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Q3V3R1 (C1TM_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 76. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Monofunctional C1-tetrahydrofolate synthase, mitochondrial

EC=6.3.4.3
Alternative name(s):
Formyltetrahydrofolate synthetase
Gene names
Name:Mthfd1l
Synonyms:Fthfsdc1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length977 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. HAMAP-Rule MF_01543

Pathway

One-carbon metabolism; tetrahydrofolate interconversion. HAMAP-Rule MF_01543

Subunit structure

Homodimer By similarity. HAMAP-Rule MF_01543

Subcellular location

Mitochondrion By similarity HAMAP-Rule MF_01543.

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. HAMAP-Rule MF_01543

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3131Mitochondrion Potential
Chain32 – 977946Monofunctional C1-tetrahydrofolate synthase, mitochondrial HAMAP-Rule MF_01543
PRO_0000343178

Regions

Nucleotide binding422 – 4298ATP By similarity
Region32 – 347316Methylenetetrahydrofolate dehydrogenase and cyclohydrolase HAMAP-Rule MF_01543
Region348 – 977630Formyltetrahydrofolate synthetase HAMAP-Rule MF_01543

Amino acid modifications

Modified residue1881N6-acetyllysine; alternate By similarity
Modified residue1881N6-succinyllysine; alternate Ref.4
Modified residue5951N6-succinyllysine Ref.4

Experimental info

Sequence conflict1371D → N in BAE35568. Ref.1
Sequence conflict2791V → A in BAE35568. Ref.1
Sequence conflict2791V → A in AAH30437. Ref.2
Sequence conflict2791V → A in AAH49936. Ref.2
Sequence conflict3531Q → H in BAE35568. Ref.1
Sequence conflict3691T → N in BAE20500. Ref.1
Sequence conflict4191I → V in BAC30053. Ref.1
Sequence conflict4221T → S in BAE35568. Ref.1
Sequence conflict6321V → A in BAE35568. Ref.1
Sequence conflict9631D → G in BAE20438. Ref.1

Secondary structure

........... 977
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q3V3R1 [UniParc].

Last modified July 1, 2008. Version 2.
Checksum: 7275EF6F9A4292D6

FASTA977105,729
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-188 AND LYS-595, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[5]"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.
CCDSCCDS56672.1.
RefSeqNP_001164256.1. NM_001170785.1.
NP_001164257.1. NM_001170786.1.
NP_758512.3. NM_172308.4.
UniGeneMm.184752.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2EO2NMR-A510-573[»]
ProteinModelPortalQ3V3R1.
SMRQ3V3R1. Positions 82-290, 358-977.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid234813. 2 interactions.
IntActQ3V3R1. 4 interactions.
MINTMINT-4114903.
STRING10090.ENSMUSP00000101210.

PTM databases

PhosphoSiteQ3V3R1.

2D gel databases

REPRODUCTION-2DPAGEQ3V3R1.

Proteomic databases

MaxQBQ3V3R1.
PaxDbQ3V3R1.
PRIDEQ3V3R1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000043735; ENSMUSP00000036178; ENSMUSG00000040675.
ENSMUST00000117291; ENSMUSP00000112870; ENSMUSG00000040675.
ENSMUST00000120585; ENSMUSP00000112897; ENSMUSG00000040675.
GeneID270685.
KEGGmmu:270685.
UCSCuc007ehj.2. mouse.

Organism-specific databases

CTD25902.
MGIMGI:1924836. Mthfd1l.

Phylogenomic databases

eggNOGCOG0190.
GeneTreeENSGT00750000117401.
HOGENOMHOG000040280.
HOVERGENHBG004916.
InParanoidQ3V3R1.
KOK13402.
OMAVNGVREF.
OrthoDBEOG76T9QN.
PhylomeDBQ3V3R1.
TreeFamTF300623.

Enzyme and pathway databases

UniPathwayUPA00193.

Gene expression databases

BgeeQ3V3R1.
GenevestigatorQ3V3R1.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
3.40.50.720. 2 hits.
HAMAPMF_01543. FTHFS.
InterProIPR000559. Formate_THF_ligase.
IPR020628. Formate_THF_ligase_CS.
IPR016040. NAD(P)-bd_dom.
IPR027417. P-loop_NTPase.
IPR000672. THF_DH/CycHdrlase.
IPR020630. THF_DH/CycHdrlase_cat_dom.
IPR020631. THF_DH/CycHdrlase_NAD-bd_dom.
[Graphical view]
PfamPF01268. FTHFS. 1 hit.
PF00763. THF_DHG_CYH. 1 hit.
PF02882. THF_DHG_CYH_C. 1 hit.
[Graphical view]
PRINTSPR00085. THFDHDRGNASE.
SUPFAMSSF52540. SSF52540. 2 hits.
PROSITEPS00721. FTHFS_1. 1 hit.
PS00722. FTHFS_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMTHFD1L. mouse.
EvolutionaryTraceQ3V3R1.
NextBio393373.
PROQ3V3R1.
SOURCESearch...

Entry information

Entry nameC1TM_MOUSE
AccessionPrimary (citable) accession number: Q3V3R1
Secondary accession number(s): Q3TVQ0 expand/collapse secondary AC list , Q3V402, Q80V98, Q8CAL0, Q8K2N5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 2008
Last sequence update: July 1, 2008
Last modified: July 9, 2014
This is version 76 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot