KEGG   ENZYME: 1.5.1.53
Entry
EC 1.5.1.53                 Enzyme                                 
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
Sysname
5-methyltetrahydrofolate:NADP+ oxidoreductase
Reaction(IUBMB)
5-methyltetrahydrofolate + NADP+ = 5,10-methylenetetrahydrofolate + NADPH + H+ [RN:R01224]
Reaction(KEGG)
R01224
Substrate
5-methyltetrahydrofolate [CPD:C00440];
NADP+ [CPD:C00006]
Product
5,10-methylenetetrahydrofolate [CPD:C00143];
NADPH [CPD:C00005];
H+ [CPD:C00080]
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
ec00670  One carbon pool by folate
ec01100  Metabolic pathways
ec01120  Microbial metabolism in diverse environments
Orthology
K25004  methylenetetrahydrofolate reductase (NADPH)
Genes
HSA4524(MTHFR)
PTR469800(MTHFR)
PPS100975693(MTHFR)
GGO101134157(MTHFR)
PON100454623(MTHFR)
NLE105738058(MTHFR)
MCC714840(MTHFR)
MCF102117536(MTHFR)
CSAB103225598(MTHFR)
CATY105580856(MTHFR)
PANU101019898(MTHFR)
TGE112616737(MTHFR)
RRO104657549(MTHFR)
RBB108539360(MTHFR)
TFN117093311(MTHFR)
PTEH111526316(MTHFR)
CJC100391000(MTHFR)
SBQ101043467(MTHFR)
CSYR103266205(MTHFR)
MMUR105882714(MTHFR)
OGA100960485(MTHFR)
MMU17769(Mthfr)
MCAL110293543(Mthfr)
MPAH110323320(Mthfr)
RNO362657(Mthfr)
MCOC116097006(Mthfr)
MUN110555748(Mthfr)
CGE100774930(Mthfr)
PLEU114709673(Mthfr)
NGI103747470(Mthfr)
HGL101719335(Mthfr)
CPOC100715703(Mthfr)
CCAN109697792(Mthfr)
DORD105997431(Mthfr)
DSP122121484(Mthfr)
NCAR124983882
OCU100352874(MTHFR)
OPI101527929(MTHFR)
TUP102476978(MTHFR)
CFA478230(MTHFR)
VVP112929750(MTHFR)
VLG121496764(MTHFR)
AML100469351(MTHFR)
UMR103666650(MTHFR)
UAH113270501(MTHFR)
UAR123779081(MTHFR)
ELK111154700
LLV125096774
MPUF101694159(MTHFR)
ORO101367692(MTHFR)
EJU114213206(MTHFR)
ZCA113933704(MTHFR)
MLX118020001(MTHFR)
FCA101100576(MTHFR)
PYU121021216(MTHFR)
PBG122479932(MTHFR)
PTG102969340(MTHFR)
PPAD109274118(MTHFR)
AJU106971872(MTHFR)
HHV120233615(MTHFR)
BTA497032(MTHFR)
BOM102286710(MTHFR)
BIU109570335(MTHFR)
BBUB102395627(MTHFR)
CHX102182523(MTHFR)
OAS101111645(MTHFR)
ODA120880227(MTHFR)
CCAD122451796(MTHFR)
SSC397180(MTHFR)
CFR102505417(MTHFR)
CBAI105070965(MTHFR)
CDK105107034(MTHFR)
VPC102532634(MTHFR)
BACU102998853(MTHFR)
LVE103079236(MTHFR)
OOR101287316(MTHFR)
DLE111187289(MTHFR)
PCAD102986652(MTHFR)
PSIU116748237(MTHFR)
ECB100050979(MTHFR)
EPZ103552183(MTHFR)
EAI106836668(MTHFR)
MYB102245334(MTHFR)
MYD102764267(MTHFR)
MMYO118675486(MTHFR)
MLF102437960(MTHFR)
MNA107531557(MTHFR)
PKL118732048(MTHFR)
HAI109381260(MTHFR)
DRO112299114(MTHFR)
SHON118986343(MTHFR)
AJM119064129(MTHFR)
PDIC114496601(MTHFR)
PHAS123831738(MTHFR)
MMF118626195(MTHFR)
RFQ117027712(MTHFR)
PALE102882062(MTHFR)
PGIG120585812(MTHFR)
PVP105294362(MTHFR)
RAY107513124(MTHFR)
MJV108385719(MTHFR)
TOD119236603(MTHFR)
SARA101554814(MTHFR)
LAV100661160(MTHFR)
TMU101359718
DNM101428504(MTHFR)
MDO100018128(MTHFR)
GAS123240311(MTHFR)
SHR100929400(MTHFR)
PCW110199057(MTHFR)
OAA100086119(MTHFR)
GGA419489(MTHFR)
PCOC116242702(MTHFR)
MGP100543073(MTHFR)
CJO107323372(MTHFR)
NMEL110408579(MTHFR)
APLA101805333(MTHFR)
ACYG106040241(MTHFR)
AFUL116497721(MTHFR)
TGU100220660(MTHFR)
LSR110479731(MTHFR)
SCAN103820847(MTHFR)
PMOA120496725(MTHFR)
OTC121343904(MTHFR)
PRUF121358379(MTHFR)
GFR102033068(MTHFR)
FAB101817361(MTHFR)
PHI102109675(MTHFR)
PMAJ107213633(MTHFR)
CCAE111938714(MTHFR)
CCW104693242(MTHFR)
ETL114056920(MTHFR)
ZAB102071430(MTHFR)
FPG101920680(MTHFR)
FCH102053108(MTHFR)
CLV102089900(MTHFR)
EGZ104133086(MTHFR)
NNI104009002(MTHFR)
ACUN113487781(MTHFR)
TALA104368439(MTHFR)
PADL103918045(MTHFR)
ACHC115343387(MTHFR)
AAM106482439(MTHFR)
AROW112970030(MTHFR)
NPD112959653(MTHFR)
DNE112980540(MTHFR)
ASN102373612(MTHFR)
AMJ102573230(MTHFR)
CPOO109314267(MTHFR)
GGN109293666(MTHFR)
PSS102448267(MTHFR)
CMY102945698(MTHFR)
CPIC101950023(MTHFR)
TST117867765(MTHFR)
CABI116821910(MTHFR)
MRV120387999(MTHFR)
ACS100554267(mthfr)
PVT110073216(MTHFR)
SUND121936126(MTHFR)
PBI103051539(MTHFR)
PMUR107294169(MTHFR)
TSR106553080
PGUT117659694(MTHFR)
VKO123031059(MTHFR)
PMUA114602804 114602982
ZVI118087419(MTHFR)
GJA107117727(MTHFR)
STOW125445948(MTHFR)
XLA108697556(mthfr.S) 379784(mthfr.L)
XTR100125082(mthfr)
NPR108799423(MTHFR)
RTEM120915514(MTHFR)
BBUF120999546(MTHFR)
BGAR122928824(MTHFR)
DRE567547(mthfr)
SRX107710792(mthfr) 107748978
SANH107687111 107691055
SGH107595790 107602465
CCAR109092734
CAUA113097248 113107832
PPRM120490013(mthfr)
MAMB125280298(mthfr)
IPU108265037(mthfr)
PHYP113533585(mthfr)
SMEO124399833(mthfr)
TFD113656298(mthfr)
AMEX103033176(mthfr)
EEE113578182(mthfr)
TRU101078210(mthfr)
TNGGSTEN00004910G001
LCO104936586(mthfr)
NCC104955699
ELY117258736(mthfr)
PLEP121947149(mthfr)
SLUC116058866(mthfr)
ECRA117948295
PFLV114558693(mthfr)
GAT120829205(mthfr)
PPUG119223711(mthfr)
MSAM119904965(mthfr)
CUD121518041(mthfr)
MZE101481615(mthfr)
ONL100706052(mthfr)
OAU116326127(mthfr)
OLA101173920(mthfr)
OML112140866(mthfr)
XMA102216417(mthfr)
XCO114141964(mthfr)
XHE116724335(mthfr)
PRET103466998(mthfr)
PFOR103154252(mthfr)
PLAI106947843(mthfr)
PMEI106926580(mthfr)
GAF122832650 122833189
CVG107102655(mthfr)
CTUL119786289(mthfr)
GMU124872528(mthfr)
NFU107391521(mthfr)
KMR108249409(mthfr)
ALIM106529348(mthfr)
NWH119429280 119429296
AOCE111566112(mthfr)
CSEM103384826(mthfr)
POV109630958
SSEN122777158(mthfr)
HHIP117765126(mthfr)
LCF108900502(mthfr)
SDU111233770(mthfr)
SLAL111658836(mthfr)
XGL120803549(mthfr)
HCQ109528734(mthfr)
BPEC110165619(mthfr)
MALB109951049(mthfr)
SASA106572128(mthfr)
OTW112215984 112221595
OMY110491842 110532243
OGO124031907 124046174
ONE115102605 115132121
