P22570 (ADRO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NADPH:adrenodoxin oxidoreductase, mitochondrial
Short name=AR
Short name=Adrenodoxin reductase
EC=1.18.1.6

Alternative name(s):
Ferredoxin--NADP(+) reductase
Short name=Ferredoxin reductase

Gene names

Name:	FDXR
Synonyms:	ADXR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	491 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 adrenodoxin + NADP+ = 2 oxidized adrenodoxin + NADPH.
Cofactor	FAD.
Pathway	Steroid metabolism; cholesterol metabolism.
Subunit structure	Monomer. Interacts directly with FDX1 By similarity.
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 Sterol metabolism Transport
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Ligand	FAD Flavoprotein NADP
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NADPH oxidation Inferred from electronic annotation. Source: Compara cholesterol metabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW generation of precursor metabolites and energy Traceable author statement Ref.1. Source: ProtInc steroid biosynthetic process Traceable author statement PubMed 1863359. Source: ProtInc
Cellular_component	mitochondrial inner membrane Inferred from electronic annotation. Source: Compara mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Traceable author statement Ref.1. Source: ProtInc
Molecular_function	NADPH binding Inferred from electronic annotation. Source: Compara NADPH-adrenodoxin reductase activity Inferred from electronic annotation. Source: Compara ferredoxin-NADP+ reductase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FHIT	P49789	4	EBI-1751533,EBI-741760

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform Short (identifier: P22570-1)

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: P22570-2)

The sequence of this isoform differs from the canonical sequence as follows:
     203-203: E → EALLLCQ

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

Isoform 3 (identifier: P22570-3)

The sequence of this isoform differs from the canonical sequence as follows:
     59-59: K → KRVEALCSQPRVLNSPALSGEGEDLGASQPLSLDPTSCHPVPQQ

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 32	32	Mitochondrion
	Chain	33 – 491	459	NADPH:adrenodoxin oxidoreductase, mitochondrial		PRO_0000019420
Regions
	Nucleotide binding	184 – 187	4	NADP By similarity
	Nucleotide binding	228 – 229	2	NADP By similarity
	Nucleotide binding	405 – 407	3	FAD By similarity
Sites
	Binding site	49	1	FAD; via amide nitrogen By similarity
	Binding site	69	1	FAD By similarity
	Binding site	77	1	FAD; via amide nitrogen By similarity
	Binding site	113	1	FAD; via amide nitrogen and carbonyl oxygen By similarity
	Binding site	240	1	NADP By similarity
	Binding site	398	1	FAD; via amide nitrogen By similarity
	Binding site	405	1	NADP; via amide nitrogen By similarity
Natural variations
	Alternative sequence	59	1	K → KRVEALCSQPRVLNSPALSG EGEDLGASQPLSLDPTSCHP VPQQ in isoform 3.		VSP_045135
	Alternative sequence	203	1	E → EALLLCQ in isoform Long.		VSP_003416
	Natural variant	7	1	R → L. Ref.3 Corresponds to variant rs28365947 [ dbSNP | Ensembl ].		VAR_025192
	Natural variant	123	1	R → Q. Ref.1 Ref.3 Corresponds to variant rs690514 [ dbSNP | Ensembl ].		VAR_004624
	Natural variant	213	1	G → V. Ref.3 Corresponds to variant rs35692345 [ dbSNP | Ensembl ].		VAR_025193
	Natural variant	248	1	P → L. Ref.3 Corresponds to variant rs35072974 [ dbSNP | Ensembl ].		VAR_025194
	Natural variant	251	1	R → W. Ref.3 Corresponds to variant rs34038065 [ dbSNP | Ensembl ].		VAR_025195
	Natural variant	301	1	R → C. Ref.3 Corresponds to variant rs34118765 [ dbSNP | Ensembl ].		VAR_025196
	Natural variant	345	1	T → M. Ref.3 Corresponds to variant rs35660143 [ dbSNP | Ensembl ].		VAR_025197
	Natural variant	352	1	P → S. Ref.3 Corresponds to variant rs35696549 [ dbSNP | Ensembl ].		VAR_025198
	Natural variant	472	1	T → A. Ref.3 Corresponds to variant rs35769464 [ dbSNP | Ensembl ].		VAR_025199

Sequences

	Sequence		Length	Mass (Da)
	Isoform Short [UniParc]. Last modified January 24, 2006. Version 3. Checksum: 15D07E714F592C9D	FASTA	491	53,837
	10 20 30 40 50 60 MASRCWRWWG WSAWPRTRLP PAGSTPSFCH HFSTQEKTPQ ICVVGSGPAG FYTAQHLLKH 70 80 90 100 110 120 PQAHVDIYEK QPVPFGLVRF GVAPDHPEVK NVINTFTQTA HSGRCAFWGN VEVGRDVTVP 130 140 150 160 170 180 ELREAYHAVV LSYGAEDHRA LEIPGEELPG VCSARAFVGW YNGLPENQEL EPDLSCDTAV 190 200 210 220 230 240 ILGQGNVALD VARILLTPPE HLERTDITKA ALGVLRQSRV KTVWLVGRRG PLQVAFTIKE 250 260 270 280 290 300 LREMIQLPGA RPILDPVDFL GLQDKIKEVP RPRKRLTELL LRTATEKPGP AEAARQASAS 310 320 330 340 350 360 RAWGLRFFRS PQQVLPSPDG RRAAGVRLAV TRLEGVDEAT RAVPTGDMED LPCGLVLSSI 370 380 390 400 410 420 GYKSRPVDPS VPFDSKLGVI PNVEGRVMDV PGLYCSGWVK RGPTGVIATT MTDSFLTGQM 430 440 450 460 470 480 LLQDLKAGLL PSGPRPGYAA IQALLSSRGV RPVSFSDWEK LDAEEVARGQ GTGKPREKLV 490 DPQEMLRLLG H
	Isoform Long [UniParc]. Checksum: 08C3D3F2C86564DA	FASTA	497	54,479
	10 20 30 40 50 60 MASRCWRWWG WSAWPRTRLP PAGSTPSFCH HFSTQEKTPQ ICVVGSGPAG FYTAQHLLKH 70 80 90 100 110 120 PQAHVDIYEK QPVPFGLVRF GVAPDHPEVK NVINTFTQTA HSGRCAFWGN VEVGRDVTVP 130 140 150 160 170 180 ELREAYHAVV LSYGAEDHRA LEIPGEELPG VCSARAFVGW YNGLPENQEL EPDLSCDTAV 190 200 210 220 230 240 ILGQGNVALD VARILLTPPE HLEALLLCQR TDITKAALGV LRQSRVKTVW LVGRRGPLQV 250 260 270 280 290 300 AFTIKELREM IQLPGARPIL DPVDFLGLQD KIKEVPRPRK RLTELLLRTA TEKPGPAEAA 310 320 330 340 350 360 RQASASRAWG LRFFRSPQQV LPSPDGRRAA GVRLAVTRLE GVDEATRAVP TGDMEDLPCG 370 380 390 400 410 420 LVLSSIGYKS RPVDPSVPFD SKLGVIPNVE GRVMDVPGLY CSGWVKRGPT GVIATTMTDS 430 440 450 460 470 480 FLTGQMLLQD LKAGLLPSGP RPGYAAIQAL LSSRGVRPVS FSDWEKLDAE EVARGQGTGK 490 PREKLVDPQE MLRLLGH
	Isoform 3 [UniParc]. Checksum: 755B0612AAD29612	FASTA	534	58,304
	10 20 30 40 50 60 MASRCWRWWG WSAWPRTRLP PAGSTPSFCH HFSTQEKTPQ ICVVGSGPAG FYTAQHLLKR 70 80 90 100 110 120 VEALCSQPRV LNSPALSGEG EDLGASQPLS LDPTSCHPVP QQHPQAHVDI YEKQPVPFGL 130 140 150 160 170 180 VRFGVAPDHP EVKNVINTFT QTAHSGRCAF WGNVEVGRDV TVPELREAYH AVVLSYGAED 190 200 210 220 230 240 HRALEIPGEE LPGVCSARAF VGWYNGLPEN QELEPDLSCD TAVILGQGNV ALDVARILLT 250 260 270 280 290 300 PPEHLERTDI TKAALGVLRQ SRVKTVWLVG RRGPLQVAFT IKELREMIQL PGARPILDPV 310 320 330 340 350 360 DFLGLQDKIK EVPRPRKRLT ELLLRTATEK PGPAEAARQA SASRAWGLRF FRSPQQVLPS 370 380 390 400 410 420 PDGRRAAGVR LAVTRLEGVD EATRAVPTGD MEDLPCGLVL SSIGYKSRPV DPSVPFDSKL 430 440 450 460 470 480 GVIPNVEGRV MDVPGLYCSG WVKRGPTGVI ATTMTDSFLT GQMLLQDLKA GLLPSGPRPG 490 500 510 520 530 YAAIQALLSS RGVRPVSFSD WEKLDAEEVA RGQGTGKPRE KLVDPQEMLR LLGH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human adrenodoxin reductase: two mRNAs encoded by a single gene on chromosome 17cen-->q25 are expressed in steroidogenic tissues." Solish S.B., Picado-Leonard J., Morel Y., Kuhn R.W., Mohandas T.K., Hanukoglu I., Miller W.L. Proc. Natl. Acad. Sci. U.S.A. 85:7104-7108(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS SHORT AND LONG), VARIANT GLN-123.
[2]	"Cloning and sequence of the human adrenodoxin reductase gene." Lin D., Shi Y., Miller W.L. Proc. Natl. Acad. Sci. U.S.A. 87:8516-8520(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	NIEHS SNPs program Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-7; GLN-123; VAL-213; LEU-248; TRP-251; CYS-301; MET-345; SER-352 AND ALA-472.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Caudate nucleus.
[5]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT). Tissue: Lung.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	J03826 mRNA. Translation: AAB59498.1. J03826 mRNA. Translation: AAB59497.1. M58509, M58508 Genomic DNA. Translation: AAA51668.1. M58509, M58508 Genomic DNA. Translation: AAA51669.1. DQ085780 Genomic DNA. Translation: AAY68215.1. AK295307 mRNA. Translation: BAG58287.1. AC068874 Genomic DNA. No translation available. BC002960 mRNA. Translation: AAH02960.1.
IPI	IPI00026958. IPI00221118.
PIR	A40487.
RefSeq	NP_001244941.1. NM_001258012.1. NP_001244942.1. NM_001258013.1. NP_001244943.1. NM_001258014.1. NP_001244944.1. NM_001258015.1. NP_004101.2. NM_004110.3. NP_077728.2. NM_024417.2.
UniGene	Hs.69745.
3D structure databases
ProteinModelPortal	P22570.
ModBase	Search...
Protein-protein interaction databases
IntAct	P22570. 2 interactions.
STRING	9606.ENSP00000293195.
PTM databases
PhosphoSite	P22570.
Polymorphism databases
DMDM	85681283.
2D gel databases
REPRODUCTION-2DPAGE	IPI00026958.
Proteomic databases
PaxDb	P22570.
PeptideAtlas	P22570.
PRIDE	P22570.
Protocols and materials databases
DNASU	2232.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000293195; ENSP00000293195; ENSG00000161513. ENST00000442102; ENSP00000416515; ENSG00000161513. ENST00000581530; ENSP00000462972; ENSG00000161513.
GeneID	2232.
KEGG	hsa:2232.
UCSC	uc002jlw.3. human. uc002jlx.3. human.
Organism-specific databases
CTD	2232.
GeneCards	GC17M072858.
HGNC	HGNC:3642. FDXR.
HPA	CAB008597.
MIM	103270. gene.
neXtProt	NX_P22570.
PharmGKB	PA28086.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0493.
HOGENOM	HOG000249250.
HOVERGEN	HBG002132.
InParanoid	P22570.
KO	K00528.
OMA	KRVEALC.
OrthoDB	EOG44J2J3.
Enzyme and pathway databases
BioCyc	MetaCyc:HS08587-MONOMER.
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00296.
Gene expression databases
ArrayExpress	P22570.
Bgee	P22570.
CleanEx	HS_FDXR.
Genevestigator	P22570.
GermOnline	ENSG00000161513. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.720. 2 hits.
InterPro	IPR021163. Adrenodoxin_Rdtase. IPR016040. NAD(P)-bd_dom. [Graphical view]
PIRSF	PIRSF000362. FNR. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	2232.
NextBio	9037.
SOURCE	Search...

Entry information

Entry name

ADRO_HUMAN

Accession

Primary (citable) accession number: P22570
Secondary accession number(s): B4DHX5 , Q13716, Q4PJI0, Q9BU12

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	January 24, 2006
Last modified:	May 1, 2013
This is version 136 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.