mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

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	Gene Summary
	Ligand Binding Site Mutation Information
	Protein Structure Related Information
	Gene Expression and Gene-Gene Network
	Phenotype Information
	Pharmacological Information
	Conservation Information for LBS

Gene summary for MET

Gene summary

Basic gene Info.	Gene symbol	MET
	Gene name	MET proto-oncogene, receptor tyrosine kinase
	Synonyms	AUTS9\|HGFR\|RCCP2\|c-Met
	Cytomap	UCSC genome browser: 7q31
	Type of gene	protein-coding
	RefGenes	NM_000245.2, NM_001127500.1,
	Description	HGF receptorHGF/SF receptorSF receptorhepatocyte growth factor receptormet proto-oncogene tyrosine kinaseproto-oncogene c-Metscatter factor receptortyrosine-protein kinase Met
	Modification date	20141222
dbXrefs	MIM : 164860
	HGNC : HGNC
	Ensembl : ENSG00000105976
	HPRD : 01280
	Vega : OTTHUMG00000023299
Protein	UniProt: P08581 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_MET
	BioGPS: 4233
Pathway	NCI Pathway Interaction Database: MET
	KEGG: MET
	REACTOME: MET
	Pathway Commons: MET
Context	iHOP: MET
	ligand binding site mutation search in PubMed: MET
	UCL Cancer Institute: MET
Assigned class in mutLBSgeneDB	A: This gene has a literature evidence and it belongs to targetable_mutLBSgenes.
References showing study about ligand binding site mutation for MET.	1. Navis, A. C., van Lith, S. A., van Duijnhoven, S. M., de Pooter, M., Yetkin-Arik, B., Wesseling, P., ... & en Henegouwen, P. V. B. (2015). Identification of a novel MET mutation in high-grade glioma resulting in an auto-active intracellular protein. Acta neuropathologica, 130(1), 131-144. 25862637 2. Minuti, G., & Landi, L. (2015). MET deregulation in breast cancer. Annals of translational medicine, 3(13). 26366398

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez

GO ID	GO Term	PubMed ID
GO:0001886	endothelial cell morphogenesis	14500721
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	22521434
GO:0050918	positive chemotaxis	15218527
GO:0071526	semaphorin-plexin signaling pathway	15218527

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Ligand binding site mutations for MET

Lollipop-style diagram of mutations at LBS in amino-acid sequence.
We represented ligand binding site mutations only. (You can see big image via clicking.)

: non-synonymous mutation on LBS, Circle size denotes number of samples.

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
D1228	D1228G	COAD	3
K1244	K1244R	COAD	2
M1160	M1160I	COAD	2
A1108	H1106R	COAD	2
Y1235	Y1235N	COAD	1
K1244	K1244E	COAD	1
Y1230	Y1230C	COAD	1
V1092	H1094R	COAD	1
L1195	L1195P	COAD	1
K1244	G1242C	COAD	1
D1204,H1202	R1203G	COAD	1
M1160	M1160V	COAD	1
A1108	H1106Y	COAD	1
M1160	M1160I	GBM	1
D1204	L1205V	KIRC	1
Y1235	Y1235H	LUAD	1
D1204	L1205W	OV	1
L1140	L1140F	SKCM	1
D1180	D1180Y	UCEC	1
A1108	A1108S	UCEC	1

cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, HNSC: Head and neck squamous cell carcinoma, KICH: Kidney chromophobe, KIRC: Kidney renal clear cell carcinoma, KIRP: Kidney renal papillary cell carcinoma, LAML: Acute myeloid leukemia, LUAD: Lung adenocarcinoma, LUSC: Lung squamous cell carcinoma, OV: Ovarian serous cystadenocarcinoma, PAAD: Pancreatic adenocarcinoma, PRAD: Prostate adenocarcinoma, SKCM: Skin cutaneous melanoma, STAD: Stomach adenocarcinoma, THCA: Thyroid carcinoma, UCEC: Uterine corpus endometrial carcinoma.

Clinical information for MET from My Cancer Genome.

