PM20D1

Peptidase M20 domain containing 1 is a circulating enzyme which in humans is encoded by the PM20D1 gene.^[5] PM20D1 regulates bioactive N-acyl amide lipids and has been implicated in obesity, type 2 diabetes, pain, and Alzheimer's disease.

PM20D1
Identifiers
Aliases	PM20D1, Cps1, peptidase M20 domain containing 1
External IDs	OMIM: 617124; MGI: 2442939; HomoloGene: 65049; GeneCards: PM20D1; OMA:PM20D1 - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q32.1 Start 205,828,025 bp[1] End 205,850,132 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 E4 Start 131,725,119 bp[2] End 131,749,211 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of thigh skin of arm vulva body of pancreas mucosa of ileum skin of abdomen granulocyte nipple islet of Langerhans body of stomach Top expressed in epithelium of small intestine left lobe of liver human kidney proximal tubule right kidney jejunum transitional epithelium of urinary bladder intestinal villus ileum lumbar subsegment of spinal cord More reference expression data BioGPS n/a
Gene ontology Molecular function peptidase activity hydrolase activity metal ion binding hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides lyase activity Cellular component extracellular region extracellular exosome extracellular space Biological process metabolism proteolysis negative regulation of neuron death cellular amino acid metabolic process amide biosynthetic process cellular amide catabolic process cellular lipid metabolic process energy homeostasis adaptive thermogenesis regulation of oxidative phosphorylation uncoupler activity nitrogen compound metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 148811 212933 Ensembl ENSG00000162877 ENSMUSG00000042251 UniProt Q6GTS8 Q8C165 RefSeq (mRNA) NM_152491 NM_178079 NM_001357478 RefSeq (protein) NP_689704 NP_835180 NP_001344407 Location (UCSC) Chr 1: 205.83 – 205.85 Mb Chr 1: 131.73 – 131.75 Mb PubMed search [3] [4]
Wikidata
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Function

PM20D1 catalyzes the biosynthesis of N-fatty acyl amino acids from free fatty acids and free amino acids.^[6] Consequently PM20D1 is involved in the generation of potent bioactive lipid metabolites from two abundant cellular energy precursors.

PM20D1 is involved in energy homeostasis. In mice, PM20D1 is highly expressed and secreted into the blood by brown fat. Its expression in adipose tissues is increased following cold exposure. Genetic elevation of circulating PM20D1 in mice leads to accumulation of multiple circulating N-acyl amino acid species and a hypermetabolic phenotype.^[6] Conversely, PM20D1-KO exhibit bidirectional dysregulation of circulating N-acyl amino acids, insulin resistance, and glucose intolerance.^[7] Mechanistically, N-fatty acyl amino acids function as UCP1-independent uncouplers of mitochondrial respiration.^[6][8][9]

PM20D1 has also been implicated in neurological diseases. PM20D1 expression is increased both in vitro and in vivo following neurotoxic insults. Forced overexpression of PM20D1 in the hippocampus results in improved learning performance in a mouse model of Alzheimer's disease whereas PM20D1 knockdown increases amyloid plaque load.^[10]

Clinical significance

In human visceral and subcutaneous adipocytes, PM20D1 is one of the most highly up-regulated genes by the anti-diabetic thiazolidinedione drug rosiglitazone, suggesting a potential role for this enzyme and/or N-fatty acyl amino acids in obesity and diabetes.^[11]

Methylation at or near the PM20D1 locus has been correlated to body mass index.^[12]

In humans, the PM20D1 locus has been associated with Alzheimer's disease.^[10]