InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MERTK

Summary

InnateDB Protein

IDBP-66032.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MERTK

Protein Name

c-mer proto-oncogene tyrosine kinase

Synonyms

c-mer; MER; RP38;

Species

Homo sapiens

Ensembl Protein

ENSP00000295408

InnateDB Gene

IDBG-66030 (MERTK)

Protein Structure

UniProt Annotation

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:0000269PubMed:17005688}.

Subcellular Localization

Membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.

Disease Associations

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:0000269PubMed:11062461}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 17 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	17 [view]
Protein-Protein	15 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0001779	natural killer cell differentiation
GO:0006468	protein phosphorylation
GO:0006909	phagocytosis
GO:0007166	cell surface receptor signaling pathway
GO:0007267	cell-cell signaling
GO:0007283	spermatogenesis
GO:0007596	blood coagulation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030168	platelet activation
GO:0032940	secretion by cell
GO:0034446	substrate adhesion-dependent cell spreading
GO:0043277	apoptotic cell clearance
GO:0043491	protein kinase B signaling
GO:0045087	innate immune response (InnateDB)
GO:0050766	positive regulation of phagocytosis
GO:0050900	leukocyte migration
GO:0051250	negative regulation of lymphocyte activation
GO:0060041	retina development in camera-type eye
GO:0060068	vagina development

Cellular Component

GO:0001750	photoreceptor outer segment
GO:0005615	extracellular space
GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0016021	integral component of membrane
GO:0016028	rhabdomere

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001763 Rhodanese-like domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR003599 Immunoglobulin subtype
IPR003961 Fibronectin, type III
IPR007110 Immunoglobulin-like domain
IPR011009 Protein kinase-like domain
IPR013098 Immunoglobulin I-set
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF00581
PF00041
PF01108
PF07679

PRINTS

PR00109

PIRSF

SMART

SM00450
SM00220
SM00409
SM00060
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt