4dkd - Revision history

OCA at 06:54, 27 November 2024

2024-11-27T06:54:14Z

← Older revision		Revision as of 06:54, 27 November 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dkd]] is a 3 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=4DKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DKD FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dkd]] is a 3 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=4DKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DKD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 3Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4dkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dkd OCA], [https://pdbe.org/4dkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dkd RCSB], [https://www.ebi.ac.uk/pdbsum/4dkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dkd 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=4dkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dkd OCA], [https://pdbe.org/4dkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dkd RCSB], [https://www.ebi.ac.uk/pdbsum/4dkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dkd ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/IL34_HUMAN IL34_HUMAN]] Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1.<ref>PMID:18467591</ref> <ref>PMID:20489731</ref> <ref>PMID:20829061</ref> <ref>PMID:20504948</ref>		[https://www.uniprot.org/uniprot/IL34_HUMAN IL34_HUMAN] Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1.<ref>PMID:18467591</ref> <ref>PMID:20489731</ref> <ref>PMID:20829061</ref> <ref>PMID:20504948</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 08:22, 21 September 2022

2022-09-21T08:22:54Z

← Older revision		Revision as of 08:22, 21 September 2022
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	==Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R==		==Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R==
	<StructureSection load='4dkd' size='340' side='right' caption='[[4dkd]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='4dkd' size='340' side='right'caption='[[4dkd]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dkd]] is a 3 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=4DKD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4DKD FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dkd]] is a 3 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=4DKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DKD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene~~></td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IL34, C16orf77 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CSF1R, FMS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4dkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dkd OCA], [https://pdbe.org/4dkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dkd RCSB], [https://www.ebi.ac.uk/pdbsum/4dkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dkd ProSAT]</span></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </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=4dkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dkd OCA], [~~http~~://pdbe.org/4dkd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4dkd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4dkd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4dkd ProSAT]</span></td></tr>
	</table>		</table>
	~~== Disease ==~~
	[[http://www.uniprot.org/uniprot/CSF1R_HUMAN CSF1R_HUMAN]] Note=Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.<ref>PMID:15117969</ref> <ref>PMID:16648572</ref> <ref>PMID:17121910</ref> <ref>PMID:18814279</ref> <ref>PMID:19934330</ref> <ref>PMID:16337366</ref> Note=Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.<ref>PMID:15117969</ref> <ref>PMID:16648572</ref> <ref>PMID:17121910</ref> <ref>PMID:18814279</ref> <ref>PMID:19934330</ref> <ref>PMID:16337366</ref> Defects in CSF1R are the cause of leukoencephalopathy, diffuse hereditary, with spheroids (HDLS) [MIM:[http://omim.org/entry/221820 221820]]. An autosomal dominant adult-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes.<ref>PMID:15117969</ref> <ref>PMID:16648572</ref> <ref>PMID:17121910</ref> <ref>PMID:18814279</ref> <ref>PMID:19934330</ref> <ref>PMID:16337366</ref> <ref>PMID:22197934</ref>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/IL34_HUMAN IL34_HUMAN]] Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1.<ref>PMID:18467591</ref> <ref>PMID:20489731</ref> <ref>PMID:20829061</ref> <ref>PMID:20504948</ref> [[http://www.uniprot.org/uniprot/CSF1R_HUMAN CSF1R_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding. Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor.<ref>PMID:7683918</ref> <ref>PMID:12882960</ref> <ref>PMID:15117969</ref> <ref>PMID:16648572</ref> <ref>PMID:17121910</ref> <ref>PMID:16170366</ref> <ref>PMID:18467591</ref> <ref>PMID:18814279</ref> <ref>PMID:19934330</ref> <ref>PMID:20489731</ref> <ref>PMID:20829061</ref> <ref>PMID:20504948</ref> <ref>PMID:16337366</ref> <ref>PMID:19193011</ref>		[[https://www.uniprot.org/uniprot/IL34_HUMAN IL34_HUMAN]] Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1.<ref>PMID:18467591</ref> <ref>PMID:20489731</ref> <ref>PMID:20829061</ref> <ref>PMID:20504948</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
	*[[Interleukin\|Interleukin]]		*[[Colony-stimulating factor receptor 3D structures\|Colony-stimulating factor receptor 3D structures]]
			*[[Interleukin 3D structures\|Interleukin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: ~~Receptor protein-tyrosine kinase~~]]		[[Category: Large Structures]]
	[[Category: Bazan~~, J F~~]]		[[Category: Bazan JF]]
	[[Category: Ma, X]]		[[Category: Ma X]]
	[[Category: Starovasnik~~, M A]]~~		[[Category: Starovasnik MA]]
	~~[[Category: Cytokine-transferase complex]]~~
	~~[[Category: Dimeric four-helix bundle cytokine]]~~
	~~[[Category: Glycosylation]]~~
	~~[[Category: Receptor tyrosine kinase~~]]

