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AKAP13

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AKAP13
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesAKAP13, A kinase (PRKA) anchor protein 13, AKAP-13, AKAP-Lbc, ARHGEF13, BRX, HA-3, Ht31, LBC, PRKA13, PROTO-LB, PROTO-LBC, c-lbc, p47, A-kinase anchoring protein 13, A-kinase anchor protein 13
External IDsOMIM: 604686; MGI: 2676556; HomoloGene: 4903; GeneCards: AKAP13; OMA:AKAP13 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

11214

75547

Ensembl

ENSG00000170776

ENSMUSG00000066406

UniProt

Q12802

E9Q394

RefSeq (mRNA)

NM_144767
NM_001270546
NM_006738
NM_007200
NM_032162

NM_029332

RefSeq (protein)

NP_001257475
NP_006729
NP_009131

NP_083608

Location (UCSC)Chr 15: 85.38 – 85.75 MbChr 7: 75.46 – 75.75 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

A-kinase anchor protein 13 is a protein that in humans, is encoded by the AKAP13 gene.[5][6][7] This protein is also called AKAP-Lbc because it encodes the lymphocyte blast crisis (Lbc) oncogene, and ARHGEF13/RhoGEF13 because it contains a guanine nucleotide exchange factor (GEF) domain for the RhoA small GTP-binding protein.

Function

A-kinase anchor protein 13/Rho guanine nucleotide exchange factor 13 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein.[8][9] Rho is a small GTPase protein that is inactive when bound to the guanine nucleotide GDP. But when acted on by Rho GEF proteins such as AKAP13, this GDP is released and replaced by GTP, leading to the active state of Rho. In this active, GTP-bound conformation, Rho can bind to and activate specific effector proteins and enzymes to regulate cellular functions.[10] In particular, active Rho is a major regulator of the cell actin cytoskeleton.[10]

AKAP13 is a member of a group of four RhoGEF proteins known to be activated by G protein coupled receptors coupled to the G12 and G13 heterotrimeric G proteins.[8][9] The others are ARHGEF1 (also known as p115-RhoGEF), ARHGEF11 (also known as PDZ-RhoGEF), and ARHGEF12 (also known as LARG). [11][8] GPCR-regulated AKAP13 (and these related GEF proteins) acts as an effector for G12 and G13 G proteins. Unlike the other three members, AKAP13 does not function as RGS family GTPase-activating proteins (GAPs) to increase the rate of GTP hydrolysis of G12/G13 alpha proteins.[12]

The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins that have the common function of binding to the regulatory subunit of protein kinase A (PKA), thus confining the holoenzyme to discrete locations within the cell. The AKAP13 gene encodes a member of the AKAP family since the protein binds tightly to PKA, especially in the heart.

Alternative splicing of this gene results in at least 3 transcript variants encoding different isoforms. All three contain the Dbl oncogene homology (DH) domain plus Pleckstrin homology (PH) domain (DH/PH domain) characteristic of Rho family GEFs, while only the longer two isoforms also contain the AKAP domain.[7] Therefore, these isoforms may function as scaffolding proteins to coordinate Rho signaling and protein kinase A signaling.

Interactions

AKAP13 has been shown to interact with:

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000170776 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000066406 – 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. ^ a b Rubino D, Driggers P, Arbit D, Kemp L, Miller B, Coso O, et al. (May 1998). "Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action". Oncogene. 16 (19): 2513–26. doi:10.1038/sj.onc.1201783. PMID 9627117.
  6. ^ Carr DW, Stofko-Hahn RE, Fraser ID, Bishop SM, Acott TS, Brennan RG, Scott JD (August 1991). "Interaction of the regulatory subunit (RII) of cAMP-dependent protein kinase with RII-anchoring proteins occurs through an amphipathic helix binding motif". The Journal of Biological Chemistry. 266 (22): 14188–92. doi:10.1016/S0021-9258(18)98665-5. PMID 1860836.
  7. ^ a b "Entrez Gene: AKAP13 A kinase (PRKA) anchor protein 13".
  8. ^ a b c Diviani D, Soderling J, Scott JD (November 2001). "AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation". The Journal of Biological Chemistry. 276 (47): 44247–57. doi:10.1074/jbc.M106629200. PMID 11546812.
  9. ^ a b c d Dutt P, Nguyen N, Toksoz D (February 2004). "Role of Lbc RhoGEF in Galpha12/13-induced signals to Rho GTPase". Cellular Signalling. 16 (2): 201–9. doi:10.1016/S0898-6568(03)00132-3. PMID 14636890.
  10. ^ a b Thumkeo D, Watanabe S, Narumiya S (Oct–Nov 2013). "Physiological roles of Rho and Rho effectors in mammals". European Journal of Cell Biology. 92 (10–11): 303–15. doi:10.1016/j.ejcb.2013.09.002. PMID 24183240.
  11. ^ Fukuhara S, Chikumi H, Gutkind JS (March 2001). "RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho?". Oncogene. 20 (13): 1661–8. doi:10.1038/sj.onc.1204182. PMID 11313914.
  12. ^ Kozasa T (April 2001). "Regulation of G protein-mediated signal transduction by RGS proteins". Life Sciences. 68 (19–20): 2309–17. doi:10.1016/S0024-3205(01)01020-7. PMID 11358341.
  13. ^ Park B, Nguyen NT, Dutt P, Merdek KD, Bashar M, Sterpetti P, et al. (November 2002). "Association of Lbc Rho guanine nucleotide exchange factor with alpha-catenin-related protein, alpha-catulin/CTNNAL1, supports serum response factor activation". The Journal of Biological Chemistry. 277 (47): 45361–70. doi:10.1074/jbc.M202447200. PMID 12270917.
  14. ^ Alto NM, Soderling SH, Hoshi N, Langeberg LK, Fayos R, Jennings PA, Scott JD (April 2003). "Bioinformatic design of A-kinase anchoring protein-in silico: a potent and selective peptide antagonist of type II protein kinase A anchoring". Proceedings of the National Academy of Sciences of the United States of America. 100 (8): 4445–50. Bibcode:2003PNAS..100.4445A. doi:10.1073/pnas.0330734100. PMC 153575. PMID 12672969.
  15. ^ Carr DW, Hausken ZE, Fraser ID, Stofko-Hahn RE, Scott JD (July 1992). "Association of the type II cAMP-dependent protein kinase with a human thyroid RII-anchoring protein. Cloning and characterization of the RII-binding domain". The Journal of Biological Chemistry. 267 (19): 13376–82. doi:10.1016/S0021-9258(18)42221-1. PMID 1618839.

Further reading

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