Entry
Name
methylenetetrahydrofolate reductase (NADPH);
MTHFR (gene name);
methylenetetrahydrofolate (reduced nicotinamide adenine dinucleotide phosphate) reductase;
5,10-methylenetetrahydrofolate reductase (NADPH);
5,10-methylenetetrahydrofolic acid reductase (ambiguous);
5,10-CH2-H4folate reductase (ambiguous);
methylenetetrahydrofolate reductase (NADPH2);
5,10-methylenetetrahydrofolate reductase (ambiguous);
methylenetetrahydrofolate reductase (ambiguous);
N5,10-methylenetetrahydrofolate reductase (ambiguous);
5,10-methylenetetrahydropteroylglutamate reductase (ambiguous);
N5,N10-methylenetetrahydrofolate reductase (ambiguous);
methylenetetrahydrofolic acid reductase (ambiguous);
5-methyltetrahydrofolate:(acceptor) oxidoreductase (incorrect);
5,10-methylenetetrahydrofolate reductase (FADH2) (ambiguous)
Class
Oxidoreductases;
Acting on the CH-NH group of donors;
With NAD+ or NADP+ as acceptor
BRITE hierarchy
Sysname
5-methyltetrahydrofolate:NADP+ oxidoreductase
Reaction(IUBMB)
5-methyltetrahydrofolate + NADP+ = 5,10-methylenetetrahydrofolate + NADPH + H+ [RN:
R01224 ]
Reaction(KEGG)
Substrate
Product
Comment
A flavoprotein (FAD). The enzyme from yeast and mammals catalyses a physiologically irreversible reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate using NADPH as the electron donor. It plays an important role in folate metabolism by regulating the distribution of one-carbon moieties between cellular methylation reactions and nucleic acid synthesis. The enzyme contains an N-terminal catalytic domain and a C-terminal allosteric regulatory domain that binds S-adenosyl-L-methionine, which acts as an inhibitor. cf. EC
1.5.1.54 , methylenetetrahydrofolate reductase (NADH); EC
1.5.1.20 , methylenetetrahydrofolate reductase [NAD(P)H]; and EC
1.5.7.1 , methylenetetrahydrofolate reductase (ferredoxin).
History
EC 1.5.1.53 created 2021
Pathway
ec01120 Microbial metabolism in diverse environments
Orthology
K25004 methylenetetrahydrofolate reductase (NADPH)
Genes
PMUA : 114602804 114602982
XLA : 108697556(mthfr.S) 379784(mthfr.L)
SRX : 107710792(mthfr) 107748978
SANH : 107687111 107691055
CAUA : 113097248 113107832
SALP : 111976745 112068446
PSPA : 121329149 121329216
ARUT : 117425554 117426084
DSI : Dsimw501_GD14304(Dsim_GD14304)
DHE : 111593115 111601129 115483195
AALB : 109397828 109418971
ACER : 107992402 107998358
DPTE : 113790060 113794623
CEL : CELE_C06A8.1(mthf-1)
BMY : BM_BM1999(Bma-mthf-1)
PCAN : 112556142 112556236
ATEN : 116304937 116305961
AMIL : 114962073 114969824
PDAM : 113668139 113679154
SPIS : 111327128 111332195
QSU : 111983405 111983801 112009590 112012001
SCE : YGL125W(MET13) YPL023C(MET12)
SEUB : DI49_1849 DI49_5433
SPAO : SPAR_G01230 SPAR_P02400
AGO : AGOS_AAR170W AGOS_AFR457W
KLA : KLLA0_D12188g KLLA0_F09647g
KMX : KLMA_20276(MET13) KLMA_60378(MET12)
LTH : KLTH0E11022g KLTH0H06446g
VPO : Kpol_1007p12 Kpol_223p6
ZRO : ZYRO0A02838g ZYRO0E01870g
CGR : CAGL0F07029g CAGL0J09504g
NCS : NCAS_0C02530(NCAS0C02530) NCAS_0D03140(NCAS0D03140)
NDI : NDAI_0E03230(NDAI0E03230) NDAI_0I01770(NDAI0I01770)
TPF : TPHA_0C01840(TPHA0C01840) TPHA_0J01830(TPHA0J01830)
TBL : TBLA_0D02780(TBLA0D02780) TBLA_0F02520(TBLA0F02520)
TDL : TDEL_0B01620(TDEL0B01620) TDEL_0G03480(TDEL0G03480)
TGB : HG536_0H01660 HG536_0H03600
KAF : KAFR_0A04630(KAFR0A04630) KAFR_0H01590(KAFR0H01590)
KNG : KNAG_0A02370(KNAG0A02370) KNAG_0F02500(KNAG0F02500)
ZMK : HG535_0B03260 HG535_0C01620
PPA : PAS_chr2-2_0145 PAS_chr2-2_0182
DHA : DEHA2F08976g DEHA2G01254g
PIC : PICST_71674 PICST_83803
PGU : PGUG_01501 PGUG_04648
SPAA : SPAPADRAFT_137530 SPAPADRAFT_51518
LEL : LELG_02112 LELG_02622
CAL : CAALFM_C210460CA(CaO19.5321) CAALFM_C302950CA(MET13)
CTP : CTRG_02026 CTRG_02573
COT : CORT_0B03880 CORT_0C03560
CDU : CD36_24470 CD36_82930
CTEN : CANTEDRAFT_118482 CANTEDRAFT_131676
YLI : YALI0B00572g YALI0B14465g
CLU : CLUG_02387 CLUG_05125
CLUS : A9F13_03g01133 A9F13_24g00066
CAUR : CJI97_000409 CJI97_003816
SLB : AWJ20_3315(MET13) AWJ20_715(MET12)
PKZ : C5L36_0B07640 C5L36_0D03770
BNN : FOA43_000536 FOA43_004528
BBRX : BRETT_001890 BRETT_003148
OPA : HPODL_00022 HPODL_02993
NTE : NEUTE1DRAFT128536(NEUTE1DRAFT_128536) NEUTE1DRAFT57029(NEUTE1DRAFT_57029)
SMP : SMAC_00862 SMAC_06582
PAN : PODANSg7263 PODANSg8765
TTT : THITE_2107143 THITE_2115191
MTM : MYCTH_2300974 MYCTH_2314160
CTHR : CTHT_0033700 CTHT_0065570
PPEI : PpBr36_01245 PpBr36_01602
TMN : UCRPA7_3085 UCRPA7_6818
SSCK : SPSK_03199 SPSK_05053
FGR : FGSG_07127 FGSG_09572
FPU : FPSE_04091 FPSE_05848
FVR : FVEG_04126 FVEG_08038
FOX : FOXG_01673 FOXG_06273
NHE : NECHADRAFT_32750 NECHADRAFT_71723
TRE : TRIREDRAFT_55055 TRIREDRAFT_81824
TRR : M419DRAFT_104048 M419DRAFT_135784
PLJ : VFPFJ_00742 VFPFJ_07817
VAL : VDBG_00123 VDBG_00853
VDA : VDAG_00463 VDAG_08410
CFJ : CFIO01_02428 CFIO01_07029
CHIG : CH63R_04201 CH63R_07780
ELA : UCREL1_6847 UCREL1_9493
PFY : PFICI_05432 PFICI_08066
SSL : SS1G_02009 SS1G_09764
BFU : BCIN_07g02820 BCIN_07g06360
PSCO : LY89DRAFT_718062 LY89DRAFT_769751
GLZ : GLAREA_11463 GLAREA_12614
AFM : AFUA_2G11300 AFUA_5G03480
ACT : ACLA_001700 ACLA_070260
NFI : NFIA_038640 NFIA_086570
AOR : AO090026000520 AO090102000557
ANG : ANI_1_1512084(An09g05860) ANI_1_2398024(An02g03270)
AFV : AFLA_005756 AFLA_011983
ALUC : AKAW2_21343A AKAW2_40591A
ACHE : ACHE_40648S ACHE_50694S
APUU : APUU_10896A APUU_60645S
PCS : Pc15g00480 Pc21g15910
PDP : PDIP_10790 PDIP_48850
TMF : PMAA_048540 PMAA_082190
TRG : TRUGW13939_07742 TRUGW13939_08425
CIM : CIMG_06560 CIMG_08202
CPW : CPC735_022180 CPC735_030300
URE : UREG_02453 UREG_03880
PBL : PAAG_03665 PAAG_04294
PBN : PADG_03172 PADG_07528
AJE : HCAG_00541 HCAG_07107
BGH : BDBG_00602 BDBG_01364
PNO : SNOG_10985(SNOG_10984) SNOG_12690
BZE : COCCADRAFT_87884 COCCADRAFT_96319
BSC : COCSADRAFT_136346 COCSADRAFT_140784
BOR : COCMIDRAFT_28378 COCMIDRAFT_4719
AALT : CC77DRAFT_1092254 CC77DRAFT_958941
ZTR : MYCGRDRAFT_109648 MYCGRDRAFT_75203
PFJ : MYCFIDRAFT_49642 MYCFIDRAFT_81197
FFU : CLAFUR5_07224 CLAFUR5_07965
BCOM : BAUCODRAFT_210105 BAUCODRAFT_237275
NPA : UCRNP2_6300 UCRNP2_9800
TML : GSTUM_00003351001 GSTUM_00010817001
SPO : SPAC343.10(met11) SPAC56F8.10(met9)
CNG : CNAG_00760 CNAG_05140
CGI : CGB_A8490W CGB_D2260W
TMS : TREMEDRAFT_38541 TREMEDRAFT_43239
TASA : A1Q1_00789 A1Q1_04951
TVS : TRAVEDRAFT_164884 TRAVEDRAFT_28907
DSQ : DICSQDRAFT_134054 DICSQDRAFT_177540
PCO : PHACADRAFT_208793 PHACADRAFT_264540
SHS : STEHIDRAFT_157081 STEHIDRAFT_75044
HIR : HETIRDRAFT_445887 HETIRDRAFT_471420
PSQ : PUNSTDRAFT_113018 PUNSTDRAFT_53586
ADL : AURDEDRAFT_106360 AURDEDRAFT_142206
FME : FOMMEDRAFT_100481 FOMMEDRAFT_88181
GTR : GLOTRDRAFT_105411 GLOTRDRAFT_71781
LBC : LACBIDRAFT_182479 LACBIDRAFT_244474
MRR : Moror_1385 Moror_17235
MORE : E1B28_007686 E1B28_009106
CCI : CC1G_00920 CC1G_01198
SCM : SCHCODRAFT_65419 SCHCODRAFT_67475
ABP : AGABI1DRAFT111963(AGABI1DRAFT_111963) AGABI1DRAFT68194(AGABI1DRAFT_68194)
ABV : AGABI2DRAFT193205(AGABI2DRAFT_193205) AGABI2DRAFT216007(AGABI2DRAFT_216007)
CPUT : CONPUDRAFT_117110 CONPUDRAFT_59824
WSE : WALSEDRAFT_37442 WALSEDRAFT_66783
WIC : J056_001516 J056_004424
UMA : UMAG_04612 UMAG_06065
PFP : PFL1_01460 PFL1_02036
MSYM : MSY001_1846 MSY001_2971
PGR : PGTG_02893 PGTG_15769
MLR : MELLADRAFT_42930 MELLADRAFT_45803
» show all
Taxonomy
Reference
Authors
DONALDSON KO, KERESZTESY JC.
Title
Naturally occurring forms of folic acid. I. "Prefolic A": preparation of concentrate and enzymatic conversion to citrovorum factor.
Journal
J Biol Chem 234:3235-40 (1959)
Reference
Authors
Kutzbach C, Stokstad EL.
Title
Mammalian methylenetetrahydrofolate reductase. Partial purification, properties, and inhibition by S-adenosylmethionine.
Journal
Reference
Authors
Daubner SC, Matthews RG.
Title
Purification and properties of methylenetetrahydrofolate reductase from pig liver.
Journal
J Biol Chem 257:140-5 (1982)
Reference
Authors
Zhou J, Kang SS, Wong PW, Fournier B, Rozen R.
Title
Purification and characterization of methylenetetrahydrofolate reductase from human cadaver liver.
Journal
Reference
Authors
Roje S, Chan SY, Kaplan F, Raymond RK, Horne DW, Appling DR, Hanson AD.
Title
Metabolic engineering in yeast demonstrates that S-adenosylmethionine controls flux through the methylenetetrahydrofolate reductase reaction in vivo.
Journal
Reference
Authors
Froese DS, Kopec J, Rembeza E, Bezerra GA, Oberholzer AE, Suormala T, Lutz S, Chalk R, Borkowska O, Baumgartner MR, Yue WW.
Title
Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition.
Journal
Sequence
Other DBs
ExplorEnz - The Enzyme Database: 1.5.1.53
ExPASy - ENZYME nomenclature database: 1.5.1.53