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O43504 (LTOR5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:LAMTOR5
Synonyms:HBXIP, XIP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length91 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.13

Subunit structure

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. 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. Ref.8 Ref.9 Ref.13 Ref.14

Subcellular location

Cytoplasm. Lysosome Ref.8 Ref.9 Ref.13.

Tissue specificity

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.

Miscellaneous

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

Sequence similarities

Belongs to the LAMTOR5 family.

Sequence caution

The sequence AAH62619.2 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 9191Ragulator complex protein LAMTOR5
PRO_0000066007

Amino acid modifications

Modified residue11N-acetylmethionine Ref.7 Ref.11

Experimental info

Mutagenesis121T → A: No change.
Mutagenesis361T → A: No interaction with XABX14-154 (truncated form of HBX).

Secondary structure

................ 91
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O43504 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 01D9E762ABC63980

FASTA919,614
        10         20         30         40         50         60 
MEATLEQHLE DTMKNPSIVG VLCTDSQGLN LGCRGTLSDE HAGVISVLAQ QAAKLTSDPT 

        70         80         90 
DIPVVCLESD NGNIMIQKHD GITVAVHKMA S 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of a novel hepatitis B virus x binding protein that inhibits viral replication."
Melegari M., Scaglioni P.P., Wands J.R.
J. Virol. 72:1737-1743(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS.
Tissue: Liver.
[2]"Clone of human uterus hepatitis B virus x interacting protein (HBXIP) gene."
Zhang X., Ye L., Shi Z.
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Uterus.
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Colon.
[7]Bienvenut W.V., Quadroni M.
Submitted (JUL-2005) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1-14, ACETYLATION AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Melanoma.
[8]"HBXIP functions as a cofactor of survivin in apoptosis suppression."
Marusawa H., Matsuzawa S., Welsh K., Zou H., Armstrong R., Tamm I., Reed J.C.
EMBO J. 22:2729-2740(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN APOPTOSIS SUPPRESSION, INTERACTION WITH BIRC5, SUBCELLULAR LOCATION.
[9]"Human ATP-dependent RNA/DNA helicase hSuv3p interacts with the cofactor of survivin HBXIP."
Minczuk M., Mroczek S., Pawlak S.D., Stepien P.P.
FEBS J. 272:5008-5019(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SUPV3L1, SUBCELLULAR LOCATION.
[10]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[11]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Ragulator is a GEF for the Rag GTPases that signal amino acid levels to mTORC1."
Bar-Peled L., Schweitzer L.D., Zoncu R., Sabatini D.M.
Cell 150:1196-1208(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MTORC1 SIGNALING, IDENTIFICATION IN RAGULATOR COMPLEX, INTERACTION WITH MTORC1 COMPLEX AND RAG GTPASES, SUBCELLULAR LOCATION.
[14]"Structural characterization of HBXIP: the protein that interacts with the anti-apoptotic protein survivin and the oncogenic viral protein HBx."
Garcia-Saez I., Lacroix F.B., Blot D., Gabel F., Skoufias D.A.
J. Mol. Biol. 405:331-340(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.51 ANGSTROMS), SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_006393.2. NM_006402.2.
UniGeneHs.439815.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3MS6X-ray2.08A1-91[»]
3MSHX-ray1.51A1-91[»]
ProteinModelPortalO43504.
SMRO43504. Positions 1-91.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115796. 17 interactions.
IntActO43504. 50 interactions.
MINTMINT-1389550.
STRING9606.ENSP00000256644.

PTM databases

PhosphoSiteO43504.

Proteomic databases

MaxQBO43504.
PaxDbO43504.
PRIDEO43504.

Protocols and materials databases

DNASU10542.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256644; ENSP00000256644; ENSG00000134248.
ENST00000602318; ENSP00000473439; ENSG00000134248.
GeneID10542.
KEGGhsa:10542.
UCSCuc001dzr.3. human.

Organism-specific databases

CTD10542.
GeneCardsGC01M110944.
H-InvDBHIX0029151.
HGNCHGNC:17955. LAMTOR5.
HPAHPA006812.
MIM608521. gene.
neXtProtNX_O43504.
PharmGKBPA29211.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG84672.
HOGENOMHOG000045746.
HOVERGENHBG010343.
InParanoidO43504.
KOK16344.
OrthoDBEOG7FNCBP.
PhylomeDBO43504.
TreeFamTF324433.

Gene expression databases

ArrayExpressO43504.
BgeeO43504.
CleanExHS_HBXIP.
GenevestigatorO43504.

Family and domain databases

InterProIPR024135. HBXIP.
[Graphical view]
PANTHERPTHR13342. PTHR13342. 1 hit.
PRINTSPR02092. HEPBVIRUSXIP.
ProtoNetSearch...

Other

EvolutionaryTraceO43504.
GeneWikiHBXIP.
GenomeRNAi10542.
NextBio39997.
PROO43504.
SOURCESearch...

Entry information

Entry nameLTOR5_HUMAN
AccessionPrimary (citable) accession number: O43504
Secondary accession number(s): Q6IBD8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: June 11, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM