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Protein

Ragulator complex protein LAMTOR3

Gene

LAMTOR3

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. Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2.2 Publications

GO - Molecular functioni

GO - Biological processi

  • activation of MAPKK activity Source: Ensembl
  • cell cycle arrest Source: Reactome
  • cellular protein localization Source: UniProtKB
  • cellular response to amino acid stimulus Source: UniProtKB
  • macroautophagy Source: Reactome
  • MAPK cascade Source: Reactome
  • positive regulation of GTPase activity Source: GOC
  • positive regulation of TOR signaling Source: UniProtKB
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109270-MONOMER.
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-5674135. MAP2K and MAPK activation.
R-HSA-6798695. Neutrophil degranulation.
SignaLinkiQ9UHA4.
SIGNORiQ9UHA4.

Names & Taxonomyi

Protein namesi
Recommended name:
Ragulator complex protein LAMTOR3
Alternative name(s):
Late endosomal/lysosomal adaptor and MAPK and MTOR activator 3
MEK-binding partner 1
Short name:
Mp1
Mitogen-activated protein kinase kinase 1-interacting protein 1
Mitogen-activated protein kinase scaffold protein 1
Gene namesi
Name:LAMTOR3
Synonyms:MAP2K1IP1, MAPKSP1
ORF Names:PRO2783
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:15606. LAMTOR3.

Subcellular locationi

GO - Cellular componenti

  • endosome membrane Source: Reactome
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • lysosomal membrane Source: Reactome
  • Ragulator complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi8649.
OpenTargetsiENSG00000109270.
PharmGKBiPA164722189.

Polymorphism and mutation databases

BioMutaiLAMTOR3.
DMDMi24418562.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002210051 – 124Ragulator complex protein LAMTOR3Add BLAST124

Proteomic databases

EPDiQ9UHA4.
PaxDbiQ9UHA4.
PeptideAtlasiQ9UHA4.
PRIDEiQ9UHA4.
TopDownProteomicsiQ9UHA4-1. [Q9UHA4-1]

PTM databases

iPTMnetiQ9UHA4.
PhosphoSitePlusiQ9UHA4.

Expressioni

Gene expression databases

BgeeiENSG00000109270.
CleanExiHS_MAPKSP1.
GenevisibleiQ9UHA4. HS.

Organism-specific databases

HPAiHPA026858.

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 (PubMed:20381137, PubMed:22980980). 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). The Ragulator complex interacts with SLC38A9; the probable amino acid sensor (PubMed:25561175, PubMed:25567906). Interacts with LAMTOR1 and LAMTOR2; the interaction is direct. Interacts with MAP2K1/MEK1 and MAPK2 (By similarity). Interacts with MORG1 (By similarity).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LAMTOR2Q9Y2Q517EBI-1038192,EBI-2643704
NIF3L1Q9GZT83EBI-1038192,EBI-740897
SLC38A9Q8NBW45EBI-1038192,EBI-9978316

Protein-protein interaction databases

BioGridi114201. 77 interactors.
IntActiQ9UHA4. 26 interactors.
STRINGi9606.ENSP00000424183.

Structurei

Secondary structure

1124
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 12Combined sources9
Helixi13 – 15Combined sources3
Beta strandi19 – 25Combined sources7
Beta strandi31 – 36Combined sources6
Helixi42 – 45Combined sources4
Helixi47 – 63Combined sources17
Beta strandi68 – 74Combined sources7
Beta strandi76 – 85Combined sources10
Beta strandi88 – 95Combined sources8
Helixi100 – 117Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SKOX-ray2.00A2-124[»]
2ZL1X-ray2.00A2-124[»]
3CPTX-ray1.90A2-124[»]
ProteinModelPortaliQ9UHA4.
SMRiQ9UHA4.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UHA4.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni57 – 70Required for interaction with LAMTOR2By similarityAdd BLAST14

Sequence similaritiesi

Belongs to the LAMTOR3 family.Curated

Phylogenomic databases

eggNOGiENOG410IWYZ. Eukaryota.
ENOG4111KCU. LUCA.
GeneTreeiENSGT00390000013159.
HOVERGENiHBG052480.
InParanoidiQ9UHA4.
KOiK04370.
OMAiDCNTGHI.
OrthoDBiEOG091G0TYL.
PhylomeDBiQ9UHA4.
TreeFamiTF324889.

Family and domain databases

InterProiIPR015019. LAMTOR3.
[Graphical view]
PANTHERiPTHR13378. PTHR13378. 1 hit.
PfamiPF08923. MAPKK1_Int. 1 hit.
[Graphical view]
SMARTiSM01278. MAPKK1_Int. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UHA4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MADDLKRFLY KKLPSVEGLH AIVVSDRDGV PVIKVANDNA PEHALRPGFL
60 70 80 90 100
STFALATDQG SKLGLSKNKS IICYYNTYQV VQFNRLPLVV SFIASSSANT
110 120
GLIVSLEKEL APLFEELRQV VEVS
Length:124
Mass (Da):13,623
Last modified:May 1, 2000 - v1
Checksum:i0A5196CF41D83D13
GO
Isoform 2 (identifier: Q9UHA4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     35-41: Missing.

Note: No experimental confirmation available.
Show »
Length:117
Mass (Da):12,941
Checksum:iBB2216FFEA408208
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti49F → L in AAG35540 (Ref. 2) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04637235 – 41Missing in isoform 2. 1 Publication7

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF201947 mRNA. Translation: AAF17239.1.
AF130115 mRNA. Translation: AAG35540.1.
AL544981 mRNA. No translation available.
AK311755 mRNA. Translation: BAG34698.1.
AP001962 Genomic DNA. No translation available.
CH471057 Genomic DNA. Translation: EAX06112.1.
BC026245 mRNA. Translation: AAH26245.1.
CCDSiCCDS3652.1. [Q9UHA4-1]
CCDS58920.1. [Q9UHA4-2]
RefSeqiNP_001230665.1. NM_001243736.1. [Q9UHA4-2]
NP_068805.1. NM_021970.3. [Q9UHA4-1]
UniGeneiHs.433332.

Genome annotation databases

EnsembliENST00000226522; ENSP00000226522; ENSG00000109270. [Q9UHA4-2]
ENST00000499666; ENSP00000424183; ENSG00000109270. [Q9UHA4-1]
GeneIDi8649.
KEGGihsa:8649.
UCSCiuc003hvg.3. human. [Q9UHA4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF201947 mRNA. Translation: AAF17239.1.
AF130115 mRNA. Translation: AAG35540.1.
AL544981 mRNA. No translation available.
AK311755 mRNA. Translation: BAG34698.1.
AP001962 Genomic DNA. No translation available.
CH471057 Genomic DNA. Translation: EAX06112.1.
BC026245 mRNA. Translation: AAH26245.1.
CCDSiCCDS3652.1. [Q9UHA4-1]
CCDS58920.1. [Q9UHA4-2]
RefSeqiNP_001230665.1. NM_001243736.1. [Q9UHA4-2]
NP_068805.1. NM_021970.3. [Q9UHA4-1]
UniGeneiHs.433332.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SKOX-ray2.00A2-124[»]
2ZL1X-ray2.00A2-124[»]
3CPTX-ray1.90A2-124[»]
ProteinModelPortaliQ9UHA4.
SMRiQ9UHA4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114201. 77 interactors.
IntActiQ9UHA4. 26 interactors.
STRINGi9606.ENSP00000424183.

PTM databases

iPTMnetiQ9UHA4.
PhosphoSitePlusiQ9UHA4.

Polymorphism and mutation databases

BioMutaiLAMTOR3.
DMDMi24418562.

Proteomic databases

EPDiQ9UHA4.
PaxDbiQ9UHA4.
PeptideAtlasiQ9UHA4.
PRIDEiQ9UHA4.
TopDownProteomicsiQ9UHA4-1. [Q9UHA4-1]

Protocols and materials databases

DNASUi8649.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000226522; ENSP00000226522; ENSG00000109270. [Q9UHA4-2]
ENST00000499666; ENSP00000424183; ENSG00000109270. [Q9UHA4-1]
GeneIDi8649.
KEGGihsa:8649.
UCSCiuc003hvg.3. human. [Q9UHA4-1]

Organism-specific databases

CTDi8649.
DisGeNETi8649.
GeneCardsiLAMTOR3.
HGNCiHGNC:15606. LAMTOR3.
HPAiHPA026858.
MIMi603296. gene.
neXtProtiNX_Q9UHA4.
OpenTargetsiENSG00000109270.
PharmGKBiPA164722189.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IWYZ. Eukaryota.
ENOG4111KCU. LUCA.
GeneTreeiENSGT00390000013159.
HOVERGENiHBG052480.
InParanoidiQ9UHA4.
KOiK04370.
OMAiDCNTGHI.
OrthoDBiEOG091G0TYL.
PhylomeDBiQ9UHA4.
TreeFamiTF324889.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109270-MONOMER.
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-5674135. MAP2K and MAPK activation.
R-HSA-6798695. Neutrophil degranulation.
SignaLinkiQ9UHA4.
SIGNORiQ9UHA4.

Miscellaneous databases

ChiTaRSiLAMTOR3. human.
EvolutionaryTraceiQ9UHA4.
GeneWikiiMAP2K1IP1.
GenomeRNAii8649.
PROiQ9UHA4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109270.
CleanExiHS_MAPKSP1.
GenevisibleiQ9UHA4. HS.

Family and domain databases

InterProiIPR015019. LAMTOR3.
[Graphical view]
PANTHERiPTHR13378. PTHR13378. 1 hit.
PfamiPF08923. MAPKK1_Int. 1 hit.
[Graphical view]
SMARTiSM01278. MAPKK1_Int. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLTOR3_HUMAN
AccessioniPrimary (citable) accession number: Q9UHA4
Secondary accession number(s): B2R4A1, J3KMX4, Q9H364
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 25, 2002
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 137 of the entry and version 1 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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.