The MET gene (MNNG-HOS transforming gene; Cooper et al. 1984) located on chromosome 7, encodes a receptor tyrosine kinase (RTK) belonging to the MET/RON family of RTKs. Binding of its ligand, hepatocyte growth factor (HGF; also called scatter factor (SF)), induces a conformational change in the MET receptor that facilitates receptor phosphorylation and activation. Activated MET then phosphorylates its substrates, resulting in activation of multiple downstream pathways within the cell, including the PI3K-AKT-mTOR pathway, which is involved in cell survival, and the RAS-RAF-MEK-ERK pathway, which is involved in cell proliferation. In the context of malignancy, aberrant signaling through the MET receptor promotes pleiotrophic effects including growth, survival, invasion, migration, angiogenesis and metastasis (Birchmeier et al. 2003; Peruzzi and Bottaro 2006).The MET receptor and/or its ligand HGF have been reported to be aberrantly activated in many human cancers (seehttp://www.vai.org/met/). Germline mutations in the tyrosine kinase domain of MET occur in 100% of hereditary papillary renal cell carcinoma, and somatic mutations in MET are found in 10–15% of sporadic papillary renal cell carcinoma (Schmidt et al. 1997). Mutations in MET have been reported at low frequencies in head and neck squamous cell carcinoma (Di Renzo et al. 2000), childhood hepatocellular carcinoma (Park et al. 1999), NSCLC (Kong-Beltran et al. 2006; Ma et al. 2003) and small cell lung cancer (Ma et al. 2003). Amplification of MET has been reported in gastric cancer (Nakajima et al. 1999), esophageal cancer (Miller et al. 2006), colorectal cancer (Umeki, Shiota, and Kawasaki 1999), gliomas (Beroukhim et al. 2007), clear cell ovarian cancer (Yamamoto et al. 2011) and NSCLC (Bean et al. 2007; Cappuzzo et al. 2009; Chen et al. 2009; Engelman et al. 2007; Kubo et al. 2009; Okuda et al. 2008; Onozato et al. 2009).Related Pathways:Receptor tyrosine kinase/growth factor signaling.Solomon, B. 2015. MET. My Cancer Genome https://www.mycancergenome.org/content/gene/met/(Updated December 2015)

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Protein structure related information for MET

Protein structure of wild type (WT) and mutant type (MT) of MET

Wild type MET

Mutant type MET

Free energy of binding of drugs to wild type and mutant tpye of MET

Gene symbol	Drug name	Free energy of binding (kcal/mol) of wild type	Free energy of binding (kcal/mol) of mutant type
MET	Cabozantinib	-8.6	-8.1
MET	Crizotinib	-9	-8.5

Relative protein structure stability change (ΔΔE) using Mupro 1.1
Mupro score denotes assessment of the effect of mutations on thermodynamic stability.
(ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability)

: nsSNV at non-LBS

: nsSNV at LBS

nsSNVs sorted by the relative stability change of protein structure by each mutation
Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene.

LBS	AAchange of nsSNV	Relative stability change
Y1230	Y1230C	-1.2469843
D1204	L1205V	-1.2224999
M1160	M1160V	-1.2174764
D1204	L1205W	-1.2115765
M1160	M1160I	-1.1896396
Y1235	Y1235H	-1.0873826
Y1235	Y1235N	-1.0581319
D1228	D1228G	-1.0385868
L1195	L1195P	-0.92310522
A1108	A1108S	-0.90558614
A1108	H1106R	-0.84727346
A1108	H1106Y	-0.82887919
D1204	R1203G	-0.62367683
H1202	R1203G	-0.62367683
L1140	L1140F	-0.57544451
K1244	G1242C	-0.31790315
D1180	D1180Y	-0.31527938
K1244	K1244R	-0.30198387
K1244	K1244E	-0.16686102
V1092	H1094R	-0.15603382

(MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132)

Structure image for MET from PDB

PDB ID	PDB title	PDB structure
1R1W	CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF THE HEPATOCYTE GROWTH FACTOR RECEPTOR C-MET

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Differential gene expression and gene-gene network for MET

Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types

MET_COAD_DE

Differential co-expressed gene network based on protein-protein interaction data (CePIN)

* Left PPI network was created from samples with mutations in the LBS of MET and the right PPI network was created from samples without mutations in the LBS of MET. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.

