ID HIF1A_HUMAN Reviewed; 826 AA. AC Q16665; C0LZJ3; Q53XP6; Q96PT9; Q9UPB1; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 11-NOV-2015, entry version 188. DE RecName: Full=Hypoxia-inducible factor 1-alpha; DE Short=HIF-1-alpha; DE Short=HIF1-alpha; DE AltName: Full=ARNT-interacting protein; DE AltName: Full=Basic-helix-loop-helix-PAS protein MOP1; DE AltName: Full=Class E basic helix-loop-helix protein 78; DE Short=bHLHe78; DE AltName: Full=Member of PAS protein 1; DE AltName: Full=PAS domain-containing protein 8; GN Name=HIF1A; Synonyms=BHLHE78, MOP1, PASD8; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 166-170; 259-289 RP AND 771-781. RX PubMed=7539918; DOI=10.1073/pnas.92.12.5510; RA Wang G.L., Jiang B.-H., Rue E.A., Semenza G.L.; RT "Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS RT heterodimer regulated by cellular O2 tension."; RL Proc. Natl. Acad. Sci. U.S.A. 92:5510-5514(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Hepatoma; RX PubMed=9079689; DOI=10.1074/jbc.272.13.8581; RA Hogenesch J.B., Chan W.K., Jackiw V.H., Brown R.C., Gu Y.-Z., RA Pray-Grant M., Perdew G.H., Bradfield C.A.; RT "Characterization of a subset of the basic-helix-loop-helix-PAS RT superfamily that interacts with components of the dioxin signaling RT pathway."; RL J. Biol. Chem. 272:8581-8593(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=9782081; DOI=10.1006/geno.1998.5416; RA Iyer N.V., Leung S.W., Semenza G.L.; RT "The human hypoxia-inducible factor 1alpha gene: HIF1A structure and RT evolutionary conservation."; RL Genomics 52:159-165(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND ALTERNATIVE SPLICING. RX PubMed=18638657; DOI=10.1016/j.humimm.2008.05.004; RA Lukashev D., Sitkovsky M.; RT "Preferential expression of the novel alternative isoform I.3 of RT hypoxia-inducible factor 1alpha in activated human T lymphocytes."; RL Hum. Immunol. 69:421-425(2008). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RA Rupert J.L., Hochachka P.W.; RT "HIF1a sequence in the Quechua, a high altitude population."; RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Glial tumor; RA Sun B., Zhao H.R., Yu R.T., Ni M.S.H.; RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Liver; RA Tanaka S., Sugimachi K.; RT "Hypoxia-inducible factor-1 alpha variant isolated from human liver RT tissue."; RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., RA Quetier F., Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Choriocarcinoma, and Placenta; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP IDENTIFICATION IN COMPLEX WITH EP300 AND CREBBP, AND INTERACTION WITH RP EP300. RX PubMed=8917528; DOI=10.1073/pnas.93.23.12969; RA Arany Z., Huang L.E., Eckner R., Bhattacharya S., Jiang C., RA Goldberg M.A., Bunn H.F., Livingston D.M.; RT "An essential role for p300/CBP in the cellular response to hypoxia."; RL Proc. Natl. Acad. Sci. U.S.A. 93:12969-12973(1996). RN [12] RP TRANSACTIVATION DOMAINS NTAD AND CTAD. RX PubMed=9235919; DOI=10.1074/jbc.272.31.19253; RA Jiang B.H., Zheng J.Z., Leung S.W., Roe R., Semenza G.L.; RT "Transactivation and inhibitory domains of hypoxia-inducible factor RT 1alpha. Modulation of transcriptional activity by oxygen tension."; RL J. Biol. Chem. 272:19253-19260(1997). RN [13] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-719. RX PubMed=9822602; DOI=10.1093/emboj/17.22.6573; RA Kallio P.J., Okamoto K., O'Brien S., Carrero P., Makino Y., Tanaka H., RA Poellinger L.; RT "Signal transduction in hypoxic cells: inducible nuclear translocation RT and recruitment of the CBP/p300 coactivator by the hypoxia-inducible RT factor-1alpha."; RL EMBO J. 17:6573-6586(1998). RN [14] RP OXYGEN-DEPENDENT DEGRADATION DOMAIN. RX PubMed=9653127; DOI=10.1073/pnas.95.14.7987; RA Huang L.E., Gu J., Schau M., Bunn H.F.; RT "Regulation of hypoxia-inducible factor 1alpha is mediated by an O2- RT dependent degradation domain via the ubiquitin-proteasome pathway."; RL Proc. Natl. Acad. Sci. U.S.A. 95:7987-7992(1998). RN [15] RP TRANSACTIVATION DOMAINS NTAD AND CTAD, INTERACTION WITH APEX, AND RP MUTAGENESIS OF CYS-800. RX PubMed=10202154; DOI=10.1093/emboj/18.7.1905; RA Ema M., Hirota K., Mimura J., Abe H., Yodoi J., Sogawa K., RA Poellinger L., Fujii-Kuriyama Y.; RT "Molecular mechanisms of transcription activation by HLF and HIF1alpha RT in response to hypoxia: their stabilization and redox signal-induced RT interaction with CBP/p300."; RL EMBO J. 18:1905-1914(1999). RN [16] RP FUNCTION, DNA-BINDING, AND INTERACTION WITH EP300. RX PubMed=9887100; DOI=10.1101/gad.13.1.64; RA Bhattacharya S., Michels C.M., Leung M.K., Arany Z.P., Kung A.L., RA Livingston D.M.; RT "Functional role of p35srj, a novel p300/CBP binding protein, during RT transactivation by HIF-1."; RL Genes Dev. 13:64-75(1999). RN [17] RP INTERACTION WITH VHL. RX PubMed=11006129; DOI=10.1006/bbrc.2000.3451; RA Aso T., Yamazaki K., Aigaki T., Kitajima S.; RT "Drosophila von Hippel-Lindau tumor suppressor complex possesses E3 RT ubiquitin ligase activity."; RL Biochem. Biophys. Res. Commun. 276:355-361(2000). RN [18] RP INTERACTION WITH VHL AND ARNT, AND MUTAGENESIS OF LYS-532; LYS-538; RP LYS-547 AND LYS-719. RX PubMed=10944113; DOI=10.1093/emboj/19.16.4298; RA Tanimoto K., Makino Y., Pereira T., Poellinger L.; RT "Mechanism of regulation of the hypoxia-inducible factor-1 alpha by RT the von Hippel-Lindau tumor suppressor protein."; RL EMBO J. 19:4298-4309(2000). RN [19] RP INTERACTION WITH NCOA1; NCOA2 AND APEX. RX PubMed=10594042; DOI=10.1128/MCB.20.1.402-415.2000; RA Carrero P., Okamoto K., Coumailleau P., O'Brien S., Tanaka H., RA Poellinger L.; RT "Redox-regulated recruitment of the transcriptional coactivators CREB- RT binding protein and SRC-1 to hypoxia-inducible factor 1alpha."; RL Mol. Cell. Biol. 20:402-415(2000). RN [20] RP MUTAGENESIS OF SER-551 AND THR-552, AND UBIQUITINATION. RX PubMed=10758161; DOI=10.1073/pnas.080072497; RA Sutter C.H., Laughner E., Semenza G.L.; RT "Hypoxia-inducible factor 1alpha protein expression is controlled by RT oxygen-regulated ubiquitination that is disrupted by deletions and RT missense mutations."; RL Proc. Natl. Acad. Sci. U.S.A. 97:4748-4753(2000). RN [21] RP HYDROXYLATION AT PRO-402 AND PRO-564, UBIQUITINATION, INTERACTION WITH RP THE VHLE COMPLEX, FUNCTION, AND MUTAGENESIS OF PRO-394; LEU-397; RP LEU-400; PRO-402 AND PRO-564. RX PubMed=11566883; DOI=10.1093/emboj/20.18.5197; RA Masson N., Willam C., Maxwell P.H., Pugh C.W., Ratcliffe P.J.; RT "Independent function of two destruction domains in hypoxia-inducible RT factor-alpha chains activated by prolyl hydroxylation."; RL EMBO J. 20:5197-5206(2001). RN [22] RP INTERACTION WITH PSMA7. RX PubMed=11389899; DOI=10.1016/S0014-5793(01)02499-1; RA Cho S., Choi Y.J., Kim J.M., Jeong S.T., Kim J.H., Kim S.H., Ryu S.E.; RT "Binding and regulation of HIF-1alpha by a subunit of the proteasome RT complex, PSMA7."; RL FEBS Lett. 498:62-66(2001). RN [23] RP UBIQUITINATION, FUNCTION, AND HYDROXYLATION AT PRO-564. RX PubMed=11292861; DOI=10.1126/science.1059796; RA Jaakkola P., Mole D.R., Tian Y.-M., Wilson M.I., Gielbert J., RA Gaskell S.J., von Kriegsheim A., Hebestreit H.F., Mukherji M., RA Schofield C.J., Maxwell P.H., Pugh C.W., Ratcliffe P.J.; RT "Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation RT complex by O2-regulated prolyl hydroxylation."; RL Science 292:468-472(2001). RN [24] RP INTERACTION WITH ARD1A. RX PubMed=12464182; DOI=10.1016/S0092-8674(02)01085-1; RA Jeong J.-W., Bae M.-K., Ahn M.-Y., Kim S.-H., Sohn T.-K., Bae M.-H., RA Yoo M.-A., Song E.-J., Lee K.-J., Kim K.-W.; RT "Regulation and destabilization of HIF-1alpha by ARD1-mediated RT acetylation."; RL Cell 111:709-720(2002). RN [25] RP HYDROXYLATION AT ASN-803, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12080085; DOI=10.1101/gad.991402; RA Lando D., Peet D.J., Gorman J.J., Whelan D.A., Whitelaw M.L., RA Bruick R.K.; RT "FIH-1 is an asparaginyl hydroxylase enzyme that regulates the RT transcriptional activity of hypoxia-inducible factor."; RL Genes Dev. 16:1466-1471(2002). RN [26] RP HYDROXYLATION AT PRO-564, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12351678; DOI=10.1073/pnas.192342099; RA Ivan M., Haberberger T., Gervasi D.C., Michelson K.S., Guenzler V., RA Kondo K., Yang H., Sorokina I., Conaway R.C., Conaway J.W., RA Kaelin W.G. Jr.; RT "Biochemical purification and pharmacological inhibition of a RT mammalian prolyl hydroxylase acting on hypoxia-inducible factor."; RL Proc. Natl. Acad. Sci. U.S.A. 99:13459-13464(2002). RN [27] RP S-NITROSYLATION AT CYS-800, AND MUTAGENESIS OF CYS-800. RX PubMed=12914934; DOI=10.1016/S0014-5793(03)00807-X; RA Yasinska I.M., Sumbayev V.V.; RT "S-nitrosation of Cys-800 of HIF-1alpha protein activates its RT interaction with p300 and stimulates its transcriptional activity."; RL FEBS Lett. 549:105-109(2003). RN [28] RP S-NITROSYLATION. RX PubMed=12560087; DOI=10.1016/S0014-5793(02)03887-5; RA Sumbayev V.V., Budde A., Zhou J., Bruene B.; RT "HIF-1 alpha protein as a target for S-nitrosation."; RL FEBS Lett. 535:106-112(2003). RN [29] RP INTERACTION WITH EP300, AND MUTAGENESIS OF LEU-795. RX PubMed=12778114; DOI=10.1038/nsb936; RA Freedman S.J., Sun Z.Y., Kung A.L., France D.S., Wagner G., Eck M.J.; RT "Structural basis for negative regulation of hypoxia-inducible factor- RT 1alpha by CITED2."; RL Nat. Struct. Biol. 10:504-512(2003). RN [30] RP SUMOYLATION AT LYS-391 AND LYS-477, FUNCTION, AND MUTAGENESIS OF RP LYS-389; LYS-391; LYS-392; LYS-442; LYS-460; LYS-477; LYS-532; LYS-538 RP AND LYS-547. RX PubMed=15465032; DOI=10.1016/j.bbrc.2004.09.068; RA Bae S.-H., Jeong J.-W., Park J.A., Kim S.-H., Bae M.-K., Choi S.-J., RA Kim K.-W.; RT "Sumoylation increases HIF-1alpha stability and its transcriptional RT activity."; RL Biochem. Biophys. Res. Commun. 324:394-400(2004). RN [31] RP INTERACTION WITH VHLL. RX PubMed=14757845; RA Qi H., Gervais M.L., Li W., DeCaprio J.A., Challis J.R.G., Ohh M.; RT "Molecular cloning and characterization of the von Hippel-Lindau-like RT protein."; RL Mol. Cancer Res. 2:43-52(2004). RN [32] RP UBIQUITINATION, DEUBIQUITINATION BY USP20, AND INTERACTION WITH USP20. RX PubMed=15776016; DOI=10.1038/sj.embor.7400377; RA Li Z., Wang D., Messing E.M., Wu G.; RT "VHL protein-interacting deubiquitinating enzyme 2 deubiquitinates and RT stabilizes HIF-1alpha."; RL EMBO Rep. 6:373-378(2005). RN [33] RP INTERACTION WITH ARD1A, AND MUTAGENESIS OF LYS-532. RX PubMed=16288748; DOI=10.1016/j.febslet.2005.10.036; RA Arnesen T., Kong X., Evjenth R., Gromyko D., Varhaug J.E., Lin Z., RA Sang N., Caro J., Lillehaug J.R.; RT "Interaction between HIF-1 alpha (ODD) and hARD1 does not induce RT acetylation and destabilization of HIF-1 alpha."; RL FEBS Lett. 579:6428-6432(2005). RN [34] RP FUNCTION, INTERACTION WITH EP300 IN THE HIF1A/EP300/CREBBP COMPLEX, RP AND MUTAGENESIS OF ASN-803. RX PubMed=16543236; DOI=10.1074/jbc.M600456200; RA Fath D.M., Kong X., Liang D., Lin Z., Chou A., Jiang Y., Fang J., RA Caro J., Sang N.; RT "Histone deacetylase inhibitors repress the transactivation potential RT of hypoxia-inducible factors independently of direct acetylation of RT HIF-alpha."; RL J. Biol. Chem. 281:13612-13619(2006). RN [35] RP UBIQUITINATION, HYDROXYLATION, FUNCTION, INTERACTION WITH CBPP, RP IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF ASN-803. RX PubMed=16973622; DOI=10.1074/jbc.M603913200; RA Choi S.M., Choi K.-O., Park Y.K., Cho H., Yang E.G., Park H.; RT "Clioquinol, a Cu(II)/Zn(II) chelator, inhibits both ubiquitination RT and asparagine hydroxylation of hypoxia-inducible factor-1alpha, RT leading to expression of vascular endothelial growth factor and RT erythropoietin in normoxic cells."; RL J. Biol. Chem. 281:34056-34063(2006). RN [36] RP SUMOYLATION AT LYS-391 AND LYS-477, FUNCTION, AND MUTAGENESIS OF RP LYS-377; LYS-391; LYS-477 AND LYS-532. RX PubMed=17610843; DOI=10.1016/j.bbrc.2007.06.103; RA Berta M.A., Mazure N., Hattab M., Pouyssegur J., Brahimi-Horn M.C.; RT "SUMOylation of hypoxia-inducible factor-1alpha reduces its RT transcriptional activity."; RL Biochem. Biophys. Res. Commun. 