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 27-MAR-2024, entry version 231. 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="https://atlasgeneticsoncology.org/gene/41339/MERTK"; 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7XHY; X-ray; 2.16 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 PDBsum; 7XHY; -. DR AlphaFoldDB; Q12866; -. DR SMR; Q12866; -. DR BioGRID; 115724; 116. DR IntAct; Q12866; 111. 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 GlyCosmos; Q12866; 17 sites, 18 glycans. 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; 9606-ENSP00000295408; -. DR PeptideAtlas; Q12866; -. DR ProteomicsDB; 58992; -. DR Pumba; Q12866; -. DR Antibodypedia; 33255; 1028 antibodies from 43 providers. DR DNASU; 10461; -. DR Ensembl; ENST00000295408.9; ENSP00000295408.4; ENSG00000153208.19. 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 AGR; HGNC:7027; -. DR CTD; 10461; -. DR DisGeNET; 10461; -. DR GeneCards; MERTK; -. DR GeneReviews; MERTK; -. DR HGNC; HGNC:7027; MERTK. DR HPA; ENSG00000153208; Tissue enhanced (choroid). 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; QETRFGN; -. DR OrthoDB; 1614410at2759; -. 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; 14 hits in 1189 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 160 other cell types or tissues. DR ExpressionAtlas; Q12866; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. 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:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl. DR GO; GO:0030168; P:platelet activation; IEA:Ensembl. DR GO; GO:0050766; P:positive regulation of phagocytosis; IDA:UniProtKB. 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 CDD; cd00096; Ig; 1. DR CDD; cd05749; IgI_2_Axl_Tyro3_like; 1. DR CDD; cd14204; PTKc_Mer; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 4. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24416:SF257; TYROSINE-PROTEIN KINASE MER; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. DR Pfam; PF00041; fn3; 1. DR Pfam; PF00047; ig; 1. DR Pfam; PF13927; Ig_3; 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; SSF49265; Fibronectin type III; 1. DR SUPFAM; SSF48726; Immunoglobulin; 2. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; Q12866; HS. 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 //