ID CSF1_HUMAN STANDARD; PRT; 554 AA. AC P09603; Q13130; Q14086; Q14806; Q9UQR8; DT 01-MAR-1989 (Rel. 10, Created) DT 01-MAR-1989 (Rel. 10, Last sequence update) DT 01-FEB-2005 (Rel. 46, Last annotation update) DE Macrophage colony stimulating factor-1 precursor (CSF-1) (MCSF) (M- DE CSF). GN Name=CSF1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE, AND PROTEIN SEQUENCE OF 33-44 (ISOFORM 3). RC TISSUE=Pancreatic carcinoma, and Urine; RX MEDLINE=86018828; PubMed=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 (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Trophoblast, and Urine; RX MEDLINE=87149084; PubMed=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., RA Ferenz C.R., Sibley B.S., Turner K.J., Hewick R.M., Clark S.C., RA Yanai N., Yokota H., Yamada M., Saito M., Motoyoshi K., Takaku F.; RT "Human CSF-1: molecular cloning and expression of 4-kb cDNA encoding RT the human urinary protein."; RL Science 235:1504-1508(1987). RN [3] RP NUCLEOTIDE SEQUENCE, ALTERNATIVE SPLICING, AND MUTAGENESIS OF ISOFORM RP 3. RC TISSUE=Pancreatic carcinoma; RX MEDLINE=89039923; 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 RT protein processing from a single gene."; RL Mol. Immunol. 25:761-770(1988). RN [4] RP NUCLEOTIDE SEQUENCE (ISOFORM 1), AND VARIANT PRO-408. RC TISSUE=T lymphoblast; RX MEDLINE=89286601; PubMed=2660794; 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 RT (M-CSF) is sufficient for its in vitro biological activity: molecular RT cloning and expression of carboxyl-terminal deletion mutants of human RT M-CSF."; RL Biochem. Biophys. Res. Commun. 161:892-901(1989). RN [5] RP NUCLEOTIDE SEQUENCE (ISOFORM 1). RC TISSUE=Kidney; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [6] RP NUCLEOTIDE SEQUENCE OF 1-13 AND 19-554 (ISOFORM 1). RC TISSUE=Pancreatic carcinoma; RX MEDLINE=88054965; PubMed=3500041; RA Ladner M.B., Martin G.A., Noble J.A., Nikoloff D.M., Tal R., RA Kawasaki E.S., White T.J.; RT "Human CSF-1: gene structure and alternative splicing of mRNA RT precursors."; RL EMBO J. 6:2693-2698(1987). RN [7] RP NUCLEOTIDE SEQUENCE OF 13-554 (ISOFORM 3). RC TISSUE=Endometrium; RX MEDLINE=92168031; PubMed=1791839; RA Pampfer S., Tabibzadeh S., Chuan F.-C., Pollard J.W.; RT "Expression of colony-stimulating factor-1 (CSF-1) messenger RNA in RT human endometrial glands during the menstrual cycle: molecular cloning RT of a novel transcript that predicts a cell surface form of CSF-1."; RL Mol. Endocrinol. 5:1931-1938(1991). RN [8] RP PROTEIN SEQUENCE OF 33-185 (ISOFORM 1). RC TISSUE=T lymphoblast; RX MEDLINE=94086474; PubMed=8262907; 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 RT macrophage colony-stimulating factor derived from mammalian cells."; RL J. Biochem. 114:255-262(1993). RN [9] RP PROTEIN SEQUENCE OF 33-76. RX MEDLINE=88005180; 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 RT urine. Amino-terminal sequence and amino acid composition."; RL FEBS Lett. 222:341-344(1987). RN [10] RP PROTEIN SEQUENCE OF 35-61. RX MEDLINE=88240361; PubMed=3259875; 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 RT lymphoblastoid cell line, CEM-ON: identification by amino-terminal RT amino acid sequence analysis."; RL Biochem. Biophys. Res. Commun. 152:1401-1409(1988). RN [11] RP CHARACTERIZATION OF ISOFORM 3. RX MEDLINE=87286871; PubMed=3039346; RA Rettenmier C.W., Roussel M.F., Ashmun R.A., Ralph P., Price K., RA 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 [12] RP CHARACTERIZATION OF ISOFORM 1. RX MEDLINE=89096876; PubMed=3264877; RA Rettenmier C.W., Roussel M.F.; RT "Differential processing of colony-stimulating factor 1 precursors RT encoded by two human cDNAs."; RL Mol. Cell. Biol. 8:5026-5034(1988). RN [13] RP CHARACTERIZATION. RX MEDLINE=92165782; PubMed=1531650; 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- RT stimulating factor as a glycosaminoglycan-containing species."; RL J. Biol. Chem. 267:4345-4348(1992). RN [14] RP DISULFIDE BONDS. RX MEDLINE=93136140; PubMed=8422357; 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 [15] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 33-190. RX MEDLINE=93088061; PubMed=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: Granulocyte/macrophage colony-stimulating factors are CC cytokines that act in hematopoiesis by controlling the production, CC differentiation, and function of 2 related white cell populations CC of the blood, the granulocytes and the monocytes-macrophages. CSF- CC 1 induces cells of the monocyte/macrophage lineage. It plays a CC role in immunological defenses, bone metabolism, lipoproteins CC clearance, fertility and pregnancy. CC -!- SUBUNIT: Homodimer or heterodimer; disulfide-linked. CC -!- SUBCELLULAR LOCATION: Predominantly extracellular. Isoform 3 CC exists as an integral membrane protein, only slowly released by CC proteolytic cleavage. 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: Glycosylation and proteolytic cleavage yield different CC soluble forms. A high molecular weight soluble form is a CC proteoglycan containing chondroitin sulfate. CC -!- PTM: Isoform 1 is N- and O-glycosylated. Isoform 3 is N- CC glycosylated. 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; -. DR EMBL; M11038; AAB59527.1; JOINED. DR EMBL; M11295; AAB59527.1; JOINED. DR EMBL; M37435; AAA52117.1; -. DR EMBL; M64592; AAA59572.1; -. DR EMBL; U22386; AAA64849.1; -. DR EMBL; M27087; AAA59573.1; -. DR EMBL; BC021117; AAH21117.1; -. DR EMBL; X05825; CAA29265.1; -. DR EMBL; X06106; CAA29479.1; -. DR EMBL; M76453; AAA52120.2; -. DR PIR; A47583; FQHUMP. DR PDB; 1HMC; X-ray; A/B=36-183. DR Ensembl; ENSG00000184371; Homo sapiens. DR Genew; HGNC:2432; CSF1. DR H-InvDB; HIX0021248; -. DR MIM; 120420; -. DR GO; GO:0016020; C:membrane; NAS. DR GO; GO:0005157; F:macrophage colony stimulating factor recept...; TAS. DR GO; GO:0030154; P:cell differentiation; NAS. DR GO; GO:0008283; P:cell proliferation; NAS. DR GO; GO:0030097; P:hemopoiesis; NAS. DR GO; GO:0030225; P:macrophage differentiation; TAS. DR GO; GO:0008284; P:positive regulation of cell proliferation; TAS. DR InterPro; IPR009079; 4_helix_cytokine. DR InterPro; IPR008001; MCSF-1. DR Pfam; PF05337; CSF-1; 2. KW 3D-structure; Alternative splicing; Cytokine; KW Direct protein sequencing; Glycoprotein; Growth factor; Polymorphism; KW Proteoglycan; Signal; Transmembrane. FT SIGNAL 1 32 FT CHAIN 33 554 Macrophage colony stimulating factor-1. FT DOMAIN 33 496 Lumenal (Potential). FT TRANSMEM 497 517 Potential. FT DOMAIN 518 554 Cytoplasmic (Potential). FT DISULFID 63 63 Interchain. FT DISULFID 39 122 FT DISULFID 80 171 FT DISULFID 134 178 FT DISULFID 189 189 Interchain. FT DISULFID 191 191 Interchain. FT CARBOHYD 154 154 N-linked (GlcNAc...) (Potential). FT CARBOHYD 172 172 N-linked (GlcNAc...) (Potential). FT VARSPLIC 182 479 Missing (in isoform 3). FT /FTId=VSP_001187. FT VARSPLIC 365 480 Missing (in isoform 2). FT /FTId=VSP_001188. FT VARIANT 408 408 L -> P (in dbSNP:1058885). FT /FTId=VAR_020454. FT VARIANT 496 496 S -> F (in dbSNP:12721516). FT /FTId=VAR_020455. FT MUTAGEN 489 554 Missing: Produces biologically active FT protein which is secreted. FT CONFLICT 69 69 F -> S (in Ref. 9). FT CONFLICT 91 91 D -> Y (in Ref. 1, 3 and 7). FT CONFLICT 104 106 PNA -> ANP (in Ref. 2). FT CONFLICT 364 364 G -> A (in Ref. 2). FT CONFLICT 374 374 R -> M (in Ref. 2). FT CONFLICT 412 412 G -> A (in Ref. 2). FT CONFLICT 450 450 R -> T (in Ref. 2). FT CONFLICT 457 458 GG -> AA (in Ref. 2). FT CONFLICT 480 480 Missing (in Ref. 4). SQ SEQUENCE 554 AA; 60119 MW; 657764E4E5492AED 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 HERQSEGSSS PQLQESVFHL LVPSVILVLL AVGGLLFYRW RRRSHQEPQR ADSPLEQPEG SPLTQDDRQV ELPV //