Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform

Details

Name
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform
Synonyms
  • Medium tumor antigen-associated 61 kDa protein
  • PP2A subunit A isoform PR65-alpha
  • PP2A subunit A isoform R1-alpha
Gene Name
PPP2R1A
UniProtKB Entry
P30153Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0012619|Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform
MAAADGDDSLYPIAVLIDELRNEDVQLRLNSIKKLSTIALALGVERTRSELLPFLTDTIY
DEDEVLLALAEQLGTFTTLVGGPEYVHCLLPPLESLATVEETVVRDKAVESLRAISHEHS
PSDLEAHFVPLVKRLAGGDWFTSRTSACGLFSVCYPRVSSAVKAELRQYFRNLCSDDTPM
VRRAAASKLGEFAKVLELDNVKSEIIPMFSNLASDEQDSVRLLAVEACVNIAQLLPQEDL
EALVMPTLRQAAEDKSWRVRYMVADKFTELQKAVGPEITKTDLVPAFQNLMKDCEAEVRA
AASHKVKEFCENLSADCRENVIMSQILPCIKELVSDANQHVKSALASVIMGLSPILGKDN
TIEHLLPLFLAQLKDECPEVRLNIISNLDCVNEVIGIRQLSQSLLPAIVELAEDAKWRVR
LAIIEYMPLLAGQLGVEFFDEKLNSLCMAWLVDHVYAIREAATSNLKKLVEKFGKEWAHA
TIIPKVLAMSGDPNYLHRMTTLFCINVLSEVCGQDITTKHMLPTVLRMAGDPVANVRFNV
AKSLQKIGPILDNSTLQSEVKPILEKLTQDQDVDVKYFAQEALTVLSLA
Number of residues
589
Molecular Weight
65307.81
Theoretical pI
4.75
GO Classification
Functions
protein antigen binding / protein phosphatase regulator activity
Processes
female meiotic nuclear division / intracellular signal transduction / negative regulation of hippo signaling / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / protein-containing complex assembly / T cell homeostasis
Components
cytoplasm / dendrite / FAR/SIN/STRIPAK complex / glutamatergic synapse / lateral plasma membrane / neuron projection / neuronal cell body
General Function
The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Upon interaction with GNA12 promotes dephosphorylation of microtubule associated protein TAU/MAPT (PubMed:15525651). Required for proper chromosome segregation and for centromeric localization of SGO1 in mitosis (PubMed:16580887). Together with RACK1 adapter, mediates dephosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and AKT-mTOR signaling pathway (By similarity). Dephosphorylation of AKT1 is essential for regulatory T-cells (Treg) homeostasis and stability (By similarity). Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753, PubMed:33633399)
Specific Function
Protein antigen binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0012620|Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A)
ATGGCGGCGGCCGACGGCGACGACTCGCTGTACCCCATCGCGGTGCTCATAGACGAACTC
CGCAATGAGGACGTTCAGCTTCGCCTCAACAGCATCAAGAAGCTGTCCACCATCGCCTTG
GCCCTTGGGGTTGAAAGGACCCGAAGTGAGCTTCTGCCTTTCCTTACAGATACCATCTAT
GATGAAGATGAGGTCCTCCTGGCCCTGGCAGAACAGCTGGGAACCTTCACTACCCTGGTG
GGAGGCCCAGAGTACGTGCACTGCCTGCTGCCACCGCTGGAGTCGCTGGCCACAGTGGAG
GAGACAGTGGTGCGGGACAAGGCAGTGGAGTCCTTACGGGCCATCTCACACGAGCACTCG
CCCTCTGACCTGGAGGCGCACTTTGTGCCGCTAGTGAAGCGGCTGGCGGGCGGCGACTGG
TTCACCTCCCGCACCTCGGCCTGCGGCCTCTTCTCCGTCTGCTACCCCCGAGTGTCCAGT
GCTGTGAAGGCGGAACTTCGACAGTACTTCCGGAACCTGTGCTCAGATGACACCCCCATG
GTGCGGCGGGCCGCAGCCTCCAAGCTGGGGGAGTTTGCCAAGGTGCTGGAGCTGGACAAC
GTCAAGAGTGAGATCATCCCCATGTTCTCCAACCTGGCCTCTGACGAGCAGGACTCGGTG
CGGCTGCTGGCGGTGGAGGCGTGCGTGAACATCGCCCAGCTTCTGCCCCAGGAGGATCTG
GAGGCCCTGGTGATGCCCACTCTGCGCCAGGCCGCTGAAGACAAGTCCTGGCGCGTCCGC
TACATGGTGGCTGACAAGTTCACAGAGCTCCAGAAAGCAGTGGGGCCTGAGATCACCAAG
ACAGACCTGGTCCCTGCCTTCCAGAACCTGATGAAAGACTGTGAGGCCGAGGTGAGGGCC
GCAGCCTCCCACAAGGTCAAAGAGTTCTGTGAAAACCTCTCAGCTGACTGTCGGGAGAAT
GTGATCATGTCCCAGATCTTGCCCTGCATCAAGGAGCTGGTGTCCGATGCCAACCAACAT
GTCAAGTCTGCCCTGGCCTCAGTCATCATGGGTCTCTCTCCCATCTTGGGCAAAGACAAC
ACCATCGAGCACCTCTTGCCCCTCTTCCTGGCTCAGCTGAAGGATGAGTGCCCTGAGGTA
CGGCTGAACATCATCTCTAACCTGGACTGTGTGAACGAGGTGATTGGCATCCGGCAGCTG
TCCCAGTCCCTGCTCCCTGCCATTGTGGAGCTGGCTGAGGACGCCAAGTGGCGGGTGCGG
CTGGCCATCATTGAGTACATGCCCCTCCTGGCTGGACAGCTGGGAGTGGAGTTCTTTGAT
GAGAAACTTAACTCCTTGTGCATGGCCTGGCTTGTGGATCATGTATATGCCATCCGCGAG
GCAGCCACCAGCAACCTGAAGAAGCTAGTGGAAAAGTTTGGGAAGGAGTGGGCCCATGCC
ACAATCATCCCCAAGGTCTTGGCCATGTCCGGAGACCCCAACTACCTGCACCGCATGACT
ACGCTCTTCTGCATCAATGTGCTGTCTGAGGTCTGTGGGCAGGACATCACCACCAAGCAC
ATGCTACCCACGGTTCTGCGCATGGCTGGGGACCCGGTTGCCAATGTCCGCTTCAATGTG
GCCAAGTCTCTGCAGAAGATAGGGCCCATCCTGGACAACAGCACCTTGCAGAGTGAAGTC
AAGCCCATCCTAGAGAAGCTGACCCAGGACCAGGATGTGGACGTCAAATACTTTGCCCAG
GAGGCTCTGACTGTTCTGTCTCTCGCCTGA
