Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q60805

- MERTK_MOUSE

UniProt

Q60805 - MERTK_MOUSE

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Tyrosine-protein kinase Mer

Gene

Mertk

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.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei610 – 6101ATPPROSITE-ProRule annotation
Active sitei718 – 7181Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi588 – 5969ATPPROSITE-ProRule annotation

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.

Protein family/group databases

MEROPSiI43.001.

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

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 497479ExtracellularSequence AnalysisAdd
BLAST
Transmembranei498 – 51821HelicalSequence AnalysisAdd
BLAST
Topological domaini519 – 994476CytoplasmicSequence AnalysisAdd
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 – 1818Sequence AnalysisAdd
BLAST
Chaini19 – 994976Tyrosine-protein kinase MerPRO_0000024444Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi91 – 911N-linked (GlcNAc...)Sequence Analysis
Glycosylationi108 – 1081N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi109 ↔ 170PROSITE-ProRule annotation
Glycosylationi165 – 1651N-linked (GlcNAc...)Sequence Analysis
Glycosylationi202 – 2021N-linked (GlcNAc...)Sequence Analysis
Glycosylationi210 – 2101N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi213 ↔ 257PROSITE-ProRule annotation
Glycosylationi229 – 2291N-linked (GlcNAc...)Sequence Analysis
Glycosylationi289 – 2891N-linked (GlcNAc...)Sequence Analysis
Glycosylationi311 – 3111N-linked (GlcNAc...)Sequence Analysis
Glycosylationi324 – 3241N-linked (GlcNAc...)Sequence Analysis
Glycosylationi331 – 3311N-linked (GlcNAc...)Sequence Analysis
Glycosylationi349 – 3491N-linked (GlcNAc...)Sequence Analysis
Glycosylationi384 – 3841N-linked (GlcNAc...)Sequence Analysis
Glycosylationi390 – 3901N-linked (GlcNAc...)Sequence Analysis
Glycosylationi437 – 4371N-linked (GlcNAc...)Sequence Analysis
Glycosylationi449 – 4491N-linked (GlcNAc...)Sequence Analysis
Modified residuei538 – 5381PhosphoserineBy similarity
Modified residuei744 – 7441Phosphotyrosine; by autocatalysisBy similarity
Modified residuei748 – 7481Phosphotyrosine; by autocatalysisBy similarity
Modified residuei749 – 7491Phosphotyrosine; by autocatalysisBy 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.By similarity1 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

BgeeiQ60805.
CleanExiMM_MERTK.
ExpressionAtlasiQ60805. baseline and differential.
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).By similarity

Protein-protein interaction databases

IntActiQ60805. 1 interaction.
STRINGi10090.ENSMUSP00000014505.

Structurei

3D structure databases

ProteinModelPortaliQ60805.
SMRiQ60805. Positions 97-276, 361-487, 533-863.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

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

eggNOGiCOG0515.
GeneTreeiENSGT00770000120499.
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

« Hide

        10         20         30         40         50
MVLAPLLLGL LLLPALWSGG TAEKWEETEL DQLFSGPLPG RLPVNHRPFS
60 70 80 90 100
APHSSRDQLP PPQTGRSHPA HTAAPQVTST ASKLLPPVAF NHTIGHIVLS
110 120 130 140 150
EHKNVKFNCS INIPNTYQET AGISWWKDGK ELLGAHHSIT QFYPDEEGVS
160 170 180 190 200
IIALFSIASV QRSDNGSYFC KMKVNNREIV SDPIYVEVQG LPYFIKQPES
210 220 230 240 250
VNVTRNTAFN LTCQAVGPPE PVNIFWVQNS SRVNEKPERS PSVLTVPGLT
260 270 280 290 300
ETAVFSCEAH NDKGLTVSKG VHINIKVIPS PPTEVHILNS TAHSILVSWV
310 320 330 340 350
PGFDGYSPLQ NCSIQVKEAD RLSNGSVMVF NTSASPHLYE IQQLQALANY
360 370 380 390 400
SIAVSCRNEI GWSAVSPWIL ASTTEGAPSV APLNITVFLN ESNNILDIRW
410 420 430 440 450
TKPPIKRQDG ELVGYRISHV WESAGTYKEL SEEVSQNGSW AQIPVQIHNA
460 470 480 490 500
TCTVRIAAIT KGGIGPFSEP VNIIIPEHSK VDYAPSSTPA PGNTDSMFII
510 520 530 540 550
LGCFCGFILI GLILCISLAL RRRVQETKFG GAFSEEDSQL VVNYRAKKSF
560 570 580 590 600
CRRAIELTLQ SLGVSEELQN KLEDVVIDRN LLVLGKVLGE GEFGSVMEGN
610 620 630 640 650
LKQEDGTSQK VAVKTMKLDN FSQREIEEFL SEAACMKDFN HPNVIRLLGV
660 670 680 690 700
CIELSSQGIP KPMVILPFMK YGDLHTFLLY SRLNTGPKYI HLQTLLKFMM
710 720 730 740 750
DIAQGMEYLS NRNFLHRDLA ARNCMLRDDM TVCVADFGLS KKIYSGDYYR
760 770 780 790 800
QGRIAKMPVK WIAIESLADR VYTSKSDVWA FGVTMWEITT RGMTPYPGVQ
810 820 830 840 850
NHEMYDYLLH GHRLKQPEDC LDELYDIMYS CWSADPLDRP TFSVLRLQLE
860 870 880 890 900
KLSESLPDAQ DKESIIYINT QLLESCEGIA NGPSLTGLDM NIDPDSIIAS
910 920 930 940 950
CTPGAAVSVV TAEVHENNLR EERYILNGGN EEWEDVSSTP FAAVTPEKDG
960 970 980 990
VLPEDRLTKN GVSWSHHSTL PLGSPSPDEL LFVDDSLEDS EVLM
Length:994
Mass (Da):110,157
Last modified:November 1, 1996 - v1
Checksum:i603C09FA11F76FE0
GO

Experimental Info

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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, 361-487, 533-863.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q60805. 1 interaction.
STRINGi 10090.ENSMUSP00000014505.

Protein family/group databases

MEROPSi I43.001.

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 ENSGT00770000120499.
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

Bgeei Q60805.
CleanExi MM_MERTK.
ExpressionAtlasi Q60805. baseline and differential.
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: November 26, 2014
This is version 145 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