Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

NADPH:adrenodoxin oxidoreductase, mitochondrial

Gene

FDXR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

Catalytic activityi

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

Cofactori

Pathwayi: cholesterol metabolism

This protein is involved in the pathway cholesterol metabolism, which is part of Steroid metabolism.
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
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Cholesterol metabolism, Electron transport, Lipid metabolism, Steroid metabolism, Sterol metabolism, Transport

Keywords - Ligandi

FAD, Flavoprotein, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS08587-MONOMER.
ZFISH: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:1.18.1.6)
Short name:
AR
Short name:
Adrenodoxin reductase
Alternative name(s):
Ferredoxin--NADP(+) reductase
Short name:
Ferredoxin reductase
Gene namesi
Name:FDXR
Synonyms:ADXR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:3642. FDXR.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

DisGeNETi2232.
OpenTargetsiENSG00000161513.
PharmGKBiPA28086.

Chemistry databases

DrugBankiDB03147. Flavin adenine dinucleotide.

Polymorphism and mutation databases

BioMutaiFDXR.
DMDMi85681283.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 32MitochondrionAdd 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.

2D gel databases

REPRODUCTION-2DPAGEIPI00026958.

PTM databases

iPTMnetiP22570.
PhosphoSitePlusiP22570.

Expressioni

Gene expression databases

BgeeiENSG00000161513.
CleanExiHS_FDXR.
ExpressionAtlasiP22570. baseline and differential.
GenevisibleiP22570. HS.

Organism-specific databases

HPAiCAB009818.
HPA044393.
HPA053673.

Interactioni

Subunit structurei

Monomer. Interacts directly with FDX1.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
FHITP497894EBI-1751533,EBI-741760

Protein-protein interaction databases

BioGridi108523. 21 interactors.
IntActiP22570. 3 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

Gene3Di3.40.50.720. 2 hits.
3.50.50.60. 1 hit.
InterProiIPR023753. FAD/NAD-binding_dom.
IPR021163. Ferredox_Rdtase_adrenod.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF07992. Pyr_redox_2. 1 hit.
[Graphical view]
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 → L.1 PublicationCorresponds to variant rs28365947dbSNPEnsembl.1
Natural variantiVAR_004624123R → Q.3 PublicationsCorresponds to variant rs690514dbSNPEnsembl.1
Natural variantiVAR_025193213G → V.1 PublicationCorresponds to variant rs35692345dbSNPEnsembl.1
Natural variantiVAR_025194248P → L.1 PublicationCorresponds to variant rs35072974dbSNPEnsembl.1
Natural variantiVAR_025195251R → W.1 PublicationCorresponds to variant rs34038065dbSNPEnsembl.1
Natural variantiVAR_025196301R → C.1 PublicationCorresponds to variant rs34118765dbSNPEnsembl.1
Natural variantiVAR_025197345T → M.1 PublicationCorresponds to variant rs35660143dbSNPEnsembl.1
Natural variantiVAR_025198352P → S.1 PublicationCorresponds to variant rs35696549dbSNPEnsembl.1
Natural variantiVAR_025199472T → A.1 PublicationCorresponds to variant rs35769464dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

NIEHS-SNPs

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.

3D structure databases

ProteinModelPortaliP22570.
SMRiP22570.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108523. 21 interactors.
IntActiP22570. 3 interactors.
STRINGi9606.ENSP00000462972.

Chemistry databases

DrugBankiDB03147. Flavin adenine dinucleotide.

PTM databases

iPTMnetiP22570.
PhosphoSitePlusiP22570.

Polymorphism and mutation databases

BioMutaiFDXR.
DMDMi85681283.

2D gel databases

REPRODUCTION-2DPAGEIPI00026958.

Proteomic databases

EPDiP22570.
PaxDbiP22570.
PeptideAtlasiP22570.
PRIDEiP22570.

Protocols and materials databases

DNASUi2232.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2232.
DisGeNETi2232.
GeneCardsiFDXR.
HGNCiHGNC:3642. FDXR.
HPAiCAB009818.
HPA044393.
HPA053673.
MIMi103270. gene.
neXtProtiNX_P22570.
OpenTargetsiENSG00000161513.
PharmGKBiPA28086.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1800. Eukaryota.
COG0493. LUCA.
GeneTreeiENSGT00390000013574.
HOGENOMiHOG000249250.
HOVERGENiHBG002132.
InParanoidiP22570.
KOiK18914.
PhylomeDBiP22570.
TreeFamiTF314193.

Enzyme and pathway databases

UniPathwayiUPA00296.
BioCyciMetaCyc:HS08587-MONOMER.
ZFISH: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).

Miscellaneous databases

GeneWikiiAdrenodoxin_reductase.
GenomeRNAii2232.
PROiP22570.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000161513.
CleanExiHS_FDXR.
ExpressionAtlasiP22570. baseline and differential.
GenevisibleiP22570. HS.

Family and domain databases

Gene3Di3.40.50.720. 2 hits.
3.50.50.60. 1 hit.
InterProiIPR023753. FAD/NAD-binding_dom.
IPR021163. Ferredox_Rdtase_adrenod.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF07992. Pyr_redox_2. 1 hit.
[Graphical view]
PIRSFiPIRSF000362. FNR. 1 hit.
SUPFAMiSSF51905. SSF51905. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiADRO_HUMAN
AccessioniPrimary (citable) accession number: P22570
Secondary accession number(s): B4DDI7
, B4DHX5, B4DQQ4, B4DX24, B7Z7G2, E7EQC1, Q13716, Q4PJI0, Q9BU12
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: January 24, 2006
Last modified: November 2, 2016
This is version 171 of the entry and version 3 of the sequence. [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

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.