PPP2R1B

PPP2R1B
Identifiers
Aliases	PPP2R1B , PP2A-Abeta, PR65B, protein phosphatase 2 scaffold subunit Abeta
External IDs	OMIM: 603113; MGI: 1920949; HomoloGene: 70244; GeneCards: PPP2R1B; OMA:PPP2R1B - orthologs
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11q23.1 Start 111,726,908 bp [1] End 111,766,389 bp [1]
Gene location (Mouse) Chr. Chromosome 9 (mouse) [2] Band 9|9 A5.3 Start 50,756,601 bp [2] End 50,805,529 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sperm right lobe of liver left testis right testis adipose tissue body of pancreas islet of Langerhans secondary oocyte abdominal fat subcutaneous adipose tissue Top expressed in primitive streak hair follicle fetal liver hematopoietic progenitor cell ureter seminal vesicula white adipose tissue spermatid condyle epithelium of stomach endothelial cell of lymphatic vessel More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding protein serine/threonine phosphatase activity protein phosphatase regulator activity Cellular component membrane raft extracellular exosome protein phosphatase type 2A complex cytoplasm Biological process apoptotic process involved in morphogenesis positive regulation of extrinsic apoptotic signaling pathway in absence of ligand protein dephosphorylation regulation of phosphoprotein phosphatase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5519 73699 Ensembl ENSG00000137713 ENSMUSG00000032058 UniProt P30154 Q7TNP2 RefSeq (mRNA) NM_001177562 NM_001177563 NM_002716 NM_181699 NM_181700 NM_001034085 NM_001286553 NM_028614 RefSeq (protein) NP_001171033 NP_001171034 NP_002707 NP_859050 NP_859051 NP_001029257 NP_001273482 NP_082890 Location (UCSC) Chr 11: 111.73 – 111.77 Mb Chr 9: 50.76 – 50.81 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform is an enzyme that in humans is encoded by the PPP2R1B gene. ^{[5] [6] [7]}

Function

This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes a beta isoform of the constant regulatory subunit A. Defects in this gene could be the cause of some lung and colon cancers. At least two transcript variants encoding different isoforms have been found for this gene. ^[7]

Discovery

The PPP2R1B gene was discovered as part of the Human Genome Project research center focused on chromosome 11. ^{[8] [9]}

Clinical significance

Somatic alterations in PPP2R1B have been identified in colorectal and lung cancer tumors and cell lines, ^[8] with evidence that these alterations affect protein function, supporting a role for PPP2R1B as a candidate tumor suppressor gene in these cancers. Experimental studies have shown that suppression of PPP2R1B expression enables immortalized human cells to become tumorigenic, and that the wild-type protein forms a complex with the small GTPase RalA. These findings support the role of PPP2R1B as a tumor suppressor involved in regulating RalA function. ^[10]

A case series described nine cancer patients with germline loss-of-function (LOF) variants in PPP2R1B, with breast cancer being the most frequently observed diagnosis. ^[11] In all documented cases, individuals also had a family history of cancers including breast, ovarian, prostate, uterine, renal, and colorectal cancer, suggesting that PPP2R1B may function as a predisposition gene in breast and potentially other cancers. ^[6]

Interactions

PPP2R1B has been shown to interact with:

• PPP2CA, ^{[12] [13]}
• PPP2CB, ^[12]
• PPP2R2A, ^{[12] [14]}
• PPP2R3B, ^[12]
• PPP2R5A, ^{[12] [13] [15]}
• PPP2R5B, ^[15]
• PPP2R5C, ^[15]
• PPP2R5D, ^[15] and
• PPP2R5E. ^[15]

References

1. GRCh38: Ensembl release 89: ENSG00000137713 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000032058 – 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. Hemmings BA, Adams-Pearson C, Maurer F, Müller P, Goris J, Merlevede W, et al. (April 1990). "alpha- and beta-forms of the 65-kDa subunit of protein phosphatase 2A have a similar 39 amino acid repeating structure". Biochemistry. 29 (13): 3166–3173. doi:10.1021/bi00465a002. PMID   2159327.
6. Baysal BE, Farr JE, Goss JR, Devlin B, Richard CW (September 1998). "Genomic organization and precise physical location of protein phosphatase 2A regulatory subunit A beta isoform gene on chromosome band 11q23". Gene. 217 (1–2): 107–116. doi:10.1016/S0378-1119(98)00350-3. PMID   9795170.
7. "Entrez Gene: PPP2R1B protein phosphatase 2 (formerly 2A), regulatory subunit A, beta isoform".
8. Wang SS, Esplin ED, Li JL, Huang L, Gazdar A, Minna J, et al. (October 1998). "Alterations of the PPP2R1B gene in human lung and colon cancer". Science. 282 (5387): 284–287. doi:10.1126/science.282.5387.284. PMID   9765152.
9. US 6743906,Evans GA, Wang SS, Esplin ED, Li JL, Huang L,"PPP2R1B is a tumor suppressor",issued 1 June 2004, assigned to University of Texas System 
10. Sablina AA, Chen W, Arroyo JD, Corral L, Hector M, Bulmer SE, et al. (June 2007). "The tumor suppressor PP2A Abeta regulates the RalA GTPase". Cell. 129 (5): 969–982. doi:10.1016/j.cell.2007.03.047. PMC   1945132 . PMID   17540176.
11. Mazhar S, O'Connor CM, Harold A, Dowdican AC, Ulintz PJ, Hanson EN, et al. (April 2025). "Germline loss-of-function mutations in PPP2R1B in patients with a personal and family history of cancer". JCI Insight: e186288. doi: 10.1172/jci.insight.186288 . PMC   12129040 . PMID   40178903.
12. Zhou J, Pham HT, Ruediger R, Walter G (January 2003). "Characterization of the Aalpha and Abeta subunit isoforms of protein phosphatase 2A: differences in expression, subunit interaction, and evolution". The Biochemical Journal. 369 (Pt 2): 387–398. doi:10.1042/BJ20021244. PMC   1223084 . PMID   12370081.
13. Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, Sanchez A, et al. (January 2009). "A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein". Molecular & Cellular Proteomics. 8 (1): 157–171. doi: 10.1074/mcp.M800266-MCP200 . PMC   2621004 . PMID   18782753.
14. Kamibayashi C, Lickteig RL, Estes R, Walter G, Mumby MC (October 1992). "Expression of the A subunit of protein phosphatase 2A and characterization of its interactions with the catalytic and regulatory subunits". The Journal of Biological Chemistry. 267 (30): 21864–21872. doi: 10.1016/S0021-9258(19)36692-X . PMID   1328247.
15. McCright B, Rivers AM, Audlin S, Virshup DM (September 1996). "The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm". The Journal of Biological Chemistry. 271 (36): 22081–22089. doi: 10.1074/jbc.271.36.22081 . PMID   8703017.

