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P11836

- CD20_HUMAN

UniProt

P11836 - CD20_HUMAN

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Protein

B-lymphocyte antigen CD20

Gene

MS4A1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiP11836.
CleanExiHS_MS4A1.
ExpressionAtlasiP11836. baseline and differential.
GenevestigatoriP11836.

Organism-specific databases

HPAiCAB000015.
HPA014341.
HPA014391.

Interactioni

Protein-protein interaction databases

BioGridi107369. 12 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.
GeneTreeiENSGT00510000048781.
HOGENOMiHOG000111479.
HOVERGENiHBG048815.
InParanoidiP11836.
KOiK06466.
OMAiIVENEWK.
PhylomeDBiP11836.
TreeFamiTF335157.

Family and domain databases

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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P11836-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTTPRNSVNG TFPAEPMKGP IAMQSGPKPL FRRMSSLVGP TQSFFMRESK
60 70 80 90 100
TLGAVQIMNG LFHIALGGLL MIPAGIYAPI CVTVWYPLWG GIMYIISGSL
110 120 130 140 150
LAATEKNSRK CLVKGKMIMN SLSLFAAISG MILSIMDILN IKISHFLKME
160 170 180 190 200
SLNFIRAHTP YINIYNCEPA NPSEKNSPST QYCYSIQSLF LGILSVMLIF
210 220 230 240 250
AFFQELVIAG IVENEWKRTC SRPKSNIVLL SAEEKKEQTI EIKEEVVGLT
260 270 280 290
ETSSQPKNEE DIEIIPIQEE EEEETETNFP EPPQDQESSP IENDSSP
Length:297
Mass (Da):33,077
Last modified:October 1, 1989 - v1
Checksum:iAC5420F8B626BDD1
GO
Isoform 2 (identifier: P11836-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     38-204: Missing.

Note: No experimental confirmation available

Show »
Length:130
Mass (Da):14,581
Checksum:i7B38C8639E2D3744
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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei38 – 204167Missing in isoform 2. 1 PublicationVSP_057058Add
BLAST

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.
AP001034 Genomic DNA. No translation available.
AK300025 mRNA. Translation: BAG61836.1.
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.

Keywords - Coding sequence diversityi

Alternative splicing

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.
AP001034 Genomic DNA. No translation available.
AK300025 mRNA. Translation: BAG61836.1 .
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. 12 interactions.
IntActi P11836. 3 interactions.
STRINGi 9606.ENSP00000314620.

Chemistry

ChEMBLi CHEMBL2058.
DrugBanki DB00078. Ibritumomab.
DB08935. Obinutuzumab.
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.
GeneTreei ENSGT00510000048781.
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

Bgeei P11836.
CleanExi HS_MS4A1.
ExpressionAtlasi P11836. baseline and differential.
Genevestigatori P11836.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  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] (ISOFORM 1).
  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] (ISOFORM 1).
  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] (ISOFORM 1).
  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. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "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] (ISOFORM 1).
    Tissue: Lymph.
  9. Cited for: EPITOPE MAPPING, MUTAGENESIS OF THR-159; ASN-163; ASN-166; ALA-170 AND PRO-172.
  10. "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.
  11. Cited for: INVOLVEMENT IN CVID5.
  12. "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.
  13. "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
, B4DT24, P08984, Q13963
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: October 29, 2014
This is version 149 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

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