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| | <StructureSection load='1scf' size='340' side='right'caption='[[1scf]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='1scf' size='340' side='right'caption='[[1scf]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1scf]] is a 4 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=1SCF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SCF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1scf]] 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=1SCF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SCF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=1scf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1scf OCA], [https://pdbe.org/1scf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1scf RCSB], [https://www.ebi.ac.uk/pdbsum/1scf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1scf 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=1scf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1scf OCA], [https://pdbe.org/1scf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1scf RCSB], [https://www.ebi.ac.uk/pdbsum/1scf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1scf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/SCF_HUMAN SCF_HUMAN]] Defects in KITLG are the cause of familial progressive hyperpigmentation (FPH) [MIM:[https://omim.org/entry/145250 145250]]; also called melanosis universalis hereditaria (MUH). FPH is an autosomal-dominantly inherited disorder characterized by hyperpigmented patches in the skin, present in early infancy and increasing in size and number with age.<ref>PMID:19375057</ref>
| + | [https://www.uniprot.org/uniprot/SCF_HUMAN SCF_HUMAN] Defects in KITLG are the cause of familial progressive hyperpigmentation (FPH) [MIM:[https://omim.org/entry/145250 145250]; also called melanosis universalis hereditaria (MUH). FPH is an autosomal-dominantly inherited disorder characterized by hyperpigmented patches in the skin, present in early infancy and increasing in size and number with age.<ref>PMID:19375057</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SCF_HUMAN SCF_HUMAN]] Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activation of STAT family members STAT1, STAT3 and STAT5. KITLG/SCF and KIT promote activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KITLG/SCF acts synergistically with other cytokines, probably interleukins.
| + | [https://www.uniprot.org/uniprot/SCF_HUMAN SCF_HUMAN] Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activation of STAT family members STAT1, STAT3 and STAT5. KITLG/SCF and KIT promote activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KITLG/SCF acts synergistically with other cytokines, probably interleukins. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gurel, O]] | + | [[Category: Gurel O]] |
| - | [[Category: Hendrickson, W A]] | + | [[Category: Hendrickson WA]] |
| - | [[Category: Jiang, X]] | + | [[Category: Jiang X]] |
| - | [[Category: Langley, K E]] | + | [[Category: Langley KE]] |
| - | [[Category: Hormone-growth factor complex]]
| + | |
| - | [[Category: Human stem cell factor]]
| + | |
| - | [[Category: Kit ligand]]
| + | |
| - | [[Category: Mast cell growth factor]]
| + | |
| - | [[Category: Steel factor]]
| + | |
| Structural highlights
Disease
SCF_HUMAN Defects in KITLG are the cause of familial progressive hyperpigmentation (FPH) [MIM:145250; also called melanosis universalis hereditaria (MUH). FPH is an autosomal-dominantly inherited disorder characterized by hyperpigmented patches in the skin, present in early infancy and increasing in size and number with age.[1]
Function
SCF_HUMAN Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activation of STAT family members STAT1, STAT3 and STAT5. KITLG/SCF and KIT promote activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KITLG/SCF acts synergistically with other cytokines, probably interleukins.
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
Stem cell factor (SCF) is an early-acting hematopoietic cytokine that elicits multiple biological effects. SCF is dimeric and occurs in soluble and membrane-bound forms. It transduces signals by ligand- mediated dimerization of its receptor, Kit, which is a receptor tyrosine kinase related to the receptors for platelet-derived growth factor (PDGF), macrophage colony-stimulating factor, Flt-3 ligand and vascular endothelial growth factor (VEGF). All of these have extracellular ligand-binding portions composed of immunoglobulin-like repeats. We have determined the crystal structure of selenomethionyl soluble human SCF at 2.2 A resolution by multiwavelength anomalous diffraction phasing. SCF has the characteristic helical cytokine topology, but the structure is unique apart from core portions. The SCF dimer has a symmetric 'head-to-head' association. Using various prior observations, we have located potential Kit-binding sites on the SCF dimer. A superimposition of this dimer onto VEGF in its complex with the receptor Flt-1 places the binding sites on SCF in positions of topographical and electrostatic complementarity with the Kit counterparts of Flt-1, and a similar model can be made for the complex of PDGF with its receptor.
Structure of the active core of human stem cell factor and analysis of binding to its receptor kit.,Jiang X, Gurel O, Mendiaz EA, Stearns GW, Clogston CL, Lu HS, Osslund TD, Syed RS, Langley KE, Hendrickson WA EMBO J. 2000 Jul 3;19(13):3192-203. PMID:10880433[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang ZQ, Si L, Tang Q, Lin D, Fu Z, Zhang J, Cui B, Zhu Y, Kong X, Deng M, Xia Y, Xu H, Le W, Hu L, Kong X. Gain-of-function mutation of KIT ligand on melanin synthesis causes familial progressive hyperpigmentation. Am J Hum Genet. 2009 May;84(5):672-7. doi: 10.1016/j.ajhg.2009.03.019. Epub 2009 , Apr 16. PMID:19375057 doi:10.1016/j.ajhg.2009.03.019
- ↑ Jiang X, Gurel O, Mendiaz EA, Stearns GW, Clogston CL, Lu HS, Osslund TD, Syed RS, Langley KE, Hendrickson WA. Structure of the active core of human stem cell factor and analysis of binding to its receptor kit. EMBO J. 2000 Jul 3;19(13):3192-203. PMID:10880433 doi:10.1093/emboj/19.13.3192
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