Q3V3R1 (C1TM_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Monofunctional C1-tetrahydrofolate synthase, mitochondrial
EC=6.3.4.3

Alternative name(s):
Formyltetrahydrofolate synthetase

Gene names

Name:	Mthfd1l
Synonyms:	Fthfsdc1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	977 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)

Function	May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism in embryonic an transformed cells complementing thus the enzymatic activities of MTHFD2. Ref.3
Catalytic activity	ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate.
Pathway	One-carbon metabolism; tetrahydrofolate interconversion.
Subunit structure	Homodimer By similarity.
Subcellular location	Mitochondrion By similarity.
Domain	This monofunctional enzyme consists of two major domains: an N-terminal inactive methylene-THF dehydrogenase and cyclohydrolase domain and an active larger formyl-THF synthetase C-terminal 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.
Sequence caution	The sequence AAH30437.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	One-carbon metabolism
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	10-formyltetrahydrofolate biosynthetic process Inferred from sequence orthology PubMed 12937168. Source: MGI one-carbon metabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome tetrahydrofolate interconversion Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	mitochondrion Inferred from direct assay PubMed 18614015. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW formate-tetrahydrofolate ligase activity Inferred from sequence orthology PubMed 12937168. Source: MGI methylenetetrahydrofolate dehydrogenase (NADP+) activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 31

31

Mitochondrion Potential

Chain

32 – 977

946

Monofunctional C1-tetrahydrofolate synthase, mitochondrial

PRO_0000343178

Regions

Nucleotide binding

422 – 429

8

ATP By similarity

Region

32 – 347

316

Methylenetetrahydrofolate dehydrogenase and cyclohydrolase

Region

348 – 977

630

Formyltetrahydrofolate synthetase

Amino acid modifications

Modified residue

188

1

N6-acetyllysine By similarity

Experimental info

Sequence conflict

137

1

D → N in BAE35568. Ref.1

Sequence conflict

279

1

V → A in BAE35568. Ref.1

Sequence conflict

279

1

V → A in AAH30437. Ref.2

Sequence conflict

279

1

V → A in AAH49936. Ref.2

Sequence conflict

353

1

Q → H in BAE35568. Ref.1

Sequence conflict

369

1

T → N in BAE20500. Ref.1

Sequence conflict

419

1

I → V in BAC30053. Ref.1

Sequence conflict

422

1

T → S in BAE35568. Ref.1

Sequence conflict

632

1

V → A in BAE35568. Ref.1

Sequence conflict

963

1

D → G in BAE20438. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

977

Helix Strand Turn

Details...

Helix

514 – 521

8

Beta strand

525 – 528

4

Helix

533 – 542

10

Turn

549 – 551

3

Helix

554 – 562

9

Sequences

	Sequence		Length	Mass (Da)
	Q3V3R1 [UniParc]. Last modified July 1, 2008. Version 2. Checksum: 7275EF6F9A4292D6	FASTA	977	105,729
	10 20 30 40 50 60 MSVRLPLLLR QLGRQQLPSG PACRLRELCR SGSRSSSSGG GDPEGLRGRR LQDGQTFSSH 70 80 90 100 110 120 GPGNPEAPGM DSIVRDVIHN SKEVLSLLQE KNPAFKPVLV VIQAGDDNLM KDMNQNLAKE 130 140 150 160 170 180 AGLDITHICL PPDSGEDEII DEILKINEDP RVHGLTLQIS EDSLSNKVLN ALKPEKDVDG 190 200 210 220 230 240 VTDINLGKLV RGDAPECFVS PLAKAAVELV EKSGITLDGK KVLVVGAHGP LEAALQWLFQ 250 260 270 280 290 300 RKGSMTMSCP WATPQLPDKL READIVVLGS PKPEEIPAVW IPSGTTILNC FHDFLSGKLS 310 320 330 340 350 360 GGSPGVPVDK LIAEESVSLL AAALRIQNMV SSGRRWLREQ QHRRWRLHCL KLQPLSPVPS 370 380 390 400 410 420 DIEISRGQTP KAVDVLAKEI GLLADEIEIY GKSKAKVQLS LLERLKDQTD GKYVLVAGIT 430 440 450 460 470 480 PTPLGEGKST VTIGLVQALT AHLKVNSFAC LRQPSQGPTF GVKGGAAGGG YAQVIPMEEF 490 500 510 520 530 540 NLHLTGDIHA ITAANNLLAA AIDTRILHES TQTDKALYNR LVPLVNGVRE FSEIQLSRLK 550 560 570 580 590 600 KLGIHKTDPS TLTEEEVRKF ARLNIDPATI TWQRVLDTND RFLRKITIGQ GSTEKGYSRQ 610 620 630 640 650 660 AQFDIAVASE IMAVLALTDS LTDMKERLGR MVVASDKDGQ PVTAEDLGVT GALTVLMKDA 670 680 690 700 710 720 IKPNLMQTLE GTPVFVHAGP FANIAHGNSS VLADKIALKL VGEEGFVVTE AGFGADIGME 730 740 750 760 770 780 KFFNIKCRAS GLVPNVVVLV ATVRALKMHG GGPSVTAGVP LKKEYTEENI QLVADGCCNL 790 800 810 820 830 840 QKQIQIAQLF GVPVVVALNV FKTDTRAEID LVCELAKRAG AFDAVPCYHW SAGGKGSVDL 850 860 870 880 890 900 ARAVREAANK RSRFQFLYDV QLPIVEKIRV IAQTVYGAKD IELSPEAQSK IDRYTQQGFG 910 920 930 940 950 960 NLPICMAKTH LSLSHEPDKK GVPRDFTLPI SDVRASIGAG FIYPLVGTMS TMPGLPTRPC 970 FYDIDLDTET EQVKGLF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Cerebellum and Hypothalamus.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 167-977. Strain: FVB/N-3. Tissue: Mammary tumor.
[3]	"Disruption of the mthfd1 gene reveals a monofunctional 10-formyltetrahydrofolate synthetase in mammalian mitochondria." Christensen K.E., Patel H., Kuzmanov U., Mejia N.R., MacKenzie R.E. J. Biol. Chem. 280:7597-7602(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[4]	"Solution structure of the insertion region (510-573) of FTHFS domain from mouse methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like protein." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 510-573.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK038579 mRNA. Translation: BAC30053.1.
AK028211 mRNA. Translation: BAE20438.1.
AK036284 mRNA. Translation: BAE20500.1.
AK160025 mRNA. Translation: BAE35568.1.
BC030437 mRNA. Translation: AAH30437.1. Different initiation.
BC049936 mRNA. Translation: AAH49936.1.

IPI

IPI00875833.

RefSeq

NP_001164256.1. NM_001170785.1.
NP_001164257.1. NM_001170786.1.
NP_758512.3. NM_172308.4.

UniGene

Mm.184752.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EO2	NMR	-	A	510-573	[»]

ProteinModelPortal

Q3V3R1.

SMR

Q3V3R1. Positions 82-290, 360-969.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q3V3R1. 1 interaction.

STRING

10090.ENSMUSP00000101210.

PTM databases

PhosphoSite

Q3V3R1.

2D gel databases

REPRODUCTION-2DPAGE

Q3V3R1.

Proteomic databases

PaxDb

Q3V3R1.

PRIDE

Q3V3R1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000043735; ENSMUSP00000036178; ENSMUSG00000040675.
ENSMUST00000117291; ENSMUSP00000112870; ENSMUSG00000040675.
ENSMUST00000120585; ENSMUSP00000112897; ENSMUSG00000040675.

GeneID

270685.

KEGG

mmu:270685.

UCSC

uc007ehj.2. mouse.

Organism-specific databases

CTD

25902.

MGI

MGI:1924836. Mthfd1l.

Phylogenomic databases

eggNOG

COG0190.

GeneTree

ENSGT00630000089834.

HOGENOM

HOG000040280.

HOVERGEN

HBG004916.

InParanoid

Q3V3R1.

KO

K13402.

OMA

VNGVREF.

OrthoDB

EOG4ZCT3W.

Enzyme and pathway databases

UniPathway

UPA00193.

Gene expression databases

Bgee

Q3V3R1.

Genevestigator

Q3V3R1.

Family and domain databases

Gene3D

3.40.50.720. 2 hits.

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.
IPR020631. THF_DH/CycHdrlase_NAD-bd_dom.
[Graphical view]

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.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

MTHFD1L. mouse.

EvolutionaryTrace

Q3V3R1.

NextBio

393373.

SOURCE

Search...

Entry information

Entry name

C1TM_MOUSE

Accession

Primary (citable) accession number: Q3V3R1
Secondary accession number(s): Q3TVQ0 , Q3V402, Q80V98, Q8CAL0, Q8K2N5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 2008
Last sequence update:	July 1, 2008
Last modified:	May 1, 2013
This is version 64 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program