C1TC_PONAB
ID C1TC_PONAB Reviewed; 935 AA.
AC Q5R8P0;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=C-1-tetrahydrofolate synthase, cytoplasmic {ECO:0000250|UniProtKB:P11586};
DE Short=C1-THF synthase;
DE Includes:
DE RecName: Full=Methylenetetrahydrofolate dehydrogenase {ECO:0000250|UniProtKB:P11586};
DE EC=1.5.1.5 {ECO:0000250|UniProtKB:P11586};
DE Includes:
DE RecName: Full=Methenyltetrahydrofolate cyclohydrolase {ECO:0000250|UniProtKB:P11586};
DE EC=3.5.4.9 {ECO:0000250|UniProtKB:P11586};
DE Includes:
DE RecName: Full=Formyltetrahydrofolate synthetase {ECO:0000250|UniProtKB:P11586};
DE EC=6.3.4.3 {ECO:0000250|UniProtKB:P11586};
GN Name=MTHFD1;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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. These derivatives of tetrahydrofolate
CC are 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.
CC {ECO:0000250|UniProtKB:P11586}.
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;
CC Evidence={ECO:0000250|UniProtKB:P11586};
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;
CC Evidence={ECO:0000250|UniProtKB:P11586};
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:0000250|UniProtKB:P11586};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000250|UniProtKB:P11586}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P11586}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P11586}.
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:0000250|UniProtKB:P11586}.
CC -!- DOMAIN: The larger C-terminal formyltetrahydrofolate synthetase domain
CC carries a third formyltetrahydrofolate synthetase activity.
CC {ECO:0000250|UniProtKB:P11586}.
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; CR859711; CAH91870.1; -; mRNA.
DR RefSeq; NP_001126083.1; NM_001132611.1.
DR AlphaFoldDB; Q5R8P0; -.
DR SMR; Q5R8P0; -.
DR STRING; 9601.ENSPPYP00000006705; -.
DR GeneID; 100173036; -.
DR KEGG; pon:100173036; -.
DR CTD; 4522; -.
DR eggNOG; KOG4230; Eukaryota.
DR InParanoid; Q5R8P0; -.
DR OrthoDB; 690393at2759; -.
DR UniPathway; UPA00193; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004329; F:formate-tetrahydrofolate ligase activity; ISS:UniProtKB.
DR GO; GO:0004477; F:methenyltetrahydrofolate cyclohydrolase activity; ISS:UniProtKB.
DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; ISS:UniProtKB.
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:0006164; P:purine nucleotide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Acetylation; Amino-acid biosynthesis; ATP-binding; Cytoplasm;
KW Histidine biosynthesis; Hydrolase; Ligase; Methionine biosynthesis;
KW Multifunctional enzyme; NADP; Nucleotide-binding; One-carbon metabolism;
KW Oxidoreductase; Phosphoprotein; Purine biosynthesis; Reference proteome.
FT CHAIN 1..935
FT /note="C-1-tetrahydrofolate synthase, cytoplasmic"
FT /id="PRO_0000265955"
FT REGION 2..291
FT /note="Methylenetetrahydrofolate dehydrogenase and
FT methenyltetrahydrofolate cyclohydrolase (D/C) domain"
FT /evidence="ECO:0000250|UniProtKB:P11586"
FT REGION 310..935
FT /note="Formyltetrahydrofolate synthetase domain"
FT /evidence="ECO:0000250|UniProtKB:P11586"
FT ACT_SITE 56
FT /evidence="ECO:0000250|UniProtKB:P11586"
FT BINDING 52..56
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11586"
FT BINDING 99..101
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11586"
FT BINDING 172..174
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P11586"
FT BINDING 197
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P11586"
FT BINDING 272..276
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11586"
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:0000250|UniProtKB:P11586"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11586"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11586"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11586"
SQ SEQUENCE 935 AA; 101341 MW; 4D98F58C5A908632 CRC64;
MAPAEILNGR EISAQIRARL KNQVTQLKEQ VPGFTPGLAI LLVGNRDDSN LYINVKLKAA
EEIGIKATHI KLPRTTTESE VIKYITSLNE DSTVHGFLVQ LPLDSENSIN TEEVINAIAP
EKDVDGLTSI SAGKLARGDL NDCFIPCTPK GCLELIKETG VPIAGRHAVV VGRSKIVGAP
MHDLLLWNNA TVTTCHSKTA NLDEEVNKGD ILVVATGRPE MVKGEWIKPG AIVIDCGINY
VPDDKKPNGR KVVGDVAYDE AKERASFITP VPGGVGPMTV AMLMQSTVES AKRFLEKFKP
GKWMIQYNNL NLKTPDPSDI DISRSCKPKP IGKLAREIGL LSEEVELYGE TKAKVLLSAL
ERLKHRPDGK YVVVTGITPT PLGEGKSTTT VGLVQALGAH LYQNVFACVR QPSQGPTFGI
KGGAAGGGYS QVIPMEEFNL HLTGDIHAFT AANNLVAAAI DARIFHELTQ TDKALFNRLV
PSVNGVRKFS DIQIRRLKRL GIEKTDPTTL TDEEINRFAR LDIDPETITW QRVLDTNDRF
LRKITIGQAP TEKGHTRTAQ FDISVASEIM AALALTTSLE DMRERLGKMV VASSKKGEPV
SAEDLGVSGA LTVLMKDAIK PNLMQTLEGT PVFVHAGPFA NIAHGNSSII ADRIALKLVG
PEGFVVTEAG FGADIGMEKF FNIKCRYSGL CPHVVVLVAT VRALKMHGGG PTVTAGLPLP
KAYIEENLEL VEKGFSNLKK QIENARMFGI PVVVAVNAFK TDTEAELDLI SRLSREHGAF
DAVKCTHWAE GGNGALALAQ AVQRAAQAPS SFQLLYDLKL PVEDKIRIIA QKIYGADDIE
LLPEAQHKAE VYTKQGFGNL PVCMAKTHLS LSHNPEQKGV PTGFILPIRD IRASVGAGFL
YPLVGTMSTM PGLPTRPCFY DIDLDPETQQ VNGLF
