MERTK_RAT
ID MERTK_RAT Reviewed; 994 AA.
AC P57097;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Tyrosine-protein kinase Mer;
DE EC=2.7.10.1;
DE AltName: Full=Proto-oncogene c-Mer;
DE AltName: Full=Receptor tyrosine kinase MerTK;
DE Flags: Precursor;
GN Name=Mertk; Synonyms=Mer;
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 STRAIN=RCS;
RX PubMed=10699188; DOI=10.1093/hmg/9.4.645;
RA D'Cruz P.M., Yasumura D., Weir J., Matthes M.T., Abderrahim H.,
RA LaVail M.M., Vollrath D.;
RT "Mutation of the receptor tyrosine kinase gene Mertk in the retinal
RT dystrophic RCS rat.";
RL Hum. Mol. Genet. 9:645-651(2000).
CC -!- FUNCTION: Receptor tyrosine kinase that transduces signals from the
CC extracellular matrix into the cytoplasm by binding to several ligands
CC including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological
CC processes including cell survival, migration, differentiation, and
CC phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the
CC cell surface induces autophosphorylation of MERTK on its intracellular
CC domain that provides docking sites for downstream signaling molecules.
CC Following activation by ligand, interacts with GRB2 or PLCG2 and
CC induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK
CC signaling plays a role in various processes such as macrophage
CC clearance of apoptotic cells, platelet aggregation, cytoskeleton
CC reorganization and engulfment. Functions in the retinal pigment
CC epithelium (RPE) as a regulator of rod outer segments fragments
CC phagocytosis. Also plays an important role in inhibition of Toll-like
CC receptors (TLRs)-mediated innate immune response by activating STAT1,
CC which selectively induces production of suppressors of cytokine
CC 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: Interacts (upon activation) with TNK2; stimulates TNK2
CC autophosphorylation. Interacts (via N-terminus) with extracellular
CC ligands LGALS3, TUB, TULP1 and GAS6. Interacts with VAV1 in a
CC phosphotyrosine-independent manner. Interacts with TIMD4; this
CC interaction enhances TIMD4-mediated efferocytosis (By similarity).
CC {ECO:0000250|UniProtKB:Q12866}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q12866};
CC Single-pass type I membrane protein {ECO:0000250}.
CC -!- PTM: Autophosphorylated on Tyr-744, Tyr-748 and Tyr-749 in the
CC activation loop allowing full activity. Autophosphorylated on Tyr-867
CC leading to recruitment of downstream partners of the signaling cascade
CC such as PLCG2 (By similarity). {ECO:0000250}.
CC -!- DISEASE: Note=Defects in Mertk are the cause of retinal dystrophy (rdy)
CC in the royal college of surgeons (RCS) rats.
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; AF208235; AAF44060.1; -; mRNA.
DR PIR; PT0194; PT0194.
DR RefSeq; NP_075232.1; NM_022943.1.
DR AlphaFoldDB; P57097; -.
DR SMR; P57097; -.
DR BioGRID; 249230; 1.
DR STRING; 10116.ENSRNOP00000023419; -.
DR GlyGen; P57097; 14 sites.
DR iPTMnet; P57097; -.
DR PhosphoSitePlus; P57097; -.
DR PaxDb; P57097; -.
DR PRIDE; P57097; -.
DR Ensembl; ENSRNOT00000097978; ENSRNOP00000076826; ENSRNOG00000017319.
DR GeneID; 65037; -.
DR KEGG; rno:65037; -.
DR UCSC; RGD:69283; rat.
DR CTD; 10461; -.
DR RGD; 69283; Mertk.
DR eggNOG; ENOG502QQQ3; Eukaryota.
DR GeneTree; ENSGT00940000155669; -.
DR HOGENOM; CLU_015796_0_0_1; -.
DR InParanoid; P57097; -.
DR OMA; LVIKWKP; -.
DR OrthoDB; 263089at2759; -.
DR PhylomeDB; P57097; -.
DR TreeFam; TF317402; -.
DR BRENDA; 2.7.10.1; 5301.
DR Reactome; R-RNO-202733; Cell surface interactions at the vascular wall.
DR PRO; PR:P57097; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000017319; Expressed in kidney and 20 other tissues.
