Hepatocyte growth factor receptor

Homo sapiensTaxon: 9606

3D-structureAlternative splicingATP-bindingChromosomal rearrangementDeafnessDisease variantDisulfide bondGlycoproteinKinaseMembraneNon-syndromic deafnessNucleotide-binding+13

Longueur de Séquence

1390

acides aminés

Poids Moléculaire

155.5 kDa

théorique

Structures Expérimentales

entrées PDB

Maladies Associées

enregistrées

Fonction

Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of neuronal precursors, angiogenesis and kidney formation. During skeletal muscle development, it is crucial for the migration of muscle progenitor cells and for the proliferation of secondary myoblasts (By similarity). In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Also promotes differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis (By similarity) (Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells

受体酪氨酸激酶，通过与肝细胞生长因子/HGF 配体结合，将信号从细胞外基质转导至细胞质。调节许多生理过程，包括增殖、散射、形态发生和存活。细胞表面的配体结合诱导 MET 在其胞内结构域上的自身磷酸化，为下游信号分子提供对接位点。被配体激活后，与 PI3 激酶亚基 PIK3R1、PLCG1、SRC、GRB2、STAT3 或接头 GAB1 相互作用。 MET 招募这些下游效应子会导致多个信号级联的激活，包括 RAS-ERK、PI3 激酶-AKT 或 PLCgamma-PKC。 RAS-ERK 激活与形态发生效应相关，而 PI3K/AKT 协调促生存效应。在胚胎发育过程中，MET 信号在原肠胚形成、神经元前体的发育和迁移、血管生成和肾脏形成中发挥作用。在骨骼肌发育过程中，它对于肌肉祖细胞的迁移和次级成肌细胞的增殖至关重要（通过相似性）。在成人中，参与伤口愈合以及器官再生和组织重塑。还促进造血细胞的分化和增殖。可能调节皮质骨成骨（通过相似性）（微生物感染）作为单核细胞增生李斯特氏菌内部 InlB 的受体，介导病原体进入细胞

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Localisation & Distribution

Spécificité Tissulaire

Expressed in normal hepatocytes as well as in epithelial cells lining the stomach, the small and the large intestine. Found also in basal keratinocytes of esophagus and skin. High levels are found in liver, gastrointestinal tract, thyroid and kidney. Also present in the brain. Expressed in metaphyseal bone (at protein level) (PubMed:26637977)

Maladies Associées

Hepatocellular carcinoma

A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes.

Renal cell carcinoma papillary

A subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium.

Deafness, autosomal recessive, 97

A form of non-syndromic sensorineural hearing loss with prelingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.

Osteofibrous dysplasia

A congenital disorder of osteogenesis characterized by non-neoplastic, radiolucent lesions that affect the cortical bone immediately under the periosteum. It usually manifests as a painless swelling or anterior bowing of the long bones, most commonly the tibia and fibula.

Arthrogryposis, distal, 11

A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA11 is an autosomal dominant form characterized mainly by camptodactyly. Other features include absent flexion creases and limited forearm supination.

Séquence d'Acides Aminés

MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEH
HIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMAL
VVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSAL
GAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPE

Format FASTA · 1390 acides aminés · masse 155.5 kDa

Structures Expérimentales

50 entrées PDB

1FYR1R0P1R1W1SHY1SSL2G152RFN2RFS2UZX2UZY2WD12WGJ2WKM3A4P3BUX3C1X3CCN3CD83CE33CTH3CTJ3DKC3DKF3DKG3EFJ3EFK3F663F823I5N3L8V3LQ83Q6U3Q6W3QTI3R7O3RHK3U6H3U6I3VW83ZBX3ZC53ZCL3ZXZ3ZZE4AOI4AP74DEG4DEH4DEI4EEV

Modifications Post-Traductionnelles

•Autophosphorylated in response to ligand binding on Tyr-1234 and Tyr-1235 in the kinase domain leading to further phosphorylation of Tyr-1349 and Tyr-1356 in the C-terminal multifunctional docking site. Dephosphorylated by PTPRJ at Tyr-1349 and Tyr-1365. Dephosphorylated by PTPN1 and PTPN2
•Ubiquitinated. Ubiquitination by CBL regulates MET endocytosis, resulting in decreasing plasma membrane receptor abundance, and in endosomal degradation and/or recycling of internalized receptors
•O-mannosylation of IPT/TIG domains by TMEM260 is required for protein maturation (PubMed:37186866). O-mannosylated residues are composed of single mannose glycans that are not elongated or modified (PubMed:37186866)
•(Microbial infection) Tyrosine phosphorylation is stimulated by L.monocytogenes InlB. Tyrosine phosphorylation is maximal 10-20 minutes after treatment with InlB and disappears by 60 minutes. The phosphorylated residues were not identified