PLEKHG5

This gene encodes a protein that activates the nuclear factor kappa B (NFKB1) signaling pathway. Multations in this gene have been found in a family with distal spinal muscular atrophy. [provided by RefSeq]

Full Name

pleckstrin homology domain containing, family G (with RhoGef domain) member 5

Function

Functions as a guanine exchange factor (GEF) for RAB26 and thus regulates autophagy of synaptic vesicles in axon terminal of motoneurons (By similarity).
Involved in the control of neuronal cell differentiation (PubMed:11704860).
Plays a role in angiogenesis through regulation of endothelial cells chemotaxis. Affects also the migration, adhesion, and matrix/bone degradation in macrophages and osteoclasts (PubMed:23777631).

Biological Process

Endothelial cell chemotaxisISS:UniProtKB
Endothelial cell migrationManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentHMP:UniProtKB
Regulation of small GTPase mediated signal transductionTAS:Reactome
Rho protein signal transductionManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

Cytoplasm
Cytoplasm, perinuclear region
Cell membrane
Cell junction
Cell projection, lamellipodium
Predominantly cytoplasmic, however when endothelial cells are stimulated with lysophosphatidic acid, PLEKHG5 is found in perinuclear regions and at the cell membrane. Localizes at cell-cell junctions in quiescent endothelial cells, and relocalizes to cytoplasmic vesicle and the leading edge of lamellipodia in migrating endothelial cells.

Involvement in disease

Distal spinal muscular atrophy, autosomal recessive, 4 (DSMA4):
A neuromuscular disorder. Distal spinal muscular atrophy, also known as distal hereditary motor neuronopathy, represents a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. DSMA4 is characterized by childhood onset, generalized muscle weakness and atrophy with denervation and normal sensation. Bulbar symptoms and pyramidal signs are absent.
Charcot-Marie-Tooth disease, recessive, intermediate type, C (CMTRIC):
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.