PYCR1

Pyrroline-5-carboxylate reductase 1

PDB rendering based on 2ger.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2GER, 2GR9, 2GRA, 2IZZ

Identifiers

Symbols

PYCR1 ; ARCL2B; ARCL3B; P5C; P5CR; PIG45; PP222; PRO3; PYCR

External IDs

OMIM: 179035 MGI: 2384795 HomoloGene: 56002 GeneCards: PYCR1 Gene

EC number

1.5.1.2

Gene ontology
Molecular function	• pyrroline-5-carboxylate reductase activity • protein binding • identical protein binding
Cellular component	• mitochondrion • mitochondrial matrix
Biological process	• proline biosynthetic process • cellular amino acid biosynthetic process • cellular response to oxidative stress • cellular nitrogen compound metabolic process • small molecule metabolic process • regulation of mitochondrial membrane potential • oxidation-reduction process • L-proline biosynthetic process
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 17:
79.89 – 79.9 Mb

Chr 11:
120.64 – 120.64 Mb

PubMed search

Pyrroline-5-carboxylate reductase 1, mitochondrial is an enzyme that in humans is encoded by the PYCR1 gene.^[1]^[2]

This gene encodes an enzyme that catalyzes the NAD(P)H-dependent conversion of pyrroline-5-carboxylate to proline. This enzyme may also play a physiologic role in the generation of NADP(+) in some cell types. The protein forms a homopolymer and localizes to the mitochondrion. Alternate splicing results in two transcript variants encoding different isoforms.^[2]

References

↑ Dougherty KM, Brandriss MC, Valle D (Feb 1992). "Cloning human pyrroline-5-carboxylate reductase cDNA by complementation in Saccharomyces cerevisiae". J Biol Chem 267 (2): 871–5. PMID 1730675.
↑ 2.0 2.1 "Entrez Gene: PYCR1 pyrroline-5-carboxylate reductase 1".

Herzfeld A, Legg MA, Greengard O (1978). "Human colon tumors: enzymic and histological characteristics". Cancer 42 (3): 1280–3. doi:10.1002/1097-0142(197809)42:3<1280::AID-CNCR2820420337>3.0.CO;2-P. PMID 212173.
Merrill MJ, Yeh GC, Phang JM (1989). "Purified human erythrocyte pyrroline-5-carboxylate reductase. Preferential oxidation of NADPH". J. Biol. Chem. 264 (16): 9352–8. PMID 2722838.
Yeh GC, Roth EF, Phang JM et al. (1984). "The effect of pyrroline-5-carboxylic acid on nucleotide metabolism in erythrocytes from normal and glucose-6-phosphate dehydrogenase-deficient subjects". J. Biol. Chem. 259 (9): 5454–8. PMID 6201483.
Herzfeld A, Greengard O (1981). "Enzyme activities in human fetal and neoplastic tissues". Cancer 46 (9): 2047–54. doi:10.1002/1097-0142(19801101)46:9<2047::AID-CNCR2820460924>3.0.CO;2-Q. PMID 6253048.
Yeh GC, Harris SC, Phang JM (1981). "Pyrroline-5-carboxylate reductase in human erythrocytes". J. Clin. Invest. 67 (4): 1042–6. doi:10.1172/JCI110115. PMC 370662. PMID 6894153.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Basch JJ, Wickham ED, Farrell HM (1997). "Pyrroline-5-carboxylate reductase in lactating bovine mammary glands". J. Dairy Sci. 79 (8): 1361–8. doi:10.3168/jds.S0022-0302(96)76493-7. PMID 8880459.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Gerhard DS, Wagner L, Feingold EA et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Meng Z, Lou Z, Liu Z et al. (2006). "Crystal structure of human pyrroline-5-carboxylate reductase". J. Mol. Biol. 359 (5): 1364–77. doi:10.1016/j.jmb.2006.04.053. PMID 16730026.

