Monofunctional C1-tetrahydrofolate synthase, mitochondrial also known as formyltetrahydrofolate synthetase, is an enzyme that in humans is encoded by the MTHFD1L gene (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like).[5][6][7]

MTHFD1L
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMTHFD1L, FTHFSDC1, MTC1THFS, dJ292B18.2, methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like, methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like
External IDsOMIM: 611427; MGI: 1924836; HomoloGene: 56706; GeneCards: MTHFD1L; OMA:MTHFD1L - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001170785
NM_001170786
NM_172308

RefSeq (protein)

NP_001164256
NP_001164257
NP_758512

Location (UCSC)Chr 6: 150.87 – 151.1 MbChr 10: 3.97 – 4.17 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

edit

One-carbon substituted forms of tetrahydrofolate (THF) are involved in the de novo synthesis of purines and thymidylate and support cellular methylation reactions through the regeneration of methionine from homocysteine. MTHFD1L is an enzyme involved in THF synthesis in mitochondria.[7]

In contrast to MTHFD1 that has trifunctional methylenetetrahydrofolate dehydrogenase, methenyltetrahydrofolate cyclohydrolase, and formyltetrahydrofolate synthetase enzymatic activities, MTHFD1L only has formyltetrahydrofolate synthetase activity.[8]

Clinical significance

edit

Certain variants of the MTHFD1L are associated neural tube defects.[9] Different alleles of SNP rs7646 in the 3′ UTR of MTHFD1L are differentially regulated by microRNAs affecting MTHFD1L expression.[10]

References

edit
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000120254Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040675Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Prasannan P, Pike S, Peng K, Shane B, Appling DR (October 2003). "Human mitochondrial C1-tetrahydrofolate synthase: gene structure, tissue distribution of the mRNA, and immunolocalization in Chinese hamster ovary calls". J. Biol. Chem. 278 (44): 43178–87. doi:10.1074/jbc.M304319200. PMC 1457088. PMID 12937168.
  6. ^ Christensen KE, Mackenzie RE (2008). "Mitochondrial methylenetetrahydrofolate dehydrogenase, methenyltetrahydrofolate cyclohydrolase, and formyltetrahydrofolate synthetases". Vitam. Horm. 79: 393–410. doi:10.1016/S0083-6729(08)00414-7. PMID 18804703.
  7. ^ a b "Entrez Gene: methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like".
  8. ^ Christensen KE, Patel H, Kuzmanov U, Mejia NR, MacKenzie RE (March 2005). "Disruption of the mthfd1 gene reveals a monofunctional 10-formyltetrahydrofolate synthetase in mammalian mitochondria". J. Biol. Chem. 280 (9): 7597–602. doi:10.1074/jbc.M409380200. PMID 15611115.
  9. ^ Parle-McDermott A, Pangilinan F, O'Brien KK, Mills JL, Magee AM, Troendle J, Sutton M, Scott JM, Kirke PN, Molloy AM, Brody LC (December 2009). "A common variant in MTHFD1L is associated with neural tube defects and mRNA splicing efficiency". Hum. Mutat. 30 (12): 1650–6. doi:10.1002/humu.21109. PMC 2787683. PMID 19777576.
  10. ^ Minguzzi, Stefano; Selcuklu, S. Duygu; Spillane, Charles; Parle-McDermott, Anne (2013-12-18). "An NTD-Associated Polymorphism in the 3′ UTR of MTHFD1L can Affect Disease Risk by Altering miRNA Binding". Human Mutation. 35 (1): 96–104. doi:10.1002/humu.22459. ISSN 1059-7794. PMID 24123340. S2CID 6583361.

Further reading

edit

This article incorporates text from the United States National Library of Medicine, which is in the public domain.