP and EP300 and preventing transcriptional
CC activation. {ECO:0000250|UniProtKB:Q16665}.
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}.
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DR EMBL; AB013746; BAA34234.2; -; mRNA.
DR PIR; JC7619; JC7619.
DR RefSeq; NP_989628.1; NM_204297.1.
DR AlphaFoldDB; Q9YIB9; -.
DR SMR; Q9YIB9; -.
DR STRING; 9031.ENSGALP00000019338; -.
DR PaxDb; 9031-ENSGALP00000019338; -.
DR GeneID; 374177; -.
DR KEGG; gga:374177; -.
DR CTD; 3091; -.
DR VEuPathDB; HostDB:geneid_374177; -.
DR eggNOG; KOG3558; Eukaryota.
DR InParanoid; Q9YIB9; -.
DR PhylomeDB; Q9YIB9; -.
DR PRO; PR:Q9YIB9; -.
DR Proteomes; UP000000539; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0001223; F:transcription coactivator binding; ISS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IBA:GO_Central.
DR GO; GO:0001678; P:intracellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB.
DR CDD; cd19727; bHLH-PAS_HIF1a_PASD8; 1.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1.
DR Gene3D; 3.30.450.20; PAS domain; 2.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR001321; HIF-1_alpha.
DR InterPro; IPR014887; HIF-1_CTAD.
DR InterPro; IPR021537; HIF_alpha-like.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR001610; PAC.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR InterPro; IPR013655; PAS_fold_3.
DR NCBIfam; TIGR00229; sensory_box; 2.
DR PANTHER; PTHR23043; HYPOXIA-INDUCIBLE FACTOR 1 ALPHA; 1.
DR PANTHER; PTHR23043:SF7; HYPOXIA-INDUCIBLE FACTOR 1-ALPHA; 1.
DR Pfam; PF11413; HIF-1; 1.
DR Pfam; PF08778; HIF-1a_CTAD; 1.
DR Pfam; PF00989; PAS; 1.
DR Pfam; PF08447; PAS_3; 1.
DR PRINTS; PR01080; HYPOXIAIF1A.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00086; PAC; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1.
DR SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 2.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 2: Evidence at transcript level;
KW Activator; Cytoplasm; DNA-binding; Hydroxylation; Nucleus;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..811
FT /note="Hypoxia-inducible factor 1-alpha"
FT /id="PRO_0000127223"
FT DOMAIN 17..70
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 80..157
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..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 401..587
FT /note="ODD"
FT REGION 490..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 529..573
FT /note="NTAD"
FT REGION 576..785
FT /note="ID"
FT REGION 634..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 771..811
FT /note="CTAD"
FT MOTIF 703..706
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 718..721
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 490..514
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 634..654
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 402
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 562
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 788
FT /note="(3S)-3-hydroxyasparagine"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
SQ SEQUENCE 811 AA; 90542 MW; D14CD9FC98F064CB CRC64;
MDSPGGVTDK KRISSERRKE KSRDAARCRR SKESEVFYEL AHQLPLPHTV SAHLDKASIM
RLTISYLRMR KLLDAGELET EANMEKELNC FYLKALDGFV MVLSEDGDMI YMSENVNKCM
GLTQFDLTGH SVFDFTHPCD HEELREMLTH RNGPVKKGKE QNTERSFFLR MKCTLTSRGR
TVNIKSATWK VLHCTGHIRV YDTCNNQTHC GYKKPPMTCL VLICEPIPHP SNIEVPLDSK
TFLSRHSLDM KFSYCDERIT ELMGYEPEEL LGRSIYEYYH ALDSDHLTKT HHDMFTKGQV
TTGQYRMLAK QGGYVWVETQ ATVIYNTKNS QPQCIVCVNY VLSGIVQKDL IFSLGQTECM
LKPVESPEMK MTKIFSKDDW DDTNSLFEKL KQEPDALTVL APAAGDTIIS LDFSSNESDE
QQCDEVPLYN DVMLPSSSEK LQNINIAMSP LPASETTKPL RSNADPALNR EVVSKLEPNT
ETLELSFTMP QVQEQPTSPS DASTSQSSPE PSSPNDYCFD VDNDMANEFK LELVEKLFAI
DTEAKNPFST QETDLDLEML APYIPMDDDF QLRSFDQLSP LESSSSGSQN AATITILQQT
QTPSTAADEI KPVAERVDDV KALIVPSSPV HVINDTSSAP ASPYSGNRSR TASPIRAGKG
TLEQTEKSCP GAPSLITVTL NKRSTAMDEE LNPKMLALHN AQRKRKMEHD GSLFQAVGIG
SLFQQTGDRG GNASLAWKRV KACKTNGHNG VEQKTIILLS TDIASKLLGQ SMDESGLPQL
TSYDCEVNAP IQGNRNLLQG EELLRALDQV N
//
