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 CCR5

Gene summary

Basic gene Info.	Gene symbol	CCR5
	Gene name	chemokine (C-C motif) receptor 5 (gene/pseudogene)
	Synonyms	CC-CKR-5\|CCCKR5\|CCR-5\|CD195\|CKR-5\|CKR5\|CMKBR5\|IDDM22
	Cytomap	UCSC genome browser: 3p21.31
	Type of gene	protein-coding
	RefGenes	NM_000579.3, NM_001100168.1,
	Description	C-C chemokine receptor type 5C-C motif chemokine receptor 5 A159AHIV-1 fusion coreceptorchemokine receptor CCR5chemr13
	Modification date	20141222
dbXrefs	MIM : 601373
	HGNC : HGNC
	HPRD : 03223
Protein	UniProt: P51681 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_CCR5
	BioGPS: 1234
Pathway	NCI Pathway Interaction Database: CCR5
	KEGG: CCR5
	REACTOME: CCR5
	Pathway Commons: CCR5
Context	iHOP: CCR5
	ligand binding site mutation search in PubMed: CCR5
	UCL Cancer Institute: CCR5
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 CCR5.	1. "Abrol R, Trzaskowski B, Goddard WA 3rd, Nesterov A, Olave I, Irons C. Ligand- and mutation-induced conformational selection in the CCR5 chemokine G protein-coupled receptor. Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13040-5. doi: 10.1073/pnas.1413216111. Epub 2014 Aug 25. PubMed PMID: 25157173; PubMed Central PMCID: PMC4246978. " 25157173

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

GO ID	GO Term	PubMed ID
GO:0006816	calcium ion transport	8699119
GO:0007267	cell-cell signaling	10679098
GO:0014808	release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	19523456
GO:0019722	calcium-mediated signaling	10679098
GO:0070098	chemokine-mediated signaling pathway	11278962

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Ligand binding site mutations for CCR5

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
I198	I198V	BLCA	1
W86	P84S	COAD	1
W86	P84T	COAD	1
W248	L246I	COAD	1
F109	F109Y	GBM	1
F112	S114C	GBM	1
T259	N258K	LUSC	1
F182	H181N	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 CCR5

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
I198	I198V	-1.1402483
W248	L246I	-1.0525548
F182	H181N	-0.96579339
W86	P84S	-0.91355024
F109	F109Y	-0.89885624
T259	N258K	-0.86054335
W86	P84T	-0.7389978
F112	S114C	-0.25075812

(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 CCR5 from PDB

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Differential gene expression and gene-gene network for CCR5

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 CCR5 and the right PPI network was created from samples without mutations in the LBS of CCR5. 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 CCR5

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0019196	Hepatitis C	23	Biomarker, GeneticVariation
umls:C0017661	Glomerulonephritis, IGA	3	Biomarker, GeneticVariation
umls:C0043124	West Nile Fever	2	Biomarker, GeneticVariation
umls:C0011615	Dermatitis, Atopic	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for CCR5

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	DB04835	Maraviroc	Small molecule
Investigational	DB05062	INCB9471	Small molecule
Investigational	DB05501	AMD-070	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of CCR5 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
MRV		4,4-DIFLUORO-N-[(1S)-3-{(3-EXO)-3-[3-METHYL-5-(PROPAN- 2-YL)-4H-1,2,4-TRIAZOL-4-YL]-8-AZABICYCLO[3.2.1]OCT-8- YL}-1-PHENYLPROPYL]CYCLOHEXANECARBOXAMIDE	4mbs	A	W86 F109 F112 F182 I198 W248 T259
MRV		4,4-DIFLUORO-N-[(1S)-3-{(3-EXO)-3-[3-METHYL-5-(PROPAN- 2-YL)-4H-1,2,4-TRIAZOL-4-YL]-8-AZABICYCLO[3.2.1]OCT-8- YL}-1-PHENYLPROPYL]CYCLOHEXANECARBOXAMIDE	4mbs	B	W86 F109 F112 F182 I198 W248 T259

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Conservation information for LBS of CCR5

Multiple alignments for P51681 in multiple species

LBS	AA sequence	# species	Species
E283	AMQVTETLGMT	5	Homo sapiens, Rattus norvegicus, Bos taurus, Pan troglodytes, Macaca mulatta
E283	AMQATETLGMT	1	Mus musculus
E283	AMQITETLGMT	1	Canis lupus familiaris
F109	LTGLYFIGFFS	3	Homo sapiens, Pan troglodytes, Macaca mulatta
F109	FTGLYHIGYFG	1	Mus musculus
F109	FTGIYHIGYFG	1	Rattus norvegicus
F109	LTGLYYIGFFT	1	Canis lupus familiaris
F109	FTGFYFIGYFG	1	Bos taurus
F112	LYFIGFFSGIF	3	Homo sapiens, Pan troglodytes, Macaca mulatta
F112	LYHIGYFGGIF	1	Mus musculus
F112	IYHIGYFGGIF	1	Rattus norvegicus
F112	LYYIGFFTGNF	1	Canis lupus familiaris
F112	FYFIGYFGGIF	1	Bos taurus
F182	TCSSHFPYSQY	3	Homo sapiens, Pan troglodytes, Macaca mulatta
F182	TCSPHFPHTQY	1	Mus musculus
F182	TCSPHFLHIQY	1	Rattus norvegicus
F182	TCSPHFPPSQH	1	Canis lupus familiaris
F182	TCSPHFPSSQY	1	Bos taurus
I198	FQTLKIVILGL	3	Homo sapiens, Bos taurus, Pan troglodytes
I198	FQTLKMVILSL	2	Mus musculus, Rattus norvegicus
I198	FQALKMSVLGL	1	Canis lupus familiaris
I198	FQTLKMVILGL	1	Macaca mulatta
K191	QYQFWKNFQTL	3	Homo sapiens, Pan troglodytes, Macaca mulatta
K191	QYHFWKSFQTL	1	Mus musculus
K191	QYRFWKHFQTL	1	Rattus norvegicus
K191	QHHFWKNFQAL	1	Canis lupus familiaris
K191	QYHFWKNFQTL	1	Bos taurus
L255	PYNIVLLLNTF	3	Homo sapiens, Pan troglodytes, Macaca mulatta
L255	PYNIVLLLTTF	2	Mus musculus, Rattus norvegicus
L255	PYNIVLLLSTF	2	Canis lupus familiaris, Bos taurus
M279	RLDQAMQVTET	5	Homo sapiens, Rattus norvegicus, Bos taurus, Pan troglodytes, Macaca mulatta
M279	RLDQAMQATET	1	Mus musculus
M279	RLDQAMQITET	1	Canis lupus familiaris
M287	TETLGMTHCCI	5	Homo sapiens, Canis lupus familiaris, Bos taurus, Pan troglodytes, Macaca mulatta
M287	TETLGMTHCCL	2	Mus musculus, Rattus norvegicus
Q194	FWKNFQTLKIV	3	Homo sapiens, Bos taurus, Pan troglodytes
Q194	FWKSFQTLKMV	1	Mus musculus
Q194	FWKHFQTLKMV	1	Rattus norvegicus
Q194	FWKNFQALKMS	1	Canis lupus familiaris
Q194	FWKNFQTLKMV	1	Macaca mulatta
T195	WKNFQTLKIVI	3	Homo sapiens, Bos taurus, Pan troglodytes
T195	WKSFQTLKMVI	1	Mus musculus
T195	WKHFQTLKMVI	1	Rattus norvegicus
T195	WKNFQALKMSV	1	Canis lupus familiaris
T195	WKNFQTLKMVI	1	Macaca mulatta
T259	VLLLNTFQEFF	3	Homo sapiens, Pan troglodytes, Macaca mulatta
T259	VLLLSTFQEFF	2	Canis lupus familiaris, Bos taurus
T259	VLLLTTFQEFF	1	Mus musculus
T259	VLLLTTFQEYF	1	Rattus norvegicus
T284	MQVTETLGMTH	5	Homo sapiens, Rattus norvegicus, Bos taurus, Pan troglodytes, Macaca mulatta
T284	MQATETLGMTH	1	Mus musculus
T284	MQITETLGMTH	1	Canis lupus familiaris
W248	VYFLFWAPYNI	5	Homo sapiens, Canis lupus familiaris, Bos taurus, Pan troglodytes, Macaca mulatta
W248	VYFLFWTPYNI	2	Mus musculus, Rattus norvegicus
W86	LTVPFWAHYAA	3	Homo sapiens, Pan troglodytes, Macaca mulatta
W86	LTLPFWAHYAA	2	Mus musculus, Rattus norvegicus
W86	LTIPFWAHYAA	1	Canis lupus familiaris
W86	ITIPFWAHYAA	1	Bos taurus
Y108	LLTGLYFIGFF	3	Homo sapiens, Pan troglodytes, Macaca mulatta
Y108	VFTGLYHIGYF	1	Mus musculus
Y108	LFTGIYHIGYF	1	Rattus norvegicus
Y108	LLTGLYYIGFF	1	Canis lupus familiaris
Y108	LFTGFYFIGYF	1	Bos taurus
Y251	LFWAPYNIVLL	5	Homo sapiens, Canis lupus familiaris, Bos taurus, Pan troglodytes, Macaca mulatta
Y251	LFWTPYNIVLL	2	Mus musculus, Rattus norvegicus
Y37	LLPPLYSLVFI	7	Homo sapiens, Mus musculus, Rattus norvegicus, Canis lupus familiaris, Bos taurus, Pan troglodytes, Macaca mulatta
Y89	PFWAHYAAAQW	3	Homo sapiens, Pan troglodytes, Macaca mulatta
Y89	PFWAHYAANEW	2	Mus musculus, Rattus norvegicus
Y89	PFWAHYAADQW	2	Canis lupus familiaris, Bos taurus