ALS2 Antibody – Rabbit Polyclonal

The protein encoded by this gene contains an ATS1/RCC1-like domain, a RhoGEF domain, and a vacuolar protein sorting 9 (VPS9) domain, all of which are guanine-nucleotide exchange factors that activate members of the Ras superfamily of GTPases. The protein functions as a guanine nucleotide exchange factor for the small GTPase RAB5. The protein localizes with RAB5 on early endosomal compartments, and functions as a modulator for endosomal dynamics. Mutations in this gene result in several forms of juvenile lateral sclerosis and infantile-onset ascending spastic paralysis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ALS2: May act as a GTPase regulator. Controls survival and growth of spinal motoneurons. Defects in ALS2 are the cause of amyotrophic lateral sclerosis type 2 (ALS2). ALS2 is a familial form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of cases leading to familial forms. Defects in ALS2 are the cause of juvenile primary lateral sclerosis (JPLS). JPLS is a neurodegenerative disorder which is closely related to but clinically distinct from amyotrophic lateral sclerosis. It is a progressive paralytic disorder which results from dysfunction of the upper motor neurons of the motor cortex while the lower neurons are unaffected. Defects in ALS2 are the cause of infantile-onset ascending spastic paralysis (IAHSP). IAHSP is characterized by progressive spasticity and weakness of limbs. 3 isoforms of the human protein are produced by alternative splicing.

Protein type: GEFs, Rab; GEFs

Chromosomal Location of Human Ortholog: 2q33.1

Cellular Component: ruffle; centrosome; growth cone; protein complex; lamellipodium; dendrite; early endosome; postsynaptic density; dendritic spine; cytosol; vesicle

Molecular Function: protein serine/threonine kinase activator activity; protein binding; protein homodimerization activity; Ran guanyl-nucleotide exchange factor activity; guanyl-nucleotide exchange factor activity; Rac guanyl-nucleotide exchange factor activity; Rab guanyl-nucleotide exchange factor activity; Rab GTPase binding

Biological Process: receptor recycling; synaptic transmission, glutamatergic; behavioral fear response; endosome organization and biogenesis; vesicle organization and biogenesis; locomotory behavior; endosome transport; protein localization; regulation of endosome size; positive regulation of protein kinase activity; response to oxidative stress; neuromuscular junction development; neurite morphogenesis

Disease: Amyotrophic Lateral Sclerosis 2, Juvenile; Spastic Paralysis, Infantile-onset Ascending; Primary Lateral Sclerosis, Juvenile