HIF3A_RAT
ID HIF3A_RAT Reviewed; 662 AA.
AC Q9JHS2;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 25-MAY-2022, entry version 131.
DE RecName: Full=Hypoxia-inducible factor 3-alpha {ECO:0000303|PubMed:11237857, ECO:0000312|RGD:70332};
DE Short=HIF-3-alpha;
DE Short=HIF3-alpha;
DE AltName: Full=HIF3-alpha-1;
GN Name=Hif3a {ECO:0000303|PubMed:11237857, ECO:0000312|RGD:70332};
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC 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 TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=12824304; DOI=10.1096/fj.02-0963fje;
RA Heidbreder M., Froehlich F., Johren O., Dendorfer A., Qadri F.,
RA Dominiak P.;
RT "Hypoxia rapidly activates HIF-3alpha mRNA expression.";
RL FASEB J. 17:1541-1543(2003).
CC -!- FUNCTION: Acts as a transcriptional regulator in adaptive response to
CC low oxygen tension. Attenuates the ability of transcription factor
CC HIF1A, EPAS1 and the HIF1A-ARNT complex to bind to hypoxia-responsive
CC elements (HRE) located within the enhancer/promoter of hypoxia-
CC inducible target genes and hence inhibits HRE-driven transcriptional
CC activation. Functions as an inhibitor of angiogenesis in hypoxic cells
CC of the cornea. Plays a role in the development of the cardiorespiratory
CC system. May also be involved in apoptosis. May act as a tumor
CC suppressor. {ECO:0000250|UniProtKB:Q0VBL6,
CC ECO:0000250|UniProtKB:Q9Y2N7}.
CC -!- SUBUNIT: Interacts with ARNT, BAD, BCL2L2, EPAS1, HIF1A, MCL1 and VHL.
CC {ECO:0000250|UniProtKB:Q0VBL6, ECO:0000250|UniProtKB:Q9Y2N7}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:11237857}. Cytoplasm {ECO:0000269|PubMed:11237857}.
CC Nucleus speckle {ECO:0000250|UniProtKB:Q0VBL6}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q0VBL6}. Note=In the nuclei of all periportal
CC and perivenous hepatocytes. In the distal perivenous zone, detected in
CC the cytoplasm of the hepatocytes (PubMed:11237857). Localized in the
CC cytoplasm and nuclei under normoxia, but increased in the nucleus under
CC hypoxic conditions. Colocalized with HIF1A in kidney tumors.
CC Colocalizes with BAD in the cytoplasm. Colocalizes with EPAS1 and HIF1A
CC in the nucleus and speckles. Shuttles between the nucleus and the
CC cytoplasm in a CRM1-dependent manner. {ECO:0000250|UniProtKB:Q0VBL6,
CC ECO:0000250|UniProtKB:Q9Y2N7}.
CC -!- TISSUE SPECIFICITY: Expressed in the perivenous zone of the liver
CC (PubMed:11237857). Expressed in all tissues examined during normoxia
CC (PubMed:12824304). Expressed in brain and lung. Expressed in periportal
CC and perivenous hepatocytes and in endothelial cells of the central vein
CC (at protein level) (PubMed:11237857). Expressed in the perivenous zone
CC of the liver (PubMed:11237857). Highest expression seen in the cerebral
CC cortex, hippocampus, and lung. Low expression in myocardial tissue and
CC liver (PubMed:12824304). {ECO:0000269|PubMed:11237857,
CC ECO:0000269|PubMed:12824304}.
CC -!- INDUCTION: Up-regulated by hypoxia. {ECO:0000269|PubMed:12824304}.
CC -!- PTM: In normoxia, hydroxylated on Pro-487 in the oxygen-dependent
CC degradation domain (ODD) by PHD. The hydroxylated proline promotes
CC interaction with VHL, initiating rapid ubiquitination and subsequent
CC proteasomal degradation. {ECO:0000250|UniProtKB:Q9Y2N7}.
CC -!- PTM: Ubiquitinated; ubiquitination occurs in a VHL- and oxygen-
CC dependent pathway and subsequently targeted for proteasomal
CC degradation. {ECO:0000250|UniProtKB:Q9Y2N7}.
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DR EMBL; AJ277827; CAB96611.1; -; mRNA.
DR RefSeq; NP_071973.1; NM_022528.2.
DR AlphaFoldDB; Q9JHS2; -.
DR SMR; Q9JHS2; -.
DR STRING; 10116.ENSRNOP00000023490; -.
DR iPTMnet; Q9JHS2; -.
DR PhosphoSitePlus; Q9JHS2; -.
DR PaxDb; Q9JHS2; -.
DR GeneID; 64345; -.
DR KEGG; rno:64345; -.
DR UCSC; RGD:70332; rat.
DR CTD; 64344; -.
DR RGD; 70332; Hif3a.
DR eggNOG; KOG3558; Eukaryota.
DR InParanoid; Q9JHS2; -.
DR OrthoDB; 547545at2759; -.
DR Reactome; R-RNO-1234158; Regulation of gene expression by Hypoxia-inducible Factor.
DR Reactome; R-RNO-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-RNO-8951664; Neddylation.
DR PRO; PR:Q9JHS2; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0016607; C:nuclear speck; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:GO_Central.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
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; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0071456; P:cellular response to hypoxia; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0001666; P:response to hypoxia; ISO:RGD.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISO:RGD.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR021537; HIF_alpha_subunit.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR InterPro; IPR013655; PAS_fold_3.
DR Pfam; PF11413; HIF-1; 1.
DR Pfam; PF00989; PAS; 1.
DR Pfam; PF08447; PAS_3; 1.
DR SMART; SM00353; HLH; 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 1: Evidence at protein level;
KW Angiogenesis; Apoptosis; Cytoplasm; Developmental protein; Hydroxylation;
KW Isopeptide bond; Mitochondrion; Nucleus; Reference proteome; Repeat;
KW Repressor; Stress response; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..662
FT /note="Hypoxia-inducible factor 3-alpha"
FT /id="PRO_0000284416"
FT DOMAIN 12..65
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 80..150
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 225..295
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 75..98
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q0VBL6"
FT REGION 228..272
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:Q0VBL6"
FT REGION 352..379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 417..445
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 448..581
FT /note="ODD"
FT REGION 450..501
FT /note="NTAD"
FT REGION 459..480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 500..595
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 410..413
FT /note="LRRLL"
FT MOTIF 485..492
FT /note="LAPYISMD"
FT COMPBIAS 352..373
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 567..588
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 487
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250"
FT CROSSLNK 463
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2N7"
FT CROSSLNK 565
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2N7"
SQ SEQUENCE 662 AA; 72888 MW; AC9672E340544010 CRC64;
MDWDQDRSST ELRKEKSRDA ARSRRSQETE VLYQLAHTLP FARGVSAHLD KASIMRLTIS
YLRMHRLCAA GEWNQVRKEG EPLDACYLKA LEGFVMVLTA EGDMAYLSEN VSKHLGLSQL
ELIGHSIFDF IHPCDQEELQ DALTPRPSLS KKKSEAATGR HFSLRMKSTL TSRGRALNLK
AATWKVLHCS GHMRAYKPPA QTSPAGSPRS EPPLQCLVLI CEAIPHPASL EPPLGRGAFL
SRHSLDMKFT YCDERIAEVA GYSPDDLIGC SAYEYIHALD SDAVSRSIHT LLSKGQAVTG
QYRFLARTGG YLWTQTQATV VSGGRGPQSE SIICVHFLIS RVEENGVVLS LEQTEQHTRR
PPQLGTSSKK GIPGNSLDPP APRILAFLHP PALSEASLAA DPRRFCSPDL RRLMAPILDG
PPTAATPSTP QAARRPQSPL PADLPDQLAV GLENAHRLST ARKNKTMETD LDIAQDPDTP
DLEMLAPYIS MDDDFQLNSS EQLPKVHRRP PRTARRPRAR SFHGLSPPIP EATLLPRWGS
DPRLNCSSPS KGDPPTAPLT PRTRKRALAQ SSEDKGLELL ETKPPKRSPR LEPGSVLLPP
LSLSFLLQGR QLPGNQPDPR APLVDSHEPL GLAPSLLSLY QHEETIQSRN HFLPAAGLAQ
TH
