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Q60805

- MERTK_MOUSE

UniProt

Q60805 - MERTK_MOUSE

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Protein
Tyrosine-protein kinase Mer
Gene
Mertk, Mer
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein 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 SOCS3.2 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei610 – 6101ATP By similarity
Active sitei718 – 7181Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi588 – 5969ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB-EC

GO - Biological processi

  1. apoptotic cell clearance Source: UniProtKB
  2. natural killer cell differentiation Source: MGI
  3. negative regulation of lymphocyte activation Source: MGI
  4. platelet activation Source: MGI
  5. positive regulation of phagocytosis Source: Ensembl
  6. protein kinase B signaling Source: MGI
  7. retina development in camera-type eye Source: MGI
  8. secretion by cell Source: MGI
  9. spermatogenesis Source: MGI
  10. substrate adhesion-dependent cell spreading Source: MGI
  11. vagina development Source: MGI
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. 3474.
ReactomeiREACT_225233. 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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 2

Organism-specific databases

MGIiMGI:96965. Mertk.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 497479Extracellular Reviewed prediction
Add
BLAST
Transmembranei498 – 51821Helical; Reviewed prediction
Add
BLAST
Topological domaini519 – 994476Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. cytoplasm Source: Ensembl
  2. extracellular space Source: Ensembl
  3. integral component of membrane Source: UniProtKB-KW
  4. photoreceptor outer segment Source: Ensembl
  5. rhabdomere Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Disruption phenotypei

knockout mice are fertile, but male animals that lack all three receptors TYRO3, AXL and MERTK produce no mature sperm.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi867 – 8671Y → F: Loss of GRB2 binding. 1 Publication

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818 Reviewed prediction
Add
BLAST
Chaini19 – 994976Tyrosine-protein kinase Mer
PRO_0000024444Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi91 – 911N-linked (GlcNAc...) Reviewed prediction
Glycosylationi108 – 1081N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi109 ↔ 170 By similarity
Glycosylationi165 – 1651N-linked (GlcNAc...) Reviewed prediction
Glycosylationi202 – 2021N-linked (GlcNAc...) Reviewed prediction
Glycosylationi210 – 2101N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi213 ↔ 257 By similarity
Glycosylationi229 – 2291N-linked (GlcNAc...) Reviewed prediction
Glycosylationi289 – 2891N-linked (GlcNAc...) Reviewed prediction
Glycosylationi311 – 3111N-linked (GlcNAc...) Reviewed prediction
Glycosylationi324 – 3241N-linked (GlcNAc...) Reviewed prediction
Glycosylationi331 – 3311N-linked (GlcNAc...) Reviewed prediction
Glycosylationi349 – 3491N-linked (GlcNAc...) Reviewed prediction
Glycosylationi384 – 3841N-linked (GlcNAc...) Reviewed prediction
Glycosylationi390 – 3901N-linked (GlcNAc...) Reviewed prediction
Glycosylationi437 – 4371N-linked (GlcNAc...) Reviewed prediction
Glycosylationi449 – 4491N-linked (GlcNAc...) Reviewed prediction
Modified residuei538 – 5381Phosphoserine By similarity
Modified residuei744 – 7441Phosphotyrosine; by autocatalysis By similarity
Modified residuei748 – 7481Phosphotyrosine; by autocatalysis By similarity
Modified residuei749 – 7491Phosphotyrosine; by autocatalysis By similarity
Modified residuei867 – 8671Phosphotyrosine; by autocatalysis1 Publication

Post-translational modificationi

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 PLCG2.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ60805.
PaxDbiQ60805.
PRIDEiQ60805.

PTM databases

PhosphoSiteiQ60805.

Expressioni

Tissue specificityi

Expressed predominantly in the hematopoietic lineages: macrophages, NK cells, NKT cells, dendritic cells and platelets.1 Publication

Developmental stagei

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.

Gene expression databases

ArrayExpressiQ60805.
BgeeiQ60805.
CleanExiMM_MERTK.
GenevestigatoriQ60805.

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.5 Publications

Protein-protein interaction databases

IntActiQ60805. 1 interaction.
STRINGi10090.ENSMUSP00000014505.

Structurei

3D structure databases

ProteinModelPortaliQ60805.
SMRiQ60805. Positions 97-276, 287-487, 533-863.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini75 – 181107Ig-like C2-type 1
Add
BLAST
Domaini192 – 26877Ig-like C2-type 2
Add
BLAST
Domaini281 – 37696Fibronectin type-III 1
Add
BLAST
Domaini381 – 47898Fibronectin type-III 2
Add
BLAST
Domaini582 – 852271Protein kinase
Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00720000108377.
HOGENOMiHOG000231685.
HOVERGENiHBG006346.
InParanoidiQ60805.
KOiK05117.
OMAiNEIGWSA.
OrthoDBiEOG77DJ5C.
PhylomeDBiQ60805.
TreeFamiTF317402.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiIPR003961. 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]
PfamiPF00041. fn3. 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]
SUPFAMiSSF49265. 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.

Q60805-1 [UniParc]FASTAAdd to Basket

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MVLAPLLLGL LLLPALWSGG TAEKWEETEL DQLFSGPLPG RLPVNHRPFS    50
APHSSRDQLP PPQTGRSHPA HTAAPQVTST ASKLLPPVAF NHTIGHIVLS 100
EHKNVKFNCS INIPNTYQET AGISWWKDGK ELLGAHHSIT QFYPDEEGVS 150
IIALFSIASV QRSDNGSYFC KMKVNNREIV SDPIYVEVQG LPYFIKQPES 200
VNVTRNTAFN LTCQAVGPPE PVNIFWVQNS SRVNEKPERS PSVLTVPGLT 250
ETAVFSCEAH NDKGLTVSKG VHINIKVIPS PPTEVHILNS TAHSILVSWV 300
PGFDGYSPLQ NCSIQVKEAD RLSNGSVMVF NTSASPHLYE IQQLQALANY 350
SIAVSCRNEI GWSAVSPWIL ASTTEGAPSV APLNITVFLN ESNNILDIRW 400
TKPPIKRQDG ELVGYRISHV WESAGTYKEL SEEVSQNGSW AQIPVQIHNA 450
TCTVRIAAIT KGGIGPFSEP VNIIIPEHSK VDYAPSSTPA PGNTDSMFII 500
LGCFCGFILI GLILCISLAL RRRVQETKFG GAFSEEDSQL VVNYRAKKSF 550
CRRAIELTLQ SLGVSEELQN KLEDVVIDRN LLVLGKVLGE GEFGSVMEGN 600
LKQEDGTSQK VAVKTMKLDN FSQREIEEFL SEAACMKDFN HPNVIRLLGV 650
CIELSSQGIP KPMVILPFMK YGDLHTFLLY SRLNTGPKYI HLQTLLKFMM 700
DIAQGMEYLS NRNFLHRDLA ARNCMLRDDM TVCVADFGLS KKIYSGDYYR 750
QGRIAKMPVK WIAIESLADR VYTSKSDVWA FGVTMWEITT RGMTPYPGVQ 800
NHEMYDYLLH GHRLKQPEDC LDELYDIMYS CWSADPLDRP TFSVLRLQLE 850
KLSESLPDAQ DKESIIYINT QLLESCEGIA NGPSLTGLDM NIDPDSIIAS 900
CTPGAAVSVV TAEVHENNLR EERYILNGGN EEWEDVSSTP FAAVTPEKDG 950
VLPEDRLTKN GVSWSHHSTL PLGSPSPDEL LFVDDSLEDS EVLM 994
Length:994
Mass (Da):110,157
Last modified:November 1, 1996 - v1
Checksum:i603C09FA11F76FE0
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti473 – 4764IIIP → SARA1 Publication
Sequence conflicti516 – 5161I → V in AAA85355. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U21301 mRNA. Translation: AAA80222.1.
L11625 mRNA. Translation: AAA85355.1.
CCDSiCCDS16716.1.
PIRiI49276.
RefSeqiNP_032613.1. NM_008587.1.
UniGeneiMm.239655.

Genome annotation databases

EnsembliENSMUST00000014505; ENSMUSP00000014505; ENSMUSG00000014361.
GeneIDi17289.
KEGGimmu:17289.
UCSCiuc008mgt.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U21301 mRNA. Translation: AAA80222.1 .
L11625 mRNA. Translation: AAA85355.1 .
CCDSi CCDS16716.1.
PIRi I49276.
RefSeqi NP_032613.1. NM_008587.1.
UniGenei Mm.239655.

3D structure databases

ProteinModelPortali Q60805.
SMRi Q60805. Positions 97-276, 287-487, 533-863.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q60805. 1 interaction.
STRINGi 10090.ENSMUSP00000014505.

PTM databases

PhosphoSitei Q60805.

Proteomic databases

MaxQBi Q60805.
PaxDbi Q60805.
PRIDEi Q60805.

Protocols and materials databases

DNASUi 17289.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000014505 ; ENSMUSP00000014505 ; ENSMUSG00000014361 .
GeneIDi 17289.
KEGGi mmu:17289.
UCSCi uc008mgt.1. mouse.

Organism-specific databases

CTDi 10461.
MGIi MGI:96965. Mertk.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00720000108377.
HOGENOMi HOG000231685.
HOVERGENi HBG006346.
InParanoidi Q60805.
KOi K05117.
OMAi NEIGWSA.
OrthoDBi EOG77DJ5C.
PhylomeDBi Q60805.
TreeFami TF317402.

Enzyme and pathway databases

BRENDAi 2.7.10.1. 3474.
Reactomei REACT_225233. Cell surface interactions at the vascular wall.

Miscellaneous databases

NextBioi 291808.
PROi Q60805.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q60805.
Bgeei Q60805.
CleanExi MM_MERTK.
Genevestigatori Q60805.

Family and domain databases

Gene3Di 2.60.40.10. 4 hits.
InterProi IPR003961. 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 ]
Pfami PF00041. fn3. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view ]
PRINTSi PR00109. TYRKINASE.
SMARTi SM00060. FN3. 2 hits.
SM00409. IG. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF49265. SSF49265. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiMERTK_MOUSE
AccessioniPrimary (citable) accession number: Q60805
Secondary accession number(s): Q62194
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: September 3, 2014
This is version 142 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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