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 MAP4K4

Gene summary

Basic gene Info.	Gene symbol	MAP4K4
	Gene name	mitogen-activated protein kinase kinase kinase kinase 4
	Synonyms	FLH21957\|HEL-S-31\|HGK\|MEKKK4\|NIK
	Cytomap	UCSC genome browser: 2q11.2-q12
	Type of gene	protein-coding
	RefGenes	NM_001242559.1, NM_001242560.1,NM_004834.4,NM_145686.3,NM_145687.3,
	Description	HPK/GCK-like kinase HGKMAPK/ERK kinase kinase kinase 4MEK kinase kinase 4Ste20 group protein kinase HGKepididymis secretory protein Li 31hepatocyte progenitor kinase-like/germinal center kinase-like kinasenck-interacting kinase
	Modification date	20141207
dbXrefs	MIM : 604666
	HGNC : HGNC
	Ensembl : ENSG00000071054
	HPRD : 05235
	Vega : OTTHUMG00000155394
Protein	UniProt: O95819 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_MAP4K4
	BioGPS: 9448
Pathway	NCI Pathway Interaction Database: MAP4K4
	KEGG: MAP4K4
	REACTOME: MAP4K4
	Pathway Commons: MAP4K4
Context	iHOP: MAP4K4
	ligand binding site mutation search in PubMed: MAP4K4
	UCL Cancer Institute: MAP4K4
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:0006468	protein phosphorylation	9890973
GO:0035556	intracellular signal transduction	9890973
GO:0046328	regulation of JNK cascade	14966141

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Ligand binding site mutations for MAP4K4

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
I82,R80	N81H	COAD	1
S77	Y76F	GBM	1
D153	R152G	SKCM	1
V31	V30A	STAD	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 MAP4K4

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
V31	V30A	-1.8207955
D153	R152G	-1.321913
I82	N81H	-0.94852495
R80	N81H	-0.94852495
S77	Y76F	-0.85392353

(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 MAP4K4 from PDB

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Differential gene expression and gene-gene network for MAP4K4

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 MAP4K4 and the right PPI network was created from samples without mutations in the LBS of MAP4K4. 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 MAP4K4

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

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Pharmacological information for MAP4K4

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

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of MAP4K4 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
ANP		AMP-PNP	4u40	A	D153
MG		MAGNESIUM(2+)	4obp	A	S77 I82
MG		MAGNESIUM(2+)	4obq	A	S77 I82
MG		MAGNESIUM(2+)	4u45	A	S77 I82
MG		MAGNESIUM(2+)	4zk5	A	S77 I82
MG		MAGNESIUM(2+)	4u40	A	S77 I82
MG		MAGNESIUM(2+)	4u41	A	S77 I82
MG		MAGNESIUM(2+)	4u42	B	S77 I82
MG		MAGNESIUM(2+)	4u42	A	S77 R80 I82
2QV		6-(3-CHLOROPHENYL)QUINAZOLIN-4-AMINE	4obo	A	V31
2QU		6-(2-FLUOROPYRIDIN-4-YL)PYRIDO[3,2-D]PYRIMIDIN-4-AMINE	4obp	A	V31
3D8		N-(PYRIDIN-3-YL)PYRROLO[2,1-F][1,2,4]TRIAZIN-4-AMINE	4u43	A	V31
3D9		6-PHENYL-N-(PYRIDIN-4-YL)PYRROLO[2,1-F][1,2,4]TRIAZIN- 4-AMINE	4u44	A	V31
3DC		6-(1H-PYRAZOL-4-YL)-N-(PYRIDIN-4-YL)PYRROLO[2,1-F][1,2, 4]TRIAZIN-4-AMINE	4u45	A	V31
3XM		3-HEXANOYL-4-HYDROXY-5-(4-HYDROXYPHENYL)PYRIDIN-2(1H)- ONE	4rvt	A	V31
4P4	GNE-495	8-AMINO-N-[1-(CYCLOPROPYLCARBONYL)AZETIDIN-3-YL]-2-(3- FLUOROPHENYL)-1,7-NAPHTHYRIDINE-5-CARBOXAMIDE	4zk5	A	V31
5DF		4-{6-AMINO-5-[4-(METHYLSULFONYL)PHENYL]PYRIDIN-3- YL}PHENOL	5di1	A	V31

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Conservation information for LBS of MAP4K4

Multiple alignments for O95819 in multiple species

LBS

AA sequence

# species

Species