C1TC_HUMAN
ID C1TC_HUMAN Reviewed; 935 AA.
AC P11586; A0A024R652; A0A384N5Y3; B2R5Y2; G3V2B8; Q86VC9; Q9BVP5;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 4.
DT 03-AUG-2022, entry version 238.
DE RecName: Full=C-1-tetrahydrofolate synthase, cytoplasmic {ECO:0000305|PubMed:1881876};
DE Short=C1-THF synthase;
DE AltName: Full=Epididymis secretory sperm binding protein {ECO:0000303|Ref.3};
DE Includes:
DE RecName: Full=Methylenetetrahydrofolate dehydrogenase {ECO:0000305|PubMed:1881876};
DE EC=1.5.1.5 {ECO:0000269|PubMed:10828945, ECO:0000269|PubMed:18767138, ECO:0000269|PubMed:1881876};
DE Includes:
DE RecName: Full=Methenyltetrahydrofolate cyclohydrolase {ECO:0000305|PubMed:1881876};
DE EC=3.5.4.9 {ECO:0000269|PubMed:10828945, ECO:0000269|PubMed:1881876};
DE Includes:
DE RecName: Full=Formyltetrahydrofolate synthetase {ECO:0000305|PubMed:1881876};
DE EC=6.3.4.3 {ECO:0000269|PubMed:18767138, ECO:0000269|PubMed:1881876};
DE Contains:
DE RecName: Full=C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed;
GN Name=MTHFD1; Synonyms=MTHFC, MTHFD;
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], PROTEIN SEQUENCE OF 2-31, VARIANT ARG-134, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Liver;
RX PubMed=3053686; DOI=10.1016/s0021-9258(18)37540-9;
RA Hum D.W., Bell A.W., Rozen R., Mackenzie R.E.;
RT "Primary structure of a human trifunctional enzyme. Isolation of a cDNA
RT encoding methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate
RT cyclohydrolase-formyltetrahydrofolate synthetase.";
RL J. Biol. Chem. 263:15946-15950(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-134 AND GLN-653.
RC TISSUE=Amygdala;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Li J.Y.;
RL Submitted (SEP-2009) to the EMBL/GenBank/DDBJ databases.
RN [4]
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., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., 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., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS ARG-134 AND
RP GLN-653.
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], AND VARIANTS ARG-134; GLN-653 AND
RP PHE-769.
RC TISSUE=Brain, Eye, and 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 PROTEIN SEQUENCE OF 2-17.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [8]
RP PROTEIN SEQUENCE OF 2-17; 251-264; 314-324; 355-362; 596-616 AND 722-733,
RP CLEAVAGE OF INITIATOR METHIONINE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Foreskin fibroblast, and Prostatic carcinoma;
RA Bienvenut W.V., Gao M., Leug H., Campbell A., Ozanne B.W.;
RL Submitted (JUL-2009) to UniProtKB.
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND DOMAIN.
RX PubMed=1881876; DOI=10.1093/protein/4.4.493;
RA Hum D.W., MacKenzie R.E.;
RT "Expression of active domains of a human folate-dependent trifunctional
RT enzyme in Escherichia coli.";
RL Protein Eng. 4:493-500(1991).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, 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., 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 [12]
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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, 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., Meinnel T.,
RA 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 [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, 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., 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).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-318; SER-413 AND SER-490, AND
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 [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [17] {ECO:0007744|PDB:1A4I}
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-302 IN COMPLEX WITH NADP.
RX PubMed=9519408; DOI=10.1016/s0969-2126(98)00019-7;
RA Allaire M., Li Y., Mackenzie R.E., Cygler M.;
RT "The 3-D structure of a folate-dependent dehydrogenase/cyclohydrolase
RT bifunctional enzyme at 1.5-A resolution.";
RL Structure 6:173-182(1998).
RN [18] {ECO:0007744|PDB:1DIA, ECO:0007744|PDB:1DIB, ECO:0007744|PDB:1DIG}
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-306 IN COMPLEX WITH NADP AND
RP SUBSTRATE ANALOGS, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBUNIT, ACTIVE
RP SITE, AND MUTAGENESIS OF SER-49; TYR-52; LYS-56 AND CYS-147.
