HIF1A_XENLA
ID HIF1A_XENLA Reviewed; 805 AA.
AC Q9I8A9;
DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 25-MAY-2022, entry version 102.
DE RecName: Full=Hypoxia-inducible factor 1-alpha;
DE Short=HIF-1-alpha;
DE Short=HIF1-alpha;
GN Name=hif1a;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kietzmann T.;
RT "Cloning and expression of the Xenopus laevis hypoxia inducible factor 1
RT alpha homologue.";
RL Submitted (MAY-2000) 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-404 and Pro-560. 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-782, 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; AJ277829; CAB96628.1; -; mRNA.
DR RefSeq; NP_001165655.1; NM_001172184.1.
DR AlphaFoldDB; Q9I8A9; -.
DR SMR; Q9I8A9; -.
DR GeneID; 100337573; -.
DR CTD; 100337573; -.
DR Proteomes; UP000186698; Genome assembly.
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:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0001223; F:transcription coactivator binding; ISS:UniProtKB.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB.
DR CDD; cd00130; PAS; 2.
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; 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; SM00086; PAC; 1.
DR SMART; SM00091; PAS; 2.
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 Activator; Cytoplasm; DNA-binding; Hydroxylation; Nucleus;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..805
FT /note="Hypoxia-inducible factor 1-alpha"
FT /id="PRO_0000127224"
FT DOMAIN 17..70
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 85..157
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 229..300
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 303..346
FT /note="PAC"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 628..669
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 628..648
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 404
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 560
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 782
FT /note="(3S)-3-hydroxyasparagine"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
SQ SEQUENCE 805 AA; 90965 MW; BABFA0BD6B44FF3B CRC64;
MEGSVVVSEK KRISSERRKE KSRDAARCRR SNESEVFYEL SHELPLPHNV SSHLDKASIM
RLDHQLPAVE KVADAGDLDG ETELDKQLNC FYLKALEGFV LVLTEEGDMI YLSENVNKCM
GLTQFELTGH SVFDFTHPCD HEELREMLTF RNGPAKKRKR TNHREKFLPS YEMYINQSWK
NREYKVSHME GPSLYRTHAC IYDNANNQNH CGYKKPPMTC MVVICEPIPH PSNIEFPLDS
KTFLSRHSLD MKFSYCDERV TELVGYEPDE LLGRSVYEYY HALDSDHLTK PNYNMFTKGQ
VTTGQYRMLA KKGGYVWVET QATVIYNSKN SQPQCIVCVN YVLSEVVEKD LILSLGQTAS
VLIPVESQEI KMPEIFTELN EENNSECLFD KLKQEPESLT VLAPDAGDEI IPLDFSSGDS
DKPYEDVPLY NDVMLHSTSN KLESTPITPL PAPEMPKPLR SNVDPALNRE VVIKMESNPR
TTCASIHHST AIQARQPFRY QFQSEPSTEP NTPEYCFDVD SEMASEFKLD LVEKLFAIDT
EAKAPFYYPG NDLDLEMLAP YIPMDDDFQL RTFDQLSSLE CDSSIPQTLG SMTTLFHQSL
SPSTSDFKPE DAMSDLKTII QSPVHMMKES TSAPVSPYNG NRSRTSSPVR PAKAVVDKTE
KSRPGTPNLP VPLNKRCTIL DEELNPKMIC FTQCTAEKRK MESDGPLFQA IGIGTLFQTN
VDPGPNSSLQ WKRVKGSDSE RLSSAEQRTI LLLSTDMASQ LLGQSFDGTV LPQLTGYDCE
VNAPVHGTRN LLQGEELLRA LDQAN
