Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q99062 (CSF3R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Granulocyte colony-stimulating factor receptor

Short name=G-CSF receptor
Short name=G-CSF-R
Alternative name(s):
CD_antigen=CD114
Gene names
Name:CSF3R
Synonyms:GCSFR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length836 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differientation and survival of cells along the neutrophilic lineage. In addition it may function in some adhesion or recognition events at the cell surface. Ref.8

Subunit structure

Homodimer. The dimeric receptor binds two CSF3 molecules. Ref.13

Subcellular location

Isoform 2: Secreted Probable.

Cell membrane; Single-pass type I membrane protein.

Tissue specificity

One or several isoforms have been found in myelogenous leukemia cell line KG-1, leukemia U-937 cell line, in bone marrow cells, placenta, and peripheral blood granulocytes. Isoform GCSFR-2is found only in leukemia U-937 cells. Isoform GCSFR-3is highly expressed in placenta.

Domain

The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. Ref.7

The box 1 motif is required for JAK interaction and/or activation. Ref.7

Involvement in disease

Hereditary neutrophilia (NEUTROPHILIA) [MIM:162830]: A form of lifelong, persistent neutrophilia, a condition characterized by an increase in the number of neutrophils in the blood.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15

Miscellaneous

Mutations in CSF3R acquired in multipotent hematopoietic progenitor cells and resulting in truncated hyper-responsive forms of the receptor, have been identified in most cases of severe congenital neutropenia (SCN). Patients carrying these mutations are at risk for developing myelodysplastic syndromes and/or acute myeloid leukemia. Constitutive mutations leading to hyporesponsive forms of the receptor are responsible for the refractoriness to CSF3 treatment observed in some SCN patients.

Sequence similarities

Belongs to the type I cytokine receptor family. Type 2 subfamily.

Contains 5 fibronectin type-III domains.

Contains 1 Ig-like C2-type (immunoglobulin-like) domain.

Binary interactions

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist. Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q99062-1)

Also known as: GCSFR-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 2 (identifier: Q99062-2)

Also known as: GCSFR-2;

The sequence of this isoform differs from the canonical sequence as follows:
     622-836: EGSELHIILG...VHGMEALGSF → APTGRIPSGQ...GSRPAPWGPW
Isoform 3 (identifier: Q99062-3)

Also known as: GCSFR-3;

The sequence of this isoform differs from the canonical sequence as follows:
     680-680: E → ELPGPRQGQWLGQTSEMSRALTPHPCVQ
Isoform 4 (identifier: Q99062-4)

Also known as: GCSFR-4; D7;

The sequence of this isoform differs from the canonical sequence as follows:
     750-783: VLYGQLLGSPTSPGPGHYLRCDSTQPLLAGLTPS → AGPPRRSAYFKDQIMLHPAPPNGLLCLFPITSVL
     784-836: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424
Chain25 – 836812Granulocyte colony-stimulating factor receptor
PRO_0000010874

Regions

Topological domain25 – 627603Extracellular Potential
Transmembrane628 – 65023Helical; Potential
Topological domain651 – 836186Cytoplasmic Potential
Domain25 – 11793Ig-like C2-type
Domain125 – 230106Fibronectin type-III 1
Domain233 – 332100Fibronectin type-III 2
Domain334 – 43097Fibronectin type-III 3
Domain431 – 52898Fibronectin type-III 4
Domain530 – 62394Fibronectin type-III 5
Motif318 – 3225WSXWS motif
Motif658 – 6669Box 1 motif

Amino acid modifications

Glycosylation511N-linked (GlcNAc...) Potential
Glycosylation931N-linked (GlcNAc...) Potential
Glycosylation1281N-linked (GlcNAc...) Potential
Glycosylation1341N-linked (GlcNAc...) Ref.13
Glycosylation3891N-linked (GlcNAc...) Potential
Glycosylation4741N-linked (GlcNAc...) Potential
Glycosylation5791N-linked (GlcNAc...) Potential
Glycosylation6101N-linked (GlcNAc...) Potential
Disulfide bond26 ↔ 52 Ref.13
Disulfide bond46 ↔ 101 Ref.13
Disulfide bond131 ↔ 142 Ref.13
Disulfide bond167 ↔ 218 Ref.13
Disulfide bond177 ↔ 186 Ref.13
Disulfide bond248 ↔ 295 Ref.13
Disulfide bond266 ↔ 309 Ref.13

