GNAI1

Function

Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades (PubMed:18434541, PubMed:33762731, PubMed:34239069, PubMed:35610220, PubMed:37935376, PubMed:37935377, PubMed:37963465, PubMed:38552625, PubMed:8774883). The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state (PubMed:18434541, PubMed:8774883). Signaling by an activated GPCR promotes GDP release and GTP binding (PubMed:18434541, PubMed:8774883). The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (PubMed:18434541, PubMed:8774883). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:18434541, PubMed:8774883). Signaling is mediated via effector proteins, such as adenylate cyclase: inhibits adenylate cyclase activity of ADCY1, ADCY5 and ADCY6, leading to decreased intracellular cAMP levels (PubMed:8119955). The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. Required for normal cytokinesis during mitosis (PubMed:17635935). Required for cortical dynein-dynactin complex recruitment during metaphase (PubMed:22327364).

Involvement in disease

Neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities

NEDHISB

An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, delayed or absent speech, hypotonia, behavioral abnormalities, and epilepsy that ranges from self-limiting to intractable. More variable features include non-specific dysmorphic facial features, distal skeletal anomalies, and brain imaging abnormalities.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Myristoylation at Gly-2 is required for membrane anchoring before palmitoylation.

Palmitoylation at Cys-3 varies with membrane lipid composition.

(Microbial infection) Deamidated at Gln-204 by Photorhabdus asymbiotica toxin PAU_02230, blocking GTP hydrolysis of heterotrimeric GNAQ or GNA11 and G-alphai (GNAI1, GNAI2 or GNAI3) proteins, thereby activating RhoA.

Sequence Similarities

Belongs to the G-alpha family. G(i/o/t/z) subfamily.

Cellular localization

• Nucleus
• Cytoplasm
• Cell membrane
• Peripheral membrane protein
• Cytoplasmic side
• Cytoplasm
• Cytoskeleton
• Microtubule organizing center
• Centrosome
• Cytoplasm
• Cell cortex
• Membrane
• Lipid-anchor
• Localizes in the centrosomes of interphase and mitotic cells, but not in centrosomes during cytokinesis. Detected at the cleavage furrow or the midbody (PubMed:17635935). Localized at the plasma membrane throughout mitosis. Colocalizes with RIC8A and RGS14 at the plasma membrane.

Alternative names

Guanine nucleotide-binding protein G(i) subunit alpha-1, Adenylate cyclase-inhibiting G alpha protein, GNAI1

Database links

swissprot:P63096 entrezGene:2771 omim:139310 omim:139360 swissprot:P04899 entrezGene:2770