OCA at 02:54, 11 December 2016

2016-12-11T02:54:18Z

← Older revision		Revision as of 02:54, 11 December 2016
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	==Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R==		==Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R==
	<StructureSection load='4dkd' size='340' side='right' caption='[[4dkd]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='4dkd' size='340' side='right' caption='[[4dkd]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4dkd]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DKD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DKD FirstGlance]. <br>		<table><tr><td colspan='2'>[[4dkd]] is a 3 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=4DKD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DKD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IL34, C16orf77 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), CSF1R, FMS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IL34, C16orf77 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CSF1R, FMS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </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=4dkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dkd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dkd RCSB], [http://www.ebi.ac.uk/pdbsum/4dkd PDBsum]</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=4dkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dkd OCA], [http://pdbe.org/4dkd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dkd RCSB], [http://www.ebi.ac.uk/pdbsum/4dkd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dkd ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 4dkd" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 27:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Bazan, J F]]		[[Category: Bazan, J F]]

OCA at 08:56, 15 February 2015

2015-02-15T08:56:10Z

← Older revision		Revision as of 08:56, 15 February 2015
Line 1:		Line 1:
	~~{{STRUCTURE_4dkd\| PDB=4dkd \| SCENE= }}~~		==Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R==
	===Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R===		<StructureSection load='4dkd' size='340' side='right' caption='[[4dkd]], [[Resolution\|resolution]] 3.00Å' scene=''>
	~~{{ABSTRACT_PUBMED_22483114}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4dkd]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DKD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DKD FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IL34, C16orf77 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CSF1R, FMS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </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=4dkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dkd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dkd RCSB], [http://www.ebi.ac.uk/pdbsum/4dkd PDBsum]</span></td></tr>
			</table>
			== Disease ==
			[[http://www.uniprot.org/uniprot/CSF1R_HUMAN CSF1R_HUMAN]] Note=Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.<ref>PMID:15117969</ref> <ref>PMID:16648572</ref> <ref>PMID:17121910</ref> <ref>PMID:18814279</ref> <ref>PMID:19934330</ref> <ref>PMID:16337366</ref> Note=Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.<ref>PMID:15117969</ref> <ref>PMID:16648572</ref> <ref>PMID:17121910</ref> <ref>PMID:18814279</ref> <ref>PMID:19934330</ref> <ref>PMID:16337366</ref> Defects in CSF1R are the cause of leukoencephalopathy, diffuse hereditary, with spheroids (HDLS) [MIM:[http://omim.org/entry/221820 221820]]. An autosomal dominant adult-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes.<ref>PMID:15117969</ref> <ref>PMID:16648572</ref> <ref>PMID:17121910</ref> <ref>PMID:18814279</ref> <ref>PMID:19934330</ref> <ref>PMID:16337366</ref> <ref>PMID:22197934</ref>
			== Function ==
			[[http://www.uniprot.org/uniprot/IL34_HUMAN IL34_HUMAN]] Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1.<ref>PMID:18467591</ref> <ref>PMID:20489731</ref> <ref>PMID:20829061</ref> <ref>PMID:20504948</ref> [[http://www.uniprot.org/uniprot/CSF1R_HUMAN CSF1R_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding. Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor.<ref>PMID:7683918</ref> <ref>PMID:12882960</ref> <ref>PMID:15117969</ref> <ref>PMID:16648572</ref> <ref>PMID:17121910</ref> <ref>PMID:16170366</ref> <ref>PMID:18467591</ref> <ref>PMID:18814279</ref> <ref>PMID:19934330</ref> <ref>PMID:20489731</ref> <ref>PMID:20829061</ref> <ref>PMID:20504948</ref> <ref>PMID:16337366</ref> <ref>PMID:19193011</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Lacking any discernible sequence similarity, interleukin-34 (IL-34) and colony stimulating factor 1 (CSF-1) signal through a common receptor CSF-1R on cells of mononuclear phagocyte lineage. Here, the crystal structure of dimeric IL-34 reveals a helical cytokine fold homologous to CSF-1, and we further show that the complex architecture of IL-34 bound to the N-terminal immunoglobulin domains of CSF-1R is similar to the CSF-1/CSF-1R assembly. However, unique conformational adaptations in the receptor domain geometry and intermolecular interface explain the cross-reactivity of CSF-1R for two such distantly related ligands. The docking adaptations of the IL-34 and CSF-1 quaternary complexes, when compared to the stem cell factor assembly, draw a common evolutionary theme for transmembrane signaling. In addition, the structure of IL-34 engaged by a Fab fragment reveals the mechanism of a neutralizing antibody that can help deconvolute IL-34 from CSF-1 biology, with implications for therapeutic intervention in diseases with myeloid pathogenic mechanisms.

	~~==Disease==~~		Structural Basis for the Dual Recognition of Helical Cytokines IL-34 and CSF-1 by CSF-1R.,Ma X, Lin WY, Chen Y, Stawicki S, Mukhyala K, Wu Y, Martin F, Bazan JF, Starovasnik MA Structure. 2012 Apr 4;20(4):676-87. Epub 2012 Apr 3. PMID:22483114<ref>PMID:22483114</ref>
	~~[[http://www.uniprot.org/uniprot/CSF1R_HUMAN CSF1R_HUMAN]] Note=Aberrant expression~~ of ~~CSF1 or CSF1R can promote cancer cell proliferation, invasion~~ and ~~formation of metastases~~. ~~Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast~~, ~~ovarian~~, ~~prostate~~, and endometrial cancers.<ref>PMID:15117969</ref><ref>PMID:16648572</ref><ref>PMID:17121910</ref><ref>PMID:18814279</ref><ref>PMID:19934330</ref><ref>PMID:16337366</ref> Note=Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, ~~such as rheumatoid arthritis~~, ~~glomerulonephritis~~, ~~atherosclerosis~~, and allograft rejection.<ref>PMID:15117969</ref><ref>PMID:16648572</ref><ref>PMID:17121910</ref><ref>PMID:18814279</ref><ref>PMID:19934330</ref><ref>PMID:16337366</ref> Defects in CSF1R are the cause of leukoencephalopathy, ~~diffuse hereditary~~, ~~with spheroids~~ (~~HDLS~~) ~~[MIM~~:~~[http://omim.org/entry/221820 221820]]. An autosomal dominant adult~~-~~onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes~~. ~~Patients often die of dementia within 6 years of onset~~. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes.<ref>PMID:15117969</ref><ref>PMID:16648572</ref><ref>PMID:17121910</ref><ref>PMID:18814279</ref><ref>PMID:~~19934330</ref><ref>PMID:16337366</ref>~~<ref>PMID:~~22197934~~</ref>

	~~==Function==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[http:/~~/~~www.uniprot.org/uniprot/IL34_HUMAN IL34_HUMAN]] Cytokine that promotes the proliferation~~, ~~survival and differentiation~~ of ~~monocytes and macrophages. Promotes~~ the ~~release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes~~. ~~Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption~~. ~~Signaling via CSF1R and its downstream effectors stimulates phosphorylation~~ of ~~MAPK1/ERK2 AND MAPK3/ERK1~~.<~~ref~~>PMID:18467591</ref><ref>PMID:20489731</ref><ref>PMID:20829061</ref><ref>PMID:20504948</ref> [[http://www.uniprot.org/uniprot/CSF1R_HUMAN CSF1R_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding. Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor.<ref>PMID:7683918</~~ref~~><ref>PMID:12882960</ref><ref>PMID:15117969</ref><ref>PMID:16648572</ref><ref>PMID:17121910</ref><ref>PMID:16170366</ref><ref>PMID:18467591</ref><ref>PMID:18814279</ref><ref>PMID:19934330</ref><ref>PMID:20489731</ref><ref>PMID:20829061</ref><ref>PMID:20504948</ref><ref>PMID:16337366</ref><ref>PMID:19193011</ref>		</div>

	~~==About this Structure==~~
	[[4dkd]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DKD OCA].

	==See Also==		==See Also==
	*[[Interleukin\|Interleukin]]		*[[Interleukin\|Interleukin]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:022483114</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Bazan, J F.]]		[[Category: Bazan, J F]]
	[[Category: Ma, X.]]		[[Category: Ma, X]]
	[[Category: Starovasnik, M A.]]		[[Category: Starovasnik, M A]]
	[[Category: Cytokine-transferase complex]]		[[Category: Cytokine-transferase complex]]
	[[Category: Dimeric four-helix bundle cytokine]]		[[Category: Dimeric four-helix bundle cytokine]]
	[[Category: Glycosylation]]		[[Category: Glycosylation]]
	[[Category: Receptor tyrosine kinase]]		[[Category: Receptor tyrosine kinase]]

OCA at 01:56, 25 March 2013

2013-03-25T01:56:37Z

← Older revision		Revision as of 01:56, 25 March 2013
Line 1:		Line 1:
	~~[[Image:4dkd.png\|left\|200px]]~~

	{{STRUCTURE_4dkd\| PDB=4dkd \| SCENE= }}		{{STRUCTURE_4dkd\| PDB=4dkd \| SCENE= }}
			===Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R===
			{{ABSTRACT_PUBMED_22483114}}

	===~~Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R~~===		==Disease==
			[[http://www.uniprot.org/uniprot/CSF1R_HUMAN CSF1R_HUMAN]] Note=Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.<ref>PMID:15117969</ref><ref>PMID:16648572</ref><ref>PMID:17121910</ref><ref>PMID:18814279</ref><ref>PMID:19934330</ref><ref>PMID:16337366</ref> Note=Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.<ref>PMID:15117969</ref><ref>PMID:16648572</ref><ref>PMID:17121910</ref><ref>PMID:18814279</ref><ref>PMID:19934330</ref><ref>PMID:16337366</ref> Defects in CSF1R are the cause of leukoencephalopathy, diffuse hereditary, with spheroids (HDLS) [MIM:[http://omim.org/entry/221820 221820]]. An autosomal dominant adult-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes.<ref>PMID:15117969</ref><ref>PMID:16648572</ref><ref>PMID:17121910</ref><ref>PMID:18814279</ref><ref>PMID:19934330</ref><ref>PMID:16337366</ref><ref>PMID:22197934</ref>

	~~{{ABSTRACT_PUBMED_22483114}}~~		==Function==
			[[http://www.uniprot.org/uniprot/IL34_HUMAN IL34_HUMAN]] Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1.<ref>PMID:18467591</ref><ref>PMID:20489731</ref><ref>PMID:20829061</ref><ref>PMID:20504948</ref> [[http://www.uniprot.org/uniprot/CSF1R_HUMAN CSF1R_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding. Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor.<ref>PMID:7683918</ref><ref>PMID:12882960</ref><ref>PMID:15117969</ref><ref>PMID:16648572</ref><ref>PMID:17121910</ref><ref>PMID:16170366</ref><ref>PMID:18467591</ref><ref>PMID:18814279</ref><ref>PMID:19934330</ref><ref>PMID:20489731</ref><ref>PMID:20829061</ref><ref>PMID:20504948</ref><ref>PMID:16337366</ref><ref>PMID:19193011</ref>

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
	<ref group="xtra">PMID:022483114</ref><references group="xtra"/>		<ref group="xtra">PMID:022483114</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]

OCA at 16:46, 20 October 2012

2012-10-20T16:46:30Z

← Older revision		Revision as of 16:46, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
	[[4dkd]] is a 3 chain structure ~~of [[Interleukin]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DKD OCA].		[[4dkd]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DKD OCA].

	==See Also==		==See Also==

OCA at 22:47, 26 July 2012

2012-07-26T22:47:37Z

← Older revision		Revision as of 22:47, 26 July 2012
Line 1:		Line 1:
	[[Image:4dkd.png\|left\|200px]]		[[Image:4dkd.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_4dkd", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_4dkd\| PDB=4dkd \| SCENE= }}		{{STRUCTURE_4dkd\| PDB=4dkd \| SCENE= }}

	===Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R===		===Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_22483114}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 22483114 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_22483114}}		{{ABSTRACT_PUBMED_22483114}}

	==About this Structure==		==About this Structure==
	[[4dkd]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DKD OCA].		[[4dkd]] is a 3 chain structure of [[Interleukin]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DKD OCA].

			==See Also==
			*[[Interleukin\|Interleukin]]

	==Reference==		==Reference==

OCA at 08:27, 25 April 2012

2012-04-25T08:27:57Z

← Older revision		Revision as of 08:27, 25 April 2012
Line 1:		Line 1:
	[[Image:4dkd.~~jpg~~\|left\|200px]]		[[Image:4dkd.png\|left\|200px]]

	<!--		<!--
Line 11:		Line 11:
	===Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R===		===Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R===


			<!--
			The line below this paragraph, {{ABSTRACT_PUBMED_22483114}}, adds the Publication Abstract to the page
			(as it appears on PubMed at http://www.pubmed.gov), where 22483114 is the PubMed ID number.
			-->
			{{ABSTRACT_PUBMED_22483114}}

	==About this Structure==		==About this Structure==
	[[4dkd]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DKD OCA].		[[4dkd]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DKD OCA].

			==Reference==
			<ref group="xtra">PMID:022483114</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]

OCA at 07:11, 11 April 2012

2012-04-11T07:11:50Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:4dkd.jpg|left|200px]]
-The entry 4dkd is ON HOLD
+<!--
-Authors: Ma, X., Bazan, J.F., Starovasnik, M.A.
+===Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R===
-Description:

OCA: Protected "4dkd" [edit=sysop:move=sysop]

2012-02-15T06:22:06Z

Protected "4dkd" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:22, 15 February 2012
(No difference)