Chromosome Location
19
Locus
19q13.41
External Identifiers
ResourceLink
UniProtKB IDP30153
UniProtKB Entry Name2AAA_HUMAN
GenBank Protein ID178663
GenBank Gene IDM31786
GeneCard IDPPP2R1A
HGNC IDHGNC:9302
PDB ID(s)1B3U, 2IE3, 2IE4, 2NPP, 2NYL, 2NYM, 2PKG, 3C5W, 3DW8, 3K7V, 3K7W, 4I5L, 4I5N, 4LAC, 5W0W, 6IUR, 6NTS, 7CUN, 7K36, 7PKS, 7SOY, 7YCX, 8RBX, 8RBZ, 8RC4, 8SO0, 8TTB, 8TWE, 8TWI, 8U1X, 8U89, 8UWB
KEGG IDhsa:5518
NCBI Gene ID5518
General References
  1. Walter G, Ferre F, Espiritu O, Carbone-Wiley A: Molecular cloning and sequence of cDNA encoding polyoma medium tumor antigen-associated 61-kDa protein. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8669-72. [Article]
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  4. Zolnierowicz S, Van Hoof C, Andjelkovic N, Cron P, Stevens I, Merlevede W, Goris J, Hemmings BA: The variable subunit associated with protein phosphatase 2A0 defines a novel multimember family of regulatory subunits. Biochem J. 1996 Jul 1;317 ( Pt 1):187-94. [Article]
  5. Ruediger R, Hentz M, Fait J, Mumby M, Walter G: Molecular model of the A subunit of protein phosphatase 2A: interaction with other subunits and tumor antigens. J Virol. 1994 Jan;68(1):123-9. [Article]
  6. Lubert EJ, Sarge KD: Interaction between protein phosphatase 2A and members of the importin beta superfamily. Biochem Biophys Res Commun. 2003 Apr 11;303(3):908-13. [Article]
  7. Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H: PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell. 2006 May;10(5):575-85. Epub 2006 Mar 30. [Article]
  8. Li HH, Cai X, Shouse GP, Piluso LG, Liu X: A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55. EMBO J. 2007 Jan 24;26(2):402-11. [Article]
  9. Nazarenko I, Schafer R, Sers C: Mechanisms of the HRSL3 tumor suppressor function in ovarian carcinoma cells. J Cell Sci. 2007 Apr 15;120(Pt 8):1393-404. Epub 2007 Mar 20. [Article]
  10. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  11. Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, Sanchez A, Chaudhry S, Chen GI, Sicheri F, Nesvizhskii AI, Aebersold R, Raught B, Gingras AC: 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. Mol Cell Proteomics. 2009 Jan;8(1):157-71. doi: 10.1074/mcp.M800266-MCP200. Epub 2008 Sep 8. [Article]
  12. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  13. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  14. Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C: Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-alpha-acetylation features. Mol Cell Proteomics. 2012 Jun;11(6):M111.015131. doi: 10.1074/mcp.M111.015131. Epub 2012 Jan 5. [Article]
  15. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
  16. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  17. Authors unspecified: Large-scale discovery of novel genetic causes of developmental disorders. Nature. 2015 Mar 12;519(7542):223-8. doi: 10.1038/nature14135. Epub 2014 Dec 24. [Article]
  18. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  19. Groves MR, Hanlon N, Turowski P, Hemmings BA, Barford D: The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs. Cell. 1999 Jan 8;96(1):99-110. [Article]
  20. Xing Y, Li Z, Chen Y, Stock JB, Jeffrey PD, Shi Y: Structural mechanism of demethylation and inactivation of protein phosphatase 2A. Cell. 2008 Apr 4;133(1):154-63. doi: 10.1016/j.cell.2008.02.041. [Article]
  21. Houge G, Haesen D, Vissers LE, Mehta S, Parker MJ, Wright M, Vogt J, McKee S, Tolmie JL, Cordeiro N, Kleefstra T, Willemsen MH, Reijnders MR, Berland S, Hayman E, Lahat E, Brilstra EH, van Gassen KL, Zonneveld-Huijssoon E, de Bie CI, Hoischen A, Eichler EE, Holdhus R, Steen VM, Doskeland SO, Hurles ME, FitzPatrick DR, Janssens V: B56delta-related protein phosphatase 2A dysfunction identified in patients with intellectual disability. J Clin Invest. 2015 Aug 3;125(8):3051-62. doi: 10.1172/JCI79860. Epub 2015 Jul 13. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
(2S,3S,4E,6E,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acidexperimentalunknowntargetDetails
2,6,8-Trimethyl-3-Amino-9-Benzyl-9-Methoxynonanoic AcidexperimentalunknowntargetDetails