AKAP9

A-kinase anchor protein 9 is a protein that in humans is encoded by the AKAP9 gene.[3][4][5] AKAP9 is also known as Centrosome- and Golgi-localized protein kinase N-associated protein (CG-NAP) or AKAP350 or AKAP450 [6]

AKAP9
Identifiers
Aliases	AKAP9, AKAP-9, AKAP350, AKAP450, CG-NAP, HYPERION, LQT11, MU-RMS-40.16A, PPP1R45, PRKA9, YOTIAO, A-kinase anchoring protein 9
External IDs	OMIM: 604001 HomoloGene: 17517 GeneCards: AKAP9
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q21.2 Start 91,940,867 bp[1] End 92,110,673 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • ion channel binding • potassium channel regulator activity • GO:0001948 protein binding • GO:0032947 molecular adaptor activity • receptor binding • protein kinase A regulatory subunit binding • Ras guanyl-nucleotide exchange factor activity • DNA binding • kinase activity Cellular component • cytoplasm • cytosol • centrosome • Golgi apparatus • intracellular membrane-bounded organelle • voltage-gated potassium channel complex • cis-Golgi network • microtubule organizing center • Golgi stack • cytoskeleton • dendritic branch • synaptic membrane • neuronal cell body • glutamatergic synapse • extrinsic component of postsynaptic density membrane Biological process • positive regulation of peptidyl-serine phosphorylation • MAPK cascade • G2/M transition of mitotic cell cycle • regulation of membrane repolarization • regulation of heart rate by cardiac conduction • cellular response to cAMP • signal transduction • positive regulation of potassium ion transmembrane transporter activity • microtubule nucleation • regulation of ventricular cardiac muscle cell membrane repolarization • chemical synaptic transmission • response to electrical stimulus • negative regulation of adenylate cyclase activity • ciliary basal body docking • regulation of cardiac muscle cell action potential involved in regulation of contraction • maintenance of centrosome location • regulation of G2/M transition of mitotic cell cycle • regulation of Golgi organization • positive regulation of microtubule polymerization • regulation of postsynaptic neurotransmitter receptor activity • cardiac conduction • phosphorylation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10142	n/a
Ensembl	ENSG00000127914	n/a
UniProt	Q99996 Q6PJH3	n/a
RefSeq (mRNA)	NM_005751 NM_147166 NM_147171 NM_147185 NM_001379277	n/a
RefSeq (protein)	NP_005742 NP_671714 NP_001366206 NP_005742.4 NP_671714.1	n/a
Location (UCSC)	Chr 7: 91.94 – 92.11 Mb	n/a
PubMed search	[2]	n/a
Wikidata
View/Edit Human

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. Alternate splicing of this gene results in many isoforms that localize to the centrosome and the Golgi apparatus, and interact with numerous signaling proteins from multiple signal transduction pathways. These signaling proteins include type II protein kinase A, serine/threonine kinase protein kinase N, protein phosphatase 1, protein phosphatase 2a, protein kinase C-epsilon and phosphodiesterase 4D3.[5]

Model organisms

Akap9 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Normal
Fertility	Normal
Body weight	Abnormal[7]
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Abnormal[8]
Glucose tolerance test	Abnormal[9]
Auditory brainstem response	Normal
DEXA	Abnormal[10]
Radiography	Abnormal[11]
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal[12]
Haematology	Normal
Peripheral blood lymphocytes	Abnormal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Eye Histopathology	Normal
Salmonella infection	Normal[13]
Citrobacter infection	Normal[14][15]
All tests and analysis from[16]

Model organisms have been used in the study of AKAP9 function. A conditional knockout mouse line, called Akap9^{tm1a(KOMP)Wtsi}[17][18] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[19][20][21]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[16][22] Twenty six tests were carried out on mutant mice and eight significant abnormalities were observed.[16] Fewer than expected homozygous mutant mice survived until weaning. The remaining tests were carried out on both homozygous and heterozygous mutant adult mice. Animals of both sex displayed decreased body fat and body weight, hematopoietic abnormalities and an atypical plasma chemistry panel. Female homozygotes also displayed abnormal tooth morphology while males heterozygous animals displayed an abnormal pelvic girdle bone morphology.[16]

