ID:CSF2_HUMAN DESCRIPTION: RecName: Full=Granulocyte-macrophage colony-stimulating factor; Short=GM-CSF; AltName: Full=Colony-stimulating factor; Short=CSF; AltName: Full=Molgramostin; AltName: Full=Sargramostim; Flags: Precursor; FUNCTION: Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes. SUBUNIT: Monomer. The signaling GM-CSF receptor complex is a dodecamer of two head-to-head hexamers of two alpha, two beta, and two ligand subunits. INTERACTION: P32927:CSF2RB; NbExp=2; IntAct=EBI-1809826, EBI-1809771; SUBCELLULAR LOCATION: Secreted. POLYMORPHISM: Variant Ile-117 may be a risk factor for atopic asthma. PHARMACEUTICAL: Available under the names Leukine (Immunex) and Leucomax (Novartis). Used in myeloid reconstitution following bone marrow transplant, bone marrow transplant engraftment failure or delay, mobilization and following transplantation of autologous peripheral blood progenitor cells, and following induction chemotherapy in older adults with acute myelogenous leukemia. SIMILARITY: Belongs to the GM-CSF family. WEB RESOURCE: Name=Leukine; Note=Clinical information on Leukine; URL="http://www.leukine.com/healthcare.aspx"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/csf2/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P04141
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000165 MAPK cascade GO:0001821 histamine secretion GO:0001892 embryonic placenta development GO:0006955 immune response GO:0008284 positive regulation of cell proliferation GO:0010468 regulation of gene expression GO:0010469 regulation of receptor activity GO:0010628 positive regulation of gene expression GO:0010744 positive regulation of macrophage derived foam cell differentiation GO:0018108 peptidyl-tyrosine phosphorylation GO:0019221 cytokine-mediated signaling pathway GO:0030223 neutrophil differentiation GO:0030224 monocyte differentiation GO:0032747 positive regulation of interleukin-23 production GO:0034021 response to silicon dioxide GO:0034405 response to fluid shear stress GO:0042045 epithelial fluid transport GO:0042116 macrophage activation GO:0042127 regulation of cell proliferation GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein GO:0043011 myeloid dendritic cell differentiation GO:0045187 regulation of circadian sleep/wake cycle, sleep GO:0045637 regulation of myeloid cell differentiation GO:0045892 negative regulation of transcription, DNA-templated GO:0045918 negative regulation of cytolysis GO:0071222 cellular response to lipopolysaccharide GO:0071803 positive regulation of podosome assembly GO:0097011 cellular response to granulocyte macrophage colony-stimulating factor stimulus GO:0097028 dendritic cell differentiation GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
Cellular Component: GO:0005576 extracellular region GO:0005615 extracellular space GO:0043231 intracellular membrane-bounded organelle
Descriptions from all associated GenBank mRNAs
E01141 - cDNA encoding human granulocyte-macrophage colony stimulating factor. E01142 - cDNA encoding human granulocyte-macrophage colony stimulating factor. E01143 - cDNA encoding human granulocyte-macrophage colony stimulating factor. JD050464 - Sequence 31488 from Patent EP1572962. M11220 - Human granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA. BC113924 - Homo sapiens colony stimulating factor 2 (granulocyte-macrophage), mRNA (cDNA clone MGC:138897 IMAGE:40084800), complete cds. BC113999 - Homo sapiens colony stimulating factor 2 (granulocyte-macrophage), mRNA (cDNA clone MGC:138896 IMAGE:40084798), complete cds. BC108724 - Homo sapiens colony stimulating factor 2 (granulocyte-macrophage), mRNA (cDNA clone MGC:131935 IMAGE:3886571), complete cds. E02287 - DNA encoding human granulocyte macrophage colony-stimulating factor (human GM-CSF). M11734 - Human granulocyte/macrophage colony-stimulating factor mRNA, complete cds. E02975 - DNA encoding human GM-CSF(colony stimulating factor). M10663 - Human T-cell granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA. E01817 - cDNA encoding hGM-CSF (human granulocyte-macrophage colony stimulating factor). AY720441 - Homo sapiens granulocyte-macrophage colony stimulating factor 2 mRNA, complete cds. KJ890978 - Synthetic construct Homo sapiens clone ccsbBroadEn_00372 CSF2 gene, encodes complete protein. KR711889 - Synthetic construct Homo sapiens clone CCSBHm_00031715 CSF2 (CSF2) mRNA, encodes complete protein. AB591004 - Synthetic construct DNA, clone: pFN21AE1628, Homo sapiens CSF2 gene for colony stimulating factor 2, without stop codon, in Flexi system. LQ884082 - Sequence 29 from Patent WO2018160540. AF510855 - Homo sapiens granulocyte-macrophage colony-stimulating factor precusor mRNA, partial cds. KP271009 - Homo sapiens clone shicr89-3 granulocyte macrophage-colony stimulating factor mRNA, partial cds. JD334901 - Sequence 315925 from Patent EP1572962. JD423751 - Sequence 404775 from Patent EP1572962. HW505605 - JP 2014502606-A/507: MELANOMA TREATMENTS. JD362213 - Sequence 343237 from Patent EP1572962. JD220569 - Sequence 201593 from Patent EP1572962. JD498466 - Sequence 479490 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_nktPathway - Selective expression of chemokine receptors during T-cell polarization h_erythPathway - Erythrocyte Differentiation Pathway h_eosinophilsPathway - The Role of Eosinophils in the Chemokine Network of Allergy h_inflamPathway - Cytokines and Inflammatory Response h_dcPathway - Dendritic cells in regulating TH1 and TH2 Development h_stemPathway - Regulation of hematopoiesis by cytokines
Reactome (by CSHL, EBI, and GO)
Protein P04141 (Reactome details) participates in the following event(s):
R-HSA-913360 GM-CSF receptor alpha subunit binds GM-CSF R-HSA-913371 GM-CSF receptor alpha:GM-CSF binds Bc R-HSA-879934 Recruitment of SHC1 is mediated by Y593 of the common beta chain R-HSA-909738 SHP1 and SHP2 bind the common beta chain R-HSA-879907 Tyrosine kinases phosphorylate the receptor R-HSA-879910 JAK2 is phosphorylated, activated R-HSA-913451 IL3RB is phosphorylated on Ser-585 R-HSA-879930 STAT5 is recruited by JAK2 R-HSA-921155 p-STAT5 dissociates from the receptor complex R-HSA-912757 p-S585-IL3RB binds 14-3-3 proteins R-HSA-879925 SHC1 bound to the common beta chain becomes tyrosine phosphorylated R-HSA-914036 SHP1 and SHP2 dephosphorylate Y628 of IL3RB R-HSA-879909 Activation of STAT5a/b by JAK2 R-HSA-914182 14-3-3 zeta binding allows recruitment of PI3K R-HSA-453111 Phosphorylated SHC recruits GRB2:SOS1 R-HSA-913374 Phosphorylated SHC1 recruits SHIP R-HSA-508247 Gab2 binds the p85 subunit of Class 1A PI3 kinases R-HSA-913424 The SHC1:SHIP1 complex is stabilized by GRB2 R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling R-HSA-8939246 RUNX1 regulates transcription of genes involved in differentiation of myeloid cells R-HSA-6783783 Interleukin-10 signaling R-HSA-449147 Signaling by Interleukins R-HSA-8878171 Transcriptional regulation by RUNX1 R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-212436 Generic Transcription Pathway R-HSA-168256 Immune System R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription) R-HSA-912526 Interleukin receptor SHC signaling R-HSA-451927 Interleukin-2 family signaling R-HSA-5673001 RAF/MAP kinase cascade R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-5683057 MAPK family signaling cascades R-HSA-162582 Signal Transduction