CD20 MS4A1 (membrane-spanning 4-domains subfamily A), B1, Bp35,Leu-16
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 3 glycoprotein, 4 span
B Cell
T Lymphocyte
Peripheral blood
33 / 33
35 / 35
37 / 37

Expression
CD20 is expressed on mature B lineage cells.  Expression occurs early in pre-B cell development and persists until terminal differentiation into plasma cells making the plasma cells absent.  A low level of expression is on peripheral blood T lymphocytes.

Structure
MOLECULAR FAMILY NAME:  Belongs to the membrane spanning 4A gene family.

CD20 is a multi-pass type-3 4 span glycoprotein.  It contains an extracellular domain between the 3rd and 4th transmembrane spanning regions, 4 highly conserved transmembrane domains and a cytoplasmic domain which are serine/threonine rich and contain multiple phosphorylation consensus sequences and containing N- and C-terminus.  CD20 is a member of the CD20/FceRIb superfamily of leukocyte surface antigens which also includes the b subunit of the high affinity receptor for IgE FceRIb and HTm4.  The CD20/FceRIb superfamily shares no sequence similarity with another superfamily of 4 transmembrane molecules, the TM4SF.  The gene for CD20 in humans maps to the same region of the genome as FceRIb and HTm4.    Differential phosphorylation is responsible for the 3 forms of CD20 of 33 kDa, 35 kDa and 37 kDa, with activated B cells showing a relative increase in the phosphorylated 35 kDa and 37 kDa forms.

MOLECULAR MASS
Cell Type Unreduced Reduced
B cell 33 kDa, 35 kDa, 37 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

There is no glycosylation but CD20 is heavily phosphorylated in normal B cells following activation and in malignant cells.

Ligands
CD20 can exist in a multimolecular complex that induces signaling the Src family tyrosine kinases Lyn, Fyn and Lck.  This association may not be direct, since it is unaffected by deletion of a large population of the CD20 cytoplasmic regions.  This is consistent with flow cytometric energy transfer analyses which show that CD20 can exist in a complex with MHC class I and II, and the TM4SF molecules CD53, CD81 and CD82.  No extracellular ligand for CD20 has been identified.

LIGANDS AND MOLECULES ASSOCIATED WITH CD20
Molecule Comment
Cell surface protein 20 kDa-30 kDa (uncharacterized)
Cell surface protein 180 kDa-200 kDa (uncharacterized)
4 cytoplasmic proteins in the range of 50 kDa-60 kDa (uncharactized)
75 kDa-80 kDa phosphoproteins Association with CD20 is not through the cytoplasmic regions
Lyn Association with CD20 is not through the cytoplasmic regions
Lck Association with CD20 is not through the cytoplasmic regions
Fyn Association with CD20 is not through the cytoplasmic regions


Function
CD20 ligation activates tyrosine kinases-dependent pathways and may have a role in B cell proliferation and differentiation into plasma cells..  CD20 regulates B lymphocyte activation and proliferation by regulating transmembrane Ca2++ channel subunit and cell-cycle progression.  CD20 can associate with class II and CD40 on B cells and may influence signaling by either class II or CD40.  CD20 plays a role in regulating B cell calcium levels.  The expression of CD20 in disparate cell types generates a qualitatively similar channel activity to that found endogenously in B cells. An ion channel function is consistent with reports that CD20 regulates cell cycle progression and exists on the cell surface as a homo-oligomer.  CD20 can form complexes with Src family of tyrosine kinases Lyn, Fyn and Lck and associates with MHC class I and II molecules as well as CD53, CD81 and CD82.

BIOCHEMICAL ACTIVITY

Homo-oligomeric complexes of CD20 may form Ca++ conductive ion channels in the plasma membrane of B lymphocytes.

DISEASE RELEVANCE AND FUNCTION OF CD20 IN INTACT ANIMAL

CD20 is a marker for follicular B cell non-Hodgkins lymphoma.  Rituximab is a therapeutic antibody for lymphoma and antibody L26 is used against intracellular immunohistochemistry.  Most anti-CD20 mAb are effective at recruiting complement and causing cell lysis as binding to CD20 enhances localization of CD20 into membrane rafts that are more susceptible to complement.  The therapeutic action of these anti-antibodies seems to be complex and to depend on features additional to complement-mediated lysis of malignant cells.

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD20: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD20: No information.

ADDITIONAL INSIGHTS

CD20 deficient mice present a normal phenotype and normal B cell function.  The CD20 family currently includes 2 other cell surface molecules, HTm4 of hematopoietic cells and the b chain of the high affinity receptor for IgE.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 931P11836
MouseA30558P19437M62541
Antibodies
2H7   View Reactivity
B-Ly1   View Reactivity
L26   View Reactivity
L27   View Reactivity

Revised June 25, 2008


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