Skip Header

 
Contribute Send feedback
Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot P16435 (NCPR_HUMAN)

Last modified June 16, 2009. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    NADPH--cytochrome P450 reductase
      Short name=CPR
      Short name=P450R
    EC=1.6.2.4
Gene names
Name: POR
Synonyms: CYPOR
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length677 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (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.

FMN.

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein. Note: Anchored to the ER membrane by its N-terminal hydrophobic region.

Involvement in 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. Ref.9 Ref.10 Ref.11 Ref.12

Defects in POR are a cause of isolated disordered steroidogenesis (IDS) [MIM:201750]. Ref.12

Sequence similarities

In the C-terminal section; belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.

Contains 1 FAD-binding FR-type domain.

Contains 1 flavodoxin-like domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.6
Chain2 – 677676NADPH--cytochrome P450 reductase
PRO_0000167596

Regions

Domain80 – 224145Flavodoxin-like
Domain279 – 521243FAD-binding FR-type
Nucleotide binding170 – 20132FMN By similarity
Nucleotide binding314 – 32512FAD By similarity
Nucleotide binding451 – 46111FAD By similarity
Nucleotide binding529 – 54719NADP By similarity
Nucleotide binding623 – 63917NADP By similarity

Amino acid modifications

Modified residue21N-acetylglycine
Modified residue5751Phosphotyrosine By similarity

Natural variations

Natural variant1781Y → D in AHV; complete loss of activity. Ref.11
VAR_021154
Natural variant2251P → L Ref.4 Ref.5
VAR_047885
Natural variant2521D → N Ref.4
VAR_047886
Natural variant2841A → P in AHV; significant reduction of activity. Ref.11 Ref.12
VAR_021155
Natural variant4541R → H in AHV; significant reduction of activity. Ref.9 Ref.10 Ref.11 Ref.12
VAR_021156
Natural variant4891V → E in AHV; significant reduction of activity. Ref.12
VAR_021157
Natural variant5001A → V: dbSNP rs1057868. Ref.10 Ref.4 Ref.5 Ref.1
VAR_004617
Natural variant5511R → Q
VAR_004618
Natural variant5661C → Y in IDS and AHV; significant reduction of activity.
VAR_021158
Natural variant5751Y → C in AHV; with abnormal genitalia. Ref.10
VAR_021159
Natural variant6051V → F in IDS; significant reduction of activity. Ref.12
VAR_021160
Natural variant609 – 6179LKQDREHLW → R in AHV.
VAR_021161

Experimental info

Sequence conflict4051M → L in BAB18572. Ref.3
Sequence conflict5181F → L in AAB21814. Ref.1
Sequence conflict5181F → L in BAB18572. Ref.3
Sequence conflict537 – 5382VA → WH in AAB21814. Ref.1

Secondary structure

................................ 677
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P16435-1 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 2F7D4B9CDFDF5A74

FASTA67776,690
        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 

« Hide

References

« Hide 'large scale' references
[1]"Quantification of cytochrome P450 reductase gene expression in human tissues."
Shephard E.A., Palmer C.N., Segall H.J., Phillips I.R.
Arch. Biochem. Biophys. 294:168-172(1992) [PubMed: 1550342] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-500.
[2]"Polymorphism of human CYPOR: expression of new allele."
Czerwinski M., Sahni M., Madan A., Parkinson A.
Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]"cDNA cloning and characterization of NADPH-cytochrome P-450 reductase in human HL-60 cell."
Murakami H.O., Ogawa H., Nisimoto Y.
Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]NIEHS SNPs program
Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-225; ASN-252 AND VAL-500.
[5]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS LEU-225 AND VAL-500.
Tissue: Lung.
[6]"Structural and functional analysis of NADPH-cytochrome P-450 reductase from human liver: complete sequence of human enzyme and NADPH-binding sites."
Haniu M., McManus M.E., Birkett D.J., Lee T.D., Shively J.E.
Biochemistry 28:8639-8645(1989) [PubMed: 2513880] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-677.
Tissue: Liver.
[7]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]"Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution."
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.
Protein Sci. 8:298-306(1999) [PubMed: 10048323] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 62-242.
[9]"Compound heterozygous mutations of cytochrome P450 oxidoreductase gene (POR) in two patients with Antley-Bixler syndrome."
Adachi M., Tachibana K., Asakura Y., Yamamoto T., Hanaki K., Oka A.
Am. J. Med. Genet. A 128:333-339(2004) [PubMed: 15264278] [Abstract]
Cited for: VARIANT AHV HIS-454.
[10]"Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: molecular and clinical studies in 10 patients."
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.
J. Clin. Endocrinol. Metab. 90:414-426(2005) [PubMed: 15483095] [Abstract]
Cited for: VARIANTS AHV HIS-454; CYS-575 AND 608-LEU--TRP-617 DELINS ARG, VARIANT VAL-500.
[11]"Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study."
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.
Lancet 363:2128-2135(2004) [PubMed: 15220035] [Abstract]
Cited for: VARIANTS AHV ASP-178; PRO-284; HIS-454 AND TYR-566, CHARACTERIZATION OF VARIANTS AHV ASP-178; PRO-284; HIS-454 AND TYR-566.
[12]"Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome."
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.
Nat. Genet. 36:228-230(2004) [PubMed: 14758361] [Abstract]
Cited for: 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, CHARACTERIZATION OF VARIANTS IDS TYR-566 AND PHE-605.
+Additional computationally mapped references.

Cross-references

Sequence databases

S90469 mRNA. Translation: AAB21814.1.
AF258341 mRNA. Translation: AAG09798.1.
AB051763 mRNA. Translation: BAB18572.1.
DQ640499 Genomic DNA. Translation: ABF70199.1.
BC034277 mRNA. Translation: AAH34277.1. Different initiation.
IPIIPI00470467.
PIRA60557. A33421.
RefSeqNP_000932.3.
UniGeneHs.354056

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1B1CX-ray1.93A61-241[»]
SMRP16435. Positions 64-677.
ModBaseSearch...

Protein-protein interaction databases

IntActP16435. 1 interaction.

PTM databases

PhosphoSiteP16435.

Proteomic databases

PRIDEP16435.

Genome annotation databases

EnsemblENSG00000127948. Homo sapiens. [Contig view]
GeneID5447.
KEGGhsa:5447.

Organism-specific databases

GeneCardsGC07P075382.
H-InvDBHIX0006782.
HGNCHGNC:9208. POR.
HPACAB004372.
HPA010136.
MIM124015. gene.
201750. phenotype.
Orphanet83. Antley-Bixler syndrome.
63269. Antley-Bixler-like syndrome - ambiguous genitalia - disordered steroidogenesis.
PharmGKBPA27834.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP16435.

Enzyme and pathway databases

BRENDA1.6.2.4. 247.

Gene expression databases

BgeeP16435.
CleanExHS_POR.
GermOnlineENSG00000127948. Homo sapiens.

Family and domain databases

InterProIPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin-like.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR015702. NADPH_Cyt_P450_Rdtase.
IPR001433. OxRdtase_FAD/NAD_bd.
[Graphical view]
PANTHERPTHR19384:SF17. NADPH_Cyt_Red. 1 hit.
PfamPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]
PRINTSPR00369. FLAVODOXIN.
PR00371. FPNCR.
PROSITEPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00865. Benzphetamine.
DB00694. Daunorubicin.
DB00166. Lipoic Acid.
DB00170. Menadione.
DB01028. Methoxyflurane.
DB00305. Mitomycin.
DB00665. Nilutamide.
NextBio21083.
SOURCESearch...

Entry information

Entry nameNCPR_HUMAN
AccessionPrimary (citable) accession number: P16435
Secondary accession number(s): Q16455 expand/collapse secondary AC list , Q197M5, Q8N181, Q9H3M8
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: January 23, 2007
Last modified: June 16, 2009
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents