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AKAP12 A kinase (PRKA) anchor protein 12

Written2006-11Irwin H Gelman
Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
Updated2014-10Irwin H Gelman
Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA

Abstract Review on AKAP1, with data on DNA, on the protein encoded, and where the gene is implicated.

(Note : for Links provided by Atlas : click)

Identity

Alias_namesA kinase (PRKA) anchor protein (gravin) 12
A kinase (PRKA) anchor protein 12
Alias_symbol (synonym)AKAP250
SSeCKS
HGNC (Hugo) AKAP12
LocusID (NCBI) 9590
Atlas_Id 607
Location 6q25.1  [Link to chromosome band 6q25]
Location_base_pair Starts at 151561134 and ends at 151679694 bp from pter ( according to hg19-Feb_2009)  [Mapping AKAP12.png]
 
  AKAP12 (6q24-25.2) in normal cells probed with a about 5Kb human AKAP12 probe. Courtesy of Irwin Gelman; adapted from Xia et al., Cancer Res.61:5644-5651, 2001.
Fusion genes
(updated 2016)
AKAP12 (6q25.1) / AKAP12 (6q25.1)AKAP12 (6q25.1) / MED12 (Xq13.1)AKAP12 (6q25.1) / MTHFD1L (6q25.1)

DNA/RNA

Note The AKAP12 gene and promoter structure is strongly conserved from fish to humans, including syntenic regions conserved in the mouse (chrom. 10) and rat (chrom. 1). No family members (homologues) other than AKAP12 exist within a given species.
 
  Human and mouse cells have similar exon/intron usage and spacing. AKAP12 has three independent promoters, α, β, and γ. The gamma promoter is active only in the testes while the α and β are co-active in most cells and tissues studied. Exons 1A1 and 1A2 combine to then splice to a common splice acceptor on Exon 2 used by Exon 1B. Exons 1A1 and 1A2 produce the N-terminal 103 amino acids of "AKAP12 alpha" whereas Exon 1B encodes the N-terminal 8 amino acids of "AKAP12 β"; the remaining amino acids are encoded in Exon 2. "AKAP12 gamma" is encoded by a read-through transcript starting in the intron upstream of Exon 2, utilizing an in-frame ATG in Exon 2. Therefore, the α, β, and γ transcripts encode proteins that only differ in their N-termini.
Transcription Human and rodent AKAP12 is expressed ubiquitously, with greater expression in mesenchymal cells, expression in specific epithelial types, such as breast and prostate, and little in most endothelial cells. Several highly specialized, differentiated cells type, such as parietal cells in the glomerulus, pericytes, astrocytes and Purkinje cells, show especially strong expression.
Pseudogene None.

Protein

 
  A: Except for testes, most cells express four major isoforms of AKAP12 protein. The 305 kDa isoforms is the myristylated AKAP12alpha whereas the 287 kDa isoforms is AKAP12beta. The 250 kDa and 43 kDa isoforms are proteolytic cleavage products common to the AKAP12alpha and beta isoforms.
B: Human AKAP12alpha encodes a 1,780 amino acids full-length protein. The first about 1,000 amino acids of human and rodent AKAP12 share 83% identity followed by about 600 amino acids with less than 20% identity. The N-terminal homology domain (green) shows about 40% identity to the Xgl (Xenopus gravin-like) gene in Xenopus. Both human and rodent AKAP12 share a shorter C-terminal domain containing the PKA-RII binding (AKAP) domain (green box in human AKAP12).
Expression AKAP12 isoforms are expressed in most tissue and organ types, with high expression levels in the testes, ovary, brain, lung and heart. Most mesenchyme, smooth muscle and some epithelial cells (breast, prostate, lung, ovary) express significant AKAP12 levels. Lower levels of AKAP12 are found in endothelial cells, although express in these cells is usually associated with wounding and/or inflammation. High expression is also found in some specialized, differentiated cells such as the parietal cells of the glomerulus, pericytes, astrocytes and Purkinje cells.
Localisation Most cell types display a cortical cytoskeletal staining pattern for AKAP12, with enrichment at the plasma membrane (associated with N-terminal myristylation and at least three N-terminal polybasic domains) and in the perinucleus. However, some staining has been observed in cell nuclei, probably directed by 4 SV40 Tag-like nuclear localization signals (NLS) found in the N-terminal third of the protein.
Function 1) Facilitates the sensitization/resensitization reaction of beta-adrenergic receptors.
2) Scaffolds protein kinase (PK) A, PKC, and SRC.
3) Autoantigen in some cases of myasthenia gravis.
4) Anti-angiogenic factor. The rodent orthologue has been shown to inhibit brain angiogenesis and induce the blood-brain barrier, and to inhibit VEGF-mediated metastasis.
5) Metastasis suppressor (see Gelman, 2012). Many studies show i) AKAP12 downregulation in metastases compared to primary-site tumors, associated with hypermethylation of promoter CpG islands, ii) AKAP12-/- mice are tumor- and metastasis-prone to skin carcinogens, iii) increased spontaneous lymph node metastasis of high-grade prostatic intraepithelial neoplasia in transgenic models, and iv) selective suppression of spontaneous and experimental metastasis following re-expression of rodent Akap12 in MAT-LyLu prostate cancer cells.
6) Effector of Polo-like kinase 1 to regulate cytokinesis.
7) Maintenance of barrier functions such as blood-brain, blood-retinal barriers and fibrotic scars in CNS repair.
8) Regulation of adhesion, chemotaxis and invasiveness through the control of actin cytoskeletal remodeling.
 
  AKAP12 is phosphorylated by PLK1 on T766 during metaphase, and shRNa knockdown of AKAP12 leads to cytokinesis failure (Canton et al., 2012).
Homology Southern blotting analysis as well as analysis of sequenced genomes indicates that vertebrates encode single AKAP12 orthologues, with no gene family members. Thus, the protein diversity of this gene stems from promoter choice, alternative splicing, proteolytic maturation and post-translational modification. AKAP12 has limited sequence homology based on short domains. For example, the C-terminal AKAP domain is homologous to the analogous domain in AKP79. Also, AKAP12 shares some so-called MARCKS protein-like effector domains- positively charged stretches of amino acids involved in plasma membrane targeting.

Mutations

Note 141 mutations (mostly point mutants and some small deletions) have been described in COSMIC, the vast majority of which are found in the major protein-coding exon ("exon 2")
ESR1-AKAP12 fusions have been recently described (Ma et al., 2014) in clinical cases of breast cancer.
. There are at least 539 single nucleotide polymorphisms (SNP). 59 study datasets for AKAP12 SNPs described in GWAS analyses For example, HGVST779 identifies AKAP12 SNPs associated with chronic myelogenous leukemia. Another study identifies AKAP12 SNPs associated with psychiatric depression (Ripke et al., 2012).
A number of QTLs have been described associated with susceptibility for prostate cancer and insulin sensitivity, and for HDL cholesterol.

Implicated in

Note
Entity Prostate cancer
Note Tumor/metastasis suppressor.
Prognosis AKAP12 downregulation correlates with earlier time-to-onset of metastasis (Ko et al., 2014).
Cytogenetics gene deletion at 6q24-25.1.
 
Left- Oncomine analysis (http://www.oncomine.org) of Lapointe prostate cancer expression data (Proc Natl Acad Sci U S A 2004;101:811-6) showing AKAP12 downregulation in human prostate cancer metastasis compared with levels in primary prostate cancer (1 prostate cancer) or normal prostate tissue. F, Kaplan-Meier plot analysis (http://www.cbioportal.org/public-portal/) of metastasis occurrence vs. time to onset in 37 prostate cancer metastasis cases from Taylor et al., 2010 in which 11 cases (29.7%) displayed AKAP12 downregulation compared with levels in primary prostate cancer lesions versus 26 cases with no change in AKAP12 levels.
Oncogenesis Presumably, the loss of AKAP12's scaffolding activity for kinases such as Src and PKC result in hyperactivated pathways that contribute to oncogenic transformation, as shown in Su et al., 2010, and Su et al., 2013.
  
Entity Melanoma
Note Tumor/metastasis suppressor/promoter.
Prognosis Some papers identify AKAP12 downregulation as a marker human melanoma progression (Hacker et al., 2008; Bonazzi et al., 2009), or that its genetic loss in transgenic models leads to a metastasis-prone condition induced by skin carcinogens (Akakura et al., 2011). However, one paper suggests that hypoxia-induced expression of AKAP12-variant 2 (β isoform) enhances melanoma migration and invasiveness.
Oncogenesis Presumably, the loss of AKAP12's scaffolding activity for kinases such as Src and PKC result in hyperactivated pathways that contribute to oncogenic transformation, as shown in Su et al., 2010 and Su et al., 2013.
  
Entity Ovarian cancer
Note Possible mediator of drug-resistance.
Prognosis AKAP12 upregulation associated with resistance to platins and taxanes (Chappell et al., 2012; Bateman et al., 2015).
 
A majority of high-grade (HG) serous ovarian cancer (SOC) patients develop resistant disease despite high initial response rates to platinum/paclitaxel-based chemotherapy. We identified shed/secreted proteins in preclinical models of paclitaxel-resistant human HGSOC models and correlated these candidate proteins with patient outcomes using public data from HGSOC patients. Proteomic analyses of a HGSOC cell line secretome was compared to those from a syngeneic paclitaxel-resistant variant and from a line established from an intrinsically chemorefractory HGSOC patient. Associations between the identified candidate proteins and patient outcome were assessed in a discovery cohort of 545 patients and two validation cohorts totaling 795 independent SOC patients. Among the 81 differentially abundant proteins identified (q < 0.05) from paclitaxel-sensitive vs -resistant HGSOC cell secretomes, AKAP12 was verified to be elevated in all models of paclitaxel-resistant HGSOC. Furthermore, elevated AKAP12 transcript expression was associated with worse progression-free and overall survival. Associations with outcome were observed in three independent cohorts and remained significant after adjusted multivariate modeling. We further provide evidence to support that differential gene methylation status is associated with elevated expression of AKAP12 in taxol-resistant ovarian cancer cells and ovarian cancer patient subsets. Elevated expression and shedding/secretion of AKAP12 is characteristic of paclitaxel-resistant HGSOC cells, and elevated AKAP12 transcript expression is a poor prognostic and predictive marker for progression-free and overall survival in SOC patients. [from Bateman et al., 2015].
Oncogenesis Presumably, the upregulation of AKAP12, and its ability to scaffold kinases such as Src and PKC, and to move them to cellular specific compartments, leads to pathways that facilitate drug resistance, as described in Le and Bast 2011.
  
Entity Pancreatic cancer
Note Possible tumor/metastasis suppressor.
Prognosis Whereas AKAP12 upregulation was noted in human pancreatic cells lines compared to immortalized human pancreatic ductal epithelial cells (Cao et al., Cancer Biol Ther. 2004, 3(11):1081-9), AKAP12 loss (due to promoter hypermethylation) correlated with increased liver metastasis in pancreatic ductal adenocarcinoma (Mardin et al., 2010).
Oncogenesis Presumably, the loss of AKAP12's scaffolding activity for kinases such as Src and PKC result in hyperactivated pathways that contribute to oncogenic transformation, as shown in Su et al. 2010, and Su et al. 2013.
  
Entity Colon cancer
Note Possible tumor/metastasis suppressor.
Prognosis Downregulation of AKAP12 correlated with colon cancer progression (Zhu et al., J Cancer Res Ther. 2013, 9(3):467-70), especially due to promoter hypermethylation (Mori et al., 2006; Liu et al., 2010). Moreover, AKAP12 expression is positively regulated by TGFβ; in a SMAD4 -dependent manner in colon cancer cell lines (Ali et al., 2010), and given that SMAD4 is often mutated or deleted in colon cancer (Bellam and Pasche, 2010), the downregulation of AKAP12 might be related to SMAD4 loss. Re-expression of AKAP12 inhibits the metastatic potential of colorectal carcinoma cells (Liu et al., 2011).
  
Entity Lung cancer
Note Possible tumor suppressor.
Prognosis ownregulation of AKAP12 due to promoter hypermethylation in lung cancer as a susceptibility (Tessema et al., 2008) or progression marker (Jo et al., 2010). As in the case of ovarian cancer, AKAP12 expression increases in cisplatin-resistant variants of lung cancer cell lines (Lopez-Ayllon et al., 2014.
Oncogenesis Presumably, the loss of AKAP12's scaffolding activity for kinases such as Src and PKC result in hyperactivated pathways that contribute to oncogenic transformation, as shown in Su et al., 2010 and Su et al., 2013.
  
Entity Gastric cancer
Note Possible tumor suppressor.
Prognosis Downregulation of AKAP12 due to promoter hypermethylation in gastric cancer (Choi et al., 2004) or in Barrett's esophagus (Jin et al., 2008).
Oncogenesis Presumably, the loss of AKAP12's scaffolding activity for kinases such as Src and PKC result in hyperactivated pathways that contribute to oncogenic transformation, as shown in Su et al., 2010 and Su et al., 2013.
  
Entity Liver cancer
Note Possible tumor suppressor.
Prognosis Downregulation of AKAP12 due to promoter hypermethylation in liver cancer (Goeppert et al., 2010; Hayashi et al., 2012).
Oncogenesis Presumably, the loss of AKAP12's scaffolding activity for kinases such as Src and PKC result in hyperactivated pathways that contribute to oncogenic transformation, as shown in Su et al., 2010 and Su et al., 2013.
  

