KAP0_MOUSE
ID KAP0_MOUSE Reviewed; 381 AA.
AC Q9DBC7; Q3UKU7; Q9JHR5; Q9JHR6;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=cAMP-dependent protein kinase type I-alpha regulatory subunit;
DE Contains:
DE RecName: Full=cAMP-dependent protein kinase type I-alpha regulatory subunit, N-terminally processed;
GN Name=Prkar1a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, Kidney, Liver, and Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-60 AND 259-382.
RX PubMed=10913627; DOI=10.1016/s0014-5793(00)01653-7;
RA Barradeau S., Imaizumi-Scherrer T., Weiss M.C., Faust D.M.;
RT "Alternative 5'-exons of the mouse cAMP-dependent protein kinase subunit
RT RIalpha gene are conserved and expressed in both a ubiquitous and tissue-
RT restricted fashion.";
RL FEBS Lett. 476:272-276(2000).
RN [4]
RP INTERACTION WITH AKAP4.
RX PubMed=9852104; DOI=10.1074/jbc.273.51.34384;
RA Miki K., Eddy E.M.;
RT "Identification of tethering domains for protein kinase A type Ialpha
RT regulatory subunits on sperm fibrous sheath protein FSC1.";
RL J. Biol. Chem. 273:34384-34390(1998).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-101, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP INTERACTION WITH CBFA2T3.
RX PubMed=20138877; DOI=10.1016/j.febslet.2010.02.007;
RA Fiedler S.E., Schillace R.V., Daniels C.J., Andrews S.F., Carr D.W.;
RT "Myeloid translocation gene 16b is a dual A-kinase anchoring protein that
RT interacts selectively with plexins in a phospho-regulated manner.";
RL FEBS Lett. 584:873-877(2010).
CC -!- FUNCTION: Regulatory subunit of the cAMP-dependent protein kinases
CC involved in cAMP signaling in cells. {ECO:0000250}.
CC -!- SUBUNIT: The inactive holoenzyme is composed of two regulatory chains
CC and two catalytic chains. Activation by cAMP releases the two active
CC catalytic monomers and the regulatory dimer. Interacts with PRKACA and
CC PRKACB (By similarity). PRKAR1A also interacts with RFC2; the complex
CC may be involved in cell survival. Interacts with AKAP4
CC (PubMed:9852104). Interacts with RARA; the interaction occurs in the
CC presence of cAMP or FSH and regulates RARA transcriptional activity.
CC Interacts with the phosphorylated form of PJA2. Interacts with PRKX;
CC regulates this cAMP-dependent protein kinase (By similarity). Interacts
CC with CBFA2T3 (PubMed:20138877). Interacts with smAKAP; this interaction
CC may target PRKAR1A to the plasma membrane. Interacts with AICDA (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P10644}.
CC -!- INTERACTION:
CC Q9DBC7; O54918-1: Bcl2l11; NbExp=2; IntAct=EBI-645677, EBI-526076;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}.
CC -!- PTM: The pseudophosphorylation site binds to the substrate-binding
CC region of the catalytic chain, resulting in the inhibition of its
CC activity. {ECO:0000250}.
CC -!- MISCELLANEOUS: Two types of regulatory chains are found: type I, which
CC predominates in skeletal muscle, and type II, which predominates in
CC cardiac muscle. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the cAMP-dependent kinase regulatory chain
CC family. {ECO:0000305}.
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DR EMBL; AK005039; BAB23766.1; -; mRNA.
DR EMBL; AK027916; BAC25664.1; -; mRNA.
DR EMBL; AK051068; BAC34516.1; -; mRNA.
DR EMBL; AK145797; BAE26655.1; -; mRNA.
DR EMBL; AK145860; BAE26704.1; -; mRNA.
DR EMBL; AK147188; BAE27748.1; -; mRNA.
DR EMBL; AK150427; BAE29550.1; -; mRNA.
DR EMBL; AK151124; BAE30132.1; -; mRNA.
DR EMBL; AK153227; BAE31820.1; -; mRNA.
DR EMBL; BC003461; AAH03461.1; -; mRNA.
DR EMBL; BC005697; AAH05697.1; -; mRNA.
DR EMBL; AJ278427; CAB94778.1; -; Genomic_DNA.
DR EMBL; AJ278429; CAB94718.1; -; Genomic_DNA.
DR CCDS; CCDS25583.1; -.
DR RefSeq; NP_001300902.1; NM_001313973.1.
DR RefSeq; NP_001300903.1; NM_001313974.1.
DR RefSeq; NP_001300904.1; NM_001313975.1.
DR RefSeq; NP_001300905.1; NM_001313976.1.
DR RefSeq; NP_068680.1; NM_021880.3.
DR RefSeq; XP_017169829.1; XM_017314340.1.
DR AlphaFoldDB; Q9DBC7; -.
DR SMR; Q9DBC7; -.
DR BioGRID; 202365; 6.
DR DIP; DIP-32450N; -.
DR IntAct; Q9DBC7; 15.
DR MINT; Q9DBC7; -.
DR STRING; 10090.ENSMUSP00000056500; -.
DR iPTMnet; Q9DBC7; -.
DR PhosphoSitePlus; Q9DBC7; -.
DR SwissPalm; Q9DBC7; -.
DR REPRODUCTION-2DPAGE; IPI00762049; -.
DR REPRODUCTION-2DPAGE; Q9DBC7; -.
DR EPD; Q9DBC7; -.
DR jPOST; Q9DBC7; -.
DR MaxQB; Q9DBC7; -.
DR PaxDb; Q9DBC7; -.
DR PRIDE; Q9DBC7; -.
DR ProteomicsDB; 268956; -.
DR Antibodypedia; 31783; 378 antibodies from 35 providers.
DR DNASU; 19084; -.
DR Ensembl; ENSMUST00000049527; ENSMUSP00000056500; ENSMUSG00000020612.
DR Ensembl; ENSMUST00000106677; ENSMUSP00000102288; ENSMUSG00000020612.
DR GeneID; 19084; -.
DR KEGG; mmu:19084; -.
DR UCSC; uc007mcu.1; mouse.
DR CTD; 5573; -.
DR MGI; MGI:104878; Prkar1a.
DR VEuPathDB; HostDB:ENSMUSG00000020612; -.
DR eggNOG; KOG1113; Eukaryota.
DR GeneTree; ENSGT00940000155148; -.
DR HOGENOM; CLU_018310_1_0_1; -.
DR InParanoid; Q9DBC7; -.
DR OMA; DQWERAN; -.
DR PhylomeDB; Q9DBC7; -.
DR TreeFam; TF314920; -.
DR Reactome; R-MMU-163615; PKA activation.
DR Reactome; R-MMU-164378; PKA activation in glucagon signalling.
DR Reactome; R-MMU-180024; DARPP-32 events.
DR Reactome; R-MMU-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR Reactome; R-MMU-442720; CREB1 phosphorylation through the activation of Adenylate Cyclase.
DR Reactome; R-MMU-5610787; Hedgehog 'off' state.
DR Reactome; R-MMU-9634597; GPER1 signaling.
DR Reactome; R-MMU-983231; Factors involved in megakaryocyte development and platelet production.
DR BioGRID-ORCS; 19084; 20 hits in 77 CRISPR screens.
DR ChiTaRS; Prkar1a; mouse.
DR PRO; PR:Q9DBC7; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9DBC7; protein.
DR Bgee; ENSMUSG00000020612; Expressed in subparaventricular zone and 287 other tissues.
DR ExpressionAtlas; Q9DBC7; baseline and differential.
DR Genevisible; Q9DBC7; MM.
DR GO; GO:0005930; C:axoneme; ISO:MGI.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IDA:MGI.
