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FLASH GENE

Symbol

AKAP12

contributors: mct/npt/pgu - updated : 06-03-2013

HGNC name	a kinase (PRKA) anchor protein (gravin) 12
HGNC id	370

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	6q25.1      Physical location : 151.561.133 - 151.679.692
Synonym name	Gravin
	kinase scaffold protein gravin
	myasthenia gravis autoantigen gravin
Synonym symbol(s)	AKAP250, SSECKS, DKFZp686M0430, DKFZp686O0331

DNA

TYPE	functioning gene
STRUCTURE	118.56 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

text structure

three separate transcription units that are governed by non-redundant promoters coordinating distinct tissue expression profiles

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005100 5 - 8450 NP_005091 191.5 1782 - 2009 19210988 NM_144497 3 - 8246 NP_653080 - 1684 - 2009 19210988

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Hearing/Equilibrium ear       highly Reproductive male system testis     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

secondary structure

an amphipathic helix binding domain

HOMOLOGY

Homologene

FAMILY

CATEGORY

chaperone/stress , antigen

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytoskeleton
	intracellular,nucleus
text	multivalent A-kinase anchoring protein (AKAP), localizing to the cell periphery in several cell types and is postulated to target PRKACA and other binding partners to the plasma membrane

basic FUNCTION	a kinase (PRKA regulatory subunits and RIIA and PRKC) anchor protein tethering the enzyme near its physiological substrates
	scaffold protein that participates in mitotic regulation and other signalling processes and probably exerts tumour suppressor function
	display a signature binding site for the RI/RII subunit of protein kinase A
	autoantigen recognized by serum from myasthenia patients
	essential for the resensitization and recycling of the receptors following agonist-induced activation, desensitization, and internalization
	involved in the regulation of cytokinesis progression
	internalized with the beta(2)-adrenergic receptor, but segregates away from the G-protein-coupled receptor upon recycling of the internalized receptor to the cell membrane
	in astrocytes differentially regulates the expression of VEGFA and TSP1 via the inhibition of PRKCZ phosphorylation and Rho kinase activity in retina microvascular endothelial cells
	regulates blood-retinal barrier formation by downregulation of hypoxia-inducible factor-1alpha (defects in this mechanism can lead to a loss of tight junction proteins and contribute to the development of retinal pathologies such as retinoblastoma)
	negative regulator of myelinating glia differentiation
	scaffold that docks PRKAA, G-protein-coupled receptors, cell membrane negatively-charged phospholipids, and catalyzes receptor resensitization and recycling
	AKAP5 and AKAP12 are capable of forming hetero-oligomeric supermolecular complexes that influence AKAP locale and function
	role as a candidate tumor suppressor gene for hepatocellular carcinoma
	regulates cellular senescence and oncogenic progression at the level of tumor cells and tumor-associated microenvironment via its multiple scaffolding functions
	scaffold protein for PKA and PKC which controls actin-cytoskeleton reorganization in a spatiotemporal manner
	acts as a tumor suppressor which regulates cell-cycle progression and inhibits SRC-mediated oncogenic signaling and cytoskeletal pathway
	kinase-anchoring protein that integrates cAMP and calcium/phospholipid signals at the plasma membrane by sequestering protein kinases A and C with G protein-coupled receptors

CELLULAR PROCESS	cell cycle, division
	cell organization/biogenesis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	target PRKACA and other binding partners to the plasma membrane
	AKAP12 is an epigenetic target of HDAC7, whose elevated levels lead to a negative regulation of HUVEC migration and inhibit formation of tube-like structures

cell & other

REGULATION

Phosphorylated by

CDK1 (CDK1 phosphorylates AKAP12 on threonine 766 to prime the recruitment of the polo-like kinase PLK1 at defined phases of mitosis)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         frequently inactivated in human gastric cancer and in several other cancers due to promoter hypermethylation tumoral     --low   in samples of acute leukaemia and associated with an inferior overall survival tumoral     --low   by promoter hypermethylation in gastric and colorectal cancers tumoral     --low   by promoter hypermethylation is a common, tissue-specific event in esophageal adenocarcinoma, occurs early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker for the early detection of esophageal adenocarcinoma tumoral imprinting       epigenetic silencing of AKAP12 may be involved in myeloid malignancies tumoral     --low   in hepatocellular carcinoma tissues through promoter hypermethylation

Susceptibility

Variant & Polymorphism

Candidate gene	gravin autoantigen recognized by serum from myasthenia patients
Marker	AKAP12 MS-HRM (methylation-specific high resolution melting) quantitative methods with excellent detection capabilities have many promising applications in the research and diagnosis of colorectal cancer
Therapy target

ANIMAL & CELL MODELS

AKAP12-null mice exhibit increased cell senescence and increased susceptibility to carcinogen-induced oncogenesis