ID   AKAP5_HUMAN             Reviewed;         427 AA.
AC   P24588; A2RRB8;
DT   01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-2009, sequence version 3.
DT   25-JAN-2012, entry version 105.
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=H21;
DE   AltName: Full=cAMP-dependent protein kinase regulatory subunit II high affinity-binding protein;
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], MUTAGENESIS, AND VARIANT ILE-203.
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 [LARGE SCALE MRNA], AND VARIANT ILE-203.
RC   TISSUE=Spleen;
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   MEDLINE=22459283; PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA   Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA   Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA   Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA   Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA   Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA   Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA   Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA   Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA   Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA   Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA   Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA   Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA   Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA   Quetier F., Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-203.
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-203.
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
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).
RN   [7]
RP   PALMITOYLATION AT CYS-36 AND CYS-129, INTERACTION WITH ADCY8, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=21771783; DOI=10.1074/jbc.M111.243899;
RA   Delint-Ramirez I., Willoughby D., Hammond G.V., Ayling L.J.,
RA   Cooper D.M.;
RT   "Palmitoylation targets AKAP79 protein to lipid rafts and promotes its
RT   regulation of calcium-sensitive adenylyl cyclase type 8.";
RL   J. Biol. Chem. 286:32962-32975(2011).
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. Part of a complex containing
CC       AKAP5, ADCY5, ADCY6 AND PDE4C (By similarity). Interacts with
CC       ADCY8, and enhances its phosphorylation at lipid rafts.
CC   -!- INTERACTION:
CC       P35561:Kcnj2 (xeno); NbExp=2; IntAct=EBI-703640, EBI-703793;
CC   -!- SUBCELLULAR LOCATION: Membrane; Lipid-anchor. Note=Associates with
CC       lipid rafts.
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   -!- PTM: Palmitoylation at Cys-36 and Cys-129 plays a key role in
CC       targeting to lipid rafts.
CC   -!- MISCELLANEOUS: The N-terminal region, which is highly basic, is
CC       required for interaction with calmodulin.
CC   -!- SIMILARITY: Contains 1 AKAP domain.
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DR   EMBL; M90359; AAA58363.1; -; mRNA.
DR   EMBL; AK315336; BAG37736.1; -; mRNA.
DR   EMBL; AL122035; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471061; EAW80862.1; -; Genomic_DNA.
DR   EMBL; BC131516; AAI31517.1; -; mRNA.
DR   IPI; IPI00307794; -.
DR   PIR; A43453; A43453.
DR   RefSeq; NP_004848.3; NM_004857.3.
DR   UniGene; Hs.656683; -.
DR   PDB; 2H9R; NMR; -; C=391-412.
DR   PDB; 3LL8; X-ray; 2.00 A; E=336-346.
DR   PDBsum; 2H9R; -.
DR   PDBsum; 3LL8; -.
DR   ProteinModelPortal; P24588; -.
DR   DIP; DIP-186N; -.
DR   IntAct; P24588; 2.
DR   MINT; MINT-1733931; -.
DR   STRING; P24588; -.
DR   PhosphoSite; P24588; -.
DR   DMDM; 281185503; -.
DR   PRIDE; P24588; -.
DR   Ensembl; ENST00000320636; ENSP00000315615; ENSG00000179841.
DR   Ensembl; ENST00000430028; ENSP00000401880; ENSG00000179841.
DR   GeneID; 9495; -.
DR   KEGG; hsa:9495; -.
DR   CTD; 9495; -.
DR   GeneCards; GC14P064932; -.
DR   H-InvDB; HIX0037749; -.
DR   HGNC; HGNC:375; AKAP5.
DR   HPA; CAB004308; -.
DR   MIM; 604688; gene.
DR   neXtProt; NX_P24588; -.
DR   HOGENOM; HBG125229; -.
DR   HOVERGEN; HBG050479; -.
DR   InParanoid; P24588; -.
DR   OMA; LVNEMAS; -.
DR   PhylomeDB; 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_111217; Metabolism.
DR   Reactome; REACT_13685; Neuronal System.
DR   ArrayExpress; P24588; -.
DR   Bgee; P24588; -.
DR   CleanEx; HS_AKAP5; -.
DR   Genevestigator; P24588; -.
DR   GermOnline; ENSG00000179841; Homo sapiens.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0008179; F:adenylate cyclase binding; IPI:UniProtKB.
DR   GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR   GO; GO:0051018; F:protein kinase A binding; TAS:ProtInc.
DR   GO; GO:0006112; P:energy reserve metabolic process; TAS:Reactome.
DR   GO; GO:0030819; P:positive regulation of cAMP biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0010739; P:positive regulation of protein kinase A signaling cascade; IMP:UniProtKB.
DR   GO; GO:0006605; P:protein targeting; IEA:InterPro.
DR   GO; GO:0050796; P:regulation of insulin secretion; TAS:Reactome.
DR   GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR   GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR   InterPro; IPR001573; Pkinase-A_anch_WSK-motif.
DR   Pfam; PF03832; WSK; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Calmodulin-binding; Complete proteome; Lipoprotein;
KW   Membrane; Palmitate; Polymorphism; Reference proteome.
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   LIPID        36     36       S-palmitoyl cysteine.
FT   LIPID       129    129       S-palmitoyl cysteine.
FT   VARIANT     100    100       P -> L (in dbSNP:rs2230491).
FT                                /FTId=VAR_056732.
FT   VARIANT     203    203       T -> I (in dbSNP:rs1256149).
FT                                /FTId=VAR_060735.
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    188    188       R -> Q (in Ref. 1; AAA58363).
FT   CONFLICT    407    407       S -> Y (in Ref. 6; no nucleotide entry).
FT   HELIX       393    408
FT   TURN        409    411
SQ   SEQUENCE   427 AA;  47088 MW;  D2A86298EAF1BE32 CRC64;
     METTISEIHV ENKDEKRSAE GSPGAERQKE KASMLCFKRR KKAAKALKPK AGSEAADVAR
     KCPQEAGASD QPEPTRGAWA SLKRLVTRRK RSESSKQQKP LEGEMQPAIN AEDADLSKKK
     AKSRLKIPCI KFPRGPKRSN HSKIIEDSDC SIKVQEEAEI LDIQTQTPLN DQATKAKSTQ
     DLSEGISRKD GDEVCESNVS NSTTSGEKVI SVELGLDNGH SAIQTGTLIL EEIETIKEKQ
     DVQPQQASPL ETSETDHQQP VLSDVPPLPA IPDQQIVEEA SNSTLESAPN GKDYESTEIV
     AEETKPKDTE LSQESDFKEN GITEEKSKSE ESKRMEPIAI IITDTEISEF DVTKSKNVPK
     QFLISAENEQ VGVFANDNGF EDRTSEQYET LLIETASSLV KNAIQLSIEQ LVNEMASDDN
     KINNLLQ
//