AKAP12

AKAP12
Identifiers
Aliases	AKAP12 , AKAP250, SSeCKS, A-kinase anchoring protein 12
External IDs	OMIM: 604698 MGI: 1932576 HomoloGene: 3740 GeneCards: AKAP12
Gene location (Human)
Chr.	Chromosome 6 (human)
End	151,358,559 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	4,359,470 bp
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• protein kinase A binding ; • GO:0001948 protein binding ; • adenylate cyclase binding ;
Cellular component	• plasma membrane ; • cell cortex ; • cytoskeleton ; • membrane ; • focal adhesion ; • cytoplasm ; • cytosol ; • Schaffer collateral - CA1 synapse ; • neuronal cell body ;
Biological process	• protein targeting ; • G protein-coupled receptor signaling pathway ; • regulation of protein kinase C signaling ; • signal transduction ; • positive regulation of protein kinase A signaling ; • adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway ; • regulation of protein kinase A signaling ; • modulation of chemical synaptic transmission ; • response to lipopolysaccharide ; • hepatic stellate cell activation ; • negative regulation of vascular permeability ; • response to electrical stimulus ; • positive regulation of nitric-oxide synthase biosynthetic process ; • positive regulation of hepatic stellate cell migration ; • positive regulation of ERK1 and ERK2 cascade ; • cellular response to interleukin-1 ; • cellular response to tumor necrosis factor ; • positive regulation of oligodendrocyte apoptotic process ;
	Sources:Amigo / QuickGO
Orthologs
	9590
	83397
	ENSG00000131016
	ENSMUSG00000038587
	Q02952
	Q9WTQ5
	NM_005100 ; NM_144497 ; NM_001370346
	NM_031185
	NP_005091 ; NP_653080 ; NP_001357275
	NP_112462
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated July 07, 2021

A-kinase anchor protein 12, aka AKAP250, is an enzyme that in humans is encoded by the AKAP12 gene.^[5]^[6]

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 encodes a member of the AKAP family. The encoded protein is expressed in endothelial cells, cultured fibroblasts, and osteosarcoma cells. It associates with protein kinase A and C and phosphatase, and serves as a scaffold protein in signal transduction. This protein and RII PKA colocalize at the cell periphery. This protein is a cell growth-related protein. Antibodies to this protein can be produced by patients with myasthenia gravis. Alternative splicing of this gene results in two transcript variants encoding different isoforms.^[6]

Interactions

AKAP12 has been shown to interact with Beta-2 adrenergic receptor.^[7]^[8]

Related Research Articles

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 beta-2 adrenergic receptor, also known as ADRB2, is a cell membrane-spanning beta-adrenergic receptor that binds epinephrine (adrenaline), a hormone and neurotransmitter whose signaling, via adenylate cyclase stimulation through trimeric Gs proteins, increased cAMP, and downstream L-type calcium channel interaction, mediates physiologic responses such as smooth muscle relaxation and bronchodilation.

Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the PTPN6 gene.

Serine/threonine-protein phosphatase PP1-alpha catalytic subunit is an enzyme that in humans is encoded by the PPP1CA gene.

Mitogen-activated protein kinase 7 also known as MAP kinase 7 is an enzyme that in humans is encoded by the MAPK7 gene.

C-jun-amino-terminal kinase-interacting protein 1 is an enzyme that in humans is encoded by the MAPK8IP1 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.

The alpha-1B adrenergic receptor, also known as ADRA1B, is an alpha-1 adrenergic receptor, and also denotes the human gene encoding it.

Arrestin, beta 1, also known as ARRB1, is a protein which in humans is encoded by the ARRB1 gene.

A-kinase anchor protein 5 is a protein that in humans is encoded by the AKAP5 gene.

This gene encodes a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinase family, and is most highly similar to GRK4 and GRK5. The protein phosphorylates the activated forms of G protein-coupled receptors to regulate their signaling.

ARF GTPase-activating protein GIT1 is an enzyme that in humans is encoded by the GIT1 gene.

A-kinase anchor protein 9 is a protein that in humans is encoded by the AKAP9 gene. AKAP9 is also known as Centrosome- and Golgi-localized protein kinase N-associated protein (CG-NAP) or AKAP350 or AKAP450

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.

Neurabin-2 is a protein that in humans is encoded by the PPP1R9B gene.

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

Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 3 is an enzyme that in humans is encoded by the MAGI3 gene.

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

Dual specificity protein phosphatase 16 is an enzyme that in humans is encoded by the DUSP16 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000131016 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000038587 - 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.
↑ Nauert JB, Klauck TM, Langeberg LK, Scott JD (Mar 1997). "Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a kinase scaffold protein". Curr. Biol. 7 (1): 52–62. doi: 10.1016/S0960-9822(06)00027-3 . PMID 9000000. S2CID 18843778.
1 2 "Entrez Gene: AKAP12 A kinase (PRKA) anchor protein (gravin) 12".
↑ Fan G, Shumay E, Wang H, Malbon CC (Jun 2001). "The scaffold protein gravin (cAMP-dependent protein kinase-anchoring protein 250) binds the beta 2-adrenergic receptor via the receptor cytoplasmic Arg-329 to Leu-413 domain and provides a mobile scaffold during desensitization". J. Biol. Chem. 276 (26): 24005–14. doi: 10.1074/jbc.M011199200 . PMID 11309381.
↑ Shih M, Lin F, Scott JD, Wang HY, Malbon CC (Jan 1999). "Dynamic complexes of beta2-adrenergic receptors with protein kinases and phosphatases and the role of gravin". J. Biol. Chem. 274 (3): 1588–95. doi: 10.1074/jbc.274.3.1588 . PMID 9880537.

External links

Human AKAP12 genome location and AKAP12 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.
Yildirim M, Paydas S, Tanriverdi K, Seydaoglu G, Disel U, Yavuz S (2007). "Gravin gene expression in acute leukaemias: clinical importance and review of the literature". Leuk. Lymphoma. 48 (6): 1167–72. doi:10.1080/10428190701377055. PMID 17577780. S2CID 35975874.
Gordon T, Grove B, Loftus JC, O'Toole T, McMillan R, Lindstrom J, Ginsberg MH (1992). "Molecular cloning and preliminary characterization of a novel cytoplasmic antigen recognized by myasthenia gravis sera". J. Clin. Invest. 90 (3): 992–9. doi:10.1172/JCI115976. PMC 329955 . PMID 1522245.
Sato N, Kokame K, Shimokado K, Kato H, Miyata T (1998). "Changes of gene expression by lysophosphatidylcholine in vascular endothelial cells: 12 up-regulated distinct genes including 5 cell growth-related, 3 thrombosis-related, and 4 others". J. Biochem. 123 (6): 1119–26. doi:10.1093/oxfordjournals.jbchem.a022051. PMID 9604001.
Shih M, Lin F, Scott JD, Wang HY, Malbon CC (1999). "Dynamic complexes of beta2-adrenergic receptors with protein kinases and phosphatases and the role of gravin". J. Biol. Chem. 274 (3): 1588–95. doi: 10.1074/jbc.274.3.1588 . PMID 9880537.
Lin F, Wang Hy, Malbon CC (2000). "Gravin-mediated formation of signaling complexes in beta 2-adrenergic receptor desensitization and resensitization". J. Biol. Chem. 275 (25): 19025–34. doi: 10.1074/jbc.275.25.19025 . PMID 10858453.
Fan G, Shumay E, Wang H, Malbon CC (2001). "The scaffold protein gravin (cAMP-dependent protein kinase-anchoring protein 250) binds the beta 2-adrenergic receptor via the receptor cytoplasmic Arg-329 to Leu-413 domain and provides a mobile scaffold during desensitization". J. Biol. Chem. 276 (26): 24005–14. doi: 10.1074/jbc.M011199200 . PMID 11309381.
Grove BD, Bruchey AK (2001). "Intracellular distribution of gravin, a PKA and PKC binding protein, in vascular endothelial cells". J. Vasc. Res. 38 (2): 163–75. doi:10.1159/000051043. PMID 11316952. S2CID 6002979.
Sasaki H, Kunimatsu M, Fujii Y, Yamakawa Y, Fukai I, Kiriyama M, Nonaka M, Sasaki M (2001). "Autoantibody to gravin is expressed more strongly in younger and nonthymomatous patients with myasthenia gravis". Surg. Today. 31 (11): 1036–7. doi:10.1007/s005950170020. PMID 11766078. S2CID 22167880.
Piontek J, Brandt R (2003). "Differential and regulated binding of cAMP-dependent protein kinase and protein kinase C isoenzymes to gravin in human model neurons: Evidence that gravin provides a dynamic platform for the localization for kinases during neuronal development". J. Biol. Chem. 278 (40): 38970–9. doi: 10.1074/jbc.M306749200 . PMID 12857743.
Tao J, Wang HY, Malbon CC (2003). "Protein kinase A regulates AKAP250 (gravin) scaffold binding to the beta2-adrenergic receptor". EMBO J. 22 (24): 6419–29. doi:10.1093/emboj/cdg628. PMC 291823 . PMID 14657015.
Choi MC, Jong HS, Kim TY, Song SH, Lee DS, Lee JW, Kim TY, Kim NK, Bang YJ (2004). "AKAP12/Gravin is inactivated by epigenetic mechanism in human gastric carcinoma and shows growth suppressor activity". Oncogene. 23 (42): 7095–103. doi: 10.1038/sj.onc.1207932 . PMID 15258566.
Ballif BA, Villén J, Beausoleil SA, Schwartz D, Gygi SP (2004). "Phosphoproteomic analysis of the developing mouse brain". Mol. Cell. Proteomics. 3 (11): 1093–101. doi: 10.1074/mcp.M400085-MCP200 . PMID 15345747.
Streb JW, Miano JM (2005). "AKAP12alpha, an atypical serum response factor-dependent target gene". J. Biol. Chem. 280 (6): 4125–34. doi: 10.1074/jbc.M412466200 . PMID 15590635.
Streb JW, Miano JM (2005). "Cross-species sequence analysis reveals multiple charged residue-rich domains that regulate nuclear/cytoplasmic partitioning and membrane localization of a kinase anchoring protein 12 (SSeCKS/Gravin)". J. Biol. Chem. 280 (30): 28007–14. doi: 10.1074/jbc.M414017200 . PMID 15923193.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000131016 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000038587 - 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.

[pmid9000000-5] Nauert JB, Klauck TM, Langeberg LK, Scott JD (Mar 1997). "Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a kinase scaffold protein". Curr. Biol. 7 (1): 52–62. doi: 10.1016/S0960-9822(06)00027-3 . PMID 9000000. S2CID 18843778.

[entrez-6] 1 2 "Entrez Gene: AKAP12 A kinase (PRKA) anchor protein (gravin) 12".

[pmid11309381-7] Fan G, Shumay E, Wang H, Malbon CC (Jun 2001). "The scaffold protein gravin (cAMP-dependent protein kinase-anchoring protein 250) binds the beta 2-adrenergic receptor via the receptor cytoplasmic Arg-329 to Leu-413 domain and provides a mobile scaffold during desensitization". J. Biol. Chem. 276 (26): 24005–14. doi: 10.1074/jbc.M011199200 . PMID 11309381.

[pmid9880537-8] Shih M, Lin F, Scott JD, Wang HY, Malbon CC (Jan 1999). "Dynamic complexes of beta2-adrenergic receptors with protein kinases and phosphatases and the role of gravin". J. Biol. Chem. 274 (3): 1588–95. doi: 10.1074/jbc.274.3.1588 . PMID 9880537.

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