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P57097 (MERTK_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase Mer

EC=2.7.10.1
Alternative name(s):
Proto-oncogene c-Mer
Receptor tyrosine kinase MerTK
Gene names
Name:Mertk
Synonyms:Mer
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length994 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

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

Subunit structure

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.

Subcellular location

Membrane; Single-pass type I membrane protein By similarity.

Post-translational modification

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.

Involvement in disease

Defects in Mertk are the cause of retinal dystrophy (rdy) in the royal college of surgeons (RCS) rats.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.

Contains 2 fibronectin type-III domains.

Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Cellular componentMembrane
   DiseaseProto-oncogene
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic cell clearance

Inferred from electronic annotation. Source: Ensembl

natural killer cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of lymphocyte activation

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine phosphorylation

Non-traceable author statement PubMed 11861639. Source: GOC

phagocytosis

Inferred from direct assay PubMed 11861639. Source: RGD

platelet activation

Inferred from electronic annotation. Source: Ensembl

positive regulation of phagocytosis

Inferred from electronic annotation. Source: Ensembl

protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay PubMed 11861639. Source: RGD

retina development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

secretion by cell

Inferred from electronic annotation. Source: Ensembl

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

substrate adhesion-dependent cell spreading

Inferred from electronic annotation. Source: Ensembl

vagina development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

photoreceptor outer segment

Inferred from direct assay PubMed 11861639. Source: RGD

rhabdomere

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

transmembrane receptor protein tyrosine kinase activity

Non-traceable author statement PubMed 11861639. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 994976Tyrosine-protein kinase Mer
PRO_0000024445

Regions

Topological domain19 – 497479Extracellular Potential
Transmembrane498 – 51821Helical; Potential
Topological domain519 – 994476Cytoplasmic Potential
Domain86 – 18196Ig-like C2-type 1
Domain192 – 26877Ig-like C2-type 2
Domain281 – 37696Fibronectin type-III 1
Domain381 – 47898Fibronectin type-III 2
Domain582 – 852271Protein kinase
Nucleotide binding588 – 5969ATP By similarity

Sites

Active site7181Proton acceptor By similarity
Binding site6101ATP By similarity

Amino acid modifications

Modified residue5381Phosphoserine By similarity
Modified residue7441Phosphotyrosine; by autocatalysis By similarity
Modified residue7481Phosphotyrosine; by autocatalysis By similarity
Modified residue7491Phosphotyrosine; by autocatalysis By similarity
Modified residue8671Phosphotyrosine; by autocatalysis By similarity
Glycosylation1081N-linked (GlcNAc...) Potential
Glycosylation1651N-linked (GlcNAc...) Potential
Glycosylation2021N-linked (GlcNAc...) Potential
Glycosylation2101N-linked (GlcNAc...) Potential
Glycosylation2291N-linked (GlcNAc...) Potential
Glycosylation2891N-linked (GlcNAc...) Potential
Glycosylation3111N-linked (GlcNAc...) Potential
Glycosylation3241N-linked (GlcNAc...) Potential
Glycosylation3311N-linked (GlcNAc...) Potential
Glycosylation3491N-linked (GlcNAc...) Potential
Glycosylation3841N-linked (GlcNAc...) Potential
Glycosylation3901N-linked (GlcNAc...) Potential
Glycosylation4371N-linked (GlcNAc...) Potential
Glycosylation4491N-linked (GlcNAc...) Potential
Disulfide bond109 ↔ 170 By similarity
Disulfide bond213 ↔ 257 By similarity

Sequences

Sequence LengthMass (Da)Tools
P57097 [UniParc].

Last modified December 1, 2000. Version 1.
Checksum: 339717117FB4242B

FASTA994109,423
        10         20         30         40         50         60 
MVLAPLLLGL LLLSALWNGG TAEKEEEIKP DQPFSGPLPG SLPADHRPFF APHSSGDQLS 

        70         80         90        100        110        120 
PSQTGRSHPA HTATPQMTSA ASNLLPPVAF KNTIGRIVLS EHKSVKFNCS INIPNVYQET 

       130        140        150        160        170        180 
AGISWWKDGK ELLGAHHSIT QFYPDEEGVS IIALFSITSV QRSDNGSYIC KMKVNDREVV 

       190        200        210        220        230        240 
SDPIYVEVQG LPYFTKQPES VNVTRNTAFN LTCQAVGPPE PVNIFWVQNS SRVNENPERS 

       250        260        270        280        290        300 
PSVLTVAGLT ETAVFSCEAH NDKGLTVSKG VQINIKVIPS PPTEVHILNS TAHSILVSWV 

       310        320        330        340        350        360 
PGFDGYSPLQ NCSIQVKEAD QLSNGSVMVF NTSASPHLYE VQQLQALANY SVTVSCRNEI 

       370        380        390        400        410        420 
GWSAVSPWIL ASTTEGAPAV APLNITVFLN ESSNNLEIRW TKPPIKRQDG ELVGYRISHV 

       430        440        450        460        470        480 
WESAGTSKEL SEEVSQNGSW AQVPVQMHNA TCTVRIAVIT KGGIGPFSEP VDVAIPEHSR 

       490        500        510        520        530        540 
VDYAPSSTPA PGNTESMLII LGCFCGFVLM GLILYLSLAI KRRVQETKFG GAFSEEDSQL 

       550        560        570        580        590        600 
VVNYRAKKSF CRRAIELTLQ SLGVSEELQN KLEDVVVDRN LLILGKVLGE GEFGSVMEGN 

       610        620        630        640        650        660 
LKQEDGTSQK VAVKTMKLDN FSLREIEEFL SEAACMKDFN HPNVIRLLGV CIELSSQGIP 

       670        680        690        700        710        720 
KPMVILPFMK YGDLHTFLLY SRIESVPKSI PLQTLLKFMV DIAQGMEYLS SRNFLHRDLA 

       730        740        750        760        770        780 
ARNCMLRDDM TVCVADFGLS KKIYSGDYYR QGRIAKMPVK WIAIESLADR VYTSKSDVWA 

       790        800        810        820        830        840 
FGVTMWEIAT RGMTPYPGVQ NHEMYDYLLH GHRLKQPEDC LDDLYEIMYS CWSADPLDRP 

       850        860        870        880        890        900 
TFSVLRLQLE KLSESLPDAQ DKESIIYINT QLLESCEGLA NRSSLAGLDM NIDPDSIIAS 

       910        920        930        940        950        960 
CTAGAAVSVV MAEVHENNLH EERYILNGGN EEWEDVASTP FATVTAGKDG VLPEDRLTKN 

       970        980        990 
GISWSHHSTL PLGSPSPDEL LFADDSSGDS EVLM 

« Hide

References

[1]"Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat."
D'Cruz P.M., Yasumura D., Weir J., Matthes M.T., Abderrahim H., LaVail M.M., Vollrath D.
Hum. Mol. Genet. 9:645-651(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: RCS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF208235 mRNA. Translation: AAF44060.1.
PIRPT0194.
RefSeqNP_075232.1. NM_022943.1.
UniGeneRn.48789.

3D structure databases

ProteinModelPortalP57097.
SMRP57097. Positions 361-487, 570-858.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249230. 1 interaction.
STRING10116.ENSRNOP00000023419.

PTM databases

PhosphoSiteP57097.

Proteomic databases

PaxDbP57097.
PRIDEP57097.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000023419; ENSRNOP00000023419; ENSRNOG00000017319.
GeneID65037.
KEGGrno:65037.
UCSCRGD:69283. rat.

Organism-specific databases

CTD10461.
RGD69283. Mertk.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00720000108377.
HOGENOMHOG000231685.
HOVERGENHBG006346.
InParanoidP57097.
KOK05117.
OMANEIGWSA.
OrthoDBEOG77DJ5C.
PhylomeDBP57097.
TreeFamTF317402.

Enzyme and pathway databases

BRENDA2.7.10.1. 5301.

Gene expression databases

GenevestigatorP57097.

Family and domain databases

Gene3D2.60.40.10. 4 hits.
InterProIPR003961. Fibronectin_type3.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
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]
PfamPF00041. fn3. 1 hit.
PF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00060. FN3. 2 hits.
SM00409. IG. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50853. 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]
ProtoNetSearch...

Other

NextBio613844.
PROP57097.

Entry information

Entry nameMERTK_RAT
AccessionPrimary (citable) accession number: P57097
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 1, 2000
Last modified: April 16, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families