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MGP Database

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MGP004250

UniProt Annotations

Entry Information

Gene Name	MER proto-oncogene, tyrosine kinase
Protein Entry	MERTK_HUMAN
UniProt ID	Q12866
Species	Human

Comments

Comment type	Description
Catalytic Activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. {ECO:0000255\|PROSITE- ProRule:PRU10028}.
Disease	Retinitis pigmentosa 38 (RP38) [MIM:613862]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269\|PubMed:11062461}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Function	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. {ECO:0000269\|PubMed:17005688}.
Ptm	Autophosphorylated on Tyr-749, Tyr-753 and Tyr-754 in the activation loop allowing full activity. Autophosphorylated on Tyr- 872 leading to recruitment of downstream partners of the signaling cascade such as PLCG2 (By similarity). {ECO:0000250}.
Similarity	Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily. {ECO:0000255\|PROSITE- ProRule:PRU00159}.
Similarity	Contains 1 protein kinase domain. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
Similarity	Contains 2 fibronectin type-III domains. {ECO:0000255\|PROSITE-ProRule:PRU00316}.
Similarity	Contains 2 Ig-like C2-type (immunoglobulin-like) domains. {ECO:0000305}.
Subcellular Location	Membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.
Subunit	Interacts (upon activation) with TNK2; stimulates TNK2 autophosphorylation. Interacts (via N-terminus) with extracellular ligands LGALS3, TUB, TULP1 and GAS6 (By similarity). Interacts with VAV1 in a phosphotyrosine-independent manner. {ECO:0000250, ECO:0000269\|PubMed:12920122, ECO:0000269\|PubMed:16288044, ECO:0000269\|PubMed:21792939, ECO:0000269\|PubMed:9160883}.
Tissue Specificity	Not expressed in normal B- and T-lymphocytes but is expressed in numerous neoplastic B- and T-cell lines. Highly expressed in testis, ovary, prostate, lung, and kidney, with lower expression in spleen, small intestine, colon, and liver.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MERTKID41339ch2q13.html";
Web Resource	Name=Mutations of the MERTK gene; Note=Retina International's Scientific Newsletter; URL="http://www.retina-international.org/files/sci-news/mertkmut.htm";