TYRO3_RAT
ID TYRO3_RAT Reviewed; 880 AA.
AC P55146;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Tyrosine-protein kinase receptor TYRO3;
DE EC=2.7.10.1;
DE AltName: Full=Tyrosine-protein kinase SKY;
DE Flags: Precursor;
GN Name=Tyro3; Synonyms=Sky;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7490270; DOI=10.1093/oxfordjournals.jbchem.a124854;
RA Ohashi K., Honda S., Ichinomiya N., Nakamura T., Mizuno K.;
RT "Molecular cloning and in situ localization in the brain of rat sky
RT receptor tyrosine kinase.";
RL J. Biochem. 117:1267-1275(1995).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-859, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Receptor tyrosine kinase that transduces signals from the
CC extracellular matrix into the cytoplasm by binding to several ligands
CC including TULP1 or GAS6. Regulates many physiological processes
CC including cell survival, migration and differentiation. Ligand binding
CC at the cell surface induces dimerization and autophosphorylation of
CC TYRO3 on its intracellular domain that provides docking sites for
CC downstream signaling molecules. Following activation by ligand,
CC interacts with PIK3R1 and thereby enhances PI3-kinase activity.
CC Activates the AKT survival pathway, including nuclear translocation of
CC NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated
CC genes. TYRO3 signaling plays a role in various processes such as neuron
CC protection from excitotoxic injury, platelet aggregation and
CC cytoskeleton reorganization. Also plays an important role in inhibition
CC of Toll-like receptors (TLRs)-mediated innate immune response by
CC activating STAT1, which selectively induces production of suppressors
CC of cytokine signaling SOCS1 and SOCS3 (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 -!- SUBUNIT: Monomer and homodimer. Interacts (via N-terminus) with
CC extracellular ligands TULP1 and GAS6 (By similarity). Interacts with
CC PIK3R1; this interaction increases PI3-kinase activity (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein.
CC -!- TISSUE SPECIFICITY: Abundant in the brain and lower levels in other
CC tissues.
CC -!- PTM: Autophosphorylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. AXL/UFO subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; D37880; BAA07119.1; -; mRNA.
DR PIR; JC4166; JC4166.
DR RefSeq; NP_058788.1; NM_017092.1.
DR AlphaFoldDB; P55146; -.
DR SMR; P55146; -.
DR BioGRID; 247273; 1.
DR STRING; 10116.ENSRNOP00000007656; -.
DR GlyGen; P55146; 8 sites.
DR iPTMnet; P55146; -.
DR PhosphoSitePlus; P55146; -.
DR PaxDb; P55146; -.
DR GeneID; 25232; -.
DR KEGG; rno:25232; -.
DR UCSC; RGD:3923; rat.
DR CTD; 7301; -.
DR RGD; 3923; Tyro3.
DR eggNOG; ENOG502QRYR; Eukaryota.
DR InParanoid; P55146; -.
DR OrthoDB; 263089at2759; -.
DR PhylomeDB; P55146; -.
DR BRENDA; 2.7.10.1; 5301.
DR PRO; PR:P55146; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IPI:RGD.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0001618; F:virus receptor activity; ISO:RGD.
DR GO; GO:0043277; P:apoptotic cell clearance; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0021885; P:forebrain cell migration; ISS:UniProtKB.
DR GO; GO:0001779; P:natural killer cell differentiation; ISO:RGD.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0045824; P:negative regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:0051250; P:negative regulation of lymphocyte activation; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0070050; P:neuron cellular homeostasis; ISS:UniProtKB.
DR GO; GO:0007218; P:neuropeptide signaling pathway; ISO:RGD.
DR GO; GO:0042698; P:ovulation cycle; ISS:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; IBA:GO_Central.
DR GO; GO:0030168; P:platelet activation; ISS:UniProtKB.
DR GO; GO:0070527; P:platelet aggregation; ISS:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:1903902; P:positive regulation of viral life cycle; ISO:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0032940; P:secretion by cell; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0060068; P:vagina development; ISO:RGD.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
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; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF00041; fn3; 2.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00409; IG; 2.
DR SMART; SM00408; IGc2; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS50835; IG_LIKE; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell adhesion; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..880
FT /note="Tyrosine-protein kinase receptor TYRO3"
FT /id="PRO_0000024480"
FT TOPO_DOM 31..419
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 420..440
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 441..880
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 31..118
FT /note="Ig-like C2-type 1"
FT DOMAIN 129..210
FT /note="Ig-like C2-type 2"
FT DOMAIN 217..310
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 315..406
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 508..785
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 804..827
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 842..864
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 645
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 514..522
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 540
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 456
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06418"
FT MOD_RES 671
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 675
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 676
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 794
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q06418"
FT MOD_RES 859
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 220
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 283
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 356
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 370
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 150..193
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 880 AA; 95919 MW; C3751E86AAE5FA5B CRC64;
MALRRSMGRP GLRPLLLAGL ASLLLPGSAA AGLKLMGAPV KMTVSQGQPV KLNCSVEGMD
DPDIHWMKDG AVVQNASQVS ISISEQNWIG LLSLKSAERS DAGLYWCQVK DGEETKISQS
VWLTVEGVPF FTVEPKDLAV PPNVPFQLSC EAVGPPEPVT IFWWRGPTKV GGPASSPSVL
NVTGVTQRTE FSCEAHNIKG LATSRPAIIR LQAPPAAPFN ITVTTISSSN ASVAWVPGAD
GLALLHSCTV QVAHAPGEWE ALAVVVPVPP FTCLLRNLAP ATNYSLRVRC ANALGPSPYG
DWVPFQTKGL APARAPQNFH AIRTDSGLIL EWEEVIPEDP GEGPLGPYKL SWVQENGTQD
ELMVEGTTAN LTDWDPQKDL VLRVCASNAI GDGPWSQPLV VSSHDHAGRQ GPPHSRTSWV
PVVLGVLTAL ITAAALALIL LRKRRKETRF GQAFDSVMAR GEPAVHFRAA RSFNRERPER
IEATLDSLGI SDELKEKLED VLIPEQQFTL GRMLGKGEFG SVREAQLKQE DGSFVKVAVK
MLKADIIASS DIEEFLREAA CMKEFDHPHV AKLVGVSLRS RAKGRLPIPM VILPFMKHGD
LHAFLLASRI GENPFNLPLQ TLVRFMVDIA CGMEYLSSRN FIHRDLAARN CMLAEDMTVC
VADFGLSRKI YSGDYYRQGC ASKLPVKWLA LESLADNLYT VHSDVWAFGV TMWEIMTRGQ
TPYAGIENAE IYNYLISGNR LKQPPECMEE VYDLMYQCWS ADPKQRPSFT CLRMELENIL
GHLSVLSTSQ DPLYINIERA GQPAENGSPE LPCGEQSSSE AGDGSGMGAI GGIPSDCRYI
FSPGGLAESP GQLEQQPESP LNENQRLLLL QQGLLPHSSC
