CSF1R_HUMAN
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 03-AUG-2022, entry version 235.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 proto-
RT 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., Isacke C.M.,
RA Verma I.M., Ullrich A.;
RT "Structural alteration of viral homologue of receptor proto-oncogene fms at
RT 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., Hu W.X.,
RA Galibert F.;
RT "Sequence analysis of two genomic regions containing the KIT and the FMS
RT 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., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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; DOI=10.1128/mcb.9.3.1336-1341.1989;
RA Visvader J., Verma I.M.;
RT "Differential transcription of exon 1 of the human c-fms gene in placental
RT trophoblasts and monocytes.";
RL Mol. Cell. Biol. 9:1336-1341(1989).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16.
RX PubMed=3525854; DOI=10.1128/jvi.59.2.224-233.1986;
RA Wheeler E.F., Roussel M.F., Hampe A., Walker M.H., Fried V.A., Look A.T.,
RA 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 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., O'Brien S.J.,
RA Sherr C.J.;
RT "Expression of the human c-fms proto-oncogene in hematopoietic cells and
RT 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 sequences
RT 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 murine
RT pluripotent hematopoietic NFS-60 cells induces long-term proliferation in
RT response to CSF-1 without loss of erythroid 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; DOI=10.1002/j.1460-2075.1993.tb05735.x;
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 their
RT 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 human
RT 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 ACTIVATION OF
RP AKT1.
RX PubMed=12882960; DOI=10.1074/jbc.m305021200;
RA Baran C.P., Tridandapani S., Helgason C.D., Humphries R.K., Krystal G.,
RA 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 SHAPE AND
RP INTEGRITY OF CELL JUNCTIONS, MUTAGENESIS OF LEU-301 AND TYR-969, AND ROLE
RP IN DISEASE.
RX PubMed=15117969; DOI=10.1083/jcb.200309102;
RA Wrobel C.N., Debnath J., Lin E., Beausoleil S., Roussel M.F., Brugge J.S.;
RT "Autocrine CSF-1R activation promotes Src-dependent disruption of mammary
RT 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., Moore R.J.,
RA 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, ROLE IN
RP DISEASE, AND ACTIVITY 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., Michaelides M.R.,
RA Davidsen S.K., Glaser K.B.;
RT "Inhibition of phosphorylation of the colony-stimulating factor-1 receptor
RT (c-Fms) tyrosine kinase in transfected cells by ABT-869 and other tyrosine
RT kinase inhibitors.";
RL Mol. Cancer Ther. 5:1007-1013(2006).
RN [21]
RP FUNCTION IN CELL PROLIFERATION, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION,
RP ROLE IN DISEASE, AND ACTIVITY 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, ACTIVITY REGULATION, AND MUTAGENESIS OF 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., Wu G.,
RA Zhou A., Behrens D., Hollenbaugh D., Linnemann T., Qin M., Wong J., Chu K.,
RA Doberstein S.K., Williams L.T.;
RT "Discovery of a cytokine and its receptor by functional screening of the
RT extracellular proteome.";
RL Science 320:807-811(2008).
RN [24]
RP ROLE IN DISEASE, AND ACTIVITY 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 and
RT autocrine loops involving the colony-stimulating factor-1 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 ACTIVITY 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, ACTIVITY
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 biological
RT activity and signal activation.";
RL Cell Death Differ. 17:1917-1927(2010).
RN [29]
RP FUNCTION IN RELEASE OF PRO-INFLAMMATORY 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 chemokines
RT in human whole blood.";
RL Cytokine 52:215-220(2010).
RN [30]
RP FUNCTION AS IL34 AND CSF1 RECEPTOR; ACTIVATION OF MAPK1/ERK2; MAPK3/ERK1;
RP 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., 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 [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., Williams C.C.,
RA Dan Q., Sanchez R., Jeffes E.W., Wepsic H.T., Myers M.P., Koths K.,
RA Jadus M.R.;
RT "Macrophage colony stimulating factor: not just for macrophages anymore! A
RT 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., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT 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., Williams N.K.,
RA 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., Petrounia I.P.,
RA 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 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 ACTIVITY 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 CSF-1R
RT 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; HIS-693;
RP ASP-920 AND GLN-921.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA 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 HDLS1 774-CYS--ASN-814 DEL; 585-GLY--LYS-619 DELINS ALA; GLU-589;
RP LYS-633; THR-766; PRO-770; ASN-775; THR-794; TYR-837; SER-849; PHE-849 DEL;
RP PRO-868; THR-875 AND THR-878, VARIANTS HIS-710; ARG-747 AND ASP-920, AND
RP CHARACTERIZATION OF VARIANTS HDLS1 LYS-633; 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 cause
RT hereditary diffuse leukoencephalopathy with spheroids.";
RL Nat. Genet. 44:200-205(2012).
