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Protein

Lipoprotein LpqH

Gene

lpqH

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Based on its structure might be involved in ligand transport (Ref. 25) (By similarity).By similarity1 Publication
A host TLR2 agonist (PubMed:10426995, PubMed:11441098, PubMed:12874328). Plays a complicated role in bacterial interactions with the host immune system; some effects favor the host (induces interleukin 1-beta and IL-12 p40 (IL12B), both increase the host's immune response) while others favor the bacteria (increases growth in monocyte-derived macrophages and decreases host MHC class II (MHC-II) expression and antigen processing) (PubMed:16177361). Induces host (human and mouse) IL-12 p40 (IL12B, a proinflammatory cytokine) release by monocyte cell lines via TLR2 and CD14 (PubMed:10426995). Induces host (human) monocytes to produce TNF-alpha, IL-6 and IL-12 p40; LpqH is a more potent inducer than PstS1 (PubMed:16622205). Inhibits MHC-II expression and antigen processing in host (mouse) macrophages via TLR2 (independently of TLR4) probably via the lipid modification (PubMed:11441098). Stimulates host (human) dendritic cell maturation to become MHC-II-positive antigen presenting cells via TLR2, which depends on lipidation; nonlipidated protein does not stimulate maturation (PubMed:11160304). Inhibits host (human and mouse) IFN-gamma signaling in macrophages via TLR2; decreases IFN-gamma stimulated MHC-II antigen processing as well as decreasing IFN-gamma-mediated up-regulation of immunoglobulin gamma Fc receptor (FCGR1A), enabling the bacteria to evade the immune system (PubMed:12874328). In resting human CD4+ T-cells lipidated (but probably not nonlipidated protein) is a costimulatory ligand (with anti-CD3 and anti-CD28) for T-cell proliferation and IFN-gamma and IL-2 production (PubMed:21078852). Human CD4+ T-cells probably use TLR1/TLR2 heterodimers to respond to mycobacterial lipoproteins (PubMed:21078852). Acting via TLR2 enhances expression of host peroxisome proliferator-activated receptor gamma (PPARG), a regulator of inflammation and immunoregulation, and increases p38 MAPK phosphorylation, IL-6 and TNF-alpha expression (PubMed:25504154). Native or nonlipidated recombinant protein missing the first 4 residues have been shown to induce apoptosis in the human macrophage cell line THP-1 and human monocyte-derived macrophages in a TLR2, caspase-3 and caspase-8-dependent manner (PubMed:12594264). Protein overexpressed in M.smegmatis (lipidated and probably glycosylated) induces apopotosis in human macrophages via TLR2 in a caspase-3/caspase-8-mediated manner, but also in a caspase-independent manner where mitochondrial apoptosis-inducing factor (AIFM1) translocates to the nucleus (PubMed:23316255). Another study found mature, native (lipidated) protein did not induce apoptosis in THP-1 macrophage cell line (PubMed:12874328). Functions as an adhesin, binds to human and mouse macrophages (PubMed:25359607).11 Publications

GO - Molecular functioni

  • host cell surface receptor binding Source: MTBBASE

GO - Biological processi

  • growth of symbiont in host Source: MTBBASE
  • modulation by symbiont of host immune response Source: MTBBASE
  • modulation by symbiont of microbe-associated molecular pattern-induced host innate immune response Source: MTBBASE
  • pathogenesis Source: UniProtKB-KW
  • positive regulation by symbiont of host apoptotic process Source: UniProtKB
  • transport Source: UniProtKB-KW

Keywordsi

Biological processTransport, Virulence

Names & Taxonomyi

Protein namesi
Recommended name:
Lipoprotein LpqH
Alternative name(s):
19 kDa lipoprotein antigen
Putative transporter LpqH1 Publication
p191 Publication
Gene namesi
Name:lpqH
Ordered Locus Names:Rv3763
ORF Names:MTV025.111
OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Taxonomic identifieri83332 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
Proteomesi
  • UP000001584 Componenti: Chromosome

Organism-specific databases

TubercuListiRv3763.

Subcellular locationi

GO - Cellular componenti

  • bacterial extracellular vesicle Source: UniProtKB
  • cell surface Source: UniProtKB-SubCell
  • cell wall Source: MTBBASE
  • host cell cytoplasm Source: UniProtKB-SubCell
  • plasma membrane Source: MTBBASE

Keywords - Cellular componenti

Cell membrane, Cell wall, Host cytoplasm, Membrane, Secreted

Pathology & Biotechi

Biotechnological usei

A disrupted strain immunizes mice against subsequent infection with wild-type H37Rv as well as the M.bovis vaccine strain BCG.1 Publication

Disruption phenotypei

No visible phenotype in culture. Grows less well than wild-type in human monocyte-derived macrophages (MDM) over 7 days; increased human monocyte MHC class II expression, decreased interleukin 1-beta secretion from monocytes and MDM (PubMed:16177361). No growth in C57BL/6 mice over 40 days, even in mice lacking gamma interferon (PubMed:17804126).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1 – 22MKRGL…GLSGC → M: Protein not exported from cytoplasm, not released into host cytoplasm (uses recombinant M.vaccae to infect mouse macrophages). 1 PublicationAdd BLAST22
Mutagenesisi22C → A: Protein not released into host cytoplasm (uses recombinant M.vaccae to infect mouse macrophages). 1 Publication1
Mutagenesisi34 – 41TTTAAGTT → VVVAAGVV: No ConA binding; altered protein processing yields 16 kDa soluble form starting on residue 40 in M.smegmatis. Protein poorly released into host cytoplasm (uses recombinant M.vaccae to infect mouse macrophages). 2 Publications8
Mutagenesisi34 – 36TTT → VVV: Decreased ConA binding; altered protein processing yields 21 and 17 kDa forms in M.smegmatis. 1 Publication3
Mutagenesisi40 – 41TT → VV: Decreased ConA binding; altered protein processing yields 21 and 16 kDa forms in M.smegmatis. 1 Publication2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21CuratedAdd BLAST21
ChainiPRO_000001812822 – 159Lipoprotein LpqHAdd BLAST138

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi22N-palmitoyl cysteine2 Publications1
Lipidationi22S-diacylglycerol cysteine1 Publication1
Disulfide bondi67 ↔ 158Combined sources

Post-translational modificationi

Triacylated with a thioether-linked diacylglycerol with C16 and C19 on Cys-22 and an amide-linked C16 fatty acid (PubMed:24093492). Modified by Lgt on Cys-22 with an S-linked diacylglycerol with a mixture of C16, C18 and C19 fatty acids (palmitic, stearic and tuberculostearic acid), signal peptide is removed by LspA, modifed by Lnt with an amide-linked mixture of C16 and C19 fatty acids, expressed in M.bovis (PubMed:24093492). Upon expression in M.smegmatis the protein is glycosylated (possibly by mannose, detected by concanavalin A (conA) binding) within the first 20 residues of the mature protein; altering the probably glycosylated Thr residues alters processing of the mature protein in M.smegmatis and slightly differently in M.vaccae (PubMed:8670858). Glycosylation may protect this region of the protein from proteolysis, which would release the lipoprotein from the cell surface (PubMed:8670858). Mannosylated upon expression in M.smegmatis; treatment with alpha-D-mannosidase decreases its apparent molecular weight (PubMed:16098710). Native protein binds conA (PubMed:16098710).3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP9WK61.

Expressioni

Inductioni

Expressed in cell culture; expressed at a steady level for 4 days following infection of human mononuclear phagocytes.1 Publication

Interactioni

GO - Molecular functioni

  • host cell surface receptor binding Source: MTBBASE

Protein-protein interaction databases

STRINGi83332.Rv3763.

Structurei

Secondary structure

1159
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi51 – 54Combined sources4
Beta strandi65 – 70Combined sources6
Beta strandi73 – 78Combined sources6
Turni81 – 83Combined sources3
Beta strandi85 – 94Combined sources10
Beta strandi97 – 105Combined sources9
Beta strandi108 – 113Combined sources6
Beta strandi116 – 118Combined sources3
Beta strandi120 – 126Combined sources7
Beta strandi129 – 138Combined sources10
Beta strandi141 – 143Combined sources3
Beta strandi148 – 157Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ZJMX-ray2.85A/B/C/D/E/F/G48-159[»]
ProteinModelPortaliP9WK61.
SMRiP9WK61.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni41 – 60Prevents bacterial uptake by a human macrophage-like cell line1 PublicationAdd BLAST20

Domaini

Forms a U-shaped beta-half-barrel with a large hydrophobic cavity.1 Publication
A fragment of the mature protein (residues 41-60) prevents uptake of M.tuberculosis by a human macrophage-like cell line; lesser effects are seen on bacterial uptake by a human lung epithelial cell line.1 Publication

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

KOiK14953.
OMAiCSDMGGN.

Family and domain databases

InterProiView protein in InterPro
IPR008691. LpqH.
PfamiView protein in Pfam
PF05481. Myco_19_kDa. 1 hit.
PROSITEiView protein in PROSITE
PS51257. PROKAR_LIPOPROTEIN. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P9WK61-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKRGLTVAVA GAAILVAGLS GCSSNKSTTG SGETTTAAGT TASPGAASGP
60 70 80 90 100
KVVIDGKDQN VTGSVVCTTA AGNVNIAIGG AATGIAAVLT DGNPPEVKSV
110 120 130 140 150
GLGNVNGVTL GYTSGTGQGN ASATKDGSHY KITGTATGVD MANPMSPVNK

SFEIEVTCS
Length:159
Mass (Da):15,147
Last modified:April 16, 2014 - v1
Checksum:iCB1A5090E14867BB
GO

Mass spectrometryi

Molecular mass is 17300 Da from positions 22 - 159. Determined by MALDI. Expressed in M.bovis, lipidated.1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X07945 Genomic DNA. Translation: CAA30766.1.
J03838 Genomic DNA. Translation: AAA25353.1.
AL123456 Genomic DNA. Translation: CCP46590.1.
PIRiD70801.
RefSeqiNP_218280.1. NC_000962.3.
WP_003420544.1. NZ_KK339374.1.

Genome annotation databases

EnsemblBacteriaiCCP46590; CCP46590; Rv3763.
GeneIDi886097.
KEGGimtu:Rv3763.

Similar proteinsi

Entry informationi

Entry nameiLPQH_MYCTU
AccessioniPrimary (citable) accession number: P9WK61
Secondary accession number(s): L0TGP1, P0A5J0, P11572
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 16, 2014
Last sequence update: April 16, 2014
Last modified: September 27, 2017
This is version 25 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
    Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families