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Protein

Ragulator complex protein LAMTOR1

Gene

LAMTOR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. LAMTOR1 is directly responsible for anchoring the Ragulator complex to membranes. Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes. May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes. May also play a role in RHOA activation.4 Publications

GO - Biological processi

  • cell cycle arrest Source: Reactome
  • cell growth Source: UniProtKB
  • cellular protein localization Source: UniProtKB
  • cellular response to amino acid stimulus Source: UniProtKB
  • cholesterol homeostasis Source: UniProtKB
  • endosome localization Source: UniProtKB
  • endosome organization Source: UniProtKB
  • lysosome localization Source: UniProtKB
  • lysosome organization Source: UniProtKB
  • macroautophagy Source: Reactome
  • positive regulation of GTPase activity Source: GOC
  • positive regulation of MAPK cascade Source: UniProtKB
  • positive regulation of TOR signaling Source: UniProtKB
  • regulation of cholesterol efflux Source: UniProtKB
  • regulation of cholesterol esterification Source: UniProtKB
  • regulation of cholesterol import Source: UniProtKB
  • regulation of receptor recycling Source: UniProtKB
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-165159. mTOR signalling.
R-HSA-166208. mTORC1-mediated signalling.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-6798695. Neutrophil degranulation.
SIGNORiQ6IAA8.

Names & Taxonomyi

Protein namesi
Recommended name:
Ragulator complex protein LAMTOR1
Alternative name(s):
Late endosomal/lysosomal adaptor and MAPK and MTOR activator 1
Lipid raft adaptor protein p18
Protein associated with DRMs and endosomes
p27Kip1-releasing factor from RhoA
Short name:
p27RF-Rho
Gene namesi
Name:LAMTOR1
Synonyms:C11orf59, PDRO
ORF Names:PP7157
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:26068. LAMTOR1.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • Golgi apparatus Source: HPA
  • intracellular membrane-bounded organelle Source: HPA
  • late endosome membrane Source: UniProtKB
  • lysosomal membrane Source: Reactome
  • lysosome Source: UniProtKB
  • membrane raft Source: UniProtKB
  • plasma membrane Source: HPA
  • Ragulator complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Lysosome, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi55004.
OpenTargetsiENSG00000149357.
PharmGKBiPA143485354.

Polymorphism and mutation databases

BioMutaiLAMTOR1.
DMDMi125863645.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00002742922 – 161Ragulator complex protein LAMTOR1Add BLAST160

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine2 Publications1
Modified residuei27PhosphoserineCombined sources1
Modified residuei42PhosphoserineCombined sources1
Modified residuei56PhosphoserineCombined sources1
Modified residuei98PhosphoserineCombined sources1
Modified residuei141PhosphoserineCombined sources1

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

EPDiQ6IAA8.
MaxQBiQ6IAA8.
PaxDbiQ6IAA8.
PeptideAtlasiQ6IAA8.
PRIDEiQ6IAA8.
TopDownProteomicsiQ6IAA8.

PTM databases

iPTMnetiQ6IAA8.
PhosphoSitePlusiQ6IAA8.
SwissPalmiQ6IAA8.

Expressioni

Inductioni

Down-regulated by cholesterol (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000149357.
CleanExiHS_C11orf59.
ExpressionAtlasiQ6IAA8. baseline and differential.
GenevisibleiQ6IAA8. HS.

Organism-specific databases

HPAiHPA002997.

Interactioni

Subunit structurei

Part of the Ragulator complex composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5. LAMTOR4 and LAMTOR5 form a heterodimer that interacts, through LAMTOR1, with a LAMTOR2, LAMTOR3 heterodimer. The Ragulator complex interacts with both the mTORC1 complex and heterodimers constituted of the Rag GTPases RRAGA, RRAGB, RRAGC and RRAGD; regulated by amino acid availability (PubMed:20381137, PubMed:22980980). The Ragulator complex interacts with SLC38A9; the probable amino acid sensor (PubMed:25561175, PubMed:25567906). Interacts with LAMTOR2 and LAMTOR3; the interaction is direct. Interacts with RRAGB and RRAGD; the interaction is direct indicating that it probably constitutes the main RAG-interacting subunit of the Ragulator complex (PubMed:22980980). Interacts with MMP14 (PubMed:19654316). Interacts with CDKN1B; prevents the interaction of CDKN1B with RHOA leaving RHOA in a form accessible to activation by ARHGEF2 (PubMed:19654316).5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RRAGAQ7L52310EBI-715385,EBI-752376
SLC38A9Q8NBW49EBI-715385,EBI-9978316

Protein-protein interaction databases

BioGridi120336. 29 interactors.
DIPiDIP-39650N.
IntActiQ6IAA8. 34 interactors.
MINTiMINT-1372069.
STRINGi9606.ENSP00000278671.

Structurei

3D structure databases

ProteinModelPortaliQ6IAA8.
SMRiQ6IAA8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni121 – 161Interaction with LAMTOR2 and LAMTOR3By similarityAdd BLAST41

Sequence similaritiesi

Belongs to the LAMTOR1 family.Curated

Phylogenomic databases

eggNOGiENOG410IH39. Eukaryota.
ENOG4112AMJ. LUCA.
GeneTreeiENSGT00390000016789.
HOVERGENiHBG081218.
InParanoidiQ6IAA8.
KOiK20397.
OMAiNVQHPSI.
OrthoDBiEOG091G0XGD.
PhylomeDBiQ6IAA8.
TreeFamiTF323788.

Family and domain databases

InterProiIPR026310. LAMTOR1-like.
IPR028209. LAMTOR1/MEH1.
[Graphical view]
PANTHERiPTHR13401. PTHR13401. 1 hit.
PfamiPF15454. LAMTOR. 1 hit.
[Graphical view]
SMARTiSM01262. LAMTOR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q6IAA8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGCCYSSENE DSDQDREERK LLLDPSSPPT KALNGAEPNY HSLPSARTDE
60 70 80 90 100
QALLSSILAK TASNIIDVSA ADSQGMEQHE YMDRARQYST RLAVLSSSLT
110 120 130 140 150
HWKKLPPLPS LTSQPHQVLA SEPIPFSDLQ QVSRIAAYAY SALSQIRVDA
160
KEELVVQFGI P
Length:161
Mass (Da):17,745
Last modified:February 6, 2007 - v2
Checksum:i610CC6C548356051
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti50E → V in CAG33528 (Ref. 2) Curated1
Sequence conflicti60K → R in AAL55767 (PubMed:15498874).Curated1
Sequence conflicti69S → P in CAG33528 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03025073S → L.Corresponds to variant rs1053443dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF289583 mRNA. Translation: AAL55767.1.
CR457247 mRNA. Translation: CAG33528.1.
AK000632 mRNA. Translation: BAA91297.1.
BC001706 mRNA. Translation: AAH01706.1.
CCDSiCCDS8209.1.
RefSeqiNP_060377.1. NM_017907.2.
UniGeneiHs.731528.

Genome annotation databases

EnsembliENST00000278671; ENSP00000278671; ENSG00000149357.
GeneIDi55004.
KEGGihsa:55004.
UCSCiuc001ort.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF289583 mRNA. Translation: AAL55767.1.
CR457247 mRNA. Translation: CAG33528.1.
AK000632 mRNA. Translation: BAA91297.1.
BC001706 mRNA. Translation: AAH01706.1.
CCDSiCCDS8209.1.
RefSeqiNP_060377.1. NM_017907.2.
UniGeneiHs.731528.

3D structure databases

ProteinModelPortaliQ6IAA8.
SMRiQ6IAA8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120336. 29 interactors.
DIPiDIP-39650N.
IntActiQ6IAA8. 34 interactors.
MINTiMINT-1372069.
STRINGi9606.ENSP00000278671.

PTM databases

iPTMnetiQ6IAA8.
PhosphoSitePlusiQ6IAA8.
SwissPalmiQ6IAA8.

Polymorphism and mutation databases

BioMutaiLAMTOR1.
DMDMi125863645.

Proteomic databases

EPDiQ6IAA8.
MaxQBiQ6IAA8.
PaxDbiQ6IAA8.
PeptideAtlasiQ6IAA8.
PRIDEiQ6IAA8.
TopDownProteomicsiQ6IAA8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000278671; ENSP00000278671; ENSG00000149357.
GeneIDi55004.
KEGGihsa:55004.
UCSCiuc001ort.3. human.

Organism-specific databases

CTDi55004.
DisGeNETi55004.
GeneCardsiLAMTOR1.
H-InvDBHIX0009905.
HGNCiHGNC:26068. LAMTOR1.
HPAiHPA002997.
MIMi613510. gene.
neXtProtiNX_Q6IAA8.
OpenTargetsiENSG00000149357.
PharmGKBiPA143485354.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IH39. Eukaryota.
ENOG4112AMJ. LUCA.
GeneTreeiENSGT00390000016789.
HOVERGENiHBG081218.
InParanoidiQ6IAA8.
KOiK20397.
OMAiNVQHPSI.
OrthoDBiEOG091G0XGD.
PhylomeDBiQ6IAA8.
TreeFamiTF323788.

Enzyme and pathway databases

ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-165159. mTOR signalling.
R-HSA-166208. mTORC1-mediated signalling.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-6798695. Neutrophil degranulation.
SIGNORiQ6IAA8.

Miscellaneous databases

GenomeRNAii55004.
PROiQ6IAA8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000149357.
CleanExiHS_C11orf59.
ExpressionAtlasiQ6IAA8. baseline and differential.
GenevisibleiQ6IAA8. HS.

Family and domain databases

InterProiIPR026310. LAMTOR1-like.
IPR028209. LAMTOR1/MEH1.
[Graphical view]
PANTHERiPTHR13401. PTHR13401. 1 hit.
PfamiPF15454. LAMTOR. 1 hit.
[Graphical view]
SMARTiSM01262. LAMTOR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLTOR1_HUMAN
AccessioniPrimary (citable) accession number: Q6IAA8
Secondary accession number(s): Q8WZ09, Q9NWT0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: November 30, 2016
This is version 107 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families
  6. Uncharacterized protein families (UPF)
    List of uncharacterized protein family (UPF) entries

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.