ID CSF3R_HUMAN Reviewed; 836 AA. AC Q99062; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1995, sequence version 1. DT 27-MAR-2024, entry version 218. DE RecName: Full=Granulocyte colony-stimulating factor receptor; DE Short=G-CSF receptor; DE Short=G-CSF-R; DE AltName: CD_antigen=CD114; DE Flags: Precursor; GN Name=CSF3R; Synonyms=GCSFR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4). RC TISSUE=Placenta; RX PubMed=2147944; DOI=10.1084/jem.172.6.1559; RA Larsen A., Davis T., Curtis B.M., Gimpel S., Sims J.E., Cosman D., Park L., RA Sorensen E., March C.J., Smith C.A.; RT "Expression cloning of a human granulocyte colony-stimulating factor RT receptor: a structural mosaic of hematopoietin receptor, immunoglobulin, RT and fibronectin domains."; RL J. Exp. Med. 172:1559-1570(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Placenta; RX PubMed=1701053; DOI=10.1073/pnas.87.22.8702; RA Fukunaga R., Seto Y., Mizushima S., Nagata S.; RT "Three different mRNAs encoding human granulocyte colony-stimulating factor RT receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 87:8702-8706(1990). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1530796; RA Seto Y., Fukunaga R., Nagata S.; RT "Chromosomal gene organization of the human granulocyte colony-stimulating RT factor receptor."; RL J. Immunol. 148:259-266(1992). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-231; ASN-320; ARG-346; RP LYS-405; GLN-440; HIS-510; HIS-562 AND CYS-583. RG SeattleSNPs variation discovery resource; RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Blood; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 234-269. RX PubMed=8554326; DOI=10.1006/abbi.1995.0047; RA Haniu M., Horan T., Arakawa T., Le J., Katta V., Rohde M.F.; RT "Extracellular domain of granulocyte-colony stimulating factor receptor. RT Interaction with its ligand and identification of a domain in close RT proximity of ligand-binding region."; RL Arch. Biochem. Biophys. 324:344-356(1995). RN [7] RP DOMAINS. RX PubMed=1717255; DOI=10.1002/j.1460-2075.1991.tb07835.x; RA Fukunaga R., Ishizaka-Ikeda E., Pan C.-X., Seto Y., Nagata S.; RT "Functional domains of the granulocyte colony-stimulating factor RT receptor."; RL EMBO J. 10:2855-2865(1991). RN [8] RP FUNCTION, AND POSSIBLE ASSOCIATION WITH SCN. RX PubMed=7514305; DOI=10.1073/pnas.91.10.4480; RA Dong F., Hoefsloot L.H., Schelen A.M., Broeders C.A., Meijer Y., RA Veerman A.J., Touw I.P., Lowenberg B.; RT "Identification of a nonsense mutation in the granulocyte-colony- RT stimulating factor receptor in severe congenital neutropenia."; RL Proc. Natl. Acad. Sci. U.S.A. 91:4480-4484(1994). RN [9] RP REVIEW. RX PubMed=17127321; DOI=10.2741/2103; RA Touw I.P., van de Geijn G.J.; RT "Granulocyte colony-stimulating factor and its receptor in normal myeloid RT cell development, leukemia and related blood cell disorders."; RL Front. Biosci. 12:800-815(2007). RN [10] RP POSSIBLE ASSOCIATION WITH SCN. RX PubMed=19120359; DOI=10.1111/j.1365-2141.2008.07425.x; RA Zeidler C., Germeshausen M., Klein C., Welte K.; RT "Clinical implications of ELA2-, HAX1-, and G-CSF-receptor (CSF3R) RT mutations in severe congenital neutropenia."; RL Br. J. Haematol. 144:459-467(2009). RN [11] RP STRUCTURE BY NMR OF 227-334. RX PubMed=9187659; DOI=10.1038/nsb0697-498; RA Yamasaki K., Naito S., Anaguchi H., Ohkubo T., Ota Y.; RT "Solution structure of an extracellular domain containing the WSxWS motif RT of the granulocyte colony-stimulating factor receptor and its interaction RT with ligand."; RL Nat. Struct. Biol. 4:498-504(1997). RN [12] RP 3D-STRUCTURE MODELING OF 125-331. RX PubMed=9368043; DOI=10.1074/jbc.272.47.29735; RA Layton J.E., Iaria J., Smith D.K., Treutlein H.R.; RT "Identification of a ligand-binding site on the granulocyte colony- RT stimulating factor receptor by molecular modeling and mutagenesis."; RL J. Biol. Chem. 272:29735-29741(1997). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 25-333 IN COMPLEX WITH CSF3, RP GLYCOSYLATION AT ASN-134, DISULFIDE BONDS, AND SUBUNIT. RX PubMed=16492764; DOI=10.1073/pnas.0511264103; RA Tamada T., Honjo E., Maeda Y., Okamoto T., Ishibashi M., Tokunaga M., RA Kuroki R.; RT "Homodimeric cross-over structure of the human granulocyte colony- RT stimulating factor (GCSF) receptor signaling complex."; RL Proc. Natl. Acad. Sci. U.S.A. 103:3135-3140(2006). RN [14] RP INVOLVEMENT IN SEVERE CONGENITAL NEUTROPENIA, VARIANT HIS-229, AND RP CHARACTERIZATION OF VARIANT HIS-229. RX PubMed=10449521; DOI=10.1084/jem.190.4.497; RA Ward A.C., van Aesch Y.M., Gits J., Schelen A.M., de Koning J.P., RA van Leeuwen D., Freedman M.H., Touw I.P.; RT "Novel point mutation in the extracellular domain of the granulocyte RT colony-stimulating factor (G-CSF) receptor in a case of severe congenital RT neutropenia hyporesponsive to G-CSF treatment."; RL J. Exp. Med. 190:497-507(1999). RN [15] RP VARIANT NEUTROPHILIA ASN-640. RX PubMed=19620628; DOI=10.1084/jem.20090693; RA Plo I., Zhang Y., Le Couedic J.P., Nakatake M., Boulet J.M., Itaya M., RA Smith S.O., Debili N., Constantinescu S.N., Vainchenker W., Louache F., RA de Botton S.; RT "An activating mutation in the CSF3R gene induces a hereditary chronic RT neutrophilia."; RL J. Exp. Med. 206:1701-1707(2009). RN [16] RP INVOLVEMENT IN SCN7, VARIANT SCN7 CYS-308, CHARACTERIZATION OF VARIANT SCN7 RP CYS-308, SUBCELLULAR LOCATION, AND GLYCOSYLATION. RX PubMed=24753537; DOI=10.1182/blood-2013-11-535419; RA Triot A., Jaervinen P.M., Arostegui J.I., Murugan D., Kohistani N., RA Dapena Diaz J.L., Racek T., Puchalka J., Gertz E.M., Schaeffer A.A., RA Kotlarz D., Pfeifer D., Diaz de Heredia Rubio C., Ozdemir M.A., RA Patiroglu T., Karakukcu M., Sanchez de Toledo Codina J., Yaguee J., RA Touw I.P., Unal E., Klein C.; RT "Inherited biallelic CSF3R mutations in severe congenital neutropenia."; RL Blood 123:3811-3817(2014). RN [17] RP INVOLVEMENT IN SCN7. RX PubMed=26324699; DOI=10.1182/blood-2015-07-661264; RA Klimiankou M., Klimenkova O., Uenalan M., Zeidler A., Mellor-Heineke S., RA Kandabarau S., Skokowa J., Zeidler C., Welte K.; RT "GM-CSF stimulates granulopoiesis in a congenital neutropenia patient with RT loss-of-function biallelic heterozygous CSF3R mutations."; RL Blood 126:1865-1867(2015). CC -!- FUNCTION: Receptor for granulocyte colony-stimulating factor (CSF3), CC essential for granulocytic maturation. Plays a crucial role in the CC proliferation, differientation and survival of cells along the CC neutrophilic lineage. In addition it may function in some adhesion or CC recognition events at the cell surface. {ECO:0000269|PubMed:7514305}. CC -!- SUBUNIT: Homodimer. The dimeric receptor binds two CSF3 molecules. CC Interacts with CEACAM1; down-regulates the CSF3R-STAT3 pathway through CC recruitment of PTPN6 that dephosphorylates CSF3R (By similarity). CC {ECO:0000250|UniProtKB:P40223, ECO:0000269|PubMed:16492764}. CC -!- INTERACTION: CC Q99062; P40763: STAT3; NbExp=4; IntAct=EBI-7331284, EBI-518675; CC Q99062; P0CG48: UBC; NbExp=2; IntAct=EBI-7331284, EBI-3390054; CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24753537}; CC Single-pass type I membrane protein {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Comment=Additional isoforms seem to exist. Experimental confirmation CC may be lacking for some isoforms.; CC Name=1; Synonyms=GCSFR-1; CC IsoId=Q99062-1; Sequence=Displayed; CC Name=2; Synonyms=GCSFR-2; CC IsoId=Q99062-2; Sequence=VSP_001674; CC Name=3; Synonyms=GCSFR-3; CC IsoId=Q99062-3; Sequence=VSP_001673; CC Name=4; Synonyms=GCSFR-4, D7; CC IsoId=Q99062-4; Sequence=VSP_001671, VSP_001672; CC -!- TISSUE SPECIFICITY: One or several isoforms have been found in CC myelogenous leukemia cell line KG-1, leukemia U-937 cell line, in bone CC marrow cells, placenta, and peripheral blood granulocytes. Isoform CC GCSFR-2 is found only in leukemia U-937 cells. Isoform GCSFR-3 is CC highly expressed in placenta. CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein CC folding and thereby efficient intracellular transport and cell-surface CC receptor binding. {ECO:0000269|PubMed:1717255}. CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or CC activation. {ECO:0000269|PubMed:1717255}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:24753537}. CC -!- DISEASE: Hereditary neutrophilia (NEUTROPHILIA) [MIM:162830]: A form of CC lifelong, persistent neutrophilia, a condition characterized by an CC increase in the number of neutrophils in the blood. CC {ECO:0000269|PubMed:19620628}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Neutropenia, severe congenital 7, autosomal recessive (SCN7) CC [MIM:617014]: A form of severe congenital neutropenia, a disorder of CC hematopoiesis characterized by maturation arrest of granulopoiesis at CC the level of promyelocytes with peripheral blood absolute neutrophil CC counts below 0.5 x 10(9)/l and early onset of severe bacterial CC infections. {ECO:0000269|PubMed:24753537, ECO:0000269|PubMed:26324699}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- MISCELLANEOUS: Mutations in CSF3R acquired in multipotent hematopoietic CC progenitor cells and resulting in truncated hyper-responsive forms of CC the receptor, have been identified in most cases of severe congenital CC neutropenia (SCN). Patients carrying these mutations are at risk for CC developing myelodysplastic syndromes and/or acute myeloid leukemia. CC Constitutive mutations leading to hyporesponsive forms of the receptor CC are responsible for the refractoriness to CSF3 treatment observed in CC some SCN patients. CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 2 CC subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/csf3r/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X55721; CAA39253.1; -; mRNA. DR EMBL; X55720; CAA39252.1; -; mRNA. DR EMBL; M59818; AAA63176.1; -; mRNA. DR EMBL; M59819; AAA63177.1; -; mRNA. DR EMBL; M59820; AAA63178.1; -; mRNA. DR EMBL; S71484; AAB20660.1; -; Genomic_DNA. DR EMBL; AY148100; AAN05790.1; -; Genomic_DNA. DR EMBL; BC053585; AAH53585.1; -; mRNA. DR CCDS; CCDS412.1; -. [Q99062-4] DR CCDS; CCDS413.1; -. [Q99062-1] DR CCDS; CCDS414.1; -. [Q99062-3] DR PIR; B38252; B38252. DR PIR; C38252; C38252. DR PIR; JH0329; JH0329. DR RefSeq; NP_000751.1; NM_000760.3. [Q99062-1] DR RefSeq; NP_724781.1; NM_156039.3. [Q99062-3] DR RefSeq; NP_758519.1; NM_172313.2. [Q99062-4] DR RefSeq; XP_011539050.1; XM_011540748.2. DR RefSeq; XP_016855859.1; XM_017000370.1. DR PDB; 2D9Q; X-ray; 2.80 A; B=25-332. DR PDBsum; 2D9Q; -. DR AlphaFoldDB; Q99062; -. DR SMR; Q99062; -. DR BioGRID; 107828; 20. DR CORUM; Q99062; -. DR DIP; DIP-5788N; -. DR ELM; Q99062; -. DR IntAct; Q99062; 3. DR MINT; Q99062; -. DR STRING; 9606.ENSP00000362195; -. DR BindingDB; Q99062; -. DR ChEMBL; CHEMBL1996; -. DR DrugBank; DB15001; Eflapegrastim. DR DrugBank; DB05249; FavId. DR DrugBank; DB00099; Filgrastim. DR DrugBank; DB13144; Lenograstim. DR DrugBank; DB13200; Lipegfilgrastim. DR DrugBank; DB00019; Pegfilgrastim. DR DrugCentral; Q99062; -. DR GuidetoPHARMACOLOGY; 1719; -. DR GlyCosmos; Q99062; 8 sites, No reported glycans. DR GlyGen; Q99062; 8 sites. DR iPTMnet; Q99062; -. DR PhosphoSitePlus; Q99062; -. DR BioMuta; CSF3R; -. DR DMDM; 729564; -. DR MassIVE; Q99062; -. DR PaxDb; 9606-ENSP00000362195; -. DR PeptideAtlas; Q99062; -. DR ProteomicsDB; 78226; -. [Q99062-1] DR ProteomicsDB; 78227; -. [Q99062-2] DR ProteomicsDB; 78228; -. [Q99062-3] DR ProteomicsDB; 78229; -. [Q99062-4] DR ABCD; Q99062; 2 sequenced antibodies. DR Antibodypedia; 4479; 714 antibodies from 41 providers. DR DNASU; 1441; -. DR Ensembl; ENST00000373103.5; ENSP00000362195.1; ENSG00000119535.20. [Q99062-3] DR Ensembl; ENST00000373104.5; ENSP00000362196.1; ENSG00000119535.20. [Q99062-4] DR Ensembl; ENST00000373106.6; ENSP00000362198.2; ENSG00000119535.20. [Q99062-1] DR GeneID; 1441; -. DR KEGG; hsa:1441; -. DR MANE-Select; ENST00000373106.6; ENSP00000362198.2; NM_000760.4; NP_000751.1. DR UCSC; uc001cav.3; human. [Q99062-1] DR AGR; HGNC:2439; -. DR CTD; 1441; -. DR DisGeNET; 1441; -. DR GeneCards; CSF3R; -. DR HGNC; HGNC:2439; CSF3R. DR HPA; ENSG00000119535; Tissue enhanced (bone marrow, lung, lymphoid tissue). DR MalaCards; CSF3R; -. DR MIM; 138971; gene. DR MIM; 162830; phenotype. DR MIM; 617014; phenotype. DR neXtProt; NX_Q99062; -. DR OpenTargets; ENSG00000119535; -. DR Orphanet; 98824; Atypical chronic myeloid leukemia. DR Orphanet; 420702; Autosomal recessive severe congenital neutropenia due to CSF3R deficiency. DR Orphanet; 86829; Chronic neutrophilic leukemia. DR Orphanet; 279943; Hereditary neutrophilia. DR PharmGKB; PA26942; -. DR VEuPathDB; HostDB:ENSG00000119535; -. DR eggNOG; ENOG502QT3H; Eukaryota. DR GeneTree; ENSGT00940000158915; -. DR HOGENOM; CLU_017990_0_0_1; -. DR InParanoid; Q99062; -. DR OMA; SYCSIPR; -. DR OrthoDB; 5354422at2759; -. DR PhylomeDB; Q99062; -. DR TreeFam; TF338122; -. DR PathwayCommons; Q99062; -. DR Reactome; R-HSA-449836; Other interleukin signaling. DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis. DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF). DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling. DR SignaLink; Q99062; -. DR SIGNOR; Q99062; -. DR BioGRID-ORCS; 1441; 12 hits in 1152 CRISPR screens. DR ChiTaRS; CSF3R; human. DR EvolutionaryTrace; Q99062; -. DR GeneWiki; Granulocyte_colony-stimulating_factor_receptor; -. DR GenomeRNAi; 1441; -. DR Pharos; Q99062; Tclin. DR PRO; PR:Q99062; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q99062; Protein. DR Bgee; ENSG00000119535; Expressed in granulocyte and 120 other cell types or tissues. DR ExpressionAtlas; Q99062; baseline and differential. DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0043235; C:receptor complex; IBA:GO_Central. DR GO; GO:0019955; F:cytokine binding; IBA:GO_Central. DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central. DR GO; GO:0051916; F:granulocyte colony-stimulating factor binding; IEA:Ensembl. DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc. DR GO; GO:0097186; P:amelogenesis; IEA:Ensembl. DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0006952; P:defense response; TAS:ProtInc. DR GO; GO:0030593; P:neutrophil chemotaxis; IEA:Ensembl. DR GO; GO:0045637; P:regulation of myeloid cell differentiation; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; NAS:ProtInc. DR CDD; cd00063; FN3; 4. DR Gene3D; 2.60.40.10; Immunoglobulins; 6. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR036116; FN3_sf. DR InterPro; IPR003529; Hematopoietin_rcpt_Gp130_CS. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR010457; IgC2-like_lig-bd. DR PANTHER; PTHR23036; CYTOKINE RECEPTOR; 1. DR PANTHER; PTHR23036:SF103; GRANULOCYTE COLONY-STIMULATING FACTOR RECEPTOR; 1. DR Pfam; PF00041; fn3; 1. DR Pfam; PF06328; Lep_receptor_Ig; 1. DR SMART; SM00060; FN3; 5. DR SUPFAM; SSF49265; Fibronectin type III; 4. DR SUPFAM; SSF48726; Immunoglobulin; 1. DR PROSITE; PS50853; FN3; 5. DR PROSITE; PS01353; HEMATOPO_REC_L_F2; 1. DR Genevisible; Q99062; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell adhesion; Cell membrane; KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; KW Immunoglobulin domain; Membrane; Receptor; Reference proteome; Repeat; KW Secreted; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..24 FT CHAIN 25..836 FT /note="Granulocyte colony-stimulating factor receptor" FT /id="PRO_0000010874" FT TOPO_DOM 25..627 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 628..650 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 651..836 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 25..117 FT /note="Ig-like C2-type" FT DOMAIN 125..230 FT /note="Fibronectin type-III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 233..332 FT /note="Fibronectin type-III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 334..430 FT /note="Fibronectin type-III 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 431..528 FT /note="Fibronectin type-III 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 530..623 FT /note="Fibronectin type-III 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT MOTIF 318..322 FT /note="WSXWS motif" FT MOTIF 658..666 FT /note="Box 1 motif" FT CARBOHYD 51 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 93 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 128 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 134 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16492764" FT CARBOHYD 389 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 474 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 579 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 610 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 26..52 FT /evidence="ECO:0000269|PubMed:16492764" FT DISULFID 46..101 FT /evidence="ECO:0000269|PubMed:16492764" FT DISULFID 131..142 FT /evidence="ECO:0000269|PubMed:16492764" FT DISULFID 167..218 FT /evidence="ECO:0000269|PubMed:16492764" FT DISULFID 177..186 FT /evidence="ECO:0000269|PubMed:16492764" FT DISULFID 248..295 FT /evidence="ECO:0000269|PubMed:16492764" FT DISULFID 266..309 FT /evidence="ECO:0000269|PubMed:16492764" FT VAR_SEQ 622..836 FT /note="EGSELHIILGLFGLLLLLTCLCGTAWLCCSPNRKNPLWPSVPDPAHSSLGSW FT VPTIMEEDAFQLPGLGTPPITKLTVLEEDEKKPVPWESHNSSETCGLPTLVQTYVLQGD FT PRAVSTQPQSQSGTSDQVLYGQLLGSPTSPGPGHYLRCDSTQPLLAGLTPSPKSYENLW FT FQASPLGTLVTPAPSQEDDCVFGPLLNFPLLQGIRVHGMEALGSF -> APTGRIPSGQ FT VSQTQLTAAWAPGCPQSWRRMPSSCPALARHPSPSSQCWRRMKRSRCPGSPITAQRPVA FT SPLWSRPMCSRGTQEQFPPSPNPSLAPAIRSFMGSCWAAPQAQGQGTISAVTPLSPSWR FT ASPPAPSPMRTSGSRPAPWGPW (in isoform 2)" FT /evidence="ECO:0000303|PubMed:1701053" FT /id="VSP_001674" FT VAR_SEQ 680 FT /note="E -> ELPGPRQGQWLGQTSEMSRALTPHPCVQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:1701053" FT /id="VSP_001673" FT VAR_SEQ 750..783 FT /note="VLYGQLLGSPTSPGPGHYLRCDSTQPLLAGLTPS -> AGPPRRSAYFKDQI FT MLHPAPPNGLLCLFPITSVL (in isoform 4)" FT /evidence="ECO:0000303|PubMed:2147944" FT /id="VSP_001671" FT VAR_SEQ 784..836 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:2147944" FT /id="VSP_001672" FT VARIANT 229 FT /note="P -> H (found in a patient with apparently autosomal FT dominant severe congenital neutropenia; likely pathogenic; FT affects CSF3 mediated proliferation and survival of myeloid FT cells; abrogates receptor signaling by altering ligand FT binding; dominant negative effect; dbSNP:rs764202764)" FT /evidence="ECO:0000269|PubMed:10449521" FT /id="VAR_062517" FT VARIANT 231 FT /note="M -> T (in dbSNP:rs3917973)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_014325" FT VARIANT 308 FT /note="R -> C (in SCN7; decreases localization to plasma FT membrane; decreases receptor signaling; dbSNP:rs606231473)" FT /evidence="ECO:0000269|PubMed:24753537" FT /id="VAR_077011" FT VARIANT 320 FT /note="D -> N (in dbSNP:rs3918018)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_014326" FT VARIANT 346 FT /note="Q -> R (in dbSNP:rs3917974)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_014327" FT VARIANT 405 FT /note="E -> K (in dbSNP:rs3918019)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_014328" FT VARIANT 440 FT /note="R -> Q (in dbSNP:rs3918020)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_014329" FT VARIANT 510 FT /note="D -> H (in dbSNP:rs3917991)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_014330" FT VARIANT 562 FT /note="Y -> H (in dbSNP:rs3917996)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_014331" FT VARIANT 583 FT /note="R -> C (in dbSNP:rs3917997)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_014332" FT VARIANT 640 FT /note="T -> N (in neutrophilia; dbSNP:rs121918426)" FT /evidence="ECO:0000269|PubMed:19620628" FT /id="VAR_063065" FT STRAND 29..32 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 34..36 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 42..46 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 62..67 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 79..81 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 85..90 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 94..119 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 127..134 FT /evidence="ECO:0007829|PDB:2D9Q" FT TURN 135..138 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 139..145 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 155..162 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 174..177 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 184..189 FT /evidence="ECO:0007829|PDB:2D9Q" FT HELIX 190..192 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 195..197 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 199..207 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 210..213 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 217..219 FT /evidence="ECO:0007829|PDB:2D9Q" FT HELIX 221..224 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 231..234 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 249..254 FT /evidence="ECO:0007829|PDB:2D9Q" FT HELIX 257..259 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 264..275 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 280..285 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 289..294 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 303..311 FT /evidence="ECO:0007829|PDB:2D9Q" FT STRAND 325..327 FT /evidence="ECO:0007829|PDB:2D9Q" SQ SEQUENCE 836 AA; 92156 MW; 3531ADDC979D4BC3 CRC64; MARLGNCSLT WAALIILLLP GSLEECGHIS VSAPIVHLGD PITASCIIKQ NCSHLDPEPQ ILWRLGAELQ PGGRQQRLSD GTQESIITLP HLNHTQAFLS CCLNWGNSLQ ILDQVELRAG YPPAIPHNLS CLMNLTTSSL ICQWEPGPET HLPTSFTLKS FKSRGNCQTQ GDSILDCVPK DGQSHCCIPR KHLLLYQNMG IWVQAENALG TSMSPQLCLD PMDVVKLEPP MLRTMDPSPE AAPPQAGCLQ LCWEPWQPGL HINQKCELRH KPQRGEASWA LVGPLPLEAL QYELCGLLPA TAYTLQIRCI RWPLPGHWSD WSPSLELRTT ERAPTVRLDT WWRQRQLDPR TVQLFWKPVP LEEDSGRIQG YVVSWRPSGQ AGAILPLCNT TELSCTFHLP SEAQEVALVA YNSAGTSRPT PVVFSESRGP ALTRLHAMAR DPHSLWVGWE PPNPWPQGYV IEWGLGPPSA SNSNKTWRME QNGRATGFLL KENIRPFQLY EIIVTPLYQD TMGPSQHVYA YSQEMAPSHA PELHLKHIGK TWAQLEWVPE PPELGKSPLT HYTIFWTNAQ NQSFSAILNA SSRGFVLHGL EPASLYHIHL MAASQAGATN STVLTLMTLT PEGSELHIIL GLFGLLLLLT CLCGTAWLCC SPNRKNPLWP SVPDPAHSSL GSWVPTIMEE DAFQLPGLGT PPITKLTVLE EDEKKPVPWE SHNSSETCGL PTLVQTYVLQ GDPRAVSTQP QSQSGTSDQV LYGQLLGSPT SPGPGHYLRC DSTQPLLAGL TPSPKSYENL WFQASPLGTL VTPAPSQEDD CVFGPLLNFP LLQGIRVHGM EALGSF //