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 ROCK1
Gene summary
Basic gene Info.Gene symbolROCK1
Gene nameRho-associated, coiled-coil containing protein kinase 1
SynonymsP160ROCK|ROCK-I
CytomapUCSC genome browser: 18q11.1
Type of geneprotein-coding
RefGenesNM_005406.2,
DescriptionRho kinasep160 ROCK-1p160-ROCKrenal carcinoma antigen NY-REN-35rho-associated protein kinase 1rho-associated, coiled-coil-containing protein kinase 1rho-associated, coiled-coil-containing protein kinase I
Modification date20141222
dbXrefs MIM : 601702
HGNC : HGNC
HPRD : 03414
ProteinUniProt: Q13464
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_ROCK1
BioGPS: 6093
PathwayNCI Pathway Interaction Database: ROCK1
KEGG: ROCK1
REACTOME: ROCK1
Pathway Commons: ROCK1
ContextiHOP: ROCK1
ligand binding site mutation search in PubMed: ROCK1
UCL Cancer Institute: ROCK1
Assigned class in mutLBSgeneDBB: This gene belongs to targetable_mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID
GO:0007159leukocyte cell-cell adhesion12082081
GO:0022614membrane to membrane docking12082081
GO:0050900leukocyte migration12082081
GO:0050901leukocyte tethering or rolling12082081


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Ligand binding site mutations for ROCK1
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
LBSAAchange of nsSNVCancer type# samples
F120S118FHNSC1
L107K109EHNSC1
M128M128ILUAD1
D216D216YLUAD1
V137Q138HLUAD1
M128A129TUCEC1
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 ROCK1
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.
LBSAAchange of nsSNVRelative stability change
D216D216Y-1.108127
M128A129T-0.90803151
M128M128I-0.84458674
L107K109E-0.55135778
V137Q138H-0.45452297
F120S118F-0.39764474
(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 ROCK1 from PDB

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Differential gene expression and gene-gene network for ROCK1
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 ROCK1 and the right PPI network was created from samples without mutations in the LBS of ROCK1. 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 ROCK1
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0086468Prenatal Injuries1Biomarker

Mutation level pathogenic information (ClinVar annotation)
Allele IDAA changeClinical significanceOriginPhenotype IDs

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Pharmacological information for ROCK1
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 statusDrugBank IDNameTypeDrug structure
ExperimentalDB04707HYDROXYFASUDILSmall molecule
ExperimentalDB07876(S)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLINE)SULFONYL]-HOMOPIPERAZINESmall molecule
ExperimentalDB081625-(1,4-DIAZEPAN-1-SULFONYL)ISOQUINOLINESmall molecule
ExperimentalDB08756(R)-TRANS-4-(1-AMINOETHYL)-N-(4-PYRIDYL) CYCLOHEXANECARBOXAMIDESmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of ROCK1 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
M77FASUDIL2esmAD216
M77FASUDIL2esmBD216
Y27(R)-TRANS-4-(1-AMINOETHYL)-N-(4-PYRIDYL)CYCLOHEXANECARBOXAMIDE2etrAD216
Y27(R)-TRANS-4-(1-AMINOETHYL)-N-(4-PYRIDYL)CYCLOHEXANECARBOXAMIDE2etrBD216
07Q1-[(1R)-1-(3-METHOXYPHENYL)ETHYL]-3-(4-PYRIDIN-4-YL-1,3-THIAZOL-2-YL)UREA3tv7AD216
07R1-[(3-HYDROXYPHENYL)METHYL]-3-(4-PYRIDIN-4-YL-1,3- THIAZOL-2-YL)UREA3twjCD216
0HD1-(1H-INDAZOL-5-YL)-3-(2-PHENYLETHYL)UREA3v8sBD216
0HD1-(1H-INDAZOL-5-YL)-3-(2-PHENYLETHYL)UREA3v8sDD216
4KH2-FLUORO-N-[4-(PYRIDIN-4-YL)-1,3-THIAZOL-2-YL]BENZAMIDE4yvcAD216
4KH2-FLUORO-N-[4-(PYRIDIN-4-YL)-1,3-THIAZOL-2-YL]BENZAMIDE4yvcBD216
4TWN-[4-(2-FLUOROPYRIDIN-4-YL)THIOPHEN-2-YL]-2-{3- [(METHYLSULFONYL)AMINO]PHENYL}ACETAMIDE5bmlBF120 V137 D216
07Q1-[(1R)-1-(3-METHOXYPHENYL)ETHYL]-3-(4-PYRIDIN-4-YL-1,3-THIAZOL-2-YL)UREA3tv7BL107 D216
07Q1-[(1R)-1-(3-METHOXYPHENYL)ETHYL]-3-(4-PYRIDIN-4-YL-1,3-THIAZOL-2-YL)UREA3tv7CL107 D216
07Q1-[(1R)-1-(3-METHOXYPHENYL)ETHYL]-3-(4-PYRIDIN-4-YL-1,3-THIAZOL-2-YL)UREA3tv7DL107 D216
0HD1-(1H-INDAZOL-5-YL)-3-(2-PHENYLETHYL)UREA3v8sAL107 D216
0HD1-(1H-INDAZOL-5-YL)-3-(2-PHENYLETHYL)UREA3v8sCL107 D216
4KK2-(3-METHOXYPHENYL)-N-[4-(PYRIDIN-4-YL)-1,3-THIAZOL-2- YL]ACETAMIDE4yveAL107 D216
4KK2-(3-METHOXYPHENYL)-N-[4-(PYRIDIN-4-YL)-1,3-THIAZOL-2- YL]ACETAMIDE4yveBL107 D216
4TWN-[4-(2-FLUOROPYRIDIN-4-YL)THIOPHEN-2-YL]-2-{3- [(METHYLSULFONYL)AMINO]PHENYL}ACETAMIDE5bmlAL107 F120 D216
07R1-[(3-HYDROXYPHENYL)METHYL]-3-(4-PYRIDIN-4-YL-1,3- THIAZOL-2-YL)UREA3twjAM128 V137 D216
HFSHYDROXYFASUDIL2etkAV137 D216
HFSHYDROXYFASUDIL2etkBV137 D216
ANPAMP-PNP2v55AV137 D216
ANPAMP-PNP2v55CV137 D216
3NCCIS-4-AMINO-N-(7-CHLORO-1-OXO-1,2-DIHYDROISOQUINOLIN-6-YL)CYCLOHEXANECARBOXAMIDE3nczAV137 D216
3NCCIS-4-AMINO-N-(7-CHLORO-1-OXO-1,2-DIHYDROISOQUINOLIN-6-YL)CYCLOHEXANECARBOXAMIDE3nczBV137 D216
3NCCIS-4-AMINO-N-(7-CHLORO-1-OXO-1,2-DIHYDROISOQUINOLIN-6-YL)CYCLOHEXANECARBOXAMIDE3nczCV137 D216
3NCCIS-4-AMINO-N-(7-CHLORO-1-OXO-1,2-DIHYDROISOQUINOLIN-6-YL)CYCLOHEXANECARBOXAMIDE3nczDV137 D216
3ND(3S,4R)-N-(7-CHLORO-1-OXO-1,4-DIHYDROISOQUINOLIN-6-YL)-4-(4-CHLOROPHENYL)PYRROLIDINE-3-CARBOXAMIDE3ndmBV137 D216
3ND(3S,4R)-N-(7-CHLORO-1-OXO-1,4-DIHYDROISOQUINOLIN-6-YL)-4-(4-CHLOROPHENYL)PYRROLIDINE-3-CARBOXAMIDE3ndmCV137 D216
3ND(3S,4R)-N-(7-CHLORO-1-OXO-1,4-DIHYDROISOQUINOLIN-6-YL)-4-(4-CHLOROPHENYL)PYRROLIDINE-3-CARBOXAMIDE3ndmDV137 D216
3J7N~1~-[2-(1H-INDAZOL-5-YL)PYRIDO[3,4-D]PYRIMIDIN-4-YL]- 2-METHYLPROPANE-1,2-DIAMINE4w7pAV137 D216
3J7N~1~-[2-(1H-INDAZOL-5-YL)PYRIDO[3,4-D]PYRIMIDIN-4-YL]- 2-METHYLPROPANE-1,2-DIAMINE4w7pBV137 D216
3J7N~1~-[2-(1H-INDAZOL-5-YL)PYRIDO[3,4-D]PYRIMIDIN-4-YL]- 2-METHYLPROPANE-1,2-DIAMINE4w7pCV137 D216
3J7N~1~-[2-(1H-INDAZOL-5-YL)PYRIDO[3,4-D]PYRIMIDIN-4-YL]- 2-METHYLPROPANE-1,2-DIAMINE4w7pDV137 D216


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Conservation information for LBS of ROCK1
Multiple alignments for Q13464 in multiple species
LBSAA sequence# speciesSpecies
A103TRKVYAMKLLS3Homo sapiens, Mus musculus, Rattus norvegicus
A215GHLKLADFGTC3Homo sapiens, Mus musculus, Rattus norvegicus
A86VIGRGAFGEVQ3Homo sapiens, Mus musculus, Rattus norvegicus
D160YMPGGDLVNLM3Homo sapiens, Mus musculus, Rattus norvegicus
D202RDVKPDNMLLD3Homo sapiens, Mus musculus, Rattus norvegicus
D216HLKLADFGTCM3Homo sapiens, Mus musculus, Rattus norvegicus
E154LYMVMEYMPGG3Homo sapiens, Mus musculus, Rattus norvegicus
E89RGAFGEVQLVR3Homo sapiens, Mus musculus, Rattus norvegicus
F120RSDSAFFWEER3Homo sapiens, Mus musculus, Rattus norvegicus
F368IDTSNFDDLEE3Homo sapiens, Mus musculus, Rattus norvegicus
F87IGRGAFGEVQL3Homo sapiens, Mus musculus, Rattus norvegicus
G83VVKVIGRGAFG3Homo sapiens, Mus musculus, Rattus norvegicus
G85KVIGRGAFGEV3Homo sapiens, Mus musculus, Rattus norvegicus
G88GRGAFGEVQLV3Homo sapiens, Mus musculus, Rattus norvegicus
I82EVVKVIGRGAF3Homo sapiens, Mus musculus, Rattus norvegicus
K105KVYAMKLLSKF3Homo sapiens, Mus musculus, Rattus norvegicus
K200IHRDVKPDNML3Homo sapiens, Mus musculus, Rattus norvegicus
L106VYAMKLLSKFE3Homo sapiens, Mus musculus, Rattus norvegicus
L107YAMKLLSKFEM3Homo sapiens, Mus musculus, Rattus norvegicus
L205KPDNMLLDKSG3Homo sapiens, Mus musculus, Rattus norvegicus
M128EERDIMAFANS3Homo sapiens, Mus musculus, Rattus norvegicus
M153YLYMVMEYMPG3Homo sapiens, Mus musculus, Rattus norvegicus
M156MVMEYMPGGDL3Homo sapiens, Mus musculus, Rattus norvegicus
N203DVKPDNMLLDK3Homo sapiens, Mus musculus, Rattus norvegicus
R84VKVIGRGAFGE3Homo sapiens, Mus musculus, Rattus norvegicus
V137NSPWVVQLFYA3Homo sapiens, Mus musculus, Rattus norvegicus
V90GAFGEVQLVRH3Homo sapiens, Mus musculus, Rattus norvegicus
Y155YMVMEYMPGGD3Homo sapiens, Mus musculus, Rattus norvegicus


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