KAP2_RAT
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 03-AUG-2022, entry version 176.
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.ENSRNOP00000027552; -.
DR GuidetoPHARMACOLOGY; 1474; -.
DR iPTMnet; P12368; -.
DR PhosphoSitePlus; P12368; -.
DR jPOST; P12368; -.
DR PaxDb; P12368; -.
DR PRIDE; P12368; -.
DR Ensembl; ENSRNOT00000027552; ENSRNOP00000027552; ENSRNOG00000020284.
DR GeneID; 29699; -.
DR KEGG; rno:29699; -.
DR UCSC; RGD:3393; rat.
DR CTD; 5576; -.
DR RGD; 3393; Prkar2a.
DR eggNOG; KOG1113; Eukaryota.
DR GeneTree; ENSGT00940000154836; -.
DR InParanoid; P12368; -.
DR OrthoDB; 1047290at2759; -.
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 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; IDA:RGD.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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: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: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; 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
