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 24-JAN-2024, entry version 130. 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}, Nepas GN {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 a positive regulator of hypoxia- CC inducible gene expression. Associates to core DNA sequence 5'-TACGTG-3' CC within the hypoxia response element (HRE) of target gene promoters in a CC ARNT-dependent manner, and hence also participates in the CC transcriptional activation of reporter genes driven by HRE CC (PubMed:9840812). {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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7V7L; X-ray; 2.30 A; B=4-358. DR PDB; 7V7W; X-ray; 2.51 A; B=4-358. DR PDBsum; 7V7L; -. DR PDBsum; 7V7W; -. 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; 10090-ENSMUSP00000104132; -. DR Antibodypedia; 18071; 439 antibodies from 31 providers. DR DNASU; 53417; -. DR Ensembl; ENSMUST00000037762.11; ENSMUSP00000048248.5; ENSMUSG00000004328.16. [Q0VBL6-1] DR Ensembl; ENSMUST00000108492.9; ENSMUSP00000104132.3; ENSMUSG00000004328.16. [Q0VBL6-3] DR GeneID; 53417; -. DR KEGG; mmu:53417; -. DR UCSC; uc009fir.2; mouse. [Q0VBL6-1] DR UCSC; uc009fit.2; mouse. [Q0VBL6-2] DR AGR; MGI:1859778; -. 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; 5396877at2759; -. 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 78 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 185 other cell types or tissues. DR ExpressionAtlas; Q0VBL6; baseline and differential. 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; cd19729; bHLH-PAS_HIF3a_PASD7; 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; IPR021537; HIF_alpha-like. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR InterPro; IPR000014; PAS. DR InterPro; IPR035965; PAS-like_dom_sf. DR InterPro; IPR013767; PAS_fold. DR NCBIfam; TIGR00229; sensory_box; 1. DR PANTHER; PTHR23043; HYPOXIA-INDUCIBLE FACTOR 1 ALPHA; 1. DR PANTHER; PTHR23043:SF18; HYPOXIA-INDUCIBLE FACTOR 3-ALPHA; 1. DR Pfam; PF11413; HIF-1; 1. DR Pfam; PF00989; PAS; 1. DR Pfam; PF14598; PAS_11; 1. DR SMART; SM00353; HLH; 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. DR Genevisible; Q0VBL6; MM. PE 1: Evidence at protein level; KW 3D-structure; 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" FT HELIX 20..37 FT /evidence="ECO:0007829|PDB:7V7L" FT STRAND 39..41 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 45..48 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 51..69 FT /evidence="ECO:0007829|PDB:7V7L" FT TURN 82..85 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 86..90 FT /evidence="ECO:0007829|PDB:7V7L" FT STRAND 92..98 FT /evidence="ECO:0007829|PDB:7V7L" FT STRAND 103..107 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 111..115 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 119..122 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 127..129 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 133..135 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 136..142 FT /evidence="ECO:0007829|PDB:7V7L" FT STRAND 159..168 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 179..181 FT /evidence="ECO:0007829|PDB:7V7L" FT STRAND 183..194 FT /evidence="ECO:0007829|PDB:7V7L" FT STRAND 216..223 FT /evidence="ECO:0007829|PDB:7V7L" FT STRAND 236..243 FT /evidence="ECO:0007829|PDB:7V7L" FT STRAND 248..252 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 256..260 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 264..267 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 272..275 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 278..280 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 281..294 FT /evidence="ECO:0007829|PDB:7V7L" FT STRAND 295..298 FT /evidence="ECO:0007829|PDB:7V7L" FT STRAND 302..305 FT /evidence="ECO:0007829|PDB:7V7L" FT STRAND 307..309 FT /evidence="ECO:0007829|PDB:7V7L" FT STRAND 311..321 FT /evidence="ECO:0007829|PDB:7V7L" FT STRAND 331..338 FT /evidence="ECO:0007829|PDB:7V7L" FT HELIX 351..357 FT /evidence="ECO:0007829|PDB:7V7L" 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 //