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Protein

B-lymphocyte antigen CD20

Gene

MS4A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

  • MHC class II protein complex binding Source: UniProtKB

GO - Biological processi

  • B cell proliferation Source: UniProtKB
  • humoral immune response Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

B-cell activation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000156738-MONOMER.
SIGNORiP11836.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:7315. MS4A1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 56CytoplasmicSequence analysisAdd BLAST56
Transmembranei57 – 78HelicalSequence analysisAdd BLAST22
Topological domaini79 – 84ExtracellularSequence analysis6
Transmembranei85 – 105HelicalSequence analysisAdd BLAST21
Topological domaini106 – 120CytoplasmicSequence analysisAdd BLAST15
Transmembranei121 – 141HelicalSequence analysisAdd BLAST21
Topological domaini142 – 188ExtracellularSequence analysisAdd BLAST47
Transmembranei189 – 209HelicalSequence analysisAdd BLAST21
Topological domaini210 – 297CytoplasmicSequence analysisAdd BLAST88

GO - Cellular componenti

  • external side of plasma membrane Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency, common variable, 5 (CVID5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613495

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)DescriptionActionsGraphical viewLength
Mutagenesisi159T → 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 Publication1
Mutagenesisi163N → D: Decreased binding of some antibodies. No effect on rituximab binding. 1 Publication1
Mutagenesisi166N → D: Decreased binding of some antibodies. No effect on rituximab binding. 1 Publication1
Mutagenesisi170A → S: Abrogates recognition by therapeutic antibodies, including rituximab; when associated with S-172. 1 Publication1
Mutagenesisi172P → S: Marked reduction in rituximab binding. Abrogates recognition by antibodies, including rituximab; when associated with S-170. 1 Publication1

Organism-specific databases

DisGeNETi931.
MalaCardsiMS4A1.
MIMi613495. phenotype.
OpenTargetsiENSG00000156738.
Orphaneti1572. Common variable immunodeficiency.
PharmGKBiPA31111.

Chemistry databases

ChEMBLiCHEMBL2058.
DrugBankiDB00078. Ibritumomab.
DB08935. Obinutuzumab.
DB06650. Ofatumumab.
DB00073. Rituximab.
DB00081. Tositumomab.
GuidetoPHARMACOLOGYi2628.

Polymorphism and mutation databases

BioMutaiMS4A1.
DMDMi115968.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001586271 – 297B-lymphocyte antigen CD20Add BLAST297

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei36PhosphoserineBy similarity1
Lipidationi111S-palmitoyl cysteine1 Publication1
Disulfide bondi167 ↔ 1831 Publication
Lipidationi220S-palmitoyl cysteine1 Publication1
Modified residuei225PhosphoserineBy similarity1
Modified residuei239PhosphothreonineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiP11836.
PaxDbiP11836.
PeptideAtlasiP11836.
PRIDEiP11836.

PTM databases

iPTMnetiP11836.
PhosphoSitePlusiP11836.
SwissPalmiP11836.

Expressioni

Tissue specificityi

Expressed on B-cells.

Gene expression databases

BgeeiENSG00000156738.
CleanExiHS_MS4A1.
ExpressionAtlasiP11836. baseline and differential.
GenevisibleiP11836. HS.

Organism-specific databases

HPAiCAB000015.
HPA014341.
HPA014391.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
CCDC155Q8N6L03EBI-2808234,EBI-749265

GO - Molecular functioni

  • MHC class II protein complex binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107369. 14 interactors.
IntActiP11836. 6 interactors.
STRINGi9606.ENSP00000314620.

Structurei

Secondary structure

1297
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi172 – 174Combined sources3
Helixi178 – 185Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1S8Bmodel-A1-297[»]
2OSLX-ray2.60P/Q163-187[»]
3BKYX-ray2.61P163-187[»]
3PP4X-ray1.60P163-187[»]
ProteinModelPortaliP11836.
SMRiP11836.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11836.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni74 – 80Epitope 17
Regioni146 – 160Epitope 2Add BLAST15
Regioni168 – 175Epitope 3 (recognized by antibodies, including Rituximab)8

Sequence similaritiesi

Belongs to the MS4A family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFXM. Eukaryota.
ENOG41119VB. LUCA.
GeneTreeiENSGT00510000048781.
HOGENOMiHOG000111479.
HOVERGENiHBG048815.
InParanoidiP11836.
KOiK06466.
OMAiGIVENEW.
OrthoDBiEOG091G0IBB.
PhylomeDBiP11836.
TreeFamiTF335157.

Family and domain databases

InterProiIPR007237. CD20-like.
IPR030417. MS4A.
IPR030418. MS4A1.
[Graphical view]
PANTHERiPTHR23320. PTHR23320. 2 hits.
PTHR23320:SF79. PTHR23320:SF79. 2 hits.
PfamiPF04103. CD20. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti13P → L in CAA30179 (PubMed:2456210).Curated1
Sequence conflicti13P → L in CAA30180 (PubMed:2456210).Curated1
Sequence conflicti71M → I in AAA88911 (PubMed:2466899).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05705838 – 204Missing in isoform 2. 1 PublicationAdd BLAST167

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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. [P11836-1]
PIRiA30586.
RefSeqiNP_068769.2. NM_021950.3. [P11836-1]
NP_690605.1. NM_152866.2. [P11836-1]
UniGeneiHs.712553.

Genome annotation databases

EnsembliENST00000345732; ENSP00000314620; ENSG00000156738. [P11836-1]
ENST00000389939; ENSP00000374589; ENSG00000156738. [P11836-1]
ENST00000528313; ENSP00000432270; ENSG00000156738. [P11836-2]
ENST00000534668; ENSP00000433277; ENSG00000156738. [P11836-1]
GeneIDi931.
KEGGihsa:931.
UCSCiuc001npq.3. human. [P11836-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Wikipedia

CD20 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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. [P11836-1]
PIRiA30586.
RefSeqiNP_068769.2. NM_021950.3. [P11836-1]
NP_690605.1. NM_152866.2. [P11836-1]
UniGeneiHs.712553.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1S8Bmodel-A1-297[»]
2OSLX-ray2.60P/Q163-187[»]
3BKYX-ray2.61P163-187[»]
3PP4X-ray1.60P163-187[»]
ProteinModelPortaliP11836.
SMRiP11836.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107369. 14 interactors.
IntActiP11836. 6 interactors.
STRINGi9606.ENSP00000314620.

Chemistry databases

ChEMBLiCHEMBL2058.
DrugBankiDB00078. Ibritumomab.
DB08935. Obinutuzumab.
DB06650. Ofatumumab.
DB00073. Rituximab.
DB00081. Tositumomab.
GuidetoPHARMACOLOGYi2628.

Protein family/group databases

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

PTM databases

iPTMnetiP11836.
PhosphoSitePlusiP11836.
SwissPalmiP11836.

Polymorphism and mutation databases

BioMutaiMS4A1.
DMDMi115968.

Proteomic databases

MaxQBiP11836.
PaxDbiP11836.
PeptideAtlasiP11836.
PRIDEiP11836.

Protocols and materials databases

DNASUi931.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000345732; ENSP00000314620; ENSG00000156738. [P11836-1]
ENST00000389939; ENSP00000374589; ENSG00000156738. [P11836-1]
ENST00000528313; ENSP00000432270; ENSG00000156738. [P11836-2]
ENST00000534668; ENSP00000433277; ENSG00000156738. [P11836-1]
GeneIDi931.
KEGGihsa:931.
UCSCiuc001npq.3. human. [P11836-1]

Organism-specific databases

CTDi931.
DisGeNETi931.
GeneCardsiMS4A1.
HGNCiHGNC:7315. MS4A1.
HPAiCAB000015.
HPA014341.
HPA014391.
MalaCardsiMS4A1.
MIMi112210. gene.
613495. phenotype.
neXtProtiNX_P11836.
OpenTargetsiENSG00000156738.
Orphaneti1572. Common variable immunodeficiency.
PharmGKBiPA31111.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFXM. Eukaryota.
ENOG41119VB. LUCA.
GeneTreeiENSGT00510000048781.
HOGENOMiHOG000111479.
HOVERGENiHBG048815.
InParanoidiP11836.
KOiK06466.
OMAiGIVENEW.
OrthoDBiEOG091G0IBB.
PhylomeDBiP11836.
TreeFamiTF335157.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000156738-MONOMER.
SIGNORiP11836.

Miscellaneous databases

EvolutionaryTraceiP11836.
GeneWikiiCD20.
GenomeRNAii931.
PROiP11836.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000156738.
CleanExiHS_MS4A1.
ExpressionAtlasiP11836. baseline and differential.
GenevisibleiP11836. HS.

Family and domain databases

InterProiIPR007237. CD20-like.
IPR030417. MS4A.
IPR030418. MS4A1.
[Graphical view]
PANTHERiPTHR23320. PTHR23320. 2 hits.
PTHR23320:SF79. PTHR23320:SF79. 2 hits.
PfamiPF04103. CD20. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 172 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.