HIF1A_ONCMY
ID HIF1A_ONCMY Reviewed; 766 AA.
AC Q98SW2;
DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 25-MAY-2022, entry version 114.
DE RecName: Full=Hypoxia-inducible factor 1-alpha;
DE Short=HIF-1-alpha;
DE Short=HIF1-alpha;
GN Name=hif1a;
OS Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Protacanthopterygii; Salmoniformes;
OC Salmonidae; Salmoninae; Oncorhynchus.
OX NCBI_TaxID=8022;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11278461; DOI=10.1074/jbc.m009057200;
RA Soitamo A.J., Rabergh C.M.I., Gassmann M., Sistonen L., Nikinmaa M.;
RT "Characterization of a hypoxia-inducible factor (HIF-1 alpha) from rainbow
RT trout: accumulation of protein occurs at normal venous oxygen tension.";
RL J. Biol. Chem. 276:19699-19705(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. {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-426 and Pro-559. 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-743, 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; AF304864; AAK30364.1; -; mRNA.
DR RefSeq; NP_001117760.1; NM_001124288.1.
DR AlphaFoldDB; Q98SW2; -.
DR SMR; Q98SW2; -.
DR PRIDE; Q98SW2; -.
DR GeneID; 100135944; -.
DR KEGG; omy:100135944; -.
DR CTD; 3091; -.
DR OrthoDB; 547545at2759; -.
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:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
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 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; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 2: Evidence at transcript level;
KW Activator; Cytoplasm; DNA-binding; Hydroxylation; Nucleus; Repeat;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..766
FT /note="Hypoxia-inducible factor 1-alpha"
FT /id="PRO_0000127225"
FT DOMAIN 17..70
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 82..159
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 230..300
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 304..347
FT /note="PAC"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 361..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 475..509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 718..721
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 475..505
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 426
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 559
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 743
FT /note="(3S)-3-hydroxyasparagine"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
SQ SEQUENCE 766 AA; 85049 MW; FC25A4984104DA5B CRC64;
MDTGVVPEKK SRVSSDRRKE KSRDAARCRR GKESEVFYEL AQELPLPHSV TSNLDKASIM
RLAISYLHMR NLLSTDNEEE QEEREMDSQL NGSYLKAIEG FLMVLSEDGD MIYLSENVNK
CLGLAQIDLT GLSVFEYTHP CDHEELREML VHRTGTSKKS KEPNTERSFF LRMKCTLTNR
GRTVNVKSAT WKVLHCSDHV RVHESPAEQI PGGHKEPSVP YLVLVCDPIP HPSNIEAPLD
TKTFLSRHTL DMKFTYCDER ITELMGYDPE DLLNRSVYEY YHALDSDHLM KTHHNLFAKG
QVSTGQYRML AKRGGFVWVE TQATVIYNNK NSQPQCVVCV NYVLSGIEEE KMMLSLEQTE
DMRPVKKELE EEESSEPEVS PVLLKEEKSP ELDVIKLFTR AVETQPLSSL YDRLKEEPEA
LTLLAPAAGD TIISLDFSSP DSDILQKEVP LYKDVMLPST SDKLALPLSL LPPSDQHLVP
NTSVDTTEVS TGPDSSSTPG SHSFTEPDSP LDFCFPMESD INAEFKLDMV ETLFAINPEP
KTPFTLQAME DLDLEMLAPY IPMDDDFQLR TLSPEEPLSC GPAQPLECSS LCSSVRLTQE
VHSYPGSPFN APGSLTASPA LAASPALAAP EPADSPCPAS LLTKTVPQMD REISLRSLAS
QNAQRKRKMS LSQAVGIGGL LQDHPGPGKK LKVSELSHAD APFNRTILLL PTDLASRLLG
ISSEGSGSPF TLPQLTRYDC EVNAPVGGRQ LLLQGEELLS ALDQVN
