O43504 (LTOR5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	LAMTOR5
Synonyms:	HBXIP, XIP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	91 AA.
Sequence status	Complete.
Protein existence	Evidence 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.12
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.12 Ref.13
Subcellular location	Cytoplasm. Lysosome Ref.8 Ref.9 Ref.12.
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.

Ontologies

Keywords
Cellular component	Cytoplasm Lysosome
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to amino acid stimulus Inferred from mutant phenotype Ref.12. Source: UniProtKB negative regulation of apoptotic process Inferred from direct assay Ref.8. Source: UniProtKB negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of TOR signaling cascade Inferred from mutant phenotype Ref.12. Source: UniProtKB protein localization to lysosome Inferred from mutant phenotype Ref.12. Source: UniProtKB regulation of cell size Inferred from mutant phenotype Ref.12. Source: UniProtKB response to virus Traceable author statement Ref.1. Source: ProtInc viral genome replication Traceable author statement Ref.1. Source: ProtInc
Cellular_component	Ragulator complex Inferred from direct assay Ref.12. Source: UniProtKB cytosol Inferred from direct assay Ref.8. Source: UniProtKB lysosome Inferred from direct assay Ref.12. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 91

91

Ragulator complex protein LAMTOR5

PRO_0000066007

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.7

Experimental info

Mutagenesis

12

1

T → A: No change.

Mutagenesis

36

1

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

Secondary structure

1

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91

Helix Strand Turn

Details...

Helix

5 – 13

9

Beta strand

18 – 24

7

Beta strand

30 – 35

6

Helix

39 – 41

3

Helix

42 – 54

13

Beta strand

65 – 69

5

Beta strand

72 – 79

8

Beta strand

82 – 88

7

Sequences

	Sequence		Length	Mass (Da)
	O43504 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 01D9E762ABC63980	FASTA	91	9,614
	10 20 30 40 50 60 MEATLEQHLE DTMKNPSIVG VLCTDSQGLN LGCRGTLSDE HAGVISVLAQ QAAKLTSDPT 70 80 90 DIPVVCLESD NGNIMIQKHD GITVAVHKMA S

References

	« Hide 'large scale' referencesShow '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. , 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, 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]	"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].
[12]	"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.
[13]	"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.

IPI

IPI00935729.

RefSeq

NP_006393.2. NM_006402.2.

UniGene

Hs.439815.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3MS6	X-ray	2.08	A	1-91	[»]
3MSH	X-ray	1.51	A	1-91	[»]

ProteinModelPortal

O43504.

ModBase

Search...

Protein-protein interaction databases

IntAct

O43504. 50 interactions.

MINT

MINT-1389550.

STRING

9606.ENSP00000256644.

PTM databases

PhosphoSite

O43504.

Proteomic databases

PaxDb

O43504.

PRIDE

O43504.

Protocols and materials databases

DNASU

10542.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256644; ENSP00000256644; ENSG00000134248.

GeneID

10542.

KEGG

hsa:10542.

UCSC

uc001dzr.3. human.

Organism-specific databases

CTD

10542.

GeneCards

GC01M110943.

H-InvDB

HIX0029151.

HGNC

HGNC:17955. LAMTOR5.

HPA

HPA006812.

MIM

608521. gene.

neXtProt

NX_O43504.

PharmGKB

PA29211.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG84672.

HOGENOM

HOG000045746.

HOVERGEN

HBG010343.

InParanoid

O43504.

KO

K16344.

OrthoDB

EOG4NKBWP.

Gene expression databases

ArrayExpress

O43504.

Bgee

O43504.

CleanEx

HS_HBXIP.

Genevestigator

O43504.

GermOnline

ENSG00000134248. Homo sapiens.

Family and domain databases

InterPro

IPR024135. Hepatitis_HBXIP.
[Graphical view]

PANTHER

PTHR13342. PTHR13342. 1 hit.

PRINTS

PR02092. HEPBVIRUSXIP.

ProtoNet

Search...

Other

EvolutionaryTrace

O43504.

GenomeRNAi

10542.

NextBio

39997.

SOURCE

Search...

Entry information

Entry name

LTOR5_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.