360:646-652(2007). RN [37] RP SUMOYLATION, AND INTERACTION WITH RWDD3. RX PubMed=17956732; DOI=10.1016/j.cell.2007.07.044; RA Carbia-Nagashima A., Gerez J., Perez-Castro C., Paez-Pereda M., RA Silberstein S., Stalla G.K., Holsboer F., Arzt E.; RT "RSUME, a small RWD-containing protein, enhances SUMO conjugation and RT stabilizes HIF-1alpha during hypoxia."; RL Cell 131:309-323(2007). RN [38] RP INTERACTION WITH GNB2L1. RX PubMed=17244529; DOI=10.1016/j.molcel.2007.01.001; RA Liu Y.V., Baek J.H., Zhang H., Diez R., Cole R.N., Semenza G.L.; RT "RACK1 competes with HSP90 for binding to HIF-1alpha and is required RT for O(2)-independent and HSP90 inhibitor-induced degradation of HIF- RT 1alpha."; RL Mol. Cell 25:207-217(2007). RN [39] RP UBIQUITINATION AT LYS-532; LYS-538 AND LYS-547, INTERACTION WITH VHL, RP AND MUTAGENESIS OF PRO-402; LYS-532; LYS-538; LYS-547 AND PRO-564. RX PubMed=16862177; DOI=10.1038/sj.onc.1209818; RA Paltoglou S., Roberts B.J.; RT "HIF-1alpha and EPAS ubiquitination mediated by the VHL tumour RT suppressor involves flexibility in the ubiquitination mechanism, RT similar to other RING E3 ligases."; RL Oncogene 26:604-609(2007). RN [40] RP INTERACTION WITH RORA. RX PubMed=18658046; DOI=10.1161/ATVBAHA.108.171546; RA Kim E.J., Yoo Y.G., Yang W.K., Lim Y.S., Na T.Y., Lee I.K., Lee M.O.; RT "Transcriptional activation of HIF-1 by RORalpha and its role in RT hypoxia signaling."; RL Arterioscler. Thromb. Vasc. Biol. 28:1796-1802(2008). RN [41] RP REVIEW ON REGULATION. RX PubMed=18809331; DOI=10.1016/j.tibs.2008.08.002; RA Yee Koh M., Spivak-Kroizman T.R., Powis G.; RT "HIF-1 regulation: not so easy come, easy go."; RL Trends Biochem. Sci. 33:526-534(2008). RN [42] RP INDUCTION BY HIPK2. RX PubMed=19046997; DOI=10.1016/j.bbamcr.2008.10.013; RA Nardinocchi L., Puca R., Guidolin D., Belloni A.S., Bossi G., RA Michiels C., Sacchi A., Onisto M., D'Orazi G.; RT "Transcriptional regulation of hypoxia-inducible factor 1alpha by RT HIPK2 suggests a novel mechanism to restrain tumor growth."; RL Biochim. Biophys. Acta 1793:368-377(2009). RN [43] RP FUNCTION IN MITOCHONDRIAL TRANSPORT. RX PubMed=19528298; DOI=10.1083/jcb.200811033; RA Li Y., Lim S., Hoffman D., Aspenstrom P., Federoff H.J., Rempe D.A.; RT "HUMMR, a hypoxia- and HIF-1alpha-inducible protein, alters RT mitochondrial distribution and transport."; RL J. Cell Biol. 185:1065-1081(2009). RN [44] RP FUNCTION. RX PubMed=20624928; DOI=10.1096/fj.10-159806; RA Gimm T., Wiese M., Teschemacher B., Deggerich A., Schodel J., RA Knaup K.X., Hackenbeck T., Hellerbrand C., Amann K., Wiesener M.S., RA Honing S., Eckardt K.U., Warnecke C.; RT "Hypoxia-inducible protein 2 is a novel lipid droplet protein and a RT specific target gene of hypoxia-inducible factor-1."; RL FASEB J. 24:4443-4458(2010). RN [45] RP PHOSPHORYLATION AT SER-551; THR-555; SER-576; SER-589 AND SER-657, AND RP MUTAGENESIS OF SER-576 AND SER-657. RX PubMed=20889502; DOI=10.1074/jbc.M110.160325; RA Xu D., Yao Y., Lu L., Costa M., Dai W.; RT "Plk3 functions as an essential component of the hypoxia regulatory RT pathway by direct phosphorylation of HIF-1alpha."; RL J. Biol. Chem. 285:38944-38950(2010). RN [46] RP PHOSPHORYLATION AT SER-247 BY CSNK1D/CK1, MUTAGENESIS OF SER-247, AND RP INTERACTION WITH ARNT. RX PubMed=20699359; DOI=10.1242/jcs.068122; RA Kalousi A., Mylonis I., Politou A.S., Chachami G., Paraskeva E., RA Simos G.; RT "Casein kinase 1 regulates human hypoxia-inducible factor HIF-1."; RL J. Cell Sci. 123:2976-2986(2010). RN [47] RP UBIQUITINATION. RX PubMed=22537386; DOI=10.1186/1741-7007-10-36; RA Bandau S., Knebel A., Gage Z.O., Wood N.T., Alexandru G.; RT "UBXN7 docks on neddylated cullin complexes using its UIM motif and RT causes HIF1alpha accumulation."; RL BMC Biol. 10:36-36(2012). RN [48] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=22009797; DOI=10.1530/ERC-11-0211; RA Shan B., Gerez J., Haedo M., Fuertes M., Theodoropoulou M., RA Buchfelder M., Losa M., Stalla G.K., Arzt E., Renner U.; RT "RSUME is implicated in HIF-1-induced VEGF-A production in pituitary RT tumour cells."; RL Endocr. Relat. Cancer 19:13-27(2012). RN [49] RP INTERACTION WITH USP19. RX PubMed=22128162; DOI=10.1074/jbc.M111.305615; RA Altun M., Zhao B., Velasco K., Liu H., Hassink G., Paschke J., RA Pereira T., Lindsten K.; RT "Ubiquitin-specific protease 19 (USP19) regulates hypoxia-inducible RT factor 1alpha (HIF-1alpha) during hypoxia."; RL J. Biol. Chem. 287:1962-1969(2012). RN [50] RP INDUCTION. RX PubMed=22286099; DOI=10.1038/ncb2424; RA Foxler D.E., Bridge K.S., James V., Webb T.M., Mee M., Wong S.C., RA Feng Y., Constantin-Teodosiu D., Petursdottir T.E., Bjornsson J., RA Ingvarsson S., Ratcliffe P.J., Longmore G.D., Sharp T.V.; RT "The LIMD1 protein bridges an association between the prolyl RT hydroxylases and VHL to repress HIF-1 activity."; RL Nat. Cell Biol. 14:201-208(2012). RN [51] RP INTERACTION WITH RWDD3. RX PubMed=23469069; DOI=10.1371/journal.pone.0057795; RA Gerez J., Fuertes M., Tedesco L., Silberstein S., Sevlever G., RA Paez-Pereda M., Holsboer F., Turjanski A.G., Arzt E.; RT "In silico structural and functional characterization of the RSUME RT splice variants."; RL PLoS ONE 8:E57795-E57795(2013). RN [52] RP ACETYLATION, DEACETYLATION AT LYS-709 BY SIRT2, HYDROXYLATION, RP INTERACTION WITH SIRT2 AND EGLN1, AND MUTAGENESIS OF PRO-402; PRO-564 RP AND LYS-709. RX PubMed=24681946; DOI=10.1038/onc.2014.76; RA Seo K.S., Park J.H., Heo J.Y., Jing K., Han J., Min K.N., Kim C., RA Koh G.Y., Lim K., Kang G.Y., Uee Lee J., Yim Y.H., Shong M., RA Kwak T.H., Kweon G.R.; RT "SIRT2 regulates tumour hypoxia response by promoting HIF-1alpha RT hydroxylation."; RL Oncogene 34:1354-1362(2015). RN [53] RP HYDROXYLATION PRO-564, UBIQUITINATION, AND INTERACTION WITH CBFA2T3 RP AND EGLN1. RX PubMed=25974097; DOI=10.1371/journal.pone.0123725; RA Kumar P., Gullberg U., Olsson I., Ajore R.; RT "Myeloid translocation gene-16 co-repressor promotes degradation of RT hypoxia-inducible factor 1."; RL PLoS ONE 10:E0123725-E0123725(2015). RN [54] RP 3D-STRUCTURE MODELING. RX PubMed=11089639; DOI=10.1080/07391102.2000.10506656; RA Michel G., Minet E., Ernest I., Roland I., Durant F., Remacle J., RA Michiels C.; RT "A model for the complex between the hypoxia-inducible factor-1 (HIF- RT 1) and its consensus DNA sequence."; RL J. Biomol. Struct. Dyn. 18:169-179(2000). RN [55] RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 775-826 IN COMPLEX WITH RP HIF1AN. RX PubMed=12446723; DOI=10.1074/jbc.C200644200; RA Elkins J.M., Hewitson K.S., McNeill L.A., Seibel J.F., RA Schlemminger I., Pugh C.W., Ratcliffe P.J., Schofield C.J.; RT "Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals RT mechanism of oxidative modification of HIF-1 alpha."; RL J. Biol. Chem. 278:1802-1806(2003). RN [56] RP STRUCTURE BY NMR OF 786-826 IN COMPLEX WITH 302-418 OF EP300. RX PubMed=11959990; DOI=10.1073/pnas.082117899; RA Freedman S.J., Sun Z.-Y.J., Poy F., Kung A.L., Livingston D.M., RA Wagner G., Eck M.J.; RT "Structural basis for recruitment of CBP/p300 by hypoxia-inducible RT factor-1 alpha."; RL Proc. Natl. Acad. Sci. U.S.A. 99:5367-5372(2002). RN [57] RP STRUCTURE BY NMR OF 776-826 IN COMPLEX WITH 345-439 OF CREBBP. RX PubMed=11959977; DOI=10.1073/pnas.082121399; RA Dames S.A., Martinez-Yamout M., De Guzman R.N., Dyson H.J., RA Wright P.E.; RT "Structural basis for Hif-1 alpha /CBP recognition in the cellular RT hypoxic response."; RL Proc. Natl. Acad. Sci. U.S.A. 99:5271-5276(2002). RN [58] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 556-575 IN COMPLEX WITH RP TCEB1; TCEB2 AND 54-213 OF VHL. RX PubMed=12004076; DOI=10.1126/science.1073440; RA Min J.-H., Yang H., Ivan M., Gertler F., Kaelin W.G. Jr., RA Pavletich N.P.; RT "Structure of an HIF-1alpha-pVHL complex: hydroxyproline recognition RT in signaling."; RL Science 296:1886-1889(2002). RN [59] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 549-582 IN COMPLEX WITH RP 17-112 OF TCEB1; TCEB2 AND 52-213 OF VHL. RX PubMed=12050673; DOI=10.1038/nature00767; RA Hon W.-C., Wilson M.I., Harlos K., Claridge T.D.W., Schofield C.J., RA Pugh C.W., Maxwell P.H., Ratcliffe P.J., Stuart D.I., Jones E.Y.; RT "Structural basis for the recognition of hydroxyproline in HIF-1 alpha RT by pVHL."; RL Nature 417:975-978(2002). CC -!- FUNCTION: Functions as a master transcriptional regulator of the CC adaptive response to hypoxia. Under hypoxic conditions, activates CC the transcription of over 40 genes, including erythropoietin, CC glucose transporters, glycolytic enzymes, vascular endothelial CC growth factor, HILPDA, and other genes whose protein products CC increase oxygen delivery or facilitate metabolic adaptation to CC hypoxia. Plays an essential role in embryonic vascularization, CC tumor angiogenesis and pathophysiology of ischemic disease. Binds CC to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response CC element (HRE) of target gene promoters. Activation requires CC recruitment of transcriptional coactivators such as CREBPB and CC EP300. Activity is enhanced by interaction with both, NCOA1 or CC NCOA2. Interaction with redox regulatory protein APEX seems to CC activate CTAD and potentiates activation by NCOA1 and CREBBP. CC Involved in the axonal distribution and transport of mitochondria CC in neurons during hypoxia. {ECO:0000269|PubMed:11292861, CC ECO:0000269|PubMed:11566883, ECO:0000269|PubMed:15465032, CC ECO:0000269|PubMed:16543236, ECO:0000269|PubMed:16973622, CC ECO:0000269|PubMed:17610843, ECO:0000269|PubMed:19528298, CC ECO:0000269|PubMed:20624928, ECO:0000269|PubMed:22009797, CC ECO:0000269|PubMed:9887100}. CC -!- SUBUNIT: Interacts with the HIF1A beta/ARNT subunit; CC heterodimerization is required for DNA binding. Interacts with CC COPS5; the interaction increases the transcriptional activity of CC HIF1A through increased stability (By similarity). Interacts with CC EP300 (via TAZ-type 1 domains); the interaction is stimulated in CC response to hypoxia and inhibited by CITED2. Interacts with CREBBP CC (via TAZ-type 1 domains). Interacts with NCOA1, NCOA2, APEX and CC HSP90. Interacts (hydroxylated within the ODD domain) with VHLL CC (via beta domain); the interaction, leads to polyubiquitination CC and subsequent HIF1A proteasomal degradation. During hypoxia, CC sumoylated HIF1A also binds VHL; the interaction promotes the CC ubiquitination of HIF1A. Interacts with SENP1; the interaction CC desumoylates HIF1A resulting in stabilization and activation of CC transcription. Interacts (Via the ODD domain) with ARD1A; the CC interaction appears not to acetylate HIF1A nor have any affect on CC protein stability, during hypoxia. Interacts with RWDD3; the CC interaction enhances HIF1A sumoylation. Interacts with TSGA10 (By CC similarity). Interacts with HIF3A (By similarity). Interacts with CC RORA (via the DNA binding domain); the interaction enhances HIF1A CC transcription under hypoxia through increasing protein stability. CC Interaction with PSMA7 inhibits the transactivation activity of CC HIF1A under both normoxic and hypoxia-mimicking conditions. CC Interacts with USP20. Interacts with GNB2L1/RACK1; promotes HIF1A CC ubiquitination and proteasome-mediated degradation. Interacts (via CC N-terminus) with USP19. Interacts with SIRT2. Interacts CC (deacetylated form) with EGLN1. Interacts with CBFA2T3. CC {ECO:0000250|UniProtKB:Q61221, ECO:0000269|PubMed:10202154, CC ECO:0000269|PubMed:10594042, ECO:0000269|PubMed:10944113, CC ECO:0000269|PubMed:11006129, ECO:0000269|PubMed:11389899, CC ECO:0000269|PubMed:11566883, ECO:0000269|PubMed:11959977, CC ECO:0000269|PubMed:11959990, ECO:0000269|PubMed:12004076, CC ECO:0000269|PubMed:12050673, ECO:0000269|PubMed:12446723, CC ECO:0000269|PubMed:12464182, ECO:0000269|PubMed:12778114, CC ECO:0000269|PubMed:14757845, ECO:0000269|PubMed:15776016, CC ECO:0000269|PubMed:16288748, ECO:0000269|PubMed:16543236, CC ECO:0000269|PubMed:16862177, ECO:0000269|PubMed:16973622, CC ECO:0000269|PubMed:17244529, ECO:0000269|PubMed:17956732, CC ECO:0000269|PubMed:18658046, ECO:0000269|PubMed:20699359, CC ECO:0000269|PubMed:22128162, ECO:0000269|PubMed:23469069, CC ECO:0000269|PubMed:24681946, ECO:0000269|PubMed:25974097, CC ECO:0000269|PubMed:8917528, ECO:0000269|PubMed:9887100}. CC -!- INTERACTION: CC P10275:AR; NbExp=2; IntAct=EBI-447269, EBI-608057; CC P27540:ARNT; NbExp=9; IntAct=EBI-447269, EBI-80809; CC P49407:ARRB1; NbExp=3; IntAct=EBI-447269, EBI-743313; CC O00257:CBX4; NbExp=15; IntAct=EBI-447269, EBI-722425; CC Q92793:CREBBP; NbExp=2; IntAct=EBI-447269, EBI-81215; CC Q6S7F2:E2f7 (xeno); NbExp=3; IntAct=EBI-447269, EBI-8030813; CC Q5RIX9:e2f7 (xeno); NbExp=2; IntAct=EBI-447269, EBI-8030618; CC Q96CJ1:EAF2; NbExp=3; IntAct=EBI-447269, EBI-1245604; CC Q9GZT9:EGLN1; NbExp=4; IntAct=EBI-447269, EBI-1174818; CC Q96KS0:EGLN2; NbExp=2; IntAct=EBI-447269, EBI-726614; CC Q9H6Z9:EGLN3; NbExp=3; IntAct=EBI-447269, EBI-1175354; CC Q09472:EP300; NbExp=16; IntAct=EBI-447269, EBI-447295; CC Q9NWT6:HIF1AN; NbExp=4; IntAct=EBI-447269, EBI-745632; CC Q92831:KAT2B; NbExp=2; IntAct=EBI-447269, EBI-477430; CC Q13330:MTA1; NbExp=6; IntAct=EBI-447269, EBI-714236; CC Q13438:OS9; NbExp=9; IntAct=EBI-447269, EBI-725454; CC Q8N2W9:PIAS4; NbExp=3; IntAct=EBI-447269, EBI-473160; CC P14618-1:PKM; NbExp=7; IntAct=EBI-447269, EBI-4304679; CC Q8BIF2:Rbfox3 (xeno); NbExp=2; IntAct=EBI-447269, EBI-4567146; CC P51450-2:Rorc (xeno); NbExp=2; IntAct=EBI-447269, EBI-4422078; CC Q9UHD8-1:SEPT9; NbExp=4; IntAct=EBI-447269, EBI-851558; CC P08047:SP1; NbExp=3; IntAct=EBI-447269, EBI-298336; CC P63165:SUMO1; NbExp=4; IntAct=EBI-447269, EBI-80140; CC O94888:UBXN7; NbExp=3; IntAct=EBI-447269, EBI-1993627; CC P40818:USP8; NbExp=2; IntAct=EBI-447269, EBI-1050865; CC P40337:VHL; NbExp=17; IntAct=EBI-447269, EBI-301246; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus speckle CC {ECO:0000250|UniProtKB:Q61221}. Note=Colocalizes with HIF3A in the CC nucleus and speckles (By similarity). Cytoplasmic in normoxia, CC nuclear translocation in response to hypoxia. Colocalizes with CC SUMO1 in the nucleus, under hypoxia. CC {ECO:0000250|UniProtKB:Q61221}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q16665-1; Sequence=Displayed; CC Name=2; CC IsoId=Q16665-2; Sequence=VSP_047335, VSP_007738; CC Note=No experimental confirmation available.; CC Name=3; Synonyms=I.3; CC IsoId=Q16665-3; Sequence=VSP_044942; CC Note=Up-regulated in peripheral T-lymphocytes after T-cell CC receptor stimulation. Highest expression in peripheral blood CC leukocytes and thymus.; CC -!- TISSUE SPECIFICITY: Expressed in most tissues with highest levels CC in kidney and heart. Overexpressed in the majority of common human CC cancers and their metastases, due to the presence of intratumoral CC hypoxia and as a result of mutations in genes encoding CC oncoproteins and tumor suppressors. A higher level expression seen CC in pituitary tumors as compared to the pituitary gland. CC {ECO:0000269|PubMed:22009797}. CC -!- INDUCTION: Under reduced oxygen tension. Induced also by various CC receptor-mediated factors such as growth factors, cytokines, and CC circulatory factors such as PDGF, EGF, FGF2, IGF2, TGFB1, HGF, CC TNF, IL1B/interleukin-1 beta, angiotensin-2 and thrombin. However, CC this induction is less intense than that stimulated by hypoxia. CC Repressed by HIPK2 and LIMD1. {ECO:0000269|PubMed:19046997, CC ECO:0000269|PubMed:22009797, ECO:0000269|PubMed:22286099}. CC -!- DOMAIN: Contains two independent C-terminal transactivation CC domains, NTAD and CTAD, which function synergistically. Their CC transcriptional activity is repressed by an intervening inhibitory CC domain (ID). CC -!- PTM: In normoxia, is hydroxylated on Pro-402 and Pro-564 in the CC oxygen-dependent degradation domain (ODD) by EGLN1/PHD2 and CC EGLN2/PHD1. EGLN3/PHD3 has also been shown to hydroxylate Pro-564. CC The hydroxylated prolines promote interaction with VHL, initiating CC rapid ubiquitination and subsequent proteasomal degradation. CC Deubiquitinated by USP20. Under hypoxia, proline hydroxylation is CC impaired and ubiquitination is attenuated, resulting in CC stabilization. {ECO:0000269|PubMed:11292861, CC ECO:0000269|PubMed:11566883, ECO:0000269|PubMed:12351678, CC ECO:0000269|PubMed:15776016, ECO:0000269|PubMed:25974097}. CC -!- PTM: In normoxia, is hydroxylated on Asn-803 by HIF1AN, thus CC abrogating interaction with CREBBP and EP300 and preventing CC transcriptional activation. This hydroxylation is inhibited by the CC Cu/Zn-chelator, Clioquinol. {ECO:0000269|PubMed:12080085}. CC -!- PTM: S-nitrosylation of Cys-800 may be responsible for increased CC recruitment of p300 coactivator necessary for transcriptional CC activity of HIF-1 complex. {ECO:0000269|PubMed:12560087, CC ECO:0000269|PubMed:12914934}. CC -!- PTM: Requires phosphorylation for DNA-binding. Phosphorylation at CC Ser-247 by CSNK1D/CK1 represses kinase activity and impairs ARNT CC binding. Phosphorylation by GSK3-beta and PLK3 promote degradation CC by the proteasome. {ECO:0000269|PubMed:20699359, CC ECO:0000269|PubMed:20889502}. CC -!- PTM: Sumoylated; with SUMO1 under hypoxia. Sumoylation is enhanced CC through interaction with RWDD3. Both sumoylation and desumoylation CC seem to be involved in the regulation of its stability during CC hypoxia. Sumoylation can promote either its stabilization or its CC VHL-dependent degradation by promoting hydroxyproline-independent CC HIF1A-VHL complex binding, thus leading to HIF1A ubiquitination CC and proteasomal degradation. Desumoylation by SENP1 increases its CC stability amd transcriptional activity. There is a disaccord CC between various publications on the effect of sumoylation and CC desumoylation on its stability and transcriptional activity. CC {ECO:0000269|PubMed:15465032, ECO:0000269|PubMed:15776016, CC ECO:0000269|PubMed:17610843, ECO:0000269|PubMed:17956732}. CC -!- PTM: Acetylation of Lys-532 by ARD1 increases interaction with VHL CC and stimulates subsequent proteasomal degradation. Deacetylation CC of Lys-709 by SIRT2 increases its interaction with and CC hydroxylation by EGLN1 thereby inactivating HIF1A activity by CC inducing its proteasomal degradation. CC {ECO:0000269|PubMed:24681946}. CC -!- PTM: Polyubiquitinated; in normoxia, following hydroxylation and CC interaction with VHL. Lys-532 appears to be the principal site of CC ubiquitination. Clioquinol, the Cu/Zn-chelator, inhibits CC ubiquitination through preventing hydroxylation at Asn-803. CC Ubiquitinated by a CUL2-based E3 ligase. CC {ECO:0000269|PubMed:12080085, ECO:0000269|PubMed:15776016, CC ECO:0000269|PubMed:16862177, ECO:0000269|PubMed:22537386, CC ECO:0000269|PubMed:25974097}. CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of CC asparagine is (S) stereospecific within HIF CTAD domains. CC -!- SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. CC {ECO:0000255|PROSITE-ProRule:PRU00981}. CC -!- SIMILARITY: Contains 1 PAC (PAS-associated C-terminal) domain. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 2 PAS (PER-ARNT-SIM) domains. CC {ECO:0000255|PROSITE-ProRule:PRU00140}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Hypoxia inducible factor entry; CC URL="https://en.wikipedia.org/wiki/Hypoxia_inducible_factor"; 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; U22431; AAC50152.1; -; mRNA. DR EMBL; U29165; AAC51210.1; -; mRNA. DR EMBL; AF050127; AAC68568.1; -; Genomic_DNA. DR EMBL; AF050115; AAC68568.1; JOINED; Genomic_DNA. DR EMBL; AF050116; AAC68568.1; JOINED; Genomic_DNA. DR EMBL; AF050117; AAC68568.1; JOINED; Genomic_DNA. DR EMBL; AF050118; AAC68568.1; JOINED; Genomic_DNA. DR EMBL; AF050119; AAC68568.1; JOINED; Genomic_DNA. DR EMBL; AF050120; AAC68568.1; JOINED; Genomic_DNA. DR EMBL; AF050121; AAC68568.1; JOINED; Genomic_DNA. DR EMBL; AF050122; AAC68568.1; JOINED; Genomic_DNA. DR EMBL; AF050123; AAC68568.1; JOINED; Genomic_DNA. DR EMBL; AF050124; AAC68568.1; JOINED; Genomic_DNA. DR EMBL; AF050125; AAC68568.1; JOINED; Genomic_DNA. DR EMBL; AF050126; AAC68568.1; JOINED; Genomic_DNA. DR EMBL; FJ790247; ACN88547.1; -; mRNA. DR EMBL; AF207601; AAF20139.1; -; mRNA. DR EMBL; AF207602; AAF20140.1; -; mRNA. DR EMBL; AF208487; AAF20149.1; -; Genomic_DNA. DR EMBL; AF304431; AAG43026.1; -; mRNA. DR EMBL; AB073325; BAB70608.1; -; mRNA. DR EMBL; BT009776; AAP88778.1; -; mRNA. DR EMBL; AL137129; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC012527; AAH12527.1; -; mRNA. DR CCDS; CCDS58324.1; -. [Q16665-3] DR CCDS; CCDS9753.1; -. [Q16665-1] DR CCDS; CCDS9754.1; -. [Q16665-2] DR PIR; I38972; I38972. DR RefSeq; NP_001230013.1; NM_001243084.1. [Q16665-3] DR RefSeq; NP_001521.1; NM_001530.3. [Q16665-1] DR RefSeq; NP_851397.1; NM_181054.2. [Q16665-2] DR UniGene; Hs.597216; -. DR UniGene; Hs.719495; -. DR PDB; 1D7G; Model; -; D=15-73. DR PDB; 1H2K; X-ray; 2.15 A; S=786-826. DR PDB; 1H2L; X-ray; 2.25 A; S=786-826. DR PDB; 1H2M; X-ray; 2.50 A; S=775-826. DR PDB; 1L3E; NMR; -; A=786-826. DR PDB; 1L8C; NMR; -; B=776-826. DR PDB; 1LM8; X-ray; 1.85 A; H=556-575. DR PDB; 1LQB; X-ray; 2.00 A; D=549-582. DR PDB; 2ILM; X-ray; 2.30 A; S=786-826. DR PDB; 3HQR; X-ray; 2.00 A; S=558-574. DR PDB; 3HQU; X-ray; 2.30 A; S=558-574. DR PDB; 4AJY; X-ray; 1.73 A; H=559-577. DR PDB; 4H6J; X-ray; 1.52 A; A=238-348. DR PDBsum; 1D7G; -. DR PDBsum; 1H2K; -. DR PDBsum; 1H2L; -. DR PDBsum; 1H2M; -. DR PDBsum; 1L3E; -. DR PDBsum; 1L8C; -. DR PDBsum; 1LM8; -. DR PDBsum; 1LQB; -. DR PDBsum; 2ILM; -. DR PDBsum; 3HQR; -. DR PDBsum; 3HQU; -. DR PDBsum; 4AJY; -. DR PDBsum; 4H6J; -. DR DisProt; DP00262; -. DR ProteinModelPortal; Q16665; -. DR SMR; Q16665; 19-374, 776-826. DR BioGrid; 109338; 136. DR DIP; DIP-29722N; -. DR IntAct; Q16665; 61. DR MINT; MINT-133270; -. DR STRING; 9606.ENSP00000338018; -. DR BindingDB; Q16665; -. DR ChEMBL; CHEMBL2221345; -. DR DrugBank; DB01136; Carvedilol. DR PhosphoSite; Q16665; -. DR BioMuta; HIF-1A; -. DR DMDM; 2498017; -. DR MaxQB; Q16665; -. DR PaxDb; Q16665; -. DR PRIDE; Q16665; -. DR DNASU; 3091; -. DR Ensembl; ENST00000323441; ENSP00000323326; ENSG00000100644. [Q16665-2] DR Ensembl; ENST00000337138; ENSP00000338018; ENSG00000100644. [Q16665-1] DR Ensembl; ENST00000539097; ENSP00000437955; ENSG00000100644. [Q16665-3] DR GeneID; 3091; -. DR KEGG; hsa:3091; -. DR UCSC; uc001xfq.2; human. [Q16665-1] DR UCSC; uc021rua.1; human. DR CTD; 3091; -. DR GeneCards; HIF1A; -. DR HGNC; HGNC:4910; HIF1A. DR HPA; CAB017442; -. DR HPA; HPA001275; -. DR MIM; 603348; gene. DR neXtProt; NX_Q16665; -. DR PharmGKB; PA29283; -. DR eggNOG; KOG3558; Eukaryota. DR eggNOG; ENOG410YK57; LUCA. DR GeneTree; ENSGT00760000118788; -. DR HOGENOM; HOG000234306; -. DR HOVERGEN; HBG060456; -. DR InParanoid; Q16665; -. DR KO; K08268; -. DR OMA; YCFDVDS; -. DR OrthoDB; EOG7JDQX8; -. DR PhylomeDB; Q16665; -. DR TreeFam; TF317772; -. DR Reactome; R-HSA-1234158; Regulation of gene expression by Hypoxia-inducible Factor. DR Reactome; R-HSA-1234162; Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha. DR Reactome; R-HSA-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha. DR Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian gene expression. DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription. DR Reactome; R-HSA-400253; Circadian Clock. DR SignaLink; Q16665; -. DR ChiTaRS; HIF1A; human. DR EvolutionaryTrace; Q16665; -. DR GeneWiki; HIF1A; -. DR GenomeRNAi; 3091; -. DR NextBio; 12265; -. DR PRO; PR:Q16665; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; Q16665; -. DR CleanEx; HS_HIF1A; -. DR ExpressionAtlas; Q16665; baseline and differential. DR Genevisible; Q16665; HS. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0031514; C:motile cilium; IEA:Ensembl. DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0090575; C:RNA polymerase II transcription factor complex; IDA:BHF-UCL. DR GO; GO:0005667; C:transcription factor complex; IPI:MGI. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0035035; F:histone acetyltransferase binding; IPI:UniProtKB. DR GO; GO:0051879; F:Hsp90 protein binding; IDA:BHF-UCL. DR GO; GO:0035257; F:nuclear hormone receptor binding; IPI:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0003705; F:transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; IDA:BHF-UCL. DR GO; GO:0001076; F:transcription factor activity, RNA polymerase II transcription factor binding; IEA:Ensembl. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0000989; F:transcription factor activity, transcription factor binding; IDA:BHF-UCL. DR GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL. DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IEA:Ensembl. DR GO; GO:0001228; F:transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding; IMP:BHF-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl. DR GO; GO:0019896; P:axon transport of mitochondrion; IMP:UniProtKB. DR GO; GO:0001922; P:B-1 B cell homeostasis; IEA:Ensembl. DR GO; GO:0003208; P:cardiac ventricle morphogenesis; IEA:Ensembl. DR GO; GO:0051216; P:cartilage development; IEA:Ensembl. DR GO; GO:0006879; P:cellular iron ion homeostasis; IEA:Ensembl. DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB. DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:BHF-UCL. DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl. DR GO; GO:0032963; P:collagen metabolic process; ISS:BHF-UCL. DR GO; GO:0002248; P:connective tissue replacement involved in inflammatory response wound healing; ISS:BHF-UCL. DR GO; GO:0048546; P:digestive tract morphogenesis; IEA:Ensembl. DR GO; GO:0071542; P:dopaminergic neuron differentiation; IEA:Ensembl. DR GO; GO:0051541; P:elastin metabolic process; ISS:BHF-UCL. DR GO; GO:0035162; P:embryonic hemopoiesis; IEA:Ensembl. DR GO; GO:0001892; P:embryonic placenta development; IEA:Ensembl. DR GO; GO:0061030; P:epithelial cell differentiation involved in mammary gland alveolus development; IEA:Ensembl. DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISS:BHF-UCL. DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl. DR GO; GO:0001947; P:heart looping; IEA:Ensembl. DR GO; GO:0042541; P:hemoglobin biosynthetic process; IEA:Ensembl. DR GO; GO:0097411; P:hypoxia-inducible factor-1alpha signaling pathway; IEA:Ensembl. DR GO; GO:0060574; P:intestinal epithelial cell maturation; IEA:Ensembl. DR GO; GO:0006089; P:lactate metabolic process; IEA:Ensembl. DR GO; GO:0007595; P:lactation; IEA:Ensembl. DR GO; GO:0042789; P:mRNA transcription from RNA polymerase II promoter; IC:BHF-UCL. DR GO; GO:0046716; P:muscle cell cellular homeostasis; IEA:Ensembl. DR GO; GO:0030502; P:negative regulation of bone mineralization; IEA:Ensembl. DR GO; GO:0045926; P:negative regulation of growth; IEA:Ensembl. DR GO; GO:2001054; P:negative regulation of mesenchymal cell apoptotic process; IEA:Ensembl. DR GO; GO:1903377; P:negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl. DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; IEA:Ensembl. DR GO; GO:0032007; P:negative regulation of TOR signaling; IEA:Ensembl. DR GO; GO:0001755; P:neural crest cell migration; IEA:Ensembl. DR GO; GO:0021502; P:neural fold elevation formation; IEA:Ensembl. DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome. DR GO; GO:0003151; P:outflow tract morphogenesis; IEA:Ensembl. DR GO; GO:0032364; P:oxygen homeostasis; IDA:HGNC. DR GO; GO:0045766; P:positive regulation of angiogenesis; IC:BHF-UCL. DR GO; GO:0032722; P:positive regulation of chemokine production; TAS:BHF-UCL. DR GO; GO:0070101; P:positive regulation of chemokine-mediated signaling pathway; IC:BHF-UCL. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IC:BHF-UCL. DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISS:BHF-UCL. DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IC:BHF-UCL. DR GO; GO:0045821; P:positive regulation of glycolytic process; IC:BHF-UCL. DR GO; GO:0046886; P:positive regulation of hormone biosynthetic process; IDA:BHF-UCL. DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl. DR GO; GO:1903599; P:positive regulation of mitophagy; IEA:Ensembl. DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IEA:Ensembl. DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; TAS:BHF-UCL. DR GO; GO:1902895; P:positive regulation of pri-miRNA transcription from RNA polymerase II promoter; IMP:BHF-UCL. DR GO; GO:0010870; P:positive regulation of receptor biosynthetic process; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0061419; P:positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; IMP:UniProtKB. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IMP:UniProtKB. DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; IC:BHF-UCL. DR GO; GO:1903715; P:regulation of aerobic respiration; IEA:Ensembl. DR GO; GO:0010468; P:regulation of gene expression; IDA:UniProtKB. DR GO; GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome. DR GO; GO:0043619; P:regulation of transcription from RNA polymerase II promoter in response to oxidative stress; IDA:BHF-UCL. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0032909; P:regulation of transforming growth factor beta2 production; IMP:BHF-UCL. DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB. DR GO; GO:0014850; P:response to muscle activity; IEA:Ensembl. DR GO; GO:0061298; P:retina vasculature development in camera-type eye; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; IMP:BHF-UCL. DR GO; GO:0010573; P:vascular endothelial growth factor production; IDA:BHF-UCL. DR GO; GO:0008542; P:visual learning; IEA:Ensembl. 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; IPR013767; PAS_fold. DR InterPro; IPR013655; PAS_fold_3. DR Pfam; PF11413; HIF-1; 1. DR Pfam; PF08778; HIF-1a_CTAD; 1. DR Pfam; PF00989; PAS; 1. DR Pfam; PF08447; PAS_3; 1. DR PRINTS; PR01080; HYPOXIAIF1A. 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; 2. DR PROSITE; PS50888; BHLH; 1. DR PROSITE; PS50112; PAS; 2. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW Complete proteome; Cytoplasm; Direct protein sequencing; DNA-binding; KW Hydroxylation; Isopeptide bond; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Repeat; S-nitrosylation; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1 826 Hypoxia-inducible factor 1-alpha. FT /FTId=PRO_0000127220. FT DOMAIN 17 70 bHLH. {ECO:0000255|PROSITE- FT ProRule:PRU00981}. FT DOMAIN 85 158 PAS 1. {ECO:0000255|PROSITE- FT ProRule:PRU00140}. FT DOMAIN 228 298 PAS 2. {ECO:0000255|PROSITE- FT ProRule:PRU00140}. FT DOMAIN 302 345 PAC. FT REGION 1 401 Interaction with TSGA10. {ECO:0000250}. FT REGION 380 417 N-terminal VHL recognition site. FT REGION 401 603 ODD. FT REGION 531 575 NTAD. FT REGION 556 572 C-terminal VHL recognition site. FT REGION 576 785 ID. FT REGION 786 826 CTAD. FT MOTIF 718 721 Nuclear localization signal. FT {ECO:0000255}. FT COMPBIAS 615 621 Poly-Thr. FT MOD_RES 247 247 Phosphoserine; by CK1. FT {ECO:0000269|PubMed:20699359}. FT MOD_RES 402 402 4-hydroxyproline. FT {ECO:0000269|PubMed:11566883}. FT MOD_RES 532 532 N6-acetyllysine. FT {ECO:0000269|PubMed:24681946}. FT MOD_RES 551 551 Phosphoserine; by GSK3-beta. FT {ECO:0000269|PubMed:20889502}. FT MOD_RES 555 555 Phosphothreonine; by GSK3-beta. FT {ECO:0000269|PubMed:20889502}. FT MOD_RES 564 564 4-hydroxyproline. FT {ECO:0000269|PubMed:11292861, FT ECO:0000269|PubMed:11566883, FT ECO:0000269|PubMed:12351678, FT ECO:0000269|PubMed:25974097}. FT MOD_RES 576 576 Phosphoserine; by PLK3. FT {ECO:0000269|PubMed:20889502}. FT MOD_RES 589 589 Phosphoserine; by GSK3-beta. FT {ECO:0000269|PubMed:20889502}. FT MOD_RES 657 657 Phosphoserine; by PLK3. FT {ECO:0000269|PubMed:20889502}. FT MOD_RES 709 709 N6-acetyllysine. FT {ECO:0000269|PubMed:24681946}. FT MOD_RES 800 800 S-nitrosocysteine. FT {ECO:0000305|PubMed:12914934}. FT MOD_RES 803 803 (3S)-3-hydroxyasparagine. FT {ECO:0000269|PubMed:12080085}. FT CROSSLNK 391 391 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT CROSSLNK 477 477 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT CROSSLNK 532 532 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000305|PubMed:16862177}. FT CROSSLNK 538 538 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000305|PubMed:16862177}. FT CROSSLNK 547 547 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000305|PubMed:16862177}. FT VAR_SEQ 1 12 MEGAGGANDKKK -> MSSQCRSLENKFVFLKEGLGNSKPE FT ELEEIRIENGR (in isoform 3). FT {ECO:0000303|PubMed:18638657}. FT /FTId=VSP_044942. FT VAR_SEQ 735 735 G -> I (in isoform 2). FT {ECO:0000303|Ref.7}. FT /FTId=VSP_047335. FT VAR_SEQ 736 826 Missing (in isoform 2). FT {ECO:0000303|Ref.7}. FT /FTId=VSP_007738. FT VARIANT 582 582 P -> S (in dbSNP:rs11549465). FT /FTId=VAR_049541. FT VARIANT 588 588 A -> T (in dbSNP:rs11549467). FT /FTId=VAR_049542. FT VARIANT 796 796 T -> A (in dbSNP:rs1802821). FT /FTId=VAR_015854. FT MUTAGEN 247 247 S->A: Constitutive kinase activity. FT {ECO:0000269|PubMed:20699359}. FT MUTAGEN 247 247 S->D: Impaired kinase activity. FT {ECO:0000269|PubMed:20699359}. FT MUTAGEN 377 377 K->R: No change in HIF1A protein turnover FT rate but increased transcriptional FT activity; when associated with R-391; R- FT 477 and R-532. FT {ECO:0000269|PubMed:17610843}. FT MUTAGEN 389 389 K->R: No change in sumoylation. FT {ECO:0000269|PubMed:15465032}. FT MUTAGEN 391 391 K->R: Abolishes 1 sumoylation. Abolishes FT 1 sumoylation; when associated with R- FT 532. Abolishes 2 sumoylations; when FT associated with R-477. No change in HIF1A FT protein turnover rate but increased FT transcriptional activity; when associated FT with R-377; R-477 and R-532. FT {ECO:0000269|PubMed:15465032, FT ECO:0000269|PubMed:17610843}. FT MUTAGEN 392 392 K->R: No change in sumoylation. FT {ECO:0000269|PubMed:15465032}. FT MUTAGEN 394 394 P->A: No change in VHLE3-dependent FT ubiquitination. FT {ECO:0000269|PubMed:11566883}. FT MUTAGEN 397 397 L->A: Abolishes VHLE3-dependent FT ubiquitination; when associated with A- FT 400. {ECO:0000269|PubMed:11566883}. FT MUTAGEN 400 400 L->A: Abolishes VHLE3-dependent FT ubiquitination; when associated with A- FT 397. {ECO:0000269|PubMed:11566883}. FT MUTAGEN 402 402 P->A: Abolishes in VHLE3-dependent FT ubiquitination, abolishes oxygen- FT dependent regulation of VP16, partially FT reduced VHLE target site ubiquitination FT and no interaction with VHL. No VHLE FT target site ubiquitination; when FT associated with G-564. Increases HIF1A FT instability and reduces HIF1A-induced FT target gene transcriptional activation; FT when associated with A-564. FT {ECO:0000269|PubMed:11566883, FT ECO:0000269|PubMed:16862177, FT ECO:0000269|PubMed:24681946}. FT MUTAGEN 442 442 K->R: No change in sumoylation. FT {ECO:0000269|PubMed:15465032}. FT MUTAGEN 460 460 K->R: No change in sumoylation nor in FT ARD1-mediated acetylation. FT {ECO:0000269|PubMed:15465032}. FT MUTAGEN 477 477 K->R: Abolishes 1 sumoylation. Abolishes FT 2 sumoylations; when associated with R- FT 391. No change in HIF1A protein turnover FT rate but increased transcriptional FT activity; when associated with R-377; R- FT 391 and R-532. FT {ECO:0000269|PubMed:15465032, FT ECO:0000269|PubMed:17610843}. FT MUTAGEN 532 532 K->R: Reduced ubiquitination. No change FT in sumoylation nor on interaction with FT ARD1A. No change in HIF1A protein FT turnover rate but increased FT transcriptional activity; when associated FT with R-377; R-391 and R-477. Complete FT loss of ubiquitination, but no change in FT VHL binding; when associated with K-538 FT and K-547. {ECO:0000269|PubMed:10944113, FT ECO:0000269|PubMed:15465032, FT ECO:0000269|PubMed:16288748, FT ECO:0000269|PubMed:16862177, FT ECO:0000269|PubMed:17610843}. FT MUTAGEN 538 538 K->R: No change in sumoylation, but FT reduced ubiquitination. Complete loss of FT ubiquitination, but no change in VHL FT binding; when associated with K-532 and FT K-547. {ECO:0000269|PubMed:10944113, FT ECO:0000269|PubMed:15465032, FT ECO:0000269|PubMed:16862177}. FT MUTAGEN 547 547 K->R: No change in sumoylation, but FT reduced ubiquitination. Complete loss of FT ubiquitination, but no change in VHL FT binding; when associated with K-532 and FT K-538. {ECO:0000269|PubMed:10944113, FT ECO:0000269|PubMed:15465032, FT ECO:0000269|PubMed:16862177}. FT MUTAGEN 551 551 S->G: Constitutive expression under FT nonhypoxic conditions by decreasing FT ubiquitination. FT {ECO:0000269|PubMed:10758161}. FT MUTAGEN 552 552 T->A: Constitutive expression under FT nonhypoxic conditions by decreasing FT ubiquitination. FT {ECO:0000269|PubMed:10758161}. FT MUTAGEN 564 564 P->A: Increases HIF1A instability and FT reduces HIF1A-induced target gene FT transcriptional activation; when FT associated with A-402. FT {ECO:0000269|PubMed:11566883, FT ECO:0000269|PubMed:16862177, FT ECO:0000269|PubMed:24681946}. FT MUTAGEN 564 564 P->G: No change in VHL-dependent FT ubiquitination. Partially reduced VHLE FT target site ubiquitination. No VHLE FT target site ubiquitination; when FT associated with A-402. FT {ECO:0000269|PubMed:11566883, FT ECO:0000269|PubMed:16862177, FT ECO:0000269|PubMed:24681946}. FT MUTAGEN 576 576 S->A: Induces stabilization of the FT protein. {ECO:0000269|PubMed:20889502}. FT MUTAGEN 657 657 S->A: Induces stabilization of the FT protein. {ECO:0000269|PubMed:20889502}. FT MUTAGEN 709 709 K->R: Abolishes SIRT2-mediated FT deacetylation, increases HIF1A FT instability and reduces HIF1A-induced FT target gene transcriptional activation. FT Increases interaction with EGLN1. FT {ECO:0000269|PubMed:24681946}. FT MUTAGEN 719 719 K->T: Dramatic reduction of accumulation FT in the nucleus in response to hypoxia. FT {ECO:0000269|PubMed:10944113, FT ECO:0000269|PubMed:9822602}. FT MUTAGEN 795 795 L->A: Inhibits interaction with EP300 and FT transactivation activity. FT {ECO:0000269|PubMed:12778114}. FT MUTAGEN 800 800 C->A: Blocks increase in transcriptional FT activation caused by nitrosylation. FT {ECO:0000269|PubMed:10202154, FT ECO:0000269|PubMed:12914934}. FT MUTAGEN 800 800 C->S: Abolishes hypoxia-inducible FT transcriptional activation of ctaD. FT {ECO:0000269|PubMed:10202154, FT ECO:0000269|PubMed:12914934}. FT MUTAGEN 803 803 N->A: Recruits CREBBP. No enhancement of FT CREBBP by Clioquinol in the presence of FT FIH1. No change in nuclear location nor FT on repression of transcriptional activity FT in the presence of histone deacetylase FT inhibitor. {ECO:0000269|PubMed:16543236, FT ECO:0000269|PubMed:16973622}. FT CONFLICT 572 572 F -> L (in Ref. 3; AAC68568). FT {ECO:0000305}. FT STRAND 241 246 {ECO:0000244|PDB:4H6J}. FT STRAND 251 255 {ECO:0000244|PDB:4H6J}. FT HELIX 258 263 {ECO:0000244|PDB:4H6J}. FT HELIX 267 270 {ECO:0000244|PDB:4H6J}. FT HELIX 275 277 {ECO:0000244|PDB:4H6J}. FT TURN 281 283 {ECO:0000244|PDB:4H6J}. FT HELIX 284 297 {ECO:0000244|PDB:4H6J}. FT STRAND 298 301 {ECO:0000244|PDB:4H6J}. FT STRAND 305 308 {ECO:0000244|PDB:4H6J}. FT STRAND 310 325 {ECO:0000244|PDB:4H6J}. FT TURN 327 329 {ECO:0000244|PDB:4H6J}. FT STRAND 332 341 {ECO:0000244|PDB:4H6J}. FT HELIX 559 561 {ECO:0000244|PDB:3HQR}. FT TURN 779 783 {ECO:0000244|PDB:1L8C}. FT HELIX 784 787 {ECO:0000244|PDB:1L8C}. FT STRAND 789 792 {ECO:0000244|PDB:1L8C}. FT HELIX 797 803 {ECO:0000244|PDB:1L3E}. FT STRAND 807 809 {ECO:0000244|PDB:1L8C}. FT HELIX 815 822 {ECO:0000244|PDB:1H2K}. SQ SEQUENCE 826 AA; 92670 MW; ABD4F7DAA135BE2D CRC64; MEGAGGANDK KKISSERRKE KSRDAARSRR SKESEVFYEL AHQLPLPHNV SSHLDKASVM RLTISYLRVR KLLDAGDLDI EDDMKAQMNC FYLKALDGFV MVLTDDGDMI YISDNVNKYM GLTQFELTGH SVFDFTHPCD HEEMREMLTH RNGLVKKGKE QNTQRSFFLR MKCTLTSRGR TMNIKSATWK VLHCTGHIHV YDTNSNQPQC GYKKPPMTCL VLICEPIPHP SNIEIPLDSK TFLSRHSLDM KFSYCDERIT ELMGYEPEEL LGRSIYEYYH ALDSDHLTKT HHDMFTKGQV TTGQYRMLAK RGGYVWVETQ ATVIYNTKNS QPQCIVCVNY VVSGIIQHDL IFSLQQTECV LKPVESSDMK MTQLFTKVES EDTSSLFDKL KKEPDALTLL APAAGDTIIS LDFGSNDTET DDQQLEEVPL YNDVMLPSPN EKLQNINLAM SPLPTAETPK PLRSSADPAL NQEVALKLEP NPESLELSFT MPQIQDQTPS PSDGSTRQSS PEPNSPSEYC FYVDSDMVNE FKLELVEKLF AEDTEAKNPF STQDTDLDLE MLAPYIPMDD DFQLRSFDQL SPLESSSASP ESASPQSTVT VFQQTQIQEP TANATTTTAT TDELKTVTKD RMEDIKILIA SPSPTHIHKE TTSATSSPYR DTQSRTASPN RAGKGVIEQT EKSHPRSPNV LSVALSQRTT VPEEELNPKI LALQNAQRKR KMEHDGSLFQ AVGIGTLLQQ PDDHAATTSL SWKRVKGCKS SEQNGMEQKT IILIPSDLAC RLLGQSMDES GLPQLTSYDC EVNAPIQGSR NLLQGEELLR ALDQVN //