6mhf

Structural highlights

Disease

[GRDN_HUMAN] PEHO-like syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

[GNAI3_RAT] Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (PubMed:2159473). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels. Stimulates the activity of receptor-regulated K(+) channels. The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.[UniProtKB:P08754]^[1] [GRDN_HUMAN] Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Enhances phosphoinositide 3-kinase (PI3K)-dependent phosphorylation and kinase activity of AKT1/PKB, but does not possess kinase activity itself (By similarity). Phosphorylation of AKT1/PKB thereby induces the phosphorylation of downstream effectors GSK3 and FOXO1/FKHR, and regulates DNA replication and cell proliferation (By similarity). Essential for the integrity of the actin cytoskeleton and for cell migration (PubMed:16139227). Required for formation of actin stress fibers and lamellipodia (PubMed:15882442). May be involved in membrane sorting in the early endosome (PubMed:15882442). Plays a role in ciliogenesis and cilium morphology and positioning and this may partly be through regulation of the localization of scaffolding protein CROCC/Rootletin (PubMed:27623382).[UniProtKB:Q5SNZ0]^{[2] [3] [4]}

References

1. ↑ Linder ME, Ewald DA, Miller RJ, Gilman AG. Purification and characterization of Go alpha and three types of Gi alpha after expression in Escherichia coli. J Biol Chem. 1990 May 15;265(14):8243-51. PMID:2159473
2. ↑ Simpson F, Martin S, Evans TM, Kerr M, James DE, Parton RG, Teasdale RD, Wicking C. A novel hook-related protein family and the characterization of hook-related protein 1. Traffic. 2005 Jun;6(6):442-58. doi: 10.1111/j.1600-0854.2005.00289.x. PMID:15882442 doi:http://dx.doi.org/10.1111/j.1600-0854.2005.00289.x
3. ↑ Enomoto A, Murakami H, Asai N, Morone N, Watanabe T, Kawai K, Murakumo Y, Usukura J, Kaibuchi K, Takahashi M. Akt/PKB regulates actin organization and cell motility via Girdin/APE. Dev Cell. 2005 Sep;9(3):389-402. PMID:16139227 doi:S1534-5807(05)00295-9
4. ↑ Nechipurenko IV, Olivier-Mason A, Kazatskaya A, Kennedy J, McLachlan IG, Heiman MG, Blacque OE, Sengupta P. A Conserved Role for Girdin in Basal Body Positioning and Ciliogenesis. Dev Cell. 2016 Sep 12;38(5):493-506. doi: 10.1016/j.devcel.2016.07.013. PMID:27623382 doi:http://dx.doi.org/10.1016/j.devcel.2016.07.013