DB code: T00255

CATH domain 1.20.890.10 : cAMP-dependent Protein Kinase, Chain A
2.60.120.10 : Jelly Rolls
2.60.120.10 : Jelly Rolls
E.C. 2.7.11.11
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.60.120.10 : Jelly Rolls S00145 S00155 D00842 D00843 M00216 T00101

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Contains RefSeq Pfam
P05132 cAMP-dependent protein kinase catalytic subunit alpha
PKA C-alpha
EC 2.7.11.11
None NP_001264827.1 (Protein)
NM_001277898.1 (DNA/RNA sequence)
NP_032880.1 (Protein)
NM_008854.5 (DNA/RNA sequence)
PF00069 (Pkinase)
[Graphical View]
P00517 cAMP-dependent protein kinase catalytic subunit alpha
PKA C-alpha
EC 2.7.11.11
None NP_777009.1 (Protein)
NM_174584.2 (DNA/RNA sequence)
PF00069 (Pkinase)
[Graphical View]
Q9DBC7 cAMP-dependent protein kinase type I-alpha regulatory subunit
None cAMP-dependent protein kinase type I-alpha regulatory subunit, N-terminally processed
NP_068680.1 (Protein)
NM_021880.2 (DNA/RNA sequence)
PF00027 (cNMP_binding)
PF02197 (RIIa)
[Graphical View]
P12849 cAMP-dependent protein kinase type I-beta regulatory subunit
None None NP_001240819.1 (Protein)
NM_001253890.1 (DNA/RNA sequence)
NP_032949.3 (Protein)
NM_008923.3 (DNA/RNA sequence)
PF00027 (cNMP_binding)
PF02197 (RIIa)
[Graphical View]
P12367 cAMP-dependent protein kinase type II-alpha regulatory subunit
None None PF00027 (cNMP_binding)
PF02197 (RIIa)
[Graphical View]
P31324 cAMP-dependent protein kinase type II-beta regulatory subunit
None None NP_035288.2 (Protein)
NM_011158.3 (DNA/RNA sequence)
PF00027 (cNMP_binding)
PF02197 (RIIa)
[Graphical View]
P00514 cAMP-dependent protein kinase type I-alpha regulatory subunit
None cAMP-dependent protein kinase type I-alpha regulatory subunit, N-terminally processed
NP_001069826.1 (Protein)
NM_001076358.1 (DNA/RNA sequence)
PF00027 (cNMP_binding)
PF02197 (RIIa)
[Graphical View]
P00515 cAMP-dependent protein kinase type II-alpha regulatory subunit
None None NP_001178296.1 (Protein)
NM_001191367.1 (DNA/RNA sequence)
PF00027 (cNMP_binding)
PF02197 (RIIa)
[Graphical View]
P31322 cAMP-dependent protein kinase type II-beta regulatory subunit
None None NP_777074.1 (Protein)
NM_174649.2 (DNA/RNA sequence)
PF00027 (cNMP_binding)
PF02197 (RIIa)
[Graphical View]

KEGG enzyme name
cAMP-dependent protein kinase
PKA
PKA C
protein kinase A
STK22

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P05132 KAPCA_MOUSE ATP + a protein = ADP + a phosphoprotein. 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. Cytoplasm (By similarity). Nucleus (By similarity). Note=Translocates into the nucleus (monomeric catalytic subunit) (By similarity). The inactive holoenzyme is found in the cytoplasm (By similarity).
P00517 KAPCA_BOVIN ATP + a protein = ADP + a phosphoprotein. 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. Cytoplasm. Nucleus. Note=Translocates into the nucleus (monomeric catalytic subunit). The inactive holoenzyme is found in the cytoplasm.
Q9DBC7 KAP0_MOUSE The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules. PRKAR1A also interacts with RFC2, the complex may be involved in cell survival (By similarity). Interacts with AKAP4.
P12849 KAP1_MOUSE The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules.
P12367 KAP2_MOUSE The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules. Interacts with AKAP4. Interacts with CBFA2T3 (By similarity).
P31324 KAP3_MOUSE The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules.
P00514 KAP0_BOVIN The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules. PRKAR1A also interacts with RFC2, the complex may be involved in cell survival. Interacts with AKAP4 (By similarity).
P00515 KAP2_BOVIN The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules. Interacts with AKAP4 and CBFA2T3 (By similarity).
P31322 KAP3_BOVIN The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00002 C00017 C00008 C00562
E.C.
Compound ATP Protein ADP Phosphoprotein
Type amine group,nucleotide peptide/protein amine group,nucleotide peptide/protein,phosphate group/phosphate ion
ChEBI 15422
15422
16761
16761
PubChem 5957
5957
6022
6022
1r2aA Unbound Unbound Unbound Unbound
1r2aB Unbound Unbound Unbound Unbound
1rgsA01 Unbound Unbound Unbound Unbound
1rgsA02 Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1r2aA
1r2aB
1rgsA01
1rgsA02

References for Catalytic Mechanism
References Sections No. of steps in catalysis

References
[1]
Resource
Comments DISULFIDE BONDS
Medline ID 88033069
PubMed ID 3667618
Journal J Biol Chem
Year 1987
Volume 262
Pages 14961-6
Authors Bubis J, Vedvick TS, Taylor SS
Title Antiparallel alignment of the two protomers of the regulatory subunit dimer of cAMP-dependent protein kinase I.
Related PDB
Related UniProtKB P00514
[2]
Resource
Comments 3D-STRUCTURE MODELING
Medline ID 87157645
PubMed ID 3030405
Journal Biochemistry
Year 1987
Volume 26
Pages 343-51
Authors Weber IT, Steitz TA, Bubis J, Taylor SS
Title Predicted structures of cAMP binding domains of type I and II regulatory subunits of cAMP-dependent protein kinase.
Related PDB
Related UniProtKB P00514
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 113-379
Medline ID
PubMed ID 7638597
Journal Science
Year 1995
Volume 269
Pages 807-13
Authors Su Y, Dostmann WR, Herberg FW, Durick K, Xuong NH, Ten Eyck L, Taylor SS, Varughese KI
Title Regulatory subunit of protein kinase A: structure of deletion mutant with cAMP binding domains.
Related PDB 1rgs
Related UniProtKB P00514
[4]
Resource
Comments
Medline ID
PubMed ID 7873523
Journal Biochemistry
Year 1995
Volume 34
Pages 2447-54
Authors Adams JA, McGlone ML, Gibson R, Taylor SS
Title Phosphorylation modulates catalytic function and regulation in the cAMP-dependent protein kinase.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 7756252
Journal Biochemistry
Year 1995
Volume 34
Pages 6267-71
Authors Yang S, Fletcher WH, Johnson DA
Title Regulation of cAMP-dependent protein kinase: enzyme activation without dissociation.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8524844
Journal Proc Natl Acad Sci U S A
Year 1995
Volume 92
Pages 11761-5
Authors Luo K, Zhou P, Lodish HF
Title The specificity of the transforming growth factor beta receptor kinases determined by a spatially addressable peptide library.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8612810
Journal FEBS Lett
Year 1996
Volume 384
Pages 138-42
Authors Sahara S, Sato K, Kaise H, Mori K, Sato A, Aoto M, Tokmakov AA, Fukami Y
Title Biochemical evidence for the interaction of regulatory subunit of cAMP-dependent protein kinase with IDA (Inter-DFG-APE) region of catalytic subunit.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 9300482
Journal Protein Sci
Year 1997
Volume 6
Pages 1825-34
Authors Gibson RM, Ji-Buechler Y, Taylor SS
Title Identification of electrostatic interaction sites between the regulatory and catalytic subunits of cyclic AMP-dependent protein kinase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 9050991
Journal Oncogene
Year 1997
Volume 14
Pages 923-8
Authors Tortora G, Damiano V, Bianco C, Baldassarre G, Bianco AR, Lanfrancone L, Pelicci PG, Ciardiello F
Title The RIalpha subunit of protein kinase A (PKA) binds to Grb2 and allows PKA interaction with the activated EGF-receptor.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 9295304
Journal J Biol Chem
Year 1997
Volume 272
Pages 23637-44
Authors Newlon MG, Roy M, Hausken ZE, Scott JD, Jennings PA
Title The A-kinase anchoring domain of type IIalpha cAMP-dependent protein kinase is highly helical.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10485331
Journal Mol Cell Biochem
Year 1999
Volume 197
Pages 117-28
Authors Nikolakaki E, Fissentzidis A, Giannakouros T, Georgatsos JG
Title Purification and characterization of a dimer form of the cAMP-dependent protein kinase from mouse liver cytosol.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 10026146
Journal J Biol Chem
Year 1999
Volume 274
Pages 5370-8
Authors Zimmermann B, Chiorini JA, Ma Y, Kotin RM, Herberg FW
Title PrKX is a novel catalytic subunit of the cAMP-dependent protein kinase regulated by the regulatory subunit type I.
Related PDB
Related UniProtKB
[13]
Resource
Comments STRUCTURE BY NMR OF 1-43.
Medline ID 99173235
PubMed ID 10074940
Journal Nat Struct Biol
Year 1999
Volume 6
Pages 222-7
Authors Newlon MG, Roy M, Morikis D, Hausken ZE, Coghlan V, Scott JD, Jennings PA
Title The molecular basis for protein kinase A anchoring revealed by solution NMR.
Related PDB 1r2a
Related UniProtKB P12367
[14]
Resource
Comments
Medline ID
PubMed ID 11206066
Journal Protein Sci
Year 2000
Volume 9
Pages 2446-56
Authors Muhonen WW, Shabb JB
Title Resonant mirror biosensor analysis of type Ialpha cAMP-dependent protein kinase B domain--cyclic nucleotide interactions.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 10801316
Journal Biochemistry
Year 2000
Volume 39
Pages 5662-71
Authors Leon DA, Canaves JM, Taylor SS
Title Probing the multidomain structure of the type I regulatory subunit of cAMP-dependent protein kinase using mutational analysis: role and environment of endogenous tryptophans.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 10753751
Journal Curr Biol
Year 2000
Volume 10
Pages 417-20
Authors Diviani D, Langeberg LK, Doxsey SJ, Scott JD
Title Pericentrin anchors protein kinase A at the centrosome through a newly identified RII-binding domain.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 10899163
Journal J Biol Chem
Year 2000
Volume 275
Pages 35146-52
Authors Banky P, Newlon MG, Roy M, Garrod S, Taylor SS, Jennings PA
Title Isoform-specific differences between the type Ialpha and IIalpha cyclic AMP-dependent protein kinase anchoring domains revealed by solution NMR.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 11342137
Journal Structure (Camb)
Year 2001
Volume 9
Pages 73-82
Authors Diller TC, Madhusudan, Xuong NH, Taylor SS
Title Molecular basis for regulatory subunit diversity in cAMP-dependent protein kinase: crystal structure of the type II beta regulatory subunit.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 11593431
Journal Oncogene
Year 2001
Volume 20
Pages 6225-32
Authors Fukuyama T, Sueoka E, Sugio Y, Otsuka T, Niho Y, Akagi K, Kozu T
Title MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 12381327
Journal J Mol Biol
Year 2002
Volume 323
Pages 377-86
Authors Anand GS, Hughes CA, Jones JM, Taylor SS, Komives EA
Title Amide H/2H exchange reveals communication between the cAMP and catalytic subunit-binding sites in the R(I)alpha subunit of protein kinase A.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 11943768
Journal J Biol Chem
Year 2002
Volume 277
Pages 22902-8
Authors Dahle MK, Gronning LM, Cederberg A, Blomhoff HK, Miura N, Enerback S, Tasken KA, Tasken K
Title Mechanisms of FOXC2- and FOXD1-mediated regulation of the RI alpha subunit of cAMP-dependent protein kinase include release of transcriptional repression and activation by protein kinase B alpha and cAMP.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 11877433
Journal J Biol Chem
Year 2002
Volume 277
Pages 16814-22
Authors Rayner TF, Gray JV, Thorner JW
Title Direct and novel regulation of cAMP-dependent protein kinase by Mck1p, a yeast glycogen synthase kinase-3.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11799117
Journal J Biol Chem
Year 2002
Volume 277
Pages 12423-31
Authors Tung CS, Walsh DA, Trewhella J
Title A structural model of the catalytic subunit-regulatory subunit dimeric complex of the cAMP-dependent protein kinase.
Related PDB
Related UniProtKB

Comments
The E.C. was transferred from 2.7.1.37 to 2.7.11.11.
This protein is a regulatory subunit. The catalytic subunit is separate from this protein (see D00114; Swiss-prot;P00517). The inactive form of the enzyme is composed of two regulatory subunits and two catalytic subunits. Activation by c-AMP results in the two active catalytic subunits and a regulatory dimer that binds four cAMP molecules. This regulatory subunit has two cAMP-binding sites.
The C-terminal domains of this protein have got the cAMP binding sites. The N-terminal domain seems to be involved in dimerization (PDB;1r2a).

Created Updated
2003-07-16 2009-03-19