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 ADAM17
Gene summary
Basic gene Info.Gene symbolADAM17
Gene nameADAM metallopeptidase domain 17
SynonymsADAM18|CD156B|CSVP|NISBD|NISBD1|TACE
CytomapUCSC genome browser: 2p25
Type of geneprotein-coding
RefGenesNM_003183.4,
DescriptionADAM metallopeptidase domain 18TNF-alpha convertaseTNF-alpha converting enzymedisintegrin and metalloproteinase domain-containing protein 17snake venom-like proteasetumor necrosis factor, alpha, converting enzyme
Modification date20141207
dbXrefs MIM : 603639
HGNC : HGNC
Ensembl : ENSG00000151694
HPRD : 04703
Vega : OTTHUMG00000090425
ProteinUniProt: P78536
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_ADAM17
BioGPS: 6868
PathwayNCI Pathway Interaction Database: ADAM17
KEGG: ADAM17
REACTOME: ADAM17
Pathway Commons: ADAM17
ContextiHOP: ADAM17
ligand binding site mutation search in PubMed: ADAM17
UCL Cancer Institute: ADAM17
Assigned class in mutLBSgeneDBB: This gene belongs to targetable_mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID
GO:0001666response to hypoxia18276953
GO:0006508proteolysis24227843
GO:0006509membrane protein ectodomain proteolysis17786981
GO:0007155cell adhesion14970227
GO:0007173epidermal growth factor receptor signaling pathway12743035
GO:0007220Notch receptor processing24226769
GO:0031659positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle18483258
GO:0032496response to lipopolysaccharide18383040
GO:0033627cell adhesion mediated by integrin14970227
GO:0045741positive regulation of epidermal growth factor-activated receptor activity18483258
GO:0051088PMA-inducible membrane protein ectodomain proteolysis14625290
GO:0055099response to high density lipoprotein particle17786981


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Ligand binding site mutations for ADAM17

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
Y436,V434M435ICOAD1
N389K388NUCEC1
D342D342YUCEC1
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.


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Protein structure related information for ADAM17
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.
LBSAAchange of nsSNVRelative stability change
V434M435I-1.1000563
Y436M435I-1.1000563
N389K388N-0.87247484
D342D342Y-0.50789674
(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 ADAM17 from PDB

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Differential gene expression and gene-gene network for ADAM17
Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types

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 ADAM17 and the right PPI network was created from samples without mutations in the LBS of ADAM17. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.


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Phenotype information for ADAM17
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0005758Blister1Biomarker

Mutation level pathogenic information (ClinVar annotation)
Allele IDAA changeClinical significanceOriginPhenotype IDs

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Pharmacological information for ADAM17
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 statusDrugBank IDNameTypeDrug structure
ExperimentalDB06943(3S)-1-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}pyrrolidine-3-thiolSmall molecule
ExperimentalDB070793-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}propane-1-thiolSmall molecule
ExperimentalDB071214-({4-[(4-AMINOBUT-2-YNYL)OXY]PHENYL}SULFONYL)-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDESmall molecule
ExperimentalDB07145(2R)-N-HYDROXY-2-[(3S)-3-METHYL-3-{4-[(2-METHYLQUINOLIN-4-YL)METHOXY]PHENYL}-2-OXOPYRROLIDIN-1-YL]PROPANAMIDESmall molecule
ExperimentalDB07147methyl (1R,2S)-2-(hydroxycarbamoyl)-1-{4-[(2-methylquinolin-4-yl)methoxy]benzyl}cyclopropanecarboxylateSmall molecule
ExperimentalDB07189(1S,3R,6S)-4-oxo-6-{4-[(2-phenylquinolin-4-yl)methoxy]phenyl}-5-azaspiro[2.4]heptane-1-carboxylic acidSmall molecule
ExperimentalDB07233N-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}-5-methyl-D-tryptophanSmall molecule
ExperimentalDB07964(3S)-4-{[4-(BUT-2-YNYLOXY)PHENYL]SULFONYL}-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDESmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of ADAM17 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
CACALCIUM(2+)2ddfAD342 N389
ZNZINC(2+)3b92AD342 N389
CACALCIUM(2+)3o64AD342 N389
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE1bkcEN389
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE2ddfAN389
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE2ddfBN389
002JMV 390-12fv9BN389
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE2i47AN389
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE2i47BN389
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE3edzAN389
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE3ewjAN389
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE3l0tAN389
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE1bkcAN389 Y436
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE1bkcCN389 Y436
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE1bkcIN389 Y436
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE2fv9AN389 Y436
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE3e8rAN389 Y436
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE3kmcAN389 Y436
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE3kmeAN389 Y436
INNN-{(2R)-2-[2-(HYDROXYAMINO)-2-OXOETHYL]-4-METHYLPENTANOYL}-3-METHYL-L-VALYL-N-(2-AMINOETHYL)-L-ALANINAMIDE3o64AN389 Y436
IH6(3S)-4-{[4-(BUT-2-YNYLOXY)PHENYL]SULFONYL}-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE1zxcAV434
IH6(3S)-4-{[4-(BUT-2-YNYLOXY)PHENYL]SULFONYL}-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE1zxcBV434
541(2R)-N-HYDROXY-2-[(3S)-3-METHYL-3-{4-[(2-METHYLQUINOLIN-4-YL)METHOXY]PHENYL}-2-OXOPYRROLIDIN-1-YL]PROPANAMIDE2fv5BV434
283(3S)-1-{[4-(BUT-2-YN-1-YLOXY)PHENYL]SULFONYL}PYRROLIDINE-3-THIOL2oi0AV434
541(2R)-N-HYDROXY-2-[(3S)-3-METHYL-3-{4-[(2-METHYLQUINOLIN-4-YL)METHOXY]PHENYL}-2-OXOPYRROLIDIN-1-YL]PROPANAMIDE2fv5AV434 Y436
615(1R,2S)-N~2~-HYDROXY-1-{4-[(2-PHENYLQUINOLIN-4-YL)METHOXY]BENZYL}CYCLOPROPANE-1,2-DICARBOXAMIDE3e8rAV434 Y436
615(1R,2S)-N~2~-HYDROXY-1-{4-[(2-PHENYLQUINOLIN-4-YL)METHOXY]BENZYL}CYCLOPROPANE-1,2-DICARBOXAMIDE3e8rBV434 Y436
550METHYL (1R,2S)-2-(HYDROXYCARBAMOYL)-1-{4-[(2-METHYLQUINOLIN-4-YL)METHOXY]BENZYL}CYCLOPROPANECARBOXYLATE3edzBV434 Y436
642(1S,3R,6S)-4-OXO-6-{4-[(2-PHENYLQUINOLIN-4-YL)METHOXY]PHENYL}-5-AZASPIRO[2.4]HEPTANE-1-CARBOXYLICACID3ewjBV434 Y436
403(2R,3R)-4-[4-(2-CHLOROPHENYL)PIPERAZIN-1-YL]-2,3-DIHYDROXY-4-OXO-N-(2-THIOPHEN-2-YLETHYL)BUTANAMIDE3kmcBV434 Y436
Z59(2R,3R)-2,3-DIHYDROXY-4-OXO-4-[(2R)-2-PHENYLPYRROLIDIN-1-YL]-N-(THIOPHEN-2-YLMETHYL)BUTANAMIDE3kmeBV434 Y436
50X(2R,3R)-4-[(2R)-2-(3-CHLOROPHENYL)PYRROLIDIN-1-YL]-2,3-DIHYDROXY-4-OXO-N-[(5-{[2-(TRIFLUOROMETHYL)-1H-BENZIMIDAZOL-1-YL]METHYL}THIOPHEN-2-YL)METHYL]BUTANAMIDE3lgpAV434 Y436
50X(2R,3R)-4-[(2R)-2-(3-CHLOROPHENYL)PYRROLIDIN-1-YL]-2,3-DIHYDROXY-4-OXO-N-[(5-{[2-(TRIFLUOROMETHYL)-1H-BENZIMIDAZOL-1-YL]METHYL}THIOPHEN-2-YL)METHYL]BUTANAMIDE3lgpBV434 Y436
786(2R,3R)-2,3-DIHYDROXY-4-{(2R)-2-[2-(METHYLAMINO)-5-(METHYLSULFONYL)-1,3-THIAZOL-4-YL]PYRROLIDIN-1-YL}-4-OXO-N-{(1R)-1-[4-(1H-PYRAZOL-1-YL)PHENYL]ETHYL}BUTANAMIDE3o64BV434 Y436
7245-[(1,3-DIHYDRO-5-METHOXY-3-OXO-2H-INDAZOL-2-YL)METHYL]-5-METHYL-2,4-IMIDAZOLIDINEDIONE3l0vAY436
7245-[(1,3-DIHYDRO-5-METHOXY-3-OXO-2H-INDAZOL-2-YL)METHYL]-5-METHYL-2,4-IMIDAZOLIDINEDIONE3l0vBY436
727(5R)-5-[(5-METHOXY-3-OXO-1,3-DIHYDRO-2H-INDAZOL-2-YL)METHYL]-5-PHENYLIMIDAZOLIDINE-2,4-DIONE3le9AY436
727(5R)-5-[(5-METHOXY-3-OXO-1,3-DIHYDRO-2H-INDAZOL-2-YL)METHYL]-5-PHENYLIMIDAZOLIDINE-2,4-DIONE3le9BY436
Z93N-[(1S)-2-AMINO-1-(2,4-DICHLOROBENZYL)ETHYL]-5-[2-(METHYLAMINO)PYRIMIDIN-4-YL]THIOPHENE-2-CARBOXAMIDE3leaAY436
Z93N-[(1S)-2-AMINO-1-(2,4-DICHLOROBENZYL)ETHYL]-5-[2-(METHYLAMINO)PYRIMIDIN-4-YL]THIOPHENE-2-CARBOXAMIDE3leaBY436


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Conservation information for LBS of ADAM17
Multiple alignments for P78536 in multiple species
LBSAA sequence# speciesSpecies
A439VMYPIAVSGDH3Homo sapiens, Mus musculus, Rattus norvegicus
A439LMYTYSVSGYD1Drosophila melanogaster
D342LFTYQDFDMGT3Homo sapiens, Mus musculus, Rattus norvegicus
D342LFTDLKFEGGI1Drosophila melanogaster
E398TILTKEADLVT3Homo sapiens, Mus musculus, Rattus norvegicus
E398RVITREADLVT1Drosophila melanogaster
E406LVTTHELGHNF3Homo sapiens, Mus musculus, Rattus norvegicus
E406LVTAHEFGHNW1Drosophila melanogaster
F343FTYQDFDMGTL3Homo sapiens, Mus musculus, Rattus norvegicus
F343FTDLKFEGGIL1Drosophila melanogaster
G346QDFDMGTLGLA3Homo sapiens, Mus musculus, Rattus norvegicus
G346LKFEGGILGLA1Drosophila melanogaster
G349DMGTLGLAYVG3Homo sapiens, Mus musculus, Rattus norvegicus
G349EGGILGLAYVG1Drosophila melanogaster
G442PIAVSGDHENN3Homo sapiens, Mus musculus, Rattus norvegicus
G442TYSVSGYDVNN1Drosophila melanogaster
H405DLVTTHELGHN3Homo sapiens, Mus musculus, Rattus norvegicus
H405DLVTAHEFGHN1Drosophila melanogaster
H409THELGHNFGAE3Homo sapiens, Mus musculus, Rattus norvegicus
H409AHEFGHNWGSE1Drosophila melanogaster
H415NFGAEHDPDGL3Homo sapiens, Mus musculus, Rattus norvegicus
H415NWGSEHDPD-I1Drosophila melanogaster
I438YVMYPIAVSGD3Homo sapiens, Mus musculus, Rattus norvegicus
I438FLMYTYSVSGY1Drosophila melanogaster
K315DAWDVKMLLEQ3Homo sapiens, Mus musculus, Rattus norvegicus
K315--WDVRNLLEV1Drosophila melanogaster
L348FDMGTLGLAYV3Homo sapiens, Mus musculus, Rattus norvegicus
L348FEGGILGLAYV1Drosophila melanogaster
L350MGTLGLAYVGS3Homo sapiens, Mus musculus, Rattus norvegicus
L350GGILGLAYVGS1Drosophila melanogaster
L401TKEADLVTTHE3Homo sapiens, Mus musculus, Rattus norvegicus
L401TREADLVTAHE1Drosophila melanogaster
M345YQDFDMGTLGL3Homo sapiens, Mus musculus, Rattus norvegicus
M345DLKFEGGILGL1Drosophila melanogaster
N389LTSTKN-YGKT3Homo sapiens, Mus musculus, Rattus norvegicus
N389LSSSRNHYGQR1Drosophila melanogaster
N447GDHENNKMFSN3Homo sapiens, Mus musculus, Rattus norvegicus
N447GYDVNNKKFSP1Drosophila melanogaster
P437KYVMYPIAVSG3Homo sapiens, Mus musculus, Rattus norvegicus
P437SFLMYTYSVSG1Drosophila melanogaster
S355LAYVGSPRANS3Homo sapiens, Mus musculus, Rattus norvegicus
S355LAYVGSPRRNS1Drosophila melanogaster
S441YPIAVSGDHEN3Homo sapiens, Mus musculus, Rattus norvegicus
S441YTYSVSGYDVN1Drosophila melanogaster
T347DFDMGTLGLAY3Homo sapiens, Mus musculus, Rattus norvegicus
T347KFEGGILGLAY1Drosophila melanogaster
V314KDAWDVKMLLE3Homo sapiens, Mus musculus, Rattus norvegicus
V314K--WDVRNLLE1Drosophila melanogaster
V353LGLAYVGSPRA3Homo sapiens, Mus musculus, Rattus norvegicus
V353LGLAYVGSPRR1Drosophila melanogaster
V402KEADLVTTHEL3Homo sapiens, Mus musculus, Rattus norvegicus
V402READLVTAHEF1Drosophila melanogaster
V434QGGKYVMYPIA3Homo sapiens, Mus musculus, Rattus norvegicus
V434QGGSFLMYTYS1Drosophila melanogaster
V440MYPIAVSGDHE3Homo sapiens, Mus musculus, Rattus norvegicus
V440MYTYSVSGYDV1Drosophila melanogaster
Y390STKN-YGKTIL3Homo sapiens, Mus musculus, Rattus norvegicus
Y390SSRNHYGQRVI1Drosophila melanogaster
Y433DQGGKYVMYPI3Homo sapiens, Mus musculus, Rattus norvegicus
Y433SQGGSFLMYTY1Drosophila melanogaster
Y436GKYVMYPIAVS3Homo sapiens, Mus musculus, Rattus norvegicus
Y436GSFLMYTYSVS1Drosophila melanogaster


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