1ygr

Structural highlights

Disease

[CD45_HUMAN] Defects in PTPRC are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-positive (T(-)B(+)NK(+) SCID) [MIM:608971]. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.^[1] Genetic variations in PTPRC are involved in multiple sclerosis susceptibility (MS) [MIM:126200]. MS is a neurodegenerative disorder characterized by the gradual accumulation of focal plaques of demyelination particularly in the periventricular areas of the brain. Peripheral nerves are not affected. Onset usually in third or fourth decade with intermittent progression over an extended period. The cause is still uncertain.^[2] [CD3Z_HUMAN] Defects in CD247 are the cause of immunodeficiency due to defect in CD3-zeta (CD3ZID) [MIM:610163]. An immunological deficiency characterized by T-cells impaired immune response to alloantigens, tetanus toxoid and mitogens.^[3]

Function

[CD45_HUMAN] Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity (By similarity).^{[4] [5]} [CD3Z_HUMAN] Probable role in assembly and expression of the TCR complex as well as signal transduction upon antigen triggering.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• CD3
• Tyrosine phosphatase

References

1. ↑ Tchilian EZ, Wallace DL, Wells RS, Flower DR, Morgan G, Beverley PC. A deletion in the gene encoding the CD45 antigen in a patient with SCID. J Immunol. 2001 Jan 15;166(2):1308-13. PMID:11145714
2. ↑ Jacobsen M, Schweer D, Ziegler A, Gaber R, Schock S, Schwinzer R, Wonigeit K, Lindert RB, Kantarci O, Schaefer-Klein J, Schipper HI, Oertel WH, Heidenreich F, Weinshenker BG, Sommer N, Hemmer B. A point mutation in PTPRC is associated with the development of multiple sclerosis. Nat Genet. 2000 Dec;26(4):495-9. PMID:11101853 doi:10.1038/82659
3. ↑ Rieux-Laucat F, Hivroz C, Lim A, Mateo V, Pellier I, Selz F, Fischer A, Le Deist F. Inherited and somatic CD3zeta mutations in a patient with T-cell deficiency. N Engl J Med. 2006 May 4;354(18):1913-21. PMID:16672702 doi:354/18/1913
4. ↑ Charbonneau H, Tonks NK, Walsh KA, Fischer EH. The leukocyte common antigen (CD45): a putative receptor-linked protein tyrosine phosphatase. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7182-6. PMID:2845400
5. ↑ Wu L, Fu J, Shen SH. SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription. Mol Cell Biol. 2002 Apr;22(8):2673-86. PMID:11909961
6. ↑ Nam HJ, Poy F, Saito H, Frederick CA. Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45. J Exp Med. 2005 Feb 7;201(3):441-52. Epub 2005 Jan 31. PMID:15684325 doi:10.1084/jem.20041890