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Lipoprotein LpqH



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


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 apoptosis 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


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
Ordered Locus Names:Rv3763
ORF Names:MTV025.111
OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Taxonomic identifieri83332 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
  • UP000001584 Componenti: Chromosome

Organism-specific databases


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


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




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


Protein-protein interaction databases



Secondary structure

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 – 124Combined sources5
Beta strandi129 – 138Combined sources10
Beta strandi141 – 143Combined sources3
Beta strandi148 – 157Combined sources10

3D structure databases

Select the link destinations:
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum

Family & Domainsi


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


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


Phylogenomic databases


Family and domain databases

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


Sequence statusi: Complete.

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

P9WK61-1 [UniParc]FASTAAdd to basket

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Mass (Da):15,147
Last modified:April 16, 2014 - v1

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:
Links Updated
X07945 Genomic DNA. Translation: CAA30766.1.
J03838 Genomic DNA. Translation: AAA25353.1.
AL123456 Genomic DNA. Translation: CCP46590.1.
RefSeqiNP_218280.1. NC_000962.3.
WP_003420544.1. NZ_KK339374.1.

Genome annotation databases

EnsemblBacteriaiCCP46590; CCP46590; 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: January 31, 2018
This is version 28 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program


Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome