P09919 (CSF3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Granulocyte colony-stimulating factor
Short name=G-CSF

Alternative name(s):
Pluripoietin
INN=Filgrastim
INN=Lenograstim

Gene names

Name:	CSF3
Synonyms:	C17orf33, GCSF

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	207 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This CSF induces granulocytes.
Subunit structure	Monomer.
Subcellular location	Secreted.
Post-translational modification	O-glycan consists of Gal-GalNAc disaccharide which can be modified with up to two sialic acid residues (done in recombinantly expressed G-CSF from CHO cells).
Pharmaceutical use	Available under the names Neupogen or Granulokine (Amgen/Roche) and Granocyte (Rhone-Poulenc). Used to treat neutropenia (a disorder characterized by an extremely low number of neutrophils in blood).
Sequence similarities	Belongs to the IL-6 superfamily.
Caution	Ref.7 misquotes the gene name as "CSF1".

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Cytokine Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Pharmaceutical Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to lipopolysaccharide Inferred from electronic annotation. Source: Compara cytokine-mediated signaling pathway Non-traceable author statement PubMed 15664994. Source: UniProtKB granulocyte differentiation Non-traceable author statement PubMed 15664994. Source: UniProtKB immune response Inferred from electronic annotation. Source: InterPro negative regulation of neuron death Inferred from electronic annotation. Source: Compara positive regulation of actin cytoskeleton reorganization Inferred from direct assay PubMed 23001182. Source: BHF-UCL positive regulation of actin filament polymerization Inferred from direct assay PubMed 23001182. Source: BHF-UCL positive regulation of cell proliferation Traceable author statement Ref.7. Source: ProtInc positive regulation of peptidyl-serine phosphorylation Inferred from direct assay PubMed 23001182. Source: BHF-UCL positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 23001182. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase cascade Inferred from direct assay PubMed 23001182. Source: BHF-UCL positive regulation of protein binding Inferred from direct assay PubMed 23001182. Source: BHF-UCL positive regulation of protein kinase B signaling cascade Inferred from direct assay PubMed 23001182. Source: BHF-UCL positive regulation of transcription factor import into nucleus Inferred from direct assay PubMed 23001182. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 23001182. Source: BHF-UCL
Cellular_component	extracellular space Traceable author statement Ref.7. Source: ProtInc
Molecular_function	cytokine activity Non-traceable author statement PubMed 15664994. Source: UniProtKB granulocyte colony-stimulating factor receptor binding Traceable author statement Ref.7. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P09919-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: P09919-2)

The sequence of this isoform differs from the canonical sequence as follows:
     66-68: Missing.

Isoform 3 (identifier: P09919-3)

The sequence of this isoform differs from the canonical sequence as follows:
     69-104: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 29

29

Probable

Chain

30 – 207

178

Granulocyte colony-stimulating factor

PRO_0000015570

Amino acid modifications

Glycosylation

166

1

O-linked (GalNAc...) By similarity

Disulfide bond

69 ↔ 75

Disulfide bond

97 ↔ 107

Natural variations

Alternative sequence

66 – 68

3

Missing in isoform Short.

VSP_002673

Alternative sequence

69 – 104

36

Missing in isoform 3.

VSP_045246

Natural variant

157

1

L → M. Ref.4
Corresponds to variant rs2227329 [ dbSNP | Ensembl ].

VAR_013073

Natural variant

174

1

A → T. Ref.4
Corresponds to variant rs2227330 [ dbSNP | Ensembl ].

VAR_013074

Experimental info

Sequence conflict

30

1

A → M AA sequence Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

207

Helix Strand Turn

Details...

Beta strand

37 – 39

3

Helix

41 – 65

25

Helix

69 – 72

4

Helix

77 – 80

4

Helix

81 – 86

6

Beta strand

96 – 100

5

Helix

105 – 124

20

Turn

125 – 127

3

Turn

130 – 132

3

Helix

133 – 156

24

Beta strand

166 – 168

3

Helix

176 – 204

29

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 421F635ECC776996	FASTA	207	22,293
	10 20 30 40 50 60 MAGPATQSPM KLMALQLLLW HSALWTVQEA TPLGPASSLP QSFLLKCLEQ VRKIQGDGAA 70 80 90 100 110 120 LQEKLVSECA TYKLCHPEEL VLLGHSLGIP WAPLSSCPSQ ALQLAGCLSQ LHSGLFLYQG 130 140 150 160 170 180 LLQALEGISP ELGPTLDTLQ LDVADFATTI WQQMEELGMA PALQPTQGAM PAFASAFQRR 190 200 AGGVLVASHL QSFLEVSYRV LRHLAQP
	Isoform Short [UniParc]. Checksum: 5F07C52F13D6A6D3	FASTA	204	21,978
	10 20 30 40 50 60 MAGPATQSPM KLMALQLLLW HSALWTVQEA TPLGPASSLP QSFLLKCLEQ VRKIQGDGAA 70 80 90 100 110 120 LQEKLCATYK LCHPEELVLL GHSLGIPWAP LSSCPSQALQ LAGCLSQLHS GLFLYQGLLQ 130 140 150 160 170 180 ALEGISPELG PTLDTLQLDV ADFATTIWQQ MEELGMAPAL QPTQGAMPAF ASAFQRRAGG 190 200 VLVASHLQSF LEVSYRVLRH LAQP
	Isoform 3 [UniParc]. Checksum: C62B366732AD7664	FASTA	171	18,434
	10 20 30 40 50 60 MAGPATQSPM KLMALQLLLW HSALWTVQEA TPLGPASSLP QSFLLKCLEQ VRKIQGDGAA 70 80 90 100 110 120 LQEKLVSEAG CLSQLHSGLF LYQGLLQALE GISPELGPTL DTLQLDVADF ATTIWQQMEE 130 140 150 160 170 LGMAPALQPT QGAMPAFASA FQRRAGGVLV ASHLQSFLEV SYRVLRHLAQ P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor." Nagata S., Tsuchiya M., Asano S., Kaziro Y., Yamazaki T., Yamamoto O., Hirata Y., Kubota N., Oheda M., Nomura H., Ono M. Nature 319:415-418(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[2]	"The chromosomal gene structure and two mRNAs for human granulocyte colony-stimulating factor." Nagata S., Tsuchiya M., Asano S., Yamamoto O., Hirata Y., Kubota N., Oheda M., Nomura H., Yamazaki T. EMBO J. 5:575-581(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM SHORT), ALTERNATIVE SPLICING.
[3]	"Expression of granulocyte colony-stimulating factor by human cell lines." Devlin J.J., Devlin P.E., Myambo K., Lilly M.B., Rado T.A., Warren M.K. J. Leukoc. Biol. 41:302-306(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[4]	SeattleSNPs variation discovery resource Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-157 AND THR-174.
[5]	"PCR isolation and cloning of novel splice variant mRNAs from known drug target genes." Jin P., Fu G.K., Wilson A.D., Yang J., Chien D., Hawkins P.R., Au-Young J., Stuve L.L. Genomics 83:566-571(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[6]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells." Souza L.M., Boone T.C., Gabrilove J., Lai P.H., Zsebo K.M., Murdock D.C., Chazin V.R., Bruszewski J., Lu H., Chen K.K., Barendt J., Platzer E., Moore M.A.S., Mertelsmann R., Welte K. Science 232:61-66(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 19-207 (ISOFORM SHORT).
[8]	"Extracellular domain of granulocyte-colony stimulating factor receptor. Interaction with its ligand and identification of a domain in close proximity of ligand-binding region." Haniu M., Horan T., Arakawa T., Le J., Katta V., Rohde M.F. Arch. Biochem. Biophys. 324:344-356(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 30-46.
[9]	"Glycosidase digestion, electrophoresis and chromatographic analysis of recombinant human granulocyte colony-stimulating factor glycoforms produced in Chinese hamster ovary cells." Clogston C.L., Hu S., Boone T.C., Lu H.S. J. Chromatogr. A 637:55-62(1993) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-166.
[10]	"Secondary structure of human granulocyte colony-stimulating factor derived from NMR spectroscopy." Zink T., Ross A., Ambrosius D., Rudolph R., Holak T.A. FEBS Lett. 314:435-439(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[11]	"Structure and dynamics of the human granulocyte colony-stimulating factor determined by NMR spectroscopy. Loop mobility in a four-helix-bundle protein." Zink T., Ross A., Luers K., Cieslar C., Rudolph R., Holak T.A. Biochemistry 33:8453-8463(1994) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[12]	"The structure of granulocyte-colony-stimulating factor and its relationship to other growth factors." Hill C.P., Osslund T.D., Eisenberg D. Proc. Natl. Acad. Sci. U.S.A. 90:5167-5171(1993) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[13]	"Atomic structure of the GCSF-receptor complex showing a new cytokine-receptor recognition scheme." Aritomi M., Kunishima N., Okamoto T., Kuroki R., Ota Y., Morikawa K. Nature 401:713-717(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 31-207 IN COMPLEX WITH CSF3R.
[14]	"Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex." Tamada T., Honjo E., Maeda Y., Okamoto T., Ishibashi M., Tokunaga M., Kuroki R. Proc. Natl. Acad. Sci. U.S.A. 103:3135-3140(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 31-207 IN COMPLEX WITH CSF3R.
+	Additional computationally mapped references.

Web resources

Neupogen/Granulokine

Clinical information on Neupogen/Granulokine

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X03438 mRNA. Translation: CAA27168.1.
X03656 Genomic DNA. Translation: CAA27291.1.
X03655 mRNA. Translation: CAA27290.1.
M17706 mRNA. Translation: AAA35882.1.
AF388025 Genomic DNA. Translation: AAK62469.1.
CD013926 mRNA. No translation available.
AC090844 Genomic DNA. No translation available.
M13008 mRNA. Translation: AAA03056.1.

IPI

IPI00018306.
IPI00172503.
IPI00793324.

PIR

A24573.
FQHUGL. A25093.

RefSeq

NP_000750.1. NM_000759.3.
NP_001171618.1. NM_001178147.1.
NP_757373.1. NM_172219.2.
NP_757374.2. NM_172220.2.

UniGene

Hs.2233.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CD9	X-ray	2.80	A/C	31-207	[»]
1GNC	NMR	-	A	31-207	[»]
1PGR	X-ray	3.50	A/C/E/G	31-207	[»]
1RHG	X-ray	2.20	A/B/C	31-207	[»]
2D9Q	X-ray	2.80	A	31-207	[»]

ProteinModelPortal

P09919.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000225474.

Protein family/group databases

Allergome

8367. Hom s G-CSF.

PTM databases

PhosphoSite

P09919.

Polymorphism databases

DMDM

117564.

Proteomic databases

PaxDb

P09919.

PRIDE

P09919.

Protocols and materials databases

DNASU

1440.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000225474; ENSP00000225474; ENSG00000108342.
ENST00000394148; ENSP00000377704; ENSG00000108342.
ENST00000394149; ENSP00000377705; ENSG00000108342.

GeneID

1440.

KEGG

hsa:1440.

UCSC

uc002htp.3. human.

Organism-specific databases

CTD

1440.

GeneCards

GC17P038171.

HGNC

HGNC:2438. CSF3.

HPA

CAB016131.
HPA001412.

MIM

138970. gene.

neXtProt

NX_P09919.

PharmGKB

PA26941.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47652.

HOGENOM

HOG000015371.

HOVERGEN

HBG005411.

InParanoid

P09919.

KO

K05423.

OMA

CHPEELV.

PhylomeDB

P09919.

Gene expression databases

ArrayExpress

P09919.

Bgee

P09919.

CleanEx

HS_CSF3.

Genevestigator

P09919.

GermOnline

ENSG00000108342. Homo sapiens.

Family and domain databases

Gene3D

1.20.1250.10. 1 hit.

InterPro

IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003573. IL6_MGF_GCSF.
[Graphical view]

Pfam

PF00489. IL6. 1 hit.
[Graphical view]

PIRSF

PIRSF001935. IL6_MGF_GCSF. 1 hit.

PRINTS

PR00433. IL6GCSFMGF.

SMART

SM00126. IL6. 1 hit.
[Graphical view]

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

PROSITE

PS00254. INTERLEUKIN_6. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00099. Filgrastim.
DB00019. Pegfilgrastim.

EvolutionaryTrace

P09919.

GenomeRNAi

1440.

NextBio

5893.

SOURCE

Search...

Entry information

Entry name

CSF3_HUMAN

Accession

Primary (citable) accession number: P09919
Secondary accession number(s): A8MXR7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	May 1, 2013
This is version 150 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.