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Protein

Ragulator complex protein LAMTOR1

Gene

LAMTOR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 - Molecular functioni

  • GTPase binding Source: CAFA

GO - Biological processi

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
R-HSA-8943724 Regulation of PTEN gene transcription
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

EuPathDBiHostDB:ENSG00000149357.9
HGNCiHGNC:26068 LAMTOR1
MIMi613510 gene
neXtProtiNX_Q6IAA8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi66364
TopDownProteomicsiQ6IAA8

PTM databases

iPTMnetiQ6IAA8
PhosphoSitePlusiQ6IAA8
SwissPalmiQ6IAA8

Expressioni

Inductioni

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

Gene expression databases

BgeeiENSG00000149357 Expressed in 200 organ(s), highest expression level in leukocyte
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120336, 59 interactors
DIPiDIP-39650N
IntActiQ6IAA8, 37 interactors
MINTiQ6IAA8
STRINGi9606.ENSP00000278671

Structurei

Secondary structure

1161
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

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
OMAiHNLEQHE
OrthoDBiEOG091G0XGD
PhylomeDBiQ6IAA8
TreeFamiTF323788

Family and domain databases

InterProiView protein in InterPro
IPR028209 LAMTOR1/MEH1
PfamiView protein in Pfam
PF15454 LAMTOR, 1 hit
SMARTiView protein in SMART
SM01262 LAMTOR, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H3Y3F5H3Y3_HUMAN
Ragulator complex protein LAMTOR1
LAMTOR1
160Annotation score:
F5H479F5H479_HUMAN
Ragulator complex protein LAMTOR1
LAMTOR1
99Annotation score:
F5GX19F5GX19_HUMAN
Ragulator complex protein LAMTOR1
LAMTOR1
142Annotation score:
H0YFI1H0YFI1_HUMAN
Ragulator complex protein LAMTOR1
LAMTOR1
79Annotation score:
F5H267F5H267_HUMAN
Ragulator complex protein LAMTOR1
LAMTOR1
76Annotation score:

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 dbSNP:rs1053443Ensembl.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

Similar proteinsi

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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5X6UX-ray2.40E42-161[»]
5X6VX-ray2.02E42-161[»]
5Y39X-ray2.65A/F76-145[»]
5Y3AX-ray2.90A/F50-161[»]
6B9XX-ray1.42A1-161[»]
6EHPX-ray2.30E21-161[»]
6EHRX-ray2.90E21-161[»]
ProteinModelPortaliQ6IAA8
SMRiQ6IAA8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120336, 59 interactors
DIPiDIP-39650N
IntActiQ6IAA8, 37 interactors
MINTiQ6IAA8
STRINGi9606.ENSP00000278671

PTM databases

iPTMnetiQ6IAA8
PhosphoSitePlusiQ6IAA8
SwissPalmiQ6IAA8

Polymorphism and mutation databases

BioMutaiLAMTOR1
DMDMi125863645

Proteomic databases

EPDiQ6IAA8
MaxQBiQ6IAA8
PaxDbiQ6IAA8
PeptideAtlasiQ6IAA8
PRIDEiQ6IAA8
ProteomicsDBi66364
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
EuPathDBiHostDB:ENSG00000149357.9
GeneCardsiLAMTOR1
H-InvDBiHIX0009905
HGNCiHGNC:26068 LAMTOR1
HPAiHPA002997
MIMi613510 gene
neXtProtiNX_Q6IAA8
OpenTargetsiENSG00000149357
PharmGKBiPA143485354
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IH39 Eukaryota
ENOG4112AMJ LUCA
GeneTreeiENSGT00390000016789
HOVERGENiHBG081218
InParanoidiQ6IAA8
KOiK20397
OMAiHNLEQHE
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
R-HSA-8943724 Regulation of PTEN gene transcription
SIGNORiQ6IAA8

Miscellaneous databases

GenomeRNAii55004
PROiPR:Q6IAA8
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000149357 Expressed in 200 organ(s), highest expression level in leukocyte
CleanExiHS_C11orf59
ExpressionAtlasiQ6IAA8 baseline and differential
GenevisibleiQ6IAA8 HS

Family and domain databases

InterProiView protein in InterPro
IPR028209 LAMTOR1/MEH1
PfamiView protein in Pfam
PF15454 LAMTOR, 1 hit
SMARTiView protein in SMART
SM01262 LAMTOR, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiLTOR1_HUMAN
AccessioniPrimary (citable) accession number: Q6IAA8
Secondary accession number(s): Q8WZ09, Q9NWT0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: November 7, 2018
This is version 125 of the entry and version 2 of the sequence. See 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Uncharacterized protein families (UPF)
    List of uncharacterized protein family (UPF) entries
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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