RX PubMed=10828945; DOI=10.1021/bi992734y;
RA Schmidt A., Wu H., MacKenzie R.E., Chen V.J., Bewly J.R., Ray J.E.,
RA Toth J.E., Cygler M.;
RT "Structures of three inhibitor complexes provide insight into the reaction
RT mechanism of the human methylenetetrahydrofolate
RT dehydrogenase/cyclohydrolase.";
RL Biochemistry 39:6325-6335(2000).
RN [19]
RP INVOLVEMENT IN SUSCEPTIBILITY TO NTDFS, AND VARIANTS NTDFS HIS-293 AND
RP GLN-653.
RX PubMed=9611072; DOI=10.1111/j.1399-0004.1998.tb02658.x;
RA Hol F.A., van der Put N.M.J., Geurds M.P.A., Heil S.G., Trijbels F.J.M.,
RA Hamel B.C.J., Mariman E.C.M., Blom H.J.;
RT "Molecular genetic analysis of the gene encoding the trifunctional enzyme
RT MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-
RT cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural
RT tube defects.";
RL Clin. Genet. 53:119-125(1998).
RN [20]
RP INVOLVEMENT IN SUSCEPTIBILITY TO NTDFS, AND VARIANT NTDFS GLN-653.
RX PubMed=12384833; DOI=10.1086/344213;
RA Brody L.C., Conley M., Cox C., Kirke P.N., McKeever M.P., Mills J.L.,
RA Molloy A.M., O'Leary V.B., Parle-McDermott A., Scott J.M., Swanson D.A.;
RT "A polymorphism, R653Q, in the trifunctional enzyme
RT methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate
RT cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk
RT factor for neural tube defects: report of the Birth Defects Research
RT Group.";
RL Am. J. Hum. Genet. 71:1207-1215(2002).
RN [21]
RP INVOLVEMENT IN SUSCEPTIBILITY TO NTDFS, AND VARIANT NTDFS GLN-653.
RX PubMed=16552426; DOI=10.1038/sj.ejhg.5201603;
RA Parle-McDermott A., Kirke P.N., Mills J.L., Molloy A.M., Cox C.,
RA O'Leary V.B., Pangilinan F., Conley M., Cleary L., Brody L.C., Scott J.M.;
RT "Confirmation of the R653Q polymorphism of the trifunctional C1-synthase
RT enzyme as a maternal risk for neural tube defects in the Irish
RT population.";
RL Eur. J. Hum. Genet. 14:768-772(2006).
RN [22]
RP ASSOCIATION WITH COLORECTAL CANCER SUSCEPTIBILITY.
RX PubMed=17000706; DOI=10.1093/hmg/ddl401;
RA Webb E.L., Rudd M.F., Sellick G.S., El Galta R., Bethke L., Wood W.,
RA Fletcher O., Penegar S., Withey L., Qureshi M., Johnson N., Tomlinson I.,
RA Gray R., Peto J., Houlston R.S.;
RT "Search for low penetrance alleles for colorectal cancer through a scan of
RT 1467 non-synonymous SNPs in 2575 cases and 2707 controls with validation by
RT kin-cohort analysis of 14 704 first-degree relatives.";
RL Hum. Mol. Genet. 15:3263-3271(2006).
RN [23]
RP CHARACTERIZATION OF VARIANT GLN-653, ASSOCIATION WITH RISK OF CONGENITAL
RP HEART DEFECTS, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP AND PATHWAY.
RX PubMed=18767138; DOI=10.1002/humu.20830;
RA Christensen K.E., Rohlicek C.V., Andelfinger G.U., Michaud J.,
RA Bigras J.-L., Richter A., Mackenzie R.E., Rozen R.;
RT "The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk
RT for congenital heart defects.";
RL Hum. Mutat. 30:212-220(2009).
RN [24]
RP INVOLVEMENT IN CIMAH, AND VARIANT CIMAH CYS-173.
RX PubMed=21813566; DOI=10.1136/jmedgenet-2011-100286;
RA Watkins D., Schwartzentruber J.A., Ganesh J., Orange J.S., Kaplan B.S.,
RA Nunez L.D., Majewski J., Rosenblatt D.S.;
RT "Novel inborn error of folate metabolism: identification by exome capture
RT and sequencing of mutations in the MTHFD1 gene in a single proband.";
RL J. Med. Genet. 48:590-592(2011).
RN [25]
RP INVOLVEMENT IN CIMAH, VARIANTS CIMAH PHE-49; 225-GLU--PHE-935 DEL AND
RP ILE-269, AND FUNCTION.
RX PubMed=25633902; DOI=10.1007/s10545-015-9810-3;
RA Burda P., Kuster A., Hjalmarson O., Suormala T., Buerer C., Lutz S.,
RA Roussey G., Christa L., Asin-Cayuela J., Kollberg G., Andersson B.A.,
RA Watkins D., Rosenblatt D.S., Fowler B., Holme E., Froese D.S.,
RA Baumgartner M.R.;
RT "Characterization and review of MTHFD1 deficiency: four new patients,
RT cellular delineation and response to folic and folinic acid treatment.";
RL J. Inherit. Metab. Dis. 38:863-872(2015).
RN [26]
RP INVOLVEMENT IN CIMAH, AND VARIANT CIMAH PRO-51.
RX PubMed=27707659; DOI=10.1016/j.jaip.2016.07.014;
RA Ramakrishnan K.A., Pengelly R.J., Gao Y., Morgan M., Patel S.V.,
RA Davies E.G., Ennis S., Faust S.N., Williams A.P.;
RT "Precision molecular diagnosis defines specific therapy in Combined
RT Immunodeficiency with Megaloblastic Anemia Secondary to MTHFD1
RT deficiency.";
RL J. Allergy Clin. Immunol. Pract. 4:1160.E10-1166.E10(2016).
CC -!- FUNCTION: Trifunctional enzyme that catalyzes the interconversion of
CC three forms of one-carbon-substituted tetrahydrofolate: (6R)-5,10-
CC methylene-5,6,7,8-tetrahydrofolate, 5,10-methenyltetrahydrofolate and
CC (6S)-10-formyltetrahydrofolate (PubMed:1881876, PubMed:10828945,
CC PubMed:18767138). These derivatives of tetrahydrofolate are
CC differentially required in nucleotide and amino acid biosynthesis,
CC (6S)-10-formyltetrahydrofolate being required for purine biosynthesis
CC while (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate is used for serine
CC and methionine biosynthesis for instance (PubMed:25633902,
CC PubMed:18767138). {ECO:0000269|PubMed:10828945,
CC ECO:0000269|PubMed:18767138, ECO:0000269|PubMed:1881876,
CC ECO:0000269|PubMed:25633902}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADP(+) = 5,10-
CC 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:10828945,
CC ECO:0000269|PubMed:18767138, ECO:0000269|PubMed:1881876};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22813;
CC Evidence={ECO:0000305|PubMed:1881876};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5,10-methenyltetrahydrofolate + H2O = (6S)-10-
CC formyltetrahydrofolate + H(+); Xref=Rhea:RHEA:23700,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57454,
CC ChEBI:CHEBI:57455; EC=3.5.4.9; Evidence={ECO:0000269|PubMed:10828945,
CC ECO:0000269|PubMed:1881876};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolate + ATP + formate = (6S)-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:57454, ChEBI:CHEBI:456216; EC=6.3.4.3;
CC Evidence={ECO:0000269|PubMed:18767138, ECO:0000269|PubMed:1881876};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30.3 uM for ATP {ECO:0000269|PubMed:10828945};
CC KM=364 uM for (6S)-5,6,7,8-tetrahydrofolate
CC {ECO:0000269|PubMed:10828945};
CC KM=36.7 mM for formate {ECO:0000269|PubMed:10828945};
CC Vmax=13.2 umol/min/mg enzyme for the methylenetetrahydrofolate
CC dehydrogenase activity {ECO:0000269|PubMed:10828945};
CC Vmax=23.0 umol/min/mg enzyme for the formyltetrahydrofolate
CC synthetase activity {ECO:0000269|PubMed:10828945};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000269|PubMed:10828945, ECO:0000269|PubMed:18767138,
CC ECO:0000269|PubMed:1881876}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10828945}.
CC -!- INTERACTION:
CC P11586; Q9WMX2; Xeno; NbExp=3; IntAct=EBI-709638, EBI-710918;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:3053686}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DOMAIN: The N-terminal methylenetetrahydrofolate dehydrogenase and
CC methenyltetrahydrofolate cyclohydrolase (D/C) domain carries both the
CC methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate
CC cyclohydrolase activities. {ECO:0000269|PubMed:1881876}.
CC -!- DOMAIN: The larger C-terminal formyltetrahydrofolate synthetase domain
CC carries a third formyltetrahydrofolate synthetase activity.
