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Q60805 (MERTK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length994 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein 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. Ref.9 Ref.11

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. Ref.4 Ref.6 Ref.7 Ref.10 Ref.12

Subcellular location

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

Tissue specificity

Expressed predominantly in the hematopoietic lineages: macrophages, NK cells, NKT cells, dendritic cells and platelets. Ref.5

Developmental stage

Expressed during most, if not all, stages of embryological development beginning in the morula and blastocyst and progressing through the yolk sac and fetal liver stages.

Post-translational modification

Autophosphorylated on Tyr-744, Tyr-748 and Tyr-749 in the activation loop allowing full activity By similarity. Autophosphorylated on Tyr-867 leading to recruitment of downstream partners of the signaling cascade such as PLCG2. Ref.8

Disruption phenotype

knockout mice are fertile, but male animals that lack all three receptors TYRO3, AXL and MERTK produce no mature sperm. Ref.3

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 mutant phenotype PubMed 18159085. Source: UniProtKB

natural killer cell differentiation

Inferred from genetic interaction PubMed 16751775. Source: MGI

negative regulation of lymphocyte activation

Inferred from genetic interaction PubMed 11452127. Source: MGI

platelet activation

Inferred from mutant phenotype PubMed 15650770. Source: MGI

positive regulation of phagocytosis

Inferred from electronic annotation. Source: Ensembl

protein kinase B signaling

Inferred from genetic interaction PubMed 15650770. Source: MGI

retina development in camera-type eye

Inferred from mutant phenotype PubMed 21052544. Source: MGI

secretion by cell

Inferred from mutant phenotype PubMed 15650770. Source: MGI

spermatogenesis

Inferred from genetic interaction Ref.3. Source: MGI

substrate adhesion-dependent cell spreading

Inferred from mutant phenotype PubMed 15650770. Source: MGI

vagina development

Inferred from genetic interaction PubMed 18393392. Source: MGI

   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 electronic annotation. Source: Ensembl

rhabdomere

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

transmembrane receptor protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 994976Tyrosine-protein kinase Mer
PRO_0000024444

Regions

Topological domain19 – 497479Extracellular Potential
Transmembrane498 – 51821Helical; Potential
Topological domain519 – 994476Cytoplasmic Potential
Domain75 – 181107Ig-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 Ref.8
Glycosylation911N-linked (GlcNAc...) Potential
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

Experimental info

Mutagenesis8671Y → F: Loss of GRB2 binding. Ref.4
Sequence conflict473 – 4764IIIP → SARA Ref.2
Sequence conflict5161I → V in AAA85355. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q60805 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 603C09FA11F76FE0

FASTA994110,157
        10         20         30         40         50         60 
MVLAPLLLGL LLLPALWSGG TAEKWEETEL DQLFSGPLPG RLPVNHRPFS APHSSRDQLP 

        70         80         90        100        110        120 
PPQTGRSHPA HTAAPQVTST ASKLLPPVAF NHTIGHIVLS EHKNVKFNCS INIPNTYQET 

       130        140        150        160        170        180 
AGISWWKDGK ELLGAHHSIT QFYPDEEGVS IIALFSIASV QRSDNGSYFC KMKVNNREIV 

       190        200        210        220        230        240 
SDPIYVEVQG LPYFIKQPES VNVTRNTAFN LTCQAVGPPE PVNIFWVQNS SRVNEKPERS 

       250        260        270        280        290        300 
PSVLTVPGLT ETAVFSCEAH NDKGLTVSKG VHINIKVIPS PPTEVHILNS TAHSILVSWV 

       310        320        330        340        350        360 
PGFDGYSPLQ NCSIQVKEAD RLSNGSVMVF NTSASPHLYE IQQLQALANY SIAVSCRNEI 

       370        380        390        400        410        420 
GWSAVSPWIL ASTTEGAPSV APLNITVFLN ESNNILDIRW TKPPIKRQDG ELVGYRISHV 

       430        440        450        460        470        480 
WESAGTYKEL SEEVSQNGSW AQIPVQIHNA TCTVRIAAIT KGGIGPFSEP VNIIIPEHSK 

       490        500        510        520        530        540 
VDYAPSSTPA PGNTDSMFII LGCFCGFILI GLILCISLAL RRRVQETKFG GAFSEEDSQL 

       550        560        570        580        590        600 
VVNYRAKKSF CRRAIELTLQ SLGVSEELQN KLEDVVIDRN LLVLGKVLGE GEFGSVMEGN 

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

       670        680        690        700        710        720 
KPMVILPFMK YGDLHTFLLY SRLNTGPKYI HLQTLLKFMM DIAQGMEYLS NRNFLHRDLA 

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

       790        800        810        820        830        840 
FGVTMWEITT RGMTPYPGVQ NHEMYDYLLH GHRLKQPEDC LDELYDIMYS CWSADPLDRP 

       850        860        870        880        890        900 
TFSVLRLQLE KLSESLPDAQ DKESIIYINT QLLESCEGIA NGPSLTGLDM NIDPDSIIAS 

       910        920        930        940        950        960 
CTPGAAVSVV TAEVHENNLR EERYILNGGN EEWEDVSSTP FAAVTPEKDG VLPEDRLTKN 

       970        980        990 
GVSWSHHSTL PLGSPSPDEL LFVDDSLEDS EVLM 

« Hide

References

[1]"Cloning and developmental expression analysis of the murine c-mer tyrosine kinase."
Graham D.K., Bowman G.W., Dawson T.L., Stanford W.L., Earp H.S., Snodgrass H.R.
Oncogene 10:2349-2359(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6.
Tissue: Spleen.
[2]"A cDNA encoding part of a novel putative receptor tyrosine kinase."
Dowds C.A., Burks D.J., Saling P.M.
Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 472-994.
Strain: CD-1.
Tissue: Testis.
[3]"Tyro-3 family receptors are essential regulators of mammalian spermatogenesis."
Lu Q., Gore M., Zhang Q., Camenisch T., Boast S., Casagranda F., Lai C., Skinner M.K., Klein R., Matsushima G.K., Earp H.S., Goff S.P., Lemke G.
Nature 398:723-728(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[4]"Biological effects of c-Mer receptor tyrosine kinase in hematopoietic cells depend on the Grb2 binding site in the receptor and activation of NF-kappaB."
Georgescu M.M., Kirsch K.H., Shishido T., Zong C., Hanafusa H.
Mol. Cell. Biol. 19:1171-1181(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRB2, MUTAGENESIS OF TYR-867.
[5]"The mer receptor tyrosine kinase: expression and function suggest a role in innate immunity."
Behrens E.M., Gadue P., Gong S.Y., Garrett S., Stein P.L., Cohen P.L.
Eur. J. Immunol. 33:2160-2167(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[6]"The receptor tyrosine kinase MerTK activates phospholipase C gamma2 during recognition of apoptotic thymocytes by murine macrophages."
Todt J.C., Hu B., Curtis J.L.
J. Leukoc. Biol. 75:705-713(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLCG2.
[7]"A role for Mer tyrosine kinase in alphavbeta5 integrin-mediated phagocytosis of apoptotic cells."
Wu Y., Singh S., Georgescu M.M., Birge R.B.
J. Cell Sci. 118:539-553(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FAK/PTK2.
[8]"Autophosphorylation docking site Tyr-867 in Mer receptor tyrosine kinase allows for dissociation of multiple signaling pathways for phagocytosis of apoptotic cells and down-modulation of lipopolysaccharide-inducible NF-kappaB transcriptional activation."
Tibrewal N., Wu Y., D'mello V., Akakura R., George T.C., Varnum B., Birge R.B.
J. Biol. Chem. 283:3618-3627(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-867.
[9]"Mertk drives myosin II redistribution during retinal pigment epithelial phagocytosis."
Strick D.J., Feng W., Vollrath D.
Invest. Ophthalmol. Vis. Sci. 50:2427-2435(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis."
Caberoy N.B., Zhou Y., Li W.
EMBO J. 29:3898-3910(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TUB AND TULP1.
[11]"Sertoli cell-initiated testicular innate immune response through toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and mer receptors."
Sun B., Qi N., Shang T., Wu H., Deng T., Han D.
Endocrinology 151:2886-2897(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN IMMUNE RESPONSE INHIBITION.
[12]"Galectin-3 is a new MerTK-specific eat-me signal."
Caberoy N.B., Alvarado G., Bigcas J.L., Li W.
J. Cell. Physiol. 227:401-407(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LGALS3.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U21301 mRNA. Translation: AAA80222.1.
L11625 mRNA. Translation: AAA85355.1.
CCDSCCDS16716.1.
PIRI49276.
RefSeqNP_032613.1. NM_008587.1.
UniGeneMm.239655.

3D structure databases

ProteinModelPortalQ60805.
SMRQ60805. Positions 97-276, 287-487, 533-863.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ60805. 1 interaction.
STRING10090.ENSMUSP00000014505.

PTM databases

PhosphoSiteQ60805.

Proteomic databases

MaxQBQ60805.
PaxDbQ60805.
PRIDEQ60805.

Protocols and materials databases

DNASU17289.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000014505; ENSMUSP00000014505; ENSMUSG00000014361.
GeneID17289.
KEGGmmu:17289.
UCSCuc008mgt.1. mouse.

Organism-specific databases

CTD10461.
MGIMGI:96965. Mertk.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00720000108377.
HOGENOMHOG000231685.
HOVERGENHBG006346.
InParanoidQ60805.
KOK05117.
OMANEIGWSA.
OrthoDBEOG77DJ5C.
PhylomeDBQ60805.
TreeFamTF317402.

Enzyme and pathway databases

BRENDA2.7.10.1. 3474.

Gene expression databases

ArrayExpressQ60805.
BgeeQ60805.
CleanExMM_MERTK.
GenevestigatorQ60805.

Family and domain databases

Gene3D2.60.40.10. 4 hits.
InterProIPR003961. Fibronectin_type3.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
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.
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

NextBio291808.
PROQ60805.
SOURCESearch...

Entry information

Entry nameMERTK_MOUSE
AccessionPrimary (citable) accession number: Q60805
Secondary accession number(s): Q62194
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 141 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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot