Reviewed, UniProtKB/Swiss-Prot Q5R8P0 (C1TC_PONAB)

Names and origin

Protein names

Recommended name:
    C-1-tetrahydrofolate synthase, cytoplasmic
      Short name=C1-THF synthase
Including the following 3 domains:
    1- Recommended name:
            Methylenetetrahydrofolate dehydrogenase
              EC=1.5.1.5
    2- Recommended name:
            Methenyltetrahydrofolate cyclohydrolase
              EC=3.5.4.9
    3- Recommended name:
            Formyltetrahydrofolate synthetase
              EC=6.3.4.3

Gene names

Name:

MTHFD1

Organism

Pongo abelii (Sumatran orangutan)

Taxonomic identifier

9601 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Pongo

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 transcript 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 By similarity.
Subcellular location	Cytoplasm By similarity.
Domain	This trifunctional enzyme consists of two major domains: a N-terminal part, containing the methylene-THF dehydrogenase and the methenyl-THF cyclohydrolase activities and a larger formyl-THF synthetase domain.
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	Multifunctional enzyme
Gene Ontology (GO)
Biological process	folic acid and derivative 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 electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW purine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW formate-tetrahydrofolate ligase activity Inferred from electronic annotation. Source: EC methenyltetrahydrofolate cyclohydrolase activity Inferred from electronic annotation. Source: EC methylenetetrahydrofolate dehydrogenase (NADP+) activity Inferred from electronic annotation. Source: EC
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_0000265955
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 By similarity
	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)
	Q5R8P0-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 4D98F58C5A908632	FASTA	935	101,341
	10 20 30 40 50 60 MAPAEILNGR EISAQIRARL KNQVTQLKEQ VPGFTPGLAI LLVGNRDDSN LYINVKLKAA 70 80 90 100 110 120 EEIGIKATHI KLPRTTTESE VIKYITSLNE DSTVHGFLVQ LPLDSENSIN TEEVINAIAP 130 140 150 160 170 180 EKDVDGLTSI SAGKLARGDL NDCFIPCTPK GCLELIKETG VPIAGRHAVV VGRSKIVGAP 190 200 210 220 230 240 MHDLLLWNNA TVTTCHSKTA NLDEEVNKGD ILVVATGRPE MVKGEWIKPG AIVIDCGINY 250 260 270 280 290 300 VPDDKKPNGR KVVGDVAYDE AKERASFITP VPGGVGPMTV AMLMQSTVES AKRFLEKFKP 310 320 330 340 350 360 GKWMIQYNNL NLKTPDPSDI DISRSCKPKP IGKLAREIGL LSEEVELYGE TKAKVLLSAL 370 380 390 400 410 420 ERLKHRPDGK YVVVTGITPT PLGEGKSTTT VGLVQALGAH LYQNVFACVR QPSQGPTFGI 430 440 450 460 470 480 KGGAAGGGYS QVIPMEEFNL HLTGDIHAFT AANNLVAAAI DARIFHELTQ TDKALFNRLV 490 500 510 520 530 540 PSVNGVRKFS DIQIRRLKRL GIEKTDPTTL TDEEINRFAR LDIDPETITW QRVLDTNDRF 550 560 570 580 590 600 LRKITIGQAP TEKGHTRTAQ FDISVASEIM AALALTTSLE DMRERLGKMV VASSKKGEPV 610 620 630 640 650 660 SAEDLGVSGA LTVLMKDAIK PNLMQTLEGT PVFVHAGPFA NIAHGNSSII ADRIALKLVG 670 680 690 700 710 720 PEGFVVTEAG FGADIGMEKF FNIKCRYSGL CPHVVVLVAT VRALKMHGGG PTVTAGLPLP 730 740 750 760 770 780 KAYIEENLEL VEKGFSNLKK QIENARMFGI PVVVAVNAFK TDTEAELDLI SRLSREHGAF 790 800 810 820 830 840 DAVKCTHWAE GGNGALALAQ AVQRAAQAPS SFQLLYDLKL PVEDKIRIIA QKIYGADDIE 850 860 870 880 890 900 LLPEAQHKAE VYTKQGFGNL PVCMAKTHLS LSHNPEQKGV PTGFILPIRD IRASVGAGFL 910 920 930 YPLVGTMSTM PGLPTRPCFY DIDLDPETQQ VNGLF

References

[1]	The German cDNA consortium Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.

Cross-references

Sequence databases
EMBL GenBank DDBJ	CR859711 mRNA. Translation: CAH91870.1.
RefSeq	NP_001126083.1.
UniGene	Pab.18928
3D structure databases
HSSP	HSSP built from PDB template 1A4I based on UniProtKB P11586.
SMR	Q5R8P0. Positions 2-296, 319-927.
ModBase	Search...
Genome annotation databases
GeneID	100173036.
Organism-specific databases
CTD	100173036.
Phylogenomic databases
HOVERGEN	Q5R8P0.
InParanoid	Q5R8P0.
Enzyme and pathway databases
BRENDA	1.5.1.5. 269192. 3.5.4.9. 269192. 6.3.4.3. 269192.
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.
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...

Entry information

Entry name

C1TC_PONAB

Accession

Primary (citable) accession number: Q5R8P0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 12, 2006
Last sequence update:	January 23, 2007
Last modified:	January 19, 2010
This is version 34 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)