KEGG   ORTHOLOGY: K07419
Entry
K07419                      KO                                     

Name
CYP2R1
Definition
vitamin D 25-hydroxylase [EC:1.14.14.24]
Pathway
ko00100  Steroid biosynthesis
ko01100  Metabolic pathways
ko01110  Biosynthesis of secondary metabolites
Module
M00103  Cholecalciferol biosynthesis
Disease
H01143  Vitamin D-dependent rickets
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09103 Lipid metabolism
   00100 Steroid biosynthesis
    K07419  CYP2R1; vitamin D 25-hydroxylase
 09180 Brite Hierarchies
  09181 Protein families: metabolism
   00199 Cytochrome P450
    K07419  CYP2R1; vitamin D 25-hydroxylase
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.14  Acting on paired donors, with incorporation or reduction of molecular oxygen
   1.14.14  With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor
    1.14.14.24  vitamin D 25-hydroxylase
     K07419  CYP2R1; vitamin D 25-hydroxylase
Cytochrome P450 [BR:ko00199]
 Cytochrome P450, animal type
  CYP2 family
   K07419  CYP2R1; vitamin D 25-hydroxylase
Other DBs
RN: R03611
GO: 0030343
Genes
HSA: 120227(CYP2R1)
PTR: 451042(CYP2R1)
PPS: 100973299
GGO: 101150033
PON: 100460063
NLE: 100593944
MCC: 698834(CYP2R1)
MCF: 102138775
CSAB: 103239784(CYP2R1)
RRO: 104681937
RBB: 108535517
CJC: 100394527(CYP2R1)
SBQ: 101037293
MMU: 244209(Cyp2r1)
MCAL: 110298348
MPAH: 110332047
RNO: 361631(Cyp2r1)
MUN: 110549426
CGE: 100772751
NGI: 103750427
HGL: 101724787
CCAN: 109695364
OCU: 100353077
TUP: 102495100
CFA: 612993(CYP2R1)
VVP: 112927044
AML: 100483022
UMR: 103682376
UAH: 113246269
ORO: 101369394
ELK: 111159482
FCA: 101093889
PTG: 102966741
PPAD: 109271176
AJU: 106989115
BTA: 541302(CYP2R1)
BOM: 102285419
BIU: 109569609
BBUB: 102394445
CHX: 102190621
OAS: 101117786
SSC: 100124375(CYP2R1)
CFR: 102514910
CDK: 105086686
BACU: 103007249
LVE: 103091120
OOR: 101270072
DLE: 111165268
PCAD: 102978739
ECB: 100146381(CYP2R1)
EPZ: 103557934
EAI: 106830430
MYB: 102258907
MYD: 102762858
MNA: 107523752
HAI: 109388260
DRO: 112303455
PALE: 102894539
RAY: 107519432
MJV: 108387781
LAV: 100673483
TMU: 101356008
MDO: 100029137
SHR: 100934288
PCW: 110220995
OAA: 100088947
GGA: 423065(CYP2R1)
CJO: 107314632
NMEL: 110401886
APLA: 101801210
ACYG: 106033854
TGU: 100229624
LSR: 110468080
SCAN: 103827030
GFR: 102036046
FAB: 101814027
PHI: 102099647
PMAJ: 107205333
CCW: 104683405
ETL: 114060398
FPG: 101919940
FCH: 102048327
CLV: 102097856
EGZ: 104123157
NNI: 104010937
ACUN: 113481193
PADL: 103923809
AAM: 106497145
ASN: 102371536
AMJ: 102564928(CYP2R1)
PSS: 102462921
CMY: 102946167
CPIC: 101933629
ACS: 100556624
PVT: 110083178
PBI: 103054995
TSR: 106547328
PMUA: 114598543
GJA: 107120114
XLA: 108713716(cyp2r1.L) 108715308(cyp2r1.S)
XTR: 100127674(cyp2r1)
NPR: 108802409
DRE: 563369(cyp2r1)
SRX: 107750548
CCAR: 109094296
IPU: 108271345(Cyp2r1)
PHYP: 113536444
AMEX: 103038630
EEE: 113575769
TRU: 101071742
LCO: 104919371
NCC: 104965174
MZE: 101470180
ONL: 100695816
OLA: 101164878
XMA: 102237962
XCO: 114143618
PRET: 103462441
CVG: 107085571
NFU: 107381435
KMR: 108250436
ALIM: 106530854
AOCE: 111563276
CSEM: 103379286
POV: 109636741
LCF: 108888818
SDU: 111236567
SLAL: 111654496
HCQ: 109525712
BPEC: 110172818
MALB: 109963208
ELS: 105022275
PKI: 111842773
LCM: 102347406
CMK: 103175087
PCAN: 112556695
 » show all
Reference
  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
Reference
  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]

KEGG   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
GGO: 101150033
PON: 100460063
NLE: 100593944
MCC: 698834(CYP2R1)
MCF: 102138775
CSAB: 103239784(CYP2R1)
RRO: 104681937
RBB: 108535517
CJC: 100394527(CYP2R1)
SBQ: 101037293
MMU: 244209(Cyp2r1)
MCAL: 110298348
MPAH: 110332047
RNO: 361631(Cyp2r1)
MUN: 110549426
CGE: 100772751
NGI: 103750427
HGL: 101724787
CCAN: 109695364
OCU: 100353077
TUP: 102495100
CFA: 612993(CYP2R1)
VVP: 112927044
AML: 100483022
UMR: 103682376
UAH: 113246269
ORO: 101369394
ELK: 111159482
FCA: 101093889
PTG: 102966741
PPAD: 109271176
AJU: 106989115
BTA: 541302(CYP2R1)
BOM: 102285419
BIU: 109569609
BBUB: 102394445
CHX: 102190621
OAS: 101117786
SSC: 100124375(CYP2R1)
CFR: 102514910
CDK: 105086686
BACU: 103007249
LVE: 103091120
OOR: 101270072
DLE: 111165268
PCAD: 102978739
ECB: 100146381(CYP2R1)
EPZ: 103557934
EAI: 106830430
MYB: 102258907
MYD: 102762858
MNA: 107523752
HAI: 109388260
DRO: 112303455
PALE: 102894539
RAY: 107519432
MJV: 108387781
LAV: 100673483
TMU: 101356008
MDO: 100029137
SHR: 100934288
PCW: 110220995
OAA: 100088947
GGA: 423065(CYP2R1)
CJO: 107314632
NMEL: 110401886
APLA: 101801210
ACYG: 106033854
TGU: 100229624
LSR: 110468080
SCAN: 103827030
GFR: 102036046
FAB: 101814027
PHI: 102099647
PMAJ: 107205333
CCW: 104683405
ETL: 114060398
FPG: 101919940
FCH: 102048327
CLV: 102097856
EGZ: 104123157
NNI: 104010937
ACUN: 113481193
PADL: 103923809
AAM: 106497145
ASN: 102371536
AMJ: 102564928(CYP2R1)
PSS: 102462921
CMY: 102946167
CPIC: 101933629
ACS: 100556624
PVT: 110083178
PBI: 103054995
TSR: 106547328
PMUA: 114598543
GJA: 107120114
XLA: 108713716(cyp2r1.L) 108715308(cyp2r1.S)
XTR: 100127674(cyp2r1)
NPR: 108802409
DRE: 563369(cyp2r1)
SRX: 107750548
CCAR: 109094296
IPU: 108271345(Cyp2r1)
PHYP: 113536444
AMEX: 103038630
EEE: 113575769
TRU: 101071742
LCO: 104919371
NCC: 104965174
MZE: 101470180
ONL: 100695816
OLA: 101164878
XMA: 102237962
XCO: 114143618
PRET: 103462441
CVG: 107085571
NFU: 107381435
KMR: 108250436
ALIM: 106530854
AOCE: 111563276
CSEM: 103379286
POV: 109636741
LCF: 108888818
SDU: 111236567
SLAL: 111654496
HCQ: 109525712
BPEC: 110172818
MALB: 109963208
ELS: 105022275
PKI: 111842773
LCM: 102347406
CMK: 103175087
PCAN: 112556695
 » 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

KEGG   REACTION: R03611
Entry
R03611                      Reaction                               

Name
calciol,NADPH-hemoprotein reductase:oxygen oxidoreductase (25-hydroxylating)
Definition
Calcidiol + [Oxidized NADPH---hemoprotein reductase] + H2O <=> Vitamin D3 + [Reduced NADPH---hemoprotein reductase] + Oxygen
Equation
Reaction class
RC00963  C01561_C05443
Enzyme
Pathway
rn00100  Steroid biosynthesis
rn01100  Metabolic pathways
rn01110  Biosynthesis of secondary metabolites
Module
M00103  Cholecalciferol biosynthesis
Orthology
K07419  vitamin D 25-hydroxylase [EC:1.14.14.24]
Other DBs
RHEA: 32906

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