SALP111976745 112068446
SNH120059363 120060956
ELS105013771(mthfr)
SFM108924892(mthfr)
PKI111859074(mthfr)
AANG118207739(mthfr)
LOC102688415(mthfr)
PSPA121329149 121329216
ARUT117425554 117426084
LCM102358326(MTHFR)
CMK103181396(mthfr)
RTP109914604(mthfr)
BFO118430292
BBEL109472626
CIN100180174
SCLV120326455
SPU115924565 589576
APLC110979147
SKO100368141(MTHFR)
DMEDmel_CG7560(CG7560)
DER6544580
DSE6605265
DSIDsimw501_GD14304(Dsim_GD14304)
DYADyak_GE21809
DAN6507885
DSR110181246
DPODpse_GA20440
DPE6598998
DMN108152200
DWI6638944
DGR6558496
DMODmoj_GI11604
DAZ108614675
DNV108652425
DHE111593115 111601129 115483195
DVI6623335
CCAT101460408
BOD106627885
MDE101899703
SCAC106085892
LCQ111684318
AGAAgaP_AGAP007479
ACOZ120953025
AARA120896047
AAG5569213
AALB109397828 109418971
CQUCpipJ_CPIJ000297
CPII120426570
AME100578936
ACER107992402 107998358
ALAB122721074
BIM100748829
BBIF117210096
BVK117241833
BVAN117156993
BTER100645686
BPYO122573640
CCAL108622149
OBB114872033
MGEN117219788
NMEA116424754
CGIG122401806
SOC105204539
MPHA105829361
AEC105154491
ACEP105621269
PBAR105430772
VEM105563068
HST105185895
DQU106745791
CFO105256449
LHU105668934
PGC109861296
OBO105277295
PCF106789672
PFUC122518885
NVI100117482
CSOL105360655
MDL103571235
FAS105270971
CCIN107270032
DPA109534565
LDC111506350
OTU111417540
BMOR101735471
BMAN114249102
DPLKGM_206647
PMAC106711396
ZCE119833059
HAW110376495
TNL113495626
PXY105388246
BTAB109032747
NLU111045770
FOC113212146
ZNE110838326
CSEC111867742
FCD110842614
DPXDAPPUDRAFT_301720
DMK116931209
PVM113812240
PJA122261979
PCHN125024515
HAME121871205
PCLA123760246
PTRU123503654
HAZT108681433
EAF111701357
TUT107360415
DPTE113790060 113794623
DFR124489958 124493973
CSCU111641837
CELCELE_C06A8.1(mthf-1)
CBRCBG_12960
BMYBM_BM1999(Bma-mthf-1)
LOALOAG_08597
NAINECAME_11843
TSPTsp_08753
HROHELRODRAFT_111699
LGILOTGIDRAFT_214878
PCAN112556142 112556236
BGT106068520
GAE121390023
HRF124132255
HRJ124273373
CRG105340188
MYI110460561
PMAX117344501
MMER123527799
OBI106882151
OSN115209099
LAK106154846 106174355
NVE5512577 5513626
EPA110252119 110252167
ATEN116304937 116305961
ADF107327049
AMIL114962073 114969824
PDAM113668139 113679154
SPIS111327128 111332195
DGT114528959 114537439
XEN124457394
HMG100207609
TADTRIADDRAFT_26971
AQU100636961
QSU111983405 111983801 112009590 112012001
SCEYGL125W(MET13) YPL023C(MET12)
SEUBDI49_1849 DI49_5433
SPAOSPAR_G01230 SPAR_P02400
AGOAGOS_AAR170W AGOS_AFR457W
ERCEcym_1400 Ecym_3063
KLAKLLA0_D12188g KLLA0_F09647g
KMXKLMA_20276(MET13) KLMA_60378(MET12)
LTHKLTH0E11022g KLTH0H06446g
VPOKpol_1007p12 Kpol_223p6
ZROZYRO0A02838g ZYRO0E01870g
CGRCAGL0F07029g CAGL0J09504g
NCSNCAS_0C02530(NCAS0C02530) NCAS_0D03140(NCAS0D03140)
NDINDAI_0E03230(NDAI0E03230) NDAI_0I01770(NDAI0I01770)
TPFTPHA_0C01840(TPHA0C01840) TPHA_0J01830(TPHA0J01830)
TBLTBLA_0D02780(TBLA0D02780) TBLA_0F02520(TBLA0F02520)
TDLTDEL_0B01620(TDEL0B01620) TDEL_0G03480(TDEL0G03480)
TGBHG536_0H01660 HG536_0H03600
KAFKAFR_0A04630(KAFR0A04630) KAFR_0H01590(KAFR0H01590)
KNGKNAG_0A02370(KNAG0A02370) KNAG_0F02500(KNAG0F02500)
ZMKHG535_0B03260 HG535_0C01620
PPAPAS_chr2-2_0145 PAS_chr2-2_0182
DHADEHA2F08976g DEHA2G01254g
PICPICST_71674 PICST_83803
PGUPGUG_01501 PGUG_04648
SPAASPAPADRAFT_137530 SPAPADRAFT_51518
LELLELG_02112 LELG_02622
CALCAALFM_C210460CA(CaO19.5321) CAALFM_C302950CA(MET13)
CTPCTRG_02026 CTRG_02573
COTCORT_0B03880 CORT_0C03560
CDUCD36_24470 CD36_82930
CTENCANTEDRAFT_118482 CANTEDRAFT_131676
YLIYALI0B00572g YALI0B14465g
CLUCLUG_02387 CLUG_05125
CLUSA9F13_03g01133 A9F13_24g00066
CAURCJI97_000409 CJI97_003816
SLBAWJ20_3315(MET13) AWJ20_715(MET12)
PKZC5L36_0B07640 C5L36_0D03770
BNNFOA43_000536 FOA43_004528
BBRXBRETT_001890 BRETT_003148
OPAHPODL_00022 HPODL_02993
NCRNCU07690 NCU09545
NTENEUTE1DRAFT128536(NEUTE1DRAFT_128536) NEUTE1DRAFT57029(NEUTE1DRAFT_57029)
SMPSMAC_00862 SMAC_06582
PANPODANSg7263 PODANSg8765
TTTTHITE_2107143 THITE_2115191
MTMMYCTH_2300974 MYCTH_2314160
CTHRCTHT_0033700 CTHT_0065570
MGRMGG_01728 MGG_08171
PPEIPpBr36_01245 PpBr36_01602
TMNUCRPA7_3085 UCRPA7_6818
SSCKSPSK_03199 SPSK_05053
FGRFGSG_07127 FGSG_09572
FPUFPSE_04091 FPSE_05848
FVRFVEG_04126 FVEG_08038
FOXFOXG_01673 FOXG_06273
NHENECHADRAFT_32750 NECHADRAFT_71723
TRETRIREDRAFT_55055 TRIREDRAFT_81824
TRRM419DRAFT_104048 M419DRAFT_135784
MAWMAC_00485 MAC_07771
MAJMAA_01221 MAA_07320
CMTCCM_04157 CCM_05621
PLJVFPFJ_00742 VFPFJ_07817
VALVDBG_00123 VDBG_00853
VDAVDAG_00463 VDAG_08410
CFJCFIO01_02428 CFIO01_07029
CHIGCH63R_04201 CH63R_07780
SAPOSAPIO_CDS7226
ELAUCREL1_6847 UCREL1_9493
PFYPFICI_05432 PFICI_08066
SSLSS1G_02009 SS1G_09764
BFUBCIN_07g02820 BCIN_07g06360
MBEMBM_01665 MBM_08501
PSCOLY89DRAFT_718062 LY89DRAFT_769751
GLZGLAREA_11463 GLAREA_12614
ANIAN5883.2 AN8215.2
AFMAFUA_2G11300 AFUA_5G03480
ACTACLA_001700 ACLA_070260
NFINFIA_038640 NFIA_086570
AORAO090026000520 AO090102000557
ANGANI_1_1512084(An09g05860) ANI_1_2398024(An02g03270)
AFVAFLA_005756 AFLA_011983
ALUCAKAW2_21343A AKAW2_40591A
ACHEACHE_40648S ACHE_50694S
APUUAPUU_10896A APUU_60645S
PCSPc15g00480 Pc21g15910
PDPPDIP_10790 PDIP_48850
TMFPMAA_048540 PMAA_082190
TRGTRUGW13939_07742 TRUGW13939_08425
CIMCIMG_06560 CIMG_08202
CPWCPC735_022180 CPC735_030300
UREUREG_02453 UREG_03880
PBLPAAG_03665 PAAG_04294
PBNPADG_03172 PADG_07528
ABEARB_01328 ARB_06846
TVETRV_05244 TRV_07376
AJEHCAG_00541 HCAG_07107
BGHBDBG_00602 BDBG_01364
PNOSNOG_10985(SNOG_10984) SNOG_12690
PTEPTT_09481 PTT_18113
BZECOCCADRAFT_87884 COCCADRAFT_96319
BSCCOCSADRAFT_136346 COCSADRAFT_140784
BORCOCMIDRAFT_28378 COCMIDRAFT_4719
AALTCC77DRAFT_1092254 CC77DRAFT_958941
ZTRMYCGRDRAFT_109648 MYCGRDRAFT_75203
PFJMYCFIDRAFT_49642 MYCFIDRAFT_81197
FFUCLAFUR5_07224 CLAFUR5_07965
BCOMBAUCODRAFT_210105 BAUCODRAFT_237275
NPAUCRNP2_6300 UCRNP2_9800
TMLGSTUM_00003351001 GSTUM_00010817001
SPOSPAC343.10(met11) SPAC56F8.10(met9)
CNECNA07390 CNL04820
CNBCNBA7210 CNBI2020
CNGCNAG_00760 CNAG_05140
CGICGB_A8490W CGB_D2260W
TMSTREMEDRAFT_38541 TREMEDRAFT_43239
TASAA1Q1_00789 A1Q1_04951
TVSTRAVEDRAFT_164884 TRAVEDRAFT_28907
DSQDICSQDRAFT_134054 DICSQDRAFT_177540
PCOPHACADRAFT_208793 PHACADRAFT_264540
SHSSTEHIDRAFT_157081 STEHIDRAFT_75044
HIRHETIRDRAFT_445887 HETIRDRAFT_471420
PSQPUNSTDRAFT_113018 PUNSTDRAFT_53586
ADLAURDEDRAFT_106360 AURDEDRAFT_142206
FMEFOMMEDRAFT_100481 FOMMEDRAFT_88181
GTRGLOTRDRAFT_105411 GLOTRDRAFT_71781
LBCLACBIDRAFT_182479 LACBIDRAFT_244474
MRRMoror_1385 Moror_17235
MOREE1B28_007686 E1B28_009106
CCICC1G_00920 CC1G_01198
SCMSCHCODRAFT_65419 SCHCODRAFT_67475
ABPAGABI1DRAFT111963(AGABI1DRAFT_111963) AGABI1DRAFT68194(AGABI1DRAFT_68194)
ABVAGABI2DRAFT193205(AGABI2DRAFT_193205) AGABI2DRAFT216007(AGABI2DRAFT_216007)
CPUTCONPUDRAFT_117110 CONPUDRAFT_59824
SLASERLADRAFT_363249
WSEWALSEDRAFT_37442 WALSEDRAFT_66783
WICJ056_001516 J056_004424
UMAUMAG_04612 UMAG_06065
PFPPFL1_01460 PFL1_02036
MGLMGL_3526 MGL_3786
MRTMRET_0589 MRET_0910
MSYMMSY001_1846 MSY001_2971
PGRPGTG_02893 PGTG_15769
MLRMELLADRAFT_42930 MELLADRAFT_45803
 » show all
Reference
1  [PMID:13817476]
  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
2  [PMID:4399897]
  Authors
Kutzbach C, Stokstad EL.
  Title
Mammalian methylenetetrahydrofolate reductase. Partial purification, properties, and inhibition by S-adenosylmethionine.
  Journal
Biochim Biophys Acta 250:459-77 (1971)
DOI:10.1016/0005-2744(71)90247-6
Reference
3  [PMID:6975779]
  Authors
Daubner SC, Matthews RG.
  Title
Purification and properties of methylenetetrahydrofolate reductase from pig liver.
  Journal
J Biol Chem 257:140-5 (1982)
Reference
4  [PMID:2383427]
  Authors
Zhou J, Kang SS, Wong PW, Fournier B, Rozen R.
  Title
Purification and characterization of methylenetetrahydrofolate reductase from human cadaver liver.
  Journal
Biochem Med Metab Biol 43:234-42 (1990)
DOI:10.1016/0885-4505(90)90029-z
Reference
5  [PMID:11729203]
  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
J Biol Chem 277:4056-61 (2002)
DOI:10.1074/jbc.M110651200
Reference
6  [PMID:29891918]
  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
Nat Commun 9:2261 (2018)
DOI:10.1038/s41467-018-04735-2
  Sequence
[hsa:4524] [sce:YPL023C]
Other DBs
ExplorEnz - The Enzyme Database: 1.5.1.53
IUBMB Enzyme Nomenclature: 1.5.1.53
ExPASy - ENZYME nomenclature database: 1.5.1.53
BRENDA, the Enzyme Database: 1.5.1.53
CAS: 71822-25-8

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