Natural variations

Alternative sequence622 – 836215EGSEL…ALGSF → APTGRIPSGQVSQTQLTAAW APGCPQSWRRMPSSCPALAR HPSPSSQCWRRMKRSRCPGS PITAQRPVASPLWSRPMCSR GTQEQFPPSPNPSLAPAIRS FMGSCWAAPQAQGQGTISAV TPLSPSWRASPPAPSPMRTS GSRPAPWGPW in isoform 2.
VSP_001674
Alternative sequence6801E → ELPGPRQGQWLGQTSEMSRA LTPHPCVQ in isoform 3.
VSP_001673
Alternative sequence750 – 78334VLYGQ…GLTPS → AGPPRRSAYFKDQIMLHPAP PNGLLCLFPITSVL in isoform 4.
VSP_001671
Alternative sequence784 – 83653Missing in isoform 4.
VSP_001672
Natural variant2291P → H in a patient with severe congenital neutropenia hyporesponsive to CSF3 treatment; affects CSF3 mediated proliferation and survival of myeloid cells; abrogates receptor signaling by altering ligand binding. Ref.14
VAR_062517
Natural variant2311M → T. Ref.4
Corresponds to variant rs3917973 [ dbSNP | Ensembl ].
VAR_014325
Natural variant3201D → N. Ref.4
Corresponds to variant rs3918018 [ dbSNP | Ensembl ].
VAR_014326
Natural variant3461Q → R. Ref.4
Corresponds to variant rs3917974 [ dbSNP | Ensembl ].
VAR_014327
Natural variant4051E → K. Ref.4
Corresponds to variant rs3918019 [ dbSNP | Ensembl ].
VAR_014328
Natural variant4401R → Q. Ref.4
Corresponds to variant rs3918020 [ dbSNP | Ensembl ].
VAR_014329
Natural variant5101D → H. Ref.4
Corresponds to variant rs3917991 [ dbSNP | Ensembl ].
VAR_014330
Natural variant5621Y → H. Ref.4
Corresponds to variant rs3917996 [ dbSNP | Ensembl ].
VAR_014331
Natural variant5831R → C. Ref.4
Corresponds to variant rs3917997 [ dbSNP | Ensembl ].
VAR_014332
Natural variant6401T → N in neutrophilia. Ref.15
Corresponds to variant rs121918426 [ dbSNP | Ensembl ].
VAR_063065

Secondary structure

.................................................... 836
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (GCSFR-1) [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 3531ADDC979D4BC3

FASTA83692,156
        10         20         30         40         50         60 
MARLGNCSLT WAALIILLLP GSLEECGHIS VSAPIVHLGD PITASCIIKQ NCSHLDPEPQ 

        70         80         90        100        110        120 
ILWRLGAELQ PGGRQQRLSD GTQESIITLP HLNHTQAFLS CCLNWGNSLQ ILDQVELRAG 

       130        140        150        160        170        180 
YPPAIPHNLS CLMNLTTSSL ICQWEPGPET HLPTSFTLKS FKSRGNCQTQ GDSILDCVPK 

       190        200        210        220        230        240 
DGQSHCCIPR KHLLLYQNMG IWVQAENALG TSMSPQLCLD PMDVVKLEPP MLRTMDPSPE 

       250        260        270        280        290        300 
AAPPQAGCLQ LCWEPWQPGL HINQKCELRH KPQRGEASWA LVGPLPLEAL QYELCGLLPA 

       310        320        330        340        350        360 
TAYTLQIRCI RWPLPGHWSD WSPSLELRTT ERAPTVRLDT WWRQRQLDPR TVQLFWKPVP 

       370        380        390        400        410        420 
LEEDSGRIQG YVVSWRPSGQ AGAILPLCNT TELSCTFHLP SEAQEVALVA YNSAGTSRPT 

       430        440        450        460        470        480 
PVVFSESRGP ALTRLHAMAR DPHSLWVGWE PPNPWPQGYV IEWGLGPPSA SNSNKTWRME 

       490        500        510        520        530        540 
QNGRATGFLL KENIRPFQLY EIIVTPLYQD TMGPSQHVYA YSQEMAPSHA PELHLKHIGK 

       550        560        570        580        590        600 
TWAQLEWVPE PPELGKSPLT HYTIFWTNAQ NQSFSAILNA SSRGFVLHGL EPASLYHIHL 

       610        620        630        640        650        660 
MAASQAGATN STVLTLMTLT PEGSELHIIL GLFGLLLLLT CLCGTAWLCC SPNRKNPLWP 

