UniProtKB - P9WK61 (LPQH_MYCTU)
Protein
Lipoprotein LpqH
Gene
lpqH
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
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 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
Keywordsi
Biological process | Transport, Virulence |
Enzyme and pathway databases
BioCyci | MTBH37RV:G185E-8054-MONOMER |
Names & Taxonomyi
Protein namesi | Recommended name: Lipoprotein LpqHAlternative name(s): 19 kDa lipoprotein antigen Putative transporter LpqH1 Publication p191 Publication |
Gene namesi | Name:lpqH Ordered Locus Names:Rv3763 ORF Names:MTV025.111 |
Organismi | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
Taxonomic identifieri | 83332 [NCBI] |
Taxonomic lineagei | Bacteria › Actinobacteria › Corynebacteriales › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex › |
Proteomesi |
|
Organism-specific databases
TubercuListi | Rv3763 |
Subcellular locationi
- Cell membrane Curated1 Publication; Lipid-anchor 1 Publication
- cell wall 2 Publications
- Cell surface 2 Publications
- Secreted 1 Publication1 Publication
- bacterial extracellular vesicle 1 Publication
- Host cytoplasm 1 Publication Note: A soluble cell wall-associated protein (PubMed:10426995). Also found in culture filtrate in increasing quantities during growth (PubMed:1906192, PubMed:16098710). Following infection of mouse macrophage cell line J774A.1 with live (but not heat-killed) bacteria the protein is released in host cytoplasm at 1 hr but decreases dramatically by 3 hrs: release into the host requires protein lipidation and traffics from the immature phagosome through the host class I MHC antigen peptide presentation pathway (PubMed:11123323). Present in bacterial extracytoplasmic vesicles, both in mouse macrophages and in culture media (PubMed:21364279). Immunoelectron microscopy indicates this protein is close to the cell surface (PubMed:25041568).6 Publications
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, SecretedPathology & 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1 – 22 | MKRGL…GLSGC → M: Protein not exported from cytoplasm, not released into host cytoplasm (uses recombinant M.vaccae to infect mouse macrophages). 1 PublicationAdd BLAST | 22 | |
Mutagenesisi | 22 | C → A: Protein not released into host cytoplasm (uses recombinant M.vaccae to infect mouse macrophages). 1 Publication | 1 | |
Mutagenesisi | 34 – 41 | TTTAAGTT → 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 Publications | 8 | |
Mutagenesisi | 34 – 36 | TTT → VVV: Decreased ConA binding; altered protein processing yields 21 and 17 kDa forms in M.smegmatis. 1 Publication | 3 | |
Mutagenesisi | 40 – 41 | TT → VV: Decreased ConA binding; altered protein processing yields 21 and 16 kDa forms in M.smegmatis. 1 Publication | 2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | CuratedAdd BLAST | 21 | |
ChainiPRO_0000018128 | 22 – 159 | Lipoprotein LpqHAdd BLAST | 138 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Lipidationi | 22 | N-palmitoyl cysteine2 Publications | 1 | |
Lipidationi | 22 | S-diacylglycerol cysteine1 Publication | 1 | |
Disulfide bondi | 67 ↔ 158 | Combined 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, PalmitateProteomic databases
PaxDbi | P9WK61 |
Expressioni
Inductioni
Expressed in cell culture; expressed at a steady level for 4 days following infection of human mononuclear phagocytes.1 Publication
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P9WK61 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 41 – 60 | Prevents bacterial uptake by a human macrophage-like cell line1 PublicationAdd BLAST | 20 |
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
Belongs to the mycobacterial 19 kDa antigen family.Curated
Keywords - Domaini
SignalPhylogenomic databases
KOi | K14953 |
OMAi | CSDMGGN |
Family and domain databases
InterProi | View protein in InterPro IPR008691 LpqH |
Pfami | View protein in Pfam PF05481 Myco_19_kDa, 1 hit |
PROSITEi | View protein in PROSITE PS51257 PROKAR_LIPOPROTEIN, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P9WK61-1 [UniParc]FASTAAdd to basket
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
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 |
PIRi | D70801 |
RefSeqi | NP_218280.1, NC_000962.3 WP_003420544.1, NZ_NVQJ01000009.1 |
Genome annotation databases
EnsemblBacteriai | CCP46590; CCP46590; Rv3763 |
GeneIDi | 886097 |
KEGGi | mtu:Rv3763 mtv:RVBD_3763 |
Similar proteinsi
Cross-referencesi
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 |
PIRi | D70801 |
RefSeqi | NP_218280.1, NC_000962.3 WP_003420544.1, NZ_NVQJ01000009.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4ZJM | X-ray | 2.85 | A/B/C/D/E/F/G | 48-159 | [»] | |
SMRi | P9WK61 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 83332.Rv3763 |
Proteomic databases
PaxDbi | P9WK61 |
Genome annotation databases
EnsemblBacteriai | CCP46590; CCP46590; Rv3763 |
GeneIDi | 886097 |
KEGGi | mtu:Rv3763 mtv:RVBD_3763 |
Organism-specific databases
TubercuListi | Rv3763 |
Phylogenomic databases
KOi | K14953 |
OMAi | CSDMGGN |
Enzyme and pathway databases
BioCyci | MTBH37RV:G185E-8054-MONOMER |
Family and domain databases
InterProi | View protein in InterPro IPR008691 LpqH |
Pfami | View protein in Pfam PF05481 Myco_19_kDa, 1 hit |
PROSITEi | View protein in PROSITE PS51257 PROKAR_LIPOPROTEIN, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | LPQH_MYCTU | |
Accessioni | P9WK61Primary (citable) accession number: P9WK61 Secondary accession number(s): L0TGP1, P0A5J0, P11572 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 16, 2014 |
Last sequence update: | April 16, 2014 | |
Last modified: | November 13, 2019 | |
This is version 34 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names - PDB cross-references
Index of Protein Data Bank (PDB) cross-references