KAP2_MOUSE
ID KAP2_MOUSE Reviewed; 401 AA.
AC P12367;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=cAMP-dependent protein kinase type II-alpha regulatory subunit;
GN Name=Prkar2a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=3037538; DOI=10.1073/pnas.84.15.5192;
RA Scott J.D., Glaccum M.B., Zoller M.J., Uhler M.D., Helfman D.M.,
RA McKnight G.S., Krebs E.G.;
RT "The molecular cloning of a type II regulatory subunit of the cAMP-
RT dependent protein kinase from rat skeletal muscle and mouse brain.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:5192-5196(1987).
RN [2]
RP INTERACTION WITH AKAP4.
RX PubMed=9852104; DOI=10.1074/jbc.273.51.34384;
RA Miki K., Eddy E.M.;
RT "Identification of tethering domains for protein kinase A type Ialpha
RT regulatory subunits on sperm fibrous sheath protein FSC1.";
RL J. Biol. Chem. 273:34384-34390(1998).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [4]
RP INTERACTION WITH MYRIP.
RX PubMed=17827149; DOI=10.1074/jbc.m705167200;
RA Goehring A.S., Pedroja B.S., Hinke S.A., Langeberg L.K., Scott J.D.;
RT "MyRIP anchors protein kinase A to the exocyst complex.";
RL J. Biol. Chem. 282:33155-33167(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96 AND SER-392, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP STRUCTURE BY NMR OF 1-44.
RX PubMed=10074940; DOI=10.1038/6663;
RA Newlon M.G., Roy M., Morikis D., Hausken Z.E., Coghlan V., Scott J.D.,
RA Jennings P.A.;
RT "The molecular basis for protein kinase A anchoring revealed by solution
RT NMR.";
RL Nat. Struct. Biol. 6:222-227(1999).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-44.
RX PubMed=17081989; DOI=10.1016/j.molcel.2006.09.006;
RA Gold M.G., Lygren B., Dokurno P., Hoshi N., McConnachie G., Tasken K.,
RA Carlson C.R., Scott J.D., Barford D.;
RT "Molecular basis of AKAP specificity for PKA regulatory subunits.";
RL Mol. Cell 24:383-395(2006).
CC -!- FUNCTION: Regulatory subunit of the cAMP-dependent protein kinases
CC involved in cAMP signaling in cells. Type II regulatory chains mediate
CC membrane association by binding to anchoring proteins, including the
CC MAP2 kinase.
CC -!- SUBUNIT: The inactive form of the enzyme is composed of two regulatory
CC chains and two catalytic chains. Activation by cAMP produces two active
CC catalytic monomers and a regulatory dimer that binds four cAMP
CC molecules. Interacts with AKAP4. Interacts with CBFA2T3 (By
CC similarity). Interacts with the phosphorylated form of PJA2 (By
CC similarity). Interacts with MYRIP. This interaction may link PKA to
CC components of the exocytosis machinery, thus facilitating exocytosis,
CC including insulin release (By similarity). Forms a complex composed of
CC PRKAR2A, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-
CC induced phosphorylation and regulates GSK3B activity (By similarity).
CC Interacts with ADCY8; inhibits adenylate cyclase activity through PKA
CC phosphorylation (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P13861}.
CC -!- INTERACTION:
CC P12367; O54931-3: Akap2; NbExp=3; IntAct=EBI-645747, EBI-645828;
CC P12367; D3YVF0: Akap5; NbExp=2; IntAct=EBI-645747, EBI-7091108;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Note=Colocalizes with PJA2 in the cytoplasm and the cell
CC membrane. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Four types of regulatory chains are found: I-alpha,
CC I-beta, II-alpha, and II-beta. Their expression varies among tissues
CC and is in some cases constitutive and in others inducible.
CC -!- PTM: Phosphorylated by the activated catalytic chain.
CC -!- SIMILARITY: Belongs to the cAMP-dependent kinase regulatory chain
CC family. {ECO:0000305}.
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DR EMBL; J02935; AAA39932.1; -; mRNA.
DR PIR; B28325; OKMS2R.
DR PDB; 1L6E; NMR; -; A/B=1-44.
DR PDB; 1R2A; NMR; -; A/B=3-44.
DR PDB; 2IZY; X-ray; 2.20 A; A/B/C/D/E/F/G/H=3-44.
DR PDB; 2QVS; X-ray; 2.50 A; B=92-401.
DR PDB; 3J4Q; EM; 35.00 A; B/C=1-401.
DR PDB; 3J4R; EM; 35.00 A; B/C=1-401.
DR PDBsum; 1L6E; -.
DR PDBsum; 1R2A; -.
DR PDBsum; 2IZY; -.
DR PDBsum; 2QVS; -.
DR PDBsum; 3J4Q; -.
DR PDBsum; 3J4R; -.
DR AlphaFoldDB; P12367; -.
DR SMR; P12367; -.
DR CORUM; P12367; -.
DR IntAct; P12367; 9.
DR MINT; P12367; -.
DR STRING; 10090.ENSMUSP00000035220; -.
DR iPTMnet; P12367; -.
DR PhosphoSitePlus; P12367; -.
DR EPD; P12367; -.
DR jPOST; P12367; -.
DR MaxQB; P12367; -.
DR PaxDb; P12367; -.
DR PeptideAtlas; P12367; -.
DR PRIDE; P12367; -.
DR ProteomicsDB; 263388; -.
DR MGI; MGI:108025; Prkar2a.
DR eggNOG; KOG1113; Eukaryota.
DR InParanoid; P12367; -.
DR PhylomeDB; P12367; -.
DR Reactome; R-MMU-163615; PKA activation.
DR Reactome; R-MMU-164378; PKA activation in glucagon signalling.
DR Reactome; R-MMU-180024; DARPP-32 events.
DR Reactome; R-MMU-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR Reactome; R-MMU-442720; CREB1 phosphorylation through the activation of Adenylate Cyclase.
DR Reactome; R-MMU-5610787; Hedgehog 'off' state.
DR Reactome; R-MMU-9634597; GPER1 signaling.
DR Reactome; R-MMU-983231; Factors involved in megakaryocyte development and platelet production.
DR ChiTaRS; Prkar2a; mouse.
DR EvolutionaryTrace; P12367; -.
DR PRO; PR:P12367; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P12367; protein.
DR GO; GO:0005930; C:axoneme; ISO:MGI.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IDA:MGI.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0044853; C:plasma membrane raft; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0045202; C:synapse; IDA:SynGO.
DR GO; GO:0030315; C:T-tubule; ISO:MGI.
DR GO; GO:0031698; F:beta-2 adrenergic receptor binding; ISO:MGI.
DR GO; GO:0030552; F:cAMP binding; ISO:MGI.
DR GO; GO:0004862; F:cAMP-dependent protein kinase inhibitor activity; ISO:MGI.
DR GO; GO:0008603; F:cAMP-dependent protein kinase regulator activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0036094; F:small molecule binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IMP:SynGO.
DR GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; ISO:MGI.
DR GO; GO:0045859; P:regulation of protein kinase activity; ISO:MGI.
DR CDD; cd00038; CAP_ED; 2.
DR Gene3D; 2.60.120.10; -; 2.
DR InterPro; IPR012198; cAMP_dep_PK_reg_su.
DR InterPro; IPR003117; cAMP_dep_PK_reg_su_I/II_a/b.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR018488; cNMP-bd_CS.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR Pfam; PF00027; cNMP_binding; 2.
DR Pfam; PF02197; RIIa; 1.
DR PIRSF; PIRSF000548; PK_regulatory; 1.
DR SMART; SM00100; cNMP; 2.
DR SMART; SM00394; RIIa; 1.
DR SUPFAM; SSF51206; SSF51206; 2.
DR PROSITE; PS00888; CNMP_BINDING_1; 2.
DR PROSITE; PS00889; CNMP_BINDING_2; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; cAMP; cAMP-binding; Cell membrane; Cytoplasm;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..401
FT /note="cAMP-dependent protein kinase type II-alpha
FT regulatory subunit"
FT /id="PRO_0000205386"
FT REGION 2..135
FT /note="Dimerization and phosphorylation"
FT REGION 61..83
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 68..82
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 136..257
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT BINDING 205
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT BINDING 214
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT BINDING 258..401
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT BINDING 335
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT BINDING 344
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P13861, ECO:0000305"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13861"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13861"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13861"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 212
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:P00515"
FT MOD_RES 347
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13861"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT HELIX 10..23
FT /evidence="ECO:0007829|PDB:2IZY"
FT HELIX 28..44
FT /evidence="ECO:0007829|PDB:2IZY"
FT HELIX 121..131
FT /evidence="ECO:0007829|PDB:2QVS"
FT HELIX 135..138
FT /evidence="ECO:0007829|PDB:2QVS"
FT HELIX 142..151
FT /evidence="ECO:0007829|PDB:2QVS"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:2QVS"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:2QVS"
FT STRAND 172..178
FT /evidence="ECO:0007829|PDB:2QVS"
FT STRAND 180..187
FT /evidence="ECO:0007829|PDB:2QVS"
FT STRAND 190..199
FT /evidence="ECO:0007829|PDB:2QVS"
FT HELIX 205..208
FT /evidence="ECO:0007829|PDB:2QVS"
FT STRAND 215..230
FT /evidence="ECO:0007829|PDB:2QVS"
FT HELIX 231..254
FT /evidence="ECO:0007829|PDB:2QVS"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:2QVS"
FT HELIX 264..273
FT /evidence="ECO:0007829|PDB:2QVS"
FT STRAND 275..279
FT /evidence="ECO:0007829|PDB:2QVS"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:2QVS"
FT STRAND 294..307
FT /evidence="ECO:0007829|PDB:2QVS"
FT STRAND 311..315
FT /evidence="ECO:0007829|PDB:2QVS"
FT STRAND 322..328
FT /evidence="ECO:0007829|PDB:2QVS"
FT HELIX 335..338
FT /evidence="ECO:0007829|PDB:2QVS"
FT STRAND 345..360
FT /evidence="ECO:0007829|PDB:2QVS"
FT HELIX 361..368
FT /evidence="ECO:0007829|PDB:2QVS"
FT HELIX 371..377
FT /evidence="ECO:0007829|PDB:2QVS"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:2QVS"
FT HELIX 382..390
FT /evidence="ECO:0007829|PDB:2QVS"
SQ SEQUENCE 401 AA; 45389 MW; E4191DAC197A9E39 CRC64;
MSHIQIPPGL TELLQGYTVE VGQQPPDLVD FAVEYFTRLR EARRQESDTF IVSPTTFHTQ
ESSAVPVIEE DGESDSDSED ADLEVPVPSK FTRRVSVCAE TFNPDEEEED NDPRVVHPKT
DEQRCRLQEA CKDILLFKNL DQEQLSQVLD AMFEKIVKTD EHVIDQGDDG DNFYVIERGT
YDILVTKDNQ TRSVGQYDNR GSFGELALMY NTPRAATIIA TSEGSLWGLD RVTFRRIIVK
NNAKKRKMFE SFIESVPLFK SLEMSERMKI VDVIGEKIYK DGERIIAQGE KADSFYIIES
GEVSILIRSK TKSNKNGGNQ EVEIAHCHKG QYFGELALVT NKPRAASAYG VGDVKCLVMD
VQAFERLLGP CMDIMKRNIS HYEEQLVKMF GSNLDLMDPG Q
