NCPR_HUMAN
ID NCPR_HUMAN Reviewed; 677 AA.
AC P16435; Q16455; Q197M5; Q8N181; Q9H3M8; Q9UDT3;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 234.
DE RecName: Full=NADPH--cytochrome P450 reductase {ECO:0000255|HAMAP-Rule:MF_03212};
DE Short=CPR {ECO:0000255|HAMAP-Rule:MF_03212};
DE Short=P450R {ECO:0000255|HAMAP-Rule:MF_03212};
DE EC=1.6.2.4 {ECO:0000255|HAMAP-Rule:MF_03212};
GN Name=POR {ECO:0000255|HAMAP-Rule:MF_03212}; Synonyms=CYPOR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-500.
RX PubMed=1550342; DOI=10.1016/0003-9861(92)90152-m;
RA Shephard E.A., Palmer C.N., Segall H.J., Phillips I.R.;
RT "Quantification of cytochrome P450 reductase gene expression in human
RT tissues.";
RL Arch. Biochem. Biophys. 294:168-172(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Czerwinski M., Sahni M., Madan A., Parkinson A.;
RT "Polymorphism of human CYPOR: expression of new allele.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Murakami H.O., Ogawa H., Nisimoto Y.;
RT "cDNA cloning and characterization of NADPH-cytochrome P-450 reductase in
RT human HL-60 cell.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-225; ASN-252 AND
RP VAL-500.
RG NIEHS SNPs program;
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LEU-225 AND VAL-500.
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-677, CLEAVAGE OF INITIATOR METHIONINE, AND
RP ACETYLATION AT GLY-2.
RC TISSUE=Liver;
RX PubMed=2513880; DOI=10.1021/bi00447a054;
RA Haniu M., McManus M.E., Birkett D.J., Lee T.D., Shively J.E.;
RT "Structural and functional analysis of NADPH-cytochrome P-450 reductase
RT from human liver: complete sequence of human enzyme and NADPH-binding
RT sites.";
RL Biochemistry 28:8639-8645(1989).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-63, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 61-241 IN COMPLEX WITH FMN.
RX PubMed=10048323; DOI=10.1110/ps.8.2.298;
RA Zhao Q., Modi S., Smith G., Paine M., McDonagh P.D., Wolf C.R., Tew D.,
RA Lian L.Y., Roberts G.C., Driessen H.P.;
RT "Crystal structure of the FMN-binding domain of human cytochrome P450
RT reductase at 1.93 A resolution.";
RL Protein Sci. 8:298-306(1999).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 232-677 IN COMPLEX WITH FAD.
RX PubMed=19483672; DOI=10.1038/embor.2009.82;
RA Aigrain L., Pompon D., Morera S., Truan G.;
RT "Structure of the open conformation of a functional chimeric NADPH
RT cytochrome P450 reductase.";
RL EMBO Rep. 10:742-747(2009).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 241-677 IN COMPLEX WITH FAD; FMN
RP AND NADP.
RX PubMed=21808038; DOI=10.1073/pnas.1106632108;
RA Xia C., Panda S.P., Marohnic C.C., Martasek P., Masters B.S., Kim J.J.;
RT "Structural basis for human NADPH-cytochrome P450 oxidoreductase
RT deficiency.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:13486-13491(2011).
RN [15]
RP VARIANT ABS1 HIS-454.
RX PubMed=15264278; DOI=10.1002/ajmg.a.30169;
RA Adachi M., Tachibana K., Asakura Y., Yamamoto T., Hanaki K., Oka A.;
RT "Compound heterozygous mutations of cytochrome P450 oxidoreductase gene
RT (POR) in two patients with Antley-Bixler syndrome.";
RL Am. J. Med. Genet. A 128:333-339(2004).
RN [16]
RP VARIANTS ABS1 HIS-454; CYS-575 AND 608-LEU--TRP-617 DELINS ARG, AND VARIANT
RP VAL-500.
RX PubMed=15483095; DOI=10.1210/jc.2004-0810;
RA Fukami M., Horikawa R., Nagai T., Tanaka T., Naiki Y., Sato N., Okuyama T.,
RA Nakai H., Soneda S., Tachibana K., Matsuo N., Sato S., Homma K.,
RA Nishimura G., Hasegawa T., Ogata T.;
RT "Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome
RT with abnormal genitalia and/or impaired steroidogenesis: molecular and
RT clinical studies in 10 patients.";
RL J. Clin. Endocrinol. Metab. 90:414-426(2005).
RN [17]
RP VARIANTS DISPORD ASP-178; PRO-284; HIS-454 AND TYR-566, AND
RP CHARACTERIZATION OF VARIANTS DISPORD ASP-178; PRO-284; HIS-454 AND TYR-566.
RX PubMed=15220035; DOI=10.1016/s0140-6736(04)16503-3;
RA Arlt W., Walker E.A., Draper N., Ivison H.E., Ride J.P., Hammer F.,
RA Chalder S.M., Borucka-Mankiewicz M., Hauffa B.P., Malunowicz E.M.,
RA Stewart P.M., Shackleton C.H.L.;
RT "Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and
RT human androgen synthesis: analytical study.";
RL Lancet 363:2128-2135(2004).
RN [18]
RP VARIANTS ABS1 PRO-284; HIS-454 AND GLU-489, VARIANTS DISPORD TYR-566 AND
RP PHE-605, CHARACTERIZATION OF VARIANTS ABS1 PRO-284; HIS-454 AND GLU-489,
RP AND CHARACTERIZATION OF VARIANTS DISPORD TYR-566 AND PHE-605.
RX PubMed=14758361; DOI=10.1038/ng1300;
RA Flueck C.E., Tajima T., Pandey A.V., Arlt W., Okuhara K., Verge C.F.,
RA Jabs E.W., Mendonca B.B., Fujieda K., Miller W.L.;
RT "Mutant P450 oxidoreductase causes disordered steroidogenesis with and
RT without Antley-Bixler syndrome.";
RL Nat. Genet. 36:228-230(2004).
RN [19]
RP VARIANT HIS-454.
RX PubMed=27610946; DOI=10.1002/humu.23116;
RA Igarashi M., Takasawa K., Hakoda A., Kanno J., Takada S., Miyado M.,
RA Baba T., Morohashi K.I., Tajima T., Hata K., Nakabayashi K., Matsubara Y.,
RA Sekido R., Ogata T., Kashimada K., Fukami M.;
RT "Identical NR5A1 missense mutations in two unrelated 46,XX individuals with
RT testicular tissues.";
RL Hum. Mutat. 38:39-42(2017).
CC -!- FUNCTION: This enzyme is required for electron transfer from NADP to
CC cytochrome P450 in microsomes. It can also provide electron transfer to
CC heme oxygenase and cytochrome B5. {ECO:0000255|HAMAP-Rule:MF_03212}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADPH + 2 oxidized [cytochrome P450] = H(+) + NADP(+) + 2
CC reduced [cytochrome P450]; Xref=Rhea:RHEA:24040, Rhea:RHEA-
CC COMP:14627, Rhea:RHEA-COMP:14628, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:55376, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:60344; EC=1.6.2.4; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03212};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03212,
CC ECO:0000269|PubMed:21808038};
CC Note=Binds 1 FAD per monomer. {ECO:0000255|HAMAP-Rule:MF_03212,
CC ECO:0000269|PubMed:21808038};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03212,
CC ECO:0000269|PubMed:21808038};
CC Note=Binds 1 FMN per monomer. {ECO:0000255|HAMAP-Rule:MF_03212,
CC ECO:0000269|PubMed:21808038};
CC -!- INTERACTION:
CC P16435; O00264: PGRMC1; NbExp=5; IntAct=EBI-726554, EBI-1045534;
CC P16435; P00181: CYP2C2; Xeno; NbExp=4; IntAct=EBI-726554, EBI-4320576;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000255|HAMAP-Rule:MF_03212}; Single-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_03212}; Cytoplasmic side {ECO:0000255|HAMAP-
CC Rule:MF_03212}.
