P16603 (NCPR_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NADPH--cytochrome P450 reductase
Short name=CPR
Short name=P450R
EC=1.6.2.4

Gene names

Name:	NCP1
Synonyms:	CPR1, NCPR1, PRD1
Ordered Locus Names:	YHR042W

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	691 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Involved in ergosterol biosynthesis. Has NADPH-dependent ferrireductase activity on the plasma membrane. Ref.5 Ref.6 Ref.7 Ref.8
Catalytic activity	NADPH + n oxidized hemoprotein = NADP+ + n reduced hemoprotein. Ref.6 Ref.7 Ref.8
Cofactor	Binds 1 FAD per monomer. Ref.7 Ref.15 Binds 1 FMN per monomer. Ref.7
Subunit structure	Interacts with PCL1. Ref.12
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein. Mitochondrion outer membrane; Single-pass membrane protein. Cell membrane; Single-pass membrane protein. Microsome Ref.6 Ref.7 Ref.8 Ref.11 Ref.13 Ref.14.
Induction	By galactose and on the plasma membrane by iron or copper deficiency. Repressed by glucose. Ref.6
Post-translational modification	Phosphorylated by the cyclin-CDK PCL1-PHO85. Ref.12
Disruption phenotype	Accumulates 20% of ergosterol of wild type. Ref.7
Miscellaneous	Present with 46600 molecules/cell in log phase SD medium.
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.
Biophysicochemical properties	Kinetic parameters: The Vmax of the reaction is 721 pmol/min/pmol enzyme towards cytochrome c, and 662 pmol/min/pmol enzyme toward NADPH. KM=1.59 µM for cytochrome c Ref.8 KM=1.46 µM for NADPH

Ontologies

Keywords
Biological process	Lipid biosynthesis Lipid metabolism Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism
Cellular component	Cell membrane Endoplasmic reticulum Membrane Microsome Mitochondrion Mitochondrion outer membrane
Domain	Transmembrane Transmembrane helix
Ligand	FAD FMN Flavoprotein NADP
Molecular function	Oxidoreductase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	ergosterol biosynthetic process Inferred from mutant phenotype Ref.7. Source: SGD
Cellular_component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Inferred from direct assay Ref.14. Source: SGD plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	FMN binding Inferred from electronic annotation. Source: InterPro NADPH-hemoprotein reductase activity Inferred from electronic annotation. Source: EC electron carrier activity Inferred from direct assay Ref.8. Source: SGD iron ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.1

Chain

2 – 691

690

NADPH--cytochrome P450 reductase

PRO_0000167608

Regions

Transmembrane

8 – 24

17

Helical; Potential

Domain

61 – 204

144

Flavodoxin-like

Domain

266 – 529

264

FAD-binding FR-type

Nucleotide binding

71 – 78

8

FMN; alternate

Nucleotide binding

116 – 119

4

FMN

Nucleotide binding

610 – 621

12

NADP

Sites

Binding site

67

1

FMN

Binding site

187

1

FMN; alternate

Binding site

441

1

FAD

Binding site

478

1

FAD

Binding site

646

1

NADP

Amino acid modifications

Cross-link

666

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.10

Natural variations

Natural variant

474

1

V → G.

Experimental info

Sequence conflict

423

1

T → N in BAA02936. Ref.1

Secondary structure

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691

Helix Strand Turn

Details...

Helix

50 – 56

7

Beta strand

60 – 66

7

Beta strand

68 – 70

3

Helix

71 – 87

17

Beta strand

91 – 95

5

Helix

96 – 98

3

Helix

104 – 106

3

Beta strand

109 – 116

8

Beta strand

119 – 121

3

Helix

125 – 127

3

Helix

128 – 136

9

Turn

139 – 144

6

Beta strand

146 – 153

8

Beta strand

157 – 159

3

Helix

162 – 173

12

Beta strand

183 – 186

4

Turn

187 – 190

4

Helix

192 – 210

19

Beta strand

223 – 226

4

Beta strand

234 – 239

6

Helix

243 – 245

3

Beta strand

271 – 278

8

Beta strand

287 – 293

7

Beta strand

306 – 309

4

Helix

315 – 325

11

Beta strand

332 – 334

3

Beta strand

337 – 339

3

Beta strand

348 – 351

4

Helix

352 – 358

7

Helix

368 – 374

7

Helix

375 – 377

3

Helix

381 – 390

10

Helix

394 – 400

7

Helix

402 – 404

3

Helix

408 – 416

9

Helix

426 – 432

7

Beta strand

439 – 443

5

Turn

447 – 449

3

Beta strand

453 – 459

7

Beta strand

469 – 471

3

Helix

477 – 489

13

Turn

494 – 496

3

Helix

508 – 510

3

Turn

511 – 515

5

Beta strand

519 – 522

4

Beta strand

536 – 541

6

Helix

542 – 545

4

Helix

546 – 560

15

Turn

564 – 566

3

Beta strand

574 – 585

12

Turn

587 – 591

5

Helix

592 – 599

8

Helix

600 – 602

3

Beta strand

603 – 610

8

Helix

620 – 626

7

Helix

628 – 635

8

Turn

636 – 638

3

Beta strand

640 – 645

6

Helix

650 – 665

16

Helix

670 – 682

13

Beta strand

685 – 690

6

Sequences

	Sequence		Length	Mass (Da)
	P16603 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 82BB847701E5438B	FASTA	691	76,772
	10 20 30 40 50 60 MPFGIDNTDF TVLAGLVLAV LLYVKRNSIK ELLMSDDGDI TAVSSGNRDI AQVVTENNKN 70 80 90 100 110 120 YLVLYASQTG TAEDYAKKFS KELVAKFNLN VMCADVENYD FESLNDVPVI VSIFISTYGE 130 140 150 160 170 180 GDFPDGAVNF EDFICNAEAG ALSNLRYNMF GLGNSTYEFF NGAAKKAEKH LSAAGAIRLG 190 200 210 220 230 240 KLGEADDGAG TTDEDYMAWK DSILEVLKDE LHLDEQEAKF TSQFQYTVLN EITDSMSLGE 250 260 270 280 290 300 PSAHYLPSHQ LNRNADGIQL GPFDLSQPYI APIVKSRELF SSNDRNCIHS EFDLSGSNIK 310 320 330 340 350 360 YSTGDHLAVW PSNPLEKVEQ FLSIFNLDPE TIFDLKPLDP TVKVPFPTPT TIGAAIKHYL 370 380 390 400 410 420 EITGPVSRQL FSSLIQFAPN ADVKEKLTLL SKDKDQFAVE ITSKYFNIAD ALKYLSDGAK 430 440 450 460 470 480 WDTVPMQFLV ESVPQMTPRY YSISSSSLSE KQTVHVTSIV ENFPNPELPD APPVVGVTTN 490 500 510 520 530 540 LLRNIQLAQN NVNIAETNLP VHYDLNGPRK LFANYKLPVH VRRSNFRLPS NPSTPVIMIG 550 560 570 580 590 600 PGTGVAPFRG FIRERVAFLE SQKKGGNNVS LGKHILFYGS RNTDDFLYQD EWPEYAKKLD 610 620 630 640 650 660 GSFEMVVAHS RLPNTKKVYV QDKLKDYEDQ VFEMINNGAF IYVCGDAKGM AKGVSTALVG 670 680 690 ILSRGKSITT DEATELIKML KTSGRYQEDV W

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of Saccharomyces cerevisiae NADPH-cytochrome P450 reductase deduced from nucleotide sequence of its cloned gene." Yabusaki Y., Murakami H., Ohkawa H. J. Biochem. 103:1004-1010(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-13 AND 45-62.
[2]	"Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII." Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z., Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T., Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P. , Louis E.J., Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L., St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P., Waterston R., Wilson R., Vaudin M. Science 265:2077-2082(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[4]	"Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae." Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J. , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J. Genome Res. 17:536-543(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[5]	"Multiple regulatory elements control expression of the gene encoding the Saccharomyces cerevisiae cytochrome P450, lanosterol 14 alpha-demethylase (ERG11)." Turi T.G., Loper J.C. J. Biol. Chem. 267:2046-2056(1992) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Cytochrome P-450 reductase is responsible for the ferrireductase activity associated with isolated plasma membranes of Saccharomyces cerevisiae." Lesuisse E., Casteras-Simon M., Labbe P. FEMS Microbiol. Lett. 156:147-152(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INDUCTION.
[7]	"The N-terminal membrane domain of yeast NADPH-cytochrome P450 (CYP) oxidoreductase is not required for catalytic activity in sterol biosynthesis or in reconstitution of CYP activity." Venkateswarlu K., Lamb D.C., Kelly D.E., Manning N.J., Kelly S.L. J. Biol. Chem. 273:4492-4496(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
[8]	"Activities and kinetic mechanisms of native and soluble NADPH-cytochrome P450 reductase." Lamb D.C., Warrilow A.G., Venkateswarlu K., Kelly D.E., Kelly S.L. Biochem. Biophys. Res. Commun. 286:48-54(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.
[9]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[10]	"A subset of membrane-associated proteins is ubiquitinated in response to mutations in the endoplasmic reticulum degradation machinery." Hitchcock A.L., Auld K., Gygi S.P., Silver P.A. Proc. Natl. Acad. Sci. U.S.A. 100:12735-12740(2003) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-666, MASS SPECTROMETRY.
[11]	"The proteome of Saccharomyces cerevisiae mitochondria." Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E., Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P., Pfanner N., Meisinger C. Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[12]	"The identification of Pcl1-interacting proteins that genetically interact with Cla4 may indicate a link between G1 progression and mitotic exit." Keniry M.E., Kemp H.A., Rivers D.M., Sprague G.F. Jr. Genetics 166:1177-1186(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH PCL1.
[13]	"Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics." Reinders J., Zahedi R.P., Pfanner N., Meisinger C., Sickmann A. J. Proteome Res. 5:1543-1554(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"Proteomic analysis of the yeast mitochondrial outer membrane reveals accumulation of a subclass of preproteins." Zahedi R.P., Sickmann A., Boehm A.M., Winkler C., Zufall N., Schoenfisch B., Guiard B., Pfanner N., Meisinger C. Mol. Biol. Cell 17:1436-1450(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MASS SPECTROMETRY.
[15]	"FMN binding site of yeast NADPH-cytochrome P450 reductase exposed at the surface is highly specific." Ivanov A.S., Gnedenko O.V., Molnar A.A., Archakov A.I., Podust L.M. ACS Chem. Biol. 5:767-776(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FMN-BINDING AND FAD-BINDING.
[16]	"A second FMN binding site in yeast NADPH-cytochrome P450 reductase suggests a mechanism of electron transfer by diflavin reductases." Lamb D.C., Kim Y., Yermalitskaya L.V., Yermalitsky V.N., Lepesheva G.I., Kelly S.L., Waterman M.R., Podust L.M. Structure 14:51-61(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.91 ANGSTROMS) OF 34-691 IN COMPLEX WITH FAD; FMN AND NADP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D13788 Genomic DNA. Translation: BAA02936.1.
U00062 Genomic DNA. Translation: AAB68904.1.
AY693091 Genomic DNA. Translation: AAT93110.1.
BK006934 Genomic DNA. Translation: DAA06734.1.

PIR

S46735.

RefSeq

NP_011908.1. NM_001179172.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BF4	X-ray	3.00	A/B	34-691	[»]
2BN4	X-ray	2.91	A/B	34-691	[»]
2BPO	X-ray	2.90	A/B	34-691	[»]
3FJO	X-ray	2.50	A	44-211	[»]

ProteinModelPortal

P16603.

SMR

P16603. Positions 47-691.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-8294N.

IntAct

P16603. 6 interactions.

MINT

MINT-2782506.

STRING

4932.YHR042W.

Proteomic databases

PaxDb

P16603.

PeptideAtlas

P16603.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YHR042W; YHR042W; YHR042W.

GeneID

856438.

KEGG

sce:YHR042W.

Organism-specific databases

SGD

S000001084. NCP1.

Phylogenomic databases

eggNOG

COG0369.

GeneTree

ENSGT00620000087711.

HOGENOM

HOG000282027.

KO

K00327.

OMA

WPEYAKK.

OrthoDB

EOG47SWP5.

Gene expression databases

Genevestigator

P16603.

GermOnline

YHR042W. Saccharomyces cerevisiae.

Family and domain databases

Gene3D

1.20.990.10. 1 hit.

InterPro

IPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR023208. P450R.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]

Pfam

PF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]

PIRSF

PIRSF000208. P450R. 1 hit.

PRINTS

PR00369. FLAVODOXIN.
PR00371. FPNCR.

SUPFAM

SSF63380. Riboflavin_synthase_like_b-brl. 1 hit.

PROSITE

PS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P16603.

NextBio

982042.

Entry information

Entry name

NCPR_YEAST

Accession

Primary (citable) accession number: P16603
Secondary accession number(s): D3DKZ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 148 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program