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 PTK2B

Gene summary

Basic gene Info.	Gene symbol	PTK2B
	Gene name	protein tyrosine kinase 2 beta
	Synonyms	CADTK\|CAKB\|FADK2\|FAK2\|PKB\|PTK\|PYK2\|RAFTK
	Cytomap	UCSC genome browser: 8p21.1
	Type of gene	protein-coding
	RefGenes	NM_004103.4, NM_173174.2,NM_173175.2,NM_173176.2,
	Description	CAK-betaFADK 2PTK2B protein tyrosine kinase 2 betacalcium-dependent tyrosine kinasecalcium-regulated non-receptor proline-rich tyrosine kinasecell adhesion kinase betafocal adhesion kinase 2proline-rich tyrosine kinase 2protein kinase Bprotein-ty
	Modification date	20141207
dbXrefs	MIM : 601212
	HGNC : HGNC
	Ensembl : ENSG00000120899
	HPRD : 03131
	Vega : OTTHUMG00000102082
Protein	UniProt: Q14289 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_PTK2B
	BioGPS: 2185
Pathway	NCI Pathway Interaction Database: PTK2B
	KEGG: PTK2B
	REACTOME: PTK2B
	Pathway Commons: PTK2B
Context	iHOP: PTK2B
	ligand binding site mutation search in PubMed: PTK2B
	UCL Cancer Institute: PTK2B
Assigned class in mutLBSgeneDB	B: This gene belongs to targetable_mutLBSgenes.

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

GO ID	GO Term	PubMed ID
GO:0010595	positive regulation of endothelial cell migration	21245381
GO:0018108	peptidyl-tyrosine phosphorylation	7544443
GO:0043267	negative regulation of potassium ion transport	7544443
GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation	21245381
GO:2000058	regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process	19880522

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Ligand binding site mutations for PTK2B

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
M957	M957I	BRCA	1
L431	L431I	BRCA	1
V439	E438D	COAD	1
G508	Y507C	HNSC	1
R889	R889W	HNSC	1
H547	H547P	LUAD	1
D925	V924L	LUAD	1
V439	E438Q	OV	1
Y505	P506S	SKCM	1
V907	G905S	UCEC	1
L565	L565M	UCEC	1
L431	L431I	UCEC	1
R918	R918W	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.

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Protein structure related information for PTK2B

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
V907	G905S	-1.7430351
Y505	P506S	-1.6602301
R918	R918W	-1.0794276
L431	L431I	-1.0152753
L565	L565M	-0.90608376
V439	E438Q	-0.80909026
V439	E438D	-0.79674253
R889	R889W	-0.56300088
G508	Y507C	-0.43157221
H547	H547P	-0.33488565
M957	M957I	-0.16528738
D925	V924L	-0.007353991

(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 PTK2B from PDB

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Differential gene expression and gene-gene network for PTK2B

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 PTK2B and the right PPI network was created from samples without mutations in the LBS of PTK2B. 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 PTK2B

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0025202	Melanoma	3	Biomarker, GeneticVariation
umls:C0037286	Skin Neoplasms	2	Biomarker, GeneticVariation
umls:C0038220	Status Epilepticus	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for PTK2B

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
Approved\|investigational	DB01097	Leflunomide	Small molecule
Investigational	DB01645	Genistein	Small molecule
Experimental	DB08341	4-{[4-{[(1R,2R)-2-(dimethylamino)cyclopentyl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-N-methylbenzenesulfonamide	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PTK2B go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
B96		1-(5-TERT-BUTYL-2-P-TOLYL-2H-PYRAZOL-3-YL)-3-[4-(2-MORPHOLIN-4-YL-ETHOXY)-NAPHTHALEN-1-YL]-UREA	3fzs	A	L431 H547 L565
3JZ		N-METHYL-N-{2-[({2-[(2-OXO-2,3-DIHYDRO-1H-INDOL-5-YL)AMINO]-5-(TRIFLUOROMETHYL)PYRIMIDIN-4-YL}AMINO)METHYL]PHENYL}METHANESULFONAMIDE	3fzr	A	L431 V439 Y505 G508
P1E		4-{[4-{[(1R,2R)-2-(DIMETHYLAMINO)CYCLOPENTYL]AMINO}-5-(TRIFLUOROMETHYL)PYRIMIDIN-2-YL]AMINO}-N-METHYLBENZENESULFONAMIDE	3h3c	A	L431 V439 Y505 G508
349		5-{[4-{[2-(PYRROLIDIN-1-YLSULFONYL)BENZYL]AMINO}-5-(TRIFLUOROMETHYL)PYRIMIDIN-2-YL]AMINO}-1,3-DIHYDRO-2H-INDOL-2-ONE	3et7	A	L431 Y505 G508
III		Peptide ligand (GLU,LEU,ASP,GLU,LEU,MET,ALA,SER,LEU,SER)	3u3f	A	R889
III		Peptide ligand (GLU,LEU,ASP,GLU,LEU,MET,ALA,SER,LEU,SER)	3u3f	B	R889
III		Peptide ligand (MET,GLU,GLU,LEU,ASP,ALA,LEU,LEU,GLU,GLU,LEU,GLU,ARG,SER,THR)	4xef	A	R889
III		Peptide ligand (SER,ALA,THR,ARG,GLU,LEU,ASP,GLU,LEU,MET,ALA,SER)	3u3f	C	R918
III		Peptide ligand (SER,ALA,THR,ARG,GLU,LEU,ASP,GLU,LEU,MET,ALA,SER,LEU)	3u3f	A	R918 D925 M957
III		Peptide ligand (SER,ALA,THR,ARG,GLU,LEU,ASP,GLU,LEU,MET,ALA,SER,LEU)	3u3f	B	R918 D925 M957
III		Peptide ligand (LYS,THR,SER,ALA,ALA,ALA,GLN,LEU,ASP,GLU,LEU,MET,ALA,HIS,LEU,THR)	4xek	A	R918 D925 M957
III		Peptide ligand (LYS,THR,SER,ALA,ALA,ALA,GLN,LEU,ASP,GLU,LEU,MET,ALA,HIS,LEU,THR,GLU,MET)	4xev	D	R918 D925 M957
III		Peptide ligand (SER,ALA,THR,ARG,GLU,LEU,ASP,GLU,LEU,MET,ALA,SER,LEU,SER)	3u3f	D	R918 M957
III		Peptide ligand (SER,ASN,LEU,SER,GLU,LEU,ASP,ARG,LEU,LEU,LEU,GLU,LEU,ASN,ALA)	4r32	A	R918 M957
0YJ		7-({[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5- YL]CARBAMOYL}AMINO)-N-(PROPAN-2-YL)-1H-INDOLE-2- CARBOXAMIDE	4h1m	A	V439 H547 L565
AGS		ADENOSINE 5'-[GAMMA-THIO]TRIPHOSPHATE	3fzp	A	V439 Y505
III		Peptide ligand (THR,ARG,GLU,LEU,ASP,GLU,LEU,MET,ALA,SER,LEU,SER)	3gm1	B	V907 R918
III		Peptide ligand (SER,ASN,LEU,SER,GLU,LEU,ASP,ARG,LEU,LEU,LEU,GLU,LEU,ASN,ALA)	3u3c	A	V907 R918
III		Peptide ligand (ALA,THR,ARG,GLU,LEU,ASP,GLU,LEU,MET,ALA,SER,LEU,SER)	3gm1	A	V907 R918 D925
III		Peptide ligand (MET,GLU,GLU,LEU,ASP,ALA,LEU,LEU,GLU,GLU,LEU,GLU,ARG)	4xef	A	V907 R918 D925
III		Peptide ligand (LYS,THR,SER,ALA,ALA,ALA,GLN,LEU,ASP,GLU,LEU,MET,ALA,HIS,LEU,THR,GLU,MET,GLN)	4xev	A	V907 R918 D925 M957
III		Peptide ligand (GLU,GLU,LEU,ASP,ALA,LEU,LEU,GLU,GLU,LEU,GLU,ARG)	4xef	D	V907 R918 M957
4JZ		1-[5-TERT-BUTYL-2-(4-METHYLPHENYL)-1,2-DIHYDRO-3H-PYRAZOL-3-YLIDENE]-3-{3-[(PYRIDIN-3-YLOXY)METHYL]-1H-PYRAZOL-5-YL}UREA	3fzt	A	Y505 L565
0YH		1-[3-TERT-BUTYL-1-(4-METHYLPHENYL)-1H-PYRAZOL-5-YL]-3- [3-(4-METHOXY-2-METHYLPHENYL)-1H-PYRAZOL-5-YL]UREA	4h1j	A	Y505 L565

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Conservation information for LBS of PTK2B

Multiple alignments for Q14289 in multiple species

LBS	AA sequence	# species	Species
A455	EKINVAVKTCK	3	Homo sapiens, Mus musculus, Rattus norvegicus
A951	LNKDLAELINK	3	Homo sapiens, Mus musculus, Rattus norvegicus
A984	ASHTLAVDAKN	3	Homo sapiens, Mus musculus, Rattus norvegicus
D567	CVKLGDFGLSR	3	Homo sapiens, Mus musculus, Rattus norvegicus
D925	LIGSVDDLLPS	3	Homo sapiens, Mus musculus, Rattus norvegicus
E433	NRILGEGFFGE	3	Homo sapiens, Mus musculus, Rattus norvegicus
E474	EKFMSEAVIMK	3	Homo sapiens, Mus musculus, Rattus norvegicus
E503	TWIIMELYPYG	2	Homo sapiens, Mus musculus
E503	TWIVMELYPYG	1	Rattus norvegicus
E509	LYPYGELGHYL	3	Homo sapiens, Mus musculus, Rattus norvegicus
F435	ILGEGFFGEVY	3	Homo sapiens, Mus musculus, Rattus norvegicus
F436	LGEGFFGEVYE	3	Homo sapiens, Mus musculus, Rattus norvegicus
F568	VKLGDFGLSRY	3	Homo sapiens, Mus musculus, Rattus norvegicus
G432	LNRILGEGFFG	3	Homo sapiens, Mus musculus, Rattus norvegicus
G434	RILGEGFFGEV	3	Homo sapiens, Mus musculus, Rattus norvegicus
G508	ELYPYGELGHY	3	Homo sapiens, Mus musculus, Rattus norvegicus
G566	ECVKLGDFGLS	3	Homo sapiens, Mus musculus, Rattus norvegicus
G914	VVKNVGLNLRK	2	Mus musculus, Rattus norvegicus
G914	VVKNVGLTLRK	1	Homo sapiens
G922	LRKLIGSVDDL	3	Homo sapiens, Mus musculus, Rattus norvegicus
H512	YGELGHYLERN	3	Homo sapiens, Mus musculus, Rattus norvegicus
H547	SINCVHRDIAV	3	Homo sapiens, Mus musculus, Rattus norvegicus
H981	MLTASHTLAVD	3	Homo sapiens, Mus musculus, Rattus norvegicus
I477	MSEAVIMKNLD	3	Homo sapiens, Mus musculus, Rattus norvegicus
I486	LDHPHIVKLIG	3	Homo sapiens, Mus musculus, Rattus norvegicus
I921	NLRKLIGSVDD	2	Mus musculus, Rattus norvegicus
I921	TLRKLIGSVDD	1	Homo sapiens
I954	DLAELINKMRL	2	Homo sapiens, Rattus norvegicus
I954	DLAELINKMKL	1	Mus musculus
K457	INVAVKTCKKD	3	Homo sapiens, Mus musculus, Rattus norvegicus
K911	YVVVVKNVGLN	2	Mus musculus, Rattus norvegicus
K911	YVVVVKNVGLT	1	Homo sapiens
K944	IEGTQKLLNKD	3	Homo sapiens, Mus musculus, Rattus norvegicus
K988	LAVDAKNLLDA	3	Homo sapiens, Mus musculus, Rattus norvegicus
L431	VLNRILGEGFF	3	Homo sapiens, Mus musculus, Rattus norvegicus
L481	VIMKNLDHPHI	3	Homo sapiens, Mus musculus, Rattus norvegicus
L504	WIIMELYPYGE	2	Homo sapiens, Mus musculus
L504	WIVMELYPYGE	1	Rattus norvegicus
L540	KAMAYLESINC	3	Homo sapiens, Mus musculus, Rattus norvegicus
L556	AVRNILVASPE	3	Homo sapiens, Mus musculus, Rattus norvegicus
L565	PECVKLGDFGL	3	Homo sapiens, Mus musculus, Rattus norvegicus
L892	LVEAVLELKNK	2	Mus musculus, Rattus norvegicus
L892	LVRAVLELKNE	1	Homo sapiens
L915	VKNVGLNLRKL	2	Mus musculus, Rattus norvegicus
L915	VKNVGLTLRKL	1	Homo sapiens
L917	NVGLNLRKLIG	2	Mus musculus, Rattus norvegicus
L917	NVGLTLRKLIG	1	Homo sapiens
L950	LLNKDLAELIN	3	Homo sapiens, Mus musculus, Rattus norvegicus
L991	DAKNLLDAVDQ	3	Homo sapiens, Mus musculus, Rattus norvegicus
M478	SEAVIMKNLDH	3	Homo sapiens, Mus musculus, Rattus norvegicus
M502	PTWIIMELYPY	2	Homo sapiens, Mus musculus
M502	PTWIVMELYPY	1	Rattus norvegicus
M885	VYHNVMTLVEA	2	Mus musculus, Rattus norvegicus
M885	VYLNVMELVRA	1	Homo sapiens
M957	ELINKMRLAQQ	2	Homo sapiens, Rattus norvegicus
M957	ELINKMKLAQQ	1	Mus musculus
N872	IQPTANLDRTD	3	Homo sapiens, Mus musculus, Rattus norvegicus
N947	TQKLLNKDLAE	3	Homo sapiens, Mus musculus, Rattus norvegicus
P869	AQSIQPTANLD	3	Homo sapiens, Mus musculus, Rattus norvegicus
Q943	EIEGTQKLLNK	3	Homo sapiens, Mus musculus, Rattus norvegicus
Q961	KMRLAQQNAVT	2	Homo sapiens, Rattus norvegicus
Q961	KMKLAQQNAVT	1	Mus musculus
R553	RDIAVRNILVA	3	Homo sapiens, Mus musculus, Rattus norvegicus
R875	TANLDRTDDLV	3	Homo sapiens, Mus musculus, Rattus norvegicus
R889	VMTLVEAVLEL	2	Mus musculus, Rattus norvegicus
R889	VMELVRAVLEL	1	Homo sapiens
R918	VGLNLRKLIGS	2	Mus musculus, Rattus norvegicus
R918	VGLTLRKLIGS	1	Homo sapiens
R958	LINKMRLAQQN	2	Homo sapiens, Rattus norvegicus
R958	LINKMKLAQQN	1	Mus musculus
S473	KEKFMSEAVIM	3	Homo sapiens, Mus musculus, Rattus norvegicus
T870	QSIQPTANLDR	3	Homo sapiens, Mus musculus, Rattus norvegicus
V439	GFFGEVYEGVY	3	Homo sapiens, Mus musculus, Rattus norvegicus
V487	DHPHIVKLIGI	3	Homo sapiens, Mus musculus, Rattus norvegicus
V884	LVYHNVMTLVE	2	Mus musculus, Rattus norvegicus
V884	LVYLNVMELVR	1	Homo sapiens
V888	NVMTLVEAVLE	2	Mus musculus, Rattus norvegicus
V888	NVMELVRAVLE	1	Homo sapiens
V907	PPEGYVVVVKN	1	Homo sapiens
V907	PPEDYVVVVKN	1	Mus musculus
V907	PPEEYVVVVKN	1	Rattus norvegicus
V910	GYVVVVKNVGL	1	Homo sapiens
V910	DYVVVVKNVGL	1	Mus musculus
V910	EYVVVVKNVGL	1	Rattus norvegicus
Y505	IIMELYPYGEL	2	Homo sapiens, Mus musculus
Y505	IVMELYPYGEL	1	Rattus norvegicus
Y881	TDDLVYHNVMT	2	Mus musculus, Rattus norvegicus
Y881	TDDLVYLNVME	1	Homo sapiens