CC {ECO:0000269|PubMed:1881876}.
CC -!- DISEASE: Neural tube defects, folate-sensitive (NTDFS) [MIM:601634]:
CC The most common NTDs are open spina bifida (myelomeningocele) and
CC anencephaly. {ECO:0000269|PubMed:12384833, ECO:0000269|PubMed:16552426,
CC ECO:0000269|PubMed:9611072}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease
CC characterized by malignant lesions arising from the inner wall of the
CC large intestine (the colon) and the rectum. Genetic alterations are
CC often associated with progression from premalignant lesion (adenoma) to
CC invasive adenocarcinoma. Risk factors for cancer of the colon and
CC rectum include colon polyps, long-standing ulcerative colitis, and
CC genetic family history. {ECO:0000269|PubMed:17000706}. Note=Disease
CC susceptibility may be associated with variants affecting the gene
CC represented in this entry. Susceptibility to colorectal cancer may be
CC associated with the missense variant p.Arg134Lys, which has been
CC observed in about 16% of the human population. The sequence shown in
CC this entry represents the minor allele, as it is reported in the
CC reference genome. {ECO:0000269|PubMed:17000706}.
CC -!- DISEASE: Combined immunodeficiency and megaloblastic anemia with or
CC without hyperhomocysteinemia (CIMAH) [MIM:617780]: An autosomal
CC recessive disorder due to an inborn error of folate metabolism.
CC Variable clinical manifestations include hemolytic uremic syndrome,
CC macrocytosis, epilepsy, hearing loss, retinopathy, mild intellectual
CC disability, and lymphopenia. {ECO:0000269|PubMed:21813566,
CC ECO:0000269|PubMed:25633902, ECO:0000269|PubMed:27707659}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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 formate--
CC tetrahydrofolate ligase family. {ECO:0000305}.
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DR EMBL; J04031; AAA59574.1; -; mRNA.
DR EMBL; AK312361; BAG35279.1; -; mRNA.
DR EMBL; GQ891332; ADO22194.1; -; mRNA.
DR EMBL; AL122035; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW80857.1; -; Genomic_DNA.
DR EMBL; CH471061; EAW80858.1; -; Genomic_DNA.
DR EMBL; BC001014; AAH01014.2; -; mRNA.
DR EMBL; BC009806; AAH09806.1; -; mRNA.
DR EMBL; BC050420; AAH50420.1; -; mRNA.
DR CCDS; CCDS9763.1; -.
DR PIR; A31903; A31903.
DR RefSeq; NP_005947.3; NM_005956.3.
DR PDB; 1A4I; X-ray; 1.50 A; A/B=1-301.
DR PDB; 1DIA; X-ray; 2.20 A; A/B=1-306.
DR PDB; 1DIB; X-ray; 2.70 A; A/B=1-306.
DR PDB; 1DIG; X-ray; 2.20 A; A/B=1-306.
DR PDB; 6ECP; X-ray; 2.20 A; A/B=1-306.
DR PDB; 6ECQ; X-ray; 2.70 A; A/B=1-296.
DR PDB; 6ECR; X-ray; 2.20 A; A/B=1-296.
DR PDBsum; 1A4I; -.
DR PDBsum; 1DIA; -.
DR PDBsum; 1DIB; -.
DR PDBsum; 1DIG; -.
DR PDBsum; 6ECP; -.
DR PDBsum; 6ECQ; -.
DR PDBsum; 6ECR; -.
DR AlphaFoldDB; P11586; -.
DR SMR; P11586; -.
DR BioGRID; 110622; 170.
DR DIP; DIP-33682N; -.
DR IntAct; P11586; 57.
DR MINT; P11586; -.
DR STRING; 9606.ENSP00000216605; -.
DR BindingDB; P11586; -.
DR ChEMBL; CHEMBL2541; -.
DR DrugBank; DB04322; LY249543.
DR DrugBank; DB02358; LY374571.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR DrugBank; DB00116; Tetrahydrofolic acid.
DR GlyGen; P11586; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P11586; -.
DR MetOSite; P11586; -.
DR PhosphoSitePlus; P11586; -.
DR SwissPalm; P11586; -.
DR BioMuta; MTHFD1; -.
DR DMDM; 115206; -.
DR REPRODUCTION-2DPAGE; IPI00218342; -.
DR SWISS-2DPAGE; P11586; -.
DR CPTAC; CPTAC-407; -.
DR CPTAC; CPTAC-408; -.
DR EPD; P11586; -.
DR jPOST; P11586; -.
DR MassIVE; P11586; -.
DR MaxQB; P11586; -.
DR PaxDb; P11586; -.
DR PeptideAtlas; P11586; -.
DR PRIDE; P11586; -.
DR ProteomicsDB; 32586; -.
DR ProteomicsDB; 52794; -.
DR ABCD; P11586; 1 sequenced antibody.
DR Antibodypedia; 52; 181 antibodies from 30 providers.
DR DNASU; 4522; -.
DR Ensembl; ENST00000651537.1; ENSP00000498511.1; ENSG00000100714.17.
DR Ensembl; ENST00000652337.1; ENSP00000498336.1; ENSG00000100714.17.
DR GeneID; 4522; -.
DR KEGG; hsa:4522; -.
DR MANE-Select; ENST00000652337.1; ENSP00000498336.1; NM_005956.4; NP_005947.3.
DR UCSC; uc001xhb.4; human.
DR CTD; 4522; -.
DR DisGeNET; 4522; -.
DR GeneCards; MTHFD1; -.
DR HGNC; HGNC:7432; MTHFD1.
DR MalaCards; MTHFD1; -.
DR MIM; 114500; phenotype.
DR MIM; 172460; gene+phenotype.
DR MIM; 601634; phenotype.
DR MIM; 617780; phenotype.
DR neXtProt; NX_P11586; -.
DR OpenTargets; ENSG00000100714; -.
DR Orphanet; 268392; Cervical spina bifida aperta.
DR Orphanet; 268762; Cervical spina bifida cystica.
DR Orphanet; 268397; Cervicothoracic spina bifida aperta.
DR Orphanet; 268766; Cervicothoracic spina bifida cystica.
DR Orphanet; 268388; Lumbosacral spina bifida aperta.
DR Orphanet; 268758; Lumbosacral spina bifida cystica.
DR Orphanet; 268384; Thoracolumbosacral spina bifida aperta.
DR Orphanet; 268752; Thoracolumbosacral spina bifida cystica.
DR Orphanet; 268377; Total spina bifida aperta.
DR Orphanet; 268748; Total spina bifida cystica.
DR Orphanet; 268740; Upper thoracic spina bifida aperta.
DR Orphanet; 268770; Upper thoracic spina bifida cystica.
DR PharmGKB; PA31236; -.
DR VEuPathDB; HostDB:ENSG00000100714; -.
DR eggNOG; KOG4230; Eukaryota.
DR GeneTree; ENSGT00940000154746; -.
DR HOGENOM; CLU_034045_3_0_1; -.
DR InParanoid; P11586; -.
DR OMA; KVDTYTK; -.
DR OrthoDB; 690393at2759; -.
DR PhylomeDB; P11586; -.
DR TreeFam; TF300623; -.
DR BioCyc; MetaCyc:HS02138-MON; -.
DR BRENDA; 1.5.1.5; 2681.
DR BRENDA; 3.5.4.9; 2681.
DR BRENDA; 6.3.3.2; 2681.
DR BRENDA; 6.3.4.3; 2681.
DR PathwayCommons; P11586; -.
DR Reactome; R-HSA-196757; Metabolism of folate and pterines.
DR SignaLink; P11586; -.
DR SIGNOR; P11586; -.
DR UniPathway; UPA00193; -.
DR BioGRID-ORCS; 4522; 192 hits in 1089 CRISPR screens.
DR ChiTaRS; MTHFD1; human.
DR EvolutionaryTrace; P11586; -.
DR GeneWiki; MTHFD1; -.
DR GenomeRNAi; 4522; -.
DR Pharos; P11586; Tchem.
DR PRO; PR:P11586; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P11586; protein.
DR Bgee; ENSG00000100714; Expressed in right lobe of liver and 200 other tissues.
DR ExpressionAtlas; P11586; baseline and differential.
DR Genevisible; P11586; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004329; F:formate-tetrahydrofolate ligase activity; IDA:UniProtKB.
DR GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; IDA:UniProtKB.
DR GO; GO:0004487; F:methylenetetrahydrofolate dehydrogenase (NAD+) activity; ISS:BHF-UCL.
DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IDA:UniProtKB.
DR GO; GO:0004486; F:methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity; IDA:BHF-UCL.
DR GO; GO:0009257; P:10-formyltetrahydrofolate biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; ISS:BHF-UCL.
DR GO; GO:0048703; P:embryonic viscerocranium morphogenesis; ISS:BHF-UCL.
DR GO; GO:0007507; P:heart development; ISS:BHF-UCL.
DR GO; GO:0000105; P:histidine biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009086; P:methionine biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0006555; P:methionine metabolic process; ISS:BHF-UCL.
DR GO; GO:0001843; P:neural tube closure; ISS:BHF-UCL.
DR GO; GO:0001780; P:neutrophil homeostasis; IEA:Ensembl.
DR GO; GO:0006730; P:one-carbon metabolic process; IMP:BHF-UCL.
DR GO; GO:0006164; P:purine nucleotide biosynthetic process; IMP:UniProtKB.
DR GO; GO:0009152; P:purine ribonucleotide biosynthetic process; IEA:Ensembl.
DR GO; GO:0009070; P:serine family amino acid biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0009069; P:serine family amino acid metabolic process; ISS:BHF-UCL.
DR GO; GO:0061053; P:somite development; ISS:BHF-UCL.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IDA:UniProtKB.
DR GO; GO:0019346; P:transsulfuration; IEA:Ensembl.
DR CDD; cd00477; FTHFS; 1.
DR CDD; cd01080; NAD_bind_m-THF_DH_Cyclohyd; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR HAMAP; MF_01543; FTHFS; 1.
DR HAMAP; MF_01576; THF_DHG_CYH; 1.
DR InterPro; IPR046346; Aminiacid_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 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; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF53223; SSF53223; 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 3D-structure; Acetylation; Amino-acid biosynthesis; ATP-binding; Cytoplasm;
KW Direct protein sequencing; Disease variant; Histidine biosynthesis;
KW Hydrolase; Ligase; Methionine biosynthesis; Multifunctional enzyme; NADP;
KW Nucleotide-binding; One-carbon metabolism; Oxidoreductase; Phosphoprotein;
KW Purine biosynthesis; Reference proteome.
FT CHAIN 1..935
FT /note="C-1-tetrahydrofolate synthase, cytoplasmic"
FT /id="PRO_0000423280"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0000269|PubMed:3053686, ECO:0000269|Ref.8"
FT CHAIN 2..935
FT /note="C-1-tetrahydrofolate synthase, cytoplasmic, N-
FT terminally processed"
FT /id="PRO_0000199321"
FT REGION 2..291
FT /note="Methylenetetrahydrofolate dehydrogenase and
FT methenyltetrahydrofolate cyclohydrolase (D/C) domain"
FT /evidence="ECO:0000269|PubMed:1881876"
FT REGION 310..935
FT /note="Formyltetrahydrofolate synthetase domain"
FT /evidence="ECO:0000269|PubMed:1881876"
FT ACT_SITE 56
FT /evidence="ECO:0000269|PubMed:10828945"
FT BINDING 52..56
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10828945,
FT ECO:0007744|PDB:1DIA, ECO:0007744|PDB:1DIB"
FT BINDING 99..101
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10828945,
FT ECO:0007744|PDB:1DIA, ECO:0007744|PDB:1DIB"
FT BINDING 172..174
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10828945,
FT ECO:0000269|PubMed:9519408, ECO:0007744|PDB:1A4I,
FT ECO:0007744|PDB:1DIA, ECO:0007744|PDB:1DIB,
FT ECO:0007744|PDB:1DIG"
FT BINDING 197
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10828945,
FT ECO:0000269|PubMed:9519408, ECO:0007744|PDB:1A4I,
FT ECO:0007744|PDB:1DIA, ECO:0007744|PDB:1DIB,
FT ECO:0007744|PDB:1DIG"
FT BINDING 272..276
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10828945,
FT ECO:0007744|PDB:1DIA, ECO:0007744|PDB:1DIB"
FT BINDING 380..387
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 49
FT /note="S -> F (in CIMAH; dbSNP:rs370444838)"
FT /evidence="ECO:0000269|PubMed:25633902"
FT /id="VAR_074075"
FT VARIANT 51
FT /note="L -> P (in CIMAH; dbSNP:rs1555336810)"
FT /evidence="ECO:0000269|PubMed:27707659"
FT /id="VAR_080873"
FT VARIANT 134
FT /note="K -> R (in dbSNP:rs1950902)"
FT /id="VAR_016232"
FT VARIANT 162
FT /note="P -> L (in dbSNP:rs4902283)"
FT /id="VAR_055458"
FT VARIANT 173
FT /note="R -> C (in CIMAH; dbSNP:rs141210410)"
FT /evidence="ECO:0000269|PubMed:21813566"
FT /id="VAR_074076"
FT VARIANT 225..935
FT /note="Missing (in CIMAH)"
FT /evidence="ECO:0000269|PubMed:25633902"
FT /id="VAR_080874"
FT VARIANT 269
FT /note="T -> I (in CIMAH; dbSNP:rs771978838)"
FT /evidence="ECO:0000269|PubMed:25633902"
FT /id="VAR_074077"
FT VARIANT 293
FT /note="R -> H (in NTDFS; associated with disease
FT susceptibility; dbSNP:rs34181110)"
FT /id="VAR_010241"
FT VARIANT 653
FT /note="R -> Q (in NTDFS; associated with disease
FT susceptibility; increases risk for congenital heart
FT defects; decreased enzyme stability; no effect on
FT methylenetetrahydrofolate dehydrogenase (NADP+) activity;
FT no effect on formyltetrahydrofolate synthetase activity;
FT dbSNP:rs2236225)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:18767138,
FT ECO:0000269|PubMed:9611072, ECO:0000269|Ref.5"
FT /id="VAR_010251"
FT VARIANT 761
FT /note="T -> M (in dbSNP:rs10813)"
FT /id="VAR_032789"
FT VARIANT 769
FT /note="L -> F (in dbSNP:rs17857382)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_032790"
FT MUTAGEN 49
FT /note="S->A: No effect on methylenetetrahydrofolate
FT dehydrogenase (NADP+) activity. No effect on
FT methenyltetrahydrofolate cyclohydrolase activity. Decreased
FT affinity for NADP."
FT /evidence="ECO:0000269|PubMed:10828945"
FT MUTAGEN 49
FT /note="S->Q: Reduced methylenetetrahydrofolate
FT dehydrogenase (NADP+) activity by 75%. Reduced
FT methenyltetrahydrofolate cyclohydrolase activity by 99%. No
FT effect on affinity for NADP and 5,10-
FT methenyltetrahydrofolate."
FT /evidence="ECO:0000269|PubMed:10828945"
FT MUTAGEN 52
FT /note="Y->A,S: Reduced methylenetetrahydrofolate
FT dehydrogenase (NADP+) activity by 99%. Reduced
FT methenyltetrahydrofolate cyclohydrolase activity by 70%. No
FT effect on affinity for NADP and 5,10-
FT methenyltetrahydrofolate."
FT /evidence="ECO:0000269|PubMed:10828945"
FT MUTAGEN 52
FT /note="Y->F: Slightly reduced methylenetetrahydrofolate
FT dehydrogenase (NADP+) activity. Slightly reduced
FT methenyltetrahydrofolate cyclohydrolase activity. Decreased
FT affinity for NADP and for 5,10-methenyltetrahydrofolate."
FT /evidence="ECO:0000269|PubMed:10828945"
FT MUTAGEN 56
FT /note="K->A,I,S,T: Decreased methylenetetrahydrofolate
FT dehydrogenase (NADP+) activity over 90%. Loss of
FT methenyltetrahydrofolate cyclohydrolase activity."
FT /evidence="ECO:0000269|PubMed:10828945"
FT MUTAGEN 56
FT /note="K->E,M,Q: Moderate decrease of
FT methylenetetrahydrofolate dehydrogenase (NADP+) activity.
FT Loss of methenyltetrahydrofolate cyclohydrolase activity.
FT Strongly decreased affinity for NADP. Increased affinity
FT for 5,10-methenyltetrahydrofolate."
FT /evidence="ECO:0000269|PubMed:10828945"
FT MUTAGEN 56
FT /note="K->R: Reduced methylenetetrahydrofolate
FT dehydrogenase (NADP+) activity. Reduced
FT methenyltetrahydrofolate cyclohydrolase activity by 99%. No
FT effect on affinity for NADP and 5,10-
FT methenyltetrahydrofolate."
FT /evidence="ECO:0000269|PubMed:10828945"
FT MUTAGEN 147
FT /note="C->Q: Reduced methylenetetrahydrofolate
FT dehydrogenase (NADP+) activity by 50%. Reduced
FT methenyltetrahydrofolate cyclohydrolase activity by 87%."
FT /evidence="ECO:0000269|PubMed:10828945"
FT HELIX 9..30
FT /evidence="ECO:0007829|PDB:1A4I"
FT STRAND 37..44
FT /evidence="ECO:0007829|PDB:1A4I"
FT HELIX 47..63
FT /evidence="ECO:0007829|PDB:1A4I"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:1A4I"
FT HELIX 78..90
FT /evidence="ECO:0007829|PDB:1A4I"
FT STRAND 96..99
FT /evidence="ECO:0007829|PDB:1A4I"
FT HELIX 111..116
FT /evidence="ECO:0007829|PDB:1A4I"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:1A4I"
FT HELIX 129..136
FT /evidence="ECO:0007829|PDB:1A4I"
FT HELIX 147..157
FT /evidence="ECO:0007829|PDB:1A4I"
FT TURN 158..160
FT /evidence="ECO:0007829|PDB:1A4I"
FT STRAND 167..171
FT /evidence="ECO:0007829|PDB:1A4I"
FT TURN 175..177
FT /evidence="ECO:0007829|PDB:1A4I"
FT HELIX 178..187
FT /evidence="ECO:0007829|PDB:1A4I"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:1A4I"
FT HELIX 202..206
FT /evidence="ECO:0007829|PDB:1A4I"
FT STRAND 210..214
FT /evidence="ECO:0007829|PDB:1A4I"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:1A4I"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:1A4I"
FT HELIX 258..261
FT /evidence="ECO:0007829|PDB:1A4I"
FT TURN 262..264
FT /evidence="ECO:0007829|PDB:1A4I"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:1A4I"
FT STRAND 271..274
FT /evidence="ECO:0007829|PDB:1A4I"
FT HELIX 275..295
FT /evidence="ECO:0007829|PDB:1A4I"
SQ SEQUENCE 935 AA; 101531 MW; B834DB504BC1869A CRC64;
MAPAEILNGK EISAQIRARL KNQVTQLKEQ VPGFTPRLAI LQVGNRDDSN LYINVKLKAA
EEIGIKATHI KLPRTTTESE VMKYITSLNE DSTVHGFLVQ LPLDSENSIN TEEVINAIAP
EKDVDGLTSI NAGKLARGDL NDCFIPCTPK GCLELIKETG VPIAGRHAVV VGRSKIVGAP
MHDLLLWNNA TVTTCHSKTA HLDEEVNKGD ILVVATGQPE MVKGEWIKPG AIVIDCGINY
VPDDKKPNGR KVVGDVAYDE AKERASFITP VPGGVGPMTV AMLMQSTVES AKRFLEKFKP
GKWMIQYNNL NLKTPVPSDI DISRSCKPKP IGKLAREIGL LSEEVELYGE TKAKVLLSAL
ERLKHRPDGK YVVVTGITPT PLGEGKSTTT IGLVQALGAH LYQNVFACVR QPSQGPTFGI
KGGAAGGGYS QVIPMEEFNL HLTGDIHAIT AANNLVAAAI DARIFHELTQ TDKALFNRLV
PSVNGVRRFS DIQIRRLKRL GIEKTDPTTL TDEEINRFAR LDIDPETITW QRVLDTNDRF
LRKITIGQAP TEKGHTRTAQ FDISVASEIM AVLALTTSLE DMRERLGKMV VASSKKGEPV
SAEDLGVSGA LTVLMKDAIK PNLMQTLEGT PVFVHAGPFA NIAHGNSSII ADRIALKLVG
PEGFVVTEAG FGADIGMEKF FNIKCRYSGL CPHVVVLVAT VRALKMHGGG PTVTAGLPLP
KAYIQENLEL VEKGFSNLKK QIENARMFGI PVVVAVNAFK TDTESELDLI SRLSREHGAF
DAVKCTHWAE GGKGALALAQ AVQRAAQAPS SFQLLYDLKL PVEDKIRIIA QKIYGADDIE
LLPEAQHKAE VYTKQGFGNL PICMAKTHLS LSHNPEQKGV PTGFILPIRD IRASVGAGFL
YPLVGTMSTM PGLPTRPCFY DIDLDPETEQ VNGLF
