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5  structures 42  species 1  interaction 64  sequences 1  architecture

Family: GM_CSF (PF01109)

Summary: Granulocyte-macrophage colony-stimulating factor

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This is the Wikipedia entry entitled "Granulocyte macrophage colony-stimulating factor". More...

Granulocyte macrophage colony-stimulating factor Edit Wikipedia article

Not to be confused with granulocyte colony-stimulating factor.
Colony stimulating factor 2 (granulocyte-macrophage)
GMCSF Crystal Structure.rsh.png
PDB rendering based on 2gmf
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CSF2 ; GMCSF
External IDs OMIM138960 MGI1339752 HomoloGene600 GeneCards: CSF2 Gene
RNA expression pattern
PBB GE CSF2 210229 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1437 12981
Ensembl ENSG00000164400 ENSMUSG00000018916
UniProt P04141 P01587
RefSeq (mRNA) NM_000758 NM_009969
RefSeq (protein) NP_000749 NP_034099
Location (UCSC) Chr 5:
131.41 – 131.41 Mb
Chr 11:
54.25 – 54.25 Mb
PubMed search [1] [2]
Granulocyte-macrophage colony-stimulating factor
PDB 1csg EBI.jpg
three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor
Identifiers
Symbol GM_CSF
Pfam PF01109
Pfam clan CL0053
InterPro IPR000773
PROSITE PDOC00584
SCOP 2gmf
SUPERFAMILY 2gmf
Granulocyte macrophage colony-stimulating factor
GMCSF Crystal Structure.rsh.png
Systematic (IUPAC) name
Human granulocyte macrophage colony stimulating factor
Clinical data
Legal status
?
Identifiers
CAS number 83869-56-1 YesY
ATC code L03AA09
DrugBank DB00020
Chemical data
Formula C639H1006N168O196S8 
Mol. mass 14434.5 g/mol
 N (what is this?)  (verify)

Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony stimulating factor 2 (CSF2), is a protein secreted by macrophages, T cells, mast cells, NK cells, endothelial cells and fibroblasts. The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim.

Function

GM-CSF is a cytokine that functions as a white blood cell growth factor.[1] GM-CSF stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Monocytes exit the circulation and migrate into tissue, whereupon they mature into macrophages and dendritic cells. Thus, it is part of the immune/inflammatory cascade, by which activation of a small number of macrophages can rapidly lead to an increase in their numbers, a process crucial for fighting infection. The active form of the protein is found extracellularly as a homodimer. GM-CSF signals via signal transducer and activator of transcription, STAT5.[2]

Genetics

The human gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. Genes in the cluster include those encoding interleukins 4, 5, and 13.[3]

Glycosylation

Human granulocyte macrophage colony-stimulating factor is glycosylated in its mature form.

Medical use

GM-CSF is manufactured using recombinant DNA technology and is marketed as a protein therapeutic called molgramostim or, when the protein is expressed in yeast cells, sargramostim. It is used as a medication to stimulate the production of white blood cells and thus prevent neutropenia following chemotherapy.[4]

GM-CSF has also recently been evaluated in clinical trials for its potential as a vaccine adjuvant in HIV-infected patients. The preliminary results have been promising[5] but GM-CSF is not presently FDA-approved for this purpose.

Sargramostim

Sargramostim, recombinant yeast-derived GM-CSF developed at Immunex (now Amgen) and first given to six humans in 1987 as part of a compassionate-use protocol for the victims of the Goiânia cesium irradiation accident.[6] It is currently manufactured by Berlex Laboratories, a subsidiary of Schering AG. Its use was approved by U.S. Food and Drug Administration for acceleration of white blood cell recovery following autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma, acute lymphocytic leukemia, or Hodgkin's disease in March 1991.[7] In November 1996, the FDA also approved sargramostim for treatment of fungal infections and replenishment of white blood cells following chemotherapy.[8]

Rheumatoid arthritis

GM-CSF is found in high levels in joints with rheumatoid arthritis and blocking GM-CSF may reduce the inflammation or damage. Some drugs (e.g. MOR103) are being developed to block GM-CSF.[9]

See also

References

  1. ^ Francisco-Cruz A, Aguilar-Santelises M, Ramos-Espinosa O, Mata-Espinosa D, Marquina-Castillo B, Barrios-Payan J, Hernandez-Pando R (2014). "Granulocyte-macrophage colony-stimulating factor: not just another haematopoietic growth factor". Med. Oncol. 31 (1): 774. doi:10.1007/s12032-013-0774-6. PMID 24264600. 
  2. ^ Voehringer D (2012). "Basophil modulation by cytokine instruction". Eur. J. Immunol. 42 (10): 2544–50. doi:10.1002/eji.201142318. PMID 23042651. 
  3. ^ "Entrez Gene: CSF2 colony stimulating factor 2 (granulocyte-macrophage)". 
  4. ^ Vacchelli E, Eggermont A, Fridman WH, Galon J, Zitvogel L, Kroemer G, Galluzzi L (2013). "Trial Watch: Immunostimulatory cytokines". Oncoimmunology 2 (7): e24850. doi:10.4161/onci.24850. PMC 3782010. PMID 24073369. 
  5. ^ Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR, Chow LQ, Nieva J, Hwang TH, Moon A, Patt R, Pelusio A, Le Boeuf F, Burns J, Evgin L, De Silva N, Cvancic S, Robertson T, Je JE, Lee YS, Parato K, Diallo JS, Fenster A, Daneshmand M, Bell JC, Kirn DH (2011). "Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans". Nature 477 (7362): 99–102. doi:10.1038/nature10358. PMID 21886163. 
  6. ^ Schmeck HM (1987-11-02). "Radiation Team Sent to Brazil Saves Two With a New Drug". New York Times. Retrieved 2012-06-20. 
  7. ^ "Approval Summary for sargramostim". Oncology Tools. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. 1991-03-05. Archived from the original on 2007-09-29. Retrieved 20 September 2009. 
  8. ^ "Newly Approved Drug Therapies (179): Leukine (sargramostim), Immunex". CenterWatch. Retrieved 2008-10-12. 
  9. ^ Deiß A, Brecht I, Haarmann A, Buttmann M (2013). "Treating multiple sclerosis with monoclonal antibodies: a 2013 update". Expert Rev Neurother 13 (3): 313–35. doi:10.1586/ern.13.17. PMID 23448220. 

External links

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Granulocyte-macrophage colony-stimulating factor Provide feedback

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000773

Granulocyte-macrophage colony-stimulating factor (GMCSF) is a cytokine that acts in hematopoiesis to stimulate growth and differentiation of hematopoietic precursor cells from various lineages including granulocytes, macrophages, eosinophils and erythrocytes [PUBMED:2458827, PUBMED:1569568]. GMCSF is a glycoprotein of ~120 residues that contains 4 conserved cysteines that participate in disulphide bond formation. The crystal structure of recombinant human GMCSF has been determined [PUBMED:1569568]. There are two molecules in the asymmetric unit, which are related by an approximate non-crystallographic 2-fold axis. The overall structure, which is highly compact and globular with a predominantly hydrophobic core, is characterised by a 4-alpha-helix bundle. The helices are arranged in a left-handed anti-parallel fashion, with two overhand connections. Within the connections is a two-stranded anti-parallel beta-sheet. The tertiary structure has a topology similar to that of Sus scrofa (pig) growth factor and interferon-beta. Most of the proposed critical regions for receptor binding are located on a continuous surface at one end of the molecule that includes the C terminus [PUBMED:1569568].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan 4H_Cytokine (CL0053), which has the following description:

Cytokines are regulatory peptides that can be produced by various cells for communicating and orchestrating the large multicellular system. Cytokines are key mediators of hematopoiesis, immunity, allergy, inflammation, tissue remodeling, angiogenesis, and embryonic development [2]. This superfamily includes both the long and short chain helical cytokines.

The clan contains the following 22 members:

CNTF EPO_TPO Flt3_lig GM_CSF Hormone_1 IFN-gamma IL10 IL11 IL12 IL13 IL2 IL22 IL3 IL34 IL4 IL5 IL6 Interferon Leptin LIF_OSM PRF SCF

Alignments

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(7)
Full
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Representative proteomes NCBI
(68)
Meta
(0)
RP15
(1)
RP35
(1)
RP55
(2)
RP75
(16)
Alignment:
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(7)
Full
(64)
Representative proteomes NCBI
(68)
Meta
(0)
RP15
(1)
RP35
(1)
RP55
(2)
RP75
(16)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Sarah Teichmann
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 7
Number in full: 64
Average length of the domain: 118.90 aa
Average identity of full alignment: 55 %
Average coverage of the sequence by the domain: 84.06 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.1 20.1
Trusted cut-off 20.1 21.2
Noise cut-off 20.0 19.4
Model length: 122
Family (HMM) version: 12
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

GM_CSF

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the GM_CSF domain has been found. There are 5 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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