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.
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.
AKAP13 has been shown to interact with:
GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a protein domain common to many GTPases.
Ras homolog gene family, member B, also known as RHOB, is a protein which in humans is encoded by the RHOB gene.
Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the RHOA gene. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. It acts upon several effectors. Among them, ROCK1 and DIAPH1 are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billion years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation.
Ras-related protein Rap-1A is a protein that in humans is encoded by the RAP1A gene.
Rho guanine nucleotide exchange factor TIAM1 is a protein that in humans is encoded by the TIAM1 gene.
cAMP-dependent protein kinase type II-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR2A gene.
RhoGEF domain describes two distinct structural domains with guanine nucleotide exchange factor (GEF) activity to regulate small GTPases in the Rho family. Rho small GTPases are inactive when bound to GDP but active when bound to GTP; RhoGEF domains in proteins are able to promote GDP release and GTP binding to activate specific Rho family members, including RhoA, Rac1 and Cdc42.
Rho guanine nucleotide exchange factor 7 is a protein that in humans is encoded by the ARHGEF7 gene.
Rho guanine nucleotide exchange factor 6 is a protein that, in humans, is encoded by the ARHGEF6 gene.
Ras-related protein Rap-2a is a protein that in humans is encoded by the RAP2A gene. RAP2A is a member of the Ras-related protein family.
Rho guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the ARHGEF1 gene. This protein is also called RhoGEF1 or p115-RhoGEF.
Rho guanine nucleotide exchange factor 11 is a protein that in humans is encoded by the ARHGEF11 gene. This protein is also called RhoGEF11 or PDZ-RhoGEF.
Rho guanine nucleotide exchange factor 12 is a protein that in humans is encoded by the ARHGEF12 gene. This protein is also called RhoGEF12 or Leukemia-associated Rho guanine nucleotide exchange factor (LARG).
RhoG is a small monomeric GTP-binding protein, and is an important component of many intracellular signalling pathways. It is a member of the Rac subfamily of the Rho family of small G proteins and is encoded by the gene RHOG.
The DBL proto-oncogene is a protein that in humans is encoded by the MCF2 gene.
Guanine nucleotide exchange factor VAV3 is a protein that in humans is encoded by the VAV3 gene.
Guanine nucleotide exchange factor DBS is a protein that in humans is encoded by the MCF2L gene.
Guanine nucleotide-binding protein subunit alpha-13 is a protein that in humans is encoded by the GNA13 gene.
Guanine nucleotide-binding protein subunit alpha-12 is a protein that in humans is encoded by the GNA12 gene.
Pleckstrin homology domain containing, family G member 2 (PLEKHG2) is a protein that in humans is encoded by the PLEKHG2 gene. It is sometimes written as ARHGEF42, FLJ00018.
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