1g83: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 17: Line 17:
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </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/chain_selection.php?pdb_ID=2ata ConSurf].
</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=1g83 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">

Revision as of 03:46, 9 February 2016

CRYSTAL STRUCTURE OF FYN SH3-SH2CRYSTAL STRUCTURE OF FYN SH3-SH2

Structural highlights

1g83 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:FYN (HUMAN)
Activity:Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[FYN_HUMAN] Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19]

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

The regulatory fragment of Src kinases, comprising Src homology (SH) 3 and SH2 domains, is responsible for controlled repression of kinase activity. We have used a multidisciplinary approach involving crystallography, NMR, and isothermal titration calorimetry to study the regulatory fragment of Fyn (FynSH32) and its interaction with a physiological activator: a fragment of focal adhesion kinase that contains both phosphotyrosine and polyproline motifs. Although flexible, the preferred disposition of SH3 and SH2 domains in FynSH32 resembles the inactive forms of Hck and Src, differing significantly from LckSH32. This difference, which results from variation in the SH3-SH2 linker sequences, will affect the potential of the regulatory fragments to repress kinase activity. This surprising result implies that the mechanism of repression of Src family members may vary, explaining functional distinctions between Fyn and Lck. The interaction between FynSH32 and focal adhesion kinase is restricted to the canonical SH3 and SH2 binding sites and does not affect the dynamic independence of the two domains. Consequently, the interaction shows no enhancement by an avidity effect. Such an interaction may have evolved to gain specificity through an extended recognition site while maintaining rapid dissociation after signaling.

The role of the Src homology 3-Src homology 2 interface in the regulation of Src kinases.,Arold ST, Ulmer TS, Mulhern TD, Werner JM, Ladbury JE, Campbell ID, Noble ME J Biol Chem. 2001 May 18;276(20):17199-205. Epub 2001 Feb 2. PMID:11278857[20]

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

See Also

References

  1. ↑ Rigley K, Slocombe P, Proudfoot K, Wahid S, Mandair K, Bebbington C. Human p59fyn(T) regulates OKT3-induced calcium influx by a mechanism distinct from PIP2 hydrolysis in Jurkat T cells. J Immunol. 1995 Feb 1;154(3):1136-45. PMID:7822789
  2. ↑ Raab M, Cai YC, Bunnell SC, Heyeck SD, Berg LJ, Rudd CE. p56Lck and p59Fyn regulate CD28 binding to phosphatidylinositol 3-kinase, growth factor receptor-bound protein GRB-2, and T cell-specific protein-tyrosine kinase ITK: implications for T-cell costimulation. Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8891-5. PMID:7568038
  3. ↑ Huang J, Tilly D, Altman A, Sugie K, Grey HM. T-cell receptor antagonists induce Vav phosphorylation by selective activation of Fyn kinase. Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10923-9. PMID:11005864
  4. ↑ Nakamura T, Yamashita H, Takahashi T, Nakamura S. Activated Fyn phosphorylates alpha-synuclein at tyrosine residue 125. Biochem Biophys Res Commun. 2001 Feb 2;280(4):1085-92. PMID:11162638 doi:10.1006/bbrc.2000.4253
  5. ↑ Wolf RM, Wilkes JJ, Chao MV, Resh MD. Tyrosine phosphorylation of p190 RhoGAP by Fyn regulates oligodendrocyte differentiation. J Neurobiol. 2001 Oct;49(1):62-78. PMID:11536198
  6. ↑ Taniguchi S, Liu H, Nakazawa T, Yokoyama K, Tezuka T, Yamamoto T. p250GAP, a neural RhoGAP protein, is associated with and phosphorylated by Fyn. Biochem Biophys Res Commun. 2003 Jun 20;306(1):151-5. PMID:12788081
  7. ↑ Piedra J, Miravet S, Castano J, Palmer HG, Heisterkamp N, Garcia de Herreros A, Dunach M. p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha-catenin Interaction. Mol Cell Biol. 2003 Apr;23(7):2287-97. PMID:12640114
  8. ↑ Hisatsune C, Kuroda Y, Nakamura K, Inoue T, Nakamura T, Michikawa T, Mizutani A, Mikoshiba K. Regulation of TRPC6 channel activity by tyrosine phosphorylation. J Biol Chem. 2004 Apr 30;279(18):18887-94. Epub 2004 Feb 3. PMID:14761972 doi:10.1074/jbc.M311274200
  9. ↑ Meriane M, Tcherkezian J, Webber CA, Danek EI, Triki I, McFarlane S, Bloch-Gallego E, Lamarche-Vane N. Phosphorylation of DCC by Fyn mediates Netrin-1 signaling in growth cone guidance. J Cell Biol. 2004 Nov 22;167(4):687-98. PMID:15557120 doi:jcb.200405053
  10. ↑ Badour K, Zhang J, Shi F, Leng Y, Collins M, Siminovitch KA. Fyn and PTP-PEST-mediated regulation of Wiskott-Aldrich syndrome protein (WASp) tyrosine phosphorylation is required for coupling T cell antigen receptor engagement to WASp effector function and T cell activation. J Exp Med. 2004 Jan 5;199(1):99-112. PMID:14707117 doi:10.1084/jem.20030976
  11. ↑ Zamora-Leon SP, Bresnick A, Backer JM, Shafit-Zagardo B. Fyn phosphorylates human MAP-2c on tyrosine 67. J Biol Chem. 2005 Jan 21;280(3):1962-70. Epub 2004 Nov 9. PMID:15536091 doi:10.1074/jbc.M411380200
  12. ↑ Yang C, Zhou W, Jeon MS, Demydenko D, Harada Y, Zhou H, Liu YC. Negative regulation of the E3 ubiquitin ligase itch via Fyn-mediated tyrosine phosphorylation. Mol Cell. 2006 Jan 6;21(1):135-41. PMID:16387660 doi:10.1016/j.molcel.2005.11.014
  13. ↑ Tang X, Feng Y, Ye K. Src-family tyrosine kinase fyn phosphorylates phosphatidylinositol 3-kinase enhancer-activating Akt, preventing its apoptotic cleavage and promoting cell survival. Cell Death Differ. 2007 Feb;14(2):368-77. Epub 2006 Jul 14. PMID:16841086 doi:10.1038/sj.cdd.4402011
  14. ↑ Castano J, Solanas G, Casagolda D, Raurell I, Villagrasa P, Bustelo XR, Garcia de Herreros A, Dunach M. Specific phosphorylation of p120-catenin regulatory domain differently modulates its binding to RhoA. Mol Cell Biol. 2007 Mar;27(5):1745-57. Epub 2006 Dec 28. PMID:17194753 doi:10.1128/MCB.01974-06
  15. ↑ Solheim SA, Torgersen KM, Tasken K, Berge T. Regulation of FynT function by dual domain docking on PAG/Cbp. J Biol Chem. 2008 Feb 1;283(5):2773-83. Epub 2007 Dec 4. PMID:18056706 doi:10.1074/jbc.M705215200
  16. ↑ Harita Y, Kurihara H, Kosako H, Tezuka T, Sekine T, Igarashi T, Hattori S. Neph1, a component of the kidney slit diaphragm, is tyrosine-phosphorylated by the Src family tyrosine kinase and modulates intracellular signaling by binding to Grb2. J Biol Chem. 2008 Apr 4;283(14):9177-86. doi: 10.1074/jbc.M707247200. Epub 2008, Feb 7. PMID:18258597 doi:10.1074/jbc.M707247200
  17. ↑ Harita Y, Kurihara H, Kosako H, Tezuka T, Sekine T, Igarashi T, Ohsawa I, Ohta S, Hattori S. Phosphorylation of Nephrin Triggers Ca2+ Signaling by Recruitment and Activation of Phospholipase C-{gamma}1. J Biol Chem. 2009 Mar 27;284(13):8951-62. doi: 10.1074/jbc.M806851200. Epub 2009 , Jan 29. PMID:19179337 doi:10.1074/jbc.M806851200
  18. ↑ Uchida Y, Ohshima T, Yamashita N, Ogawara M, Sasaki Y, Nakamura F, Goshima Y. Semaphorin3A signaling mediated by Fyn-dependent tyrosine phosphorylation of collapsin response mediator protein 2 at tyrosine 32. J Biol Chem. 2009 Oct 2;284(40):27393-401. Epub 2009 Aug 3. PMID:19652227 doi:M109.000240
  19. ↑ Goh YM, Cinghu S, Hong ET, Lee YS, Kim JH, Jang JW, Li YH, Chi XZ, Lee KS, Wee H, Ito Y, Oh BC, Bae SC. Src kinase phosphorylates RUNX3 at tyrosine residues and localizes the protein in the cytoplasm. J Biol Chem. 2010 Mar 26;285(13):10122-9. doi: 10.1074/jbc.M109.071381. Epub 2010, Jan 25. PMID:20100835 doi:10.1074/jbc.M109.071381
  20. ↑ Arold ST, Ulmer TS, Mulhern TD, Werner JM, Ladbury JE, Campbell ID, Noble ME. The role of the Src homology 3-Src homology 2 interface in the regulation of Src kinases. J Biol Chem. 2001 May 18;276(20):17199-205. Epub 2001 Feb 2. PMID:11278857 doi:10.1074/jbc.M011185200

1g83, 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=1g83&oldid=2552380"