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P24588 (AKAP5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:AKAP5
Synonyms:AKAP79
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length427 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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. Ref.7

Subcellular location

Membrane; Lipid-anchor. Note: Associates with lipid rafts. Ref.7

Tissue specificity

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

Domain

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.

Post-translational modification

Palmitoylation at Cys-36 and Cys-129 plays a key role in targeting to lipid rafts. Ref.7

Sequence similarities

Contains 1 AKAP domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Kcnj2P355612EBI-703640,EBI-703793From a different organism.
RXFP1Q9HBX92EBI-703640,EBI-8088969

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 427427A-kinase anchor protein 5
PRO_0000064529

Regions

Domain73 – 10331AKAP
Region1 – 170170Essential to the intracellular anchoring function By similarity
Region392 – 40514PKA-RII subunit binding domain

Amino acid modifications

Lipidation361S-palmitoyl cysteine Ref.7
Lipidation1291S-palmitoyl cysteine Ref.7

Natural variations

Natural variant1001P → L.
Corresponds to variant rs2230491 [ dbSNP | Ensembl ].
VAR_056732
Natural variant2031T → I. Ref.1 Ref.2 Ref.4 Ref.5
Corresponds to variant rs1256149 [ dbSNP | Ensembl ].
VAR_060735
Natural variant3141E → K.
Corresponds to variant rs34433837 [ dbSNP | Ensembl ].
VAR_056733

Experimental info

Mutagenesis3921L → P: Prevents or diminishes RII binding.
Mutagenesis3961A → P: Prevents or diminishes RII binding.
Mutagenesis4001V → P: Prevents or diminishes RII binding.
Mutagenesis4051Q → P: Prevents or diminishes RII binding.
Mutagenesis4081I → P: Prevents or diminishes RII binding.
Sequence conflict1881R → Q in AAA58363. Ref.1
Sequence conflict4071S → Y no nucleotide entry Ref.6

Secondary structure

...... 427
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P24588 [UniParc].

Last modified December 15, 2009. Version 3.
Checksum: D2A86298EAF1BE32

FASTA42747,088
        10         20         30         40         50         60 
METTISEIHV ENKDEKRSAE GSPGAERQKE KASMLCFKRR KKAAKALKPK AGSEAADVAR 

        70         80         90        100        110        120 
KCPQEAGASD QPEPTRGAWA SLKRLVTRRK RSESSKQQKP LEGEMQPAIN AEDADLSKKK 

       130        140        150        160        170        180 
AKSRLKIPCI KFPRGPKRSN HSKIIEDSDC SIKVQEEAEI LDIQTQTPLN DQATKAKSTQ 

       190        200        210        220        230        240 
DLSEGISRKD GDEVCESNVS NSTTSGEKVI SVELGLDNGH SAIQTGTLIL EEIETIKEKQ 

       250        260        270        280        290        300 
DVQPQQASPL ETSETDHQQP VLSDVPPLPA IPDQQIVEEA SNSTLESAPN GKDYESTEIV 

       310        320        330        340        350        360 
AEETKPKDTE LSQESDFKEN GITEEKSKSE ESKRMEPIAI IITDTEISEF DVTKSKNVPK 

       370        380        390        400        410        420 
QFLISAENEQ VGVFANDNGF EDRTSEQYET LLIETASSLV KNAIQLSIEQ LVNEMASDDN 


KINNLLQ 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA43453.
RefSeqNP_004848.3. NM_004857.3.
UniGeneHs.656683.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2H9RNMR-C391-412[»]
3LL8X-ray2.00E336-346[»]
ProteinModelPortalP24588.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114874. 14 interactions.
DIPDIP-186N.
IntActP24588. 8 interactions.
MINTMINT-1733931.
STRING9606.ENSP00000315615.

PTM databases

PhosphoSiteP24588.

Polymorphism databases

DMDM281185503.

Proteomic databases

PaxDbP24588.
PRIDEP24588.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000320636; ENSP00000315615; ENSG00000179841.
ENST00000394718; ENSP00000378207; ENSG00000179841.
GeneID9495.
KEGGhsa:9495.
UCSCuc001xhd.4. human.

Organism-specific databases

CTD9495.
GeneCardsGC14P064932.
H-InvDBHIX0037749.
HGNCHGNC:375. AKAP5.
HPACAB004308.
MIM604688. gene.
neXtProtNX_P24588.
PharmGKBPA24669.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG25796.
HOGENOMHOG000168350.
HOVERGENHBG050479.
InParanoidP24588.
KOK16522.
OMAEMASDDN.
OrthoDBEOG73V6JZ.
PhylomeDBP24588.
TreeFamTF105404.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_13685. Neuronal System.
SignaLinkP24588.

Gene expression databases

BgeeP24588.
CleanExHS_AKAP5.
GenevestigatorP24588.

Family and domain databases

InterProIPR001573. Pkinase-A_anch_WSK-motif.
[Graphical view]
PfamPF03832. WSK. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP24588.
GeneWikiAKAP5.
GenomeRNAi9495.
NextBio35572.
PROP24588.
SOURCESearch...

Entry information

Entry nameAKAP5_HUMAN
AccessionPrimary (citable) accession number: P24588
Secondary accession number(s): A2RRB8
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: December 15, 2009
Last modified: February 19, 2014
This is version 126 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM