Entrez Summary: This gene belongs to the melastatin subfamily of transient receptor potential family of ion channels. The protein encoded by this gene is both an ion channel and a serine/threonine protein kinase. The kinase activity is essential for the ion channel function, which serves to increase intracellular calcium levels and to help regulate magnesium ion homeostasis. The encoded protein is involved in cytoskeletal organization, cell adhesion, cell migration and organogenesis. Defects in this gene are a cause of amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam. The gene may also be associated with defects of cardiac function. [provided by RefSeq, Aug 2017].
UniProt Summary: Essential ion channel and serine/threonine-protein kinase. Divalent cation channel permeable to calcium and magnesium. Has a central role in magnesium ion homeostasis and in the regulation of anoxic neuronal cell death. Involved in TNF- induced necroptosis downstream of MLKL by mediating calcium influx. The kinase activity is essential for the channel function. May be involved in a fundamental process that adjusts plasma membrane divalent cation fluxes according to the metabolic state of the cell. Phosphorylates annexin A1 (ANXA1). {ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:24316671}.
Pfam DomainsGO Terms
Pfam Domains
Alpha kinase
Ion trans
GO Terms
calcium-dependent cell-matrix adhesion
cellular magnesium ion homeostasis
magnesium ion homeostasis
necroptotic process
myosin binding
programmed necrotic cell death
necrotic cell death
calcium channel activity
ruffle
actomyosin structure organization
cell-matrix adhesion
protein tetramerization
cell-substrate adhesion
protein autophosphorylation
calcium ion transmembrane transport
calcium ion transport
actin binding
divalent metal ion transport
divalent inorganic cation transport
protein serine/threonine kinase activity
cellular divalent inorganic cation homeostasis
divalent inorganic cation homeostasis
actin cytoskeleton organization
protein complex oligomerization
cellular metal ion homeostasis
inorganic cation transmembrane transport
actin filament-based process
cation transmembrane transport
metal ion homeostasis
cellular cation homeostasis
metal ion transport
cellular ion homeostasis
inorganic ion transmembrane transport
cation homeostasis
inorganic ion homeostasis
cellular chemical homeostasis
ion homeostasis
cation transport
cellular homeostasis
cell adhesion
biological adhesion
ion transmembrane transport
protein phosphorylation
programmed cell death
cell death
cytoskeleton organization
chemical homeostasis
transmembrane transport
phosphorylation
ion transport
ATP binding
protein-containing complex assembly
homeostatic process
protein-containing complex subunit organization
CRISPR Data
Compound HitMost Correlated Genes in ChemogenomicsTissues where Essential in the Avana Dataset (DepMap 20Q1)