CSF1R_DANRE
ID CSF1R_DANRE Reviewed; 977 AA.
AC Q9I8N6;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Macrophage colony-stimulating factor 1 receptor;
DE AltName: Full=CSF-1 receptor;
DE Short=CSF-1-R;
DE Short=CSF-1R;
DE Short=M-CSF-R;
DE EC=2.7.10.1;
DE AltName: Full=Proto-oncogene c-Fms homolog;
DE Flags: Precursor;
GN Name=csf1r; Synonyms=fms;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC STRAIN=AB;
RX PubMed=10862741; DOI=10.1242/dev.127.14.3031;
RA Parichy D.M., Ransom D.G., Paw B., Zon L.I., Johnson S.L.;
RT "An orthologue of the kit-related gene fms is required for development of
RT neural crest-derived xanthophores and a subpopulation of adult melanocytes
RT in the zebrafish, Danio rerio.";
RL Development 127:3031-3044(2000).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor
CC for CSF1 and plays an essential role in the regulation of survival,
CC proliferation and differentiation of hematopoietic precursor cells,
CC especially mononuclear phagocytes, such as macrophages and monocytes.
CC Plays an important role in innate immunity and in inflammatory
CC processes. Plays an important role in the regulation of osteoclast
CC proliferation and differentiation, the regulation of bone resorption,
CC and is required for normal bone development. Promotes reorganization of
CC the actin cytoskeleton, regulates formation of membrane ruffles, cell
CC adhesion and cell migration. Activates several signaling pathways in
CC response to ligand binding (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:10862741}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC of bound ligand. CSF1 binding leads to dimerization and activation by
CC autophosphorylation on tyrosine residues (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Homodimer. Interacts with CSF1 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Note=The autophosphorylated receptor is
CC ubiquitinated and internalized, leading to its degradation.
CC {ECO:0000250}.
CC -!- DOMAIN: The juxtamembrane domain functions as autoinhibitory region.
CC Phosphorylation of tyrosine residues in this region leads to a
CC conformation change and activation of the kinase (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: The activation loop plays an important role in the regulation
CC of kinase activity. Phosphorylation of tyrosine residues in this region
CC leads to a conformation change and activation of the kinase (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Autophosphorylated in response to CSF1 binding.
CC autophosphorylation, leading to its degradation. {ECO:0000250}.
CC -!- PTM: Ubiquitinated. Becomes rapidly polyubiquitinated after
CC autophosphorylation, leading to its degradation (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; AF240639; AAF76872.1; -; mRNA.
DR RefSeq; NP_571747.1; NM_131672.1.
DR AlphaFoldDB; Q9I8N6; -.
DR SMR; Q9I8N6; -.
DR STRING; 7955.ENSDARP00000089365; -.
DR PaxDb; Q9I8N6; -.
DR GeneID; 64274; -.
DR KEGG; dre:64274; -.
DR CTD; 64274; -.
DR ZFIN; ZDB-GENE-001205-1; csf1ra.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; Q9I8N6; -.
DR OrthoDB; 236292at2759; -.
DR PhylomeDB; Q9I8N6; -.
DR Reactome; R-DRE-449836; Other interleukin signaling.
DR PRO; PR:Q9I8N6; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:1990682; C:CSF1-CSF1R complex; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019955; F:cytokine binding; IEA:InterPro.
DR GO; GO:0005011; F:macrophage colony-stimulating factor receptor activity; IBA:GO_Central.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0048066; P:developmental pigmentation; IMP:ZFIN.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IBA:GO_Central.
DR GO; GO:0002383; P:immune response in brain or nervous system; IMP:ZFIN.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0048246; P:macrophage chemotaxis; IMP:ZFIN.
DR GO; GO:0030318; P:melanocyte differentiation; IMP:ZFIN.
DR GO; GO:0097324; P:melanocyte migration; IMP:ZFIN.
DR GO; GO:0014004; P:microglia differentiation; IMP:ZFIN.
DR GO; GO:0036035; P:osteoclast development; IMP:ZFIN.
DR GO; GO:0030316; P:osteoclast differentiation; IBA:GO_Central.
DR GO; GO:0043473; P:pigmentation; IMP:ZFIN.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IMP:ZFIN.
DR GO; GO:0061075; P:positive regulation of neural retina development; IMP:ZFIN.
DR GO; GO:0048070; P:regulation of developmental pigmentation; IMP:ZFIN.
DR GO; GO:0042481; P:regulation of odontogenesis; IGI:ZFIN.
DR GO; GO:2001204; P:regulation of osteoclast development; IMP:ZFIN.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0050936; P:xanthophore differentiation; IMP:ZFIN.
DR Gene3D; 2.60.40.10; -; 5.
DR InterPro; IPR030658; CSF-1_receptor.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF500947; CSF-1_receptor; 1.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 5.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Disulfide bond; Glycoprotein; Immunity;
KW Immunoglobulin domain; Inflammatory response; Innate immunity; Kinase;
KW Membrane; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome;
KW Repeat; Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..977
FT /note="Macrophage colony-stimulating factor 1 receptor"
FT /id="PRO_0000249006"
FT TOPO_DOM 19..519
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 520..540
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 541..977
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 22..109
FT /note="Ig-like C2-type 1"
FT DOMAIN 120..198
FT /note="Ig-like C2-type 2"
FT DOMAIN 213..305
FT /note="Ig-like C2-type 3"
FT DOMAIN 316..407
FT /note="Ig-like C2-type 4"
FT DOMAIN 408..513
FT /note="Ig-like C2-type 5"
FT DOMAIN 584..917
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 544..576
FT /note="Regulatory juxtamembrane domain"
FT /evidence="ECO:0000250"
FT REGION 799..821
FT /note="Activation loop"
FT /evidence="ECO:0000250"
FT REGION 919..977
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 919..938
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 942..956
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 781
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 590..598
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 618
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 563
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 701
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 725
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 812
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 929
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 974
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 286
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 361
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 424
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 455
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 48..92
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 138..187
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 234..289
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 430..495
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 977 AA; 110188 MW; C91A2F339E746A58 CRC64;
MFFALLFLIG ILLGQVQGWS EPRIRLSSGA LAGTDVILES GSPLQLVCEG DGPVTFLPRL
AKHKRYISKE VGKIRSFRVE KTTVDFTGTY KCVYMNGNDS NLSSSVHVFV RDSRVLFVSP
STSLRYVRKE GEDLLLPCLL TDPEATDFTF RMDNGSAAPY GMNITYDPRK GVLIRNVHPG
FNADYICCAR IGGAEKVSKI FSINIIQRLR FPPYVYLKRN EYVKLVGERL QISCTTNNPN
FYYNVTWTHS SRMLPKAEEK STMEGDRLAI ESILTIPSVQ LSHTGNITCT GQNEAGANSS
TTQLLVVEEP YIRLSPKLSS KLTHRGLSIE VSEGDDVDLG VLIEAYPPLT SHKWETPTSH
NASLPENRFF NHNDRYEALL LLKRLNFEEI GQYTLNVKNS MKSASITFDI KMYTKPVARV
KWENVTTLSC RSYGYPAPSI LWYQCTGIRT TCPENTTDLQ PIQTQTVEFQ KESFGAVGVE
SVLTVGPNRR MTVVCVAFNL VGQGSDTFSM EVSDQIFTSA MCGSTVAMVV LGLLLIFMIY
KYKQKPRYEI RWKIIEATNG NNYTFIDPTQ LPYNEKWEFP RDKLKLGKTL GAGAFGKVVE
ATAYGLGKED NITRVAVKML KASAHPDERE ALMSELKILS HLGQHKNIVN LLGACTHGGP
VLVITEYCCH GDLLNFLRSK AENFLNFVMT IPNFPEPMTD YKNVSTERMF VRSDSGISST
CSDHYLDMRP VTSRPTNSAL DSSSECQEDS WPLDMDDLLR FSSQVAQGLD FLAAKNCIHR
DVAARNVLLT NSRVAKICDF GLARDIMNDS NYVVKGNARL PVKWMAPESI FECVYTVQSD
VWSYGIMLWE IFSLGKSPYP NILVDSKFYK MIKCGYQMSR PDFAPPEMYT IMKMCWNLDA
AERPTFSKIS QMIQRMLGET SEQQDTQEYK NIPTEAEAEQ QLESCDPVKH EDESFETSCD
QEEEDQPLMK PNNYQFC
