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P11836 (CD20_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:MS4A1
Synonyms:CD20
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length297 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell membrane; Lipid-anchor Ref.11.

Tissue specificity

Expressed on B-cells.

Post-translational modification

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

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Pharmaceutical use

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.

Sequence similarities

Belongs to the MS4A family.

Caution

Epitope 1, mapped in Ref.8, is predicted to be buried in the membrane. Its accessibility to the extracellular space, and thus to antibody recognition, is not explained.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 297297B-lymphocyte antigen CD20
PRO_0000158627

Regions

Topological domain1 – 5656Cytoplasmic Potential
Transmembrane57 – 7822Helical; Potential
Topological domain79 – 846Extracellular Potential
Transmembrane85 – 10521Helical; Potential
Topological domain106 – 12015Cytoplasmic Potential
Transmembrane121 – 14121Helical; Potential
Topological domain142 – 18847Extracellular Potential
Transmembrane189 – 20921Helical; Potential
Topological domain210 – 29788Cytoplasmic Potential
Region74 – 807Epitope 1
Region146 – 16015Epitope 2
Region168 – 1758Epitope 3 (recognized by antibodies, including Rituximab)

Amino acid modifications

Lipidation1111S-palmitoyl cysteine Probable
Lipidation2201S-palmitoyl cysteine Ref.11
Disulfide bond167 ↔ 183 Ref.12

Experimental info

Mutagenesis1591T → 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. Ref.8
Mutagenesis1631N → D: Decreased binding of some antibodies. No effect on rituximab binding. Ref.8
Mutagenesis1661N → D: Decreased binding of some antibodies. No effect on rituximab binding. Ref.8
Mutagenesis1701A → S: Abrogates recognition by therapeutic antibodies, including rituximab; when associated with S-172. Ref.8
Mutagenesis1721P → S: Marked reduction in rituximab binding. Abrogates recognition by antibodies, including rituximab; when associated with S-170. Ref.8
Sequence conflict131P → L in CAA30179. Ref.3
Sequence conflict131P → L in CAA30180. Ref.3
Sequence conflict711M → I in AAA88911. Ref.4

Secondary structure

..... 297
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P11836 [UniParc].

Last modified October 1, 1989. Version 1.
Checksum: AC5420F8B626BDD1

FASTA29733,077
        10         20         30         40         50         60 
MTTPRNSVNG TFPAEPMKGP IAMQSGPKPL FRRMSSLVGP TQSFFMRESK TLGAVQIMNG 

        70         80         90        100        110        120 
LFHIALGGLL MIPAGIYAPI CVTVWYPLWG GIMYIISGSL LAATEKNSRK CLVKGKMIMN 

       130        140        150        160        170        180 
SLSLFAAISG MILSIMDILN IKISHFLKME SLNFIRAHTP YINIYNCEPA NPSEKNSPST 

       190        200        210        220        230        240 
QYCYSIQSLF LGILSVMLIF AFFQELVIAG IVENEWKRTC SRPKSNIVLL SAEEKKEQTI 

       250        260        270        280        290 
EIKEEVVGLT ETSSQPKNEE DIEIIPIQEE EEEETETNFP EPPQDQESSP IENDSSP 

« Hide

References

« Hide 'large scale' references
[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]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20."
Teeling J.L., Mackus W.J.M., Wiegman L.J.J.M., van den Brakel J.H.N., Beers S.A., French R.R., van Meerten T., Ebeling S., Vink T., Slootstra J.W., Parren P.W.H.I., Glennie M.J., van de Winkel J.G.J.
J. Immunol. 177:362-371(2006) [PubMed] [Europe PMC] [Abstract]
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]"CD20 deficiency in humans results in impaired T cell-independent antibody responses."
Kuijpers T.W., Bende R.J., Baars P.A., Grummels A., Derks I.A.M., Dolman K.M., Beaumont T., Tedder T.F., van Noesel C.J.M., Eldering E., van Lier R.A.W.
J. Clin. Invest. 120:214-222(2010) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Wikipedia

CD20 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X12530 mRNA. Translation: CAA31046.1.
M27394 Genomic DNA. Translation: AAA35581.1.
X07203 mRNA. Translation: CAA30179.1.
X07204 mRNA. Translation: CAA30180.1.
L23419 expand/collapse EMBL AC list , 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.
CCDSCCDS31570.1.
PIRA30586.
RefSeqNP_068769.2. NM_021950.3.
NP_690605.1. NM_152866.2.
UniGeneHs.712553.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1S8Bmodel-A1-297[»]
2OSLX-ray2.60P/Q163-187[»]
3BKYX-ray2.61P163-187[»]
3PP4X-ray1.60P163-187[»]
ProteinModelPortalP11836.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107369. 9 interactions.
IntActP11836. 3 interactions.
STRING9606.ENSP00000314620.

Chemistry

ChEMBLCHEMBL2058.
DrugBankDB00078. Ibritumomab.
DB00073. Rituximab.
DB00081. Tositumomab.
GuidetoPHARMACOLOGY2628.

Protein family/group databases

TCDB1.A.37.1.1. the cd20 ca(2+) channel (cd20) family.

PTM databases

PhosphoSiteP11836.

Polymorphism databases

DMDM115968.

Proteomic databases

MaxQBP11836.
PaxDbP11836.
PRIDEP11836.

Protocols and materials databases

DNASU931.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000345732; ENSP00000314620; ENSG00000156738.
ENST00000389939; ENSP00000374589; ENSG00000156738.
ENST00000524807; ENSP00000433179; ENSG00000156738.
ENST00000534668; ENSP00000433277; ENSG00000156738.
GeneID931.
KEGGhsa:931.
UCSCuc001npp.3. human.

Organism-specific databases

CTD931.
GeneCardsGC11P060225.
HGNCHGNC:7315. MS4A1.
HPACAB000015.
HPA014341.
HPA014391.
MIM112210. gene.
613495. phenotype.
neXtProtNX_P11836.
Orphanet1572. Common variable immunodeficiency.
PharmGKBPA31111.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG43290.
HOGENOMHOG000111479.
HOVERGENHBG048815.
InParanoidP11836.
KOK06466.
OMAIVENEWK.
PhylomeDBP11836.
TreeFamTF335157.

Gene expression databases

ArrayExpressP11836.
BgeeP11836.
CleanExHS_MS4A1.
GenevestigatorP11836.

Family and domain databases

InterProIPR007237. CD20-like.
[Graphical view]
PfamPF04103. CD20. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP11836.
GeneWikiCD20.
GenomeRNAi931.
NextBio3860.
PROP11836.
SOURCESearch...

Entry information

Entry nameCD20_HUMAN
AccessionPrimary (citable) accession number: P11836
Secondary accession number(s): A6NMS4, P08984, Q13963
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: July 9, 2014
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries