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 SIAH1

Gene summary

Basic gene Info.	Gene symbol	SIAH1
	Gene name	siah E3 ubiquitin protein ligase 1
	Synonyms	SIAH1A
	Cytomap	UCSC genome browser: 16q12.1
	Type of gene	protein-coding
	RefGenes	NM_001006610.1, NM_003031.3,
	Description	E3 ubiquitin-protein ligase SIAH1seven in absentia homolog 1siah-1a
	Modification date	20141207
dbXrefs	MIM : 602212
	HGNC : HGNC
	Ensembl : ENSG00000196470
	HPRD : 03736
	Vega : OTTHUMG00000175417
Protein	UniProt: Q8IUQ4 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_SIAH1
	BioGPS: 6477
Pathway	NCI Pathway Interaction Database: SIAH1
	KEGG: SIAH1
	REACTOME: SIAH1
	Pathway Commons: SIAH1
Context	iHOP: SIAH1
	ligand binding site mutation search in PubMed: SIAH1
	UCL Cancer Institute: SIAH1
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
GO:0006511	ubiquitin-dependent protein catabolic process	23001567
GO:0030163	protein catabolic process	11389840
GO:0043065	positive regulation of apoptotic process	21185211

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Ligand binding site mutations for SIAH1

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
L158	L158I	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 SIAH1

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
L158	L158I	-0.99511067

(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 SIAH1 from PDB

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Differential gene expression and gene-gene network for SIAH1

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 SIAH1 and the right PPI network was created from samples without mutations in the LBS of SIAH1. 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 SIAH1

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 SIAH1

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 SIAH1 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
III		Peptide ligand (LYS,PRO,ALA,ALA,VAL,VAL,ALA,PRO,ILE)	2a25	A	L158
III		Peptide ligand (LEU,ARG,PRO,VAL,ALA,MET,VAL,ARG,PRO,THR,VAL)	4i7b	A	L158
III		Peptide ligand (LEU,ARG,PRO,VAL,ALA,MET,VAL,ARG,PRO,THR,VAL)	4i7b	C	L158
III		Peptide ligand (LYS,LEU,ARG,PRO,VAL,ALA,MET,VAL,ARG,PRO,TRP,VAL,ARG)	4i7c	A	L158
III		Peptide ligand (LYS,LEU,ARG,PRO,VAL,ALA,MET,VAL,ARG,PRO,TRP,VAL,ARG)	4i7c	C	L158
III		Peptide ligand (ACE,LYS,LEU,ARG,PRO,VAL,ALA,MET,VAL,ARG,PRO,LYS,VAL,ARG)	4i7d	A	L158
III		Peptide ligand (ACE,LYS,LEU,ARG,PRO,VAL,ALA,MET,VAL,ARG,PRO,LYS,VAL,ARG)	4i7d	C	L158
III		Peptide ligand (PRO,LYS,PRO,THR,CYS,MET,VAL,PRO,PRO,MET,PRO)	4x3g	A	L158
III		Peptide ligand (LYS,PRO,THR,CYS,MET,VAL,PRO,PRO,MET,PRO)	4x3g	B	L158

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Conservation information for LBS of SIAH1

Multiple alignments for Q8IUQ4 in multiple species

LBS	AA sequence	# species	Species
A167	DIVFLATDINL	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
A175	INLPGAVDWVM	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
C130	PYSCPCPGASC	4	Homo sapiens, Danio rerio, Mus musculus, Rattus norvegicus
C130	PYCCPCPGASC	1	Caenorhabditis elegans
C130	PYLCPCPGASC	1	Drosophila melanogaster
D162	TLQGEDIVFLA	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
D169	VFLATDINLPG	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
D177	LPGAVDWVMMQ	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
E161	TTLQGEDIVFL	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
E194	FMLVLEKQEKY	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
E226	FAYRLELNGHR	4	Homo sapiens, Danio rerio, Mus musculus, Rattus norvegicus
E226	FVYRLELSASR	1	Caenorhabditis elegans
E226	FVYRLELNGNR	1	Drosophila melanogaster
F165	GEDIVFLATDI	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
I155	HQHKSITTLQG	4	Homo sapiens, Danio rerio, Mus musculus, Rattus norvegicus
I155	KIHKSITTLQG	1	Caenorhabditis elegans
I155	MSHKSITTLQG	1	Drosophila melanogaster
I163	LQGEDIVFLAT	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
L158	KSITTLQGEDI	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
L166	EDIVFLATDIN	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
L172	ATDINLPGAVD	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
M180	AVDWVMMQSCF	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
N276	GNLGINVTISM	4	Homo sapiens, Danio rerio, Mus musculus, Rattus norvegicus
N276	GNLGINVTISR	1	Caenorhabditis elegans
N276	GNLGINVTISL	1	Drosophila melanogaster
P131	YSCPCPGASCK	4	Homo sapiens, Danio rerio, Mus musculus, Rattus norvegicus
P131	YCCPCPGASCK	1	Caenorhabditis elegans
P131	YLCPCPGASCK	1	Drosophila melanogaster
Q159	SITTLQGEDIV	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
R224	ENFAYRLELNG	4	Homo sapiens, Danio rerio, Mus musculus, Rattus norvegicus
R224	DNFVYRLELSA	1	Caenorhabditis elegans
R224	ENFVYRLELNG	1	Drosophila melanogaster
T156	QHKSITTLQGE	4	Homo sapiens, Danio rerio, Mus musculus, Rattus norvegicus
T156	IHKSITTLQGE	1	Caenorhabditis elegans
T156	SHKSITTLQGE	1	Drosophila melanogaster
T157	HKSITTLQGED	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
T168	IVFLATDINLP	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
T278	LGINVTISMC-	4	Homo sapiens, Danio rerio, Mus musculus, Rattus norvegicus
T278	LGINVTISRID	1	Caenorhabditis elegans
T278	LGINVTISLV-	1	Drosophila melanogaster
V164	QGEDIVFLATD	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
V176	NLPGAVDWVMM	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
V179	GAVDWVMMQSC	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus
V277	NLGINVTISMC	4	Homo sapiens, Danio rerio, Mus musculus, Rattus norvegicus
V277	NLGINVTISRI	1	Caenorhabditis elegans
V277	NLGINVTISLV	1	Drosophila melanogaster
W178	PGAVDWVMMQS	6	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, Rattus norvegicus