EKS-MUM-00185
Eukaryotic Protein Kinase & Protein Phosphatase Database
TagContent
EKPD IDEKS-MUM-00185
Classification
Group/FamilyScoreE-ValueStartEndDomain Length
AGC/PKA484.12.2E-14544298255
StatusReviewed
Ensembl ProteinENSMUSP00000005606
UniProt AccessionP05132; Q9JID0;
Protein NamecAMP-dependent protein kinase catalytic subunit alpha
Protein Synonyms/Alias PKA C-alpha;
Gene NamePrkaca
Gene Synonyms/Alias Prkaca; Pkaca;
Ensembl Information
Ensembl Gene IDEnsembl Protein IDEnsembl Transcript ID
ENSMUSG00000005469ENSMUSP00000005606ENSMUST00000005606
OrganismMus musculus
Functional DescriptionPhosphorylates a large number of substrates in thecytoplasm 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 redumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT).
Protein Length351
Protein Sequence
(FASTA)
MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WETPSQNTAQ LDQFDRIKTL GTGSFGRVML 60
VKHKESGNHY AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVKLEFS FKDNSNLYMV 120
MEYVAGGEMF SHLRRIGRFS EPHARFYAAQ IVLTFEYLHS LDLIYRDLKP ENLLIDQQGY 180
IQVTDFGFAK RVKGRTWTLC GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF 240
ADQPIQIYEK IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVN DIKNHKWFAT 300
TDWIAIYQRK VEAPFIPKFK GPGDTSNFDD YEEEEIRVSI NEKCGKEFTE F 351
Nucleotide Sequence
(FASTA)
ATGGGCAACG CCGCCGCCGC CAAGAAGGGC AGCGAGCAGG AGAGCGTGAA AGAGTTCCTA 60
GCCAAAGCCA AGGAAGATTT CCTGAAAAAA TGGGAGACCC CTTCTCAGAA TACAGCCCAG 120
TTGGATCAGT TTGATAGAAT CAAGACCCTT GGCACCGGCT CCTTTGGGCG AGTGATGCTG 180
GTGAAGCACA AGGAGAGTGG GAACCACTAC GCCATGAAGA TCTTAGACAA GCAGAAGGTG 240
GTGAAGCTAA AGCAGATCGA GCACACTCTG AATGAGAAGC GCATCCTGCA GGCCGTCAAC 300
TTCCCGTTCC TGGTCAAACT TGAATTCTCC TTCAAGGACA ACTCAAACCT GTACATGGTC 360
ATGGAGTATG TAGCTGGTGG CGAGATGTTC TCCCACCTAC GGCGGATTGG AAGGTTCAGC 420
GAGCCCCATG CCCGTTTCTA CGCGGCGCAG ATCGTCCTGA CCTTTGAGTA TCTGCACTCC 480
CTGGACCTCA TCTACCGGGA CCTGAAGCCC GAGAATCTTC TCATCGACCA GCAGGGCTAT 540
ATTCAGGTGA CAGACTTCGG TTTTGCCAAG CGTGTGAAAG GCCGTACTTG GACCTTGTGT 600
GGGACCCCTG AGTACTTGGC CCCCGAGATT ATCCTGAGCA AAGGCTACAA CAAGGCTGTG 660
GACTGGTGGG CTCTCGGAGT CCTCATCTAC GAGATGGCTG CTGGTTACCC ACCCTTCTTC 720
GCTGACCAGC CTATCCAGAT CTATGAGAAA ATCGTCTCTG GGAAGGTGCG GTTCCCATCC 780
CACTTCAGCT CTGACTTGAA GGACCTGCTG CGGAACCTTC TGCAGGTGGA TCTCACCAAG 840
CGCTTTGGGA ACCTCAAGAA CGGGGTCAAT GACATCAAGA ACCACAAGTG GTTTGCCACG 900
ACTGACTGGA TTGCCATCTA TCAGAGAAAG GTGGAAGCTC CCTTCATACC AAAGTTTAAA 960
GGCCCTGGGG ACACGAGTAA CTTTGACGAC TATGAGGAGG AAGAGATCCG GGTCTCCATC 1020
AATGAGAAGT GTGGCAAGGA GTTTACTGAG TTTTAG 1056
Domain Profile
S: 1     ferlktlGtGsfGrvelvrekeskkyyalkvlskekvvklkqvehvknekrvlkavefpf  60
         f+r+ktlGtGsfGrv+lv++kes+++ya+k+l+k+kvvklkq+eh+ nekr+l+av+fpf
Q: 44    FDRIKTLGTGSFGRVMLVKHKESGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPF  103
         789*********************************************************
S: 61    lvkllasfkdesnlylvleyveGGelfsylrkvrrfsekaarfyaaeivlaleylhsldl  120
         lvkl++sfkd+snly+v+eyv+GGe+fs+lr+++rfse++arfyaa+ivl++eylhsldl
Q: 104   LVKLEFSFKDNSNLYMVMEYVAGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDL  163
         ************************************************************
S: 121   iyrdlkpenllldkeGyikvtdfGfakkvkdrtwtlcGtpeylapeiiqskgynkavdww  180
         iyrdlkpenll+d++Gyi+vtdfGfak+vk+rtwtlcGtpeylapeii skgynkavdww
Q: 164   IYRDLKPENLLIDQQGYIQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSKGYNKAVDWW  223
         ************************************************************
S: 181   alGvliyellaGyppffddqpikiyekivsgklkfpsklssdlkdllkkllqvdltkrlg  240
         alGvliye++aGyppff+dqpi+iyekivsgk++fps++ssdlkdll++llqvdltkr+g
Q: 224   ALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDLKDLLRNLLQVDLTKRFG  283
         ************************************************************
S: 241   nlkngvedikehkwf  255
         nlkngv+dik+hkwf
Q: 284   NLKNGVNDIKNHKWF  298
         **************9
Domain Sequence
(FASTA)
FDRIKTLGTG SFGRVMLVKH KESGNHYAMK ILDKQKVVKL KQIEHTLNEK RILQAVNFPF 60
LVKLEFSFKD NSNLYMVMEY VAGGEMFSHL RRIGRFSEPH ARFYAAQIVL TFEYLHSLDL 120
IYRDLKPENL LIDQQGYIQV TDFGFAKRVK GRTWTLCGTP EYLAPEIILS KGYNKAVDWW 180
ALGVLIYEMA AGYPPFFADQ PIQIYEKIVS GKVRFPSHFS SDLKDLLRNL LQVDLTKRFG 240
NLKNGVNDIK NHKWF 255
Keyword3D-structure; Alternative splicing; ATP-binding; cAMP; Cell membrane; Complete proteome; Cytoplasm; Kinase; Lipoprotein; Membrane; Mitochondrion; Myristate; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase.
Sequence SourceEnsembl
Orthology
Ortholog group
Ailuropoda melanoleuca"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Dipodomys ordii"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macropus eugenii"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Procavia capensis"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>
EKS-AIM-00171
EKS-BOT-00180
EKS-CAE-00173
EKS-CAF-00187
EKS-CAP-00207
EKS-CII-00117
EKS-CIS-00209
EKS-DAR-00479
EKS-DIO-00090
EKS-DRM-00091
EKS-EQC-00178
EKS-FEC-00169
EKS-GAM-00098
EKS-GAA-00223
EKS-GOG-00178
EKS-HOS-00186
EKS-ICT-00176
EKS-LAC-00191
EKS-LOA-00180
EKS-MAE-00062
EKS-MOD-00179
EKS-MUP-00183
EKS-ORN-00231
EKS-ORA-00159
EKS-ORL-00216
EKS-OTG-00187
EKS-PAT-00170
EKS-PES-00158
EKS-PEM-00096
EKS-PRC-00056
EKS-PTV-00152
EKS-RAN-00176
EKS-SAH-00173
EKS-SUS-00157
EKS-TAR-00236
EKS-TEN-00233
EKS-TUT-00156
EKS-XET-00213
EKS-XIM-00226
Gene Ontology
GO:0005952; C:cAMP-dependent protein kinase complex
GO:0005813; C:centrosome
GO:0005829; C:cytosol
GO:0005794; C:Golgi apparatus
GO:0005739; C:mitochondrion
GO:0031594; C:neuromuscular junction
GO:0005654; C:nucleoplasm
GO:0048471; C:perinuclear region of cytoplasm
GO:0005886; C:plasma membrane
GO:0005524; F:ATP binding
GO:0004691; F:cAMP-dependent protein kinase activity
GO:0071333; P:cellular response to glucose stimulus
GO:0071374; P:cellular response to parathyroid hormone stimulus
GO:0001707; P:mesoderm formation
GO:0051447; P:negative regulation of meiotic cell cycle
GO:0018105; P:peptidyl-serine phosphorylation
GO:0071158; P:positive regulation of cell cycle arrest
GO:0046827; P:positive regulation of protein export from nucleus
GO:0046777; P:protein autophosphorylation
GO:0043457; P:regulation of cellular respiration
GO:0045667; P:regulation of osteoblast differentiation
GO:0061136; P:regulation of proteasomal protein catabolic process
GO:0050804; P:regulation of synaptic transmission
GO:0051966; P:regulation of synaptic transmission, glutamatergic
GO:2000810; P:regulation of tight junction assembly
GO:0048240; P:sperm capacitation
KEGG
mmu:18747;
InterPros
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; 1.
SMARTs
SM00133; S_TK_X; 1.
SM00220; S_TKc; 1.
Prosites
PS51285; AGC_KINASE_CTER; 1.
PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
Prints
Created Date20-Feb-2013