Further reading

• Zolnierowicz S (October 2000). "Type 2A protein phosphatase, the complex regulator of numerous signaling pathways". Biochemical Pharmacology. 60 (8): 1225–1235. doi:10.1016/S0006-2952(00)00424-X. PMID   11007961.
• Kamibayashi C, Lickteig RL, Estes R, Walter G, Mumby MC (October 1992). "Expression of the A subunit of protein phosphatase 2A and characterization of its interactions with the catalytic and regulatory subunits". The Journal of Biological Chemistry. 267 (30): 21864–21872. doi: 10.1016/S0021-9258(19)36692-X . PMID   1328247.
• Tung HY, De Rocquigny H, Zhao LJ, Cayla X, Roques BP, Ozon R (January 1997). "Direct activation of protein phosphatase-2A0 by HIV-1 encoded protein complex NCp7:vpr". FEBS Letters. 401 (2–3): 197–201. Bibcode:1997FEBSL.401..197T. doi: 10.1016/S0014-5793(96)01470-6 . PMID   9013886. S2CID   23293768.
• Adler HT, Nallaseth FS, Walter G, Tkachuk DC (November 1997). "HRX leukemic fusion proteins form a heterocomplex with the leukemia-associated protein SET and protein phosphatase 2A". The Journal of Biological Chemistry. 272 (45): 28407–28414. doi: 10.1074/jbc.272.45.28407 . PMID   9353299.
• Ruediger R, Brewis N, Ohst K, Walter G (November 1997). "Increasing the ratio of PP2A core enzyme to holoenzyme inhibits Tat-stimulated HIV-1 transcription and virus production". Virology. 238 (2): 432–443. doi: 10.1006/viro.1997.8873 . PMID   9400615.
• Wang SS, Esplin ED, Li JL, Huang L, Gazdar A, Minna J, et al. (October 1998). "Alterations of the PPP2R1B gene in human lung and colon cancer". Science. 282 (5387): 284–287. Bibcode:1998Sci...282..284W. doi:10.1126/science.282.5387.284. PMID   9765152.
• Takahashi M, Shibata H, Shimakawa M, Miyamoto M, Mukai H, Ono Y (June 1999). "Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus". The Journal of Biological Chemistry. 274 (24): 17267–17274. doi: 10.1074/jbc.274.24.17267 . PMID   10358086.
• Campbell IG, Manolitsas T (November 1999). "Absence of PPP2R1B gene alterations in primary ovarian cancers". Oncogene. 18 (46): 6367–6369. doi: 10.1038/sj.onc.1203070 . PMID   10597236.
• Takagi Y, Futamura M, Yamaguchi K, Aoki S, Takahashi T, Saji S (August 2000). "Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers". Gut. 47 (2): 268–271. doi:10.1136/gut.47.2.268. PMC   1727986 . PMID   10896920.
• Baysal BE, Willett-Brozick JE, Taschner PE, Dauwerse JG, Devilee P, Devlin B (February 2001). "A high-resolution integrated map spanning the SDHD gene at 11q23: a 1.1-Mb BAC contig, a partial transcript map and 15 new repeat polymorphisms in a tumour-suppressor region". European Journal of Human Genetics. 9 (2): 121–129. doi: 10.1038/sj.ejhg.5200585 . PMID   11313745.
• Ruediger R, Pham HT, Walter G (April 2001). "Alterations in protein phosphatase 2A subunit interaction in human carcinomas of the lung and colon with mutations in the A beta subunit gene". Oncogene. 20 (15): 1892–1899. doi: 10.1038/sj.onc.1204279 . PMID   11313937.
• Yokoyama N, Reich NC, Miller WT (June 2001). "Involvement of protein phosphatase 2A in the interleukin-3-stimulated Jak2-Stat5 signaling pathway". Journal of Interferon & Cytokine Research. 21 (6): 369–378. doi:10.1089/107999001750277844. PMID   11440634.
• Elder RT, Yu M, Chen M, Zhu X, Yanagida M, Zhao Y (September 2001). "HIV-1 Vpr induces cell cycle G2 arrest in fission yeast (Schizosaccharomyces pombe) through a pathway involving regulatory and catalytic subunits of PP2A and acting on both Wee1 and Cdc25". Virology. 287 (2): 359–370. doi: 10.1006/viro.2001.1007 . PMID   11531413.
• Yang J, Fan GH, Wadzinski BE, Sakurai H, Richmond A (December 2001). "Protein phosphatase 2A interacts with and directly dephosphorylates RelA". The Journal of Biological Chemistry. 276 (51): 47828–47833. doi: 10.1074/jbc.M106103200 . PMC   2665282 . PMID   11591705.
• Strack S, Ruediger R, Walter G, Dagda RK, Barwacz CA, Cribbs JT (June 2002). "Protein phosphatase 2A holoenzyme assembly: identification of contacts between B-family regulatory and scaffolding A subunits". The Journal of Biological Chemistry. 277 (23): 20750–20755. doi: 10.1074/jbc.M202992200 . PMID   11929880.
• Hemmer S, Wasenius VM, Haglund C, Zhu Y, Knuutila S, Franssila K, et al. (April 2002). "Alterations in the suppressor gene PPP2R1B in parathyroid hyperplasias and adenomas". Cancer Genetics and Cytogenetics. 134 (1): 13–17. doi:10.1016/S0165-4608(01)00597-0. PMID   11996789.