PPP5C

PPP5C
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1A17, 1S95, 1WAO, 2BUG, 3H60, 3H61, 3H62, 3H63, 3H64, 3H66, 3H67, 3H68, 3H69, 4ZX2, 4ZVZ
Identifiers
Aliases	PPP5C , PP5, PPP5, PPT, protein phosphatase 5 catalytic subunit
External IDs	OMIM: 600658 MGI: 102666 HomoloGene: 4550 GeneCards: PPP5C
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19q13.32 Start 46,347,087 bp [1] End 46,392,981 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7 A2|7 9.15 cM Start 16,738,565 bp [2] End 16,761,849 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right uterine tube ganglionic eminence anterior pituitary stromal cell of endometrium right adrenal gland left adrenal gland gastric mucosa right lobe of thyroid gland body of stomach transverse colon Top expressed in yolk sac superior frontal gyrus cerebellar cortex somite lip neural tube primitive streak stomach right ventricle submandibular gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phosphoprotein phosphatase activity heat shock protein binding microtubule binding ADP binding protein serine/threonine phosphatase activity signal transducer activity metal ion binding protein binding RNA binding identical protein binding G-protein alpha-subunit binding hydrolase activity ATP binding lipid binding Hsp90 protein binding Cellular component perikaryon membrane intracellular membrane-bounded organelle plasma membrane neuronal cell body proximal dendrite neuron projection nucleus cell periphery nucleoplasm cytoplasm cytosol Biological process negative regulation of protein phosphorylation positive regulation of glucocorticoid receptor signaling pathway protein heterooligomerization protein dephosphorylation negative regulation of cell death cellular response to cadmium ion transcription, DNA-templated MAPK cascade cellular response to DNA damage stimulus response to morphine response to lead ion protein complex oligomerization positive regulation of I-kappaB kinase/NF-kappaB signaling cellular response to hydrogen peroxide negative regulation of neuron death DNA repair mitotic cell cycle Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5536 19060 Ensembl ENSG00000011485 ENSMUSG00000003099 UniProt P53041 Q60676 RefSeq (mRNA) NM_006247 NM_001204284 NM_011155 RefSeq (protein) NP_001191213 NP_006238 NP_035285 Location (UCSC) Chr 19: 46.35 – 46.39 Mb Chr 7: 16.74 – 16.76 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Serine/threonine-protein phosphatase 5 is an enzyme that in humans is encoded by the PPP5C gene. ^{[5] [6]}

Model organisms

Ppp5c knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Homozygous Fertility	Normal
Body weight	Abnormal [7]
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal [8]
Indirect calorimetry	Abnormal [9]
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Abnormal [10]
Radiography	Abnormal [11]
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Abnormal [12]
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
MicroCT & Quantitative Faxitron	Normal
Citrobacter infection	Normal [13]
All tests and analysis from [14] [15]

Model organisms have been used in the study of PPP5C function. A conditional knockout mouse line, called Ppp5c^{tm1a(EUCOMM)Wtsi [16] [17]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. ^{[18] [19] [20]}

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. ^{[14] [21]} Twenty five tests were carried out on mutant mice and five significant abnormalities were observed. ^[14] Homozygous mutant males had decreased body weight, body length and respiratory quotient. Both sexes had increased T cell numbers and a range of skeletal abnormalities identified by radiography. ^[14]

Interactions

PPP5C has been shown to interact with ASK1, ^[22] CRY2 ^[23] GNA12. ^[24] and Rac1, ^[25]

References

1. GRCh38: Ensembl release 89: ENSG00000011485 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000003099 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Yong WH, Ueki K, Chou D, Reeves SA, von Deimling A, Gusella JF, Mohrenweiser HW, Buckler AJ, Louis DN (Sep 1995). "Cloning of a highly conserved human protein serine-threonine phosphatase gene from the glioma candidate region on chromosome 19q13.3". Genomics. 29 (2): 533–6. doi:10.1006/geno.1995.9972. PMID   8666404.
6. "Entrez Gene: PPP5C Protein phosphatase 5, catalytic subunit".
7. "Body weight data for Ppp5c". Wellcome Trust Sanger Institute.
8. "Dysmorphology data for Ppp5c". Wellcome Trust Sanger Institute.
9. "Indirect calorimetry data for Ppp5c". Wellcome Trust Sanger Institute.
10. "DEXA data for Ppp5c". Wellcome Trust Sanger Institute.
11. "Radiography data for Ppp5c". Wellcome Trust Sanger Institute.
12. "Peripheral blood lymphocytes data for Ppp5c". Wellcome Trust Sanger Institute.
13. "Citrobacter infection data for Ppp5c". Wellcome Trust Sanger Institute.
14. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID   85911512.
15. Mouse Resources Portal, Wellcome Trust Sanger Institute.
16. "International Knockout Mouse Consortium".
17. "Mouse Genome Informatics".
18. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC   3572410 . PMID   21677750.
19. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID   21677718. S2CID   39281705.
20. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi: 10.1016/j.cell.2006.12.018 . PMID   17218247. S2CID   18872015.
21. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi: 10.1186/gb-2011-12-6-224 . PMC   3218837 . PMID   21722353.
22. Morita K, Saitoh M, Tobiume K, Matsuura H, Enomoto S, Nishitoh H, Ichijo H (Nov 2001). "Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress". The EMBO Journal. 20 (21): 6028–36. doi:10.1093/emboj/20.21.6028. PMC   125685 . PMID   11689443.
23. Zhao S, Sancar A (Nov 1997). "Human blue-light photoreceptor hCRY2 specifically interacts with protein serine/threonine phosphatase 5 and modulates its activity". Photochemistry and Photobiology. 66 (5): 727–31. doi:10.1111/j.1751-1097.1997.tb03214.x. PMID   9383998. S2CID   32804361.
24. Yamaguchi Y, Katoh H, Mori K, Negishi M (Aug 2002). "Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity". Current Biology. 12 (15): 1353–8. doi: 10.1016/S0960-9822(02)01034-5 . PMID   12176367. S2CID   11485795.
25. Chatterjee A, Wang L, Armstrong DL, Rossie S (Feb 2010). "Activated Rac1 GTPase translocates protein phosphatase 5 to the cell membrane and stimulates phosphatase activity in vitro". The Journal of Biological Chemistry. 285 (6): 3872–82. doi: 10.1074/jbc.M109.088427 . PMC   2823530 . PMID   19948726.

