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Protein

Ragulator complex protein LAMTOR5

Gene

LAMTOR5

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. When complexed to BIRC5, interferes with apoptosome assembly, preventing recruitment of pro-caspase-9 to oligomerized APAF1, thereby selectively suppressing apoptosis initiated via the mitochondrial/cytochrome c pathway. Down-regulates hepatitis B virus (HBV) replication.2 Publications

GO - Biological processi

  • cell cycle arrest Source: Reactome
  • cellular response to amino acid stimulus Source: UniProtKB
  • macroautophagy Source: Reactome
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • positive regulation of GTPase activity Source: GOC
  • positive regulation of TOR signaling Source: UniProtKB
  • protein localization to lysosome Source: UniProtKB
  • regulation of cell size Source: UniProtKB
  • response to virus Source: ProtInc
  • viral genome replication Source: ProtInc
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134248-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.
SIGNORiO43504.

Names & Taxonomyi

Protein namesi
Recommended name:
Ragulator complex protein LAMTOR5
Alternative name(s):
Hepatitis B virus X-interacting protein
Short name:
HBV X-interacting protein
Short name:
HBX-interacting protein
Late endosomal/lysosomal adaptor and MAPK and MTOR activator 5
Gene namesi
Name:LAMTOR5
Synonyms:HBXIP, XIP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:17955. LAMTOR5.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • lysosomal membrane Source: Reactome
  • lysosome Source: UniProtKB
  • Ragulator complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Lysosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi12T → A: No change. 1 Publication1
Mutagenesisi36T → A: No interaction with XABX14-154 (truncated form of HBX). 1 Publication1

Organism-specific databases

DisGeNETi10542.
OpenTargetsiENSG00000134248.
PharmGKBiPA29211.

Polymorphism and mutation databases

BioMutaiLAMTOR5.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000660071 – 91Ragulator complex protein LAMTOR5Add BLAST91

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1 Publication1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiO43504.
MaxQBiO43504.
PaxDbiO43504.
PeptideAtlasiO43504.
PRIDEiO43504.
TopDownProteomicsiO43504.

PTM databases

iPTMnetiO43504.
PhosphoSitePlusiO43504.

Expressioni

Tissue specificityi

Highly expressed in skeletal and cardiac muscle, followed by pancreas, kidney, liver, brain, placenta and lung. Elevated levels in both cancerous and non-cancerous liver tissue of patients with chronic HBV infection compared with hepatic tissue without HBV infection.

Gene expression databases

BgeeiENSG00000134248.
CleanExiHS_HBXIP.
ExpressionAtlasiO43504. baseline and differential.
GenevisibleiO43504. HS.

Interactioni

Subunit structurei

Homodimer (Probable). 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. The Ragulator complex interacts with SLC38A9; the probable amino acid sensor (PubMed:25561175, PubMed:25567906). Interacts with phosphorylated BIRC5; the resulting complex binds pro-caspase-9, as well as active caspase-9, but much less efficiently. Interacts with SUPV3L1. Interacts with hepatitis B virus (HBV) oncoprotein HBX C-terminus.Curated6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Q9WMX22EBI-713382,EBI-9028527From a different organism.
LAMTOR4Q0VGL13EBI-713382,EBI-5658976
SLC38A9Q8NBW43EBI-713382,EBI-9978316
STAT4Q147652EBI-713382,EBI-1186538

Protein-protein interaction databases

BioGridi115796. 49 interactors.
DIPiDIP-61482N.
IntActiO43504. 61 interactors.
MINTiMINT-1389550.
STRINGi9606.ENSP00000256644.

Structurei

Secondary structure

191
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi5 – 13Combined sources9
Beta strandi18 – 24Combined sources7
Beta strandi30 – 35Combined sources6
Helixi39 – 41Combined sources3
Helixi42 – 54Combined sources13
Beta strandi65 – 69Combined sources5
Beta strandi72 – 79Combined sources8
Beta strandi82 – 88Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MS6X-ray2.08A1-91[»]
3MSHX-ray1.51A1-91[»]
ProteinModelPortaliO43504.
SMRiO43504.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43504.

Family & Domainsi

Sequence similaritiesi

Belongs to the LAMTOR5 family.Curated

Phylogenomic databases

eggNOGiENOG410IZVH. Eukaryota.
ENOG4111WFD. LUCA.
GeneTreeiENSGT00390000006247.
HOGENOMiHOG000045746.
HOVERGENiHBG010343.
InParanoidiO43504.
KOiK16344.
PhylomeDBiO43504.
TreeFamiTF324433.

Family and domain databases

InterProiIPR024135. LAMTOR5.
[Graphical view]
PANTHERiPTHR13342. PTHR13342. 1 hit.
PfamiPF16672. LAMTOR5. 1 hit.
[Graphical view]
PRINTSiPR02092. HEPBVIRUSXIP.

Sequencei

Sequence statusi: Complete.

O43504-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEATLEQHLE DTMKNPSIVG VLCTDSQGLN LGCRGTLSDE HAGVISVLAQ
60 70 80 90
QAAKLTSDPT DIPVVCLESD NGNIMIQKHD GITVAVHKMA S
Length:91
Mass (Da):9,614
Last modified:June 1, 1998 - v1
Checksum:i01D9E762ABC63980
GO

Sequence cautioni

The sequence AAH62619 differs from that shown. Reason: Erroneous initiation.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF029890 mRNA. Translation: AAC52032.1.
AY623819 mRNA. Translation: AAV30683.1.
CR456866 mRNA. Translation: CAG33147.1.
CR542130 mRNA. Translation: CAG46927.1.
AL390797 Genomic DNA. Translation: CAH71488.1.
BC062619 mRNA. Translation: AAH62619.2. Different initiation.
RefSeqiNP_006393.2. NM_006402.2.
UniGeneiHs.439815.

Genome annotation databases

EnsembliENST00000602318; ENSP00000473439; ENSG00000134248.
GeneIDi10542.
KEGGihsa:10542.
UCSCiuc001dzr.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF029890 mRNA. Translation: AAC52032.1.
AY623819 mRNA. Translation: AAV30683.1.
CR456866 mRNA. Translation: CAG33147.1.
CR542130 mRNA. Translation: CAG46927.1.
AL390797 Genomic DNA. Translation: CAH71488.1.
BC062619 mRNA. Translation: AAH62619.2. Different initiation.
RefSeqiNP_006393.2. NM_006402.2.
UniGeneiHs.439815.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MS6X-ray2.08A1-91[»]
3MSHX-ray1.51A1-91[»]
ProteinModelPortaliO43504.
SMRiO43504.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115796. 49 interactors.
DIPiDIP-61482N.
IntActiO43504. 61 interactors.
MINTiMINT-1389550.
STRINGi9606.ENSP00000256644.

PTM databases

iPTMnetiO43504.
PhosphoSitePlusiO43504.

Polymorphism and mutation databases

BioMutaiLAMTOR5.

Proteomic databases

EPDiO43504.
MaxQBiO43504.
PaxDbiO43504.
PeptideAtlasiO43504.
PRIDEiO43504.
TopDownProteomicsiO43504.

Protocols and materials databases

DNASUi10542.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000602318; ENSP00000473439; ENSG00000134248.
GeneIDi10542.
KEGGihsa:10542.
UCSCiuc001dzr.4. human.

Organism-specific databases

CTDi10542.
DisGeNETi10542.
GeneCardsiLAMTOR5.
H-InvDBHIX0029151.
HGNCiHGNC:17955. LAMTOR5.
MIMi608521. gene.
neXtProtiNX_O43504.
OpenTargetsiENSG00000134248.
PharmGKBiPA29211.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IZVH. Eukaryota.
ENOG4111WFD. LUCA.
GeneTreeiENSGT00390000006247.
HOGENOMiHOG000045746.
HOVERGENiHBG010343.
InParanoidiO43504.
KOiK16344.
PhylomeDBiO43504.
TreeFamiTF324433.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134248-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.
SIGNORiO43504.

Miscellaneous databases

EvolutionaryTraceiO43504.
GeneWikiiHBXIP.
GenomeRNAii10542.
PROiO43504.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134248.
CleanExiHS_HBXIP.
ExpressionAtlasiO43504. baseline and differential.
GenevisibleiO43504. HS.

Family and domain databases

InterProiIPR024135. LAMTOR5.
[Graphical view]
PANTHERiPTHR13342. PTHR13342. 1 hit.
PfamiPF16672. LAMTOR5. 1 hit.
[Graphical view]
PRINTSiPR02092. HEPBVIRUSXIP.
ProtoNetiSearch...

Entry informationi

Entry nameiLTOR5_HUMAN
AccessioniPrimary (citable) accession number: O43504
Secondary accession number(s): Q6IBD8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: November 2, 2016
This is version 134 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

Miscellaneous

Suppression of caspase activation by the BIRC5/HBXIP complex is increased in the presence of HBX.

Keywords - Technical termi

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

Documents

  1. Human chromosome 1
    Human chromosome 1: 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.