KEGG ENZYME: 1.14.14.24

ENZYME: 1.14.14.24

Entry

EC 1.14.14.24               Enzyme

Name

vitamin D 25-hydroxylase;
vitamin D2 25-hydroxylase;
vitamin D3 25-hydroxylase;
CYP2R1

Class

Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor

Sysname

calciol,NADPH---hemoprotein reductase:oxygen oxidoreductase (25-hydroxylating)

Reaction(IUBMB)

calciol + O2 + [reduced NADPH---hemoprotein reductase] = calcidiol + [oxidized NADPH---hemoprotein reductase] + H2O [RN:R03611]

Reaction(KEGG)

R03611

Substrate

calciol [CPD:C05443];
O2 [CPD:C00007];
[reduced NADPH---hemoprotein reductase] [CPD:C03024]

Product

calcidiol [CPD:C01561];
[oxidized NADPH---hemoprotein reductase] [CPD:C03161];
H2O [CPD:C00001]

Comment

A microsomal enzyme isolated from human and mouse liver that bioactivates vitamin D3. While multiple isoforms (CYP27A1, CYP2J2/3, CYP3A4, CYP2D25 and CYP2C11) are able to catalyse the reaction in vitro, only CYP2R1 is thought to catalyse the reaction in humans in vivo [4]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH---hemoprotein reductase.

History

EC 1.14.14.24 created 2012 as EC 1.14.13.159, transferred 2016 to EC 1.14.14.24

Pathway

ec00100

Steroid biosynthesis

ec01100

Metabolic pathways

ec01110

Biosynthesis of secondary metabolites

Orthology

K07419

vitamin D 25-hydroxylase

Genes

HSA:	120227(CYP2R1)

PTR:	451042(CYP2R1)

PPS:	100973299(CYP2R1)

GGO:

101150033

PON:

100460063

NLE:

100593944

HMH:

116476484

MCC:	698834(CYP2R1)

MCF:	102138775(CYP2R1)

MTHB:

126936604

MNI:

105486927

CSAB:

103239784(CYP2R1)

CATY:

105595724

PANU:

101019230

TGE:

112606070

MLEU:

105553481

RRO:

104681937

RBB:

108535517

TFN:

117080292

PTEH:

111555069

CANG:

105521908

CJC:	100394527(CYP2R1)

SBQ:

101037293

CIMI:

108302167(CYP2R1)

CSYR:

103270405

MMUR:

105879993

LCAT:

123642477

PCOQ:

105818445

OGA:

100961883

MMU:	244209(Cyp2r1)

MCAL:

110298348

MPAH:

110332047

MCOC:

116102828

ANU:

117697704

MUN:

110549426

CGE:

100772751

MAUA:

101831768

PROB:

127228219

PLEU:

114697605

MORG:

121457797

MFOT:

126502291

AAMP:

119823353

NGI:

103750427

HGL:

101724787

CPOC:

100714928

CCAN:

109695364

DORD:

105999202

DSP:

122117854

PLOP:

125360687 125362006

NCAR:

124958302

MMMA:

107135669

OCU:

100353077

OPI:

101521015

TUP:

102495100

GVR:

103603085

CFA:	612993(CYP2R1)

CLUD:

112667671

VVP:

112927044

VLG:

121476561

NPO:

129504706

AML:

100483022

UMR:

103682376

UAH:

113246269

UAR:

123791666

ELK:

111159482

LLV:

125079613

MPUF:

101694301

MNP:

132022625

MLK:

131809658

NVS:

122912746

ORO:

101369394

EJU:

114219310

ZCA:

113914132

MLX:

118004151

NSU:

110576584

LWW:

102736800

FCA:	101093889(CYP2R1)

PYU:

121018173

PCOO:

112865643

PBG:

122483590

PVIV:

125147201

LRUF:

124506182

PTG:

102966741

PPAD:

109271176

PUC:

125935633

AJU:

106989115

HHV:

120244981

BTA:	541302(CYP2R1)

BOM:

102285419

BIU:

109569609

BBUB:

102394445

BBIS:

104981447

CHX:

102190621

OAS:

101117786

BTAX:

128060219

ODA:

120876423

CCAD:

122450097

MBEZ:

129554484

SSC:	100124375(CYP2R1)

CFR:

102514910

CBAI:

105076609

CDK:

105086686

VPC:

102538766

BACU:

103007249

BMUS:

118900197

LVE:

103091120

OOR:

101270072

DLE:

111165268

PCAD:

102978739

PSIU:

116758785

NASI:

112407660

ECB:	100146381(CYP2R1)

EPZ:

103557934

EAI:

106830430

MYB:

102258907

MYD:

102762858

MMYO:

118664863

MLF:

102430832

PKL:

118712446

EFUS:

103294602

MNA:

107523752

DRO:

112303455

SHON:

118989725

AJM:

119053117

PDIC:

114499905

PHAS:

123810105

MMF:

118628167

PPAM:

129080777

HAI:

109388260

RFQ:

117029588

PALE:

102894539

PGIG:

120603242

PVP:

105301484

RAY:

107519432

MJV:

108386837

TOD:

119255496

SARA:

101554146

SETR:

126018922

LAV:

100673483

TMU:

101356008

ETF:

101658824

DNM:

101439538

MDO:

100029137

GAS:

123251568

SHR:

100934288

AFZ:

127540416

PCW:

110220995

OAA:

100088947

GGA:	423065(CYP2R1)

PCOC:

116242990

MGP:	100547524 104910999

CJO:

107314632

TPAI:

128087054

LMUT:

125694662

NMEL:

110401886

APLA:

101801210

ACYG:

106033854

CATA:

118249771

AFUL:

116489859

TGU:

100229624

LSR:

110468080

SCAN:

103827030

PMOA:

120501096

OTC:

121341489

PRUF:

121360922

GFR:

102036046

FAB:

101814027

OMA:

130254318

PHI:

102099647

PMAJ:

107205333

CCW:

104683405

CBRC:

103625457

ETL:

114060398

ZAB:

102073058

ACHL:

103809552

SVG:

106853173

MMEA:

130575643

FPG:

101919940

FCH:

102048327

CLV:

102097856

EGZ:

104123157

NNI:

104010937

PCRI:

104030893

PLET:

104620107

EHS:

104504787

PCAO:

104041023

ACUN:

113481193

TALA:

104356256

PADL:

103923809

AFOR:

103906838

ACHC:

115352090

HALD:

104320456

HLE:

104829596

AGEN:

126046888

GCL:

127016618

CCRI:

104159955

CSTI:

104560569

CMAC:

104479450

MUI:

104542598

BREG:

104639866

FGA:

104083213

GSTE:

104257651

LDI:

104342735

MNB:

103781454

OHA:

104330140

NNT:

104400923

SHAB:

115606396

DPUB:

104304430

PGUU:

104466110

ACAR:

104522608

CPEA:

104386761

AVIT:

104274069

CVF:

104291711

RTD:

128909395

CUCA:

104068952

TEO:

104379461

BRHI:

104497814

AAM:

106497145

AROW:

112968449

NPD:

112948840

TGT:

104578017

DNE:

112985674

SCAM:

104150454

ASN:

102371536

AMJ:	102564928(CYP2R1)

CPOO:

109321085

GGN:

109299111

PSS:

102462921

CMY:

102946167

CCAY:

125638148

DCC:

119857155

CPIC:

101933629

TST:

117877234

CABI:

116829045

MRV:

120403720

ACS:

100556624

ASAO:

132770506

PVT:

110083178

SUND:

121918991

PBI:

103054995

PMUR:

107295021 107295024

CTIG:

120308484

TSR:

106547328

PGUT:

117666157

APRI:

131185997

PTEX:

113440238

NSS:

113412480

VKO:

123021385

PMUA:

114598543

PRAF:

128415685

ZVI:

118087326

HCG:

128339634

GJA:

107120114

STOW:

125425779

EMC:

129324563

XLA:	108713716(cyp2r1.L) 108715308(cyp2r1.S)

XTR:	100127674(cyp2r1)

NPR:

108802409

RTEM:

120916935

BBUF:

120980988

BGAR:

122920379

MUO:

115468906

GSH:

117352411

DRE:	563369(cyp2r1)

SRX:

107750548

SANH:

107688167 107700616

SGH:	107585944 107594282

CCAR:

109094296

CAUA:

113049462 113052025

CGIB:

127961447 128017038

PTET:

122348327 122349639

LROH:

127168282

OMC:

131545049

PPRM:

120490959

RKG:

130102651

MAMB:

125264640

CIDE:

127515288

MASI:

127413295

TROS:

130564435

TDW:

130421272

MANU:

129441898

IPU:

108271345

IFU:

128613378

PHYP:

113536444

SMEO:

124391715

TFD:

113662954

TVC:

132849855

AMEX:

103038630

CMAO:

118818967

EEE:

113575769

CHAR:

122132043

TRU:

101071742

TFS:

130521380

TNG:	GSTEN00017808G001

LCO:

104919371

NCC:

104965174

TBEN:

117471692

CGOB:

115004751

PGEO:

117468460

GACU:

117547741

EMAC:

134862709

ELY:

117257992

EFO:

125901428

PLEP:

121944915

SLUC:

116067667

ECRA:

117951119

ESP:

116693663

PFLV:

114557871

GAT:

120807653

PPUG:

119226474

AFB:

129103562

CLUM:

117751469

PSWI:

130192723

MSAM:

119890509

SCHU:

122873263

CUD:

121510343

ALAT:

119017554

MZE:

101470180

ONL:

100695816

OAU:

116327197

OLA:

101164878

OML:

112160760

CSAI:

133461755

XMA:

102237962

XCO:

114143618

XHE:

116719072

PRET:

103462441

PFOR:

103139442

PLAI:

106960642

PMEI:

106921706

GAF:

122821740

PPRL:

129364044

CVG:

107085571

CTUL:

119782678

GMU:

124867186

NFU:

107381435

KMR:

108250436

ALIM:

106530854

NWH:

119427863

AOCE:

111563276

MCEP:

125005498

CSEM:

103379286

POV:

109636741

SSEN:

122772047

HHIP:

117755397

HSP:

118107013

SMAU:

118302817

LCF:

108888818

SDU:

111236567

SLAL:

111654496

XGL:

120795484

HCQ:

109525712

SSCV:

125967561

SBIA:

133497901

PEE:

133416703

PTAO:

133466895

BPEC:

110172818

MALB:

109963208

BSPL:

114851861

SJO:

128363921

SASA:

106562333 106587531

STRU:

115167088 115203237

OTW:	112235131 112263818

OMY:	110506679 110526546

OGO:	124033625 124035615

ONE:	115116668 115121138

OKI:	109874864 109895334

OKE:	118371435 118372852

SALP:

111969491 111975524

SNH:	120025336 120056899

CCLU:

121556199 121582909

ELS:

105022275

SFM:	108934550 108940274

PKI:

111842773

AANG:

118227173

LOC:

102694258

PSPA:

121294963

ARUT:

117432425

PSEX:

120516858

LCM:

102347406

CMK:

103175087

RTP:

109926988

CPLA:

122557785

HOC:

132824209

LERI:

129694568 129705981

PMRN:

116945652

SCLV:

120335125

LPIC:

129263282 129267144

BCOO:

119085253

DSV:

119459200

RSAN:

119406501

UDV:

129233752

SDM:

118179738

CRQ:	GCK72_015232

HRF:

124143094

MMER:

123525246 123537876 123537877

RPHI:

132725786 132754871

» show all

Reference

1 [PMID:12867411]

Authors

Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW

Title

De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase.

Journal

J Biol Chem 278:38084-93 (2003)
DOI:10.1074/jbc.M307028200

Sequence

[hsa:120227] [mmu:244209]

Reference

2 [PMID:15465040]

Authors

Shinkyo R, Sakaki T, Kamakura M, Ohta M, Inouye K

Title

Metabolism of vitamin D by human microsomal CYP2R1.

Journal

Biochem Biophys Res Commun 324:451-7 (2004)
DOI:10.1016/j.bbrc.2004.09.073

Sequence

[hsa:120227]

Reference

3 [PMID:18511070]

Authors

Strushkevich N, Usanov SA, Plotnikov AN, Jones G, Park HW

Title

Structural analysis of CYP2R1 in complex with vitamin D3.

Journal

J Mol Biol 380:95-106 (2008)
DOI:10.1016/j.jmb.2008.03.065

Sequence

[hsa:120227]

Reference

4 [PMID:22310641]

Authors

Zhu J, Deluca HF

Title

Vitamin D 25-hydroxylase - Four decades of searching, are we there yet?

Journal

Arch Biochem Biophys 523:30-6 (2012)
DOI:10.1016/j.abb.2012.01.013

Other DBs

ExplorEnz - The Enzyme Database:

1.14.14.24

IUBMB Enzyme Nomenclature:

1.14.14.24

ExPASy - ENZYME nomenclature database:

1.14.14.24

BRENDA, the Enzyme Database:

1.14.14.24

DBGET integrated database retrieval system