1bu1: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
Line 3: Line 3:
<StructureSection load='1bu1' size='340' side='right'caption='[[1bu1]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='1bu1' size='340' side='right'caption='[[1bu1]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1bu1]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BU1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BU1 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1bu1]] is a 6 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=1BU1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BU1 FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HUMAN HCK ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.6&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Transferase Transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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=1bu1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bu1 OCA], [https://pdbe.org/1bu1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bu1 RCSB], [https://www.ebi.ac.uk/pdbsum/1bu1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bu1 ProSAT]</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=1bu1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bu1 OCA], [https://pdbe.org/1bu1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bu1 RCSB], [https://www.ebi.ac.uk/pdbsum/1bu1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bu1 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>  Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>
[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN] Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>  Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>  
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.<ref>PMID:8132624</ref> <ref>PMID:7535819</ref> <ref>PMID:9406996</ref> <ref>PMID:9407116</ref> <ref>PMID:10092522</ref> <ref>PMID:10779760</ref> <ref>PMID:10973280</ref> <ref>PMID:12411494</ref> <ref>PMID:11741929</ref> <ref>PMID:11904303</ref> <ref>PMID:11896602</ref> <ref>PMID:15010462</ref> <ref>PMID:15952790</ref> <ref>PMID:15998323</ref> <ref>PMID:17535448</ref> <ref>PMID:17310994</ref> <ref>PMID:19114024</ref> <ref>PMID:19903482</ref> <ref>PMID:20452982</ref>
[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN] Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.<ref>PMID:8132624</ref> <ref>PMID:7535819</ref> <ref>PMID:9406996</ref> <ref>PMID:9407116</ref> <ref>PMID:10092522</ref> <ref>PMID:10779760</ref> <ref>PMID:10973280</ref> <ref>PMID:12411494</ref> <ref>PMID:11741929</ref> <ref>PMID:11904303</ref> <ref>PMID:11896602</ref> <ref>PMID:15010462</ref> <ref>PMID:15952790</ref> <ref>PMID:15998323</ref> <ref>PMID:17535448</ref> <ref>PMID:17310994</ref> <ref>PMID:19114024</ref> <ref>PMID:19903482</ref> <ref>PMID:20452982</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Line 38: Line 37:
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Transferase]]
[[Category: Arold S]]
[[Category: Arold, S]]
[[Category: Dumas C]]
[[Category: Dumas, C]]
[[Category: Franken P]]
[[Category: Franken, P]]
[[Category: Sh3]]
[[Category: Signal transduction]]
[[Category: Tyrosine-protein kinase]]

Latest revision as of 08:42, 9 August 2023

SRC FAMILY KINASE HCK SH3 DOMAINSRC FAMILY KINASE HCK SH3 DOMAIN

Structural highlights

1bu1 is a 6 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 2.6Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

HCK_HUMAN Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.[1] [2] Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.[3] [4]

Function

HCK_HUMAN Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.[5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23]

Evolutionary Conservation

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

Publication Abstract from PubMed

Understanding the issue of specificity imposed in the interactions of SH3 domains has largely been addressed in studies investigating the interaction of proline-rich amino acid sequences derived from potential ligands for these domains. Although the interaction with this motif forms an essential platform in the binding of SH3 domains, in many cases little specificity is observed and the difference in affinity for so-called specific and nonspecific proline-rich sequences is not great. Furthermore, the binding interface between an SH3 domain and a protein ligand appears to encompass more interactions than are represented by that involving the proline-rich motif. Here we investigate the issue of specificity from the opposite point of view; namely, how does a ligand recognize different SH3 domains? We present the crystal structure of the unbound SH3 domain from hemopoietic cell kinase (Hck) which is a member of the Src family of tyrosine kinases. This structure reveals that, unlike the structures of other Src kinase SH3 domains, the RT loop region is highly mobile and lacks a network of hydrogen bonds that is elsewhere apparent. The RT loop has been shown to form a major part of the binding interface between SH3 domains and HIV-1 Nef. Thermodynamic data, derived from isothermal titration calorimetry, for the binding of Hck SH3 to HIV-1 Nef show that the binding of Hck (KD = 1.5 microM) is approximately an order of magnitude tighter than those of other Src family kinases that were investigated (Fyn, Lck, and Src). This increase in affinity is attributed to, among other effects, the inherent flexibility in the RT loop which does not require breaking the network of hydrogen bonds to adopt the conformation required for binding.

RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef.,Arold S, O'Brien R, Franken P, Strub MP, Hoh F, Dumas C, Ladbury JE Biochemistry. 1998 Oct 20;37(42):14683-91. PMID:9778343[24]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Poincloux R, Al Saati T, Maridonneau-Parini I, Le Cabec V. The oncogenic activity of the Src family kinase Hck requires the cooperative action of the plasma membrane- and lysosome-associated isoforms. Eur J Cancer. 2009 Feb;45(3):321-7. doi: 10.1016/j.ejca.2008.11.020. Epub 2008, Dec 26. PMID:19114024 doi:10.1016/j.ejca.2008.11.020
  2. ↑ Pene-Dumitrescu T, Smithgall TE. Expression of a Src family kinase in chronic myelogenous leukemia cells induces resistance to imatinib in a kinase-dependent manner. J Biol Chem. 2010 Jul 9;285(28):21446-57. doi: 10.1074/jbc.M109.090043. Epub 2010, May 7. PMID:20452982 doi:10.1074/jbc.M109.090043
  3. ↑ Poincloux R, Al Saati T, Maridonneau-Parini I, Le Cabec V. The oncogenic activity of the Src family kinase Hck requires the cooperative action of the plasma membrane- and lysosome-associated isoforms. Eur J Cancer. 2009 Feb;45(3):321-7. doi: 10.1016/j.ejca.2008.11.020. Epub 2008, Dec 26. PMID:19114024 doi:10.1016/j.ejca.2008.11.020
  4. ↑ Pene-Dumitrescu T, Smithgall TE. Expression of a Src family kinase in chronic myelogenous leukemia cells induces resistance to imatinib in a kinase-dependent manner. J Biol Chem. 2010 Jul 9;285(28):21446-57. doi: 10.1074/jbc.M109.090043. Epub 2010, May 7. PMID:20452982 doi:10.1074/jbc.M109.090043
  5. ↑ Ghazizadeh S, Bolen JB, Fleit HB. Physical and functional association of Src-related protein tyrosine kinases with Fc gamma RII in monocytic THP-1 cells. J Biol Chem. 1994 Mar 25;269(12):8878-84. PMID:8132624
  6. ↑ Durden DL, Kim HM, Calore B, Liu Y. The Fc gamma RI receptor signals through the activation of hck and MAP kinase. J Immunol. 1995 Apr 15;154(8):4039-47. PMID:7535819
  7. ↑ Hallek M, Neumann C, Schaffer M, Danhauser-Riedl S, von Bubnoff N, de Vos G, Druker BJ, Yasukawa K, Griffin JD, Emmerich B. Signal transduction of interleukin-6 involves tyrosine phosphorylation of multiple cytosolic proteins and activation of Src-family kinases Fyn, Hck, and Lyn in multiple myeloma cell lines. Exp Hematol. 1997 Dec;25(13):1367-77. PMID:9406996
  8. ↑ Warmuth M, Bergmann M, Priess A, Hauslmann K, Emmerich B, Hallek M. The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent mechanism and phosphorylates the Grb2-binding site of Bcr. J Biol Chem. 1997 Dec 26;272(52):33260-70. PMID:9407116
  9. ↑ Howlett CJ, Bisson SA, Resek ME, Tigley AW, Robbins SM. The proto-oncogene p120(Cbl) is a downstream substrate of the Hck protein-tyrosine kinase. Biochem Biophys Res Commun. 1999 Apr 2;257(1):129-38. PMID:10092522 doi:10.1006/bbrc.1999.0427
  10. ↑ Bosco MC, Curiel RE, Zea AH, Malabarba MG, Ortaldo JR, Espinoza-Delgado I. IL-2 signaling in human monocytes involves the phosphorylation and activation of p59hck. J Immunol. 2000 May 1;164(9):4575-85. PMID:10779760
  11. ↑ Barlic J, Andrews JD, Kelvin AA, Bosinger SE, DeVries ME, Xu L, Dobransky T, Feldman RD, Ferguson SS, Kelvin DJ. Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI. Nat Immunol. 2000 Sep;1(3):227-33. PMID:10973280 doi:10.1038/79767
  12. ↑ Klejman A, Schreiner SJ, Nieborowska-Skorska M, Slupianek A, Wilson M, Smithgall TE, Skorski T. The Src family kinase Hck couples BCR/ABL to STAT5 activation in myeloid leukemia cells. EMBO J. 2002 Nov 1;21(21):5766-74. PMID:12411494
  13. ↑ Poghosyan Z, Robbins SM, Houslay MD, Webster A, Murphy G, Edwards DR. Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases. J Biol Chem. 2002 Feb 15;277(7):4999-5007. Epub 2001 Dec 10. PMID:11741929 doi:10.1074/jbc.M107430200
  14. ↑ Carreno S, Caron E, Cougoule C, Emorine LJ, Maridonneau-Parini I. p59Hck isoform induces F-actin reorganization to form protrusions of the plasma membrane in a Cdc42- and Rac-dependent manner. J Biol Chem. 2002 Jun 7;277(23):21007-16. Epub 2002 Mar 19. PMID:11904303 doi:10.1074/jbc.M201212200
  15. ↑ Howlett CJ, Robbins SM. Membrane-anchored Cbl suppresses Hck protein-tyrosine kinase mediated cellular transformation. Oncogene. 2002 Mar 7;21(11):1707-16. PMID:11896602 doi:10.1038/sj.onc.1205228
  16. ↑ Podar K, Mostoslavsky G, Sattler M, Tai YT, Hayashi T, Catley LP, Hideshima T, Mulligan RC, Chauhan D, Anderson KC. Critical role for hematopoietic cell kinase (Hck)-mediated phosphorylation of Gab1 and Gab2 docking proteins in interleukin 6-induced proliferation and survival of multiple myeloma cells. J Biol Chem. 2004 May 14;279(20):21658-65. Epub 2004 Mar 9. PMID:15010462 doi:10.1074/jbc.M305783200
  17. ↑ Yokoyama N, deBakker CD, Zappacosta F, Huddleston MJ, Annan RS, Ravichandran KS, Miller WT. Identification of tyrosine residues on ELMO1 that are phosphorylated by the Src-family kinase Hck. Biochemistry. 2005 Jun 21;44(24):8841-9. PMID:15952790 doi:10.1021/bi0500832
  18. ↑ Cougoule C, Carreno S, Castandet J, Labrousse A, Astarie-Dequeker C, Poincloux R, Le Cabec V, Maridonneau-Parini I. Activation of the lysosome-associated p61Hck isoform triggers the biogenesis of podosomes. Traffic. 2005 Aug;6(8):682-94. PMID:15998323 doi:10.1111/j.1600-0854.2005.00307.x
  19. ↑ Paliwal P, Radha V, Swarup G. Regulation of p73 by Hck through kinase-dependent and independent mechanisms. BMC Mol Biol. 2007 May 30;8:45. PMID:17535448 doi:10.1186/1471-2199-8-45
  20. ↑ Hausherr A, Tavares R, Schaffer M, Obermeier A, Miksch C, Mitina O, Ellwart J, Hallek M, Krause G. Inhibition of IL-6-dependent growth of myeloma cells by an acidic peptide repressing the gp130-mediated activation of Src family kinases. Oncogene. 2007 Jul 26;26(34):4987-98. Epub 2007 Feb 19. PMID:17310994 doi:10.1038/sj.onc.1210306
  21. ↑ Poincloux R, Al Saati T, Maridonneau-Parini I, Le Cabec V. The oncogenic activity of the Src family kinase Hck requires the cooperative action of the plasma membrane- and lysosome-associated isoforms. Eur J Cancer. 2009 Feb;45(3):321-7. doi: 10.1016/j.ejca.2008.11.020. Epub 2008, Dec 26. PMID:19114024 doi:10.1016/j.ejca.2008.11.020
  22. ↑ Baruzzi A, Iacobucci I, Soverini S, Lowell CA, Martinelli G, Berton G. c-Abl and Src-family kinases cross-talk in regulation of myeloid cell migration. FEBS Lett. 2010 Jan 4;584(1):15-21. doi: 10.1016/j.febslet.2009.11.009. Epub . PMID:19903482 doi:10.1016/j.febslet.2009.11.009
  23. ↑ Pene-Dumitrescu T, Smithgall TE. Expression of a Src family kinase in chronic myelogenous leukemia cells induces resistance to imatinib in a kinase-dependent manner. J Biol Chem. 2010 Jul 9;285(28):21446-57. doi: 10.1074/jbc.M109.090043. Epub 2010, May 7. PMID:20452982 doi:10.1074/jbc.M109.090043
  24. ↑ Arold S, O'Brien R, Franken P, Strub MP, Hoh F, Dumas C, Ladbury JE. RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef. Biochemistry. 1998 Oct 20;37(42):14683-91. PMID:9778343 doi:10.1021/bi980989q

1bu1, resolution 2.60Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=1bu1&oldid=3820243"