ID MAP2_HUMAN Reviewed; 478 AA. AC P50579; B2RDI8; B4DUX5; G3XA91; Q8NB11; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 27-MAR-2024, entry version 218. DE RecName: Full=Methionine aminopeptidase 2 {ECO:0000255|HAMAP-Rule:MF_03175}; DE Short=MAP 2 {ECO:0000255|HAMAP-Rule:MF_03175}; DE Short=MetAP 2 {ECO:0000255|HAMAP-Rule:MF_03175}; DE EC=3.4.11.18 {ECO:0000255|HAMAP-Rule:MF_03175}; DE AltName: Full=Initiation factor 2-associated 67 kDa glycoprotein {ECO:0000255|HAMAP-Rule:MF_03175}; DE Short=p67 {ECO:0000255|HAMAP-Rule:MF_03175}; DE Short=p67eIF2 {ECO:0000255|HAMAP-Rule:MF_03175}; DE AltName: Full=Peptidase M {ECO:0000255|HAMAP-Rule:MF_03175}; GN Name=METAP2 {ECO:0000255|HAMAP-Rule:MF_03175}; GN Synonyms=MNPEP, P67EIF2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=7644482; DOI=10.1073/pnas.92.17.7714; RA Arfin S.M., Kendall R.L., Hall L., Weaver L.H., Stewart A.E., RA Matthews B.W., Bradshaw R.A.; RT "Eukaryotic methionyl aminopeptidases: two classes of cobalt-dependent RT enzymes."; RL Proc. Natl. Acad. Sci. U.S.A. 92:7714-7718(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=7873610; DOI=10.1016/0167-4781(94)00227-t; RA Li X., Chang Y.; RT "Molecular cloning of a human complementary DNA encoding an initiation RT factor 2-associated protein (p67)."; RL Biochim. Biophys. Acta 1260:333-336(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Heart, Placenta, and Small intestine; 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION IN EIF2S1 PROTECTION, AND GLYCOSYLATION. RX PubMed=2511207; DOI=10.1016/s0021-9258(19)47108-1; RA Datta B., Ray M.K., Chakrabarti D., Wylie D.E., Gupta N.K.; RT "Glycosylation of eukaryotic peptide chain initiation factor 2 (eIF-2)- RT associated 67-kDa polypeptide (p67) and its possible role in the inhibition RT of eIF-2 kinase-catalyzed phosphorylation of the eIF-2 alpha-subunit."; RL J. Biol. Chem. 264:20620-20624(1989). RN [8] RP COFACTOR. RX PubMed=12718546; DOI=10.1021/bi020670c; RA Wang J., Sheppard G.S., Lou P., Kawai M., Park C., Egan D.A., Schneider A., RA Bouska J., Lesniewski R., Henkin J.; RT "Physiologically relevant metal cofactor for methionine aminopeptidase-2 is RT manganese."; RL Biochemistry 42:5035-5042(2003). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45; SER-60; SER-63 AND RP SER-74, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [11] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=20521764; DOI=10.1021/bi1005464; RA Xiao Q., Zhang F., Nacev B.A., Liu J.O., Pei D.; RT "Protein N-terminal processing: substrate specificity of Escherichia coli RT and human methionine aminopeptidases."; RL Biochemistry 49:5588-5599(2010). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45 AND SER-74, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=21537465; DOI=10.4331/wjbc.v1.i10.313; RA Wu S.; RT "Localization and function of a eukaryotic-initiation-factor-2-associated RT 67-kDa glycoprotein."; RL World J. Biol. Chem. 1:313-320(2010). RN [14] 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., Buerckstuemmer T., RA 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45; SER-63 AND SER-74, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH FUMAGILLIN, AND RP COFACTOR. RX PubMed=9812898; DOI=10.1126/science.282.5392.1324; RA Liu S., Widom J., Kemp C.W., Crews C.M., Clardy J.; RT "Structure of human methionine aminopeptidase-2 complexed with RT fumagillin."; RL Science 282:1324-1327(1998). RN [18] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH COBALT IONS AND RP BENGAMIDE, AND FUNCTION. RX PubMed=14534293; DOI=10.1074/jbc.m309039200; RA Towbin H., Bair K.W., DeCaprio J.A., Eck M.J., Kim S., Kinder F.R., RA Morollo A., Mueller D.R., Schindler P., Song H.K., van Oostrum J., RA Versace R.W., Voshol H., Wood J., Zabludoff S., Phillips P.E.; RT "Proteomics-based target identification: bengamides as a new class of RT methionine aminopeptidase inhibitors."; RL J. Biol. Chem. 278:52964-52971(2003). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 110-478 IN COMPLEX WITH INHIBITOR RP A-357300. RX PubMed=15012983; DOI=10.1016/j.bmcl.2003.12.031; RA Sheppard G.S., Wang J., Kawai M., BaMaung N.Y., Craig R.A., Erickson S.A., RA Lynch L., Patel J., Yang F., Searle X.B., Lou P., Park C., Kim K.H., RA Henkin J., Lesniewski R.; RT "3-amino-2-hydroxyamides and related compounds as inhibitors of methionine RT aminopeptidase-2."; RL Bioorg. Med. Chem. Lett. 14:865-868(2004). RN [20] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 110-478 IN COMPLEX WITH RP 4-ARYL-1,2,3-TRIAZOLE AND COBALT IONS. RX PubMed=16134930; DOI=10.1021/jm050408c; RA Kallander L.S., Lu Q., Chen W., Tomaszek T., Yang G., Tew D., Meek T.D., RA Hofmann G.A., Schulz-Pritchard C.K., Smith W.W., Janson C.A., Ryan M.D., RA Zhang G.-F., Johanson K.O., Kirkpatrick R.B., Ho T.F., Fisher P.W., RA Mattern M.R., Johnson R.K., Hansbury M.J., Winkler J.D., Ward K.W., RA Veber D.F., Thompson S.K.; RT "4-aryl-1,2,3-triazole: a novel template for a reversible methionine RT aminopeptidase 2 inhibitor, optimized to inhibit angiogenesis in vivo."; RL J. Med. Chem. 48:5644-5647(2005). RN [21] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEXES WITH ZINC IONS AND RP METHIONINE, AND PARTIAL PROTEIN SEQUENCE. RX PubMed=16540317; DOI=10.1016/j.bmcl.2006.02.047; RA Nonato M.C., Widom J., Clardy J.; RT "Human methionine aminopeptidase type 2 in complex with L- and D- RT methionine."; RL Bioorg. Med. Chem. Lett. 16:2580-2583(2006). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 110-478 IN COMPLEX WITH MANGANESE RP AND INHIBITOR. RX PubMed=17350258; DOI=10.1016/j.bmcl.2007.02.062; RA Wang G.T., Mantei R.A., Kawai M., Tedrow J.S., Barnes D.M., Wang J., RA Zhang Q., Lou P., Garcia L.A., Bouska J., Yates M., Park C., Judge R.A., RA Lesniewski R., Sheppard G.S., Bell R.L.; RT "Lead optimization of methionine aminopeptidase-2 (MetAP2) inhibitors RT containing sulfonamides of 5,6-disubstituted anthranilic acids."; RL Bioorg. Med. Chem. Lett. 17:2817-2822(2007). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 110-478 IN COMPLEX WITH COBALT RP IONS AND INHIBITOR, COFACTOR, AND FUNCTION. RX PubMed=17636946; DOI=10.1021/jm061182w; RA Marino J.P. Jr., Fisher P.W., Hofmann G.A., Kirkpatrick R.B., Janson C.A., RA Johnson R.K., Ma C., Mattern M., Meek T.D., Ryan M.D., Schulz C., RA Smith W.W., Tew D.G., Tomazek T.A. Jr., Veber D.F., Xiong W.C., RA Yamamoto Y., Yamashita K., Yang G., Thompson S.K.; RT "Highly potent inhibitors of methionine aminopeptidase-2 based on a 1,2,4- RT triazole pharmacophore."; RL J. Med. Chem. 50:3777-3785(2007). CC -!- FUNCTION: Cotranslationally removes the N-terminal methionine from CC nascent proteins. The N-terminal methionine is often cleaved when the CC second residue in the primary sequence is small and uncharged (Met- CC Ala-, Cys, Gly, Pro, Ser, Thr, or Val). The catalytic activity of human CC METAP2 toward Met-Val peptides is consistently two orders of magnitude CC higher than that of METAP1, suggesting that it is responsible for CC processing proteins containing N-terminal Met-Val and Met-Thr sequences CC in vivo. CC -!- FUNCTION: Protects eukaryotic initiation factor EIF2S1 from CC translation-inhibiting phosphorylation by inhibitory kinases such as CC EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of CC protein synthesis. CC -!- CATALYTIC ACTIVITY: CC Reaction=Release of N-terminal amino acids, preferentially methionine, CC from peptides and arylamides.; EC=3.4.11.18; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03175, CC ECO:0000269|PubMed:20521764}; CC -!- COFACTOR: CC Name=Co(2+); Xref=ChEBI:CHEBI:48828; Evidence={ECO:0000255|HAMAP- CC Rule:MF_03175, ECO:0000269|PubMed:12718546, CC ECO:0000269|PubMed:17636946, ECO:0000269|PubMed:9812898}; CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000255|HAMAP- CC Rule:MF_03175, ECO:0000269|PubMed:12718546, CC ECO:0000269|PubMed:17636946, ECO:0000269|PubMed:9812898}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|HAMAP- CC Rule:MF_03175, ECO:0000269|PubMed:12718546, CC ECO:0000269|PubMed:17636946, ECO:0000269|PubMed:9812898}; CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000255|HAMAP- CC Rule:MF_03175, ECO:0000269|PubMed:12718546, CC ECO:0000269|PubMed:17636946, ECO:0000269|PubMed:9812898}; CC Note=Binds 2 divalent metal cations per subunit. Has a high-affinity CC and a low affinity metal-binding site. The true nature of the CC physiological cofactor is under debate. The enzyme is active with CC cobalt, zinc, manganese or divalent iron ions. Most likely, methionine CC aminopeptidases function as mononuclear Fe(2+)-metalloproteases under CC physiological conditions, and the catalytically relevant metal-binding CC site has been assigned to the histidine-containing high-affinity site. CC Also manganese has been proposed to be the physiological cofactor for CC human METAP2. {ECO:0000255|HAMAP-Rule:MF_03175, CC ECO:0000269|PubMed:12718546, ECO:0000269|PubMed:17636946, CC ECO:0000269|PubMed:9812898}; CC -!- SUBUNIT: Interacts strongly with the eIF-2 gamma-subunit EIF2S3 (By CC similarity). Binds EIF2S1 at low magnesium concentrations. CC {ECO:0000250, ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:15012983, CC ECO:0000269|PubMed:16134930, ECO:0000269|PubMed:17350258, CC ECO:0000269|PubMed:17636946, ECO:0000269|PubMed:9812898}. CC -!- INTERACTION: CC P50579; P21917: DRD4; NbExp=3; IntAct=EBI-2214155, EBI-8592297; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03175, CC ECO:0000269|PubMed:21537465}. Note=About 30% of expressed METAP2 CC associates with polysomes. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P50579-1; Sequence=Displayed; CC Name=2; CC IsoId=P50579-2; Sequence=VSP_055467, VSP_055468; CC Name=3; CC IsoId=P50579-3; Sequence=VSP_057353; CC -!- PTM: Contains approximately 12 O-linked N-acetylglucosamine (GlcNAc) CC residues. O-glycosylation is required for EIF2S1 binding. CC {ECO:0000255|HAMAP-Rule:MF_03175, ECO:0000269|PubMed:2511207}. CC -!- SIMILARITY: Belongs to the peptidase M24A family. Methionine CC aminopeptidase eukaryotic type 2 subfamily. {ECO:0000255|HAMAP- CC Rule:MF_03175}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/46053/METAP2"; 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; U29607; AAA82930.1; -; mRNA. DR EMBL; U13261; AAC63402.1; -; mRNA. DR EMBL; AK091730; BAC03733.1; -; mRNA. DR EMBL; AK300836; BAG62487.1; -; mRNA. DR EMBL; AK315559; BAG37935.1; -; mRNA. DR EMBL; AC018475; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471054; EAW97537.1; -; Genomic_DNA. DR EMBL; CH471054; EAW97538.1; -; Genomic_DNA. DR EMBL; BC013782; AAH13782.1; -; mRNA. DR CCDS; CCDS81723.1; -. [P50579-3] DR CCDS; CCDS81725.1; -. [P50579-2] DR CCDS; CCDS9052.1; -. [P50579-1] DR PIR; S52112; DPHUM2. DR RefSeq; NP_001304111.1; NM_001317182.1. [P50579-3] DR RefSeq; NP_001304112.1; NM_001317183.1. [P50579-2] DR RefSeq; NP_001317175.1; NM_001330246.1. DR RefSeq; NP_006829.1; NM_006838.3. [P50579-1] DR PDB; 1B59; X-ray; 1.80 A; A=109-478. DR PDB; 1B6A; X-ray; 1.60 A; A=1-478. DR PDB; 1BN5; X-ray; 1.80 A; A=1-478. DR PDB; 1BOA; X-ray; 1.80 A; A=1-478. DR PDB; 1KQ0; X-ray; 2.00 A; A=1-478. DR PDB; 1KQ9; X-ray; 1.90 A; A=1-478. DR PDB; 1QZY; X-ray; 1.60 A; A=1-478. DR PDB; 1R58; X-ray; 1.90 A; A=110-478. DR PDB; 1R5G; X-ray; 2.00 A; A=110-478. DR PDB; 1R5H; X-ray; 2.40 A; A=110-478. DR PDB; 1YW7; X-ray; 1.85 A; A=110-478. DR PDB; 1YW8; X-ray; 2.65 A; A=110-478. DR PDB; 1YW9; X-ray; 1.64 A; A=110-478. DR PDB; 2ADU; X-ray; 1.90 A; A=110-478. DR PDB; 2EA2; X-ray; 2.50 A; A=110-478. DR PDB; 2EA4; X-ray; 2.35 A; A=110-478. DR PDB; 2GA2; X-ray; 1.95 A; A=110-478. DR PDB; 2OAZ; X-ray; 1.90 A; A=110-478. DR PDB; 5CLS; X-ray; 1.75 A; A=108-478. DR PDB; 5D6E; X-ray; 1.49 A; A=108-478. DR PDB; 5D6F; X-ray; 1.55 A; A=108-478. DR PDB; 5JFR; X-ray; 1.60 A; A=110-478. DR PDB; 5JHU; X-ray; 1.80 A; A=110-478. DR PDB; 5JI6; X-ray; 2.15 A; A=110-478. DR PDB; 5LYW; X-ray; 1.69 A; A=108-478. DR PDB; 5LYX; X-ray; 1.90 A; A=108-478. DR PDB; 6QED; X-ray; 1.80 A; A=108-478. DR PDB; 6QEF; X-ray; 1.79 A; A=108-478. DR PDB; 6QEG; X-ray; 2.08 A; A=108-478. DR PDB; 6QEH; X-ray; 2.17 A; A=108-478. DR PDB; 6QEI; X-ray; 1.80 A; A=108-478. DR PDB; 6QEJ; X-ray; 1.62 A; A=108-478. DR PDB; 7A12; X-ray; 2.00 A; A=108-478. DR PDB; 7A13; X-ray; 2.04 A; A=108-478. DR PDB; 7A14; X-ray; 2.14 A; A=108-478. DR PDB; 7A15; X-ray; 2.15 A; A=108-478. DR PDB; 7A16; X-ray; 1.90 A; A=108-478. DR PDBsum; 1B59; -. DR PDBsum; 1B6A; -. DR PDBsum; 1BN5; -. DR PDBsum; 1BOA; -. DR PDBsum; 1KQ0; -. DR PDBsum; 1KQ9; -. DR PDBsum; 1QZY; -. DR PDBsum; 1R58; -. DR PDBsum; 1R5G; -. DR PDBsum; 1R5H; -. DR PDBsum; 1YW7; -. DR PDBsum; 1YW8; -. DR PDBsum; 1YW9; -. DR PDBsum; 2ADU; -. DR PDBsum; 2EA2; -. DR PDBsum; 2EA4; -. DR PDBsum; 2GA2; -. DR PDBsum; 2OAZ; -. DR PDBsum; 5CLS; -. DR PDBsum; 5D6E; -. DR PDBsum; 5D6F; -. DR PDBsum; 5JFR; -. DR PDBsum; 5JHU; -. DR PDBsum; 5JI6; -. DR PDBsum; 5LYW; -. DR PDBsum; 5LYX; -. DR PDBsum; 6QED; -. DR PDBsum; 6QEF; -. DR PDBsum; 6QEG; -. DR PDBsum; 6QEH; -. DR PDBsum; 6QEI; -. DR PDBsum; 6QEJ; -. DR PDBsum; 7A12; -. DR PDBsum; 7A13; -. DR PDBsum; 7A14; -. DR PDBsum; 7A15; -. DR PDBsum; 7A16; -. DR AlphaFoldDB; P50579; -. DR SMR; P50579; -. DR BioGRID; 116184; 273. DR IntAct; P50579; 36. DR MINT; P50579; -. DR STRING; 9606.ENSP00000325312; -. DR BindingDB; P50579; -. DR ChEMBL; CHEMBL3922; -. DR DrugBank; DB03396; (2R,3R,4S,5R,6E)-3,4,5-Trihydroxy-N-[(3S,6R)-6-hydroxy-2-oxo-3-azepanyl]-2-methoxy-8,8-dimethyl-6-nonenamide. DR DrugBank; DB04108; (2s,3r)-3-Amino-2-Hydroxy-5-(Ethylsulfanyl)Pentanoyl-((S)-(-)-(1-Naphthyl)Ethyl)Amide. DR DrugBank; DB07322; 2-[(PHENYLSULFONYL)AMINO]-5,6,7,8-TETRAHYDRONAPHTHALENE-1-CARBOXYLIC ACID. DR DrugBank; DB07323; 2-[({2-[(1Z)-3-(DIMETHYLAMINO)PROP-1-ENYL]-4-FLUOROPHENYL}SULFONYL)AMINO]-5,6,7,8-TETRAHYDRONAPHTHALENE-1-CARBOXYLIC ACID. DR DrugBank; DB02310; 3,5,6,8-Tetramethyl-N-Methyl Phenanthrolinium. DR DrugBank; DB07746; 3-ETHYL-6-{[(4-FLUOROPHENYL)SULFONYL]AMINO}-2-METHYLBENZOIC ACID. DR DrugBank; DB07309; 5-BROMO-2-{[(4-CHLOROPHENYL)SULFONYL]AMINO}BENZOIC ACID. DR DrugBank; DB07313; 5-METHYL-2-[(PHENYLSULFONYL)AMINO]BENZOIC ACID. DR DrugBank; DB02893; D-Methionine. DR DrugBank; DB02640; Fumagillin. DR DrugBank; DB00134; Methionine. DR DrugBank; DB07377; N'-((2S,3R)-3-AMINO-2-HYDROXY-5-(ISOPROPYLSULFANYL)PENTANOYL)-N-3-CHLOROBENZOYL HYDRAZIDE. DR DrugBank; DB03086; N'-(2s,3r)-3-Amino-4-Cyclohexyl-2-Hydroxy-Butano-N-(4-Methylphenyl)Hydrazide. DR DrugBank; DB01422; Nitroxoline. DR DrugBank; DB04324; Ovalicin. DR DrugBank; DB05864; PPI-2458. DR DrugBank; DB03900; tert-butanol. DR DrugBank; DB08633; TNP-470. DR DrugCentral; P50579; -. DR GuidetoPHARMACOLOGY; 1573; -. DR MEROPS; M24.002; -. DR GlyCosmos; P50579; 2 sites, No reported glycans. DR GlyGen; P50579; 3 sites, 1 O-linked glycan (1 site). DR iPTMnet; P50579; -. DR MetOSite; P50579; -. DR PhosphoSitePlus; P50579; -. DR SwissPalm; P50579; -. DR BioMuta; METAP2; -. DR DMDM; 1703273; -. DR REPRODUCTION-2DPAGE; IPI00033036; -. DR EPD; P50579; -. DR jPOST; P50579; -. DR MassIVE; P50579; -. DR MaxQB; P50579; -. DR PaxDb; 9606-ENSP00000325312; -. DR PeptideAtlas; P50579; -. DR ProteomicsDB; 33683; -. DR ProteomicsDB; 5231; -. DR ProteomicsDB; 56252; -. [P50579-1] DR Pumba; P50579; -. DR TopDownProteomics; P50579-1; -. [P50579-1] DR Antibodypedia; 4578; 352 antibodies from 34 providers. DR DNASU; 10988; -. DR Ensembl; ENST00000261220.13; ENSP00000261220.9; ENSG00000111142.14. [P50579-2] DR Ensembl; ENST00000323666.10; ENSP00000325312.5; ENSG00000111142.14. [P50579-1] DR Ensembl; ENST00000546753.5; ENSP00000448169.1; ENSG00000111142.14. [P50579-3] DR GeneID; 10988; -. DR KEGG; hsa:10988; -. DR MANE-Select; ENST00000323666.10; ENSP00000325312.5; NM_006838.4; NP_006829.1. DR UCSC; uc001tec.4; human. [P50579-1] DR AGR; HGNC:16672; -. DR CTD; 10988; -. DR DisGeNET; 10988; -. DR GeneCards; METAP2; -. DR HGNC; HGNC:16672; METAP2. DR HPA; ENSG00000111142; Low tissue specificity. DR MIM; 601870; gene. DR neXtProt; NX_P50579; -. DR OpenTargets; ENSG00000111142; -. DR PharmGKB; PA30765; -. DR VEuPathDB; HostDB:ENSG00000111142; -. DR eggNOG; KOG2775; Eukaryota. DR GeneTree; ENSGT00940000155016; -. DR InParanoid; P50579; -. DR OMA; WQDYRRS; -. DR OrthoDB; 5473250at2759; -. DR PhylomeDB; P50579; -. DR TreeFam; TF300426; -. DR BioCyc; MetaCyc:HS03371-MONOMER; -. DR BRENDA; 3.4.11.18; 2681. DR PathwayCommons; P50579; -. DR Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade. DR SABIO-RK; P50579; -. DR SignaLink; P50579; -. DR BioGRID-ORCS; 10988; 495 hits in 1187 CRISPR screens. DR ChiTaRS; METAP2; human. DR EvolutionaryTrace; P50579; -. DR GeneWiki; METAP2; -. DR GenomeRNAi; 10988; -. DR Pharos; P50579; Tchem. DR PRO; PR:P50579; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P50579; Protein. DR Bgee; ENSG00000111142; Expressed in sural nerve and 204 other cell types or tissues. DR ExpressionAtlas; P50579; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:HGNC-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0004177; F:aminopeptidase activity; IDA:UniProtKB. DR GO; GO:0004239; F:initiator methionyl aminopeptidase activity; IEA:UniProtKB-UniRule. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0070006; F:metalloaminopeptidase activity; IEA:UniProtKB-UniRule. DR GO; GO:0008235; F:metalloexopeptidase activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0031365; P:N-terminal protein amino acid modification; IDA:HGNC-UCL. DR GO; GO:0018206; P:peptidyl-methionine modification; IDA:HGNC-UCL. DR GO; GO:0016485; P:protein processing; IDA:HGNC-UCL. DR CDD; cd01088; MetAP2; 1. DR Gene3D; 3.90.230.10; Creatinase/methionine aminopeptidase superfamily; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR HAMAP; MF_03175; MetAP_2_euk; 1. DR InterPro; IPR036005; Creatinase/aminopeptidase-like. DR InterPro; IPR000994; Pept_M24. DR InterPro; IPR001714; Pept_M24_MAP. DR InterPro; IPR002468; Pept_M24A_MAP2. DR InterPro; IPR018349; Pept_M24A_MAP2_BS. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR NCBIfam; TIGR00501; met_pdase_II; 1. DR PANTHER; PTHR45777; METHIONINE AMINOPEPTIDASE 2; 1. DR PANTHER; PTHR45777:SF2; METHIONINE AMINOPEPTIDASE 2; 1. DR Pfam; PF00557; Peptidase_M24; 1. DR PRINTS; PR00599; MAPEPTIDASE. DR SUPFAM; SSF55920; Creatinase/aminopeptidase; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS01202; MAP_2; 1. DR Genevisible; P50579; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Aminopeptidase; Cytoplasm; KW Direct protein sequencing; Glycoprotein; Hydrolase; Metal-binding; KW Phosphoprotein; Protease; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..478 FT /note="Methionine aminopeptidase 2" FT /id="PRO_0000148982" FT REGION 1..123 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 16..35 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 47..78 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 231 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175, FT ECO:0000269|PubMed:16540317" FT BINDING 251 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175, FT ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, FT ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, FT ECO:0000269|PubMed:17636946" FT BINDING 262 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175, FT ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, FT ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, FT ECO:0000269|PubMed:17636946" FT BINDING 262 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175, FT ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, FT ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, FT ECO:0000269|PubMed:17636946" FT BINDING 331 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175, FT ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, FT ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, FT ECO:0000269|PubMed:17636946" FT BINDING 339 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175, FT ECO:0000269|PubMed:16540317" FT BINDING 364 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175, FT ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, FT ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, FT ECO:0000269|PubMed:17636946" FT BINDING 459 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175, FT ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, FT ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, FT ECO:0000269|PubMed:17636946" FT BINDING 459 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03175, FT ECO:0000269|PubMed:14534293, ECO:0000269|PubMed:16134930, FT ECO:0000269|PubMed:16540317, ECO:0000269|PubMed:17350258, FT ECO:0000269|PubMed:17636946" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 45 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 60 FT /note="Phosphoserine; alternate" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 63 FT /note="Phosphoserine; alternate" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 74 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT CARBOHYD 60 FT /note="O-linked (GlcNAc) serine; alternate" FT /evidence="ECO:0000250" FT CARBOHYD 63 FT /note="O-linked (GlcNAc) serine; alternate" FT /evidence="ECO:0000250" FT VAR_SEQ 50 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055467" FT VAR_SEQ 87..109 FT /note="DGDGDGDGATGKKKKKKKKKRGP -> A (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055468" FT VAR_SEQ 109..132 FT /note="PKVQTDPPSVPICDLYPNGVFPKG -> R (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057353" FT CONFLICT 434 FT /note="N -> D (in Ref. 3; BAC03733)" FT /evidence="ECO:0000305" FT HELIX 120..123 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 124..127 FT /evidence="ECO:0007829|PDB:6QEJ" FT STRAND 133..135 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 141..143 FT /evidence="ECO:0007829|PDB:1R58" FT HELIX 147..151 FT /evidence="ECO:0007829|PDB:5D6E" FT HELIX 153..160 FT /evidence="ECO:0007829|PDB:5D6E" FT HELIX 163..186 FT /evidence="ECO:0007829|PDB:5D6E" FT HELIX 193..208 FT /evidence="ECO:0007829|PDB:5D6E" FT HELIX 212..214 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 215..225 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 228..231 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 248..256 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 259..267 FT /evidence="ECO:0007829|PDB:5D6E" FT HELIX 271..273 FT /evidence="ECO:0007829|PDB:5D6E" FT HELIX 274..290 FT /evidence="ECO:0007829|PDB:5D6E" FT HELIX 297..309 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 312..315 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 318..321 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 330..334 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 337..339 FT /evidence="ECO:0007829|PDB:1QZY" FT STRAND 346..349 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 360..370 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 382..385 FT /evidence="ECO:0007829|PDB:5D6E" FT HELIX 397..409 FT /evidence="ECO:0007829|PDB:5D6E" FT TURN 410..412 FT /evidence="ECO:0007829|PDB:5D6E" FT HELIX 417..421 FT /evidence="ECO:0007829|PDB:5D6E" FT TURN 422..424 FT /evidence="ECO:0007829|PDB:5D6E" FT HELIX 429..437 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 440..444 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 455..464 FT /evidence="ECO:0007829|PDB:5D6E" FT STRAND 469..471 FT /evidence="ECO:0007829|PDB:5D6E" SQ SEQUENCE 478 AA; 52892 MW; 5788E4BB83E48F9A CRC64; MAGVEEVAAS GSHLNGDLDP DDREEGAAST AEEAAKKKRR KKKKSKGPSA AGEQEPDKES GASVDEVARQ LERSALEDKE RDEDDEDGDG DGDGATGKKK KKKKKKRGPK VQTDPPSVPI CDLYPNGVFP KGQECEYPPT QDGRTAAWRT TSEEKKALDQ ASEEIWNDFR EAAEAHRQVR KYVMSWIKPG MTMIEICEKL EDCSRKLIKE NGLNAGLAFP TGCSLNNCAA HYTPNAGDTT VLQYDDICKI DFGTHISGRI IDCAFTVTFN PKYDTLLKAV KDATNTGIKC AGIDVRLCDV GEAIQEVMES YEVEIDGKTY QVKPIRNLNG HSIGQYRIHA GKTVPIVKGG EATRMEEGEV YAIETFGSTG KGVVHDDMEC SHYMKNFDVG HVPIRLPRTK HLLNVINENF GTLAFCRRWL DRLGESKYLM ALKNLCDLGI VDPYPPLCDI KGSYTAQFEH TILLRPTCKE VVSRGDDY //