ADRO_BOVIN
ID ADRO_BOVIN Reviewed; 492 AA.
AC P08165; Q58CY0; Q95KN8;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=NADPH:adrenodoxin oxidoreductase, mitochondrial;
DE Short=AR;
DE Short=Adrenodoxin reductase;
DE EC=1.18.1.6 {ECO:0000269|PubMed:7811729};
DE AltName: Full=Ferredoxin--NADP(+) reductase;
DE Short=Ferredoxin reductase;
DE Flags: Precursor;
GN Name=FDXR; Synonyms=ADXR;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=3448086; DOI=10.1093/oxfordjournals.jbchem.a122178;
RA Sagara Y., Takata Y., Miyata T., Hara T., Horiuchi T.;
RT "Cloning and sequence analysis of adrenodoxin reductase cDNA from bovine
RT adrenal cortex.";
RL J. Biochem. 102:1333-1336(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3038094; DOI=10.1016/0006-291x(87)91570-1;
RA Nonaka Y., Murakami H., Yabusaki Y., Kuramitsu S., Kagamiyama H.,
RA Yamano T., Okamoto M.;
RT "Molecular cloning and sequence analysis of full-length cDNA for mRNA of
RT adrenodoxin oxidoreductase from bovine adrenal cortex.";
RL Biochem. Biophys. Res. Commun. 145:1239-1247(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adrenal cortex;
RX PubMed=2924777; DOI=10.1111/j.1432-1033.1989.tb14671.x;
RA Hanukoglu I., Gutfinger T.;
RT "cDNA sequence of adrenodoxin reductase. Identification of NADP-binding
RT sites in oxidoreductases.";
RL Eur. J. Biochem. 180:479-484(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=8130767; DOI=10.1248/bpb.16.1200;
RA Takata Y., Sagara Y., Kono A., Sekimizu K., Horiuchi T.;
RT "Gene structure of bovine adrenodoxin reductase.";
RL Biol. Pharm. Bull. 16:1200-1206(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [6]
RP PROTEIN SEQUENCE OF 33-62; 254-276 AND 487-492.
RX PubMed=3355838; DOI=10.1016/0167-4838(88)90026-x;
RA Hamamoto I., Kurokohchi K., Tanaka S., Ichikawa Y.;
RT "Adrenoferredoxin-binding peptide of NADPH-adrenoferredoxin reductase.";
RL Biochim. Biophys. Acta 953:207-213(1988).
RN [7]
RP PROTEIN SEQUENCE OF 33-51 AND 298-320, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=7811729; DOI=10.1016/0167-4838(94)00178-j;
RA Warburton R.J., Seybert D.W.;
RT "Structural and functional characterization of bovine adrenodoxin reductase
RT by limited proteolysis.";
RL Biochim. Biophys. Acta 1246:39-46(1995).
RN [8]
RP PROTEIN SEQUENCE OF N-TERMINUS, AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Adrenal cortex;
RX PubMed=3691502; DOI=10.1111/j.1432-1033.1987.tb13632.x;
RA Hanukoglu I., Gutfinger T., Haniu M., Shively J.E.;
RT "Isolation of a cDNA for adrenodoxin reductase (ferredoxin-NADP+
RT reductase). Implications for mitochondrial cytochrome P-450 systems.";
RL Eur. J. Biochem. 169:449-455(1987).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=3011431; DOI=10.1111/j.1432-1033.1986.tb09633.x;
RA Hanukoglu I., Hanukoglu Z.;
RT "Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and
RT adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for
RT membrane organization and gene regulation.";
RL Eur. J. Biochem. 157:27-31(1986).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 33-492 IN COMPLEX WITH FAD.
RX PubMed=10369776; DOI=10.1006/jmbi.1999.2807;
RA Ziegler G.A., Vonrhein C., Hanukoglu I., Schulz G.E.;
RT "The structure of adrenodoxin reductase of mitochondrial P450 systems:
RT electron transfer for steroid biosynthesis.";
RL J. Mol. Biol. 289:981-990(1999).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 33-492 IN COMPLEX WITH NADP.
RX PubMed=10998235; DOI=10.1021/bi000079k;
RA Ziegler G.A., Schulz G.E.;
RT "Crystal structures of adrenodoxin reductase in complex with NADP+ and
RT NADPH suggesting a mechanism for the electron transfer of an enzyme
RT family.";
RL Biochemistry 39:10986-10995(2000).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 33-492 IN COMPLEX WITH FDX1.
RX PubMed=11053423; DOI=10.1074/jbc.m008501200;
RA Mueller J.J., Lapko A., Bourenkov G., Ruckpaul K., Heinemann U.;
RT "Adrenodoxin reductase-adrenodoxin complex structure suggests electron
RT transfer path in steroid biosynthesis.";
RL J. Biol. Chem. 276:2786-2789(2001).
CC -!- FUNCTION: Serves as the first electron transfer protein in all the
CC mitochondrial P450 systems including cholesterol side chain cleavage in
CC all steroidogenic tissues, steroid 11-beta hydroxylation in the adrenal
CC cortex, 25-OH-vitamin D3-24 hydroxylation in the kidney, and sterol C-
CC 27 hydroxylation in the liver. {ECO:0000269|PubMed:7811729}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADP(+) + 2 reduced [adrenodoxin] = NADPH + 2 oxidized
CC [adrenodoxin]; Xref=Rhea:RHEA:42312, Rhea:RHEA-COMP:9998, Rhea:RHEA-
CC COMP:9999, ChEBI:CHEBI:15378, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.18.1.6;
CC Evidence={ECO:0000269|PubMed:7811729};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:10369776};
CC -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC {ECO:0000269|PubMed:7811729}.
CC -!- SUBUNIT: Monomer. Interacts directly with FDX1.
CC {ECO:0000269|PubMed:10369776, ECO:0000269|PubMed:10998235,
CC ECO:0000269|PubMed:11053423}.
CC -!- INTERACTION:
CC P08165; P00257: FDX1; NbExp=2; IntAct=EBI-593948, EBI-593992;
CC P08165; P0A3E0: isiB; Xeno; NbExp=3; IntAct=EBI-593948, EBI-593907;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P48360}; Peripheral membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Short;
CC IsoId=P08165-1; Sequence=Displayed;
CC Name=Long;
CC IsoId=P08165-2; Sequence=VSP_003415;
CC -!- TISSUE SPECIFICITY: Detected in adrenal cortex and corpus luteum (at
CC protein level). {ECO:0000269|PubMed:3011431}.
CC -!- MISCELLANEOUS: [Isoform Long]: Represents 10-20% of all adrenodoxin
CC reductase mRNAs and seems to be inactive. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ferredoxin--NADP reductase type 1 family.
CC {ECO:0000305}.
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DR EMBL; M17029; AAA30362.1; -; mRNA.
DR EMBL; D00211; BAA00150.1; -; mRNA.
DR EMBL; X13736; CAA32002.1; -; mRNA.
DR EMBL; D83475; BAA11921.1; -; Genomic_DNA.
DR EMBL; BT021817; AAX46664.1; -; mRNA.
DR PIR; JT0751; JT0751.
DR RefSeq; NP_777116.1; NM_174691.1.
DR PDB; 1CJC; X-ray; 1.70 A; A=33-492.
DR PDB; 1E1K; X-ray; 1.95 A; A=33-492.
DR PDB; 1E1L; X-ray; 2.30 A; A=33-492.
DR PDB; 1E1M; X-ray; 1.85 A; A=33-492.
DR PDB; 1E1N; X-ray; 2.40 A; A=33-492.
DR PDB; 1E6E; X-ray; 2.30 A; A/C=33-492.
DR PDBsum; 1CJC; -.
DR PDBsum; 1E1K; -.
DR PDBsum; 1E1L; -.
DR PDBsum; 1E1M; -.
DR PDBsum; 1E1N; -.
DR PDBsum; 1E6E; -.
DR AlphaFoldDB; P08165; -.
DR SMR; P08165; -.
DR IntAct; P08165; 2.
DR STRING; 9913.ENSBTAP00000056258; -.
DR PaxDb; P08165; -.
DR GeneID; 282604; -.
DR KEGG; bta:282604; -.
DR CTD; 2232; -.
DR eggNOG; KOG1800; Eukaryota.
DR InParanoid; P08165; -.
DR OrthoDB; 1324510at2759; -.
DR BRENDA; 1.18.1.6; 908.
DR SABIO-RK; P08165; -.
DR UniPathway; UPA00296; -.
DR EvolutionaryTrace; P08165; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:UniProtKB.
DR GO; GO:0050661; F:NADP binding; IDA:UniProtKB.
DR GO; GO:0015039; F:NADPH-adrenodoxin reductase activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0022900; P:electron transport chain; IDA:UniProtKB.
DR GO; GO:0006694; P:steroid biosynthetic process; TAS:UniProtKB.
DR GO; GO:0006744; P:ubiquinone biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR021163; Ferredox_Rdtase_adrenod.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR PIRSF; PIRSF000362; FNR; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cholesterol metabolism;
KW Direct protein sequencing; Electron transport; FAD; Flavoprotein;
KW Lipid metabolism; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW NADP; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Steroid metabolism; Sterol metabolism; Transit peptide; Transport.
FT TRANSIT 1..32
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:3355838,
FT ECO:0000269|PubMed:3691502, ECO:0000269|PubMed:7811729"
FT CHAIN 33..492
FT /note="NADPH:adrenodoxin oxidoreductase, mitochondrial"
FT /id="PRO_0000019419"
FT BINDING 49
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10369776"
FT BINDING 70
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10369776"
FT BINDING 78
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10369776"
FT BINDING 114
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10369776"
FT BINDING 185..188
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10998235"
FT BINDING 229..230
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10998235"
FT BINDING 241
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10998235"
FT BINDING 399
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10369776"
FT BINDING 406..408
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:10369776"
FT BINDING 406
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10998235"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22570"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22570"
FT VAR_SEQ 204
FT /note="E -> EVLLLCQ (in isoform Long)"
FT /evidence="ECO:0000305"
FT /id="VSP_003415"
FT CONFLICT 42
FT /note="C -> S (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 77
FT /note="G -> R (in Ref. 2; AAA30362)"
FT /evidence="ECO:0000305"
FT CONFLICT 81..94
FT /note="FGVAPDHPEVKNVI -> VWLALTTPRSRMLL (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 124..128
FT /note="QDAYH -> RVYRLT (in Ref. 2; AAA30362)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="K -> R (in Ref. 2; AAA30362)"
FT /evidence="ECO:0000305"
FT CONFLICT 317..318
FT /note="PS -> RL (in Ref. 2; AAA30362)"
FT /evidence="ECO:0000305"
FT CONFLICT 323..333
FT /note="RAAGIRLAVTR -> ARRSAWQSPE (in Ref. 2; AAA30362)"
FT /evidence="ECO:0000305"
FT CONFLICT 341..352
FT /note="TRAVPTGDVEDL -> HPGSAHWGCGGP (in Ref. 2; AAA30362)"
FT /evidence="ECO:0000305"
FT CONFLICT 488..489
FT /note="RL -> TM (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 491
FT /note="G -> R (in Ref. 5; AAX46664)"
FT /evidence="ECO:0000305"
FT STRAND 40..44
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 48..60
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 65..69
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 71..75
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 88..92
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 93..101
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 106..111
FT /evidence="ECO:0007829|PDB:1CJC"
FT TURN 114..116
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 120..126
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 127..132
FT /evidence="ECO:0007829|PDB:1CJC"
FT TURN 145..148
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 155..162
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 177..184
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 187..197
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 200..203
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 210..217
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 223..227
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 239..246
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 251..254
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 257..260
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 263..266
FT /evidence="ECO:0007829|PDB:1CJC"
FT TURN 267..269
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 272..286
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 291..298
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 301..307
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 309..317
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 321..337
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 338..340
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 342..353
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 355..359
FT /evidence="ECO:0007829|PDB:1CJC"
FT TURN 376..379
FT /evidence="ECO:0007829|PDB:1CJC"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 399..402
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 408..428
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 439..449
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 456..473
FT /evidence="ECO:0007829|PDB:1CJC"
FT HELIX 483..489
FT /evidence="ECO:0007829|PDB:1CJC"
SQ SEQUENCE 492 AA; 54338 MW; E68F6F5D18F53131 CRC64;
MAPRCWRWWP WSSWTRTRLP PSRSIQNFGQ HFSTQEQTPQ ICVVGSGPAG FYTAQHLLKH
HSRAHVDIYE KQLVPFGLVR FGVAPDHPEV KNVINTFTQT ARSDRCAFYG NVEVGRDVTV
QELQDAYHAV VLSYGAEDHQ ALDIPGEELP GVFSARAFVG WYNGLPENRE LAPDLSCDTA
VILGQGNVAL DVARILLTPP DHLEKTDITE AALGALRQSR VKTVWIVGRR GPLQVAFTIK
ELREMIQLPG TRPMLDPADF LGLQDRIKEA ARPRKRLMEL LLRTATEKPG VEEAARRASA
SRAWGLRFFR SPQQVLPSPD GRRAAGIRLA VTRLEGIGEA TRAVPTGDVE DLPCGLVLSS
IGYKSRPIDP SVPFDPKLGV VPNMEGRVVD VPGLYCSGWV KRGPTGVITT TMTDSFLTGQ
ILLQDLKAGH LPSGPRPGSA FIKALLDSRG VWPVSFSDWE KLDAEEVSRG QASGKPREKL
LDPQEMLRLL GH