DR GO; GO:0005813; C:centrosome; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0001772; C:immunological synapse; ISO:MGI.
DR GO; GO:0005771; C:multivesicular body; IDA:MGI.
DR GO; GO:0031594; C:neuromuscular junction; IDA:MGI.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; ISO:MGI.
DR GO; GO:0044853; C:plasma membrane raft; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0097224; C:sperm connecting piece; IDA:MGI.
DR GO; GO:0045202; C:synapse; IDA:SynGO.
DR GO; GO:0030552; F:cAMP binding; ISO:MGI.
DR GO; GO:0004862; F:cAMP-dependent protein kinase inhibitor activity; ISO:MGI.
DR GO; GO:0008603; F:cAMP-dependent protein kinase regulator activity; IDA:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; IPI:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:MGI.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0010463; P:mesenchymal cell proliferation; TAS:MGI.
DR GO; GO:0001707; P:mesoderm formation; IMP:MGI.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISO:MGI.
DR GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; TAS:MGI.
DR GO; GO:0045859; P:regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0045214; P:sarcomere organization; IMP:MGI.
DR CDD; cd00038; CAP_ED; 2.
DR Gene3D; 2.60.120.10; -; 2.
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 SMART; SM00100; cNMP; 2.
DR SMART; SM00394; RIIa; 1.
DR SUPFAM; SSF51206; SSF51206; 2.
DR PROSITE; PS00888; CNMP_BINDING_1; 2.
DR PROSITE; PS00889; CNMP_BINDING_2; 2.
DR PROSITE; PS50042; CNMP_BINDING_3; 2.
PE 1: Evidence at protein level;
KW Acetylation; cAMP; cAMP-binding; Cell membrane; Disulfide bond; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..381
FT /note="cAMP-dependent protein kinase type I-alpha
FT regulatory subunit"
FT /id="PRO_0000421786"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00514"
FT CHAIN 2..381
FT /note="cAMP-dependent protein kinase type I-alpha
FT regulatory subunit, N-terminally processed"
FT /id="PRO_0000205378"
FT REGION 2..136
FT /note="Dimerization and phosphorylation"
FT REGION 73..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 96..100
FT /note="Pseudophosphorylation motif"
FT BINDING 137..254
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT BINDING 202
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT BINDING 211
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT BINDING 255..381
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT BINDING 326
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT BINDING 335
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P10644"
FT MOD_RES 2
FT /note="N-acetylalanine; in cAMP-dependent protein kinase
FT type I-alpha regulatory subunit, N-terminally processed"
FT /evidence="ECO:0000250|UniProtKB:P00514"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09456"
FT MOD_RES 75
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10644"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10644"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15345747"
FT MOD_RES 258
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09456"
FT DISULFID 18
FT /note="Interchain (with C-39)"
FT /evidence="ECO:0000250"
FT DISULFID 39
FT /note="Interchain (with C-18)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 381 AA; 43185 MW; 08F164BB4528C63B CRC64;
MASGSMATSE EERSLRECEL YVQKHNIQAL LKDSIVQLCT TRPERPMAFL REYFERLEKE
EARQIQCLQK TGIRTDSRED EISPPPPNPV VKGRRRRGAI SAEVYTEEDA ASYVRKVIPK
DYKTMAALAK AIEKNVLFSH LDDNERSDIF DAMFPVSFIA GETVIQQGDE GDNFYVIDQG
EMDVYVNNEW ATSVGEGGSF GELALIYGTP RAATVKAKTN VKLWGIDRDS YRRILMGSTL
RKRKMYEEFL SKVSILESLD KWERLTVADA LEPVQFEDGQ KIVVQGEPGD EFFIILEGTA
AVLQRRSENE EFVEVGRLGP SDYFGEIALL MNRPRAATVV ARGPLKCVKL DRPRFERVLG
PCSDILKRNI QQYNSFVSLS V