Interactions

AKAP9 has been shown to interact with:

• CALM2,[23]
• CALM1,[23]
• FNBP1,[24]
• KvLQT1[25]
• PRKAR2A,[26][27]
• PKN1,[26] and
• TRIP10.[24]

References

1. GRCh38: Ensembl release 89: ENSG00000127914 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. Lin JW, Wyszynski M, Madhavan R, Sealock R, Kim JU, Sheng M (Apr 1998). "Yotiao, a novel protein of neuromuscular junction and brain that interacts with specific splice variants of NMDA receptor subunit NR1". J Neurosci. 18 (6): 2017–27. PMID 9482789.
4. Westphal RS, Tavalin SJ, Lin JW, Alto NM, Fraser ID, Langeberg LK, Sheng M, Scott JD (Jul 1999). "Regulation of NMDA receptors by an associated phosphatase-kinase signaling complex". Science. 285 (5424): 93–6. doi:10.1126/science.285.5424.93. PMID 10390370.
5. "Entrez Gene: AKAP9 A kinase (PRKA) anchor protein (yotiao) 9".
6. Ong ST, Chalasani ML, Fazil MH, Prasannan P, Kizhakeyil A, Wright GD, Kelleher D, Verma NK (Mar 2018). "Centrosome- and Golgi-Localized Protein Kinase N-Associated Protein Serves As a Docking Platform for Protein Kinase A Signaling and Microtubule Nucleation in Migrating T-Cells". Front. Immunol. 9 (397): 397. doi:10.3389/fimmu.2018.00397. PMC 5837996. PMID 29545805.
7. "Body weight data for Akap9". Wellcome Trust Sanger Institute.
8. "Indirect calorimetry data for Akap9". Wellcome Trust Sanger Institute.
9. "Glucose tolerance test data for Akap9". Wellcome Trust Sanger Institute.
10. "DEXA data for Akap9". Wellcome Trust Sanger Institute.
11. "Radiography data for Akap9". Wellcome Trust Sanger Institute.
12. "Clinical chemistry data for Akap9". Wellcome Trust Sanger Institute.
13. "Salmonella infection data for Akap9". Wellcome Trust Sanger Institute.
14. "Citrobacter infection data for Akap9". Wellcome Trust Sanger Institute.
15. Mouse Resources Portal, Wellcome Trust Sanger Institute.
16. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
17. "International Knockout Mouse Consortium".
18. "Mouse Genome Informatics".
19. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
20. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
21. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
22. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
23. Takahashi M, Yamagiwa A, Nishimura T, Mukai H, Ono Y (Sep 2002). "Centrosomal proteins CG-NAP and kendrin provide microtubule nucleation sites by anchoring gamma-tubulin ring complex". Mol. Biol. Cell. 13 (9): 3235–45. doi:10.1091/mbc.E02-02-0112. PMC 124155. PMID 12221128.
24. Larocca MC, Shanks RA, Tian L, Nelson DL, Stewart DM, Goldenring JR (Jun 2004). "AKAP350 interaction with cdc42 interacting protein 4 at the Golgi apparatus". Mol. Biol. Cell. 15 (6): 2771–81. doi:10.1091/mbc.E03-10-0757. PMC 420101. PMID 15047863.
25. Marx SO, Kurokawa J, Reiken S, Motoike H, D'Armiento J, Marks AR, Kass RS (Jan 2002). "Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel". Science. 295 (5554): 496–9. doi:10.1126/science.1066843. PMID 11799244.
26. Takahashi M, Shibata H, Shimakawa M, Miyamoto M, Mukai H, Ono Y (Jun 1999). "Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus". J. Biol. Chem. 274 (24): 17267–74. doi:10.1074/jbc.274.24.17267. PMID 10358086.
27. Alto NM, Soderling SH, Hoshi N, Langeberg LK, Fayos R, Jennings PA, Scott JD (Apr 2003). "Bioinformatic design of A-kinase anchoring protein-in silico: a potent and selective peptide antagonist of type II protein kinase A anchoring". Proc. Natl. Acad. Sci. U.S.A. 100 (8): 4445–50. doi:10.1073/pnas.0330734100. PMC 153575. PMID 12672969.

