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Protein

Tyrosine-protein kinase Mer

Gene

Mertk

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

Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
LigandATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:96965 Mertk

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 497ExtracellularSequence analysisAdd BLAST479
Transmembranei498 – 518HelicalSequence analysisAdd BLAST21
Topological domaini519 – 994CytoplasmicSequence analysisAdd BLAST476

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...) asparagineSequence analysis1
Glycosylationi108N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi109 ↔ 170PROSITE-ProRule annotation
Glycosylationi165N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi202N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi210N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi213 ↔ 257PROSITE-ProRule annotation
Glycosylationi229N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi289N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi311N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi324N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi331N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi349N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi384N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi390N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi437N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi449N-linked (GlcNAc...) asparagineSequence 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 Expressed in 266 organ(s), highest expression level in stroma of bone marrow
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

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

CDDicd00063 FN3, 2 hits
Gene3Di2.60.40.10, 4 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR013151 Immunoglobulin
IPR011009 Kinase-like_dom_sf
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
PfamiView protein in Pfam
PF00041 fn3, 1 hit
PF00047 ig, 1 hit
PF13895 Ig_2, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00060 FN3, 2 hits
SM00409 IG, 2 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
SSF49265 SSF49265, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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

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_008587.2
UniGeneiMm.239655

Genome annotation databases

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

Similar proteinsi

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_008587.2
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
OMAiNEIGWSA
OrthoDBiEOG091G016X
PhylomeDBiQ60805
TreeFamiTF317402

Enzyme and pathway databases

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

Miscellaneous databases

PROiPR:Q60805
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000014361 Expressed in 266 organ(s), highest expression level in stroma of bone marrow
CleanExiMM_MERTK
GenevisibleiQ60805 MM

Family and domain databases

CDDicd00063 FN3, 2 hits
Gene3Di2.60.40.10, 4 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR013151 Immunoglobulin
IPR011009 Kinase-like_dom_sf
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
PfamiView protein in Pfam
PF00041 fn3, 1 hit
PF00047 ig, 1 hit
PF13895 Ig_2, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00060 FN3, 2 hits
SM00409 IG, 2 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
SSF49265 SSF49265, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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
ProtoNetiSearch...

Entry informationi

Entry nameiMERTK_MOUSE
AccessioniPrimary (citable) accession number: Q60805
Secondary accession number(s): Q62194
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: September 12, 2018
This is version 172 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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