3h2x
Crystal Structure of The Human Lymphoid Tyrosine Phosphatase Catalytic DomainCrystal Structure of The Human Lymphoid Tyrosine Phosphatase Catalytic Domain
Template:ABSTRACT PUBMED 19371084
DiseaseDisease
[PTN22_HUMAN] Defects in PTPN22 are a cause of susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. SLE is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system.[1]
FunctionFunction
[PTN22_HUMAN] Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules. Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue. Dephosphorylates ZAP70 at its activating 'Tyr-493' residue. Dephosphorylates the immune system activator SKAP2.[2][3][4][5]
About this StructureAbout this Structure
3h2x is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
See AlsoSee Also
ReferenceReference
- ↑ Tsai SJ, Sen U, Zhao L, Greenleaf WB, Dasgupta J, Fiorillo E, Orru V, Bottini N, Chen XS. Crystal structure of the human lymphoid tyrosine phosphatase catalytic domain: insights into redox regulation . Biochemistry. 2009 Jun 9;48(22):4838-45. PMID:19371084 doi:10.1021/bi900166y
- ↑ Stanford SM, Krishnamurthy D, Falk MD, Messina R, Debnath B, Li S, Liu T, Kazemi R, Dahl R, He Y, Yu X, Chan AC, Zhang ZY, Barrios AM, Woods VL Jr, Neamati N, Bottini N. Discovery of a novel series of inhibitors of lymphoid tyrosine phosphatase with activity in human T cells. J Med Chem. 2011 Mar 24;54(6):1640-54. Epub 2011 Feb 22. PMID:21341673 doi:10.1021/jm101202j
- ↑ Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE, Chang M, Ramos P, Baechler EC, Batliwalla FM, Novitzke J, Williams AH, Gillett C, Rodine P, Graham RR, Ardlie KG, Gaffney PM, Moser KL, Petri M, Begovich AB, Gregersen PK, Behrens TW. Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet. 2004 Sep;75(3):504-7. Epub 2004 Jul 23. PMID:15273934 doi:10.1086/423790
- ↑ Wu J, Katrekar A, Honigberg LA, Smith AM, Conn MT, Tang J, Jeffery D, Mortara K, Sampang J, Williams SR, Buggy J, Clark JM. Identification of substrates of human protein-tyrosine phosphatase PTPN22. J Biol Chem. 2006 Apr 21;281(16):11002-10. Epub 2006 Feb 6. PMID:16461343 doi:10.1074/jbc.M600498200
- ↑ Yu X, Sun JP, He Y, Guo X, Liu S, Zhou B, Hudmon A, Zhang ZY. Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19767-72. Epub 2007 Dec 3. PMID:18056643 doi:10.1073/pnas.0706233104
- ↑ Barr AJ, Ugochukwu E, Lee WH, King ON, Filippakopoulos P, Alfano I, Savitsky P, Burgess-Brown NA, Muller S, Knapp S. Large-scale structural analysis of the classical human protein tyrosine phosphatome. Cell. 2009 Jan 23;136(2):352-63. PMID:19167335 doi:http://dx.doi.org/10.1016/j.cell.2008.11.038
- ↑ Yu X, Chen M, Zhang S, Yu ZH, Sun JP, Wang L, Liu S, Imasaki T, Takagi Y, Zhang ZY. Substrate Specificity of Lymphoid-specific Tyrosine Phosphatase (Lyp) and Identification of Src Kinase-associated Protein of 55 kDa Homolog (SKAP-HOM) as a Lyp Substrate. J Biol Chem. 2011 Sep 2;286(35):30526-34. Epub 2011 Jun 30. PMID:21719704 doi:10.1074/jbc.M111.254722