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Protein

Monofunctional C1-tetrahydrofolate synthase, mitochondrial

Gene

Mthfd1l

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 MTHFD2.1 Publication

Catalytic activityi

ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate.

Pathwayi

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi422 – 4298ATPBy similarity

GO - Molecular functioni

  1. ATP binding Source: MGI
  2. formate-tetrahydrofolate ligase activity Source: MGI
  3. protein homodimerization activity Source: MGI

GO - Biological processi

  1. 10-formyltetrahydrofolate biosynthetic process Source: MGI
  2. folic acid-containing compound metabolic process Source: MGI
  3. formate metabolic process Source: MGI
  4. one-carbon metabolic process Source: GO_Central
  5. oxidation-reduction process Source: InterPro
  6. tetrahydrofolate interconversion Source: UniProtKB-UniPathway
  7. tetrahydrofolate metabolic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

One-carbon metabolism

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

UniPathwayiUPA00193.

Names & Taxonomyi

Protein namesi
Recommended name:
Monofunctional C1-tetrahydrofolate synthase, mitochondrial (EC:6.3.4.3)
Alternative name(s):
Formyltetrahydrofolate synthetase
Gene namesi
Name:Mthfd1l
Synonyms:Fthfsdc1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 10

Organism-specific databases

MGIiMGI:1924836. Mthfd1l.

Subcellular locationi

Mitochondrion By similarity

GO - Cellular componenti

  1. membrane Source: MGI
  2. mitochondrion Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3131MitochondrionSequence AnalysisAdd
BLAST
Chaini32 – 977946Monofunctional C1-tetrahydrofolate synthase, mitochondrialPRO_0000343178Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei188 – 1881N6-acetyllysine; alternateBy similarity
Modified residuei188 – 1881N6-succinyllysine; alternate1 Publication
Modified residuei595 – 5951N6-succinyllysine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ3V3R1.
PaxDbiQ3V3R1.
PRIDEiQ3V3R1.

2D gel databases

REPRODUCTION-2DPAGEQ3V3R1.

PTM databases

PhosphoSiteiQ3V3R1.

Expressioni

Gene expression databases

BgeeiQ3V3R1.
GenevestigatoriQ3V3R1.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi234813. 2 interactions.
IntActiQ3V3R1. 4 interactions.
MINTiMINT-4114903.
STRINGi10090.ENSMUSP00000101210.

Structurei

Secondary structure

1
977
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi514 – 5218Combined sources
Beta strandi525 – 5284Combined sources
Helixi533 – 54210Combined sources
Turni549 – 5513Combined sources
Helixi554 – 5629Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2EO2NMR-A510-573[»]
ProteinModelPortaliQ3V3R1.
SMRiQ3V3R1. Positions 82-290, 358-977.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ3V3R1.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni32 – 347316Methylenetetrahydrofolate dehydrogenase and cyclohydrolaseAdd
BLAST
Regioni348 – 977630Formyltetrahydrofolate synthetaseAdd
BLAST

Domaini

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 similaritiesi

In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.Curated
In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0190.
GeneTreeiENSGT00750000117401.
HOGENOMiHOG000040280.
HOVERGENiHBG004916.
InParanoidiQ3V3R1.
KOiK13402.
OMAiLHENTQT.
OrthoDBiEOG76T9QN.
PhylomeDBiQ3V3R1.
TreeFamiTF300623.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
3.40.50.720. 2 hits.
HAMAPiMF_01543. FTHFS.
InterProiIPR000559. 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]
PfamiPF01268. FTHFS. 1 hit.
PF00763. THF_DHG_CYH. 1 hit.
PF02882. THF_DHG_CYH_C. 1 hit.
[Graphical view]
PRINTSiPR00085. THFDHDRGNASE.
SUPFAMiSSF52540. SSF52540. 2 hits.
PROSITEiPS00721. FTHFS_1. 1 hit.
PS00722. FTHFS_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q3V3R1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSVRLPLLLR QLGRQQLPSG PACRLRELCR SGSRSSSSGG GDPEGLRGRR
60 70 80 90 100
LQDGQTFSSH GPGNPEAPGM DSIVRDVIHN SKEVLSLLQE KNPAFKPVLV
110 120 130 140 150
VIQAGDDNLM KDMNQNLAKE AGLDITHICL PPDSGEDEII DEILKINEDP
160 170 180 190 200
RVHGLTLQIS EDSLSNKVLN ALKPEKDVDG VTDINLGKLV RGDAPECFVS
210 220 230 240 250
PLAKAAVELV EKSGITLDGK KVLVVGAHGP LEAALQWLFQ RKGSMTMSCP
260 270 280 290 300
WATPQLPDKL READIVVLGS PKPEEIPAVW IPSGTTILNC FHDFLSGKLS
310 320 330 340 350
GGSPGVPVDK LIAEESVSLL AAALRIQNMV SSGRRWLREQ QHRRWRLHCL
360 370 380 390 400
KLQPLSPVPS DIEISRGQTP KAVDVLAKEI GLLADEIEIY GKSKAKVQLS
410 420 430 440 450
LLERLKDQTD GKYVLVAGIT PTPLGEGKST VTIGLVQALT AHLKVNSFAC
460 470 480 490 500
LRQPSQGPTF GVKGGAAGGG YAQVIPMEEF NLHLTGDIHA ITAANNLLAA
510 520 530 540 550
AIDTRILHES TQTDKALYNR LVPLVNGVRE FSEIQLSRLK KLGIHKTDPS
560 570 580 590 600
TLTEEEVRKF ARLNIDPATI TWQRVLDTND RFLRKITIGQ GSTEKGYSRQ
610 620 630 640 650
AQFDIAVASE IMAVLALTDS LTDMKERLGR MVVASDKDGQ PVTAEDLGVT
660 670 680 690 700
GALTVLMKDA IKPNLMQTLE GTPVFVHAGP FANIAHGNSS VLADKIALKL
710 720 730 740 750
VGEEGFVVTE AGFGADIGME KFFNIKCRAS GLVPNVVVLV ATVRALKMHG
760 770 780 790 800
GGPSVTAGVP LKKEYTEENI QLVADGCCNL QKQIQIAQLF GVPVVVALNV
810 820 830 840 850
FKTDTRAEID LVCELAKRAG AFDAVPCYHW SAGGKGSVDL ARAVREAANK
860 870 880 890 900
RSRFQFLYDV QLPIVEKIRV IAQTVYGAKD IELSPEAQSK IDRYTQQGFG
910 920 930 940 950
NLPICMAKTH LSLSHEPDKK GVPRDFTLPI SDVRASIGAG FIYPLVGTMS
960 970
TMPGLPTRPC FYDIDLDTET EQVKGLF
Length:977
Mass (Da):105,729
Last modified:July 1, 2008 - v2
Checksum:i7275EF6F9A4292D6
GO

Sequence cautioni

The sequence AAH30437.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti137 – 1371D → N in BAE35568 (PubMed:16141072).Curated
Sequence conflicti279 – 2791V → A in BAE35568 (PubMed:16141072).Curated
Sequence conflicti279 – 2791V → A in AAH30437 (PubMed:15489334).Curated
Sequence conflicti279 – 2791V → A in AAH49936 (PubMed:15489334).Curated
Sequence conflicti353 – 3531Q → H in BAE35568 (PubMed:16141072).Curated
Sequence conflicti369 – 3691T → N in BAE20500 (PubMed:16141072).Curated
Sequence conflicti419 – 4191I → V in BAC30053 (PubMed:16141072).Curated
Sequence conflicti422 – 4221T → S in BAE35568 (PubMed:16141072).Curated
Sequence conflicti632 – 6321V → A in BAE35568 (PubMed:16141072).Curated
Sequence conflicti963 – 9631D → G in BAE20438 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS56672.1.
RefSeqiNP_001164256.1. NM_001170785.1.
NP_001164257.1. NM_001170786.1.
NP_758512.3. NM_172308.4.
UniGeneiMm.184752.

Genome annotation databases

EnsembliENSMUST00000043735; ENSMUSP00000036178; ENSMUSG00000040675.
ENSMUST00000117291; ENSMUSP00000112870; ENSMUSG00000040675.
ENSMUST00000120585; ENSMUSP00000112897; ENSMUSG00000040675.
GeneIDi270685.
KEGGimmu:270685.
UCSCiuc007ehj.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS56672.1.
RefSeqiNP_001164256.1. NM_001170785.1.
NP_001164257.1. NM_001170786.1.
NP_758512.3. NM_172308.4.
UniGeneiMm.184752.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2EO2NMR-A510-573[»]
ProteinModelPortaliQ3V3R1.
SMRiQ3V3R1. Positions 82-290, 358-977.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi234813. 2 interactions.
IntActiQ3V3R1. 4 interactions.
MINTiMINT-4114903.
STRINGi10090.ENSMUSP00000101210.

PTM databases

PhosphoSiteiQ3V3R1.

2D gel databases

REPRODUCTION-2DPAGEQ3V3R1.

Proteomic databases

MaxQBiQ3V3R1.
PaxDbiQ3V3R1.
PRIDEiQ3V3R1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000043735; ENSMUSP00000036178; ENSMUSG00000040675.
ENSMUST00000117291; ENSMUSP00000112870; ENSMUSG00000040675.
ENSMUST00000120585; ENSMUSP00000112897; ENSMUSG00000040675.
GeneIDi270685.
KEGGimmu:270685.
UCSCiuc007ehj.2. mouse.

Organism-specific databases

CTDi25902.
MGIiMGI:1924836. Mthfd1l.

Phylogenomic databases

eggNOGiCOG0190.
GeneTreeiENSGT00750000117401.
HOGENOMiHOG000040280.
HOVERGENiHBG004916.
InParanoidiQ3V3R1.
KOiK13402.
OMAiLHENTQT.
OrthoDBiEOG76T9QN.
PhylomeDBiQ3V3R1.
TreeFamiTF300623.

Enzyme and pathway databases

UniPathwayiUPA00193.

Miscellaneous databases

ChiTaRSiMthfd1l. mouse.
EvolutionaryTraceiQ3V3R1.
NextBioi393373.
PROiQ3V3R1.
SOURCEiSearch...

Gene expression databases

BgeeiQ3V3R1.
GenevestigatoriQ3V3R1.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
3.40.50.720. 2 hits.
HAMAPiMF_01543. FTHFS.
InterProiIPR000559. 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]
PfamiPF01268. FTHFS. 1 hit.
PF00763. THF_DHG_CYH. 1 hit.
PF02882. THF_DHG_CYH_C. 1 hit.
[Graphical view]
PRINTSiPR00085. THFDHDRGNASE.
SUPFAMiSSF52540. SSF52540. 2 hits.
PROSITEiPS00721. FTHFS_1. 1 hit.
PS00722. FTHFS_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. "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.

Entry informationi

Entry nameiC1TM_MOUSE
AccessioniPrimary (citable) accession number: Q3V3R1
Secondary accession number(s): Q3TVQ0
, Q3V402, Q80V98, Q8CAL0, Q8K2N5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 2008
Last sequence update: July 1, 2008
Last modified: March 4, 2015
This is version 81 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.