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Protein

Tyrosine-protein kinase Mer

Gene

Mertk

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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)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

GO - Biological processi

  • apoptotic cell clearance Source: UniProtKB
  • natural killer cell differentiation Source: MGI
  • negative regulation of cytokine production Source: MGI
  • negative regulation of leukocyte apoptotic process Source: MGI
  • negative regulation of lymphocyte activation Source: MGI
  • neutrophil clearance Source: MGI
  • phagocytosis Source: MGI
  • platelet activation Source: MGI
  • positive regulation of phagocytosis Source: MGI
  • protein kinase B signaling Source: MGI
  • retina development in camera-type eye Source: MGI
  • secretion by cell Source: MGI
  • spermatogenesis Source: MGI
  • substrate adhesion-dependent cell spreading Source: MGI
  • 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.
ReactomeiR-MMU-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:96965. 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

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)DescriptionActionsGraphical viewLength
Mutagenesisi867Y → F: Loss of GRB2 binding. 1 Publication1

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000002444419 – 994Tyrosine-protein kinase MerAdd BLAST976

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi91N-linked (GlcNAc...)Sequence analysis1
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 autocatalysis1 Publication1

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.
PeptideAtlasiQ60805.
PRIDEiQ60805.

PTM databases

iPTMnetiQ60805.
PhosphoSitePlusiQ60805.

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

BgeeiENSMUSG00000014361.
CleanExiMM_MERTK.
GenevisibleiQ60805. MM.

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 interactor.
STRINGi10090.ENSMUSP00000014505.

Structurei

3D structure databases

ProteinModelPortaliQ60805.
SMRiQ60805.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini75 – 181Ig-like C2-type 1Add BLAST107
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.
InParanoidiQ60805.
KOiK05117.
OMAiKHIPLQT.
OrthoDBiEOG091G016X.
PhylomeDBiQ60805.
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.

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)DescriptionActionsGraphical viewLength
Sequence conflicti473 – 476IIIP → SARA (Ref. 2) Curated4
Sequence conflicti516I → V in AAA85355 (Ref. 2) Curated1

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.
CCDSiCCDS16716.1.
PIRiI49276.
RefSeqiNP_032613.1. NM_008587.1.
UniGeneiMm.239655.

3D structure databases

ProteinModelPortaliQ60805.
SMRiQ60805.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ60805. 1 interactor.
STRINGi10090.ENSMUSP00000014505.

PTM databases

iPTMnetiQ60805.
PhosphoSitePlusiQ60805.

Proteomic databases

MaxQBiQ60805.
PaxDbiQ60805.
PeptideAtlasiQ60805.
PRIDEiQ60805.

Protocols and materials databases

DNASUi17289.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi10461.
MGIiMGI:96965. Mertk.

Phylogenomic databases

eggNOGiENOG410IG6I. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00810000125384.
HOGENOMiHOG000231685.
HOVERGENiHBG006346.
InParanoidiQ60805.
KOiK05117.
OMAiKHIPLQT.
OrthoDBiEOG091G016X.
PhylomeDBiQ60805.
TreeFamiTF317402.

Enzyme and pathway databases

BRENDAi2.7.10.1. 3474.
ReactomeiR-MMU-202733. Cell surface interactions at the vascular wall.

Miscellaneous databases

PROiQ60805.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000014361.
CleanExiMM_MERTK.
GenevisibleiQ60805. MM.

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_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 30, 2016
This is version 163 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

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.