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CSF2_MOUSE
ID   CSF2_MOUSE              Reviewed;         141 AA.
AC   P01587;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1988, sequence version 1.
DT   03-AUG-2022, entry version 168.
DE   RecName: Full=Granulocyte-macrophage colony-stimulating factor;
DE            Short=GM-CSF;
DE   AltName: Full=Colony-stimulating factor;
DE            Short=CSF;
DE   Flags: Precursor;
GN   Name=Csf2; Synonyms=Csfgm;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3876930; DOI=10.1002/j.1460-2075.1985.tb03971.x;
RA   Miyatake S., Otsuka T., Yokota T., Lee F., Arai K.;
RT   "Structure of the chromosomal gene for granulocyte-macrophage colony
RT   stimulating factor: comparison of the mouse and human genes.";
RL   EMBO J. 4:2561-2568(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3876931; DOI=10.1002/j.1460-2075.1985.tb03972.x;
RA   Stanley E.R., Metcalf D., Sobieszczuk P., Gough N.M., Dunn A.R.;
RT   "The structure and expression of the murine gene encoding granulocyte-
RT   macrophage colony stimulating factor: evidence for utilisation of
RT   alternative promoters.";
RL   EMBO J. 4:2569-2573(1985).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=3902470; DOI=10.1002/j.1460-2075.1985.tb03973.x;
RA   Delamarter J.F., Mermod J.-J., Liang C.M., Eliason J.F., Thatcher D.R.;
RT   "Recombinant murine GM-CSF from E. coli has biological activity and is
RT   neutralized by a specific antiserum.";
RL   EMBO J. 4:2575-2581(1985).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ;
RX   PubMed=3874057; DOI=10.1002/j.1460-2075.1985.tb03678.x;
RA   Gough N.M., Metcalf D., Gough J., Grail D., Dunn A.R.;
RT   "Structure and expression of the mRNA for murine granulocyte-macrophage
RT   colony stimulating factor.";
RL   EMBO J. 4:645-653(1985).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 24-141.
RC   TISSUE=Lung;
RX   PubMed=6610831; DOI=10.1038/309763a0;
RA   Gough N.M., Gough J., Metcalf D., Kelso A., Grail D., Nicola N.A.,
RA   Burgess A.W., Dunn A.R.;
RT   "Molecular cloning of cDNA encoding a murine haematopoietic growth
RT   regulator, granulocyte-macrophage colony stimulating factor.";
RL   Nature 309:763-767(1984).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 18-141.
RX   PubMed=3898082; DOI=10.1073/pnas.82.18.6250;
RA   Cantrell M.A., Anderson D., Cerretti D.P., Price V., McKereghan K.,
RA   Tushinski R.J., Mochizuki D.Y., Larsen A., Grabstein S., Gillis S.,
RA   Cosman D.;
RT   "Cloning, sequence, and expression of a human granulocyte/macrophage
RT   colony-stimulating factor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:6250-6254(1985).
RN   [7]
RP   PROTEIN SEQUENCE OF 24-57.
RX   PubMed=3871523; DOI=10.1073/pnas.82.2.292;
RA   Sparrow L.G., Metcalf D., Hunkapiller M.W., Hood L.E., Burgess A.W.;
RT   "Purification and partial amino acid sequence of asialo murine granulocyte-
RT   macrophage colony stimulating factor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:292-296(1985).
RN   [8]
RP   DISULFIDE BONDS.
RX   PubMed=3318813; DOI=10.1042/bj2470195;
RA   Schrimser J.L., Rose K., Simona M.G., Wingfield P.;
RT   "Characterization of human and mouse granulocyte-macrophage-colony-
RT   stimulating factors derived from Escherichia coli.";
RL   Biochem. J. 247:195-199(1987).
RN   [9]
RP   MUTAGENESIS.
RX   PubMed=2002066; DOI=10.1016/s0021-9258(19)67792-6;
RA   Altmann S.W., Johnson G.D., Prystowsky M.B.;
RT   "Single proline substitutions in predicted alpha-helices of murine
RT   granulocyte-macrophage colony-stimulating factor result in a loss in
RT   bioactivity and altered glycosylation.";
RL   J. Biol. Chem. 266:5333-5341(1991).
CC   -!- FUNCTION: Cytokine that stimulates the growth and differentiation of
CC       hematopoietic precursor cells from various lineages, including
CC       granulocytes, macrophages, eosinophils and erythrocytes.
CC   -!- SUBUNIT: Monomer. The signaling GM-CSF receptor complex is a dodecamer
CC       of two head-to-head hexamers of two alpha, two beta, and two ligand
CC       subunits (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- SIMILARITY: Belongs to the GM-CSF family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA26192.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; X03020; CAA26821.1; -; Genomic_DNA.
DR   EMBL; X03019; CAA26820.1; -; mRNA.
DR   EMBL; X02333; CAA26193.1; -; mRNA.
DR   EMBL; X02333; CAA26192.1; ALT_INIT; mRNA.
DR   EMBL; X05906; CAA29336.1; -; mRNA.
DR   EMBL; M11848; AAA37483.1; -; mRNA.
DR   CCDS; CCDS24692.1; -.
DR   PIR; I48368; FQMSGM.
DR   RefSeq; NP_034099.2; NM_009969.4.
DR   AlphaFoldDB; P01587; -.
DR   SMR; P01587; -.
DR   STRING; 10090.ENSMUSP00000019060; -.
DR   GlyGen; P01587; 4 sites.
DR   PhosphoSitePlus; P01587; -.
DR   PaxDb; P01587; -.
DR   PRIDE; P01587; -.
DR   Antibodypedia; 14363; 1838 antibodies from 49 providers.
DR   DNASU; 12981; -.
DR   Ensembl; ENSMUST00000019060; ENSMUSP00000019060; ENSMUSG00000018916.
DR   GeneID; 12981; -.
DR   KEGG; mmu:12981; -.
DR   UCSC; uc007ixm.1; mouse.
DR   CTD; 1437; -.
DR   MGI; MGI:1339752; Csf2.
DR   VEuPathDB; HostDB:ENSMUSG00000018916; -.
DR   eggNOG; ENOG502TDUI; Eukaryota.
DR   GeneTree; ENSGT00390000013425; -.
DR   HOGENOM; CLU_152286_0_0_1; -.
DR   InParanoid; P01587; -.
DR   OMA; VTRPWKH; -.
DR   PhylomeDB; P01587; -.
DR   TreeFam; TF338611; -.
DR   Reactome; R-MMU-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR   Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-MMU-912526; Interleukin receptor SHC signaling.
DR   BioGRID-ORCS; 12981; 1 hit in 76 CRISPR screens.
DR   ChiTaRS; Csf2; mouse.
DR   PRO; PR:P01587; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; P01587; protein.
DR   Bgee; ENSMUSG00000018916; Expressed in left lung lobe and 20 other tissues.
DR   ExpressionAtlas; P01587; baseline and differential.
DR   Genevisible; P01587; MM.
DR   GO; GO:0005615; C:extracellular space; IDA:MGI.
DR   GO; GO:0030526; C:granulocyte macrophage colony-stimulating factor receptor complex; ISO:MGI.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0005125; F:cytokine activity; IDA:MGI.
DR   GO; GO:0005129; F:granulocyte macrophage colony-stimulating factor receptor binding; IEA:InterPro.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0008283; P:cell population proliferation; IDA:MGI.
DR   GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; ISO:MGI.
DR   GO; GO:0097028; P:dendritic cell differentiation; ISO:MGI.
DR   GO; GO:0001892; P:embryonic placenta development; IMP:MGI.
DR   GO; GO:0042045; P:epithelial fluid transport; ISO:MGI.
DR   GO; GO:0038157; P:granulocyte-macrophage colony-stimulating factor signaling pathway; ISO:MGI.
DR   GO; GO:0001821; P:histamine secretion; ISO:MGI.
DR   GO; GO:0006955; P:immune response; IEA:InterPro.
DR   GO; GO:0042116; P:macrophage activation; ISO:MGI.
DR   GO; GO:0030225; P:macrophage differentiation; ISO:MGI.
DR   GO; GO:0030224; P:monocyte differentiation; IDA:MGI.
DR   GO; GO:0030099; P:myeloid cell differentiation; IBA:GO_Central.
DR   GO; GO:0043011; P:myeloid dendritic cell differentiation; IDA:MGI.
DR   GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:MGI.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR   GO; GO:0030223; P:neutrophil differentiation; IDA:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR   GO; GO:0032747; P:positive regulation of interleukin-23 production; ISO:MGI.
DR   GO; GO:0070665; P:positive regulation of leukocyte proliferation; ISO:MGI.
DR   GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; ISO:MGI.
DR   GO; GO:0071803; P:positive regulation of podosome assembly; ISO:MGI.
DR   GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR   GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR   GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; ISO:MGI.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IGI:MGI.
DR   GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; ISO:MGI.
DR   GO; GO:0010468; P:regulation of gene expression; IDA:MGI.
DR   CDD; cd00040; CSF2; 1.
DR   Gene3D; 1.20.1250.10; -; 1.
DR   InterPro; IPR009079; 4_helix_cytokine-like_core.
DR   InterPro; IPR000773; GM_colony-stim-fac.
DR   PANTHER; PTHR10059; PTHR10059; 1.
DR   Pfam; PF01109; GM_CSF; 1.
DR   PRINTS; PR00693; GMCSFACTOR.
DR   SMART; SM00040; CSF2; 1.
DR   SUPFAM; SSF47266; SSF47266; 1.
DR   PROSITE; PS00702; GM_CSF; 1.
PE   1: Evidence at protein level;
KW   Cytokine; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Growth factor; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..17
FT   CHAIN           18..141
FT                   /note="Granulocyte-macrophage colony-stimulating factor"
FT                   /id="PRO_0000005866"
FT   CARBOHYD        22
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        27
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        83
FT                   /note="N-linked (GlcNAc...) asparagine"
FT   CARBOHYD        92
FT                   /note="N-linked (GlcNAc...) asparagine"
FT   DISULFID        68..110
FT                   /evidence="ECO:0000269|PubMed:3318813"
FT   DISULFID        102..135
FT                   /evidence="ECO:0000269|PubMed:3318813"
FT   MUTAGEN         38
FT                   /note="E->P: Reduction in bioactivity."
FT                   /evidence="ECO:0000269|PubMed:2002066"
FT   MUTAGEN         73
FT                   /note="L->P: 25-fold reduction in bioactivity."
FT                   /evidence="ECO:0000269|PubMed:2002066"
FT   MUTAGEN         77
FT                   /note="E->P: 50-fold reduction in bioactivity."
FT                   /evidence="ECO:0000269|PubMed:2002066"
FT   MUTAGEN         80
FT                   /note="L->P: 450-fold reduction in bioactivity."
FT                   /evidence="ECO:0000269|PubMed:2002066"
FT   MUTAGEN         124
FT                   /note="L->P: 5500-fold reduction in bioactivity."
FT                   /evidence="ECO:0000269|PubMed:2002066"
FT   CONFLICT        25
FT                   /note="T -> I (in Ref. 5; CAA29336 and 7; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        114
FT                   /note="V -> A (in Ref. 6; AAA37483)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        139
FT                   /note="G -> S (in Ref. 5; CAA29336)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        139
FT                   /note="G -> V (in Ref. 2; CAA26820, 3; no nucleotide entry,
FT                   4; CAA26192/CAA26193 and 6; AAA37483)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   141 AA;  16091 MW;  209C7CBB4FF77349 CRC64;
     MWLQNLLFLG IVVYSLSAPT RSPITVTRPW KHVEAIKEAL NLLDDMPVTL NEEVEVVSNE
     FSFKKLTCVQ TRLKIFEQGL RGNFTKLKGA LNMTASYYQT YCPPTPETDC ETQVTTYADF
     IDSLKTFLTD IPFECKKPGQ K
 
 
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