CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004584
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 cAMP-dependent protein kinase catalytic subunit alpha 
Protein Synonyms/Alias
 PKA C-alpha 
Gene Name
 PRKACA 
Gene Synonyms/Alias
 PKACA 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
24KEFLAKAKEDFLKKWubiquitination[1, 2]
48LDQFERIKTLGTGSFubiquitination[2]
84KQKVVKLKQIEHTLNubiquitination[1, 2]
93IEHTLNEKRILQAVNubiquitination[1, 2]
214APEIILSKGYNKAVDubiquitination[2]
267SHFSSDLKDLLRNLLacetylation[3]
267SHFSSDLKDLLRNLLubiquitination[1]
280LLQVDLTKRFGNLKNubiquitination[1]
286TKRFGNLKNGVNDIKubiquitination[1, 4]
293KNGVNDIKNHKWFATubiquitination[5]
310WIAIYQRKVEAPFIPubiquitination[2]
320APFIPKFKGPGDTSNubiquitination[1]
346SINEKCGKEFSEF**ubiquitination[2]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 
Functional Description
 Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, TRPC1 and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B- alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha- difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). TRPC1 activation by phosphorylation promotes Ca(2+) influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT). Phosphorylates APOBEC3G and AICDA. 
Sequence Annotation
 DOMAIN 44 298 Protein kinase.
 DOMAIN 299 351 AGC-kinase C-terminal.
 NP_BIND 50 58 ATP.
 NP_BIND 122 128 ATP (By similarity).
 NP_BIND 169 172 ATP (By similarity).
 ACT_SITE 167 167 Proton acceptor (By similarity).
 BINDING 73 73 ATP (By similarity).
 MOD_RES 3 3 Deamidated asparagine (By similarity).
 MOD_RES 11 11 Phosphoserine; by autocatalysis (By
 MOD_RES 49 49 Phosphothreonine.
 MOD_RES 140 140 Phosphoserine (By similarity).
 MOD_RES 196 196 Phosphothreonine.
 MOD_RES 198 198 Phosphothreonine; by PDPK1.
 MOD_RES 202 202 Phosphothreonine.
 MOD_RES 331 331 Phosphotyrosine (By similarity).
 MOD_RES 339 339 Phosphoserine.
 LIPID 2 2 N-myristoyl glycine (By similarity).  
Keyword
 3D-structure; Alternative splicing; ATP-binding; cAMP; Cell membrane; Complete proteome; Cytoplasm; Kinase; Lipoprotein; Membrane; Mitochondrion; Myristate; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 351 AA 
Protein Sequence
MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WESPAQNTAH LDQFERIKTL GTGSFGRVML 60
VKHKETGNHY AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVKLEFS FKDNSNLYMV 120
MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ IVLTFEYLHS LDLIYRDLKP ENLLIDQQGY 180
IQVTDFGFAK RVKGRTWTLC GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF 240
ADQPIQIYEK IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVN DIKNHKWFAT 300
TDWIAIYQRK VEAPFIPKFK GPGDTSNFDD YEEEEIRVSI NEKCGKEFSE F 351 
Gene Ontology
 GO:0005952; C:cAMP-dependent protein kinase complex; NAS:UniProtKB.
 GO:0005813; C:centrosome; IDA:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
 GO:0031594; C:neuromuscular junction; IEA:Compara.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; NAS:UniProtKB.
 GO:0004691; F:cAMP-dependent protein kinase activity; ISS:UniProtKB.
 GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB.
 GO:0007202; P:activation of phospholipase C activity; TAS:Reactome.
 GO:0034199; P:activation of protein kinase A activity; TAS:Reactome.
 GO:0007596; P:blood coagulation; TAS:Reactome.
 GO:0071377; P:cellular response to glucagon stimulus; TAS:Reactome.
 GO:0071333; P:cellular response to glucose stimulus; IDA:UniProtKB.
 GO:0071374; P:cellular response to parathyroid hormone stimulus; IEA:Compara.
 GO:0006112; P:energy reserve metabolic process; TAS:Reactome.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
 GO:0006094; P:gluconeogenesis; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0007243; P:intracellular protein kinase cascade; TAS:Reactome.
 GO:0001707; P:mesoderm formation; IEA:Compara.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
 GO:0071158; P:positive regulation of cell cycle arrest; ISS:UniProtKB.
 GO:0046827; P:positive regulation of protein export from nucleus; IEA:Compara.
 GO:0046777; P:protein autophosphorylation; IEA:Compara.
 GO:0050796; P:regulation of insulin secretion; TAS:Reactome.
 GO:0045667; P:regulation of osteoblast differentiation; IDA:UniProtKB.
 GO:0061136; P:regulation of proteasomal protein catabolic process; IDA:UniProtKB.
 GO:0050804; P:regulation of synaptic transmission; IEA:Compara.
 GO:2000810; P:regulation of tight junction assembly; IDA:UniProtKB.
 GO:0044281; P:small molecule metabolic process; TAS:Reactome.
 GO:0048240; P:sperm capacitation; ISS:UniProtKB.
 GO:0055085; P:transmembrane transport; TAS:Reactome.
 GO:0019433; P:triglyceride catabolic process; TAS:Reactome.
 GO:0006833; P:water transport; TAS:Reactome. 
Interpro
 IPR000961; AGC-kinase_C.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00069; Pkinase 
SMART
 SM00133; S_TK_X
 SM00220; S_TKc 
PROSITE
 PS51285; AGC_KINASE_CTER
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS