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Protein

NADPH:adrenodoxin oxidoreductase, mitochondrial

Gene

FDXR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity

Catalytic activityi

2 reduced adrenodoxin + NADP+ = 2 oxidized adrenodoxin + NADPH.By similarity

Cofactori

FADBy similarity

Pathwayi: cholesterol metabolism

This protein is involved in the pathway cholesterol metabolism, which is part of Steroid metabolism.By similarity
View all proteins of this organism that are known to be involved in the pathway cholesterol metabolism and in Steroid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei49FAD; via amide nitrogenBy similarity1
Binding sitei69FADBy similarity1
Binding sitei77FAD; via amide nitrogenBy similarity1
Binding sitei113FAD; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei240NADPBy similarity1
Binding sitei398FAD; via amide nitrogenBy similarity1
Binding sitei405NADP; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi184 – 187NADPBy similarity4
Nucleotide bindingi228 – 229NADPBy similarity2
Nucleotide bindingi405 – 407FADBy similarity3

GO - Molecular functioni

  • ferredoxin-NADP+ reductase activity Source: ProtInc
  • NADPH-adrenodoxin reductase activity Source: GO_Central

GO - Biological processi

  • C21-steroid hormone biosynthetic process Source: Reactome
  • cholesterol metabolic process Source: UniProtKB-UniPathway
  • generation of precursor metabolites and energy Source: ProtInc
  • oxidation-reduction process Source: ProtInc
  • steroid biosynthetic process Source: ProtInc
  • sterol metabolic process Source: Reactome
  • ubiquinone biosynthetic process Source: GO_Central

Keywordsi

Molecular functionOxidoreductase
Biological processCholesterol metabolism, Electron transport, Lipid metabolism, Steroid metabolism, Sterol metabolism, Transport
LigandFAD, Flavoprotein, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS08587-MONOMER
ReactomeiR-HSA-196108 Pregnenolone biosynthesis
R-HSA-211976 Endogenous sterols
R-HSA-2395516 Electron transport from NADPH to Ferredoxin
R-HSA-5579026 Defective CYP11A1 causes Adrenal insufficiency, congenital, with 46,XY sex reversal (AICSR)
UniPathwayiUPA00296

Names & Taxonomyi

Protein namesi
Recommended name:
NADPH:adrenodoxin oxidoreductase, mitochondrial (EC:1.18.1.6By similarity)
Short name:
AR
Short name:
Adrenodoxin reductase1 Publication
Alternative name(s):
Ferredoxin--NADP(+) reductase
Short name:
Ferredoxin reductase
Gene namesi
Name:FDXRImported
Synonyms:ADXR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000161513.11
HGNCiHGNC:3642 FDXR
MIMi103270 gene
neXtProtiNX_P22570

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Involvement in diseasei

Auditory neuropathy and optic atrophy (ANOA)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disease characterized by hearing loss, visual impairment and optic atrophy, with onset in the first or second decades of life. Optic atrophy is caused by degeneration of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts.
See also OMIM:617717
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080376215L → V in ANOA. 1 Publication1
Natural variantiVAR_080377242R → W in ANOA. 1 Publication1
Natural variantiVAR_080378306R → C in ANOA. 1 Publication1
Natural variantiVAR_080379327R → S in ANOA. 1 Publication1
Natural variantiVAR_080380419 – 491Missing in ANOA. 1 PublicationAdd BLAST73

Keywords - Diseasei

Deafness, Disease mutation, Neuropathy

Organism-specific databases

DisGeNETi2232
MalaCardsiFDXR
MIMi617717 phenotype
OpenTargetsiENSG00000161513
PharmGKBiPA28086

Chemistry databases

DrugBankiDB03461 2'-Monophosphoadenosine 5'-Diphosphoribose
DB03147 Flavin adenine dinucleotide

Polymorphism and mutation databases

BioMutaiFDXR
DMDMi85681283

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 32MitochondrionBy similarityAdd BLAST32
ChainiPRO_000001942033 – 491NADPH:adrenodoxin oxidoreductase, mitochondrialAdd BLAST459

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei310PhosphoserineCombined sources1
Modified residuei317PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP22570
PaxDbiP22570
PeptideAtlasiP22570
PRIDEiP22570
ProteomicsDBi54003
54004 [P22570-2]

2D gel databases

REPRODUCTION-2DPAGEiIPI00026958

PTM databases

iPTMnetiP22570
PhosphoSitePlusiP22570

Expressioni

Gene expression databases

BgeeiENSG00000161513
CleanExiHS_FDXR
ExpressionAtlasiP22570 baseline and differential
GenevisibleiP22570 HS

Organism-specific databases

HPAiCAB008597
CAB009818
HPA044393
HPA053673

Interactioni

Subunit structurei

Monomer. Interacts directly with FDX1.By similarity

Protein-protein interaction databases

BioGridi108523, 26 interactors
IntActiP22570, 2 interactors
STRINGi9606.ENSP00000462972

Structurei

3D structure databases

ProteinModelPortaliP22570
SMRiP22570
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1800 Eukaryota
COG0493 LUCA
GeneTreeiENSGT00390000013574
HOGENOMiHOG000249250
HOVERGENiHBG002132
InParanoidiP22570
KOiK18914
PhylomeDBiP22570
TreeFamiTF314193

Family and domain databases

Gene3Di3.50.50.60, 2 hits
InterProiView protein in InterPro
IPR036188 FAD/NAD-bd_sf
IPR023753 FAD/NAD-binding_dom
IPR021163 Ferredox_Rdtase_adrenod
PfamiView protein in Pfam
PF07992 Pyr_redox_2, 1 hit
PIRSFiPIRSF000362 FNR, 1 hit
SUPFAMiSSF51905 SSF51905, 1 hit

Sequences (7)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Short (identifier: P22570-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MASRCWRWWG WSAWPRTRLP PAGSTPSFCH HFSTQEKTPQ ICVVGSGPAG
60 70 80 90 100
FYTAQHLLKH PQAHVDIYEK QPVPFGLVRF GVAPDHPEVK NVINTFTQTA
110 120 130 140 150
HSGRCAFWGN VEVGRDVTVP ELREAYHAVV LSYGAEDHRA LEIPGEELPG
160 170 180 190 200
VCSARAFVGW YNGLPENQEL EPDLSCDTAV ILGQGNVALD VARILLTPPE
210 220 230 240 250
HLERTDITKA ALGVLRQSRV KTVWLVGRRG PLQVAFTIKE LREMIQLPGA
260 270 280 290 300
RPILDPVDFL GLQDKIKEVP RPRKRLTELL LRTATEKPGP AEAARQASAS
310 320 330 340 350
RAWGLRFFRS PQQVLPSPDG RRAAGVRLAV TRLEGVDEAT RAVPTGDMED
360 370 380 390 400
LPCGLVLSSI GYKSRPVDPS VPFDSKLGVI PNVEGRVMDV PGLYCSGWVK
410 420 430 440 450
RGPTGVIATT MTDSFLTGQM LLQDLKAGLL PSGPRPGYAA IQALLSSRGV
460 470 480 490
RPVSFSDWEK LDAEEVARGQ GTGKPREKLV DPQEMLRLLG H
Length:491
Mass (Da):53,837
Last modified:January 24, 2006 - v3
Checksum:i15D07E714F592C9D
GO
Isoform Long (identifier: P22570-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:497
Mass (Da):54,479
Checksum:i08C3D3F2C86564DA
GO
Isoform 3 (identifier: P22570-3) [UniParc]FASTAAdd to basket

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

Show »
Length:534
Mass (Da):58,304
Checksum:i755B0612AAD29612
GO
Isoform 4 (identifier: P22570-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: MASRCWRWWGWSAWPRTRLPPAGSTPSFCHHFSTQEKTPQICVVGSGPAGFYTAQHLLK → MEDKDRE

Show »
Length:439
Mass (Da):48,056
Checksum:i20D88F1A91909900
GO
Isoform 5 (identifier: P22570-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     91-98: Missing.

Show »
Length:483
Mass (Da):52,919
Checksum:i8AD11CAC35C3E4C1
GO
Isoform 6 (identifier: P22570-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     59-59: K → KQ
     91-131: Missing.

Note: No experimental confirmation available.
Show »
Length:451
Mass (Da):49,425
Checksum:i367CE00CA673D9E2
GO
Isoform 7 (identifier: P22570-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     27-34: SFCHHFST → TFGGSDEVRDPANAKALRNKRRRMQVRVKLGKFQLLLDI

Note: No experimental confirmation available.
Show »
Length:522
Mass (Da):57,370
Checksum:i1D82107E5C08C814
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti223V → G in BAG56748 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0251927R → L1 PublicationCorresponds to variant dbSNP:rs28365947Ensembl.1
Natural variantiVAR_004624123R → Q3 PublicationsCorresponds to variant dbSNP:rs690514Ensembl.1
Natural variantiVAR_025193213G → V1 PublicationCorresponds to variant dbSNP:rs35692345Ensembl.1
Natural variantiVAR_080376215L → V in ANOA. 1 Publication1
Natural variantiVAR_080377242R → W in ANOA. 1 Publication1
Natural variantiVAR_025194248P → L1 PublicationCorresponds to variant dbSNP:rs35072974Ensembl.1
Natural variantiVAR_025195251R → W1 PublicationCorresponds to variant dbSNP:rs34038065Ensembl.1
Natural variantiVAR_025196301R → C1 PublicationCorresponds to variant dbSNP:rs34118765Ensembl.1
Natural variantiVAR_080378306R → C in ANOA. 1 Publication1
Natural variantiVAR_080379327R → S in ANOA. 1 Publication1
Natural variantiVAR_025197345T → M1 PublicationCorresponds to variant dbSNP:rs35660143Ensembl.1
Natural variantiVAR_025198352P → S1 PublicationCorresponds to variant dbSNP:rs35696549Ensembl.1
Natural variantiVAR_080380419 – 491Missing in ANOA. 1 PublicationAdd BLAST73
Natural variantiVAR_025199472T → A1 PublicationCorresponds to variant dbSNP:rs35769464Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0466691 – 59MASRC…QHLLK → MEDKDRE in isoform 4. 1 PublicationAdd BLAST59
Alternative sequenceiVSP_04667027 – 34SFCHHFST → TFGGSDEVRDPANAKALRNK RRRMQVRVKLGKFQLLLDI in isoform 7. 1 Publication8
Alternative sequenceiVSP_04513559K → KRVEALCSQPRVLNSPALSG EGEDLGASQPLSLDPTSCHP VPQQ in isoform 3. 1 Publication1
Alternative sequenceiVSP_04667159K → KQ in isoform 6. 1 Publication1
Alternative sequenceiVSP_04667291 – 131Missing in isoform 6. 1 PublicationAdd BLAST41
Alternative sequenceiVSP_04667391 – 98Missing in isoform 5. 1 Publication8
Alternative sequenceiVSP_003416203E → EALLLCQ in isoform Long. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
AK293208 mRNA Translation: BAG56748.1
AK295307 mRNA Translation: BAG58287.1
AK298908 mRNA Translation: BAG61016.1
AK301779 mRNA Translation: BAG63236.1
AK301977 mRNA Translation: BAH13598.1
AC068874 Genomic DNA No translation available.
BC002960 mRNA Translation: AAH02960.1
CCDSiCCDS11707.1 [P22570-2]
CCDS58591.1 [P22570-4]
CCDS58592.1 [P22570-5]
CCDS58593.1 [P22570-1]
CCDS58594.1 [P22570-6]
CCDS58595.1 [P22570-3]
CCDS58596.1 [P22570-7]
PIRiA40487
RefSeqiNP_001244941.2, NM_001258012.3
NP_001244942.2, NM_001258013.3
NP_001244943.2, NM_001258014.3
NP_001244944.1, NM_001258015.2 [P22570-6]
NP_001244945.2, NM_001258016.3
NP_004101.3, NM_004110.5
NP_077728.3, NM_024417.4
UniGeneiHs.69745

Genome annotation databases

EnsembliENST00000420580; ENSP00000414172; ENSG00000161513 [P22570-6]
GeneIDi2232
KEGGihsa:2232
UCSCiuc002jlx.4 human [P22570-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiADRO_HUMAN
AccessioniPrimary (citable) accession number: P22570
Secondary accession number(s): B4DDI7
, B4DHX5, B4DQQ4, B4DX24, B7Z7G2, E7EQC1, Q13716, Q4PJI0, Q9BU12
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: January 24, 2006
Last modified: June 20, 2018
This is version 184 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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