CC -!- DISEASE: Antley-Bixler syndrome, with genital anomalies and disordered
CC steroidogenesis (ABS1) [MIM:201750]: A disease characterized by the
CC association of Antley-Bixler syndrome with steroidogenesis defects and
CC abnormal genitalia. Antley-Bixler syndrome is characterized by
CC craniosynostosis, radiohumeral synostosis present from the perinatal
CC period, midface hypoplasia, choanal stenosis or atresia, femoral bowing
CC and multiple joint contractures. {ECO:0000269|PubMed:14758361,
CC ECO:0000269|PubMed:15264278, ECO:0000269|PubMed:15483095}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Disordered steroidogenesis due to cytochrome P450
CC oxidoreductase deficiency (DISPORD) [MIM:613571]: A disorder resulting
CC in a rare variant of congenital adrenal hyperplasia, with apparent
CC combined P450C17 and P450C21 deficiency and accumulation of steroid
CC metabolites. Affected girls are born with ambiguous genitalia, but
CC their circulating androgens are low and virilization does not progress.
CC Conversely, affected boys are sometimes born undermasculinized. Boys
CC and girls can present with bone malformations, in some cases resembling
CC the pattern seen in patients with Antley-Bixler syndrome.
CC {ECO:0000269|PubMed:14758361, ECO:0000269|PubMed:15220035}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the NADPH--cytochrome P450 reductase family.
CC {ECO:0000255|HAMAP-Rule:MF_03212}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the flavodoxin
CC family. {ECO:0000255|HAMAP-Rule:MF_03212}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the flavoprotein
CC pyridine nucleotide cytochrome reductase family. {ECO:0000255|HAMAP-
CC Rule:MF_03212}.
CC -!- CAUTION: An alternative upstream Met is found in primates and
CC translation may initiate from the upstream Met which would give rise to
CC a 680-residue protein. However, the upstream codon has a weak Kozak
CC signal while the codon used for translation of the shorter 677-residue
CC sequence has a strong Kozak signal and is widely conserved. In
CC addition, protein sequencing indicates that this is the preferred start
CC codon in vivo. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH34277.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/por/";
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DR EMBL; S90469; AAB21814.1; -; mRNA.
DR EMBL; AF258341; AAG09798.1; -; mRNA.
DR EMBL; AB051763; BAB18572.1; -; mRNA.
DR EMBL; DQ640499; ABF70199.1; -; Genomic_DNA.
DR EMBL; AC005067; AAD45961.1; -; Genomic_DNA.
DR EMBL; AC006330; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034277; AAH34277.1; ALT_INIT; mRNA.
DR CCDS; CCDS5579.1; -.
DR PIR; A33421; A60557.
DR RefSeq; NP_000932.3; NM_000941.2.
DR PDB; 1B1C; X-ray; 1.93 A; A=61-241.
DR PDB; 3FJO; X-ray; 2.50 A; A=232-677.
DR PDB; 3QE2; X-ray; 1.75 A; A/B=64-677.
DR PDB; 3QFC; X-ray; 1.80 A; A/B=64-677.
DR PDB; 3QFR; X-ray; 2.40 A; A/B=64-677.
DR PDB; 3QFS; X-ray; 1.40 A; A=241-677.
DR PDB; 3QFT; X-ray; 1.40 A; A=241-677.
DR PDB; 5EMN; X-ray; 2.20 A; A/B=64-677.
DR PDB; 5FA6; X-ray; 2.30 A; A/B=64-677.
DR PDBsum; 1B1C; -.
DR PDBsum; 3FJO; -.
DR PDBsum; 3QE2; -.
DR PDBsum; 3QFC; -.
DR PDBsum; 3QFR; -.
DR PDBsum; 3QFS; -.
DR PDBsum; 3QFT; -.
DR PDBsum; 5EMN; -.
DR PDBsum; 5FA6; -.
DR AlphaFoldDB; P16435; -.
DR BMRB; P16435; -.
DR SMR; P16435; -.
DR BioGRID; 111443; 206.
DR DIP; DIP-29682N; -.
DR IntAct; P16435; 27.
DR MINT; P16435; -.
DR STRING; 9606.ENSP00000419970; -.
DR BindingDB; P16435; -.
DR ChEMBL; CHEMBL2169731; -.
DR DrugBank; DB06263; Amrubicin.
DR DrugBank; DB00865; Benzphetamine.
DR DrugBank; DB00694; Daunorubicin.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB01466; Ethylmorphine.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR DrugBank; DB03247; Flavin mononucleotide.
DR DrugBank; DB09332; Kappadione.
DR DrugBank; DB00166; Lipoic acid.
DR DrugBank; DB00305; Mitomycin.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR DrugBank; DB00665; Nilutamide.
DR DrugBank; DB00698; Nitrofurantoin.
DR GlyConnect; 1535; 1 N-Linked glycan (1 site).
DR GlyGen; P16435; 2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; P16435; -.
DR PhosphoSitePlus; P16435; -.
DR SwissPalm; P16435; -.
DR BioMuta; POR; -.
DR DMDM; 2851393; -.
DR EPD; P16435; -.
DR jPOST; P16435; -.
DR MassIVE; P16435; -.
DR MaxQB; P16435; -.
DR PaxDb; P16435; -.
DR PeptideAtlas; P16435; -.
DR PRIDE; P16435; -.
DR ProteomicsDB; 53360; -.
DR Antibodypedia; 2433; 454 antibodies from 35 providers.
DR DNASU; 5447; -.
DR Ensembl; ENST00000394893.5; ENSP00000378355.1; ENSG00000127948.16.
DR Ensembl; ENST00000412064.6; ENSP00000404731.2; ENSG00000127948.16.
DR Ensembl; ENST00000412521.5; ENSP00000409238.1; ENSG00000127948.16.
DR Ensembl; ENST00000414186.5; ENSP00000399327.1; ENSG00000127948.16.
DR Ensembl; ENST00000418341.1; ENSP00000389719.1; ENSG00000127948.16.
DR Ensembl; ENST00000432753.5; ENSP00000389409.1; ENSG00000127948.16.
DR Ensembl; ENST00000439963.5; ENSP00000390540.1; ENSG00000127948.16.
DR Ensembl; ENST00000449920.5; ENSP00000399556.1; ENSG00000127948.16.
DR Ensembl; ENST00000453773.5; ENSP00000395813.1; ENSG00000127948.16.
DR Ensembl; ENST00000454934.5; ENSP00000414263.1; ENSG00000127948.16.
DR Ensembl; ENST00000461988.6; ENSP00000419970.1; ENSG00000127948.16.
DR GeneID; 5447; -.
DR UCSC; uc003udy.4; human.
DR CTD; 5447; -.
DR DisGeNET; 5447; -.
DR GeneCards; POR; -.
DR GeneReviews; POR; -.
DR HGNC; HGNC:9208; POR.
DR HPA; ENSG00000127948; Tissue enhanced (liver).
DR MalaCards; POR; -.
DR MIM; 124015; gene.
DR MIM; 201750; phenotype.
DR MIM; 613571; phenotype.
DR neXtProt; NX_P16435; -.
DR Orphanet; 63269; Antley-Bixler syndrome with genital anomaly and disorder of steroidogenesis.
DR Orphanet; 95699; Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency.
DR PharmGKB; PA33532; -.
DR VEuPathDB; HostDB:ENSG00000127948; -.
DR eggNOG; KOG1158; Eukaryota.
DR HOGENOM; CLU_001570_17_3_1; -.
DR InParanoid; P16435; -.
DR OrthoDB; 318396at2759; -.
DR PhylomeDB; P16435; -.
DR TreeFam; TF105719; -.
DR BioCyc; MetaCyc:HS05140-MON; -.
DR BRENDA; 1.6.2.4; 2681.
DR PathwayCommons; P16435; -.
DR Reactome; R-HSA-211897; Cytochrome P450 - arranged by substrate type.
DR SABIO-RK; P16435; -.
DR SignaLink; P16435; -.
DR SIGNOR; P16435; -.
DR BioGRID-ORCS; 5447; 15 hits in 1083 CRISPR screens.
DR ChiTaRS; POR; human.
DR EvolutionaryTrace; P16435; -.
