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FLASH GENE

Symbol

MERTK

contributors: mct/shn - updated : 12-10-2010

HGNC name	c-mer proto-oncogene tyrosine kinase
HGNC id	7027

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	RPMR retinitis pigmentosa, MERTK related
Location	2q13      Physical location : 112.656.190 - 112.786.945
Synonym name	MER receptor tyrosine kinase
	receptor tyrosine kinase MerTK
	STK kinase
	proto-oncogene c-Mer
Synonym symbol(s)	MER, c-mer, RP38, MGC133349
EC.number	2.7.10.1

DNA

TYPE	functioning gene
STRUCTURE	130.76 kb     19 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D2S1888 - D2S1892 - MERTK - D2S1896 - D2S2269 - qter

RNA

TRANSCRIPTS	type	messenger

text	one alternative transcript with an insert in the membrane proximal region encoding for a truncated form

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006343 19 - 3632 NP_006334 - 999 - -

EXPRESSION

Rna function	retinal pigmentary epithelium and macrophages
Type	widely

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine     lowly Homo sapiens   liver       lowly Homo sapiens Lymphoid/Immune spleen       lowly Homo sapiens   thymus       lowly Homo sapiens Reproductive female system ovary     highly Homo sapiens   female system placenta     moderately Homo sapiens   male system testis     highly Homo sapiens   male system prostate     moderately Homo sapiens Respiratory lung       highly Homo sapiens Urinary kidney       highly Homo sapiens Visual eye retina     highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining retinal pigment epithelium (RPE)     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte Homo sapiens Blood/Hematopoietic monocyte Visual epithelial cell

cell lineage	cells of reproductive origin
cell lines	neoplastic B and T cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N glycosylation sites
	two Ig-like C2-type (immunoglobulin-like) domains
	two fibronectin type III domains
	one tyrosine kinase domain

HOMOLOGY

interspecies	ortholog to Mertk, Rattus norvegicus
	ortholog to Mertk, Mus musculus
	ortholog to MERTK, Pantroglodytes
	ortholog to mertk, Danio rerio

Homologene

FAMILY	MER/AXL/TYRO3 receptor kinase family
	TAM receptor tyrosine kinase (RTK) subfamily

CATEGORY

enzyme , regulatory , protooncogene , receptor membrane

SUBCELLULAR LOCALIZATION	plasma membrane
text	transmembrane protein

basic FUNCTION	participates in an inhibitory pathway in macrophages important for regulating TNF-alpha secretion and attenuating endotoxic shock
	critical for the engulfment and efficient clearance of apoptotic cells
	plays an essential immunoregulatory role
	an integral component of the retinal pigmentary epithelium phagocytic process tnat triggers ingestion of bound outer segments

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

immunity/defense

PATHWAY

metabolism

signaling

sensory transduction/vision

a component

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP

protein	growth arrest-specific gene 6, GAS6 (
	C-terminal region of the guanine nucleotide-exchange factor (GEF) V,av1 (
	TULP1 interacts with TYRO3, AXL and MERTK of the TAM receptor tyrosine kinase subfamily, whereas tubby binds only to MERTK (
	tubby and TULP1 are new MERTK ligands and facilitate phagocytosis in a MERTK-dependent manner (

cell & other

REGULATION

activated by	growth arrest-specific gene 6, GAS6 and protein S
	TUB and TULP1 potentially (activation induced by tubby and TULP1 facilitate MERTK-dependent cytoskeletal reorganization)

Other

cleaved in the extracellular domain via a metalloproteinase

ASSOCIATED DISORDERS

corresponding disease(s)

RPMR

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   may reflect an increased demand for removal of apoptotic cells in smokers, an observation with implications for the development of chronic obstructive pulmonary disease, a disorder associated with dysregulated apoptosis of lung parenchymal cells

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed blood coagulation   potential therapeutic use for soluble MERTK in the treatment of clotting disorders

ANIMAL & CELL MODELS

	mice that lack the Merk signaling tyrosine kinase domain exhibit edema, leukocyte infiltration, and signs of endotoxic shock then die of endotoxic shock
	viral gene transfer of Mertk to a RCS rat retina can correct both functional cellular defect (phagocytosis) and photoreceptor degeneration
	mutation of the Mertk in Royal College of Surgeons (RCS) rat leads to retinal degeneration in which the RPE fails to phagocytose shed outer segments
	mer(kd) mice with a cytoplasmic truncation of Mer have macrophages deficient in the clearance of apoptotic thymocytes
	mice with disruption of Mertk gene manifest a retinal dystrophy phenotype similar to RCS rats
	MerTK-deficient mice develop retinal degeneration due to defective RPE phagocytosis, whereas ablation of Axl or Tyro3 appears to have minimal impact on retinal homeostasis