UniProtKB - P57097 (MERTK_RAT)
Protein
Tyrosine-protein kinase Mer
Gene
Mertk
Organism
Rattus norvegicus (Rat)
Status
Functioni
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3 (By similarity).By similarity
Catalytic activityi
- EC:2.7.10.1PROSITE-ProRule annotation
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 610 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 718 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 588 – 596 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- transmembrane receptor protein tyrosine kinase activity Source: GO_Central
GO - Biological processi
- apoptotic cell clearance Source: RGD
- cell migration Source: GO_Central
- multicellular organism development Source: GO_Central
- natural killer cell differentiation Source: RGD
- negative regulation of cytokine production Source: RGD
- negative regulation of leukocyte apoptotic process Source: RGD
- negative regulation of lymphocyte activation Source: RGD
- nervous system development Source: GO_Central
- neutrophil clearance Source: RGD
- phagocytosis Source: RGD
- platelet activation Source: RGD
- positive regulation of kinase activity Source: GO_Central
- positive regulation of phagocytosis Source: RGD
- protein kinase B signaling Source: RGD
- protein phosphorylation Source: RGD
- retina development in camera-type eye Source: RGD
- secretion by cell Source: RGD
- spermatogenesis Source: RGD
- substrate adhesion-dependent cell spreading Source: RGD
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
- vagina development Source: RGD
Keywordsi
Molecular function | Kinase, Receptor, Transferase, Tyrosine-protein kinase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.10.1, 5301 |
Reactomei | R-RNO-202733, Cell surface interactions at the vascular wall |
Names & Taxonomyi
Protein namesi | Recommended name: Tyrosine-protein kinase Mer (EC:2.7.10.1)Alternative name(s): Proto-oncogene c-Mer Receptor tyrosine kinase MerTK |
Gene namesi | Name:Mertk Synonyms:Mer |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 69283, Mertk |
Subcellular locationi
Other locations
- Membrane By similarity; Single-pass type I membrane protein By similarity
Extracellular region or secreted
- extracellular space Source: RGD
Plasma Membrane
- integral component of plasma membrane Source: GO_Central
Other locations
- cytoplasm Source: RGD
- photoreceptor outer segment Source: RGD
- receptor complex Source: GO_Central
- rhabdomere Source: RGD
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 19 – 497 | ExtracellularSequence analysisAdd BLAST | 479 | |
Transmembranei | 498 – 518 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 519 – 994 | CytoplasmicSequence analysisAdd BLAST | 476 |
Keywords - Cellular componenti
MembranePathology & Biotechi
Involvement in diseasei
Defects in Mertk are the cause of retinal dystrophy (rdy) in the royal college of surgeons (RCS) rats.
Keywords - Diseasei
Proto-oncogenePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 18 | Sequence analysisAdd BLAST | 18 | |
ChainiPRO_0000024445 | 19 – 994 | Tyrosine-protein kinase MerAdd BLAST | 976 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 108 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 109 ↔ 170 | PROSITE-ProRule annotation | ||
Glycosylationi | 165 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 202 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 210 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 213 ↔ 257 | PROSITE-ProRule annotation | ||
Glycosylationi | 229 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 289 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 311 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 324 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 331 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 349 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 384 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 390 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 437 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 449 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 538 | PhosphoserineBy similarity | 1 | |
Modified residuei | 744 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 748 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 749 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 867 | Phosphotyrosine; by autocatalysisBy similarity | 1 |
Post-translational modificationi
Autophosphorylated on Tyr-744, Tyr-748 and Tyr-749 in the activation loop allowing full activity. Autophosphorylated on Tyr-867 leading to recruitment of downstream partners of the signaling cascade such as PLCG2 (By similarity).By similarity
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
PaxDbi | P57097 |
PRIDEi | P57097 |
PTM databases
GlyGeni | P57097, 14 sites |
iPTMneti | P57097 |
PhosphoSitePlusi | P57097 |
Expressioni
Gene expression databases
Bgeei | ENSRNOG00000017319, Expressed in kidney and 21 other tissues |
Genevisiblei | P57097, RN |
Interactioni
Subunit structurei
Interacts (upon activation) with TNK2; stimulates TNK2 autophosphorylation.
Interacts (via N-terminus) with extracellular ligands LGALS3, TUB, TULP1 and GAS6.
Interacts with VAV1 in a phosphotyrosine-independent manner (By similarity).
By similarityProtein-protein interaction databases
BioGRIDi | 249230, 1 interactor |
STRINGi | 10116.ENSRNOP00000023419 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 86 – 181 | Ig-like C2-type 1Add BLAST | 96 | |
Domaini | 192 – 268 | Ig-like C2-type 2Add BLAST | 77 | |
Domaini | 281 – 376 | Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST | 96 | |
Domaini | 381 – 478 | Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST | 98 | |
Domaini | 582 – 852 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 271 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.PROSITE-ProRule annotation
Keywords - Domaini
Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502QQQ3, Eukaryota |
GeneTreei | ENSGT00940000155669 |
HOGENOMi | CLU_015796_0_0_1 |
InParanoidi | P57097 |
OMAi | KLQDVMI |
OrthoDBi | 263089at2759 |
PhylomeDBi | P57097 |
TreeFami | TF317402 |
Family and domain databases
CDDi | cd00063, FN3, 2 hits |
Gene3Di | 2.60.40.10, 4 hits |
InterProi | View protein in InterPro IPR003961, FN3_dom IPR036116, FN3_sf IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR003599, Ig_sub IPR013151, Immunoglobulin IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR001245, Ser-Thr/Tyr_kinase_cat_dom IPR008266, Tyr_kinase_AS IPR020635, Tyr_kinase_cat_dom |
Pfami | View protein in Pfam PF00041, fn3, 1 hit PF00047, ig, 1 hit PF13895, Ig_2, 1 hit PF07714, PK_Tyr_Ser-Thr, 1 hit |
PRINTSi | PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00060, FN3, 2 hits SM00409, IG, 2 hits SM00219, TyrKc, 1 hit |
SUPFAMi | SSF48726, SSF48726, 2 hits SSF49265, SSF49265, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50853, FN3, 2 hits PS50835, IG_LIKE, 2 hits PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00109, PROTEIN_KINASE_TYR, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P57097-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MVLAPLLLGL LLLSALWNGG TAEKEEEIKP DQPFSGPLPG SLPADHRPFF
60 70 80 90 100
APHSSGDQLS PSQTGRSHPA HTATPQMTSA ASNLLPPVAF KNTIGRIVLS
110 120 130 140 150
EHKSVKFNCS INIPNVYQET AGISWWKDGK ELLGAHHSIT QFYPDEEGVS
160 170 180 190 200
IIALFSITSV QRSDNGSYIC KMKVNDREVV SDPIYVEVQG LPYFTKQPES
210 220 230 240 250
VNVTRNTAFN LTCQAVGPPE PVNIFWVQNS SRVNENPERS PSVLTVAGLT
260 270 280 290 300
ETAVFSCEAH NDKGLTVSKG VQINIKVIPS PPTEVHILNS TAHSILVSWV
310 320 330 340 350
PGFDGYSPLQ NCSIQVKEAD QLSNGSVMVF NTSASPHLYE VQQLQALANY
360 370 380 390 400
SVTVSCRNEI GWSAVSPWIL ASTTEGAPAV APLNITVFLN ESSNNLEIRW
410 420 430 440 450
TKPPIKRQDG ELVGYRISHV WESAGTSKEL SEEVSQNGSW AQVPVQMHNA
460 470 480 490 500
TCTVRIAVIT KGGIGPFSEP VDVAIPEHSR VDYAPSSTPA PGNTESMLII
510 520 530 540 550
LGCFCGFVLM GLILYLSLAI KRRVQETKFG GAFSEEDSQL VVNYRAKKSF
560 570 580 590 600
CRRAIELTLQ SLGVSEELQN KLEDVVVDRN LLILGKVLGE GEFGSVMEGN
610 620 630 640 650
LKQEDGTSQK VAVKTMKLDN FSLREIEEFL SEAACMKDFN HPNVIRLLGV
660 670 680 690 700
CIELSSQGIP KPMVILPFMK YGDLHTFLLY SRIESVPKSI PLQTLLKFMV
710 720 730 740 750
DIAQGMEYLS SRNFLHRDLA ARNCMLRDDM TVCVADFGLS KKIYSGDYYR
760 770 780 790 800
QGRIAKMPVK WIAIESLADR VYTSKSDVWA FGVTMWEIAT RGMTPYPGVQ
810 820 830 840 850
NHEMYDYLLH GHRLKQPEDC LDDLYEIMYS CWSADPLDRP TFSVLRLQLE
860 870 880 890 900
KLSESLPDAQ DKESIIYINT QLLESCEGLA NRSSLAGLDM NIDPDSIIAS
910 920 930 940 950
CTAGAAVSVV MAEVHENNLH EERYILNGGN EEWEDVASTP FATVTAGKDG
960 970 980 990
VLPEDRLTKN GISWSHHSTL PLGSPSPDEL LFADDSSGDS EVLM
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF208235 mRNA Translation: AAF44060.1 |
PIRi | PT0194 |
RefSeqi | NP_075232.1, NM_022943.1 |
Genome annotation databases
Ensembli | ENSRNOT00000023419; ENSRNOP00000023419; ENSRNOG00000017319 |
GeneIDi | 65037 |
KEGGi | rno:65037 |
UCSCi | RGD:69283, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF208235 mRNA Translation: AAF44060.1 |
PIRi | PT0194 |
RefSeqi | NP_075232.1, NM_022943.1 |
3D structure databases
SMRi | P57097 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 249230, 1 interactor |
STRINGi | 10116.ENSRNOP00000023419 |
PTM databases
GlyGeni | P57097, 14 sites |
iPTMneti | P57097 |
PhosphoSitePlusi | P57097 |
Proteomic databases
PaxDbi | P57097 |
PRIDEi | P57097 |
Genome annotation databases
Ensembli | ENSRNOT00000023419; ENSRNOP00000023419; ENSRNOG00000017319 |
GeneIDi | 65037 |
KEGGi | rno:65037 |
UCSCi | RGD:69283, rat |
Organism-specific databases
CTDi | 10461 |
RGDi | 69283, Mertk |
Phylogenomic databases
eggNOGi | ENOG502QQQ3, Eukaryota |
GeneTreei | ENSGT00940000155669 |
HOGENOMi | CLU_015796_0_0_1 |
InParanoidi | P57097 |
OMAi | KLQDVMI |
OrthoDBi | 263089at2759 |
PhylomeDBi | P57097 |
TreeFami | TF317402 |
Enzyme and pathway databases
BRENDAi | 2.7.10.1, 5301 |
Reactomei | R-RNO-202733, Cell surface interactions at the vascular wall |
Miscellaneous databases
PROi | PR:P57097 |
Gene expression databases
Bgeei | ENSRNOG00000017319, Expressed in kidney and 21 other tissues |
Genevisiblei | P57097, RN |
Family and domain databases
CDDi | cd00063, FN3, 2 hits |
Gene3Di | 2.60.40.10, 4 hits |
InterProi | View protein in InterPro IPR003961, FN3_dom IPR036116, FN3_sf IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR003599, Ig_sub IPR013151, Immunoglobulin IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR001245, Ser-Thr/Tyr_kinase_cat_dom IPR008266, Tyr_kinase_AS IPR020635, Tyr_kinase_cat_dom |
Pfami | View protein in Pfam PF00041, fn3, 1 hit PF00047, ig, 1 hit PF13895, Ig_2, 1 hit PF07714, PK_Tyr_Ser-Thr, 1 hit |
PRINTSi | PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00060, FN3, 2 hits SM00409, IG, 2 hits SM00219, TyrKc, 1 hit |
SUPFAMi | SSF48726, SSF48726, 2 hits SSF49265, SSF49265, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50853, FN3, 2 hits PS50835, IG_LIKE, 2 hits PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00109, PROTEIN_KINASE_TYR, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MERTK_RAT | |
Accessioni | P57097Primary (citable) accession number: P57097 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | December 1, 2000 | |
Last modified: | December 2, 2020 | |
This is version 155 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families