P11836 (CD20_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 119.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | 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 names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 297 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | This protein may be involved in the regulation of B-cell activation and proliferation. |
| Subcellular location | |
| Tissue specificity | Expressed on B-cells. |
| Post-translational modification | Phosphorylated. Might be functionally regulated by protein kinase(s). Ref.9 |
| Involvement in disease | Defects in MS4A1 are the cause of immunodeficiency common variable type 5 (CVID5) [MIM:613495]; also called antibody deficiency due to CD20 defect. CVID5 is 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. 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. |
Ontologies
| Keywords | |
|---|---|
| Biological process | B-cell activation |
| Cellular component | Membrane |
| Domain | Transmembrane Transmembrane helix |
| PTM | Disulfide bond Phosphoprotein |
| Technical term | 3D-structure Complete proteome Pharmaceutical Reference proteome |
| Gene Ontology (GO) | |
| Biological process | B cell activation Inferred from electronic annotation. Source: UniProtKB-KW immune responseTraceable author statement. Source: ProtInc |
| Cellular component | integral to plasma membrane Traceable author statement. Source: ProtInc nucleolusInferred from direct assay. Source: HPA |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||
Molecule processing | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 297 | 297 | B-lymphocyte antigen CD20 | PRO_0000158627 | |||||||||
Regions | |||||||||||||
| Topological domain | 1 – 63 | 63 | Cytoplasmic Potential | ||||||||||
| Transmembrane | 64 – 84 | 21 | Helical; Potential | ||||||||||
| Transmembrane | 85 – 105 | 21 | Helical; Potential | ||||||||||
| Transmembrane | 121 – 141 | 21 | Helical; Potential | ||||||||||
| Transmembrane | 189 – 209 | 21 | Helical; Potential | ||||||||||
| Topological domain | 210 – 297 | 88 | Cytoplasmic Potential | ||||||||||
| Region | 74 – 80 | 7 | Epitope 1 | ||||||||||
| Region | 146 – 160 | 15 | Epitope 2 | ||||||||||
| Region | 168 – 175 | 8 | Epitope 3 (recognized by antibodies, including Rituximab) | ||||||||||
Amino acid modifications | |||||||||||||
| Modified residue | 35 | 1 | Phosphoserine Ref.9 | ||||||||||
| Modified residue | 36 | 1 | Phosphoserine Ref.9 | ||||||||||
| Disulfide bond | 111 ↔ 220 | Probable | |||||||||||
Experimental info | |||||||||||||
| Mutagenesis | 159 | 1 | T → 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 | ||||||||||
| Mutagenesis | 163 | 1 | N → D: Decreased binding of some antibodies. No effect on rituximab binding. Ref.8 | ||||||||||
| Mutagenesis | 166 | 1 | N → D: Decreased binding of some antibodies. No effect on rituximab binding. Ref.8 | ||||||||||
| Mutagenesis | 170 | 1 | A → S: Abrogates recognition by therapeutic antibodies, including rituximab; when associated with S-172. Ref.8 | ||||||||||
| Mutagenesis | 172 | 1 | P → S: Marked reduction in rituximab binding. Abrogates recognition by antibodies, including rituximab; when associated with S-170. Ref.8 | ||||||||||
| Sequence conflict | 13 | 1 | P → L in CAA30179. Ref.3 | ||||||||||
| Sequence conflict | 13 | 1 | P → L in CAA30180. Ref.3 | ||||||||||
| Sequence conflict | 71 | 1 | M → I in AAA88911. Ref.4 | ||||||||||
Secondary structure | |||||||||||||
Helix Strand Turn | |||||||||||||
| Helix | 172 – 174 | 3 | |||||||||||
| Helix | 178 – 184 | 7 | |||||||||||
Sequences
| ||||||||||||||||||
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: 3260267] [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: 2448768] [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: 2456210] [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: 2466899] [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. Sakaki Y.Nature 440:497-500(2006) [PubMed: 16554811] [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. 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: 15489334] [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: 16785532] [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: 19367720] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35 AND SER-36, MASS SPECTROMETRY. 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: 20038800] [Abstract] Cited for: INVOLVEMENT IN CVID5. |
| + | 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 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. | ||||||||||||||||||||||||||||||
| IPI | IPI00007880. | ||||||||||||||||||||||||||||||
| PIR | A30586. | ||||||||||||||||||||||||||||||
| RefSeq | NP_068769.2. NM_021950.3. NP_690605.1. NM_152866.2. | ||||||||||||||||||||||||||||||
| UniGene | Hs.712553. | ||||||||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||||||||||||||||||||
| ProteinModelPortal | P11836. | ||||||||||||||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||||||||
| IntAct | P11836. 2 interactions. | ||||||||||||||||||||||||||||||
| STRING | P11836. | ||||||||||||||||||||||||||||||
Protein family/group databases | |||||||||||||||||||||||||||||||
| TCDB | 1.A.37.1.1. CD20 Ca2+ channel (CD20) family. | ||||||||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||||||||
| PhosphoSite | P11836. | ||||||||||||||||||||||||||||||
Polymorphism databases | |||||||||||||||||||||||||||||||
| DMDM | 115968. | ||||||||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||||||||
| PRIDE | P11836. | ||||||||||||||||||||||||||||||
Protocols and materials databases | |||||||||||||||||||||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||||||||
| Ensembl | ENST00000345732; ENSP00000314620; ENSG00000156738. ENST00000389939; ENSP00000374589; ENSG00000156738. | ||||||||||||||||||||||||||||||
| GeneID | 931. | ||||||||||||||||||||||||||||||
| KEGG | hsa:931. | ||||||||||||||||||||||||||||||
| UCSC | uc001npp.1. human. | ||||||||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||||||||
| CTD | 931. | ||||||||||||||||||||||||||||||
| GeneCards | GC11P060225. | ||||||||||||||||||||||||||||||
| H-InvDB | HIX0009670. | ||||||||||||||||||||||||||||||
| HGNC | HGNC:7315. MS4A1. | ||||||||||||||||||||||||||||||
| HPA | CAB000015. HPA014341. HPA014391. | ||||||||||||||||||||||||||||||
| MIM | 112210. gene. 613495. phenotype. | ||||||||||||||||||||||||||||||
| neXtProt | NX_P11836. | ||||||||||||||||||||||||||||||
| Orphanet | 99831. Common variable immunodeficiency due to an intrinsic T cell defect. | ||||||||||||||||||||||||||||||
| PharmGKB | PA31111. | ||||||||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||||||||
| eggNOG | prNOG05555. | ||||||||||||||||||||||||||||||
| GeneTree | ENSGT00510000048781. | ||||||||||||||||||||||||||||||
| HOGENOM | HBG282650. | ||||||||||||||||||||||||||||||
| HOVERGEN | HBG048815. | ||||||||||||||||||||||||||||||
| InParanoid | P11836. | ||||||||||||||||||||||||||||||
| OMA | FFMRESK. | ||||||||||||||||||||||||||||||
| OrthoDB | EOG4MW86T. | ||||||||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||||||||
| ArrayExpress | P11836. | ||||||||||||||||||||||||||||||
| Bgee | P11836. | ||||||||||||||||||||||||||||||
| CleanEx | HS_MS4A1. | ||||||||||||||||||||||||||||||
| Genevestigator | P11836. | ||||||||||||||||||||||||||||||
| GermOnline | ENSG00000156738. Homo sapiens. | ||||||||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||||||||
| InterPro | IPR007237. CD20-like. [Graphical view] | ||||||||||||||||||||||||||||||
| KO | K06466. | ||||||||||||||||||||||||||||||
| Pfam | PF04103. CD20. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||||||||
Other | |||||||||||||||||||||||||||||||
| DrugBank | DB00078. Ibritumomab. DB00073. Rituximab. DB00081. Tositumomab. | ||||||||||||||||||||||||||||||
| NextBio | 3860. | ||||||||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||||||||
Entry information
| Entry name | CD20_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P11836 Secondary accession number(s): A6NMS4, P08984, Q13963 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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
| Human cell differentiation molecules CD nomenclature of surface proteins of human leucocytes and list of entries |
| Human chromosome 11 Human chromosome 11: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with