AKAP5

AKAP5
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2H9R, 3LL8
Identifiers
Aliases	AKAP5 , AKAP75, AKAP79, H21, A-kinase anchoring protein 5
External IDs	OMIM: 604688 MGI: 2685104 HomoloGene: 15854 GeneCards: AKAP5
Gene location (Human)
Chr.	Chromosome 14 (human)
End	64,474,503 bp
Gene location (Mouse)
Chr.	Chromosome 12 (mouse)
End	76,380,927 bp
RNA expression pattern
	Top expressed in
	middle temporal gyrus; ; Brodmann area 23; ; entorhinal cortex; ; superior frontal gyrus; ; postcentral gyrus; ; nucleus accumbens; ; endothelial cell; ; caudate nucleus; ; prefrontal cortex; ; dorsolateral prefrontal cortex;
	Top expressed in
	left lung lobe; ; olfactory tubercle; ; nucleus accumbens; ; right lung; ; right lung lobe; ; globus pallidus; ; temporal lobe; ; Region I of hippocampus proper; ; amygdala; ; piriform cortex;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein kinase A binding ; calmodulin binding ; protein binding ; protein kinase A regulatory subunit binding ; adenylate cyclase binding ; SH3 domain binding ; protein phosphatase 2B binding ; beta-2 adrenergic receptor binding ; molecular adaptor activity ; glutamate receptor binding ; GABA receptor binding ; scaffold protein binding ;
Cellular component	cytosol ; membrane ; plasma membrane ; cytoplasmic side of plasma membrane ; postsynaptic density ; dendrite membrane ; dendritic spine ; membrane raft ; excitatory synapse ; intracellular anatomical structure ;
Biological process	protein targeting ; signal transduction ; positive regulation of protein kinase A signaling ; chemical synaptic transmission ; adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway ; negative regulation of adenylate cyclase activity ; regulation of protein kinase A signaling ; positive regulation of adenylate cyclase activity ; positive regulation of protein localization to plasma membrane ;
	Sources:Amigo / QuickGO
Orthologs
	9495
	238276
	ENSG00000179841
	ENSMUSG00000021057
	P24588 ; Q6PG46
	D3YVF0
	NM_004857
	NM_001101471
	NP_004848 ; NP_004848.3
	NP_001094941
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated January 30, 2023

A-kinase anchor protein 5 is a protein that in humans is encoded by the AKAP5 gene.^[5]^[6]^[7]

Function

The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene is intronless and encodes a member of the AKAP family. The encoded protein binds to the RII-beta regulatory subunit of PKA, and also to protein kinase C and the phosphatase calcineurin. It is predominantly expressed in cerebral cortex and may anchor the PKA protein at postsynaptic densities (PSD) and be involved in the regulation of postsynaptic events. It is also expressed in T lymphocytes and may function to inhibit interleukin 2 transcription by disrupting calcineurin-dependent dephosphorylation of NFAT.^[7]

Interactions

AKAP5 has been shown to interact with:

Calcineurin ^[8] and
GABRB3.^[9]

Related Research Articles

<span class="mw-page-title-main">Protein kinase A</span> Family of enzymes

In cell biology, protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase. PKA has several functions in the cell, including regulation of glycogen, sugar, and lipid metabolism. It should not be confused with 5'-AMP-activated protein kinase.

Calcineurin (CaN) is a calcium and calmodulin dependent serine/threonine protein phosphatase. It activates the T cells of the immune system and can be blocked by drugs. Calcineurin activates nuclear factor of activated T cell cytoplasmic (NFATc), a transcription factor, by dephosphorylating it. The activated NFATc is then translocated into the nucleus, where it upregulates the expression of interleukin 2 (IL-2), which, in turn, stimulates the growth and differentiation of the T cell response. Calcineurin is the target of a class of drugs called calcineurin inhibitors, which include ciclosporin, voclosporin, pimecrolimus and tacrolimus.

The catalytic subunit α of protein kinase A is a key regulatory enzyme that in humans is encoded by the PRKACA gene. This enzyme is responsible for phosphorylating other proteins and substrates, changing their activity. Protein kinase A catalytic subunit is a member of the AGC kinase family, and contributes to the control of cellular processes that include glucose metabolism, cell division, and contextual memory. PKA Cα is part of a larger protein complex that is responsible for controlling when and where proteins are phosphorylated. Defective regulation of PKA holoenzyme activity has been linked to the progression of cardiovascular disease, certain endocrine disorders and cancers.

Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene.

Sodium-hydrogen exchange regulatory cofactor NHE-RF2 (NHERF-2) also known as tyrosine kinase activator protein 1 (TKA-1) or SRY-interacting protein 1 (SIP-1) is a protein that in humans is encoded by the SLC9A3R2 gene.

cAMP-dependent protein kinase type I-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR1A gene.

cAMP-dependent protein kinase type II-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR2A gene.

Calcium/calmodulin-dependent protein kinase type II gamma chain is an enzyme that in humans is encoded by the CAMK2G gene.

cAMP-dependent protein kinase type II-beta regulatory subunit is an enzyme that in humans is encoded by the PRKAR2B gene.

A-kinase anchor protein 13 is a protein that in humans is encoded by the AKAP13 gene. This protein is also called AKAP-Lbc because it encodes the lymphocyte blast crisis (Lbc) oncogene, and ARHGEF13/RhoGEF13 because it contains a guanine nucleotide exchange factor (GEF) domain for the RhoA small GTP-binding protein.

cAMP-dependent protein kinase catalytic subunit beta is an enzyme that in humans is encoded by the PRKACB gene.

A-kinase anchor protein 12, aka AKAP250, is an enzyme that in humans is encoded by the AKAP12 gene.

cAMP-dependent protein kinase type I-beta regulatory subunit is an enzyme that in humans is encoded by the PRKAR1B gene.

A kinase anchor protein 1, mitochondrial is an enzyme that in humans is encoded by the AKAP1 gene.

A-kinase anchor protein 8 is an enzyme that, in humans, is encoded by the AKAP8 gene.

cAMP-dependent protein kinase catalytic subunit gamma is an enzyme that in humans is encoded by the PRKACG gene.

cAMP-dependent protein kinase inhibitor alpha is a protein that in humans is encoded by the PKIA gene.

A-kinase anchor protein 3 is an enzyme that in humans is encoded by the AKAP3 gene.

A-kinase anchor protein 11 is an enzyme that in humans is encoded by the AKAP11 gene.

A-kinase anchor protein 6 is an enzyme that in humans is encoded by the AKAP6 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000179841 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021057 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Carr DW, Stofko-Hahn RE, Fraser ID, Cone RD, Scott JD (Sep 1992). "Localization of the cAMP-dependent protein kinase to the postsynaptic densities by A-kinase anchoring proteins. Characterization of AKAP 79". J Biol Chem. 267 (24): 16816–23. doi: 10.1016/S0021-9258(18)41856-X . PMID 1512224.
↑ Carr DW, Hausken ZE, Fraser ID, Stofko-Hahn RE, Scott JD (Aug 1992). "Association of the type II cAMP-dependent protein kinase with a human thyroid RII-anchoring protein. Cloning and characterization of the RII-binding domain". J Biol Chem. 267 (19): 13376–82. doi: 10.1016/S0021-9258(18)42221-1 . PMID 1618839.
1 2 "Entrez Gene: AKAP5 A kinase (PRKA) anchor protein 5".
↑ Kashishian A, Howard M, Loh C, Gallatin WM, Hoekstra MF, Lai Y (Oct 1998). "AKAP79 inhibits calcineurin through a site distinct from the immunophilin-binding region". J. Biol. Chem. 273 (42): 27412–9. doi: 10.1074/jbc.273.42.27412 . PMID 9765270.
↑ Brandon NJ, Jovanovic JN, Colledge M, Kittler JT, Brandon JM, Scott JD, Moss SJ (Jan 2003). "A-kinase anchoring protein 79/150 facilitates the phosphorylation of GABA(A) receptors by cAMP-dependent protein kinase via selective interaction with receptor beta subunits". Mol. Cell. Neurosci. 22 (1): 87–97. doi:10.1016/s1044-7431(02)00017-9. PMID 12595241. S2CID 6172436.

External links

Human AKAP5 genome location and AKAP5 gene details page in the UCSC Genome Browser .

Lester LB, Scott JD (1997). "Anchoring and scaffold proteins for kinases and phosphatases". Recent Prog. Horm. Res. 52: 409–29, discussion 429–30. PMID 9238861.
Michel JJ, Scott JD (2002). "AKAP mediated signal transduction". Annu. Rev. Pharmacol. Toxicol. 42: 235–57. doi:10.1146/annurev.pharmtox.42.083101.135801. PMID 11807172.
Hirsch AH, Glantz SB, Li Y, et al. (1992). "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". J. Biol. Chem. 267 (4): 2131–4. doi: 10.1016/S0021-9258(18)45852-8 . PMID 1733921.
Carr DW, Stofko-Hahn RE, Fraser ID, et al. (1991). "Interaction of the regulatory subunit (RII) of cAMP-dependent protein kinase with RII-anchoring proteins occurs through an amphipathic helix binding motif". J. Biol. Chem. 266 (22): 14188–92. doi: 10.1016/S0021-9258(18)98665-5 . PMID 1860836.
Coghlan VM, Perrino BA, Howard M, et al. (1995). "Association of protein kinase A and protein phosphatase 2B with a common anchoring protein". Science. 267 (5194): 108–11. doi:10.1126/science.7528941. PMID 7528941.
Glantz SB, Li Y, Rubin CS (1993). "Characterization of distinct tethering and intracellular targeting domains in AKAP75, a protein that links cAMP-dependent protein kinase II beta to the cytoskeleton". J. Biol. Chem. 268 (17): 12796–804. doi: 10.1016/S0021-9258(18)31458-3 . PMID 8509414.
Faux MC, Scott JD (1997). "Regulation of the AKAP79-protein kinase C interaction by Ca2+/Calmodulin". J. Biol. Chem. 272 (27): 17038–44. doi: 10.1074/jbc.272.27.17038 . PMID 9202019.
Kashishian A, Howard M, Loh C, et al. (1998). "AKAP79 inhibits calcineurin through a site distinct from the immunophilin-binding region". J. Biol. Chem. 273 (42): 27412–9. doi: 10.1074/jbc.273.42.27412 . PMID 9765270.
Paolillo M, Feliciello A, Porcellini A, et al. (1999). "The type and the localization of cAMP-dependent protein kinase regulate transmission of cAMP signals to the nucleus in cortical and cerebellar granule cells". J. Biol. Chem. 274 (10): 6546–52. doi: 10.1074/jbc.274.10.6546 . PMID 10037748.
Dodge KL, Carr DW, Sanborn BM (1999). "Protein kinase A anchoring to the myometrial plasma membrane is required for cyclic adenosine 3',5'-monophosphate regulation of phosphatidylinositide turnover". Endocrinology. 140 (11): 5165–70. doi: 10.1210/endo.140.11.7133 . PMID 10537145.
Fraser ID, Cong M, Kim J, et al. (2000). "Assembly of an A kinase-anchoring protein-beta(2)-adrenergic receptor complex facilitates receptor phosphorylation and signaling". Curr. Biol. 10 (7): 409–12. doi: 10.1016/S0960-9822(00)00419-X . PMID 10753752.
Sík A, Gulácsi A, Lai Y, et al. (2000). "Localization of the A kinase anchoring protein AKAP79 in the human hippocampus". Eur. J. Neurosci. 12 (4): 1155–64. doi:10.1046/j.1460-9568.2000.00002.x. PMID 10762347. S2CID 40933732.
Colledge M, Dean RA, Scott GK, et al. (2000). "Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex". Neuron. 27 (1): 107–19. doi: 10.1016/S0896-6273(00)00013-1 . PMID 10939335.
Indolfi C, Stabile E, Coppola C, et al. (2001). "Membrane-bound protein kinase A inhibits smooth muscle cell proliferation in vitro and in vivo by amplifying cAMP-protein kinase A signals". Circ. Res. 88 (3): 319–24. doi: 10.1161/01.res.88.3.319 . PMID 11179200.
Dart C, Leyland ML (2001). "Targeting of an A kinase-anchoring protein, AKAP79, to an inwardly rectifying potassium channel, Kir2.1". J. Biol. Chem. 276 (23): 20499–505. doi: 10.1074/jbc.M101425200 . PMID 11287423.
Xie G, Raufman JP (2001). "Association of protein kinase A with AKAP150 facilitates pepsinogen secretion from gastric chief cells". Am. J. Physiol. Gastrointest. Liver Physiol. 281 (4): G1051–8. doi: 10.1152/ajpgi.2001.281.4.G1051 . PMID 11557526. S2CID 20939022.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000179841 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021057 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1512224-5] Carr DW, Stofko-Hahn RE, Fraser ID, Cone RD, Scott JD (Sep 1992). "Localization of the cAMP-dependent protein kinase to the postsynaptic densities by A-kinase anchoring proteins. Characterization of AKAP 79". J Biol Chem. 267 (24): 16816–23. doi: 10.1016/S0021-9258(18)41856-X . PMID 1512224.

[pmid1618839-6] Carr DW, Hausken ZE, Fraser ID, Stofko-Hahn RE, Scott JD (Aug 1992). "Association of the type II cAMP-dependent protein kinase with a human thyroid RII-anchoring protein. Cloning and characterization of the RII-binding domain". J Biol Chem. 267 (19): 13376–82. doi: 10.1016/S0021-9258(18)42221-1 . PMID 1618839.

[entrez-7] 1 2 "Entrez Gene: AKAP5 A kinase (PRKA) anchor protein 5".

[pmid9765270-8] Kashishian A, Howard M, Loh C, Gallatin WM, Hoekstra MF, Lai Y (Oct 1998). "AKAP79 inhibits calcineurin through a site distinct from the immunophilin-binding region". J. Biol. Chem. 273 (42): 27412–9. doi: 10.1074/jbc.273.42.27412 . PMID 9765270.

[pmid12595241-9] Brandon NJ, Jovanovic JN, Colledge M, Kittler JT, Brandon JM, Scott JD, Moss SJ (Jan 2003). "A-kinase anchoring protein 79/150 facilitates the phosphorylation of GABA(A) receptors by cAMP-dependent protein kinase via selective interaction with receptor beta subunits". Mol. Cell. Neurosci. 22 (1): 87–97. doi:10.1016/s1044-7431(02)00017-9. PMID 12595241. S2CID 6172436.

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