KEGG ENZYME: 1.16.1.8

ENZYME: 1.16.1.8

Entry

EC 1.16.1.8                 Enzyme

Name

[methionine synthase] reductase;
methionine synthase cob(II)alamin reductase (methylating);
methionine synthase reductase;
[methionine synthase]-cobalamin methyltransferase (cob(II)alamin reducing);
[methionine synthase]-methylcob(I)alamin,S-adenosylhomocysteine:NADP+ oxidoreductase

Class

Oxidoreductases;
Oxidizing metal ions;
With NAD+ or NADP+ as acceptor

Sysname

[methionine synthase]-methylcob(III)alamin,S-adenosyl-L-homocysteine:NADP+ oxidoreductase

Reaction(IUBMB)

2 [methionine synthase]-methylcob(III)alamin + 2 S-adenosyl-L-homocysteine + NADP+ = 2 [methionine synthase]-cob(II)alamin + NADPH + H+ + 2 S-adenosyl-L-methionine [RN:R05182]

Reaction(KEGG)

R05182

Substrate

[methionine synthase]-methylcob(III)alamin [CPD:C06410];
S-adenosyl-L-homocysteine [CPD:C00021];
NADP+ [CPD:C00006]

Product

[methionine synthase]-cob(II)alamin [CPD:C06409];
NADPH [CPD:C00005];
H+ [CPD:C00080];
S-adenosyl-L-methionine [CPD:C00019]

Comment

In humans, the enzyme is a flavoprotein containing FAD and FMN. The substrate of the enzyme is the inactivated cobalt(II) form of EC 2.1.1.13, methionine synthase. Electrons are transferred from NADPH to FAD to FMN. Defects in this enzyme lead to hereditary hyperhomocysteinemia.

History

EC 1.16.1.8 created 1999 as EC 2.1.1.135, transferred 2003 to EC 1.16.1.8, modified 2020

Orthology

K00597

methionine synthase reductase

Genes

HSA:	4552(MTRR)

PTR:	461717(MTRR)

PPS:	100990677(MTRR)

GGO:	101138335(MTRR)

PON:	100174319(MTRR)

PPYG:

129036480(MTRR)

NLE:	100605425(MTRR)

HMH:	116457012(MTRR)

SSYN:

129464956(MTRR)

MCC:	100430789(MTRR)

MCF:	101925754(MTRR)

MTHB:

126956057

MNI:	105489477(MTRR)

CSAB:

103214983(MTRR)

CATY:

105585969(MTRR)

PANU:

101008135(MTRR)

TGE:	112626561(MTRR)

MLEU:

105535659(MTRR)

RRO:	104674086(MTRR)

RBB:	108536959(MTRR)

TFN:	117064737(MTRR)

PTEH:

111546734(MTRR)

CANG:

105510966(MTRR)

CJC:	100389974(MTRR)

SBQ:	101042701(MTRR)

CIMI:

108281389(MTRR)

ANAN:

105732982(MTRR)

CSYR:

103274646(MTRR)

MMUR:

105885839(MTRR)

LCAT:

123648029(MTRR)

PCOQ:

105813261 105821319(MTRR)

OGA:	100940712(MTRR)

MMU:	210009(Mtrr)

MCAL:

110307972(Mtrr)

MPAH:

110329102(Mtrr)

RNO:	290947(Mtrr)

MCOC:

116083549(Mtrr)

ANU:	117724003(Mtrr)

MUN:	110550967(Mtrr)

CGE:	100773236(Mtrr)

MAUA:

101837109(Mtrr)

PROB:

127220709(Mtrr)

PLEU:

114696124(Mtrr)

MORG:

121433733(Mtrr)

MFOT:

126503181

AAMP:

119809960(Mtrr)

NGI:	103735353(Mtrr)

HGL:	101720530(Mtrr)

CPOC:

100732821(Mtrr)

CCAN:

109688199(Mtrr)

DORD:

105983780(Mtrr)

DSP:	122120995(Mtrr)

PLOP:

125367698(Mtrr)

NCAR:

124986755

MMMA:

107146369(Mtrr)

OCU:

100350605

TUP:	102491380(MTRR)

GVR:	103597915(MTRR)

CFA:	478623(MTRR)

CLUD:

112662624(MTRR)

VVP:	112934268(MTRR)

VLG:	121477419(MTRR)

NPO:	129498612(MTRR)

AML:	100484655(MTRR)

UMR:	103662251(MTRR)

UAH:	113260809(MTRR)

UAR:	123791267(MTRR)

ELK:

111153446

LLV:

125099992

MPUF:

101674005(MTRR)

MNP:	132028202(MTRR)

MLK:	131831572(MTRR)

NVS:	122896012(MTRR)

ORO:	101366274(MTRR)

EJU:	114223671(MTRR)

ZCA:	113929503(MTRR)

MLX:	118006296(MTRR)

NSU:	110591583(MTRR)

LWW:

102749796

FCA:	101098359(MTRR)

PYU:	121042463(MTRR)

PCOO:

112861128(MTRR)

PBG:	122495505(MTRR)

PVIV:

125167884(MTRR)

LRUF:

124522602

PTG:	102949230(MTRR)

PPAD:

109267828(MTRR)

PUC:

125934724

AJU:

106971266

HHV:	120225094(MTRR)

BTA:	507991(MTRR)

BOM:	102272980(MTRR)

BIU:	109574962(MTRR)

BBUB:

102411193(MTRR)

BBIS:

105001005(MTRR)

CHX:	102171193(MTRR)

OAS:	101123409(MTRR)

BTAX:

128066100(MTRR)

ODA:	120879371(MTRR)

CCAD:

122454368(MTRR)

MBEZ:

129553374(MTRR)

SSC:	100516580(MTRR)

CFR:	102511463(MTRR)

CBAI:

105081237(MTRR)

CDK:	105094043(MTRR)

VPC:	102539936(MTRR)

BACU:

103019188(MTRR)

BMUS:

118892397(MTRR)

LVE:	103085843(MTRR)

OOR:	101285453(MTRR)

DLE:	111178558(MTRR)

PCAD:

102990472(MTRR)

PSIU:

116751336(MTRR)

NASI:

112404523(MTRR)

ECB:	100071310(MTRR)

EPZ:	103540506(MTRR)

EAI:	106823000(MTRR)

MYB:	102241177(MTRR)

MYD:	102763596(MTRR)

MMYO:

118656738(MTRR)

MLF:	102430988(MTRR)

MDT:	132233657(MTRR)

PKL:	118703331(MTRR)

EFUS:

103305100(MTRR)

MNA:	107540559(MTRR)

DRO:	112321035(MTRR)

SHON:

118998677(MTRR)

AJM:	119049315(MTRR)

PDIC:

114498869(MTRR)

PHAS:

123824930(MTRR)

MMF:	118642804(MTRR)

PPAM:

129074540(MTRR)

RFQ:	117024848(MTRR)

PALE:

102892778(MTRR)

PGIG:

120586285(MTRR)

PVP:	105299590(MTRR)

RAY:	107502702(MTRR)

MJV:	108384628(MTRR)

TOD:	119260625(MTRR)

SARA:

101558683(MTRR)

SETR:

126000778(MTRR)

LAV:	100654114(MTRR)

TMU:

101359820

ETF:	101644091(MTRR)

DNM:	101425735(MTRR) 101428450 101442305

MDO:	100013254(MTRR)

GAS:	123231587(MTRR)

SHR:	100923220(MTRR)

AFZ:

127543618

PCW:	110220385(MTRR)

TVP:	118850609(MTRR)

OAA:	100089744(MTRR)

GGA:	428502(MTRR)

PCOC:

116226344(MTRR)

MGP:	100540427(MTRR)

CJO:	107309523(MTRR)

TPAI:

128091008(MTRR)

LMUT:

125691018(MTRR)

NMEL:

110393327(MTRR)

APLA:

101802959(MTRR)

ACYG:

106036580(MTRR)

CATA:

118250991(MTRR)

TGU:	100228556(MTRR)

LSR:	110479512(MTRR)

SCAN:

103822476(MTRR)

PMOA:

120504886(MTRR)

OTC:	121339731(MTRR)

PRUF:

121358093(MTRR)

GFR:	102038689(MTRR)

FAB:	101807366(MTRR)

OMA:	130249406(MTRR)

PHI:	102113343(MTRR)

PMAJ:

107200311(MTRR)

CCAE:

111925671(MTRR)

CCW:	104685872(MTRR)

CBRC:

103618767(MTRR)

ETL:	114055131(MTRR)

ZAB:	102073177(MTRR)

ZLE:	135444211(MTRR)

ACHL:

103811102(MTRR)

SVG:	106850753(MTRR)

MMEA:

130576261(MTRR)

HRT:	120749197(MTRR)

SATI:

136365912(MTRR)

FPG:	101910301(MTRR)

FCH:	102047448(MTRR)

CCRI:

104158620(MTRR)

NNT:	104399477(MTRR)

SHAB:

115608717(MTRR)

ACUN:

113476799(MTRR)

TALA:

104361405(MTRR)

ACHC:

115352899(MTRR)

HALD:

104325095(MTRR)

HLE:	104834255(MTRR)

AGEN:

126048602

GCL:

127013551

CSTI:

104549738(MTRR)

LDI:	104347081(MTRR)

MNB:	103769290(MTRR)

DPUB:

104299268(MTRR)

AVIT:

104267393(MTRR)

BRHI:

104499171(MTRR)

EGZ:	104126205(MTRR)

NNI:	104018869(MTRR)

PCRI:

104028347(MTRR)

PCAO:

104040068 104044877

PADL:

103915149(MTRR)

AFOR:

103898434(MTRR)

FGA:	104074282(MTRR)

GSTE:

104255238(MTRR)

CLV:	102096989(MTRR)

MUI:	104539545(MTRR)

PGUU:

104463218(MTRR)

PLET:

104613825(MTRR)

EHS:	104502728(MTRR)

CMAC:

104485556

CUCA:

104067541(MTRR)

TEO:	104372610(MTRR)

BREG:

104641988(MTRR)

OHA:	104333156(MTRR)

ACAR:

104527875(MTRR)

CPEA:

104398259(MTRR)

CVF:	104285329(MTRR)

RTD:	128906288(MTRR)

AAM:	106492684(MTRR)

AROW:

112974047(MTRR)

NPD:	112955282(MTRR)

TGT:	104570113(MTRR)

DNE:	112982725(MTRR)

SCAM:

104137821(MTRR)

ASN:	102383326(MTRR)

AMJ:	102561574(MTRR)

CPOO:

109314303(MTRR)

GGN:	109300378(MTRR)

PSS:	102457990(MTRR)

CMY:	102929534(MTRR)

CCAY:

125631994(MTRR)

CPIC:

101951331(MTRR)

TST:	117872759(MTRR)

CABI:

116828362(MTRR)

MRV:	120397426(MTRR)

ACS:	100563923(mtrr)

ASAO:

132774203(MTRR)

PVT:	110089599(MTRR)

SUND:

121929530(MTRR)

PBI:	103055371(MTRR)

PMUR:

107297701(MTRR)

CTIG:

120301703(MTRR)

PGUT:

117662381(MTRR)

APRI:

131195506(MTRR)

PTEX:

113436534(MTRR)

NSS:	113415192(MTRR)

VKO:	123029692(MTRR)

PMUA:

114601218(MTRR)

PRAF:

128418088(MTRR)

ZVI:	118077646(MTRR)

HCG:	128322474(MTRR)

GJA:	107108830(MTRR)

STOW:

125443447(MTRR)

EMC:	129333378(MTRR)

XLA:	108719055(mtrr.L)

XTR:	733716(mtrr)

NPR:	108802102(MTRR)

