MERTK_HUMAN » Tyrosine-protein kinase Mer

MERTK_HUMAN » Tyrosine-protein kinase Mer
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
MERTK_HUMAN » Tyrosine-protein kinase Mer » Proto-oncogene c-Mer;Receptor tyrosine kinase MerTK;
Hydrophobic Thickness 35.6 ± 1.6 Å
Tilt Angle 3 ± 3°
ΔGtransfer -38.9 kcal/mol
ΔGfold -17.8 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 499-523 (499-528)
Pathways

Hemostasis (Reactome)

PDB 2dbj (373-483), 2p0c (570-864), 3bpr (570-864), 3brb (570-864), 3tcp (570-864), 4m3q (570-864), 4mh7 (570-864), 4mha (570-864)
OPM none
Complexes none
Interactions

BMPR2, Complex: MERTK:BMPR2, PubMed

ITB5, Complex: MERTK:ITB5

UFO, Complex: UFO:MERTK, PubMed

Domains

AA: 102-187, PDBID: 1N26, Subunit A, Seq Identity:25%, Immunoglobulin domain

AA: 197-266, PDBID: 2OM5, Subunit A, Seq Identity:28%, Immunoglobulin domain

AA: 285-371, PDBID: 3LPW, Subunit B, Seq Identity:26%, Fibronectin type III domain

AA: 587-854, PDBID: 2P0C, Subunit A, Seq Identity:100%, Protein tyrosine kinase

UniProt annotation for MERTK_HUMAN » Tyrosine-protein kinase Mer
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.

CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

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.

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.

DISEASE: Retinitis pigmentosa 38 (RP38) OMIM: 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. caused by mutations affecting the gene represented in this entry.

UniProt features for MERTK_HUMAN » Tyrosine-protein kinase Mer
SIGNAL 1 20 Potential.
CHAIN 21 999 Tyrosine-protein kinase Mer.
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.
ACT_SITE 723 723 Proton acceptor (By similarity).
DISULFID 115 175 By similarity.
DISULFID 218 262 By similarity.
Amino Acid Sequence for MERTK_HUMAN » Tyrosine-protein kinase Mer
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