DR GeneWiki; Cytochrome_P450_reductase; -.
DR GenomeRNAi; 5447; -.
DR Pharos; P16435; Tbio.
DR PRO; PR:P16435; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P16435; protein.
DR Bgee; ENSG00000127948; Expressed in adrenal tissue and 181 other tissues.
DR ExpressionAtlas; P16435; baseline and differential.
DR Genevisible; P16435; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; IEA:Ensembl.
DR GO; GO:0009055; F:electron transfer activity; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0010181; F:FMN binding; IBA:GO_Central.
DR GO; GO:0016787; F:hydrolase activity; IEA:Ensembl.
DR GO; GO:0047726; F:iron-cytochrome-c reductase activity; IEA:Ensembl.
DR GO; GO:0050661; F:NADP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003958; F:NADPH-hemoprotein reductase activity; IDA:UniProtKB.
DR GO; GO:0008941; F:nitric oxide dioxygenase activity; IEA:Ensembl.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0009437; P:carnitine metabolic process; IEA:Ensembl.
DR GO; GO:0090346; P:cellular organofluorine metabolic process; IDA:BHF-UCL.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEA:Ensembl.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEA:Ensembl.
DR GO; GO:0070988; P:demethylation; IEA:Ensembl.
DR GO; GO:0022900; P:electron transport chain; IDA:UniProtKB.
DR GO; GO:0019395; P:fatty acid oxidation; IEA:Ensembl.
DR GO; GO:0009812; P:flavonoid metabolic process; IEA:Ensembl.
DR GO; GO:0018393; P:internal peptidyl-lysine acetylation; IEA:Ensembl.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl.
DR GO; GO:0060192; P:negative regulation of lipase activity; IEA:Ensembl.
DR GO; GO:0043602; P:nitrate catabolic process; IEA:Ensembl.
DR GO; GO:0046210; P:nitric oxide catabolic process; IEA:Ensembl.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; IEA:Ensembl.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0032770; P:positive regulation of monooxygenase activity; IDA:BHF-UCL.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0090031; P:positive regulation of steroid hormone biosynthetic process; IEA:Ensembl.
DR GO; GO:0003420; P:regulation of growth plate cartilage chondrocyte proliferation; IEA:Ensembl.
DR GO; GO:0071548; P:response to dexamethasone; IEA:Ensembl.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR Gene3D; 1.20.990.10; -; 1.
DR Gene3D; 3.40.50.360; -; 1.
DR Gene3D; 3.40.50.80; -; 1.
DR HAMAP; MF_03212; NCPR; 1.
DR InterPro; IPR003097; CysJ-like_FAD-binding.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR001094; Flavdoxin-like.
DR InterPro; IPR008254; Flavodoxin/NO_synth.
DR InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase.
DR InterPro; IPR029039; Flavoprotein-like_sf.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR023173; NADPH_Cyt_P450_Rdtase_alpha.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR023208; P450R.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR Pfam; PF00667; FAD_binding_1; 1.
DR Pfam; PF00258; Flavodoxin_1; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR PIRSF; PIRSF000208; P450R; 1.
DR PRINTS; PR00369; FLAVODOXIN.
DR PRINTS; PR00371; FPNCR.
DR SUPFAM; SSF52218; SSF52218; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
DR PROSITE; PS50902; FLAVODOXIN_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Congenital adrenal hyperplasia;
KW Craniosynostosis; Direct protein sequencing; Disease variant;
KW Endoplasmic reticulum; FAD; Flavoprotein; FMN; Membrane; NADP;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2513880"
FT CHAIN 2..677
FT /note="NADPH--cytochrome P450 reductase"
FT /id="PRO_0000167596"
FT TOPO_DOM 2..21
FT /note="Lumenal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT TOPO_DOM 43..677
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT DOMAIN 80..224
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT DOMAIN 279..521
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212"
FT BINDING 86..91
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:10048323, ECO:0000269|PubMed:21808038"
FT BINDING 138..141
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:10048323, ECO:0000269|PubMed:21808038"
FT BINDING 173..182
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:10048323, ECO:0000269|PubMed:21808038"
FT BINDING 208
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:10048323, ECO:0000269|PubMed:21808038"
FT BINDING 298
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:21808038"
FT BINDING 424
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:19483672, ECO:0000269|PubMed:21808038"
FT BINDING 454..457
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:19483672, ECO:0000269|PubMed:21808038"
FT BINDING 472..474
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:19483672, ECO:0000269|PubMed:21808038"
FT BINDING 478
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:19483672, ECO:0000269|PubMed:21808038"
FT BINDING 488..491
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:19483672, ECO:0000269|PubMed:21808038"
FT BINDING 535
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:21808038"
FT BINDING 596..597
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:21808038"
FT BINDING 602..606
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:21808038"
FT BINDING 638
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:21808038"
FT BINDING 676
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03212,
FT ECO:0000269|PubMed:19483672, ECO:0000269|PubMed:21808038"
FT MOD_RES 2
FT /note="N-acetylglycine"
FT /evidence="ECO:0000269|PubMed:2513880"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 178
FT /note="Y -> D (in DISPORD; complete loss of activity)"
FT /evidence="ECO:0000269|PubMed:15220035"
FT /id="VAR_021154"
FT VARIANT 225
FT /note="P -> L (in dbSNP:rs782427303)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4"
FT /id="VAR_047885"
FT VARIANT 252
FT /note="D -> N"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_047886"
FT VARIANT 284
FT /note="A -> P (in ABS1 and DISPORD; significant reduction
FT of activity)"
FT /evidence="ECO:0000269|PubMed:14758361,
FT ECO:0000269|PubMed:15220035"
FT /id="VAR_021155"
FT VARIANT 454
FT /note="R -> H (in ABS1 and DISPORD; significant reduction
FT of activity)"
FT /evidence="ECO:0000269|PubMed:14758361,
FT ECO:0000269|PubMed:15220035, ECO:0000269|PubMed:15264278,
FT ECO:0000269|PubMed:15483095, ECO:0000269|PubMed:27610946"
FT /id="VAR_021156"
FT VARIANT 489
FT /note="V -> E (in ABS1; significant reduction of activity)"
FT /evidence="ECO:0000269|PubMed:14758361"
FT /id="VAR_021157"
FT VARIANT 500
FT /note="A -> V (in dbSNP:rs1057868)"
FT /evidence="ECO:0000269|PubMed:15483095,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:1550342,
FT ECO:0000269|Ref.4"
FT /id="VAR_004617"
FT VARIANT 551
FT /note="R -> Q"
FT /id="VAR_004618"
FT VARIANT 566
FT /note="C -> Y (in DISPORD; significant reduction of
FT activity; dbSNP:rs72552772)"
FT /evidence="ECO:0000269|PubMed:14758361,
FT ECO:0000269|PubMed:15220035"
FT /id="VAR_021158"
FT VARIANT 575
FT /note="Y -> C (in ABS1)"
FT /evidence="ECO:0000269|PubMed:15483095"
FT /id="VAR_021159"
FT VARIANT 605
FT /note="V -> F (in DISPORD; significant reduction of
FT activity)"
FT /evidence="ECO:0000269|PubMed:14758361"
FT /id="VAR_021160"
FT VARIANT 609..617
FT /note="LKQDREHLW -> R (in ABS1)"
FT /id="VAR_021161"
FT CONFLICT 405
FT /note="M -> L (in Ref. 3; BAB18572)"
FT /evidence="ECO:0000305"
FT CONFLICT 518
FT /note="F -> L (in Ref. 1; AAB21814 and 3; BAB18572)"
FT /evidence="ECO:0000305"
FT CONFLICT 537..538
FT /note="VA -> WH (in Ref. 1; AAB21814)"
FT /evidence="ECO:0000305"
FT HELIX 69..76
FT /evidence="ECO:0007829|PDB:3QE2"
FT STRAND 79..85
FT /evidence="ECO:0007829|PDB:3QE2"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:3QE2"
FT HELIX 90..101
FT /evidence="ECO:0007829|PDB:3QE2"
FT HELIX 102..105
FT /evidence="ECO:0007829|PDB:3QE2"
FT STRAND 109..112
FT /evidence="ECO:0007829|PDB:3QE2"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:3QE2"
FT HELIX 119..127
FT /evidence="ECO:0007829|PDB:3QE2"
FT STRAND 132..138
FT /evidence="ECO:0007829|PDB:3QE2"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:3QE2"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:3QE2"
FT HELIX 150..158
FT /evidence="ECO:0007829|PDB:3QE2"
FT STRAND 167..174
FT /evidence="ECO:0007829|PDB:3QE2"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:3QE2"
FT HELIX 183..194
FT /evidence="ECO:0007829|PDB:3QE2"
FT STRAND 198..201
FT /evidence="ECO:0007829|PDB:3QE2"
FT STRAND 204..207
FT /evidence="ECO:0007829|PDB:3QE2"
FT TURN 208..210
FT /evidence="ECO:0007829|PDB:5EMN"
FT HELIX 212..231
FT /evidence="ECO:0007829|PDB:3QE2"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:3QFS"
FT TURN 266..270
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 282..291
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 294..298
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 300..306
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 319..322
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 328..338
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 345..352
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 360..366
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 367..373
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 383..389
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 390..392
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 396..406
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 407..409
FT /evidence="ECO:0007829|PDB:5FA6"
FT HELIX 410..419
FT /evidence="ECO:0007829|PDB:3QFS"
FT TURN 420..424
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 427..433
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 441..447
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 454..457
FT /evidence="ECO:0007829|PDB:3QFS"
FT TURN 462..464
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 468..474
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 477..479
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 485..487
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 489..495
FT /evidence="ECO:0007829|PDB:3QFS"
FT TURN 501..503
FT /evidence="ECO:0007829|PDB:3QE2"
FT STRAND 508..514
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 528..531
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 534..537
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 538..553
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 560..567
FT /evidence="ECO:0007829|PDB:3QFS"
FT TURN 569..571
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 576..584
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 587..595
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 598..601
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 605..611
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 613..621
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 625..631
FT /evidence="ECO:0007829|PDB:3QFS"
FT TURN 632..634
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 635..650
FT /evidence="ECO:0007829|PDB:3QFS"
FT HELIX 655..667
FT /evidence="ECO:0007829|PDB:3QFS"
FT STRAND 670..676
FT /evidence="ECO:0007829|PDB:3QFS"
SQ SEQUENCE 677 AA; 76690 MW; 2F7D4B9CDFDF5A74 CRC64;
MGDSHVDTSS TVSEAVAEEV SLFSMTDMIL FSLIVGLLTY WFLFRKKKEE VPEFTKIQTL
TSSVRESSFV EKMKKTGRNI IVFYGSQTGT AEEFANRLSK DAHRYGMRGM SADPEEYDLA
DLSSLPEIDN ALVVFCMATY GEGDPTDNAQ DFYDWLQETD VDLSGVKFAV FGLGNKTYEH
FNAMGKYVDK RLEQLGAQRI FELGLGDDDG NLEEDFITWR EQFWPAVCEH FGVEATGEES
SIRQYELVVH TDIDAAKVYM GEMGRLKSYE NQKPPFDAKN PFLAAVTTNR KLNQGTERHL
MHLELDISDS KIRYESGDHV AVYPANDSAL VNQLGKILGA DLDVVMSLNN LDEESNKKHP
FPCPTSYRTA LTYYLDITNP PRTNVLYELA QYASEPSEQE LLRKMASSSG EGKELYLSWV
VEARRHILAI LQDCPSLRPP IDHLCELLPR LQARYYSIAS SSKVHPNSVH ICAVVVEYET
KAGRINKGVA TNWLRAKEPA GENGGRALVP MFVRKSQFRL PFKATTPVIM VGPGTGVAPF
IGFIQERAWL RQQGKEVGET LLYYGCRRSD EDYLYREELA QFHRDGALTQ LNVAFSREQS
HKVYVQHLLK QDREHLWKLI EGGAHIYVCG DARNMARDVQ NTFYDIVAEL GAMEHAQAVD
YIKKLMTKGR YSLDVWS
