CSF1R_MOUSE - dbPTM
CSF1R_MOUSE - PTM Information in dbPTM
Basic Information of Protein
UniProt ID CSF1R_MOUSE
UniProt AC P09581
Protein Name Macrophage colony-stimulating factor 1 receptor
Gene Name Csf1r
Organism Mus musculus (Mouse).
Sequence Length 977
Subcellular Localization Cell membrane
Single-pass type I membrane protein . The autophosphorylated receptor is ubiquitinated and internalized, leading to its degradation.
Protein Description 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..
Protein Sequence MELGPPLVLLLATVWHGQGAPVIEPSGPELVVEPGETVTLRCVSNGSVEWDGPISPYWTLDPESPGSTLTTRNATFKNTGTYRCTELEDPMAGSTTIHLYVKDPAHSWNLLAQEVTVVEGQEAVLPCLITDPALKDSVSLMREGGRQVLRKTVYFFSPWRGFIIRKAKVLDSNTYVCKTMVNGRESTSTGIWLKVNRVHPEPPQIKLEPSKLVRIRGEAAQIVCSATNAEVGFNVILKRGDTKLEIPLNSDFQDNYYKKVRALSLNAVDFQDAGIYSCVASNDVGTRTATMNFQVVESAYLNLTSEQSLLQEVSVGDSLILTVHADAYPSIQHYNWTYLGPFFEDQRKLEFITQRAIYRYTFKLFLNRVKASEAGQYFLMAQNKAGWNNLTFELTLRYPPEVSVTWMPVNGSDVLFCDVSGYPQPSVTWMECRGHTDRCDEAQALQVWNDTHPEVLSQKPFDKVIIQSQLPIGTLKHNMTYFCKTHNSVGNSSQYFRAVSLGQSKQLPDESLFTPVVVACMSVMSLLVLLLLLLLYKYKQKPKYQVRWKIIERYEGNSYTFIDPTQLPYNEKWEFPRNNLQFGKTLGAGAFGKVVEATAFGLGKEDAVLKVAVKMLKSTAHADEKEALMSELKIMSHLGQHENIVNLLGACTHGGPVLVITEYCCYGDLLNFLRRKAEAMLGPSLSPGQDSEGDSSYKNIHLEKKYVRRDSGFSSQGVDTYVEMRPVSTSSSDSFFKQDLDKEASRPLELWDLLHFSSQVAQGMAFLASKNCIHRDVAARNVLLTSGHVAKIGDFGLARDIMNDSNYVVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGLNPYPGILVNNKFYKLVKDGYQMAQPVFAPKNIYSIMQSCWDLEPTRRPTFQQICFLLQEQARLERRDQDYANLPSSGGSSGSDSGGGSSGGSSSEPEEESSSEHLACCEPGDIAQPLLQPNNYQFC
Overview of Protein Modification Sites with Functional and Structural Information
Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations Modification Substrate Peptides
&
Secondary Structure		 ASA (%) Reference Orthologous
Protein Cluster
45N-linked_GlycosylationVTLRCVSNGSVEWDG
EEEEEEECCCEEECC		26.7619017797
73N-linked_GlycosylationGSTLTTRNATFKNTG
CCCEEECCEEECCCC		41.0419017797
302N-linked_GlycosylationVVESAYLNLTSEQSL
EEEEHHCCCCCCCHH		28.70-
335N-linked_GlycosylationYPSIQHYNWTYLGPF
CCCCCCCCCEEECCC		23.61-
353PhosphorylationQRKLEFITQRAIYRY
HHHHHHHHHHHHHHH		19.8123140645
358PhosphorylationFITQRAIYRYTFKLF
HHHHHHHHHHHHHHH		9.1523140645
360PhosphorylationTQRAIYRYTFKLFLN
HHHHHHHHHHHHHHH		10.2723140645
361PhosphorylationQRAIYRYTFKLFLNR
HHHHHHHHHHHHHHH		12.8023140645
377PhosphorylationKASEAGQYFLMAQNK
CHHHHHHEEEEEECC		9.5829895711
389N-linked_GlycosylationQNKAGWNNLTFELTL
ECCCCCCCEEEEEEE		33.67-
410N-linked_GlycosylationSVTWMPVNGSDVLFC
EEEEEECCCCCEEEE		38.08-
449N-linked_GlycosylationAQALQVWNDTHPEVL
HHHHHHHHCCCHHHH		45.50-
478N-linked_GlycosylationPIGTLKHNMTYFCKT
CCCCCCCCEEEEEEC		23.93-
491N-linked_GlycosylationKTHNSVGNSSQYFRA
ECCCCCCCHHHHEEE		36.0116944957
495PhosphorylationSVGNSSQYFRAVSLG
CCCCHHHHEEEEECC		9.29-
544PhosphorylationKYKQKPKYQVRWKII
HHCCCCCCEEEEEEE		22.2921610095
559PhosphorylationERYEGNSYTFIDPTQ
EECCCCCEEEECCCC		15.0710727433
572UbiquitinationTQLPYNEKWEFPRNN
CCCCCCCCCCCCCCC		48.6722790023
584UbiquitinationRNNLQFGKTLGAGAF
CCCCCCCCEECCCCC		41.6922790023
598PhosphorylationFGKVVEATAFGLGKE
CHHHHHHHHCCCCCH		14.7125777480
604UbiquitinationATAFGLGKEDAVLKV
HHHCCCCCHHHHHHH		58.4222790023
610UbiquitinationGKEDAVLKVAVKMLK
CCHHHHHHHHHHHHH		22.88-
691PhosphorylationSLSPGQDSEGDSSYK
CCCCCCCCCCCCCCC		35.27-
695PhosphorylationGQDSEGDSSYKNIHL
CCCCCCCCCCCCEEE		46.5625367039
696PhosphorylationQDSEGDSSYKNIHLE
CCCCCCCCCCCEEEE		44.8825367039
697PhosphorylationDSEGDSSYKNIHLEK
CCCCCCCCCCEEEEE		16.4111297560
698UbiquitinationSEGDSSYKNIHLEKK
CCCCCCCCCEEEEEE		51.9122790023
706PhosphorylationNIHLEKKYVRRDSGF
CEEEEEEEEECCCCC		15.402140428
711PhosphorylationKKYVRRDSGFSSQGV
EEEEECCCCCCCCCC		39.6725521595
714PhosphorylationVRRDSGFSSQGVDTY
EECCCCCCCCCCCCE		25.8525159016
715PhosphorylationRRDSGFSSQGVDTYV
ECCCCCCCCCCCCEE		28.7925159016
720PhosphorylationFSSQGVDTYVEMRPV
CCCCCCCCEEEEEEC		27.3625159016
721PhosphorylationSSQGVDTYVEMRPVS
CCCCCCCEEEEEECC		7.029000134
728PhosphorylationYVEMRPVSTSSSDSF
EEEEEECCCCCCCCH		25.8429472430
729PhosphorylationVEMRPVSTSSSDSFF
EEEEECCCCCCCCHH		32.6323375375
730PhosphorylationEMRPVSTSSSDSFFK
EEEECCCCCCCCHHC		21.9729472430
731PhosphorylationMRPVSTSSSDSFFKQ
EEECCCCCCCCHHCC		37.9525159016
732PhosphorylationRPVSTSSSDSFFKQD
EECCCCCCCCHHCCC		36.7225159016
734PhosphorylationVSTSSSDSFFKQDLD
CCCCCCCCHHCCCCC		34.2329472430
737UbiquitinationSSSDSFFKQDLDKEA
CCCCCHHCCCCCHHC		40.67-
791UbiquitinationLTSGHVAKIGDFGLA
ECCCCEEEECCCHHH		46.2422790023
807PhosphorylationDIMNDSNYVVKGNAR
HHHCCCCCEEECCCC		15.579000134
810UbiquitinationNDSNYVVKGNARLPV
CCCCCEEECCCCCCC		36.0822790023
868UbiquitinationNKFYKLVKDGYQMAQ
CCHHHHHCCCCCCCC		56.7422790023
871PhosphorylationYKLVKDGYQMAQPVF
HHHHCCCCCCCCCCC		12.7826026062
884PhosphorylationVFAPKNIYSIMQSCW
CCCCHHHHHHHHHHC		11.0926026062
921PhosphorylationLERRDQDYANLPSSG
HHHCCCCCCCCCCCC		7.5517420255
974PhosphorylationPLLQPNNYQFC----
CCCCCCCCCCC----		15.0321610095
Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)
Modified Location Modified Residue Modification Type of Upstream Proteins Gene Name of Upstream Proteins UniProt AC of Upstream Proteins Sources
559YPhosphorylationKinaseCSF1RP09581
GPS
697YPhosphorylationKinaseCSF1RP09581
PhosphoELM
706YPhosphorylationKinaseCSF1RP09581
PhosphoELM
721YPhosphorylationKinaseCSF1RP09581
PhosphoELM
807YPhosphorylationKinaseCSF1RP09581
PhosphoELM
921YPhosphorylationKinaseCSF1RP09581
PhosphoELM
974YPhosphorylationKinaseCSF1RP09581
PhosphoELM
-KUbiquitinationE3 ubiquitin ligaseCblP22682
PMID:22199232
Functions of PTM Sites
Modified Location Modified Residue Modification Function Reference

Oops, there are no descriptions of PTM sites of CSF1R_MOUSE !!
Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location Modification Variant Position
(Distance <= 10) 		Residue Change SAP Related Disease Reference

Oops, there are no SNP-PTM records of CSF1R_MOUSE !!
Protein-Protein Interaction
Interacting Protein Gene Name Interaction Type PPI Reference Domain-Domain Interactions
CSF1R_MOUSECsf1rphysical
21041311
STAT3_MOUSEStat3physical
10330148
P85A_MOUSEPik3r1physical
10330148
GRB2_MOUSEGrb2physical
10330148
SHC1_MOUSEShc1physical
10330148
FYN_MOUSEFynphysical
15297464
THOC5_MOUSEThoc5physical
10597251
DOK1_MOUSEDok1physical
10585470
P85A_MOUSEPik3r1physical
17420256
PTN6_MOUSEPtpn6physical
10330148
P85A_MOUSEPik3r1physical
8947469
P85A_MOUSEPik3r1physical
9312046
PLCG2_MOUSEPlcg2physical
9312046
Drug and Disease Associations
Kegg Drug
DrugBank
There are no disease associations of PTM sites.
Regulatory Network of CSF1R_MOUSE

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Related Literatures of Post-Translational Modification
N-linked Glycosylation
ReferencePubMed
"Structure of macrophage colony stimulating factor bound to FMS:diverse signaling assemblies of class III receptor tyrosine kinases.";
Chen X., Liu H., Focia P.J., Shim A.H., He X.;
Proc. Natl. Acad. Sci. U.S.A. 105:18267-18272(2008).
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 20-296 IN COMPLEX WITH CSF1,GLYCOSYLATION AT ASN-45 AND ASN-73, SUBUNIT, AND DISULFIDE BONDS.
"Proteome-wide characterization of N-glycosylation events by diagonalchromatography.";
Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J.,Gevaert K.;
J. Proteome Res. 5:2438-2447(2006).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-491, AND MASSSPECTROMETRY.
Phosphorylation
ReferencePubMed
"The phagosomal proteome in interferon-gamma-activated macrophages.";
Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,Thibault P.;
Immunity 30:143-154(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-714, AND MASSSPECTROMETRY.
"Phosphorylation of CSF-1R Y721 mediates its association with PI3K toregulate macrophage motility and enhancement of tumor cell invasion.";
Sampaio N.G., Yu W., Cox D., Wyckoff J., Condeelis J., Stanley E.R.,Pixley F.J.;
J. Cell Sci. 124:2021-2031(2011).
Cited for: FUNCTION IN REGULATION OF CELL MOTILITY; CELL SHAPE; ACTINCYTOSKELETON REORGANIZATION; PHOSPHORYLATION OF AKT1 AND REGULATION OFPHOSPHATIDYLINOSITOL METABOLISM, INTERACTION WITH PIK3R1 ANS PLCG2,PHOSPHORYLATION AT TYR-706 AND TYR-721, AND MUTAGENESIS OF TYR-721.
"Functional overlap but differential expression of CSF-1 and IL-34 intheir CSF-1 receptor-mediated regulation of myeloid cells.";
Wei S., Nandi S., Chitu V., Yeung Y.G., Yu W., Huang M.,Williams L.T., Lin H., Stanley E.R.;
J. Leukoc. Biol. 88:495-505(2010).
Cited for: FUNCTION AS IL34 AND CSF1 RECEPTOR, FUNCTION IN ACTIVATION OFMAPK1/ERK2 AND MAPK3/ERK1, PHOSPHORYLATION AT TYR-559; TYR-807 ANDTYR-721, AUTOPHOSPHORYLATION, AND TISSUE SPECIFICITY.
"A juxtamembrane tyrosine in the colony stimulating factor-1 receptorregulates ligand-induced Src association, receptor kinase function,and down-regulation.";
Rohde C.M., Schrum J., Lee A.W.;
J. Biol. Chem. 279:43448-43461(2004).
Cited for: MUTAGENESIS OF TYR-559, PHOSPHORYLATION AT TYR-559, DOMAIN, AND ENZYMEREGULATION.
"C-Cbl binds the CSF-1 receptor at tyrosine 973, a novelphosphorylation site in the receptor's carboxy-terminus.";
Wilhelmsen K., Burkhalter S., van der Geer P.;
Oncogene 21:1079-1089(2002).
Cited for: INTERACTION WITH CBL, AND PHOSPHORYLATION AT TYR-974.
"Tyrosine 569 in the c-Fms juxtamembrane domain is essential forkinase activity and macrophage colony-stimulating factor-dependentinternalization.";
Myles G.M., Brandt C.S., Carlberg K., Rohrschneider L.R.;
Mol. Cell. Biol. 14:4843-4854(1994).
Cited for: FUNCTION AS CSF1 RECEPTOR IN CELL PROLIFERATION AND IN ACTIVATION OFAKT1; MAPK1/ERK2; MAPK3/ERK1; STAT3; STAT5A AND STAT5B, INTERACTIONWITH CBL; YES1; FYN AND SRC, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY,AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-559 AND TYR-807,UBIQUITINATION, AND MUTAGENESIS OF TYR-559.
"Mutation of Tyr697, a GRB2-binding site, and Tyr721, a PI 3-kinasebinding site, abrogates signal transduction by the murine CSF-1receptor expressed in Rat-2 fibroblasts.";
van der Geer P., Hunter T.;
EMBO J. 12:5161-5172(1993).
Cited for: FUNCTION AS CSF1 RECEPTOR, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION,PHOSPHORYLATION AT TYR-697; TYR-706; TYR-721 AND TYR-807, MUTAGENESISOF LYS-614; TYR-697 AND TYR-721, AND INTERACTION WITH GRB2.
"Tyrosine 706 and 807 phosphorylation site mutants in the murinecolony-stimulating factor-1 receptor are unaffected in their abilityto bind or phosphorylate phosphatidylinositol-3 kinase but showdifferential defects in their ability to induce early response genetranscription.";
van der Geer P., Hunter T.;
Mol. Cell. Biol. 11:4698-4709(1991).
Cited for: FUNCTION IN CELL PROLIFERATION AND PHOSPHORYLATION OF PIK3R1,INTERACTION WITH PIK3R1, PHOSPHORYLATION AT TYR-706 AND TYR-807, ANDMUTAGENESIS OF TYR-706 AND TYR-807.
"Identification of tyrosine 706 in the kinase insert as the majorcolony-stimulating factor 1 (CSF-1)-stimulated autophosphorylationsite in the CSF-1 receptor in a murine macrophage cell line.";
van der Geer P., Hunter T.;
Mol. Cell. Biol. 10:2991-3002(1990).
Cited for: PHOSPHORYLATION AT TYR-706 AND TYR-807.

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