DegronMD - P07333(CSF1R)

FUNCTION: 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 pro-inflammatory 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, including the ERK1/2 and the JNK pathway (PubMed:20504948, PubMed:30982609). 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. In the central nervous system, may play a role in the development of microglia macrophages (PubMed:30982608). {ECO:0000269|PubMed:12882960, ECO:0000269|PubMed:15117969, ECO:0000269|PubMed:16170366, ECO:0000269|PubMed:16337366, ECO:0000269|PubMed:16648572, ECO:0000269|PubMed:17121910, ECO:0000269|PubMed:18467591, ECO:0000269|PubMed:18814279, ECO:0000269|PubMed:19193011, ECO:0000269|PubMed:19934330, ECO:0000269|PubMed:20489731, ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:20829061, ECO:0000269|PubMed:30982608, ECO:0000269|PubMed:30982609, ECO:0000269|PubMed:7683918}. View more >>

GO - Biological processes (BP): axon guidance [GO:0007411]; cell-cell junction maintenance [GO:0045217]; cell population proliferation [GO:0008283]; cellular response to cytokine stimulus [GO:0071345]; cellular response to macrophage colony-stimulating factor stimulus [GO:0036006]; cytokine-mediated signaling pathway [GO:0019221]; forebrain neuron differentiation [GO:0021879]; hematopoietic progenitor cell differentiation [GO:0002244]; hemopoiesis [GO:0030097]; inflammatory response [GO:0006954]; innate immune response [GO:0045087]; macrophage colony-stimulating factor signaling pathway [GO:0038145]; macrophage differentiation [GO:0030225]; mammary gland duct morphogenesis [GO:0060603]; microglial cell proliferation [GO:0061518]; monocyte differentiation [GO:0030224]; negative regulation of apoptotic process [GO:0043066]; negative regulation of cell population proliferation [GO:0008285]; olfactory bulb development [GO:0021772]; osteoclast differentiation [GO:0030316]; peptidyl-tyrosine phosphorylation [GO:0018108]; phosphatidylinositol-mediated signaling [GO:0048015]; phosphatidylinositol metabolic process [GO:0046488]; positive regulation by host of viral process [GO:0044794]; positive regulation of cell migration [GO:0030335]; positive regulation of cell motility [GO:2000147]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of chemokine production [GO:0032722]; positive regulation of ERK1 and ERK2 cascade [GO:0070374]; positive regulation of kinase activity [GO:0033674]; positive regulation of macrophage chemotaxis [GO:0010759]; positive regulation of macrophage proliferation [GO:0120041]; positive regulation of protein phosphorylation [GO:0001934]; positive regulation of protein serine/threonine kinase activity [GO:0071902]; positive regulation of protein tyrosine kinase activity [GO:0061098]; positive regulation of tyrosine phosphorylation of STAT protein [GO:0042531]; protein autophosphorylation [GO:0046777]; regulation of actin cytoskeleton reorganization [GO:2000249]; regulation of bone resorption [GO:0045124]; regulation of cell shape [GO:0008360]; response to ischemia [GO:0002931]; ruffle organization [GO:0031529]; signal transduction [GO:0007165]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.D122N	TCGA-06-5416	GBM	TCGA	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.2778
p.D122N	DO10880	GBM	ICGC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.2778
p.K706N	TCGA-19-5956	GBM	TCGA	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation substituting flanking lysine	0.2778
p.K706N	DO13863	GBM	ICGC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation substituting flanking lysine	0.2778
p.S937R	TCGA-24-1426	OV	TCGA	DRRERDYTNLP	CBL_PTK	917:927	Mutation rewiring degron network	0.0556
p.S937R	DO30010	OV	ICGC	DRRERDYTNLP	CBL_PTK	917:927	Mutation rewiring degron network	0.0556
p.T731N	TCGA-55-7994	LUAD	TCGA	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation altering degron motif	0.7055
p.T731N	DO45311	LUAD	ICGC	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation altering degron motif	0.7055
p.A354P	TCGA-60-2719	LUSC	TCGA	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation rewiring degron network	0.0556
p.A354P	DO27453	LUSC	ICGC	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation rewiring degron network	0.0556
p.A352G	TCGA-AJ-A2QO	UCEC	TCGA	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation rewiring degron network	0.1111
p.A352G	DO42177	UCEC	ICGC	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation rewiring degron network	0.1111
p.P728H	TCGA-AX-A1CE	UCEC	TCGA	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation altering degron motif	0.7694
p.P728H	DO42280	UCEC	ICGC	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation altering degron motif	0.7694
p.R921W	TCGA-BA-A6DL	HNSC	TCGA	DRRERDYTNLP	CBL_PTK	917:927	Mutation altering degron motif	0.7523
p.R921W	DO52035	HNSC	ICGC	DRRERDYTNLP	CBL_PTK	917:927	Mutation altering degron motif	0.7523
p.R921W	SIDM01613	Colorectal Carcinoma	GDSC	DRRERDYTNLP	CBL_PTK	917:927	Mutation altering degron motif	0.7523
p.R710H	TCGA-BG-A222	UCEC	TCGA	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.2778
p.R710H	TCGA-BR-4184	STAD	TCGA	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.2778
p.R710H	DO233903	GACA	ICGC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.2778
p.R710H	DO38328	STAD	ICGC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.2778
p.R710H	DO42977	UCEC	ICGC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.2778
p.R710H	SIDM00504	Glioma	GDSC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.2778
p.R710H	SIDM00507	Other Solid Cancers	GDSC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.2778
p.R710H	ACH-001126	Brain Cancer	CCLE	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.2778
p.R710H	ACH-001490	Lung Cancer	CCLE	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.2778
p.R710H	COR-L321	NS	COSMIC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.2778
p.R710H	MOG-G-UVW	central nervous system	COSMIC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.2778
p.A123T	TCGA-BR-4184	STAD	TCGA	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.25
p.A123T	DO38328	STAD	ICGC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.25
p.M726I	TCGA-BT-A20T	BLCA	TCGA	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.0833
p.M726I	TCGA-BT-A20T	BLCA	TCGA	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation rewiring degron network	0.2778
p.M726I	DO804	BLCA	ICGC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.0833
p.M726I	DO804	BLCA	ICGC	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation rewiring degron network	0.2778
p.M726I	SIDM00114	Non-Small Cell Lung Carcinoma	GDSC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.0833
p.M726I	SIDM00114	Non-Small Cell Lung Carcinoma	GDSC	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation rewiring degron network	0.2778
p.M726I	H513	pleura	COSMIC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.0833
p.M726I	H513	pleura	COSMIC	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation rewiring degron network	0.2778
p.E119K	TCGA-CA-6715	COAD	TCGA	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation altering degron motif	0.591
p.E119K	TCGA-CK-5916	COAD	TCGA	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation altering degron motif	0.591
p.E119K	DO8786	COAD	ICGC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation altering degron motif	0.591
p.E119K	DO9690	COAD	ICGC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation altering degron motif	0.591
p.S343Y	TCGA-EO-A3B0	UCEC	TCGA	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation altering degron motif	0.6009
p.S343Y	DO219773	UCEC	ICGC	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation altering degron motif	0.6009
p.L351P	TCGA-EY-A215	UCEC	TCGA	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation rewiring degron network	0.1389
p.L351P	DO42665	UCEC	ICGC	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation rewiring degron network	0.1389
p.A354D	TCGA-J2-8194	LUAD	TCGA	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation rewiring degron network	0.0556
p.A354D	DO23971	LUAD	ICGC	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation rewiring degron network	0.0556
p.Q911E	TCGA-K4-A3WS	BLCA	TCGA	DRRERDYTNLP	CBL_PTK	917:927	Mutation rewiring degron network	0.1667
p.Q911E	DO480	BLCA	ICGC	DRRERDYTNLP	CBL_PTK	917:927	Mutation rewiring degron network	0.1667
p.V115M	TCGA-S5-A6DX	BLCA	TCGA	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation altering degron motif	0.6097
p.V115M	DO51903	BLCA	ICGC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation altering degron motif	0.6097
p.V110M	TCGA-VR-AA4D	ESCA	TCGA	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.1944
p.G340V	DO1158	BRCA	ICGC	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation altering degron motif	0.6421
p.G936S	DO228581	GACA	ICGC	DRRERDYTNLP	CBL_PTK	917:927	Mutation rewiring degron network	0.0833
p.G936S	DO233693	GACA	ICGC	DRRERDYTNLP	CBL_PTK	917:927	Mutation rewiring degron network	0.0833
p.G936S	SIDM01608	Endometrial Carcinoma	GDSC	DRRERDYTNLP	CBL_PTK	917:927	Mutation rewiring degron network	0.0833
p.G936S	ACH-000990	Endometrial/Uterine Cancer	CCLE	DRRERDYTNLP	CBL_PTK	917:927	Mutation rewiring degron network	0.0833
p.P341T	DO229024	LICA	ICGC	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation altering degron motif	0.7031
p.A352D	DO229026	LICA	ICGC	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation rewiring degron network	0.1111
p.P107T	DO229031	LICA	ICGC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.1111
p.S932R	DO229038	LICA	ICGC	DRRERDYTNLP	CBL_PTK	917:927	Mutation rewiring degron network	0.1944
p.G333D	DO220913	MELA	ICGC	LGPFSD	LIG_APCC_ABBA_1	339:344	Mutation rewiring degron network	0.1667
p.D721N	DO222710	MELA	ICGC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.2222
p.D721N	DO222710	MELA	ICGC	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation rewiring degron network	0.1389
p.M726V	DO232761	PBCA	ICGC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.0833
p.M726V	DO232761	PBCA	ICGC	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation rewiring degron network	0.2778
p.E725D	DO233506	PRAD	ICGC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.1111
p.E725D	DO233506	PRAD	ICGC	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation rewiring degron network	0.25
p.T731S	DO229446	SKCA	ICGC	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation altering degron motif	0.6005
p.E920D	SIDM00762	Non-Small Cell Lung Carcinoma	GDSC	DRRERDYTNLP	CBL_PTK	917:927	Mutation altering degron motif	0.5647
p.E920D	SIDM01878	Non-Cancerous	GDSC	DRRERDYTNLP	CBL_PTK	917:927	Mutation altering degron motif	0.5647
p.E920D	SIDM01007	T-Lymphoblastic Leukemia	GDSC	DRRERDYTNLP	CBL_PTK	917:927	Mutation altering degron motif	0.5647
p.E920D	SIDM00333	Endometrial Carcinoma	GDSC	DRRERDYTNLP	CBL_PTK	917:927	Mutation altering degron motif	0.5647
p.E920D	SIDM00382	Glioblastoma	GDSC	DRRERDYTNLP	CBL_PTK	917:927	Mutation altering degron motif	0.5647
p.E920D	SIDM00053	Pancreatic Carcinoma	GDSC	DRRERDYTNLP	CBL_PTK	917:927	Mutation altering degron motif	0.5647
p.E920D	SIDM00228	Thyroid Gland Carcinoma	GDSC	DRRERDYTNLP	CBL_PTK	917:927	Mutation altering degron motif	0.5647
p.G714S	SIDM00742	Non-Small Cell Lung Carcinoma	GDSC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation altering degron motif	0.6993
p.G714S	ACH-000021	Lung Cancer	CCLE	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation altering degron motif	0.6993
p.G714S	NCI-H1693	lung	COSMIC	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation altering degron motif	0.6993
p.A105V	SIDM00690	Head and Neck Carcinoma	GDSC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.0556
p.A105V	JHU-029	upper aerodigestive tract	COSMIC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.0556
p.A123G	SIDM01011	B-Cell Non-Hodgkin's Lymphoma	GDSC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.25
p.A123G	KARPAS-1106P	haematopoietic and lymphoid tissue	COSMIC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.25
p.R106L	SIDM00250	Esophageal Squamous Cell Carcinoma	GDSC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.0833
p.R106L	ACH-000917	Esophageal Cancer	CCLE	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.0833
p.R106L	TE-4	oesophagus	COSMIC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.0833
p.R106Q	SIDM00940	Breast Carcinoma	GDSC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.0833
p.R106Q	CAL-120	breast	COSMIC	VVVFED	LIG_APCC_ABBA_1	115:120	Mutation rewiring degron network	0.0833
p.S937G	SIDM00780	Colorectal Carcinoma	GDSC	DRRERDYTNLP	CBL_PTK	917:927	Mutation rewiring degron network	0.0556
p.S937G	ACH-000967	Colon/Colorectal Cancer	CCLE	DRRERDYTNLP	CBL_PTK	917:927	Mutation rewiring degron network	0.0556
p.S937G	ACH-001199	Colon/Colorectal Cancer	CCLE	DRRERDYTNLP	CBL_PTK	917:927	Mutation rewiring degron network	0.0556
p.S937G	ACH-001518	Endometrial/Uterine Cancer	CCLE	DRRERDYTNLP	CBL_PTK	917:927	Mutation rewiring degron network	0.0556
p.R727K	ACH-001232	Brain Cancer	CCLE	DSGFSS	DEG_SCF_TRCP1_1	712:717	Mutation rewiring degron network	0.0556
p.R727K	ACH-001232	Brain Cancer	CCLE	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation rewiring degron network	0.3056
p.L742M	ACH-001441	Eye Cancer	CCLE	PVSTS	DEG_SPOP_SBC_1	728:732	Mutation rewiring degron network	0.0556

Kaplan plot for CSF1R in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

CSF1R

UniProt ID: P07333

Entrez ID: 1436

Protein name: Macrophage colony-stimulating factor 1 receptor (CSF-1 receptor) (CSF-1-R) (CSF-1R) (M-CSF-R) (EC 2.7.10.1) (Proto-oncogene c-Fms) (CD antigen CD115)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for CSF1R in