LAMTOR1 late endosomal/lysosomal adaptor, MAPK and MTOR activator 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LAMTOR1provided by HGNC
Official Full Name: late endosomal/lysosomal adaptor, MAPK and MTOR activator 1provided by HGNC
Primary source: HGNC:HGNC:26068
See related: Ensembl:ENSG00000149357 MIM:613510; AllianceGenome:HGNC:26068
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: p18; PDRO; C11orf59; p27RF-Rho; Ragulator1
Summary: Enables GTPase binding activity. Contributes to guanyl-nucleotide exchange factor activity and molecular adaptor activity. Involved in several processes, including cholesterol homeostasis; positive regulation of TOR signaling; and regulation of cholesterol transport. Located in lysosome. Part of Ragulator complex. [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in thyroid (RPKM 58.6), adrenal (RPKM 40.5) and 25 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 11q13.4

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
110	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (72097292..72103297, complement)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (72024182..72030187, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (71808338..71814343, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

N-myristoyltransferase-1 deficiency blocks myristoylation of LAMTOR1 and inhibits bladder cancer progression.
Title: N-myristoyltransferase-1 deficiency blocks myristoylation of LAMTOR1 and inhibits bladder cancer progression.
A novel gene fusion between the LAMTOR1 and AKT1 was identified in a histopathologically indeterminate epithelioid neoplasm of a patient. This fusion resulted in oncogenic activatin of AKT1.
Title: Patient-Driven Discovery, Therapeutic Targeting, and Post-Clinical Validation of a Novel <i>AKT1</i> Fusion-Driven Cancer.
The Lamtor1 dynamically controls cellular function via mTORC1 activation and lipid signaling.
Title: Roles of Lamtor1 in Macrophages, CD4+ T-cells, and Regulatory T-cells.
We found that under nutrient-rich conditions TMEM127 expression reduces mTORC1 recruitment to Rags. In addition, TMEM127 interacts with LAMTOR in an amino acid-dependent manner and decreases the LAMTOR1-vATPase association, while TMEM127-vATPase binding requires intact lysosomal acidification but is amino acid independent
Title: The TMEM127 human tumor suppressor is a component of the mTORC1 lysosomal nutrient-sensing complex.
In vitro reconstitution and experiments with site-directed mutagenesis defined the physiological importance of LAMTOR1 in assembling the remaining components to ensure fidelity of mTORC1 signaling.
Title: Crystal structure of the human lysosomal mTORC1 scaffold complex and its impact on signaling.
LAMTOR1 is a negative regulator of Arl8b- and BORC-dependent late endosomal positioning.
Title: LAMTOR/Ragulator is a negative regulator of Arl8b- and BORC-dependent late endosomal positioning.
Study found that NF1 negatively regulates mTOR signaling in a LAMTOR1-dependent manner. In addition, the cell growth and survival of NF1-deficient cells have become dependent on hyperactivation of the mTOR pathway, and the tumorigenic properties of these cells have become dependent on LAMTOR1.
Title: Clustered, Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9-coupled Affinity Purification/Mass Spectrometry Analysis Revealed a Novel Role of Neurofibromin in mTOR Signaling.
Western blot experiments designed to detect flotillin 2, TMEM256, Rab3B and LAMTOR1 showed that the level of these proteins was higher in urinary exosomes from prostate cancer patients compared to healthy males
Title: Exosomal proteins as prostate cancer biomarkers in urine: From mass spectrometry discovery to immunoassay-based validation.
Data suggest that ablation of p18/LAMTOR1 suppresses starvation-induced cell death by stimulating autophagy through modulation of p27(kip1) activity.
Title: Depletion of p18/LAMTOR1 promotes cell survival via activation of p27(kip1) -dependent autophagy under starvation.
LAMTOR1 expression affects the tuning of lysosomal activation that can lead to p53-dependent apoptosis through excessive catabolism.
Title: LAMTOR1 depletion induces p53-dependent apoptosis via aberrant lysosomal activation.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Phenotypes

Go to the top of the page Help

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

Review eQTL and phenotype association data in this region using PheGenI

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

G20526 (e-PCR)
- UniSTS:45889

A005V05 (e-PCR)
- UniSTS:45890

MARC_24275-24276:1044473527:2 (e-PCR)
- UniSTS:268869

D11S2238E (e-PCR)
- UniSTS:22521

Homology

Homologs of the LAMTOR1 gene: The LAMTOR1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 410 organisms have orthologs with human gene LAMTOR1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTPase binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to guanyl-nucleotide exchange factor activity	IDA Inferred from Direct Assay more info	PubMed
contributes_to molecular adaptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to molecular adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in TORC1 signaling	IC Inferred by Curator more info	PubMed
involved_in cellular protein localization	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in cellular protein localization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to amino acid stimulus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in cellular response to amino acid stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to amino acid stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cholesterol homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endosomal transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in endosome organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in lysosome localization	ISS Inferred from Sequence or Structural Similarity more info
involved_in lysosome organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in positive regulation of MAPK cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of TOR signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of catalytic activity	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell growth	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cholesterol efflux	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cholesterol esterification	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cholesterol import	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of receptor recycling	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in regulation of receptor recycling	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
part_of Ragulator complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
part_of Ragulator complex	IDA Inferred from Direct Assay more info	PubMed
part_of Ragulator complex	IPI Inferred from Physical Interaction more info	PubMed
located_in azurophil granule membrane	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in ficolin-1-rich granule membrane	TAS Traceable Author Statement more info
located_in late endosome membrane	IC Inferred by Curator more info	PubMed
located_in late endosome membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in lysosomal membrane	IC Inferred by Curator more info	PubMed
located_in lysosomal membrane	TAS Traceable Author Statement more info
is_active_in lysosome	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in membrane raft	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in specific granule membrane	TAS Traceable Author Statement more info

General protein information

Go to the top of the page Help

Preferred Names: ragulator complex protein LAMTOR1

Names: RhoA activator C11orf59; late endosomal/lysosomal adaptor and MAPK and MTOR activator 1; lipid raft adaptor protein p18; p27Kip1-releasing factor from RhoA; p27kip1 releasing factor from RhoA; protein associated with DRMs and endosomes; ragulator complex protein PDRO

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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.