Por cytochrome p450 oxidoreductase [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Porprovided by RGD
Official Full Name: cytochrome p450 oxidoreductaseprovided by RGD
Primary source: RGD:68335
See related: Ensembl:ENSRNOG00000001442 AllianceGenome:RGD:68335
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: CYPOR
Summary: Enables several functions, including iron-cytochrome-c reductase activity; nucleotide binding activity; and oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor. Involved in several processes, including cellular response to hormone stimulus; negative regulation of hydrolase activity; and positive regulation of steroid biosynthetic process. Located in membrane and mitochondrion. Human ortholog(s) of this gene implicated in congenital adrenal hyperplasia and cytochrome P450 oxidoreductase deficiency. Orthologous to human POR (cytochrome p450 oxidoreductase). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Adrenal (RPKM 568.9), Kidney (RPKM 295.8) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 12q12

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	12	NC_086030.1 (26587674..26655612, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	12	NC_051347.1 (20951058..20999198, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	12	NC_005111.4 (23998411..24017063, complement)

Chromosome 12 - NC_086030.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Structural Dynamics of Cytochrome P450 3A4 in the Presence of Substrates and Cytochrome P450 Reductase.
Title: Structural Dynamics of Cytochrome P450 3A4 in the Presence of Substrates and Cytochrome P450 Reductase.
The structure of four-electron-reduced, NADP(+)-bound wild type CYPOR shows the plane of the nicotinamide ring positioned perpendicular to the FAD isoalloxazine with its carboxamide group forming H-bonds with N1 of the flavin ring and the Thr535 hydroxyl group.
Title: Structural and Kinetic Studies of Asp632 Mutants and Fully Reduced NADPH-Cytochrome P450 Oxidoreductase Define the Role of Asp632 Loop Dynamics in the Control of NADPH Binding and Hydride Transfer.
the N-terminus of CYP2J2 is very important to form a productive CYP-CPR complex to facilitate electron transfer.
Title: CYP2J2 epoxygenase membrane anchor plays an important role in facilitating electron transfer from CPR.
Data suggest CYP17A1, with electron donor NADPH-P450 reductase, is inherently distributive enzyme but that some processivity is present; some 17alpha-hydroxy pregnenolone formed does not dissociate from CYP17A1 before conversion to dehydroepiandrosterone; CYB5A does not enhance reaction by decreasing k(off) of ligands of CYP17A1. (CYP17A1 = cytochrome P450, family 17, subfamily A, polypeptide 1; CYB5A = cytochrome b5)
Title: Kinetic processivity of the two-step oxidations of progesterone and pregnenolone to androgens by human cytochrome P450 17A1.
The DeltaGly-143 protein had moderately decreased activity with cytochrome P450 and cytochrome c. It formed a flexible loop, which transiently interacts with the flavin N5, resulting in the generation of both an unstable neutral blue semiquinone and hydroquinone.
Title: Mutants of Cytochrome P450 Reductase Lacking Either Gly-141 or Gly-143 Destabilize Its FMN Semiquinone.
The findings provide insights into the function of CPR and CPR-cyt c interaction on a structural basis.
Title: Kinetic and structural characterization of the interaction between the FMN binding domain of cytochrome P450 reductase and cytochrome c.
the structure and dynamics of the full-length NADPH-cytochrome P450 oxidoreductase
Title: Probing the transmembrane structure and dynamics of microsomal NADPH-cytochrome P450 oxidoreductase by solid-state NMR.
Study of the role of P450 hydrophobic residues in complex formation with CPR uncovers novel roles for surface-exposed residues Val267 and Leu270 of CYP2B4 in mediating CYP2B4-CPR interactions.
Title: Uncovering the role of hydrophobic residues in cytochrome P450-cytochrome P450 reductase interactions.
Conformational changes of NADPH-cytochrome P450 oxidoreductase are essential for catalysis and cofactor binding.
Title: Conformational changes of NADPH-cytochrome P450 oxidoreductase are essential for catalysis and cofactor binding.
Studies indicate that CPR conformational changes involving a combination of a "swinging" and "rotating" model and enables CPR to serve as an effective electron transferring "nano-machine".
Title: Conformational changes of the NADPH-dependent cytochrome P450 reductase in the course of electron transfer to cytochromes P450.

Submit: New GeneRIF Correction See all GeneRIFs (17)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC180925P1 (e-PCR)
- UniSTS:271671

Por (e-PCR), detects polymorphism
- UniSTS:256629

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables FMN binding	IBA Inferred from Biological aspect of Ancestor more info
enables FMN binding	IEA Inferred from Electronic Annotation more info
enables FMN binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables NADP binding	IDA Inferred from Direct Assay more info	PubMed
enables NADP binding	IEA Inferred from Electronic Annotation more info
enables NADP binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables NADPH-hemoprotein reductase activity	IBA Inferred from Biological aspect of Ancestor more info
enables NADPH-hemoprotein reductase activity	IDA Inferred from Direct Assay more info	PubMed
enables NADPH-hemoprotein reductase activity	IEA Inferred from Electronic Annotation more info
enables NADPH-hemoprotein reductase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables NADPH-hemoprotein reductase activity	ISO Inferred from Sequence Orthology more info
enables cytochrome-b5 reductase activity, acting on NAD(P)H	IDA Inferred from Direct Assay more info	PubMed
enables electron transfer activity	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables flavin adenine dinucleotide binding	IBA Inferred from Biological aspect of Ancestor more info
enables flavin adenine dinucleotide binding	IEA Inferred from Electronic Annotation more info
enables flavin adenine dinucleotide binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables hydrolase activity	IDA Inferred from Direct Assay more info	PubMed
enables iron-cytochrome-c reductase activity	IDA Inferred from Direct Assay more info	PubMed
enables nitric oxide dioxygenase NAD(P)H activity	IDA Inferred from Direct Assay more info	PubMed
enables oxidoreductase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in carnitine metabolic process	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular organofluorine metabolic process	IEA Inferred from Electronic Annotation more info
involved_in cellular organofluorine metabolic process	ISO Inferred from Sequence Orthology more info
involved_in cellular response to follicle-stimulating hormone stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to gonadotropin stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to peptide hormone stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in demethylation	IDA Inferred from Direct Assay more info	PubMed
involved_in electron transport chain	IEA Inferred from Electronic Annotation more info
involved_in electron transport chain	ISO Inferred from Sequence Orthology more info
involved_in fatty acid oxidation	IDA Inferred from Direct Assay more info	PubMed
involved_in flavonoid metabolic process	IEP Inferred from Expression Pattern more info	PubMed
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nitrate catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in nitric oxide catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in nitric oxide catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cholesterol biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of chondrocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of smoothened signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of steroid hormone biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cholesterol metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of growth plate cartilage chondrocyte proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to dexamethasone	IDA Inferred from Direct Assay more info	PubMed
involved_in response to hormone	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to nutrient	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to xenobiotic stimulus	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: NADPH--cytochrome P450 reductase

Names: CPR; P450 (cytochrome) oxidoreductase; P450R; cytochrome P450 reductase

NP_113764.1

EC 1.6.2.4

XP_063127299.1

EC 1.6.2.4

XP_063127300.1

EC 1.6.2.4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_031576.2 → NP_113764.1 NADPH--cytochrome P450 reductase

See identical proteins and their annotated locations for NP_113764.1

Status: VALIDATED

Source sequence(s)

JAXUCZ010000012

UniProtKB/Swiss-Prot

P00388

UniProtKB/TrEMBL

A0A8L2Q089, A6J0C1

Related

ENSRNOP00000078537.1, ENSRNOT00000101964.1

Conserved Domains (3) summary

cd06204
Location:277 → 677

CYPOR; NADPH cytochrome p450 reductase (CYPOR) serves as an electron donor in several oxygenase systems and is a component of nitric oxide synthases and methionine synthase reductases. CYPOR transfers two electrons from NADPH to the heme of cytochrome p450 via ...

COG0369
Location:52 → 677

CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]

pfam00258
Location:82 → 219

Flavodoxin_1; Flavodoxin

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCr8

Genomic

NC_086030.1 Reference GRCr8

Range

26587674..26655612 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063271229.1 → XP_063127299.1 NADPH--cytochrome P450 reductase isoform X1

UniProtKB/Swiss-Prot

P00388

UniProtKB/TrEMBL

A6J0C1
XM_063271230.1 → XP_063127300.1 NADPH--cytochrome P450 reductase isoform X1

UniProtKB/Swiss-Prot

P00388

UniProtKB/TrEMBL

A6J0C1