PDB gallery

2ger: Crystal Structure and Oxidative Mechanism of Human Pyrroline-5-carboxylate Reductase

2gr9: Crystal structure of P5CR complexed with NADH

2gra: crystal structure of Human Pyrroline-5-carboxylate Reductase complexed with nadp

2izz: CRYSTAL STRUCTURE OF HUMAN PYRROLINE-5-CARBOXYLATE REDUCTASE

Metabolism: Protein metabolism, synthesis and catabolism enzymes

Essential amino acids are in Capitals

K→acetyl-CoA

LYSINE→	Saccharopine dehydrogenase Glutaryl-CoA dehydrogenase

LEUCINE→	Branched chain aminotransferase Branched-chain alpha-keto acid dehydrogenase complex Isovaleryl coenzyme A dehydrogenase Methylcrotonyl-CoA carboxylase Methylglutaconyl-CoA hydratase 3-hydroxy-3-methylglutaryl-CoA lyase

TRYPTOPHAN→	Indoleamine 2,3-dioxygenase/Tryptophan 2,3-dioxygenase Arylformamidase Kynureninase 3-hydroxyanthranilate oxidase Aminocarboxymuconate-semialdehyde decarboxylase Aminomuconate-semialdehyde dehydrogenase

PHENYLALANINE→tyrosine→	(see below)

G→pyruvate
→citrate

glycine→serine→	Serine hydroxymethyltransferase Serine dehydratase glycine→creatine: Guanidinoacetate N-methyltransferase Creatine kinase

alanine→	Alanine transaminase

cysteine→	D-cysteine desulfhydrase

threonine→	L-threonine dehydrogenase

G→glutamate→
α-ketoglutarate

HISTIDINE→	Histidine ammonia-lyase Urocanate hydratase Formiminotransferase cyclodeaminase

proline→	Proline oxidase Pyrroline-5-carboxylate reductase 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1 PYCR1

arginine→	Ornithine aminotransferase Ornithine decarboxylase Agmatinase

→alpha-ketoglutarate→TCA	Glutamate dehydrogenase

Other	cysteine+glutamate→glutathione: Gamma-glutamylcysteine synthetase Glutathione synthetase Gamma-glutamyl transpeptidase glutamate→glutamine: Glutamine synthetase Glutaminase

G→propionyl-CoA→
succinyl-CoA

VALINE→	Branched chain aminotransferase Branched-chain alpha-keto acid dehydrogenase complex Enoyl-CoA hydratase 3-hydroxyisobutyryl-CoA hydrolase 3-hydroxyisobutyrate dehydrogenase Methylmalonate semialdehyde dehydrogenase

ISOLEUCINE→	Branched chain aminotransferase Branched-chain alpha-keto acid dehydrogenase complex 3-hydroxy-2-methylbutyryl-CoA dehydrogenase

METHIONINE→	generation of homocysteine: Methionine adenosyltransferase Adenosylhomocysteinase regeneration of methionine: Methionine synthase/Homocysteine methyltransferase Betaine-homocysteine methyltransferase conversion to cysteine: Cystathionine beta synthase Cystathionine gamma-lyase

THREONINE→	Threonine aldolase

→succinyl-CoA→TCA	Propionyl-CoA carboxylase Methylmalonyl CoA epimerase Methylmalonyl-CoA mutase

G→fumarate

PHENYLALANINE→tyrosine→	Phenylalanine hydroxylase Tyrosine aminotransferase 4-Hydroxyphenylpyruvate dioxygenase Homogentisate 1,2-dioxygenase Fumarylacetoacetate hydrolase tyrosine→melanin: Tyrosinase

G→oxaloacetate

asparagine→aspartate→	Asparaginase/Asparagine synthetase Aspartate transaminase

Index of inborn errors of metabolism

Description	Metabolism Enzymes and pathways: citric acid cycle enzymes pentose phosphate intermediates glycoproteins enzymes glycosaminoglycans proteoglycan enzymes phospholipid metabolism cholesterol and steroid intermediates sphingolipids enzymes eicosanoids enzymes amino acid intermediates urea cycle enzymes nucleotide intermediates

Disorders	Citric acid cycle and electron transport chain Glycoprotein Proteoglycan Fatty-acid Phospholipid Cholesterol and steroid Eicosanoid Amino acid Purine-pyrimidine Heme metabolism Symptoms and signs

Treatment	Drugs other

PYCR1

References

Further reading