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[[Image:3brh.jpg|left|200px]]


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==Protein Tyrosine Phosphatase PTPN-22 (Lyp) bound to the mono-Phosphorylated Lck active site peptide==
The line below this paragraph, containing "STRUCTURE_3brh", creates the "Structure Box" on the page.
<StructureSection load='3brh' size='340' side='right'caption='[[3brh]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[3brh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BRH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BRH FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
{{STRUCTURE_3brh| PDB=3brh |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3brh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3brh OCA], [https://pdbe.org/3brh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3brh RCSB], [https://www.ebi.ac.uk/pdbsum/3brh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3brh ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PTN22_HUMAN PTN22_HUMAN] Defects in PTPN22 are a cause of susceptibility to systemic lupus erythematosus (SLE) [MIM:[https://omim.org/entry/152700 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.<ref>PMID:15273934</ref>
== Function ==
[https://www.uniprot.org/uniprot/PTN22_HUMAN 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.<ref>PMID:16461343</ref> <ref>PMID:18056643</ref> <ref>PMID:19167335</ref> <ref>PMID:21719704</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/br/3brh_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3brh ConSurf].
<div style="clear:both"></div>


===Protein Tyrosine Phosphatase PTPN-22 (Lyp) bound to the mono-Phosphorylated Lck active site peptide===
==See Also==
 
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
 
== References ==
==About this Structure==
<references/>
3BRH is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BRH OCA].
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein-tyrosine-phosphatase]]
[[Category: Large Structures]]
[[Category: Cowburn, D.]]
[[Category: Cowburn D]]
[[Category: Love, J.]]
[[Category: Love J]]
[[Category: Piserchio, A.]]
[[Category: Piserchio A]]
[[Category: Seidel, R D.]]
[[Category: Seidel RD]]
[[Category: Alternative splicing]]
[[Category: Cytoplasm]]
[[Category: Hydrolase]]
[[Category: Lck]]
[[Category: Lyp]]
[[Category: Phosphatase]]
[[Category: Polymorphism]]
[[Category: Protein phosphatase]]
[[Category: Ptpn22]]
[[Category: Systemic lupus erythematosus]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 09:19:49 2009''

Latest revision as of 12:30, 21 February 2024

Protein Tyrosine Phosphatase PTPN-22 (Lyp) bound to the mono-Phosphorylated Lck active site peptideProtein Tyrosine Phosphatase PTPN-22 (Lyp) bound to the mono-Phosphorylated Lck active site peptide

Structural highlights

3brh is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

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]

Function

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]

Evolutionary Conservation

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

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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

3brh, resolution 2.20Å

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