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Entry version 28 (16 Oct 2019)
Sequence version 1 (16 Apr 2014)
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Protein

PE-PGRS family protein PE_PGRS33

Gene

PE_PGRS33

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Induces TNF-alpha release through human Toll-like receptor 2 (TLR2) signaling pathway, leading to macrophage apoptosis (PubMed:17095513, PubMed:17223373, PubMed:24106104). The signaling pathway involves TLR2-dependent activation of the mitogen-activated protein kinase kinase kinase 5 (ASK1), which activates the p38 and JNK MAPKs, leading to enhanced expression of TNF-alpha and tumor necrosis factor receptor superfamily member 1A (TNFRI) genes. Signals are amplified through classical caspase 8-dependent mitochondrial release of cytochrome c, leading to the activation of caspases 9 and 3 (PubMed:17095513). Mediates Ca2+-dependent up-regulation of the anti-inflammatory cytokine IL-10 (PubMed:27483162). Mediates entry into macrophages in a TLR2-dependent mechanism and activates the TLR2-dependent pro-adhesive pathway (PubMed:26978522).5 Publications

Miscellaneous

Expression of this gene in M.smegmatis leads to low levels of NO and IL-12, increased level of IL-10 and better survival of recombinant strains in macrophages.1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Binding of Ca2+ to PE_PGRS33 induces conformational changes and increases affinity for TLR2.1 Publication

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processVirulence
LigandCalcium

Enzyme and pathway databases

BioCyc Collection of Pathway/Genome Databases

More...
BioCyci
MTBH37RV:G185E-6013-MONOMER

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
PE-PGRS family protein PE_PGRS33Curated
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:PE_PGRS33Imported
Ordered Locus Names:Rv1818cImported
ORF Names:MTCY1A11.25c
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri83332 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000001584 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome

Organism-specific databases

Mycobacterium tuberculosis strain H37Rv genome database

More...
TubercuListi
Rv1818c

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Cell outer membrane, Cell wall, Membrane, Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section describes the use of a specific protein in the biotechnological industry.<p><a href='/help/biotechnological_use' target='_top'>More...</a></p>Biotechnological usei

PE domain induces protective cellular immune response and PGRS domain induces humoral immune response during infection in mice, suggesting that this protein is a promising candidate for the development of M.tuberculosis vaccines (PubMed:11500435). Immunization of mice with the PE_PGRS33 protein stimulated CD4+ and CD8+ T-cell proliferation as well as IFN-gamma secretion, supporting the potential use of PE_PGRS33 as a vaccine candidate for tuberculosis (PubMed:24904584). Elicits a strong B-cell humoral response among different clinical categories of both adult and child tuberculosis patients, indicating that it could be used in the serodiagnosis of tuberculosis (PubMed:17687113).3 Publications

<p>This subsection of the ‘Pathology and Biotech’ section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

Deletion mutant is strongly impaired in its ability to enter macrophages. Deletion does not affect the intracellular growth in macrophages.1 Publication

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00002161641 – 498PE-PGRS family protein PE_PGRS33Add BLAST498

Proteomic databases

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
P9WIF5

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Constitutively expressed in vitro, suggesting that it could be an essential gene (PubMed:11967065, PubMed:16672626). Expression is regulated by SigA. Down-regulated during stationary phase, under nutrient starvation and oxygen depletion (PubMed:19068228).3 Publications

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with human TLR2.

3 Publications

Protein-protein interaction databases

STRING: functional protein association networks

More...
STRINGi
83332.Rv1818c

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P9WIF5

Database of comparative protein structure models

More...
ModBasei
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini1 – 93PESequence analysisAdd BLAST93

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 30Essential for translocation to the cell surface1 PublicationAdd BLAST30
Regioni140 – 260Interacts with TLR21 PublicationAdd BLAST121

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

Contains an N-terminal PE domain, followed by a conserved linker region and a C-terminal PGRS domain (PubMed:18028308, PubMed:21081760). The PE domain is responsible for the export and localization to the cell wall (PubMed:15101979, PubMed:18028308, PubMed:22110736). The PGRS domain is required for TNF-alpha secretion and is responsible for the main immunomodulatory properties of the protein (PubMed:17095513, PubMed:24106104). Variations within the PGRS domain alter the levels of TNF-alpha induction and are likely to have an impact on the innate immune response (PubMed:17095513). PGRS domain is also required to mediate cell entry into macrophages (PubMed:26978522). Colocalization to the mitochondria of host cells is dependent on the linker region and the PGRS domain, but not the PE domain (PubMed:21081760).7 Publications

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the mycobacterial PE family. PGRS subfamily.Curated

Phylogenomic databases

Identification of Orthologs from Complete Genome Data

More...
OMAi
DQYANQN

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR000084 PE-PGRS_N

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00934 PE, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

P9WIF5-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSFVVTIPEA LAAVATDLAG IGSTIGTANA AAAVPTTTVL AAAADEVSAA
60 70 80 90 100
MAALFSGHAQ AYQALSAQAA LFHEQFVRAL TAGAGSYAAA EAASAAPLEG
110 120 130 140 150
VLDVINAPAL ALLGRPLIGN GANGAPGTGA NGGDGGILIG NGGAGGSGAA
160 170 180 190 200
GMPGGNGGAA GLFGNGGAGG AGGNVASGTA GFGGAGGAGG LLYGAGGAGG
210 220 230 240 250
AGGRAGGGVG GIGGAGGAGG NGGLLFGAGG AGGVGGLAAD AGDGGAGGDG
260 270 280 290 300
GLFFGVGGAG GAGGTGTNVT GGAGGAGGNG GLLFGAGGVG GVGGDGVAFL
310 320 330 340 350
GTAPGGPGGA GGAGGLFGVG GAGGAGGIGL VGNGGAGGSG GSALLWGDGG
360 370 380 390 400
AGGAGGVGST TGGAGGAGGN AGLLVGAGGA GGAGALGGGA TGVGGAGGNG
410 420 430 440 450
GTAGLLFGAG GAGGFGFGGA GGAGGLGGKA GLIGDGGDGG AGGNGTGAKG
460 470 480 490
GDGGAGGGAI LVGNGGNGGN AGSGTPNGSA GTGGAGGLLG KNGMNGLP
Length:498
Mass (Da):40,755
Last modified:April 16, 2014 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i4F6F78F2482586BA
GO

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
AL123456 Genomic DNA Translation: CCP44584.1

Protein sequence database of the Protein Information Resource

More...
PIRi
C70720

NCBI Reference Sequences

More...
RefSeqi
WP_010886133.1, NZ_KK339370.1
YP_177846.1, NC_000962.3

Genome annotation databases

Ensembl bacterial and archaeal genome annotation project

More...
EnsemblBacteriai
CCP44584; CCP44584; Rv1818c

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
885551

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
mtu:Rv1818c
mtv:RVBD_1818c

Pathosystems Resource Integration Center (PATRIC)

More...
PATRICi
fig|83332.111.peg.2023

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL123456 Genomic DNA Translation: CCP44584.1
PIRiC70720
RefSeqiWP_010886133.1, NZ_KK339370.1
YP_177846.1, NC_000962.3

3D structure databases

SMRiP9WIF5
ModBaseiSearch...

Protein-protein interaction databases

STRINGi83332.Rv1818c

Proteomic databases

PaxDbiP9WIF5

Genome annotation databases

EnsemblBacteriaiCCP44584; CCP44584; Rv1818c
GeneIDi885551
KEGGimtu:Rv1818c
mtv:RVBD_1818c
PATRICifig|83332.111.peg.2023

Organism-specific databases

TubercuListiRv1818c

Phylogenomic databases

OMAiDQYANQN

Enzyme and pathway databases

BioCyciMTBH37RV:G185E-6013-MONOMER

Family and domain databases

InterProiView protein in InterPro
IPR000084 PE-PGRS_N
PfamiView protein in Pfam
PF00934 PE, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiPG33_MYCTU
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P9WIF5
Secondary accession number(s): L0TAP6, Q50615
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 16, 2014
Last sequence update: April 16, 2014
Last modified: October 16, 2019
This is version 28 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
    Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
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