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 PAK4
Gene summary
Basic gene Info.Gene symbolPAK4
Gene namep21 protein (Cdc42/Rac)-activated kinase 4
Synonyms-
CytomapUCSC genome browser: 19q13.2
Type of geneprotein-coding
RefGenesNM_001014831.2,
NM_001014832.1,NM_001014834.2,NM_001014835.1,NM_005884.3,
NM_001014833.1,
DescriptionPAK-4p21(CDKN1A)-activated kinase 4p21-activated kinase 4protein kinase related to S. cerevisiae STE20, effector for Cdc42Hsserine/threonine-protein kinase PAK 4
Modification date20141207
dbXrefs MIM : 605451
HGNC : HGNC
Ensembl : ENSG00000130669
HPRD : 05675
Vega : OTTHUMG00000182800
ProteinUniProt: O96013
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_PAK4
BioGPS: 10298
PathwayNCI Pathway Interaction Database: PAK4
KEGG: PAK4
REACTOME: PAK4
Pathway Commons: PAK4
ContextiHOP: PAK4
ligand binding site mutation search in PubMed: PAK4
UCL Cancer Institute: PAK4
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


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Ligand binding site mutations for PAK4
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
T332T332MKIRC1
E512D510NKIRC1
G401,E399G400ESKCM1
R489P491LSKCM1
R586L584FSKCM1
M482A483TSTAD1
R359,E361R360HSTAD1
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 PAK4
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
T332T332M0.21164899
R489P491L-1.1196502
R586L584F-0.79298261
M482A483T-0.58049348
E399G400E-0.48570423
G401G400E-0.48570423
E512D510N-0.47279229
E361R360H-0.25450801
R359R360H-0.25450801
(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 PAK4 from PDB

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Differential gene expression and gene-gene network for PAK4
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 PAK4 and the right PPI network was created from samples without mutations in the LBS of PAK4. 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 PAK4
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type

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

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Pharmacological information for PAK4
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

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PAK4 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
23DN2-[(1R,2S)-2-AMINOCYCLOHEXYL]-N6-(3-CHLOROPHENYL)-9-ETHYL-9H-PURINE-2,6-DIAMINE2cdzAE399 G401
N53N-[6,6-DIMETHYL-5-[(2S)-4-METHYL-2- (PHENYLMETHYL)PIPERAZIN-1-YL]CARBONYL-2,4- DIHYDROPYRROLO[3,4-C]PYRAZOL-3-YL]-3-PHENOXY- BENZAMIDE4appAE399 G401 R586
IIIPeptide ligand (ARG,ARG,ARG,ARG,SER,TRP)4jdiAE512
2OL1-({1-(2-AMINOPYRIMIDIN-4-YL)-2-[(2-METHOXYETHYL) AMINO]-1H-BENZIMIDAZOL-6-YL}ETHYNYL)CYCLOHEXANOL4o0vAG401
NJDN-(1H-INDAZOL-5-YL)-N'-[2-(1H-INDOL-3-YL)ETHYL]-6- METHOXY-1,3,5-TRIAZINE-2,4-DIAMINE4njdAG401
4T6N~2~-[(7-CHLORO-1H-BENZIMIDAZOL-6-YL)METHYL]-N~4~-(5- CYCLOPROPYL-1H-PYRAZOL-3-YL)PYRIMIDINE-2,4-DIAMINE5bmsAG401
IIIPeptide ligand (ARG,PRO,LYS,PRO,LEU,VAL,ASP)4fifAR359
IIIPeptide ligand (ARG,PRO,LYS,PRO,LEU,VAL,ASP)4fifBR359
IIIPeptide ligand (ARG,ARG,ARG,SER,TRP,TYR)4jdkAR359
IIIPeptide ligand (GLY,ARG,SER,ARG,GLN,PRO,LEU,VAL,LEU,GLY,ASP,ASN,CYS)4xbuAR359 E361 R489 E512
IIIPeptide ligand (ARG,ARG,ARG,ARG,ARG,SER,TRP,TYR,PHE,ASP,GLY)2q0nAR359 M482 E512
IIIPeptide ligand (ARG,ARG,ARG,THR,TRP,TYR,PHE,GLY,GLY)4jdhAR359 R489
ANPAMP-PNP4fieAT332
ANPAMP-PNP4fieBT332
ANPAMP-PNP4fifAT332
ANPAMP-PNP4fifBT332
ANPAMP-PNP4figAT332
ANPAMP-PNP4figBT332
ANPAMP-PNP4jdiAT332
ATPATP4xbrAT332
X4ZPF-03758302x4zAT332 E399 G401
IIIPeptide ligand (ARG,ARG,ARG,THR,TRP,TYR)4jdjAT332 R359


