MERTK_HUMAN
ID MERTK_HUMAN Reviewed; 999 AA.
AC Q12866; Q9HBB4;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Tyrosine-protein kinase Mer;
DE EC=2.7.10.1;
DE AltName: Full=Proto-oncogene c-Mer;
DE AltName: Full=Receptor tyrosine kinase MerTK;
DE Flags: Precursor;
GN Name=MERTK; Synonyms=MER;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ASN-118.
RC TISSUE=Peripheral blood leukocyte;
RX PubMed=8086340;
RA Graham D.K., Dawson T.L., Mullaney D.L., Snodgrass H.R., Earp H.S.;
RT "Cloning and mRNA expression analysis of a novel human protooncogene, c-
RT mer.";
RL Cell Growth Differ. 5:647-657(1994).
RN [2]
RP ERRATUM OF PUBMED:8086340.
RA Graham D.K., Dawson T.L., Mullaney D.L., Snodgrass H.R., Earp H.S.;
RL Cell Growth Differ. 5:1022-1022(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 22-999, VARIANTS RP38 LYS-540; CYS-661
RP AND THR-871, AND VARIANTS SER-20; ASN-118; THR-282; HIS-293; LYS-466;
RP SER-498; VAL-518 AND VAL-871.
RX PubMed=11062461; DOI=10.1038/81555;
RA Gal A., Li Y., Thompson D.A., Weir J., Orth U., Jacobson S.G.,
RA Apfelstedt-Sylla E., Vollrath D.;
RT "Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy
RT gene, cause retinitis pigmentosa.";
RL Nat. Genet. 26:270-271(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP PHOSPHORYLATION AT TYR-749; TYR-753 AND TYR-754.
RX PubMed=8702477; DOI=10.1074/jbc.271.31.18355;
RA Ling L., Templeton D., Kung H.J.;
RT "Identification of the major autophosphorylation sites of Nyk/Mer, an NCAM-
RT related receptor tyrosine kinase.";
RL J. Biol. Chem. 271:18355-18362(1996).
RN [6]
RP INTERACTION WITH GAS6.
RX PubMed=9160883; DOI=10.1038/sj.onc.1201039;
RA Chen J., Carey K., Godowski P.J.;
RT "Identification of Gas6 as a ligand for Mer, a neural cell adhesion
RT molecule related receptor tyrosine kinase implicated in cellular
RT transformation.";
RL Oncogene 14:2033-2039(1997).
RN [7]
RP INTERACTION WITH VAV1.
RX PubMed=12920122; DOI=10.1074/jbc.m305817200;
RA Mahajan N.P., Earp H.S.;
RT "An SH2 domain-dependent, phosphotyrosine-independent interaction between
RT Vav1 and the Mer receptor tyrosine kinase: a mechanism for localizing
RT guanine nucleotide-exchange factor action.";
RL J. Biol. Chem. 278:42596-42603(2003).
RN [8]
RP INTERACTION WITH TNK2.
RX PubMed=16288044; DOI=10.1158/0008-5472.can-05-1127;
RA Mahajan N.P., Whang Y.E., Mohler J.L., Earp H.S.;
RT "Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of
RT Ack1 in polyubiquitination of tumor suppressor Wwox.";
RL Cancer Res. 65:10514-10523(2005).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-442.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [10]
RP REVIEW ON FUNCTION.
RX PubMed=16737840; DOI=10.1016/j.cytogfr.2006.04.004;
RA Hafizi S., Dahlback B.;
RT "Signalling and functional diversity within the Axl subfamily of receptor
RT tyrosine kinases.";
RL Cytokine Growth Factor Rev. 17:295-304(2006).
RN [11]
RP FUNCTION AS CELL ENTRY FACTOR IN FILOVIRUS INFECTION.
RX PubMed=17005688; DOI=10.1128/jvi.01157-06;
RA Shimojima M., Takada A., Ebihara H., Neumann G., Fujioka K., Irimura T.,
RA Jones S., Feldmann H., Kawaoka Y.;
RT "Tyro3 family-mediated cell entry of Ebola and Marburg viruses.";
RL J. Virol. 80:10109-10116(2006).
RN [12]
RP REVIEW ON FUNCTION.
RX PubMed=18421305; DOI=10.1038/nri2303;
RA Lemke G., Rothlin C.V.;
RT "Immunobiology of the TAM receptors.";
RL Nat. Rev. Immunol. 8:327-336(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-543 AND SER-935, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [14]
RP INTERACTION WITH LGALS3.
RX PubMed=21792939; DOI=10.1002/jcp.22955;
RA Caberoy N.B., Alvarado G., Bigcas J.L., Li W.;
RT "Galectin-3 is a new MerTK-specific eat-me signal.";
RL J. Cell. Physiol. 227:401-407(2012).
RN [15]
RP FUNCTION, INTERACTION WITH TIMD4, AND SUBCELLULAR LOCATION.
RX PubMed=32640697; DOI=10.3390/cells9071625;
RA Moon B., Lee J., Lee S.A., Min C., Moon H., Kim D., Yang S., Moon H.,
RA Jeon J., Joo Y.E., Park D.;
RT "Mertk Interacts with Tim-4 to Enhance Tim-4-Mediated Efferocytosis.";
RL Cells 9:0-0(2020).
RN [16]
RP STRUCTURE BY NMR OF 366-483.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structures of the FN3 domain of human proto-oncogene tyrosine-
RT protein kinase MER precursor.";
RL Submitted (DEC-2006) to the PDB data bank.
RN [17]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-20; ASN-118; MET-185; THR-282; LYS-289;
RP HIS-293; GLY-446; LEU-452; LYS-466; SER-498; VAL-518; GLU-662; SER-708;
RP GLN-823; TRP-865 AND ILE-870.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [18]
RP VARIANTS VAL-214 AND LEU-958.
RX PubMed=21602930; DOI=10.1371/journal.pone.0019458;
RA Li L., Xiao X., Li S., Jia X., Wang P., Guo X., Jiao X., Zhang Q.,
RA Hejtmancik J.F.;
RT "Detection of variants in 15 genes in 87 unrelated Chinese patients with
RT Leber congenital amaurosis.";
RL PLoS ONE 6:E19458-E19458(2011).
CC -!- FUNCTION: Receptor tyrosine kinase that transduces signals from the
CC extracellular matrix into the cytoplasm by binding to several ligands
CC including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological
CC processes including cell survival, migration, differentiation, and
CC phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the
CC cell surface induces autophosphorylation of MERTK on its intracellular
CC domain that provides docking sites for downstream signaling molecules.
CC Following activation by ligand, interacts with GRB2 or PLCG2 and
CC induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK
CC signaling plays a role in various processes such as macrophage
CC clearance of apoptotic cells, platelet aggregation, cytoskeleton
CC reorganization and engulfment (PubMed:32640697). Functions in the
CC retinal pigment epithelium (RPE) as a regulator of rod outer segments
CC fragments phagocytosis. Also plays an important role in inhibition of
CC Toll-like receptors (TLRs)-mediated innate immune response by
CC activating STAT1, which selectively induces production of suppressors
CC of cytokine signaling SOCS1 and SOCS3. {ECO:0000269|PubMed:17005688,
CC ECO:0000269|PubMed:32640697}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- SUBUNIT: Interacts (upon activation) with TNK2; stimulates TNK2
CC autophosphorylation. Interacts (via N-terminus) with extracellular
CC ligands LGALS3, TUB, TULP1 and GAS6 (By similarity). Interacts with
CC VAV1 in a phosphotyrosine-independent manner. Interacts with TIMD4;
CC this interaction enhances TIMD4-mediated efferocytosis
CC (PubMed:32640697). {ECO:0000250, ECO:0000269|PubMed:12920122,
CC ECO:0000269|PubMed:16288044, ECO:0000269|PubMed:21792939,
CC ECO:0000269|PubMed:32640697, ECO:0000269|PubMed:9160883}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:32640697};
CC Single-pass type I membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Not expressed in normal B- and T-lymphocytes but is
CC expressed in numerous neoplastic B- and T-cell lines. Highly expressed
CC in testis, ovary, prostate, lung, and kidney, with lower expression in
CC spleen, small intestine, colon, and liver.