Further reading

• Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (1999). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 5 (5): 277–86. doi:10.1093/dnares/5.5.277. PMID 9872452.
• Schmidt PH, Dransfield DT, Claudio JO, Hawley RG, Trotter KW, Milgram SL, Goldenring JR (1999). "AKAP350, a multiply spliced protein kinase A-anchoring protein associated with centrosomes". J. Biol. Chem. 274 (5): 3055–66. doi:10.1074/jbc.274.5.3055. PMID 9915845.
• Witczak O, Skålhegg BS, Keryer G, Bornens M, Taskén K, Jahnsen T, Orstavik S (1999). "Cloning and characterization of a cDNA encoding an A-kinase anchoring protein located in the centrosome, AKAP450". EMBO J. 18 (7): 1858–68. doi:10.1093/emboj/18.7.1858. PMC 1171271. PMID 10202149.
• Takahashi M, Shibata H, Shimakawa M, Miyamoto M, Mukai H, Ono Y (1999). "Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus". J. Biol. Chem. 274 (24): 17267–74. doi:10.1074/jbc.274.24.17267. PMID 10358086.
• Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG (2000). "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes". Nat. Neurosci. 3 (7): 661–9. doi:10.1038/76615. hdl:1842/742. PMID 10862698.
• Takahashi M, Mukai H, Oishi K, Isagawa T, Ono Y (2000). "Association of immature hypophosphorylated protein kinase cepsilon with an anchoring protein CG-NAP". J. Biol. Chem. 275 (44): 34592–6. doi:10.1074/jbc.M005285200. PMID 10945988.
• Marx SO, Kurokawa J, Reiken S, Motoike H, D'Armiento J, Marks AR, Kass RS (2002). "Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel". Science. 295 (5554): 496–9. doi:10.1126/science.1066843. PMID 11799244.
• Steadman BT, Schmidt PH, Shanks RA, Lapierre LA, Goldenring JR (2002). "Transforming acidic coiled-coil-containing protein 4 interacts with centrosomal AKAP350 and the mitotic spindle apparatus". J. Biol. Chem. 277 (33): 30165–76. doi:10.1074/jbc.M201914200. PMID 12015314.
• Bray JD, Chennathukuzhi VM, Hecht NB (2002). "Identification and characterization of cDNAs encoding four novel proteins that interact with translin associated factor-X". Genomics. 79 (6): 799–808. doi:10.1006/geno.2002.6779. PMID 12036294.
• Shanks RA, Larocca MC, Berryman M, Edwards JC, Urushidani T, Navarre J, Goldenring JR (2002). "AKAP350 at the Golgi apparatus. II. Association of AKAP350 with a novel chloride intracellular channel (CLIC) family member". J. Biol. Chem. 277 (43): 40973–80. doi:10.1074/jbc.M112277200. PMID 12163479.
• Takahashi M, Yamagiwa A, Nishimura T, Mukai H, Ono Y (2003). "Centrosomal Proteins CG-NAP and Kendrin Provide Microtubule Nucleation Sites by Anchoring γ-Tubulin Ring Complex". Mol. Biol. Cell. 13 (9): 3235–45. doi:10.1091/mbc.E02-02-0112. PMC 124155. PMID 12221128.
• Sillibourne JE, Milne DM, Takahashi M, Ono Y, Meek DW (2002). "Centrosomal anchoring of the protein kinase CK1delta mediated by attachment to the large, coiled-coil scaffolding protein CG-NAP/AKAP450". J. Mol. Biol. 322 (4): 785–97. doi:10.1016/S0022-2836(02)00857-4. PMID 12270714.
• Tu H, Tang TS, Wang Z, Bezprozvanny I (2004). "Association of type 1 inositol 1,4,5-trisphosphate receptor with AKAP9 (Yotiao) and protein kinase A". J. Biol. Chem. 279 (18): 19375–82. doi:10.1074/jbc.M313476200. PMID 14982933.

External links

• AKAP9 human gene location in the UCSC Genome Browser.
• AKAP9 human gene details in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.