ID C1TC_YEAST Reviewed; 946 AA. AC P07245; D6VUY6; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1988, sequence version 1. DT 27-MAR-2024, entry version 215. DE RecName: Full=C-1-tetrahydrofolate synthase, cytoplasmic; DE Short=C1-THF synthase; DE Includes: DE RecName: Full=Methylenetetrahydrofolate dehydrogenase; DE EC=1.5.1.5 {ECO:0000269|PubMed:3514599, ECO:0000269|PubMed:8464869}; DE Includes: DE RecName: Full=Methenyltetrahydrofolate cyclohydrolase; DE EC=3.5.4.9 {ECO:0000269|PubMed:3514599, ECO:0000305|PubMed:8464869}; DE Includes: DE RecName: Full=Formyltetrahydrofolate synthetase; DE EC=6.3.4.3 {ECO:0000269|PubMed:3514599, ECO:0000269|PubMed:8464869}; GN Name=ADE3; OrderedLocusNames=YGR204W; ORFNames=G7733; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-10, FUNCTION, RP CATALYTIC ACTIVITY, AND DOMAIN. RX PubMed=3514599; DOI=10.1016/s0021-9258(17)38548-4; RA Staben C., Rabinowitz J.C.; RT "Nucleotide sequence of the Saccharomyces cerevisiae ADE3 gene encoding C1- RT tetrahydrofolate synthase."; RL J. Biol. Chem. 261:4629-4637(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=8904340; RX DOI=10.1002/(sici)1097-0061(19960315)12:3<273::aid-yea898>3.0.co;2-1; RA Guerreiro P., Barreiros T., Soares H., Cyrne L., Maia e Silva A., RA Rodrigues-Pousada C.; RT "Sequencing of a 17.6 kb segment on the right arm of yeast chromosome VII RT reveals 12 ORFs, including CCT, ADE3 and TR-I genes, homologues of the RT yeast PMT and EF1G genes, of the human and bacterial electron-transferring RT flavoproteins (beta-chain) and of the Escherichia coli phosphoserine RT phosphohydrolase, and five new ORFs."; RL Yeast 12:273-280(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169869; RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H., RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII."; RL Nature 387:81-84(1997). RN [4] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=17322287; DOI=10.1101/gr.6037607; RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J., RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., RA LaBaer J.; RT "Approaching a complete repository of sequence-verified protein-encoding RT clones for Saccharomyces cerevisiae."; RL Genome Res. 17:536-543(2007). RN [6] RP PROTEIN SEQUENCE OF 2-4, FUNCTION, AND SUBUNIT. RX PubMed=329838; DOI=10.1016/s0006-291x(77)80176-9; RA Paukert J.L., Williams G.R., Rabinowitz J.C.; RT "Formyl-methenyl-methylenetetrahydrofolate synthetase (combined); RT correlation of enzymic activities with limited proteolytic degradation of RT the protein from yeast."; RL Biochem. Biophys. Res. Commun. 77:147-154(1977). RN [7] RP MUTAGENESIS. RX PubMed=2541774; DOI=10.1021/bi00431a020; RA Barlowe C.K., Williams M.E., Rabinowitz J.C., Appling D.R.; RT "Site-directed mutagenesis of yeast C1-tetrahydrofolate synthase: analysis RT of an overlapping active site in a multifunctional enzyme."; RL Biochemistry 28:2099-2106(1989). RN [8] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=8464869; DOI=10.1073/pnas.90.7.2636; RA Song J.M., Rabinowitz J.C.; RT "Function of yeast cytoplasmic C1-tetrahydrofolate synthase."; RL Proc. Natl. Acad. Sci. U.S.A. 90:2636-2640(1993). RN [9] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=14562095; DOI=10.1038/nature02026; RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., RA Weissman J.S., O'Shea E.K.; RT "Global analysis of protein localization in budding yeast."; RL Nature 425:686-691(2003). RN [10] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., RA O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC STRAIN=ADR376; RX PubMed=17330950; DOI=10.1021/pr060559j; RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., RA Elias J.E., Gygi S.P.; RT "Large-scale phosphorylation analysis of alpha-factor-arrested RT Saccharomyces cerevisiae."; RL J. Proteome Res. 6:1190-1197(2007). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-176, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200; RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; RT "A multidimensional chromatography technology for in-depth phosphoproteome RT analysis."; RL Mol. Cell. Proteomics 7:1389-1396(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-176; THR-318 AND SER-322, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19779198; DOI=10.1126/science.1172867; RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.; RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights RT into evolution."; RL Science 325:1682-1686(2009). RN [14] RP IDENTIFICATION BY MASS 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., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). CC -!- FUNCTION: Cytoplasmic isozyme of C-1-tetrahydrofolate synthase. The CC trifunctional enzyme catalyzes the interconversion of the one-carbon CC derivatives of tetrahydrofolate (THF) between different oxidation CC states by the enzymatic activities 10-formyltetrahydrofolate CC synthetase, 5,lO-methenyltetrahydrofolate cyclohydrolase, and 5,lO- CC methylenetetrahydrofolate dehydrogenase. Involved in the generation of CC one-carbon intermediates in the biosynthesis of the purine bases. CC {ECO:0000269|PubMed:329838, ECO:0000269|PubMed:3514599, CC ECO:0000269|PubMed:8464869}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADP(+) = (6R)- CC 5,10-methenyltetrahydrofolate + NADPH; Xref=Rhea:RHEA:22812, CC ChEBI:CHEBI:15636, ChEBI:CHEBI:57455, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349; EC=1.5.1.5; Evidence={ECO:0000269|PubMed:3514599, CC ECO:0000269|PubMed:8464869}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22813; CC Evidence={ECO:0000305|PubMed:3514599, ECO:0000305|PubMed:8464869}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22814; CC Evidence={ECO:0000305|PubMed:3514599, ECO:0000305|PubMed:8464869}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-5,10-methenyltetrahydrofolate + H2O = (6R)-10- CC formyltetrahydrofolate + H(+); Xref=Rhea:RHEA:23700, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57455, CC ChEBI:CHEBI:195366; EC=3.5.4.9; Evidence={ECO:0000269|PubMed:3514599, CC ECO:0000305|PubMed:8464869}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23701; CC Evidence={ECO:0000305|PubMed:3514599, ECO:0000305|PubMed:8464869}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23702; CC Evidence={ECO:0000305|PubMed:3514599, ECO:0000305|PubMed:8464869}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(6S)-5,6,7,8-tetrahydrofolate + ATP + formate = (6R)-10- CC formyltetrahydrofolate + ADP + phosphate; Xref=Rhea:RHEA:20221, CC ChEBI:CHEBI:15740, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:57453, ChEBI:CHEBI:195366, ChEBI:CHEBI:456216; CC EC=6.3.4.3; Evidence={ECO:0000269|PubMed:3514599, CC ECO:0000269|PubMed:8464869}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20222; CC Evidence={ECO:0000305|PubMed:3514599, ECO:0000305|PubMed:8464869}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20223; CC Evidence={ECO:0000305|PubMed:3514599, ECO:0000305|PubMed:8464869}; CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:329838}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus CC {ECO:0000269|PubMed:14562095}. CC -!- DOMAIN: This trifunctional enzyme consists of two major domains: an N- CC terminal part containing the methylene-THF dehydrogenase and CC cyclohydrolase activities and a larger C-terminal part containing CC formyl-THF synthetase activity. {ECO:0000305|PubMed:3514599}. CC -!- MISCELLANEOUS: Present with 35600 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: In the N-terminal section; belongs to the tetrahydrofolate CC dehydrogenase/cyclohydrolase family. {ECO:0000305}. CC -!- SIMILARITY: In the C-terminal section; belongs to the CC formate--tetrahydrofolate ligase family. {ECO:0000305}. 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; M12878; AAA66316.1; -; Genomic_DNA. DR EMBL; Z49133; CAA88997.1; -; Genomic_DNA. DR EMBL; Z72989; CAA97231.1; -; Genomic_DNA. DR EMBL; AY692966; AAT92985.1; -; Genomic_DNA. DR EMBL; BK006941; DAA08297.1; -; Genomic_DNA. DR PIR; A29550; A29550. DR RefSeq; NP_011720.3; NM_001181333.3. DR AlphaFoldDB; P07245; -. DR SMR; P07245; -. DR BioGRID; 33457; 83. DR DIP; DIP-3867N; -. DR IntAct; P07245; 14. DR MINT; P07245; -. DR STRING; 4932.YGR204W; -. DR iPTMnet; P07245; -. DR MaxQB; P07245; -. DR PaxDb; 4932-YGR204W; -. DR PeptideAtlas; P07245; -. DR EnsemblFungi; YGR204W_mRNA; YGR204W; YGR204W. DR GeneID; 853118; -. DR KEGG; sce:YGR204W; -. DR AGR; SGD:S000003436; -. DR SGD; S000003436; ADE3. DR VEuPathDB; FungiDB:YGR204W; -. DR eggNOG; KOG4230; Eukaryota. DR HOGENOM; CLU_003601_2_0_1; -. DR InParanoid; P07245; -. DR OMA; CKQIANI; -. DR OrthoDB; 651667at2759; -. DR BioCyc; YEAST:YGR204W-MONOMER; -. DR BRENDA; 3.5.4.9; 984. DR BRENDA; 6.3.4.3; 984. DR Reactome; R-SCE-196757; Metabolism of folate and pterines. DR UniPathway; UPA00193; -. DR BioGRID-ORCS; 853118; 4 hits in 10 CRISPR screens. DR PRO; PR:P07245; -. DR Proteomes; UP000002311; Chromosome VII. DR RNAct; P07245; Protein. DR GO; GO:0005737; C:cytoplasm; HDA:SGD. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; HDA:SGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004329; F:formate-tetrahydrofolate ligase activity; IMP:SGD. DR GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; IMP:SGD. DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IMP:SGD. DR GO; GO:0006760; P:folic acid-containing compound metabolic process; IMP:SGD. DR GO; GO:0000105; P:histidine biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0009086; P:methionine biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0009113; P:purine nucleobase biosynthetic process; IMP:SGD. DR GO; GO:0006164; P:purine nucleotide biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central. DR CDD; cd00477; FTHFS; 1. DR CDD; cd01080; NAD_bind_m-THF_DH_Cyclohyd; 1. DR Gene3D; 3.10.410.10; Formyltetrahydrofolate synthetase, domain 3; 1. DR Gene3D; 3.40.50.10860; Leucine Dehydrogenase, chain A, domain 1; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR HAMAP; MF_01543; FTHFS; 1. DR HAMAP; MF_01576; THF_DHG_CYH; 1. DR InterPro; IPR046346; Aminoacid_DH-like_N_sf. DR InterPro; IPR000559; Formate_THF_ligase. DR InterPro; IPR020628; Formate_THF_ligase_CS. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR000672; THF_DH/CycHdrlase. DR InterPro; IPR020630; THF_DH/CycHdrlase_cat_dom. DR InterPro; IPR020867; THF_DH/CycHdrlase_CS. DR InterPro; IPR020631; THF_DH/CycHdrlase_NAD-bd_dom. DR PANTHER; PTHR48099:SF8; C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC; 1. DR PANTHER; PTHR48099; C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC-RELATED; 1. DR Pfam; PF01268; FTHFS; 1. DR Pfam; PF00763; THF_DHG_CYH; 1. DR Pfam; PF02882; THF_DHG_CYH_C; 1. DR PRINTS; PR00085; THFDHDRGNASE. DR SUPFAM; SSF53223; Aminoacid dehydrogenase-like, N-terminal domain; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00721; FTHFS_1; 1. DR PROSITE; PS00722; FTHFS_2; 1. DR PROSITE; PS00766; THF_DHG_CYH_1; 1. DR PROSITE; PS00767; THF_DHG_CYH_2; 1. PE 1: Evidence at protein level; KW Amino-acid biosynthesis; ATP-binding; Cytoplasm; Direct protein sequencing; KW Histidine biosynthesis; Hydrolase; Ligase; Methionine biosynthesis; KW Multifunctional enzyme; NADP; Nucleotide-binding; Nucleus; KW One-carbon metabolism; Oxidoreductase; Phosphoprotein; Purine biosynthesis; KW Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:329838, FT ECO:0000269|PubMed:3514599" FT CHAIN 2..946 FT /note="C-1-tetrahydrofolate synthase, cytoplasmic" FT /id="PRO_0000199326" FT REGION 2..319 FT /note="Methylenetetrahydrofolate dehydrogenase and FT cyclohydrolase" FT /evidence="ECO:0000305|PubMed:3514599" FT REGION 320..946 FT /note="Formyltetrahydrofolate synthetase" FT /evidence="ECO:0000305|PubMed:3514599" FT BINDING 51..55 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 98..100 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 169..171 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 194 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 277..281 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 384..391 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT MOD_RES 176 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18407956, FT ECO:0007744|PubMed:19779198" FT MOD_RES 318 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19779198" FT MOD_RES 322 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19779198" FT MUTAGEN 11 FT /note="C->S: Almost no effect on activity." FT /evidence="ECO:0000269|PubMed:2541774" FT MUTAGEN 144 FT /note="C->S: Cyclohydrolase activity is reduced 20-fold. FT Dehydrogenase Km is increased 7-fold." FT /evidence="ECO:0000269|PubMed:2541774" FT MUTAGEN 257 FT /note="C->S: Cyclohydrolase activity is increased 2-fold. FT Dehydrogenase Km is increased 2-fold." FT /evidence="ECO:0000269|PubMed:2541774" FT CONFLICT 4 FT /note="Q -> P (in Ref. 6; AA sequence)" FT /evidence="ECO:0000305" SQ SEQUENCE 946 AA; 102205 MW; BC2897EC380CBA6F CRC64; MAGQVLDGKA CAQQFRSNIA NEIKSIQGHV PGFAPNLAII QVGNRPDSAT YVRMKRKAAE EAGIVANFIH LDESATEFEV LRYVDQLNED PHTHGIIVQL PLPAHLDEDR ITSRVLAEKD VDGFGPTNIG ELNKKNGHPF FLPCTPKGII ELLHKANVTI EGSRSVVIGR SDIVGSPVAE LLKSLNSTVT ITHSKTRDIA SYLHDADIVV VAIGQPEFVK GEWFKPRDGT SSDKKTVVID VGTNYVADPS KKSGFKCVGD VEFNEAIKYV HLITPVPGGV GPMTVAMLMQ NTLIAAKRQM EESSKPLQIP PLPLKLLTPV PSDIDISRAQ QPKLINQLAQ ELGIYSHELE LYGHYKAKIS PKVIERLQTR QNGKYILVSG ITPTPLGEGK STTTMGLVQA LTAHLGKPAI ANVRQPSLGP TLGVKGGAAG GGYSQVIPMD EFNLHLTGDI HAIGAANNLL AAAIDTRMFH ETTQKNDATF YNRLVPRKNG KRKFTPSMQR RLNRLGIQKT NPDDLTPEEI NKFARLNIDP DTITIKRVVD INDRMLRQIT IGQAPTEKNH TRVTGFDITV ASELMAILAL SKDLRDMKER IGRVVVAADV NRSPVTVEDV GCTGALTALL RDAIKPNLMQ TLEGTPVLVH AGPFANISIG ASSVIADRVA LKLVGTEPEA KTEAGYVVTE AGFDFTMGGE RFFNIKCRSS GLTPNAVVLV ATVRALKSHG GAPDVKPGQP LPSAYTEENI EFVEKGAANM CKQIANIKQF GVPVVVAINK FETDTEGEIA AIRKAALEAG AFEAVTSNHW AEGGKGAIDL AKAVIEASNQ PVDFHFLYDV NSSVEDKLTT IVQKMYGGAA IDILPEAQRK IDMYKEQGFG NLPICIAKTQ YSLSHDATLK GVPTGFTFPI RDVRLSNGAG YLYALAAEIQ TIPGLATYAG YMAVEVDDDG EIDGLF //