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FLASH GENE

Symbol

MET

contributors: mct/shn - updated : 28-10-2018

HGNC name	met proto-oncogene (hepatocyte growth factor receptor)
HGNC id	7029

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	head to head
STRUCTURE	126.00 kb     21 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	seven repeats of the consensus binding site for the Sp family
	a LINE regulator sequence in intron 2

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	cen - D7S486 - D7S522 - MET - D7S633 - D7S677 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000245 21 splicing 6641 NP_000236 - 1390 - 2009 19002214 NM_001127500 21 splicing 6695 NP_001120972 - 1408 - 2009 19002214

EXPRESSION

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 esophagus       highly Hearing/Equilibrium ear       highly Reproductive male system male genital tract epididymis     Homo sapiens Respiratory respiratory tract trachea     highly

cells

System Cell Pubmed Species Stage Rna symbol Reproductive spermatozoa Homo sapiens

cell lineage
cell lines	normal human neuronal progenitor cells, NHNPs
fluid/secretion

at STAGE

Text	restricted to midgestation fetal cerebral cortex in portions of the temporal and occipital lobes

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a putative 24-amino acid signal peptide
	a plexin repeat and a SEMA domain
	a large glycosylated extracellular ligand-binding domain, derived from the alpha and the N terminal portion of beta chains
	a single hydrophobic transmembrane domain
	a Death Defying Domain (DDD), entraping the active site of CASP3 and blocking apoptosis in hepatocytes
	a cytoplasmic domain with intrinsic tyrosine kinase activity
	C-terminal domain report nuclear localization

secondary structure

a 50 kda alpha chain and a 145 kda a beta chain

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	ortholog to Met, Mus musculus
	ortholog to MET, Pan troglodytes
	ortholog to Met , Rattus norvegicus

intraspecies

homolog to MST1R

Homologene

FAMILY	protein kinase superfamily
	Tyr protein kinase family

CATEGORY

enzyme , protooncogene , receptor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm
	intracellular,nucleus
text	type 1 membrane protein
	C-terminal domain report nuclear localization

basic FUNCTION	role in late myogenesis
	important regulator of cell proliferation and differentiation, organ regeneration, embryogenesis and tumorogenesis
	may play a role in autism susceptibility
	might be one of the long sought oncogenes controlling progression of primary cancers to metastasis
	transmembrane receptor tyrosine kinase of the hepatocyte growth factor/scatter factor
	participates in immune function, peripheral organ development and repair, and the development of the cerebral cortex and cerebellum
	high-affinity transmembrane receptor tyrosine kinase of the hepatocyte growth factor/scatter factor
	may play a role in autism susceptibility
	involvement of MET in the pathogenesis of myopia in general, as well as more rapid progression in refractive error regardless of the initial refractory ability
	playing a role in human salivary gland development
	possible role of MET in the pathogenesis of ASD (autism spectrum disorders)
	may act in consort with EGFR and/or be activated as a compensatory pathway in the presence of EGFR blockade in head and neck carcinoma cells
	critical effector of TP53, suggesting that inhibition of MET may be an effective antimetastatic approach to treat cancers with TP53 mutations
	transmembrane tyrosine kinase that can promote cell scattering, migration, and invasion
	is a tyrosine kinase receptor that may play a role at fertilization

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	embryogenesis and carcinogenesis

PATHWAY

metabolism

signaling

receptor tyrosine kinase pathway

a component

protein constituent of transmembrane

INTERACTION

DNA	FOXP2 binds directly to the 5prime regulatory region of MET, and overexpression of FOXP2 results in transcriptional repression of MET

RNA

small molecule

protein	Grb2
	c-Src kinase
	Gab1
	HGF (Scatter factor 1) and MSP (Scatter Factor 2)
	E-cadherin/catenin
	FAP68
	alpha6beta4
	Cbl proto-oncogene
	beta-catenin
	Plexin B1
	RanBPM/RanBP9
	hepatocyte growth factor
	MUC20P MID:15314156
	SNAPIN, DCOHM, VAV-1, Sorting nexin 2, Death associated protein kinase 3, SMC-1, Centromeric protein C, and hTID-1
	SPRY domain-containing SOCS box protein 1, SSB-1
	SH2-domain-containing inositol 5-phosphatase (SHIP)-2,
	LRIG1
	decorinP MID:19433454
	C-terminus of heat shock protein 70-interacting protein? CHIP
	role for PPLXNB1 in maintenance of melanocyte survival and proliferation in the skin, suggesting that SEMA4D and PLXNB1 act cooperatively with HGF and MET to regulate MET-dependent effects in human melanocytes
	MUC1 drives MET-dependent migration and scattering
	SMYD3 modulates MSTN and MET transcription in primary skeletal muscle cells
	can directly inhibit CASP3 by way of a novel mechanism and promote hepatocyte survival
	OVOL1 and OVOL2, are critical inducers of MET in human cancers (pMID: 24124593)
	is an important regulator of MET receptor tyrosine kinase levels and signaling
	USP8 is involved in deubiquitination of LRIG1, influencing the efficiency of MET degradation
	SEMA3C drives activation of multiple RTKs including EGFR, ERBB2, and MET in a cognate ligand-independent manner via PLXNB1
	TNS4 recruits signaling molecules, such as DLC1, to focal adhesions, modulates homeostasis of receptor tyrosine kinases, including EGFR and MET, and promotes cell migration
	importance of ASAP2 in sustaining MET signaling, which can facilitate hepatocellular carcinoma (HCC) progression

cell & other

REGULATION

Other	FOXP2
	MUC20P MID:15314156
	suppressed by LRIG1

ASSOCIATED DISORDERS

corresponding disease(s)

HPRC , AUTS9 , OSFD , DFNB97

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral somatic mutation   --over   in sporadic PRC tumoral   amplification     amplified in glioblastomas tumoral somatic mutation       in childhood hepatocellular carcinomas tumoral     --over   with LRRK2 in papillary renal cell carcinoma, and in papillary thyroid carcinoma tumoral   amplification     highly selective and commonly occurs in clear-cell adenocarcinoma tumoral somatic mutation     gain of function MET activating mutations are genetic markers associated with the cancers of unknown primary origin (CUPs)

Susceptibility

to autism

Variant & Polymorphism other	CC genotype increasing the risk of autism (C allele results in a 2-fold decrease in MET promoter activity and altered binding of specific transcription factor complexes)

Candidate gene
Marker	could serve as a biomarker for the prognostication of patients with clear-cell adenocarcinoma and tumor progression
Therapy target
	System Type Disorder Pubmed cancer head and neck   dual blockade of MET and EGFR may be a promising clinical therapeutic strategy for treating HNSCC cancer reproductive ovary novel therapeutic target for ovarian clear-cell carcinoma cancer reproductive prostate c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer

ANIMAL & CELL MODELS

Mutation of Met tyrosine kinase in the mouse genome caused embryonal death, with placenta, liver, and limb muscle defects