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
16761
PubChem 5957
6022
1r2aA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1r2aB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1rgsA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1rgsA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain 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 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1r2aB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1rgsA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1rgsA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

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