P11836 (CD20_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names 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

Name:	MS4A1
Synonyms:	CD20

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	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.

Ontologies

Keywords
Biological process	B-cell activation
Cellular component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
PTM	Disulfide bond Lipoprotein Palmitate 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 response Traceable author statement PubMed 7920628. Source: ProtInc
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement PubMed 1535625. Source: ProtInc nucleolus Inferred 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 – 56

56

Cytoplasmic Potential

Transmembrane

57 – 78

22

Helical; Potential

Topological domain

79 – 84

6

Extracellular Potential

Transmembrane

85 – 105

21

Helical; Potential

Topological domain

106 – 120

15

Cytoplasmic Potential

Transmembrane

121 – 141

21

Helical; Potential

Topological domain

142 – 188

47

Extracellular 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

Lipidation

111

1

S-palmitoyl cysteine Probable

Lipidation

220

1

S-palmitoyl cysteine Ref.11

Disulfide bond

167 ↔ 183

Ref.12

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

1

.

.

.

.

.

297

Helix Strand Turn

Details...

Helix

172 – 174

3

Helix

178 – 185

8

Sequences

	Sequence		Length	Mass (Da)
	P11836 [UniParc]. Last modified October 1, 1989. Version 1. Checksum: AC5420F8B626BDD1	FASTA	297	33,077
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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 , 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.

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

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	[»]

ProteinModelPortal

P11836.

ModBase

Search...

Protein-protein interaction databases

IntAct

P11836. 2 interactions.

STRING

9606.ENSP00000314620.

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

PaxDb

P11836.

PRIDE

P11836.

Protocols and materials databases

DNASU

931.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000345732; ENSP00000314620; ENSG00000156738.
ENST00000389939; ENSP00000374589; ENSG00000156738.
ENST00000524807; ENSP00000433179; ENSG00000156738.
ENST00000534668; ENSP00000433277; ENSG00000156738.

GeneID

931.

KEGG

hsa:931.

UCSC

uc001npp.3. human.

Organism-specific databases

CTD

931.

GeneCards

GC11P060225.

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

NOG43290.

HOGENOM

HOG000111479.

HOVERGEN

HBG048815.

InParanoid

P11836.

KO

K06466.

OMA

VMLIFAF.

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]

Pfam

PF04103. CD20. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL2058.

DrugBank

DB00078. Ibritumomab.
DB00073. Rituximab.
DB00081. Tositumomab.

EvolutionaryTrace

P11836.

GenomeRNAi

931.

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

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	October 1, 1989
Last modified:	May 1, 2013
This is version 134 of the entry and version 1 of the sequence. [Complete 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.