Full text data of PRKAR2A
PRKAR2A
(PKR2, PRKAR2)
[Confidence: low (only semi-automatic identification from reviews)]
cAMP-dependent protein kinase type II-alpha regulatory subunit
cAMP-dependent protein kinase type II-alpha regulatory subunit
UniProt
P13861
ID KAP2_HUMAN Reviewed; 404 AA.
AC P13861; Q16823;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=cAMP-dependent protein kinase type II-alpha regulatory subunit;
GN Name=PRKAR2A; Synonyms=PKR2, PRKAR2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=2540040; DOI=10.1016/0014-5793(89)80253-4;
RA Oyen O., Myklebust F., Scott J.D., Hansson V., Jahnsen T.;
RT "Human testis cDNA for the regulatory subunit RII alpha of cAMP-
RT dependent protein kinase encodes an alternate amino-terminal region.";
RL FEBS Lett. 246:57-64(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-87.
RX PubMed=9003463; DOI=10.1016/S0167-4781(96)00152-2;
RA Foss K.B., Solberg R., Simard J., Myklebust F., Hansson V.,
RA Jahnsen T., Tasken K.;
RT "Molecular cloning, upstream sequence and promoter studies of the
RT human gene for the regulatory subunit RII alpha of cAMP-dependent
RT protein kinase.";
RL Biochim. Biophys. Acta 1350:98-108(1997).
RN [3]
RP INTERACTION WITH CBFA2T3.
RX PubMed=11823486;
RA Schillace R.V., Andrews S.F., Liberty G.A., Davey M.P., Carr D.W.;
RT "Identification and characterization of myeloid translocation gene 16b
RT as a novel a kinase anchoring protein in T lymphocytes.";
RL J. Immunol. 168:1590-1599(2002).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pituitary;
RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x;
RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
RT "Phosphoproteomic analysis of the human pituitary.";
RL Pituitary 9:109-120(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Prostate cancer;
RX PubMed=17487921; DOI=10.1002/elps.200600782;
RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
RT "Toward a global characterization of the phosphoproteome in prostate
RT cancer cells: identification of phosphoproteins in the LNCaP cell
RT line.";
RL Electrophoresis 28:2027-2034(2007).
RN [7]
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-54; SER-58; SER-78;
RP SER-80 AND SER-99, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78; SER-80 AND SER-99,
RP AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48; THR-54; SER-58;
RP SER-78 AND SER-80, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PJA2.
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78 AND SER-80, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Regulatory subunit of the cAMP-dependent protein kinases
CC involved in cAMP signaling in cells. Type II regulatory chains
CC mediate membrane association by binding to anchoring proteins,
CC including the MAP2 kinase.
CC -!- SUBUNIT: The inactive form of the enzyme is composed of two
CC regulatory chains and two catalytic chains. Activation by cAMP
CC produces two active catalytic monomers and a regulatory dimer that
CC binds four cAMP molecules. Interacts with AKAP4 and CBFA2T3.
CC Interacts with the phosphorylated form of PJA2. Interacts with
CC MYRIP. This interaction may link PKA to components of the
CC exocytosis machinery, thus facilitating exocytosis, including
CC insulin release (By similarity).
CC -!- INTERACTION:
CC P03259-2:- (xeno); NbExp=5; IntAct=EBI-2556122, EBI-7225021;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Colocalizes
CC with PJA2 in the cytoplasm and the cell membrane.
CC -!- TISSUE SPECIFICITY: Four types of regulatory chains are found: I-
CC alpha, I-beta, II-alpha, and II-beta. Their expression varies
CC among tissues and is in some cases constitutive and in others
CC inducible.
CC -!- PTM: Phosphorylated by the activated catalytic chain.
CC -!- SIMILARITY: Belongs to the cAMP-dependent kinase regulatory chain
CC family.
CC -!- SIMILARITY: Contains 2 cyclic nucleotide-binding domains.
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DR EMBL; X14968; CAA33094.1; -; mRNA.
DR EMBL; X99455; CAA67817.1; -; Genomic_DNA.
DR PIR; S03885; OKHU2R.
DR RefSeq; NP_004148.1; NM_004157.2.
DR RefSeq; XP_005265370.1; XM_005265313.1.
DR UniGene; Hs.631923; -.
DR PDB; 2IZX; X-ray; 1.30 A; A/B=4-43.
DR PDB; 2KYG; NMR; -; A/B=1-45.
DR PDBsum; 2IZX; -.
DR PDBsum; 2KYG; -.
DR ProteinModelPortal; P13861; -.
DR SMR; P13861; 4-44, 96-396.
DR DIP; DIP-552N; -.
DR IntAct; P13861; 17.
DR MINT; MINT-5000495; -.
DR STRING; 9606.ENSP00000265563; -.
DR BindingDB; P13861; -.
DR PhosphoSite; P13861; -.
DR DMDM; 125198; -.
DR OGP; P13861; -.
DR PaxDb; P13861; -.
DR PRIDE; P13861; -.
DR DNASU; 5576; -.
DR Ensembl; ENST00000265563; ENSP00000265563; ENSG00000114302.
DR Ensembl; ENST00000454963; ENSP00000394041; ENSG00000114302.
DR GeneID; 5576; -.
DR KEGG; hsa:5576; -.
DR UCSC; uc003cux.1; human.
DR CTD; 5576; -.
DR GeneCards; GC03M048762; -.
DR HGNC; HGNC:9391; PRKAR2A.
DR HPA; CAB005023; -.
DR MIM; 176910; gene.
DR neXtProt; NX_P13861; -.
DR PharmGKB; PA33757; -.
DR eggNOG; COG0664; -.
DR HOGENOM; HOG000196668; -.
DR HOVERGEN; HBG002025; -.
DR InParanoid; P13861; -.
DR KO; K04739; -.
DR OMA; LEMSERM; -.
DR PhylomeDB; P13861; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P13861; -.
DR ChiTaRS; PRKAR2A; human.
DR EvolutionaryTrace; P13861; -.
DR GeneWiki; PRKAR2A; -.
DR GenomeRNAi; 5576; -.
DR NextBio; 21620; -.
DR PRO; PR:P13861; -.
DR ArrayExpress; P13861; -.
DR Bgee; P13861; -.
DR CleanEx; HS_PRKAR2A; -.
DR Genevestigator; P13861; -.
DR GO; GO:0031588; C:AMP-activated protein kinase complex; IDA:BHF-UCL.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IEA:InterPro.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR GO; GO:0004862; F:cAMP-dependent protein kinase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0008603; F:cAMP-dependent protein kinase regulator activity; NAS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB.
DR GO; GO:0007202; P:activation of phospholipase C activity; TAS:Reactome.
DR GO; GO:0034199; P:activation of protein kinase A activity; TAS:Reactome.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0071377; P:cellular response to glucagon stimulus; TAS:Reactome.
DR GO; GO:0006112; P:energy reserve metabolic process; TAS:Reactome.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0050796; P:regulation of insulin secretion; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR GO; GO:0006833; P:water transport; TAS:Reactome.
DR Gene3D; 2.60.120.10; -; 2.
DR InterPro; IPR002373; cAMP/cGMP_kin.
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 PRINTS; PR00103; CAMPKINASE.
DR SMART; SM00100; cNMP; 2.
DR SMART; SM00394; RIIa; 1.
DR SUPFAM; SSF47391; SSF47391; 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;
KW Complete proteome; Cytoplasm; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 404 cAMP-dependent protein kinase type II-
FT alpha regulatory subunit.
FT /FTId=PRO_0000205385.
FT NP_BIND 139 260 cAMP 1.
FT NP_BIND 261 404 cAMP 2.
FT REGION 2 138 Dimerization and phosphorylation.
FT BINDING 208 208 cAMP 1.
FT BINDING 217 217 cAMP 1.
FT BINDING 338 338 cAMP 2.
FT BINDING 347 347 cAMP 2.
FT MOD_RES 2 2 N-acetylserine (Probable).
FT MOD_RES 48 48 Phosphoserine.
FT MOD_RES 54 54 Phosphothreonine.
FT MOD_RES 58 58 Phosphoserine.
FT MOD_RES 78 78 Phosphoserine.
FT MOD_RES 80 80 Phosphoserine.
FT MOD_RES 99 99 Phosphoserine; by PKA.
FT MOD_RES 215 215 Phosphothreonine; by PDPK1 (By
FT similarity).
FT HELIX 10 24
FT HELIX 29 43
SQ SEQUENCE 404 AA; 45518 MW; C7D6E8E476E1DB65 CRC64;
MSHIQIPPGL TELLQGYTVE VLRQQPPDLV EFAVEYFTRL REARAPASVL PAATPRQSLG
HPPPEPGPDR VADAKGDSES EEDEDLEVPV PSRFNRRVSV CAETYNPDEE EEDTDPRVIH
PKTDEQRCRL QEACKDILLF KNLDQEQLSQ VLDAMFERIV KADEHVIDQG DDGDNFYVIE
RGTYDILVTK DNQTRSVGQY DNRGSFGELA LMYNTPRAAT IVATSEGSLW GLDRVTFRRI
IVKNNAKKRK MFESFIESVP LLKSLEVSER MKIVDVIGEK IYKDGERIIT QGEKADSFYI
IESGEVSILI RSRTKSNKDG GNQEVEIARC HKGQYFGELA LVTNKPRAAS AYAVGDVKCL
VMDVQAFERL LGPCMDIMKR NISHYEEQLV KMFGSSVDLG NLGQ
//
ID KAP2_HUMAN Reviewed; 404 AA.
AC P13861; Q16823;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=cAMP-dependent protein kinase type II-alpha regulatory subunit;
GN Name=PRKAR2A; Synonyms=PKR2, PRKAR2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=2540040; DOI=10.1016/0014-5793(89)80253-4;
RA Oyen O., Myklebust F., Scott J.D., Hansson V., Jahnsen T.;
RT "Human testis cDNA for the regulatory subunit RII alpha of cAMP-
RT dependent protein kinase encodes an alternate amino-terminal region.";
RL FEBS Lett. 246:57-64(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-87.
RX PubMed=9003463; DOI=10.1016/S0167-4781(96)00152-2;
RA Foss K.B., Solberg R., Simard J., Myklebust F., Hansson V.,
RA Jahnsen T., Tasken K.;
RT "Molecular cloning, upstream sequence and promoter studies of the
RT human gene for the regulatory subunit RII alpha of cAMP-dependent
RT protein kinase.";
RL Biochim. Biophys. Acta 1350:98-108(1997).
RN [3]
RP INTERACTION WITH CBFA2T3.
RX PubMed=11823486;
RA Schillace R.V., Andrews S.F., Liberty G.A., Davey M.P., Carr D.W.;
RT "Identification and characterization of myeloid translocation gene 16b
RT as a novel a kinase anchoring protein in T lymphocytes.";
RL J. Immunol. 168:1590-1599(2002).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pituitary;
RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x;
RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
RT "Phosphoproteomic analysis of the human pituitary.";
RL Pituitary 9:109-120(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Prostate cancer;
RX PubMed=17487921; DOI=10.1002/elps.200600782;
RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
RT "Toward a global characterization of the phosphoproteome in prostate
RT cancer cells: identification of phosphoproteins in the LNCaP cell
RT line.";
RL Electrophoresis 28:2027-2034(2007).
RN [7]
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-54; SER-58; SER-78;
RP SER-80 AND SER-99, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78; SER-80 AND SER-99,
RP AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48; THR-54; SER-58;
RP SER-78 AND SER-80, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PJA2.
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78 AND SER-80, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Regulatory subunit of the cAMP-dependent protein kinases
CC involved in cAMP signaling in cells. Type II regulatory chains
CC mediate membrane association by binding to anchoring proteins,
CC including the MAP2 kinase.
CC -!- SUBUNIT: The inactive form of the enzyme is composed of two
CC regulatory chains and two catalytic chains. Activation by cAMP
CC produces two active catalytic monomers and a regulatory dimer that
CC binds four cAMP molecules. Interacts with AKAP4 and CBFA2T3.
CC Interacts with the phosphorylated form of PJA2. Interacts with
CC MYRIP. This interaction may link PKA to components of the
CC exocytosis machinery, thus facilitating exocytosis, including
CC insulin release (By similarity).
CC -!- INTERACTION:
CC P03259-2:- (xeno); NbExp=5; IntAct=EBI-2556122, EBI-7225021;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Colocalizes
CC with PJA2 in the cytoplasm and the cell membrane.
CC -!- TISSUE SPECIFICITY: Four types of regulatory chains are found: I-
CC alpha, I-beta, II-alpha, and II-beta. Their expression varies
CC among tissues and is in some cases constitutive and in others
CC inducible.
CC -!- PTM: Phosphorylated by the activated catalytic chain.
CC -!- SIMILARITY: Belongs to the cAMP-dependent kinase regulatory chain
CC family.
CC -!- SIMILARITY: Contains 2 cyclic nucleotide-binding domains.
CC -----------------------------------------------------------------------
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DR EMBL; X14968; CAA33094.1; -; mRNA.
DR EMBL; X99455; CAA67817.1; -; Genomic_DNA.
DR PIR; S03885; OKHU2R.
DR RefSeq; NP_004148.1; NM_004157.2.
DR RefSeq; XP_005265370.1; XM_005265313.1.
DR UniGene; Hs.631923; -.
DR PDB; 2IZX; X-ray; 1.30 A; A/B=4-43.
DR PDB; 2KYG; NMR; -; A/B=1-45.
DR PDBsum; 2IZX; -.
DR PDBsum; 2KYG; -.
DR ProteinModelPortal; P13861; -.
DR SMR; P13861; 4-44, 96-396.
DR DIP; DIP-552N; -.
DR IntAct; P13861; 17.
DR MINT; MINT-5000495; -.
DR STRING; 9606.ENSP00000265563; -.
DR BindingDB; P13861; -.
DR PhosphoSite; P13861; -.
DR DMDM; 125198; -.
DR OGP; P13861; -.
DR PaxDb; P13861; -.
DR PRIDE; P13861; -.
DR DNASU; 5576; -.
DR Ensembl; ENST00000265563; ENSP00000265563; ENSG00000114302.
DR Ensembl; ENST00000454963; ENSP00000394041; ENSG00000114302.
DR GeneID; 5576; -.
DR KEGG; hsa:5576; -.
DR UCSC; uc003cux.1; human.
DR CTD; 5576; -.
DR GeneCards; GC03M048762; -.
DR HGNC; HGNC:9391; PRKAR2A.
DR HPA; CAB005023; -.
DR MIM; 176910; gene.
DR neXtProt; NX_P13861; -.
DR PharmGKB; PA33757; -.
DR eggNOG; COG0664; -.
DR HOGENOM; HOG000196668; -.
DR HOVERGEN; HBG002025; -.
DR InParanoid; P13861; -.
DR KO; K04739; -.
DR OMA; LEMSERM; -.
DR PhylomeDB; P13861; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P13861; -.
DR ChiTaRS; PRKAR2A; human.
DR EvolutionaryTrace; P13861; -.
DR GeneWiki; PRKAR2A; -.
DR GenomeRNAi; 5576; -.
DR NextBio; 21620; -.
DR PRO; PR:P13861; -.
DR ArrayExpress; P13861; -.
DR Bgee; P13861; -.
DR CleanEx; HS_PRKAR2A; -.
DR Genevestigator; P13861; -.
DR GO; GO:0031588; C:AMP-activated protein kinase complex; IDA:BHF-UCL.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IEA:InterPro.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR GO; GO:0004862; F:cAMP-dependent protein kinase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0008603; F:cAMP-dependent protein kinase regulator activity; NAS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB.
DR GO; GO:0007202; P:activation of phospholipase C activity; TAS:Reactome.
DR GO; GO:0034199; P:activation of protein kinase A activity; TAS:Reactome.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0071377; P:cellular response to glucagon stimulus; TAS:Reactome.
DR GO; GO:0006112; P:energy reserve metabolic process; TAS:Reactome.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0050796; P:regulation of insulin secretion; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR GO; GO:0006833; P:water transport; TAS:Reactome.
DR Gene3D; 2.60.120.10; -; 2.
DR InterPro; IPR002373; cAMP/cGMP_kin.
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 PRINTS; PR00103; CAMPKINASE.
DR SMART; SM00100; cNMP; 2.
DR SMART; SM00394; RIIa; 1.
DR SUPFAM; SSF47391; SSF47391; 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;
KW Complete proteome; Cytoplasm; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 404 cAMP-dependent protein kinase type II-
FT alpha regulatory subunit.
FT /FTId=PRO_0000205385.
FT NP_BIND 139 260 cAMP 1.
FT NP_BIND 261 404 cAMP 2.
FT REGION 2 138 Dimerization and phosphorylation.
FT BINDING 208 208 cAMP 1.
FT BINDING 217 217 cAMP 1.
FT BINDING 338 338 cAMP 2.
FT BINDING 347 347 cAMP 2.
FT MOD_RES 2 2 N-acetylserine (Probable).
FT MOD_RES 48 48 Phosphoserine.
FT MOD_RES 54 54 Phosphothreonine.
FT MOD_RES 58 58 Phosphoserine.
FT MOD_RES 78 78 Phosphoserine.
FT MOD_RES 80 80 Phosphoserine.
FT MOD_RES 99 99 Phosphoserine; by PKA.
FT MOD_RES 215 215 Phosphothreonine; by PDPK1 (By
FT similarity).
FT HELIX 10 24
FT HELIX 29 43
SQ SEQUENCE 404 AA; 45518 MW; C7D6E8E476E1DB65 CRC64;
MSHIQIPPGL TELLQGYTVE VLRQQPPDLV EFAVEYFTRL REARAPASVL PAATPRQSLG
HPPPEPGPDR VADAKGDSES EEDEDLEVPV PSRFNRRVSV CAETYNPDEE EEDTDPRVIH
PKTDEQRCRL QEACKDILLF KNLDQEQLSQ VLDAMFERIV KADEHVIDQG DDGDNFYVIE
RGTYDILVTK DNQTRSVGQY DNRGSFGELA LMYNTPRAAT IVATSEGSLW GLDRVTFRRI
IVKNNAKKRK MFESFIESVP LLKSLEVSER MKIVDVIGEK IYKDGERIIT QGEKADSFYI
IESGEVSILI RSRTKSNKDG GNQEVEIARC HKGQYFGELA LVTNKPRAAS AYAVGDVKCL
VMDVQAFERL LGPCMDIMKR NISHYEEQLV KMFGSSVDLG NLGQ
//
MIM
176910
*RECORD*
*FIELD* NO
176910
*FIELD* TI
*176910 PROTEIN KINASE, cAMP-DEPENDENT, REGULATORY, TYPE II, ALPHA; PRKAR2A
;;PROTEIN KINASE A, RII-ALPHA SUBUNIT
read more*FIELD* TX
See 188830. Phosphorylation by cAMP-dependent protein kinases is
essential for sperm motility. A cAMP-dependent protein kinase is bound
to sperm flagella by a regulatory subunit (RII). Oyen et al. (1989)
observed high testis-specific expression of a human homolog to the rat
RII-alpha mRNA induced in haploid germ cells. They cloned a human cDNA
that encodes a 404-amino acid polypeptide with a region (amino acids
45-75) divergent from that of the previously published mouse and rat
sequences.
By PCR and Southern blot analysis of somatic cell hybrid mapping panels
and by radiation hybrid analysis, Tasken et al. (1998) mapped the
PRKAR2A gene to chromosome 3p21.3-p21.2.
*FIELD* RF
1. Oyen, O.; Myklebust, F.; Scott, J. D.; Hansson, V.; Jahnsen, T.
: Human testis cDNA for the regulatory subunit RII alpha of cAMP-dependent
protein kinase encodes an alternate amino-terminal region. FEBS Lett. 246:
57-64, 1989.
2. Tasken, K.; Naylor, S. L.; Solberg, R.; Jahnsen, T.: Mapping of
the gene encoding the regulatory subunit RII-alpha of cAMP-dependent
protein kinase (locus PRKAR2A) to human chromosome region 3p21.3-p21.2. Genomics 50:
378-381, 1998.
*FIELD* CN
Carol A. Bocchini - updated: 4/4/1999
Mark H. Paalman - updated: 9/5/1996
*FIELD* CD
Victor A. McKusick: 12/9/1987
*FIELD* ED
alopez: 07/24/2001
mgross: 4/6/1999
carol: 4/4/1999
mark: 9/5/1996
terry: 9/5/1996
carol: 3/18/1993
supermim: 3/16/1992
carol: 10/30/1991
carol: 9/17/1991
supermim: 3/20/1990
ddp: 10/27/1989
*RECORD*
*FIELD* NO
176910
*FIELD* TI
*176910 PROTEIN KINASE, cAMP-DEPENDENT, REGULATORY, TYPE II, ALPHA; PRKAR2A
;;PROTEIN KINASE A, RII-ALPHA SUBUNIT
read more*FIELD* TX
See 188830. Phosphorylation by cAMP-dependent protein kinases is
essential for sperm motility. A cAMP-dependent protein kinase is bound
to sperm flagella by a regulatory subunit (RII). Oyen et al. (1989)
observed high testis-specific expression of a human homolog to the rat
RII-alpha mRNA induced in haploid germ cells. They cloned a human cDNA
that encodes a 404-amino acid polypeptide with a region (amino acids
45-75) divergent from that of the previously published mouse and rat
sequences.
By PCR and Southern blot analysis of somatic cell hybrid mapping panels
and by radiation hybrid analysis, Tasken et al. (1998) mapped the
PRKAR2A gene to chromosome 3p21.3-p21.2.
*FIELD* RF
1. Oyen, O.; Myklebust, F.; Scott, J. D.; Hansson, V.; Jahnsen, T.
: Human testis cDNA for the regulatory subunit RII alpha of cAMP-dependent
protein kinase encodes an alternate amino-terminal region. FEBS Lett. 246:
57-64, 1989.
2. Tasken, K.; Naylor, S. L.; Solberg, R.; Jahnsen, T.: Mapping of
the gene encoding the regulatory subunit RII-alpha of cAMP-dependent
protein kinase (locus PRKAR2A) to human chromosome region 3p21.3-p21.2. Genomics 50:
378-381, 1998.
*FIELD* CN
Carol A. Bocchini - updated: 4/4/1999
Mark H. Paalman - updated: 9/5/1996
*FIELD* CD
Victor A. McKusick: 12/9/1987
*FIELD* ED
alopez: 07/24/2001
mgross: 4/6/1999
carol: 4/4/1999
mark: 9/5/1996
terry: 9/5/1996
carol: 3/18/1993
supermim: 3/16/1992
carol: 10/30/1991
carol: 9/17/1991
supermim: 3/20/1990
ddp: 10/27/1989