Full text data of PRKAR2B
PRKAR2B
[Confidence: low (only semi-automatic identification from reviews)]
cAMP-dependent protein kinase type II-beta regulatory subunit
cAMP-dependent protein kinase type II-beta regulatory subunit
UniProt
P31323
ID KAP3_HUMAN Reviewed; 418 AA.
AC P31323; A4D0R9;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-SEP-2008, sequence version 3.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=cAMP-dependent protein kinase type II-beta regulatory subunit;
GN Name=PRKAR2B;
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=2851102;
RA Levy F.O., Oeyen O., Sandberg M., Tasken K., Eskild W., Hansson V.,
RA Jahnsen T.;
RT "Molecular cloning, complementary deoxyribonucleic acid structure and
RT predicted full-length amino acid sequence of the hormone-inducible
RT regulatory subunit of 3'-5'-cyclic adenosine monophosphate-dependent
RT protein kinase from human testis.";
RL Mol. Endocrinol. 2:1364-1373(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA Mural R.J., Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114, 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 [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114, AND MASS
RP 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 [8]
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 [9]
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83; SER-85 AND SER-114,
RP AND MASS 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 the phosphorylated form
CC of PJA2.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Colocalizes
CC with PJA2 in the cytoplasm and at 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; M31158; AAA60099.1; -; mRNA.
DR EMBL; AK291441; BAF84130.1; -; mRNA.
DR EMBL; CH236947; EAL24395.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83390.1; -; Genomic_DNA.
DR PIR; A40915; OKHUR2.
DR RefSeq; NP_002727.2; NM_002736.2.
DR UniGene; Hs.433068; -.
DR ProteinModelPortal; P31323; -.
DR SMR; P31323; 8-39, 78-414.
DR DIP; DIP-554N; -.
DR IntAct; P31323; 6.
DR MINT; MINT-2782562; -.
DR STRING; 9606.ENSP00000265717; -.
DR BindingDB; P31323; -.
DR PhosphoSite; P31323; -.
DR DMDM; 206729918; -.
DR OGP; P31323; -.
DR PaxDb; P31323; -.
DR PRIDE; P31323; -.
DR DNASU; 5577; -.
DR Ensembl; ENST00000265717; ENSP00000265717; ENSG00000005249.
DR GeneID; 5577; -.
DR KEGG; hsa:5577; -.
DR UCSC; uc003vdx.3; human.
DR CTD; 5577; -.
DR GeneCards; GC07P106685; -.
DR H-InvDB; HIX0025309; -.
DR HGNC; HGNC:9392; PRKAR2B.
DR HPA; HPA008421; -.
DR MIM; 176912; gene.
DR neXtProt; NX_P31323; -.
DR PharmGKB; PA33758; -.
DR eggNOG; COG0664; -.
DR HOGENOM; HOG000196668; -.
DR HOVERGEN; HBG002025; -.
DR InParanoid; P31323; -.
DR KO; K04739; -.
DR OMA; PMHSDSE; -.
DR OrthoDB; EOG76T9RR; -.
DR PhylomeDB; P31323; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_115566; Cell Cycle.
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 GeneWiki; PRKAR2B; -.
DR GenomeRNAi; 5577; -.
DR NextBio; 21624; -.
DR PRO; PR:P31323; -.
DR ArrayExpress; P31323; -.
DR Bgee; P31323; -.
DR CleanEx; HS_PRKAR2B; -.
DR Genevestigator; P31323; -.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IEA:Ensembl.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
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; IDA:BHF-UCL.
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:0006631; P:fatty acid metabolic process; IEA:Ensembl.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; 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:0007612; P:learning; IEA:Ensembl.
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:0097332; P:response to antipsychotic drug; IEA:Ensembl.
DR GO; GO:0097338; P:response to clozapine; IEA:Ensembl.
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 Acetylation; cAMP; cAMP-binding; Cell membrane; Complete proteome;
KW Cytoplasm; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat.
FT INIT_MET 1 1 Removed (Probable).
FT CHAIN 2 418 cAMP-dependent protein kinase type II-
FT beta regulatory subunit.
FT /FTId=PRO_0000205390.
FT NP_BIND 154 275 cAMP 1.
FT NP_BIND 276 418 cAMP 2.
FT REGION 2 153 Dimerization and phosphorylation.
FT BINDING 223 223 cAMP 1.
FT BINDING 232 232 cAMP 1.
FT BINDING 352 352 cAMP 2.
FT BINDING 361 361 cAMP 2.
FT MOD_RES 2 2 N-acetylserine (Probable).
FT MOD_RES 83 83 Phosphoserine.
FT MOD_RES 85 85 Phosphoserine.
FT MOD_RES 114 114 Phosphoserine.
FT VARIANT 335 335 E -> D (in dbSNP:rs3729881).
FT /FTId=VAR_046549.
FT CONFLICT 341 342 IA -> MP (in Ref. 1; AAA60099).
SQ SEQUENCE 418 AA; 46302 MW; 83F402CCFFEFD186 CRC64;
MSIEIPAGLT ELLQGFTVEV LRHQPADLLE FALQHFTRLQ QENERKGTAR FGHEGRTWGD
LGAAAGGGTP SKGVNFAEEP MQSDSEDGEE EEAAPADAGA FNAPVINRFT RRASVCAEAY
NPDEEEDDAE SRIIHPKTDD QRNRLQEACK DILLFKNLDP EQMSQVLDAM FEKLVKDGEH
VIDQGDDGDN FYVIDRGTFD IYVKCDGVGR CVGNYDNRGS FGELALMYNT PRAATITATS
PGALWGLDRV TFRRIIVKNN AKKRKMYESF IESLPFLKSL EFSERLKVVD VIGTKVYNDG
EQIIAQGDSA DSFFIVESGE VKITMKRKGK SEVEENGAVE IARCSRGQYF GELALVTNKP
RAASAHAIGT VKCLAMDVQA FERLLGPCME IMKRNIATYE EQLVALFGTN MDIVEPTA
//
ID KAP3_HUMAN Reviewed; 418 AA.
AC P31323; A4D0R9;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-SEP-2008, sequence version 3.
DT 22-JAN-2014, entry version 132.
DE RecName: Full=cAMP-dependent protein kinase type II-beta regulatory subunit;
GN Name=PRKAR2B;
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=2851102;
RA Levy F.O., Oeyen O., Sandberg M., Tasken K., Eskild W., Hansson V.,
RA Jahnsen T.;
RT "Molecular cloning, complementary deoxyribonucleic acid structure and
RT predicted full-length amino acid sequence of the hormone-inducible
RT regulatory subunit of 3'-5'-cyclic adenosine monophosphate-dependent
RT protein kinase from human testis.";
RL Mol. Endocrinol. 2:1364-1373(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA Mural R.J., Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114, 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 [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114, AND MASS
RP 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 [8]
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 [9]
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83; SER-85 AND SER-114,
RP AND MASS 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 the phosphorylated form
CC of PJA2.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Colocalizes
CC with PJA2 in the cytoplasm and at 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 -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M31158; AAA60099.1; -; mRNA.
DR EMBL; AK291441; BAF84130.1; -; mRNA.
DR EMBL; CH236947; EAL24395.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83390.1; -; Genomic_DNA.
DR PIR; A40915; OKHUR2.
DR RefSeq; NP_002727.2; NM_002736.2.
DR UniGene; Hs.433068; -.
DR ProteinModelPortal; P31323; -.
DR SMR; P31323; 8-39, 78-414.
DR DIP; DIP-554N; -.
DR IntAct; P31323; 6.
DR MINT; MINT-2782562; -.
DR STRING; 9606.ENSP00000265717; -.
DR BindingDB; P31323; -.
DR PhosphoSite; P31323; -.
DR DMDM; 206729918; -.
DR OGP; P31323; -.
DR PaxDb; P31323; -.
DR PRIDE; P31323; -.
DR DNASU; 5577; -.
DR Ensembl; ENST00000265717; ENSP00000265717; ENSG00000005249.
DR GeneID; 5577; -.
DR KEGG; hsa:5577; -.
DR UCSC; uc003vdx.3; human.
DR CTD; 5577; -.
DR GeneCards; GC07P106685; -.
DR H-InvDB; HIX0025309; -.
DR HGNC; HGNC:9392; PRKAR2B.
DR HPA; HPA008421; -.
DR MIM; 176912; gene.
DR neXtProt; NX_P31323; -.
DR PharmGKB; PA33758; -.
DR eggNOG; COG0664; -.
DR HOGENOM; HOG000196668; -.
DR HOVERGEN; HBG002025; -.
DR InParanoid; P31323; -.
DR KO; K04739; -.
DR OMA; PMHSDSE; -.
DR OrthoDB; EOG76T9RR; -.
DR PhylomeDB; P31323; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_115566; Cell Cycle.
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 GeneWiki; PRKAR2B; -.
DR GenomeRNAi; 5577; -.
DR NextBio; 21624; -.
DR PRO; PR:P31323; -.
DR ArrayExpress; P31323; -.
DR Bgee; P31323; -.
DR CleanEx; HS_PRKAR2B; -.
DR Genevestigator; P31323; -.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IEA:Ensembl.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
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; IDA:BHF-UCL.
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:0006631; P:fatty acid metabolic process; IEA:Ensembl.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; 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:0007612; P:learning; IEA:Ensembl.
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:0097332; P:response to antipsychotic drug; IEA:Ensembl.
DR GO; GO:0097338; P:response to clozapine; IEA:Ensembl.
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 Acetylation; cAMP; cAMP-binding; Cell membrane; Complete proteome;
KW Cytoplasm; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat.
FT INIT_MET 1 1 Removed (Probable).
FT CHAIN 2 418 cAMP-dependent protein kinase type II-
FT beta regulatory subunit.
FT /FTId=PRO_0000205390.
FT NP_BIND 154 275 cAMP 1.
FT NP_BIND 276 418 cAMP 2.
FT REGION 2 153 Dimerization and phosphorylation.
FT BINDING 223 223 cAMP 1.
FT BINDING 232 232 cAMP 1.
FT BINDING 352 352 cAMP 2.
FT BINDING 361 361 cAMP 2.
FT MOD_RES 2 2 N-acetylserine (Probable).
FT MOD_RES 83 83 Phosphoserine.
FT MOD_RES 85 85 Phosphoserine.
FT MOD_RES 114 114 Phosphoserine.
FT VARIANT 335 335 E -> D (in dbSNP:rs3729881).
FT /FTId=VAR_046549.
FT CONFLICT 341 342 IA -> MP (in Ref. 1; AAA60099).
SQ SEQUENCE 418 AA; 46302 MW; 83F402CCFFEFD186 CRC64;
MSIEIPAGLT ELLQGFTVEV LRHQPADLLE FALQHFTRLQ QENERKGTAR FGHEGRTWGD
LGAAAGGGTP SKGVNFAEEP MQSDSEDGEE EEAAPADAGA FNAPVINRFT RRASVCAEAY
NPDEEEDDAE SRIIHPKTDD QRNRLQEACK DILLFKNLDP EQMSQVLDAM FEKLVKDGEH
VIDQGDDGDN FYVIDRGTFD IYVKCDGVGR CVGNYDNRGS FGELALMYNT PRAATITATS
PGALWGLDRV TFRRIIVKNN AKKRKMYESF IESLPFLKSL EFSERLKVVD VIGTKVYNDG
EQIIAQGDSA DSFFIVESGE VKITMKRKGK SEVEENGAVE IARCSRGQYF GELALVTNKP
RAASAHAIGT VKCLAMDVQA FERLLGPCME IMKRNIATYE EQLVALFGTN MDIVEPTA
//
MIM
176912
*RECORD*
*FIELD* NO
176912
*FIELD* TI
*176912 PROTEIN KINASE, cAMP-DEPENDENT, REGULATORY, TYPE II, BETA; PRKAR2B
;;PRKAR2;;
read moreRII-BETA
*FIELD* TX
DESCRIPTION
The cAMP-dependent protein kinase system is believed to mediate most, if
not all, cellular effects of the second messenger cAMP. The kinase
holoenzyme consists of 2 regulatory (R) and 2 catalytic (C) subunits
that dissociate upon the binding of 2 cAMP molecules to each of the R
subunits. The free, activated C subunits then catalyze the
phosphorylation of specific substrate proteins on serine and threonine
residues and thereby alter their activity or function. PRKAR2B is 1 of
several R subunits (Levy et al., 1988).
CLONING
Using rat Prkar2b as probe, Levy et al. (1988) cloned PRKAR2B, which
they designated RII-beta, from a human testis cDNA library. The deduced
418-amino acid protein has a calculated molecular mass of about 54 kD.
PRKAR2B contains an N-terminal dimerization domain, an
autophosphorylation site (ser114), and 7 potential polyadenylation
signals. The human and rat proteins share 97% homology. Northern blot
analysis revealed a 3.3-kb transcript expressed at highest levels in
testis, fallopian tubes, and ovary. Low or undetectable levels were
found in myocardium, parotid gland, parotid tumor, epididymis, uterus,
placenta, and umbilical cord. Northern blot analysis also detected
cAMP-stimulated Prkar2b expression in rat Sertoli cell cultures.
GENE STRUCTURE
Levy et al. (1988) estimated the size of the PRKAR2B gene to be close to
28 kb.
MAPPING
Using both a rat skeletal muscle clone and a human clone of type II
regulatory subunit of cyclic AMP-dependent protein kinase, Scambler et
al. (1987) demonstrated that the human gene is located on chromosome 7,
close to but separate from the cystic fibrosis locus (219700). These
conclusions were based on Southern blot analysis of DNA from hybrid cell
lines containing only chromosome 7 or parts thereof, as well as
human/mouse hybrid cell lines established by means of
chromosome-mediated gene transfer (CMGT) using MET (164860) as a
dominant selectable marker. Independence of PKR2 from CF was also
indicated by family linkage studies using a RFLP of the PKR2 probe.
Wainwright et al. (1987) showed that PKR2 is linked to several markers
on 7q. The closest and strongest linkage was to TCRB (see 186930), which
showed a maximum lod score of 3.01 at theta = 0.00.
Using RFLPs in the CEPH panel of 40 families, Solberg et al. (1992)
mapped the regulatory subunit RII-beta of cAMP-dependent protein kinase
to 7q. They constructed a 7-point framework map including PRKAR2B and
demonstrated the following order: cen--D7S371--(COL1A2,
D7S79)--PRKAR2B--MET--D7S87--TCRB--qter. Furthermore, by in situ
hybridization to metaphase chromosomes, Solberg et al. (1992) physically
mapped PRKAR2B to 7q22.
BIOCHEMICAL FEATURES
- Crystal Structure
Zhang et al. (2012) described the 2.3-angstrom structure of full-length
tetrameric RII-beta(2):catalytic subunit-alpha(2) (see 601639)
holoenzyme. The structure showing a dimer of dimers provided a
mechanistic understanding of allosteric activation by cAMP. The
heterodimers are anchored together by an interface created by the
beta-4/beta-5 loop in the RII-beta subunit, which docks onto the
carboxyl-terminal tail of the adjacent C subunit, thereby forcing the C
subunit into a fully closed conformation in the absence of nucleotide.
Diffusion of magnesium ATP into these crystals trapped not ATP but the
reaction products adenosine diphosphate and the phosphorylated RII-beta
subunit. This complex has implications for the
dissociation-reassociation cycling of PKA. The quaternary structure of
the RII-beta tetramer differs appreciably from the model of the RI-alpha
tetramer, confirming the small-angle x-ray scattering prediction that
the structures of each PKA tetramer are different.
ANIMAL MODEL
Cummings et al. (1996) generated knockout mice for the cyclic AMP
dependent protein kinase regulatory subunit type II-beta (designated
RII-beta by them). They reported that the mutants appeared healthy but
had markedly diminished white adipose tissue despite normal food intake
and were protected against developing diet-induced obesity and fatty
livers. In the mutant mice, brown adipose tissue demonstrated a
compensatory increase in RI-alpha (188830). Cummings et al. (1996)
reported that RII-beta mutants exhibited markedly reduced leptin
(164160) mRNA and plasma levels; however, only mild hyperphagia was
present.
Mice bearing a targeted disruption of the Prkar2b gene were used by
Adams et al. (1997) to evaluate the importance of cAMP-dependent
signaling in transducing the effects of haloperidol on striatal gene
expression and behavioral responses. In wildtype mice, haloperidol
treatment induces the expression of Fos (164810) and neurotensin
(162650) in the dorsal lateral region of the striatum and produces an
acute cataleptic response that correlates with the motor side effects of
haloperidol in humans. However, Adams et al. (1997) did not observe
these responses in mice lacking Prka2b. Prkar2b-deficient mice were able
to generate a cataleptic response to intracerebral injections of
neurotensin, suggesting that the Prkar2b subunit is required to
transduce the acute response to haloperidol in both gene expression and
behavior.
A chromosomal deletion in agouti lethal yellow (Ay) mice causes ectopic
expression of agouti (ASIP; 600201), which is normally expressed in
skin. Agouti antagonizes melanocortin-4 receptor (MC4R; 155541) in
neurons, resulting in hyperphagia, hypoactivity, and increased fat mass
in Ay mice. Czyzyk et al. (2008) found that RII-beta deletion rescued
elevated body weight, hyperphagia, and obesity of Ay mice. Partial
rescue of these Ay phenotypes was observed in RII-beta heterozygotes.
*FIELD* RF
1. Adams, M. R.; Brandon, E. P.; Chartoff, E. H.; Idzerda, R. L.;
Dorsa, D. M.; McKnight, G. S.: Loss of haloperidol induced gene expression
and catalepsy in protein kinase A-deficient mice. Proc. Nat. Acad.
Sci. 94: 12157-12161, 1997.
2. Cummings, D. E.; Brandon, E. P.; Planas, J. V.; Motamed, K.; Idzerda,
R. L.; McKnight, G. S.: Genetically lean mice result from targeted
disruption of the RII-beta subunit of protein kinase A. Nature 382:
:622-626, 1996.
3. Czyzyk, T. A.; Sikorski, M. A.; Yang, L.; McKnight, G. S.: Disruption
of the RII-beta subunit of PKA reverses the obesity syndrome of agouti
lethal yellow mice. Proc. Nat. Acad. Sci. 105: 276-281, 2008.
4. Levy, F. O.; Oyen, O.; Sandberg, M.; Tasken, K.; Eskild, W.; Hansson,
V.; Jahnsen, T.: Molecular cloning, complementary deoxyribonucleic
acid structure and predicted full-length amino acid sequence of the
hormone-inducible regulatory subunit of 3-prime-5-prime-cyclic adenosine
monophosphate-dependent protein kinase from human testis. Molec.
Endocr. 2: 1364-1373, 1988.
5. Scambler, P.; Oyen, O.; Wainwright, B.; Farrall, M.; Law, H.-Y.;
Estivill, X.; Sandberg, M.; Williamson, R.; Jahnsen, T.: Exclusion
of catalytic and regulatory subunits of cAMP-dependent protein kinase
as candidate genes for the defect causing cystic fibrosis. Am. J.
Hum. Genet. 41: 925-932, 1987.
6. Solberg, R.; Sistonen, P.; Traskelin, A.-L.; Berube, D.; Simard,
J.; Krajci, P.; Jahnsen, T.; de la Chapelle, A.: Mapping of the regulatory
subunits RI-beta and RII-beta of cAMP-dependent protein kinase genes
on human chromosome 7. Genomics 14: 63-69, 1992.
7. Wainwright, B.; Lench, N.; Davies, K.; Scambler, P.; Kruyer, H.;
Williamson, R.; Jahnsen, T.; Farrall, M.: A human regulatory subunit
of type II cAMP-dependent protein kinase localized by its linkage
relationship to several cloned chromosome 7q markers. Cytogenet.
Cell Genet. 45: 237-239, 1987.
8. Zhang, P.; Smith-Nguyen, E. V.; Keshwani, M. M.; Deal, M. S.; Kornev,
A. P.; Taylor, S. S.: Structure and allostery of the PKA RII-beta
tetrameric holoenzyme. Science 335: 712-716, 2012.
*FIELD* CN
Ada Hamosh - updated: 2/27/2012
Patricia A. Hartz - updated: 4/18/2008
Patricia A. Hartz - updated: 2/27/2003
*FIELD* CD
Victor A. McKusick: 3/18/1993
*FIELD* ED
mgross: 10/07/2013
alopez: 2/28/2012
terry: 2/27/2012
mgross: 4/18/2008
terry: 4/18/2008
mgross: 2/27/2003
terry: 9/5/1996
carol: 3/18/1993
*RECORD*
*FIELD* NO
176912
*FIELD* TI
*176912 PROTEIN KINASE, cAMP-DEPENDENT, REGULATORY, TYPE II, BETA; PRKAR2B
;;PRKAR2;;
read moreRII-BETA
*FIELD* TX
DESCRIPTION
The cAMP-dependent protein kinase system is believed to mediate most, if
not all, cellular effects of the second messenger cAMP. The kinase
holoenzyme consists of 2 regulatory (R) and 2 catalytic (C) subunits
that dissociate upon the binding of 2 cAMP molecules to each of the R
subunits. The free, activated C subunits then catalyze the
phosphorylation of specific substrate proteins on serine and threonine
residues and thereby alter their activity or function. PRKAR2B is 1 of
several R subunits (Levy et al., 1988).
CLONING
Using rat Prkar2b as probe, Levy et al. (1988) cloned PRKAR2B, which
they designated RII-beta, from a human testis cDNA library. The deduced
418-amino acid protein has a calculated molecular mass of about 54 kD.
PRKAR2B contains an N-terminal dimerization domain, an
autophosphorylation site (ser114), and 7 potential polyadenylation
signals. The human and rat proteins share 97% homology. Northern blot
analysis revealed a 3.3-kb transcript expressed at highest levels in
testis, fallopian tubes, and ovary. Low or undetectable levels were
found in myocardium, parotid gland, parotid tumor, epididymis, uterus,
placenta, and umbilical cord. Northern blot analysis also detected
cAMP-stimulated Prkar2b expression in rat Sertoli cell cultures.
GENE STRUCTURE
Levy et al. (1988) estimated the size of the PRKAR2B gene to be close to
28 kb.
MAPPING
Using both a rat skeletal muscle clone and a human clone of type II
regulatory subunit of cyclic AMP-dependent protein kinase, Scambler et
al. (1987) demonstrated that the human gene is located on chromosome 7,
close to but separate from the cystic fibrosis locus (219700). These
conclusions were based on Southern blot analysis of DNA from hybrid cell
lines containing only chromosome 7 or parts thereof, as well as
human/mouse hybrid cell lines established by means of
chromosome-mediated gene transfer (CMGT) using MET (164860) as a
dominant selectable marker. Independence of PKR2 from CF was also
indicated by family linkage studies using a RFLP of the PKR2 probe.
Wainwright et al. (1987) showed that PKR2 is linked to several markers
on 7q. The closest and strongest linkage was to TCRB (see 186930), which
showed a maximum lod score of 3.01 at theta = 0.00.
Using RFLPs in the CEPH panel of 40 families, Solberg et al. (1992)
mapped the regulatory subunit RII-beta of cAMP-dependent protein kinase
to 7q. They constructed a 7-point framework map including PRKAR2B and
demonstrated the following order: cen--D7S371--(COL1A2,
D7S79)--PRKAR2B--MET--D7S87--TCRB--qter. Furthermore, by in situ
hybridization to metaphase chromosomes, Solberg et al. (1992) physically
mapped PRKAR2B to 7q22.
BIOCHEMICAL FEATURES
- Crystal Structure
Zhang et al. (2012) described the 2.3-angstrom structure of full-length
tetrameric RII-beta(2):catalytic subunit-alpha(2) (see 601639)
holoenzyme. The structure showing a dimer of dimers provided a
mechanistic understanding of allosteric activation by cAMP. The
heterodimers are anchored together by an interface created by the
beta-4/beta-5 loop in the RII-beta subunit, which docks onto the
carboxyl-terminal tail of the adjacent C subunit, thereby forcing the C
subunit into a fully closed conformation in the absence of nucleotide.
Diffusion of magnesium ATP into these crystals trapped not ATP but the
reaction products adenosine diphosphate and the phosphorylated RII-beta
subunit. This complex has implications for the
dissociation-reassociation cycling of PKA. The quaternary structure of
the RII-beta tetramer differs appreciably from the model of the RI-alpha
tetramer, confirming the small-angle x-ray scattering prediction that
the structures of each PKA tetramer are different.
ANIMAL MODEL
Cummings et al. (1996) generated knockout mice for the cyclic AMP
dependent protein kinase regulatory subunit type II-beta (designated
RII-beta by them). They reported that the mutants appeared healthy but
had markedly diminished white adipose tissue despite normal food intake
and were protected against developing diet-induced obesity and fatty
livers. In the mutant mice, brown adipose tissue demonstrated a
compensatory increase in RI-alpha (188830). Cummings et al. (1996)
reported that RII-beta mutants exhibited markedly reduced leptin
(164160) mRNA and plasma levels; however, only mild hyperphagia was
present.
Mice bearing a targeted disruption of the Prkar2b gene were used by
Adams et al. (1997) to evaluate the importance of cAMP-dependent
signaling in transducing the effects of haloperidol on striatal gene
expression and behavioral responses. In wildtype mice, haloperidol
treatment induces the expression of Fos (164810) and neurotensin
(162650) in the dorsal lateral region of the striatum and produces an
acute cataleptic response that correlates with the motor side effects of
haloperidol in humans. However, Adams et al. (1997) did not observe
these responses in mice lacking Prka2b. Prkar2b-deficient mice were able
to generate a cataleptic response to intracerebral injections of
neurotensin, suggesting that the Prkar2b subunit is required to
transduce the acute response to haloperidol in both gene expression and
behavior.
A chromosomal deletion in agouti lethal yellow (Ay) mice causes ectopic
expression of agouti (ASIP; 600201), which is normally expressed in
skin. Agouti antagonizes melanocortin-4 receptor (MC4R; 155541) in
neurons, resulting in hyperphagia, hypoactivity, and increased fat mass
in Ay mice. Czyzyk et al. (2008) found that RII-beta deletion rescued
elevated body weight, hyperphagia, and obesity of Ay mice. Partial
rescue of these Ay phenotypes was observed in RII-beta heterozygotes.
*FIELD* RF
1. Adams, M. R.; Brandon, E. P.; Chartoff, E. H.; Idzerda, R. L.;
Dorsa, D. M.; McKnight, G. S.: Loss of haloperidol induced gene expression
and catalepsy in protein kinase A-deficient mice. Proc. Nat. Acad.
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R. L.; McKnight, G. S.: Genetically lean mice result from targeted
disruption of the RII-beta subunit of protein kinase A. Nature 382:
:622-626, 1996.
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of the RII-beta subunit of PKA reverses the obesity syndrome of agouti
lethal yellow mice. Proc. Nat. Acad. Sci. 105: 276-281, 2008.
4. Levy, F. O.; Oyen, O.; Sandberg, M.; Tasken, K.; Eskild, W.; Hansson,
V.; Jahnsen, T.: Molecular cloning, complementary deoxyribonucleic
acid structure and predicted full-length amino acid sequence of the
hormone-inducible regulatory subunit of 3-prime-5-prime-cyclic adenosine
monophosphate-dependent protein kinase from human testis. Molec.
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Estivill, X.; Sandberg, M.; Williamson, R.; Jahnsen, T.: Exclusion
of catalytic and regulatory subunits of cAMP-dependent protein kinase
as candidate genes for the defect causing cystic fibrosis. Am. J.
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6. Solberg, R.; Sistonen, P.; Traskelin, A.-L.; Berube, D.; Simard,
J.; Krajci, P.; Jahnsen, T.; de la Chapelle, A.: Mapping of the regulatory
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on human chromosome 7. Genomics 14: 63-69, 1992.
7. Wainwright, B.; Lench, N.; Davies, K.; Scambler, P.; Kruyer, H.;
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8. Zhang, P.; Smith-Nguyen, E. V.; Keshwani, M. M.; Deal, M. S.; Kornev,
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*FIELD* CN
Ada Hamosh - updated: 2/27/2012
Patricia A. Hartz - updated: 4/18/2008
Patricia A. Hartz - updated: 2/27/2003
*FIELD* CD
Victor A. McKusick: 3/18/1993
*FIELD* ED
mgross: 10/07/2013
alopez: 2/28/2012
terry: 2/27/2012
mgross: 4/18/2008
terry: 4/18/2008
mgross: 2/27/2003
terry: 9/5/1996
carol: 3/18/1993