ID KAP0_BOVIN Reviewed; 380 AA. AC P00514; A5D9F4; Q17QP8; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 17-APR-2007, sequence version 2. DT 27-MAR-2024, entry version 201. 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 Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=16305752; DOI=10.1186/1471-2164-6-166; RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.; RT "Characterization of 954 bovine full-CDS cDNA sequences."; RL BMC Genomics 6:166-166(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Basal ganglia; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases. RN [3] RP PROTEIN SEQUENCE OF 2-380, AND ACETYLATION AT ALA-2. RX PubMed=6487597; DOI=10.1021/bi00313a028; RA Titani K., Sasagawa T., Ericsson L.H., Kumar S., Smith S.B., Krebs E.G., RA Walsh K.A.; RT "Amino acid sequence of the regulatory subunit of bovine type I adenosine RT cyclic 3',5'-phosphate dependent protein kinase."; RL Biochemistry 23:4193-4199(1984). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 214-232. RX PubMed=6190178; DOI=10.1073/pnas.80.12.3608; RA Lee D.C., Carmichael D.F., Krebs E.G., McKnight G.S.; RT "Isolation of a cDNA clone for the type I regulatory subunit of bovine RT cAMP-dependent protein kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 80:3608-3612(1983). RN [5] RP 3D-STRUCTURE MODELING. RX PubMed=3030405; DOI=10.1021/bi00376a003; RA Weber I.T., Steitz T.A., Bubis J., Taylor S.S.; RT "Predicted structures of cAMP binding domains of type I and II regulatory RT subunits of cAMP-dependent protein kinase."; RL Biochemistry 26:343-351(1987). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 114-380. RX PubMed=7638597; DOI=10.1126/science.7638597; RA Su Y., Dostmann W.R., Herberg F.W., Durick K., Xuong N.H., ten Eyck L., RA Taylor S.S., Varughese K.I.; RT "Regulatory subunit of protein kinase A: structure of deletion mutant with RT cAMP binding domains."; RL Science 269:807-813(1995). RN [7] RP DISULFIDE BONDS. RX PubMed=3667618; DOI=10.1016/s0021-9258(18)48122-7; RA Bubis J., Vedvick T.S., Taylor S.S.; RT "Antiparallel alignment of the two protomers of the regulatory subunit RT dimer of cAMP-dependent protein kinase I."; RL J. Biol. Chem. 262:14961-14966(1987). CC -!- FUNCTION: Regulatory subunit of the cAMP-dependent protein kinases CC involved in cAMP signaling in cells. 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. Interacts with CC RARA; the interaction occurs in the presence of cAMP or FSH and CC regulates RARA transcriptional activity. Interacts with the CC phosphorylated form of PJA2. Interacts with CBFA2T3. Interacts with CC PRKX; regulates this cAMP-dependent protein kinase (By similarity). CC Interacts with smAKAP; this interaction may target PRKAR1A to the CC plasma membrane. Interacts with AICDA (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:P10644}. CC -!- INTERACTION: CC P00514; P00514: PRKAR1A; NbExp=5; IntAct=EBI-1041635, EBI-1041635; CC P00514; O43572: AKAP10; Xeno; NbExp=2; IntAct=EBI-1041635, EBI-752153; CC P00514; P05132: Prkaca; Xeno; NbExp=6; IntAct=EBI-1041635, EBI-400564; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Four types of regulatory chains are found: I-alpha, CC I-beta, II-alpha, and II-beta. Their expression varies among tissues CC and is in some cases constitutive and in others inducible. CC -!- PTM: The pseudophosphorylation site binds to the substrate-binding CC region of the catalytic chain, resulting in the inhibition of its CC activity. The physiological significance of the in vitro CC phosphorylation of a proximal serine is unclear. CC -!- SIMILARITY: Belongs to the cAMP-dependent kinase regulatory chain CC family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BT030573; ABQ13013.1; -; mRNA. DR EMBL; BC118242; AAI18243.1; -; mRNA. DR EMBL; K00833; AAA30708.1; -; mRNA. DR PIR; A00617; OKBO1R. DR PIR; I45957; I45957. DR RefSeq; NP_001069826.1; NM_001076358.1. DR PDB; 1NE4; X-ray; 2.40 A; A=95-377. DR PDB; 1NE6; X-ray; 2.30 A; A=95-377. DR PDB; 1RGS; X-ray; 2.80 A; A=93-380. DR PDB; 1RL3; X-ray; 2.70 A; A/B=93-380. DR PDB; 2EZW; NMR; -; A/B=13-62. DR PDB; 2QCS; X-ray; 2.20 A; B=91-380. DR PDB; 3FHI; X-ray; 2.00 A; B=92-245. DR PDB; 3IIA; X-ray; 2.70 A; A=92-245. DR PDB; 3IM3; X-ray; 2.00 A; A=13-62. DR PDB; 3IM4; X-ray; 2.28 A; A/B=13-62. DR PDB; 3PLQ; X-ray; 2.30 A; A=92-245. DR PDB; 3PNA; X-ray; 1.50 A; A/B=92-245. DR PDB; 3PVB; X-ray; 3.30 A; B=85-244. DR PDB; 4JV4; X-ray; 2.95 A; A=93-380. DR PDB; 4MX3; X-ray; 3.88 A; A/B=2-380. DR PDB; 4X6R; X-ray; 2.40 A; B=91-380. DR PDB; 5HVZ; X-ray; 2.00 A; A/B=13-62. DR PDB; 5JR7; X-ray; 3.56 A; B/D=92-366. DR PDB; 6BYR; X-ray; 3.66 A; B/D=2-380. DR PDB; 6BYS; X-ray; 4.75 A; B/D/F/H=2-380. DR PDB; 6NO7; X-ray; 3.55 A; B/D/F/H=1-380. DR PDB; 7LZ4; X-ray; 4.16 A; A/B/C/D/E/F/G/H=109-377. DR PDBsum; 1NE4; -. DR PDBsum; 1NE6; -. DR PDBsum; 1RGS; -. DR PDBsum; 1RL3; -. DR PDBsum; 2EZW; -. DR PDBsum; 2QCS; -. DR PDBsum; 3FHI; -. DR PDBsum; 3IIA; -. DR PDBsum; 3IM3; -. DR PDBsum; 3IM4; -. DR PDBsum; 3PLQ; -. DR PDBsum; 3PNA; -. DR PDBsum; 3PVB; -. DR PDBsum; 4JV4; -. DR PDBsum; 4MX3; -. DR PDBsum; 4X6R; -. DR PDBsum; 5HVZ; -. DR PDBsum; 5JR7; -. DR PDBsum; 6BYR; -. DR PDBsum; 6BYS; -. DR PDBsum; 6NO7; -. DR PDBsum; 7LZ4; -. DR AlphaFoldDB; P00514; -. DR SMR; P00514; -. DR DIP; DIP-36644N; -. DR IntAct; P00514; 3. DR MINT; P00514; -. DR STRING; 9913.ENSBTAP00000011371; -. DR BindingDB; P00514; -. DR iPTMnet; P00514; -. DR PaxDb; 9913-ENSBTAP00000011371; -. DR Ensembl; ENSBTAT00000011371.6; ENSBTAP00000011371.5; ENSBTAG00000008621.6. DR GeneID; 615074; -. DR KEGG; bta:615074; -. DR CTD; 5573; -. DR VEuPathDB; HostDB:ENSBTAG00000008621; -. DR VGNC; VGNC:33324; PRKAR1A. DR eggNOG; KOG1113; Eukaryota. DR GeneTree; ENSGT00940000155148; -. DR HOGENOM; CLU_018310_1_0_1; -. DR InParanoid; P00514; -. DR OMA; EHIVMAS; -. DR OrthoDB; 55978at2759; -. DR TreeFam; TF314920; -. DR Reactome; R-BTA-163615; PKA activation. DR Reactome; R-BTA-164378; PKA activation in glucagon signalling. DR Reactome; R-BTA-180024; DARPP-32 events. DR Reactome; R-BTA-432040; Vasopressin regulates renal water homeostasis via Aquaporins. DR Reactome; R-BTA-442720; CREB1 phosphorylation through the activation of Adenylate Cyclase. DR Reactome; R-BTA-5610787; Hedgehog 'off' state. DR Reactome; R-BTA-9634597; GPER1 signaling. DR Reactome; R-BTA-983231; Factors involved in megakaryocyte development and platelet production. DR EvolutionaryTrace; P00514; -. DR PRO; PR:P00514; -. DR Proteomes; UP000009136; Chromosome 19. DR Bgee; ENSBTAG00000008621; Expressed in prefrontal cortex and 106 other cell types or tissues. DR ExpressionAtlas; P00514; baseline and differential. DR GO; GO:0005930; C:axoneme; IEA:Ensembl. DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IMP:CAFA. DR GO; GO:0005813; C:centrosome; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:CAFA. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0001772; C:immunological synapse; IEA:Ensembl. DR GO; GO:0005771; C:multivesicular body; IEA:Ensembl. DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl. DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; IEA:Ensembl. DR GO; GO:0044853; C:plasma membrane raft; IEA:Ensembl. DR GO; GO:0097224; C:sperm connecting piece; IEA:Ensembl. DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW. DR GO; GO:0004862; F:cAMP-dependent protein kinase inhibitor activity; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl. DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; IPI:CAFA. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl. DR GO; GO:0071377; P:cellular response to glucagon stimulus; IEA:Ensembl. DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl. DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl. DR GO; GO:0001932; P:regulation of protein phosphorylation; IEA:InterPro. DR GO; GO:0045214; P:sarcomere organization; IEA:Ensembl. DR CDD; cd00038; CAP_ED; 2. DR CDD; cd12101; DD_RIalpha_PKA; 1. DR DisProt; DP00245; -. DR Gene3D; 1.20.890.10; cAMP-dependent protein kinase regulatory subunit, dimerization-anchoring domain; 1. DR Gene3D; 2.60.120.10; Jelly Rolls; 2. DR InterPro; IPR012198; cAMP_dep_PK_reg_su. DR InterPro; IPR003117; cAMP_dep_PK_reg_su_I/II_a/b. DR InterPro; IPR018488; cNMP-bd_CS. DR InterPro; IPR000595; cNMP-bd_dom. DR InterPro; IPR018490; cNMP-bd_dom_sf. DR InterPro; IPR014710; RmlC-like_jellyroll. DR PANTHER; PTHR11635; CAMP-DEPENDENT PROTEIN KINASE REGULATORY CHAIN; 1. DR PANTHER; PTHR11635:SF129; CAMP-DEPENDENT PROTEIN KINASE TYPE I-ALPHA REGULATORY SUBUNIT; 1. 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; SSF51206; cAMP-binding domain-like; 2. DR SUPFAM; SSF47391; Dimerization-anchoring domain of cAMP-dependent PK regulatory subunit; 1. 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 Direct protein sequencing; Disulfide bond; Membrane; Nucleotide-binding; KW Phosphoprotein; Reference proteome; Repeat. FT CHAIN 1..380 FT /note="cAMP-dependent protein kinase type I-alpha FT regulatory subunit" FT /id="PRO_0000423216" FT INIT_MET 1 FT /note="Removed; alternate" FT /evidence="ECO:0000269|PubMed:6487597" FT CHAIN 2..380 FT /note="cAMP-dependent protein kinase type I-alpha FT regulatory subunit, N-terminally processed" FT /id="PRO_0000205376" FT REGION 2..135 FT /note="Dimerization and phosphorylation" FT REGION 64..96 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 95..99 FT /note="Pseudophosphorylation motif" FT BINDING 136..253 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /ligand_label="1" FT BINDING 201 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /ligand_label="1" FT BINDING 210 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /ligand_label="1" FT BINDING 254..380 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /ligand_label="2" FT BINDING 325 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /ligand_label="2" FT BINDING 334 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:0000269|PubMed:6487597" FT MOD_RES 3 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09456" FT MOD_RES 76 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P10644" FT MOD_RES 82 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P10644" FT MOD_RES 100 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9DBC7" FT MOD_RES 257 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09456" FT DISULFID 17 FT /note="Interchain (with C-37)" FT /evidence="ECO:0000269|PubMed:3667618" FT DISULFID 38 FT /note="Interchain (with C-16)" FT /evidence="ECO:0000269|PubMed:3667618" FT CONFLICT 230 FT /note="Y -> N (in Ref. 4; AAA30708)" FT /evidence="ECO:0000305" FT HELIX 14..23 FT /evidence="ECO:0007829|PDB:3IM3" FT HELIX 26..40 FT /evidence="ECO:0007829|PDB:3IM3" FT HELIX 45..61 FT /evidence="ECO:0007829|PDB:3IM3" FT HELIX 106..109 FT /evidence="ECO:0007829|PDB:3FHI" FT HELIX 121..133 FT /evidence="ECO:0007829|PDB:3PNA" FT HELIX 135..137 FT /evidence="ECO:0007829|PDB:3PNA" FT STRAND 138..140 FT /evidence="ECO:0007829|PDB:3IIA" FT HELIX 142..151 FT /evidence="ECO:0007829|PDB:3PNA" FT STRAND 153..157 FT /evidence="ECO:0007829|PDB:3PNA" FT STRAND 162..164 FT /evidence="ECO:0007829|PDB:3PNA" FT STRAND 172..179 FT /evidence="ECO:0007829|PDB:3PNA" FT STRAND 181..185 FT /evidence="ECO:0007829|PDB:3PNA" FT STRAND 188..193 FT /evidence="ECO:0007829|PDB:3PNA" FT HELIX 202..206 FT /evidence="ECO:0007829|PDB:3PNA" FT STRAND 211..218 FT /evidence="ECO:0007829|PDB:3PNA" FT STRAND 220..226 FT /evidence="ECO:0007829|PDB:3PNA" FT HELIX 227..233 FT /evidence="ECO:0007829|PDB:3PNA" FT HELIX 235..240 FT /evidence="ECO:0007829|PDB:3PNA" FT HELIX 246..250 FT /evidence="ECO:0007829|PDB:1RL3" FT HELIX 253..255 FT /evidence="ECO:0007829|PDB:2QCS" FT HELIX 260..269 FT /evidence="ECO:0007829|PDB:2QCS" FT STRAND 271..275 FT /evidence="ECO:0007829|PDB:2QCS" FT STRAND 277..279 FT /evidence="ECO:0007829|PDB:1RL3" FT STRAND 280..282 FT /evidence="ECO:0007829|PDB:2QCS" FT STRAND 284..286 FT /evidence="ECO:0007829|PDB:1NE4" FT STRAND 290..304 FT /evidence="ECO:0007829|PDB:2QCS" FT STRAND 305..309 FT /evidence="ECO:0007829|PDB:1NE4" FT STRAND 311..317 FT /evidence="ECO:0007829|PDB:2QCS" FT STRAND 322..324 FT /evidence="ECO:0007829|PDB:1RGS" FT HELIX 326..328 FT /evidence="ECO:0007829|PDB:2QCS" FT STRAND 335..350 FT /evidence="ECO:0007829|PDB:2QCS" FT HELIX 351..358 FT /evidence="ECO:0007829|PDB:2QCS" FT HELIX 361..365 FT /evidence="ECO:0007829|PDB:2QCS" FT HELIX 369..375 FT /evidence="ECO:0007829|PDB:2QCS" SQ SEQUENCE 380 AA; 42893 MW; B086A291809422F4 CRC64; MASGTTASEE ERSLRECELY VQKHNIQALL KDSIVQLCTA RPERPMAFLR EYFEKLEKEE AKQIQNLQKA GSRADSREDE ISPPPPNPVV KGRRRRGAIS AEVYTEEDAA SYVRKVIPKD YKTMAALAKA IEKNVLFSHL DDNERSDIFD AMFPVSFIAG ETVIQQGDEG DNFYVIDQGE MDVYVNNEWA TSVGEGGSFG ELALIYGTPR AATVKAKTNV KLWGIDRDSY RRILMGSTLR KRKMYEEFLS KVSILESLDK WERLTVADAL EPVQFEDGQK IVVQGEPGDE FFIILEGSAA VLQRRSENEE FVEVGRLGPS DYFGEIALLM NRPRAATVVA RGPLKCVKLD RPRFERVLGP CSDILKRNIQ QYNSFVSLSV //