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FLASH GENE
Symbol ALS2 contributors: mct - updated : 04-09-2012
HGNC name amyotrophic lateral sclerosis 2 (juvenile)
HGNC id 443
Corresponding disease
ALS2 familial amyotrophic lateral sclerosis
IAHSP spastic paralysis, infantile onset ascending
PLSJ primary lateral sclerosis, juvenile
Location 2q33.1      Physical location : 202.564.986 - 202.645.895
Synonym name
  • alsin
  • amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 6
  • amyotrophic lateral sclerosis 2 protein
    • Synonym symbol(s) ALSJ, PLSJ, KIAA1563, FLJ31851, MGC87187, IAHSP, ALS2CR6
    DNA
    TYPE functioning gene
    STRUCTURE 80.91 kb     34 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    34 - 6935 184 1657 - 2011 21907703
  • also called ALS2CR6L, LF or long form or alsin isoform 1
  • protected motor neuronal cells from toxicity induced by mutants of the Cu/Zn-superoxide dismutase (SOD1) gene
  • bound to SOD1 mutants, but not to wtSOD1, via the RhoGEF domain
    • 4 splicing 2908 - 396 spinal cord, heart, lung, liver, placenta 2011 21907703
  • also called ALS2CR6S, short form or alsin isoform 2
  • carries only the RCC1 domain
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Lymphoid/Immunelymph node   highly
    Nervousbrain   highly
     spinal cord    
    Skin/Tegumentskin   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    Nervouscentral   
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal RLD motif, regulator of chromatin condensation (RCC1) domain
  • three guanine nucleotide exchange factor domains, specifically binding to small GTPase RAB5A and acting as a GEF for RAB5A
  • PH domain (pectrin homology domain)
  • one Rho-GEF (guanine nucleotide exchange factor) and RCC1- GEF domain
  • three cell signaling motifs
  • eight MORN repeats
  • a VPS9 (vacuolar sorting protein 9) domain at the C-terminus, having RAB5A and RAC1 guanine nucleotide exchange activity
  • five RCC1 repeats
    • mono polymer homomer , octamer
    HOMOLOGY
    interspecies homolog to murine Als2
    Homologene
    FAMILY
  • guanine nucleotide exchange factors family for the small GTPase RAB5
    • CATEGORY regulatory , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text
  • cytosolic protein, with a significant portion associated with small, punctate membrane structures, also present in membrane ruffles and lamellipodia
  • colocalization with the centrosomal markers gamma-tubulin and A kinase anchoring protein (AKAP-450)
    • basic FUNCTION
  • involved in the endosomal dynamics and probably also in the control of nuclear organization
  • implicated in intracellular membrane trafficking or microtubule dynamics
  • may be involved in membrane transport events, potentially linking endocytic processes and actin cytoskeleton remodeling
  • promoting neurite outgrowth, playing an essential role in the maintenance of motor neurons
  • may act as a modulator in neuronal differentiation and/or development through regulation of membrane dynamics
  • acting as a guanine nucleotide exchange factor (GEF) for the small GTPase Rab5 and is implicated in endosome dynamics in cells
  • contributes to macropinocytosis and is implicated in axonal growth in neurons
  • negatively regulatory mechanism of ALS2 in RAB5-mediated endosomal traffickingb
  • plays a role in neuroprotection against motor neuron diseases-associated pathological insults, such as toxicity induced by mutant SOD1
  • potentially implicated in endolysosomal trafficking through the fusion between endosomes and autophagosomes, thereby regulating endolysosomal protein degradation
  • potentially playing a role in a certain intracellular signal transduction pathway and/or a cytoplasmic transport system
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • homo-oligomerization of ALS2 through its unique carboxyl-terminal regions is essential for the ALS2-associated RAB5A guanine nucleotide exchange activity and its regulatory function on endosome trafficking
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to small GTPase RAB5A
  • specifically acting as a GEF (guanine nucleotide exchange factor) for RAB5A
  • interacts with Rac1, a member of the Rho-type GTPase family, via its DH/PH domain and acts as an effector for Rac1, rather than a Rac1GEF
  • UXTis a novel interacting partner of DH/PH domain of ALS2 protein (ALS2 and UXT transcriptional levels are directly correlated through cell cycle)
    • cell & other
    REGULATION
    induced by pheromone
    ASSOCIATED DISORDERS
    corresponding disease(s) ALS2 , PLSJ , IAHSP
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS