ID AKAP5_HUMAN Reviewed; 427 AA. AC P24588; DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 2. DT 03-NOV-2009, entry version 85. DE RecName: Full=A-kinase anchor protein 5; DE Short=AKAP-5; DE AltName: Full=A-kinase anchor protein 79 kDa; DE Short=AKAP 79; DE AltName: Full=cAMP-dependent protein kinase regulatory subunit II high affinity-binding protein; DE AltName: Full=H21; GN Name=AKAP5; Synonyms=AKAP79; 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], AND MUTAGENESIS. RC TISSUE=Thyroid; RX MEDLINE=92380978; PubMed=1512224; RA Carr D.W., Stofko-Hahn R.E., Fraser I.D.C., Cone R.D., Scott J.D.; RT "Localization of the cAMP-dependent protein kinase to the postsynaptic RT densities by A-kinase anchoring proteins. Characterization of AKAP RT 79."; RL J. Biol. Chem. 267:16816-16823(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 332-427. RC TISSUE=Kidney; RX MEDLINE=92129278; PubMed=1733921; RA Hirsch A.H., Glantz S.B., Li Y., You Y., Rubin C.S.; RT "Cloning and expression of an intron-less gene for AKAP 75, an anchor RT protein for the regulatory subunit of cAMP-dependent protein kinase II RT beta."; RL J. Biol. Chem. 267:2131-2134(1992). CC -!- FUNCTION: May anchor the PKA protein to cytoskeletal and/or CC organelle-associated proteins, targeting the signal carried by CC cAMP to specific intracellular effectors. Association with to the CC beta2-adrenergic receptor (beta2-AR) not only regulates beta2-AR CC signaling pathway, but also the activation by PKA by switching off CC the beta2-AR signaling cascade. CC -!- SUBUNIT: Binding protein for dimer of the RII-beta regulatory CC subunit of cAMP-dependent protein kinase (PKA) and also for the CC protein kinase C (PKC) and the phosphatase calcineurin (PP2B). CC Each enzyme is inhibited when bound to the anchoring protein. Also CC binds the beta2-adrenergic receptor. CC -!- INTERACTION: CC P63252:KCNJ2; NbExp=1; IntAct=EBI-703640, EBI-703457; CC P35561:Kcnj2 (xeno); NbExp=2; IntAct=EBI-703640, EBI-703793; CC -!- SUBCELLULAR LOCATION: Membrane. Note=Associated with particulate CC fractions. CC -!- TISSUE SPECIFICITY: Predominantly in the cerebral cortex and the CC postsynaptic densities of the forebrain, and to a lesser extent in CC adrenal medulla, lung and anterior pituitary. CC -!- DOMAIN: RII-alpha binding site, predicted to form an amphipathic CC helix, could participate in protein-protein interactions with a CC complementary surface on the R-subunit dimer. CC -!- MISCELLANEOUS: The N-terminal region, which is highly basic, is CC required for interaction with calmodulin. CC -!- SIMILARITY: Contains 1 AKAP domain. 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; M90359; AAA58363.1; -; mRNA. DR IPI; IPI00307794; -. DR PIR; A43453; A43453. DR UniGene; Hs.656683; -. DR PDB; 2H9R; NMR; -; C=391-412. DR PDBsum; 2H9R; -. DR DIP; DIP:186N; -. DR IntAct; P24588; 2. DR STRING; P24588; -. DR PRIDE; P24588; -. DR Ensembl; ENST00000320636; ENSP00000315615; ENSG00000179841; Homo sapiens. DR Ensembl; ENST00000394718; ENSP00000378207; ENSG00000179841; Homo sapiens. DR Ensembl; ENST00000430028; ENSP00000401880; ENSG00000179841; Homo sapiens. DR KEGG; hsa:9495; -. DR GeneCards; GC14P064003; -. DR H-InvDB; HIX0037749; -. DR HGNC; HGNC:375; AKAP5. DR HPA; CAB004308; -. DR MIM; 604688; gene. DR PharmGKB; PA24669; -. DR HOGENOM; P24588; -. DR HOVERGEN; P24588; -. DR Pathway_Interaction_DB; tcrcalciumpathway; Calcium signaling in the CD4+ TCR pathway. DR Pathway_Interaction_DB; nfat_3pathway; Role of Calcineurin-dependent NFAT signaling in lymphocytes. DR Reactome; REACT_13685; Synaptic Transmission. DR Reactome; REACT_15380; Diabetes pathways. DR ArrayExpress; P24588; -. DR Bgee; P24588; -. DR CleanEx; HS_AKAP5; -. DR Genevestigator; P24588; -. DR GermOnline; ENSG00000179841; Homo sapiens. DR GO; GO:0005829; C:cytosol; EXP:Reactome. DR GO; GO:0005886; C:plasma membrane; EXP:Reactome. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0051018; F:protein kinase A binding; TAS:ProtInc. DR GO; GO:0006605; P:protein targeting; IEA:InterPro. DR GO; GO:0007165; P:signal transduction; NAS:ProtInc. DR GO; GO:0007268; P:synaptic transmission; TAS:ProtInc. DR InterPro; IPR001573; Pkinase-A_anch_WSK-motif. DR InterPro; IPR018459; RII_binding_1. DR Pfam; PF10522; RII_binding_1; 1. DR Pfam; PF03832; WSK; 1. PE 1: Evidence at protein level; KW 3D-structure; Calmodulin-binding; Complete proteome; Membrane; KW Polymorphism. FT CHAIN 1 427 A-kinase anchor protein 5. FT /FTId=PRO_0000064529. FT DOMAIN 73 103 AKAP. FT REGION 1 170 Essential to the intracellular anchoring FT function (By similarity). FT REGION 392 405 PKA-RII subunit binding domain. FT VARIANT 100 100 P -> L (in dbSNP:rs2230491). FT /FTId=VAR_056732. FT VARIANT 314 314 E -> K (in dbSNP:rs34433837). FT /FTId=VAR_056733. FT MUTAGEN 392 392 L->P: Prevents or diminishes RII binding. FT MUTAGEN 396 396 A->P: Prevents or diminishes RII binding. FT MUTAGEN 400 400 V->P: Prevents or diminishes RII binding. FT MUTAGEN 405 405 Q->P: Prevents or diminishes RII binding. FT MUTAGEN 408 408 I->P: Prevents or diminishes RII binding. FT CONFLICT 407 407 S -> Y (in Ref. 2). FT HELIX 393 408 FT TURN 409 411 SQ SEQUENCE 427 AA; 47072 MW; A3D08AE8D0521408 CRC64; METTISEIHV ENKDEKRSAE GSPGAERQKE KASMLCFKRR KKAAKALKPK AGSEAADVAR KCPQEAGASD QPEPTRGAWA SLKRLVTRRK RSESSKQQKP LEGEMQPAIN AEDADLSKKK AKSRLKIPCI KFPRGPKRSN HSKIIEDSDC SIKVQEEAEI LDIQTQTPLN DQATKAKSTQ DLSEGISQKD GDEVCESNVS NSITSGEKVI SVELGLDNGH SAIQTGTLIL EEIETIKEKQ DVQPQQASPL ETSETDHQQP VLSDVPPLPA IPDQQIVEEA SNSTLESAPN GKDYESTEIV AEETKPKDTE LSQESDFKEN GITEEKSKSE ESKRMEPIAI IITDTEISEF DVTKSKNVPK QFLISAENEQ VGVFANDNGF EDRTSEQYET LLIETASSLV KNAIQLSIEQ LVNEMASDDN KINNLLQ //