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P11836

- CD20_HUMAN

UniProt

P11836 - CD20_HUMAN

Protein

B-lymphocyte antigen CD20

Gene

MS4A1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 148 (01 Oct 2014)
      Sequence version 1 (01 Oct 1989)
      Previous versions | rss
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    Functioni

    This protein may be involved in the regulation of B-cell activation and proliferation.

    GO - Molecular functioni

    1. MHC class II protein complex binding Source: UniProt

    GO - Biological processi

    1. B cell proliferation Source: UniProt
    2. humoral immune response Source: UniProt

    Keywords - Biological processi

    B-cell activation

    Protein family/group databases

    TCDBi1.A.37.1.1. the cd20 ca(2+) channel (cd20) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    B-lymphocyte antigen CD20
    Alternative name(s):
    B-lymphocyte surface antigen B1
    Bp35
    Leukocyte surface antigen Leu-16
    Membrane-spanning 4-domains subfamily A member 1
    CD_antigen: CD20
    Gene namesi
    Name:MS4A1
    Synonyms:CD20
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:7315. MS4A1.

    Subcellular locationi

    Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication. Cell membrane 1 Publication; Lipid-anchor 1 Publication

    GO - Cellular componenti

    1. external side of plasma membrane Source: Ensembl
    2. extracellular space Source: UniProt
    3. extracellular vesicular exosome Source: UniProt
    4. integral component of plasma membrane Source: UniProt

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Immunodeficiency, common variable, 5 (CVID5) [MIM:613495]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Pharmaceutical usei

    Monoclonal antibodies (mAb) against CD20 are used to treat B-cell non-Hodgkin lymphoma (NHL). These antibodies include Rituximab (Mabthera), Britumomab (Zevalin) and Tositumomab (Bexxar). CD20 engaged by mAb can generate transmembrane signals capable of directly controlling cell growth and triggering cell death in certain tumors. Alternatively, mAb can mediate complement-dependent cytotoxicity.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi159 – 1591T → K: Abrogates recognition by some antibodies; when associated with D-163 and D-166. Slight decrease of rituximab binding; when associated with D-163 and D-166. 1 Publication
    Mutagenesisi163 – 1631N → D: Decreased binding of some antibodies. No effect on rituximab binding. 1 Publication
    Mutagenesisi166 – 1661N → D: Decreased binding of some antibodies. No effect on rituximab binding. 1 Publication
    Mutagenesisi170 – 1701A → S: Abrogates recognition by therapeutic antibodies, including rituximab; when associated with S-172. 1 Publication
    Mutagenesisi172 – 1721P → S: Marked reduction in rituximab binding. Abrogates recognition by antibodies, including rituximab; when associated with S-170. 1 Publication

    Organism-specific databases

    MIMi613495. phenotype.
    Orphaneti1572. Common variable immunodeficiency.
    PharmGKBiPA31111.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 297297B-lymphocyte antigen CD20PRO_0000158627Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi111 – 1111S-palmitoyl cysteine1 Publication
    Disulfide bondi167 ↔ 1831 Publication
    Lipidationi220 – 2201S-palmitoyl cysteine1 Publication

    Post-translational modificationi

    Phosphorylated. Might be functionally regulated by protein kinase(s).

    Keywords - PTMi

    Disulfide bond, Lipoprotein, Palmitate, Phosphoprotein

    Proteomic databases

    MaxQBiP11836.
    PaxDbiP11836.
    PRIDEiP11836.

    PTM databases

    PhosphoSiteiP11836.

    Expressioni

    Tissue specificityi

    Expressed on B-cells.

    Gene expression databases

    ArrayExpressiP11836.
    BgeeiP11836.
    CleanExiHS_MS4A1.
    GenevestigatoriP11836.

    Organism-specific databases

    HPAiCAB000015.
    HPA014341.
    HPA014391.

    Interactioni

    Protein-protein interaction databases

    BioGridi107369. 11 interactions.
    IntActiP11836. 3 interactions.
    STRINGi9606.ENSP00000314620.

    Structurei

    Secondary structure

    1
    297
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi172 – 1743
    Helixi178 – 1858

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1S8Bmodel-A1-297[»]
    2OSLX-ray2.60P/Q163-187[»]
    3BKYX-ray2.61P163-187[»]
    3PP4X-ray1.60P163-187[»]
    ProteinModelPortaliP11836.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP11836.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 5656CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini79 – 846ExtracellularSequence Analysis
    Topological domaini106 – 12015CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini142 – 18847ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini210 – 29788CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei57 – 7822HelicalSequence AnalysisAdd
    BLAST
    Transmembranei85 – 10521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei121 – 14121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei189 – 20921HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni74 – 807Epitope 1
    Regioni146 – 16015Epitope 2Add
    BLAST
    Regioni168 – 1758Epitope 3 (recognized by antibodies, including Rituximab)

    Sequence similaritiesi

    Belongs to the MS4A family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG43290.
    HOGENOMiHOG000111479.
    HOVERGENiHBG048815.
    InParanoidiP11836.
    KOiK06466.
    OMAiIVENEWK.
    PhylomeDBiP11836.
    TreeFamiTF335157.

    Family and domain databases

    InterProiIPR007237. CD20-like.
    [Graphical view]
    PfamiPF04103. CD20. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P11836-1 [UniParc]FASTAAdd to Basket

    « Hide

    MTTPRNSVNG TFPAEPMKGP IAMQSGPKPL FRRMSSLVGP TQSFFMRESK    50
    TLGAVQIMNG LFHIALGGLL MIPAGIYAPI CVTVWYPLWG GIMYIISGSL 100
    LAATEKNSRK CLVKGKMIMN SLSLFAAISG MILSIMDILN IKISHFLKME 150
    SLNFIRAHTP YINIYNCEPA NPSEKNSPST QYCYSIQSLF LGILSVMLIF 200
    AFFQELVIAG IVENEWKRTC SRPKSNIVLL SAEEKKEQTI EIKEEVVGLT 250
    ETSSQPKNEE DIEIIPIQEE EEEETETNFP EPPQDQESSP IENDSSP 297
    Length:297
    Mass (Da):33,077
    Last modified:October 1, 1989 - v1
    Checksum:iAC5420F8B626BDD1
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti13 – 131P → L in CAA30179. (PubMed:2456210)Curated
    Sequence conflicti13 – 131P → L in CAA30180. (PubMed:2456210)Curated
    Sequence conflicti71 – 711M → I in AAA88911. (PubMed:2466899)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X12530 mRNA. Translation: CAA31046.1.
    M27394 Genomic DNA. Translation: AAA35581.1.
    X07203 mRNA. Translation: CAA30179.1.
    X07204 mRNA. Translation: CAA30180.1.
    L23419
    , L23415, L23416, L23417 Genomic DNA. Translation: AAA88911.1.
    M27395 Genomic DNA. No translation available.
    AP003127 Genomic DNA. No translation available.
    CH471076 Genomic DNA. Translation: EAW73889.1.
    BC002807 mRNA. Translation: AAH02807.1.
    CCDSiCCDS31570.1.
    PIRiA30586.
    RefSeqiNP_068769.2. NM_021950.3.
    NP_690605.1. NM_152866.2.
    UniGeneiHs.712553.

    Genome annotation databases

    EnsembliENST00000345732; ENSP00000314620; ENSG00000156738.
    ENST00000389939; ENSP00000374589; ENSG00000156738.
    ENST00000524807; ENSP00000433179; ENSG00000156738.
    ENST00000534668; ENSP00000433277; ENSG00000156738.
    GeneIDi931.
    KEGGihsa:931.
    UCSCiuc001npp.3. human.

    Polymorphism databases

    DMDMi115968.

    Cross-referencesi

    Web resourcesi

    Wikipedia

    CD20 entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X12530 mRNA. Translation: CAA31046.1 .
    M27394 Genomic DNA. Translation: AAA35581.1 .
    X07203 mRNA. Translation: CAA30179.1 .
    X07204 mRNA. Translation: CAA30180.1 .
    L23419
    , L23415 , L23416 , L23417 Genomic DNA. Translation: AAA88911.1 .
    M27395 Genomic DNA. No translation available.
    AP003127 Genomic DNA. No translation available.
    CH471076 Genomic DNA. Translation: EAW73889.1 .
    BC002807 mRNA. Translation: AAH02807.1 .
    CCDSi CCDS31570.1.
    PIRi A30586.
    RefSeqi NP_068769.2. NM_021950.3.
    NP_690605.1. NM_152866.2.
    UniGenei Hs.712553.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1S8B model - A 1-297 [» ]
    2OSL X-ray 2.60 P/Q 163-187 [» ]
    3BKY X-ray 2.61 P 163-187 [» ]
    3PP4 X-ray 1.60 P 163-187 [» ]
    ProteinModelPortali P11836.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107369. 11 interactions.
    IntActi P11836. 3 interactions.
    STRINGi 9606.ENSP00000314620.

    Chemistry

    ChEMBLi CHEMBL2058.
    DrugBanki DB00078. Ibritumomab.
    DB00073. Rituximab.
    DB00081. Tositumomab.
    GuidetoPHARMACOLOGYi 2628.

    Protein family/group databases

    TCDBi 1.A.37.1.1. the cd20 ca(2+) channel (cd20) family.

    PTM databases

    PhosphoSitei P11836.

    Polymorphism databases

    DMDMi 115968.

    Proteomic databases

    MaxQBi P11836.
    PaxDbi P11836.
    PRIDEi P11836.

    Protocols and materials databases

    DNASUi 931.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000345732 ; ENSP00000314620 ; ENSG00000156738 .
    ENST00000389939 ; ENSP00000374589 ; ENSG00000156738 .
    ENST00000524807 ; ENSP00000433179 ; ENSG00000156738 .
    ENST00000534668 ; ENSP00000433277 ; ENSG00000156738 .
    GeneIDi 931.
    KEGGi hsa:931.
    UCSCi uc001npp.3. human.

    Organism-specific databases

    CTDi 931.
    GeneCardsi GC11P060225.
    HGNCi HGNC:7315. MS4A1.
    HPAi CAB000015.
    HPA014341.
    HPA014391.
    MIMi 112210. gene.
    613495. phenotype.
    neXtProti NX_P11836.
    Orphaneti 1572. Common variable immunodeficiency.
    PharmGKBi PA31111.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG43290.
    HOGENOMi HOG000111479.
    HOVERGENi HBG048815.
    InParanoidi P11836.
    KOi K06466.
    OMAi IVENEWK.
    PhylomeDBi P11836.
    TreeFami TF335157.

    Miscellaneous databases

    EvolutionaryTracei P11836.
    GeneWikii CD20.
    GenomeRNAii 931.
    NextBioi 3860.
    PROi P11836.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P11836.
    Bgeei P11836.
    CleanExi HS_MS4A1.
    Genevestigatori P11836.

    Family and domain databases

    InterProi IPR007237. CD20-like.
    [Graphical view ]
    Pfami PF04103. CD20. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Analysis of two cDNA clones encoding the B lymphocyte antigen CD20 (B1, Bp35), a type III integral membrane protein."
      Stamenkovic I., Seed B.
      J. Exp. Med. 167:1975-1980(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Isolation and structure of a cDNA encoding the B1 (CD20) cell-surface antigen of human B lymphocytes."
      Tedder T.F., Streuli M., Schlossman S.F., Saito H.
      Proc. Natl. Acad. Sci. U.S.A. 85:208-212(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Molecular cloning of the human B cell CD20 receptor predicts a hydrophobic protein with multiple transmembrane domains."
      Einfeld D.A., Brown J.P., Valentine M.A., Clark E.A., Ledbetter J.A.
      EMBO J. 7:711-717(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "Structure of the gene encoding the human B lymphocyte differentiation antigen CD20 (B1)."
      Tedder T.F., Klejman G., Schlossman S.F., Saito H.
      J. Immunol. 142:2560-2568(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Lymph.
    8. Cited for: EPITOPE MAPPING, MUTAGENESIS OF THR-159; ASN-163; ASN-166; ALA-170 AND PRO-172.
    9. "Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment."
      Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.
      J. Proteome Res. 7:5167-5176(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: T-cell.
    10. Cited for: INVOLVEMENT IN CVID5.
    11. "Proteomic analysis of S-acylated proteins in human B cells reveals palmitoylation of the immune regulators CD20 and CD23."
      Ivaldi C., Martin B.R., Kieffer-Jaquinod S., Chapel A., Levade T., Garin J., Journet A.
      PLoS ONE 7:E37187-E37187(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: PALMITOYLATION AT CYS-111 AND CYS-220, TOPOLOGY, SUBCELLULAR LOCATION.
      Tissue: B-cell.
    12. "Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for type I/II distinction of CD20 antibodies."
      Niederfellner G., Lammens A., Mundigl O., Georges G.J., Schaefer W., Schwaiger M., Franke A., Wiechmann K., Jenewein S., Slootstra J.W., Timmerman P., Brannstrom A., Lindstrom F., Mossner E., Umana P., Hopfner K.P., Klein C.
      Blood 118:358-367(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 163-187 IN COMPLEX WITH ANTIBODY, DISULFIDE BOND.

    Entry informationi

    Entry nameiCD20_HUMAN
    AccessioniPrimary (citable) accession number: P11836
    Secondary accession number(s): A6NMS4, P08984, Q13963
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: October 1, 1989
    Last modified: October 1, 2014
    This is version 148 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Caution

    Epitope 1, mapped in PubMed:16785532, is predicted to be buried in the membrane. Its accessibility to the extracellular space, and thus to antibody recognition, is not explained.Curated

    Keywords - Technical termi

    3D-structure, Complete proteome, Pharmaceutical, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3