PPP1R14A

Protein phosphatase 1 regulatory subunit 14A also known as CPI-17 (C-kinase potentiated Protein phosphatase-1 Inhibitor Mr = 17 kDa) is a protein that in humans is encoded by the PPP1R14A gene.^[4][5][6]

PPP1R14A
Identifiers
Aliases	PPP1R14A, CPI-17, CPI17, PPP1INL, protein phosphatase 1 regulatory inhibitor subunit 14A
External IDs	OMIM: 608153; MGI: 1931139; HomoloGene: 12267; GeneCards: PPP1R14A; OMA:PPP1R14A - orthologs
Gene location (Mouse) Chr. Chromosome 7 (mouse)[1] Band 7|7 B1 Start 28,988,733 bp[1] End 28,993,226 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right coronary artery ascending aorta popliteal artery left coronary artery saphenous vein inferior ganglion of vagus nerve gastric mucosa right lung substantia nigra left uterine tube Top expressed in tunica media of zone of aorta ascending aorta umbilical cord lumbar subsegment of spinal cord right lung left lung lobe aortic valve right lung lobe anterior horn of spinal cord deep cerebellar nuclei More reference expression data BioGPS n/a
Gene ontology Molecular function protein phosphatase inhibitor activity protein serine/threonine phosphatase inhibitor activity Cellular component cytoplasm cytosol Biological process regulation of phosphorylation negative regulation of phosphoprotein phosphatase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 94274 68458 Ensembl n/a ENSMUSG00000037166 UniProt Q96A00 Q91VC7 RefSeq (mRNA) NM_033256 NM_001243947 NM_026731 RefSeq (protein) NP_001230876 NP_150281 NP_081007 Location (UCSC) n/a Chr 7: 28.99 – 28.99 Mb PubMed search [2] [3]
Wikidata
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Function

CPI-17 is a phosphorylation-dependent inhibitor protein of smooth muscle myosin phosphatase, discovered in pig aortic homogenates. Phosphorylation of the Thr-38 residue converts the protein into a potent inhibitor for myosin phosphatase. A single phosphorylation of CPI-17 at Thr-38 triggers a global conformational change that causes re-alignment of four helices. Multiple kinases are identified to phosphorylate CPI-17, such as PKC, ROCK, PKN, ZIPK, ILK, and PAK. Agonist stimulation of smooth muscle enhances CPI-17 phosphorylation mainly through PKC and ROCK. Myosin phosphatase inhibition increases myosin phosphorylation and smooth muscle contraction in the absence of increased intracellular Ca²⁺ concentration. This phenomenon is known as Ca²⁺ sensitization, which occurs in response to agonist stimulation of smooth muscle. In Purkinje neuron, CPI-17 is involved in long-term synaptic depression.

There are three homologues of CPI-17:

• Phosphatase Holoenzyme Inhibitor (PHI: PPP1R14B),
• Kinase Enhanced Phosphatase Inhibitor (KEPI: PPP1R14C), and
• Gastric-Brain Phosphatase Inhibitor (GBPI: PPP1R14D).

Clinical significance

CPI-17 is up-regulated some cancer cells, and causes hyperphosphorylation of tumor suppressor merlin/NF2.^[7][6] In prostate cancer, CPI-17 expressions are reported to be associated with GWAS risk SNP rs7247241 T allele and increase cell proliferation. ^[8]