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P17612 (KAPCA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 169. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
cAMP-dependent protein kinase catalytic subunit alpha

Short name=PKA C-alpha
EC=2.7.11.11
Gene names
Name:PRKACA
Synonyms:PKACA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length351 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 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 Ca2+, leading to reduced amplitude and increased frequency of store overload-induced Ca2+ release (SOICR) characterized by an increased rate of Ca2+ release and propagation velocity of spontaneous Ca2+ waves, despite reduced wave amplitude and resting cytosolic Ca2+. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Negatively regulates tight junctions (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. 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. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.19 Ref.24 Ref.25 Ref.27 Ref.28 Ref.29

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Allosterically activated by various compounds, including ATP. Activated by cAMP; the nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis. Inhibited by H89 (N-[2-[[3-(4-Bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide), spiroindoline, azole-based inhibitors, (3s)-amino-aminomethylbenzamide analogs, ARC-1032 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-carbamoylbutyl]hexanamide), ARC-1034 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]hexanamide), ARC-582, ARC-902 (Adc-6-aminohexanoic acid-(D-Arg)(6)-NH2), ARC-1012 ((2R)-6-amino-2-(6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}hexanamido)-N-(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)hexanamide) and ARC-1039 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-1-[(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)carbamoyl]ethyl]he xanamide). Ref.16 Ref.20 Ref.25 Ref.31 Ref.32 Ref.33

Subunit structure

A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. The cAMP-dependent protein kinase catalytic subunit binds PJA2. Both isoforms 1 and 2 forms activate cAMP-sensitive PKAI and PKAII holoenzymes by interacting with regulatory subunit (R) of PKA, PRKAR1A/PKR1 and PRKAR2A/PKR2, respectively. Interacts with NFKB1, NFKB2 and NFKBIA in platelets; these interactions are disrupted by thrombin and collagen. Binds to ABL1 in spermatozoa and with CDC25B in oocytes. Interacts with APOBEC3G and AICDA. Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly. Ref.10 Ref.13 Ref.19 Ref.24 Ref.28

Subcellular location

Cytoplasm. Cell membrane. Nucleus By similarity. Mitochondrion By similarity. Note: Translocates into the nucleus (monomeric catalytic subunit). The inactive holoenzyme is found in the cytoplasm. Distributed throughout the cytoplasm in meiotically incompetent oocytes. Associated to mitochondrion as meiotic competence is acquired. Aggregates around the germinal vesicles (GV) at the immature GV stage oocytes By similarity. Ref.6 Ref.21 Ref.29

Isoform 2: Cell projectionciliumflagellum. Note: Expressed in the midpiece region of the sperm flagellum. Ref.6 Ref.21 Ref.29

Tissue specificity

Isoform 1 is ubiquitous. Isoform 2 is sperm-specific and is enriched in pachytene spermatocytes but is not detected in round spermatids. Ref.6 Ref.28

Post-translational modification

Asn-3 is partially deaminated to Asp giving rise to 2 major isoelectric variants, called CB and CA respectively By similarity.

Autophosphorylated. Phosphorylation is enhanced by vitamin K2. Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity. Ref.9 Ref.16 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35

Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficienncy By similarity. Ref.9 Ref.16 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Cellular componentCell membrane
Cell projection
Cilium
Cytoplasm
Flagellum
Membrane
Mitochondrion
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
cAMP
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMLipoprotein
Myristate
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG2/M transition of mitotic cell cycle

Traceable author statement. Source: Reactome

activation of phospholipase C activity

Traceable author statement. Source: Reactome

activation of protein kinase A activity

Traceable author statement. Source: Reactome

blood coagulation

Traceable author statement. Source: Reactome

calcium-mediated signaling using intracellular calcium source

Traceable author statement PubMed 23507255. Source: BHF-UCL

carbohydrate metabolic process

Traceable author statement. Source: Reactome

cell communication by electrical coupling involved in cardiac conduction

Traceable author statement PubMed 23507255. Source: BHF-UCL

cellular response to epinephrine stimulus

Traceable author statement PubMed 23507255. Source: BHF-UCL

cellular response to glucagon stimulus

Traceable author statement. Source: Reactome

cellular response to glucose stimulus

Inferred from direct assay Ref.25. Source: UniProtKB

cellular response to parathyroid hormone stimulus

Inferred from electronic annotation. Source: Ensembl

cytosolic calcium ion homeostasis

Traceable author statement PubMed 23507255. Source: BHF-UCL

energy reserve metabolic process

Traceable author statement. Source: Reactome

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

gluconeogenesis

Traceable author statement. Source: Reactome

glucose metabolic process

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

intracellular signal transduction

Traceable author statement. Source: Reactome

mesoderm formation

Inferred from electronic annotation. Source: Ensembl

mitotic cell cycle

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

peptidyl-serine phosphorylation

Inferred from direct assay Ref.28. Source: BHF-UCL

positive regulation of cell cycle arrest

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein export from nucleus

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Non-traceable author statement Ref.1. Source: UniProtKB

regulation of cardiac muscle contraction

Traceable author statement PubMed 23507255. Source: BHF-UCL

regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion

Traceable author statement PubMed 23507255. Source: BHF-UCL

regulation of heart rate

Traceable author statement PubMed 23507255. Source: BHF-UCL

regulation of insulin secretion

Traceable author statement. Source: Reactome

regulation of osteoblast differentiation

Inferred from direct assay Ref.25. Source: UniProtKB

regulation of proteasomal protein catabolic process

Inferred from direct assay Ref.14. Source: UniProtKB

regulation of protein binding

Traceable author statement PubMed 23507255. Source: BHF-UCL

regulation of ryanodine-sensitive calcium-release channel activity

Traceable author statement PubMed 23507255. Source: BHF-UCL

regulation of synaptic transmission

Inferred from electronic annotation. Source: Ensembl

regulation of tight junction assembly

Inferred from direct assay Ref.12. Source: UniProtKB

signal transduction

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

sperm capacitation

Inferred from sequence or structural similarity. Source: UniProtKB

transmembrane transport

Traceable author statement. Source: Reactome

triglyceride catabolic process

Traceable author statement. Source: Reactome

water transport

Traceable author statement. Source: Reactome

   Cellular_componentAMP-activated protein kinase complex

Inferred from direct assay Ref.28. Source: BHF-UCL

cAMP-dependent protein kinase complex

Non-traceable author statement Ref.1. Source: UniProtKB

calcium channel complex

Traceable author statement PubMed 23507255. Source: BHF-UCL

centrosome

Inferred from direct assay PubMed 21399614. Source: UniProtKB

cilium

Inferred from electronic annotation. Source: UniProtKB-KW

cytosol

Traceable author statement. Source: Reactome

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

neuromuscular junction

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 21630459. Source: UniProt

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

sperm midpiece

Inferred from direct assay Ref.6. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cAMP-dependent protein kinase activity

Inferred from direct assay Ref.28. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.28. Source: BHF-UCL

protein kinase A regulatory subunit binding

Inferred from physical interaction Ref.28. Source: BHF-UCL

protein kinase binding

Inferred from physical interaction PubMed 11035810. Source: BHF-UCL

ubiquitin protein ligase binding

Inferred from direct assay Ref.29. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P17612-1)

Also known as: C-alpha-1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P17612-2)

Also known as: C-alpha-2; C-alpha-S; C(s);

The sequence of this isoform differs from the canonical sequence as follows:
     2-15: GNAAAAKKGSEQES → MASNSSD

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 351350cAMP-dependent protein kinase catalytic subunit alpha
PRO_0000086052

Regions

Domain44 – 298255Protein kinase
Domain299 – 35153AGC-kinase C-terminal
Nucleotide binding50 – 589ATP
Nucleotide binding122 – 1287ATP By similarity
Nucleotide binding169 – 1724ATP By similarity

Sites

Active site1671Proton acceptor By similarity
Binding site731ATP By similarity

Amino acid modifications

Modified residue31Deamidated asparagine By similarity
Modified residue111Phosphoserine; by autocatalysis By similarity
Modified residue491Phosphothreonine Ref.18
Modified residue1401Phosphoserine By similarity
Modified residue1961Phosphothreonine Ref.9
Modified residue1981Phosphothreonine; by PDPK1 Ref.9 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35
Modified residue2021Phosphothreonine
Modified residue3311Phosphotyrosine By similarity
Modified residue3391Phosphoserine Ref.18 Ref.23 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35
Lipidation21N-myristoyl glycine By similarity

Natural variations

Alternative sequence2 – 1514GNAAA…SEQES → MASNSSD in isoform 2.
VSP_004759
Natural variant411L → V. Ref.37
Corresponds to variant rs56029020 [ dbSNP | Ensembl ].
VAR_040591
Natural variant461R → Q. Ref.37
Corresponds to variant rs56085217 [ dbSNP | Ensembl ].
VAR_040592
Natural variant2641S → C. Ref.37
Corresponds to variant rs35635531 [ dbSNP | Ensembl ].
VAR_040593

Experimental info

Mutagenesis481K → R: Enhanced basal kinase activity; when associated with Q-96, L-121, A-124, K-182 and A-184. Ref.34
Mutagenesis961L → Q: Enhanced basal kinase activity; when associated with R-48, L-121, A-124, K-182 and A-184. Ref.34
Mutagenesis1211M → L: Enhanced basal kinase activity; when associated with R-48, Q-96, A-124, K-182 and A-184. Ref.34
Mutagenesis1241V → A: Enhanced basal kinase activity; when associated with R-48, Q-96, L-121, K-182 and A-184. Ref.34
Mutagenesis1821Q → K: Enhanced basal kinase activity; when associated with R-48, Q-96, L-121, A-124 and A-184. Ref.34
Mutagenesis1841T → A: Enhanced basal kinase activity; when associated with R-48, Q-96, L-121, A-124 and K-182. Ref.34
Mutagenesis1951R → A: No phosphorylation. Ref.9
Mutagenesis2011G → A: No phosphorylation. Ref.9
Mutagenesis2021T → A: No phosphorylation. Ref.9
Mutagenesis2051Y → A: Loss of allosteric regulation. Ref.20

Secondary structure

..................................................... 351
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (C-alpha-1) [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: BF6D3ECD2614E5AB

FASTA35140,590
        10         20         30         40         50         60 
MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WESPAQNTAH LDQFERIKTL GTGSFGRVML 

        70         80         90        100        110        120 
VKHKETGNHY AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVKLEFS FKDNSNLYMV 

       130        140        150        160        170        180 
MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ IVLTFEYLHS LDLIYRDLKP ENLLIDQQGY 

       190        200        210        220        230        240 
IQVTDFGFAK RVKGRTWTLC GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF 

       250        260        270        280        290        300 
ADQPIQIYEK IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVN DIKNHKWFAT 

       310        320        330        340        350 
TDWIAIYQRK VEAPFIPKFK GPGDTSNFDD YEEEEIRVSI NEKCGKEFSE F 

« Hide

Isoform 2 (C-alpha-2) (C-alpha-S) (C(s)) [UniParc].

Checksum: D10578641CB00E9C
Show »

FASTA34439,953

References

« Hide 'large scale' references
[1]"A cDNA clone encoding human cAMP-dependent protein kinase catalytic subunit C alpha."
Maldonado F., Hanks S.K.
Nucleic Acids Res. 16:8189-8190(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Thalamus.
[3]SeattleSNPs variation discovery resource
Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Eye and Testis.
[6]"A novel isoform of human cyclic 3',5'-adenosine monophosphate-dependent protein kinase, c alpha-s, localizes to sperm midpiece."
Reinton N., Orstavik S., Haugen T.B., Jahnsen T., Tasken K., Skalhegg B.S.
Biol. Reprod. 63:607-611(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-189 (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]"The unique catalytic subunit of sperm cAMP-dependent protein kinase is the product of an alternative C-alpha mRNA expressed specifically in spermatogenic cells."
San Agustin J.T., Wilkerson C.G., Witman G.B.
Mol. Biol. Cell 11:3031-3044(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-152 (ISOFORM 2).
Tissue: Testis.
[8]"Expression of a nonmyristylated variant of the catalytic subunit of protein kinase A during male germ-cell development."
Desseyn J.-L., Burton K.A., McKnight G.S.
Proc. Natl. Acad. Sci. U.S.A. 97:6433-6438(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-39 (ISOFORM 2).
Tissue: Testis.
[9]"Phosphorylation of the catalytic subunit of protein kinase A. Autophosphorylation versus phosphorylation by phosphoinositide-dependent kinase-1."
Moore M.J., Kanter J.R., Jones K.C., Taylor S.S.
J. Biol. Chem. 277:47878-47884(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPHOSPHORYLATION, PHOSPHORYLATION AT THR-196, PHOSPHORYLATION AT THR-198 BY PDK1, MUTAGENESIS OF ARG-195; GLY-201 AND THR-202.
[10]"Rab13 regulates PKA signaling during tight junction assembly."
Koehler K., Louvard D., Zahraoui A.
J. Cell Biol. 165:175-180(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAB13.
[11]"DNA binding of repressor nuclear factor-kappaB p50/p50 depends on phosphorylation of Ser337 by the protein kinase A catalytic subunit."
Guan H., Hou S., Ricciardi R.P.
J. Biol. Chem. 280:9957-9962(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS NFKB1 KINASE.
[12]"Phosphorylation of claudin-3 at threonine 192 by cAMP-dependent protein kinase regulates tight junction barrier function in ovarian cancer cells."
D'Souza T., Agarwal R., Morin P.J.
J. Biol. Chem. 280:26233-26240(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS CLDN3 KINASE.
[13]"PKA-mediated phosphorylation regulates the function of activation-induced deaminase (AID) in B cells."
Pasqualucci L., Kitaura Y., Gu H., Dalla-Favera R.
Proc. Natl. Acad. Sci. U.S.A. 103:395-400(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AICDA.
[14]"Proteasome function is regulated by cyclic AMP-dependent protein kinase through phosphorylation of Rpt6."
Zhang F., Hu Y., Huang P., Toleman C.A., Paterson A.J., Kudlow J.E.
J. Biol. Chem. 282:22460-22471(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PROTEASOME REGULATION, FUNCTION AS PSMC5/RPT6 KINASE.
[15]"Functional consequence of protein kinase A-dependent phosphorylation of the cardiac ryanodine receptor: sensitization of store overload-induced Ca2+ release."
Xiao B., Tian X., Xie W., Jones P.P., Cai S., Wang X., Jiang D., Kong H., Zhang L., Chen K., Walsh M.P., Cheng H., Chen S.R.W.
J. Biol. Chem. 282:30256-30264(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS RYR2 KINASE.
[16]"Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells."
Ichikawa T., Horie-Inoue K., Ikeda K., Blumberg B., Inoue S.
J. Mol. Endocrinol. 39:239-247(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, ENZYME REGULATION.
[17]"Activation of protein kinase A (PKA) signaling mitigates the antiproliferative and antiinvasive effects of alpha-difluoromethylornithine in breast cancer cells."
Xu H., Washington S., Verderame M.F., Manni A.
Breast Cancer Res. Treat. 107:63-70(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS ALPHA-DIFLUOROMETHYLORNITHINE ANTAGONIST.
[18]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-49 AND SER-339, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[19]"Phosphorylation of APOBEC3G by protein kinase A regulates its interaction with HIV-1 Vif."
Shirakawa K., Takaori-Kondo A., Yokoyama M., Izumi T., Matsui M., Io K., Sato T., Sato H., Uchiyama T.
Nat. Struct. Mol. Biol. 15:1184-1191(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH APOBEC3G.
[20]"Allosteric cooperativity in protein kinase A."
Masterson L.R., Mascioni A., Traaseth N.J., Taylor S.S., Veglia G.
Proc. Natl. Acad. Sci. U.S.A. 105:506-511(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, MUTAGENESIS OF TYR-205.
[21]"Gravin dynamics regulates the subcellular distribution of PKA."
Yan X., Walkiewicz M., Carlson J., Leiphon L., Grove B.
Exp. Cell Res. 315:1247-1259(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[22]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[24]"Thrombin and collagen induce a feedback inhibitory signaling pathway in platelets involving dissociation of the catalytic subunit of protein kinase A from an NFkappaB-IkappaB complex."
Gambaryan S., Kobsar A., Rukoyatkina N., Herterich S., Geiger J., Smolenski A., Lohmann S.M., Walter U.
J. Biol. Chem. 285:18352-18363(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PLATELETS, FUNCTION AS VASP KINASE, INTERACTION WITH NFKB1; NFKB2 AND NFKBIA.
[25]"High glucose stimulates adipogenic and inhibits osteogenic differentiation in MG-63 cells through cAMP/protein kinase A/extracellular signal-regulated kinase pathway."
Wang W., Zhang X., Zheng J., Yang J.
Mol. Cell. Biochem. 338:115-122(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN OSTEOBLAST DIFFERENTIATION, ENZYME REGULATION.
[26]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"Protein kinase A activates and phosphorylates ROR?4 in vitro and takes part in ROR? activation by CaMK-IV."
Ermisch M., Firla B., Steinhilber D.
Biochem. Biophys. Res. Commun. 408:442-446(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS RORA KINASE.
[28]"The testis-specific C?2 subunit of PKA is kinetically indistinguishable from the common C?1 subunit of PKA."
Vetter M.M., Zenn H.-M., Mendez E., van den Boom H., Herberg F.W., Skaalhegg B.S.
BMC Biochem. 12:40-40(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS KINASE, TISSUE SPECIFICITY, INTERACTION WITH PRKAR1A/PKR1 AND PRKAR2A/PKR2.
[29]"Control of PKA stability and signalling by the RING ligase praja2."
Lignitto L., Carlucci A., Sepe M., Stefan E., Cuomo O., Nistico R., Scorziello A., Savoia C., Garbi C., Annunziato L., Feliciello A.
Nat. Cell Biol. 13:412-422(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[30]"Discovery of 2-pyrimidyl-5-amidothiophenes as potent inhibitors for AKT: synthesis and SAR studies."
Lin X., Murray J.M., Rico A.C., Wang M.X., Chu D.T., Zhou Y., Del Rosario M., Kaufman S., Ma S., Fang E., Crawford K., Jefferson A.B.
Bioorg. Med. Chem. Lett. 16:4163-4168(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 15-351, PHOSPHORYLATION AT THR-198 AND SER-339.
[31]"Azole-based inhibitors of AKT/PKB for the treatment of cancer."
Zeng Q., Allen J.G., Bourbeau M.P., Wang X., Yao G., Tadesse S., Rider J.T., Yuan C.C., Hong F.-T., Lee M.R., Zhang S., Lofgren J.A., Freeman D.J., Yang S., Li C., Tominey E., Huang X., Hoffman D. expand/collapse author list , Yamane H.K., Fotsch C., Dominguez C., Hungate R., Zhang X.
Bioorg. Med. Chem. Lett. 20:1559-1564(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS), PHOSPHORYLATION AT THR-198 AND SER-339, ENZYME REGULATION.
[32]"Design of selective, ATP-competitive inhibitors of Akt."
Freeman-Cook K.D., Autry C., Borzillo G., Gordon D., Barbacci-Tobin E., Bernardo V., Briere D., Clark T., Corbett M., Jakubczak J., Kakar S., Knauth E., Lippa B., Luzzio M.J., Mansour M., Martinelli G., Marx M., Nelson K. expand/collapse author list , Pandit J., Rajamohan F., Robinson S., Subramanyam C., Wei L., Wythes M., Morris J.
J. Med. Chem. 53:4615-4622(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS), PHOSPHORYLATION AT THR-198 AND SER-339, ENZYME REGULATION.
[33]"Diversity of bisubstrate binding modes of adenosine analogue-oligoarginine conjugates in protein kinase a and implications for protein substrate interactions."
Pflug A., Rogozina J., Lavogina D., Enkvist E., Uri A., Engh R.A., Bossemeyer D.
J. Mol. Biol. 403:66-77(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH ADENOSINE ANALOG, PHOSPHORYLATION AT SER-11; THR-198 AND SER-339, ENZYME REGULATION.
[34]"Mutants of protein kinase A that mimic the ATP-binding site of Aurora kinase."
Pflug A., de Oliveira T.M., Bossemeyer D., Engh R.A.
Biochem. J. 440:85-93(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH AURORA KINASE INHIBITORS, PHOSPHORYLATION AT SER-11; THR-198 AND SER-339, MUTAGENESIS OF LYS-48; LEU-96; MET-121; VAL-124; GLN-182 AND THR-184.
[35]"Experimental active site mapping as a starting point to fragment-based lead discovery."
Behnen J., Koester H., Ritschel T., Neudert G., Heine A., Klebe G.
Submitted (JUL-2010) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS), PHOSPHORYLATION AT THR-198 AND SER-339.
[36]"Fragment based drug design on PKA."
Koester H., Craan T., Brass S., Heine A., Klebe G.
Submitted (SEP-2010) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS).
[37]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-41; GLN-46 AND CYS-264.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X07767 mRNA. Translation: CAA30597.1.
AK290147 mRNA. Translation: BAF82836.1.
DQ667173 Genomic DNA. Translation: ABG25918.1.
CH471106 Genomic DNA. Translation: EAW84399.1.
BC039846 mRNA. Translation: AAH39846.1.
BC108259 mRNA. Translation: AAI08260.1.
AF208004 mRNA. Translation: AAG35720.1.
AF239744 mRNA. Translation: AAF76426.1.
AF224718 mRNA. Translation: AAF75622.1.
CCDSCCDS12304.1. [P17612-1]
CCDS12305.1. [P17612-2]
PIROKHU2C. S01404.
RefSeqNP_002721.1. NM_002730.3. [P17612-1]
NP_997401.1. NM_207518.1.
UniGeneHs.631630.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2GU8X-ray2.20A15-351[»]
3AGLX-ray2.10A/B1-351[»]
3AGMX-ray2.00A1-351[»]
3AMAX-ray1.75A1-351[»]
3AMBX-ray2.25A1-351[»]
3L9LX-ray2.00A/B1-351[»]
3L9MX-ray1.90A/B1-351[»]
3L9NX-ray2.00A1-351[»]
3MVJX-ray2.49A/B/E1-351[»]
3NX8X-ray2.00A1-351[»]
3OOGX-ray2.00A1-351[»]
3OVVX-ray1.58A1-351[»]
3OWPX-ray1.88A1-351[»]
3OXTX-ray2.20A1-351[»]
3P0MX-ray2.03A1-351[»]
3POOX-ray1.60A1-351[»]
3VQHX-ray1.95A1-351[»]
4AE6X-ray2.10A/B16-351[»]
4AE9X-ray2.30A/B16-351[»]
ProteinModelPortalP17612.
SMRP17612. Positions 15-351.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111553. 181 interactions.
DIPDIP-33878N.
IntActP17612. 56 interactions.
MINTMINT-95365.
STRING9606.ENSP00000309591.

Chemistry

BindingDBP17612.
ChEMBLCHEMBL2094138.
GuidetoPHARMACOLOGY1476.

PTM databases

PhosphoSiteP17612.

Polymorphism databases

DMDM125205.

Proteomic databases

MaxQBP17612.
PaxDbP17612.
PRIDEP17612.

Protocols and materials databases

DNASU5566.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000308677; ENSP00000309591; ENSG00000072062. [P17612-1]
ENST00000589994; ENSP00000466651; ENSG00000072062. [P17612-2]
GeneID5566.
KEGGhsa:5566.
UCSCuc002myb.3. human. [P17612-2]
uc002myc.3. human. [P17612-1]

Organism-specific databases

CTD5566.
GeneCardsGC19M014202.
HGNCHGNC:9380. PRKACA.
HPACAB010361.
MIM601639. gene.
neXtProtNX_P17612.
PharmGKBPA33748.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidP17612.
KOK04345.
OMAGQHFAMK.
OrthoDBEOG7VX8WD.
PhylomeDBP17612.
TreeFamTF313399.

Enzyme and pathway databases

BRENDA2.7.11.11. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_13685. Neuronal System.
REACT_15518. Transmembrane transport of small molecules.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkP17612.

Gene expression databases

ArrayExpressP17612.
BgeeP17612.
CleanExHS_PRKACA.
GenevestigatorP17612.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPRKACA. human.
EvolutionaryTraceP17612.
GeneWikiPRKACA.
GenomeRNAi5566.
NextBio21564.
PROP17612.
SOURCESearch...

Entry information

Entry nameKAPCA_HUMAN
AccessionPrimary (citable) accession number: P17612
Secondary accession number(s): Q32P54 expand/collapse secondary AC list , Q9H2Y0, Q9NRB4, Q9NRH9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 169 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM