CSF1R_MOUSE
ID CSF1R_MOUSE Reviewed; 977 AA.
AC P09581; Q3U3P1; Q9DBH9;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2002, sequence version 3.
DT 03-AUG-2022, entry version 233.
DE RecName: Full=Macrophage colony-stimulating factor 1 receptor;
DE AltName: Full=CSF-1 receptor;
DE Short=CSF-1-R;
DE Short=CSF-1R;
DE Short=M-CSF-R;
DE EC=2.7.10.1;
DE AltName: Full=Proto-oncogene c-Fms;
DE AltName: CD_antigen=CD115;
DE Flags: Precursor;
GN Name=Csf1r; Synonyms=Csfmr, Fms;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2966922;
RA Rothwell V.M., Rohrschneider L.R.;
RT "Murine c-fms cDNA: cloning, sequence analysis and retroviral expression.";
RL Oncogene Res. 1:311-324(1987).
RN [2]
RP SEQUENCE REVISION.
RA Rothwell V.M.;
RL Submitted (SEP-1988) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SEQUENCE REVISION.
RX PubMed=8441691; DOI=10.1093/nar/21.3.750;
RA de Parseval N., Bordereaux D., Gisselbrecht S., Sola B.;
RT "Reassessment of the murine c-fms proto-oncogene sequence.";
RL Nucleic Acids Res. 21:750-750(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Liver, and Urinary bladder;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16.
RX PubMed=8497248; DOI=10.1128/mcb.13.6.3191-3201.1993;
RA Yue X., Favot P., Dunn T.L., Cassady A.I., Hume D.A.;
RT "Expression of mRNA encoding the macrophage colony-stimulating factor
RT receptor (c-fms) is controlled by a constitutive promoter and tissue-
RT specific transcription elongation.";
RL Mol. Cell. Biol. 13:3191-3201(1993).
RN [7]
RP PHOSPHORYLATION AT TYR-706 AND TYR-807.
RX PubMed=2160591; DOI=10.1128/mcb.10.6.2991-3002.1990;
RA van der Geer P., Hunter T.;
RT "Identification of tyrosine 706 in the kinase insert as the major colony-
RT stimulating factor 1 (CSF-1)-stimulated autophosphorylation site in the
RT CSF-1 receptor in a murine macrophage cell line.";
RL Mol. Cell. Biol. 10:2991-3002(1990).
RN [8]
RP FUNCTION IN CELL PROLIFERATION AND PHOSPHORYLATION OF PIK3R1, INTERACTION
RP WITH PIK3R1, PHOSPHORYLATION AT TYR-706 AND TYR-807, AND MUTAGENESIS OF
RP TYR-706 AND TYR-807.
RX PubMed=1652061; DOI=10.1128/mcb.11.9.4698-4709.1991;
RA van der Geer P., Hunter T.;
RT "Tyrosine 706 and 807 phosphorylation site mutants in the murine colony-
RT stimulating factor-1 receptor are unaffected in their ability to bind or
RT phosphorylate phosphatidylinositol-3 kinase but show differential defects
RT in their ability to induce early response gene transcription.";
RL Mol. Cell. Biol. 11:4698-4709(1991).
RN [9]
RP FUNCTION AS CSF1 RECEPTOR, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION,
RP PHOSPHORYLATION AT TYR-697; TYR-706; TYR-721 AND TYR-807, MUTAGENESIS OF
RP LYS-614; TYR-697 AND TYR-721, AND INTERACTION WITH GRB2.
RX PubMed=8262059;
RA van der Geer P., Hunter T.;
RT "Mutation of Tyr697, a GRB2-binding site, and Tyr721, a PI 3-kinase binding
RT site, abrogates signal transduction by the murine CSF-1 receptor expressed
RT in Rat-2 fibroblasts.";
RL EMBO J. 12:5161-5172(1993).
RN [10]
RP FUNCTION AS CSF1 RECEPTOR IN CELL PROLIFERATION AND IN ACTIVATION OF AKT1;
RP MAPK1/ERK2; MAPK3/ERK1; STAT3; STAT5A AND STAT5B, INTERACTION WITH CBL;
RP YES1; FYN AND SRC, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY,
RP AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-559 AND TYR-807,
RP UBIQUITINATION, AND MUTAGENESIS OF TYR-559.
RX PubMed=8007983; DOI=10.1128/mcb.14.7.4843-4854.1994;
RA Myles G.M., Brandt C.S., Carlberg K., Rohrschneider L.R.;
RT "Tyrosine 569 in the c-Fms juxtamembrane domain is essential for kinase
RT activity and macrophage colony-stimulating factor-dependent
RT internalization.";
RL Mol. Cell. Biol. 14:4843-4854(1994).
