CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002802
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
 Csfmr; Fms 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
572TQLPYNEKWEFPRNNubiquitination[1]
584RNNLQFGKTLGAGAFubiquitination[1]
604ATAFGLGKEDAVLKVubiquitination[1]
698SEGDSSYKNIHLEKKubiquitination[1]
791LTSGHVAKIGDFGLAubiquitination[1]
810NDSNYVVKGNARLPVubiquitination[1]
868NKFYKLVKDGYQMAQubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
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 24 104 Ig-like C2-type 1.
 DOMAIN 107 197 Ig-like C2-type 2.
 DOMAIN 204 298 Ig-like C2-type 3.
 DOMAIN 299 397 Ig-like C2-type 4.
 DOMAIN 398 503 Ig-like C2-type 5.
 DOMAIN 580 913 Protein kinase.
 NP_BIND 586 594 ATP (By similarity).
 REGION 540 572 Regulatory juxtamembrane domain (By
 REGION 794 816 Activation loop (By similarity).
 ACT_SITE 776 776 Proton acceptor (By similarity).
 BINDING 614 614 ATP (Probable).
 MOD_RES 544 544 Phosphotyrosine; by autocatalysis (By
 MOD_RES 559 559 Phosphotyrosine; by autocatalysis.
 MOD_RES 697 697 Phosphotyrosine; by autocatalysis.
 MOD_RES 706 706 Phosphotyrosine; by autocatalysis.
 MOD_RES 711 711 Phosphoserine (By similarity).
 MOD_RES 714 714 Phosphoserine.
 MOD_RES 721 721 Phosphotyrosine; by autocatalysis.
 MOD_RES 807 807 Phosphotyrosine; by autocatalysis.
 MOD_RES 921 921 Phosphotyrosine; by autocatalysis.
 MOD_RES 974 974 Phosphotyrosine; by autocatalysis.
 CARBOHYD 45 45 N-linked (GlcNAc...).
 CARBOHYD 73 73 N-linked (GlcNAc...).
 CARBOHYD 302 302 N-linked (GlcNAc...) (Potential).
 CARBOHYD 335 335 N-linked (GlcNAc...) (Potential).
 CARBOHYD 389 389 N-linked (GlcNAc...) (Potential).
 CARBOHYD 410 410 N-linked (GlcNAc...) (Potential).
 CARBOHYD 449 449 N-linked (GlcNAc...) (Potential).
 CARBOHYD 478 478 N-linked (GlcNAc...) (Potential).
 CARBOHYD 491 491 N-linked (GlcNAc...).
 DISULFID 42 84
 DISULFID 127 177
 DISULFID 224 278
 DISULFID 417 483 By similarity.  
Keyword
 3D-structure; ATP-binding; Cell membrane; Complete proteome; Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Inflammatory response; Innate immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; 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
 977 AA 
Protein Sequence
MELGPPLVLL LATVWHGQGA PVIEPSGPEL VVEPGETVTL RCVSNGSVEW DGPISPYWTL 60
DPESPGSTLT TRNATFKNTG TYRCTELEDP MAGSTTIHLY VKDPAHSWNL LAQEVTVVEG 120
QEAVLPCLIT DPALKDSVSL MREGGRQVLR KTVYFFSPWR GFIIRKAKVL DSNTYVCKTM 180
VNGRESTSTG IWLKVNRVHP EPPQIKLEPS KLVRIRGEAA QIVCSATNAE VGFNVILKRG 240
DTKLEIPLNS DFQDNYYKKV RALSLNAVDF QDAGIYSCVA SNDVGTRTAT MNFQVVESAY 300
LNLTSEQSLL QEVSVGDSLI LTVHADAYPS IQHYNWTYLG PFFEDQRKLE FITQRAIYRY 360
TFKLFLNRVK ASEAGQYFLM AQNKAGWNNL TFELTLRYPP EVSVTWMPVN GSDVLFCDVS 420
GYPQPSVTWM ECRGHTDRCD EAQALQVWND THPEVLSQKP FDKVIIQSQL PIGTLKHNMT 480
YFCKTHNSVG NSSQYFRAVS LGQSKQLPDE SLFTPVVVAC MSVMSLLVLL LLLLLYKYKQ 540
KPKYQVRWKI IERYEGNSYT FIDPTQLPYN EKWEFPRNNL QFGKTLGAGA FGKVVEATAF 600
GLGKEDAVLK VAVKMLKSTA HADEKEALMS ELKIMSHLGQ HENIVNLLGA CTHGGPVLVI 660
TEYCCYGDLL NFLRRKAEAM LGPSLSPGQD SEGDSSYKNI HLEKKYVRRD SGFSSQGVDT 720
YVEMRPVSTS SSDSFFKQDL DKEASRPLEL WDLLHFSSQV AQGMAFLASK NCIHRDVAAR 780
NVLLTSGHVA KIGDFGLARD IMNDSNYVVK GNARLPVKWM APESIFDCVY TVQSDVWSYG 840
ILLWEIFSLG LNPYPGILVN NKFYKLVKDG YQMAQPVFAP KNIYSIMQSC WDLEPTRRPT 900
FQQICFLLQE QARLERRDQD YANLPSSGGS SGSDSGGGSS GGSSSEPEEE SSSEHLACCE 960
PGDIAQPLLQ PNNYQFC 977 
Gene Ontology
 GO:0009986; C:cell surface; IDA:UniProtKB.
 GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
 GO:0005886; C:plasma membrane; IDA:MGI.
 GO:0043235; C:receptor complex; IDA: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:0008283; P:cell proliferation; IEA:Compara.
 GO:0045217; P:cell-cell junction maintenance; IEA:Compara.
 GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
 GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
 GO:0030316; P:osteoclast differentiation; IMP:UniProtKB.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
 GO:0046488; P:phosphatidylinositol metabolic process; IMP:UniProtKB.
 GO:0048015; P:phosphatidylinositol-mediated signaling; IMP:UniProtKB.
 GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; IMP:UniProtKB.
 GO:0090197; P:positive regulation of chemokine secretion; IEA:Compara.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
 GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IMP:UniProtKB.
 GO:0061098; P:positive regulation of protein tyrosine kinase activity; IEA:Compara.
 GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 protein; IMP:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:2000249; P:regulation of actin cytoskeleton reorganization; IMP:UniProtKB.
 GO:0045124; P:regulation of bone resorption; ISS:UniProtKB.
 GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
 GO:0031529; P:ruffle organization; IMP:UniProtKB.
 GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IMP:UniProtKB. 
Interpro
 IPR007110; Ig-like_dom.
 IPR013783; Ig-like_fold.
 IPR013098; Ig_I-set.
 IPR003599; Ig_sub.
 IPR003598; Ig_sub2.
 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
 PF07679; I-set
 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