4v0g: Difference between revisions

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<StructureSection load='4v0g' size='340' side='right'caption='[[4v0g]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
<StructureSection load='4v0g' size='340' side='right'caption='[[4v0g]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4v0g]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4V0G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4V0G FirstGlance]. <br>
<table><tr><td colspan='2'>[[4v0g]] is a 2 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=4V0G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4V0G FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=G9B:N-[3-(2-{3-AMINO-6-[1-(1-METHYLPIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]PYRAZIN-2-YL}-1H-BENZIMIDAZOL-1-YL)PHENYL]PROPANAMIDE'>G9B</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G9B:N-[3-(2-{3-AMINO-6-[1-(1-METHYLPIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]PYRAZIN-2-YL}-1H-BENZIMIDAZOL-1-YL)PHENYL]PROPANAMIDE'>G9B</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4v0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v0g OCA], [https://pdbe.org/4v0g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4v0g RCSB], [https://www.ebi.ac.uk/pdbsum/4v0g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4v0g ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4v0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v0g OCA], [http://pdbe.org/4v0g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4v0g RCSB], [http://www.ebi.ac.uk/pdbsum/4v0g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4v0g ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/JAK3_HUMAN JAK3_HUMAN]] Defects in JAK3 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) [MIM:[http://omim.org/entry/600802 600802]]. 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.<ref>PMID:15121872</ref> <ref>PMID:18250158</ref> <ref>PMID:15831699</ref> [:]<ref>PMID:7659163</ref> <ref>PMID:9354668</ref> <ref>PMID:9753072</ref> <ref>PMID:10982185</ref> <ref>PMID:14615376</ref>
[https://www.uniprot.org/uniprot/JAK3_HUMAN JAK3_HUMAN] Defects in JAK3 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) [MIM:[https://omim.org/entry/600802 600802]. 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.<ref>PMID:15121872</ref> <ref>PMID:18250158</ref> <ref>PMID:15831699</ref> [:]<ref>PMID:7659163</ref> <ref>PMID:9354668</ref> <ref>PMID:9753072</ref> <ref>PMID:10982185</ref> <ref>PMID:14615376</ref>  
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/JAK3_HUMAN JAK3_HUMAN]] Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.<ref>PMID:8022485</ref> <ref>PMID:7662955</ref> <ref>PMID:20440074</ref>
[https://www.uniprot.org/uniprot/JAK3_HUMAN JAK3_HUMAN] Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.<ref>PMID:8022485</ref> <ref>PMID:7662955</ref> <ref>PMID:20440074</ref>  


==See Also==
==See Also==
*[[Janus kinase|Janus kinase]]
*[[Janus kinase 3D structures|Janus kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Non-specific protein-tyrosine kinase]]
[[Category: Ashton S]]
[[Category: Ashton, S]]
[[Category: Chuaquini C]]
[[Category: Chuaquini, C]]
[[Category: Coclough N]]
[[Category: Coclough, N]]
[[Category: Cross DAE]]
[[Category: Cross, D A.E]]
[[Category: Debreczeni JE]]
[[Category: Debreczeni, J E]]
[[Category: Eberlein C]]
[[Category: Eberlein, C]]
[[Category: Gingipalli L]]
[[Category: Gingipalli, L]]
[[Category: Hennessy EJ]]
[[Category: Hennessy, E J]]
[[Category: Klinowska TCM]]
[[Category: Klinowska, T C.M]]
[[Category: Orme JP]]
[[Category: Orme, J P]]
[[Category: Sha L]]
[[Category: Sha, L]]
[[Category: Wu X]]
[[Category: Wu, X]]
[[Category: Egfr mutant]]
[[Category: T790m]]
[[Category: Transferase]]

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