CC -!- PTM: Autophosphorylated on Tyr-749, Tyr-753 and Tyr-754 in the
CC activation loop allowing full activity. Autophosphorylated on Tyr-872
CC leading to recruitment of downstream partners of the signaling cascade
CC such as PLCG2 (By similarity). {ECO:0000250}.
CC -!- DISEASE: Retinitis pigmentosa 38 (RP38) [MIM:613862]: A retinal
CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis
CC pigmentosa is characterized by retinal pigment deposits visible on
CC fundus examination and primary loss of rod photoreceptor cells followed
CC by secondary loss of cone photoreceptors. Patients typically have night
CC vision blindness and loss of midperipheral visual field. As their
CC condition progresses, they lose their far peripheral visual field and
CC eventually central vision as well. {ECO:0000269|PubMed:11062461}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. AXL/UFO subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MERTKID41339ch2q13.html";
CC -!- WEB RESOURCE: Name=Mutations of the MERTK gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/mertkmut.htm";
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DR EMBL; U08023; AAB60430.1; -; mRNA.
DR EMBL; AH010001; AAG33129.1; -; Genomic_DNA.
DR EMBL; AC093675; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104651; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS2094.1; -.
DR PIR; I38547; I38547.
DR RefSeq; NP_006334.2; NM_006343.2.
DR PDB; 2DBJ; NMR; -; A=373-483.
DR PDB; 2P0C; X-ray; 2.40 A; A/B=570-864.
DR PDB; 3BPR; X-ray; 2.80 A; A/B/C/D=570-864.
DR PDB; 3BRB; X-ray; 1.90 A; A/B=570-864.
DR PDB; 3TCP; X-ray; 2.69 A; A/B=570-864.
DR PDB; 4M3Q; X-ray; 2.72 A; A/B=570-864.
DR PDB; 4MH7; X-ray; 2.51 A; A/B=570-864.
DR PDB; 4MHA; X-ray; 2.59 A; A/B=570-864.
DR PDB; 5K0K; X-ray; 2.54 A; A/B=570-864.
DR PDB; 5K0X; X-ray; 2.23 A; A/B=570-864.
DR PDB; 5TC0; X-ray; 2.24 A; A/B=570-864.
DR PDB; 5TD2; X-ray; 2.68 A; A/B=577-861.
DR PDB; 5U6C; X-ray; 2.10 A; A/B=570-864.
DR PDB; 6MEP; X-ray; 2.89 A; A/B=570-864.
DR PDB; 7AAX; X-ray; 1.76 A; A=571-864.
DR PDB; 7AAY; X-ray; 1.87 A; A=571-864.
DR PDB; 7AAZ; X-ray; 1.85 A; A=570-864.
DR PDB; 7AB0; X-ray; 1.74 A; A=571-864.
DR PDB; 7AB1; X-ray; 1.93 A; A=571-864.
DR PDB; 7AB2; X-ray; 1.78 A; A=571-864.
DR PDB; 7AVX; X-ray; 2.44 A; A/B=570-864.
DR PDB; 7AVY; X-ray; 2.31 A; A=570-864.
DR PDB; 7AVZ; X-ray; 2.04 A; A=571-864.
DR PDB; 7AW0; X-ray; 1.89 A; A=571-864.
DR PDB; 7AW1; X-ray; 1.98 A; A=571-864.
DR PDB; 7AW2; X-ray; 2.10 A; A=571-864.
DR PDB; 7AW3; X-ray; 1.99 A; A=571-864.
DR PDB; 7AW4; X-ray; 1.98 A; A/B=570-864.
DR PDB; 7CQE; X-ray; 2.69 A; A/C=571-864.
DR PDB; 7DXL; X-ray; 3.15 A; A/B=570-864.
DR PDB; 7M5Z; X-ray; 3.06 A; A/B=570-864.
DR PDB; 7OAM; X-ray; 2.65 A; A/B=571-864.
DR PDB; 7OLS; X-ray; 1.89 A; A=571-864.
DR PDB; 7OLV; X-ray; 2.13 A; A=571-864.
DR PDB; 7OLX; X-ray; 1.98 A; A=571-864.
DR PDBsum; 2DBJ; -.
DR PDBsum; 2P0C; -.
DR PDBsum; 3BPR; -.
DR PDBsum; 3BRB; -.
DR PDBsum; 3TCP; -.
DR PDBsum; 4M3Q; -.
DR PDBsum; 4MH7; -.
DR PDBsum; 4MHA; -.
DR PDBsum; 5K0K; -.
DR PDBsum; 5K0X; -.
DR PDBsum; 5TC0; -.
DR PDBsum; 5TD2; -.
DR PDBsum; 5U6C; -.
DR PDBsum; 6MEP; -.
DR PDBsum; 7AAX; -.
DR PDBsum; 7AAY; -.
DR PDBsum; 7AAZ; -.
DR PDBsum; 7AB0; -.
DR PDBsum; 7AB1; -.
DR PDBsum; 7AB2; -.
DR PDBsum; 7AVX; -.
DR PDBsum; 7AVY; -.
DR PDBsum; 7AVZ; -.
DR PDBsum; 7AW0; -.
DR PDBsum; 7AW1; -.
DR PDBsum; 7AW2; -.
DR PDBsum; 7AW3; -.
DR PDBsum; 7AW4; -.
DR PDBsum; 7CQE; -.
DR PDBsum; 7DXL; -.
DR PDBsum; 7M5Z; -.
DR PDBsum; 7OAM; -.
DR PDBsum; 7OLS; -.
DR PDBsum; 7OLV; -.
DR PDBsum; 7OLX; -.
DR AlphaFoldDB; Q12866; -.
DR SMR; Q12866; -.
DR BioGRID; 115724; 14.
DR IntAct; Q12866; 17.
DR MINT; Q12866; -.
DR STRING; 9606.ENSP00000295408; -.
DR BindingDB; Q12866; -.
DR ChEMBL; CHEMBL5331; -.
DR DrugBank; DB08325; 2-({6-[(3-Chlorophenyl)amino]-9-isopropyl-9H-purin-2-yl}amino)ethanol.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q12866; -.
DR GuidetoPHARMACOLOGY; 1837; -.
DR CarbonylDB; Q12866; -.
DR GlyConnect; 1870; 15 N-Linked glycans (7 sites).
DR GlyGen; Q12866; 18 sites, 16 N-linked glycans (7 sites), 2 O-linked glycans (2 sites).
DR iPTMnet; Q12866; -.
DR PhosphoSitePlus; Q12866; -.
DR BioMuta; MERTK; -.
DR DMDM; 160332297; -.
DR EPD; Q12866; -.
DR jPOST; Q12866; -.
DR MassIVE; Q12866; -.
DR MaxQB; Q12866; -.
DR PaxDb; Q12866; -.
DR PeptideAtlas; Q12866; -.
DR PRIDE; Q12866; -.
DR ProteomicsDB; 58992; -.
DR Antibodypedia; 33255; 870 antibodies from 43 providers.
DR DNASU; 10461; -.
DR Ensembl; ENST00000295408.9; ENSP00000295408.4; ENSG00000153208.18.
DR Ensembl; ENST00000421804.6; ENSP00000389152.2; ENSG00000153208.18.
DR GeneID; 10461; -.
DR KEGG; hsa:10461; -.
DR MANE-Select; ENST00000295408.9; ENSP00000295408.4; NM_006343.3; NP_006334.2.
DR UCSC; uc002thk.2; human.
DR CTD; 10461; -.
DR DisGeNET; 10461; -.
DR GeneCards; MERTK; -.
DR GeneReviews; MERTK; -.
DR HGNC; HGNC:7027; MERTK.
DR HPA; ENSG00000153208; Low tissue specificity.
DR MalaCards; MERTK; -.
DR MIM; 604705; gene.
DR MIM; 613862; phenotype.
DR neXtProt; NX_Q12866; -.
DR OpenTargets; ENSG00000153208; -.
DR Orphanet; 791; Retinitis pigmentosa.
DR PharmGKB; PA30759; -.
DR VEuPathDB; HostDB:ENSG00000153208; -.
DR eggNOG; ENOG502QQQ3; Eukaryota.
DR GeneTree; ENSGT00940000155669; -.
DR InParanoid; Q12866; -.
DR OMA; LVIKWKP; -.
DR OrthoDB; 263089at2759; -.
DR PhylomeDB; Q12866; -.
DR TreeFam; TF317402; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; Q12866; -.
DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR SignaLink; Q12866; -.
DR SIGNOR; Q12866; -.
DR BioGRID-ORCS; 10461; 13 hits in 1108 CRISPR screens.
DR ChiTaRS; MERTK; human.
DR EvolutionaryTrace; Q12866; -.
DR GeneWiki; MERTK; -.
DR GenomeRNAi; 10461; -.
DR Pharos; Q12866; Tchem.
DR PRO; PR:Q12866; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q12866; protein.
DR Bgee; ENSG00000153208; Expressed in right adrenal gland cortex and 158 other tissues.
DR ExpressionAtlas; Q12866; baseline and differential.
DR Genevisible; Q12866; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0001750; C:photoreceptor outer segment; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0001779; P:natural killer cell differentiation; IEA:Ensembl.
DR GO; GO:0001818; P:negative regulation of cytokine production; IEA:Ensembl.
DR GO; GO:2000107; P:negative regulation of leukocyte apoptotic process; IMP:CACAO.
DR GO; GO:0051250; P:negative regulation of lymphocyte activation; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0097350; P:neutrophil clearance; IEA:Ensembl.
DR GO; GO:0006909; P:phagocytosis; IMP:BHF-UCL.
DR GO; GO:0030168; P:platelet activation; IEA:Ensembl.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IDA:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
DR GO; GO:0032940; P:secretion by cell; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IEA:Ensembl.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0060068; P:vagina development; IEA:Ensembl.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013151; Immunoglobulin.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF00041; fn3; 1.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF13895; Ig_2; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00409; IG; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS50835; IG_LIKE; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane; Disease variant; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Proto-oncogene; Receptor; Reference proteome; Repeat;
KW Retinitis pigmentosa; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..999
FT /note="Tyrosine-protein kinase Mer"
FT /id="PRO_0000024443"
FT TOPO_DOM 21..505
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 506..526
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 527..999
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 81..186
FT /note="Ig-like C2-type 1"
FT DOMAIN 197..273
FT /note="Ig-like C2-type 2"
FT DOMAIN 286..381
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 386..484
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 587..858
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 723
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 593..601
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 615
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 543
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 749
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8702477"
FT MOD_RES 753
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8702477"
FT MOD_RES 754
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:8702477"
FT MOD_RES 872
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q60805"
FT MOD_RES 935
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 234
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 316
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 336
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 354
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 395
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 442
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 454
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 115..175
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 218..262
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VARIANT 20
FT /note="R -> S (in dbSNP:rs35898499)"
FT /evidence="ECO:0000269|PubMed:11062461,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_021039"
FT VARIANT 118
FT /note="S -> N (in dbSNP:rs13027171)"
FT /evidence="ECO:0000269|PubMed:11062461,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:8086340"
FT /id="VAR_021040"
FT VARIANT 185
FT /note="V -> M (in dbSNP:rs56205303)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041741"
FT VARIANT 214
FT /note="F -> V (found in a patient with Leber congenital
FT amaurosis; dbSNP:rs1475870132)"
FT /evidence="ECO:0000269|PubMed:21602930"
FT /id="VAR_067194"
FT VARIANT 282
FT /note="A -> T (in dbSNP:rs7588635)"
FT /evidence="ECO:0000269|PubMed:11062461,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_021041"
FT VARIANT 289
FT /note="E -> K (in dbSNP:rs766215580)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041742"
FT VARIANT 293
FT /note="R -> H (in dbSNP:rs34072093)"
FT /evidence="ECO:0000269|PubMed:11062461,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_021042"
FT VARIANT 329
FT /note="N -> S (in dbSNP:rs34943572)"
FT /id="VAR_051698"
FT VARIANT 446
FT /note="A -> G (in a renal clear cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041743"
FT VARIANT 452
FT /note="V -> L (in dbSNP:rs34010621)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041744"
FT VARIANT 466
FT /note="R -> K (in dbSNP:rs7604639)"
FT /evidence="ECO:0000269|PubMed:11062461,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_021043"
FT VARIANT 498
FT /note="N -> S (in dbSNP:rs35858762)"
FT /evidence="ECO:0000269|PubMed:11062461,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_021044"
FT VARIANT 518
FT /note="I -> V (in dbSNP:rs2230515)"
FT /evidence="ECO:0000269|PubMed:11062461,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_021045"
FT VARIANT 540
FT /note="E -> K (in RP38; dbSNP:rs113485015)"
FT /evidence="ECO:0000269|PubMed:11062461"
FT /id="VAR_021046"
FT VARIANT 661
FT /note="S -> C (in RP38)"
FT /evidence="ECO:0000269|PubMed:11062461"
FT /id="VAR_021047"
FT VARIANT 662
FT /note="Q -> E (in dbSNP:rs56209758)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041745"
FT VARIANT 708
FT /note="A -> S (in a head & Neck squamous cell carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041746"
FT VARIANT 823
FT /note="E -> Q (in dbSNP:rs55924349)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041747"
FT VARIANT 865
FT /note="R -> W (in dbSNP:rs2230516)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_020285"
FT VARIANT 870
FT /note="V -> I (in dbSNP:rs2230517)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_029237"
FT VARIANT 871
FT /note="I -> T (in RP38; dbSNP:rs377341255)"
FT /evidence="ECO:0000269|PubMed:11062461"
FT /id="VAR_021048"
FT VARIANT 871
FT /note="I -> V"
FT /evidence="ECO:0000269|PubMed:11062461"
FT /id="VAR_021049"
FT VARIANT 958
FT /note="P -> L (found in a patient with Leber congenital
FT amaurosis; dbSNP:rs201460398)"
FT /evidence="ECO:0000269|PubMed:21602930"
FT /id="VAR_067195"
FT CONFLICT 140
FT /note="A -> G (in Ref. 1; AAB60430)"
FT /evidence="ECO:0000305"
FT CONFLICT 143
FT /note="A -> R (in Ref. 1; AAB60430)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="S -> G (in Ref. 1; AAB60430)"
