AKAP12

Protein-coding gene in the species Homo sapiens
AKAP12
Identifiers
AliasesAKAP12, AKAP250, SSeCKS, A-kinase anchoring protein 12
External IDsOMIM: 604698; MGI: 1932576; HomoloGene: 3740; GeneCards: AKAP12; OMA:AKAP12 - orthologs
Gene location (Human)
Chromosome 6 (human)
Chr.Chromosome 6 (human)[1]
Chromosome 6 (human)
Genomic location for AKAP12
Genomic location for AKAP12
Band6q25.1Start151,239,967 bp[1]
End151,358,559 bp[1]
Gene location (Mouse)
Chromosome 10 (mouse)
Chr.Chromosome 10 (mouse)[2]
Chromosome 10 (mouse)
Genomic location for AKAP12
Genomic location for AKAP12
Band10|10 A1Start4,216,380 bp[2]
End4,309,470 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • pons

  • lateral nuclear group of thalamus

  • spinal ganglia

  • trigeminal ganglion

  • vena cava

  • Pars compacta

  • saphenous vein

  • superior vestibular nucleus

  • pericardium

  • epithelium of colon
Top expressed in
  • efferent ductule

  • seminiferous tubule

  • vas deferens

  • stroma of bone marrow

  • external carotid artery

  • left lung lobe

  • spermatid

  • superior cervical ganglion

  • endothelial cell of lymphatic vessel

  • dermis
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • protein kinase A binding
  • 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
SpeciesHumanMouse
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 MbChr 10: 4.22 – 4.31 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000131016 – Ensembl, May 2017
  2. ^ a b c 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. Bibcode:1997CBio....7...52N. doi:10.1016/S0960-9822(06)00027-3. PMID 9000000. S2CID 18843778.
  6. ^ a b "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.

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. 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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