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UniProtKB/Swiss-Prot entry P16435


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name NCPR_HUMAN
Primary accession number P16435
Secondary accession numbers Q16455 Q8N181 Q9H3M8
Integrated into Swiss-Prot on August 1, 1990
Sequence was last modified on January 23, 2007 (Sequence version 2)
Annotations were last modified on    July 22, 2008 (Entry version 109)
Name and origin of the protein
Protein name NADPH--cytochrome P450 reductase
Synonyms CPR
P450R
EC 1.6.2.4
Gene name
Name: POR
Synonyms: CYPOR
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1016/0003-9861(92)90152-M; PubMed=1550342 [NCBI, ExPASy, EBI, Israel, Japan]
Shephard E.A., Palmer C.N., Segall H.J., Phillips I.R.;
"Quantification of cytochrome P450 reductase gene expression in human tissues.";
Arch. Biochem. Biophys. 294:168-172(1992).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Liver;
Czerwinski M., Sahni M., Madan A., Parkinson A.;
"Polymorphism of human CYPOR: expression of new allele.";
Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [MRNA].
Murakami H.O., Ogawa H., Nisimoto Y.;
"cDNA cloning and characterization of NADPH-cytochrome P-450 reductase in human HL-60 cell.";
Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-500.
TISSUE=Lung;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
PROTEIN SEQUENCE OF 2-677.
TISSUE=Liver;
DOI=10.1021/bi00447a054; PubMed=2513880 [NCBI, ExPASy, EBI, Israel, Japan]
Haniu M., McManus M.E., Birkett D.J., Lee T.D., Shively J.E.;
"Structural and functional analysis of NADPH-cytochrome P-450 reductase from human liver: complete sequence of human enzyme and NADPH-binding sites.";
Biochemistry 28:8639-8645(1989).
[6]
X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 62-242.
PubMed=10048323 [NCBI, ExPASy, EBI, Israel, Japan]
Zhao Q., Modi S., Smith G., Paine M., McDonagh P.D., Wolf C.R., Tew D., Lian L.Y., Roberts G.C., Driessen H.P.;
"Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution.";
Protein Sci. 8:298-306(1999).
[7]
VARIANT AHV HIS-454.
DOI=10.1002/ajmg.a.30169; PubMed=15264278 [NCBI, ExPASy, EBI, Israel, Japan]
Adachi M., Tachibana K., Asakura Y., Yamamoto T., Hanaki K., Oka A.;
"Compound heterozygous mutations of cytochrome P450 oxidoreductase gene (POR) in two patients with Antley-Bixler syndrome.";
Am. J. Med. Genet. A 128:333-339(2004).
[8]
VARIANTS AHV HIS-454; CYS-575 AND 608-LEU--TRP-617 DELINS ARG, AND VARIANT VAL-500.
DOI=10.1210/jc.2004-0810; PubMed=15483095 [NCBI, ExPASy, EBI, Israel, Japan]
Fukami M., Horikawa R., Nagai T., Tanaka T., Naiki Y., Sato N., Okuyama T., Nakai H., Soneda S., Tachibana K., Matsuo N., Sato S., Homma K., Nishimura G., Hasegawa T., Ogata T.;
"Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: molecular and clinical studies in 10 patients.";
J. Clin. Endocrinol. Metab. 90:414-426(2005).
[9]
VARIANTS AHV ASP-178; PRO-284; HIS-454 AND TYR-566, AND CHARACTERIZATION OF VARIANTS AHV ASP-178; PRO-284; HIS-454 AND TYR-566.
DOI=10.1016/S0140-6736(04)16503-3; PubMed=15220035 [NCBI, ExPASy, EBI, Israel, Japan]
Arlt W., Walker E.A., Draper N., Ivison H.E., Ride J.P., Hammer F., Chalder S.M., Borucka-Mankiewicz M., Hauffa B.P., Malunowicz E.M., Stewart P.M., Shackleton C.H.L.;
"Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study.";
Lancet 363:2128-2135(2004).
[10]
VARIANTS AHV PRO-284; HIS-454 AND GLU-489, VARIANTS IDS TYR-566 AND PHE-605, CHARACTERIZATION OF VARIANTS AHV PRO-284; HIS-454 AND GLU-489, AND CHARACTERIZATION OF VARIANTS IDS TYR-566 AND PHE-605.
DOI=10.1038/ng1300; PubMed=14758361 [NCBI, ExPASy, EBI, Israel, Japan]
Flueck C.E., Tajima T., Pandey A.V., Arlt W., Okuhara K., Verge C.F., Jabs E.W., Mendonca B.B., Fujieda K., Miller W.L.;
"Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome.";
Nat. Genet. 36:228-230(2004).
Comments
  • FUNCTION: This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
  • CATALYTIC ACTIVITY: NADPH + n oxidized hemoprotein = NADP+ + n reduced hemoprotein.
  • COFACTOR: FAD.
  • COFACTOR: FMN.
  • SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Note=Anchored to the ER membrane by its N-terminal hydrophobic region.
  • DISEASE: Defects in POR are the cause of adrenal hyperplasia variant type (AHV) [MIM:201750]; also known as Antley-Bixler syndrome-like phenotype with disordered steroidogenesis. AHV is a rare variant of congenital adrenal hyperplasia. It is an autosomal recessive disorder with apparent combined P450C17 and P450C21 deficiency. Affected girls are born with ambiguous genitalia, but their circulating androgens are low and virilization does not progress. Conversely, affected boys are sometimes born undermasculinized. Boys and girls can also present with bone malformations, in some cases resembling the pattern seen in patients with Antley-Bixler syndrome.
  • DISEASE: Defects in POR are a cause of isolated disordered steroidogenesis (IDS) [MIM:201750].
  • SIMILARITY: In the C-terminal section; belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
  • SIMILARITY: Contains 1 FAD-binding FR-type domain.
  • SIMILARITY: Contains 1 flavodoxin-like domain.
  • WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=POR";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
S90469; AAB21814.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF258341; AAG09798.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB051763; BAB18572.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC034277; AAH34277.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A33421; A60557.
RefSeq NP_000932.3; -.
UniGene Hs.354056
3D structure databases
PDB
1B1C; X-ray; 1.93 A; A=61-241.[ExPASy / RCSB / EBI]
PDBsum 1B1C; -.
SMR P16435; 64-677.
ModBase P16435.
PTM databases
PhosphoSite P16435; -.
Organism-specific databases
H-InvDB HIX0006782; -.
HGNC HGNC:9208; POR.
GenAtlas POR.
HPA CAB004372; -.
HPA010136; -.
MIM 124015; gene. [NCBI / EBI]
201750; phenotype. [NCBI / EBI]
Orphanet 418; Adrenal hyperplasia, congenital.
83; Antley-Bixler syndrome.
63269; Antley-Bixler-like syndrome - ambiguous genitalia - disordered steroidogenesis.
PharmGKB PA27834; -.
GeneCards P16435.
Gene expression databases
CleanEx HS_POR; -.
GermOnline ENSG00000127948; Homo sapiens.
Ontologies
GO
GO:0005783; Cellular component: endoplasmic reticulum (traceable author statement from UniProtKB).
GO:0003958; Molecular function: NADPH-hemoprotein reductase activity (traceable author statement from UniProtKB).
GO:0055114; Biological process: oxidation reduction (traceable author statement from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR003097; FAD-binding_1.
IPR001094; Flavdoxin_like.
IPR008254; Flavodoxin/NO_synth.
IPR001709; FPN_cyt_redctse.
IPR015702; NADPH_Cyt_Red.
IPR001433; OxRdtase_FAD/NAD_bd.
Graphical view of domain structure.
PANTHER PTHR19384:SF17; NADPH_Cyt_Red; 1.
Pfam PF00667; FAD_binding_1; 1.
PF00258; Flavodoxin_1; 1.
PF00175; NAD_binding_1; 1.
Pfam graphical view of domain structure.
PRINTS PR00369; FLAVODOXIN.
PR00371; FPNCR.
PROSITE PS51384; FAD_FR; 1.
PS50902; FLAVODOXIN_LIKE; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P16435.
Genome annotation databases
Ensembl ENSG00000127948; Homo sapiens. [Contig view]
GeneID 5447; -.
KEGG hsa:5447; -.
Phylogenomic databases
HOVERGEN P16435; -.
Other
DrugBank DB00865; Benzphetamine.
DB00694; Daunorubicin.
DB00166; Lipoic Acid.
DB00170; Menadione.
DB01028; Methoxyflurane.
DB00305; Mitomycin.
DB00665; Nilutamide.
SOURCE POR; Homo sapiens.
ProtoNet P16435.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Acetylation; Congenital adrenal hyperplasia; Direct protein sequencing; Disease mutation; Endoplasmic reticulum; FAD; Flavoprotein; FMN; Membrane; NADP; Oxidoreductase; Phosphoprotein; Polymorphism.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
INIT_MET   1     1        Removed. 
CHAIN   2   677  676     NADPH--cytochrome P450 reductase. PRO_0000167596
DOMAIN   80   224  145     Flavodoxin-like. 
DOMAIN   279   521  243     FAD-binding FR-type. 
NP_BIND   170   201  32     FMN (By similarity). 
NP_BIND   314   325  12     FAD (By similarity). 
NP_BIND   451   461  11     FAD (By similarity). 
NP_BIND   529   547  19     NADP (By similarity). 
NP_BIND   623   639  17     NADP (By similarity). 
MOD_RES   2     2        N-acetylglycine. 
MOD_RES   575   575        Phosphotyrosine (By similarity). 
VARIANT   178   178  1     Y -> D (in AHV; complete loss of activity). VAR_021154 [3D]
VARIANT   284   284  1     A -> P (in AHV; significant reduction of activity). VAR_021155 
VARIANT   454   454  1     R -> H (in AHV; significant reduction of activity). VAR_021156 
VARIANT   489   489  1     V -> E (in AHV; significant reduction of activity). VAR_021157 
VARIANT   500   500  1     A -> V (in dbSNP:rs1057868 [NCBI]). VAR_004617 
VARIANT   551   551  1     R -> Q. VAR_004618 
VARIANT   566   566  1     C -> Y (in IDS and AHV; significant reduction of activity). VAR_021158 
VARIANT   575   575  1     Y -> C (in AHV; with abnormal genitalia). VAR_021159 
VARIANT   605   605  1     V -> F (in IDS; significant reduction of activity). VAR_021160 
VARIANT   609   617  9     LKQDREHLW -> R (in AHV). VAR_021161
CONFLICT   225   225        P -> L (in Ref. 4; AAH34277). 
CONFLICT   405   405        M -> L (in Ref. 3; BAB18572). 
CONFLICT   518   518        F -> L (in Ref. 1 and 3). 
CONFLICT   537   538        VA -> WH (in Ref. 1; AAB21814). 
HELIX   69    75  7      
STRAND   80    85  6      
STRAND   87    89  3      
HELIX   90   101  12      
HELIX   102   105  4      
STRAND   109   112  4      
HELIX   114   116  3      
HELIX   119   127  9      
STRAND   132   138  7      
TURN   141   143  3      
HELIX   147   149  3      
HELIX   150   158  9      
STRAND   167   174  8      
STRAND   178   180  3      
HELIX   183   194  12      
STRAND   204   207  4      
HELIX   212   231  20      
Sequence information
Length: 677 AA [This is the length of the unprocessed precursor] Molecular weight: 76690 Da [This is the MW of the unprocessed precursor] CRC64: 2F7D4B9CDFDF5A74 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MGDSHVDTSS TVSEAVAEEV SLFSMTDMIL FSLIVGLLTY WFLFRKKKEE VPEFTKIQTL 

        70         80         90        100        110        120 
TSSVRESSFV EKMKKTGRNI IVFYGSQTGT AEEFANRLSK DAHRYGMRGM SADPEEYDLA 

       130        140        150        160        170        180 
DLSSLPEIDN ALVVFCMATY GEGDPTDNAQ DFYDWLQETD VDLSGVKFAV FGLGNKTYEH 

       190        200        210        220        230        240 
FNAMGKYVDK RLEQLGAQRI FELGLGDDDG NLEEDFITWR EQFWPAVCEH FGVEATGEES 

       250        260        270        280        290        300 
SIRQYELVVH TDIDAAKVYM GEMGRLKSYE NQKPPFDAKN PFLAAVTTNR KLNQGTERHL 

       310        320        330        340        350        360 
MHLELDISDS KIRYESGDHV AVYPANDSAL VNQLGKILGA DLDVVMSLNN LDEESNKKHP 

       370        380        390        400        410        420 
FPCPTSYRTA LTYYLDITNP PRTNVLYELA QYASEPSEQE LLRKMASSSG EGKELYLSWV 

       430        440        450        460        470        480 
VEARRHILAI LQDCPSLRPP IDHLCELLPR LQARYYSIAS SSKVHPNSVH ICAVVVEYET 

       490        500        510        520        530        540 
KAGRINKGVA TNWLRAKEPA GENGGRALVP MFVRKSQFRL PFKATTPVIM VGPGTGVAPF 

       550        560        570        580        590        600 
IGFIQERAWL RQQGKEVGET LLYYGCRRSD EDYLYREELA QFHRDGALTQ LNVAFSREQS 

       610        620        630        640        650        660 
HKVYVQHLLK QDREHLWKLI EGGAHIYVCG DARNMARDVQ NTFYDIVAEL GAMEHAQAVD 

       670 
YIKKLMTKGR YSLDVWS 

P16435 in FASTA format

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