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Entry version 114 (18 Sep 2019)
Sequence version 1 (01 Jul 1997)
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Protein

Outer membrane channel protein CpnT

Gene

cpnT

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

Has a dual function in uptake of nutrients and induction of host cell death. The N-terminal domain (NTD) forms an outer membrane channel and is used for uptake of nutrients across the outer membrane. The secreted C-terminal toxic domain (TNT) acts as a glycohydrolase, which hydrolyzes the essential cellular coenzyme NAD+ in the cytosol of infected macrophages, leading to necrotic host cell death. Both functions are required for survival, replication and cytotoxicity of M.tuberculosis in macrophages.2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<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

Glycohydrolase activity is completely inhibited by interaction with the immunity factor for TNT (IFT). This inhibition protects M.tuberculosis from self-poisoning.1 Publication

<p>This subsection of the ‘Function’ section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

kcat is 52 sec(-1).1 Publication
  1. KM=614 µM for NAD+1 Publication

    pH dependencei

    Optimum pH is 6.5.1 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

    Molecular functionHydrolase, Porin, Toxin
    Biological processIon transport, Transport, Virulence
    LigandNAD

    Enzyme and pathway databases

    BioCyc Collection of Pathway/Genome Databases

    More...
    BioCyci
    MTBH37RV:G185E-8201-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:
    Outer membrane channel protein CpnTCurated
    Alternative name(s):
    Channel protein with necrosis-inducing toxin1 Publication
    Cleaved into the following 2 chains:
    Tuberculosis necrotizing toxin1 Publication
    Short name:
    TNT1 Publication
    Alternative name(s):
    NAD(+) glycohydrolase1 Publication (EC:3.2.2.51 Publication)
    <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:cpnT1 Publication
    Ordered Locus Names:Rv3903cImported
    <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
    Rv3903c

    <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

    N-terminal channel domain :
    Tuberculosis necrotizing toxin :

    GO - Cellular componenti

    Keywords - Cellular componenti

    Cell outer membrane, Host cytoplasm, 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 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 reduces growth on glycerol and glucose as sole carbon sources. Deletion mutant does not replicate in differentiated THP-1 macrophages and lacks cytotoxicity (PubMed:24753609). Lack of cpnT does not increase drug resistance in vitro (PubMed:25645841). Deletion mutant does not decrease NAD+ levels in infected macrophages (PubMed:26237511).3 Publications

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi765Y → A: Decreases glycohydrolase activity and cytotoxicity in macrophages. 1 Publication1
    Mutagenesisi792H → N: Lack of glycohydrolase activity and of cytotoxicity; when associated with K-822. 1 Publication1
    Mutagenesisi818G → V: Unfolded. Lack of glycohydrolase activity. Abolishes toxicity. 2 Publications1
    Mutagenesisi822Q → A: 2-fold decrease in glycohydrolase activity. Intermediate cytotoxicity. 1 Publication1
    Mutagenesisi822Q → K: Lack of glycohydrolase activity and of cytotoxicity; when associated with N-792. 1 Publication1

    <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_00004377821 – 846Outer membrane channel protein CpnTAdd BLAST846
    ChainiPRO_00004377831 – ?N-terminal channel domainCurated
    ChainiPRO_0000437784? – 846Tuberculosis necrotizing toxinCurated

    <p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

    The C-terminal toxic domain is cleaved, probably after integration of CpnT into the outer membrane.1 Publication

    Proteomic databases

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

    More...
    PaxDbi
    O05442

    <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 the immunity factor for TNT (IFT) (PubMed:26237511). Oligomer formation is required for channel activity (PubMed:24753609).

    2 Publications

    <p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

    WithEntry#Exp.IntActNotes
    O054435EBI-16167127,EBI-16167151

    Protein-protein interaction databases

    Protein interaction database and analysis system

    More...
    IntActi
    O05442, 1 interactor

    STRING: functional protein association networks

    More...
    STRINGi
    83332.Rv3903c

    <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

    Secondary structure

    1846
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

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

    More...
    SMRi
    O05442

    Database of comparative protein structure models

    More...
    ModBasei
    Search...

    Protein Data Bank in Europe - Knowledge Base

    More...
    PDBe-KBi
    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

    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 – 443NTD1 PublicationAdd BLAST443
    Regioni651 – 846TNT2 PublicationsAdd BLAST196

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi2 – 229Ala-richPROSITE-ProRule annotationAdd BLAST228
    Compositional biasi445 – 586Pro-richPROSITE-ProRule annotationAdd BLAST142

    Keywords - Domaini

    Transmembrane, Transmembrane beta strand

    Phylogenomic databases

    The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

    More...
    HOGENOMi
    HOG000047781

    Identification of Orthologs from Complete Genome Data

    More...
    OMAi
    RNGLCSI

    Family and domain databases

    Integrated resource of protein families, domains and functional sites

    More...
    InterProi
    View protein in InterPro
    IPR025331 TNT

    Pfam protein domain database

    More...
    Pfami
    View protein in Pfam
    PF14021 TNT, 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.

    <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 in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

    O05442-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MAPLAVDPAA LDSAGGAVVA AGAGLGAVIS SLTAALAGCA GMAGDDPAGA
    60 70 80 90 100
    VFGRSYDGSA AALVQAMSVA RNGLCNLGDG VRMSAHNYSL AEAMSDVAGR
    110 120 130 140 150
    AAPLPAPPPS GCVGVGAPPS AVGGGGGAPK GWGWVAPYIG MIWPNGDSTK
    160 170 180 190 200
    LRAAAVAWRS AGTQFALTEI QSTAGPMGVI RAQQLPEAGL IESAFADAYA
    210 220 230 240 250
    STTAVVGQCH QLAAQLDAYA ARIDAVHAAV LDLLARICDP LTGIKEVWEF
    260 270 280 290 300
    LTDQDEDEIQ RIAHDIAVVV DQFSGEVDAL AAEITAVVSH AEAVITAMAD
    310 320 330 340 350
    HAGKQWDRFL HSNPVGVVID GTGQQLKGFG EEAFGMAKDS WDLGPLRASI
    360 370 380 390 400
    DPFGWYRSWE EMLTGMAPLA GLGGENAPGV VESWKQFGKS LIHWDEWTTN
    410 420 430 440 450
    PNEALGKTVF DAATLALPGG PLSKLGSKGR DILAGVRGLK ERLEPTTPHL
    460 470 480 490 500
    EPPATPPRPG PQPPRIEPPE SGHPAPAPAA KPAPVPANGP LPHSPTESKP
    510 520 530 540 550
    PPVDRPAEPV APSSASAGQP RVSAATTPGT HVPHGLPQPG EHVPAQAPPA
    560 570 580 590 600
    TTLLGGPPVE SAPATAHQPQ WATTPAAPAA APHSTPGGVH STESGPHGRS
    610 620 630 640 650
    LSAHGSEPTH DGASHGSGHG SGSEPPGLHA PHREQQLAMH SNEPAGEGWH
    660 670 680 690 700
    RLSDEAVDPQ YGEPLSRHWD FTDNPADRSR INPVVAQLME DPNAPFGRDP
    710 720 730 740 750
    QGQPYTQERY QERFNSVGPW GQQYSNFPPN NGAVPGTRIA YTNLEKFLSD
    760 770 780 790 800
    YGPQLDRIGG DQGKYLAIME HGRPASWEQR ALHVTSLRDP YHAYTIDWLP
    810 820 830 840
    EGWFIEVSEV APGCGQPGGS IQVRIFDHQN EMRKVEELIR RGVLRQ
    Length:846
    Mass (Da):88,335
    Last modified:July 1, 1997 - 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:iCB7DF1D77C7C9A25
    GO

    Sequence databases

    Select the link destinations:

    EMBL nucleotide sequence database

    More...
    EMBLi

    GenBank nucleotide sequence database

    More...
    GenBanki

    DNA Data Bank of Japan; a nucleotide sequence database

    More...
    DDBJi
    Links Updated
    AL123456 Genomic DNA Translation: CCP46732.1

    NCBI Reference Sequences

    More...
    RefSeqi
    NP_218420.1, NC_000962.3
    WP_003899759.1, NZ_NVQJ01000005.1

    Genome annotation databases

    Ensembl bacterial and archaeal genome annotation project

    More...
    EnsemblBacteriai
    CCP46732; CCP46732; Rv3903c

    Database of genes from NCBI RefSeq genomes

    More...
    GeneIDi
    886229

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...
    KEGGi
    mtu:Rv3903c
    mtv:RVBD_3903c

    Pathosystems Resource Integration Center (PATRIC)

    More...
    PATRICi
    fig|83332.111.peg.4347

    <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: CCP46732.1
    RefSeqiNP_218420.1, NC_000962.3
    WP_003899759.1, NZ_NVQJ01000005.1

    3D structure databases

    Select the link destinations:

    Protein Data Bank Europe

    More...
    PDBei

    Protein Data Bank RCSB

    More...
    RCSB PDBi

    Protein Data Bank Japan

    More...
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4QLPX-ray1.10B651-846[»]
    SMRiO05442
    ModBaseiSearch...
    PDBe-KBiSearch...

    Protein-protein interaction databases

    IntActiO05442, 1 interactor
    STRINGi83332.Rv3903c

    Proteomic databases

    PaxDbiO05442

    Genome annotation databases

    EnsemblBacteriaiCCP46732; CCP46732; Rv3903c
    GeneIDi886229
    KEGGimtu:Rv3903c
    mtv:RVBD_3903c
    PATRICifig|83332.111.peg.4347

    Organism-specific databases

    TubercuListiRv3903c

    Phylogenomic databases

    HOGENOMiHOG000047781
    OMAiRNGLCSI

    Enzyme and pathway databases

    BioCyciMTBH37RV:G185E-8201-MONOMER

    Family and domain databases

    InterProiView protein in InterPro
    IPR025331 TNT
    PfamiView protein in Pfam
    PF14021 TNT, 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 nameiCPNT_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: O05442
    Secondary accession number(s): F2GDR4, I6Y4T3, Q7D4M4
    <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: November 2, 2016
    Last sequence update: July 1, 1997
    Last modified: September 18, 2019
    This is version 114 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

    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
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