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 16-OCT-2019, entry version 195. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Park L., 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, RT immunoglobulin, 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 RT factor 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- RT stimulating factor receptor."; RL J. Immunol. 148:259-266(1992). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-231; ASN-320; RP ARG-346; 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 RT project: 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 RT receptor. Interaction with its ligand and identification of a domain RT in close 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 RT myeloid 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 RT motif of the granulocyte colony-stimulating factor receptor and its RT interaction 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 RT congenital 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., RA Louache F., 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 RP SCN7 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 RT 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., RA Mellor-Heineke S., Kandabarau S., Skokowa J., Zeidler C., Welte K.; RT "GM-CSF stimulates granulopoiesis in a congenital neutropenia patient RT with loss-of-function biallelic heterozygous CSF3R mutations."; RL Blood 126:1865-1867(2015). CC -!- FUNCTION: Receptor for granulocyte colony-stimulating factor CC (CSF3), essential for granulocytic maturation. Plays a crucial CC role in the proliferation, differientation and survival of cells CC along the neutrophilic lineage. In addition it may function in CC some adhesion or recognition events at the cell surface. CC {ECO:0000269|PubMed:7514305}. CC -!- SUBUNIT: Homodimer. The dimeric receptor binds two CSF3 molecules. CC Interacts with CEACAM1; down-regulates the CSF3R-STAT3 pathway CC through recruitment of PTPN6 that dephosphorylates CSF3R (By CC similarity). {ECO:0000250|UniProtKB:P40223, CC ECO:0000269|PubMed:16492764}. CC -!- INTERACTION: CC P40763:STAT3; NbExp=4; IntAct=EBI-7331284, EBI-518675; CC 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 CC confirmation 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 CC bone marrow cells, placenta, and peripheral blood granulocytes. CC Isoform GCSFR-2 is found only in leukemia U-937 cells. Isoform CC GCSFR-3 is 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- CC surface 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 CC form of lifelong, persistent neutrophilia, a condition CC characterized by an increase in the number of neutrophils in the CC blood. {ECO:0000269|PubMed:19620628}. Note=The disease is caused CC by mutations affecting the gene represented in this entry. CC -!- DISEASE: Neutropenia, severe congenital 7, autosomal recessive CC (SCN7) [MIM:617014]: A form of severe congenital neutropenia, a CC disorder of hematopoiesis characterized by maturation arrest of CC granulopoiesis at the level of promyelocytes with peripheral blood CC absolute neutrophil counts below 0.5 x 10(9)/l and early onset of CC severe bacterial infections. {ECO:0000269|PubMed:24753537, CC ECO:0000269|PubMed:26324699}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Mutations in CSF3R acquired in multipotent CC hematopoietic progenitor cells and resulting in truncated hyper- CC responsive forms of the receptor, have been identified in most CC cases of severe congenital neutropenia (SCN). Patients carrying CC these mutations are at risk for developing myelodysplastic CC syndromes and/or acute myeloid leukemia. Constitutive mutations CC leading to hyporesponsive forms of the receptor are responsible CC for the refractoriness to CSF3 treatment observed in some SCN CC 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. [Q99062-3] DR RefSeq; XP_016855859.1; XM_017000370.1. [Q99062-3] DR PDB; 1AZ7; Model; -; A=125-331. DR PDB; 2D9Q; X-ray; 2.80 A; B=25-332. DR PDBsum; 1AZ7; -. DR PDBsum; 2D9Q; -. 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; DB05249; FavId. DR DrugBank; DB00099; Filgrastim. DR DrugBank; DB13144; Lenograstim. DR DrugBank; DB13200; Lipegfilgrastim. DR DrugBank; DB00019; Pegfilgrastim. DR DrugCentral; Q99062; -. DR iPTMnet; Q99062; -. DR PhosphoSitePlus; Q99062; -. DR BioMuta; CSF3R; -. DR DMDM; 729564; -. DR MassIVE; Q99062; -. DR PaxDb; Q99062; -. DR PeptideAtlas; Q99062; -. DR PRIDE; Q99062; -. DR ProteomicsDB; 78226; -. [Q99062-1] DR ProteomicsDB; 78227; -. [Q99062-2] DR ProteomicsDB; 78228; -. [Q99062-3] DR ProteomicsDB; 78229; -. [Q99062-4] DR Ensembl; ENST00000331941; ENSP00000332180; ENSG00000119535. [Q99062-4] DR Ensembl; ENST00000361632; ENSP00000355406; ENSG00000119535. [Q99062-1] DR Ensembl; ENST00000373103; ENSP00000362195; ENSG00000119535. [Q99062-3] DR Ensembl; ENST00000373104; ENSP00000362196; ENSG00000119535. [Q99062-4] DR Ensembl; ENST00000373106; ENSP00000362198; ENSG00000119535. [Q99062-1] DR GeneID; 1441; -. DR KEGG; hsa:1441; -. DR UCSC; uc001cav.3; human. [Q99062-1] DR CTD; 1441; -. DR DisGeNET; 1441; -. DR GeneCards; CSF3R; -. DR HGNC; HGNC:2439; CSF3R. DR HPA; CAB017116; -. DR HPA; HPA048086; -. 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 eggNOG; ENOG410IGHT; Eukaryota. DR eggNOG; ENOG410XVIU; LUCA. DR GeneTree; ENSGT00940000158915; -. DR HOGENOM; HOG000231142; -. DR InParanoid; Q99062; -. DR KO; K05061; -. DR OMA; LQMRCIR; -. DR OrthoDB; 144839at2759; -. DR PhylomeDB; Q99062; -. DR TreeFam; TF338122; -. DR Reactome; R-HSA-449836; Other interleukin signaling. DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis. DR SignaLink; Q99062; -. DR SIGNOR; Q99062; -. DR ChiTaRS; CSF3R; human. DR EvolutionaryTrace; Q99062; -. DR GeneWiki; Granulocyte_colony-stimulating_factor_receptor; -. DR GenomeRNAi; 1441; -. DR Pharos; Q99062; -. DR PRO; PR:Q99062; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000119535; Expressed in 145 organ(s), highest expression level in blood. DR ExpressionAtlas; Q99062; baseline and differential. DR Genevisible; Q99062; HS. 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:0005887; C:integral component of plasma membrane; TAS:ProtInc. 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; TAS:Reactome. 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; -; 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 Pfam; PF00041; fn3; 1. DR Pfam; PF06328; Lep_receptor_Ig; 1. DR SMART; SM00060; FN3; 5. DR SUPFAM; SSF48726; SSF48726; 1. DR SUPFAM; SSF49265; SSF49265; 4. DR PROSITE; PS50853; FN3; 5. DR PROSITE; PS01353; HEMATOPO_REC_L_F2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell adhesion; Cell membrane; KW Complete proteome; Direct protein sequencing; Disease mutation; KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane; KW Polymorphism; Receptor; Reference proteome; Repeat; Secreted; Signal; KW Transmembrane; Transmembrane helix. FT SIGNAL 1 24 FT CHAIN 25 836 Granulocyte colony-stimulating factor FT receptor. FT /FTId=PRO_0000010874. FT TOPO_DOM 25 627 Extracellular. {ECO:0000255}. FT TRANSMEM 628 650 Helical. {ECO:0000255}. FT TOPO_DOM 651 836 Cytoplasmic. {ECO:0000255}. FT DOMAIN 25 117 Ig-like C2-type. FT DOMAIN 125 230 Fibronectin type-III 1. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 233 332 Fibronectin type-III 2. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 334 430 Fibronectin type-III 3. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 431 528 Fibronectin type-III 4. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 530 623 Fibronectin type-III 5. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT MOTIF 318 322 WSXWS motif. FT MOTIF 658 666 Box 1 motif. FT CARBOHYD 51 51 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 93 93 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 128 128 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 134 134 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16492764}. FT CARBOHYD 389 389 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 474 474 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 579 579 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 610 610 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 26 52 {ECO:0000269|PubMed:16492764}. FT DISULFID 46 101 {ECO:0000269|PubMed:16492764}. FT DISULFID 131 142 {ECO:0000269|PubMed:16492764}. FT DISULFID 167 218 {ECO:0000269|PubMed:16492764}. FT DISULFID 177 186 {ECO:0000269|PubMed:16492764}. FT DISULFID 248 295 {ECO:0000269|PubMed:16492764}. FT DISULFID 266 309 {ECO:0000269|PubMed:16492764}. FT VAR_SEQ 622 836 EGSELHIILGLFGLLLLLTCLCGTAWLCCSPNRKNPLWPSV FT PDPAHSSLGSWVPTIMEEDAFQLPGLGTPPITKLTVLEEDE FT KKPVPWESHNSSETCGLPTLVQTYVLQGDPRAVSTQPQSQS FT GTSDQVLYGQLLGSPTSPGPGHYLRCDSTQPLLAGLTPSPK FT SYENLWFQASPLGTLVTPAPSQEDDCVFGPLLNFPLLQGIR FT VHGMEALGSF -> APTGRIPSGQVSQTQLTAAWAPGCPQS FT WRRMPSSCPALARHPSPSSQCWRRMKRSRCPGSPITAQRPV FT ASPLWSRPMCSRGTQEQFPPSPNPSLAPAIRSFMGSCWAAP FT QAQGQGTISAVTPLSPSWRASPPAPSPMRTSGSRPAPWGPW FT (in isoform 2). FT {ECO:0000303|PubMed:1701053}. FT /FTId=VSP_001674. FT VAR_SEQ 680 680 E -> ELPGPRQGQWLGQTSEMSRALTPHPCVQ (in FT isoform 3). {ECO:0000303|PubMed:1701053}. FT /FTId=VSP_001673. FT VAR_SEQ 750 783 VLYGQLLGSPTSPGPGHYLRCDSTQPLLAGLTPS -> AGP FT PRRSAYFKDQIMLHPAPPNGLLCLFPITSVL (in FT isoform 4). {ECO:0000303|PubMed:2147944}. FT /FTId=VSP_001671. FT VAR_SEQ 784 836 Missing (in isoform 4). FT {ECO:0000303|PubMed:2147944}. FT /FTId=VSP_001672. FT VARIANT 229 229 P -> H (probable disease-associated FT mutation found in a patient with FT apparently autosomal dominant severe FT congenital neutropenia; affects CSF3 FT mediated proliferation and survival of FT myeloid cells; abrogates receptor FT signaling by altering ligand binding; FT dominant negative effect; FT dbSNP:rs764202764). FT {ECO:0000269|PubMed:10449521}. FT /FTId=VAR_062517. FT VARIANT 231 231 M -> T (in dbSNP:rs3917973). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_014325. FT VARIANT 308 308 R -> C (in SCN7; decreases localization FT to plasma membrane; decreases receptor FT signaling; dbSNP:rs606231473). FT {ECO:0000269|PubMed:24753537}. FT /FTId=VAR_077011. FT VARIANT 320 320 D -> N (in dbSNP:rs3918018). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_014326. FT VARIANT 346 346 Q -> R (in dbSNP:rs3917974). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_014327. FT VARIANT 405 405 E -> K (in dbSNP:rs3918019). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_014328. FT VARIANT 440 440 R -> Q (in dbSNP:rs3918020). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_014329. FT VARIANT 510 510 D -> H (in dbSNP:rs3917991). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_014330. FT VARIANT 562 562 Y -> H (in dbSNP:rs3917996). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_014331. FT VARIANT 583 583 R -> C (in dbSNP:rs3917997). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_014332. FT VARIANT 640 640 T -> N (in neutrophilia; FT dbSNP:rs121918426). FT {ECO:0000269|PubMed:19620628}. FT /FTId=VAR_063065. FT STRAND 29 32 {ECO:0000244|PDB:2D9Q}. FT STRAND 34 36 {ECO:0000244|PDB:2D9Q}. FT STRAND 42 46 {ECO:0000244|PDB:2D9Q}. FT STRAND 62 67 {ECO:0000244|PDB:2D9Q}. FT STRAND 79 81 {ECO:0000244|PDB:2D9Q}. FT STRAND 85 90 {ECO:0000244|PDB:2D9Q}. FT STRAND 94 119 {ECO:0000244|PDB:2D9Q}. FT STRAND 127 134 {ECO:0000244|PDB:2D9Q}. FT TURN 135 138 {ECO:0000244|PDB:2D9Q}. FT STRAND 139 145 {ECO:0000244|PDB:2D9Q}. FT STRAND 155 162 {ECO:0000244|PDB:2D9Q}. FT STRAND 174 177 {ECO:0000244|PDB:2D9Q}. FT STRAND 184 189 {ECO:0000244|PDB:2D9Q}. FT HELIX 190 192 {ECO:0000244|PDB:2D9Q}. FT STRAND 195 197 {ECO:0000244|PDB:2D9Q}. FT STRAND 199 207 {ECO:0000244|PDB:2D9Q}. FT STRAND 210 213 {ECO:0000244|PDB:2D9Q}. FT STRAND 217 219 {ECO:0000244|PDB:2D9Q}. FT HELIX 221 224 {ECO:0000244|PDB:2D9Q}. FT STRAND 231 234 {ECO:0000244|PDB:2D9Q}. FT STRAND 249 254 {ECO:0000244|PDB:2D9Q}. FT HELIX 257 259 {ECO:0000244|PDB:2D9Q}. FT STRAND 264 275 {ECO:0000244|PDB:2D9Q}. FT STRAND 280 285 {ECO:0000244|PDB:2D9Q}. FT STRAND 289 294 {ECO:0000244|PDB:2D9Q}. FT STRAND 303 311 {ECO:0000244|PDB:2D9Q}. FT STRAND 325 327 {ECO:0000244|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 //