PYCR2

PYCR2
Identifiers
Aliases	PYCR2, P5CR2, HLD10, pyrroline-5-carboxylate reductase family member 2, pyrroline-5-carboxylate reductase 2
External IDs	OMIM: 616406; MGI: 1277956; HomoloGene: 8343; GeneCards: PYCR2; OMA:PYCR2 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1q42.12 Start 225,919,877 bp End 225,924,340 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1|1 H4 Start 180,731,858 bp End 180,735,653 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cardiac muscle tissue of right atrium right uterine tube myocardium of left ventricle C1 segment right adrenal gland anterior pituitary left adrenal gland right adrenal cortex left adrenal cortex granulocyte Top expressed in fetal liver hematopoietic progenitor cell islet of Langerhans endocardial cushion lacrimal gland condyle seminal vesicula endothelial cell of lymphatic vessel fossa somite internal carotid artery More reference expression data BioGPS n/a
Gene ontology Molecular function pyrroline-5-carboxylate reductase activity oxidoreductase activity protein binding Cellular component mitochondrial matrix cytoplasm mitochondrion Biological process L-proline biosynthetic process cellular response to oxidative stress proline biosynthetic process cellular amino acid biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 29920 69051 Ensembl ENSG00000143811 ENSMUSG00000026520 UniProt Q96C36 Q922Q4 RefSeq (mRNA) NM_013328 NM_001271681 NM_133705 RefSeq (protein) NP_001258610 NP_037460 NP_598466 Location (UCSC) Chr 1: 225.92 – 225.92 Mb Chr 1: 180.73 – 180.74 Mb PubMed search
Wikidata
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Pyrroline-5-carboxylate reductase family, member 2 is a protein that in humans is encoded by the PYCR2 gene.

Function

This gene belongs to the pyrroline-5-carboxylate reductase family. The encoded mitochondrial protein catalyzes the conversion of pyrroline-5-carboxylate to proline, which is the last step in proline biosynthesis. Loss of PYCR2 does not lead to a gross defect in mitochondrial protein synthesis, but loss of function of PYCR2 leads to increased apoptosis under oxidative stress.

Clinical significance

Mutations in the PYCR2 gene have been identified as the cause of a unique syndrome characterized by postnatal microcephaly, hypomyelination, and reduced cerebral white-matter volume. Hypomyelination and the absence of wrinkly skin makes this condition distinct from that caused by previously reported mutations in the gene encoding PYCR2’s isozyme, PYCR1, suggesting a unique and indispensable role for PYCR2 in the human CNS during development. This is substantiated by the fact that PYCR2 mRNA is moderately expressed in the developing human brain, and in much higher forms than either of the other two isoforms. Although PYCR2 is an enzyme for proline biosynthesis, systemic deprivation of proline does not appear to be the pathogenetic mechanism of this condition, given that plasma amino acid analysis in two affected individuals did not show low proline levels. Furthermore, mitochondrial protein synthesis was not affected in PYCR2-deficient cells. Therefore, deficiency of proline, as a building block of proteins, might not be the major pathophysiology. However, proline has been reported as a non-enzymatic antioxidant that suppresses apoptosis, and therefore local proline biosynthesis in neurons might be important for neuronal protection against oxidative stress.

The PYCR family also has been correlated with melanoma cells. PYCR2 as well as PYCR are abundant in melanoma cells but not detected in melanocytes.

Further reading

• Potapova IA, Cohen IS, Doronin SV (September 2007). "Voltage-gated ion channel Kv4.3 is associated with Rap guanine nucleotide exchange factors and regulates angiotensin receptor type 1 signaling to small G-protein Rap". The FEBS Journal. 274 (17): 4375–4384. doi:10.1111/j.1742-4658.2007.05966.x. PMID 17725712.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.