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Li X, Yan M, Hu L, Sun L, Zhang F, Ji H, Jiang J, Wang P, Liu H, Gao Y, Tao T, He X, Cheng C, Shen A
J Neurosci Res 2010 Jul;88(9):1858-71
PMID 20155814
 
Anti-cancer mechanisms of clinically acceptable colchicine concentrations on hepatocellular carcinoma
Lin ZY, Wu CC, Chuang YH, Chuang WL
Life Sci 2013 Sep 3;93(8):323-8
PMID 23871804
 
Dexamethasone inhibits proliferation and stimulates SSeCKS expression in C6 rat glioma cell line
Liu H, Huang X, Wang H, Shen A, Cheng C
Brain Res 2009 Apr 10;1265:1-12
 
Quantitative assessment of AKAP12 promoter methylation in human prostate cancer using methylation-sensitive high-resolution melting: correlation with Gleason score
Liu W, Gong J, Hu J, Hu T, Sun Y, Du J, Sun C, Guan M, Jiang H, Lu Y
Urology 2011 Apr;77(4):1006
PMID 21310466
 
Re-expression of AKAP12 inhibits progression and metastasis potential of colorectal carcinoma in vivo and in vitro
Liu W, Guan M, Hu T, Gu X, Lu Y
PLoS One 2011;6(8):e24015
PMID 21918680
 
Cancer stem cells and cisplatin-resistant cells isolated from non-small-lung cancer cell lines constitute related cell populations
Lopez-Ayllon BD, Moncho-Amor V, Abarrategi A, Ibañez de Cáceres I, Castro-Carpeño J, Belda-Iniesta C, Perona R, Sastre L
Cancer Med 2014 Oct;3(5):1099-111
PMID 24961511
 
HSPA12B: a novel facilitator of lung tumor growth
Ma H, Lu T, Zhang X, Li C, Xiong J, Huang L, Liu P, Li Y, Liu L, Ding Z
Oncotarget 2015 Apr 30;6(12):9924-36
PMID 25909170
 
Alternative splicing in bone following mechanical loading
Mantila Roosa SM, Liu Y, Turner CH
Bone 2011 Mar 1;48(3):543-51
PMID 21095247
 
SERPINB5 and AKAP12 - expression and promoter methylation of metastasis suppressor genes in pancreatic ductal adenocarcinoma
Mardin WA, Petrov KO, Enns A, Senninger N, Haier J, Mees ST
BMC Cancer 2010 Oct 12;10:549
PMID 20939879
 
Identification and validation of genes with expression patterns inverse to multiple metastasis suppressor genes in breast cancer cell lines
Marino N, Collins JW, Shen C, Caplen NJ, Merchant AS, Gökmen-Polar Y, Goswami CP, Hoshino T, Qian Y, Sledge GW Jr, Steeg PS
Clin Exp Metastasis 2014 Oct;31(7):771-86
PMID 25086928
 
Src supports UDP-glucuronosyltransferase-2B7 detoxification of catechol estrogens associated with breast cancer
Mitra PS, Basu NK, Owens IS
Biochem Biophys Res Commun 2009 May 15;382(4):651-6
PMID 19289110
 
Gravin gene expression in acute myeloid leukemia
Mostafa MR, Yahia RS, Abd El Messih HM, El-Sisy E, El Ghannam DM
Med Oncol 2013 Jun;30(2):548
PMID 23543478
 
Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a kinase scaffold protein.
Nauert JB, Klauck TM, Langeberg LK, Scott JD
Current biology : CB. 1997 ; 7 (1) : 52-62.
PMID 9000000
 
A-kinase anchoring proteins contribute to loss of E-cadherin and bronchial epithelial barrier by cigarette smoke
Oldenburger A, Poppinga WJ, Kos F, de Bruin HG, Rijks WF, Heijink IH, Timens W, Meurs H, Maarsingh H, Schmidt M
Am J Physiol Cell Physiol 2014 Mar 15;306(6):C585-97
PMID 24452374
 
Ensemble of gene signatures identifies novel biomarkers in colorectal cancer activated through PPAR and TNF signaling
Pagnotta SM, Laudanna C, Pancione M, Sabatino L, Votino C, Remo A, Cerulo L, Zoppoli P, Manfrin E, Colantuoni V, Ceccarelli M
PLoS One 2013 Aug 19;8(8):e72638
PMID 24133572
 
The macromolecular state of A-kinase anchoring protein
Patel TR, Winzor DJ
J Mol Recognit 2012 Jan;25(1):11-4
PMID 22213446
 
A-kinase anchoring proteins: cAMP compartmentalization in neurodegenerative and obstructive pulmonary diseases
Poppinga WJ, Muñoz-Llancao P, González-Billault C, Schmidt M
Br J Pharmacol 2014 Dec;171(24):5603-23
PMID 25132049
 
PKA compartmentalization via AKAP220 and AKAP12 contributes to endothelial barrier regulation
Radeva MY, Kugelmann D, Spindler V, Waschke J
PLoS One 2014 Sep 4;9(9):e106733
PMID 25188285
 
Receptor-mediated Ca2+ and PKC signaling triggers the loss of cortical PKA compartmentalization through the redistribution of gravin
Schott MB, Grove B
Cell Signal 2013 Nov;25(11):2125-35
PMID 23838009
 
The relationship between Src-suppressed C kinase substrate and -1,4 galactosyltransferase-I in the process of lipopolysaccharide-induced TNF- secretion in rat primary astrocytes
Shao B, Li C, Yang H, Shen A, Wu X, Yuan Q, Wu X, Kang L, Liu Z, Zhang G, Lu X, Cheng C
Cell Mol Neurobiol 2011 Oct;31(7):1047-56
PMID 21573722
 
Dynamic complexes of beta2-adrenergic receptors with protein kinases and phosphatases and the role of gravin.
Shih M, Lin F, Scott JD, Wang HY, Malbon CC
The Journal of biological chemistry. 1999 ; 274 (3) : 1588-1595.
PMID 9880537
 
Detection of activated parietal epithelial cells on the glomerular tuft distinguishes early focal segmental glomerulosclerosis from minimal change disease
Smeets B, Stucker F, Wetzels J, Brocheriou I, Ronco P, Gröne HJ, D'Agati V, Fogo AB, van Kuppevelt TH, Fischer HP, Boor P, Floege J, Ostendorf T, Moeller MJ
Am J Pathol 2014 Dec;184(12):3239-48
PMID 25307344
 
Multiple promoters direct expression of three AKAP12 isoforms with distinct subcellular and tissue distribution profiles.
Streb JW, Kitchen CM, Gelman IH, Miano JM
The Journal of biological chemistry. 2004 ; 279 (53) : 56014-56023.
PMID 15496411
 
Retinoid-induced expression and activity of an immediate early tumor suppressor gene in vascular smooth muscle cells
Streb JW, Long X, Lee TH, Sun Q, Kitchen CM, Georger MA, Slivano OJ, Blaner WS, Carr DW, Gelman IH, Miano JM
PLoS One 2011 Apr 5;6(4):e18538
PMID 21483686
 
SSeCKS/Gravin/AKAP12 inhibits cancer cell invasiveness and chemotaxis by suppressing a protein kinase C- Raf/MEK/ERK pathway
Su B, Bu Y, Engelberg D, Gelman IH
J Biol Chem 2010 Feb 12;285(7):4578-86
PMID 20018890
 
Adhesion-mediated cytoskeletal remodeling is controlled by the direct scaffolding of Src from FAK complexes to lipid rafts by SSeCKS/AKAP12
Su B, Gao L, Meng F, Guo LW, Rothschild J, Gelman IH
Oncogene 2013 Apr 18;32(16):2016-26
PMID 22710722
 
SSeCKS metastasis-suppressing activity in MatLyLu prostate cancer cells correlates with vascular endothelial growth factor inhibition.
Su B, Zheng Q, Vaughan MM, Bu Y, Gelman IH
Cancer research. 2006 ; 66 (11) : 5599-5607.
PMID 16740695
 
Src suppressed C kinase substrate regulates the lipopolysaccharide-induced TNF-alpha biosynthesis in rat astrocytes
Sun LL, Cheng C, Liu HO, Shen CC, Xiao F, Qin J, Yang JL, Shen AG
J Mol Neurosci 2007;32(1):16-24
PMID 17873284
 
Lack of relation of AKAP12 with p53 and Bcl-2 in colorectal carcinoma
Suren D, Yildirim M, Alikanoglu AS, Kaya V, Yildiz M, Dilli UD, Sezer C
Asian Pac J Cancer Prev 2014;15(8):3415-8
PMID 24870731
 
G-protein-coupled receptor-associated A-kinase anchoring proteins AKAP5 and AKAP12: differential signaling to MAPK and GPCR recycling
Tao J, Malbon CC
J Mol Signal 2008 Dec 2;3:19
PMID 19055733
 
AKAR2-AKAP12 fusion protein "biosenses" dynamic phosphorylation and localization of a GPCR-based scaffold
Tao J, Wang HY, Malbon CC
J Mol Signal 2010 Apr 22;5:3
PMID 20412577
 
Tumor necrosis factor-alpha inhibits Schwann cell proliferation by up-regulating Src-suppressed protein kinase C substrate expression
Tao T, Ji Y, Cheng C, Yang H, Liu H, Sun L, Qin Y, Yang J, Wang H, Shen A
J Neurochem 2009 Nov;111(3):647-55
PMID 19694904
 
Mining the epigenome for methylated genes in lung cancer
Tessema M, Belinsky SA
Proc Am Thorac Soc 2008 Dec 1;5(8):806-10
PMID 19017733
 
Promoter methylation of genes in and around the candidate lung cancer susceptibility locus 6q23-25
Tessema M, Willink R, Do K, Yu YY, Yu W, Machida EO, Brock M, Van Neste L, Stidley CA, Baylin SB, Belinsky SA
Cancer Res 2008 Mar 15;68(6):1707-14
PMID 18339850
 
The angiogenesis suppressor gene AKAP12 is under the epigenetic control of HDAC7 in endothelial cells
Turtoi A, Mottet D, Matheus N, Dumont B, Peixoto P, Hennequière V, Deroanne C, Colige A, De Pauw E, Bellahcène A, Castronovo V
Angiogenesis 2012 Dec;15(4):543-54
PMID 22584896
 
Involvement of SRC-suppressed C kinase substrate in neuronal death caused by the lipopolysaccharide-induced reactive astrogliosis
Wang P, Sun L, Shen A, Yang J, Li X, Liu H, Tao T, Cheng C, Lu X
Inflammation 2010 Dec;33(6):359-73
PMID 20204485
 
Cell shape regulation by Gravin requires N-terminal membrane effector domains
Weiser DC, St Julien KR, Lang JS, Kimelman D
Biochem Biophys Res Commun 2008 Oct 31;375(4):512-6
PMID 18725198
 
HIF-dependent regulation of AKAP12 (gravin) in the control of human vascular endothelial function
Weissmüller T, Glover LE, Fennimore B, Curtis VF, MacManus CF, Ehrentraut SF, Campbell EL, Scully M, Grove BD, Colgan SP
FASEB J 2014 Jan;28(1):256-64
PMID 24029533
 
Examination of AKAP12 promoter methylation in skin cancer using methylation-sensitive high-resolution melting analysis
Wu W, Zhang J, Yang H, Shao Y, Yu B
Clin Exp Dermatol 2011 Jun;36(4):381-5
PMID 21198787
 
A critical role of SRC-suppressed C kinase substrate in rat astrocytes after chronic constriction injury
Xia Y, Liu H, Shen A, Liu Y, Sun L, Tao T, Ke Q, Cheng C
Neuromolecular Med 2010 Sep;12(3):205-16
PMID 19937403
 
Spatiotemporal patterns of SSeCKS expression after rat spinal cord injury
Xiao F, Fei M, Cheng C, Ji Y, Sun L, Qin J, Yang J, Liu Y, Zhang L, Xia Y, Shen A
Neurochem Res 2008 Sep;33(9):1735-48
PMID 18307037
 
Essential role of SRC suppressed C kinase substrates in Schwann cells adhesion, spreading and migration
Yan M, Cheng C, Jiang J, Liu Y, Gao Y, Guo Z, Liu H, Shen A
Neurochem Res 2009 May;34(5):1002-10
PMID 18979197
 
The role of TNF-alpha and its receptors in the production of Src-suppressed C kinase substrate by rat primary type-2 astrocytes
Yan M, Xia C, Cheng C, Shao X, Niu S, Liu H, Shen A
Brain Res 2007 Dec 12;1184:28-37
PMID 17980351
 
Expression of SRC suppressed C kinase substrate in rat neural tissues during inflammation
Yan M, Zhao J, Zhu S, Shao X, Zhang L, Gao H, Yao D
Neurochem Res 2014 Apr;39(4):748-57
PMID 24623461
 
Gravin dynamics regulates the subcellular distribution of PKA
Yan X, Walkiewicz M, Carlson J, Leiphon L, Grove B
Exp Cell Res 2009 Apr 15;315(7):1247-59
PMID 19210988
 
AKAP12/Gravin gene expression in colorectal cancer: clinical importance and review of the literature
Yildirim M, Suren D, Yildiz M, Sezgin Alikanoglu A, Eryilmaz R, Goktas S, Bulbuller N, Sezer C
J BUON 2013 Jul-Sep;18(3):635-40
PMID 24065476
 
AKAP12 induces apoptotic cell death in human fibrosarcoma cells by regulating CDKI-cyclin D1 and caspase-3 activity
Yoon DK, Jeong CH, Jun HO, Chun KH, Cha JH, Seo JH, Lee HY, Choi YK, Ahn BJ, Lee SK, Kim KW
Cancer Lett 2007 Aug 28;254(1):111-8
PMID 17442483
 
Association of gene polymorphisms with chronic kidney disease in Japanese individuals
Yoshida T, Kato K, Yokoi K, Oguri M, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Nozawa Y, Yamada Y
Int J Mol Med 2009 Oct;24(4):539-47
PMID 19724895
 
Role of src-suppressed C kinase substrate in rat pulmonary microvascular endothelial hyperpermeability stimulated by inflammatory cytokines
You QH, Sun GY, Wang N, Chen S, Luo QL
Inflamm Res 2010 Nov;59(11):949-58
PMID 20454828
 
Temporal profile of Src, SSeCKS, and angiogenic factors after focal cerebral ischemia: correlations with angiogenesis and cerebral edema
Zan L, Wu H, Jiang J, Zhao S, Song Y, Teng G, Li H, Jia Y, Zhou M, Zhang X, Qi J, Wang J
Neurochem Int 2011 Jul;58(8):872-9
PMID 21334414
 
2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes astrocyte activation and the secretion of tumor necrosis factor- via PKC/SSeCKS-dependent mechanisms
Zhang Y, Nie X, Tao T, Qian W, Jiang S, Jiang J, Li A, Guo A, Xu G, Wu Q
J Neurochem 2014 Jun;129(5):839-49
PMID 24673440
 
SSeCKS promotes tumor necrosis factor-alpha autocrine via activating p38 and JNK pathways in Schwann cells
Zhou Z, Tao T, Ji Y, Yang H, Wang Y, Cheng C, Shen A, Lu X
Cell Mol Neurobiol 2010 Jul;30(5):701-7
PMID 20111901
 
Expression profiling based on graph-clustering approach to determine colon cancer pathway
Zhu XQ, Hu ML, Zhang F, Tao Y, Wu CM, Lin SZ, He FL
J Cancer Res Ther 2013 Jul-Sep;9(3):467-70
PMID 24125984
 

Citation

This paper should be referenced as such :
Gelman IH
AKAP12 A kinase (PRKA) anchor protein 12;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/AKAP12ID607ch6q25.html
History of this paper:
Gelman, IH. AKAP12 (A kinase (PRKA) anchor protein 12). Atlas Genet Cytogenet Oncol Haematol. 2007;11(2):80-83.
http://documents.irevues.inist.fr/bitstream/handle/2042/38398/11-2006-AKAP12ID607ch6q25.pdf


External links

Nomenclature
HGNC (Hugo)AKAP12   370
Cards
AtlasAKAP12ID607ch6q25
Entrez_Gene (NCBI)AKAP12  9590  A-kinase anchoring protein 12
AliasesAKAP250; SSeCKS
GeneCards (Weizmann)AKAP12
Ensembl hg19 (Hinxton)ENSG00000131016 [Gene_View]  chr6:151561134-151679694 [Contig_View]  AKAP12 [Vega]
Ensembl hg38 (Hinxton)ENSG00000131016 [Gene_View]  chr6:151561134-151679694 [Contig_View]  AKAP12 [Vega]
ICGC DataPortalENSG00000131016
TCGA cBioPortalAKAP12
AceView (NCBI)AKAP12
Genatlas (Paris)AKAP12
WikiGenes9590
SOURCE (Princeton)AKAP12
Genetics Home Reference (NIH)AKAP12
Genomic and cartography
GoldenPath hg19 (UCSC)AKAP12  -     chr6:151561134-151679694 +  6q24-q25   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)AKAP12  -     6q24-q25   [Description]    (hg38-Dec_2013)
EnsemblAKAP12 - 6q24-q25 [CytoView hg19]  AKAP12 - 6q24-q25 [CytoView hg38]
Mapping of homologs : NCBIAKAP12 [Mapview hg19]  AKAP12 [Mapview hg38]
OMIM604698   
Gene and transcription
Genbank (Entrez)AB003476 AB210003 AF001504 AF086250 AK024598
RefSeq transcript (Entrez)NM_005100 NM_144497
RefSeq genomic (Entrez)NC_000006 NC_018917 NG_029875 NT_025741 NW_004929328
Consensus coding sequences : CCDS (NCBI)AKAP12
Cluster EST : UnigeneHs.371240 [ NCBI ]
CGAP (NCI)Hs.371240
Alternative Splicing GalleryENSG00000131016
Gene ExpressionAKAP12 [ NCBI-GEO ]   AKAP12 [ EBI - ARRAY_EXPRESS ]   AKAP12 [ SEEK ]   AKAP12 [ MEM ]
Gene Expression Viewer (FireBrowse)AKAP12 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9590
GTEX Portal (Tissue expression)AKAP12
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ02952   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ02952  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ02952
Splice isoforms : SwissVarQ02952
PhosPhoSitePlusQ02952
Domains : Interpro (EBI)AKAP12    Pkinase-A_anch_WSK-motif    RII_binding_1   
Domain families : Pfam (Sanger)RII_binding_1 (PF10522)    WSK (PF03832)   
Domain families : Pfam (NCBI)pfam10522    pfam03832   
Conserved Domain (NCBI)AKAP12
DMDM Disease mutations9590
Blocks (Seattle)AKAP12
SuperfamilyQ02952
Human Protein AtlasENSG00000131016
Peptide AtlasQ02952
HPRD05263
IPIIPI00237884   IPI00867627   IPI00940222   IPI00431688   
Protein Interaction databases
DIP (DOE-UCLA)Q02952
IntAct (EBI)Q02952
FunCoupENSG00000131016
BioGRIDAKAP12
STRING (EMBL)AKAP12
ZODIACAKAP12
Ontologies - Pathways
QuickGOQ02952
Ontology : AmiGOprotein binding  cytoplasm  cytoskeleton  plasma membrane  focal adhesion  cell cortex  protein targeting  G-protein coupled receptor signaling pathway  adenylate cyclase binding  positive regulation of protein kinase A signaling  positive regulation of cAMP biosynthetic process  protein kinase A binding  regulation of protein kinase C signaling  
Ontology : EGO-EBIprotein binding  cytoplasm  cytoskeleton  plasma membrane  focal adhesion  cell cortex  protein targeting  G-protein coupled receptor signaling pathway  adenylate cyclase binding  positive regulation of protein kinase A signaling  positive regulation of cAMP biosynthetic process  protein kinase A binding  regulation of protein kinase C signaling  
NDEx NetworkAKAP12
Atlas of Cancer Signalling NetworkAKAP12
Wikipedia pathwaysAKAP12
Orthology - Evolution
OrthoDB9590
GeneTree (enSembl)ENSG00000131016
Phylogenetic Trees/Animal Genes : TreeFamAKAP12
HOVERGENQ02952
HOGENOMQ02952
Homologs : HomoloGeneAKAP12
Homology/Alignments : Family Browser (UCSC)AKAP12
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerAKAP12 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)AKAP12
dbVarAKAP12
ClinVarAKAP12
1000_GenomesAKAP12 
Exome Variant ServerAKAP12
ExAC (Exome Aggregation Consortium)AKAP12 (select the gene name)
Genetic variants : HAPMAP9590
Genomic Variants (DGV)AKAP12 [DGVbeta]
DECIPHER (Syndromes)6:151561134-151679694  ENSG00000131016
CONAN: Copy Number AnalysisAKAP12 
Mutations
ICGC Data PortalAKAP12 
TCGA Data PortalAKAP12 
Broad Tumor PortalAKAP12
OASIS PortalAKAP12 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICAKAP12  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDAKAP12
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch AKAP12
DgiDB (Drug Gene Interaction Database)AKAP12
DoCM (Curated mutations)AKAP12 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)AKAP12 (select a term)
intoGenAKAP12
NCG5 (London)AKAP12
Cancer3DAKAP12(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM604698   
Orphanet
MedgenAKAP12
Genetic Testing Registry AKAP12
NextProtQ02952 [Medical]
TSGene9590
GENETestsAKAP12
Huge Navigator AKAP12 [HugePedia]
snp3D : Map Gene to Disease9590
BioCentury BCIQAKAP12
ClinGenAKAP12
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9590
Chemical/Pharm GKB GenePA24664
Clinical trialAKAP12
Miscellaneous
canSAR (ICR)AKAP12 (select the gene name)
Other databaseGeneCards
Other databaseWikipedia
Other databaseNextProt
Other databaseImmunobase
Other databaseOmim
Other databaseDGIdb
Probes
Litterature
PubMed73 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineAKAP12
EVEXAKAP12
GoPubMedAKAP12
iHOPAKAP12
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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