Smcr8 Smith-Magenis syndrome chromosome region, candidate 8 homolog (human) [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Smcr8provided by MGI
Official Full Name: Smith-Magenis syndrome chromosome region, candidate 8 homolog (human)provided by MGI
Primary source: MGI:MGI:2444720
See related: Ensembl:ENSMUSG00000049323 AllianceGenome:MGI:2444720
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: 2310076G09Rik; D030073L15Rik
Summary: Predicted to enable protein kinase binding activity and protein kinase inhibitor activity. Predicted to contribute to guanyl-nucleotide exchange factor activity. Involved in regulation of autophagy. Located in cytoplasm. Orthologous to human SMCR8 (SMCR8-C9orf72 complex subunit). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in thymus adult (RPKM 8.7), mammary gland adult (RPKM 6.6) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 11 B2; 11 37.83 cM

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	11	NC_000077.7 (60668351..60679113)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	11	NC_000077.6 (60777525..60788287)

Chromosome 11 - NC_000077.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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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?

ALS-linked C9orf72-SMCR8 complex is a negative regulator of primary ciliogenesis.
Title: ALS-linked C9orf72-SMCR8 complex is a negative regulator of primary ciliogenesis.
C9orf72 and smcr8 mutant mice reveal MTORC1 activation due to impaired lysosomal degradation and exocytosis.
Title: C9orf72 and smcr8 mutant mice reveal MTORC1 activation due to impaired lysosomal degradation and exocytosis.
Study discovered that Smcr8 deficiency disrupts motor neurons axonal transport and lysosomal functions, leading to axonal swellings then motor behavior deficits in mice. The expression of Smcr8, like that of C9orf72, is reduced in mouse models and patient tissues. Smcr8 deficiency exacerbates axonal swellings and C9ALS/FTD gain of toxicity, providing new insights into the pathogenesis of C9ALS/FTD.
Title: Smcr8 deficiency disrupts axonal transport-dependent lysosomal function and promotes axonal swellings and gain of toxicity in C9ALS/FTD mouse models.
A key role of SMCR8 in regulating MTORC1 and AKT signaling and tissue homeostasis.
Title: SMCR8 negatively regulates AKT and MTORC1 signaling to modulate lysosome biogenesis and tissue homeostasis.
C9ORF72 and SMCR8 have interdependent functions in suppressing autoimmunity as well as negatively regulating lysosomal exocytosis-processes of potential importance to amyotrophic lateral sclerosis.
Title: The C9orf72-interacting protein Smcr8 is a negative regulator of autoimmunity and lysosomal exocytosis.
We created Smcr8 knockout mice and found that Smcr8 mutant cells exhibit impaired autophagy induction, which is similarly observed in C9orf72 knockdown cells. Mechanistically, SMCR8/C9ORF72 interacts with the key autophagy initiation ULK1 complex and regulates expression and activity of ULK1
Title: A C9ORF72/SMCR8-containing complex regulates ULK1 and plays a dual role in autophagy.
These results demonstrate that the C9orf72-SMCR8 protein complex functions in the regulation of metabolism and provide evidence that loss of C9orf72 function may contribute to the pathogenesis of relevant diseases
Title: Loss of C9orf72 Enhances Autophagic Activity via Deregulated mTOR and TFEB Signaling.

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Variation

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Alleles

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

Chemically induced (ENU) (3) 1 citation
Endonuclease-mediated (5) 1 citation
Targeted (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH128681 (e-PCR)
- UniSTS:211989

AI642055 (e-PCR)
- UniSTS:180219

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables GTPase activator activity	IEA Inferred from Electronic Annotation more info
contributes_to guanyl-nucleotide exchange factor activity	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables protein kinase inhibitor activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within autophagy	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of autophagosome assembly	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of exocytosis	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of immune response	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of macroautophagy	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein kinase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of GTPase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of TOR signaling	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of autophagosome maturation	ISO Inferred from Sequence Orthology more info
involved_in regulation of TORC1 signaling	ISO Inferred from Sequence Orthology more info
involved_in regulation of autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of autophagy	ISO Inferred from Sequence Orthology more info
involved_in regulation of autophagy	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of Atg1/ULK1 kinase complex	ISO Inferred from Sequence Orthology more info
located_in cell projection	IEA Inferred from Electronic Annotation more info
part_of chromatin	ISO Inferred from Sequence Orthology 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 cytoplasm	NAS Non-traceable Author Statement more info	PubMed
part_of guanyl-nucleotide exchange factor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of guanyl-nucleotide exchange factor complex	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in postsynapse	IDA Inferred from Direct Assay more info	PubMed
located_in presynapse	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: guanine nucleotide exchange protein SMCR8

Names: smith-Magenis syndrome chromosomal region candidate gene 8 protein 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.