       670        680        690        700        710        720 
SVPDPAHSSL GSWVPTIMEE DAFQLPGLGT PPITKLTVLE EDEKKPVPWE SHNSSETCGL 

       730        740        750        760        770        780 
PTLVQTYVLQ GDPRAVSTQP QSQSGTSDQV LYGQLLGSPT SPGPGHYLRC DSTQPLLAGL 

       790        800        810        820        830 
TPSPKSYENL WFQASPLGTL VTPAPSQEDD CVFGPLLNFP LLQGIRVHGM EALGSF 

« Hide

Isoform 2 (GCSFR-2) [UniParc].

Checksum: 2483E94E3A57322A
Show »

FASTA77185,120
Isoform 3 (GCSFR-3) [UniParc].

Checksum: 6951B4F2C9FED675
Show »

FASTA86395,114
Isoform 4 (GCSFR-4) (D7) [UniParc].

Checksum: 9D85EC2298D42BF3
Show »

FASTA78386,609

References

« Hide 'large scale' references
[1]"Expression cloning of a human granulocyte colony-stimulating factor receptor: a structural mosaic of hematopoietin receptor, immunoglobulin, and fibronectin domains."
Larsen A., Davis T., Curtis B.M., Gimpel S., Sims J.E., Cosman D., Park L., Sorensen E., March C.J., Smith C.A.
J. Exp. Med. 172:1559-1570(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4).
Tissue: Placenta.
[2]"Three different mRNAs encoding human granulocyte colony-stimulating factor receptor."
Fukunaga R., Seto Y., Mizushima S., Nagata S.
Proc. Natl. Acad. Sci. U.S.A. 87:8702-8706(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Placenta.
[3]"Chromosomal gene organization of the human granulocyte colony-stimulating factor receptor."
Seto Y., Fukunaga R., Nagata S.
J. Immunol. 148:259-266(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]SeattleSNPs variation discovery resource
Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-231; ASN-320; ARG-346; LYS-405; GLN-440; HIS-510; HIS-562 AND CYS-583.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Blood.
[6]"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 234-269.
[7]"Functional domains of the granulocyte colony-stimulating factor receptor."
Fukunaga R., Ishizaka-Ikeda E., Pan C.-X., Seto Y., Nagata S.
EMBO J. 10:2855-2865(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAINS.
[8]"Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia."
Dong F., Hoefsloot L.H., Schelen A.M., Broeders C.A., Meijer Y., Veerman A.J., Touw I.P., Lowenberg B.
Proc. Natl. Acad. Sci. U.S.A. 91:4480-4484(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, POSSIBLE ASSOCIATION WITH SCN.
[9]"Granulocyte colony-stimulating factor and its receptor in normal myeloid cell development, leukemia and related blood cell disorders."
Touw I.P., van de Geijn G.J.
Front. Biosci. 12:800-815(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[10]"Clinical implications of ELA2-, HAX1-, and G-CSF-receptor (CSF3R) mutations in severe congenital neutropenia."
Zeidler C., Germeshausen M., Klein C., Welte K.
Br. J. Haematol. 144:459-467(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE ASSOCIATION WITH SCN.
[11]"Solution structure of an extracellular domain containing the WSxWS motif of the granulocyte colony-stimulating factor receptor and its interaction with ligand."
Yamasaki K., Naito S., Anaguchi H., Ohkubo T., Ota Y.
Nat. Struct. Biol. 4:498-504(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 227-334.
[12]"Identification of a ligand-binding site on the granulocyte colony-stimulating factor receptor by molecular modeling and mutagenesis."
Layton J.E., Iaria J., Smith D.K., Treutlein H.R.
J. Biol. Chem. 272:29735-29741(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING OF 125-331.
[13]"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 25-333 IN COMPLEX WITH CSF3, GLYCOSYLATION AT ASN-134, DISULFIDE BONDS, SUBUNIT.
[14]"Novel point mutation in the extracellular domain of the granulocyte colony-stimulating factor (G-CSF) receptor in a case of severe congenital neutropenia hyporesponsive to G-CSF treatment."
Ward A.C., van Aesch Y.M., Gits J., Schelen A.M., de Koning J.P., van Leeuwen D., Freedman M.H., Touw I.P.
J. Exp. Med. 190:497-507(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HIS-229, CHARACTERIZATION OF VARIANT HIS-229, POSSIBLE ASSOCIATION WITH SCN.
[15]"An activating mutation in the CSF3R gene induces a hereditary chronic neutrophilia."
Plo I., Zhang Y., Le Couedic J.P., Nakatake M., Boulet J.M., Itaya M., Smith S.O., Debili N., Constantinescu S.N., Vainchenker W., Louache F., de Botton S.
J. Exp. Med. 206:1701-1707(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NEUTROPHILIA ASN-640.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X55721 mRNA. Translation: CAA39253.1.
X55720 mRNA. Translation: CAA39252.1.
M59818 mRNA. Translation: AAA63176.1.
M59819 mRNA. Translation: AAA63177.1.
M59820 mRNA. Translation: AAA63178.1.
S71484 Genomic DNA. Translation: AAB20660.1.
AY148100 Genomic DNA. Translation: AAN05790.1.
BC053585 mRNA. Translation: AAH53585.1.
PIRB38252.
C38252.
JH0329.
RefSeqNP_000751.1. NM_000760.3.
NP_724781.1. NM_156039.3.
NP_758519.1. NM_172313.2.
UniGeneHs.524517.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AZ7model-A125-331[»]
2D9QX-ray2.80B25-333[»]
ProteinModelPortalQ99062.
SMRQ99062. Positions 23-618.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107828. 14 interactions.
DIPDIP-5788N.
IntActQ99062. 2 interactions.
MINTMINT-4787360.
STRING9606.ENSP00000342623.

Chemistry

BindingDBQ99062.
ChEMBLCHEMBL1996.
DrugBankDB00099. Filgrastim.
DB00019. Pegfilgrastim.
GuidetoPHARMACOLOGY1719.

PTM databases

PhosphoSiteQ99062.

Polymorphism databases

DMDM729564.

Proteomic databases

PaxDbQ99062.
PRIDEQ99062.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000331941; ENSP00000332180; ENSG00000119535. [Q99062-4]
ENST00000361632; ENSP00000355406; ENSG00000119535. [Q99062-1]
ENST00000373103; ENSP00000362195; ENSG00000119535. [Q99062-3]
ENST00000373104; ENSP00000362196; ENSG00000119535. [Q99062-4]
ENST00000373106; ENSP00000362198; ENSG00000119535. [Q99062-1]
ENST00000418048; ENSP00000401588; ENSG00000119535. [Q99062-1]
ENST00000440588; ENSP00000397568; ENSG00000119535. [Q99062-3]
GeneID1441.
KEGGhsa:1441.
UCSCuc001cav.2. human. [Q99062-4]
uc001caw.2. human. [Q99062-1]
uc001cax.2. human. [Q99062-3]

Organism-specific databases

CTD1441.
GeneCardsGC01M036931.
HGNCHGNC:2439. CSF3R.
HPACAB017116.
HPA048086.
MIM138971. gene.
162830. phenotype.
neXtProtNX_Q99062.
Orphanet98824. Atypical chronic myeloid leukemia.
86829. Chronic neutrophilic leukemia.
279943. Hereditary neutrophilia.
PharmGKBPA26942.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG29566.
HOGENOMHOG000231142.
HOVERGENHBG051130.
KOK05061.
OMAYLRCDST.
OrthoDBEOG7FXZXN.
PhylomeDBQ99062.
TreeFamTF338122.

Enzyme and pathway databases

SignaLinkQ99062.

Gene expression databases

ArrayExpressQ99062.
BgeeQ99062.
CleanExHS_CSF3R.
GenevestigatorQ99062.

Family and domain databases

Gene3D2.60.40.10. 6 hits.
InterProIPR003961. Fibronectin_type3.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR013783. Ig-like_fold.
IPR010457. IgC2-like_lig-bd.
[Graphical view]
PfamPF00041. fn3. 1 hit.
PF06328. Lep_receptor_Ig. 1 hit.
[Graphical view]
SMARTSM00060. FN3. 5 hits.
[Graphical view]
SUPFAMSSF49265. SSF49265. 4 hits.
PROSITEPS50853. FN3. 5 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCSF3R. human.
EvolutionaryTraceQ99062.
GeneWikiGranulocyte_colony-stimulating_factor_receptor.
GenomeRNAi1441.
NextBio5901.
PROQ99062.
SOURCESearch...

Entry information

Entry nameCSF3R_HUMAN
AccessionPrimary (citable) accession number: Q99062
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: April 16, 2014
This is version 152 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries