NADPH--cytochrome P450 reductase

Details

Name
NADPH--cytochrome P450 reductase
Synonyms
  • 1.6.2.4
  • CPR
  • CYPOR
Gene Name
POR
Organism
Humans
Amino acid sequence
>lcl|BSEQ0004643|NADPH--cytochrome P450 reductase
MGDSHVDTSSTVSEAVAEEVSLFSMTDMILFSLIVGLLTYWFLFRKKKEEVPEFTKIQTL
TSSVRESSFVEKMKKTGRNIIVFYGSQTGTAEEFANRLSKDAHRYGMRGMSADPEEYDLA
DLSSLPEIDNALVVFCMATYGEGDPTDNAQDFYDWLQETDVDLSGVKFAVFGLGNKTYEH
FNAMGKYVDKRLEQLGAQRIFELGLGDDDGNLEEDFITWREQFWPAVCEHFGVEATGEES
SIRQYELVVHTDIDAAKVYMGEMGRLKSYENQKPPFDAKNPFLAAVTTNRKLNQGTERHL
MHLELDISDSKIRYESGDHVAVYPANDSALVNQLGKILGADLDVVMSLNNLDEESNKKHP
FPCPTSYRTALTYYLDITNPPRTNVLYELAQYASEPSEQELLRKMASSSGEGKELYLSWV
VEARRHILAILQDCPSLRPPIDHLCELLPRLQARYYSIASSSKVHPNSVHICAVVVEYET
KAGRINKGVATNWLRAKEPAGENGGRALVPMFVRKSQFRLPFKATTPVIMVGPGTGVAPF
IGFIQERAWLRQQGKEVGETLLYYGCRRSDEDYLYREELAQFHRDGALTQLNVAFSREQS
HKVYVQHLLKQDREHLWKLIEGGAHIYVCGDARNMARDVQNTFYDIVAELGAMEHAQAVD
YIKKLMTKGRYSLDVWS
Number of residues
677
Molecular Weight
76689.12
Theoretical pI
5.28
GO Classification
Functions
cytochrome-b5 reductase activity, acting on NAD(P)H / electron carrier activity / flavin adenine dinucleotide binding / FMN binding / hydrolase activity / iron ion binding / iron-cytochrome-c reductase activity / NADP binding / NADPH-hemoprotein reductase activity / nitric oxide dioxygenase activity / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen
Processes
carnitine metabolic process / cellular organofluorine metabolic process / cellular response to follicle-stimulating hormone stimulus / cellular response to peptide hormone stimulus / demethylation / fatty acid oxidation / flavonoid metabolic process / internal peptidyl-lysine acetylation / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of lipase activity / nitrate catabolic process / nitric oxide catabolic process / oxidation-reduction process / positive regulation of cholesterol biosynthetic process / positive regulation of chondrocyte differentiation / positive regulation of monooxygenase activity / positive regulation of smoothened signaling pathway / positive regulation of steroid hormone biosynthetic process / regulation of growth plate cartilage chondrocyte proliferation / response to drug / response to nutrient
Components
cytosol / endoplasmic reticulum membrane / intracellular membrane-bounded organelle / membrane / mitochondrion
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific 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.
Pfam Domain Function
Transmembrane Regions
22-42
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0011696|NADPH--cytochrome P450 reductase (POR)
ATGATCAACATGGGAGACTCCCACGTGGACACCAGCTCCACCGTGTCCGAGGCGGTGGCC
GAAGAAGTATCTCTTTTCAGCATGACGGACATGATTCTGTTTTCGCTCATCGTGGGTCTC
CTAACCTACTGGTTCCTCTTCAGAAAGAAAAAAGAAGAAGTCCCCGAGTTCACCAAAATT
CAGACATTGACCTCCTCTGTCAGAGAGAGCAGCTTTGTGGAAAAGATGAAGAAAACGGGG
AGGAACATCATCGTGTTCTACGGCTCCCAGACGGGGACTGCAGAGGAGTTTGCCAACCGC
CTGTCCAAGGACGCCCACCGCTACGGGATGCGAGGCATGTCAGCGGACCCTGAGGAGTAT
GACCTGGCCGACCTGAGCAGCCTGCCAGAGATCGACAACGCCCTGGTGGTTTTCTGCATG
GCCACCTACGGTGAGGGAGACCCCACCGACAATGCCCAGGACTTCTACGACTGGCTGCAG
GAGACAGACGTGGATCTCTCTGGGGTCAAGTTCGCGGTGTTTGGTCTTGGGAACAAGACC
TACGAGCACTTCAATGCCATGGGCAAGTACGTGGACAAGCGGCTGGAGCAGCTCGGCGCC
CAGCGCATCTTTGAGCTGGGGTTGGGCGACGACGATGGGAACTTGGAGGAGGACTTCATC
ACCTGGCGAGAGCAGTTCTGGCCGGCCGTGTGTGAACACTTTGGGGTGGAAGCCACTGGC
GAGGAGTCCAGCATTCGCCAGTACGAGCTTGTGGTCCACACCGACATAGATGCGGCCAAG
GTGTACATGGGGGAGATGGGCCGGCTGAAGAGCTACGAGAACCAGAAGCCCCCCTTTGAT
GCCAAGAATCCGTTCCTGGCTGCAGTCACCACCAACCGGAAGCTGAACCAGGGAACCGAG
CGCCACCTCATGCACCTGGAATTGGACATCTCGGACTCCAAAATCAGGTATGAATCTGGG
GACCACGTGGCTGTGTACCCAGCCAACGACTCTGCTCTCGTCAACCAGCTGGGCAAAATC
CTGGGTGCCGACCTGGACGTCGTCATGTCCCTGAACAACCTGGATGAGGAGTCCAACAAG
AAGCACCCATTCCCGTGCCCTACGTCCTACCGCACGGCCCTCACCTACTACCTGGACATC
ACCAACCCGCCGCGTACCAACGTGCTGTACGAGCTGGCGCAGTACGCCTCGGAGCCCTCG
GAGCAGGAGCTGCTGCGCAAGATGGCCTCCTCCTCCGGCGAGGGCAAGGAGCTGTACCTG
AGCTGGGTGGTGGAGGCCCGGAGGCACATCCTGGCCATCCTGCAGGACTGCCCGTCCCTG
CGGCCCCCCATCGACCACCTGTGTGAGCTGCTGCCGCGCCTGCAGGCCCGCTACTACTCC
ATCGCCTCATCCTCCAAGGTCCACCCCAACTCTGTGCACATCTGTGCGGTGGTTGTGGAG
TACGAGACCAAGGCTGGCCGCATCAACAAGGGCGTGGCCACCAACTGGCTGCGGGCCAAG
GAGCCTGCCGGGGAGAACGGCGGCCGTGCGCTGGTGCCCATGTTCGTGCGCAAGTCCCAG
TTCCGCCTGCCCTTCAAGGCCACCACGCCTGTCATCATGGTGGGCCCCGGCACCGGGGTG
GCACCCTTCATAGGCTTCATCCAGGAGCGGGCCTGGCTGCGACAGCAGGGCAAGGAGGTG
GGGGAGACGCTGCTGTACTACGGCTGCCGCCGCTCGGATGAGGACTACCTGTACCGGGAG
GAGCTGGCGCAGTTCCACAGGGACGGTGCGCTCACCCAGCTCAACGTGGCCTTCTCCCGG
GAGCAGTCCCACAAGGTCTACGTCCAGCACCTGCTAAAGCAAGACCGAGAGCACCTGTGG
AAGTTGATCGAAGGCGGTGCCCACATCTACGTCTGTGGGGATGCACGGAACATGGCCAGG
GATGTGCAGAACACCTTCTACGACATCGTGGCTGAGCTCGGGGCCATGGAGCACGCGCAG
GCGGTGGACTACATCAAGAAACTGATGACCAAGGGCCGCTACTCCCTGGACGTGTGGAGC
TAG
Chromosome Location
7
Locus
7q11.2
External Identifiers
ResourceLink
UniProtKB IDP16435
UniProtKB Entry NameNCPR_HUMAN
GenBank Protein ID247307
GenBank Gene IDS90469
GenAtlas IDPOR
HGNC IDHGNC:9208
General References
  1. Shephard EA, Palmer CN, Segall HJ, Phillips IR: Quantification of cytochrome P450 reductase gene expression in human tissues. Arch Biochem Biophys. 1992 Apr;294(1):168-72. [PubMed:1550342]
  2. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [PubMed:12853948]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  4. Haniu M, McManus ME, Birkett DJ, Lee TD, Shively JE: Structural and functional analysis of NADPH-cytochrome P-450 reductase from human liver: complete sequence of human enzyme and NADPH-binding sites. Biochemistry. 1989 Oct 17;28(21):8639-45. [PubMed:2513880]
  5. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  6. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  7. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [PubMed:25944712]
  8. Zhao Q, Modi S, Smith G, Paine M, McDonagh PD, Wolf CR, Tew D, Lian LY, Roberts GC, Driessen HP: Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution. Protein Sci. 1999 Feb;8(2):298-306. [PubMed:10048323]
  9. Aigrain L, Pompon D, Morera S, Truan G: Structure of the open conformation of a functional chimeric NADPH cytochrome P450 reductase. EMBO Rep. 2009 Jul;10(7):742-7. doi: 10.1038/embor.2009.82. Epub 2009 May 29. [PubMed:19483672]
  10. Xia C, Panda SP, Marohnic CC, Martasek P, Masters BS, Kim JJ: Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13486-91. doi: 10.1073/pnas.1106632108. Epub 2011 Aug 1. [PubMed:21808038]
  11. 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. 2004 Aug 1;128A(4):333-9. [PubMed:15264278]
  12. 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. 2005 Jan;90(1):414-26. Epub 2004 Oct 13. [PubMed:15483095]
  13. Arlt W, Walker EA, Draper N, Ivison HE, Ride JP, Hammer F, Chalder SM, Borucka-Mankiewicz M, Hauffa BP, Malunowicz EM, Stewart PM, Shackleton CH: Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study. Lancet. 2004 Jun 26;363(9427):2128-35. [PubMed:15220035]
  14. Fluck CE, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF, Jabs EW, Mendonca BB, Fujieda K, Miller WL: Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nat Genet. 2004 Mar;36(3):228-30. Epub 2004 Feb 1. [PubMed:14758361]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB03147Flavin adenine dinucleotideapprovedunknownDetails
DB034612'-Monophosphoadenosine 5'-DiphosphoriboseexperimentalunknownDetails
DB03247Flavin mononucleotideapproved, investigationalunknownDetails
DB00305MitomycinapprovedunknownsubstrateDetails
DB00166Lipoic Acidapproved, investigational, nutraceuticalunknowninhibitorDetails
DB00665Nilutamideapproved, investigationalunknownsubstrateDetails
DB00694DaunorubicinapprovedunknownsubstrateDetails
DB01466Ethylmorphineexperimental, illicitunknownDetails
DB03247Flavin mononucleotideapproved, investigationalunknownDetails
DB00865Benzphetamineapproved, illicitunknownsubstrateDetails
DB00698Nitrofurantoinapproved, vet_approvedunknownsubstrateDetails
DB00997Doxorubicinapproved, investigationalunknownsubstrateDetails
DB09332KappadioneapprovedunknownsubstrateDetails
DB06263AmrubicininvestigationalunknownsubstrateDetails