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Protein

A-kinase anchor protein 5

Gene

AKAP5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • adenylate cyclase binding Source: UniProtKB
  • calmodulin binding Source: UniProtKB-KW
  • glutamate receptor binding Source: SynGO-UCL
  • protein kinase A binding Source: ProtInc
  • protein kinase A regulatory subunit binding Source: UniProtKB
  • protein phosphatase 2B binding Source: SynGO-UCL
  • scaffold protein binding Source: SynGO-UCL
  • SH3 domain binding Source: SynGO-UCL

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding

Enzyme and pathway databases

ReactomeiR-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-399719 Trafficking of AMPA receptors
R-HSA-9010642 ROBO receptors bind AKAP5
SignaLinkiP24588

Protein family/group databases

TCDBi8.A.28.1.6 the ankyrin (ankyrin) family

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
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000179841.8
HGNCiHGNC:375 AKAP5
MIMi604688 gene
neXtProtiNX_P24588

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi392L → P: Prevents or diminishes RII binding. 1 Publication1
Mutagenesisi396A → P: Prevents or diminishes RII binding. 1 Publication1
Mutagenesisi400V → P: Prevents or diminishes RII binding. 1 Publication1
Mutagenesisi405Q → P: Prevents or diminishes RII binding. 1 Publication1
Mutagenesisi408I → P: Prevents or diminishes RII binding. 1 Publication1

Organism-specific databases

DisGeNETi9495
OpenTargetsiENSG00000179841
PharmGKBiPA24669

Polymorphism and mutation databases

BioMutaiAKAP5
DMDMi281185503

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000645291 – 427A-kinase anchor protein 5Add BLAST427

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei22PhosphoserineBy similarity1
Lipidationi36S-palmitoyl cysteine1 Publication1
Lipidationi129S-palmitoyl cysteine1 Publication1

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, Phosphoprotein

Proteomic databases

EPDiP24588
MaxQBiP24588
PaxDbiP24588
PeptideAtlasiP24588
PRIDEiP24588
ProteomicsDBi54217

PTM databases

iPTMnetiP24588
PhosphoSitePlusiP24588
SwissPalmiP24588

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

BgeeiENSG00000179841 Expressed in 181 organ(s), highest expression level in caudate nucleus
CleanExiHS_AKAP5
GenevisibleiP24588 HS

Organism-specific databases

HPAiCAB004308
HPA053891

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114874, 39 interactors
ComplexPortaliCPX-1112 Calcineurin-Calmodulin-AKAP5 complex, gamma-R1 variant
CPX-1114 Calcineurin-Calmodulin-AKAP5 complex, alpha-R2 variant
CPX-1116 Calcineurin-Calmodulin-AKAP5 complex, beta-R2 variant
CPX-1118 Calcineurin-Calmodulin-AKAP5 complex, gamma-R2 variant
CPX-674 Calcineurin-Calmodulin-AKAP5 complex, alpha-R1 variant
CPX-998 Calcineurin-Calmodulin-AKAP5 complex, beta-R1 variant
CORUMiP24588
DIPiDIP-186N
IntActiP24588, 30 interactors
MINTiP24588
STRINGi9606.ENSP00000315615

Structurei

Secondary structure

1427
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP24588
SMRiP24588
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP24588

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini73 – 103AKAPAdd BLAST31

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 170Essential to the intracellular anchoring functionBy similarityAdd BLAST170
Regioni392 – 405PKA-RII subunit binding domainAdd BLAST14

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.

Phylogenomic databases

eggNOGiENOG410IIWH Eukaryota
ENOG4111833 LUCA
GeneTreeiENSGT00390000019941
HOGENOMiHOG000168350
HOVERGENiHBG050479
InParanoidiP24588
KOiK16522
OMAiEMASDDN
OrthoDBiEOG091G05II
PhylomeDBiP24588
TreeFamiTF105404

Family and domain databases

InterProiView protein in InterPro
IPR001573 Pkinase-A_anch_WSK-motif
PfamiView protein in Pfam
PF03832 WSK, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti188R → Q in AAA58363 (PubMed:1512224).Curated1
Sequence conflicti407S → Y no nucleotide entry (PubMed:1733921).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_056732100P → L. Corresponds to variant dbSNP:rs2230491Ensembl.1
Natural variantiVAR_060735203T → I4 PublicationsCorresponds to variant dbSNP:rs1256149Ensembl.1
Natural variantiVAR_056733314E → K. Corresponds to variant dbSNP:rs34433837Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H9RNMR-C391-412[»]
3LL8X-ray2.00E336-346[»]
5NINX-ray1.70C/D77-92[»]
ProteinModelPortaliP24588
SMRiP24588
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114874, 39 interactors
ComplexPortaliCPX-1112 Calcineurin-Calmodulin-AKAP5 complex, gamma-R1 variant
CPX-1114 Calcineurin-Calmodulin-AKAP5 complex, alpha-R2 variant
CPX-1116 Calcineurin-Calmodulin-AKAP5 complex, beta-R2 variant
CPX-1118 Calcineurin-Calmodulin-AKAP5 complex, gamma-R2 variant
CPX-674 Calcineurin-Calmodulin-AKAP5 complex, alpha-R1 variant
CPX-998 Calcineurin-Calmodulin-AKAP5 complex, beta-R1 variant
CORUMiP24588
DIPiDIP-186N
IntActiP24588, 30 interactors
MINTiP24588
STRINGi9606.ENSP00000315615

Protein family/group databases

TCDBi8.A.28.1.6 the ankyrin (ankyrin) family

PTM databases

iPTMnetiP24588
PhosphoSitePlusiP24588
SwissPalmiP24588

Polymorphism and mutation databases

BioMutaiAKAP5
DMDMi281185503

Proteomic databases

EPDiP24588
MaxQBiP24588
PaxDbiP24588
PeptideAtlasiP24588
PRIDEiP24588
ProteomicsDBi54217

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9495
DisGeNETi9495
EuPathDBiHostDB:ENSG00000179841.8
GeneCardsiAKAP5
H-InvDBiHIX0037749
HGNCiHGNC:375 AKAP5
HPAiCAB004308
HPA053891
MIMi604688 gene
neXtProtiNX_P24588
OpenTargetsiENSG00000179841
PharmGKBiPA24669
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IIWH Eukaryota
ENOG4111833 LUCA
GeneTreeiENSGT00390000019941
HOGENOMiHOG000168350
HOVERGENiHBG050479
InParanoidiP24588
KOiK16522
OMAiEMASDDN
OrthoDBiEOG091G05II
PhylomeDBiP24588
TreeFamiTF105404

Enzyme and pathway databases

ReactomeiR-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-399719 Trafficking of AMPA receptors
R-HSA-9010642 ROBO receptors bind AKAP5
SignaLinkiP24588

Miscellaneous databases

EvolutionaryTraceiP24588
GeneWikiiAKAP5
GenomeRNAii9495
PROiPR:P24588
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000179841 Expressed in 181 organ(s), highest expression level in caudate nucleus
CleanExiHS_AKAP5
GenevisibleiP24588 HS

Family and domain databases

InterProiView protein in InterPro
IPR001573 Pkinase-A_anch_WSK-motif
PfamiView protein in Pfam
PF03832 WSK, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiAKAP5_HUMAN
AccessioniPrimary (citable) accession number: P24588
Secondary accession number(s): A2RRB8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: December 15, 2009
Last modified: September 12, 2018
This is version 167 of the entry and version 3 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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