P27653 (C1TC_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-1-tetrahydrofolate synthase, cytoplasmic
Short name=C1-THF synthase

Including the following 3 domains:

1. Methylenetetrahydrofolate dehydrogenase
   EC=1.5.1.5
2. Methenyltetrahydrofolate cyclohydrolase
   EC=3.5.4.9
3. Formyltetrahydrofolate synthetase
   EC=6.3.4.3

Gene names

Name:	Mthfd1
Synonyms:	Mthfd

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	935 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	5,10-methylenetetrahydrofolate + NADP+ = 5,10-methenyltetrahydrofolate + NADPH. 5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate. ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate.
Pathway	One-carbon metabolism; tetrahydrofolate interconversion.
Subunit structure	Homodimer.
Subcellular location	Cytoplasm.
Domain	This trifunctional enzyme consists of two major domains: an N-terminal part containing the methylene-THF dehydrogenase and cyclohydrolase activities and a larger C-terminal part containing formyl-THF synthetase activity.
Sequence similarities	In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family. In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Histidine biosynthesis Methionine biosynthesis One-carbon metabolism Purine biosynthesis
Cellular component	Cytoplasm
Ligand	ATP-binding NADP Nucleotide-binding
Molecular function	Hydrolase Ligase Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	folic acid-containing compound biosynthetic process Inferred from electronic annotation. Source: InterPro histidine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW methionine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW one-carbon metabolic process Inferred from expression pattern. Source: RGD purine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW tetrahydrofolate metabolic process Traceable author statement Ref.1. Source: RGD
Cellular component	cytoplasm Traceable author statement Ref.1. Source: RGD
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW formate-tetrahydrofolate ligase activity Traceable author statement Ref.1. Source: RGD methenyltetrahydrofolate cyclohydrolase activity Traceable author statement Ref.1. Source: RGD methylenetetrahydrofolate dehydrogenase (NADP+) activity Inferred from electronic annotation. Source: EC methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity Traceable author statement Ref.1. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 935	934	C-1-tetrahydrofolate synthase, cytoplasmic		PRO_0000199323
Regions
	Nucleotide binding	172 – 174	3	NADP By similarity
	Nucleotide binding	380 – 387	8	ATP By similarity
	Region	2 – 305	304	Methylenetetrahydrofolate dehydrogenase and cyclohydrolase
	Region	52 – 56	5	Substrate binding By similarity
	Region	99 – 101	3	Substrate binding By similarity
	Region	272 – 276	5	Substrate binding By similarity
	Region	306 – 935	630	Formyltetrahydrofolate synthetase
Sites
	Binding site	197	1	NADP By similarity
Amino acid modifications
	Modified residue	553	1	N6-acetyllysine By similarity
	Modified residue	786	1	Phosphothreonine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P27653 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 6E42A56C10A4059E	FASTA	935	100,996
	10 20 30 40 50 60 MAPAGILNGK VVSAQIRNRL KTQVTQMQEQ VPGFTPGLAI LQVGDRDDSN LYINVKLKAA 70 80 90 100 110 120 QEIGIKATHI KLPRTSTESE VLKYVISLNE DATVHGFIVQ LPLDSENSIN TEAVINAIAP 130 140 150 160 170 180 EKDVDGLTSI NAGKLARGDL KDCFIPCTPK GCLELIKETG VQIAGRHAVV VGRSKIVGAP 190 200 210 220 230 240 MHDLLLWNNA TVTTCHSKTA DLDKEVNKGD ILVVATGQPE MVKGEWIKPG AVVIDCGINY 250 260 270 280 290 300 VPDDTKPNGR KVVGDVAYDE AKEKASFITP VPGGVGPMTV AMLMQSTVES AQRFLKKFKP 310 320 330 340 350 360 GKWTIQYNKL NLKTPVPSDI AISRSCKPKL IGNLAREIGL LTEEVELYGE TKAKVLLSAL 370 380 390 400 410 420 DRLKHQPDGK YVVVTGITPT PLGEGKSTTT IGLVQALGAH LHQNVFACVR QPSQGPTFGI 430 440 450 460 470 480 KGGAAGGGYS QVIPMEEFNL HLTGDIHAIT AANNLVAAAI DARIFHELTQ TDKALFNRLV 490 500 510 520 530 540 PSVNGVRKFS DIQIRRLRRL GIEKTDPAAL TDDEINRFAR LDIDPETITW QRVLDTNDRF 550 560 570 580 590 600 LRKITIGQAP TEKGHTRTAQ FDISVASEIM AVLALTSSLE DMRARLGKMV VASSKKGEPI 610 620 630 640 650 660 SCEDLGVSGA LTVLMKDAIK PNLMQTLEGT PVFVHAGPFA NIAHGNSSII ADRIALKLVG 670 680 690 700 710 720 PEGFVVTEAG FGADIGMEKF FNIKCRYSGL QPHVVVLVAT VRALKMHGGG PTVTAGLPLP 730 740 750 760 770 780 KAYTEEDLDL VEKGFSNLRK QIENARMFGV PVVVAMNAFK TDTDTELDLI GRLSREHGAF 790 800 810 820 830 840 DAVKCTHWAE GGQGALALAQ AVQRASQAPS SFQLLYDLKL SVEDKIRIIA QKIYGADDIE 850 860 870 880 890 900 LLPEAQNKAE IYTKQGFGNL PICMAKTHLS LSHNPEQKGV PTGFVLPIRD IRASVGAGFL 910 920 930 YPLVGTMSTM PGLPTRPCFY DIDLDPETEQ VNGLF

References

[1]	"Rat C1-tetrahydrofolate synthase. cDNA isolation, tissue-specific levels of the mRNA, and expression of the protein in yeast." Thigpen A.E., West M.G., Appling D.R. J. Biol. Chem. 265:7907-7913(1990) [PubMed: 2186031] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	Appling D.R. Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 19 AND 24.
[3]	Lubec G., Afjehi-Sadat L. Submitted (NOV-2006) to UniProtKB Cited for: PROTEIN SEQUENCE OF 521-532, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Spinal cord.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J05519 mRNA. Translation: AAA74248.1. U31032 Genomic DNA. Translation: AAA74744.1.
IPI	IPI00231356.
PIR	A35367.
RefSeq	NP_071953.1. NM_022508.1.
UniGene	Rn.1114.
3D structure databases
ProteinModelPortal	P27653.
SMR	P27653. Positions 2-296, 469-531.
ModBase	Search...
Protein-protein interaction databases
IntAct	P27653. 1 interaction.
STRING	P27653.
Proteomic databases
PRIDE	P27653.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	64300.
KEGG	rno:64300.
UCSC	NM_022508. rat.
Organism-specific databases
CTD	4522.
RGD	708531. Mthfd1.
Phylogenomic databases
eggNOG	roNOG06531.
HOVERGEN	HBG004916.
InParanoid	P27653.
OrthoDB	EOG4GB75D.
PhylomeDB	P27653.
Gene expression databases
Genevestigator	P27653.
GermOnline	ENSRNOG00000005602. Rattus norvegicus.
Family and domain databases
InterPro	IPR000559. Formate_THF_ligase. IPR020628. Formate_THF_ligase_CS. IPR016040. NAD(P)-bd_dom. IPR000672. THF_DH/CycHdrlase. IPR020630. THF_DH/CycHdrlase_cat_dom. IPR020867. THF_DH/CycHdrlase_CS. IPR020631. THF_DH/CycHdrlase_NAD-bd_dom. [Graphical view]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
KO	K00288.
Pfam	PF01268. FTHFS. 1 hit. PF00763. THF_DHG_CYH. 1 hit. PF02882. THF_DHG_CYH_C. 1 hit. [Graphical view]
PRINTS	PR00085. THFDHDRGNASE.
PROSITE	PS00721. FTHFS_1. 1 hit. PS00722. FTHFS_2. 1 hit. PS00766. THF_DHG_CYH_1. 1 hit. PS00767. THF_DHG_CYH_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	612926.

Entry information

Entry name

C1TC_RAT

Accession

Primary (citable) accession number: P27653
Secondary accession number(s): Q62808

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	January 23, 2007
Last modified:	November 16, 2011
This is version 96 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program