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P24588

- AKAP5_HUMAN

UniProt

P24588 - AKAP5_HUMAN

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Protein

A-kinase anchor protein 5

Gene

AKAP5

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

May anchor the PKA protein to cytoskeletal and/or organelle-associated proteins, targeting the signal carried by cAMP to specific intracellular effectors. Association with to the beta2-adrenergic receptor (beta2-AR) not only regulates beta2-AR signaling pathway, but also the activation by PKA by switching off the beta2-AR signaling cascade.

GO - Molecular functioni

  1. adenylate cyclase binding Source: UniProtKB
  2. protein kinase A binding Source: ProtInc

GO - Biological processi

  1. energy reserve metabolic process Source: Reactome
  2. positive regulation of cAMP biosynthetic process Source: UniProtKB
  3. positive regulation of protein kinase A signaling Source: UniProtKB
  4. protein targeting Source: InterPro
  5. regulation of insulin secretion Source: Reactome
  6. signal transduction Source: ProtInc
  7. small molecule metabolic process Source: Reactome
  8. synaptic transmission Source: Reactome
Complete GO annotation...

Keywords - Ligandi

Calmodulin-binding

Enzyme and pathway databases

ReactomeiREACT_18274. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
REACT_18307. Trafficking of AMPA receptors.
SignaLinkiP24588.

Names & Taxonomyi

Protein namesi
Recommended name:
A-kinase anchor protein 5
Short name:
AKAP-5
Alternative name(s):
A-kinase anchor protein 79 kDa
Short name:
AKAP 79
H21
cAMP-dependent protein kinase regulatory subunit II high affinity-binding protein
Gene namesi
Name:AKAP5
Synonyms:AKAP79
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 14

Organism-specific databases

HGNCiHGNC:375. AKAP5.

Subcellular locationi

Membrane 1 Publication; Lipid-anchor 1 Publication
Note: Associates with lipid rafts.

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi392 – 3921L → P: Prevents or diminishes RII binding. 1 Publication
Mutagenesisi396 – 3961A → P: Prevents or diminishes RII binding. 1 Publication
Mutagenesisi400 – 4001V → P: Prevents or diminishes RII binding. 1 Publication
Mutagenesisi405 – 4051Q → P: Prevents or diminishes RII binding. 1 Publication
Mutagenesisi408 – 4081I → P: Prevents or diminishes RII binding. 1 Publication

Organism-specific databases

PharmGKBiPA24669.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 427427A-kinase anchor protein 5PRO_0000064529Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi36 – 361S-palmitoyl cysteine1 Publication
Lipidationi129 – 1291S-palmitoyl cysteine1 Publication

Post-translational modificationi

Palmitoylation at Cys-36 and Cys-129 plays a key role in targeting to lipid rafts.1 Publication

Keywords - PTMi

Lipoprotein, Palmitate

Proteomic databases

MaxQBiP24588.
PaxDbiP24588.
PRIDEiP24588.

PTM databases

PhosphoSiteiP24588.

Expressioni

Tissue specificityi

Predominantly in the cerebral cortex and the postsynaptic densities of the forebrain, and to a lesser extent in adrenal medulla, lung and anterior pituitary.

Gene expression databases

BgeeiP24588.
CleanExiHS_AKAP5.
GenevestigatoriP24588.

Organism-specific databases

HPAiCAB004308.

Interactioni

Subunit structurei

Binding protein for dimer of the RII-beta regulatory subunit of cAMP-dependent protein kinase (PKA) and also for the protein kinase C (PKC) and the phosphatase calcineurin (PP2B). Each enzyme is inhibited when bound to the anchoring protein. Also binds the beta2-adrenergic receptor. Part of a complex containing AKAP5, ADCY5, ADCY6 AND PDE4C By similarity. Interacts with ADCY8, and enhances its phosphorylation at lipid rafts.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Kcnj2P355612EBI-703640,EBI-703793From a different organism.
RXFP1Q9HBX92EBI-703640,EBI-8088969

Protein-protein interaction databases

BioGridi114874. 14 interactions.
DIPiDIP-186N.
IntActiP24588. 8 interactions.
MINTiMINT-1733931.
STRINGi9606.ENSP00000315615.

Structurei

Secondary structure

1
427
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi339 – 3446
Helixi393 – 40816
Turni409 – 4113

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2H9RNMR-C391-412[»]
3LL8X-ray2.00E336-346[»]
ProteinModelPortaliP24588.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP24588.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini73 – 10331AKAPAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 170170Essential to the intracellular anchoring functionBy similarityAdd
BLAST
Regioni392 – 40514PKA-RII subunit binding domainAdd
BLAST

Domaini

RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer.
The N-terminal region, which is highly basic, is required for interaction with calmodulin.

Sequence similaritiesi

Contains 1 AKAP domain.Curated

Phylogenomic databases

eggNOGiNOG25796.
GeneTreeiENSGT00390000019941.
HOGENOMiHOG000168350.
HOVERGENiHBG050479.
InParanoidiP24588.
KOiK16522.
OMAiEMASDDN.
OrthoDBiEOG73V6JZ.
PhylomeDBiP24588.
TreeFamiTF105404.

Family and domain databases

InterProiIPR001573. Pkinase-A_anch_WSK-motif.
[Graphical view]
PfamiPF03832. WSK. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P24588-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
METTISEIHV ENKDEKRSAE GSPGAERQKE KASMLCFKRR KKAAKALKPK
60 70 80 90 100
AGSEAADVAR KCPQEAGASD QPEPTRGAWA SLKRLVTRRK RSESSKQQKP
110 120 130 140 150
LEGEMQPAIN AEDADLSKKK AKSRLKIPCI KFPRGPKRSN HSKIIEDSDC
160 170 180 190 200
SIKVQEEAEI LDIQTQTPLN DQATKAKSTQ DLSEGISRKD GDEVCESNVS
210 220 230 240 250
NSTTSGEKVI SVELGLDNGH SAIQTGTLIL EEIETIKEKQ DVQPQQASPL
260 270 280 290 300
ETSETDHQQP VLSDVPPLPA IPDQQIVEEA SNSTLESAPN GKDYESTEIV
310 320 330 340 350
AEETKPKDTE LSQESDFKEN GITEEKSKSE ESKRMEPIAI IITDTEISEF
360 370 380 390 400
DVTKSKNVPK QFLISAENEQ VGVFANDNGF EDRTSEQYET LLIETASSLV
410 420
KNAIQLSIEQ LVNEMASDDN KINNLLQ
Length:427
Mass (Da):47,088
Last modified:December 15, 2009 - v3
Checksum:iD2A86298EAF1BE32
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti188 – 1881R → Q in AAA58363. (PubMed:1512224)Curated
Sequence conflicti407 – 4071S → Y no nucleotide entry (PubMed:1733921)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti100 – 1001P → L.
Corresponds to variant rs2230491 [ dbSNP | Ensembl ].
VAR_056732
Natural varianti203 – 2031T → I.4 Publications
Corresponds to variant rs1256149 [ dbSNP | Ensembl ].
VAR_060735
Natural varianti314 – 3141E → K.
Corresponds to variant rs34433837 [ dbSNP | Ensembl ].
VAR_056733

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M90359 mRNA. Translation: AAA58363.1.
AK315336 mRNA. Translation: BAG37736.1.
AL122035 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW80862.1.
BC131516 mRNA. Translation: AAI31517.1.
CCDSiCCDS9764.1.
PIRiA43453.
RefSeqiNP_004848.3. NM_004857.3.
UniGeneiHs.656683.

Genome annotation databases

EnsembliENST00000320636; ENSP00000315615; ENSG00000179841.
ENST00000394718; ENSP00000378207; ENSG00000179841.
GeneIDi9495.
KEGGihsa:9495.
UCSCiuc001xhd.4. human.

