ID   KAP2_RAT                Reviewed;         401 AA.
AC   P12368; G3V8Q6; Q8K1M2;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   30-AUG-2017, sequence version 4.
DT   24-JAN-2024, entry version 184.
DE   RecName: Full=cAMP-dependent protein kinase type II-alpha regulatory subunit;
GN   Name=Prkar2a;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Testis;
RA   Ziemba A.J., Collard M.W.;
RT   "cDNA sequence and complete coding region of cAMP-dependent protein kinase
RT   type II regulatory subunit from a rat testicular germ cell cDNA library.";
RL   Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 32-401.
RC   TISSUE=Skeletal muscle;
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   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-97, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA   Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT   "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT   regulation of aquaporin-2 phosphorylation at two sites.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN   [6]
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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-97 AND SER-392, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
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 and CBFA2T3 (By similarity). Interacts
CC       with the phosphorylated form of PJA2 (By similarity). Interacts with
CC       MYRIP; his interaction may link PKA to components of the exocytosis
CC       machinery, thus facilitating exocytosis, including insulin release.
CC       Forms a complex composed of PRKAR2A, GSK3B and GSKIP through GSKIP
CC       interaction; facilitates PKA-induced phosphorylation and regulates
CC       GSK3B activity (By similarity). Interacts with ADCY8; inhibits
CC       adenylate cyclase activity through PKA phosphorylation (By similarity).
CC       {ECO:0000250, ECO:0000250|UniProtKB:P13861,
CC       ECO:0000269|PubMed:17827149}.
CC   -!- INTERACTION:
CC       P12368; Q5VU43-11: PDE4DIP; Xeno; NbExp=2; IntAct=EBI-919521, EBI-10769071;
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; AF533978; AAM97689.1; -; mRNA.
DR   EMBL; AC107280; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH473954; EDL77148.1; -; Genomic_DNA.
DR   EMBL; CH473954; EDL77146.1; -; Genomic_DNA.
DR   EMBL; J02934; AAA41856.1; -; mRNA.
DR   PIR; A28325; OKRT2R.
DR   RefSeq; NP_062137.1; NM_019264.2.
DR   PDB; 2DRN; NMR; -; A/B=1-45.
DR   PDB; 2H9R; NMR; -; A/B=1-45.
DR   PDB; 2HWN; X-ray; 1.60 A; A/B/C/D=1-45.
DR   PDB; 3TMH; X-ray; 3.80 A; B/C/F/G=1-45.
DR   PDBsum; 2DRN; -.
DR   PDBsum; 2H9R; -.
DR   PDBsum; 2HWN; -.
DR   PDBsum; 3TMH; -.
DR   AlphaFoldDB; P12368; -.
DR   BMRB; P12368; -.
DR   SMR; P12368; -.
DR   BioGRID; 248317; 1.
DR   CORUM; P12368; -.
DR   DIP; DIP-555N; -.
DR   IntAct; P12368; 6.
DR   MINT; P12368; -.
DR   STRING; 10116.ENSRNOP00000072848; -.
DR   GuidetoPHARMACOLOGY; 1474; -.
DR   iPTMnet; P12368; -.
DR   PhosphoSitePlus; P12368; -.
DR   jPOST; P12368; -.
DR   PaxDb; 10116-ENSRNOP00000027552; -.
DR   Ensembl; ENSRNOT00000027552.4; ENSRNOP00000027552.2; ENSRNOG00000020284.8.
DR   Ensembl; ENSRNOT00055011315; ENSRNOP00055008884; ENSRNOG00055006869.
DR   Ensembl; ENSRNOT00060048689; ENSRNOP00060040602; ENSRNOG00060028005.
DR   Ensembl; ENSRNOT00065010568; ENSRNOP00065007789; ENSRNOG00065006794.
DR   GeneID; 29699; -.
DR   KEGG; rno:29699; -.
DR   UCSC; RGD:3393; rat.
DR   AGR; RGD:3393; -.
DR   CTD; 5576; -.
DR   RGD; 3393; Prkar2a.
DR   eggNOG; KOG1113; Eukaryota.
DR   GeneTree; ENSGT00940000154836; -.
DR   InParanoid; P12368; -.
DR   OrthoDB; 55978at2759; -.
DR   PhylomeDB; P12368; -.
DR   TreeFam; TF314920; -.
DR   Reactome; R-RNO-163615; PKA activation.
DR   Reactome; R-RNO-164378; PKA activation in glucagon signalling.
DR   Reactome; R-RNO-180024; DARPP-32 events.
DR   Reactome; R-RNO-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR   Reactome; R-RNO-442720; CREB1 phosphorylation through the activation of Adenylate Cyclase.
DR   Reactome; R-RNO-5610787; Hedgehog 'off' state.
DR   Reactome; R-RNO-9634597; GPER1 signaling.
DR   Reactome; R-RNO-983231; Factors involved in megakaryocyte development and platelet production.
DR   EvolutionaryTrace; P12368; -.
DR   PRO; PR:P12368; -.
DR   Proteomes; UP000002494; Chromosome 8.
DR   Proteomes; UP000234681; Chromosome 8.
DR   Bgee; ENSRNOG00000020284; Expressed in skeletal muscle tissue and 18 other cell types or tissues.
DR   ExpressionAtlas; P12368; baseline and differential.
DR   GO; GO:0005952; C:cAMP-dependent protein kinase complex; IDA:RGD.
DR   GO; GO:0005813; C:centrosome; ISO:RGD.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR   GO; GO:0031588; C:nucleotide-activated protein kinase complex; ISO:RGD.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0044853; C:plasma membrane raft; ISO:RGD.
DR   GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR   GO; GO:0045202; C:synapse; ISO:RGD.
DR   GO; GO:0030315; C:T-tubule; IDA:RGD.
DR   GO; GO:0031698; F:beta-2 adrenergic receptor binding; IPI:ARUK-UCL.
DR   GO; GO:0030552; F:cAMP binding; IDA:RGD.
DR   GO; GO:0004862; F:cAMP-dependent protein kinase inhibitor activity; ISO:RGD.
DR   GO; GO:0008603; F:cAMP-dependent protein kinase regulator activity; IDA:RGD.
DR   GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR   GO; GO:0019904; F:protein domain specific binding; IDA:RGD.
DR   GO; GO:0034236; F:protein kinase A catalytic subunit binding; ISO:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR   GO; GO:0036094; F:small molecule binding; IDA:RGD.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR   GO; GO:0050804; P:modulation of chemical synaptic transmission; ISO:RGD.
DR   GO; GO:0001932; P:regulation of protein phosphorylation; IEA:InterPro.
DR   CDD; cd00038; CAP_ED; 2.
DR   CDD; cd12103; DD_RIIalpha_PKA; 1.
DR   Gene3D; 1.20.890.10; cAMP-dependent protein kinase regulatory subunit, dimerization-anchoring domain; 1.
DR   Gene3D; 2.60.120.10; Jelly Rolls; 2.
DR   InterPro; IPR012198; cAMP_dep_PK_reg_su.
DR   InterPro; IPR003117; cAMP_dep_PK_reg_su_I/II_a/b.
DR   InterPro; IPR018488; cNMP-bd_CS.
DR   InterPro; IPR000595; cNMP-bd_dom.
DR   InterPro; IPR018490; cNMP-bd_dom_sf.
DR   InterPro; IPR014710; RmlC-like_jellyroll.
DR   PANTHER; PTHR11635; CAMP-DEPENDENT PROTEIN KINASE REGULATORY CHAIN; 1.
DR   PANTHER; PTHR11635:SF153; CAMP-DEPENDENT PROTEIN KINASE TYPE II-ALPHA REGULATORY SUBUNIT; 1.
DR   Pfam; PF00027; cNMP_binding; 2.
DR   Pfam; PF02197; RIIa; 1.
DR   PIRSF; PIRSF000548; PK_regulatory; 1.
DR   PRINTS; PR00103; CAMPKINASE.
DR   SMART; SM00100; cNMP; 2.
DR   SMART; SM00394; RIIa; 1.
DR   SUPFAM; SSF51206; cAMP-binding domain-like; 2.
DR   SUPFAM; SSF47391; Dimerization-anchoring domain of cAMP-dependent PK regulatory subunit; 1.
DR   PROSITE; PS00888; CNMP_BINDING_1; 2.
DR   PROSITE; PS00889; CNMP_BINDING_2; 2.
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                   /evidence="ECO:0000250|UniProtKB:P13861"
FT   CHAIN           2..401
FT                   /note="cAMP-dependent protein kinase type II-alpha
FT                   regulatory subunit"
FT                   /id="PRO_0000205388"
FT   REGION          2..135
FT                   /note="Dimerization and phosphorylation"
FT   REGION          55..85
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        69..83
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                   /evidence="ECO:0000250"
FT   BINDING         205
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         214
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         258..401
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         335
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         344
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000250|UniProtKB:P13861"
FT   MOD_RES         48
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P13861"
FT   MOD_RES         75
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P13861"
FT   MOD_RES         77
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P13861"
FT   MOD_RES         97
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:16641100,
FT                   ECO:0007744|PubMed:22673903"
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:22673903"
FT   CONFLICT        74
FT                   /note="E -> Q (in Ref. 4; AAA41856)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        90
FT                   /note="S -> A (in Ref. 4; AAA41856)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        125
FT                   /note="C -> Y (in Ref. 1; AAM97689)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        154..155
FT                   /note="EK -> KR (in Ref. 4; AAA41856)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        198
FT                   /note="D -> A (in Ref. 4; AAA41856)"
FT                   /evidence="ECO:0000305"
FT   HELIX           10..24
FT                   /evidence="ECO:0007829|PDB:2HWN"
FT   HELIX           29..43
FT                   /evidence="ECO:0007829|PDB:2HWN"
SQ   SEQUENCE   401 AA;  45480 MW;  0D711A1CFEAFB79D CRC64;
     MSHIQIPPGL TELLQGYTVE VLRQQPPDLV DFAVEYFTRL REARRQESDS FIAPPTTFHA
     QESSGVPVIE EDGESESDSD DEDLEVPIPS KFTRRVSVCA ETFNPDEEED NDPRVVHPKT
     DEQRCRLQEA CKDILLFKNL DQEQLSQVLD AMFEKIVKTD EHVIDQGDDG DNFYVIERGT
     YDILVTKDNQ TRSVGQYDNR GSFGELALMY NTPRAATIVA TSDGSLWGLD RVTFRRIIVK
     NNAKKRKMFE SFIESVPLFK SLEMSERMKI VDVIGEKIYK DGERIITQGE KADSFYIIES
     GEVSILIRSK TKTNKNGGNQ EVEIAHCHKG QYFGELALVT NKPRAASAYA VGDVKCLVMD
     VQAFERLLGP CMDIMKRNIS HYEEQLVKMF GSNLDLLDPG Q
//