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 YWHAZ

Gene summary

Basic gene Info.	Gene symbol	YWHAZ
	Gene name	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta
	Synonyms	14-3-3-zeta\|HEL-S-3\|HEL4\|KCIP-1\|YWHAD
	Cytomap	UCSC genome browser: 8q23.1
	Type of gene	protein-coding
	RefGenes	NM_001135699.1, NM_001135700.1,NM_001135701.1,NM_001135702.1,NM_003406.3, NM_145690.2,
	Description	14-3-3 delta14-3-3 protein zeta/delta14-3-3 protein/cytosolic phospholipase A214-3-3 zetaepididymis luminal protein 4epididymis secretory protein Li 3phospholipase A2protein kinase C inhibitor protein 1protein kinase C inhibitor protein-1tyrosine
	Modification date	20141222
dbXrefs	MIM : 601288
	HGNC : HGNC
	Ensembl : ENSG00000164924
	HPRD : 03183
	Vega : OTTHUMG00000134291
Protein	UniProt: P63104 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_YWHAZ
	BioGPS: 7534
Pathway	NCI Pathway Interaction Database: YWHAZ
	KEGG: YWHAZ
	REACTOME: YWHAZ
	Pathway Commons: YWHAZ
Context	iHOP: YWHAZ
	ligand binding site mutation search in PubMed: YWHAZ
	UCL Cancer Institute: YWHAZ
Assigned class in mutLBSgeneDB	C: This gene just belongs to mutLBSgenes.

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

GO ID

GO Term

PubMed ID

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Ligand binding site mutations for YWHAZ

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
E31	G33A	BRCA	1
E208	S207I	HNSC	1
S210	S210L	HNSC	1
W228	S230L	STAD	1
I217	I217T	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 YWHAZ

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
E208	S207I	0.053532654
I217	I217T	-1.3095894
S210	S210L	-0.96087521
E31	G33A	-0.40586548
W228	S230L	-0.34939378

(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 YWHAZ from PDB

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Differential gene expression and gene-gene network for YWHAZ

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

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0007097	Carcinoma	2	AlteredExpression, Biomarker
umls:C0017661	Glomerulonephritis, IGA	1	Biomarker
umls:C0024667	Mammary Neoplasms, Animal	1	Biomarker
umls:C0024668	Mammary Neoplasms, Experimental	1	Biomarker
umls:C0027643	Neoplasm Recurrence, Local	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for YWHAZ

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.

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 YWHAZ go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
III		Peptide ligand (GLY,HIS,GLY,GLN,GLY,LEU,LEU,ASP,ALA,LEU,ASP,LEU,ALA,SER)	2o02	A	E208 S210 I217
CA		CALCIUM(2+)	2wh0	D	E31
III		Peptide ligand (GLY,LEU,LEU,ASP,ALA,LEU,ASP,LEU,ALA,SER)	2o02	B	I217
3RD		(2-AMINO-4-FORMYL-5-HYDROXY-6-METHYLPYRIDIN-3-YL)METHYL DIHYDROGEN PHOSPHATE	3rdh	A	I217
3RD		(2-AMINO-4-FORMYL-5-HYDROXY-6-METHYLPYRIDIN-3-YL)METHYL DIHYDROGEN PHOSPHATE	3rdh	B	I217
3RD		(2-AMINO-4-FORMYL-5-HYDROXY-6-METHYLPYRIDIN-3-YL)METHYL DIHYDROGEN PHOSPHATE	3rdh	C	I217
III		Peptide ligand (HIS,ARG,TYR,SER,THR,PRO)	4fj3	B	I217
FAR		2-TRANS,6-TRANS-FARNESYL GROUP	4bg6	A	I217
FAR		2-TRANS,6-TRANS-FARNESYL GROUP	4bg6	B	I217
1F5	COTYLENIN A	(1R,3AS,4R,5R,6R,9AR,10E)-6-({(1S,2R,4S,5R,6R,8S,9S)-5- HYDROXY-2-(METHOXYMETHYL)-9-METHYL-9-[(2S)-OXIRAN-2- YL]-3,7,10,11-TETRAOXATRICYCLO[6.2.1.0~1,6~]UNDEC-4- YL}OXY)-1-(METHOXYMETHYL)-4,9A-DIMETHYL-7-(PROPAN-2- YL)-1,2,3,3A,4,5,6,8,9,9A-DECAHYDRODICYC	4ihl	B	I217
III		Peptide ligand (GLN,GLY,LEU,LEU,ASP,ALA,LEU,ASP,LEU,ALA,SER)	4n7g	A	I217
III		Peptide ligand (GLN,GLY,2JN,LEU,ASP,LEU,LEU,ASP,LEU,ALA,SER)	4n7y	B	I217
III		Peptide ligand (GLY,MKD,LEU,ASP,MKD,LEU,ASP,LEU,ALA,SER)	4n84	A	I217
III		Peptide ligand (ARG,LEU,TYR,HIS,SER,LEU,PRO,ALA)	1qja	A	I217 W228
III		Peptide ligand (ARG,LEU,TYR,HIS,SER,LEU,PRO,ALA)	1qja	B	I217 W228
III		Peptide ligand (ALA,ARG,SER,HIS,SER,TYR,PRO,ALA)	1qjb	A	I217 W228
III		Peptide ligand (ARG,SER,HIS,SER,TYR,PRO,ALA)	1qjb	B	I217 W228
III		Peptide ligand (LYS,ASP,LYS,ALA,LYS,SER,CYS)	4bg6	A	I217 W228
III		Peptide ligand (LYS,ARG,GLN,TYR,LYS,SER,ILE,LEU)	4hkc	A	I217 W228
III		Peptide ligand (SER,ALA,SEP,LEU,SER,ASN,LEU,HIS)	4wrq	B	I217 W228
III		Peptide ligand (ARG,SER,LYS,SER,ALA)	2wh0	A	W228
III		Peptide ligand (ARG,SER,LYS,SER,ALA)	2wh0	C	W228
III		Peptide ligand (ALA,LEU,SER,PHE)	2wh0	D	W228
III		Peptide ligand (ARG,SER,THR,SER,THR,PRO,ASN,VAL,HIS)	3cu8	A	W228
III		Peptide ligand (ARG,SER,THR,SER,THR,PRO,ASN,VAL)	3cu8	B	W228
III		Peptide ligand (ARG,SER,THR,SER,THR,PRO,ASN,VAL,HIS)	3nkx	A	W228
III		Peptide ligand (ARG,SER,THR,SER,THR,PRO,ASN,VAL)	3nkx	B	W228
III		Peptide ligand (ARG,SER,THR,SER,THR,PRO,ASN,VAL)	4fj3	A	W228
III		Peptide ligand (LYS,ASP,LYS,ALA,LYS,SER,CYS)	4bg6	B	W228
III		Peptide ligand (GLN,ARG,SER,THR,SER,THR,PRO,ASN,VAL)	4ihl	A	W228

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Conservation information for LBS of YWHAZ

Multiple alignments for P63104 in multiple species

LBS	AA sequence	# species	Species
D213	EESYKDSTLIM	6	Homo sapiens, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
D213	EDSYKDSTLIM	3	Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster
D223	MQLLRDNLTLW	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
D96	RDICNDVLSLL	5	Homo sapiens, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
D96	NDICQDVLKLL	1	Caenorhabditis elegans
D96	RDICQDVLNLL	1	Caenorhabditis elegans
D96	REICYEVLGLL	1	Drosophila melanogaster
D96	REICNDVLNLL	1	Xenopus tropicalis
E131	YRYLAEVAAGD	5	Homo sapiens, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
E131	YRYLAEVASGD	2	Caenorhabditis elegans, Xenopus tropicalis
E131	YRYLAEVAS-E	1	Caenorhabditis elegans
E131	YRYLAEVATGD	1	Drosophila melanogaster
E14	KAKLAEQAERY	6	Homo sapiens, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
E14	RAKLAEQAERY	2	Caenorhabditis elegans, Caenorhabditis elegans
E14	KAKLAEQSERY	1	Drosophila melanogaster
E180	SVFYYEILNSP	6	Homo sapiens, Drosophila melanogaster, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
E180	SVFYYEILNTP	1	Caenorhabditis elegans
E180	SVFFYEILNAP	1	Caenorhabditis elegans
E180	SVFYYEILNCP	1	Xenopus tropicalis
E208	LDTLSEESYKD	6	Homo sapiens, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
E208	LDTLNEDSYKD	3	Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster
E209	DTLSEESYKDS	6	Homo sapiens, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
E209	DTLNEDSYKDS	3	Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster
E31	MKSVTEQGAEL	5	Homo sapiens, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
E31	MKKVTEQGQEL	1	Caenorhabditis elegans
E31	MKKVTELGAEL	1	Caenorhabditis elegans
E31	MKSVTETGVEL	1	Drosophila melanogaster
E31	MKRVTEEGGEL	1	Xenopus tropicalis
F117	AESKVFYLKMK	5	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Gallus gallus, Bos taurus
F117	PESKVFYLKMK	4	Drosophila melanogaster, Xenopus tropicalis, Mus musculus, Rattus norvegicus
G169	HPIRLGLALNF	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
I166	QPTHPIRLGLA	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
I217	KDSTLIMQLLR	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
K120	KVFYLKMKGDY	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
K212	SEESYKDSTLI	6	Homo sapiens, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
K212	NEDSYKDSTLI	3	Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster
K27	MAACMKSVTEQ	4	Homo sapiens, Bos taurus, Mus musculus, Rattus norvegicus
K27	MAAAMKKVTEQ	1	Caenorhabditis elegans
K27	MAASMKKVTEL	1	Caenorhabditis elegans
K27	MAQAMKSVTET	1	Drosophila melanogaster
K27	MAACMKRVTEE	1	Xenopus tropicalis
K27	MASCMKSVTEQ	1	Gallus gallus
K49	LSVAYKNVVGA	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
L172	RLGLALNFSVF	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
L216	YKDSTLIMQLL	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
L220	TLIMQLLRDNL	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
L227	RDNLTLWTSDT	7	Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
L227	RDNLTLWTSDV	1	Caenorhabditis elegans
L227	RDNLTLWTSDA	1	Caenorhabditis elegans
L43	NEERNLLSVAY	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
M121	VFYLKMKGDYY	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
N173	LGLALNFSVFY	8	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
N173	LGLALNFSVFF	1	Caenorhabditis elegans
N224	QLLRDNLTLWT	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
N42	SNEERNLLSVA	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
N50	SVAYKNVVGAR	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
P165	MQPTHPIRLGL	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
R127	KGDYYRYLAEV	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
R41	LSNEERNLLSV	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
R56	VVGARRSSWRV	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
R60	RRSSWRVVSSI	6	Homo sapiens, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
R60	RRSSWRVISSI	3	Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster
S210	TLSEESYKDST	6	Homo sapiens, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
S210	TLNEDSYKDST	3	Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster
S45	ERNLLSVAYKN	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
V176	ALNFSVFYYEI	8	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
V176	ALNFSVFFYEI	1	Caenorhabditis elegans
V46	RNLLSVAYKNV	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
W228	DNLTLWTSDTQ	7	Homo sapiens, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
W228	DNLTLWTSDVG	1	Caenorhabditis elegans
W228	DNLTLWTSDAA	1	Caenorhabditis elegans
Y128	GDYYRYLAEVA	9	Homo sapiens, Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
Y179	FSVFYYEILNS	6	Homo sapiens, Drosophila melanogaster, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
Y179	FSVFYYEILNT	1	Caenorhabditis elegans
Y179	FSVFFYEILNA	1	Caenorhabditis elegans
Y179	FSVFYYEILNC	1	Xenopus tropicalis
Y211	LSEESYKDSTL	6	Homo sapiens, Xenopus tropicalis, Gallus gallus, Bos taurus, Mus musculus, Rattus norvegicus
Y211	LNEDSYKDSTL	3	Caenorhabditis elegans, Caenorhabditis elegans, Drosophila melanogaster