ID CSF1_HUMAN Reviewed; 554 AA. AC P09603; A8K6J5; Q13130; Q14086; Q14806; Q5VVF3; Q5VVF4; Q9UQR8; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 02-NOV-2010, sequence version 2. DT 02-SEP-2026, entry version 240. DE RecName: Full=Macrophage colony-stimulating factor 1; DE Short=CSF-1; DE Short=M-CSF; DE Short=MCSF; DE AltName: Full=Lanimostim; DE AltName: Full=Proteoglycan macrophage colony-stimulating factor {ECO:0000303|PubMed:8051056}; DE Short=PG-M-CSF {ECO:0000303|PubMed:8051056}; DE Contains: DE RecName: Full=Processed macrophage colony-stimulating factor 1; DE Contains: DE RecName: Full=Macrophage colony-stimulating factor 1 43 kDa subunit {ECO:0000303|PubMed:8051056}; DE Flags: Precursor; GN Name=CSF1; 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], PROTEIN SEQUENCE OF 33-44 (ISOFORM 3), RP AND VARIANT SER-489. RC TISSUE=Pancreatic carcinoma, and Urine; RX PubMed=2996129; DOI=10.1126/science.2996129; RA Kawasaki E.S., Ladner M.B., Wang A.M., van Arsdell J.N., Warren M.K., RA Coyne M.Y., Schweickart V.L., Lee M.-T., Wilson K.J., Boosman A., RA Stanley E.R., Ralph P., Mark D.F.; RT "Molecular cloning of a complementary DNA encoding human macrophage- RT specific colony-stimulating factor (CSF-1)."; RL Science 230:291-296(1985). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND RP VARIANT SER-489. RC TISSUE=Trophoblast, and Urine; RX PubMed=3493529; DOI=10.1126/science.3493529; RA Wong G.G., Temple P.A., Leary A.C., Witek-Giannotti J.S., Yang Y.C., RA Ciarletta A.B., Chung M., Murtha P., Kriz R., Kaufman R.J., Ferenz C.R., RA Sibley B.S., Turner K.J., Hewick R.M., Clark S.C., Yanai N., Yokota H., RA Yamada M., Saito M., Motoyoshi K., Takaku F.; RT "Human CSF-1: molecular cloning and expression of 4-kb cDNA encoding the RT human urinary protein."; RL Science 235:1504-1508(1987). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, MUTAGENESIS OF ISOFORM 3, RP AND VARIANT SER-489. RC TISSUE=Pancreatic carcinoma; RX PubMed=2460758; DOI=10.1016/0161-5890(88)90112-5; RA Cerretti D.P., Wignall J., Anderson D., Tushinski R.J., Gallis B.M., RA Stya M., Gillis S., Urdal D.L., Cosman D.; RT "Human macrophage-colony stimulating factor: alternative RNA and protein RT processing from a single gene."; RL Mol. Immunol. 25:761-770(1988). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS PRO-408 AND SER-489. RC TISSUE=T lymphoblast; RX PubMed=2660794; DOI=10.1016/0006-291x(89)92683-1; RA Takahashi M., Hirato T., Takano M., Nishida T., Nagamura K., RA Kamogashira T., Nakai S., Hirai Y.; RT "Amino-terminal region of human macrophage colony-stimulating factor (M- RT CSF) is sufficient for its in vitro biological activity: molecular cloning RT and expression of carboxyl-terminal deletion mutants of human M-CSF."; RL Biochem. Biophys. Res. Commun. 161:892-901(1989). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-489. RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-489. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-489. RC TISSUE=Kidney; 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 [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-13 AND 19-554 (ISOFORM 1), RP AND VARIANT SER-489. RC TISSUE=Pancreatic carcinoma; RX PubMed=3500041; DOI=10.1002/j.1460-2075.1987.tb02561.x; RA Ladner M.B., Martin G.A., Noble J.A., Nikoloff D.M., Tal R., Kawasaki E.S., RA White T.J.; RT "Human CSF-1: gene structure and alternative splicing of mRNA precursors."; RL EMBO J. 6:2693-2698(1987). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-554 (ISOFORM 3), AND VARIANT SER-489. RC TISSUE=Endometrium; RX PubMed=1791839; DOI=10.1210/mend-5-12-1931; RA Pampfer S., Tabibzadeh S., Chuan F.-C., Pollard J.W.; RT "Expression of colony-stimulating factor-1 (CSF-1) messenger RNA in human RT endometrial glands during the menstrual cycle: molecular cloning of a novel RT transcript that predicts a cell surface form of CSF-1."; RL Mol. Endocrinol. 5:1931-1938(1991). RN [11] RP PROTEIN SEQUENCE OF 33-185 (ISOFORM 1). RC TISSUE=T lymphoblast; RX PubMed=8262907; DOI=10.1093/oxfordjournals.jbchem.a124163; RA Yamanishi K., Yasuda S., Masui Y., Nishida T., Shindo Y., Takano M., RA Ohmoto Y., Takahashi M., Adachi M.; RT "The structure of recombinant human carboxy-terminal-truncated macrophage RT colony-stimulating factor derived from mammalian cells."; RL J. Biochem. 114:255-262(1993). RN [12] RP PROTEIN SEQUENCE OF 33-76. RX PubMed=3498652; DOI=10.1016/0014-5793(87)80398-8; RA Sakai N., Umeda T., Suzuki H., Ishimatsu Y., Shikita M.; RT "Macrophage colony-stimulating factor purified from normal human urine. RT Amino-terminal sequence and amino acid composition."; RL FEBS Lett. 222:341-344(1987). RN [13] RP PROTEIN SEQUENCE OF 33-38, FUNCTION, SUBUNIT, GLYCOSYLATION AT SER-309, AND RP MUTAGENESIS OF ARG-252; SER-309 AND ARG-444. RX PubMed=8051056; DOI=10.1016/s0021-9258(17)32085-9; RA Kimura F., Suzu S., Nakamura Y., Wakimoto N., Kanatani Y., Yanai N., RA Nagata N., Motoyoshi K.; RT "Structural analysis of proteoglycan macrophage colony-stimulating RT factor."; RL J. Biol. Chem. 269:19751-19756(1994). RN [14] RP PROTEIN SEQUENCE OF 35-61. RX PubMed=3259875; DOI=10.1016/s0006-291x(88)80441-8; RA Takahashi M., Hong Y.M., Yasuda S., Takano M., Kawai K., Nakai S., RA Hirai Y.; RT "Macrophage colony-stimulating factor is produced by human T lymphoblastoid RT cell line, CEM-ON: identification by amino-terminal amino acid sequence RT analysis."; RL Biochem. Biophys. Res. Commun. 152:1401-1409(1988). RN [15] RP CHARACTERIZATION (ISOFORM 3). RX PubMed=3039346; DOI=10.1128/mcb.7.7.2378-2387.1987; RA Rettenmier C.W., Roussel M.F., Ashmun R.A., Ralph P., Price K., Sherr C.J.; RT "Synthesis of membrane-bound colony-stimulating factor 1 (CSF-1) and RT downmodulation of CSF-1 receptors in NIH 3T3 cells transformed by RT cotransfection of the human CSF-1 and c-fms (CSF-1 receptor) genes."; RL Mol. Cell. Biol. 7:2378-2387(1987). RN [16] RP PROTEOLYTIC PROCESSING, SUBUNIT, GLYCOSYLATION, AND SUBCELLULAR LOCATION. RX PubMed=3264877; DOI=10.1128/mcb.8.11.5026-5034.1988; RA Rettenmier C.W., Roussel M.F.; RT "Differential processing of colony-stimulating factor 1 precursors encoded RT by two human cDNAs."; RL Mol. Cell. Biol. 8:5026-5034(1988). RN [17] RP PROTEOLYTIC PROCESSING, SUBUNIT, SUBCELLULAR LOCATION, AND STRUCTURE OF RP CARBOHYDRATES. RX PubMed=1531650; DOI=10.1016/s0021-9258(18)42841-4; RA Suzu S., Ohtsuki T., Yanai N., Takatsu Z., Kawashima T., Takaku F., RA Nagata N., Motoyoshi K.; RT "Identification of a high molecular weight macrophage colony-stimulating RT factor as a glycosaminoglycan-containing species."; RL J. Biol. Chem. 267:4345-4348(1992). RN [18] RP DISULFIDE BONDS. RX PubMed=8422357; DOI=10.1021/bi00053a012; RA Glocker M.O., Arbogast B., Schreurs J., Deinzer M.L.; RT "Assignment of the inter- and intramolecular disulfide linkages in RT recombinant human macrophage colony stimulating factor using fast atom RT bombardment mass spectrometry."; RL Biochemistry 32:482-488(1993). RN [19] RP REVIEW ON FUNCTION AND SIGNALING PATHWAYS. 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 [20] 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 [21] RP REVIEW ON FUNCTION AND SIGNALING PATHWAYS. 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 [22] 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 [23] 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 [24] RP FUNCTION, AND INTERACTION WITH CSF1R. 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 [25] RP GLYCOSYLATION AT THR-363 AND THR-365, STRUCTURE OF CARBOHYDRATES, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=22171320; DOI=10.1074/mcp.m111.013649; RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.; RT "Human urinary glycoproteomics; attachment site specific analysis of N- and RT O-linked glycosylations by CID and ECD."; RL Mol. Cell. Proteomics 11:1-17(2012). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [27] RP GLYCOSYLATION, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=23234360; DOI=10.1021/pr300963h; RA Halim A., Ruetschi U., Larson G., Nilsson J.; RT "LC-MS/MS characterization of O-glycosylation sites and glycan structures RT of human cerebrospinal fluid glycoproteins."; RL J. Proteome Res. 12:573-584(2013). RN [28] RP PHOSPHORYLATION AT THR-266. RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028; RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., RA Pinna L.A., Pagliarini D.J., Dixon J.E.; RT "A single kinase generates the majority of the secreted phosphoproteome."; RL Cell 161:1619-1632(2015). RN [29] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 33-190. RX PubMed=1455231; DOI=10.1126/science.1455231; RA Pandit J., Bohm A., Jancarik J., Halenbeck R., Koths K., Kim S.H.; RT "Three-dimensional structure of dimeric human recombinant macrophage RT colony-stimulating factor."; RL Science 258:1358-1362(1992). CC -!- FUNCTION: Cytokine that 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, and CC thereby plays an important role in innate immunity and in inflammatory CC processes. Plays an important role in the regulation of osteoclast CC proliferation and differentiation, the regulation of bone resorption, CC and is required for normal bone development. Required for normal male CC and female fertility. Promotes reorganization of the actin CC cytoskeleton, regulates formation of membrane ruffles, cell adhesion CC and cell migration. Plays a role in lipoprotein clearance. CC {ECO:0000269|PubMed:16337366, ECO:0000269|PubMed:19934330, CC ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:20829061, CC ECO:0000269|PubMed:8051056}. CC -!- SUBUNIT: Homodimer or heterodimer; disulfide-linked (PubMed:1531650, CC PubMed:3264877, PubMed:8422357). Likely to exist in multiple forms: CC homodimer consisting of 2 identical 150-200 kDa proteoglycan subunits, CC heterodimer consisting of a 150-200 kDa proteoglycan subunit and a CC truncated 43 kDa subunit, and homodimer consisting of 2 identical 43 CC kDa subunits (PubMed:8051056). Interacts with CSF1R (PubMed:20504948). CC {ECO:0000269|PubMed:1531650, ECO:0000269|PubMed:20504948, CC ECO:0000269|PubMed:3264877, ECO:0000269|PubMed:8051056, CC ECO:0000269|PubMed:8422357}. CC -!- INTERACTION: CC P09603; P09603: CSF1; NbExp=8; IntAct=EBI-2872294, EBI-2872294; CC P09603; P07333: CSF1R; NbExp=14; IntAct=EBI-2872294, EBI-2835440; CC P09603; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-2872294, EBI-3867333; CC P09603; Q13643: FHL3; NbExp=3; IntAct=EBI-2872294, EBI-741101; CC P09603; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-2872294, EBI-11959885; CC P09603; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-2872294, EBI-10171774; CC P09603; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-2872294, EBI-11522433; CC P09603; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-2872294, EBI-945833; CC P09603; O43765: SGTA; NbExp=6; IntAct=EBI-2872294, EBI-347996; CC P09603; P03228: BARF1; Xeno; NbExp=9; IntAct=EBI-2872294, EBI-16007073; CC P09603; P0CW72: BARF1; Xeno; NbExp=3; IntAct=EBI-2872294, EBI-2620133; CC P09603; P09581: Csf1r; Xeno; NbExp=2; IntAct=EBI-2872294, EBI-6305373; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1531650, CC ECO:0000269|PubMed:3264877}; Single-pass type I membrane protein CC {ECO:0000269|PubMed:1531650, ECO:0000269|PubMed:3264877}. CC -!- SUBCELLULAR LOCATION: [Processed macrophage colony-stimulating factor CC 1]: Secreted, extracellular space. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P09603-1; Sequence=Displayed; CC Name=2; CC IsoId=P09603-2; Sequence=VSP_001188; CC Name=3; CC IsoId=P09603-3; Sequence=VSP_001187; CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:3264877}. CC -!- PTM: [Isoform 1]: N-glycosylated. {ECO:0000269|PubMed:3264877}. CC -!- PTM: [Isoform 3]: N-glycosylated. {ECO:0000269|PubMed:3264877}. CC -!- PTM: O-glycosylated; contains chondroitin sulfate (PubMed:1531650, CC PubMed:8051056). O-glycosylated with core 1 or possibly core 8 glycans CC (PubMed:22171320, PubMed:23234360, PubMed:3264877). CC {ECO:0000269|PubMed:1531650, ECO:0000269|PubMed:22171320, CC ECO:0000269|PubMed:23234360, ECO:0000269|PubMed:3264877, CC ECO:0000269|PubMed:8051056}. CC -!- PTM: [Isoform 1]: O-glycosylated. {ECO:0000269|PubMed:3264877}. 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 --------------------------------------------------------------------------- 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; M11296; AAB59527.1; -; Genomic_DNA. DR EMBL; M11038; AAB59527.1; JOINED; Genomic_DNA. DR EMBL; M11295; AAB59527.1; JOINED; Genomic_DNA. DR EMBL; M37435; AAA52117.1; -; mRNA. DR EMBL; M64592; AAA59572.1; -; mRNA. DR EMBL; U22386; AAA64849.1; -; mRNA. DR EMBL; M27087; AAA59573.1; -; mRNA. DR EMBL; AK291660; BAF84349.1; -; mRNA. DR EMBL; AL450468; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471122; EAW56416.1; -; Genomic_DNA. DR EMBL; BC021117; AAH21117.1; -; mRNA. DR EMBL; X05825; CAA29265.1; -; mRNA. DR EMBL; X06106; CAA29479.1; -; Genomic_DNA. DR EMBL; M76453; AAA52120.2; -; mRNA. DR CCDS; CCDS30797.1; -. [P09603-3] DR CCDS; CCDS816.1; -. [P09603-1] DR CCDS; CCDS817.1; -. [P09603-2] DR PIR; A47583; FQHUMP. DR RefSeq; NP_000748.4; NM_000757.6. [P09603-1] DR RefSeq; NP_757349.2; NM_172210.3. [P09603-2] DR RefSeq; NP_757350.2; NM_172211.4. [P09603-3] DR RefSeq; NP_757351.2; NM_172212.3. [P09603-1] DR RefSeq; XP_047302708.1; XM_047446752.1. [P09603-3] DR PDB; 1HMC; X-ray; 2.50 A; A/B=36-181. DR PDB; 3UEZ; X-ray; 3.41 A; E/F/G/H=33-181. DR PDB; 3UF2; X-ray; 2.75 A; A/B/C/D/E/F/G/H/I/J=33-181. DR PDB; 4ADF; X-ray; 4.40 A; G/H/I/J/K/L/S/T/U/V/W/X=33-181. DR PDB; 4FA8; X-ray; 2.20 A; E/F/G=36-180. DR PDB; 4WRL; X-ray; 2.80 A; B/D=33-181. DR PDB; 4WRM; X-ray; 6.85 A; B=33-181. DR PDB; 5LXF; X-ray; 2.00 A; A/B=33-181. DR AlphaFoldDB; P09603; -. DR SMR; P09603; -. DR BioGRID; 107822; 23. DR ComplexPortal; CPX-25717; Macrophage colony-stimulating factor-1 receptor-ligand complex. DR DIP; DIP-41860N; -. DR FunCoup; P09603; 1316. DR IntAct; P09603; 17. DR NDEx; IQUERY-CP-CSF1; 24 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000327513; -. DR ChEMBL; CHEMBL3989382; -. DR GlyConnect; P09603; 4 N-Linked glycans (1 site), 1 O-Linked glycan (1 site). DR GlyCosmos; P09603; 19 sites, 3 glycans. DR GlyGen; P09603; 38 sites, 3 N-linked glycans (1 site), 4 O-linked glycans (34 sites). DR iPTMnet; P09603; -. DR PhosphoSitePlus; P09603; -. DR BioMuta; CSF1; -. DR DMDM; 311033367; -. DR jPOST; P09603; -. DR MassIVE; P09603; -. DR PaxDb; 9606-ENSP00000327513; -. DR PeptideAtlas; P09603; -. DR ProteomicsDB; 52250; -. [P09603-1] DR ProteomicsDB; 52251; -. [P09603-2] DR ProteomicsDB; 52252; -. [P09603-3] DR ABCD; P09603; 32 sequenced antibodies. DR Antibodypedia; 20082; 972 antibodies from 48 providers. DR CPTC; P09603; 1 antibody. DR DNASU; 1435; -. DR Ensembl; ENST00000329608.11; ENSP00000327513.6; ENSG00000184371.15. [P09603-1] DR Ensembl; ENST00000369801.1; ENSP00000358816.1; ENSG00000184371.15. [P09603-2] DR Ensembl; ENST00000369802.7; ENSP00000358817.3; ENSG00000184371.15. [P09603-1] DR Ensembl; ENST00000420111.6; ENSP00000407317.2; ENSG00000184371.15. [P09603-3] DR Ensembl; ENST00000875284.1; ENSP00000545343.1; ENSG00000184371.15. [P09603-1] DR GeneID; 1435; -. DR KEGG; hsa:1435; -. DR MANE-Select; ENST00000329608.11; ENSP00000327513.6; NM_000757.6; NP_000748.4. DR UCSC; uc001dyt.3; human. [P09603-1] DR AGR; HGNC:2432; -. DR CIViC; 1435; 1 evidence item across 1 molecular profile. DR ClinPGx; PA26935; -. DR CTD; 1435; -. DR DisGeNET; 1435; -. DR GeneCards; CSF1; -. DR HGNC; HGNC:2432; CSF1. DR HPA; ENSG00000184371; Low tissue specificity. DR MalaCards; CSF1; -. DR MIM; 120420; gene. DR OpenTargets; ENSG00000184371; -. DR VEuPathDB; HostDB:ENSG00000184371; -. DR eggNOG; ENOG502S271; Eukaryota. DR GeneTree; ENSGT00390000015805; -. DR HOGENOM; CLU_095000_0_0_1; -. DR InParanoid; P09603; -. DR OMA; CQIAYEF; -. DR OrthoDB; 8702024at2759; -. DR PAN-GO; P09603; 4 GO annotations based on evolutionary models. DR PhylomeDB; P09603; -. DR PathwayCommons; P09603; -. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-449836; Other interleukin signaling. DR Reactome; R-HSA-6783783; Interleukin-10 signaling. DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR Reactome; R-HSA-9680350; Signaling by CSF1 (M-CSF) in myeloid cells. DR Reactome; R-HSA-9856649; Transcriptional and post-translational regulation of MITF-M expression and activity. DR SignaLink; P09603; -. DR SIGNOR; P09603; -. DR Agora; ENSG00000184371; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 1435; 10 hits in 1159 CRISPR screens. DR ChiTaRS; CSF1; human. DR EvolutionaryTrace; P09603; -. DR GeneWiki; Macrophage_colony-stimulating_factor; -. DR GenomeRNAi; 1435; -. DR Pharos; P09603; Tbio. DR PRO; PR:P09603; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P09603; protein. DR Bgee; ENSG00000184371; Expressed in omental fat pad and 151 other cell types or tissues. DR ExpressionAtlas; P09603; baseline and differential. DR GO; GO:1990682; C:CSF1-CSF1R complex; IDA:ComplexPortal. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; IDA:BHF-UCL. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0043235; C:signaling receptor complex; IDA:ComplexPortal. DR GO; GO:0005125; F:cytokine activity; IDA:MGI. DR GO; GO:0008083; F:growth factor activity; IDA:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005157; F:macrophage colony-stimulating factor receptor binding; ISS:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL. DR GO; GO:0007169; P:cell surface receptor protein tyrosine kinase signaling pathway; IDA:BHF-UCL. DR GO; GO:0003006; P:developmental process involved in reproduction; ISS:BHF-UCL. DR GO; GO:0045087; P:innate immune response; NAS:ComplexPortal. DR GO; GO:0038145; P:macrophage colony-stimulating factor signaling pathway; IEA:Ensembl. DR GO; GO:0030225; P:macrophage differentiation; TAS:UniProtKB. DR GO; GO:0061518; P:microglial cell proliferation; IEA:Ensembl. DR GO; GO:0042117; P:monocyte activation; NAS:BHF-UCL. DR GO; GO:0030316; P:osteoclast differentiation; IDA:BHF-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; ISS:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI. DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; ISS:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IDA:BHF-UCL. DR GO; GO:1902228; P:positive regulation of macrophage colony-stimulating factor signaling pathway; IDA:BHF-UCL. DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IDA:BHF-UCL. DR GO; GO:0045651; P:positive regulation of macrophage differentiation; IDA:BHF-UCL. DR GO; GO:1905523; P:positive regulation of macrophage migration; IMP:BHF-UCL. DR GO; GO:1904141; P:positive regulation of microglial cell migration; IDA:BHF-UCL. DR GO; GO:0045657; P:positive regulation of monocyte differentiation; ISS:BHF-UCL. DR GO; GO:0032946; P:positive regulation of mononuclear cell proliferation; IDA:BHF-UCL. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IDA:BHF-UCL. DR GO; GO:0051247; P:positive regulation of protein metabolic process; IDA:BHF-UCL. DR GO; GO:0010743; P:regulation of macrophage derived foam cell differentiation; NAS:BHF-UCL. DR GO; GO:0002931; P:response to ischemia; IDA:ARUK-UCL. DR FunFam; 1.20.1250.10:FF:000010; Macrophage colony-stimulating factor 1; 1. DR Gene3D; 1.20.1250.10; -; 1. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR008001; MCSF-1. DR PANTHER; PTHR10058; MACROPHAGE COLONY STIMULATING FACTOR; 1. DR PANTHER; PTHR10058:SF0; MACROPHAGE COLONY-STIMULATING FACTOR 1; 1. DR Pfam; PF05337; CSF-1; 1. DR PIRSF; PIRSF001948; MCSF-1; 1. DR SUPFAM; SSF47266; 4-helical cytokines; 1. DR PDBsum; 1HMC; -. DR PDBsum; 3UEZ; -. DR PDBsum; 3UF2; -. DR PDBsum; 4ADF; -. DR PDBsum; 4FA8; -. DR PDBsum; 4WRL; -. DR PDBsum; 4WRM; -. DR PDBsum; 5LXF; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cytokine; KW Direct protein sequencing; Disulfide bond; Glycoprotein; Growth factor; KW Immunity; Inflammatory response; Innate immunity; Membrane; Phosphoprotein; KW Proteoglycan; Proteomics identification; Reference proteome; Secreted; KW Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..32 FT /evidence="ECO:0000269|PubMed:3498652, FT ECO:0000269|PubMed:8051056" FT CHAIN 33..554 FT /note="Macrophage colony-stimulating factor 1" FT /id="PRO_0000005857" FT CHAIN 33..450 FT /note="Processed macrophage colony-stimulating factor 1" FT /evidence="ECO:0000250|UniProtKB:Q8JZQ0" FT /id="PRO_0000296231" FT CHAIN 33..255 FT /note="Macrophage colony-stimulating factor 1 43 kDa FT subunit" FT /evidence="ECO:0000269|PubMed:8051056" FT /id="PRO_0000457791" FT TOPO_DOM 33..496 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 497..517 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 518..554 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 224..488 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 406..426 FT /note="O-glycosylated at one site" FT REGION 526..554 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 344..354 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 404..433 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 440..453 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 545..554 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 266 FT /note="Phosphothreonine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039" FT CARBOHYD 154 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 172 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 309 FT /note="O-linked (Xyl...) (chondroitin sulfate) serine" FT /evidence="ECO:0000269|PubMed:8051056" FT CARBOHYD 363 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:22171320" FT CARBOHYD 365 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:22171320" FT DISULFID 39..122 FT /evidence="ECO:0000269|PubMed:8422357" FT DISULFID 63 FT /note="Interchain" FT /evidence="ECO:0000269|PubMed:8422357" FT DISULFID 80..171 FT /evidence="ECO:0000269|PubMed:8422357" FT DISULFID 134..178 FT /evidence="ECO:0000269|PubMed:8422357" FT DISULFID 189 FT /note="Interchain" FT /evidence="ECO:0000269|PubMed:8422357" FT DISULFID 191 FT /note="Interchain" FT /evidence="ECO:0000269|PubMed:8422357" FT VAR_SEQ 182..479 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:1791839" FT /id="VSP_001187" FT VAR_SEQ 365..480 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_001188" FT VARIANT 341 FT /note="S -> N (in dbSNP:rs12565736)" FT /id="VAR_048810" FT VARIANT 408 FT /note="L -> P (in dbSNP:rs1058885)" FT /evidence="ECO:0000269|PubMed:2660794" FT /id="VAR_020454" FT VARIANT 438 FT /note="G -> R (in dbSNP:rs2229165)" FT /id="VAR_029320" FT VARIANT 489 FT /note="F -> S (in dbSNP:rs333971)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:1791839, FT ECO:0000269|PubMed:2460758, ECO:0000269|PubMed:2660794, FT ECO:0000269|PubMed:2996129, ECO:0000269|PubMed:3493529, FT ECO:0000269|PubMed:3500041, ECO:0000269|Ref.7" FT /id="VAR_048811" FT VARIANT 496 FT /note="S -> F (in dbSNP:rs12721516)" FT /id="VAR_020455" FT VARIANT 531 FT /note="A -> V (in dbSNP:rs2229167)" FT /id="VAR_022146" FT MUTAGEN 252 FT /note="R->A: Loss of 43 kDa subunit." FT /evidence="ECO:0000269|PubMed:8051056" FT MUTAGEN 309 FT /note="S->A: Loss of chondroitin sulfate attachment." FT /evidence="ECO:0000269|PubMed:8051056" FT MUTAGEN 444 FT /note="R->A: Does not affect production of 150-200 kDa FT subunit." FT /evidence="ECO:0000269|PubMed:8051056" FT MUTAGEN 489..554 FT /note="Missing: Produces biologically active protein which FT is secreted." FT /evidence="ECO:0000269|PubMed:2460758" FT CONFLICT 69 FT /note="F -> S (in Ref. 12; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 91 FT /note="D -> Y (in Ref. 1; AAB59527, 3; AAA59572/AAA64849 FT and 10; AAA52120)" FT /evidence="ECO:0000305" FT CONFLICT 104..106 FT /note="PNA -> ANP (in Ref. 2; AAA52117)" FT /evidence="ECO:0000305" FT CONFLICT 364 FT /note="G -> A (in Ref. 2; AAA52117)" FT /evidence="ECO:0000305" FT CONFLICT 374 FT /note="R -> M (in Ref. 2; AAA52117)" FT /evidence="ECO:0000305" FT CONFLICT 412 FT /note="G -> A (in Ref. 2; AAA52117)" FT /evidence="ECO:0000305" FT CONFLICT 450 FT /note="R -> T (in Ref. 2; AAA52117)" FT /evidence="ECO:0000305" FT CONFLICT 457..458 FT /note="GG -> AA (in Ref. 2; AAA52117)" FT /evidence="ECO:0000305" FT CONFLICT 480 FT /note="Missing (in Ref. 4; AAA59573)" FT /evidence="ECO:0000305" FT HELIX 37..41 FT /evidence="ECO:0007829|PDB:5LXF" FT HELIX 45..56 FT /evidence="ECO:0007829|PDB:5LXF" FT STRAND 65..70 FT /evidence="ECO:0007829|PDB:5LXF" FT TURN 72..74 FT /evidence="ECO:0007829|PDB:5LXF" FT HELIX 78..95 FT /evidence="ECO:0007829|PDB:5LXF" FT HELIX 104..119 FT /evidence="ECO:0007829|PDB:5LXF" FT HELIX 120..122 FT /evidence="ECO:0007829|PDB:5LXF" FT HELIX 128..130 FT /evidence="ECO:0007829|PDB:5LXF" FT STRAND 135..140 FT /evidence="ECO:0007829|PDB:5LXF" FT HELIX 142..162 FT /evidence="ECO:0007829|PDB:5LXF" FT HELIX 166..168 FT /evidence="ECO:0007829|PDB:5LXF" FT HELIX 172..176 FT /evidence="ECO:0007829|PDB:5LXF" SQ SEQUENCE 554 AA; 60179 MW; 656B0894F9255AED CRC64; MTAPGAAGRC PPTTWLGSLL LLVCLLASRS ITEEVSEYCS HMIGSGHLQS LQRLIDSQME TSCQITFEFV DQEQLKDPVC YLKKAFLLVQ DIMEDTMRFR DNTPNAIAIV QLQELSLRLK SCFTKDYEEH DKACVRTFYE TPLQLLEKVK NVFNETKNLL DKDWNIFSKN CNNSFAECSS QDVVTKPDCN CLYPKAIPSS DPASVSPHQP LAPSMAPVAG LTWEDSEGTE GSSLLPGEQP LHTVDPGSAK QRPPRSTCQS FEPPETPVVK DSTIGGSPQP RPSVGAFNPG MEDILDSAMG TNWVPEEASG EASEIPVPQG TELSPSRPGG GSMQTEPARP SNFLSASSPL PASAKGQQPA DVTGTALPRV GPVRPTGQDW NHTPQKTDHP SALLRDPPEP GSPRISSLRP QGLSNPSTLS AQPQLSRSHS SGSVLPLGEL EGRRSTRDRR SPAEPEGGPA SEGAARPLPR FNSVPLTDTG HERQSEGSFS PQLQESVFHL LVPSVILVLL AVGGLLFYRW RRRSHQEPQR ADSPLEQPEG SPLTQDDRQV ELPV //