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Protein

Ragulator complex protein LAMTOR3

Gene

LAMTOR3

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. 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
  • MAPK cascade Source: Reactome
  • neutrophil degranulation Source: Reactome
  • positive regulation of TOR signaling Source: UniProtKB
  • regulation of macroautophagy Source: Reactome

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-5674135 MAP2K and MAPK activation
R-HSA-6798695 Neutrophil degranulation
R-HSA-8943724 Regulation of PTEN gene transcription
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

EuPathDBiHostDB:ENSG00000109270.12
HGNCiHGNC:15606 LAMTOR3
MIMi603296 gene
neXtProtiNX_Q9UHA4

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

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
ProteomicsDBi84292
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

Show more details

Protein-protein interaction databases

BioGridi114201, 86 interactors
CORUMiQ9UHA4
IntActiQ9UHA4, 33 interactors
MINTiQ9UHA4
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
Turni27 – 29Combined sources3
Beta strandi31 – 36Combined sources6
Helixi42 – 45Combined sources4
Helixi47 – 50Combined sources4
Helixi52 – 60Combined sources9
Beta strandi63 – 65Combined sources3
Beta strandi67 – 74Combined sources8
Beta strandi76 – 85Combined sources10
Beta strandi88 – 95Combined sources8
Helixi100 – 119Combined sources20

3D structure databases

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
OMAiYQVIQMN
OrthoDBiEOG091G0TYL
PhylomeDBiQ9UHA4
TreeFamiTF324889

Family and domain databases

InterProiView protein in InterPro
IPR015019 LAMTOR3
PANTHERiPTHR13378 PTHR13378, 1 hit
PfamiView protein in Pfam
PF08923 MAPKK1_Int, 1 hit
SMARTiView protein in SMART
SM01278 MAPKK1_Int, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiLTOR3_HUMAN
AccessioniPrimary (citable) accession number: Q9UHA4
Secondary accession number(s): B2R4A1, J3KMX4, Q9H364
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 25, 2002
Last sequence update: May 1, 2000
Last modified: June 20, 2018
This is version 149 of the entry and version 1 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, 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

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