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FLASH GENE

Symbol

GNAI2

contributors: mct - updated : 13-09-2017

HGNC name	guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2
HGNC id	4385

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	three regions named switches 1, 2 and 3 and including the sites for guanine nucleotide binding and effector interaction
	an helical domain

HOMOLOGY

Homologene

FAMILY	G-alpha family
	G(i/o/t/z) subfamily

CATEGORY

signaling

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,nucleus,nucleoplasm

basic FUNCTION	regulates a number of cellular functions including cell migration, proliferation, and differentiation
	negative modifier of Ras activation
	required for chemokine-induced neutrophil arrest
	having an important role in regulating thymic homing and pre-thymic and early thymocyte differentiation
	exhibited a more prominent role than GNAI3 in guidance of CD4-CD8--double negative (DN) 1 cell migration and early thymic differentiation
	involved specifically in the activation of TRPC4
	variations in GNAI2 and RGS1 expression affect chemokine receptor signaling and the organization of secondary lymphoid organs
	GNAI2 gene chromatin is a direct target of MTA1 and MTA1 might stimulate the Ras pathway, in part, by repressing the expression of GNAI2, which in turn is a negative regulator of the Raf pathway
	is a novel CLDN5 partner required for TJ integrity in brain endothelial cells
	GNAI2 plays an essential role in OXT and EGF signaling to induce prostate cancer cell migration
	GNAI2, GNAI3 contribute to inflammation by redundant, overlapping, and GNAI-isoform-specific mechanism
	GNAI2, GNAI3 are therefore critical for B cell chemoattractant receptor signaling and for normal B cell function
	GNAI2 signaling is required for skeletal muscle growth, regeneration, and satellite cell proliferation and differentiation
	potential role in the brain development, and impairment of its function might cause defects in neuronal functions which lead to neurodevelopmental disorders

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	guanine nucleotide binding
	binding UNC5B (inhibitor of G protein signaling that may have broad significance for axonal guidance and chemotaxis)
	GNAI2 and ZAP70 mediate RASGRP1 membrane localization and activation of CXCL12-induced T cell functions
	GNAI2 interacts with CLDN5 and association is correlated with TJ (tight junctions) integrity in brain endothelial cell line
	CEBPA plays a dual role as an activator and as a repressor of GNAI2 gene transcription
	essential role for RGS protein/GNAI2 interactions in B lymphocyte-directed cell migration and trafficking

cell & other

REGULATION

repressed by

MTA1 (MTA1 behaves as a co-repressor of GNAI2)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       in periventricular nodular heterotopia and intellectual disability

Susceptibility

to high systolic blood pression

Variant & Polymorphism SNP	-318 C>G SNP impairs transcriptional activity through specific binding of Sp1 and is associated with high Systolic blood pression

Candidate gene	candidate genes for Noonan syndrome
Marker
Therapy target

ANIMAL & CELL MODELS

	Galpha(i2) (-/-) mice have a reduced ventricular effective refractory period and a predisposition to ventricular tachycardia when challenged with programmed electrical stimulation
	lack of Gnai2 leads to dilative cardiomyopathy and increased mortality in Adrb1 overexpressing mice