CSF12_TAKRU
ID CSF12_TAKRU Reviewed; 1019 AA.
AC Q8UVR8;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Macrophage colony-stimulating factor 1 receptor 2;
DE Short=CSF-1-R 2;
DE EC=2.7.10.1;
DE Flags: Precursor;
GN Name=csf1r2;
OS Takifugu rubripes (Japanese pufferfish) (Fugu rubripes).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC Eupercaria; Tetraodontiformes; Tetradontoidea; Tetraodontidae; Takifugu.
OX NCBI_TaxID=31033;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12354661; DOI=10.1016/s0378-1119(02)00736-9;
RA Williams H., Brenner S., Venkatesh B.;
RT "Identification and analysis of additional copies of the platelet-derived
RT growth factor receptor and colony stimulating factor 1 receptor genes in
RT fugu.";
RL Gene 295:255-264(2002).
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 -!- 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; AF411927; AAL50568.1; -; Genomic_DNA.
DR AlphaFoldDB; Q8UVR8; -.
DR SMR; Q8UVR8; -.
DR STRING; 31033.ENSTRUP00000006673; -.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; Q8UVR8; -.
DR Proteomes; UP000005226; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019955; F:cytokine binding; IEA:InterPro.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0019221; P:cytokine-mediated 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:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IEA:InterPro.
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; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 4.
DR SUPFAM; SSF56112; SSF56112; 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; 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..1019
FT /note="Macrophage colony-stimulating factor 1 receptor 2"
FT /id="PRO_0000249008"
FT TOPO_DOM 19..576
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 577..597
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 598..1019
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 37..109
FT /note="Ig-like C2-type 1"
FT DOMAIN 106..212
FT /note="Ig-like C2-type 2"
FT DOMAIN 224..312
FT /note="Ig-like C2-type 3"
FT DOMAIN 383..474
FT /note="Ig-like C2-type 4"
FT DOMAIN 487..567
FT /note="Ig-like C2-type 5"
FT DOMAIN 641..963
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 601..633
FT /note="Regulatory juxtamembrane domain"
FT /evidence="ECO:0000250"
FT REGION 845..867
FT /note="Activation loop"
FT /evidence="ECO:0000250"
FT REGION 970..1001
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 977..1001
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 827
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 647..655
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 674
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 620
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 756
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 778
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 858
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 974
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1016
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 249
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 346
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 355
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 369
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 408
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 422
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 429
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 514
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 52..92
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 139..193
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 239..294
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 490..552
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 1019 AA; 114264 MW; 699DEB24A38C2E8B CRC64;
MKSYCLLLSI TLSCCCSAED LPDPPSIHLN SKYLPNQAEA ILTAGTPFTL RCTGASSVHW
SSSAFCLLYH GRLVDPIDVQ RADPRHTGTY CCGYTNQSLE HLSTWIHLYV KDPADPSTVF
VTPRNSPRVK EGQDFLYRCL LTDPSVTNLT FQPEDNIQGS GQHLPVGMNV TVDPQRGALI
QDVQRSFSGQ YVCSGWKDGR HFISRSFHLL VAPRLPPPSV AIHQNKAVRL EGEKFEVTCV
SSSTTHLFNV TWTHLTKKNF DVAVTREYRN SHMYISSTLM IAAVSQEDRG TYTCAAASED
GVTTATTHLI VLDSRFMTTY LKTWHANTKA KNKEISKEID GNLTANSTSI DIEANRSSKL
HMKMELIANV STDGVHVNNI SSSTTVEAYE GLDVILTFVT ESYPPLSNQS WTKPTKVNNN
NNVTMYQENY SINDTRSEAS LLLRRVRQED HGSYTFHFSN SFFSGSQNID LRIYRSPSAI
ISVEKNTLTC SSSGYPVPTI AWYSCPGILK TCGNLTTTES SEADPTSEHD EENVRKLLNL
PLSTGGDVTA ECIASNQVGA FRKVFHLREH NSAFMSALIG AGSTAAILFL LLLVVFYKWR
QKPKYEIRWK IIESTEGNHY TFVDPTLLPY NYKWEFPRDK LRLGAVLGSG AFGKVVEATA
YGLGTDDVTR VAVKMLKPRA LSEEREALMS ELKILSHLGY HDNIVNLLGA CTQGGPMLMI
TEYCSYGDLL NFLRARAQDF MASILSADEM EGDPFYKNMA TLYGRLRSDS GISCCSDYQE
MQPILGSAEK QQGVQMGGLS FGDLLSFSHQ VAQGLDFLST RNCIHRDVAA RNVLLTDHRV
AKICDFGLAR DIQNDDSYIV QGNARLPVKW MAPESIFQCV YTVQSDVWSY GVLLWEIFSL
GKSPYPNVAV DTHFYKMIKD GRHMTQPDFA PVEMYQLMTH CWSLEPTDRP TFKMICQLID
RLLQSNDDTN HQSYSNINET KKDDFKGGKS QRRGEEEEQR RQRGNLWIPL SVTNIYQLS
