CASTOR1 cytosolic arginine sensor for mTORC1 subunit 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CASTOR1provided by HGNC
Official Full Name: cytosolic arginine sensor for mTORC1 subunit 1provided by HGNC
Primary source: HGNC:HGNC:34423
See related: Ensembl:ENSG00000239282 MIM:617034; AllianceGenome:HGNC:34423
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GATSL3
Summary: Enables arginine binding activity and identical protein binding activity. Involved in cellular response to L-arginine and negative regulation of TORC1 signaling. Located in cytosol. Colocalizes with GATOR2 complex. [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in esophagus (RPKM 13.7), placenta (RPKM 8.5) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q12.2

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (30285117..30289505, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (30748432..30752844, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (30681106..30685494, complement)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

RNF167 activates mTORC1 and promotes tumorigenesis by targeting CASTOR1 for ubiquitination and degradation.
Title: RNF167 activates mTORC1 and promotes tumorigenesis by targeting CASTOR1 for ubiquitination and degradation.
the KSHV-encoded miRNA miR-K4-5p, and probably miR-K1-5p, directly targeted CASTOR1 to inhibit its expression. Knockdown of miR-K1-5p and -K4-5p restored CASTOR1 expression and thereby attenuated mTORC1 activation.
Title: Kaposi sarcoma-associated herpesvirus miRNAs suppress CASTOR1-mediated mTORC1 inhibition to promote tumorigenesis.
The binding free energy calculations revealed that Nalpha-acetyl-arginine, citrulline, and norarginine have sufficient binding affinity with CASTOR1 to compete with arginine. The hydrogen bond analysis revealed that norarginine, Nalpha-acetyl-arginine and D-arginine have proficient H-bonds that can facilitate their entering the narrow binding pocket.
Title: Seeking mTORC1 Inhibitors Through Molecular Dynamics Simulation of Arginine Analogs Inhibiting CASTOR1.
these findings demonstrated that CASTOR1 inhibits the tumorigenesis of lung adenocarcinoma cells and might serve as a potential therapeutic target or prognostic marker for human patients with lung adenocarcinoma.
Title: CASTOR1 suppresses the progression of lung adenocarcinoma and predicts poor prognosis.
Report crystal structures of arginine sensor CASTOR1 in arginine-bound and ligand free states at 2.05A and 2.8A, respectively. Structural comparison of CASTOR1 between two states reveals near identical conformations, except in two loop regions. It indicates CASTOR1 does not undergo large conformational change during arginine binding.
Title: Crystal structures of arginine sensor CASTOR1 in arginine-bound and ligand free states.
1.8 A crystal structure of arginine-bound CASTOR1
Title: Mechanism of arginine sensing by CASTOR1 upstream of mTORC1.
Study establishes the CASTOR1 homodimer and CASTOR1-CASTOR2 heterodimer as arginine sensors for the mTORC1 pathway.
Title: The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway.
This genome wide association study identified a new rheumatoid arthritis susceptibility locus mapping to 22q12 in the GATSL3 gene.
Title: Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables arginine binding	IBA Inferred from Biological aspect of Ancestor more info
enables arginine binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein sequestering activity	IDA Inferred from Direct Assay more info	PubMed
enables small molecule sensor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in cellular response to L-arginine	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to L-arginine	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to L-arginine	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to amino acid starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of TORC1 signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of TORC1 signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of TORC1 signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of TORC1 signaling	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of GATOR2 complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info

General protein information

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Preferred Names: cytosolic arginine sensor for mTORC1 subunit 1

Names: GATS protein like 3; GATS-like protein 3; cellular arginine sensor for mTORC1 protein 1

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.