CSF1_HUMAN
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 03-AUG-2022, entry version 221.
DE RecName: Full=Macrophage colony-stimulating factor 1;
DE Short=CSF-1;
DE Short=M-CSF;
DE Short=MCSF;
DE AltName: Full=Lanimostim;
DE Contains:
DE RecName: Full=Processed macrophage colony-stimulating factor 1;
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 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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 -!- SUBUNIT: Homodimer or heterodimer; disulfide-linked. Interacts with
CC CSF1R. {ECO:0000269|PubMed:1531650, ECO:0000269|PubMed:20504948,
CC ECO:0000269|PubMed:3264877, ECO:0000269|PubMed:8422357}.
CC -!- INTERACTION:
CC P09603; P09603: CSF1; NbExp=8; IntAct=EBI-2872294, EBI-2872294;
CC P09603; P07333: CSF1R; NbExp=13; 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- and O-glycosylated. Glycosylation and proteolytic cleavage
CC yield different soluble forms. One high molecular weight soluble form
CC is a proteoglycan containing chondroitin sulfate. O-glycosylated with
CC core 1 or possibly core 8 glycans. Isoform 1 is N- and O-glycosylated.
CC Isoform 3 is only N-glycosylated. {ECO:0000269|PubMed:1531650,
CC ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:23234360,
CC 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.
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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_000748.3; NM_000757.5. [P09603-1]
DR RefSeq; NP_757349.1; NM_172210.2. [P09603-2]
DR RefSeq; NP_757350.1; NM_172211.3. [P09603-3]
DR RefSeq; NP_757351.1; NM_172212.2. [P09603-1]
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 PDBsum; 1HMC; -.
DR PDBsum; 3UEZ; -.
DR PDBsum; 3UF2; -.
DR PDBsum; 4ADF; -.
DR PDBsum; 4FA8; -.
DR PDBsum; 4WRL; -.
DR PDBsum; 4WRM; -.
DR PDBsum; 5LXF; -.
DR AlphaFoldDB; P09603; -.
DR SMR; P09603; -.
DR BioGRID; 107822; 22.
DR DIP; DIP-41860N; -.
DR IntAct; P09603; 16.
DR STRING; 9606.ENSP00000327513; -.
DR ChEMBL; CHEMBL3989382; -.
DR GlyConnect; 2925; 1 O-Linked glycan (1 site).
DR GlyGen; P09603; 20 sites, 3 O-linked glycans (17 sites).
DR iPTMnet; P09603; -.
DR PhosphoSitePlus; P09603; -.
DR BioMuta; CSF1; -.
DR DMDM; 311033367; -.
DR EPD; P09603; -.
DR jPOST; P09603; -.
DR MassIVE; P09603; -.
DR MaxQB; P09603; -.
DR PaxDb; P09603; -.
DR PeptideAtlas; P09603; -.
DR PRIDE; 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; 902 antibodies from 43 providers.
DR CPTC; P09603; 1 antibody.
DR DNASU; 1435; -.
DR Ensembl; ENST00000329608.11; ENSP00000327513.6; ENSG00000184371.14. [P09603-1]
DR Ensembl; ENST00000369801.1; ENSP00000358816.1; ENSG00000184371.14. [P09603-2]
DR Ensembl; ENST00000369802.7; ENSP00000358817.3; ENSG00000184371.14. [P09603-1]
DR Ensembl; ENST00000420111.6; ENSP00000407317.2; ENSG00000184371.14. [P09603-3]
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 CTD; 1435; -.
DR DisGeNET; 1435; -.
DR GeneCards; CSF1; -.
DR HGNC; HGNC:2432; CSF1.
DR HPA; ENSG00000184371; Low tissue specificity.
DR MIM; 120420; gene.
DR neXtProt; NX_P09603; -.
DR OpenTargets; ENSG00000184371; -.
DR PharmGKB; PA26935; -.
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; 715874at2759; -.
DR PhylomeDB; P09603; -.
DR TreeFam; TF337718; -.
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 SignaLink; P09603; -.
DR SIGNOR; P09603; -.
DR BioGRID-ORCS; 1435; 10 hits in 1081 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 149 other tissues.
DR ExpressionAtlas; P09603; baseline and differential.
DR Genevisible; P09603; HS.
DR GO; GO:1990682; C:CSF1-CSF1R complex; ISS:BHF-UCL.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL.
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:0060444; P:branching involved in mammary gland duct morphogenesis; IEA:Ensembl.
DR GO; GO:0003006; P:developmental process involved in reproduction; ISS:BHF-UCL.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0038145; P:macrophage colony-stimulating factor signaling pathway; IEA:Ensembl.
DR GO; GO:0030225; P:macrophage differentiation; TAS:UniProtKB.
DR GO; GO:0061519; P:macrophage homeostasis; IEA:Ensembl.
DR GO; GO:0060763; P:mammary duct terminal end bud growth; IEA:Ensembl.
DR GO; GO:0060611; P:mammary gland fat development; IEA:Ensembl.
DR GO; GO:0061518; P:microglial cell proliferation; IEA:Ensembl.
DR GO; GO:0042117; P:monocyte activation; NAS:BHF-UCL.
DR GO; GO:0030224; P:monocyte differentiation; IEA:Ensembl.
DR GO; GO:0035702; P:monocyte homeostasis; IEA:Ensembl.
DR GO; GO:0097529; P:myeloid leukocyte migration; IEA:Ensembl.
DR GO; GO:1901215; P:negative regulation of neuron death; IDA:ARUK-UCL.
DR GO; GO:0001780; P:neutrophil homeostasis; IEA:Ensembl.
DR GO; GO:0042476; P:odontogenesis; IEA:Ensembl.
DR GO; GO:0001503; P:ossification; IEA:Ensembl.
DR GO; GO:0030316; P:osteoclast differentiation; IDA:BHF-UCL.
DR GO; GO:0002158; P:osteoclast proliferation; IEA:Ensembl.
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:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0042488; P:positive regulation of odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IDA:BHF-UCL.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISS:BHF-UCL.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; IDA:BHF-UCL.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IEA:Ensembl.
DR GO; GO:0007265; P:Ras protein signal transduction; IEA:Ensembl.
DR GO; GO:0010743; P:regulation of macrophage derived foam cell differentiation; NAS:BHF-UCL.
DR GO; GO:0030278; P:regulation of ossification; IEA:Ensembl.
DR GO; GO:0002931; P:response to ischemia; IDA:ARUK-UCL.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IDA:BHF-UCL.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR008001; MCSF-1.
DR PANTHER; PTHR10058; PTHR10058; 1.
DR Pfam; PF05337; CSF-1; 1.
DR PIRSF; PIRSF001948; MCSF-1; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
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; Reference proteome; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..32
FT /evidence="ECO:0000269|PubMed:3498652"
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 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 325..360
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 407..433
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 441..455
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 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 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
