Als2 alsin Rho guanine nucleotide exchange factor [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Als2provided by MGI
Official Full Name: alsin Rho guanine nucleotide exchange factorprovided by MGI
Primary source: MGI:MGI:1921268
See related: Ensembl:ENSMUSG00000026024 AllianceGenome:MGI:1921268
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Alsin; Als2cr6; mKIAA1563; 3222402C23Rik; 9430073A21Rik
Summary: Predicted to enable several functions, including GTPase regulator activity; protein homodimerization activity; and small GTPase binding activity. Involved in regulation of postsynaptic membrane neurotransmitter receptor levels. Acts upstream of or within several processes, including behavioral fear response; glutamatergic synaptic transmission; and neuromuscular junction development. Located in several cellular components, including centrosome; lamellipodium; and ruffle. Is active in glutamatergic synapse and postsynaptic density. Is expressed in several structures, including central nervous system; genitourinary system; hemolymphoid system; liver; and retina. Human ortholog(s) of this gene implicated in amyotrophic lateral sclerosis and amyotrophic lateral sclerosis type 2. Orthologous to human ALS2 (alsin Rho guanine nucleotide exchange factor ALS2). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in cerebellum adult (RPKM 19.3), liver adult (RPKM 7.8) and 25 other tissues See more
Orthologs: human all
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Genomic context

Location:: 1 C1.3; 1 29.33 cM

Exon count:: 35

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (59201915..59276390, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (59162756..59237231, complement)

Chromosome 1 - NC_000067.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The RabGEF ALS2 is a hypoxia inducible target associated with the acquisition of aggressive traits in tumor cells.
Title: The RabGEF ALS2 is a hypoxia inducible target associated with the acquisition of aggressive traits in tumor cells.
two ALS-linked factors, SQSTM1 and ALS2, have distinct but additive protective roles against mutant SOD1-mediated toxicity by modulating neuronal proteostasis possibly through the autophagy-endolysosomal system.
Title: Functional links between SQSTM1 and ALS2 in the pathogenesis of ALS: cumulative impact on the protection against mutant SOD1-mediated motor dysfunction in mice.
By taking advantage of this CSMN reporter line of AlsinKO, authors reveal that apical dendrite degeneration is a common cellular pathology for CSMN that become diseased for different causes.
Title: Absence of alsin function leads to corticospinal motor neuron vulnerability via novel disease mechanisms.
alsin and spartin may interact each other physically.
Title: Are alsin and spartin novel interaction partners?
Alsin and SOD1(G93A) proteins regulate endosomal reactive oxygen species production by glial cells and proinflammatory pathways responsible for neurotoxicity.
Title: Alsin and SOD1(G93A) proteins regulate endosomal reactive oxygen species production by glial cells and proinflammatory pathways responsible for neurotoxicity.
these results suggest that Als2 is a binding partner of Uxt and Als2/Uxt interaction could be important for the activation of Nf-kappaB pathway.
Title: Alfa-class prefoldin protein UXT is a novel interacting partner of Amyotrophic Lateral Sclerosis 2 (Als2) protein.
Rab5-mediated endocytosis was severely altered in ALS2(-/-) neurons.
Title: Regulation of endosomal motility and degradation by amyotrophic lateral sclerosis 2/alsin.
ALS2/Alsin exacerbates motor dysfunction in a SOD1-expressing mouse ALS model by disturbing endolysosomal trafficking
Title: Loss of ALS2/Alsin exacerbates motor dysfunction in a SOD1-expressing mouse ALS model by disturbing endolysosomal trafficking.
Als2(-/-) mice showed a significantly lower spontaneous rearing activity than wild-type litters. These genetic background- and/or gender-specific findings suggest the presence of modifiers for life span and motor activities in Als2(-/-) mice.
Title: Genetic background and gender effects on gross phenotypes in congenic lines of ALS2/alsin-deficient mice.
Als2-depleted spinal motor neurons can be rescued by co-cultured astrocytes.
Title: Astrocytic protection of spinal motor neurons but not cortical neurons against loss of Als2/alsin function.

Submit: New GeneRIF Correction See all GeneRIFs (25)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Gene trapped (1)
Targeted (6) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11Bhm20 (e-PCR), detects polymorphism
- UniSTS:141619

D9Mit34.1 (e-PCR), detects polymorphism
- UniSTS:131903

NoName (e-PCR)
- UniSTS:234135

D1Mit161 (e-PCR), detects polymorphism
- UniSTS:128500

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables GTPase activator activity	ISO Inferred from Sequence Orthology more info
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
contributes_to guanyl-nucleotide exchange factor activity	ISO Inferred from Sequence Orthology more info
enables guanyl-nucleotide exchange factor activity	ISO Inferred from Sequence Orthology more info
contributes_to guanyl-nucleotide exchange factor activity	ISS Inferred from Sequence or Structural Similarity more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein serine/threonine kinase activator activity	ISO Inferred from Sequence Orthology more info
enables protein serine/threonine kinase activator activity	ISS Inferred from Sequence or Structural Similarity more info
enables small GTPase binding	IBA Inferred from Biological aspect of Ancestor more info
enables small GTPase binding	ISO Inferred from Sequence Orthology more info
enables small GTPase binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in Rac protein signal transduction	ISO Inferred from Sequence Orthology more info
involved_in axonogenesis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within behavioral fear response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endosomal transport	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within endosomal transport	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within endosome organization	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within locomotory behavior	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lysosomal transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neuromuscular junction development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron projection morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in neuron projection morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of GTPase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of GTPase activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of protein kinase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein kinase activity	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within protein homooligomerization	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein localization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within receptor recycling	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of GTPase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of endosome size	ISO Inferred from Sequence Orthology more info
involved_in regulation of endosome size	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of postsynaptic membrane neurotransmitter receptor levels	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of postsynaptic membrane neurotransmitter receptor levels	IEP Inferred from Expression Pattern more info	PubMed
involved_in regulation of postsynaptic membrane neurotransmitter receptor levels	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within synaptic transmission, glutamatergic	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within vesicle organization	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in axon	ISO Inferred from Sequence Orthology more info
is_active_in centrosome	IBA Inferred from Biological aspect of Ancestor more info
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
located_in centrosome	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in dendritic spine	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome	ISO Inferred from Sequence Orthology more info
located_in early endosome	ISS Inferred from Sequence or Structural Similarity more info
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IEP Inferred from Expression Pattern more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
located_in growth cone	ISO Inferred from Sequence Orthology more info
located_in growth cone	ISS Inferred from Sequence or Structural Similarity more info
is_active_in intracellular membrane-bounded organelle	IBA Inferred from Biological aspect of Ancestor more info
located_in lamellipodium	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	ISO Inferred from Sequence Orthology more info
located_in neuronal cell body	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
is_active_in postsynaptic density	IDA Inferred from Direct Assay more info	PubMed
located_in postsynaptic density	IDA Inferred from Direct Assay more info	PubMed
is_active_in postsynaptic density	IMP Inferred from Mutant Phenotype more info	PubMed
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	ISS Inferred from Sequence or Structural Similarity more info
located_in ruffle	IDA Inferred from Direct Assay more info	PubMed
located_in vesicle	ISO Inferred from Sequence Orthology more info
located_in vesicle	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: alsin

Names: amyotrophic lateral sclerosis 2 (juvenile) homolog; amyotrophic lateral sclerosis 2 protein homolog; amyotrophic lateral sclerosis protein 2 homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001159948.2 → NP_001153420.2 alsin isoform 1

See identical proteins and their annotated locations for NP_001153420.2

Status: VALIDATED

Description

Transcript Variant: This variant (3) represents the longest transcript and encodes the longer isoform (1). Variants 1 and 3 both encode the same protein.

Source sequence(s)

AB053307, AK029858, BC046828, DV648961

Consensus CDS

CCDS35583.1

UniProtKB/Swiss-Prot

G5E868, Q8JZR1, Q920R0, Q9CXJ3

Related

ENSMUSP00000125753.2, ENSMUST00000163058.2

Conserved Domains (8) summary

COG4642
Location:1043 → 1182

COG4642; Uncharacterized conserved protein [Function unknown]

cd13269
Location:899 → 1004

PH_alsin; Alsin Pleckstrin homology (PH) domain

pfam00169
Location:920 → 998

PH; PH domain

pfam00415
Location:521 → 568

RCC1; Regulator of chromosome condensation (RCC1) repeat

pfam02204
Location:1548 → 1647

VPS9; Vacuolar sorting protein 9 (VPS9) domain

pfam02493
Location:1094 → 1114

MORN; MORN repeat

pfam13540
Location:93 → 122

RCC1_2; Regulator of chromosome condensation (RCC1) repeat

cl02571
Location:689 → 873

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.
NM_028717.6 → NP_082993.4 alsin isoform 1

See identical proteins and their annotated locations for NP_082993.4

Status: VALIDATED

Source sequence(s)

AB053307, AC153652, BC046828

Consensus CDS

CCDS35583.1

UniProtKB/Swiss-Prot

G5E868, Q8JZR1, Q920R0, Q9CXJ3

Related

ENSMUSP00000027178.7, ENSMUST00000027178.13

Conserved Domains (8) summary

COG4642
Location:1043 → 1182

COG4642; Uncharacterized conserved protein [Function unknown]

cd13269
Location:899 → 1004

PH_alsin; Alsin Pleckstrin homology (PH) domain

pfam00169
Location:920 → 998

PH; PH domain

pfam00415
Location:521 → 568

RCC1; Regulator of chromosome condensation (RCC1) repeat

pfam02204
Location:1548 → 1647

VPS9; Vacuolar sorting protein 9 (VPS9) domain

pfam02493
Location:1094 → 1114

MORN; MORN repeat

pfam13540
Location:93 → 122

RCC1_2; Regulator of chromosome condensation (RCC1) repeat

cl02571
Location:689 → 873

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.
NM_146109.3 → NP_666221.1 alsin isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, 3' UTR, and 3' coding sequence compared to variant 3. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1.

Source sequence(s)

AC153652, BC046828, CD543795

UniProtKB/Swiss-Prot

Q920R0

Related

ENSMUST00000159166.8

Conserved Domains (3) summary

pfam00415
Location:521 → 568

RCC1; Regulator of chromosome condensation (RCC1) repeat

pfam13540
Location:93 → 122

RCC1_2; Regulator of chromosome condensation (RCC1) repeat

cl02571
Location:689 → 847

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.