AKAP12

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

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)[1] Band 6q25.1 Start 151,239,967 bp[1] End 151,358,559 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10|10 A1 Start 4,266,380 bp[2] End 4,359,470 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • protein kinase A binding • GO:0001948 protein binding • adenylate cyclase binding Cellular component • cell 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 • positive regulation of tumor necrosis factor biosynthetic process • 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 • positive regulation of tumor necrosis factor secretion Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	9590	83397
Ensembl	ENSG00000131016	ENSMUSG00000038587
UniProt	Q02952	Q9WTQ5
RefSeq (mRNA)	NM_005100 NM_144497 NM_001370346	NM_031185
RefSeq (protein)	NP_005091 NP_653080 NP_001357275	NP_112462
Location (UCSC)	Chr 6: 151.24 – 151.36 Mb	Chr 10: 4.27 – 4.36 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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]

References

1. GRCh38: Ensembl release 89: ENSG00000131016 - Ensembl, May 2017
2. 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.
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.
6. "Entrez Gene: AKAP12 A kinase (PRKA) anchor protein (gravin) 12".
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.
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.

External links

• Human AKAP12 genome location and AKAP12 gene details page in the UCSC Genome Browser.

Further reading

• 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.
• 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.
• 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.
• 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.