ID HIF1N_HUMAN Reviewed; 349 AA. AC Q9NWT6; D3DR69; Q5W147; Q969Q7; Q9NPV5; DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot. DT 16-JUN-2003, sequence version 2. DT 27-SEP-2017, entry version 159. DE RecName: Full=Hypoxia-inducible factor 1-alpha inhibitor; DE EC=1.14.11.30; DE EC=1.14.11.n4; DE AltName: Full=Factor inhibiting HIF-1; DE Short=FIH-1; DE AltName: Full=Hypoxia-inducible factor asparagine hydroxylase; GN Name=HIF1AN; Synonyms=FIH1; 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 INTERACTION WITH HIF1A; VHL AND RP HISTONE DEACETYLASES. RC TISSUE=Brain; RX PubMed=11641274; DOI=10.1101/gad.924501; RA Mahon P.C., Hirota K., Semenza G.L.; RT "FIH-1: a novel protein that interacts with HIF-1alpha and VHL to RT mediate repression of HIF-1 transcriptional activity."; RL Genes Dev. 15:2675-2686(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Signet-ring cell carcinoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-41. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Muscle; 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 89-349. RC TISSUE=Melanoma; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [7] RP CATALYTIC ACTIVITY, FUNCTION, AND MUTAGENESIS OF HIS-199 AND ASP-201. 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 [8] RP CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=12042299; DOI=10.1074/jbc.C200273200; RA Hewitson K.S., McNeill L.A., Riordan M.V., Tian Y.-M., Bullock A.N., RA Welford R.W., Elkins J.M., Oldham N.J., Bhattacharya S., Gleadle J.M., RA Ratcliffe P.J., Pugh C.W., Schofield C.J.; RT "Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to RT factor inhibiting HIF (FIH) and is related to the cupin structural RT family."; RL J. Biol. Chem. 277:26351-26355(2002). RN [9] RP DIMERIZATION, MASS SPECTROMETRY, AND MUTAGENESIS OF LEU-340 AND RP ILE-344. RX PubMed=15239670; DOI=10.1042/BJ20040735; RA Lancaster D.E., McNeill L.A., McDonough M.A., Aplin R.T., RA Hewitson K.S., Pugh C.W., Ratcliffe P.J., Schofield C.J.; RT "Disruption of dimerization and substrate phosphorylation inhibit RT factor inhibiting hypoxia-inducible factor (FIH) activity."; RL Biochem. J. 383:429-437(2004). RN [10] RP CATALYTIC ACTIVITY, SUBUNIT, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=14701857; DOI=10.1074/jbc.M312254200; RA Koivunen P., Hirsila M., Gunzler V., Kivirikko K.I., Myllyharju J.; RT "Catalytic properties of the asparaginyl hydroxylase (FIH) in the RT oxygen sensing pathway are distinct from those of its prolyl 4- RT hydroxylases."; RL J. Biol. Chem. 279:9899-9904(2004). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=14734545; DOI=10.1074/jbc.M313614200; RA Linke S., Stojkoski C., Kewley R.J., Booker G.W., Whitelaw M.L., RA Peet D.J.; RT "Substrate requirements of the oxygen-sensing asparaginyl hydroxylase RT factor-inhibiting hypoxia-inducible factor."; RL J. Biol. Chem. 279:14391-14397(2004). RN [12] RP FUNCTION, AND INTERACTION WITH NFKB1 AND NFKBIA. RX PubMed=17003112; DOI=10.1073/pnas.0606877103; RA Cockman M.E., Lancaster D.E., Stolze I.P., Hewitson K.S., RA McDonough M.A., Coleman M.L., Coles C.H., Yu X., Hay R.T., Ley S.C., RA Pugh C.W., Oldham N.J., Masson N., Schofield C.J., Ratcliffe P.J.; RT "Posttranslational hydroxylation of ankyrin repeats in IkappaB RT proteins by the hypoxia-inducible factor (HIF) asparaginyl RT hydroxylase, factor inhibiting HIF (FIH)."; RL Proc. Natl. Acad. Sci. U.S.A. 103:14767-14772(2006). RN [13] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=18299578; DOI=10.1073/pnas.0711591105; RA Zheng X., Linke S., Dias J.M., Zheng X., Gradin K., Wallis T.P., RA Hamilton B.R., Gustafsson M., Ruas J.L., Wilkins S., Bilton R.L., RA Brismar K., Whitelaw M.L., Pereira T., Gorman J.J., Ericson J., RA Peet D.J., Lendahl U., Poellinger L.; RT "Interaction with factor inhibiting HIF-1 defines an additional mode RT of cross-coupling between the Notch and hypoxia signaling pathways."; RL Proc. Natl. Acad. Sci. U.S.A. 105:3368-3373(2008). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [15] RP FUNCTION, AND INTERACTION WITH PPP1R12A. RX PubMed=19245366; DOI=10.1042/BJ20081905; RA Webb J.D., Muranyi A., Pugh C.W., Ratcliffe P.J., Coleman M.L.; RT "MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is RT a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia- RT inducible factor (FIH)."; RL Biochem. J. 420:327-333(2009). RN [16] RP INTERACTION WITH APBA3, AND SUBCELLULAR LOCATION. RX PubMed=19726677; DOI=10.1074/jbc.M109.019216; RA Sakamoto T., Seiki M.; RT "Mint3 enhances the activity of hypoxia-inducible factor-1 (HIF-1) in RT macrophages by suppressing the activity of factor inhibiting HIF-1."; RL J. Biol. Chem. 284:30350-30359(2009). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [18] RP INTERACTION WITH UBE3A. RX PubMed=22645313; DOI=10.1128/MCB.00201-12; RA Martinez-Noel G., Galligan J.T., Sowa M.E., Arndt V., Overton T.M., RA Harper J.W., Howley P.M.; RT "Identification and proteomic analysis of distinct UBE3A/E6AP protein RT complexes."; RL Mol. Cell. Biol. 32:3095-3106(2012). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.M111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., RA Meinnel T., Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [20] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [21] RP INTERACTION WITH NECAB3. RX PubMed=26948053; DOI=10.1038/srep22784; RA Nakaoka H.J., Hara T., Yoshino S., Kanamori A., Matsui Y., RA Shimamura T., Sato H., Murakami Y., Seiki M., Sakamoto T.; RT "NECAB3 promotes activation of hypoxia-inducible factor-1 during RT normoxia and enhances tumourigenicity of cancer cells."; RL Sci. Rep. 6:22784-22784(2016). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH IRON AND RP 2-OXOGLUTARATE, AND SUBUNIT. RX PubMed=12432100; DOI=10.1073/pnas.202614999; RA Dann C.E. III, Bruick R.K., Deisenhofer J.; RT "Structure of factor-inhibiting hypoxia-inducible factor 1: an RT asparaginyl hydroxylase involved in the hypoxic response pathway."; RL Proc. Natl. Acad. Sci. U.S.A. 99:15351-15356(2002). RN [23] RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH 786-826 OF RP HIF1A; IRON; ZINC AND 2-OXOGLUTARATE. 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 [24] RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS), AND SUBUNIT. RX PubMed=12482756; DOI=10.1074/jbc.M210385200; RA Lee C., Kim S.J., Jeong D.G., Lee S.M., Ryu S.E.; RT "Structure of human FIH-1 reveals a unique active site pocket and RT interaction sites for HIF-1 and von Hippel-Lindau."; RL J. Biol. Chem. 278:7558-7563(2003). RN [25] RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) IN COMPLEX WITH IRON AND RP INHIBITOR. RX PubMed=15913349; DOI=10.1021/ja050841b; RA McDonough M.A., McNeill L.A., Tilliet M., Papamicael C.A., Chen Q.Y., RA Banerji B., Hewitson K.S., Schofield C.J.; RT "Selective inhibition of factor inhibiting hypoxia-inducible factor."; RL J. Am. Chem. Soc. 127:7680-7681(2005). RN [26] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH IRON; SUCCINATE RP AND FUMARATE. RX PubMed=17135241; DOI=10.1074/jbc.M608337200; RA Hewitson K.S., Lienard B.M., McDonough M.A., Clifton I.J., Butler D., RA Soares A.S., Oldham N.J., McNeill L.A., Schofield C.J.; RT "Structural and mechanistic studies on the inhibition of the hypoxia- RT inducible transcription factor hydroxylases by tricarboxylic acid RT cycle intermediates."; RL J. Biol. Chem. 282:3293-3301(2007). RN [27] RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEXES WITH 1930-1949 OR RP 1997-2016 OF MOUSE NOTCH1; IRON AND 2-OXOGLUTARATE, FUNCTION, AND RP SUBUNIT. RX PubMed=17573339; DOI=10.1074/jbc.M704102200; RA Coleman M.L., McDonough M.A., Hewitson K.S., Coles C., Mecinovic J., RA Edelmann M., Cook K.M., Cockman M.E., Lancaster D.E., Kessler B.M., RA Oldham N.J., Ratcliffe P.J., Schofield C.J.; RT "Asparaginyl hydroxylation of the Notch ankyrin repeat domain by RT factor inhibiting hypoxia-inducible factor."; RL J. Biol. Chem. 282:24027-24038(2007). RN [28] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 11-349 OF MUTANTS ALA-201 RP AND GLY-201 IN COMPLEXES WITH 786-826 OR 788-806 OF HIF1A; IRON OR RP ZINC AND 2-OXOGLUTARATE, AND MUTAGENESIS OF ASP-201; TRP-296 AND RP LEU-340. RX PubMed=18611856; DOI=10.1074/jbc.M804999200; RA Hewitson K.S., Holmes S.L., Ehrismann D., Hardy A.P., Chowdhury R., RA Schofield C.J., McDonough M.A.; RT "Evidence that two enzyme-derived histidine ligands are sufficient for RT iron binding and catalysis by factor inhibiting HIF (FIH)."; RL J. Biol. Chem. 283:25971-25978(2008). RN [29] RP X-RAY CRYSTALLOGRAPHY (2.12 ANGSTROMS) IN COMPLEX WITH IRON AND RP 2-OXOGLUTARATE ANALOGS. RX PubMed=20822901; DOI=10.1016/j.bmcl.2010.08.032; RA Conejo-Garcia A., McDonough M.A., Loenarz C., McNeill L.A., RA Hewitson K.S., Ge W., Lienard B.M., Schofield C.J., Clifton I.J.; RT "Structural basis for binding of cyclic 2-oxoglutarate analogues to RT factor-inhibiting hypoxia-inducible factor."; RL Bioorg. Med. Chem. Lett. 20:6125-6128(2010). RN [30] RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 15-349 IN COMPLEX WITH IRON RP AND QUINOL FAMILY INHIBITORS. RX PubMed=20396966; DOI=10.1007/s10059-010-0058-3; RA Moon H., Han S., Park H., Choe J.; RT "Crystal structures of human FIH-1 in complex with quinol family RT inhibitors."; RL Mol. Cells 29:471-474(2010). RN [31] RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH IRON AND RP INHIBITORS. RX PubMed=21460794; DOI=10.1038/embor.2011.43; RA Chowdhury R., Yeoh K.K., Tian Y.M., Hillringhaus L., Bagg E.A., RA Rose N.R., Leung I.K., Li X.S., Woon E.C., Yang M., McDonough M.A., RA King O.N., Clifton I.J., Klose R.J., Claridge T.D., Ratcliffe P.J., RA Schofield C.J., Kawamura A.; RT "The oncometabolite 2-hydroxyglutarate inhibits histone lysine RT demethylases."; RL EMBO Rep. 12:463-469(2011). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) IN COMPLEX WITH IRON; RP 2-OXOGLUTARATE AND 538-558 OF TNKS2, AND FUNCTION. RX PubMed=21251231; DOI=10.1111/j.1742-4658.2011.08022.x; RA Yang M., Chowdhury R., Ge W., Hamed R.B., McDonough M.A., RA Claridge T.D., Kessler B.M., Cockman M.E., Ratcliffe P.J., RA Schofield C.J.; RT "Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post- RT translational hydroxylation of histidinyl residues within ankyrin RT repeat domains."; RL FEBS J. 278:1086-1097(2011). RN [33] RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF MUTANT HIS-239 IN COMPLEX RP WITH ZINC; N-OXALYLGLYCINE AND PEPTIDE SUBSTRATE, FUNCTION, RP INTERACTION WITH ANK1, AND MUTAGENESIS OF ASP-201 AND GLN-239. RX PubMed=21177872; DOI=10.1074/jbc.M110.193540; RA Yang M., Ge W., Chowdhury R., Claridge T.D., Kramer H.B., RA Schmierer B., McDonough M.A., Gong L., Kessler B.M., Ratcliffe P.J., RA Coleman M.L., Schofield C.J.; RT "Asparagine and aspartate hydroxylation of the cytoskeletal ankyrin RT family is catalyzed by factor-inhibiting hypoxia-inducible factor."; RL J. Biol. Chem. 286:7648-7660(2011). CC -!- FUNCTION: Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal CC transactivation domain (CAD). Functions as an oxygen sensor and, CC under normoxic conditions, the hydroxylation prevents interaction CC of HIF-1 with transcriptional coactivators including Cbp/p300- CC interacting transactivator. Involved in transcriptional repression CC through interaction with HIF1A, VHL and histone deacetylases. CC Hydroxylates specific Asn residues within ankyrin repeat domains CC (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other CC ARD-containing proteins. Also hydroxylates Asp and His residues CC within ARDs of ANK1 and TNKS2, respectively. Negatively regulates CC NOTCH1 activity, accelerating myogenic differentiation. Positively CC regulates ASB4 activity, promoting vascular differentiation. CC {ECO:0000269|PubMed:12042299, ECO:0000269|PubMed:12080085, CC ECO:0000269|PubMed:17003112, ECO:0000269|PubMed:17573339, CC ECO:0000269|PubMed:18299578, ECO:0000269|PubMed:19245366, CC ECO:0000269|PubMed:21177872, ECO:0000269|PubMed:21251231}. CC -!- CATALYTIC ACTIVITY: Hypoxia-inducible factor-L-asparagine + 2- CC oxoglutarate + O(2) = hypoxia-inducible factor-(3S)-3-hydroxy-L- CC asparagine + succinate + CO(2). CC -!- CATALYTIC ACTIVITY: Ankyrin-repeat-L-histidine + 2-oxoglutarate + CC O(2) = ankyrin-repeat-(3S)-3-hydroxy-L-histidine + succinate + CC CO(2). CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000269|PubMed:12432100, CC ECO:0000269|PubMed:12446723, ECO:0000269|PubMed:15913349, CC ECO:0000269|PubMed:17135241, ECO:0000269|PubMed:20396966, CC ECO:0000269|PubMed:20822901, ECO:0000269|PubMed:21251231, CC ECO:0000269|PubMed:21460794}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=100 uM for HIF1A (788-822) peptide CC {ECO:0000269|PubMed:14701857}; CC KM=160 uM for HIF2A (832-866) peptide CC {ECO:0000269|PubMed:14701857}; CC KM=0.5 uM for Fe(2+) {ECO:0000269|PubMed:14701857}; CC KM=25 uM for 2-oxoglutarate {ECO:0000269|PubMed:14701857}; CC KM=260 uM for ascorbate {ECO:0000269|PubMed:14701857}; CC KM=90 uM for O(2) {ECO:0000269|PubMed:14701857}; CC Note=The kinetic constants are determined for the recombinant CC FLAG-His-tagged protein.; CC -!- SUBUNIT: Homodimer; homodimerization is essential for catalytic CC activity. Interacts with VHL and HIF1A. Part of a complex with CC VHL, HIF1A and HDAC1 or HDAC2 or HDAC3. Interacts with NFKB1 and CC NFKBIA. Interacts with NOTCH1, NOTCH2 and NOTCH3 but not with CC NOTCH4. Interacts with APBA3; binding inhibits HIF1AN binding to CC HIF1A. Interacts with TNKS2. Interacts with PPP1R12A. Interacts CC with ASB4 (By similarity). Interacts with UBE3A. Interacts with CC ANKS3 (By similarity). Interacts with NECAB3; the interaction is CC indirect and seems to be mediated by APBA3. CC {ECO:0000250|UniProtKB:Q8BLR9, ECO:0000269|PubMed:11641274, CC ECO:0000269|PubMed:12432100, ECO:0000269|PubMed:12446723, CC ECO:0000269|PubMed:12482756, ECO:0000269|PubMed:14701857, CC ECO:0000269|PubMed:15913349, ECO:0000269|PubMed:17003112, CC ECO:0000269|PubMed:17135241, ECO:0000269|PubMed:17573339, CC ECO:0000269|PubMed:19245366, ECO:0000269|PubMed:19726677, CC ECO:0000269|PubMed:20396966, ECO:0000269|PubMed:20822901, CC ECO:0000269|PubMed:21177872, ECO:0000269|PubMed:21251231, CC ECO:0000269|PubMed:21460794, ECO:0000269|PubMed:22645313, CC ECO:0000269|PubMed:26948053}. CC -!- INTERACTION: CC O96018:APBA3; NbExp=3; IntAct=EBI-745632, EBI-6115839; CC Q96DX5:ASB9; NbExp=3; IntAct=EBI-745632, EBI-745641; CC Q16665:HIF1A; NbExp=6; IntAct=EBI-745632, EBI-447269; CC Q96FW1:OTUB1; NbExp=4; IntAct=EBI-745632, EBI-1058491; CC P57078:RIPK4; NbExp=4; IntAct=EBI-745632, EBI-4422308; CC O95271:TNKS; NbExp=3; IntAct=EBI-745632, EBI-1105254; CC Q9H2K2:TNKS2; NbExp=4; IntAct=EBI-745632, EBI-4398527; CC P47086:YJR011C (xeno); NbExp=3; IntAct=EBI-745632, EBI-26299; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasm, perinuclear CC region. Note=Mainly cytoplasmic localization, but interaction with CC NOTCH1 results in nuclear localization and interaction with ABPA3 CC results in perinuclear localization in macrophages. CC -!- MASS SPECTROMETRY: Mass=40566; Method=Electrospray; Range=1-349; CC Evidence={ECO:0000269|PubMed:15239670}; 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; AF395830; AAL27308.1; -; mRNA. DR EMBL; AK000622; BAA91291.1; -; mRNA. DR EMBL; AL133352; CAH73566.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49817.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49818.1; -; Genomic_DNA. DR EMBL; BC007719; AAH07719.1; -; mRNA. DR EMBL; AL359615; CAB94885.1; -; mRNA. DR CCDS; CCDS7498.1; -. DR PIR; T50633; T50633. DR RefSeq; NP_060372.2; NM_017902.2. DR UniGene; Hs.500788; -. DR PDB; 1H2K; X-ray; 2.15 A; A=1-349. DR PDB; 1H2L; X-ray; 2.25 A; A=1-349. DR PDB; 1H2M; X-ray; 2.50 A; A=1-349. DR PDB; 1H2N; X-ray; 2.84 A; A=1-349. DR PDB; 1IZ3; X-ray; 2.80 A; A=1-349. DR PDB; 1MZE; X-ray; 2.20 A; A=1-349. DR PDB; 1MZF; X-ray; 2.40 A; A=1-349. DR PDB; 1YCI; X-ray; 2.70 A; A=1-349. DR PDB; 2CGN; X-ray; 2.40 A; A=1-349. DR PDB; 2CGO; X-ray; 2.30 A; A=1-349. DR PDB; 2ILM; X-ray; 2.30 A; A=1-349. DR PDB; 2W0X; X-ray; 2.12 A; A=1-349. DR PDB; 2WA3; X-ray; 2.50 A; A=1-349. DR PDB; 2WA4; X-ray; 2.50 A; A=1-349. DR PDB; 2XUM; X-ray; 2.20 A; A=1-349. DR PDB; 2Y0I; X-ray; 2.28 A; A=1-349. DR PDB; 2YC0; X-ray; 2.15 A; A=1-349. DR PDB; 2YDE; X-ray; 2.28 A; A=1-349. DR PDB; 3D8C; X-ray; 2.10 A; A=11-349. DR PDB; 3KCX; X-ray; 2.60 A; A=15-349. DR PDB; 3KCY; X-ray; 2.59 A; A=15-349. DR PDB; 3OD4; X-ray; 2.20 A; A=1-349. DR PDB; 3P3N; X-ray; 2.40 A; A=1-349. DR PDB; 3P3P; X-ray; 2.60 A; A=1-349. DR PDB; 4AI8; X-ray; 2.40 A; A=1-349. DR PDB; 4B7E; X-ray; 2.50 A; A=1-349. DR PDB; 4B7K; X-ray; 2.39 A; A=1-349. DR PDB; 4BIO; X-ray; 2.45 A; A=1-349. DR PDB; 4JAA; X-ray; 2.39 A; A=1-349. DR PDB; 4NR1; X-ray; 2.68 A; A=1-349. DR PDB; 4Z1V; X-ray; 2.10 A; A=1-349. DR PDB; 4Z2W; X-ray; 2.50 A; A=1-349. DR PDB; 5JWK; X-ray; 2.30 A; A=1-349. DR PDB; 5JWL; X-ray; 2.40 A; A=1-349. DR PDB; 5JWP; X-ray; 2.10 A; A=1-349. DR PDBsum; 1H2K; -. DR PDBsum; 1H2L; -. DR PDBsum; 1H2M; -. DR PDBsum; 1H2N; -. DR PDBsum; 1IZ3; -. DR PDBsum; 1MZE; -. DR PDBsum; 1MZF; -. DR PDBsum; 1YCI; -. DR PDBsum; 2CGN; -. DR PDBsum; 2CGO; -. DR PDBsum; 2ILM; -. DR PDBsum; 2W0X; -. DR PDBsum; 2WA3; -. DR PDBsum; 2WA4; -. DR PDBsum; 2XUM; -. DR PDBsum; 2Y0I; -. DR PDBsum; 2YC0; -. DR PDBsum; 2YDE; -. DR PDBsum; 3D8C; -. DR PDBsum; 3KCX; -. DR PDBsum; 3KCY; -. DR PDBsum; 3OD4; -. DR PDBsum; 3P3N; -. DR PDBsum; 3P3P; -. DR PDBsum; 4AI8; -. DR PDBsum; 4B7E; -. DR PDBsum; 4B7K; -. DR PDBsum; 4BIO; -. DR PDBsum; 4JAA; -. DR PDBsum; 4NR1; -. DR PDBsum; 4Z1V; -. DR PDBsum; 4Z2W; -. DR PDBsum; 5JWK; -. DR PDBsum; 5JWL; -. DR PDBsum; 5JWP; -. DR ProteinModelPortal; Q9NWT6; -. DR SMR; Q9NWT6; -. DR BioGrid; 120794; 79. DR DIP; DIP-35527N; -. DR IntAct; Q9NWT6; 138. DR MINT; MINT-1465958; -. DR STRING; 9606.ENSP00000299163; -. DR BindingDB; Q9NWT6; -. DR ChEMBL; CHEMBL5909; -. DR DrugBank; DB01694; D-tartaric acid. DR DrugBank; DB08263; N-(carboxycarbonyl)-D-phenylalanine. DR DrugBank; DB09459; Tartaric acid. DR iPTMnet; Q9NWT6; -. DR PhosphoSitePlus; Q9NWT6; -. DR BioMuta; HIF1AN; -. DR DMDM; 32129605; -. DR EPD; Q9NWT6; -. DR MaxQB; Q9NWT6; -. DR PaxDb; Q9NWT6; -. DR PeptideAtlas; Q9NWT6; -. DR PRIDE; Q9NWT6; -. DR DNASU; 55662; -. DR Ensembl; ENST00000299163; ENSP00000299163; ENSG00000166135. DR GeneID; 55662; -. DR KEGG; hsa:55662; -. DR UCSC; uc001krj.5; human. DR CTD; 55662; -. DR DisGeNET; 55662; -. DR EuPathDB; HostDB:ENSG00000166135.13; -. DR GeneCards; HIF1AN; -. DR HGNC; HGNC:17113; HIF1AN. DR HPA; CAB069903; -. DR HPA; HPA048742; -. DR HPA; HPA065302; -. DR MIM; 606615; gene. DR neXtProt; NX_Q9NWT6; -. DR OpenTargets; ENSG00000166135; -. DR PharmGKB; PA29284; -. DR eggNOG; KOG2132; Eukaryota. DR eggNOG; ENOG410XQDR; LUCA. DR GeneTree; ENSGT00530000062914; -. DR HOGENOM; HOG000008146; -. DR HOVERGEN; HBG051903; -. DR InParanoid; Q9NWT6; -. DR KO; K18055; -. DR OMA; MIKGRYD; -. DR OrthoDB; EOG091G0C8E; -. DR PhylomeDB; Q9NWT6; -. DR TreeFam; TF329609; -. DR BioCyc; MetaCyc:HS15407-MONOMER; -. DR BRENDA; 1.14.11.16; 2681. DR Reactome; R-HSA-1234162; Oxygen-dependent asparagine hydroxylation of Hypoxia-inducible Factor Alpha. DR SIGNOR; Q9NWT6; -. DR ChiTaRS; HIF1AN; human. DR EvolutionaryTrace; Q9NWT6; -. DR GeneWiki; HIF1AN; -. DR GenomeRNAi; 55662; -. DR PRO; PR:Q9NWT6; -. DR Proteomes; UP000005640; Chromosome 10. DR Bgee; ENSG00000166135; -. DR CleanEx; HS_HIF1AN; -. DR ExpressionAtlas; Q9NWT6; baseline and differential. DR Genevisible; Q9NWT6; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0071532; F:ankyrin repeat binding; IPI:UniProtKB. DR GO; GO:0031406; F:carboxylic acid binding; IDA:UniProtKB. DR GO; GO:0048037; F:cofactor binding; IDA:UniProtKB. DR GO; GO:0102113; F:hypoxia-inducible factor-asparagine oxygenase activity; IEA:UniProtKB-EC. DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB. DR GO; GO:0051059; F:NF-kappaB binding; IPI:UniProtKB. DR GO; GO:0005112; F:Notch binding; IPI:UniProtKB. DR GO; GO:0016706; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors; EXP:Reactome. DR GO; GO:0019826; F:oxygen sensor activity; NAS:UniProtKB. DR GO; GO:0036140; F:peptidyl-asparagine 3-dioxygenase activity; IDA:UniProtKB. DR GO; GO:0036139; F:peptidyl-histidine dioxygenase activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IDA:UniProtKB. DR GO; GO:0061428; P:negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; IDA:UniProtKB. DR GO; GO:0055114; P:oxidation-reduction process; IDA:UniProtKB. DR GO; GO:0042265; P:peptidyl-asparagine hydroxylation; IDA:UniProtKB. DR GO; GO:0042264; P:peptidyl-aspartic acid hydroxylation; IDA:UniProtKB. DR GO; GO:0036138; P:peptidyl-histidine hydroxylation; IDA:UniProtKB. DR GO; GO:0045663; P:positive regulation of myoblast differentiation; IDA:UniProtKB. DR GO; GO:2001214; P:positive regulation of vasculogenesis; NAS:UniProtKB. DR GO; GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 1.10.287.1010; -; 1. DR InterPro; IPR027445; FIH-1. DR InterPro; IPR027452; FIH-1_domII. DR InterPro; IPR003347; JmjC_dom. DR PANTHER; PTHR12461:SF72; PTHR12461:SF72; 1. DR SMART; SM00558; JmjC; 1. DR PROSITE; PS51184; JMJC; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Complete proteome; Cytoplasm; Dioxygenase; KW Iron; Metal-binding; Nucleus; Oxidoreductase; Polymorphism; KW Reference proteome; Transcription; Transcription regulation. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22223895, FT ECO:0000244|PubMed:22814378}. FT CHAIN 2 349 Hypoxia-inducible factor 1-alpha FT inhibitor. FT /FTId=PRO_0000083974. FT DOMAIN 142 312 JmjC. {ECO:0000255|PROSITE- FT ProRule:PRU00538}. FT REGION 2 125 Interaction with VHL. FT {ECO:0000269|PubMed:11641274}. FT REGION 181 183 Substrate binding. FT {ECO:0000269|PubMed:21177872}. FT REGION 201 203 Substrate binding. FT {ECO:0000269|PubMed:21177872}. FT REGION 238 239 Substrate binding. FT {ECO:0000269|PubMed:21177872}. FT METAL 199 199 Iron; via tele nitrogen; catalytic. FT {ECO:0000269|PubMed:12432100, FT ECO:0000269|PubMed:12446723, FT ECO:0000269|PubMed:15913349, FT ECO:0000269|PubMed:17135241, FT ECO:0000269|PubMed:20396966, FT ECO:0000269|PubMed:20822901, FT ECO:0000269|PubMed:21251231, FT ECO:0000269|PubMed:21460794}. FT METAL 201 201 Iron; catalytic. FT {ECO:0000269|PubMed:12432100, FT ECO:0000269|PubMed:12446723, FT ECO:0000269|PubMed:15913349, FT ECO:0000269|PubMed:17135241, FT ECO:0000269|PubMed:20396966, FT ECO:0000269|PubMed:20822901, FT ECO:0000269|PubMed:21251231, FT ECO:0000269|PubMed:21460794}. FT METAL 279 279 Iron; via tele nitrogen; catalytic. FT {ECO:0000269|PubMed:12432100, FT ECO:0000269|PubMed:12446723, FT ECO:0000269|PubMed:15913349, FT ECO:0000269|PubMed:17135241, FT ECO:0000269|PubMed:20396966, FT ECO:0000269|PubMed:20822901, FT ECO:0000269|PubMed:21251231, FT ECO:0000269|PubMed:21460794}. FT BINDING 145 145 2-oxoglutarate. FT {ECO:0000269|PubMed:12432100, FT ECO:0000269|PubMed:12446723, FT ECO:0000269|PubMed:21251231}. FT BINDING 152 152 Substrate. {ECO:0000269|PubMed:21177872}. FT BINDING 196 196 2-oxoglutarate. FT {ECO:0000269|PubMed:12432100, FT ECO:0000269|PubMed:12446723, FT ECO:0000269|PubMed:21251231}. FT BINDING 205 205 2-oxoglutarate. FT {ECO:0000269|PubMed:12432100, FT ECO:0000269|PubMed:12446723, FT ECO:0000269|PubMed:21251231}. FT BINDING 214 214 2-oxoglutarate. FT {ECO:0000269|PubMed:12432100, FT ECO:0000269|PubMed:12446723, FT ECO:0000269|PubMed:21251231}. FT BINDING 294 294 2-oxoglutarate. FT {ECO:0000269|PubMed:12432100, FT ECO:0000269|PubMed:12446723, FT ECO:0000269|PubMed:21251231}. FT BINDING 300 300 Substrate; via amide nitrogen. FT {ECO:0000269|PubMed:21177872}. FT BINDING 321 321 Substrate. {ECO:0000269|PubMed:21177872}. FT SITE 340 340 Important for dimer formation. FT MOD_RES 2 2 N-acetylalanine. FT {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22223895, FT ECO:0000244|PubMed:22814378}. FT VARIANT 41 41 P -> A (in dbSNP:rs2295778). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_051028. FT MUTAGEN 199 199 H->A: Prevents suppression of HIF CAD FT activity. Strongly stimulates 2- FT oxoglutarate turnover. No stimulation of FT 2-oxoglutarate turnover; when associated FT with R-340. FT {ECO:0000269|PubMed:12080085}. FT MUTAGEN 201 201 D->A: Prevents suppression of HIF CAD FT activity. {ECO:0000269|PubMed:12080085, FT ECO:0000269|PubMed:18611856, FT ECO:0000269|PubMed:21177872}. FT MUTAGEN 201 201 D->E: Loss of HIF1A Asn hydroxylation FT activity. Slightly stimulates 2- FT oxoglutarate turnover. FT {ECO:0000269|PubMed:12080085, FT ECO:0000269|PubMed:18611856, FT ECO:0000269|PubMed:21177872}. FT MUTAGEN 201 201 D->G: No impact on HIF1A Asn FT hydroxylation activity. Loss of Asp FT hydroxylation ability. Strongly FT stimulates 2-oxoglutarate turnover. Loss FT of HIF1A Asn hydroxylation activity and FT slight stimulation of 2-oxoglutarate FT turnover; when associated with R-296. FT {ECO:0000269|PubMed:12080085, FT ECO:0000269|PubMed:18611856, FT ECO:0000269|PubMed:21177872}. FT MUTAGEN 239 239 Q->H: No effect on Asp hydroxylation FT ability. {ECO:0000269|PubMed:21177872}. FT MUTAGEN 296 296 W->R: Loss of HIF1A Asn hydroxylation FT activity and slight stimulation of 2- FT oxoglutarate turnover; when associated FT with G-201. FT {ECO:0000269|PubMed:18611856}. FT MUTAGEN 340 340 L->R: Impairs dimer formation, leading to FT loss of HIF1A Asn hydroxylation activity. FT No stimulation of 2-oxoglutarate FT turnover; when associated with A-201. FT {ECO:0000269|PubMed:15239670, FT ECO:0000269|PubMed:18611856}. FT MUTAGEN 344 344 I->R: No effect on dimer formation and FT HIF1A Asn hydroxylation activity. FT {ECO:0000269|PubMed:15239670}. FT CONFLICT 10 10 A -> T (in Ref. 2; BAA91291). FT {ECO:0000305}. FT CONFLICT 28 28 D -> H (in Ref. 2; BAA91291). FT {ECO:0000305}. FT CONFLICT 156 156 R -> G (in Ref. 2; BAA91291). FT {ECO:0000305}. FT HELIX 2 9 {ECO:0000244|PDB:2YC0}. FT TURN 20 22 {ECO:0000244|PDB:3D8C}. FT STRAND 24 26 {ECO:0000244|PDB:3OD4}. FT HELIX 29 31 {ECO:0000244|PDB:3D8C}. FT STRAND 39 41 {ECO:0000244|PDB:3D8C}. FT HELIX 50 57 {ECO:0000244|PDB:3D8C}. FT STRAND 62 65 {ECO:0000244|PDB:3D8C}. FT HELIX 71 75 {ECO:0000244|PDB:3D8C}. FT HELIX 78 84 {ECO:0000244|PDB:3D8C}. FT STRAND 85 88 {ECO:0000244|PDB:3P3P}. FT STRAND 90 99 {ECO:0000244|PDB:3D8C}. FT HELIX 105 107 {ECO:0000244|PDB:3D8C}. FT TURN 108 110 {ECO:0000244|PDB:2YC0}. FT STRAND 111 113 {ECO:0000244|PDB:3KCY}. FT STRAND 117 123 {ECO:0000244|PDB:3D8C}. FT HELIX 125 138 {ECO:0000244|PDB:3D8C}. FT STRAND 143 149 {ECO:0000244|PDB:3D8C}. FT STRAND 151 154 {ECO:0000244|PDB:1MZE}. FT HELIX 156 163 {ECO:0000244|PDB:3D8C}. FT HELIX 167 176 {ECO:0000244|PDB:3D8C}. FT STRAND 182 184 {ECO:0000244|PDB:3D8C}. FT STRAND 186 190 {ECO:0000244|PDB:3D8C}. FT STRAND 195 199 {ECO:0000244|PDB:3D8C}. FT STRAND 202 212 {ECO:0000244|PDB:3D8C}. FT STRAND 214 219 {ECO:0000244|PDB:3D8C}. FT HELIX 221 223 {ECO:0000244|PDB:3D8C}. FT HELIX 224 227 {ECO:0000244|PDB:3D8C}. FT TURN 235 238 {ECO:0000244|PDB:4Z1V}. FT STRAND 239 242 {ECO:0000244|PDB:4Z1V}. FT STRAND 244 246 {ECO:0000244|PDB:4Z1V}. FT TURN 249 251 {ECO:0000244|PDB:3D8C}. FT HELIX 253 257 {ECO:0000244|PDB:3D8C}. FT STRAND 260 265 {ECO:0000244|PDB:3D8C}. FT STRAND 270 273 {ECO:0000244|PDB:3D8C}. FT STRAND 278 283 {ECO:0000244|PDB:3D8C}. FT STRAND 290 298 {ECO:0000244|PDB:3D8C}. FT HELIX 312 329 {ECO:0000244|PDB:3D8C}. FT STRAND 330 332 {ECO:0000244|PDB:2WA3}. FT HELIX 333 335 {ECO:0000244|PDB:3D8C}. FT HELIX 336 344 {ECO:0000244|PDB:3D8C}. FT TURN 345 347 {ECO:0000244|PDB:3D8C}. SQ SEQUENCE 349 AA; 40285 MW; 96A033BA7B3BD8C7 CRC64; MAATAAEAVA SGSGEPREEA GALGPAWDES QLRSYSFPTR PIPRLSQSDP RAEELIENEE PVVLTDTNLV YPALKWDLEY LQENIGNGDF SVYSASTHKF LYYDEKKMAN FQNFKPRSNR EEMKFHEFVE KLQDIQQRGG EERLYLQQTL NDTVGRKIVM DFLGFNWNWI NKQQGKRGWG QLTSNLLLIG MEGNVTPAHY DEQQNFFAQI KGYKRCILFP PDQFECLYPY PVHHPCDRQS QVDFDNPDYE RFPNFQNVVG YETVVGPGDV LYIPMYWWHH IESLLNGGIT ITVNFWYKGA PTPKRIEYPL KAHQKVAIMR NIEKMLGEAL GNPQEVGPLL NTMIKGRYN //