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Hepatocyte growth factor receptor structure
P08581
MET_HUMAN
MET

Hepatocyte growth factor receptor

Homo sapiensTaxon: 9606

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

1390

氨基酸

分子量

155.5 kDa

理论值

实验结构

50

PDB 条目

相关疾病

5

已记录

功能描述

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

定位与分布

组织特异性

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)

相关疾病

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.

氨基酸序列

MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEH
HIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMAL
VVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSAL
GAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPE

FASTA 格式 · 1390 个氨基酸 · 分子量 155.5 kDa

实验结构

50 PDB 条目
1FYR1R0P1R1W1SHY1SSL2G152RFN2RFS2UZX2UZY2WD12WGJ2WKM3A4P3BUX3C1X3CCN3CD83CE33CTH3CTJ3DKC3DKF3DKG3EFJ3EFK3F663F823I5N3L8V3LQ83Q6U3Q6W3QTI3R7O3RHK3U6H3U6I3VW83ZBX3ZC53ZCL3ZXZ3ZZE4AOI4AP74DEG4DEH4DEI4EEV

翻译后修饰

  • •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