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Tbio A-kinase anchor protein 10, mitochondrial

Differentially targeted protein that binds to type I and II regulatory subunits of protein kinase A and anchors them to the mitochondria or the plasma membrane. Although the physiological relevance between PKA and AKAPS with mitochondria is not fully understood, one idea is that BAD, a proapoptotic member, is phosphorylated and inactivated by mitochondria-anchored PKA. It cannot be excluded too that it may facilitate PKA as well as G protein signal transduction, by acting as an adapter for assembling multiprotein complexes. With its RGS domain, it could lead to the interaction to G-alpha proteins, providing a link between the signaling machinery and the downstream kinase (By similarity).

This gene encodes a member of the A-kinase anchor protein family. A-kinase anchor proteins bind to the regulatory subunits of protein kinase A (PKA) and confine the holoenzyme to discrete locations within the cell. The encoded protein is localized to mitochondria and interacts with both the type I and type II regulatory subunits of PKA. Polymorphisms in this gene may be associated with increased risk of arrhythmias and sudden cardiac death. [provided by RefSeq, May 2012]

 Comments

Property Summary

NCBI Gene PubMed Count 38
PubMed Score 26.39
PubTator Score 35.19

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (4)

Disease Target Count
Conduction disorder of the heart 1
Disease Target Count
Cardiac Conduction Defect 1
Disease Target Count
Sudden Cardiac Death 8

Expression

  Differential Expression (13)

Disease log2 FC p
astrocytic glioma 2.000 5.3e-03
ependymoma 2.200 1.9e-03
oligodendroglioma 2.400 1.2e-03
glioblastoma multiforme 1.100 1.3e-19
osteosarcoma -1.147 6.7e-03
medulloblastoma, large-cell -1.500 9.9e-04
ulcerative colitis -1.455 3.6e-02
intraductal papillary-mucinous adenoma (... 2.500 3.2e-04
intraductal papillary-mucinous carcinoma... 2.400 2.6e-04
intraductal papillary-mucinous neoplasm ... 1.400 3.3e-02
lung cancer 1.100 1.0e-02
Pick disease 1.300 8.6e-05
ovarian cancer -3.000 2.8e-14

Synonym

Accession O43572 B2R650 Q96AJ7 AKAP-10
Symbols PRKA10
AKAP-10
D-AKAP2
D-AKAP-2

Gene

AKAP10

PDB

3IM4   3TMH  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (10)

 GO Component (4)

 GO Process (3)

 Compartment GO Term (16)

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 IMPC Phenotype (6)

 MGI Phenotype (3)

 HCA RNA Cell Line (56)

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Pathway (4)

Protein-protein Interaction (7)

PRKAR1A   PRKAR2A   PRKACA   PRKACG   PRKACB   PRKAR1B   PRKAR2B  

Gene RIF (28)

PMID Text
26110499 Significant association between the AKAP10 polymorphisms and reduced risk of Preterm birth in the Malays was observed.
25348485 Described is a structure of D-AKAP2 in complex with two interacting partners and the exact mechanism by which a segment that on its own is disordered presents an alpha-helix to PKA and a beta-strand to PDZK1.
25213315 Its signaling pathway is associated with the progression and prognosis of colorectal neoplasms.
23468363 Studied the clinicopathologic significance of A-kinase anchoring proteins 10 (AKAP 10) expression and the relationship with its polymorphism in colorectal cancer.
23095189 Questioned whether 1936A>G is associated with metabolic changes in newborns that are predictive of the metabolic phenotype in adults. Demonstrate an association between 1936G variant and total cholesterol level in cord blood of Polish newborns.
23092224 No significant differences were found in AKAP10 genotype or allele distribution between the age groups (newborn vs. nonagenerian) for either gender.
22817328 There is possible association between a 1936G AKAP10 variant and blood pressure in Polish newborns.
21701445 Results suggest G1936 polymorphism in A-kinase-anchoring protein is preventative factor against preterm birth, in contrast with previously asserted negative effects in adults.
20877624 Observational study of gene-disease association. (HuGE Navigator)
20453000 Observational study of gene-disease association. (HuGE Navigator)
20159461 Results describe the structures of the protein kinase A RIalpha subunit D/D domain alone and in complex with D-AKAP2.
19857670 AKAP10 single nucleotide polymorphism is associated with increased risk of arrhythmia during kidney transplantation.
19857670 Observational study of gene-disease association. (HuGE Navigator)
19797056 D-AKAP2 promotes accumulation of recycling proteins in the Rab4/Rab11-positive endocytic recycling compartment
19578796 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19496216 the AKAP10 Val allele predicted greater resting heart rate and heart rate variability
19496216 Observational study of gene-disease association. (HuGE Navigator)
19462906 There was a significant association between AKAP10 gene 2073A/G polymorphism and colorectal cancer.
19209010 AKAP10 2073A>G variation is associated with an increased risk of colorectal cancer in the Chinese population.
19209010 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19056482 Observational study of gene-disease association. (HuGE Navigator)
17786291 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
17485678 These studies suggest a role for AKAP10 in heart rhythm control.
17143557 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
16956908 Observational study of gene-disease association. (HuGE Navigator)
15488188 Results describe the structural features of dual-specificity A kinase-anchoring protein 2 (D-AKAP2) and its interaction with protein kinase A (PKA).
12646697 A variant of the kinase-binding domain of this enzyme involves a disease susceptibility polymorphism.
12206784 deuterium exchange-mass spectrometry (DXMS) and limited proteolysis to probe the folded regions of D-AKAP2, providing for the first time insight into the intra-domain dynamics of a scaffold protein

AA Sequence 

MRGAGPSPRQSPRTLRPDPGPAMSFFRRKVKGKEQEKTSDVKSIKASISVHSPQKSTKNHALLEAAGPSH      1 - 70
VAINAISANMDSFSSSRTATLKKQPSHMEAAHFGDLGRSCLDYQTQETKSSLSKTLEQVLHDTIVLPYFI     71 - 140
QFMELRRMEHLVKFWLEAESFHSTTWSRIRAHSLNTVKQSSLAEPVSPSKKHETTASFLTDSLDKRLEDS    141 - 210
GSAQLFMTHSEGIDLNNRTNSTQNHLLLSQECDSAHSLRLEMARAGTHQVSMETQESSSTLTVASRNSPA    211 - 280
SPLKELSGKLMKSIEQDAVNTFTKYISPDAAKPIPITEAMRNDIIARICGEDGQVDPNCFVLAQSIVFSA    281 - 350
MEQEHFSEFLRSHHFCKYQIEVLTSGTVYLADILFCESALFYFSEYMEKEDAVNILQFWLAADNFQSQLA    351 - 420
AKKGQYDGQEAQNDAMILYDKYFSLQATHPLGFDDVVRLEIESNICREGGPLPNCFTTPLRQAWTTMEKV    421 - 490
FLPGFLSSNLYYKYLNDLIHSVRGDEFLGGNVSLTAPGSVGPPDESHPGSSDSSASQSSVKKASIKILKN    491 - 560
FDEAIIVDAASLDPESLYQRTYAGKMTFGRVSDLGQFIRESEPEPDVRKSKGSMFSQAMKKWVQGNTDEA    561 - 630
QEELAWKIAKMIVSDIMQQAQYDQPLEKSTKL                                          631 - 662
//

Text Mined References (42)

PMID Year Title
26871637 2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
26110499 2015 Genetic association of AKAP10 gene polymorphism with reduced risk of preterm birth.
25348485 2015 D-AKAP2:PKA RII:PDZK1 ternary complex structure: insights from the nucleation of a polyvalent scaffold.
25213315 2015 PKA RI?/A-kinase anchoring proteins 10 signaling pathway and the prognosis of colorectal cancer.
23468363 2013 A-kinase anchoring proteins 10 expression in relation to 2073A/G polymorphism and tumor progression in patients with colorectal cancer.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23095189 2013 Polymorphism 1936A > G in the AKAP10 gene (encoding A-kinase-anchoring protein 10) is associated with higher cholesterol cord blood concentration in Polish full-term newsborns.
23092224 2012 1936A?G (I646 V) polymorphism in the AKAP10 gene encoding A-kinase-anchoring protein 10 in very long-lived poles is similar to that in newborns.
22817328 2013 Association of 1936A > G in AKAP10 (A-kinase anchoring protein 10) and blood pressure in Polish full-term newborns.
22139419 2011 New gene functions in megakaryopoiesis and platelet formation.
21701445 2012 Possible counter effect in newborns of 1936A>G (I646V) polymorphism in the AKAP10 gene encoding A-kinase-anchoring protein 10.
20877624 2010 Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
20453000 2010 A Large-scale genetic association study of esophageal adenocarcinoma risk.
20159461 2010 Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and selectivity.
19857670 2009 Association of the A1936G (rs203462) of A-kinase anchoring protein 10 polymorphisms with QT interval prolongation during kidney transplantation.
19797056 2009 D-AKAP2 interacts with Rab4 and Rab11 through its RGS domains and regulates transferrin receptor recycling.
19578796 2009 Association of genetic variants with chronic kidney disease in individuals with different lipid profiles.
19496216 2009 AKAP10 (I646V) functional polymorphism predicts heart rate and heart rate variability in apparently healthy, middle-aged European-Americans.
19462906 2009 [Genotyping of AKAP10 gene 2073A/G single nucleotide polymorphism by TaqMan probe real-time PCR].
19209010 2009 The Ile646Val (2073A>G) polymorphism in the kinase-binding domain of A-kinase anchoring protein 10 and the risk of colorectal cancer.
19056482 2009 Association of a polymorphism of the apolipoprotein E gene with chronic kidney disease in Japanese individuals with metabolic syndrome.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17786291 2007 Association of gene polymorphisms with myocardial infarction in individuals with different lipid profiles.
17485678 2007 Gene-trapped mouse embryonic stem cell-derived cardiac myocytes and human genetics implicate AKAP10 in heart rhythm regulation.
17143557 2007 Association of gene polymorphisms with myocardial infarction in individuals with or without conventional coronary risk factors.
16956908 2007 The functional genetic variant Ile646Val located in the kinase binding domain of the A-kinase anchoring protein 10 is associated with familial breast cancer.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15488188 2004 Identification and functional analysis of dual-specific A kinase-anchoring protein-2.
15342556 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14531806 2003 PDZK1: I. a major scaffolder in brush borders of proximal tubular cells.
12646697 2003 Amino acid variant in the kinase binding domain of dual-specific A kinase-anchoring protein 2: a disease susceptibility polymorphism.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12206784 2002 Domain organization of D-AKAP2 revealed by enhanced deuterium exchange-mass spectrometry (DXMS).
11807172 2002 AKAP mediated signal transduction.
11248059 2001 Cloning and mitochondrial localization of full-length D-AKAP2, a protein kinase A anchoring protein.
9326583 1997 D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain.
9238861 1997 Anchoring and scaffold proteins for kinases and phosphatases.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
7505766 1994 Expression of (cac)n/(gtg)n simple repetitive sequences in mRNA of human lymphocytes.