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FLASH GENE

Symbol

ALS2

contributors: mct - updated : 04-09-2012

HGNC name	amyotrophic lateral sclerosis 2 (juvenile)
HGNC id	443

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_020919 34 - 6935 NP_065970 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 NM_001135745 4 splicing 2908 NP_001129217 - 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)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly Lymphoid/Immune lymph node       highly Nervous brain       highly   spinal cord         Skin/Tegument skin       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal     Nervous central       Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron

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