|CD45||PTPRC (protein tyrosine phosphatase receptor type C), LCA (leukocyte common antigen), B220, T200, EC 3.1.34, CD45(R,RA,RB,RC,R0), Ly-5(mouse)|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|180 / 180|
220 / 220
|CD45 proteins are expressed at high levels on all cells of hematopoietic origin, except erythrocytes. CD45 is a major component of the glycocalyx. Expression is highest on lymphocytes with 10% of their surface area comprising CD45 but expression is lower on other leukocytyes. Expression of different isoforms differs on differentiated subsets of hematopoietic cells like CD45RA on naive/resting T cells and on medullary thymocytes, and on CD45R0 on memory/activated T cells and on cortical thymocytes. The proportion of CD45R0+ cells increases with age to ultimately 40-60% of the total T cell population in adults. The isoform pattern can change in response to cytokines. Thus the expression patterns for a given population are generalities and are not absolute. Multiple isoforms may occur on a single cell type. CD45RB+ is expressed at high levels by peripheral CD4+ T cells and CD8+ T cells and at moderate levels by thymic CD4+ cells and CD4+CD8+ T cells. It is also expressed on B cells, granulocytes and monocytes. CD45RC is expressed on a subset of T cells, B cells and NK cells.|
|MOLECULAR FAMILY NAME: Belongs to the protein tyrosine phosphatase receptor family.|
CD45 is a single-pass type-1 glycoprotein. It contains a 391-552 aa extracellular domain which contains 3 potential fibronectin type-III domains which are highly glucosylated, a transmembrnae domain and a 707 aa cytoplasmic domain containing 2 phosphatase catalytic domains. The 1st domain has significant phosphatase activity and the 2nd domain can not have significant activity since the critical aa necessary for catalytic activity is lacking.
The different isoforms of CD45 arise from variable splicing of exons 4, 5 and 6, which encode A, B and C, determinants respectively and are recognized by CD45RA, CD45RB and CD45RC antibodies respectively. The 220 kDa isoform contains A, B and C determinants, the 210 kDa isoform contains either A and B or B and C determinants and the 200 kDa isoform contains the B determinant. The 180 kDa isoform lacks A, B and C determinants and is recognized by CD45R0 antibodies. Various isoforms of CD45 are generated by alternative splicing of 3 exons that can be inserted immediately after an N-terminal sequences of 8 aa found on all isoforms. Of the 8 possible combinations of exons, 7 have been found at the mRNA level. The isoforms are expressed differentially on leukocytes and their expression can be followed with mAbs specific for protein encoded by the alternate exons or by a mAb that recognizes the junction of the 8 aa N-terminal conserved sequence and the rest of the conserved part of the protein. Other mAbs react with the common part of the structure and recognize all CD45 isoforms. B cells express 1 isoform, including the A, B and C exon encoded sequences. Among peripheral CD4+ T cells, various combinations including 1 or 2 of the alternate exons are found. This differential expression has been of use in defining subsets of CD4+ T cells, in which naïve T cells express forms of CD45 including these exons, whereas activated cells and most memory T cells express forms including these exons at low levels and label with mAbs specific for the CD45R0 epitope. Thymocytes express primarily the low Mr, isoform of CD45.
There is extensive serine/threonine glycosylation near the N-terminus, particularly of differentially spliced exons and extensive N-glycosylation of the extracellular domain, especially in the membrane proximal FN type 3 domain. Phosphorylation of the cytoplasmic domain on serine and tyrosine has been observed.
|CD45 has been reported to be associated at the cell surface with several cell surface antigens such as CD4, TCR, CD2, CD90 (Thy-1) and CD26. CD22 can bind CD45R0 and other glycoproteins through carbohydrate sialic acid residues. CD45 associates non-covalently with a lymphocyte-specific protein termed lymphocyte phosphatase-associated phosphoprotein (CD22/LPAP) or CD45-associated protein (CD45-AP) through an interaction involving the transmembrane region of CD45. CD45 is also associated with a phosphorylated glycoprotein of Mr 116 kDa present in all hematopoietic cells|
LIGANDS AND MOLECULES ASSOCIATED WITH CD45
|CD45 is a signaling molecule that regulates a variety of cellular processes including cell growth, differentiation, mitotic cycle and oncogenic transformation. CD45 has an intrinsic cytoplasmic protein tyrosine phosphatase activity and probably functions in specific signal transduction pathways via protein tyrosine dephosphorylation. CD45 is a critical requirement for T and B cell antigen receptor-mediated activation and is the possible requirement for receptor-mediated activation in other leukocytes. CD45 requires Src-kinases which are necessary for T- and B-cell receptor signal transduction. CD45 associates with CD2, CD3 and CD4 in the extracellular region correlate with functional subpopulations of lymphocytes and may affect threshold of activation.|
CD45 is a tyrosine phosphatase, EC 3.1.34. It probably is the dominant leukocyte plasma membrane located phosphatase.
DISEASE RELEVANCE AND FUNCTION OF CD45 IN INTACT ANIMAL
Knockout mice have defective thymocyte development, reduced numbers of mature T cells, and absent responses to T and B cell antigen receptor-mediated activation. Isoforms are the best available individual discriminators of naïve and memory T cells, so clinical monitoring is being explored. CD45 is a target of immunosuppressive antibody treatment. Defects of CD45 are a cause of SCID.
|CD45 occurs in multiple isoforms due to alternative splicing of 3 exons. When referring to antibodies: CD45RA pertains to antibodies which detect molecules that include exon A ( = exon 4), CD45RB pertains to antibodies which detect antibodies that include exon B ( = exon 5), CD45RC pertains to antibodies which detect molecules that include exon C ( = exon 6), and CD45R0 pertains to antibodies which detect molecules lacking any of exons A, B or C. CD45R is intentionally ambiguous, referring to mAb recognizing a poorly understood subset of CD45 forms. Because the specificities of mAb can be complex and recognize combinations of exons and glycoyslation differences, this nomenclature is not ideal.|
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD45: No information.
ENZYMES WHICH MODIFY CD45: No information:
The major unresolved issue still is the physiological function of the extracellular domain and the significance of the different isoforms. CD45-deficient macrophages are dysregulated in integrin-mediated adhesion due to the inability to regulate the Lyn and Hck kinases.
Database accession numbers
Revised June 25, 2008