Further reading

• Chen MX, McPartlin AE, Brown L, Chen YH, Barker HM, Cohen PT (Sep 1994). "A novel human protein serine/threonine phosphatase, which possesses four tetratricopeptide repeat motifs and localizes to the nucleus". The EMBO Journal. 13 (18): 4278–90. doi:10.1002/j.1460-2075.1994.tb06748.x. PMC   395355 . PMID   7925273.
• Skinner J, Sinclair C, Romeo C, Armstrong D, Charbonneau H, Rossie S (Sep 1997). "Purification of a fatty acid-stimulated protein-serine/threonine phosphatase from bovine brain and its identification as a homolog of protein phosphatase 5". The Journal of Biological Chemistry. 272 (36): 22464–71. doi: 10.1074/jbc.272.36.22464 . PMID   9278397.
• Shah BH, Catt KJ (Dec 2006). "Protein phosphatase 5 as a negative key regulator of Raf-1 activation". Trends in Endocrinology and Metabolism. 17 (10): 382–4. doi:10.1016/j.tem.2006.10.013. PMID   17084641. S2CID   45060016.
• Goedert M, Cohen ES, Jakes R, Cohen P (Nov 1992). "p42 MAP kinase phosphorylation sites in microtubule-associated protein tau are dephosphorylated by protein phosphatase 2A1. Implications for Alzheimer's disease [corrected]". FEBS Letters. 312 (1): 95–9. doi: 10.1016/0014-5793(92)81418-L . PMID   1330687. S2CID   34940651.
• Maruyama K, Sugano S (Jan 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.
• Xu X, Lagercrantz J, Zickert P, Bajalica-Lagercrantz S, Zetterberg A (Jan 1996). "Chromosomal localization and 5' sequence of the human protein serine/threonine phosphatase 5' gene". Biochemical and Biophysical Research Communications. 218 (2): 514–7. doi:10.1006/bbrc.1996.0092. PMID   8561788.
• Silverstein AM, Galigniana MD, Chen MS, Owens-Grillo JK, Chinkers M, Pratt WB (Jun 1997). "Protein phosphatase 5 is a major component of glucocorticoid receptor.hsp90 complexes with properties of an FK506-binding immunophilin". The Journal of Biological Chemistry. 272 (26): 16224–30. doi: 10.1074/jbc.272.26.16224 . PMID   9195923.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 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.
• Zhao S, Sancar A (Nov 1997). "Human blue-light photoreceptor hCRY2 specifically interacts with protein serine/threonine phosphatase 5 and modulates its activity". Photochemistry and Photobiology. 66 (5): 727–31. doi:10.1111/j.1751-1097.1997.tb03214.x. PMID   9383998. S2CID   32804361.
• Ollendorff V, Donoghue DJ (Dec 1997). "The serine/threonine phosphatase PP5 interacts with CDC16 and CDC27, two tetratricopeptide repeat-containing subunits of the anaphase-promoting complex". The Journal of Biological Chemistry. 272 (51): 32011–8. doi: 10.1074/jbc.272.51.32011 . PMID   9405394.
• Das AK, Cohen PW, Barford D (Mar 1998). "The structure of the tetratricopeptide repeats of protein phosphatase 5: implications for TPR-mediated protein-protein interactions". The EMBO Journal. 17 (5): 1192–9. doi:10.1093/emboj/17.5.1192. PMC   1170467 . PMID   9482716.
• Russell LC, Whitt SR, Chen MS, Chinkers M (Jul 1999). "Identification of conserved residues required for the binding of a tetratricopeptide repeat domain to heat shock protein 90". The Journal of Biological Chemistry. 274 (29): 20060–3. doi: 10.1074/jbc.274.29.20060 . PMID   10400612.
• Lubert EJ, Hong Y, Sarge KD (Oct 2001). "Interaction between protein phosphatase 5 and the A subunit of protein phosphatase 2A: evidence for a heterotrimeric form of protein phosphatase 5". The Journal of Biological Chemistry. 276 (42): 38582–7. doi: 10.1074/jbc.M106906200 . PMID   11504734.
• Morita K, Saitoh M, Tobiume K, Matsuura H, Enomoto S, Nishitoh H, Ichijo H (Nov 2001). "Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress". The EMBO Journal. 20 (21): 6028–36. doi:10.1093/emboj/20.21.6028. PMC   125685 . PMID   11689443.
• Sanchez-Ortiz E, Hahm BK, Armstrong DL, Rossie S (Oct 2009). "Protein phosphatase 5 protects neurons against amyloid-beta toxicity". Journal of Neurochemistry. 111 (2): 391–402. doi:10.1111/j.1471-4159.2009.06337.x. PMC   3044491 . PMID   19686245.
• Yamaguchi Y, Katoh H, Mori K, Negishi M (Aug 2002). "Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity". Current Biology. 12 (15): 1353–8. doi: 10.1016/S0960-9822(02)01034-5 . PMID   12176367. S2CID   11485795.
• Gentile S, Darden T, Erxleben C, Romeo C, Russo A, Martin N, Rossie S, Armstrong DL (Mar 2006). "Rac GTPase signaling through the PP5 protein phosphatase". Proceedings of the National Academy of Sciences of the United States of America. 103 (13): 5202–6. Bibcode:2006PNAS..103.5202G. doi: 10.1073/pnas.0600080103 . PMC   1458818 . PMID   16549782.
• Liu F, Zaidi T, Iqbal K, Grundke-Iqbal I, Gong CX (2003). "Aberrant glycosylation modulates phosphorylation of tau by protein kinase A and dephosphorylation of tau by protein phosphatase 2A and 5". Neuroscience. 115 (3): 829–37. doi:10.1016/S0306-4522(02)00510-9. PMID   12435421. S2CID   26118803.
• Urban G, Golden T, Aragon IV, Cowsert L, Cooper SR, Dean NM, Honkanen RE (Mar 2003). "Identification of a functional link for the p53 tumor suppressor protein in dexamethasone-induced growth suppression". The Journal of Biological Chemistry. 278 (11): 9747–53. doi: 10.1074/jbc.M210993200 . PMID   12519780.
• Tomsig JL, Snyder SL, Creutz CE (Mar 2003). "Identification of targets for calcium signaling through the copine family of proteins. Characterization of a coiled-coil copine-binding motif". The Journal of Biological Chemistry. 278 (12): 10048–54. doi: 10.1074/jbc.M212632200 . PMID   12522145.
• Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H, Sugano S (May 2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways". Oncogene. 22 (21): 3307–18. doi:10.1038/sj.onc.1206406. PMID   12761501. S2CID   38880905.