RN [11]
RP FUNCTION IN MACROPHAGE PROLIFERATION; MACROPHAGE DIFFERENTIATION;
RP PHOSPHORYLATION OF PLCG2; PHOSPHORYLATION OF PIK3R1 AND PHOSPHORYLATION OF
RP GRB2, CATALYTIC ACTIVITY, INTERACTION WITH PIK3R1; GRB2; PLCG2 AND FYN, AND
RP MUTAGENESIS OF LYS-614; TYR-697; TYR-721 AND TYR-807.
RX PubMed=9312046; DOI=10.1093/emboj/16.19.5880;
RA Bourette R.P., Myles G.M., Choi J.L., Rohrschneider L.R.;
RT "Sequential activation of phoshatidylinositol 3-kinase and phospholipase C-
RT gamma2 by the M-CSF receptor is necessary for differentiation signaling.";
RL EMBO J. 16:5880-5893(1997).
RN [12]
RP INTERACTION WITH THOC5, AND MUTAGENESIS OF TYR-544; LYS-614; TYR-706;
RP TYR-721 AND TYR-807.
RX PubMed=10597251; DOI=10.1038/sj.onc.1203062;
RA Tamura T., Mancini A., Joos H., Koch A., Hakim C., Dumanski J.,
RA Weidner K.M., Niemann H.;
RT "FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage
RT differentiation.";
RL Oncogene 18:6488-6495(1999).
RN [13]
RP FUNCTION.
RX PubMed=10958675; DOI=10.1128/mcb.20.18.6779-6798.2000;
RA Lee A.W., States D.J.;
RT "Both src-dependent and -independent mechanisms mediate
RT phosphatidylinositol 3-kinase regulation of colony-stimulating factor 1-
RT activated mitogen-activated protein kinases in myeloid progenitors.";
RL Mol. Cell. Biol. 20:6779-6798(2000).
RN [14]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=11756160; DOI=10.1182/blood.v99.1.111;
RA Dai X.M., Ryan G.R., Hapel A.J., Dominguez M.G., Russell R.G., Kapp S.,
RA Sylvestre V., Stanley E.R.;
RT "Targeted disruption of the mouse colony-stimulating factor 1 receptor gene
RT results in osteopetrosis, mononuclear phagocyte deficiency, increased
RT primitive progenitor cell frequencies, and reproductive defects.";
RL Blood 99:111-120(2002).
RN [15]
RP INTERACTION WITH CBL, AND PHOSPHORYLATION AT TYR-974.
RX PubMed=11850825; DOI=10.1038/sj.onc.1205166;
RA Wilhelmsen K., Burkhalter S., van der Geer P.;
RT "C-Cbl binds the CSF-1 receptor at tyrosine 973, a novel phosphorylation
RT site in the receptor's carboxy-terminus.";
RL Oncogene 21:1079-1089(2002).
RN [16]
RP MUTAGENESIS OF TYR-559, PHOSPHORYLATION AT TYR-559, DOMAIN, AND ACTIVITY
RP REGULATION.
RX PubMed=15297464; DOI=10.1074/jbc.m314170200;
RA Rohde C.M., Schrum J., Lee A.W.;
RT "A juxtamembrane tyrosine in the colony stimulating factor-1 receptor
RT regulates ligand-induced Src association, receptor kinase function, and
RT down-regulation.";
RL J. Biol. Chem. 279:43448-43461(2004).
RN [17]
RP INTERACTION WITH INPPL1.
RX PubMed=15557176; DOI=10.4049/jimmunol.173.11.6820;
RA Wang Y., Keogh R.J., Hunter M.G., Mitchell C.A., Frey R.S., Javaid K.,
RA Malik A.B., Schurmans S., Tridandapani S., Marsh C.B.;
RT "SHIP2 is recruited to the cell membrane upon macrophage colony-stimulating
RT factor (M-CSF) stimulation and regulates M-CSF-induced signaling.";
RL J. Immunol. 173:6820-6830(2004).
RN [18]
RP FUNCTION.
RX PubMed=16950670; DOI=10.1016/j.bone.2006.06.012;
RA Sakai H., Chen Y., Itokawa T., Yu K.P., Zhu M.L., Insogna K.;
RT "Activated c-Fms recruits Vav and Rac during CSF-1-induced cytoskeletal
RT remodeling and spreading in osteoclasts.";
RL Bone 39:1290-1301(2006).
RN [19]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-491.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=16944957; DOI=10.1021/pr060186m;
RA Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.;
RT "Proteome-wide characterization of N-glycosylation events by diagonal
RT chromatography.";
RL J. Proteome Res. 5:2438-2447(2006).
RN [20]
RP PHOSPHORYLATION, AND DEPHOSPHORYLATION BY PTPN2.