DR Genevisible; P57097; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0001750; C:photoreceptor outer segment; IDA:RGD.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0043277; P:apoptotic cell clearance; ISO:RGD.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0001779; P:natural killer cell differentiation; ISO:RGD.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISO:RGD.
DR GO; GO:2000107; P:negative regulation of leukocyte apoptotic process; ISO:RGD.
DR GO; GO:0051250; P:negative regulation of lymphocyte activation; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0097350; P:neutrophil clearance; ISO:RGD.
DR GO; GO:0006909; P:phagocytosis; IDA:RGD.
DR GO; GO:0030168; P:platelet activation; ISO:RGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IDA:RGD.
DR GO; GO:0043491; P:protein kinase B signaling; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0060041; P:retina development in camera-type eye; ISO:RGD.
DR GO; GO:0032940; P:secretion by cell; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; ISO:RGD.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISO:RGD.
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; IPR003599; Ig_sub.
DR InterPro; IPR013151; Immunoglobulin.
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; 1.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF13895; Ig_2; 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; 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 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Proto-oncogene; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..994
FT /note="Tyrosine-protein kinase Mer"
FT /id="PRO_0000024445"
FT TOPO_DOM 19..497
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 498..518
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 519..994
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 86..181
FT /note="Ig-like C2-type 1"
FT DOMAIN 192..268
FT /note="Ig-like C2-type 2"
FT DOMAIN 281..376
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 381..478
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 582..852
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 24..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 55..77
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 718
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 588..596
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 610
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 538
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12866"
FT MOD_RES 744
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q12866"
FT MOD_RES 748
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q12866"
FT MOD_RES 749
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q12866"
FT MOD_RES 867
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q60805"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 165
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 229
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 289
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 311
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 331
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 349
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 384
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 390
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 437
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 449
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 109..170
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 213..257
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 994 AA; 109423 MW; 339717117FB4242B CRC64;
MVLAPLLLGL LLLSALWNGG TAEKEEEIKP DQPFSGPLPG SLPADHRPFF APHSSGDQLS
PSQTGRSHPA HTATPQMTSA ASNLLPPVAF KNTIGRIVLS EHKSVKFNCS INIPNVYQET
AGISWWKDGK ELLGAHHSIT QFYPDEEGVS IIALFSITSV QRSDNGSYIC KMKVNDREVV
SDPIYVEVQG LPYFTKQPES VNVTRNTAFN LTCQAVGPPE PVNIFWVQNS SRVNENPERS
PSVLTVAGLT ETAVFSCEAH NDKGLTVSKG VQINIKVIPS PPTEVHILNS TAHSILVSWV
PGFDGYSPLQ NCSIQVKEAD QLSNGSVMVF NTSASPHLYE VQQLQALANY SVTVSCRNEI
GWSAVSPWIL ASTTEGAPAV APLNITVFLN ESSNNLEIRW TKPPIKRQDG ELVGYRISHV
WESAGTSKEL SEEVSQNGSW AQVPVQMHNA TCTVRIAVIT KGGIGPFSEP VDVAIPEHSR
VDYAPSSTPA PGNTESMLII LGCFCGFVLM GLILYLSLAI KRRVQETKFG GAFSEEDSQL
VVNYRAKKSF CRRAIELTLQ SLGVSEELQN KLEDVVVDRN LLILGKVLGE GEFGSVMEGN
LKQEDGTSQK VAVKTMKLDN FSLREIEEFL SEAACMKDFN HPNVIRLLGV CIELSSQGIP
KPMVILPFMK YGDLHTFLLY SRIESVPKSI PLQTLLKFMV DIAQGMEYLS SRNFLHRDLA
ARNCMLRDDM TVCVADFGLS KKIYSGDYYR QGRIAKMPVK WIAIESLADR VYTSKSDVWA
FGVTMWEIAT RGMTPYPGVQ NHEMYDYLLH GHRLKQPEDC LDDLYEIMYS CWSADPLDRP
TFSVLRLQLE KLSESLPDAQ DKESIIYINT QLLESCEGLA NRSSLAGLDM NIDPDSIIAS
CTAGAAVSVV MAEVHENNLH EERYILNGGN EEWEDVASTP FATVTAGKDG VLPEDRLTKN
GISWSHHSTL PLGSPSPDEL LFADDSSGDS EVLM
