KEGG   ORTHOLOGY: K00089
Entry
K00089                      KO                                     
Symbol
AKR1C2
Name
3alpha-hydroxysteroid 3-dehydrogenase [EC:1.1.1.213 1.1.1.357]
Pathway
map00140  Steroid hormone biosynthesis
map01100  Metabolic pathways
map05204  Chemical carcinogenesis - DNA adducts
map05208  Chemical carcinogenesis - reactive oxygen species
Module
M00977  C19-Steroid hormone biosynthesis (androgen backdoor pathway), pregnenolone => androsterone => dihydrotestosterone
Reaction
R02476  androsterone:NAD+ oxidoreductase
R02477  androsterone:NADP+ oxidoreductase
R04330  androstan-3alpha,17beta-diol:NAD+ oxidoreductase
R08955  3alpha,21-dihydroxy-5alpha-pregnan-20-one:NADP+ 3-oxidoreductase (A-specific)
R08957  3alpha-hydroxy-5alpha-pregnan-20-one:NADP+ 3-oxidoreductase (A-specific)
R08960  5alpha-pregnane-3alpha,20alpha-diol:NADP+ oxidoreductase (A-specific)
R08963  androstan-3alpha,17beta-diol:NADP+ oxidoreductase
R13216  5alpha-pregnane-3alpha,17alpha-diol-20-one:NAD+ oxidoreductase
R13217  5alpha-pregnane-3alpha,17alpha-diol-20-one:NADP+ 3-oxidoreductase
Disease
H00607  46,XY gonadal dysgenesis
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09103 Lipid metabolism
   00140 Steroid hormone biosynthesis
    K00089  AKR1C2; 3alpha-hydroxysteroid 3-dehydrogenase
 09160 Human Diseases
  09161 Cancer: overview
   05204 Chemical carcinogenesis - DNA adducts
    K00089  AKR1C2; 3alpha-hydroxysteroid 3-dehydrogenase
   05208 Chemical carcinogenesis - reactive oxygen species
    K00089  AKR1C2; 3alpha-hydroxysteroid 3-dehydrogenase
Enzymes [BR:ko01000]
 1. Oxidoreductases
  1.1  Acting on the CH-OH group of donors
   1.1.1  With NAD+ or NADP+ as acceptor
    1.1.1.213  3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)
     K00089  AKR1C2; 3alpha-hydroxysteroid 3-dehydrogenase
    1.1.1.357  3alpha-hydroxysteroid 3-dehydrogenase
     K00089  AKR1C2; 3alpha-hydroxysteroid 3-dehydrogenase
Other DBs
GO: 0047026
Genes
HSA: 1646(AKR1C2)
PTR: 100612191(AKR1C2)
PPS: 103783188
NLE: 100603603
HMH: 116457046
SSYN: 129491832
DNM: 101429786
Reference
PMID:7998972
  Authors
Del Bello B, Maellaro E, Sugherini L, Santucci A, Comporti M, Casini AF
  Title
Purification of NADPH-dependent dehydroascorbate reductase from rat liver and its identification with 3 alpha-hydroxysteroid dehydrogenase.
  Journal
Biochem J 304 ( Pt 2):385-90 (1994)
DOI:10.1042/bj3040385
Reference
PMID:8274401
  Authors
Qin KN, New MI, Cheng KC
  Title
Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase.
  Journal
J Steroid Biochem Mol Biol 46:673-9 (1993)
DOI:10.1016/0960-0760(93)90308-j
  Sequence
[hsa:1646]
LinkDB

KEGG   ENZYME: 1.1.1.357
Entry
EC 1.1.1.357                Enzyme                                 
Name
3alpha-hydroxysteroid 3-dehydrogenase;
3alpha-hydroxysteroid dehydrogenase;
AKR1C4 (gene name);
AKR1C2 (gene name);
hsdA (gene name)
Class
Oxidoreductases;
Acting on the CH-OH group of donors;
With NAD+ or NADP+ as acceptor
Sysname
3alpha-hydroxysteroid:NAD(P)+ 3-oxidoreductase
Reaction(IUBMB)
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+ [RN:R10422 R10423]
Reaction(KEGG)
R10422 > R02476 R04330 R13216;
R10423 > R02477 R08963 R13217
Substrate
3alpha-hydroxysteroid [CPD:C03072];
NAD+ [CPD:C00003];
NADP+ [CPD:C00006]
Product
3-oxosteroid [CPD:C01876];
NADH [CPD:C00004];
NADPH [CPD:C00005];
H+ [CPD:C00080]
Comment
The enzyme acts on multiple 3alpha-hydroxysteroids, such as androsterone and 5 alpha-dihydrotestosterone. The mammalian enzymes are involved in inactivation of steroid hormones, while the bacterial enzymes are involved in steroid degradation. This entry stands for enzymes whose stereo-specificity with respect to NAD+ or NADP+ is not known. [cf. EC 1.1.1.50, 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific) and EC 1.1.1.213, 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)].
History
EC 1.1.1.357 created 2013
Pathway
ec00140  Steroid hormone biosynthesis
ec01100  Metabolic pathways
Orthology
K00037  3alpha-hydroxysteroid 3-dehydrogenase / chlordecone reductase
K00089  3alpha-hydroxysteroid 3-dehydrogenase
K00212  20alpha/3alpha-hydroxysteroid dehydrogenase / dihydrodiol dehydrogenase
K04119  aldo-keto reductase family 1 member C3
K19811  3alpha-hydroxysteroid 3-dehydrogenase
Genes
HSA: 1109(AKR1C4) 1645(AKR1C1) 1646(AKR1C2) 340811(AKR1C8) 8644(AKR1C3)
PTR: 100607996 100612191(AKR1C2) 100612718(AKR1C3) 100612887 450274(AKR1C4) 746545
PPS: 100971300 100986388(AKR1C3) 100986729 100987632 100987989(AKR1C4) 100988315 103783188
GGO: 101144878(AKR1C3) 101146324 101147265(AKR1C8) 101148343 101152195 115936027
PON: 100171658(AKR1C1) 100174617(AKR1C3) 100189776 100432652 100434557(AKR1C4) 100461633 100462259
PPYG: 129006137 129006867 129006869 129006872 129006873 129006874(AKR1C8) 129006876(AKR1C4)
NLE: 100593325 100603603 100604844 100605385 100605934 100606512
HMH: 116457046 116457717 116460197(AKR1C8) 116461800(AKR1C4)
SSYN: 129491830 129491831 129491832 129491834 129491837 129491838
MCC: 100430336 711198(AKR1C1) 711360(AKR1C2) 711440 722483 722485 722490(AKR1C4) 722496
MCF: 101865536(AKR1C1) 102116465 102116844 102117205 102141103 102142023(HSD17B5) 102143072(AKR1C8) 102144231
MTHB: 126963005 126963006 126963007 126963008 126963009 126963422
MNI: 105490778 105490779 105490780 105490781 105490782 105490783 105494391 112428206
CSAB: 103237807 103237808 103237812 103237813 103237814 103237816
CATY: 105587685 105587688 105587690 105597444 105597446 105597447 105597481
PANU: 100997485 101022585 101022938 101023297 101024707
TGE: 112631307 112631308 112631309 112631314 112631750
MLEU: 105532487 105532488 105532490 105532496 105535734 105535762 105535763
RRO: 104674747 104674748 104678924 104678925
RBB: 108521035 108521036 108532990 108532991 108532992
TFN: 117082052 117082118 117082119 117082359 117083437 117083548 117083560 117087703 117087714
PTEH: 111528130 111528985 113224919
CANG: 105521699 105521700 105521701 105521702 105521704 105521705
CJC: 100404656(AKR1C1) 100405255 100405615(AKR1C4) 100406962 100409025 100409384
SBQ: 101041594 101041915 101042225 101042532 101049957
CIMI: 108285104 108285106 108292323 108292324(AKR1C4) 108292325 108292357
ANAN: 105710839 105710841 105710885 105710886 105710887 105710891
CSYR: 103261879 103261880 103261882 103261883 103263298 103263300
MMUR: 105858219 105858220 105858221 105858224
LCAT: 123623042 123623043 123623044 123623047
ERUF: 138375334 138375336 138375337 138375338 138375390
PCOQ: 105826891 105826910 105826913
OGA: 100940488 100942491 100967071
MMU: 77337(Akr1c21)
MCAL: 110308148 110308710
MPAH: 110315750 110333790 110333839 110333848
RNO: 291283(Akr1c2) 307092(Akr1c1) 361267(Akr1c15)
MCOC: 116081731 116081947
ANU: 117713832 117713854
ASYL: 127664685 127664762
MUN: 110539888 110540933 110542801 110560700 132649305
CGE: 100768090 100768376 100770100 100770388
MAUA: 101839651 101841267 101843587
PROB: 127229800 127229804
PLEU: 114707814 114708002 114708030 114708096
PMAV: 102909418
MORG: 121432600 121432606 121432658 121432668
MFOT: 126501679 126501680 126501681 126501693 126506800
AAMP: 119816160 119816243 119817583 119826549
CNL: 130885465
NGI: 103725884 103725890 103725892 103725895 103746652
HGL: 101702106 101716553
CPOC: 100722094 100724342 100724620 100727454
CCAN: 109678869 109680334 109680485 109680990
DSP: 122113031
DMER: 138805664
PLOP: 125366785
NCAR: 124961142 124961655
MMMA: 107134068 107150202 107150203
ITI: 101954502 101978171
OCU: 100348607(PGER1) 100352716 108176284
OPI: 101524567 101525116 101525279 101525842 101526245 101526664 101526901 101527313 101527569 101527977 118759111
OCZ: 121148047 121148048 121148053 121148054 121148056 121161958 121167473 121167481 121167482 121167486
TUP: 102478063 102478495 102491222 102491650
GVR: 103581518 103602898 103610229 103610426
CFA: 497070(AKR1C3)
CLUD: 112658979
VVP: 112933725
VLG: 121496638
NPO: 129514265
AML: 100483758
UMR: 103676234
UAH: 113241124
UAR: 123802294(AKR1C8)
ELK: 111158636
LLV: 125107753
MPUF: 101678776
MNP: 132020017
MLK: 131838054
NVS: 122891768(AKR1C4)
ORO: 101377633 101379669
EJU: 114217720
ZCA: 113921662
MLX: 118021623 118021905
MANO: 123842005 123842017
LWW: 102748666 102748964
FCA: 100510801(AKR1C3)
PYU: 121014878
PCOO: 112867557
PBG: 122473163
PVIV: 125169528
LRUF: 124502362
LGF: 123591606
AJU: 106988139
PTG: 102963188
PPAD: 109273789
PUC: 125918575
PLEZ: 122223817
HHV: 120237198
CCRU: 144226934
BTA: 100139386(20ALPHA-HSD) 112441538 112449293 132342088 132342107 282138(AKR1C4) 506594 527068 538060 617917(AKR1C3) 782884
BOM: 102269337 102271453 102271733 102272308 102272594 102272882 102273443
BIU: 109567627 109568074 109568076 109568077 109568079 109568080 109568087
BBUB: 102389138 102395293 102395635 102396460 102396772 102399119 102400645 102404780 102415234
BBIS: 104985980 104985985 104985990 104985991 104985992 104985994 104985995 104985998 104985999 104986133
CHX: 102176340 102177638 102186942 102187204 102187504 102187932 102188418 102188684 102189109 102189495 102190498
OAS: 101107119 101107541 101109111 101109377 101110434 101110693 105614315 106990122 114108656
BTAX: 128058197 128058202 128058203 128058208 128058211 128058212 128058213 128058216
CSUM: 138091116 138091651 138091745 138091796 138091808 138091833 138091836 138091865 138091869
ODA: 120860627 120868601 120869467 120869469 120869471
CCAD: 122447956 122447958 122447959 122448269 122448454 122448455 122448456 122448511 122448512 122448583
MREE: 136157847 136157852 136157854 136157856 136157857 136159311 136159313 136159314 136159316 136159318
OVR: 110127514 110142553 110142554 110142557 110142558 110142563 139029592
MBEZ: 129547517 129555459 129559457 129559483 129559564 129559569 129559578 129559602 129559618 129559630 129559646
SSC: 654406(AKR1CL1) 733634(AKR1C1) 733635 733694(AKR1C1)
CFR: 102511678 116656624 116661570
CBAI: 105074137 105074417 105074427 105074728
CDK: 105104488 105104489 105105880
VPC: 102531609 102541232 102541486
BACU: 103002145 103003050
BMUS: 118891073 118891271
LVE: 103069218
OOR: 101273575 101281536
LALB: 132525824 132525832
GMF: 115842191 115842192
DDP: 132421005 132421006
DLE: 111170128 111170129
PCAD: 102978533
PSIU: 116748968 116749098
PPHC: 136118038 136119112
NASI: 112407550 112407551
ECB: 100057212 100057251 100070491 100070501 100070509 100070570 100070616 111771771 111771772
EPZ: 103540777 103540778 103541472 103541473 103542048 139080563
EAI: 106824650 106827241 106827243 106827244 106827468 106846832 106846833 106846834 123281999
MYB: 102254990 102255491
MYD: 102751586 102763642
MMYO: 118672630 118672665
MLF: 102421358 102428982
MDT: 132215226 132215243
MYUM: 138992421 138992439
PKL: 118702292 118702295
EFUS: 103300835 103300840
MNA: 107542430 107542432
DRO: 112321159 112323007
SHON: 118977133
AJM: 119057712
PDIC: 114492418
PHAS: 123824859 123831227(AKR1C8)
MMF: 118632067 118632135
PPAM: 129084610 129084627
HAI: 109378613
PALE: 102889546
PGIG: 120608988
PVP: 105299187
MJV: 108384939 108393830 108407235 108407237 108407238 140847881
TOD: 119244650 119245260
SARA: 101543981 101545704 101551007 101551999 101555320 101555749
SFUM: 130024001 130024071 130024072 130024073 130024074
SETR: 126013285
LAV: 100659630 100659914 100660861
TMU: 101342771 101360332
ETF: 101653259 101653576
DNM: 101426998 101428157 101429786 101433437 101433871 101435315
GAS: 123247018 123248678
AFZ: 127564339
TVP: 118850247 118850334
PBRV: 138165825 138165836 138165837 138165895
OAA: 100085065 100085983
PSS: 102446010 102446253 102446483
CIZ: 142007201
CMY: 102943008 102946053 119563672
CCAY: 125625831
LKP: 140906277
NDS: 141985386
DCC: 119843778 119849865
CPIC: 101940001 101940260 101940524
TST: 117882842
CABI: 116815619
MRV: 120395343 120395491 120395494 120395542
PVT: 110070400 110071420 110088827
PMUA: 114590236 114604979 114604980 114604981 114605230 114605592
PRAF: 128421905 128421906 128421907 128421908 128421909 128422029
ZVI: 118090693 118090694 118090915
GJA: 107108026
EMC: 129335705
XLA: 100049750(XB5895996.L) 108704368 108712557(akr1c4.S) 379255(akr1c2.L) 379425(akr1c8p.S) 443571(akr1c3.L) 447277(akr1c1.L) 779224(akr1c2.S)
XTR: 100127714(akr1c1) 100490956 100494522 101733893 116406435 116409681 448368(akr1c8p) 496490(akr1c4) 734139 779627(akr1c3) 779650(akr1c2)
NPR: 108789947 108789948 108789949 108799287 108799288 108799289 108799290 108799291 108799292
RTEM: 120921832 120921837 120932840 120932841 120932842 120932844 120932845 120932846 120932847 120932848 120932850 120932852 120932853
ACAT: 141132846 141132847 141132848 141132849 141132850 141132853 141132854 141132855 141132856
PADS: 140323237 140323238 140323239 140323241 140323242 140323244 140323246 140324974 140324976 140324978
BBUF: 120986929 121003640 121003647 121003666 121005304 121005315 121005327 121005417
BGAR: 122926123 122926509 122926510 122926607 122926608 122926609 122926626 122926627 122928540 122928541 122928561
DTC: 141083281 141083283 141083284 141083285 141083286 141083287 141083290 141083294 141083296 141083297 141083298 141083300 141083311 141083702
HSQ: 130267626 130267627 130267628 130267629 130267632 130267633 130267634 130267638 130267640 130267641
PWL: 138287475 138287510 138287511 138287512 138287514 138288486
MUO: 115477556
GSH: 117364122
CPLA: 122559456
HOC: 132825023
SCAU: 119963304
BBEL: 109473367
PFLL: 139134268
PPYR: 116168970
DMK: 116918341
PMEO: 129593135
PVUL: 126823863 130010387
HASI: 137266197
PMAX: 117329343 117329344 117331065
AIRR: 138327949
YBA: 132545179 132545188 132560261
MCAF: 127727738
MMER: 123536211
CCLM: 134183966
PSAO: SK095_03285
CTT: CtCNB1_1322
CTES: O987_07590
 » show all
Reference
1  [PMID:8172617]
  Authors
Deyashiki Y, Ogasawara A, Nakayama T, Nakanishi M, Miyabe Y, Sato K, Hara A
  Title
Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder.
  Journal
Biochem J 299 ( Pt 2):545-52 (1994)
DOI:10.1042/bj2990545
  Sequence
[hsa:1645 1109]
Reference
2  [PMID:7650035]
  Authors
Khanna M, Qin KN, Wang RW, Cheng KC
  Title
Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 alpha-hydroxysteroid dehydrogenases.
  Journal
J Biol Chem 270:20162-8 (1995)
DOI:10.1074/jbc.270.34.20162
  Sequence
[hsa:8644]
Reference
3  [PMID:8944761]
  Authors
Oppermann UC, Maser E
  Title
Characterization of a 3 alpha-hydroxysteroid dehydrogenase/carbonyl reductase from the gram-negative bacterium Comamonas testosteroni.
  Journal
Eur J Biochem 241:744-9 (1996)
DOI:10.1111/j.1432-1033.1996.00744.x
  Sequence
[ctt:CtCNB1_1322]
Reference
4  [PMID:9812981]
  Authors
Mobus E, Maser E
  Title
Molecular cloning, overexpression, and characterization of steroid-inducible 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni. A novel member of the short-chain dehydrogenase/reductase superfamily.
  Journal
J Biol Chem 273:30888-96 (1998)
DOI:10.1074/jbc.273.47.30888
  Sequence
[ctt:CtCNB1_1322]
Reference
5  [PMID:11514561]
  Authors
Nahoum V, Gangloff A, Legrand P, Zhu DW, Cantin L, Zhorov BS, Luu-The V, Labrie F, Breton R, Lin SX
  Title
Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolution.
  Journal
J Biol Chem 276:42091-8 (2001)
DOI:10.1074/jbc.M105610200
  Sequence
[hsa:1646]
Other DBs
ExplorEnz - The Enzyme Database: 1.1.1.357
IUBMB Enzyme Nomenclature: 1.1.1.357
ExPASy - ENZYME nomenclature database: 1.1.1.357
BRENDA, the Enzyme Database: 1.1.1.357
LinkDB

KEGG   REACTION: R04330
Entry
R04330                      Reaction                               
Name
androstan-3alpha,17beta-diol:NAD+ oxidoreductase
Definition
Androstan-3alpha,17beta-diol + NAD+ <=> Dihydrotestosterone + NADH + H+
Equation
C03852 + C00003 <=> C03917 + C00004 + C00080
Reaction class
RC00001  C00003_C00004
RC00144  C03852_C03917
Enzyme
1.1.1.53        1.1.1.239       1.1.1.357
Pathway
rn00140  Steroid hormone biosynthesis
rn01100  Metabolic pathways
Module
M00977  C19-Steroid hormone biosynthesis (androgen backdoor pathway), pregnenolone => androsterone => dihydrotestosterone
Brite
Enzymatic reactions [BR:br08201]
 1. Oxidoreductase reactions
  1.1  Acting on the CH-OH group of donors
   1.1.1  With NAD+ or NADP+ as acceptor
    1.1.1.53
     R04330  Androstan-3alpha,17beta-diol + NAD+ <=> Dihydrotestosterone + NADH + H+
    1.1.1.239
     R04330  Androstan-3alpha,17beta-diol + NAD+ <=> Dihydrotestosterone + NADH + H+
    1.1.1.357
     R04330  Androstan-3alpha,17beta-diol + NAD+ <=> Dihydrotestosterone + NADH + H+
IUBMB reaction hierarchy [BR:br08202]
 1. Oxidoreductase reactions
  1.1.1.357
   R10422  3alpha-Hydroxysteroid <=> 3-Oxosteroid
    R04330  Androstan-3alpha,17beta-diol <=> Dihydrotestosterone
Orthology
K00089  3alpha-hydroxysteroid 3-dehydrogenase [EC:1.1.1.213 1.1.1.357]
K13369  17beta-estradiol 17-dehydrogenase / all-trans-retinol dehydrogenase (NAD+) / 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+) [EC:1.1.1.62 1.1.1.105 1.1.1.239]
Other DBs
RHEA: 42007
LinkDB

KEGG   REACTION: R08963
Entry
R08963                      Reaction                               
Name
androstan-3alpha,17beta-diol:NADP+ oxidoreductase
Definition
Androstan-3alpha,17beta-diol + NADP+ <=> Dihydrotestosterone + NADPH + H+
Equation
C03852 + C00006 <=> C03917 + C00005 + C00080
Reaction class
RC00001  C00005_C00006
RC00144  C03852_C03917
Enzyme
1.1.1.50        1.1.1.357
Pathway
rn00140  Steroid hormone biosynthesis
rn01100  Metabolic pathways
Module
M00977  C19-Steroid hormone biosynthesis (androgen backdoor pathway), pregnenolone => androsterone => dihydrotestosterone
Brite
Enzymatic reactions [BR:br08201]
 1. Oxidoreductase reactions
  1.1  Acting on the CH-OH group of donors
   1.1.1  With NAD+ or NADP+ as acceptor
    1.1.1.50
     R08963  Androstan-3alpha,17beta-diol + NADP+ <=> Dihydrotestosterone + NADPH + H+
    1.1.1.357
     R08963  Androstan-3alpha,17beta-diol + NADP+ <=> Dihydrotestosterone + NADPH + H+
IUBMB reaction hierarchy [BR:br08202]
 1. Oxidoreductase reactions
  1.1.1.50
   R10423  3alpha-Hydroxysteroid <=> 3-Oxosteroid
    R08963  Androstan-3alpha,17beta-diol <=> Dihydrotestosterone
  1.1.1.357
   R10423  3alpha-Hydroxysteroid <=> 3-Oxosteroid
    R08963  Androstan-3alpha,17beta-diol <=> Dihydrotestosterone
Orthology
K00037  3alpha-hydroxysteroid 3-dehydrogenase / chlordecone reductase [EC:1.1.1.50 1.1.1.357 1.1.1.225]
K00089  3alpha-hydroxysteroid 3-dehydrogenase [EC:1.1.1.213 1.1.1.357]
LinkDB

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