RTEM:

120941649(MTRR)

BBUF:

121001007(MTRR)

BGAR:

122937714(MTRR)

MUO:	115471629(MTRR)

GSH:	117353594(MTRR)

DRE:	560667(mtrr)

SRX:	107727200 107741721

SANH:

107686717(mtrr) 107695375

SGH:	107549192 107595114(mtrr)

CCAR:

109049376 109070639

CAUA:

113042285(mtrr) 113066006

CGIB:

127946451 128013383

PTET:

122330005(mtrr)

LROH:

127156073(mtrr)

OMC:	131532970(mtrr)

PPRM:

120475933(mtrr)

RKG:	130087657(mtrr)

MAMB:

125258479(mtrr)

CIDE:

127506272

CERY:

137014360(mtrr)

MASI:

127432104

TROS:

130547352(mtrr)

TDW:	130413571(mtrr)

MANU:

129426642(mtrr)

IPU:

108256395

IFU:	128600017(mtrr)

PHYP:

113541137(mtrr)

SMEO:

124375585(mtrr)

TFD:	113660435(mtrr)

TVC:	132840456(mtrr)

TRN:	134301080(mtrr)

AMEX:

103046907(mtrr)

CMAO:

118798578(mtrr)

EEE:	113588751(mtrr)

CHAR:

105890298

TRU:	101070210(mtrr)

TFS:	130513394(mtrr)

TNG:	GSTEN00015528G001

LCO:	104921714(mtrr)

NCC:	104954888(mtrr)

TBEN:

117484139(mtrr)

CGOB:

115025297(mtrr)

PGEO:

117465808(mtrr)

EMAC:

134883718(mtrr)

ELY:	117264346(mtrr)

EFO:	125881776(mtrr)

PLEP:

121960422(mtrr)

SLUC:

116037854(mtrr)

ECRA:

117937681(mtrr)

ESP:	116672097(mtrr)

PFLV:

114549124(mtrr)

GAT:	120811570(mtrr)

PPUG:

119198462(mtrr)

AFB:	129110569(mtrr)

CLUM:

117749553(mtrr)

PSWI:

130205937(mtrr)

MSAM:

119908963(mtrr) 119916723

SCHU:

122866850(mtrr)

CUD:	121527283(mtrr)

ALAT:

119008643(mtrr)

MZE:	101481719(mtrr)

ONL:	100709326(mtrr)

OAU:	116328322(mtrr)

OLA:	101167253(mtrr)

OML:	112151255(mtrr)

CSAI:

133423279(mtrr)

XMA:	102232227(mtrr)

XCO:	114136999(mtrr)

XHE:	116711923(mtrr)

PRET:

103482452(mtrr)

PFOR:

103135214(mtrr)

PLAI:

106945836(mtrr)

PMEI:

106915713(mtrr)

GAF:	122823890(mtrr)

PPRL:

129364709(mtrr)

CVG:	107096083(mtrr)

CTUL:

119786007(mtrr)

GMU:	124857865(mtrr)

NFU:	107382941(mtrr)

KMR:	108243160(mtrr)

ALIM:

106513500(mtrr)

NWH:	119426553(mtrr)

AOCE:

111581030(mtrr)

MCEP:

124995404(mtrR)

CSEM:

103377015(mtrr)

POV:	109629723(mtrr)

SSEN:

122768035(mtrr)

HHIP:

117753534(mtrr)

HSP:	118098418(mtrr)

PPLT:

128426083(mtrr)

SMAU:

118291125(mtrr)

LCF:

108902055

SDU:	111237220(mtrr)

SLAL:

111662991(mtrr)

XGL:	120789616(mtrr)

HCQ:	109511817(mtrr)

SSCV:

125985662

SBIA:

133492524(mtrr)

PEE:	133396651(mtrr)

PTAO:

133470071(mtrr)

BPEC:

110160921(mtrr)

MALB:

109965535(mtrr)

BSPL:

114853480(mtrr)

SJO:	128382742(mtrr)

SASA:

106578438 106590608

STRU:

115152674 115195377

OTW:	112227637 112234917

OMY:	110489568 110535451(mtrr)

OGO:	123991222(mtrr) 124039468

ONE:	115105024 115119947

OKI:	109899196 109909942

OKE:	118361646 118381360

SALP:

111972954 112069456

SNH:	120028000 120050923

CCLU:

121549907 121569343(mtrr)

ELS:	105019455(mtrr)

SFM:	108935528(mtrr)

PKI:	111849508(mtrr)

AANG:

118226350(mtrr)

LOC:	102683394(mtrr)

PSPA:

121312733 121314194

ARUT:

117400543 117435804 117972350

PSEX:

120530158(mtrr)

LCM:	102351804(MTRR)

CMK:	103186339(mtrr)

RTP:	109935699(mtrr)

CPLA:

122549854(mtrr)

HOC:	132816054(mtrr)

LERI:

129713735(mtrr)

PMRN:

116940837(MTRR)

LRJ:	133344596(MTRR)

BFO:

118403551

BBEL:

109475814

CIN:

100182690

SCLV:

120333702

SPU:

581957

LPIC:

129257126

APLC:

110975926

ARUN:

117288471

AJC:

117100775

SKO:

100371498

DME:	Dmel_CG14882(CG14882)

DER:

6553357

DSE:

6616881

DSI:	Dsimw501_GD19100(Dsim_GD19100)

DYA:	Dyak_GE24396

DSR:

110177283

DPO:

4802548

DPE:

6592026

DMN:

108155099

DWI:

6651662

DGR:

6563834

DMO:	Dmoj_GI22554

DAZ:

108608773

DNV:

108653072

DHE:

111604956

CCAT:

101460713

BOD:

106621643

BDR:

105227060

RZE:

108359714

AOQ:

129235633

TDA:

119681733

MDE:

101896273

SCAC:

106081791

LCQ:

111676765

LSQ:

119605785

GFS:

119639594

ECOE:

129938463

CLON:

129612987

AGA:	1281330 5667537

ACOZ:

120947327 120950664

AARA:

120894669 120906299

AMER:

121589425 121603667

ASTE:

118507709 118507710

AFUN:

125765621 125766171

AMOU:

128297364 128299583

AALI:

118468823 118468824

AAG:	110678628 110678731 5578477 5578478

AALB:

109401790 109406154 109406159

ASUA:

134226328 134226501

CQU:	CpipJ_CPIJ006043 CpipJ_CPIJ006044

CPII:

120414000 120414020

CNS:

116339537

BCOO:

119077885

TCA:

655238

DPA:

109546268

SOY:

115888852

AGRG:

126733869

ATD:

109594433

CSET:

123319121

AGB:

108911566

NVL:

108558885

APLN:

108736342

PPYR:

116166330 116166874

OTU:

111428153

BMOR:

101743356

BMAN:

114248178

MSEX:

115441099

DPL:	KGM_203279

BANY:

112058113

MJU:

123870173

NIQ:

126772355

VCD:

124543954

MCIX:

123658646

PMAC:

106717667

PPOT:

106105687

PXU:

106121932

ZCE:

119833735

CCRC:

123696597

LSIN:

126974450

AAGE:

121733516

HAW:

110376093

HZE:

124633976

TNL:

113505823

SLIU:

111357378

OFU:

114362733

ATRA:

106137350

GMW:

113509748

PXY:

105386469

PGW:

126371270

LGLY:

125229619

CCRN:

123297254

CLEC:

106670593

HHAL:

106681556

PHU:	Phum_PHUM317650

TPAL:

117647078

ZNE:

110830537

CSEC:

111869859

IEL:

124166861

FCD:

110845930

DPX:	DAPPUDRAFT_308706

DMK:

116922820

DPZ:

124341060

PVM:

113810127

PJA:

122265754

PCHN:

125040353

PMOO:

119575084

HAME:

121863726

PCLA:

123755462

CQD:

128691779

PTRU:

123511512

ESN:

127008217

MNZ:

135213547

HAZT:

108673187

EAF:

111698950

LSM:

121126949

DSV:

119446402

RSAN:

119389554

VDE:

111252907

VJA:

111273928

TUT:

107363566

DPTE:

113789801

DFR:

124499097

CSCU:

111614502

CVS:

136975553

PTEP:

107450790

ABRU:

129969209

UDV:

129234243

SDM:

118194194

LPOL:

106474232

CEL:	CELE_C01G6.6(mtrr-1)

CBR:	CBG_00882(Cbr-mtrr-1)

CRQ:	GCK72_004711

BMY:	BM_BM1887(Bma-mtrr-1)

LOA:	LOAG_00690

TSP:

Tsp_01287

HRO:	HELRODRAFT_192212

LGI:	LOTGIDRAFT_225295

PVUL:

126821848

PCAN:

112556068

BGT:

106065660

GAE:

121385605

HRF:

124113360

HRJ:

124281376

CRG:	105333103 117689136

CANU:

128178419

CVN:

111130109

OED:

125651723

MYI:

110450395

PMAX:

117318294

MMER:

123561042

RPHI:

132746759

DPOL:

127831755 127831822

MAEA:

128236250

OBI:

106882104

OSN:

115221088

LJP:

135464449

LAK:	106162590 106162591

SMM:	Smp_034220

SHX:	MS3_00006893

OVI:	T265_02681

EGL:

EGR_00462

LLON:

135497568

NVE:

5511985

EPA:

110247156

ATEN:

116300168

ADF:

107342874

AMIL:

114954870

PDAM:

113682435

SPIS:

111320968

DGT:

114526309

XEN:

124445181

HMG:

100207049

HSY:

130622767

RES:

135682074

TAD:	TRIADDRAFT_21300

AQU:

100635303

GSL:	Gasu_27190

CCP:	CHC_T00009055001

ECU:	ECU09_1710

EIN:	Eint_091730

EHE:	EHEL_091730

ERO:	EROM_091710

NCE:	NCER_101456

RIE:	OCT59_001954

MBR:	MONBRDRAFT_34058

SRE:	PTSG_06101

DDI:	DDB_G0267824 DDB_G0286763

DPP:	DICPUDRAFT_16710 DICPUDRAFT_43883

DFA:	DFA_03150 DFA_03353

ACAN:

ACA1_167060

PIF:	PITG_06954 PITG_20722

PSOJ:

PHYSODRAFT_359519

SPAR:

SPRG_03729

GTT:	GUITHDRAFT_108699

NGR:	NAEGRDRAFT_59563(FM177)

» show all

Reference

1 [PMID:9501215]

Authors

Leclerc D, Wilson A, Dumas R, Gafuik C, Song D, Watkins D, Heng HH, Rommens JM, Scherer SW, Rosenblatt DS, Gravel RA

Title

Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria.

Journal

Proc Natl Acad Sci U S A 95:3059-64 (1998)
DOI:10.1073/pnas.95.6.3059

Sequence

[hsa:4552]

Reference

2 [PMID:11466310]

Authors

Olteanu H, Banerjee R.

Title

Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation.

Journal

J Biol Chem 276:35558-63 (2001)
DOI:10.1074/jbc.M103707200

Reference

3 [PMID:12416982]

Authors

Olteanu H, Munson T, Banerjee R.

Title

Differences in the efficiency of reductive activation of methionine synthase and exogenous electron acceptors between the common polymorphic variants of human methionine synthase reductase.

Journal

Biochemistry 41:13378-85 (2002)
DOI:10.1021/bi020536s

Other DBs

ExplorEnz - The Enzyme Database:

1.16.1.8

IUBMB Enzyme Nomenclature:

1.16.1.8

ExPASy - ENZYME nomenclature database:

1.16.1.8

BRENDA, the Enzyme Database:

1.16.1.8

CAS:	207004-87-3

DBGET integrated database retrieval system