KAP3_RAT
ID KAP3_RAT Reviewed; 416 AA.
AC P12369;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=cAMP-dependent protein kinase type II-beta regulatory subunit;
GN Name=Prkar2b;
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].
RX PubMed=3401231; DOI=10.1016/0006-291x(88)90197-0;
RA Sandberg M., Levy F.O., Oeyen O., Hansson V., Jahnsen T.;
RT "Molecular cloning, cDNA structure and deduced amino acid sequence for the
RT hormone-induced regulatory subunit (RII beta) of cAMP-dependent protein
RT kinase from rat ovarian granulosa cells.";
RL Biochem. Biophys. Res. Commun. 154:705-711(1988).
RN [2]
RP PRELIMINARY NUCLEOTIDE SEQUENCE OF 16-416.
RC TISSUE=Ovarian granulosa cell;
RX PubMed=2427518; DOI=10.1016/s0021-9258(18)67247-3;
RA Jahnsen T., Hedin L., Kidd V.J., Beattie W.G., Lohmann S.M., Walter U.,
RA Durica J., Schulz T.Z., Schiltz E., Browner M., Lawrence C.B., Goldman D.,
RA Ratoosh S.L., Richards J.S.;
RT "Molecular cloning, cDNA structure, and regulation of the regulatory
RT subunit of type II cAMP-dependent protein kinase from rat ovarian granulosa
RT cells.";
RL J. Biol. Chem. 261:12352-12361(1986).
RN [3]
RP ERRATUM OF PUBMED:2427518.
RA Jahnsen T., Hedin L., Kidd V.J., Beattie W.G., Lohmann S.M., Walter U.,
RA Durica J., Schulz T.Z., Schiltz E., Browner M., Lawrence C.B., Goldman D.,
RA Ratoosh S.L., Richards J.S.;
RL J. Biol. Chem. 263:4041-4041(1988).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112, 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 [5]
RP TISSUE SPECIFICITY.
RX PubMed=21423175; DOI=10.1038/ncb2209;
RA Lignitto L., Carlucci A., Sepe M., Stefan E., Cuomo O., Nistico R.,
RA Scorziello A., Savoia C., Garbi C., Annunziato L., Feliciello A.;
RT "Control of PKA stability and signalling by the RING ligase praja2.";
RL Nat. Cell Biol. 13:412-422(2011).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83; SER-85 AND SER-112, 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).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 112-416.
RX PubMed=11342137; DOI=10.1016/s0969-2126(00)00556-6;
RA Diller T.C., Madhusudan X., Xuong N.H., Taylor S.S.;
RT "Molecular basis for regulatory subunit diversity in cAMP-dependent protein
RT kinase: crystal structure of the type II beta regulatory subunit.";
RL Structure 9:73-82(2001).
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 PRKACA and PRKACB. Interacts with the
CC phosphorylated form of PJA2. Forms a complex composed of PRKAR2B, GSK3B
CC and GSKIP through GSKIP interaction; facilitates PKA-induced
CC phosphorylation and regulates GSK3B activity.
CC {ECO:0000250|UniProtKB:P31323}.
CC -!- INTERACTION:
CC P12369; Q5S007: LRRK2; Xeno; NbExp=3; IntAct=EBI-6096160, EBI-5323863;
CC P12369; P17612: PRKACA; Xeno; NbExp=2; IntAct=EBI-6096160, EBI-476586;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Note=Colocalizes with PJA2 in the cytoplasm and at the
CC cell 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. Brain.
CC Present in a few pyramidal neurons and mostly in mossy fibers.
CC Colocalizes with PJA2 in dentate granule cells and at postsynaptic
CC sites of primary hippocampal neurons. {ECO:0000269|PubMed:21423175}.
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; M12492; AAA42047.1; -; mRNA.
DR PIR; A28893; OKRTR2.
DR RefSeq; NP_001025191.1; NM_001030020.1.
DR PDB; 1CX4; X-ray; 2.45 A; A=112-416.
DR PDB; 3IDB; X-ray; 1.62 A; B=108-268.
DR PDB; 3IDC; X-ray; 2.70 A; B=102-265.
DR PDB; 4JVA; X-ray; 2.50 A; A=112-416.
DR PDB; 6WJF; EM; 7.50 A; C/D=1-416.
DR PDB; 6WJG; EM; 6.20 A; C/D=1-416.
DR PDBsum; 1CX4; -.
DR PDBsum; 3IDB; -.
DR PDBsum; 3IDC; -.
DR PDBsum; 4JVA; -.
DR PDBsum; 6WJF; -.
DR PDBsum; 6WJG; -.
DR AlphaFoldDB; P12369; -.
DR SMR; P12369; -.
DR BioGRID; 246811; 2.
DR CORUM; P12369; -.
DR DIP; DIP-61323N; -.
DR IntAct; P12369; 3.
DR STRING; 10116.ENSRNOP00000012415; -.
DR GuidetoPHARMACOLOGY; 1475; -.
DR iPTMnet; P12369; -.
DR PhosphoSitePlus; P12369; -.
DR jPOST; P12369; -.
DR PaxDb; P12369; -.
DR PRIDE; P12369; -.
DR Ensembl; ENSRNOT00000012415; ENSRNOP00000012415; ENSRNOG00000009079.
DR GeneID; 24679; -.
DR KEGG; rno:24679; -.
DR UCSC; RGD:3394; rat.
DR CTD; 5577; -.
DR RGD; 3394; Prkar2b.
DR eggNOG; KOG1113; Eukaryota.
DR GeneTree; ENSGT00940000158160; -.
DR HOGENOM; CLU_018310_2_0_1; -.
DR InParanoid; P12369; -.
DR OMA; YDNWSPP; -.
DR OrthoDB; 1047290at2759; -.
DR PhylomeDB; P12369; -.
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-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-RNO-380259; Loss of Nlp from mitotic centrosomes.
DR Reactome; R-RNO-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-RNO-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
DR Reactome; R-RNO-380320; Recruitment of NuMA to mitotic centrosomes.
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-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-RNO-8854518; AURKA Activation by TPX2.
DR Reactome; R-RNO-9634597; GPER1 signaling.
DR Reactome; R-RNO-983231; Factors involved in megakaryocyte development and platelet production.
DR EvolutionaryTrace; P12369; -.
DR PRO; PR:P12369; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000009079; Expressed in ovary and 19 other tissues.
DR ExpressionAtlas; P12369; baseline and differential.
DR Genevisible; P12369; RN.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IDA:RGD.
DR GO; GO:0005813; C:centrosome; ISO:RGD.
DR GO; GO:0097546; C:ciliary base; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0043198; C:dendritic shaft; ISS:ParkinsonsUK-UCL.
DR GO; GO:0043197; C:dendritic spine; ISS:ParkinsonsUK-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0098794; C:postsynapse; IDA:SynGO.
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:0019904; F:protein domain specific binding; IDA:RGD.
DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0006631; P:fatty acid metabolic process; ISO:RGD.
DR GO; GO:0007612; P:learning; ISO:RGD.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISO:RGD.
DR GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; ISO:RGD.
DR GO; GO:0045859; P:regulation of protein kinase activity; IDA:RGD.
DR GO; GO:0097332; P:response to antipsychotic drug; IEP:RGD.
DR GO; GO:0097338; P:response to clozapine; IEP:RGD.
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 3D-structure; cAMP; cAMP-binding; Cell membrane; Cytoplasm; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..416
FT /note="cAMP-dependent protein kinase type II-beta
FT regulatory subunit"
FT /id="PRO_0000205392"
FT REGION 2..151
FT /note="Dimerization and phosphorylation"
FT REGION 53..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 152..273
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT BINDING 221
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT BINDING 230
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT BINDING 274..416
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT BINDING 350
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT BINDING 359
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT MOD_RES 69
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P31323"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 112
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100,
FT ECO:0007744|PubMed:22673903"
FT HELIX 137..147
FT /evidence="ECO:0007829|PDB:3IDB"
FT HELIX 151..154
FT /evidence="ECO:0007829|PDB:3IDB"
FT HELIX 158..167
FT /evidence="ECO:0007829|PDB:3IDB"
FT STRAND 169..173
FT /evidence="ECO:0007829|PDB:3IDB"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:3IDB"
FT STRAND 188..203
FT /evidence="ECO:0007829|PDB:3IDB"
FT STRAND 206..215
FT /evidence="ECO:0007829|PDB:3IDB"
FT HELIX 221..224
FT /evidence="ECO:0007829|PDB:3IDB"
FT STRAND 231..246
FT /evidence="ECO:0007829|PDB:3IDB"
FT HELIX 247..259
FT /evidence="ECO:0007829|PDB:3IDB"
FT HELIX 273..275
FT /evidence="ECO:0007829|PDB:1CX4"
FT STRAND 276..278
FT /evidence="ECO:0007829|PDB:4JVA"
FT HELIX 280..289
FT /evidence="ECO:0007829|PDB:1CX4"
FT STRAND 291..295
FT /evidence="ECO:0007829|PDB:1CX4"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:1CX4"
FT STRAND 310..324
FT /evidence="ECO:0007829|PDB:1CX4"
FT STRAND 336..342
FT /evidence="ECO:0007829|PDB:1CX4"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:1CX4"
FT HELIX 351..355
FT /evidence="ECO:0007829|PDB:1CX4"
FT STRAND 360..375
FT /evidence="ECO:0007829|PDB:1CX4"
FT HELIX 376..382
FT /evidence="ECO:0007829|PDB:1CX4"
FT HELIX 384..386
FT /evidence="ECO:0007829|PDB:1CX4"
FT HELIX 387..405
FT /evidence="ECO:0007829|PDB:1CX4"
SQ SEQUENCE 416 AA; 46123 MW; 8BC984E325FA3612 CRC64;
MSIEIPAGLT ELLQGFTVEV LRHQPADLLE FALQHFTRLQ QENERKGAAR FGHEGRTWGD
AGAAAGGGTP SKGVNFAEEP MRSDSENGEE EEAAEAGAFN APVINRFTRR ASVCAEAYNP
DEEEDDAESR IIHPKTDDQR NRLQEACKDI LLFKNLDPEQ MSQVLDAMFE KLVKEGEHVI
DQGDDGDNFY VIDRGTFDIY VKCDGVGRCV GNYDNRGSFG ELALMYNTPR AATITATSPG
ALWGLDRVTF RRIIVKNNAK KRKMYESFIE SLPFLKSLEV SERLKVVDVI GTKVYNDGEQ
IIAQGDSADS FFIVESGEVR ITMKRKGKSD IEENGAVEIA RCLRGQYFGE LALVTNKPRA
ASAHAIGTVK CLAMDVQAFE RLLGPCMEIM KRNIATYEEQ LVALFGTNMD IVEPTA
