ID A0A3Q3W5X5_MOLML Unreviewed; 977 AA.
AC A0A3Q3W5X5;
DT 10-APR-2019, integrated into UniProtKB/TrEMBL.
DT 10-APR-2019, sequence version 1.
DT 28-JAN-2026, entry version 36.
DE RecName: Full=receptor protein-tyrosine kinase {ECO:0000256|ARBA:ARBA00011902};
DE EC=2.7.10.1 {ECO:0000256|ARBA:ARBA00011902};
OS Mola mola (Ocean sunfish) (Tetraodon mola).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC Eupercaria; Tetraodontiformes; Molidae; Mola.
OX NCBI_TaxID=94237 {ECO:0000313|Ensembl:ENSMMOP00000003949.1, ECO:0000313|Proteomes:UP000261620};
RN [1] {ECO:0000313|Ensembl:ENSMMOP00000003949.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (AUG-2025) to UniProtKB.
RN [2] {ECO:0000313|Ensembl:ENSMMOP00000003949.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-2025) to UniProtKB.
CC -!- FUNCTION: Tyrosine-protein kinase that acts as a 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. {ECO:0000256|ARBA:ARBA00058066}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] +
CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:61978, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000256|ARBA:ARBA00051243};
CC -!- SUBUNIT: Monomer. Homodimer. Interacts with CSF1.
CC {ECO:0000256|ARBA:ARBA00062014}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|ARBA:ARBA00004251};
CC Single-pass type I membrane protein {ECO:0000256|ARBA:ARBA00004251}.
CC Membrane {ECO:0000256|RuleBase:RU000311}; Single-pass type I membrane
CC protein {ECO:0000256|RuleBase:RU000311}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSF-1/PDGF receptor subfamily.
CC {ECO:0000256|RuleBase:RU000311}.
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DR AlphaFoldDB; A0A3Q3W5X5; -.
DR STRING; 94237.ENSMMOP00000003949; -.
DR Ensembl; ENSMMOT00000004021.1; ENSMMOP00000003949.1; ENSMMOG00000003160.1.
DR OMA; TIHKAKY; -.
DR Proteomes; UP000261620; Unplaced.
DR GO; GO:1990682; C:CSF1-CSF1R complex; IEA:TreeGrafter.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043235; C:receptor complex; IEA:TreeGrafter.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0019955; F:cytokine binding; IEA:InterPro.
DR GO; GO:0019838; F:growth factor binding; IEA:TreeGrafter.
DR GO; GO:0005011; F:macrophage colony-stimulating factor receptor activity; IEA:TreeGrafter.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0048513; P:animal organ development; IEA:UniProtKB-ARBA.
DR GO; GO:0007169; P:cell surface receptor protein tyrosine kinase signaling pathway; IEA:InterPro.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0030318; P:melanocyte differentiation; IEA:UniProtKB-ARBA.
DR GO; GO:0097324; P:melanocyte migration; IEA:UniProtKB-ARBA.
DR GO; GO:0030316; P:osteoclast differentiation; IEA:TreeGrafter.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:TreeGrafter.
DR GO; GO:0022603; P:regulation of anatomical structure morphogenesis; IEA:UniProtKB-ARBA.
DR GO; GO:1905521; P:regulation of macrophage migration; IEA:UniProtKB-ARBA.
DR GO; GO:0043408; P:regulation of MAPK cascade; IEA:TreeGrafter.
DR FunFam; 2.60.40.10:FF:001029; Macrophage colony-stimulating factor 1 receptor; 1.
DR FunFam; 2.60.40.10:FF:002322; macrophage colony-stimulating factor 1 receptor; 1.
DR FunFam; 1.10.510.10:FF:000177; Mast/stem cell growth factor receptor; 1.
DR FunFam; 3.30.200.20:FF:000025; Platelet-derived growth factor receptor alpha; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 5.
DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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; IPR013098; Ig_I-set.
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; IPR050122; RTK.
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 PANTHER; PTHR24416:SF47; MACROPHAGE COLONY-STIMULATING FACTOR 1 RECEPTOR; 1.
DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF25305; Ig_PDGFR_d4; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF500947; CSF-1_receptor; 1.
DR PIRSF; PIRSF000615; TyrPK_CSF1-R; 1.
DR PRINTS; PR01832; VEGFRECEPTOR.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; Immunoglobulin; 4.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS50835; IG_LIKE; 1.
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 3: Inferred from homology;
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PIRSR:PIRSR000615-
KW 2}; Cell membrane {ECO:0000256|ARBA:ARBA00022475};
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157,
KW ECO:0000256|PIRSR:PIRSR500947-52};
KW Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW Immunity {ECO:0000256|ARBA:ARBA00022859};
KW Immunoglobulin domain {ECO:0000256|ARBA:ARBA00023319,
KW ECO:0000256|RuleBase:RU000311};
KW Inflammatory response {ECO:0000256|ARBA:ARBA00023198};
KW Innate immunity {ECO:0000256|ARBA:ARBA00022588};
KW Kinase {ECO:0000256|ARBA:ARBA00022777};
KW Magnesium {ECO:0000256|PIRSR:PIRSR000615-3};
KW Membrane {ECO:0000256|ARBA:ARBA00023136};
KW Metal-binding {ECO:0000256|PIRSR:PIRSR000615-3};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741,
KW ECO:0000256|PIRSR:PIRSR000615-2};
KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW Receptor {ECO:0000256|ARBA:ARBA00023170, ECO:0000256|RuleBase:RU000311};
KW Reference proteome {ECO:0000313|Proteomes:UP000261620};
KW Repeat {ECO:0000256|ARBA:ARBA00022737};
KW Signal {ECO:0000256|ARBA:ARBA00022729, ECO:0000256|SAM:SignalP};
KW Transferase {ECO:0000256|ARBA:ARBA00022679};
KW Transmembrane {ECO:0000256|ARBA:ARBA00022692,
KW ECO:0000256|RuleBase:RU000311};
KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989};
KW Tyrosine-protein kinase {ECO:0000256|ARBA:ARBA00023137};
KW Ubl conjugation {ECO:0000256|ARBA:ARBA00022843}.
FT SIGNAL 1..21
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 22..977
FT /note="receptor protein-tyrosine kinase"
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5018616270"
FT DOMAIN 218..313
FT /note="Ig-like"
FT /evidence="ECO:0000259|PROSITE:PS50835"
FT DOMAIN 591..921
FT /note="Protein kinase"
FT /evidence="ECO:0000259|PROSITE:PS50011"
FT ACT_SITE 785
FT /note="Proton acceptor"
FT /evidence="ECO:0000256|PIRSR:PIRSR000615-1"
FT BINDING 570
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|PIRSR:PIRSR000615-3"
FT BINDING 597..605
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR500947-51"
FT BINDING 598..605
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR000615-2"
FT BINDING 626
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR000615-2,
FT ECO:0000256|PROSITE-ProRule:PRU10141"
FT BINDING 674..680
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR000615-2"
FT BINDING 789
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR000615-2"
FT BINDING 790
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|PIRSR:PIRSR000615-3"
FT BINDING 803
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|PIRSR:PIRSR000615-3"
FT SITE 932
FT /note="Important for interaction with phosphotyrosine-
FT binding proteins"
FT /evidence="ECO:0000256|PIRSR:PIRSR000615-4"
FT DISULFID 52..96
FT /evidence="ECO:0000256|PIRSR:PIRSR500947-52"
FT DISULFID 143..192
FT /evidence="ECO:0000256|PIRSR:PIRSR500947-52"
FT DISULFID 239..297
FT /evidence="ECO:0000256|PIRSR:PIRSR500947-52"
FT DISULFID 438..507
FT /evidence="ECO:0000256|PIRSR:PIRSR500947-52"
SQ SEQUENCE 977 AA; 111606 MW; 5B75249BBFAD4690 CRC64;
MYDAFLLHVF VIDFCSLSVL AEWRHPVIKF NSKVVESSEV VVKPGTSLDL QCEGDGPVNW
QTRLAKHRRF VSKGQANVRT LRVDRPSAEF TGTYKCFYNP VSLHRHLTSS VHVYVKDPNR
LFWTSSTSLR VVRKEGEDYL LPCLLTDPEA TDLGLRMDND TTVPSGMNFT VYRHRGVLIH
NLQPSFNADY VCTAKVKGVE GTSKAFSINV IQKLRFPPYV FLETDEYVRI VGEELKICCM
THNPNFNYNV TWKYTTKSVS VRHFEERVRS SGENRLDIQS ILTISAVDLT DTGNLSCIGT
NEAGVNSSTT YLLVVDKPYI RLLPQLSPKL THQGLLIEVN EGEDLELSVI IEAYPHIIEH
RWHTPTSPNT STQEQKFVRY NNRYQASLQL KRLNAQEQGQ YTFYAKSDLA NASITFQVQM
YQRPVAVVRW ENVTTLTCTS FGYPAPRIIW YQCFGIRSTC NGNTTGLQMA TPLQAPTVEV
QREEYGAVEV ESILFVGPSN RRMTVECVAF NLAGVSSDTF AMEVSGECWM SGRHFAVPPL
FYTIFSNGYL QKPRYEIRWK IIEARDGNNY TFIDPTQLPY NEKWEFPRDK LKLGKILGAG
AFGKVVEATA YGLGEDKDNT MRVAVKMLKA NAHSDEREAL MSELKILSHL GHHKNIVNLL
GACTYRGPVL VITEYCSLGD LLNFLRQRAE TFVNFVMNIP EYSFLMDNSS DYKNICNQKC
FIRSDSGISS TSSSTYLEMR PNSHPDSLSE QTADWPLDIL DLLRFSFQVA QGLDFLADKN
CIHRDVAARN VLLTDRREAK ICDFGLARDI MNDSNYVVKG NARLPVKWMA PESIFDCVYT
VQSDVWSYGI LLWEIFSIGK SPYPSMAVDS RFYKMVKRGY QMSQPDFAPL EIYTIMKMCW
NLEPTERPTF NKISQMIEKL LGEQSEQEQL IYQNVQQQIT EDEVCDEPKC CDGPYDQSCD
HEEEEQPLMK TNNYQFC
//
