C1TM_BOVIN
ID C1TM_BOVIN Reviewed; 975 AA.
AC Q0VCR7; A6QNK9;
DT 01-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Monofunctional C1-tetrahydrofolate synthase, mitochondrial {ECO:0000305};
DE EC=6.3.4.3 {ECO:0000250|UniProtKB:Q6UB35};
DE AltName: Full=Formyltetrahydrofolate synthetase;
DE Flags: Precursor;
GN Name=MTHFD1L;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal liver, and Thymus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: May provide the missing metabolic reaction required to link
CC the mitochondria and the cytoplasm in the mammalian model of one-carbon
CC folate metabolism complementing thus the enzymatic activities of
CC MTHFD2. {ECO:0000250|UniProtKB:Q6UB35}.
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:Q6UB35};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20222;
CC Evidence={ECO:0000250|UniProtKB:Q6UB35};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000250|UniProtKB:Q6UB35}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q6UB35}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q6UB35}.
CC -!- DOMAIN: This monofunctional enzyme consists of two major domains: an N-
CC terminal inactive methylene-THF dehydrogenase and cyclohydrolase domain
CC and an active larger formyl-THF synthetase C-terminal domain.
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; BC120038; AAI20039.1; -; mRNA.
DR EMBL; BC148878; AAI48879.1; -; mRNA.
DR RefSeq; NP_001069486.1; NM_001076018.2.
DR AlphaFoldDB; Q0VCR7; -.
DR SMR; Q0VCR7; -.
DR STRING; 9913.ENSBTAP00000052260; -.
DR PaxDb; Q0VCR7; -.
DR PeptideAtlas; Q0VCR7; -.
DR PRIDE; Q0VCR7; -.
DR Ensembl; ENSBTAT00000052076; ENSBTAP00000052260; ENSBTAG00000009846.
DR GeneID; 534296; -.
DR KEGG; bta:534296; -.
DR CTD; 25902; -.
DR VEuPathDB; HostDB:ENSBTAG00000009846; -.
DR VGNC; VGNC:53798; MTHFD1L.
DR eggNOG; KOG4230; Eukaryota.
DR GeneTree; ENSGT00940000157477; -.
DR InParanoid; Q0VCR7; -.
DR OMA; CGEIMTM; -.
DR OrthoDB; 690393at2759; -.
DR UniPathway; UPA00193; -.
DR Proteomes; UP000009136; Chromosome 9.
DR Bgee; ENSBTAG00000009846; Expressed in corpus epididymis and 105 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004329; F:formate-tetrahydrofolate ligase activity; IEA:UniProtKB-EC.
DR GO; GO:0004488; F:methylenetetrahydrofolate dehydrogenase (NADP+) activity; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0009257; P:10-formyltetrahydrofolate biosynthetic process; IEA:Ensembl.
DR GO; GO:0048702; P:embryonic neurocranium morphogenesis; IEA:Ensembl.
DR GO; GO:0048703; P:embryonic viscerocranium morphogenesis; IEA:Ensembl.
DR GO; GO:0015942; P:formate metabolic process; IEA:Ensembl.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
DR CDD; cd00477; FTHFS; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR HAMAP; MF_01543; FTHFS; 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; 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.
PE 2: Evidence at transcript level;
KW Acetylation; ATP-binding; Ligase; Mitochondrion; Nucleotide-binding;
KW One-carbon metabolism; Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..30
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:Q6UB35"
FT CHAIN 31..975
FT /note="Monofunctional C1-tetrahydrofolate synthase,
FT mitochondrial"
FT /id="PRO_0000343176"
FT REGION 13..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 31..345
FT /note="Methylenetetrahydrofolate dehydrogenase and
FT cyclohydrolase"
FT REGION 346..975
FT /note="Formyltetrahydrofolate synthetase"
FT BINDING 420..427
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 187
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q6UB35"
FT MOD_RES 187
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3V3R1"
FT MOD_RES 354
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6UB35"
FT MOD_RES 593
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3V3R1"
FT CONFLICT 195
FT /note="E -> G (in Ref. 1; AAI20039)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 975 AA; 105227 MW; 4B7D0B35164A580B CRC64;
MSARLPFVLR RLARPQHPGS PRRLPSLCRA SSGRGSGCGG GEGLLGQQRL RDTQAGSSRG
PGSPAPPARD SIVREVIQNS KEVLSLLQEK TPTFKPVLAI IQAGDDNLMQ EVNQNLAEEA
GLNITHICLP AESGEDEIID EILKINEDSR VHGLALQIAE TSFSNKILNA LKPEKDVDGL
TDVNLGKLVR GDAHECFISP VARAVIELLE KSGVSLDGKK ILVIGAHGSL EATLQCLFQR
KGSMTMSSQW KTPQLQGKLQ EADIVVLGSP KPEEIPLSWI QPGTTVFNCS HDFLSGKAAC
ISSGVHGISP IAEDVSLLAA ALRIQNMVSS GRRWLREQQH RRWRLHCLKL QPLSPVPSDI
EISRAQTPKA VEILAKEIGL LADEIEIYGK SKAKVRLSLL ERLKDQADGK YVLVAGITPT
PLGEGKSTVT IGLVQALTAH LNVNSFACLR QPSQGPTFGV KGGAAGGGYA QVIPMEEFNL
HLTGDIHAIT AANNLLAAAI DARILHENTQ TDKALYNRLV PSVNGVREFS KIQLARLKRL
GINKTDPSAL TEEEMRKFAR LDIDPSTITW QRVVDTNDRF LRKITIGQAN TEKGCSRQAQ
FDIAVASEIM AVLALTDSLS DMKERLGRMV VASDRNGQPV TADDLGVTGA LTVLMKDAIK
PNLMQTLEGT PVFVHAGPFA NIAHGNSSVL ADKIALKLVG EGGFVVTEAG FGADIGMEKF
FNIKCRASGL VPSVVVLVAT VRALKMHGGG PSVTAGVPLR KEYTEENLQL VADGCCNLEK
QIQIAQLFGV PVVVALNVFK TDTRAEIDLV CELAKRAGAF NAVPCYHWSI GGKGSVDLAW
AVREAASKES RFQFLYDVQL PIVEKIRTIA QSVYGAKDIE LSPEAQSKID RYTEQGFGNL
PICMAKTHLS LSHQPDKKGV PKGFILPISD VRASIGAGFI YPLVGTMSTM PGLPTRPCFY
DIDLDTETEQ VKGLF
