AKAP13
Description
The AKAP13 (A-kinase anchoring protein 13) is a protein-coding gene located on chromosome 15.
A-kinase anchor protein 13 is a protein that in humans, is encoded by the AKAP13 gene. 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. 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. In particular, active Rho is a major regulator of the cell actin cytoskeleton. 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. The others are ARHGEF1 (also known as p115-RhoGEF), ARHGEF11 (also known as PDZ-RhoGEF), and ARHGEF12 (also known as LARG). 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.
AKAP13, also known as AKAP-Lbc, plays a key role in assembling signaling complexes downstream of G protein-coupled receptors. It activates RHOA in response to G protein-coupled receptor signaling via its function as a Rho guanine nucleotide exchange factor (GEF). It may also activate other Rho family members. AKAP13 is involved in various signaling pathways, including those linked to adrenergic receptor signaling, lysophosphatidic acid (LPA) signaling, and cAMP and EGFR signaling. It functions as a scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1, promoting the activation of PRKD1 and ultimately contributing to cardiomyocyte hypertrophy. AKAP13 is required for normal embryonic heart development, including sarcomere formation in developing cardiomyocytes. It plays a role in cardiomyocyte growth and cardiac hypertrophy in response to beta-adrenergic receptor activation and pressure overload. AKAP13 is also involved in osteogenesis. AKAP13 interacts with various proteins, including PKA, RHOA, PRKAR2A, BRAF, KSR1, PKN1, MAPK14, ZAK, MAP2K3, YWHAB, YWHAZ, GNA12, IKBKB, ESR1, THRA, PPARA, NME2, MEF2C, and RXRB. Interactions with YWHAB and YWHAZ inhibit RHOA activation and interfere with PKN1 binding and MAP kinase activation.
AKAP13 is also known as AKAP-13, AKAP-Lbc, ARHGEF13, BRX, HA-3, Ht31, LBC, PRKA13, PROTO-LB, PROTO-LBC, c-lbc, p47.
