GNA15 is a protein encoded by the GNA15 gene that functions as a G protein alpha subunit primarily expressed in hematopoietic cells. It activates phospholipase C beta, leading to calcium signaling. While mainly studied in immune cells, GNA15-mediated signaling has emerging roles in neuroinflammation and neurodegenerative diseases. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
Gene: GNA15
UniProt: P30679
PDB: 1AZT
Molecular Weight: 41.3 kDa
Subcellular Localization: Plasma membrane
Protein Family: G alpha q/11 family
The GNA15 protein is a G protein alpha subunit characterized by canonical G protein domain architecture[1]. Key structural features include:
The protein adopts a similar fold to other Gα subunits, with six β-strands and five α-helices forming the core GTPase domain[2].
GNA15 is a G protein alpha subunit primarily expressed in hematopoietic cells, including microglia, the resident immune cells of the brain[3]. Its normal functions include:
GNA15 plays emerging roles in neurodegenerative diseases through its functions in microglial activation and neuroinflammation:
G protein subunits represent emerging therapeutic targets for neurodegenerative diseases[4]. Potential approaches include:
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Wall MA, Coleman DE, Lee E, et al. The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2. Cell. 1995. ↩︎
Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007. ↩︎
Syrovatkina V, Alegre KO, Dey R, Huang XY. Regulation, Functions, and Disease Mechanisms of G Protein-Coupled Receptor Kinases. Adv Exp Med Biol. 2020. ↩︎