RN [43]
RP VARIANTS HDLS1 THR-766 AND HIS-782, CHARACTERIZATION OF VARIANTS HDLS1
RP HIS-782 AND THR-875, AND AUTOPHOSPHORYLATION.
RX PubMed=23408870; DOI=10.1212/wnl.0b013e31828726a7;
RA Nicholson A.M., Baker M.C., Finch N.A., Rutherford N.J., Wider C.,
RA Graff-Radford N.R., Nelson P.T., Clark H.B., Wszolek Z.K., Dickson D.W.,
RA Knopman D.S., Rademakers R.;
RT "CSF1R mutations link POLD and HDLS as a single disease entity.";
RL Neurology 80:1033-1040(2013).
RN [44]
RP VARIANTS HDLS1 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 CSF1R
RT gene.";
RL J. Neurol. 261:768-772(2014).
RN [45]
RP VARIANTS HDLS1 ASP-765; GLU-781; THR-794 AND SER-824, CHARACTERIZATION OF
RP VARIANTS HDLS1 ASP-765; GLU-781; THR-794 AND SER-824, AND
RP AUTOPHOSPHORYLATION.
RX PubMed=24336230; DOI=10.1212/wnl.0000000000000046;
RA Konno T., Tada M., Tada M., Koyama A., Nozaki H., Harigaya Y.,
RA Nishimiya J., Matsunaga A., Yoshikura N., Ishihara K., Arakawa M.,
RA Isami A., Okazaki K., Yokoo H., Itoh K., Yoneda M., Kawamura M.,
RA Inuzuka T., Takahashi H., Nishizawa M., Onodera O., Kakita A., Ikeuchi T.;
RT "Haploinsufficiency of CSF-1R and clinicopathologic characterization in
RT patients with HDLS.";
RL Neurology 82:139-148(2014).
RN [46]
RP INVOLVEMENT IN BANDDOS, VARIANTS BANDDOS LEU-132; GLN-481--972-CYS DEL AND
RP LYS-627 DEL, CHARACTERIZATION OF VARIANTS BANDDOS LEU-132 AND LYS-627 DEL,
RP AND FUNCTION.
RX PubMed=30982609; DOI=10.1016/j.ajhg.2019.03.004;
RA Guo L., Bertola D.R., Takanohashi A., Saito A., Segawa Y., Yokota T.,
RA Ishibashi S., Nishida Y., Yamamoto G.L., Franco J.F.D.S., Honjo R.S.,
RA Kim C.A., Musso C.M., Timmons M., Pizzino A., Taft R.J., Lajoie B.,
RA Knight M.A., Fischbeck K.H., Singleton A.B., Ferreira C.R., Wang Z.,
RA Yan L., Garbern J.Y., Simsek-Kiper P.O., Ohashi H., Robey P.G., Boyde A.,
RA Matsumoto N., Miyake N., Spranger J., Schiffmann R., Vanderver A.,
RA Nishimura G., Passos-Bueno M.R.D.S., Simons C., Ishikawa K., Ikegawa S.;
RT "Bi-allelic CSF1R Mutations Cause Skeletal Dysplasia of Dysosteosclerosis-
RT Pyle Disease Spectrum and Degenerative Encephalopathy with Brain
RT Malformation.";
RL Am. J. Hum. Genet. 104:925-935(2019).
RN [47]
RP VARIANT BANDDOS GLN-643, AND FUNCTION.
RX PubMed=30982608; DOI=10.1016/j.ajhg.2019.03.010;
RA Oosterhof N., Chang I.J., Karimiani E.G., Kuil L.E., Jensen D.M., Daza R.,
RA Young E., Astle L., van der Linde H.C., Shivaram G.M., Demmers J.,
RA Latimer C.S., Keene C.D., Loter E., Maroofian R., van Ham T.J.,
RA Hevner R.F., Bennett J.T.;
RT "Homozygous Mutations in CSF1R Cause a Pediatric-Onset Leukoencephalopathy
RT and Can Result in Congenital Absence of Microglia.";
RL Am. J. Hum. Genet. 104:936-947(2019).
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 (PubMed:20504948, PubMed:30982609).
CC Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2
CC leads to the production of the cellular signaling molecules
CC diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the
CC activation of protein kinase C family members, especially PRKCD.
CC Phosphorylation of PIK3R1, the regulatory subunit of
CC phosphatidylinositol 3-kinase, leads to activation of the AKT1
CC signaling pathway. Activated CSF1R also mediates activation of the MAP
CC kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases
CC SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins
CC that directly interact with phosphorylated tyrosine residues in its
CC intracellular domain, or via adapter proteins, such as GRB2. Promotes
CC activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes
CC tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling
CC is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that
CC dephosphorylate the receptor and its downstream effectors, and by rapid
CC internalization of the activated receptor. In the central nervous
CC system, may play a role in the development of microglia macrophages
CC (PubMed:30982608). {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:30982608, ECO:0000269|PubMed:30982609,
CC ECO:0000269|PubMed:7683918}.
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:16170366, ECO:0000269|PubMed:16648572,
CC ECO:0000269|PubMed:17121910, ECO:0000269|PubMed:18342505,
CC ECO:0000269|PubMed:19193011, ECO:0000269|PubMed:20137931};
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:16170366, ECO:0000269|PubMed:16648572,
CC ECO:0000269|PubMed:17121910, ECO:0000269|PubMed:18814279,
CC ECO:0000269|PubMed:20137931, ECO:0000269|PubMed:20156689,
CC 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, ECO:0000269|PubMed:19193011,
CC ECO:0000269|PubMed:20489731, ECO:0000269|PubMed:7681396}.
CC -!- INTERACTION:
CC P07333; P09603: CSF1; NbExp=13; IntAct=EBI-2835440, EBI-2872294;
CC P07333; Q6ZMJ4-1: IL34; NbExp=9; IntAct=EBI-2835440, EBI-15978980;
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 region.
CC Phosphorylation of tyrosine residues in this region leads to a
CC conformation change and activation of the kinase.
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.
CC -!- PTM: Autophosphorylated in response to CSF1 or IL34 binding
CC (PubMed:24336230, PubMed:20489731, PubMed:23408870). Phosphorylation at
CC Tyr-561 is important for normal down-regulation of signaling by
CC ubiquitination, internalization and degradation. Phosphorylation at
CC Tyr-561 and Tyr-809 is important for interaction with SRC family
CC members, including FYN, YES1 and SRC, and for subsequent activation of
CC these protein kinases. Phosphorylation at Tyr-699 and Tyr-923 is
CC important for interaction with GRB2. Phosphorylation at Tyr-723 is
CC important for interaction with PIK3R1. Phosphorylation at Tyr-708 is
CC important for normal receptor degradation. Phosphorylation at Tyr-723
CC and Tyr-809 is important for interaction with PLCG2. Phosphorylation at
CC Tyr-969 is important for interaction with CBL. Dephosphorylation by
CC PTPN2 negatively regulates downstream signaling and macrophage
CC differentiation. {ECO:0000269|PubMed:16170366,
CC ECO:0000269|PubMed:20489731, ECO:0000269|PubMed:23408870,
CC ECO:0000269|PubMed:24336230}.
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 cancer
CC cell proliferation, invasion and formation of metastases.
CC Overexpression of CSF1 or CSF1R is observed in a significant percentage
CC of breast, ovarian, prostate, and endometrial cancers.
CC -!- DISEASE: Note=Aberrant expression of CSF1 or CSF1R may play a role in
CC inflammatory diseases, such as rheumatoid arthritis,
CC glomerulonephritis, atherosclerosis, and allograft rejection.
CC -!- DISEASE: Leukoencephalopathy, hereditary diffuse, with spheroids 1
CC (HDLS1) [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 affecting the
CC frontal and parietal lobes. {ECO:0000269|PubMed:22197934,
CC ECO:0000269|PubMed:23408870, ECO:0000269|PubMed:24336230,
CC ECO:0000269|PubMed:24532199}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Brain abnormalities, neurodegeneration, and dysosteosclerosis
CC (BANDDOS) [MIM:618476]: An autosomal recessive disease with variable
CC manifestations. Main features are brain malformations with calcifying
CC leukoencephalopathy, progressive neurodegeneration, and bone sclerotic
CC features. The age at onset ranges from infancy to early adulthood.
CC Neurologic features include loss of previous motor and language skills,
CC cognitive impairment, spasticity, and focal seizures. Brain imaging
CC shows periventricular white matter abnormalities and calcifications,
CC large cisterna magna or Dandy-Walker malformation, and sometimes
CC agenesis of the corpus callosum. {ECO:0000269|PubMed:30982608,
CC ECO:0000269|PubMed:30982609}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CSF1RID40161ch5q32.html";
CC ---------------------------------------------------------------------------
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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_001288705.2. [P07333-1]
DR RefSeq; NP_005202.2; NM_005211.3. [P07333-1]
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 PDB; 6IG8; X-ray; 1.80 A; A=550-919.
DR PDB; 6N33; X-ray; 2.25 A; A=542-919.
DR PDB; 6T2W; X-ray; 1.70 A; A=542-919.
DR PDB; 6WXJ; X-ray; 2.62 A; A=538-678, A=753-922.
DR PDB; 7MFC; X-ray; 2.80 A; A=542-919.
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 PDBsum; 6IG8; -.
DR PDBsum; 6N33; -.
DR PDBsum; 6T2W; -.
DR PDBsum; 6WXJ; -.
DR PDBsum; 7MFC; -.
DR AlphaFoldDB; P07333; -.
DR SMR; P07333; -.
DR BioGRID; 107823; 31.
DR DIP; DIP-59421N; -.
DR IntAct; P07333; 32.
DR MINT; P07333; -.
DR STRING; 9606.ENSP00000286301; -.
DR BindingDB; P07333; -.
DR ChEMBL; CHEMBL1844; -.
DR DrugBank; DB07167; 5-CYANO-FURAN-2-CARBOXYLIC ACID [5-HYDROXYMETHYL-2-(4-METHYL-PIPERIDIN-1-YL)-PHENYL]-AMIDE.
DR DrugBank; DB07202; 6-CHLORO-3-(3-METHYLISOXAZOL-5-YL)-4-PHENYLQUINOLIN-2(1H)-ONE.
DR DrugBank; DB12147; Erdafitinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB00619; Imatinib.
DR DrugBank; DB06080; Linifanib.
DR DrugBank; DB12978; Pexidartinib.
DR DrugBank; DB01268; Sunitinib.
DR DrugCentral; P07333; -.
DR GuidetoPHARMACOLOGY; 1806; -.
DR GlyConnect; 1955; 14 N-Linked glycans (3 sites).
DR GlyGen; P07333; 12 sites, 14 N-linked glycans (3 sites).
DR iPTMnet; P07333; -.
DR PhosphoSitePlus; P07333; -.
DR BioMuta; CSF1R; -.
DR DMDM; 547770; -.
DR EPD; P07333; -.
DR jPOST; P07333; -.
DR MassIVE; P07333; -.
DR PaxDb; P07333; -.
DR PeptideAtlas; P07333; -.
DR PRIDE; P07333; -.
DR ProteomicsDB; 51993; -. [P07333-1]
DR ProteomicsDB; 5930; -.
DR ABCD; P07333; 61 sequenced antibodies.
DR Antibodypedia; 1201; 1818 antibodies from 45 providers.
DR DNASU; 1436; -.
DR Ensembl; ENST00000286301.7; ENSP00000286301.3; ENSG00000182578.14. [P07333-1]
DR Ensembl; ENST00000543093.1; ENSP00000445282.1; ENSG00000182578.14. [P07333-2]
DR Ensembl; ENST00000675795.1; ENSP00000501699.1; ENSG00000182578.14. [P07333-1]
DR GeneID; 1436; -.
DR KEGG; hsa:1436; -.
DR MANE-Select; ENST00000675795.1; ENSP00000501699.1; NM_001288705.3; NP_001275634.1.
DR UCSC; uc003lrm.3; human. [P07333-1]
DR CTD; 1436; -.
DR DisGeNET; 1436; -.
DR GeneCards; CSF1R; -.
DR GeneReviews; CSF1R; -.
DR HGNC; HGNC:2433; CSF1R.
DR HPA; ENSG00000182578; Tissue enhanced (lymphoid tissue, placenta).
DR MalaCards; CSF1R; -.
DR MIM; 164770; gene.
DR MIM; 221820; phenotype.
DR MIM; 618476; phenotype.
DR neXtProt; NX_P07333; -.
DR OpenTargets; ENSG00000182578; -.
DR Orphanet; 556985; Early-onset calcifying leukoencephalopathy-skeletal dysplasia.
DR Orphanet; 313808; Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia.
DR PharmGKB; PA26936; -.
DR VEuPathDB; HostDB:ENSG00000182578; -.
DR eggNOG; KOG0200; Eukaryota.
DR GeneTree; ENSGT00940000155506; -.
DR HOGENOM; CLU_000288_49_0_1; -.
DR InParanoid; P07333; -.
DR OMA; EQLACCE; -.
DR OrthoDB; 236292at2759; -.
DR PhylomeDB; P07333; -.
DR TreeFam; TF325768; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; P07333; -.
DR Reactome; R-HSA-449836; Other interleukin signaling.
DR Reactome; R-HSA-8853884; Transcriptional Regulation by VENTX.
DR SignaLink; P07333; -.
DR SIGNOR; P07333; -.
DR BioGRID-ORCS; 1436; 11 hits in 1105 CRISPR screens.
DR ChiTaRS; CSF1R; human.
DR EvolutionaryTrace; P07333; -.
DR GeneWiki; Colony_stimulating_factor_1_receptor; -.
DR GenomeRNAi; 1436; -.
DR Pharos; P07333; Tclin.
DR PRO; PR:P07333; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P07333; protein.
DR Bgee; ENSG00000182578; Expressed in granulocyte and 164 other tissues.
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; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
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; IMP:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:BHF-UCL.
DR GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
DR GO; GO:0004713; F:protein tyrosine kinase activity; TAS:ARUK-UCL.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR GO; GO:0008283; P:cell population 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:0021879; P:forebrain neuron differentiation; IEA:Ensembl.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IBA:GO_Central.
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:0061518; P:microglial cell proliferation; IEA:Ensembl.
DR GO; GO:0030224; P:monocyte differentiation; TAS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0021772; P:olfactory bulb development; IEA:Ensembl.
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:0044794; P:positive regulation by host of viral process; IEA:Ensembl.
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 population proliferation; IMP:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; IMP:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IGI:ARUK-UCL.
DR GO; GO:0120041; P:positive regulation of macrophage proliferation; IGI:ARUK-UCL.
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:0042531; P:positive regulation of tyrosine phosphorylation of STAT 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:0002931; P:response to ischemia; ISS:ARUK-UCL.
DR GO; GO:0031529; P:ruffle organization; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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; 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; 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 Disease variant; Disulfide bond; Glycoprotein; Immunity;
KW Immunoglobulin domain; Inflammatory response; Innate immunity; Kinase;
KW Membrane; Neurodegeneration; Nucleotide-binding; Phosphoprotein;
KW Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..972
FT /note="Macrophage colony-stimulating factor 1 receptor"
FT /id="PRO_0000016765"
FT TOPO_DOM 20..517
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 518..538
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 539..972
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..104
FT /note="Ig-like C2-type 1"
FT DOMAIN 107..197
FT /note="Ig-like C2-type 2"
FT DOMAIN 203..290
FT /note="Ig-like C2-type 3"
FT DOMAIN 299..399
FT /note="Ig-like C2-type 4"
FT DOMAIN 402..502
FT /note="Ig-like C2-type 5"
FT DOMAIN 582..910
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 542..574
FT /note="Regulatory juxtamembrane domain"
FT REGION 796..818
FT /note="Activation loop"
FT REGION 918..950
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 926..942
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 778
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 588..596
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 616
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 546
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:20489731"
FT MOD_RES 561
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09581"
FT MOD_RES 699
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:20489731,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 708
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:20489731"
FT MOD_RES 713
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 723
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:20489731"
FT MOD_RES 809
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:20489731"
FT MOD_RES 923
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09581"
FT MOD_RES 969
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P09581"
FT CARBOHYD 45
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 275
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 302
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 412
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 428
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 42..84
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 127..177
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 224..278
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 419..485
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 297..306
FT /note="ESAYLNLSSE -> GTPSPSLCPA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_047757"
FT VAR_SEQ 307..972
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18593464"
FT /id="VSP_047758"
FT VARIANT 32
FT /note="V -> G (in dbSNP:rs56048668)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042038"
FT VARIANT 132
FT /note="P -> L (in BANDDOS; impairs phosphorylation of JNK
FT kinases upon stimulation with CSF1; dbSNP:rs1351319114)"
FT /evidence="ECO:0000269|PubMed:30982609"
FT /id="VAR_083140"
FT VARIANT 245
FT /note="A -> S (in dbSNP:rs41338945)"
FT /id="VAR_061290"
FT VARIANT 279
FT /note="V -> M (in dbSNP:rs3829986)"
FT /id="VAR_049718"
FT VARIANT 362
FT /note="H -> R (in dbSNP:rs10079250)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042039"
FT VARIANT 413
FT /note="G -> S (in dbSNP:rs34951517)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042040"
FT VARIANT 481..972
FT /note="Missing (in BANDDOS; dbSNP:rs917027829)"
FT /evidence="ECO:0000269|PubMed:30982609"
FT /id="VAR_083141"
FT VARIANT 536
FT /note="L -> V (in dbSNP:rs55942044)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042041"
FT VARIANT 585..619
FT /note="GKTLGAGAFGKVVEATAFGLGKEDAVLKVAVKMLK -> A (in HDLS1)"
FT /evidence="ECO:0000269|PubMed:22197934"
FT /id="VAR_067396"
FT VARIANT 589
FT /note="G -> E (in HDLS1; dbSNP:rs281860268)"
FT /evidence="ECO:0000269|PubMed:22197934"
FT /id="VAR_067397"
FT VARIANT 627
FT /note="Missing (in BANDDOS; impairs phosphorylation of JNK
FT kinases upon stimulation with CSF1; dbSNP:rs1554101963)"
FT /evidence="ECO:0000269|PubMed:30982609"
FT /id="VAR_083142"
FT VARIANT 633
FT /note="E -> K (in HDLS1; impairs autophosphorylation upon
FT stimulation with CSF1; dbSNP:rs281860269)"
FT /evidence="ECO:0000269|PubMed:22197934"
FT /id="VAR_067398"
FT VARIANT 643
FT /note="H -> Q (in BANDDOS; dbSNP:rs184499252)"
FT /evidence="ECO:0000269|PubMed:30982608"
FT /id="VAR_083143"
FT VARIANT 653
FT /note="C -> R (in HDLS1; dbSNP:rs690016559)"
FT /evidence="ECO:0000269|PubMed:24532199"
FT /id="VAR_072081"
FT VARIANT 693
FT /note="P -> H (in a lung squamous cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042042"
FT VARIANT 710
FT /note="R -> H (in dbSNP:rs201569135)"
FT /evidence="ECO:0000269|PubMed:22197934"
FT /id="VAR_067399"
FT VARIANT 747
FT /note="G -> R (in dbSNP:rs41355444)"
FT /evidence="ECO:0000269|PubMed:22197934"
FT /id="VAR_067400"
FT VARIANT 765
FT /note="G -> D (in HDLS1; impairs autophosphorylation upon
FT stimulation with CSF1; dbSNP:rs690016566)"
FT /evidence="ECO:0000269|PubMed:24336230"
FT /id="VAR_083144"
FT VARIANT 766
FT /note="M -> T (in HDLS1; impairs autophosphorylation upon
FT stimulation with CSF1; dbSNP:rs281860270)"
FT /evidence="ECO:0000269|PubMed:22197934,
FT ECO:0000269|PubMed:23408870"
FT /id="VAR_067401"
FT VARIANT 770
FT /note="A -> P (in HDLS1; dbSNP:rs281860271)"
FT /evidence="ECO:0000269|PubMed:22197934"
FT /id="VAR_067402"
FT VARIANT 774..814
FT /note="Missing (in HDLS1)"
FT /evidence="ECO:0000269|PubMed:22197934"
FT /id="VAR_067403"
FT VARIANT 775
FT /note="I -> N (in HDLS1; impairs autophosphorylation upon
FT stimulation with CSF1; dbSNP:rs281860273)"
FT /evidence="ECO:0000269|PubMed:22197934"
FT /id="VAR_067404"
FT VARIANT 781
FT /note="A -> E (in HDLS1; impairs autophosphorylation upon
FT stimulation with CSF1; dbSNP:rs587777247)"
FT /evidence="ECO:0000269|PubMed:24336230"
FT /id="VAR_083145"
FT VARIANT 782
FT /note="R -> H (in HDLS1; impairs autophosphorylation upon
FT stimulation with CSF1; dbSNP:rs281860281)"
FT /evidence="ECO:0000269|PubMed:23408870"
FT /id="VAR_083146"
FT VARIANT 794
FT /note="I -> T (in HDLS1; impairs autophosphorylation upon
FT stimulation with CSF1; dbSNP:rs281860274)"
FT /evidence="ECO:0000269|PubMed:22197934,
FT ECO:0000269|PubMed:24336230"
FT /id="VAR_067405"
FT VARIANT 824
FT /note="P -> S (in HDLS1; impairs autophosphorylation upon
FT stimulation with CSF1)"
FT /evidence="ECO:0000269|PubMed:24336230"
FT /id="VAR_083147"
FT VARIANT 837
FT /note="D -> Y (in HDLS1; dbSNP:rs387906662)"
FT /evidence="ECO:0000269|PubMed:22197934"
FT /id="VAR_067406"
FT VARIANT 843
FT /note="I -> F (in HDLS1; dbSNP:rs690016558)"
FT /evidence="ECO:0000269|PubMed:24532199"
FT /id="VAR_072082"
FT VARIANT 849
FT /note="F -> S (in HDLS1; dbSNP:rs281860277)"
FT /evidence="ECO:0000269|PubMed:22197934"
FT /id="VAR_067407"
FT VARIANT 849
FT /note="Missing (in HDLS1)"
FT /evidence="ECO:0000269|PubMed:22197934"
FT /id="VAR_067408"
FT VARIANT 868
FT /note="L -> P (in HDLS1; dbSNP:rs281860278)"
FT /evidence="ECO:0000269|PubMed:22197934"
FT /id="VAR_067409"
FT VARIANT 875
FT /note="M -> T (in HDLS1; impairs autophosphorylation upon
FT stimulation with CSF1; dbSNP:rs281860279)"
FT /evidence="ECO:0000269|PubMed:22197934,
FT ECO:0000269|PubMed:23408870"
FT /id="VAR_067410"
FT VARIANT 878
FT /note="P -> T (in HDLS1; dbSNP:rs281860280)"
FT /evidence="ECO:0000269|PubMed:22197934"
FT /id="VAR_067411"
FT VARIANT 906
FT /note="I -> T (in HDLS1; dbSNP:rs690016560)"
FT /evidence="ECO:0000269|PubMed:24532199"
FT /id="VAR_072083"
FT VARIANT 920
FT /note="E -> D (in dbSNP:rs34030164)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:22197934"
FT /id="VAR_042043"
FT VARIANT 921
FT /note="R -> Q (in dbSNP:rs56059682)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042044"
FT VARIANT 969
FT /note="Y -> C (in dbSNP:rs1801271)"
FT /id="VAR_011953"
FT MUTAGEN 301
FT /note="L->S: Constitutive kinase activity."
FT /evidence="ECO:0000269|PubMed:15117969"
FT MUTAGEN 708
FT /note="Y->F: Impairs degradation of activated CSF1R."
FT /evidence="ECO:0000269|PubMed:10340379"
FT MUTAGEN 802
FT /note="D->V: Constitutive kinase activity. Loss of
FT inhibition by imatinib."
FT /evidence="ECO:0000269|PubMed:10340379,
FT ECO:0000269|PubMed:16170366"
FT MUTAGEN 809
FT /note="Y->F: Reduced kinase activity. Reduced interaction
FT with SRC, FYN and YES1."
FT /evidence="ECO:0000269|PubMed:7681396"
FT MUTAGEN 969
FT /note="Y->F: Abolishes down-regulation of activated CSF1R."
FT /evidence="ECO:0000269|PubMed:15117969"
FT CONFLICT 54
FT /note="P -> A (in Ref. 2; CAA27300)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="P -> H (in Ref. 7; AAH47521)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="A -> V (in Ref. 7; AAH47521)"
FT /evidence="ECO:0000305"
FT CONFLICT 629
FT /note="A -> S (in Ref. 7; AAH47521)"
FT /evidence="ECO:0000305"
FT STRAND 22..25
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 38..43
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:4LIQ"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 58..62
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 64..73
FT /evidence="ECO:0007829|PDB:4LIQ"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 95..101
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 113..118
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 127..130
FT /evidence="ECO:0007829|PDB:4LIQ"
FT HELIX 132..137
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 139..142
FT /evidence="ECO:0007829|PDB:4LIQ"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:4WRL"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:4LIQ"
FT TURN 158..160
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 161..166
FT /evidence="ECO:0007829|PDB:4LIQ"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 173..181
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 191..196
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 210..215
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:4DKD"
FT STRAND 220..231
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 234..239
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 248..252
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 257..267
FT /evidence="ECO:0007829|PDB:4LIQ"
FT TURN 270..272
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 274..282
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 285..298
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 300..304
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 309..314
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 319..329
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 332..338
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 340..342
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 351..354
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 361..368
FT /evidence="ECO:0007829|PDB:4LIQ"
FT HELIX 373..375
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 377..385
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 388..411
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 414..425
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 428..437
FT /evidence="ECO:0007829|PDB:4LIQ"
FT TURN 443..445
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 446..454
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 456..459
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 466..473
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 479..488
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 493..498
FT /evidence="ECO:0007829|PDB:4LIQ"
FT STRAND 551..553
FT /evidence="ECO:0007829|PDB:6IG8"
FT STRAND 556..560
FT /evidence="ECO:0007829|PDB:3BEA"
FT HELIX 566..568
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 573..575
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 579..581
FT /evidence="ECO:0007829|PDB:6T2W"
FT STRAND 582..590
FT /evidence="ECO:0007829|PDB:6T2W"
FT STRAND 592..604
FT /evidence="ECO:0007829|PDB:6T2W"
FT TURN 605..608
FT /evidence="ECO:0007829|PDB:6T2W"
FT STRAND 609..618
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 624..640
FT /evidence="ECO:0007829|PDB:6T2W"
FT STRAND 649..653
FT /evidence="ECO:0007829|PDB:6T2W"
FT STRAND 655..658
FT /evidence="ECO:0007829|PDB:6T2W"
FT STRAND 660..664
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 671..680
FT /evidence="ECO:0007829|PDB:6T2W"
FT TURN 684..686
FT /evidence="ECO:0007829|PDB:6IG8"
FT TURN 742..744
FT /evidence="ECO:0007829|PDB:2OGV"
FT HELIX 752..771
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 781..783
FT /evidence="ECO:0007829|PDB:6T2W"
FT STRAND 784..787
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 788..790
FT /evidence="ECO:0007829|PDB:6T2W"
FT STRAND 791..794
FT /evidence="ECO:0007829|PDB:6T2W"
FT TURN 798..800
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 803..805
FT /evidence="ECO:0007829|PDB:2I1M"
FT TURN 806..808
FT /evidence="ECO:0007829|PDB:3LCO"
FT STRAND 809..812
FT /evidence="ECO:0007829|PDB:6T2W"
FT STRAND 815..817
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 819..821
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 824..829
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 834..849
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 863..870
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 883..892
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 897..899
FT /evidence="ECO:0007829|PDB:6T2W"
FT HELIX 903..915
FT /evidence="ECO:0007829|PDB:6T2W"
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
