KAPR2_DROME
ID KAPR2_DROME Reviewed; 377 AA.
AC P81900; A1A6P8; A1A6T9; A2RVH2; A4UZA6; A8DY87; A8DY88; Q9NB18; Q9V5E8;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=cAMP-dependent protein kinase type II regulatory subunit;
GN Name=Pka-R2; Synonyms=pka-RII; ORFNames=CG15862;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), AND FUNCTION.
RX PubMed=10781603; DOI=10.1074/jbc.m002460200;
RA Park S.K., Sedore S.A., Cronmiller C., Hirsh J.;
RT "Type II cAMP-dependent protein kinase-deficient Drosophila are viable but
RT show developmental, circadian, and drug response phenotypes.";
RL J. Biol. Chem. 275:20588-20596(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS D AND E).
RC STRAIN=Berkeley;
RA Stapleton M., Carlson J.W., Frise E., Kapadia B., Park S., Wan K.H., Yu C.,
RA Celniker S.E.;
RL Submitted (JAN-2007) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 131-143 AND 353-365, FUNCTION, SUBUNIT, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=Canton-S; TISSUE=Head;
RX PubMed=9196067; DOI=10.1006/bbrc.1997.6764;
RA Inoue H., Yoshioka T.;
RT "Purification of a regulatory subunit of type II cAMP-dependent protein
RT kinase from Drosophila heads.";
RL Biochem. Biophys. Res. Commun. 235:223-226(1997).
RN [7]
RP INTERACTION WITH AKAP200, AND SUBCELLULAR LOCATION.
RX PubMed=10480936; DOI=10.1074/jbc.274.38.27191;
RA Li Z., Rossi E.A., Hoheisel J.D., Kalderon D., Rubin C.S.;
RT "Generation of a novel A kinase anchor protein and a myristoylated alanine-
RT rich C kinase substrate-like analog from a single gene.";
RL J. Biol. Chem. 274:27191-27200(1999).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12223401; DOI=10.1242/dev.129.19.4423;
RA Jackson S.M., Berg C.A.;
RT "An A-kinase anchoring protein is required for protein kinase A regulatory
RT subunit localization and morphology of actin structures during oogenesis in
RT Drosophila.";
RL Development 129:4423-4433(2002).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-58; SER-64; SER-67;
RP SER-84 AND TYR-90, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29444420; DOI=10.1016/j.celrep.2018.01.049;
RA Parkhurst S.J., Adhikari P., Navarrete J.S., Legendre A., Manansala M.,
RA Wolf F.W.;
RT "Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-
RT Dependent Manner to Promote Tolerance.";
RL Cell Rep. 22:1647-1656(2018).
CC -!- FUNCTION: Regulatory subunit of the cAMP-dependent protein kinases
CC involved in cAMP signaling in cells (PubMed:10781603, PubMed:9196067).
CC Mediates membrane association by binding to anchoring proteins, such as
CC Akap200 (PubMed:9196067, PubMed:12223401). Might play an essential role
CC in the regulation of neuronal activity in the brain (PubMed:10781603,
CC PubMed:9196067). {ECO:0000269|PubMed:10781603,
CC ECO:0000269|PubMed:12223401, ECO:0000269|PubMed:9196067}.
CC -!- SUBUNIT: Tetramer, composed of 2 regulatory (R) and 2 catalytic (C)
CC subunits (PubMed:9196067). In the presence of cAMP it dissociates into
CC 2 active monomeric C subunits and an R dimer (By similarity). Interacts
CC with Akap200 (PubMed:10480936). {ECO:0000250|UniProtKB:Q95ZQ4,
CC ECO:0000269|PubMed:10480936, ECO:0000269|PubMed:9196067}.
CC -!- INTERACTION:
CC P81900; Q9VW17: BcDNA:RH51268; NbExp=4; IntAct=EBI-129349, EBI-3409728;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10480936,
CC ECO:0000269|PubMed:9196067}. Cell membrane
CC {ECO:0000269|PubMed:12223401}. Note=Localization to the membrane
CC depends on Akap200. {ECO:0000269|PubMed:12223401}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A {ECO:0000312|FlyBase:FBgn0022382}; Synonyms=B
CC {ECO:0000312|FlyBase:FBgn0022382};
CC IsoId=P81900-1; Sequence=Displayed;
CC Name=E {ECO:0000312|FlyBase:FBgn0022382};
CC IsoId=P81900-2; Sequence=VSP_026945, VSP_026946;
CC Name=D {ECO:0000312|FlyBase:FBgn0022382};
CC IsoId=P81900-5; Sequence=VSP_058165;
CC -!- TISSUE SPECIFICITY: Detected in follicle cells, germline-derived cells,
CC germline line stem cells and outer rim of ring canals of nurse cells
CC throughout oogenesis (at protein level). {ECO:0000269|PubMed:12223401}.
CC -!- PTM: The pseudophosphorylation site binds to the substrate-binding
CC region of the catalytic chain but is not phosphorylated. The
CC physiological significance of phosphorylations by other kinases is
CC unclear (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown increases ethanol
CC sedation sensitivity when first exposed to ethanol and decreases
CC ethanol tolerance following repeated ethanol exposure.
CC {ECO:0000269|PubMed:29444420}.
CC -!- SIMILARITY: Belongs to the cAMP-dependent kinase regulatory chain
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABL75628.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
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DR EMBL; AF274008; AAF86976.1; -; mRNA.
DR EMBL; AE013599; AAF58862.2; -; Genomic_DNA.
DR EMBL; AE013599; AAM71046.3; -; Genomic_DNA.
DR EMBL; AE013599; ABV53747.1; -; Genomic_DNA.
DR EMBL; AE013599; ABV53748.1; -; Genomic_DNA.
DR EMBL; AY069669; AAL39814.1; -; mRNA.
DR EMBL; BT029569; ABL75628.1; ALT_SEQ; mRNA.
DR EMBL; BT029610; ABL75669.1; -; mRNA.
DR EMBL; BT029637; ABL75696.1; -; mRNA.
DR EMBL; BT029963; ABM92837.1; -; mRNA.
DR RefSeq; NP_001097251.1; NM_001103781.3. [P81900-5]
DR RefSeq; NP_001097252.1; NM_001103782.2. [P81900-2]
DR RefSeq; NP_523671.1; NM_078947.4. [P81900-1]
DR RefSeq; NP_724860.2; NM_165723.4. [P81900-1]
DR AlphaFoldDB; P81900; -.
DR SMR; P81900; -.
DR BioGRID; 61869; 9.
DR IntAct; P81900; 24.
DR STRING; 7227.FBpp0087524; -.
DR iPTMnet; P81900; -.
DR PaxDb; P81900; -.
DR PRIDE; P81900; -.
DR DNASU; 36041; -.
DR EnsemblMetazoa; FBtr0088437; FBpp0087523; FBgn0022382. [P81900-1]
DR EnsemblMetazoa; FBtr0088438; FBpp0087524; FBgn0022382. [P81900-1]
DR EnsemblMetazoa; FBtr0112901; FBpp0111814; FBgn0022382. [P81900-5]
DR EnsemblMetazoa; FBtr0112902; FBpp0111815; FBgn0022382. [P81900-2]
DR GeneID; 36041; -.
DR KEGG; dme:Dmel_CG15862; -.
DR UCSC; CG15862-RD; d. melanogaster.
DR UCSC; CG15862-RE; d. melanogaster.
DR CTD; 36041; -.
DR FlyBase; FBgn0022382; Pka-R2.
DR VEuPathDB; VectorBase:FBgn0022382; -.
DR eggNOG; KOG1113; Eukaryota.
DR GeneTree; ENSGT00940000154836; -.
DR HOGENOM; CLU_018310_1_1_1; -.
