mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

Home

	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 LCK

Gene summary

Basic gene Info.	Gene symbol	LCK
	Gene name	LCK proto-oncogene, Src family tyrosine kinase
	Synonyms	IMD22\|LSK\|YT16\|p56lck\|pp58lck
	Cytomap	UCSC genome browser: 1p34.3
	Type of gene	protein-coding
	RefGenes	NM_001042771.2, NM_005356.4,
	Description	T-lymphocyte specific protein tyrosine kinase p56lckleukocyte C-terminal Src kinaselymphocyte cell-specific protein-tyrosine kinaselymphocyte-specific protein tyrosine kinasep56(LSTRA) protein-tyrosine kinaseproto-oncogene tyrosine-protein kinase LCK
	Modification date	20141207
dbXrefs	MIM : 153390
	HGNC : HGNC
	Ensembl : ENSG00000182866
	HPRD : 01080
	Vega : OTTHUMG00000007463
Protein	UniProt: P06239 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_LCK
	BioGPS: 3932
Pathway	NCI Pathway Interaction Database: LCK
	KEGG: LCK
	REACTOME: LCK
	Pathway Commons: LCK
Context	iHOP: LCK
	ligand binding site mutation search in PubMed: LCK
	UCL Cancer Institute: LCK
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 LCK.	1. Bauer, F., & Sticht, H. (2007). A proline to glycine mutation in the Lck SH3-domain affects conformational sampling and increases ligand binding affinity.FEBS letters, 581(8), 1555-1560. 17382937

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

GO ID	GO Term	PubMed ID
GO:0006468	protein phosphorylation	214242
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process	16116473
GO:0016311	dephosphorylation	8506364
GO:0042493	response to drug	16116473
GO:0050870	positive regulation of T cell activation	8943371

Top

Ligand binding site mutations for LCK

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
S164	F163S	COAD	2
A271	K269N	COAD	1
S164	S166L	COAD	1
A271	K269E	COAD	1
W233	P232L	COAD	1
A271	K269R	COAD	1
I193	F191L	LUAD	1
H76	D77V	LUSC	1
M292	M292I	SKCM	1
M319	M319I	SKCM	1
L371	V372M	SKCM	1
A271	K269E	SKCM	1
Y181	Y181S	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.

Top

Protein structure related information for LCK

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
H76	D77V	0.16840655
Y181	Y181S	-1.3222816
L371	V372M	-0.99848959
A271	K269N	-0.96814785
M292	M292I	-0.74539655
I193	F191L	-0.69331517
M319	M319I	-0.63717288
A271	K269R	-0.52362151
A271	K269E	-0.42686407
W233	P232L	-0.42652771
S164	S166L	-0.35445444
S164	F163S	-0.050907491

(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 LCK from PDB

PDB ID	PDB title	PDB structure
1CWE	HUMAN P56LCK TYROSINE KINASE COMPLEXED WITH PHOSPHOPEPTIDE

Top

Differential gene expression and gene-gene network for LCK

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

Top

Phenotype information for LCK

Gene level disease information (DisGeNet)

Disease ID

Disease name

# PubMed

Association type

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

Top

Pharmacological information for LCK

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	DB01254	Dasatinib	Small molecule
Experimental	DB01830	{4-[2-Acetylamino-2-(3-Carbamoyl-2-Cyclohexylmethoxy-6,7,8,9-Tetrahydro-5h-Benzocyclohepten-5ylcarbamoyl)-Ethyl]-2-Phosphono-Phenyl}-Phosphonic Acid	Small molecule
Experimental	DB02010	Staurosporine	Small molecule
Experimental	DB03023	1-Tert-Butyl-3-(4-Chloro-Phenyl)-1h-Pyrazolo[3,4-D]Pyrimidin-4-Ylamine	Small molecule
Experimental	DB04003	(4-{2-Acetylamino-2-[1-(3-Carbamoyl-4-Cyclohexylmethoxy-Phenyl)-Ethylcarbamoyl}-Ethyl}-2-Phosphono-Phenoxy)-Acetic Acid	Small molecule
Experimental	DB04395	Phosphoaminophosphonic Acid-Adenylate Ester	Small molecule
Experimental	DB06925	3-(2-AMINOQUINAZOLIN-6-YL)-4-METHYL-N-[3-(TRIFLUOROMETHYL)PHENYL]BENZAMIDE	Small molecule
Experimental	DB07146	2,3-DIPHENYL-N-(2-PIPERAZIN-1-YLETHYL)FURO[2,3-B]PYRIDIN-4-AMINE	Small molecule
Experimental	DB07297	5,6-DIPHENYL-N-(2-PIPERAZIN-1-YLETHYL)FURO[2,3-D]PYRIMIDIN-4-AMINE	Small molecule
Experimental	DB08055	N-(2-chlorophenyl)-5-phenylimidazo[1,5-a]pyrazin-8-amine	Small molecule
Experimental	DB08056	N-(2,6-dimethylphenyl)-5-phenylimidazo[1,5-a]pyrazin-8-amine	Small molecule
Experimental	DB08057	N-(2-chloro-6-methylphenyl)-8-[(3S)-3-methylpiperazin-1-yl]imidazo[1,5-a]quinoxalin-4-amine	Small molecule
Approved	DB08901	Ponatinib	Small molecule
Approved	DB09079	Nintedanib	Small molecule

Gene-centered ligand-gene interaction network

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

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
STI		IMATINIB	2pl0	A	A271 M292 M319
242		AMINOQUINAZOLINE 1	2ofv	A	A271 M292 M319 L371
242		AMINOQUINAZOLINE 1	2ofv	B	A271 M292 M319 L371
1N8		AMINOQUINAZOLINE 36	2og8	A	A271 M292 M319 L371
1N8		AMINOQUINAZOLINE 36	2og8	B	A271 M292 M319 L371
KSF		N-(2-CHLOROPHENYL)-5-PHENYLIMIDAZO[1,5-A]PYRAZIN-8-AMINE	2zm1	A	A271 M292 M319 L371
9NH		N-[5-({[2-FLUORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)-2-METHYLPHENYL]-4-METHOXY-2-[(4-PIPERAZIN-1-YLPHENYL)AMINO]PYRIMIDINE-5-CARBOXAMIDE	3b2w	A	A271 M292 M319 L371
AM0		N-PHENYL-1-{4-[(3,4,5-TRIMETHOXYPHENYL)AMINO]-1,3,5-TRIAZIN-2-YL}-1H-BENZIMIDAZOL-2-AMINE	3bym	A	A271 M292 M319 L371
AM5		4-METHYL-N~3~-(2-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-5-YL)-N~1~-[3-(TRIFLUOROMETHYL)PHENYL]BENZENE-1,3-DICARBOXAMIDE	3bys	A	A271 M292 M319 L371
AM6		2-METHYL-N-{4-METHYL-3-[(2-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-5-YL)CARBAMOYL]PHENYL}-3-(TRIFLUOROMETHYL)BENZAMIDE	3byu	A	A271 M292 M319 L371
LHL		3-(2,6-DICHLOROPHENYL)-7-({4-[2-(DIETHYLAMINO)ETHOXY]PHENYL}AMINO)-1-METHYL-3,4-DIHYDROPYRIMIDO[4,5-D]PYRIMIDIN-2(1H)-ONE	3kmm	A	A271 M292 M319 L371
ANP		AMP-PNP	1qpc	A	A271 M319 L371
STU		STAUROSPORINE	1qpd	A	A271 M319 L371
PP2		1-TERT-BUTYL-3-(4-CHLORO-PHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-YLAMINE	1qpe	A	A271 M319 L371
STU		STAUROSPORINE	1qpj	A	A271 M319 L371
547		2,3-DIPHENYL-N-(2-PIPERAZIN-1-YLETHYL)FURO[2,3-B]PYRIDIN-4-AMINE	2of2	A	A271 M319 L371
979		5,6-DIPHENYL-N-(2-PIPERAZIN-1-YLETHYL)FURO[2,3-D]PYRIMIDIN-4-AMINE	2of4	A	A271 M319 L371
1N9		2,6-DIMETHYLPHENYL 2-(3,5-DIMETHOXY-4-(3-(4-METHYLPIPERAZIN-1-YL)PROPOXY)PHENYLAMINO)PYRIMIDIN- 4-YL(2,4-DIMETHOXYPHENYL)CARBAMATE	2ofu	A	A271 M319 L371
KSM		N-(2-CHLORO-6-METHYLPHENYL)-8-[(3S)-3-METHYLPIPERAZIN-1-YL]IMIDAZO[1,5-A]QUINOXALIN-4-AMINE	2zm4	A	A271 M319 L371
KSL		N-(2,6-DIMETHYLPHENYL)-5-PHENYLIMIDAZO[1,5-A]PYRAZIN-8-AMINE	2zyb	A	A271 M319 L371
KZI		5-{[(1R,2S)-2-AMINOCYCLOHEXYL]AMINO}-3-[(3,5-DIMETHOXYPHENYL)AMINO]PYRAZINE-2-CARBOXAMIDE	3ac1	A	A271 M319 L371
KSE		7-[(2-AMINO-2-METHYLPROPYL)AMINO]-2-[(3,5-DIMETHOXYPHENYL)AMINO]-5-METHYLPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXAMIDE	3ac2	A	A271 M319 L371
KSH		2-[(3,5-DIMETHOXYPHENYL)AMINO]-5-ETHYL-7-[(2R)-2-(HYDROXYMETHYL)PYRROLIDIN-1-YL]PYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXAMIDE	3ac3	A	A271 M319 L371
KZL		5-[(2-AMINO-1,1-DIMETHYLETHYL)AMINO]-7-[(3,5-DIMETHOXYPHENYL)AMINO][1,2,4]TRIAZOLO[4,3-C]PYRIMIDINE-8-CARBOXAMIDE	3ac4	A	A271 M319 L371
KZM		5-{[(1R,2S)-2-AMINOCYCLOHEXYL]AMINO}-7-[(3,5-DIMETHOXYPHENYL)AMINO]-2-(3-HYDROXYPHENYL)[1,2,4]TRIAZOLO[1,5-C]PYRIMIDINE-8-CARBOXAMIDE	3ac5	A	A271 M319 L371
KSK		7-[(2-AMINO-2-METHYLPROPYL)AMINO]-5-CYCLOPROPYL-2-[(3,5-DIMETHOXYPHENYL)AMINO]PYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXAMIDE	3ac8	A	A271 M319 L371
KSS		7-(3,4-DIMETHOXYPHENYL)-5-(ETHYLSULFANYL)IMIDAZO[1,2-C]PYRIMIDINE	3acj	A	A271 M319 L371
KSR		6-(5-METHOXY-1-METHYL-1H-INDOL-3-YL)-5H-PYRROLO[2,3-B]PYRAZINE	3ack	A	A271 M319 L371
KBM		(4-CHLOROPHENYL)(5-METHOXY-1-BENZOFURAN-2-YL)METHANONE	3ad4	A	A271 M319 L371
5PB		4-[4-(BENZYLOXY)PHENYL]-5-{[2-(4-CHLOROPHENYL)-2-OXOETHYL]SULFANYL}-2,4-DIHYDRO-3H-1,2,4-TRIAZOL-3-ONE	3ad5	A	A271 M319 L371
KSC		7-[(CYCLOPROPYLMETHYL)AMINO]-2-[(4-METHOXYPHENYL)AMINO]-5-METHYLPYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXAMIDE	3ad6	A	A271 M319 L371
AM9		6-(2,6-DIMETHYLPHENYL)-2-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDO[5',4':5,6]PYRIMIDO[1,2-A]BENZIMIDAZOL-5(6H)-ONE	3byo	A	A271 M319 L371
925		N-(1-HYDROXY-2,2,6,6-TETRAMETHYLPIPERIDIN-4-YL)-3-(7-(3-HYDROXYPHENYLAMINO)PYRAZOLO[1,5-A]PYRIMIDIN-2-YL)BENZAMIDE	3kxz	A	A271 M319 L371
5LK		4-{(6R,7R)-7-AMINO-3-[3-(4-METHYLPIPERAZIN-1-YL)PHENYL]-6,7-DIHYDROPYRAZOLO[1,5-A]PYRIMIDIN-6-YL}PHENOL	3mpm	A	A271 M319 L371
7KW		N-PHENYL-4-(5-PHENYL-1H-PYRAZOL-4-YL) PYRIMIDIN-2-AMINE	4c3f	A	A271 M319 L371
III		Peptide ligand (TYR,ASP,TYR,VAL,HIS)	1x27	A	H76
ZN		ZINC(2+)	2iim	A	H76
III		Peptide ligand (ACE,TYR,GLU,GLU,GLY)	1lkl	A	S164 Y181
III		Peptide ligand (TYR,ASP,TYR,VAL,HIS)	1x27	C	S164 Y181
III		Peptide ligand (TYR,ASP,TYR,VAL,HIS)	1x27	E	S164 Y181
III		Peptide ligand (ACE,PHE,GLU,GLU,ILE)	1bhf	A	S164 Y181 I193
III		Peptide ligand (GLU,PRO,GLN,TYR,GLU,GLU,ILE,PRO,ILE,TYR,LEU)	1lcj	A	S164 Y181 I193
III		Peptide ligand (GLU,GLY,GLN,TYR,GLN,PRO,GLN,PRO,ALA)	1lck	A	S164 Y181 I193
III		Peptide ligand (ACE,TYR,GLU,GLU,ILE)	1lkk	A	S164 Y181 I193
III		Peptide ligand (ASP,TYR,ASP,TYR,VAL)	1x27	A	S164 Y181 I193
III		Peptide ligand (ASP,TYR,ASP,TYR,VAL,HIS)	1x27	B	S164 Y181 I193
III		Peptide ligand (ASP,TYR,ASP,TYR,VAL,HIS)	1x27	D	S164 Y181 I193
III		Peptide ligand (ASP,TYR,ASP,TYR,VAL,HIS)	1x27	F	S164 Y181 I193
DMS		DIMETHYL SULFOXIDE	2zm1	A	W233
DMS		DIMETHYL SULFOXIDE	2zm4	A	W233

Top

Conservation information for LBS of LCK

Multiple alignments for P06239 in multiple species

LBS

AA sequence

# species

Species