* In COAD

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Phenotype information for MET

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0027627	Neoplasm Metastasis	62	AlteredExpression, Biomarker
umls:C0007131	Carcinoma, Non-Small-Cell Lung	58	Biomarker
umls:C0007097	Carcinoma	50	AlteredExpression, Biomarker, GeneticVariation
umls:C2239176	Carcinoma, Hepatocellular	32	AlteredExpression, Biomarker, GeneticVariation
umls:C0007134	Carcinoma, Renal Cell	28	Biomarker, GeneticVariation
umls:C0001418	Adenocarcinoma	25	AlteredExpression, Biomarker, GeneticVariation
umls:C0017636	Glioblastoma	21	Biomarker
umls:C0004352	Autistic Disorder	15	AlteredExpression, Biomarker, GeneticVariation
umls:C0007137	Carcinoma, Squamous Cell	14	Biomarker, GeneticVariation
umls:C0024121	Lung Neoplasms	11	AlteredExpression, Biomarker, GeneticVariation
umls:C0029463	Osteosarcoma	10	Biomarker
umls:C0038356	Stomach Neoplasms	5	AlteredExpression, Biomarker
umls:C0023467	Leukemia, Myeloid, Acute	3	Biomarker
umls:C0036341	Schizophrenia	2	Biomarker, GeneticVariation
umls:C0919267	Ovarian Neoplasms	2	AlteredExpression, Biomarker
umls:C0037199	Sinusitis	2	Biomarker, GeneticVariation
umls:C0014859	Esophageal Neoplasms	2	Biomarker
umls:C0009241	Cognition Disorders	1	Biomarker
umls:C0023904	Liver Neoplasms, Experimental	1	Biomarker
umls:C0027626	Neoplasm Invasiveness	1	Biomarker
umls:C0027819	Neuroblastoma	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID	AA change	Clinical significance	Origin	Phenotype IDs
186068	H1106R	Uncertain significance	Germline	MedGen:C0007134 OMIM:605074 Orphanet:ORPHA47044 SNOMED CT:41607009

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Pharmacological information for MET

Gene expression profile of anticancer drug treated cell-lines (CCLE)
Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient.

Gene-centered drug-gene interaction network

Drug information targeting mutLBSgene (Approved drugs only)

Drug status	DrugBank ID	Name	Type	Drug structure
Experimental	DB02152	K-252a	Small molecule
Investigational	DB05153	XL184	Small molecule
Investigational	DB05216	MP470	Small molecule
Experimental	DB06896	1-(4-fluorophenyl)-N-[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxamide	Small molecule
Experimental	DB06995	N-({4-[(2-aminopyridin-4-yl)oxy]-3-fluorophenyl}carbamoyl)-2-(4-fluorophenyl)acetamide	Small molecule
Experimental	DB06997	2-(4-fluorophenyl)-N-{[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]carbamoyl}acetamide	Small molecule
Experimental	DB07369	N-(3-chlorophenyl)-N-methyl-2-oxo-3-[(3,4,5-trimethyl-1H-pyrrol-2-yl)methyl]-2H-indole-5-sulfonamide	Small molecule
Experimental	DB07969	3-[3-(4-methylpiperazin-1-yl)-7-(trifluoromethyl)quinoxalin-5-yl]phenol	Small molecule
Experimental	DB08584	6-{[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulfanyl}quinoline	Small molecule
Experimental	DB08700	3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)pyridin-2-amine	Small molecule
Experimental	DB08791	1-[(2-NITROPHENYL)SULFONYL]-1H-PYRROLO[3,2-B]PYRIDINE-6-CARBOXAMIDE	Small molecule
Approved	DB08865	Crizotinib	Small molecule
Approved	DB08875	Cabozantinib	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of MET go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
DF6		N-({4-[(6,7-DIMETHOXYQUINOLIN-4-YL) OXY]PHENYL}CARBAMOTHIOYL)-2-PHENYLACETAMIDE	3vw8	A	A1108 L1140 M1160 H1202
IHX		3-[3-(4-METHYLPIPERAZIN-1-YL)-7-(TRIFLUOROMETHYL)QUINOXALIN-5-YL]PHENOL	3f66	A	A1108 L1140 M1160 Y1230
3QT		6-{[6-(1-METHYL-1H-PYRAZOL-4-YL)IMIDAZO[1,2-B]PYRIDAZIN-3-YL]METHYL}QUINOLINE	3qti	A	A1108 L1140 M1160 Y1230
0J3		3-(4-METHYLPIPERAZIN-1-YL)-N-(3-NITROBENZYL)-7- (TRIFLUOROMETHYL)QUINOLIN-5-AMINE	4gg5	A	A1108 L1140 M1160 Y1230
0J8		N-(3-NITROBENZYL)-6-[1-(PIPERIDIN-4-YL)-1H-PYRAZOL-4- YL]-2-(TRIFLUOROMETHYL)PYRIDO[2,3-D]PYRIMIDIN-4-AMINE	4gg7	A	A1108 L1140 M1160 Y1230
1RU		7-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-3-[1- (PIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]FURO[3,2-C]PYRIDIN-6- AMINE	4knb	A	A1108 L1140 M1160 Y1230
1RU		7-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-3-[1- (PIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]FURO[3,2-C]PYRIDIN-6- AMINE	4knb	C	A1108 L1140 M1160 Y1230
3E8		3-[1-(3-{5-[(1-METHYLPIPERIDIN-4-YL)METHOXY]PYRIMIDIN- 2-YL}BENZYL)-6-OXO-1,6-DIHYDROPYRIDAZIN-3- YL]BENZONITRILE	4r1v	A	A1108 L1140 M1160 Y1230
3EH		3-(DIETHYLAMINO)PROPYL (3-{[5-(3,4-DIMETHOXYPHENYL)-2- OXO-2H-1,3,4-THIADIAZIN-3(6H)-YL]METHYL}PHENYL) CARBAMATE	4r1y	A	A1108 L1140 M1160 Y1230
SX8		6-{[6-(1-METHYL-1H-PYRAZOL-4-YL)[1,2,4]TRIAZOLO[4,3-B]PYRIDAZIN-3-YL]SULFANYL}QUINOLINE	3dkg	A	A1108 M1160
IHX		3-[3-(4-METHYLPIPERAZIN-1-YL)-7-(TRIFLUOROMETHYL)QUINOXALIN-5-YL]PHENOL	3f66	B	A1108 M1160 Y1230
0JJ		7-METHOXY-N-{[6-(3-METHYL-1,2-THIAZOL-5-YL)[1,2, 4]TRIAZOLO[4,3-B]PYRIDAZIN-3-YL]METHYL}-1,5- NAPHTHYRIDIN-4-AMINE	4deg	A	A1108 M1160 Y1230
0JK		5-PHENYL-3-(QUINOLIN-6-YLMETHYL)-3,5,6,7-TETRAHYDRO-4H- [1,2,3]TRIAZOLO[4,5-C]PYRIDIN-4-ONE	4deh	A	A1108 M1160 Y1230
GBL		GAMMA-BUTYROLACTONE	3f66	A	D1180
GBL		GAMMA-BUTYROLACTONE	3f66	B	D1180
GBL		GAMMA-BUTYROLACTONE	4knb	A	D1180
GBL		GAMMA-BUTYROLACTONE	2wd1	A	D1204 D1228 Y1235 K1244
GBL		GAMMA-BUTYROLACTONE	4r1v	A	D1228 Y1235 K1244
GBL		GAMMA-BUTYROLACTONE	2wd1	A	L1140
GBL		GAMMA-BUTYROLACTONE	3f66	A	L1140
GBL		GAMMA-BUTYROLACTONE	4knb	B	L1140
GBL		GAMMA-BUTYROLACTONE	4r1v	A	L1140
AM7		2-BENZYL-5-(3-FLUORO-4-{[6-METHOXY-7-(3-MORPHOLIN-4-YLPROPOXY)QUINOLIN-4-YL]OXY}PHENYL)-3-METHYLPYRIMIDIN-4(3H)-ONE	2rfn	A	V1092 A1108 L1140 M1160
AM7		2-BENZYL-5-(3-FLUORO-4-{[6-METHOXY-7-(3-MORPHOLIN-4-YLPROPOXY)QUINOLIN-4-YL]OXY}PHENYL)-3-METHYLPYRIMIDIN-4(3H)-ONE	2rfn	B	V1092 A1108 L1140 M1160
MT3		2-BENZYL-5-{4-[(6,7-DIMETHOXYQUINOLIN-4-YL)OXY]-3-FLUOROPHENYL}-3-METHYLPYRIMIDIN-4(3H)-ONE	3efj	B	V1092 A1108 L1140 M1160
MT4		5-{4-[(6,7-DIMETHOXYQUINOLIN-4-YL)OXY]-3-FLUOROPHENYL}-2-[(4-FLUOROPHENYL)AMINO]-3-METHYLPYRIMIDIN-4(3H)-ONE	3efk	A	V1092 A1108 L1140 M1160
MT4		5-{4-[(6,7-DIMETHOXYQUINOLIN-4-YL)OXY]-3-FLUOROPHENYL}-2-[(4-FLUOROPHENYL)AMINO]-3-METHYLPYRIMIDIN-4(3H)-ONE	3efk	B	V1092 A1108 L1140 M1160
Q6W		3-{5-OXO-3-[1-(PIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]-5H-BENZO[4,5]CYCLOHEPTA[1,2-B]PYRIDIN-7-YL}-N-(PYRIDIN-2-YLMETHYL)PROPANAMIDE	3q6w	A	V1092 A1108 L1140 M1160
M61		MK-2461	3r7o	A	V1092 A1108 L1140 M1160
M97		1-[(3R,4R)-4-(1H-INDOL-3-YL)-2,5-DIOXOPYRROLIDIN-3-YL]PYRROLO[3,2,1-IJ]QUINOLINIUM	3rhk	A	V1092 A1108 L1140 M1160
M97		1-[(3R,4R)-4-(1H-INDOL-3-YL)-2,5-DIOXOPYRROLIDIN-3-YL]PYRROLO[3,2,1-IJ]QUINOLINIUM	3rhk	B	V1092 A1108 L1140 M1160
03X		N-{4-[(6,7-DIMETHOXYQUINOLIN-4-YL)OXY]-3-FLUOROPHENYL}-1,5-DIMETHYL-3-OXO-2-PHENYL-2,3-DIHYDRO-1H-PYRAZOLE-4-CARBOXAMIDE	3u6h	A	V1092 A1108 L1140 M1160
044		N-{3-FLUORO-4-[(7-METHOXYQUINOLIN-4-YL)OXY]PHENYL}-1-[(2R)-2-HYDROXYPROPYL]-5-METHYL-3-OXO-2-PHENYL-2,3-DIHYDRO-1H-PYRAZOLE-4-CARBOXAMIDE	3u6i	A	V1092 A1108 L1140 M1160
1JC		1-{5-OXO-3-[1-(PIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]-5H- BENZO[4,5]CYCLOHEPTA[1,2-B]PYRIDIN-7-YL}-N-(PYRIDIN-2- YLMETHYL)METHANESULFONAMIDE	4iwd	A	V1092 A1108 L1140 M1160
1RU		7-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-3-[1- (PIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]FURO[3,2-C]PYRIDIN-6- AMINE	4knb	D	V1092 A1108 L1140 M1160
CKK		N-{[4-({5-[(4-AMINOPIPERIDIN-1-YL)METHYL]PYRROLO[2,1-F][1,2,4]TRIAZIN-4-YL}OXY)-3-FLUOROPHENYL]CARBAMOYL}-2-(4-FLUOROPHENYL)ACETAMIDE	3c1x	A	V1092 A1108 L1140 M1160 L1195 H1202
319		N-({4-[(2-AMINOPYRIDIN-4-YL)OXY]-3-FLUOROPHENYL}CARBAMOYL)-2-(4-FLUOROPHENYL)ACETAMIDE	3cth	A	V1092 A1108 L1140 M1160 L1195 H1202
320		2-(4-FLUOROPHENYL)-N-{[3-FLUORO-4-(1H-PYRROLO[2,3-B]PYRIDIN-4-YLOXY)PHENYL]CARBAMOYL}ACETAMIDE	3ctj	A	V1092 A1108 L1140 M1160 L1195 H1202
353		N-{4-[(2-AMINO-3-CHLOROPYRIDIN-4-YL)OXY]-3-FLUOROPHENYL}-4-ETHOXY-1-(4-FLUOROPHENYL)-2-OXO-1,2-DIHYDROPYRIDINE-3-CARBOXAMIDE	3f82	A	V1092 A1108 L1140 M1160 L1195 H1202
88Z		N-(3-FLUORO-4-{[6-METHOXY-7-(3-MORPHOLIN-4-YLPROPOXY)QUINOLIN-4-YL]OXY}PHENYL)-N'-(4-FLUOROPHENYL)CYCLOPROPANE-1,1-DICARBOXAMIDE	3lq8	A	V1092 A1108 L1140 M1160 L1195 H1202
DWF		N-(3-FLUORO-4-{[2-({3-[(METHYLSULFONYL) METHYL]PHENYL}AMINO)PYRIMIDIN-4-YL]OXY}PHENYL)-N'-(4- FLUOROPHENYL)CYCLOPROPANE-1,1-DICARBOXAMIDE	4mxc	A	V1092 A1108 L1140 M1160 L1195 Y1230
AM8		N-(3-CHLOROPHENYL)-N-METHYL-2-OXO-3-[(3,4,5-TRIMETHYL-1H-PYRROL-2-YL)METHYL]-2H-INDOLE-5-SULFONAMIDE	2rfs	A	V1092 A1108 L1140 M1160 Y1230
ZZY		1-[(2-NITROPHENYL)SULFONYL]-1H-PYRROLO[3,2-B]PYRIDINE-6-CARBOXAMIDE	2wd1	A	V1092 A1108 L1140 M1160 Y1230
VGH		CRIZOTINIB	2wgj	A	V1092 A1108 L1140 M1160 Y1230
PFY		(3Z)-5-[(2,6-DICHLOROBENZYL)SULFONYL]-3-[(3,5-DIMETHYL-4-{[(2S)-2-(PYRROLIDIN-1-YLMETHYL)PYRROLIDIN-1-YL]CARBONYL}-1H-PYRROL-2-YL)METHYLIDENE]-1,3-DIHYDRO-2H-INDOL-2-ONE	2wkm	A	V1092 A1108 L1140 M1160 Y1230
DFQ		(E)-3-{6-[(1R)-1-(2,6-DICHLORO-3-FLUORO-PHENYL)-ETHOXY]-QUINOLIN-3-YL}-N-METHYL-ACRYLAMIDE	3a4p	A	V1092 A1108 L1140 M1160 Y1230
SX8		6-{[6-(1-METHYL-1H-PYRAZOL-4-YL)[1,2,4]TRIAZOLO[4,3-B]PYRIDAZIN-3-YL]SULFANYL}QUINOLINE	3dkf	A	V1092 A1108 L1140 M1160 Y1230
3QT		6-{[6-(1-METHYL-1H-PYRAZOL-4-YL)IMIDAZO[1,2-B]PYRIDAZIN-3-YL]METHYL}QUINOLINE	3qti	B	V1092 A1108 L1140 M1160 Y1230
6XP		(2S)-N'-[(3R)-4-CHLORO-7-METHYL-2-OXO-2,3-DIHYDRO-1H-INDOL-3-YL]-2-(4-HYDROXYPHENYL)PROPANEHYDRAZIDE	3zze	A	V1092 A1108 L1140 M1160 Y1230
1RU		7-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-3-[1- (PIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]FURO[3,2-C]PYRIDIN-6- AMINE	4knb	B	V1092 A1108 L1140 M1160 Y1230
MT3		2-BENZYL-5-{4-[(6,7-DIMETHOXYQUINOLIN-4-YL)OXY]-3-FLUOROPHENYL}-3-METHYLPYRIMIDIN-4(3H)-ONE	3efj	A	V1092 A1108 M1160
ATP		ATP	3dkc	A	V1092 A1108 M1160 D1204
1FN		1-(4-FLUOROPHENYL)-N-[3-FLUORO-4-(1H-PYRROLO[2,3-B]PYRIDIN-4-YLOXY)PHENYL]-2-OXO-1,2-DIHYDROPYRIDINE-3-CARBOXAMIDE	3ce3	A	V1092 A1108 M1160 L1195
L8V		2-({4-[(2-AMINOPYRIDIN-4-YL)OXY]-3-FLUOROPHENYL}AMINO)-N-(2,4-DIFLUOROPHENYL)PYRIDINE-3-CARBOXAMIDE	3l8v	A	V1092 A1108 M1160 L1195 H1202
L1X		N-(3-FLUORO-4-{[1-METHYL-6-(1H-PYRAZOL-4-YL)-1H- INDAZOL-5-YL]OXY}PHENYL)-1-(4-FLUOROPHENYL)-6-METHYL- 2-OXO-1,2-DIHYDROPYRIDINE-3-CARBOXAMIDE	4eev	A	V1092 A1108 M1160 L1195 H1202
KSA		K-252A	1r0p	A	V1092 A1108 M1160 Y1230
LKG		4-[(6-PHENYL[1,2,4]TRIAZOLO[4,3-B]PYRIDAZIN-3-YL)METHYL]PHENOL	3ccn	A	V1092 A1108 M1160 Y1230
L5G		7-METHOXY-4-[(6-PHENYL[1,2,4]TRIAZOLO[4,3-B]PYRIDAZIN-3-YL)METHOXY]QUINOLINE	3cd8	A	V1092 A1108 M1160 Y1230
B2D		7-METHOXY-N-[(6-PHENYL[1,2,4]TRIAZOLO[4,3-B]PYRIDAZIN-3-YL)METHYL]-1,5-NAPHTHYRIDIN-4-AMINE	3i5n	A	V1092 A1108 M1160 Y1230
KRW		2-{4-[1-(QUINOLIN-6-YLMETHYL)-1H-[1,2,3]TRIAZOLO[4,5-B]PYRAZIN-6-YL]-1H-PYRAZOL-1-YL}ETHANOL	3zxz	A	V1092 A1108 M1160 Y1230
4K0		4-[3-(1H-PYRROLO[2,3-B]PYRIDIN-3-YLMETHYL)- [1,2,4]TRIAZOLO[4,3-B][1,2,4]TRIAZIN-6-YL] BENZENECARBONITRILE	4aoi	A	V1092 A1108 M1160 Y1230
F47		4-[[6-(4-FLUOROPHENYL)-[1,2,4]TRIAZOLO[4,3-B] [1,2,4]TRIAZIN-3-YL]METHYL]PHENOL	4ap7	A	V1092 A1108 M1160 Y1230
0JL		3-{(1S)-1-[3-(2-METHOXYETHOXY)QUINOLIN-6-YL]ETHYL}-5- (3-METHYL-1,2-THIAZOL-5-YL)-3,5-DIHYDRO-4H-[1,2, 3]TRIAZOLO[4,5-C]PYRIDIN-4-ONE	4dei	A	V1092 A1108 M1160 Y1230
6XE		6-[[6-(4-FLUOROPHENYL)-[1,2,4]TRIAZOLO[4,3-B] [1,2,4]TRIAZIN-3-YL]METHYL]QUINOLINE	3zbx	A	V1092 A1108 M1160 Y1230
W9Z		6-{(1S)-1-[6-(1-METHYL-1H-PYRAZOL-4-YL)[1,2, 4]TRIAZOLO[4,3-B]PYRIDAZIN-3-YL]ETHYL} QUINOLINE	3zc5	A	V1092 A1108 M1160 Y1230
5TF		(S)-3-(1-(1H-PYRROLO(2,3-B)PYRIDIN-3-YL) ETHYL)-N-ISOPROPYL-(1,2,4)TRIAZOLO(4,3-B) PYRIDAZIN-6-AMINE	3zcl	A	V1092 A1108 M1160 Y1230
46G		6-{(1R)-1-FLUORO-1-[8-FLUORO-6-(3-METHYL-1,2-OXAZOL-5- YL)[1,2,4]TRIAZOLO[4,3-A]PYRIDIN-3-YL]ETHYL}-3- METHOXYQUINOLINE	4xmo	A	V1092 A1108 M1160 Y1230
44X		6-{(1S)-1-[8-FLUORO-6-(3-METHYL-1,2-OXAZOL-5-YL)[1,2, 4]TRIAZOLO[4,3-A]PYRIDIN-3-YL]ETHYL}-3-(2- METHOXYETHOXY)QUINOLINE	4xyf	A	V1092 A1108 M1160 Y1230
GBL		GAMMA-BUTYROLACTONE	3f66	A	Y1230
GBL		GAMMA-BUTYROLACTONE	3f66	B	Y1230

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Conservation information for LBS of MET

Multiple alignments for P08581 in multiple species

LBS	AA sequence	# species	Species
A1108	KKIHCAVKSLN	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
A1221	FTVKVADFGLA	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
A1226	ADFGLARDMYD	4	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris
A1226	ADFGLARDVYD	1	Bos taurus
D1164	YMKHGDLRNFI	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
D1180	NPTVKDLIGFG	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
D1204	KFVHRDLAARN	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
D1222	TVKVADFGLAR	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
D1228	FGLARDMYDKE	4	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris
D1228	FGLARDVYDKE	1	Bos taurus
D1231	ARDMYDKEYYS	4	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris
D1231	ARDVYDKEYYS	1	Bos taurus
E1127	SQFLTEGIIMK	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
E1332	RPSFSELVSRI	4	Homo sapiens, Pan troglodytes, Canis lupus familiaris, Bos taurus
E1332	RPSVSELVSRI	1	Rattus norvegicus
F1089	IGRGHFGCVYH	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
F1124	GEVSQFLTEGI	4	Homo sapiens, Pan troglodytes, Canis lupus familiaris, Bos taurus
F1124	EEVSQFLTEGI	1	Rattus norvegicus
F1134	IIMKDFSHPNV	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
F1168	GDLRNFIRNET	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
F1184	KDLIGFGLQVA	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
F1200	LASKKFVHRDL	4	Homo sapiens, Pan troglodytes, Canis lupus familiaris, Bos taurus
F1200	LVSKKFVHRDL	1	Rattus norvegicus
F1216	MLDEKFTVKVA	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
F1223	VKVADFGLARD	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
F1341	RISAIFSTFIG	3	Homo sapiens, Pan troglodytes, Canis lupus familiaris
F1341	RISSIFSTFIG	1	Rattus norvegicus
F1341	RISVIFSTFIG	1	Bos taurus
G1085	FNEVIGRGHFG	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
G1087	EVIGRGHFGCV	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
G1090	GRGHFGCVYHG	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
G1128	QFLTEGIIMKD	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
G1163	PYMKHGDLRNF	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
G1183	VKDLIGFGLQV	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
G1224	KVADFGLARDM	4	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris
G1224	KVADFGLARDV	1	Bos taurus
H1088	VIGRGHFGCVY	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
H1162	LPYMKHGDLRN	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
H1174	IRNETHNPTVK	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
H1202	SKKFVHRDLAA	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
I1084	HFNEVIGRGHF	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
I1130	LTEGIIMKDFS	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
I1145	LSLLGICLRSE	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
K1110	IHCAVKSLNRI	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
K1161	VLPYMKHGDLR	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
K1244	NKTGAKLPVKW	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
L1140	SHPNVLSLLGI	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
L1142	PNVLSLLGICL	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
L1157	SPLVVLPYMKH	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
L1195	KGMKYLASKKF	3	Homo sapiens, Pan troglodytes, Canis lupus familiaris
L1195	KGMKYLVSKKF	1	Rattus norvegicus
L1195	KGMEYLASKKF	1	Bos taurus
L1225	VADFGLARDMY	4	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris
L1225	VADFGLARDVY	1	Bos taurus
M1131	TEGIIMKDFSH	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
M1160	VVLPYMKHGDL	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
M1211	AARNCMLDEKF	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
M1229	GLARDMYDKEY	4	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris
M1229	GLARDVYDKEY	1	Bos taurus
N1167	HGDLRNFIRNE	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
N1171	RNFIRNETHNP	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
N1209	DLAARNCMLDE	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
P1158	PLVVLPYMKHG	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
P1176	NETHNPTVKDL	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
Q1187	IGFGLQVAKGM	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
R1086	NEVIGRGHFGC	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
R1208	RDLAARNCMLD	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
R1227	DFGLARDMYDK	4	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris
R1227	DFGLARDVYDK	1	Bos taurus
S1331	MRPSFSELVSR	2	Homo sapiens, Pan troglodytes
S1331	LRPSFSELVSR	2	Canis lupus familiaris, Bos taurus
S1331	MRPSVSELVSR	1	Rattus norvegicus
S1335	FSELVSRISAI	3	Homo sapiens, Pan troglodytes, Canis lupus familiaris
S1335	VSELVSRISSI	1	Rattus norvegicus
S1335	FSELVSRISVI	1	Bos taurus
V1092	GHFGCVYHGTL	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
V1139	FSHPNVLSLLG	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
V1155	EGSPLVVLPYM	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
V1220	KFTVKVADFGL	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
Y1159	LVVLPYMKHGD	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
Y1230	LARDMYDKEYY	4	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris
Y1230	LARDVYDKEYY	1	Bos taurus
Y1235	YDKEYYSVHNK	5	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris, Bos taurus
Y41	NVNMKYQLPNF	4	Homo sapiens, Rattus norvegicus, Pan troglodytes, Canis lupus familiaris
Y41	NVNMQYQLPNF	1	Bos taurus