DR InParanoid; P81900; -.
DR OMA; YDNWSPP; -.
DR PhylomeDB; P81900; -.
DR Reactome; R-DME-163615; PKA activation.
DR Reactome; R-DME-164378; PKA activation in glucagon signalling.
DR Reactome; R-DME-180024; DARPP-32 events.
DR Reactome; R-DME-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR Reactome; R-DME-442720; CREB1 phosphorylation through the activation of Adenylate Cyclase.
DR Reactome; R-DME-5610787; Hedgehog 'off' state.
DR Reactome; R-DME-9634597; GPER1 signaling.
DR Reactome; R-DME-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; P81900; -.
DR BioGRID-ORCS; 36041; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 36041; -.
DR PRO; PR:P81900; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0022382; Expressed in brain and 34 other tissues.
DR Genevisible; P81900; DM.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; HDA:FlyBase.
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:0034236; F:protein kinase A catalytic subunit binding; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IMP:FlyBase.
DR GO; GO:0048148; P:behavioral response to cocaine; IMP:UniProtKB.
DR GO; GO:0048149; P:behavioral response to ethanol; IMP:UniProtKB.
DR GO; GO:0071361; P:cellular response to ethanol; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; NAS:FlyBase.
DR GO; GO:0045475; P:locomotor rhythm; IMP:UniProtKB.
DR GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0007622; P:rhythmic behavior; TAS:FlyBase.
DR CDD; cd00038; CAP_ED; 2.
DR Gene3D; 2.60.120.10; -; 2.
DR InterPro; IPR012198; cAMP_dep_PK_reg_su.
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 PIRSF; PIRSF000548; PK_regulatory; 1.
DR SMART; SM00100; cNMP; 2.
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 Alternative splicing; Biological rhythms; cAMP; cAMP-binding;
KW Cell membrane; Cytoplasm; Direct protein sequencing; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..377
FT /note="cAMP-dependent protein kinase type II regulatory
FT subunit"
FT /id="PRO_0000205397"
FT REGION 48..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 81..85
FT /note="Pseudophosphorylation motif"
FT COMPBIAS 48..69
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 124..239
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT BINDING 189
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 198
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 242..362
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT BINDING 311
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 320
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 84
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 90
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT VAR_SEQ 338..377
FT /note="VKAFERLLGPCMDIMKRNIDDYESQLVKIFGSKNNITDTR -> TEAFERIM
FT GFLTDVLKRNIVIYEQMFTDMARRNTNL (in isoform D)"
FT /evidence="ECO:0000305"
FT /id="VSP_058165"
FT VAR_SEQ 339..340
FT /note="KA -> IC (in isoform E)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_026945"
FT VAR_SEQ 345..377
FT /note="LGPCMDIMKRNIDDYESQLVKIFGSKNNITDTR -> MGKCSGGIQRSISGY
FT RYLEQDLREYFGNLPLN (in isoform E)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_026946"
SQ SEQUENCE 377 AA; 42748 MW; 26C9EF6562CCACCC CRC64;
MSSDSSRRIQ VPEELKEVLL QFSISFLVEQ PPDVIDYAVE YFTKLQSERP SVSHTDQSTD
DQLSVNSQDA DAEPPVMASS RRKSVFAEAY DPEADDDDDG ATAVFPKTDE QRARLVESVK
NVLLFRSLEK EQMNQVLDAM FERKVQPGDF IIRQGDDGDN FYVIESGVYK VYINDKHINT
YNHTGLFGEL ALLYNMPRAA TVQAETSGLL WAMDRQTFRR ILLKSAFRKR KMYEELLNSV
PMLKALQNYE RMNLADALVS KSYDNGERII KQGDAADGMY FIEEGTVSVR MDQDDAEVEI
SQLGKGQYFG ELALVTHRPR AASVYATGGV VKLAFLDVKA FERLLGPCMD IMKRNIDDYE
SQLVKIFGSK NNITDTR
