HIF3A_MOUSE
ID HIF3A_MOUSE Reviewed; 662 AA.
AC Q0VBL6; A1IM61; E9QLB1; Q3UN40; Q8VHR1; Q9QX54; Q9Z2I5;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Hypoxia-inducible factor 3-alpha {ECO:0000303|PubMed:9840812};
DE Short=HIF-3-alpha;
DE Short=HIF3-alpha;
DE AltName: Full=Basic-helix-loop-helix-PAS protein MOP7;
DE AltName: Full=HIF3-alpha-1;
DE AltName: Full=Inhibitory PAS domain protein {ECO:0000303|PubMed:12119283};
DE Short=IPAS {ECO:0000303|PubMed:12119283};
DE AltName: Full=Member of PAS protein 7;
DE AltName: Full=Neonatal and embryonic PAS protein {ECO:0000303|PubMed:18070924};
GN Name=Hif3a {ECO:0000312|MGI:MGI:1859778};
GN Synonyms=Mop7 {ECO:0000303|PubMed:9840812},
GN Nepas {ECO:0000303|PubMed:18070924};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION (ISOFORM 1),
RP TISSUE SPECIFICITY, AND INTERACTION WITH ARNT (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=9840812;
RA Gu Y.Z., Moran S.M., Hogenesch J.B., Wartman L., Bradfield C.A.;
RT "Molecular characterization and chromosomal localization of a third alpha-
RT class hypoxia inducible factor subunit, HIF3alpha.";
RL Gene Expr. 7:205-213(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORM 2), TISSUE
RP SPECIFICITY (ISOFORM 2), INTERACTION WITH HIF1A (ISOFORM 2), AND INDUCTION
RP (ISOFORM 2).
RC STRAIN=C57BL/6J;
RX PubMed=11734856; DOI=10.1038/35107085;
RA Makino Y., Cao R., Svensson K., Bertilsson G., Asman M., Tanaka H., Cao Y.,
RA Berkenstam A., Poellinger L.;
RT "Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible
RT gene expression.";
RL Nature 414:550-554(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION (ISOFORM 3), TISSUE
RP SPECIFICITY (ISOFORM 3), DEVELOPMENTAL STAGE (ISOFORM 3), INDUCTION
RP (ISOFORM 3), AND DISRUPTION PHENOTYPE.
RC TISSUE=Embryo;
RX PubMed=18070924; DOI=10.1128/mcb.01332-07;
RA Yamashita T., Ohneda O., Nagano M., Iemitsu M., Makino Y., Tanaka H.,
RA Miyauchi T., Goto K., Ohneda K., Fujii-Kuriyama Y., Poellinger L.,
RA Yamamoto M.;
RT "Abnormal heart development and lung remodeling in mice lacking the
RT hypoxia-inducible factor-related basic helix-loop-helix PAS protein
RT NEPAS.";
RL Mol. Cell. Biol. 28:1285-1297(2008).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 193-662 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [7]
RP TISSUE SPECIFICITY (ISOFORM 2), AND INDUCTION (ISOFORM 2).
RX PubMed=12119283; DOI=10.1074/jbc.c200328200;
RA Makino Y., Kanopka A., Wilson W.J., Tanaka H., Poellinger L.;
RT "Inhibitory PAS domain protein (IPAS) is a hypoxia-inducible splicing
RT variant of the hypoxia-inducible factor-3alpha locus.";
RL J. Biol. Chem. 277:32405-32408(2002).
RN [8]
RP INDUCTION (ISOFORM 2).
RX PubMed=17355974; DOI=10.1074/jbc.m700732200;
RA Makino Y., Uenishi R., Okamoto K., Isoe T., Hosono O., Tanaka H.,
RA Kanopka A., Poellinger L., Haneda M., Morimoto C.;
RT "Transcriptional up-regulation of inhibitory PAS domain protein gene
RT expression by hypoxia-inducible factor 1 (HIF-1): a negative feedback
RT regulatory circuit in HIF-1-mediated signaling in hypoxic cells.";
RL J. Biol. Chem. 282:14073-14082(2007).
RN [9]
RP FUNCTION (ISOFORM 2), INTERACTION WITH BAD; BCL2L2; EPAS1; HIF1A AND MCL1
RP (ISOFORM 2), AND SUBCELLULAR LOCATION (ISOFORM 2).
RX PubMed=21546903; DOI=10.1038/cdd.2011.47;
RA Torii S., Goto Y., Ishizawa T., Hoshi H., Goryo K., Yasumoto K.,
RA Fukumura H., Sogawa K.;
RT "Pro-apoptotic activity of inhibitory PAS domain protein (IPAS), a negative
RT regulator of HIF-1, through binding to pro-survival Bcl-2 family
RT proteins.";
RL Cell Death Differ. 18:1711-1725(2011).
RN [10]
RP SUBCELLULAR LOCATION (ISOFORM 2), DOMAIN (ISOFORM 2), AND MUTAGENESIS
RP (ISOFORM 2).
RX PubMed=24092767; DOI=10.1093/jb/mvt088;
RA Torii S., Sakaki K., Otomo M., Saka K., Yasumoto K., Sogawa K.;
RT "Nucleocytoplasmic shuttling of IPAS by its unique nuclear import and
RT export signals unshared with other HIF-3alpha splice variants.";
RL J. Biochem. 154:561-567(2013).
CC -!- FUNCTION: Acts as a transcriptional regulator in adaptive response to
CC low oxygen tension. Acts as a regulator of hypoxia-inducible gene
CC expression (PubMed:9840812, PubMed:11734856, PubMed:21546903). Plays a
CC role in the development of the cardiorespiratory system
CC (PubMed:18070924). {ECO:0000269|PubMed:11734856,
CC ECO:0000269|PubMed:18070924, ECO:0000269|PubMed:21546903,
CC ECO:0000269|PubMed:9840812}.
CC -!- FUNCTION: [Isoform 1]: Acts as positive regulator of hypoxia-inducible
CC gene expression. Associates to core DNA sequence 5'-TACGTG-3' within
CC the hypoxia response element (HRE) of target gene promoters in a ARNT-
CC dependent manner, and hence also participates in the transcriptional
CC activation of reporter genes driven by HRE (PubMed:9840812).
CC {ECO:0000269|PubMed:9840812}.
CC -!- FUNCTION: [Isoform 2]: 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. May act as a tumor suppressor (PubMed:11734856). May
CC also be involved in apoptosis (PubMed:21546903).
CC {ECO:0000269|PubMed:11734856, ECO:0000269|PubMed:21546903}.
CC -!- FUNCTION: [Isoform 3]: 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 (PubMed:18070924). Also plays a role in the development of
CC the lung and heart during embryonic and neonatal stages
CC (PubMed:18070924). {ECO:0000269|PubMed:18070924}.
CC -!- SUBUNIT: Isoform 1 interacts with ARNT (PubMed:9840812). Isoform 2
CC interacts with HIF1A (PubMed:11734856, PubMed:21546903). Isoform 2
CC interacts EPAS1 (PubMed:21546903). Isoform 2 interacts (via C-terminus
CC domain) with BAD; the interaction reduces the binding between BAD and
CC BAX (PubMed:21546903). Isoform 2 (via C-terminus domain) interacts with
CC BCL2L2 and MCL1 (PubMed:21546903). Interacts with VHL (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y2N7, ECO:0000269|PubMed:11734856,
CC ECO:0000269|PubMed:21546903, ECO:0000269|PubMed:9840812}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y2N7}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9Y2N7}. Note=In the nuclei of all periportal
CC and perivenous hepatocytes. In the distal perivenous zone, detected in
CC the cytoplasm of the hepatocytes. Localized in the cytoplasm and nuclei
CC under normoxia, but increased in the nucleus under hypoxic conditions.
CC Colocalized with HIF1A in kidney tumors. {ECO:0000250|UniProtKB:Q9JHS2,
CC ECO:0000250|UniProtKB:Q9Y2N7}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus
CC {ECO:0000269|PubMed:21546903, ECO:0000269|PubMed:24092767}. Cytoplasm
CC {ECO:0000269|PubMed:21546903, ECO:0000269|PubMed:24092767}. Nucleus
CC speckle {ECO:0000269|PubMed:21546903}. Mitochondrion
CC {ECO:0000269|PubMed:21546903}. Note=Colocalizes with BAD in the
CC cytoplasm (PubMed:21546903). Colocalizes with EPAS1 and HIF1A in the
CC nucleus and speckles (PubMed:21546903). Shuttles between the nucleus
CC and the cytoplasm in a CRM1-dependent manner (PubMed:24092767).
CC {ECO:0000269|PubMed:21546903, ECO:0000269|PubMed:24092767}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q0VBL6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q0VBL6-2; Sequence=VSP_024528, VSP_024529, VSP_024530,
CC VSP_024531;
CC Name=3;
CC IsoId=Q0VBL6-3; Sequence=VSP_024528;
CC -!- TISSUE SPECIFICITY: Isoform 3 is expressed in endothelial cells of
CC vessels and capillaries in alveoli of the neonatal lung (at protein
CC level) (PubMed:18070924). Expressed in lung, brain, heart and kidney
CC (PubMed:9840812). Isoform 2 is expressed in heart and lung
CC (PubMed:12119283). Isoform 2 is highly expressed in the epithelial cell
CC layer of the cornea with lower expression in the layers of ganglion
CC cells, inner nuclear cells, and rods and cones of the retina
CC (PubMed:11734856). Isoform 2 is expressed in the cerebellum only in the
CC Purkinje cell layer (PubMed:11734856). {ECO:0000269|PubMed:11734856,
CC ECO:0000269|PubMed:12119283, ECO:0000269|PubMed:18070924,
CC ECO:0000269|PubMed:9840812}.
CC -!- DEVELOPMENTAL STAGE: Isoform 3 is expressed in brain, heart, lung,
CC liver and kidney at 15.5 dpc. Isoform 3 is expressed in heart, lung,
CC liver and kidney at 18.5 dpc. {ECO:0000269|PubMed:18070924}.
CC -!- INDUCTION: Isoform 2 is up-regulated in corneal epithelium cells under
CC hypoxia (at protein level) (PubMed:11734856). Isoform 2 is up-regulated
CC by hypoxia in a HIF1A-dependent manner (PubMed:12119283,
CC PubMed:17355974). Isoform 3 is up-regulated by hypoxia
CC (PubMed:18070924). {ECO:0000269|PubMed:11734856,
CC ECO:0000269|PubMed:12119283, ECO:0000269|PubMed:17355974,
CC ECO:0000269|PubMed:18070924}.
CC -!- DOMAIN: [Isoform 2]: Contains a nuclear localization signal between
CC amino acid positions 75 and 98. Contains a nuclear export signal
CC between amino acid positions 228 and 272.
CC {ECO:0000269|PubMed:24092767}.
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 (By similarity).
CC {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}.
CC -!- DISRUPTION PHENOTYPE: Mice appeared outwardly normal and are viable and
CC fertile. Show hypertrophy of the right atrium and ventricle,
CC disarrangement of striated muscle fibers in the heart, and pulmonary
CC hyperplasia (PubMed:18070924). {ECO:0000269|PubMed:18070924}.
CC -!- MISCELLANEOUS: [Isoform 2]: Mutagenesis of Lys-75, Arg-76, Arg-97 and
CC Arg-98 increase strongly cytoplasmic localization. Mutagenesis of Pro-
CC 228, Pro-229, Leu-271 and Leu-272 increase strongly nuclear
CC localization. {ECO:0000269|PubMed:24092767}.
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DR EMBL; AF060194; AAC72734.1; -; mRNA.
DR EMBL; AH008971; AAF21782.1; -; Genomic_DNA.
DR EMBL; AF416641; AAL39015.1; -; mRNA.
DR EMBL; AB289606; BAF44519.1; -; mRNA.
DR EMBL; AC148976; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC120587; AAI20588.1; -; mRNA.
DR EMBL; AK144472; BAE25907.1; -; mRNA.
DR CCDS; CCDS20860.1; -. [Q0VBL6-1]
DR CCDS; CCDS52045.1; -. [Q0VBL6-3]
DR RefSeq; NP_001156422.1; NM_001162950.1. [Q0VBL6-3]
DR RefSeq; NP_058564.2; NM_016868.3. [Q0VBL6-1]
DR AlphaFoldDB; Q0VBL6; -.
DR SMR; Q0VBL6; -.
DR BioGRID; 207311; 6.
DR STRING; 10090.ENSMUSP00000104132; -.
DR iPTMnet; Q0VBL6; -.
DR PhosphoSitePlus; Q0VBL6; -.
DR EPD; Q0VBL6; -.
DR PaxDb; Q0VBL6; -.
DR PRIDE; Q0VBL6; -.
DR ProteomicsDB; 269749; -. [Q0VBL6-1]
DR ProteomicsDB; 269751; -. [Q0VBL6-3]
DR Antibodypedia; 18071; 386 antibodies from 31 providers.
DR DNASU; 53417; -.
DR Ensembl; ENSMUST00000037762; ENSMUSP00000048248; ENSMUSG00000004328. [Q0VBL6-1]
DR Ensembl; ENSMUST00000108492; ENSMUSP00000104132; ENSMUSG00000004328. [Q0VBL6-3]
DR GeneID; 53417; -.
DR KEGG; mmu:53417; -.
DR UCSC; uc009fir.2; mouse. [Q0VBL6-1]
DR UCSC; uc009fit.2; mouse. [Q0VBL6-2]
DR CTD; 64344; -.
DR MGI; MGI:1859778; Hif3a.
DR VEuPathDB; HostDB:ENSMUSG00000004328; -.
DR eggNOG; KOG3558; Eukaryota.
DR GeneTree; ENSGT00940000161745; -.
DR HOGENOM; CLU_010044_5_0_1; -.
DR InParanoid; Q0VBL6; -.
DR OMA; AEPRSHF; -.
DR OrthoDB; 547545at2759; -.
DR Reactome; R-MMU-1234158; Regulation of gene expression by Hypoxia-inducible Factor.
DR Reactome; R-MMU-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-MMU-8951664; Neddylation.
DR BioGRID-ORCS; 53417; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Hif3a; mouse.
DR PRO; PR:Q0VBL6; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q0VBL6; protein.
DR Bgee; ENSMUSG00000004328; Expressed in fetal liver hematopoietic progenitor cell and 182 other tissues.
DR ExpressionAtlas; Q0VBL6; baseline and differential.
DR Genevisible; Q0VBL6; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IPI:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IPI:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
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:MGI.
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; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; IDA:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IPI:MGI.
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 Alternative splicing; Angiogenesis; Apoptosis; Cytoplasm;
KW Developmental protein; Hydroxylation; Isopeptide bond; Mitochondrion;
KW Nucleus; Reference proteome; Repeat; Repressor; Stress response;
KW Transcription; Transcription regulation; Tumor suppressor; Ubl conjugation.
FT CHAIN 1..662
FT /note="Hypoxia-inducible factor 3-alpha"
FT /id="PRO_0000284415"
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 (isoform 2)"
FT /evidence="ECO:0000269|PubMed:24092767"
FT REGION 228..272
FT /note="Nuclear export signal (isoform 2)"
FT /evidence="ECO:0000269|PubMed:24092767"
FT REGION 352..377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 416..446
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 500..595
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 414..418
FT /note="LRRLL"
FT MOTIF 485..492
FT /note="LAPYISMD"
FT COMPBIAS 352..375
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 568..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"
FT VAR_SEQ 1..6
FT /note="MDWDQD -> MALGLQRV (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11734856,
FT ECO:0000303|PubMed:18070924"
FT /id="VSP_024528"
FT VAR_SEQ 72..119
FT /note="EWNQVEKGGEPLDACYLKALEGFVMVLTAEGDMAYLSENVSKHLGLSQ ->
FT GKRGRATGRLLPEGPGGFRHGTHRRGRHGLPVGKCQQAPGPQSVDLCSSSLIHNPTPGT
FT NFS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11734856"
FT /id="VSP_024529"
FT VAR_SEQ 226..291
FT /note="HPASLEPPLGRGAFLSRHSLDMKFTYCDERIAEVAGYSPDDLIGCSAYEYIH
FT ALDSDAVSRSIHTL -> QLPFHDGATLGLPQEKTPISTLFTPLWKALLCLVKRWPVQV
FT LQGKGTESSLPSWVLWALNRKNCPG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11734856"
FT /id="VSP_024530"
FT VAR_SEQ 292..662
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11734856"
FT /id="VSP_024531"
FT CONFLICT 345
FT /note="T -> N (in Ref. 6; BAE25907)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="T -> A (in Ref. 1; AAC72734/AAF21782, 5; AAI20588
FT and 3; BAF44519)"
FT /evidence="ECO:0000305"
FT CONFLICT 477
FT /note="P -> S (in Ref. 1; AAC72734/AAF21782, 5; AAI20588
FT and 3; BAF44519)"
FT /evidence="ECO:0000305"
FT CONFLICT 484
FT /note="M -> I (in Ref. 6; BAE25907)"
FT /evidence="ECO:0000305"
FT CONFLICT 582
FT /note="T -> I (in Ref. 1; AAC72734/AAF21782)"
FT /evidence="ECO:0000305"
FT CONFLICT 613
FT /note="P -> L (in Ref. 1; AAC72734/AAF21782, 5; AAI20588
FT and 3; BAF44519)"
FT /evidence="ECO:0000305"
FT CONFLICT 651
FT /note="R -> H (in Ref. 1; AAC72734 and 3; BAF44519)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 662 AA; 73044 MW; D05E2B9CB2B63E4E CRC64;
MDWDQDRSNT ELRKEKSRDA ARSRRSQETE VLYQLAHTLP FARGVSAHLD KASIMRLTIS
YLRMHRLCAA GEWNQVEKGG EPLDACYLKA LEGFVMVLTA EGDMAYLSEN VSKHLGLSQL
ELIGHSIFDF IHPCDQEELQ DALTPRPNLS KKKLEAPTER HFSLRMKSTL TSRGRTLNLK
AATWKVLHCS GHMRAYKPPA QTSPAGSPRS EPPLQCLVLI CEAIPHPASL EPPLGRGAFL
SRHSLDMKFT YCDERIAEVA GYSPDDLIGC SAYEYIHALD SDAVSRSIHT LLSKGQAVTG
QYRFLARTGG YLWTQTQATV VSGGRGPQSE SIICVHFLIS RVEETGVVLS LEQTEQHTRR
PPRLSASSQK GIPGNSVDSP APRILAFLHP PALSEASLAA DPRRFCSPDL RRLMAPILDG
PPPAATPSTP QATRRPQSPL PADLPDKLTV GLENAHRLST AQKNKTVETD LDIAQDPDTL
DLEMLAPYIS MDDDFQLNSS EQLPKVHRRP PRVARRPRAR SFHGLSPPIP EPSLLPRWGS
DPRLNCSSPS RGDRPTASLM PGTRKRALAQ SSEDKGLELL ETKPPKRSPR LEPGSFLLPP
LSLSFLLQGR QLPGNQQDPR APLVHSHEPL GLAPSLLSLC QHEETVQPRN RFPPAAGLGQ
TH
