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Protein

Tyrosine-protein kinase Mer

Gene

Mertk

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

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

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei610ATPPROSITE-ProRule annotation1
Active sitei718Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi588 – 596ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • transmembrane receptor protein tyrosine kinase activity Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.
ReactomeiR-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi69283. Mertk.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 497ExtracellularSequence analysisAdd BLAST479
Transmembranei498 – 518HelicalSequence analysisAdd BLAST21
Topological domaini519 – 994CytoplasmicSequence analysisAdd BLAST476

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & 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-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000002444519 – 994Tyrosine-protein kinase MerAdd BLAST976

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi108N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi109 ↔ 170PROSITE-ProRule annotation
Glycosylationi165N-linked (GlcNAc...)Sequence analysis1
Glycosylationi202N-linked (GlcNAc...)Sequence analysis1
Glycosylationi210N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi213 ↔ 257PROSITE-ProRule annotation
Glycosylationi229N-linked (GlcNAc...)Sequence analysis1
Glycosylationi289N-linked (GlcNAc...)Sequence analysis1
Glycosylationi311N-linked (GlcNAc...)Sequence analysis1
Glycosylationi324N-linked (GlcNAc...)Sequence analysis1
Glycosylationi331N-linked (GlcNAc...)Sequence analysis1
Glycosylationi349N-linked (GlcNAc...)Sequence analysis1
Glycosylationi384N-linked (GlcNAc...)Sequence analysis1
Glycosylationi390N-linked (GlcNAc...)Sequence analysis1
Glycosylationi437N-linked (GlcNAc...)Sequence analysis1
Glycosylationi449N-linked (GlcNAc...)Sequence analysis1
Modified residuei538PhosphoserineBy similarity1
Modified residuei744Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei748Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei749Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei867Phosphotyrosine; by autocatalysisBy similarity1

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, Phosphoprotein

Proteomic databases

PaxDbiP57097.
PRIDEiP57097.

PTM databases

iPTMnetiP57097.
PhosphoSitePlusiP57097.

Expressioni

Gene expression databases

BgeeiENSRNOG00000017319.
GenevisibleiP57097. 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 similarity

Protein-protein interaction databases

BioGridi249230. 1 interactor.
STRINGi10116.ENSRNOP00000023419.

Structurei

3D structure databases

ProteinModelPortaliP57097.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini86 – 181Ig-like C2-type 1Add BLAST96
Domaini192 – 268Ig-like C2-type 2Add BLAST77
Domaini281 – 376Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST96
Domaini381 – 478Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST98
Domaini582 – 852Protein kinasePROSITE-ProRule annotationAdd BLAST271

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.PROSITE-ProRule annotation
Contains 2 fibronectin type-III domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IG6I. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00810000125384.
HOGENOMiHOG000231685.
HOVERGENiHBG006346.
InParanoidiP57097.
KOiK05117.
OMAiWTPGHDG.
OrthoDBiEOG091G016X.
PhylomeDBiP57097.
TreeFamiTF317402.

Family and domain databases

CDDicd00063. FN3. 2 hits.
Gene3Di2.60.40.10. 4 hits.
InterProiIPR003961. FN3_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013151. Immunoglobulin.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PfamiPF00041. fn3. 1 hit.
PF00047. ig. 1 hit.
PF13895. Ig_2. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00060. FN3. 2 hits.
SM00409. IG. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
SSF49265. SSF49265. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50853. 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.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P57097-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:994
Mass (Da):109,423
Last modified:December 1, 2000 - v1
Checksum:i339717117FB4242B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF208235 mRNA. Translation: AAF44060.1.
PIRiPT0194.
RefSeqiNP_075232.1. NM_022943.1.
UniGeneiRn.48789.

Genome annotation databases

EnsembliENSRNOT00000023419; ENSRNOP00000023419; ENSRNOG00000017319.
GeneIDi65037.
KEGGirno:65037.
UCSCiRGD:69283. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF208235 mRNA. Translation: AAF44060.1.
PIRiPT0194.
RefSeqiNP_075232.1. NM_022943.1.
UniGeneiRn.48789.

3D structure databases

ProteinModelPortaliP57097.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249230. 1 interactor.
STRINGi10116.ENSRNOP00000023419.

PTM databases

iPTMnetiP57097.
PhosphoSitePlusiP57097.

Proteomic databases

PaxDbiP57097.
PRIDEiP57097.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000023419; ENSRNOP00000023419; ENSRNOG00000017319.
GeneIDi65037.
KEGGirno:65037.
UCSCiRGD:69283. rat.

Organism-specific databases

CTDi10461.
RGDi69283. Mertk.

Phylogenomic databases

eggNOGiENOG410IG6I. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00810000125384.
HOGENOMiHOG000231685.
HOVERGENiHBG006346.
InParanoidiP57097.
KOiK05117.
OMAiWTPGHDG.
OrthoDBiEOG091G016X.
PhylomeDBiP57097.
TreeFamiTF317402.

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.
ReactomeiR-RNO-202733. Cell surface interactions at the vascular wall.

Miscellaneous databases

PROiP57097.

Gene expression databases

BgeeiENSRNOG00000017319.
GenevisibleiP57097. RN.

Family and domain databases

CDDicd00063. FN3. 2 hits.
Gene3Di2.60.40.10. 4 hits.
InterProiIPR003961. FN3_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013151. Immunoglobulin.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PfamiPF00041. fn3. 1 hit.
PF00047. ig. 1 hit.
PF13895. Ig_2. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00060. FN3. 2 hits.
SM00409. IG. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
SSF49265. SSF49265. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50853. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMERTK_RAT
AccessioniPrimary (citable) accession number: P57097
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 1, 2000
Last modified: November 30, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.