Search Results

Overview

Uniprot IDP11586
Protein NameC-1-tetrahydrofolate synthase, cytoplasmic
Gene NameMTHFD1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
10 PAEILNGKEISAQIR
157 KGCLELIKETGVPIA
175 AVVVGRSKIVGAPMH
21 AQIRARLKNQVTQLK
251 DKKPNGRKVVGDVAY
262 DVAYDEAKERASFIT
28 KNQVTQLKEQVPGFT
333 CKPKPIGKLAREIGL
354 LYGETKAKVLLSALE
370 LKHRPDGKYVVVTGI
473 HELTQTDKALFNRLV
543 TNDRFLRKITIGQAP
553 IGQAPTEKGHTRTAQ
58 LYINVKLKAAEEIGI
595 KMVVASSKKGEPVSA
66 AAEEIGIKATHIKLP
705 VATVRALKMHGGGPT
71 GIKATHIKLPRTTTE
739 EKGFSNLKKQIENAR
784 HGAFDAVKCTHWAEG
793 THWAEGGKGALALAQ
825 LKLPVEDKIRIIAQK
832 KIRIIAQKIYGADDI

Function

Trifunctional enzyme that catalyzes the interconversion of three forms of one-carbon-substituted tetrahydrofolate: (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate, 5,10-methenyltetrahydrofolate and (6S)-10-formyltetrahydrofolate (PubMed:10828945, PubMed:18767138, PubMed:1881876). These derivatives of tetrahydrofolate are differentially required in nucleotide and amino acid biosynthesis, (6S)-10-formyltetrahydrofolate being required for purine biosynthesis while (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate is used for serine and methionine biosynthesis for instance (PubMed:18767138, PubMed:25633902)

Protein Sequence

10 MAPAEILNGK 20 EISAQIRARL 30 KNQVTQLKEQ 40 VPGFTPRLAI 50 LQVGNRDDSN 60 LYINVKLKAA 70 EEIGIKATHI 80 KLPRTTTESE 90 VMKYITSLNE 100 DSTVHGFLVQ 110 LPLDSENSIN 120 TEEVINAIAP 130 EKDVDGLTSI 140 NAGKLARGDL 150 NDCFIPCTPK 160 GCLELIKETG 170 VPIAGRHAVV 180 VGRSKIVGAP 190 MHDLLLWNNA 200 TVTTCHSKTA 210 HLDEEVNKGD 220 ILVVATGQPE 230 MVKGEWIKPG 240 AIVIDCGINY 250 VPDDKKPNGR 260 KVVGDVAYDE 270 AKERASFITP 280 VPGGVGPMTV 290 AMLMQSTVES 300 AKRFLEKFKP 310 GKWMIQYNNL 320 NLKTPVPSDI 330 DISRSCKPKP 340 IGKLAREIGL 350 LSEEVELYGE 360 TKAKVLLSAL 370 ERLKHRPDGK 380 YVVVTGITPT 390 PLGEGKSTTT 400 IGLVQALGAH 410 LYQNVFACVR 420 QPSQGPTFGI 430 KGGAAGGGYS 440 QVIPMEEFNL 450 HLTGDIHAIT 460 AANNLVAAAI 470 DARIFHELTQ 480 TDKALFNRLV 490 PSVNGVRRFS 500 DIQIRRLKRL 510 GIEKTDPTTL 520 TDEEINRFAR 530 LDIDPETITW 540 QRVLDTNDRF 550 LRKITIGQAP 560 TEKGHTRTAQ 570 FDISVASEIM 580 AVLALTTSLE 590 DMRERLGKMV 600 VASSKKGEPV 610 SAEDLGVSGA 620 LTVLMKDAIK 630 PNLMQTLEGT 640 PVFVHAGPFA 650 NIAHGNSSII 660 ADRIALKLVG 670 PEGFVVTEAG 680 FGADIGMEKF 690 FNIKCRYSGL 700 CPHVVVLVAT 710 VRALKMHGGG 720 PTVTAGLPLP 730 KAYIQENLEL 740 VEKGFSNLKK 750 QIENARMFGI 760 PVVVAVNAFK 770 TDTESELDLI 780 SRLSREHGAF 790 DAVKCTHWAE 800 GGKGALALAQ 810 AVQRAAQAPS 820 SFQLLYDLKL 830 PVEDKIRIIA 840 QKIYGADDIE 850 LLPEAQHKAE 860 VYTKQGFGNL 870 PICMAKTHLS 880 LSHNPEQKGV 890 PTGFILPIRD 900 IRASVGAGFL 910 YPLVGTMSTM 920 PGLPTRPCFY 930 DIDLDPETEQ VNGLF

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005829 cytosol
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0016020 membrane
Cellular Component GO:0005739 mitochondrion
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0004329 formate-tetrahydrofolate ligase activity
Molecular Function GO:0004477 methenyltetrahydrofolate cyclohydrolase activity
Molecular Function GO:0004488 methylenetetrahydrofolate dehydrogenase (NADP+) activity
Biological Process GO:0009257 10-formyltetrahydrofolate biosynthetic process
Biological Process GO:0048702 embryonic neurocranium morphogenesis
Biological Process GO:0048703 embryonic viscerocranium morphogenesis
Biological Process GO:0046655 folic acid metabolic process
Biological Process GO:0007507 heart development
Biological Process GO:0009086 methionine biosynthetic process
Biological Process GO:0006555 methionine metabolic process
Biological Process GO:0001843 neural tube closure
Biological Process GO:0001780 neutrophil homeostasis
Biological Process GO:0006164 purine nucleotide biosynthetic process
Biological Process GO:0061053 somite development
Biological Process GO:0035999 tetrahydrofolate interconversion
Biological Process GO:0019346 transsulfuration

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.