Tyrosine phosphatase

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{{STRUCTURE_3i7z| PDB=3i7z | SIZE=400| SCENE= |right|CAPTION=Human tyrosine phosphatase 1B catalytic domain (grey) complex with EGFR peptide (in green), VO4, glycerol, Tris, 2-amino-2-hydroxymethyl-1,3-diol, [[3i7z]] }}
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<StructureSection load='3i7z' size='340' side='right' caption='Human tyrosine phosphatase 1B catalytic domain (grey) complex with EGFR peptide (in green), VO4, glycerol, Tris, 2-amino-2-hydroxymethyl-1,3-diol, [[3i7z]]' scene='' >
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__TOC__
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==Function==
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'''Tyrosine phosphatase''' (PTP) is an enzyme which removes phosphate from phosphorylated tyrosine residues. It is a key regulatory component of signal transduction pathways. PTPs are divided to 4 subfamilies. PTP class I contains receptor PTPs (RPTP) and dual-specificity PTP which removes phosphate from Ser/Thr and tyrosine. PTP class III contains CDC25 which removes phosphate from Thr and tyrosine. PTP containing SH2 domains are called PTP SHP. For details on ''Yersinia'' PTP see [[Yersinia YopH]].
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'''Tyrosine phosphatase''' or '''Protein tyrosine phosphatase''' (PTP) is an enzyme which removes phosphate from phosphorylated tyrosine residues. It is a key regulatory component of signal transduction pathways<ref>PMID:14625689</ref>. PTPs are divided to 4 subfamilies.
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*'''PTP class I''' contains receptor PTPs (RPTP) and dual-specificity PTP which removes phosphate from Ser/Thr and tyrosine. Human '''PTP PRL''' is found in regenerating liver.
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*'''PTP class II''' are low molecular weight PTP ('''LMW-PTP''') which dephosphorylate a number of growth factors and modulate their signalling processes<ref>PMID:27421795</ref>.
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*'''PTP class III''' contains CDC25 which removes phosphate from Thr and tyrosine. PTP containing SH2 domains are called PTP SHP.
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*'''Yersinia PTP''' see [[Yersinia YopH]].<br />
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*'''Non-receptor type PTPs''' are coded by the PTPN genes. <br />
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*'''T-cell PTP''' is a non-receptor type PTP expressed in hematopoietic tissues influencing most cells in the immune system<ref>PMID:19290937</ref>.
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== 3D Structures of tyrosine phosphatase ==
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For details of PTP complex with inhibitor see [[Student Projects for UMass Chemistry 423 Spring 2012-9]].
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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== Disease ==
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===Class I===
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PTP mutations are involved in cancers<ref>PMID:16557282</ref>.
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== 3D Structures of tyrosine phosphatase ==
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====Non-receptor type PTP====
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[[Tyrosine phosphatase 3D structures]]
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[[1a5y]], [[2hnp]], [[2hnq]], [[1oem]], [[1oeo]], [[1oes]], [[1oet]], [[1oeu]], [[1oev]], [[1sug]], [[2cm2]], [[2cm3]], [[3eu0]], [[3i80]], [[3a5j]], [[1bzc]] - hPTP-b catalytic domain – human<br />
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[[1gfy]], [[1i57]], [[1pa1]], [[2f6f]], [[3a5k]], [[3zv2]], [[3qkp]], [[3qkq]] - hPTP-b catalytic domain (mutant) <br />
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[[1wch]] – hPTP-e<br />
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[[3pdz]] - hPTP-e PDZ2 domain – NMR<BR />
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[[1gm1]] - mPTP-BL PDZ2 domain – mouse – NMR<BR />
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[[1ozi]] - mPTP-BL PDZ2 domain (mutant) – NMR<BR />
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[[3rgo]] – mPTP-1<br />
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[[2yz1]] – mPTP SHPS-1 catalytic domain<br />
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[[1gwz]], [[2b3o]] – hPTP SHP-1 catalytic domain<br />
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[[1x6c]] - hPTP SHP-1 SH2 domain – NMR<BR />
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[[2shp]] - hPTP SHP-2 (mutant)<br />
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[[2b49]] – hPTPN3 catalytic domain<br />
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[[2i75]] – hPTPN4<br />
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[[2cs5]] – hPTPN4 PDZ domain – NMR<BR />
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[[2vph]] - hPTPN4 PDZ domain<br />
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[[2bij]] – hPTPN5 catalytic domain<br />
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[[2bv5]] - hPTPN5 catalytic domain (mutant) <br />
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[[3ps5]] – hPTPN6 (mutant) <br />
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[[4hjp]] – hPTPN6 catalytic domain <br />
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[[4gry]], [[4grz]], [[4hjq]] – hPTPN6 catalytic domain (mutant)<br />
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[[2dn7]] - hPTPN6 FN3 #6 domain - NMR<br />
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[[2dju]], [[2edy]] - hPTPN6 FN3 domain - NMR<br />
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[[2a3k]], [[1zc0]] – hPTPN7 catalytic domain<br />
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[[2gp0]], [[2hvl]], [[2qdc]], [[2qdm]], [[2qdp]], [[2qds]], [[2qdt]], [[2qdu]], [[3o4s]], [[3o4t]], [[3o4u]] – hPTPN7 catalytic domain (mutant) <br />
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[[2pa5]] – hPTPN9 catalytic domain<br />
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[[3b7o]], [[3zm0]], [[3zm1]], [[3zm2]], [[3zm3]] - hPTPN11 catalytic domain<br />
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[[4dgp]] - hPTPN11 SH2+catalytic domains<br />
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[[4dgx]], [[4gwf]], [[4h1o]], [[4h34]] - hPTPN11 SH2+catalytic domains (mutant)<br />
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[[3lnx]] – hPTPN13 PDZ2 domain<br />
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[[2m0z]] - hPTPN13 PDZ2 domain (mutant) – NMR<br />
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[[2bzl]] – hPTPN14 catalytic domain<br />
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[[2oc3]] – hPTPN18<br />
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[[2p6x]], [[2qcj]], [[3h2x]] – hPTPN22 catalytic domain<br />
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[[3rau]] - hPTPN23 His domain
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[[1xm2]] – hPTP PRL-1<br />
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[[1r6h]], [[1v3a]], [[2mbc]] – hPTP IVA-3 – NMR<BR />
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[[1rxd]] - hPTP IVA-1<br />
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[[1zck]], [[1x24]] – rPTP 4A1 – rat<br />
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[[3i36]] – rPTP-η catalytic domain<br />
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[[1c0e]] – bPTP (mutant) – bovine<br />
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[[1d1p]], [[2j16]] – yPTP - yeast<br />
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[[2j17]] - yPTP (mutant)<br />
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[[1g4w]] – StPTP – ''Salmonella typhimurium''<br />
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[[2i6i]], [[3ro1]] – SsPTP – ''Sulfolobus solfataricus''<br />
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[[2pi7]] – cPTP CRYP-2 catalytic domain <br />
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[[2z72]], [[1v73]], [[2zbm]] – PTP residues 22-361 – ''Shewanella''<br />
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[[3js5]], [[3jvi]] – EhPTP – ''Entamoeba histolytica''<br />
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[[2wjd]], [[2wje]], [[2wjf]] – PTP – ''Streptococcus pneumonia''<br />
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[[3qy6]], [[3qy7]], [[3qy8]] – BsPTP – ''Bacillus subtilis''
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''Non-receptor type PTP complex with peptide''
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[[1ptt]], [[1ptu]], [[1g1f]], [[1g1g]], [[1g1h]], [[1een]], [[1eeo ]] - hPTP-b catalytic domain (mutant) + peptide<br />
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[[3i7z]] - hPTP-b catalytic domain + peptide<br />
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[[3zmp]], [[3zmq]] – hPTPN1 catalytic domain + peptide<br />
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[[1bzh]] - hPTP 1B catalytic domain + fluoromalonyl tyrosine peptide<br />
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[[1bzj]] - hPTP 1B catalytic domain + phosphotyrosine mimetic<br />
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[[3nfk]], [[3nfl]] - hPTPN4 PDZ domain + peptide<br />
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[[2yu7]], [[2rmx]] – hPTPN6 SH2 domain + peptide – NMR<BR />
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[[4gs0]] – hPTPN6 catalytic domain + peptide<br />
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[[3d42]], [[3d44]] – hPTPN7 catalytic domain (mutant) + peptide<br />
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[[4icz]] – hPTPN9 catalytic domain + peptide<br />
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[[3tl0]], [[3tkz]] – hPTPN11 SH2 domain + peptide<br />
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[[3lny]] - hPTPN13 PDZ2 domain + peptide<br />
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[[4gfu]], [[4gfv]] - hPTPN18 residues 6-300 + peptide<br />
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[[3brh]], [[3olr]] - hPTPN22 catalytic domain + peptide<br />
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[[3omh]] - hPTPN22 catalytic domain (mutant) + peptide<br />
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[[3rz2]] - rPTP 4A1 + peptide<br />
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[[1fpr]] - hPTP SHP-1 catalytic domain + peptide<br />
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[[1aya]], [[1ayb]], [[1ayc]], [[1ayd]] – mPTP Syp N terminal SH2 domain + peptide<br />
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[[1vj6]] – mPTP PDZ2 domain + APC C terminal – NMR<br />
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[[2dxp]], [[2i6o]] – SsPTP (mutant) + peptide<br />
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''Non-receptor type PTP complex with small molecule''
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[[1ptv]], [[1pty]] - hPTP-b catalytic domain (mutant) + phosphotyrosine<br />
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[[1aax]] - hPTP-b catalytic domain (mutant) + bis-phosphophenyl methane<br />
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[[1ecv]], [[1c83]], [[1c84]], [[1c85]], [[1c86]], [[1c87]], [[1c88]], [[1g7f]], [[1g7g]], [[1jf7]], [[1l8g]], [[1kak]], [[1kav]], [[1lqf]], [[1nl9]], [[1nny]], [[1no6]], [[1nz7]], [[1ony]], [[1onz]], [[1ph0]], [[1pxh]], [[1pyn]], [[1q1m]], [[1q6j]], [[1q6m]], [[1q6n]], [[1q6p]], [[1q6s]], [[1q6t]], [[1qxk]], [[1t48]], [[1t49]], [[1t4j]], [[1xbo]], [[1wax]], [[2bgd]], [[2bge]], [[2azr]], [[2b07]], [[2f6t]], [[2f6v]], [[2f6w]], [[2f6y]], [[2f6z]], [[2f70]], [[2f71]], [[2fjn]], [[2cm7]], [[2cm8]], [[2cma]], [[2cmb]], [[2cmc]], [[2h4g]], [[2h4k]], [[2hb1]], [[2cne]], [[2cnf]], [[2cng]], [[2cnh]], [[2cni]], [[2nt7]], [[2nta]], [[2veu]], [[2vev]], [[2vew]], [[2vex]], [[2vey]], [[2qbp]], [[2qbq]], [[2qbr]], [[2qbs]], [[3cwe]], [[3d9c]], [[2zmm]], [[2zn7]], [[3eax]], [[3eb1]], [[3sme]], [[4i8n]] - hPTP-b catalytic domain + inhibitor<br />
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[[1nwl]], [[1nwe]], [[2fjm]] - hPTP-b catalytic domain (mutant) + inhibitor<br />
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[[4bjo]] – hPTP1 catalytic domain + NO3<br />
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[[3rgq]] – mPTP-1 + Pi(5)P<br />
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[[2cjz]] - hPTPN5 catalytic domain (mutant) + phosphotyrosine<br />
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[[4ge2]], [[4ge5]], [[4ge6]] – hPTP9 catalytic domain + inhibitor<br />
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[[3o5x]] – hPTPN11 catalytic domain + inhibitor<br />
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[[3mow]] - hPTPN11 catalytic domain + tautomycetin analog<br />
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[[2m10]] - hPTPN13 PDZ2 domain (mutant) + azobenzene derivative – NMR<br />
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[[2qct]], [[4j51]] – hPTPN22 catalytic domain + inhibitor<br />
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[[1zcl]] - rPTP 4A1 (mutant) + sulfate<br />
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[[1dg9]] – bPTP + HEPES<br />
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[[1d2a]] – yPTP + adenine <br />
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[[1d1q]] – yPTP (mutant) + PNPP<br />
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[[2i6p]] - SsPTP (mutant) + PNPP<br />
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[[2i6j]] – SsPTP + phosphate<br />
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[[2i6m]] – SsPTP + WO4<BR />
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[[3ido]] – EhPTP + HEPES<br />
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''Non-receptor type PTP complex with protein''
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[[2b4s]] - hPTP-b catalytic domain + insulin receptor<br />
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[[2gph]] - hPTPN7 catalytic domain (mutant) + MAPK2<br />
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[[1g4u]] – StPTP + RAS-related C3 botulinum toxin substrate <br />
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[[1jyo]] – StPTP + secretion chaperone SICP<br />
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[[4je4]], [[4jeg]] – hPTPN11 catalytic domain + monobody<br />
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====Yersinia PTP Yop====
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[[1yts]], [[2i42]], [[3f99]] - YePTP catalytic domain (mutant) – ''Yersinia enterocolitica''<br />
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[[1xxp]], [[1xxv]] - YePTP catalytic domain (mutant) + peptide<br />
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[[2i42]] – YePTP (mutant) + VO4<br />
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[[1ypt]], [[1ytw]] – YePTP catalytic domain + WO4<BR />
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[[1ytn]] - YePTP catalytic domain + NO3<br />
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[[1lyv]] - YePTP catalytic domain (mutant) + phosphate<br />
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[[3f9a]] – YeYop catalytic domain (mutant) + tungstate<br />
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[[3f9b]] – YeYop catalytic domain (mutant) + divanadate<br />
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[[1pa9]], [[3bm8]] - YePTP catalytic domain (mutant) + inhibitor<br />
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[[3blu]], [[3blt]] - YeYopH catalytic domain + inhibitor<br />
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[[3u96]] - YeYopH catalytic domain (mutant) + inhibitor<br />
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[[4gf3]] – YeYop residues 21-63 + YeYop targeting protein SYNCH<br />
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[[1huf]] – YpYopH N terminal – ''Yersinia pestis''<br />
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[[1qz0]] - YpYopH catalytic domain (mutant) + peptide<br />
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[[2y2f]] - YpYopH catalytic domain + inhibitor<br />
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[[1k46]] - YptYopH N terminal – ''Yersinia pseudotuberculosis''<br />
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[[1m0v]] - YptYopH N terminal + phosphopeptide - NMR
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====Receptor-type PTP====
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[[1yfo]], [[2i1y]] – mRPTP-α catalytic domain<br />
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[[1p15]] - mRPTP-α D2 domain<br />
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[[3pxh]] - mRPTP Ig domains<br />
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[[2nv5]] – RPRP - rat<br />
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[[2ahs]] – hRPTP-β<br />
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[[2i3r]], [[2i5x]] - hRPTP-β catalytic domain<br />
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[[2hc1]], [[2hc2]] - hRPTP-β catalytic domain (mutant) <br />
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[[2h4v]], [[2pbn]] – hRPTP-γ domain 1<br />
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[[3qcn]] - hRPTP-γ domain 1 (mutant) <br />
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[[2nlk]] - hRPTP-γ catalytic domain<br />
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[[3jxg]], [[3jxh]] - mRPTP-γ CA-like domain<br />
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[[3jxh]] - hRPTP-γ CA-like domain<br />
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[[1x5z]] - hRPTP-δ fibronectin type-III domain – NMR<BR />
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[[2dlh]] - hRPTP-δ FN3 domain – NMR<BR />
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[[2yd6]], [[2yd7]] - hRPTP-δ Ig1-2 domain<br />
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[[2jjd]] - hRPTP-ε residues 107-697<br />
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[[2c7s]] - hRPTP-κ residues 865-1154<br />
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[[1rpm]] - hRPTP-μ catalytic domain<br />
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[[2c9a]] - hRPTP-μ MAM-IG module<br />
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[[2v5y]] - hRPTP-μ extracellular region<br />
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[[2g59]], [[2gjt]] - hRPTP-ο catalytic domain<br />
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[[2cfv]] – hRPTP-η residues 1019-1311<br />
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[[2nz6]] - hRPTP-η residues 1019-1311 (mutant) <br />
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[[2dle]] - hRPTP-η FN3 domain – NMR<BR />
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[[2qep]] – hRPTP-ν2 D1 domain<br />
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[[4hti]], [[4htj]] – hRPTP-ν2 membrane proximal ectodomain<br />
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[[2ooq]] – hRPTP-ρ<br />
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[[2fh7]], [[4bpc]] - hRPTP-σ catalytic domain (mutant) <br />
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[[2yd9]] - hRPTP-σ Ig1-3 domain (mutant) <br />
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[[2yd3]], [[2yd5]] - hRPTP-σ Ig1-2 domain<br />
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[[2yd4]] - cRPTP-σ Ig1-2 domain – chicken<br />
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[[3jxf]] - hRPTP-ζ CA-like domain<br />
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[[2qt7]], [[3n01]], [[3n4w]], [[3ng8]], [[3np5]] – hRPTP IA-2<br />
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[[1jln]], [[2a8b]] - mRPTP-R catalytic domain<br />
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[[3sr9]] - mRPTP-σ residues 1326 – 1901<br />
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[[2edx]] - hRPTP-F fibronectin type-III domain – NMR<BR />
