Reviewed, UniProtKB/Swiss-Prot P08165 (ADRO_BOVIN)

Names and origin

Protein names

Recommended name:
    NADPH:adrenodoxin oxidoreductase, mitochondrial
      Short name=Adrenodoxin reductase
      Short name=AR
    EC=1.18.1.2
Alternative name(s):
    Ferredoxin--NADP(+) reductase
      Short name=Ferredoxin reductase

Gene names

Name:	FDXR
Synonyms:	ADXR

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	492 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Serves as the first electron transfer protein in all the mitochondrial P450 systems. Including cholesterol side chain cleavage in all steroidogenic tissues, steroid 11-beta hydroxylation in the adrenal cortex, 25-OH-vitamin D3-24 hydroxylation in the kidney, and sterol C-27 hydroxylation in the liver.
Catalytic activity	2 reduced ferredoxin + NADP+ + H+ = 2 oxidized ferredoxin + NADPH.
Cofactor	FAD.
Pathway	Steroid metabolism; cholesterol metabolism.
Subunit structure	Monomer. Interacts directly with FDX1.
Subcellular location	Mitochondrion matrix.
Sequence similarities	Belongs to the ferredoxin--NADP reductase type 1 family.

Ontologies

Keywords
Biological process	Cholesterol metabolism Electron transport Lipid metabolism Steroid metabolism Transport
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Domain	Transit peptide
Ligand	FAD Flavoprotein NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cholesterol metabolic process Inferred from electronic annotation. Source: UniProtKB-KW electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW steroid biosynthetic process Traceable author statement. Source: UniProtKB transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	FAD binding Inferred from direct assay. Source: UniProtKB NADP or NADPH binding Inferred from direct assay. Source: UniProtKB electron carrier activity Inferred from electronic annotation. Source: InterPro ferredoxin-NADP+ reductase activity Traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FDX1	P00257	1	EBI-593948,EBI-593992
isiB	P0A3E0	3	EBI-593948,EBI-593907	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Short (identifier: P08165-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Long (identifier: P08165-2)

The sequence of this isoform differs from the canonical sequence as follows:
     204-204: E → EVLLLCQ

Note: Represents 10-20% of all adrenodoxin reductase mRNAs and seems to be inactive.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 32

32

Mitochondrion Ref.6 Ref.7

Chain

33 – 492

460

NADPH:adrenodoxin oxidoreductase, mitochondrial

PRO_0000019419

Regions

Nucleotide binding

185 – 188

4

NADP

Nucleotide binding

229 – 230

2

NADP

Nucleotide binding

406 – 408

3

FAD

Sites

Binding site

49

1

FAD; via amide nitrogen

Binding site

70

1

FAD

Binding site

78

1

FAD; via amide nitrogen

Binding site

114

1

FAD; via amide nitrogen and carbonyl oxygen

Binding site

241

1

NADP

Binding site

399

1

FAD; via amide nitrogen

Binding site

406

1

NADP; via amide nitrogen

Natural variations

Alternative sequence

204

1

E → EVLLLCQ in isoform Long.

VSP_003415

Experimental info

Sequence conflict

42

1

C → S AA sequence Ref.6

Sequence conflict

77

1

G → R in AAA30362. Ref.2

Sequence conflict

81 – 94

14

FGVAP…VKNVI → VWLALTTPRSRMLL Ref.2

Sequence conflict

124 – 128

5

QDAYH → RVYRLT in AAA30362. Ref.2

Sequence conflict

268

1

K → R in AAA30362. Ref.2

Sequence conflict

317 – 318

2

PS → RL in AAA30362. Ref.2

Sequence conflict

323 – 333

11

RAAGIRLAVTR → ARRSAWQSPE in AAA30362. Ref.2

Sequence conflict

341 – 352

12

TRAVP…DVEDL → HPGSAHWGCGGP in AAA30362. Ref.2

Sequence conflict

488 – 489

2

RL → TM AA sequence Ref.6

Sequence conflict

491

1

G → R in AAX46664. Ref.5

Secondary structure

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492

Helix Strand Turn

Details...

Beta strand

40 – 44

5

Helix

48 – 60

13

Beta strand

65 – 69

5

Beta strand

71 – 75

5

Helix

78 – 81

4

Helix

88 – 92

5

Helix

93 – 101

9

Beta strand

106 – 111

6

Turn

114 – 116

3

Helix

120 – 126

7

Beta strand

127 – 132

6

Turn

145 – 148

4

Beta strand

152 – 154

3

Helix

155 – 162

8

Helix

166 – 168

3

Beta strand

177 – 184

8

Helix

187 – 197

11

Helix

200 – 203

4

Helix

210 – 217

8

Beta strand

223 – 227

5

Helix

232 – 234

3

Helix

239 – 246

8

Beta strand

251 – 254

4

Helix

257 – 260

4

Helix

263 – 266

4

Turn

267 – 269

3

Helix

272 – 286

15

Helix

291 – 298

8

Beta strand

301 – 307

7

Beta strand

309 – 317

9

Beta strand

321 – 337

17

Helix

338 – 340

3

Beta strand

342 – 353

12

Beta strand

355 – 359

5

Turn

376 – 379

4

Beta strand

394 – 396

3

Helix

399 – 402

4

Helix

408 – 428

21

Helix

439 – 449

11

Helix

456 – 473

18

Helix

483 – 489

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform Short [UniParc]. Last modified July 15, 1998. Version 3. Checksum: E68F6F5D18F53131	FASTA	492	54,338
	10 20 30 40 50 60 MAPRCWRWWP WSSWTRTRLP PSRSIQNFGQ HFSTQEQTPQ ICVVGSGPAG FYTAQHLLKH 70 80 90 100 110 120 HSRAHVDIYE KQLVPFGLVR FGVAPDHPEV KNVINTFTQT ARSDRCAFYG NVEVGRDVTV 130 140 150 160 170 180 QELQDAYHAV VLSYGAEDHQ ALDIPGEELP GVFSARAFVG WYNGLPENRE LAPDLSCDTA 190 200 210 220 230 240 VILGQGNVAL DVARILLTPP DHLEKTDITE AALGALRQSR VKTVWIVGRR GPLQVAFTIK 250 260 270 280 290 300 ELREMIQLPG TRPMLDPADF LGLQDRIKEA ARPRKRLMEL LLRTATEKPG VEEAARRASA 310 320 330 340 350 360 SRAWGLRFFR SPQQVLPSPD GRRAAGIRLA VTRLEGIGEA TRAVPTGDVE DLPCGLVLSS 370 380 390 400 410 420 IGYKSRPIDP SVPFDPKLGV VPNMEGRVVD VPGLYCSGWV KRGPTGVITT TMTDSFLTGQ 430 440 450 460 470 480 ILLQDLKAGH LPSGPRPGSA FIKALLDSRG VWPVSFSDWE KLDAEEVSRG QASGKPREKL 490 LDPQEMLRLL GH
	Isoform Long. Checksum: BB3238129E92F3D1	FASTA	498	55,008
	10 20 30 40 50 60 MAPRCWRWWP WSSWTRTRLP PSRSIQNFGQ HFSTQEQTPQ ICVVGSGPAG FYTAQHLLKH 70 80 90 100 110 120 HSRAHVDIYE KQLVPFGLVR FGVAPDHPEV KNVINTFTQT ARSDRCAFYG NVEVGRDVTV 130 140 150 160 170 180 QELQDAYHAV VLSYGAEDHQ ALDIPGEELP GVFSARAFVG WYNGLPENRE LAPDLSCDTA 190 200 210 220 230 240 VILGQGNVAL DVARILLTPP DHLEVLLLCQ KTDITEAALG ALRQSRVKTV WIVGRRGPLQ 250 260 270 280 290 300 VAFTIKELRE MIQLPGTRPM LDPADFLGLQ DRIKEAARPR KRLMELLLRT ATEKPGVEEA 310 320 330 340 350 360 ARRASASRAW GLRFFRSPQQ VLPSPDGRRA AGIRLAVTRL EGIGEATRAV PTGDVEDLPC 370 380 390 400 410 420 GLVLSSIGYK SRPIDPSVPF DPKLGVVPNM EGRVVDVPGL YCSGWVKRGP TGVITTTMTD 430 440 450 460 470 480 SFLTGQILLQ DLKAGHLPSG PRPGSAFIKA LLDSRGVWPV SFSDWEKLDA EEVSRGQASG 490 KPREKLLDPQ EMLRLLGH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequence analysis of adrenodoxin reductase cDNA from bovine adrenal cortex." Sagara Y., Takata Y., Miyata T., Hara T., Horiuchi T. J. Biochem. 102:1333-1336(1987) [PubMed: 3448086] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"Molecular cloning and sequence analysis of full-length cDNA for mRNA of adrenodoxin oxidoreductase from bovine adrenal cortex." Nonaka Y., Murakami H., Yabusaki Y., Kuramitsu S., Kagamiyama H., Yamano T., Okamoto M. Biochem. Biophys. Res. Commun. 145:1239-1247(1987) [PubMed: 3038094] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases." Hanukoglu I., Gutfinger T. Eur. J. Biochem. 180:479-484(1989) [PubMed: 2924777] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Adrenal cortex.
[4]	"Gene structure of bovine adrenodoxin reductase." Takata Y., Sagara Y., Kono A., Sekimizu K., Horiuchi T. Biol. Pharm. Bull. 16:1200-1206(1993) [PubMed: 8130767] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
[5]	"Characterization of 954 bovine full-CDS cDNA sequences." Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L. BMC Genomics 6:166-166(2005) [PubMed: 16305752] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Adrenoferredoxin-binding peptide of NADPH-adrenoferredoxin reductase." Hamamoto I., Kurokohchi K., Tanaka S., Ichikawa Y. Biochim. Biophys. Acta 953:207-213(1988) [PubMed: 3355838] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-62; 254-276 AND 487-492.
[7]	"Structural and functional characterization of bovine adrenodoxin reductase by limited proteolysis." Warburton R.J., Seybert D.W. Biochim. Biophys. Acta 1246:39-46(1995) [PubMed: 7811729] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-51 AND 298-320.
[8]	"Isolation of a cDNA for adrenodoxin reductase (ferredoxin-NADP+ reductase). Implications for mitochondrial cytochrome P-450 systems." Hanukoglu I., Gutfinger T., Haniu M., Shively J.E. Eur. J. Biochem. 169:449-455(1987) [PubMed: 3691502] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS, PARTIAL PROTEIN SEQUENCE. Tissue: Adrenal cortex.
[9]	"The structure of adrenodoxin reductase of mitochondrial P450 systems: electron transfer for steroid biosynthesis." Ziegler G.A., Vonrhein C., Hanukoglu I., Schulz G.E. J. Mol. Biol. 289:981-990(1999) [PubMed: 10369776] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 33-492 IN COMPLEX WITH FAD.
[10]	"Crystal structures of adrenodoxin reductase in complex with NADP+ and NADPH suggesting a mechanism for the electron transfer of an enzyme family." Ziegler G.A., Schulz G.E. Biochemistry 39:10986-10995(2000) [PubMed: 10998235] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 33-492 IN COMPLEX WITH NADP.
[11]	"Adrenodoxin reductase-adrenodoxin complex structure suggests electron transfer path in steroid biosynthesis." Mueller J.J., Lapko A., Bourenkov G., Ruckpaul K., Heinemann U. J. Biol. Chem. 276:2786-2789(2001) [PubMed: 11053423] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 33-492 IN COMPLEX WITH FDX1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M17029 mRNA. Translation: AAA30362.1.
D00211 mRNA. Translation: BAA00150.1.
X13736 mRNA. Translation: CAA32002.1.
D83475 Genomic DNA. Translation: BAA11921.1.
BT021817 mRNA. Translation: AAX46664.1.

IPI

IPI00697194.
IPI00698450.

PIR

JT0751.

RefSeq

NP_777116.1.

UniGene

Bt.64647

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CJC	X-ray	1.70	A	33-492	[»]
1E1K	X-ray	1.95	A	33-492	[»]
1E1L	X-ray	2.30	A	33-492	[»]
1E1M	X-ray	1.85	A	33-492	[»]
1E1N	X-ray	2.40	A	33-492	[»]
1E6E	X-ray	2.30	A/C	33-492	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P08165. 2 interactions.

Genome annotation databases

Ensembl

ENSBTAT00000034683; ENSBTAP00000034569; ENSBTAG00000006525; Bos taurus. [Genome view]

GeneID

282604.

KEGG

bta:282604.

Organism-specific databases

CTD

282604.

Phylogenomic databases

HOVERGEN

P08165.

Enzyme and pathway databases

BRENDA

1.18.1.2. 251.

Family and domain databases

InterPro

IPR000759. Adrndx_reductase.
[Graphical view]

PRINTS

PR00419. ADXRDTASE.

ProtoNet

Search...

Entry information

Entry name

ADRO_BOVIN

Accession

Primary (citable) accession number: P08165
Secondary accession number(s): Q58CY0, Q95KN8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	July 15, 1998
Last modified:	September 1, 2009
This is version 106 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)