UniProt Accession

 MERTK_HUMAN; Q12866; Q9HBB4 

Genbank Protein ID

 U08023; AH010001; AC093675; AC104651 

Genbank Nucleotide ID

 AAB60430.1; AAG33129.1 

Protein Name

 Tyrosine-protein kinase Mer 

Protein Synonyms/Alias

 Proto-oncogene c-Mer; Receptor tyrosine kinase MerTK 

Gene Name

 MERTK 

Gene Synonyms/Alias

 MER 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
591	RNLLILGKILGEGEF	ubiquitination	[1]
607	SVMEGNLKQEDGTSL	ubiquitination	[1]
765	RIAKMPVKWIAIESL	ubiquitination	[1]
856	VLRLQLEKLLESLPD	ubiquitination	[1, 2, 3, 4]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 81 186 Ig-like C2-type 1.
 DOMAIN 197 273 Ig-like C2-type 2.
 DOMAIN 284 379 Fibronectin type-III 1.
 DOMAIN 383 482 Fibronectin type-III 2.
 DOMAIN 587 858 Protein kinase.
 NP_BIND 593 601 ATP (By similarity).
 ACT_SITE 723 723 Proton acceptor (By similarity).
 BINDING 615 615 ATP (By similarity).
 MOD_RES 543 543 Phosphoserine.
 MOD_RES 749 749 Phosphotyrosine; by autocatalysis.
 MOD_RES 753 753 Phosphotyrosine; by autocatalysis.
 MOD_RES 754 754 Phosphotyrosine; by autocatalysis.
 MOD_RES 872 872 Phosphotyrosine; by autocatalysis (By
 MOD_RES 935 935 Phosphoserine.
 CARBOHYD 114 114 N-linked (GlcNAc...) (Potential).
 CARBOHYD 170 170 N-linked (GlcNAc...) (Potential).
 CARBOHYD 207 207 N-linked (GlcNAc...) (Potential).
 CARBOHYD 215 215 N-linked (GlcNAc...) (Potential).
 CARBOHYD 234 234 N-linked (GlcNAc...) (Potential).
 CARBOHYD 294 294 N-linked (GlcNAc...) (Potential).
 CARBOHYD 316 316 N-linked (GlcNAc...) (Potential).
 CARBOHYD 329 329 N-linked (GlcNAc...) (Potential).
 CARBOHYD 336 336 N-linked (GlcNAc...) (Potential).
 CARBOHYD 354 354 N-linked (GlcNAc...) (Potential).
 CARBOHYD 389 389 N-linked (GlcNAc...) (Potential).
 CARBOHYD 395 395 N-linked (GlcNAc...) (Potential).
 CARBOHYD 442 442 N-linked (GlcNAc...).
 CARBOHYD 454 454 N-linked (GlcNAc...) (Potential).
 DISULFID 115 175 By similarity.
 DISULFID 218 262 By similarity.  

Keyword

 3D-structure; ATP-binding; Complete proteome; Disease mutation; Disulfide bond; Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Proto-oncogene; Receptor; Reference proteome; Repeat; Retinitis pigmentosa; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 999 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IDA:UniProtKB.
 GO:0005615; C:extracellular space; IDA:UniProtKB.
 GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
 GO:0001750; C:photoreceptor outer segment; IEA:Compara.
 GO:0016028; C:rhabdomere; IDA:BHF-UCL.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; TAS:ProtInc.
 GO:0043277; P:apoptotic cell clearance; IEA:Compara.
 GO:0007596; P:blood coagulation; TAS:Reactome.
 GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
 GO:0007267; P:cell-cell signaling; TAS:ProtInc.
 GO:0050900; P:leukocyte migration; TAS:Reactome.
 GO:0001779; P:natural killer cell differentiation; IEA:Compara.
 GO:0051250; P:negative regulation of lymphocyte activation; IEA:Compara.
 GO:0006909; P:phagocytosis; IMP:BHF-UCL.
 GO:0030168; P:platelet activation; IEA:Compara.
 GO:0050766; P:positive regulation of phagocytosis; IDA:UniProtKB.
 GO:0043491; P:protein kinase B signaling cascade; IEA:Compara.
 GO:0060041; P:retina development in camera-type eye; IEA:Compara.
 GO:0032940; P:secretion by cell; IEA:Compara.
 GO:0007283; P:spermatogenesis; IEA:Compara.
 GO:0034446; P:substrate adhesion-dependent cell spreading; IEA:Compara.
 GO:0060068; P:vagina development; IEA:Compara. 

Interpro

 IPR003961; Fibronectin_type3.
 IPR007110; Ig-like_dom.
 IPR013783; Ig-like_fold.
 IPR013098; Ig_I-set.
 IPR003599; Ig_sub.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom. 

Pfam

 PF00041; fn3
 PF07679; I-set
 PF07714; Pkinase_Tyr 

SMART

 SM00060; FN3
 SM00409; IG
 SM00219; TyrKc 

PROSITE

 PS50853; FN3
 PS50835; IG_LIKE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR 

PRINTS

 PR00109; TYRKINASE.