ID CSF1R_HUMAN Reviewed; 972 AA. AC P07333; B5A955; D3DQG2; Q6LDW5; Q6LDY4; Q86VW7; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 2. DT 11-NOV-2015, entry version 187. 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=FMS; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2524025; RA Hampe A., Shamoon B.M., Gobet M., Sherr C.J., Galibert F.; RT "Nucleotide sequence and structural organization of the human FMS RT proto-oncogene."; RL Oncogene Res. 4:9-17(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2421165; DOI=10.1038/320277a0; RA Coussens L., van Beveren C., Smith D., Chen E., Mitchell R.L., RA Isacke C.M., Verma I.M., Ullrich A.; RT "Structural alteration of viral homologue of receptor proto-oncogene RT fms at carboxyl terminus."; RL Nature 320:277-280(1986). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Placenta; RX PubMed=9027509; DOI=10.1006/geno.1996.4482; RA Andre C., Hampe A., Lachaume P., Martin E., Wang X.P., Manus V., RA Hu W.X., Galibert F.; RT "Sequence analysis of two genomic regions containing the KIT and the RT FMS receptor tyrosine kinase genes."; RL Genomics 39:216-226(1997). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=18593464; DOI=10.1186/ar2447; RA Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., RA Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.; RT "Novel splice variants derived from the receptor tyrosine kinase RT superfamily are potential therapeutics for rheumatoid arthritis."; RL Arthritis Res. Ther. 10:R73-R73(2008). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16. RX PubMed=2524648; RA Visvader J., Verma I.M.; RT "Differential transcription of exon 1 of the human c-fms gene in RT placental trophoblasts and monocytes."; RL Mol. Cell. Biol. 9:1336-1341(1989). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16. RX PubMed=3525854; RA Wheeler E.F., Roussel M.F., Hampe A., Walker M.H., Fried V.A., RA Look A.T., Rettenmier C.W., Sherr C.J.; RT "The amino-terminal domain of the v-fms oncogene product includes a RT functional signal peptide that directs synthesis of a transforming RT glycoprotein in the absence of feline leukemia virus gag sequences."; RL J. Virol. 59:224-233(1986). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16. RC TISSUE=Placenta; RA Flick M.B., Sapi E., Kacinski B.M.; RT "Expression of a novel exon in the 5' UTR of human c-fms RT transcripts."; RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 244-295. RX PubMed=4028159; DOI=10.1016/0092-8674(85)90099-6; RA Nienhuis A.W., Bunn H.F., Turner P.H., Gopal T.V., Nash W.G., RA O'Brien S.J., Sherr C.J.; RT "Expression of the human c-fms proto-oncogene in hematopoietic cells RT and its deletion in the 5q- syndrome."; RL Cell 42:421-428(1985). RN [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 874-972 (ISOFORM 1). RX PubMed=3532121; DOI=10.1073/pnas.83.20.7800; RA Browning P.J., Bunn H.F., Cline A., Shuman M., Nienhuis A.W.; RT "'Replacement' of COOH-terminal truncation of v-fms with c-fms RT sequences markedly reduces transformation potential."; RL Proc. Natl. Acad. Sci. U.S.A. 83:7800-7804(1986). RN [13] RP FUNCTION IN CELL PROLIFERATION. RX PubMed=7683918; RA Bourette R.P., Mouchiroud G., Ouazana R., Morle F., Godet J., RA Blanchet J.P.; RT "Expression of human colony-stimulating factor-1 (CSF-1) receptor in RT murine pluripotent hematopoietic NFS-60 cells induces long-term RT proliferation in response to CSF-1 without loss of erythroid RT differentiation potential."; RL Blood 81:2511-2520(1993). RN [14] RP INTERACTION WITH SRC; FYN AND YES1, AND MUTAGENESIS OF TYR-809. RX PubMed=7681396; RA Courtneidge S.A., Dhand R., Pilat D., Twamley G.M., Waterfield M.D., RA Roussel M.F.; RT "Activation of Src family kinases by colony stimulating factor-1, and RT their association with its receptor."; RL EMBO J. 12:943-950(1993). RN [15] RP INDUCTION BY GLUCOCORTICOIDS. RX PubMed=7845678; RA Sapi E., Flick M.B., Gilmore-Hebert M., Rodov S., Kacinski B.M.; RT "Transcriptional regulation of the c-fms (CSF-1R) proto-oncogene in RT human breast carcinoma cells by glucocorticoids."; RL Oncogene 10:529-542(1995). RN [16] RP MUTAGENESIS OF TYR-708 AND ASP-802. RX PubMed=10340379; DOI=10.1038/sj.onc.1202646; RA Morley G.M., Uden M., Gullick W.J., Dibb N.J.; RT "Cell specific transformation by c-fms activating loop mutations is RT attributable to constitutive receptor degradation."; RL Oncogene 18:3076-3084(1999). RN [17] RP FUNCTION IN CELLULAR SIGNALING; PHOSPHORYLATION OF INPP5D AND RP ACTIVATION OF AKT1. RX PubMed=12882960; DOI=10.1074/jbc.M305021200; RA Baran C.P., Tridandapani S., Helgason C.D., Humphries R.K., RA Krystal G., Marsh C.B.; RT "The inositol 5'-phosphatase SHIP-1 and the Src kinase Lyn negatively RT regulate macrophage colony-stimulating factor-induced Akt activity."; RL J. Biol. Chem. 278:38628-38636(2003). RN [18] RP FUNCTION IN REGULATION OF CELL PROLIFERATION; CELL ADHESION; CELL RP SHAPE AND INTEGRITY OF CELL JUNCTIONS, MUTAGENESIS OF LEU-301 AND RP TYR-969, AND ROLE IN DISEASE. RX PubMed=15117969; DOI=10.1083/jcb.200309102; RA Wrobel C.N., Debnath J., Lin E., Beausoleil S., Roussel M.F., RA Brugge J.S.; RT "Autocrine CSF-1R activation promotes Src-dependent disruption of RT mammary epithelial architecture."; RL J. Cell Biol. 165:263-273(2004). RN [19] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-302 AND ASN-353. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., RA Moore R.J., Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [20] RP FUNCTION AS CSF1 RECEPTOR, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, RP ROLE IN DISEASE, AND ENZYME REGULATION. RX PubMed=16648572; DOI=10.1158/1535-7163.MCT-05-0359; RA Guo J., Marcotte P.A., McCall J.O., Dai Y., Pease L.J., RA Michaelides M.R., Davidsen S.K., Glaser K.B.; RT "Inhibition of phosphorylation of the colony-stimulating factor-1 RT receptor (c-Fms) tyrosine kinase in transfected cells by ABT-869 and RT other tyrosine kinase inhibitors."; RL Mol. Cancer Ther. 5:1007-1013(2006). RN [21] RP FUNCTION IN CELL PROLIFERATION, CATALYTIC ACTIVITY, RP AUTOPHOSPHORYLATION, ROLE IN DISEASE, AND ENZYME REGULATION. RX PubMed=17121910; DOI=10.1158/1535-7163.MCT-05-0313; RA Ohno H., Kubo K., Murooka H., Kobayashi Y., Nishitoba T., Shibuya M., RA Yoneda T., Isoe T.; RT "A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast RT differentiation and osteolytic bone destruction in a bone metastasis RT model."; RL Mol. Cancer Ther. 5:2634-2643(2006). RN [22] RP FUNCTION IN REGULATION OF CELL PROLIFERATION AND CELL SHAPE, CATALYTIC RP ACTIVITY, UBIQUITINATION, ENZYME REGULATION, AND MUTAGENESIS OF RP ASP-802. RX PubMed=16170366; DOI=10.1038/sj.onc.1209007; RA Taylor J.R., Brownlow N., Domin J., Dibb N.J.; RT "FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor RT imatinib and mutation of Asp-802 to Val confers resistance."; RL Oncogene 25:147-151(2006). RN [23] RP FUNCTION AS IL34 RECEPTOR. RX PubMed=18467591; DOI=10.1126/science.1154370; RA Lin H., Lee E., Hestir K., Leo C., Huang M., Bosch E., Halenbeck R., RA Wu G., Zhou A., Behrens D., Hollenbaugh D., Linnemann T., Qin M., RA Wong J., Chu K., Doberstein S.K., Williams L.T.; RT "Discovery of a cytokine and its receptor by functional screening of RT the extracellular proteome."; RL Science 320:807-811(2008). RN [24] RP ROLE IN DISEASE, AND ENZYME 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 [25] RP ROLE IN DISEASE. RX PubMed=19934330; DOI=10.1158/0008-5472.CAN-09-1868; RA Patsialou A., Wyckoff J., Wang Y., Goswami S., Stanley E.R., RA Condeelis J.S.; RT "Invasion of human breast cancer cells in vivo requires both paracrine RT and autocrine loops involving the colony-stimulating factor-1 RT receptor."; RL Cancer Res. 69:9498-9506(2009). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-699 AND SER-713, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [27] RP AUTOPHOSPHORYLATION, AND ENZYME REGULATION. RX PubMed=20156689; DOI=10.1016/j.bmc.2010.01.056; RA Mashkani B., Griffith R., Ashman L.K.; RT "Colony stimulating factor-1 receptor as a target for small molecule RT inhibitors."; RL Bioorg. Med. Chem. 18:1789-1797(2010). RN [28] RP FUNCTION AS RECEPTOR FOR IL34 AND CSF1, PHOSPHORYLATION AT TYR-546; RP TYR-699; TYR-708; TYR-723 AND TYR-809, AUTOPHOSPHORYLATION, ENZYME RP REGULATION, AND INTERACTION WITH IL34 AND CSF1. RX PubMed=20489731; DOI=10.1038/cdd.2010.60; RA Chihara T., Suzu S., Hassan R., Chutiwitoonchai N., Hiyoshi M., RA Motoyoshi K., Kimura F., Okada S.; RT "IL-34 and M-CSF share the receptor Fms but are not identical in RT biological activity and signal activation."; RL Cell Death Differ. 17:1917-1927(2010). RN [29] RP FUNCTION IN RELEASE OF PROINFLAMMATORY CHEMOKINES. RX PubMed=20829061; DOI=10.1016/j.cyto.2010.08.005; RA Eda H., Zhang J., Keith R.H., Michener M., Beidler D.R., Monahan J.B.; RT "Macrophage-colony stimulating factor and interleukin-34 induce RT chemokines in human whole blood."; RL Cytokine 52:215-220(2010). RN [30] RP FUNCTION AS IL34 AND CSF1 RECEPTOR; ACTIVATION OF MAPK1/ERK2; RP MAPK3/ERK1; PHOSPHORYLATION AT TYR-723, AND AUTOPHOSPHORYLATION. RX PubMed=20504948; DOI=10.1189/jlb.1209822; RA Wei S., Nandi S., Chitu V., Yeung Y.G., Yu W., Huang M., RA Williams L.T., Lin H., Stanley E.R.; RT "Functional overlap but differential expression of CSF-1 and IL-34 in RT their CSF-1 receptor-mediated regulation of myeloid cells."; RL J. Leukoc. Biol. 88:495-505(2010). RN [31] RP REVIEW ON FUNCTION; SIGNALING PATHWAYS AND PHOSPHORYLATION. RX PubMed=15519852; DOI=10.1016/j.tcb.2004.09.016; RA Pixley F.J., Stanley E.R.; RT "CSF-1 regulation of the wandering macrophage: complexity in action."; RL Trends Cell Biol. 14:628-638(2004). RN [32] RP REVIEW ON FUNCTION IN IMMUNITY AND INFLAMMATION, AND ROLE IN DISEASE. RX PubMed=16337366; DOI=10.1016/j.coi.2005.11.006; RA Chitu V., Stanley E.R.; RT "Colony-stimulating factor-1 in immunity and inflammation."; RL Curr. Opin. Immunol. 18:39-48(2006). RN [33] RP REVIEW ON FUNCTION; SIGNALING PATHWAYS AND PHOSPHORYLATION. RX PubMed=18687298; DOI=10.1016/j.intimp.2008.04.016; RA Douglass T.G., Driggers L., Zhang J.G., Hoa N., Delgado C., RA Williams C.C., Dan Q., Sanchez R., Jeffes E.W., Wepsic H.T., RA Myers M.P., Koths K., Jadus M.R.; RT "Macrophage colony stimulating factor: not just for macrophages RT anymore! A gateway into complex biologies."; RL Int. Immunopharmacol. 8:1354-1376(2008). RN [34] RP REVIEW. RX PubMed=19132917; DOI=10.1146/annurev.immunol.021908.132557; RA Auffray C., Sieweke M.H., Geissmann F.; RT "Blood monocytes: development, heterogeneity, and relationship with RT dendritic cells."; RL Annu. Rev. Immunol. 27:669-692(2009). RN [35] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [36] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 538-922 IN COMPLEXES WITH RP ARYLAMIDE AND QUINOLONE INHIBITORS, AND DOMAIN. RX PubMed=17132624; DOI=10.1074/jbc.M608183200; RA Schubert C., Schalk-Hihi C., Struble G.T., Ma H.C., Petrounia I.P., RA Brandt B., Deckman I.C., Patch R.J., Player M.R., Spurlino J.C., RA Springer B.A.; RT "Crystal structure of the tyrosine kinase domain of colony-stimulating RT factor-1 receptor (cFMS) in complex with two inhibitors."; RL J. Biol. Chem. 282:4094-4101(2007). RN [37] RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 543-918 IN AUTOINHIBITED RP CONFORMATION, AND DOMAIN. RX PubMed=17292918; DOI=10.1016/j.jmb.2007.01.036; RA Walter M., Lucet I.S., Patel O., Broughton S.E., Bamert R., RA Williams N.K., Fantino E., Wilks A.F., Rossjohn J.; RT "The 2.7 A crystal structure of the autoinhibited human c-Fms kinase RT domain."; RL J. Mol. Biol. 367:839-847(2007). RN [38] RP X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 538-922 IN COMPLEX WITH RP PYRIMIDINOPYRIDONE INHIBITOR, AND CATALYTIC ACTIVITY. RX PubMed=18342505; DOI=10.1016/j.bmcl.2008.02.070; RA Huang H., Hutta D.A., Hu H., DesJarlais R.L., Schubert C., RA Petrounia I.P., Chaikin M.A., Manthey C.L., Player M.R.; RT "Design and synthesis of a pyrido[2,3-d]pyrimidin-5-one class of anti- RT inflammatory FMS inhibitors."; RL Bioorg. Med. Chem. Lett. 18:2355-2361(2008). RN [39] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 538-922 IN COMPLEX WITH RP INHIBITOR, CATALYTIC ACTIVITY, AND FUNCTION IN INFLAMMATION AND RP DISEASE. RX PubMed=19193011; DOI=10.1021/jm801406h; RA Huang H., Hutta D.A., Rinker J.M., Hu H., Parsons W.H., Schubert C., RA DesJarlais R.L., Crysler C.S., Chaikin M.A., Donatelli R.R., Chen Y., RA Cheng D., Zhou Z., Yurkow E., Manthey C.L., Player M.R.; RT "Pyrido[2,3-d]pyrimidin-5-ones: a novel class of antiinflammatory RT macrophage colony-stimulating factor-1 receptor inhibitors."; RL J. Med. Chem. 52:1081-1099(2009). RN [40] RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 538-922 IN COMPLEXES WITH RP INHIBITORS, CATALYTIC ACTIVITY, AND ENZYME REGULATION. RX PubMed=20137931; DOI=10.1016/j.bmcl.2010.01.078; RA Meyers M.J., Pelc M., Kamtekar S., Day J., Poda G.I., Hall M.K., RA Michener M.L., Reitz B.A., Mathis K.J., Pierce B.S., Parikh M.D., RA Mischke D.A., Long S.A., Parlow J.J., Anderson D.R., Thorarensen A.; RT "Structure-based drug design enables conversion of a DFG-in binding RT CSF-1R kinase inhibitor to a DFG-out binding mode."; RL Bioorg. Med. Chem. Lett. 20:1543-1547(2010). RN [41] RP VARIANTS [LARGE SCALE ANALYSIS] GLY-32; ARG-362; SER-413; VAL-536; RP HIS-693; ASP-920 AND GLN-921. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [42] RP VARIANTS HDLS 774-CYS--ASN-814 DEL; 585-GLY--LYS-619 DELINS ALA; RP GLU-589; LYS-633; THR-766; PRO-770; ASN-775; THR-794; TYR-837; RP SER-849; PHE-849 DEL; PRO-868; THR-875 AND THR-878, VARIANTS HIS-710; RP ARG-747 AND ASP-920, AND CHARACTERIZATION OF VARIANTS HDLS LYS-633; RP THR-766 AND THR-875. RX PubMed=22197934; DOI=10.1038/ng.1027; RA Rademakers R., Baker M., Nicholson A.M., Rutherford N.J., Finch N., RA Soto-Ortolaza A., Lash J., Wider C., Wojtas A., DeJesus-Hernandez M., RA Adamson J., Kouri N., Sundal C., Shuster E.A., Aasly J., MacKenzie J., RA Roeber S., Kretzschmar H.A., Boeve B.F., Knopman D.S., Petersen R.C., RA Cairns N.J., Ghetti B., Spina S., Garbern J., Tselis A.C., Uitti R., RA Das P., Van Gerpen J.A., Meschia J.F., Levy S., Broderick D.F., RA Graff-Radford N., Ross O.A., Miller B.B., Swerdlow R.H., Dickson D.W., RA Wszolek Z.K.; RT "Mutations in the colony stimulating factor 1 receptor (CSF1R) gene RT cause hereditary diffuse leukoencephalopathy with spheroids."; RL Nat. Genet. 44:200-205(2012). RN [43] RP VARIANTS HDLS ARG-653; PHE-843 AND THR-906. RX PubMed=24532199; DOI=10.1007/s00415-014-7257-3; RA Battisti C., Di Donato I., Bianchi S., Monti L., Formichi P., Rufa A., RA Taglia I., Cerase A., Dotti M.T., Federico A.; RT "Hereditary diffuse leukoencephalopathy with axonal spheroids: three RT patients with stroke-like presentation carrying new mutations in the RT CSF1R gene."; RL J. Neurol. 261:768-772(2014). CC -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface CC receptor for CSF1 and IL34 and plays an essential role in the CC regulation of survival, proliferation and differentiation of CC hematopoietic precursor cells, especially mononuclear phagocytes, CC such as macrophages and monocytes. Promotes the release of CC proinflammatory chemokines in response to IL34 and CSF1, and CC thereby plays an important role in innate immunity and in CC inflammatory processes. Plays an important role in the regulation CC of osteoclast proliferation and differentiation, the regulation of CC bone resorption, and is required for normal bone and tooth CC 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 CC actin cytoskeleton, regulates formation of membrane ruffles, cell CC adhesion and cell migration, and promotes cancer cell invasion. CC Activates several signaling pathways in response to ligand CC binding. Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. CC Activation of PLCG2 leads to the production of the cellular CC signaling molecules diacylglycerol and inositol 1,4,5- CC trisphosphate, that then lead to the activation of protein kinase CC C 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 CC mediates activation of the MAP kinases MAPK1/ERK2 and/or CC MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. CC Activated CSF1R transmits signals both via proteins that directly CC interact with phosphorylated tyrosine residues in its CC intracellular domain, or via adapter proteins, such as GRB2. CC Promotes activation of STAT family members STAT3, STAT5A and/or CC STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP- CC 1. Receptor signaling is down-regulated by protein phosphatases, CC such as INPP5D/SHIP-1, that dephosphorylate the receptor and its CC downstream effectors, and by rapid internalization of the CC activated receptor. {ECO:0000269|PubMed:12882960, CC ECO:0000269|PubMed:15117969, ECO:0000269|PubMed:16170366, CC ECO:0000269|PubMed:16337366, ECO:0000269|PubMed:16648572, CC ECO:0000269|PubMed:17121910, ECO:0000269|PubMed:18467591, CC ECO:0000269|PubMed:18814279, ECO:0000269|PubMed:19193011, CC ECO:0000269|PubMed:19934330, ECO:0000269|PubMed:20489731, CC ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:20829061, CC ECO:0000269|PubMed:7683918}. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- CC ProRule:PRU10028, ECO:0000269|PubMed:16170366, CC ECO:0000269|PubMed:16648572, ECO:0000269|PubMed:17121910, CC ECO:0000269|PubMed:18342505, ECO:0000269|PubMed:19193011, CC ECO:0000269|PubMed:20137931}. CC -!- ENZYME REGULATION: Present in an inactive conformation in the CC absence of bound ligand. CSF1 or IL34 binding leads to CC dimerization and activation by autophosphorylation on tyrosine CC residues. Inhibited by imatinib/STI-571 (Gleevec), dasatinib, CC sunitinib/SU11248, lestaurtinib/CEP-701, midostaurin/PKC-412, CC Ki20227, linifanib/ABT-869, Axitinib/AG013736, sorafenib/BAY 43- CC 9006 and GW2580. {ECO:0000269|PubMed:16170366, CC ECO:0000269|PubMed:16648572, ECO:0000269|PubMed:17121910, CC ECO:0000269|PubMed:18814279, ECO:0000269|PubMed:20137931, CC ECO:0000269|PubMed:20156689, ECO:0000269|PubMed:20489731}. CC -!- SUBUNIT: Interacts with INPPL1/SHIP2 and THOC5 (By similarity). CC Monomer. Homodimer. Interacts with CSF1 and IL34. Interaction with CC dimeric CSF1 or IL34 leads to receptor homodimerization. Interacts CC (tyrosine phosphorylated) with PLCG2 (via SH2 domain). Interacts CC (tyrosine phosphorylated) with PIK3R1 (via SH2 domain). Interacts CC (tyrosine phosphorylated) with FYN, YES1 and SRC (via SH2 domain). CC Interacts (tyrosine phosphorylated) with CBL, GRB2 and SLA2. CC {ECO:0000250, ECO:0000269|PubMed:18342505, CC ECO:0000269|PubMed:19193011, ECO:0000269|PubMed:20489731, CC ECO:0000269|PubMed:7681396}. CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane CC protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P07333-1; Sequence=Displayed; CC Name=2; CC IsoId=P07333-2; Sequence=VSP_047757, VSP_047758; CC -!- TISSUE SPECIFICITY: Expressed in bone marrow and in differentiated CC blood mononuclear cells. CC -!- INDUCTION: Up-regulated by glucocorticoids. CC {ECO:0000269|PubMed:7845678}. CC -!- DOMAIN: The juxtamembrane domain functions as autoinhibitory CC region. Phosphorylation of tyrosine residues in this region leads CC to a conformation change and activation of the kinase. CC -!- DOMAIN: The activation loop plays an important role in the CC regulation of kinase activity. Phosphorylation of tyrosine CC residues in this region leads to a conformation change and CC activation of the kinase. CC -!- PTM: Autophosphorylated in response to CSF1 or IL34 binding. CC Phosphorylation at Tyr-561 is important for normal down-regulation CC of signaling by ubiquitination, internalization and degradation. CC Phosphorylation at Tyr-561 and Tyr-809 is important for CC interaction with SRC family members, including FYN, YES1 and SRC, CC and for subsequent activation of these protein kinases. CC Phosphorylation at Tyr-699 and Tyr-923 is important for CC interaction with GRB2. Phosphorylation at Tyr-723 is important for CC interaction with PIK3R1. Phosphorylation at Tyr-708 is important CC for normal receptor degradation. Phosphorylation at Tyr-723 and CC Tyr-809 is important for interaction with PLCG2. Phosphorylation CC at Tyr-969 is important for interaction with CBL. CC Dephosphorylation by PTPN2 negatively regulates downstream CC signaling and macrophage differentiation. CC {ECO:0000269|PubMed:16170366, ECO:0000269|PubMed:20489731}. CC -!- PTM: Ubiquitinated. Becomes rapidly polyubiquitinated after CC autophosphorylation, leading to its degradation. CC {ECO:0000269|PubMed:16170366}. CC -!- DISEASE: Note=Aberrant expression of CSF1 or CSF1R can promote CC cancer cell proliferation, invasion and formation of metastases. CC Overexpression of CSF1 or CSF1R is observed in a significant CC percentage of breast, ovarian, prostate, and endometrial cancers. CC -!- DISEASE: Note=Aberrant expression of CSF1 or CSF1R may play a role CC in inflammatory diseases, such as rheumatoid arthritis, CC glomerulonephritis, atherosclerosis, and allograft rejection. CC -!- DISEASE: Leukoencephalopathy, diffuse hereditary, with spheroids CC (HDLS) [MIM:221820]: An autosomal dominant adult-onset rapidly CC progressive neurodegenerative disorder characterized by variable CC behavioral, cognitive, and motor changes. Patients often die of CC dementia within 6 years of onset. Brain imaging shows patchy CC abnormalities in the cerebral white matter, predominantly CC affecting the frontal and parietal lobes. CC {ECO:0000269|PubMed:22197934, ECO:0000269|PubMed:24532199}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. CSF-1/PDGF receptor subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SIMILARITY: Contains 5 Ig-like C2-type (immunoglobulin-like) CC domains. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/CSF1RID40161ch5q32.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X03663; CAA27300.1; -; mRNA. DR EMBL; U63963; AAB51696.1; -; Genomic_DNA. DR EMBL; M25786; AAA58421.1; -; mRNA. DR EMBL; EU826593; ACF47629.1; -; mRNA. DR EMBL; AC011382; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471062; EAW61749.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61750.1; -; Genomic_DNA. DR EMBL; BC047521; AAH47521.1; -; mRNA. DR EMBL; M14002; AAA35849.1; -; Genomic_DNA. DR EMBL; U78096; AAB51235.1; -; Genomic_DNA. DR EMBL; M11067; AAA35848.1; -; Genomic_DNA. DR EMBL; M14193; AAA35834.1; -; mRNA. DR CCDS; CCDS4302.1; -. [P07333-1] DR PIR; S08123; TVHUMD. DR RefSeq; NP_001275634.1; NM_001288705.1. [P07333-1] DR RefSeq; NP_005202.2; NM_005211.3. [P07333-1] DR UniGene; Hs.586219; -. DR PDB; 2I0V; X-ray; 2.80 A; A=538-678, A=753-922. DR PDB; 2I0Y; X-ray; 1.90 A; A=538-678, A=753-922. DR PDB; 2I1M; X-ray; 1.80 A; A=538-678, A=753-922. DR PDB; 2OGV; X-ray; 2.70 A; A=543-918. DR PDB; 3BEA; X-ray; 2.02 A; A=538-678, A=753-922. DR PDB; 3DPK; X-ray; 1.95 A; A=538-678, A=771-922. DR PDB; 3KRJ; X-ray; 2.10 A; A=538-678, A=753-922. DR PDB; 3KRL; X-ray; 2.40 A; A=538-678, A=753-922. DR PDB; 3LCD; X-ray; 2.50 A; A=538-919. DR PDB; 3LCO; X-ray; 3.40 A; A=550-919. DR PDB; 4DKD; X-ray; 3.00 A; C=20-299. DR PDB; 4HW7; X-ray; 2.90 A; A=542-919. DR PDB; 4LIQ; X-ray; 2.60 A; E=2-512. DR PDB; 4R7H; X-ray; 2.80 A; A=542-919. DR PDB; 4R7I; X-ray; 2.75 A; A=542-919. DR PDB; 4WRL; X-ray; 2.80 A; A/C=20-296. DR PDB; 4WRM; X-ray; 6.85 A; A=20-504. DR PDBsum; 2I0V; -. DR PDBsum; 2I0Y; -. DR PDBsum; 2I1M; -. DR PDBsum; 2OGV; -. DR PDBsum; 3BEA; -. DR PDBsum; 3DPK; -. DR PDBsum; 3KRJ; -. DR PDBsum; 3KRL; -. DR PDBsum; 3LCD; -. DR PDBsum; 3LCO; -. DR PDBsum; 4DKD; -. DR PDBsum; 4HW7; -. DR PDBsum; 4LIQ; -. DR PDBsum; 4R7H; -. DR PDBsum; 4R7I; -. DR PDBsum; 4WRL; -. DR PDBsum; 4WRM; -. DR ProteinModelPortal; P07333; -. DR SMR; P07333; 20-500, 544-945. DR BioGrid; 107823; 17. DR DIP; DIP-59421N; -. DR IntAct; P07333; 12. DR MINT; MINT-8019993; -. DR STRING; 9606.ENSP00000286301; -. DR BindingDB; P07333; -. DR ChEMBL; CHEMBL1844; -. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB01268; Sunitinib. DR GuidetoPHARMACOLOGY; 1806; -. DR PhosphoSite; P07333; -. DR BioMuta; CSF1R; -. DR DMDM; 547770; -. DR PaxDb; P07333; -. DR PeptideAtlas; P07333; -. DR PRIDE; P07333; -. DR DNASU; 1436; -. DR Ensembl; ENST00000286301; ENSP00000286301; ENSG00000182578. [P07333-1] DR Ensembl; ENST00000543093; ENSP00000445282; ENSG00000182578. [P07333-2] DR GeneID; 1436; -. DR KEGG; hsa:1436; -. DR UCSC; uc003lrl.3; human. [P07333-1] DR UCSC; uc011dce.1; human. DR CTD; 1436; -. DR GeneCards; CSF1R; -. DR GeneReviews; CSF1R; -. DR HGNC; HGNC:2433; CSF1R. DR HPA; CAB008970; -. DR HPA; HPA012323; -. DR MIM; 164770; gene. DR MIM; 221820; phenotype. DR neXtProt; NX_P07333; -. DR Orphanet; 313808; Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia. DR PharmGKB; PA26936; -. DR eggNOG; KOG0200; Eukaryota. DR eggNOG; COG0515; LUCA. DR GeneTree; ENSGT00760000118923; -. DR HOGENOM; HOG000112008; -. DR HOVERGEN; HBG004335; -. DR InParanoid; P07333; -. DR KO; K05090; -. DR OMA; WKIIESY; -. DR PhylomeDB; P07333; -. DR TreeFam; TF325768; -. DR BRENDA; 2.7.10.1; 2681. DR SignaLink; P07333; -. DR ChiTaRS; CSF1R; human. DR EvolutionaryTrace; P07333; -. DR GeneWiki; Colony_stimulating_factor_1_receptor; -. DR GenomeRNAi; 1436; -. DR NextBio; 35477774; -. DR PRO; PR:P07333; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; P07333; -. DR CleanEx; HS_CSF1R; -. DR ExpressionAtlas; P07333; baseline and differential. DR Genevisible; P07333; HS. DR GO; GO:0009986; C:cell surface; ISS:UniProtKB. DR GO; GO:1990682; C:CSF1-CSF1R complex; ISS:BHF-UCL. DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc. DR GO; GO:0005622; C:intracellular; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc. 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; IMP:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:BHF-UCL. DR GO; GO:0008283; P:cell proliferation; IMP:UniProtKB. DR GO; GO:0045217; P:cell-cell junction maintenance; IMP:UniProtKB. DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISS: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; IMP:UniProtKB. DR GO; GO:0030097; P:hemopoiesis; IMP:UniProtKB. DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0038145; P:macrophage colony-stimulating factor signaling pathway; ISS:BHF-UCL. DR GO; GO:0030225; P:macrophage differentiation; TAS:UniProtKB. DR GO; GO:0060603; P:mammary gland duct morphogenesis; TAS:UniProtKB. DR GO; GO:0030224; P:monocyte differentiation; TAS:UniProtKB. DR GO; GO:0007275; P:multicellular organismal development; TAS:ProtInc. DR GO; GO:0030316; P:osteoclast differentiation; ISS:UniProtKB. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0046488; P:phosphatidylinositol metabolic process; ISS:UniProtKB. DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; ISS:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB. DR GO; GO:2000147; P:positive regulation of cell motility; IMP:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell proliferation; IMP:UniProtKB. DR GO; GO:0090197; P:positive regulation of chemokine secretion; IMP:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IEA:Ensembl. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB. DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; ISS:UniProtKB. DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IMP:UniProtKB. DR GO; GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 protein; ISS:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; ISS: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:0031529; P:ruffle organization; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0007519; P:skeletal muscle tissue development; IEA:Ensembl. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; ISS:UniProtKB. DR Gene3D; 2.60.40.10; -; 5. DR InterPro; IPR030658; CSF-1_receptor. DR InterPro; IPR007110; Ig-like_dom. 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. 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; IPR016243; Tyr_kinase_CSF1/PDGF_rcpt. DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS. DR PANTHER; PTHR24416:SF47; PTHR24416:SF47; 3. DR Pfam; PF00047; ig; 1. DR Pfam; PF07714; Pkinase_Tyr; 1. DR PIRSF; PIRSF500947; CSF-1_receptor; 1. DR PIRSF; PIRSF000615; TyrPK_CSF1-R; 1. DR SMART; SM00409; IG; 3. DR SMART; SM00408; IGc2; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF48726; SSF48726; 5. DR SUPFAM; SSF56112; SSF56112; 2. DR PROSITE; PS50835; IG_LIKE; 3. 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; Alternative splicing; ATP-binding; Cell membrane; KW Complete proteome; Disease mutation; Disulfide bond; Glycoprotein; KW Immunity; Immunoglobulin domain; Inflammatory response; KW Innate immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; KW Polymorphism; Proto-oncogene; Receptor; Reference proteome; Repeat; KW Signal; Transferase; Transmembrane; Transmembrane helix; KW Tyrosine-protein kinase; Ubl conjugation. FT SIGNAL 1 19 {ECO:0000255}. FT CHAIN 20 972 Macrophage colony-stimulating factor 1 FT receptor. FT /FTId=PRO_0000016765. FT TOPO_DOM 20 517 Extracellular. {ECO:0000255}. FT TRANSMEM 518 538 Helical. {ECO:0000255}. FT TOPO_DOM 539 972 Cytoplasmic. {ECO:0000255}. FT DOMAIN 21 104 Ig-like C2-type 1. FT DOMAIN 107 197 Ig-like C2-type 2. FT DOMAIN 203 290 Ig-like C2-type 3. FT DOMAIN 299 399 Ig-like C2-type 4. FT DOMAIN 402 502 Ig-like C2-type 5. FT DOMAIN 582 910 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 588 596 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 542 574 Regulatory juxtamembrane domain. FT REGION 796 818 Activation loop. FT ACT_SITE 778 778 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10028}. FT BINDING 616 616 ATP. {ECO:0000305}. FT MOD_RES 546 546 Phosphotyrosine; by autocatalysis. FT {ECO:0000269|PubMed:20489731}. FT MOD_RES 561 561 Phosphotyrosine; by autocatalysis. FT {ECO:0000250}. FT MOD_RES 699 699 Phosphotyrosine; by autocatalysis. FT {ECO:0000244|PubMed:19369195, FT ECO:0000269|PubMed:20489731}. FT MOD_RES 708 708 Phosphotyrosine; by autocatalysis. FT {ECO:0000269|PubMed:20489731}. FT MOD_RES 713 713 Phosphoserine. FT {ECO:0000244|PubMed:19369195}. FT MOD_RES 723 723 Phosphotyrosine; by autocatalysis. FT {ECO:0000269|PubMed:20489731}. FT MOD_RES 809 809 Phosphotyrosine; by autocatalysis. FT {ECO:0000269|PubMed:20489731}. FT MOD_RES 923 923 Phosphotyrosine; by autocatalysis. FT {ECO:0000250}. FT MOD_RES 969 969 Phosphotyrosine; by autocatalysis. FT {ECO:0000250}. FT CARBOHYD 45 45 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 73 73 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 153 153 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 240 240 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 275 275 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 302 302 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:16335952}. FT CARBOHYD 335 335 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 353 353 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:16335952}. FT CARBOHYD 412 412 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 428 428 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 480 480 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 42 84 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 127 177 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 224 278 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 419 485 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT VAR_SEQ 297 306 ESAYLNLSSE -> GTPSPSLCPA (in isoform 2). FT {ECO:0000303|PubMed:18593464}. FT /FTId=VSP_047757. FT VAR_SEQ 307 972 Missing (in isoform 2). FT {ECO:0000303|PubMed:18593464}. FT /FTId=VSP_047758. FT VARIANT 32 32 V -> G (in dbSNP:rs56048668). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_042038. FT VARIANT 245 245 A -> S (in dbSNP:rs41338945). FT /FTId=VAR_061290. FT VARIANT 279 279 V -> M (in dbSNP:rs3829986). FT /FTId=VAR_049718. FT VARIANT 362 362 H -> R (in dbSNP:rs10079250). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_042039. FT VARIANT 413 413 G -> S (in dbSNP:rs34951517). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_042040. FT VARIANT 536 536 L -> V (in dbSNP:rs55942044). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_042041. FT VARIANT 585 619 GKTLGAGAFGKVVEATAFGLGKEDAVLKVAVKMLK -> A FT (in HDLS). {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067396. FT VARIANT 589 589 G -> E (in HDLS). FT {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067397. FT VARIANT 633 633 E -> K (in HDLS; impairs FT autophosphorylation upon stimulation with FT CSF1). {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067398. FT VARIANT 653 653 C -> R (in HDLS). FT {ECO:0000269|PubMed:24532199}. FT /FTId=VAR_072081. FT VARIANT 693 693 P -> H (in a lung squamous cell carcinoma FT sample; somatic mutation). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_042042. FT VARIANT 710 710 R -> H. {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067399. FT VARIANT 747 747 G -> R (in dbSNP:rs41355444). FT {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067400. FT VARIANT 766 766 M -> T (in HDLS; impairs FT autophosphorylation upon stimulation with FT CSF1). {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067401. FT VARIANT 770 770 A -> P (in HDLS). FT {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067402. FT VARIANT 774 814 Missing (in HDLS). FT {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067403. FT VARIANT 775 775 I -> N (in HDLS; impairs FT autophosphorylation upon stimulation with FT CSF1). {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067404. FT VARIANT 794 794 I -> T (in HDLS). FT {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067405. FT VARIANT 837 837 D -> Y (in HDLS). FT {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067406. FT VARIANT 843 843 I -> F (in HDLS). FT {ECO:0000269|PubMed:24532199}. FT /FTId=VAR_072082. FT VARIANT 849 849 F -> S (in HDLS). FT {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067407. FT VARIANT 849 849 Missing (in HDLS). FT {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067408. FT VARIANT 868 868 L -> P (in HDLS). FT {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067409. FT VARIANT 875 875 M -> T (in HDLS). FT {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067410. FT VARIANT 878 878 P -> T (in HDLS). FT {ECO:0000269|PubMed:22197934}. FT /FTId=VAR_067411. FT VARIANT 906 906 I -> T (in HDLS). FT {ECO:0000269|PubMed:24532199}. FT /FTId=VAR_072083. FT VARIANT 920 920 E -> D (in dbSNP:rs34030164). FT {ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:22197934}. FT /FTId=VAR_042043. FT VARIANT 921 921 R -> Q (in dbSNP:rs56059682). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_042044. FT VARIANT 969 969 Y -> C (in dbSNP:rs1801271). FT /FTId=VAR_011953. FT MUTAGEN 301 301 L->S: Constitutive kinase activity. FT {ECO:0000269|PubMed:15117969}. FT MUTAGEN 708 708 Y->F: Impairs degradation of activated FT CSF1R. {ECO:0000269|PubMed:10340379}. FT MUTAGEN 802 802 D->V: Constitutive kinase activity. Loss FT of inhibition by imatinib. FT {ECO:0000269|PubMed:10340379, FT ECO:0000269|PubMed:16170366}. FT MUTAGEN 809 809 Y->F: Reduced kinase activity. Reduced FT interaction with SRC, FYN and YES1. FT {ECO:0000269|PubMed:7681396}. FT MUTAGEN 969 969 Y->F: Abolishes down-regulation of FT activated CSF1R. FT {ECO:0000269|PubMed:15117969}. FT CONFLICT 54 54 P -> A (in Ref. 2; CAA27300). FT {ECO:0000305}. FT CONFLICT 247 247 P -> H (in Ref. 7; AAH47521). FT {ECO:0000305}. FT CONFLICT 354 354 A -> V (in Ref. 7; AAH47521). FT {ECO:0000305}. FT CONFLICT 629 629 A -> S (in Ref. 7; AAH47521). FT {ECO:0000305}. FT STRAND 22 25 {ECO:0000244|PDB:4LIQ}. FT STRAND 27 32 {ECO:0000244|PDB:4LIQ}. FT STRAND 38 43 {ECO:0000244|PDB:4LIQ}. FT STRAND 49 51 {ECO:0000244|PDB:4LIQ}. FT TURN 55 57 {ECO:0000244|PDB:4LIQ}. FT STRAND 58 62 {ECO:0000244|PDB:4LIQ}. FT STRAND 64 73 {ECO:0000244|PDB:4LIQ}. FT HELIX 76 78 {ECO:0000244|PDB:4LIQ}. FT STRAND 80 85 {ECO:0000244|PDB:4LIQ}. FT STRAND 95 101 {ECO:0000244|PDB:4LIQ}. FT STRAND 108 111 {ECO:0000244|PDB:4LIQ}. FT STRAND 113 118 {ECO:0000244|PDB:4LIQ}. FT STRAND 123 125 {ECO:0000244|PDB:4LIQ}. FT STRAND 127 130 {ECO:0000244|PDB:4LIQ}. FT HELIX 132 137 {ECO:0000244|PDB:4LIQ}. FT STRAND 139 142 {ECO:0000244|PDB:4LIQ}. FT HELIX 143 145 {ECO:0000244|PDB:4WRL}. FT STRAND 154 157 {ECO:0000244|PDB:4LIQ}. FT TURN 158 160 {ECO:0000244|PDB:4LIQ}. FT STRAND 161 166 {ECO:0000244|PDB:4LIQ}. FT HELIX 169 171 {ECO:0000244|PDB:4LIQ}. FT STRAND 173 181 {ECO:0000244|PDB:4LIQ}. FT STRAND 184 187 {ECO:0000244|PDB:4LIQ}. FT STRAND 191 196 {ECO:0000244|PDB:4LIQ}. FT STRAND 204 208 {ECO:0000244|PDB:4LIQ}. FT STRAND 210 215 {ECO:0000244|PDB:4LIQ}. FT STRAND 216 218 {ECO:0000244|PDB:4DKD}. FT STRAND 220 231 {ECO:0000244|PDB:4LIQ}. FT STRAND 234 239 {ECO:0000244|PDB:4LIQ}. FT STRAND 248 252 {ECO:0000244|PDB:4LIQ}. FT STRAND 257 267 {ECO:0000244|PDB:4LIQ}. FT TURN 270 272 {ECO:0000244|PDB:4LIQ}. FT STRAND 274 282 {ECO:0000244|PDB:4LIQ}. FT STRAND 285 298 {ECO:0000244|PDB:4LIQ}. FT STRAND 300 304 {ECO:0000244|PDB:4LIQ}. FT STRAND 309 314 {ECO:0000244|PDB:4LIQ}. FT STRAND 319 329 {ECO:0000244|PDB:4LIQ}. FT STRAND 332 338 {ECO:0000244|PDB:4LIQ}. FT STRAND 340 342 {ECO:0000244|PDB:4LIQ}. FT STRAND 351 354 {ECO:0000244|PDB:4LIQ}. FT STRAND 361 368 {ECO:0000244|PDB:4LIQ}. FT HELIX 373 375 {ECO:0000244|PDB:4LIQ}. FT STRAND 377 385 {ECO:0000244|PDB:4LIQ}. FT STRAND 388 411 {ECO:0000244|PDB:4LIQ}. FT STRAND 414 425 {ECO:0000244|PDB:4LIQ}. FT STRAND 428 437 {ECO:0000244|PDB:4LIQ}. FT TURN 443 445 {ECO:0000244|PDB:4LIQ}. FT STRAND 446 454 {ECO:0000244|PDB:4LIQ}. FT STRAND 456 459 {ECO:0000244|PDB:4LIQ}. FT STRAND 466 473 {ECO:0000244|PDB:4LIQ}. FT STRAND 479 488 {ECO:0000244|PDB:4LIQ}. FT STRAND 493 498 {ECO:0000244|PDB:4LIQ}. FT STRAND 551 553 {ECO:0000244|PDB:4R7H}. FT STRAND 556 560 {ECO:0000244|PDB:3BEA}. FT HELIX 566 568 {ECO:0000244|PDB:3KRJ}. FT HELIX 573 575 {ECO:0000244|PDB:2I1M}. FT STRAND 581 590 {ECO:0000244|PDB:2I1M}. FT STRAND 592 601 {ECO:0000244|PDB:2I1M}. FT STRAND 605 607 {ECO:0000244|PDB:2I1M}. FT STRAND 612 618 {ECO:0000244|PDB:2I1M}. FT HELIX 624 640 {ECO:0000244|PDB:2I1M}. FT STRAND 649 653 {ECO:0000244|PDB:2I1M}. FT STRAND 655 658 {ECO:0000244|PDB:2I1M}. FT STRAND 660 664 {ECO:0000244|PDB:2I1M}. FT HELIX 671 678 {ECO:0000244|PDB:2I1M}. FT TURN 684 686 {ECO:0000244|PDB:4R7I}. FT TURN 742 744 {ECO:0000244|PDB:2OGV}. FT HELIX 753 771 {ECO:0000244|PDB:2I1M}. FT HELIX 781 783 {ECO:0000244|PDB:2I1M}. FT STRAND 785 787 {ECO:0000244|PDB:2I1M}. FT HELIX 788 790 {ECO:0000244|PDB:2I1M}. FT STRAND 791 794 {ECO:0000244|PDB:2I1M}. FT HELIX 798 800 {ECO:0000244|PDB:2I1M}. FT HELIX 803 805 {ECO:0000244|PDB:2I1M}. FT TURN 806 808 {ECO:0000244|PDB:3LCO}. FT STRAND 809 811 {ECO:0000244|PDB:2I1M}. FT STRAND 815 817 {ECO:0000244|PDB:3BEA}. FT HELIX 819 821 {ECO:0000244|PDB:2I1M}. FT HELIX 824 829 {ECO:0000244|PDB:2I1M}. FT HELIX 834 848 {ECO:0000244|PDB:2I1M}. FT TURN 849 851 {ECO:0000244|PDB:2I1M}. FT HELIX 863 871 {ECO:0000244|PDB:2I1M}. FT HELIX 883 892 {ECO:0000244|PDB:2I1M}. FT HELIX 897 899 {ECO:0000244|PDB:2I1M}. FT HELIX 903 920 {ECO:0000244|PDB:2I1M}. SQ SEQUENCE 972 AA; 107984 MW; A8D99BE237573FE8 CRC64; MGPGVLLLLL VATAWHGQGI PVIEPSVPEL VVKPGATVTL RCVGNGSVEW DGPPSPHWTL YSDGSSSILS TNNATFQNTG TYRCTEPGDP LGGSAAIHLY VKDPARPWNV LAQEVVVFED QDALLPCLLT DPVLEAGVSL VRVRGRPLMR HTNYSFSPWH GFTIHRAKFI QSQDYQCSAL MGGRKVMSIS IRLKVQKVIP GPPALTLVPA ELVRIRGEAA QIVCSASSVD VNFDVFLQHN NTKLAIPQQS DFHNNRYQKV LTLNLDQVDF QHAGNYSCVA SNVQGKHSTS MFFRVVESAY LNLSSEQNLI QEVTVGEGLN LKVMVEAYPG LQGFNWTYLG PFSDHQPEPK LANATTKDTY RHTFTLSLPR LKPSEAGRYS FLARNPGGWR ALTFELTLRY PPEVSVIWTF INGSGTLLCA ASGYPQPNVT WLQCSGHTDR CDEAQVLQVW DDPYPEVLSQ EPFHKVTVQS LLTVETLEHN QTYECRAHNS VGSGSWAFIP ISAGAHTHPP DEFLFTPVVV ACMSIMALLL LLLLLLLYKY KQKPKYQVRW KIIESYEGNS YTFIDPTQLP YNEKWEFPRN NLQFGKTLGA GAFGKVVEAT AFGLGKEDAV LKVAVKMLKS TAHADEKEAL MSELKIMSHL GQHENIVNLL GACTHGGPVL VITEYCCYGD LLNFLRRKAE AMLGPSLSPG QDPEGGVDYK NIHLEKKYVR RDSGFSSQGV DTYVEMRPVS TSSNDSFSEQ DLDKEDGRPL ELRDLLHFSS QVAQGMAFLA SKNCIHRDVA ARNVLLTNGH VAKIGDFGLA RDIMNDSNYI VKGNARLPVK WMAPESIFDC VYTVQSDVWS YGILLWEIFS LGLNPYPGIL VNSKFYKLVK DGYQMAQPAF APKNIYSIMQ ACWALEPTHR PTFQQICSFL QEQAQEDRRE RDYTNLPSSS RSGGSGSSSS ELEEESSSEH LTCCEQGDIA QPLLQPNNYQ FC //