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[[2yd1]], [[2yd2]], [[3pxj]] – DmRPTP Ig1-2 domain – ''Drosophila melanogaster''<br />
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[[3s3e]] – DmRPTP-10D catalytic domain<br />
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''Receptor type PTP complexes''
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[[3s3f]] - DmRPTP-10D catalytic domain + VO4<BR />
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[[3s3h]] - DmRPTP-10D catalytic domain + peptide<br />
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[[3s3k]] - DmRPTP-10D catalytic domain + inhibitor<br />
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[[2h02]], [[2h04]], [[2i3u]], [[2i4e]], [[2i4g]], [[2i4h]] - hRPTP-β catalytic domain + inhibitor<br />
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[[2h03]] - hRPTP-β catalytic domain (mutant) + inhibitor<br />
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[[2hy3]], [[3qcb]], [[3qcc]], [[3qcd]] - hRPTP-γ domain 1 + VO4<BR />
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[[3qce]], [[3qcf]], [[3qcg]], [[3qch]], [[3qci]], [[3qcj]], [[3qck]] - hRPTP-γ domain 1 + inhibitor<br />
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[[3qcl]], [[3qcm]] - hRPTP-γ domain 1 (mutant) + inhibitor<br />
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[[3kld]] - mRPTP-γ CA-like domain + contactin 4<br />
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[[2yd8]] - hRPTP-σ Ig1-2 domain + sucrose octasulfate<br />
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[[3s97]] - hRPTP-ζ CA-like domain + congtactin Ig domains<br />
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[[1ygr]] – hRPTP CD45 cytoplasmic domain (mutant) + T-cell receptor peptide<br />
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====Dual-specificity PTP====
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[[1t3k]] – DUSP (mutant) – ''Arabidopsis thaliana''<br />
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[[2g6z]] – DUSP-5<br />
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[[3lj8]] – DUSP-9<br />
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[[2wgp]] – hDUSP-14 residues 2-191
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===Class II – Low molecular weight PTP===
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[[1p8a]] – PTP (mutant) – ''Tritrichomonas foetus'' – NMR<BR />
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[[2cwd]] – PTP – ''Thermus thermophilus''<br />
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[[1phr]] - bPTP<br />
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[[1xww]] - hPTP <br />
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[[1z12]] - bPTP + VO4<br />
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[[1z13]] - bPTP + MoO4<br />
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[[3rof]] – PTP-A + peptide – ''Staphylococcus aureus''<br />
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[[1u2p]], [[2luo]] – MtPTP – ''Mycobacterium tuberculosis''<br />
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[[1u2q]] – MtPTP + glycerol<br />
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[[2oz5]] – MtPTP + inhibitor<br />
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[[2fek]] – PTP – ''Escherichia coli''<br />
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[[4eti]], [[4etm]], [[4kk3]] – BsPTP<br />
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[[4etn]], [[4kk4]] – BsPTP (mutant)<br />
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===Class III – CDC25===
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[[1c25]] – hCDC25A catalytic domain (mutant) <br />
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[[1qb0]], [[1cwr]], [[1ym9]], [[1ymd]], [[1ymk]], [[1yml]], [[1ys0]], [[2uzq]] - hCDC25B catalytic domain<br />
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[[2a2k]], [[2ifd]], [[2ifv]] - hCDC25B catalytic domain (mutant) <br />
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[[1cwr]], [[1cws]] - hCDC25B catalytic domain + WO4<BR />
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[[1cwt]] - hCDC25B catalytic domain + Methyl-Hg<br />
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[[3op3]] – hCDC25C residues 270-462
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===T-cell PTP===
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[[1l8k]] – hTC-PTP
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[[4az1]] – PTP – ''Trypanosoma cruzi''<br />
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== References ==
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<references/>
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</StructureSection>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Human tyrosine phosphatase 1B catalytic domain (grey) complex with EGFR peptide (in green), VO4, glycerol, Tris, 2-amino-2-hydroxymethyl-1,3-diol, 3i7z

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Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Joel L. Sussman

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