CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002491
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Macrophage colony-stimulating factor 1 receptor 
Protein Synonyms/Alias
 CSF-1 receptor; CSF-1-R; CSF-1R; M-CSF-R; Proto-oncogene c-Fms; CD115 
Gene Name
 CSF1R 
Gene Synonyms/Alias
 FMS 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
586RNNLQFGKTLGAGAFubiquitination[1, 2]
812NDSNYIVKGNARLPVubiquitination[1, 2]
867LVNSKFYKLVKDGYQubiquitination[1, 2]
870SKFYKLVKDGYQMAQubiquitination[1, 2]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
Functional 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. 
Sequence Annotation
 DOMAIN 21 104 Ig-like C2-type 1.
 DOMAIN 107 197 Ig-like C2-type 2.
 DOMAIN 203 290 Ig-like C2-type 3.
 DOMAIN 299 399 Ig-like C2-type 4.
 DOMAIN 402 502 Ig-like C2-type 5.
 DOMAIN 582 910 Protein kinase.
 NP_BIND 588 596 ATP (By similarity).
 REGION 542 574 Regulatory juxtamembrane domain.
 REGION 796 818 Activation loop.
 ACT_SITE 778 778 Proton acceptor (By similarity).
 BINDING 616 616 ATP (Probable).
 MOD_RES 546 546 Phosphotyrosine; by autocatalysis.
 MOD_RES 561 561 Phosphotyrosine; by autocatalysis.
 MOD_RES 699 699 Phosphotyrosine; by autocatalysis.
 MOD_RES 708 708 Phosphotyrosine; by autocatalysis.
 MOD_RES 713 713 Phosphoserine.
 MOD_RES 716 716 Phosphoserine (By similarity).
 MOD_RES 723 723 Phosphotyrosine; by autocatalysis.
 MOD_RES 809 809 Phosphotyrosine; by autocatalysis.
 MOD_RES 923 923 Phosphotyrosine; by autocatalysis.
 MOD_RES 969 969 Phosphotyrosine; by autocatalysis.
 CARBOHYD 45 45 N-linked (GlcNAc...) (Potential).
 CARBOHYD 73 73 N-linked (GlcNAc...) (Potential).
 CARBOHYD 153 153 N-linked (GlcNAc...) (Potential).
 CARBOHYD 240 240 N-linked (GlcNAc...) (Potential).
 CARBOHYD 275 275 N-linked (GlcNAc...) (Potential).
 CARBOHYD 302 302 N-linked (GlcNAc...).
 CARBOHYD 335 335 N-linked (GlcNAc...) (Potential).
 CARBOHYD 353 353 N-linked (GlcNAc...).
 CARBOHYD 412 412 N-linked (GlcNAc...) (Potential).
 CARBOHYD 428 428 N-linked (GlcNAc...) (Potential).
 CARBOHYD 480 480 N-linked (GlcNAc...) (Potential).
 DISULFID 42 84 By similarity.
 DISULFID 127 177 By similarity.
 DISULFID 224 278 By similarity.
 DISULFID 419 485 By similarity.  
Keyword
 3D-structure; ATP-binding; Cell membrane; Complete proteome; Disease mutation; Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Inflammatory response; Innate immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 972 AA 
Protein Sequence
MGPGVLLLLL VATAWHGQGI PVIEPSVPEL VVKPGATVTL RCVGNGSVEW DGPPSPHWTL 60
YSDGSSSILS TNNATFQNTG TYRCTEPGDP LGGSAAIHLY VKDPARPWNV LAQEVVVFED 120
QDALLPCLLT DPVLEAGVSL VRVRGRPLMR HTNYSFSPWH GFTIHRAKFI QSQDYQCSAL 180
MGGRKVMSIS IRLKVQKVIP GPPALTLVPA ELVRIRGEAA QIVCSASSVD VNFDVFLQHN 240
NTKLAIPQQS DFHNNRYQKV LTLNLDQVDF QHAGNYSCVA SNVQGKHSTS MFFRVVESAY 300
LNLSSEQNLI QEVTVGEGLN LKVMVEAYPG LQGFNWTYLG PFSDHQPEPK LANATTKDTY 360
RHTFTLSLPR LKPSEAGRYS FLARNPGGWR ALTFELTLRY PPEVSVIWTF INGSGTLLCA 420
ASGYPQPNVT WLQCSGHTDR CDEAQVLQVW DDPYPEVLSQ EPFHKVTVQS LLTVETLEHN 480
QTYECRAHNS VGSGSWAFIP ISAGAHTHPP DEFLFTPVVV ACMSIMALLL LLLLLLLYKY 540
KQKPKYQVRW KIIESYEGNS YTFIDPTQLP YNEKWEFPRN NLQFGKTLGA GAFGKVVEAT 600
AFGLGKEDAV LKVAVKMLKS TAHADEKEAL MSELKIMSHL GQHENIVNLL GACTHGGPVL 660
VITEYCCYGD LLNFLRRKAE AMLGPSLSPG QDPEGGVDYK NIHLEKKYVR RDSGFSSQGV 720
DTYVEMRPVS TSSNDSFSEQ DLDKEDGRPL ELRDLLHFSS QVAQGMAFLA SKNCIHRDVA 780
ARNVLLTNGH VAKIGDFGLA RDIMNDSNYI VKGNARLPVK WMAPESIFDC VYTVQSDVWS 840
YGILLWEIFS LGLNPYPGIL VNSKFYKLVK DGYQMAQPAF APKNIYSIMQ ACWALEPTHR 900
PTFQQICSFL QEQAQEDRRE RDYTNLPSSS RSGGSGSSSS ELEEESSSEH LTCCEQGDIA 960
QPLLQPNNYQ FC 972 
Gene Ontology
 GO:0009986; C:cell surface; ISS:UniProtKB.
 GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
 GO:0043235; C:receptor complex; ISS:BHF-UCL.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0019955; F:cytokine binding; IDA:UniProtKB.
 GO:0005011; F:macrophage colony-stimulating factor receptor activity; IMP:UniProtKB.
 GO:0042803; F:protein homodimerization activity; ISS:BHF-UCL.
 GO:0008283; P:cell proliferation; IMP:UniProtKB.
 GO:0045217; P:cell-cell junction maintenance; IMP:UniProtKB.
 GO:0006954; P:inflammatory response; TAS:UniProtKB.
 GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
 GO:0030225; P:macrophage differentiation; TAS:UniProtKB.
 GO:0060603; P:mammary gland duct morphogenesis; TAS:UniProtKB.
 GO:0030224; P:monocyte differentiation; TAS:UniProtKB.
 GO:0030316; P:osteoclast differentiation; ISS:UniProtKB.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
 GO:0046488; P:phosphatidylinositol metabolic process; ISS:UniProtKB.
 GO:0048015; P:phosphatidylinositol-mediated signaling; ISS:UniProtKB.
 GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; IMP:UniProtKB.
 GO:0090197; P:positive regulation of chemokine secretion; IMP:UniProtKB.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
 GO:0071902; P:positive regulation of protein serine/threonine kinase activity; ISS:UniProtKB.
 GO:0061098; P:positive regulation of protein tyrosine kinase activity; IMP:UniProtKB.
 GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 protein; ISS:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:2000249; P:regulation of actin cytoskeleton reorganization; ISS:UniProtKB.
 GO:0045124; P:regulation of bone resorption; ISS:UniProtKB.
 GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
 GO:0031529; P:ruffle organization; ISS:UniProtKB.
 GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; ISS:UniProtKB. 
Interpro
 IPR007110; Ig-like_dom.
 IPR013783; Ig-like_fold.
 IPR003599; Ig_sub.
 IPR003598; Ig_sub2.
 IPR013151; Immunoglobulin.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom.
 IPR016243; Tyr_kinase_CSF1/PDGF_rcpt.
 IPR001824; Tyr_kinase_rcpt_3_CS. 
Pfam
 PF00047; ig
 PF07714; Pkinase_Tyr 
SMART
 SM00409; IG
 SM00408; IGc2
 SM00219; TyrKc 
PROSITE
 PS50835; IG_LIKE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS00240; RECEPTOR_TYR_KIN_III 
PRINTS