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Conservation information for LBS of PAK4
Multiple alignments for O96013 in multiple species
LBSAA sequence# speciesSpecies
A348SGKLVAVKKMD2Homo sapiens, Mus musculus
A348TGRQVAVKKMD1Drosophila melanogaster
A402FLEGGALTDIV2Homo sapiens, Mus musculus
A402YLEGGALTDIV1Drosophila melanogaster
D405GGALTDIVTHT2Homo sapiens, Mus musculus
D405GGALTDIVTHS1Drosophila melanogaster
D440GVIHRDIKSDS3Homo sapiens, Drosophila melanogaster, Mus musculus
D444RDIKSDSILLT2Homo sapiens, Mus musculus
D444RDIKSDSILLA1Drosophila melanogaster
D458RVKLSDFGFCA3Homo sapiens, Drosophila melanogaster, Mus musculus
E329FIKIGEGSTGI2Homo sapiens, Mus musculus
E329FNKIGEGSTGT1Drosophila melanogaster
E361KQQRRELLFNE3Homo sapiens, Drosophila melanogaster, Mus musculus
E366ELLFNEVVIMR3Homo sapiens, Drosophila melanogaster, Mus musculus
E396LWVVMEFLEGG2Homo sapiens, Mus musculus
E396LWVVMEYLEGG1Drosophila melanogaster
E399VMEFLEGGALT2Homo sapiens, Mus musculus
E399VMEYLEGGALT1Drosophila melanogaster
E507GIMVIEMVDGE2Homo sapiens, Drosophila melanogaster
E507GVMVIEMVDGE1Mus musculus
E512EMVDGEPPYFN2Homo sapiens, Mus musculus
E512EMVDGEPPFFN1Drosophila melanogaster
E518PPYFNEPPLKA2Homo sapiens, Mus musculus
E518PPFFNEPPLQA1Drosophila melanogaster
F397WVVMEFLEGGA2Homo sapiens, Mus musculus
F397WVVMEYLEGGA1Drosophila melanogaster
F459VKLSDFGFCAQ3Homo sapiens, Drosophila melanogaster, Mus musculus
F461LSDFGFCAQVS3Homo sapiens, Drosophila melanogaster, Mus musculus
F516GEPPYFNEPPL2Homo sapiens, Mus musculus
F516GEPPFFNEPPL1Drosophila melanogaster
G328NFIKIGEGSTG2Homo sapiens, Mus musculus
G328HFNKIGEGSTG1Drosophila melanogaster
G330IKIGEGSTGIV2Homo sapiens, Mus musculus
G330NKIGEGSTGTV1Drosophila melanogaster
G333GEGSTGIVCIA2Homo sapiens, Mus musculus
G333GEGSTGTVCIA1Drosophila melanogaster
G401EFLEGGALTDI2Homo sapiens, Mus musculus
G401EYLEGGALTDI1Drosophila melanogaster
G460KLSDFGFCAQV3Homo sapiens, Drosophila melanogaster, Mus musculus
G477RKSLVGTPYWM3Homo sapiens, Drosophila melanogaster, Mus musculus
I327DNFIKIGEGST2Homo sapiens, Mus musculus
I327DHFNKIGEGST1Drosophila melanogaster
I334EGSTGIVCIAT2Homo sapiens, Mus musculus
I334EGSTGTVCIAT1Drosophila melanogaster
K350KLVAVKKMDLR2Homo sapiens, Mus musculus
K350RQVAVKKMDLR1Drosophila melanogaster
K442IHRDIKSDSIL3Homo sapiens, Drosophila melanogaster, Mus musculus
L362QQRRELLFNEV3Homo sapiens, Drosophila melanogaster, Mus musculus
L398VVMEFLEGGAL2Homo sapiens, Mus musculus
L398VVMEYLEGGAL1Drosophila melanogaster
L447KSDSILLTHDG2Homo sapiens, Mus musculus
L447KSDSILLAADG1Drosophila melanogaster
L475PRRKSLVGTPY2Homo sapiens, Mus musculus
L475PKRKSLVGTPY1Drosophila melanogaster
L521FNEPPLKAMKM2Homo sapiens, Mus musculus
L521FNEPPLQAMRR1Drosophila melanogaster
M381ENVVEMYNSYL2Homo sapiens, Mus musculus
M381PNIVETYSSFL1Drosophila melanogaster
M395ELWVVMEFLEG2Homo sapiens, Mus musculus
M395ELWVVMEYLEG1Drosophila melanogaster
M482GTPYWMAPELI2Homo sapiens, Mus musculus
M482GTPYWMSPEVI1Drosophila melanogaster
M524PPLKAMKMIRD2Homo sapiens, Mus musculus
M524PPLQAMRRIRD1Drosophila melanogaster
N517EPPYFNEPPLK2Homo sapiens, Mus musculus
N517EPPFFNEPPLQ1Drosophila melanogaster
P479SLVGTPYWMAP2Homo sapiens, Mus musculus
P479SLVGTPYWMSP1Drosophila melanogaster
P519PYFNEPPLKAM2Homo sapiens, Mus musculus
P519PFFNEPPLQAM1Drosophila melanogaster
P520YFNEPPLKAMK2Homo sapiens, Mus musculus
P520FFNEPPLQAMR1Drosophila melanogaster
Q358DLRKQQRRELL3Homo sapiens, Drosophila melanogaster, Mus musculus
R359LRKQQRRELLF3Homo sapiens, Drosophila melanogaster, Mus musculus
R489PELISRLPYGP2Homo sapiens, Mus musculus
R489PEVISRLPYGP1Drosophila melanogaster
R586IVPLMRQNRTR1Homo sapiens
R586LVPLMRNARHH1Drosophila melanogaster
R586IVPLMRQHRTR1Mus musculus
S331KIGEGSTGIVC2Homo sapiens, Mus musculus
S331KIGEGSTGTVC1Drosophila melanogaster
S443HRDIKSDSILL3Homo sapiens, Drosophila melanogaster, Mus musculus
S457GRVKLSDFGFC3Homo sapiens, Drosophila melanogaster, Mus musculus
S474VPRRKSLVGTP2Homo sapiens, Mus musculus
S474LPKRKSLVGTP1Drosophila melanogaster
T332IGEGSTGIVCI2Homo sapiens, Mus musculus
T332IGEGSTGTVCI1Drosophila melanogaster
T404EGGALTDIVTH3Homo sapiens, Drosophila melanogaster, Mus musculus
T478KSLVGTPYWMA2Homo sapiens, Mus musculus
T478KSLVGTPYWMS1Drosophila melanogaster
V335GSTGIVCIATV2Homo sapiens, Mus musculus
V335GSTGTVCIATD1Drosophila melanogaster
V379QHENVVEMYNS1Homo sapiens
V379HHPNIVETYSS1Drosophila melanogaster
V379RHENVVEMYNS1Mus musculus
V393GDELWVVMEFL2Homo sapiens, Mus musculus
V393NDELWVVMEYL1Drosophila melanogaster
V476RRKSLVGTPYW2Homo sapiens, Mus musculus
V476KRKSLVGTPYW1Drosophila melanogaster
W481VGTPYWMAPEL2Homo sapiens, Mus musculus
W481VGTPYWMSPEV1Drosophila melanogaster
Y480LVGTPYWMAPE2Homo sapiens, Mus musculus
Y480LVGTPYWMSPE1Drosophila melanogaster


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