RX PubMed=16705167; DOI=10.1128/mcb.01932-05;
RA Simoncic P.D., Bourdeau A., Lee-Loy A., Rohrschneider L.R., Tremblay M.L.,
RA Stanley E.R., McGlade C.J.;
RT "T-cell protein tyrosine phosphatase (Tcptp) is a negative regulator of
RT colony-stimulating factor 1 signaling and macrophage differentiation.";
RL Mol. Cell. Biol. 26:4149-4160(2006).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF SLA2, INTERACTION WITH SLA2 AND CBL,
RP SUBCELLULAR LOCATION, AND UBIQUITINATION.
RX PubMed=17353186; DOI=10.1074/jbc.m701182200;
RA Pakuts B., Debonneville C., Liontos L.M., Loreto M.P., McGlade C.J.;
RT "The Src-like adaptor protein 2 regulates colony-stimulating factor-1
RT receptor signaling and down-regulation.";
RL J. Biol. Chem. 282:17953-17963(2007).
RN [22]
RP FUNCTION, MUTAGENESIS OF TYR-559, AND PHOSPHORYLATION AT TYR-921.
RX PubMed=17420255; DOI=10.1074/jbc.m610938200;
RA Takeshita S., Faccio R., Chappel J., Zheng L., Feng X., Weber J.D.,
RA Teitelbaum S.L., Ross F.P.;
RT "c-Fms tyrosine 559 is a major mediator of M-CSF-induced proliferation of
RT primary macrophages.";
RL J. Biol. Chem. 282:18980-18990(2007).
RN [23]
RP FUNCTION.
RX PubMed=17420256; DOI=10.1074/jbc.m610937200;
RA Faccio R., Takeshita S., Colaianni G., Chappel J., Zallone A.,
RA Teitelbaum S.L., Ross F.P.;
RT "M-CSF regulates the cytoskeleton via recruitment of a multimeric signaling
RT complex to c-Fms Tyr-559/697/721.";
RL J. Biol. Chem. 282:18991-18999(2007).
RN [24]
RP FUNCTION, AND SIGNALING PATHWAY.
RX PubMed=17972959; DOI=10.1038/sj.leu.2404986;
RA Bourgin-Hierle C., Gobert-Gosse S., Therier J., Grasset M.F.,
RA Mouchiroud G.;
RT "Src-family kinases play an essential role in differentiation signaling
RT downstream of macrophage colony-stimulating factor receptors mediating
RT persistent phosphorylation of phospholipase C-gamma2 and MAP kinases ERK1
RT and ERK2.";
RL Leukemia 22:161-169(2008).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [26]
RP FUNCTION IN OSTEOCLAST DIFFERENTIATION, ROLE IN DISEASE, AND ACTIVITY
RP REGULATION.
RX PubMed=18814279; DOI=10.1002/ijc.23903;
RA Hiraga T., Nakamura H.;
RT "Imatinib mesylate suppresses bone metastases of breast cancer by
RT inhibiting osteoclasts through the blockade of c-Fms signals.";
RL Int. J. Cancer 124:215-222(2009).
RN [27]
RP ROLE IN DISEASE.
RX PubMed=20181277; DOI=10.1186/ar2940;
RA Paniagua R.T., Chang A., Mariano M.M., Stein E.A., Wang Q., Lindstrom T.M.,
RA Sharpe O., Roscow C., Ho P.P., Lee D.M., Robinson W.H.;
RT "c-Fms-mediated differentiation and priming of monocyte lineage cells play
RT a central role in autoimmune arthritis.";
RL Arthritis Res. Ther. 12:R32-R32(2010).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-711, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [29]
RP FUNCTION AS IL34 AND CSF1 RECEPTOR, FUNCTION IN ACTIVATION OF MAPK1/ERK2
RP AND MAPK3/ERK1, PHOSPHORYLATION AT TYR-559; TYR-807 AND TYR-721,
RP AUTOPHOSPHORYLATION, AND TISSUE SPECIFICITY.
RX PubMed=20504948; DOI=10.1189/jlb.1209822;
RA Wei S., Nandi S., Chitu V., Yeung Y.G., Yu W., Huang M., Williams L.T.,
RA Lin H., Stanley E.R.;
RT "Functional overlap but differential expression of CSF-1 and IL-34 in their
RT CSF-1 receptor-mediated regulation of myeloid cells.";
RL J. Leukoc. Biol. 88:495-505(2010).
RN [30]
RP FUNCTION.
RX PubMed=21727904; DOI=10.1038/icb.2011.58;
RA Lenzo J.C., Turner A.L., Cook A.D., Vlahos R., Anderson G.P.,
RA Reynolds E.C., Hamilton J.A.;
RT "Control of macrophage lineage populations by CSF-1 receptor and GM-CSF in
RT homeostasis and inflammation.";
RL Immunol. Cell Biol. 90:429-440(2012).
RN [31]
RP UBIQUITINATION.
RX PubMed=21041311; DOI=10.1074/jbc.m110.166702;
RA Xiong Y., Song D., Cai Y., Yu W., Yeung Y.G., Stanley E.R.;
RT "A CSF-1 receptor phosphotyrosine 559 signaling pathway regulates receptor
RT ubiquitination and tyrosine phosphorylation.";
RL J. Biol. Chem. 286:952-960(2011).
RN [32]
RP FUNCTION IN REGULATION OF CELL MOTILITY; CELL SHAPE; ACTIN CYTOSKELETON
RP REORGANIZATION; PHOSPHORYLATION OF AKT1 AND REGULATION OF
RP PHOSPHATIDYLINOSITOL METABOLISM, INTERACTION WITH PIK3R1 AND PLCG2,
RP PHOSPHORYLATION AT TYR-706 AND TYR-721, AND MUTAGENESIS OF TYR-721.
RX PubMed=21610095; DOI=10.1242/jcs.075309;
RA Sampaio N.G., Yu W., Cox D., Wyckoff J., Condeelis J., Stanley E.R.,
RA Pixley F.J.;
RT "Phosphorylation of CSF-1R Y721 mediates its association with PI3K to
RT regulate macrophage motility and enhancement of tumor cell invasion.";
RL J. Cell Sci. 124:2021-2031(2011).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 20-296 IN COMPLEX WITH CSF1,
RP GLYCOSYLATION AT ASN-45 AND ASN-73, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=19017797; DOI=10.1073/pnas.0807762105;
RA Chen X., Liu H., Focia P.J., Shim A.H., He X.;
RT "Structure of macrophage colony stimulating factor bound to FMS: diverse
RT signaling assemblies of class III receptor tyrosine kinases.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:18267-18272(2008).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor
CC for CSF1 and IL34 and plays an essential role in the regulation of
CC survival, proliferation and differentiation of hematopoietic precursor
CC cells, especially mononuclear phagocytes, such as macrophages and
CC monocytes. Promotes the release of pro-inflammatory chemokines in
CC response to IL34 and CSF1, and thereby plays an important role in
CC innate immunity and in inflammatory processes. Plays an important role
CC in the regulation of osteoclast proliferation and differentiation, the
CC regulation of bone resorption, and is required for normal bone and
CC tooth development. Required for normal male and female fertility, and
CC for normal development of milk ducts and acinar structures in the
CC mammary gland during pregnancy. Promotes reorganization of the actin
CC cytoskeleton, regulates formation of membrane ruffles, cell adhesion
CC and cell migration, and promotes cancer cell invasion. Activates
CC several signaling pathways in response to ligand binding, including the
CC ERK1/2 and the JNK pathway (By similarity). Phosphorylates PIK3R1,
CC PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production
CC of the cellular signaling molecules diacylglycerol and inositol 1,4,5-
CC trisphosphate, that then lead to the activation of protein kinase C
CC family members, especially PRKCD. Phosphorylation of PIK3R1, the
CC regulatory subunit of phosphatidylinositol 3-kinase, leads to
CC activation of the AKT1 signaling pathway. Activated CSF1R also mediates
CC activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the
CC SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals
CC both via proteins that directly interact with phosphorylated tyrosine
CC residues in its intracellular domain, or via adapter proteins, such as
CC GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or
CC STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1.
CC Receptor signaling is down-regulated by protein phosphatases, such as
CC INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream
CC effectors, and by rapid internalization of the activated receptor. In
CC the central nervous system, may play a role in the development of
CC microglia macrophages (By similarity). {ECO:0000250|UniProtKB:P07333,
CC ECO:0000269|PubMed:10958675, ECO:0000269|PubMed:11756160,
CC ECO:0000269|PubMed:1652061, ECO:0000269|PubMed:16950670,
CC ECO:0000269|PubMed:17353186, ECO:0000269|PubMed:17420255,
CC ECO:0000269|PubMed:17420256, ECO:0000269|PubMed:17972959,
CC ECO:0000269|PubMed:18814279, ECO:0000269|PubMed:20181277,
CC ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:21610095,
CC ECO:0000269|PubMed:21727904, ECO:0000269|PubMed:8007983,
CC ECO:0000269|PubMed:8262059, ECO:0000269|PubMed:9312046}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:8007983, ECO:0000269|PubMed:8262059,
CC ECO:0000269|PubMed:9312046};
CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC of bound ligand. CSF1 or IL34 binding leads to dimerization and
CC activation by autophosphorylation on tyrosine residues. Inhibited by
CC imatinib/STI-571 (Gleevec), dasatinib, sunitinib/SU11248,
CC lestaurtinib/CEP-701, midostaurin/PKC-412, Ki20227, linifanib/ABT-869,
CC Axitinib/AG013736, sorafenib/BAY 43-9006 and GW2580.
CC {ECO:0000269|PubMed:15297464, ECO:0000269|PubMed:18814279}.
CC -!- SUBUNIT: Monomer. Homodimer. Interacts with CSF1 and IL34. Interaction
CC with dimeric CSF1 or IL34 leads to receptor homodimerization. Interacts
CC with INPPL1/SHIP2 and THOC5. Interacts (tyrosine phosphorylated) with
CC PLCG2 (via SH2 domain). Interacts (tyrosine phosphorylated) with PIK3R1
CC (via SH2 domain). Interacts (tyrosine phosphorylated) with FYN, YES1
CC and SRC (via SH2 domain). Interacts (tyrosine phosphorylated) with CBL,
CC GRB2 and SLA2. {ECO:0000269|PubMed:10597251,
CC ECO:0000269|PubMed:11850825, ECO:0000269|PubMed:15557176,
CC ECO:0000269|PubMed:1652061, ECO:0000269|PubMed:17353186,
CC ECO:0000269|PubMed:19017797, ECO:0000269|PubMed:21610095,
CC ECO:0000269|PubMed:8007983, ECO:0000269|PubMed:8262059,
CC ECO:0000269|PubMed:9312046}.
CC -!- INTERACTION:
CC P09581; P07141: Csf1; NbExp=6; IntAct=EBI-6305373, EBI-777188;
CC P09581; P09603: CSF1; Xeno; NbExp=2; IntAct=EBI-6305373, EBI-2872294;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17353186,
CC ECO:0000269|PubMed:8007983}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:17353186, ECO:0000269|PubMed:8007983}. Note=The
CC autophosphorylated receptor is ubiquitinated and internalized, leading
CC to its degradation.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:20504948}.
CC -!- DOMAIN: The juxtamembrane domain functions as autoinhibitory region.
CC Phosphorylation of tyrosine residues in this region leads to a
CC conformation change and activation of the kinase (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: The activation loop plays an important role in the regulation
CC of kinase activity. Phosphorylation of tyrosine residues in this region
CC leads to a conformation change and activation of the kinase (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Autophosphorylated in response to CSF1 or IL34 binding.
CC Phosphorylation at Tyr-559 is important for normal down-regulation of
CC signaling by ubiquitination, internalization and degradation.
CC Phosphorylation at Tyr-559 and Tyr-807 is important for interaction
CC with SRC family members, including FYN, YES1 and SRC, and for
CC subsequent activation of these protein kinases. Phosphorylation at Tyr-
CC 697 and Tyr-921 is important for interaction with GRB2. Phosphorylation
CC at Tyr-721 is important for interaction with PIK3R1. Phosphorylation at
CC Tyr-721 and Tyr-807 is important for interaction with PLCG2.
CC Phosphorylation at Tyr-974 is important for interaction with CBL.
CC Dephosphorylation by PTPN2 negatively regulates downstream signaling
CC and macrophage differentiation. {ECO:0000269|PubMed:11850825,
CC ECO:0000269|PubMed:15297464, ECO:0000269|PubMed:1652061,
CC ECO:0000269|PubMed:17420255, ECO:0000269|PubMed:20504948,
CC ECO:0000269|PubMed:2160591, ECO:0000269|PubMed:21610095,
CC ECO:0000269|PubMed:8007983, ECO:0000269|PubMed:8262059}.
CC -!- PTM: Ubiquitinated. Becomes rapidly polyubiquitinated after
CC autophosphorylation, leading to its degradation.
CC -!- DISRUPTION PHENOTYPE: Mice are born at slightly less than the expected
CC Mendelian rate, and the number of surviving mice is significantly
CC reduced after three weeks. Mice are considerably smaller than wild-type
CC littermates and suffer from general skeletal deformities with shortened
CC limbs, increased bone density, and decreased volume of femoral bone
CC marrow. Mice have decreased numbers of circulating monocytes and
CC lymphocytes, decreased numbers of tissue macrophages, paired with an
CC increase in the number of circulating granulocytes. In addition, mice
CC are deaf and have reduced male and female fertility. In females, the
CC duration of the diestrous period is increased, and in pregnant females
CC the lactating mammary gland fails to develop normally. Males mate less
CC frequently and give rise to fewer pregnant females.
CC {ECO:0000269|PubMed:11756160}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; X06368; CAA29666.1; -; mRNA.
DR EMBL; AK004947; BAB23691.1; -; mRNA.
DR EMBL; AK079247; BAC37587.1; -; mRNA.
DR EMBL; AK143545; BAE25430.1; -; mRNA.
DR EMBL; AK154653; BAE32744.1; -; mRNA.
DR EMBL; BC043054; AAH43054.1; -; mRNA.
DR EMBL; S62219; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS29280.1; -.
DR PIR; S01880; TVMSMD.
DR RefSeq; NP_001032948.2; NM_001037859.2.
DR RefSeq; XP_006525647.1; XM_006525584.1.
DR RefSeq; XP_006525648.1; XM_006525585.3.
DR RefSeq; XP_006525649.1; XM_006525586.3.
DR RefSeq; XP_017173299.1; XM_017317810.1.
DR PDB; 3EJJ; X-ray; 2.40 A; X=20-296.
DR PDB; 4EXP; X-ray; 2.80 A; X=20-298.
DR PDBsum; 3EJJ; -.
DR PDBsum; 4EXP; -.
DR AlphaFoldDB; P09581; -.
DR SMR; P09581; -.
DR BioGRID; 198928; 21.
DR DIP; DIP-46415N; -.
DR IntAct; P09581; 8.
DR MINT; P09581; -.
DR STRING; 10090.ENSMUSP00000025523; -.
DR BindingDB; P09581; -.
DR ChEMBL; CHEMBL5570; -.
DR GlyGen; P09581; 9 sites.
DR iPTMnet; P09581; -.
DR PhosphoSitePlus; P09581; -.
DR CPTAC; non-CPTAC-3547; -.
DR CPTAC; non-CPTAC-3548; -.
DR PaxDb; P09581; -.
DR PeptideAtlas; P09581; -.
DR PRIDE; P09581; -.
DR ProteomicsDB; 285343; -.
DR Antibodypedia; 1201; 1818 antibodies from 45 providers.
DR DNASU; 12978; -.
DR Ensembl; ENSMUST00000025523; ENSMUSP00000025523; ENSMUSG00000024621.
DR Ensembl; ENSMUST00000115268; ENSMUSP00000110923; ENSMUSG00000024621.
DR GeneID; 12978; -.
DR KEGG; mmu:12978; -.
DR UCSC; uc008fbn.1; mouse.
DR CTD; 1436; -.
DR MGI; MGI:1339758; Csf1r.
DR VEuPathDB; HostDB:ENSMUSG00000024621; -.
DR eggNOG; KOG0200; Eukaryota.
DR GeneTree; ENSGT00940000155506; -.
DR HOGENOM; CLU_000288_49_0_1; -.
DR InParanoid; P09581; -.
DR OMA; EQLACCE; -.
DR OrthoDB; 236292at2759; -.
DR PhylomeDB; P09581; -.
DR TreeFam; TF325768; -.
DR BRENDA; 2.7.10.1; 3474.
DR Reactome; R-MMU-449836; Other interleukin signaling.
DR BioGRID-ORCS; 12978; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Csf1r; mouse.
DR EvolutionaryTrace; P09581; -.
DR PRO; PR:P09581; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; P09581; protein.
DR Bgee; ENSMUSG00000024621; Expressed in stroma of bone marrow and 256 other tissues.
DR ExpressionAtlas; P09581; baseline and differential.
DR Genevisible; P09581; MM.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:1990682; C:CSF1-CSF1R complex; IDA:BHF-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019955; F:cytokine binding; IDA:UniProtKB.
DR GO; GO:0005011; F:macrophage colony-stimulating factor receptor activity; IDA:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:MGI.
DR GO; GO:0007411; P:axon guidance; IMP:ParkinsonsUK-UCL.
DR GO; GO:0008283; P:cell population proliferation; ISO:MGI.
DR GO; GO:0045217; P:cell-cell junction maintenance; ISO:MGI.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IMP:UniProtKB.
DR GO; GO:0036006; P:cellular response to macrophage colony-stimulating factor stimulus; IMP:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:MGI.
DR GO; GO:0021542; P:dentate gyrus development; ISO:MGI.
DR GO; GO:0021879; P:forebrain neuron differentiation; IMP:ParkinsonsUK-UCL.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IBA:GO_Central.
DR GO; GO:0030097; P:hemopoiesis; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0038145; P:macrophage colony-stimulating factor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0014005; P:microglia development; ISO:MGI.
DR GO; GO:0061518; P:microglial cell proliferation; IGI:ARUK-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:ParkinsonsUK-UCL.
DR GO; GO:1990138; P:neuron projection extension; ISO:MGI.
DR GO; GO:0021772; P:olfactory bulb development; IMP:ParkinsonsUK-UCL.
DR GO; GO:0030316; P:osteoclast differentiation; IMP:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; IMP:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IMP:UniProtKB.
DR GO; GO:0044794; P:positive regulation by host of viral process; IGI:ARUK-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:2000147; P:positive regulation of cell motility; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; ISO:MGI.
DR GO; GO:0120041; P:positive regulation of macrophage proliferation; ISO:MGI.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IMP:UniProtKB.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0045124; P:regulation of bone resorption; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0032944; P:regulation of mononuclear cell proliferation; ISO:MGI.
DR GO; GO:0002931; P:response to ischemia; IDA:ARUK-UCL.
DR GO; GO:0031529; P:ruffle organization; IMP:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IDA:BHF-UCL.
DR Gene3D; 2.60.40.10; -; 5.
DR InterPro; IPR030658; CSF-1_receptor.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013151; Immunoglobulin.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF500947; CSF-1_receptor; 1.
DR SMART; SM00409; IG; 5.
DR SMART; SM00408; IGc2; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 5.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 4.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunity; Immunoglobulin domain; Inflammatory response; Innate immunity;
KW Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Proto-oncogene;
KW Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..977
FT /note="Macrophage colony-stimulating factor 1 receptor"
FT /id="PRO_0000016766"
FT TOPO_DOM 20..515
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 516..536
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 537..977
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..104
FT /note="Ig-like C2-type 1"
FT DOMAIN 107..197
FT /note="Ig-like C2-type 2"
FT DOMAIN 204..298
FT /note="Ig-like C2-type 3"
FT DOMAIN 299..397
FT /note="Ig-like C2-type 4"
FT DOMAIN 398..503
FT /note="Ig-like C2-type 5"
FT DOMAIN 580..913
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 540..572
FT /note="Regulatory juxtamembrane domain"
FT /evidence="ECO:0000250"
FT REGION 794..816
FT /note="Activation loop"
FT /evidence="ECO:0000250"
FT REGION 921..957
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 923..947
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 776
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 586..594
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 614
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 544
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P07333"
FT MOD_RES 559
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15297464,
FT ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:8007983"
FT MOD_RES 697
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8262059"
FT MOD_RES 706
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:1652061,
FT ECO:0000269|PubMed:2160591, ECO:0000269|PubMed:21610095,
FT ECO:0000269|PubMed:8262059"
FT MOD_RES 711
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 721
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:20504948,
FT ECO:0000269|PubMed:21610095, ECO:0000269|PubMed:8262059"
FT MOD_RES 807
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:1652061,
FT ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:2160591,
FT ECO:0000269|PubMed:8007983, ECO:0000269|PubMed:8262059"
FT MOD_RES 921
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:17420255"
FT MOD_RES 974
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11850825"
FT CARBOHYD 45
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19017797"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19017797"
FT CARBOHYD 302
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 410
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 449
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 478
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 491
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957"
FT DISULFID 42..84
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:19017797"
FT DISULFID 127..177
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:19017797"
FT DISULFID 224..278
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:19017797"
FT DISULFID 417..483
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT MUTAGEN 544
FT /note="Y->F: No effect on binding to THOC5."
FT /evidence="ECO:0000269|PubMed:10597251"
FT MUTAGEN 559
FT /note="Y->F: Reduced interaction with CBL. Prolonged
FT signaling, due to reduced internalization and degradation.
FT Reduced interaction with FYN. Promotes cell proliferation.
FT Reduced autophosphorylation at Tyr-807."
FT /evidence="ECO:0000269|PubMed:15297464,
FT ECO:0000269|PubMed:17420255, ECO:0000269|PubMed:8007983"
FT MUTAGEN 614
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:10597251,
FT ECO:0000269|PubMed:8262059, ECO:0000269|PubMed:9312046"
FT MUTAGEN 614
FT /note="K->M: Loss of kinase activity. Abolishes binding to
FT THOC5."
FT /evidence="ECO:0000269|PubMed:10597251,
FT ECO:0000269|PubMed:8262059, ECO:0000269|PubMed:9312046"
FT MUTAGEN 697
FT /note="Y->F: Abolishes interaction with GRB2."
FT /evidence="ECO:0000269|PubMed:8262059,
FT ECO:0000269|PubMed:9312046"
FT MUTAGEN 706
FT /note="Y->F: No effect on binding to THOC5. Slightly
FT reduced enhancement of cell proliferation."
FT /evidence="ECO:0000269|PubMed:10597251,
FT ECO:0000269|PubMed:1652061"
FT MUTAGEN 706
FT /note="Y->G: Slightly impaired signaling."
FT /evidence="ECO:0000269|PubMed:10597251,
FT ECO:0000269|PubMed:1652061"
FT MUTAGEN 721
FT /note="Y->F: Abolishes interaction with PIK3R1. Strongly
FT reduced phosphorylation of PLCG2. No effect on binding to
FT THOC5."
FT /evidence="ECO:0000269|PubMed:10597251,
FT ECO:0000269|PubMed:21610095, ECO:0000269|PubMed:8262059,
FT ECO:0000269|PubMed:9312046"
FT MUTAGEN 807
FT /note="Y->F: Reduced kinase activity. Strongly reduced
FT phosphorylation of PLCG2. Diminishes binding to THOC5."
FT /evidence="ECO:0000269|PubMed:10597251,
FT ECO:0000269|PubMed:1652061, ECO:0000269|PubMed:9312046"
FT MUTAGEN 807
FT /note="Y->G: May alter protein folding or stability. Loss
FT of kinase activity. No effect on interaction with PIK3R1."
FT /evidence="ECO:0000269|PubMed:10597251,
FT ECO:0000269|PubMed:1652061, ECO:0000269|PubMed:9312046"
FT CONFLICT 57
FT /note="Y -> I (in Ref. 1; CAA29666)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="R -> S (in Ref. 1; CAA29666)"
FT /evidence="ECO:0000305"
FT CONFLICT 162
FT /note="F -> S (in Ref. 1; CAA29666)"
FT /evidence="ECO:0000305"
FT CONFLICT 446..447
FT /note="QV -> HL (in Ref. 1; CAA29666)"
FT /evidence="ECO:0000305"
FT CONFLICT 474
FT /note="T -> P (in Ref. 1; CAA29666)"
FT /evidence="ECO:0000305"
FT CONFLICT 660
FT /note="I -> Y (in Ref. 1; CAA29666)"
FT /evidence="ECO:0000305"
FT CONFLICT 669
FT /note="L -> H (in Ref. 1; CAA29666)"
FT /evidence="ECO:0000305"
FT CONFLICT 744
FT /note="A -> H (in Ref. 1; CAA29666)"
FT /evidence="ECO:0000305"
FT CONFLICT 814
FT /note="Missing (in Ref. 1; CAA29666)"
FT /evidence="ECO:0000305"
FT CONFLICT 830
FT /note="Y -> I (in Ref. 1; CAA29666)"
FT /evidence="ECO:0000305"
FT CONFLICT 858
FT /note="L -> H (in Ref. 1; CAA29666)"
FT /evidence="ECO:0000305"
FT STRAND 22..25
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 38..43
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 55..60
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:4EXP"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:3EJJ"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 95..101
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 107..111
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 113..118
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 127..130
FT /evidence="ECO:0007829|PDB:3EJJ"
FT HELIX 132..136
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:3EJJ"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:3EJJ"
FT TURN 158..160
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 161..166
FT /evidence="ECO:0007829|PDB:3EJJ"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 173..181
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 204..213
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 220..231
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 234..239
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 248..252
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 254..267
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 270..272
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 274..281
FT /evidence="ECO:0007829|PDB:3EJJ"
FT STRAND 286..294
FT /evidence="ECO:0007829|PDB:3EJJ"
SQ SEQUENCE 977 AA; 109179 MW; 7EDF8310CCF98906 CRC64;
MELGPPLVLL LATVWHGQGA PVIEPSGPEL VVEPGETVTL RCVSNGSVEW DGPISPYWTL
DPESPGSTLT TRNATFKNTG TYRCTELEDP MAGSTTIHLY VKDPAHSWNL LAQEVTVVEG
QEAVLPCLIT DPALKDSVSL MREGGRQVLR KTVYFFSPWR GFIIRKAKVL DSNTYVCKTM
VNGRESTSTG IWLKVNRVHP EPPQIKLEPS KLVRIRGEAA QIVCSATNAE VGFNVILKRG
DTKLEIPLNS DFQDNYYKKV RALSLNAVDF QDAGIYSCVA SNDVGTRTAT MNFQVVESAY
LNLTSEQSLL QEVSVGDSLI LTVHADAYPS IQHYNWTYLG PFFEDQRKLE FITQRAIYRY
TFKLFLNRVK ASEAGQYFLM AQNKAGWNNL TFELTLRYPP EVSVTWMPVN GSDVLFCDVS
GYPQPSVTWM ECRGHTDRCD EAQALQVWND THPEVLSQKP FDKVIIQSQL PIGTLKHNMT
YFCKTHNSVG NSSQYFRAVS LGQSKQLPDE SLFTPVVVAC MSVMSLLVLL LLLLLYKYKQ
KPKYQVRWKI IERYEGNSYT FIDPTQLPYN EKWEFPRNNL QFGKTLGAGA FGKVVEATAF
GLGKEDAVLK VAVKMLKSTA HADEKEALMS ELKIMSHLGQ HENIVNLLGA CTHGGPVLVI
TEYCCYGDLL NFLRRKAEAM LGPSLSPGQD SEGDSSYKNI HLEKKYVRRD SGFSSQGVDT
YVEMRPVSTS SSDSFFKQDL DKEASRPLEL WDLLHFSSQV AQGMAFLASK NCIHRDVAAR
NVLLTSGHVA KIGDFGLARD IMNDSNYVVK GNARLPVKWM APESIFDCVY TVQSDVWSYG
ILLWEIFSLG LNPYPGILVN NKFYKLVKDG YQMAQPVFAP KNIYSIMQSC WDLEPTRRPT
FQQICFLLQE QARLERRDQD YANLPSSGGS SGSDSGGGSS GGSSSEPEEE SSSEHLACCE
PGDIAQPLLQ PNNYQFC