FT /evidence="ECO:0000305"
FT CONFLICT 274
FT /note="K -> Q (in Ref. 1; AAB60430)"
FT /evidence="ECO:0000305"
FT CONFLICT 328
FT /note="S -> G (in Ref. 1; AAB60430)"
FT /evidence="ECO:0000305"
FT CONFLICT 628
FT /note="Q -> H (in Ref. 1; AAB60430)"
FT /evidence="ECO:0000305"
FT CONFLICT 794
FT /note="A -> R (in Ref. 1; AAB60430)"
FT /evidence="ECO:0000305"
FT CONFLICT 888
FT /note="S -> P (in Ref. 1; AAB60430)"
FT /evidence="ECO:0000305"
FT STRAND 388..394
FT /evidence="ECO:0007829|PDB:2DBJ"
FT STRAND 396..406
FT /evidence="ECO:0007829|PDB:2DBJ"
FT STRAND 417..428
FT /evidence="ECO:0007829|PDB:2DBJ"
FT STRAND 431..441
FT /evidence="ECO:0007829|PDB:2DBJ"
FT STRAND 446..449
FT /evidence="ECO:0007829|PDB:2DBJ"
FT STRAND 453..459
FT /evidence="ECO:0007829|PDB:2DBJ"
FT STRAND 461..467
FT /evidence="ECO:0007829|PDB:2DBJ"
FT STRAND 476..479
FT /evidence="ECO:0007829|PDB:2DBJ"
FT HELIX 571..580
FT /evidence="ECO:0007829|PDB:7AB0"
FT HELIX 584..586
FT /evidence="ECO:0007829|PDB:7AB0"
FT STRAND 587..595
FT /evidence="ECO:0007829|PDB:7AB0"
FT STRAND 600..607
FT /evidence="ECO:0007829|PDB:7AB0"
FT STRAND 613..620
FT /evidence="ECO:0007829|PDB:7AB0"
FT STRAND 624..626
FT /evidence="ECO:0007829|PDB:7AVX"
FT HELIX 628..643
FT /evidence="ECO:0007829|PDB:7AB0"
FT STRAND 654..659
FT /evidence="ECO:0007829|PDB:7AB0"
FT STRAND 661..663
FT /evidence="ECO:0007829|PDB:7OLS"
FT STRAND 665..672
FT /evidence="ECO:0007829|PDB:7AB0"
FT HELIX 679..685
FT /evidence="ECO:0007829|PDB:7AB0"
FT STRAND 688..692
FT /evidence="ECO:0007829|PDB:7AB0"
FT HELIX 697..716
FT /evidence="ECO:0007829|PDB:7AB0"
FT HELIX 726..728
FT /evidence="ECO:0007829|PDB:7AB0"
FT STRAND 729..731
FT /evidence="ECO:0007829|PDB:7AB0"
FT TURN 733..735
FT /evidence="ECO:0007829|PDB:7M5Z"
FT STRAND 737..739
FT /evidence="ECO:0007829|PDB:7AB0"
FT HELIX 758..761
FT /evidence="ECO:0007829|PDB:7AAZ"
FT HELIX 764..766
FT /evidence="ECO:0007829|PDB:7AB0"
FT HELIX 769..773
FT /evidence="ECO:0007829|PDB:7AB0"
FT HELIX 779..794
FT /evidence="ECO:0007829|PDB:7AB0"
FT STRAND 800..804
FT /evidence="ECO:0007829|PDB:7M5Z"
FT HELIX 806..808
FT /evidence="ECO:0007829|PDB:7AB0"
FT HELIX 809..814
FT /evidence="ECO:0007829|PDB:7AB0"
FT STRAND 822..824
FT /evidence="ECO:0007829|PDB:7AVX"
FT HELIX 827..835
FT /evidence="ECO:0007829|PDB:7AB0"
FT HELIX 841..843
FT /evidence="ECO:0007829|PDB:7AB0"
FT HELIX 847..860
FT /evidence="ECO:0007829|PDB:7AB0"
SQ SEQUENCE 999 AA; 110249 MW; 05BC339F05DFD355 CRC64;
MGPAPLPLLL GLFLPALWRR AITEAREEAK PYPLFPGPFP GSLQTDHTPL LSLPHASGYQ
PALMFSPTQP GRPHTGNVAI PQVTSVESKP LPPLAFKHTV GHIILSEHKG VKFNCSISVP
NIYQDTTISW WKDGKELLGA HHAITQFYPD DEVTAIIASF SITSVQRSDN GSYICKMKIN
NEEIVSDPIY IEVQGLPHFT KQPESMNVTR NTAFNLTCQA VGPPEPVNIF WVQNSSRVNE
QPEKSPSVLT VPGLTEMAVF SCEAHNDKGL TVSKGVQINI KAIPSPPTEV SIRNSTAHSI
LISWVPGFDG YSPFRNCSIQ VKEADPLSNG SVMIFNTSAL PHLYQIKQLQ ALANYSIGVS
CMNEIGWSAV SPWILASTTE GAPSVAPLNV TVFLNESSDN VDIRWMKPPT KQQDGELVGY
RISHVWQSAG ISKELLEEVG QNGSRARISV QVHNATCTVR IAAVTRGGVG PFSDPVKIFI
PAHGWVDYAP SSTPAPGNAD PVLIIFGCFC GFILIGLILY ISLAIRKRVQ ETKFGNAFTE
EDSELVVNYI AKKSFCRRAI ELTLHSLGVS EELQNKLEDV VIDRNLLILG KILGEGEFGS
VMEGNLKQED GTSLKVAVKT MKLDNSSQRE IEEFLSEAAC MKDFSHPNVI RLLGVCIEMS
SQGIPKPMVI LPFMKYGDLH TYLLYSRLET GPKHIPLQTL LKFMVDIALG MEYLSNRNFL
HRDLAARNCM LRDDMTVCVA DFGLSKKIYS GDYYRQGRIA KMPVKWIAIE SLADRVYTSK
SDVWAFGVTM WEIATRGMTP YPGVQNHEMY DYLLHGHRLK QPEDCLDELY EIMYSCWRTD
PLDRPTFSVL RLQLEKLLES LPDVRNQADV IYVNTQLLES SEGLAQGSTL APLDLNIDPD
SIIASCTPRA AISVVTAEVH DSKPHEGRYI LNGGSEEWED LTSAPSAAVT AEKNSVLPGE
RLVRNGVSWS HSSMLPLGSS LPDELLFADD SSEGSEVLM