Polymorphism databases

DMDMi281185503.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M90359 mRNA. Translation: AAA58363.1 .
AK315336 mRNA. Translation: BAG37736.1 .
AL122035 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW80862.1 .
BC131516 mRNA. Translation: AAI31517.1 .
CCDSi CCDS9764.1.
PIRi A43453.
RefSeqi NP_004848.3. NM_004857.3.
UniGenei Hs.656683.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2H9R NMR - C 391-412 [» ]
3LL8 X-ray 2.00 E 336-346 [» ]
ProteinModelPortali P24588.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114874. 14 interactions.
DIPi DIP-186N.
IntActi P24588. 8 interactions.
MINTi MINT-1733931.
STRINGi 9606.ENSP00000315615.

PTM databases

PhosphoSitei P24588.

Polymorphism databases

DMDMi 281185503.

Proteomic databases

MaxQBi P24588.
PaxDbi P24588.
PRIDEi P24588.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000320636 ; ENSP00000315615 ; ENSG00000179841 .
ENST00000394718 ; ENSP00000378207 ; ENSG00000179841 .
GeneIDi 9495.
KEGGi hsa:9495.
UCSCi uc001xhd.4. human.

Organism-specific databases

CTDi 9495.
GeneCardsi GC14P064932.
H-InvDB HIX0037749.
HGNCi HGNC:375. AKAP5.
HPAi CAB004308.
MIMi 604688. gene.
neXtProti NX_P24588.
PharmGKBi PA24669.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG25796.
GeneTreei ENSGT00390000019941.
HOGENOMi HOG000168350.
HOVERGENi HBG050479.
InParanoidi P24588.
KOi K16522.
OMAi EMASDDN.
OrthoDBi EOG73V6JZ.
PhylomeDBi P24588.
TreeFami TF105404.

Enzyme and pathway databases

Reactomei REACT_18274. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
REACT_18307. Trafficking of AMPA receptors.
SignaLinki P24588.

Miscellaneous databases

EvolutionaryTracei P24588.
GeneWikii AKAP5.
GenomeRNAii 9495.
NextBioi 35572.
PROi P24588.
SOURCEi Search...

Gene expression databases

Bgeei P24588.
CleanExi HS_AKAP5.
Genevestigatori P24588.

Family and domain databases

InterProi IPR001573. Pkinase-A_anch_WSK-motif.
[Graphical view ]
Pfami PF03832. WSK. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Localization of the cAMP-dependent protein kinase to the postsynaptic densities by A-kinase anchoring proteins. Characterization of AKAP 79."
    Carr D.W., Stofko-Hahn R.E., Fraser I.D.C., Cone R.D., Scott J.D.
    J. Biol. Chem. 267:16816-16823(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS, VARIANT ILE-203.
    Tissue: Thyroid.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-203.
    Tissue: Spleen.
  3. "The DNA sequence and analysis of human chromosome 14."
    Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
    , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
    Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-203.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-203.
  6. "Cloning and expression of an intron-less gene for AKAP 75, an anchor protein for the regulatory subunit of cAMP-dependent protein kinase II beta."
    Hirsch A.H., Glantz S.B., Li Y., You Y., Rubin C.S.
    J. Biol. Chem. 267:2131-2134(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 332-427.
    Tissue: Kidney.
  7. "Palmitoylation targets AKAP79 protein to lipid rafts and promotes its regulation of calcium-sensitive adenylyl cyclase type 8."
    Delint-Ramirez I., Willoughby D., Hammond G.V., Ayling L.J., Cooper D.M.
    J. Biol. Chem. 286:32962-32975(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PALMITOYLATION AT CYS-36 AND CYS-129, INTERACTION WITH ADCY8, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiAKAP5_HUMAN
AccessioniPrimary (citable) accession number: P24588
Secondary accession number(s): A2RRB8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: December 15, 2009
Last modified: October 29, 2014
This is version 133 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3