CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-009821
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform 
Protein Synonyms/Alias
 PP2A-alpha; Replication protein C; RP-C 
Gene Name
 PPP2CA 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
4****MDEKVFTKELDacetylation[1]
4****MDEKVFTKELDubiquitination[2, 3]
8MDEKVFTKELDQWIEubiquitination[2, 3, 4, 5]
21IEQLNECKQLSESQVubiquitination[2, 3, 4, 5, 6]
29QLSESQVKSLCEKAKubiquitination[2, 3, 4, 5, 7]
34QVKSLCEKAKEILTKubiquitination[5]
36KSLCEKAKEILTKESubiquitination[5]
41KAKEILTKESNVQEVubiquitination[2, 4, 5, 8, 9]
74ELFRIGGKSPDTNYLubiquitination[2, 5]
136FYDECLRKYGNANVWubiquitination[5]
283MELDDTLKYSFLQFDubiquitination[5, 6, 9]
Reference
 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [6] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [7] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [8] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [9] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 
Functional Description
 PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGOL2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'. 
Sequence Annotation
 ACT_SITE 118 118 Proton donor (By similarity).
 METAL 57 57 Iron (By similarity).
 METAL 59 59 Iron (By similarity).
 METAL 85 85 Iron (By similarity).
 METAL 85 85 Manganese (By similarity).
 METAL 117 117 Manganese (By similarity).
 METAL 167 167 Manganese (By similarity).
 METAL 241 241 Manganese (By similarity).
 MOD_RES 307 307 Phosphotyrosine.
 MOD_RES 309 309 Leucine methyl ester.  
Keyword
 3D-structure; Alternative splicing; Centromere; Chromosome; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; Hydrolase; Iron; Manganese; Meiosis; Metal-binding; Methylation; Nucleus; Phosphoprotein; Polymorphism; Protein phosphatase; Reference proteome. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 309 AA 
Protein Sequence
MDEKVFTKEL DQWIEQLNEC KQLSESQVKS LCEKAKEILT KESNVQEVRC PVTVCGDVHG 60
QFHDLMELFR IGGKSPDTNY LFMGDYVDRG YYSVETVTLL VALKVRYRER ITILRGNHES 120
RQITQVYGFY DECLRKYGNA NVWKYFTDLF DYLPLTALVD GQIFCLHGGL SPSIDTLDHI 180
RALDRLQEVP HEGPMCDLLW SDPDDRGGWG ISPRGAGYTF GQDISETFNH ANGLTLVSRA 240
HQLVMEGYNW CHDRNVVTIF SAPNYCYRCG NQAAIMELDD TLKYSFLQFD PAPRRGEPHV 300
TRRTPDYFL 309 
Gene Ontology
 GO:0000775; C:chromosome, centromeric region; IEA:UniProtKB-SubCell.
 GO:0005829; C:cytosol; TAS:UniProtKB.
 GO:0016020; C:membrane; NAS:UniProtKB.
 GO:0015630; C:microtubule cytoskeleton; NAS:UniProtKB.
 GO:0005739; C:mitochondrion; NAS:UniProtKB.
 GO:0005634; C:nucleus; NAS:UniProtKB.
 GO:0005886; C:plasma membrane; IEA:Compara.
 GO:0000159; C:protein phosphatase type 2A complex; IDA:UniProtKB.
 GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0004722; F:protein serine/threonine phosphatase activity; IEA:Compara.
 GO:0006672; P:ceramide metabolic process; NAS:UniProtKB.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0000188; P:inactivation of MAPK activity; NAS:UniProtKB.
 GO:0006917; P:induction of apoptosis; TAS:UniProtKB.
 GO:0007126; P:meiosis; IEA:UniProtKB-KW.
 GO:0007498; P:mesoderm development; IEA:Compara.
 GO:0007084; P:mitotic nuclear envelope reassembly; TAS:Reactome.
 GO:0030308; P:negative regulation of cell growth; NAS:UniProtKB.
 GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IMP:BHF-UCL.
 GO:0042518; P:negative regulation of tyrosine phosphorylation of Stat3 protein; NAS:UniProtKB.
 GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome.
 GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IMP:BHF-UCL.
 GO:0006470; P:protein dephosphorylation; TAS:UniProtKB.
 GO:0070208; P:protein heterotrimerization; IEA:Compara.
 GO:0030155; P:regulation of cell adhesion; NAS:UniProtKB.
 GO:0006275; P:regulation of DNA replication; NAS:UniProtKB.
 GO:0031952; P:regulation of protein autophosphorylation; IEA:Compara.
 GO:0042176; P:regulation of protein catabolic process; IEA:Compara.
 GO:0010469; P:regulation of receptor activity; IEA:Compara.
 GO:0006355; P:regulation of transcription, DNA-dependent; NAS:UniProtKB.
 GO:0030111; P:regulation of Wnt receptor signaling pathway; NAS:UniProtKB.
 GO:0008380; P:RNA splicing; NAS:UniProtKB.
 GO:0019932; P:second-messenger-mediated signaling; NAS:UniProtKB. 
Interpro
 IPR004843; Metallo_PEstase_dom.
 IPR006186; Ser/Thr-sp_prot-phosphatase. 
Pfam
 PF00149; Metallophos 
SMART
 SM00156; PP2Ac 
PROSITE
 PS00125; SER_THR_PHOSPHATASE 
PRINTS
 PR00114; STPHPHTASE.