ID   KAP2_BOVIN              Reviewed;         401 AA.
AC   P00515;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   17-APR-2007, sequence version 2.
DT   03-AUG-2022, entry version 179.
DE   RecName: Full=cAMP-dependent protein kinase type II-alpha regulatory subunit;
GN   Name=PRKAR2A;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   PROTEIN SEQUENCE OF 2-401.
RC   TISSUE=Heart muscle;
RX   PubMed=6283532; DOI=10.1073/pnas.79.8.2544;
RA   Takio K., Smith S.B., Krebs E.G., Walsh K.A., Titani K.;
RT   "Primary structure of the regulatory subunit of type II cAMP-dependent
RT   protein kinase from bovine cardiac muscle.";
RL   Proc. Natl. Acad. Sci. U.S.A. 79:2544-2548(1982).
RN   [2]
RP   PROTEIN SEQUENCE OF 155-166, AND PHOSPHORYLATION AT THR-212.
RX   PubMed=1654846; DOI=10.1016/0003-9861(91)90460-z;
RA   Braun R.K., Vulliet P.R., Carbonaro-Hall D.A., Hall F.L.;
RT   "Phosphorylation of RII subunit and attenuation of cAMP-dependent protein
RT   kinase activity by proline-directed protein kinase.";
RL   Arch. Biochem. Biophys. 289:187-191(1991).
RN   [3]
RP   3D-STRUCTURE MODELING.
RX   PubMed=3030405; DOI=10.1021/bi00376a003;
RA   Weber I.T., Steitz T.A., Bubis J., Taylor S.S.;
RT   "Predicted structures of cAMP binding domains of type I and II regulatory
RT   subunits of cAMP-dependent protein kinase.";
RL   Biochemistry 26:343-351(1987).
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 (By similarity). {ECO:0000250}.
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; this interaction may link PKA to components of the exocytosis
CC       machinery, thus facilitating exocytosis, including insulin release (By
CC       similarity). Forms a complex composed of PRKAR2A, GSK3B and GSKIP
CC       through GSKIP interaction; facilitates PKA-induced phosphorylation and
CC       regulates GSK3B activity (By similarity). Interacts with ADCY8;
CC       inhibits adenylate cyclase activity through PKA phosphorylation (By
CC       similarity). {ECO:0000250, ECO:0000250|UniProtKB:P13861}.
CC   -!- INTERACTION:
CC       P00515; Q6XGM8: C; Xeno; NbExp=3; IntAct=EBI-7634955, EBI-8037154;
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: A second phosphorylation site has not been located.
CC       {ECO:0000269|PubMed:1654846}.
CC   -!- PTM: Phosphorylation of Thr-212 by PDPK1 seems to attenuate the
CC       activity of PKA, perhaps by strengthening interaction between the
CC       regulatory and the catalytic subunits. {ECO:0000269|PubMed:1654846}.
CC   -!- SIMILARITY: Belongs to the cAMP-dependent kinase regulatory chain
CC       family. {ECO:0000305}.
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DR   PIR; A00618; OKBO2R.
DR   RefSeq; NP_001178296.1; NM_001191367.1.
DR   AlphaFoldDB; P00515; -.
DR   SMR; P00515; -.
DR   DIP; DIP-546N; -.
DR   ELM; P00515; -.
DR   IntAct; P00515; 4.
DR   MINT; P00515; -.
DR   STRING; 9913.ENSBTAP00000018886; -.
DR   ChEMBL; CHEMBL2111446; -.
DR   DrugCentral; P00515; -.
DR   iPTMnet; P00515; -.
DR   PaxDb; P00515; -.
DR   PeptideAtlas; P00515; -.
DR   PRIDE; P00515; -.
DR   Ensembl; ENSBTAT00000018886; ENSBTAP00000018886; ENSBTAG00000014205.
DR   GeneID; 100139910; -.
DR   KEGG; bta:100139910; -.
DR   CTD; 5576; -.
DR   VEuPathDB; HostDB:ENSBTAG00000014205; -.
DR   VGNC; VGNC:33325; PRKAR2A.
DR   eggNOG; KOG1113; Eukaryota.
DR   GeneTree; ENSGT00940000154836; -.
DR   HOGENOM; CLU_018310_2_0_1; -.
DR   InParanoid; P00515; -.
DR   OMA; REAVSHN; -.
DR   OrthoDB; 1047290at2759; -.
DR   TreeFam; TF314920; -.
DR   PRO; PR:P00515; -.
DR   Proteomes; UP000009136; Chromosome 22.
DR   Bgee; ENSBTAG00000014205; Expressed in spermatid and 107 other tissues.
DR   GO; GO:0005930; C:axoneme; IEA:Ensembl.
DR   GO; GO:0005952; C:cAMP-dependent protein kinase complex; IBA:GO_Central.
DR   GO; GO:0005813; C:centrosome; IEA:Ensembl.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0031588; C:nucleotide-activated protein kinase complex; IEA:Ensembl.
DR   GO; GO:0044853; C:plasma membrane raft; IEA:Ensembl.
DR   GO; GO:0030552; F:cAMP binding; IBA:GO_Central.
DR   GO; GO:0004862; F:cAMP-dependent protein kinase inhibitor activity; IBA:GO_Central.
DR   GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR   GO; GO:0034236; F:protein kinase A catalytic subunit binding; IBA:GO_Central.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR   GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; IBA:GO_Central.
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; 2.
DR   PROSITE; PS50042; CNMP_BINDING_3; 2.
PE   1: Evidence at protein level;
KW   Acetylation; cAMP; cAMP-binding; Cell membrane; Cytoplasm;
KW   Direct protein sequencing; Membrane; Nucleotide-binding; Phosphoprotein;
KW   Reference proteome; Repeat.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P13861,
FT                   ECO:0000269|PubMed:6283532"
FT   CHAIN           2..401
FT                   /note="cAMP-dependent protein kinase type II-alpha
FT                   regulatory subunit"
FT                   /id="PRO_0000205384"
FT   REGION          2..135
FT                   /note="Dimerization and phosphorylation"
FT   REGION          43..65
FT                   /note="Disordered"
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"
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         96
FT                   /note="Phosphoserine; by PKA"
FT                   /evidence="ECO:0000250|UniProtKB:P13861"
FT   MOD_RES         212
FT                   /note="Phosphothreonine; by PDPK1"
FT                   /evidence="ECO:0000269|PubMed:1654846"
FT   MOD_RES         347
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P13861"
FT   MOD_RES         392
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P13861"
SQ   SEQUENCE   401 AA;  45094 MW;  8FEA32E5B39A545A CRC64;
     MSHIQIPPGL TELLQGYTVE VLRQRPPDLV DFAVDYFTRL REARSRASTP PAAPPSGSQD
     FDPGAGLVAD AVADSESEDE EDLDVPIPGR FDRRVSVCAE TYNPDEEEED TDPRVIHPKT
     DQQRCRLQEA CKDILLFKNL DPEQLSQVLD AMFERTVKVD EHVIDQGDDG DNFYVIERGT
     YDILVTKDNQ TRSVGQYDNH GSFGELALMY NTPRAATIVA TSEGSLWGLD RVTFRRIIVK
     NNAKKRKMFE SFIESVPLLK SLEVSERMKI VDVIGEKVYK DGERIITQGE KADSFYIIES
     GEVSILIKSK TKVNKDGENQ EVEIARCHKG QYFGELALVT NKPRAASAYA VGDVKCLVMD
     VQAFERLLGP CMDIMKRNIS HYEEQLVKMF GSSMDLIDPG Q