mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

Home

Download

 Statistics

Help

About Us
Bioinformatics and Systems Medicine Laboratory Bioinformatics and Systems Medicine Laboratory

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 PARK2
Gene summary
Basic gene Info.Gene symbolPARK2
Gene nameparkin RBR E3 ubiquitin protein ligase
SynonymsAR-JP|LPRS2|PDJ|PRKN
CytomapUCSC genome browser: 6q25.2-q27
Type of geneprotein-coding
RefGenesNM_004562.2,
NM_013987.2,NM_013988.2,
DescriptionE3 ubiquitin-protein ligase parkinParkinson disease (autosomal recessive, juvenile) 2, parkinparkinson juvenile disease protein 2parkinson protein 2, E3 ubiquitin protein ligase (parkin)
Modification date20141219
dbXrefs MIM : 602544
HGNC : HGNC
Ensembl : ENSG00000185345
HPRD : 03967
Vega : OTTHUMG00000015970
ProteinUniProt: O60260
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_PARK2
BioGPS: 5071
PathwayNCI Pathway Interaction Database: PARK2
KEGG: PARK2
REACTOME: PARK2
Pathway Commons: PARK2
ContextiHOP: PARK2
ligand binding site mutation search in PubMed: PARK2
UCL Cancer Institute: PARK2
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:0000209protein polyubiquitination12150907
GO:0001933negative regulation of protein phosphorylation17512523
GO:0006513protein monoubiquitination20889974
GO:0010506regulation of autophagy20889974
GO:0010821regulation of mitochondrion organization21113145
GO:0016567protein ubiquitination12628165
GO:0032232negative regulation of actin filament bundle assembly17512523
GO:0033132negative regulation of glucokinase activity24187134
GO:0042787protein ubiquitination involved in ubiquitin-dependent protein catabolic process17097639
GO:0043123positive regulation of I-kappaB kinase/NF-kappaB signaling17314283
GO:0043161proteasome-mediated ubiquitin-dependent protein catabolic process21376232
GO:0043388positive regulation of DNA binding17314283
GO:0043524negative regulation of neuron apoptotic process12628165
GO:0045944positive regulation of transcription from RNA polymerase II promoter23453807
GO:0046676negative regulation of insulin secretion24187134
GO:0051865protein autoubiquitination12628165
GO:0060548negative regulation of cell death12150907
GO:0070534protein K63-linked ubiquitination15728840
GO:0070936protein K48-linked ubiquitination21376232
GO:0090201negative regulation of release of cytochrome c from mitochondria19880420
GO:1902236negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway23453807
GO:1903265positive regulation of tumor necrosis factor-mediated signaling pathway23453807
GO:1903377negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway17314283


Top
Ligand binding site mutations for PARK2

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
C150V148LBLCA1
H373A371VCOAD1
C293P294SCOAD1
C293N295KCOAD1
C352G354RLUAD1
C212G213VLUAD1
L358G357CLUAD1
H257R256HLUAD1
C201H200PLUSC1
C212K211NLUSC1
C377S378GSKCM1
C337P335LSKCM1
H373A371TSKCM1
C293P294LSKCM1
C293P294SSTAD1
H257R256LSTAD1
C293G292DUCEC1
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.


Top
Protein structure related information for PARK2
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
C293P294L0.30262577
H257R256H-1.7832774
H373A371T-1.4725036
H373A371V-1.1965223
H257R256L-1.196297
C150V148L-1.0395789
C293G292D-0.94856202
C212K211N-0.75065297
C201H200P-0.71160943
C377S378G-0.61340962
C337P335L-0.53982543
C352G354R-0.52443426
C293P294S-0.33097583
C212G213V-0.22625629
C293N295K-0.17231913
L358G357C-0.16007735
(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 PARK2 from PDB

Top
Differential gene expression and gene-gene network for PARK2
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 PARK2 and the right PPI network was created from samples without mutations in the LBS of PARK2. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.


Top

Top
Phenotype information for PARK2
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0030567Parkinson Disease137AlteredExpression, Biomarker, GeneticVariation
umls:C0242422Parkinsonian Disorders78Biomarker, GeneticVariation, Therapeutic
umls:C1868675PARKINSON DISEASE 2, AUTOSOMAL RECESSIVE JUVENILE52Biomarker, GeneticVariation
umls:C0023343Leprosy10Biomarker, GeneticVariation
umls:C0004352Autistic Disorder4Biomarker
umls:C0919267Ovarian Neoplasms3AlteredExpression, Biomarker, GeneticVariation
umls:C0024121Lung Neoplasms2AlteredExpression, Biomarker
umls:C0017636Glioblastoma2Biomarker
umls:C3160718PARKINSON DISEASE, LATE-ONSET1GeneticVariation
umls:C0009375Colonic Neoplasms1Biomarker
umls:C0012644Disease Models, Animal1Biomarker
umls:C0023186Learning Disorders1Biomarker
umls:C0677050Manganese Poisoning1Therapeutic
umls:C0025261Memory Disorders1Biomarker
umls:C0027746Nerve Degeneration1Biomarker
umls:C0029927Ovarian Cysts1Biomarker
umls:C0030569Parkinson Disease, Secondary1Biomarker

Mutation level pathogenic information (ClinVar annotation)
Allele IDAA changeClinical significanceOriginPhenotype IDs
22090K211NPathogenicGermlineGeneReviews:NBK1478
MedGen:C1868675
OMIM:600116
Orphanet:ORPHA2828

Top
Pharmacological information for PARK2
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 statusDrugBank IDNameTypeDrug structure

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of PARK2 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
ZNZINC(2+)4bm9AC150 C212
ZNZINC(2+)4i1fAC150 C212
ZNZINC(2+)4i1hAC150 C212
ZNZINC(2+)5c9vAC150 C212
ZNZINC(2+)4bm9AC201
ZNZINC(2+)4i1fAC201
ZNZINC(2+)4i1hAC201
ZNZINC(2+)5c9vAC201
ZNZINC(2+)4bm9AC337 C352
ZNZINC(2+)4i1fAC337 C352
ZNZINC(2+)4i1hAC337 C352
ZNZINC(2+)5c9vAC337 C352
ZNZINC(2+)4bm9AH257 C293
ZNZINC(2+)4i1fAH257 C293
ZNZINC(2+)4i1hAH257 C293
ZNZINC(2+)5c9vAH257 C293
ZNZINC(2+)4bm9AH373 C377
ZNZINC(2+)4i1fAH373 C377
ZNZINC(2+)4i1hAH373 C377
ZNZINC(2+)5c9vAH373 C377


Top
Conservation information for LBS of PARK2
Multiple alignments for O60260 in multiple species
LBSAA sequence# speciesSpecies
C150SFYVYCKGPCQ1Homo sapiens
C150SFFIYCKGPCH1Mus musculus
C150SFFVYCKGPCH1Rattus norvegicus
C154YCKGPCHKVQP2Mus musculus, Rattus norvegicus
C154YCKGPCQRVQP1Homo sapiens
C166KLRVQCSTCRQ1Homo sapiens
C166KLRVQCGTCKQ1Mus musculus
C166KLRVQCGTCRQ1Rattus norvegicus
C169VQCSTCRQATL1Homo sapiens
C169VQCGTCKQATL1Mus musculus
C169VQCGTCRQATL1Rattus norvegicus
C196RMSGECQSPDC2Mus musculus, Rattus norvegicus
C196RMSGECQSPHC1Homo sapiens
C201CQSPDCPGTRA2Mus musculus, Rattus norvegicus
C201CQSPHCPGTSA1Homo sapiens
C212EFFFKCGAHPT3Homo sapiens, Mus musculus, Rattus norvegicus
C253VLVFQCNHRHV2Mus musculus, Rattus norvegicus
C253VLVFQCNSRHV1Homo sapiens
C289GYSLPCVAGCP3Homo sapiens, Mus musculus, Rattus norvegicus
C293PCVAGCPNSLI3Homo sapiens, Mus musculus, Rattus norvegicus
C332MGGVLCPRPGC3Homo sapiens, Mus musculus, Rattus norvegicus
C337CPRPGCGAGLL3Homo sapiens, Mus musculus, Rattus norvegicus
C352QRKVTCEGGNG2Homo sapiens, Mus musculus
C352QKKVTCEGGNG1Rattus norvegicus
C360GNGLGCGFVFC2Mus musculus, Rattus norvegicus
C360GNGLGCGFAFC1Homo sapiens
C365CGFVFCRDCKE2Mus musculus, Rattus norvegicus
C365CGFAFCRECKE1Homo sapiens
C368VFCRDCKEAYH2Mus musculus, Rattus norvegicus
C368AFCRECKEAYH1Homo sapiens
C377YHEGECSAVFE1Homo sapiens
C377YHEGDCDSLLE1Mus musculus
C377YHEGECDSMFE1Rattus norvegicus
H215FKCGAHPTSDK3Homo sapiens, Mus musculus, Rattus norvegicus
H257QCNHRHVICLD2Mus musculus, Rattus norvegicus
H257QCNSRHVICLD1Homo sapiens
H373CKEAYHEGECS1Homo sapiens
H373CKEAYHEGDCD1Mus musculus
H373CKEAYHEGECD1Rattus norvegicus
L358EGGNGLGCGFV2Mus musculus, Rattus norvegicus
L358EGGNGLGCGFA1Homo sapiens


Copyright © 2016-Present - The University of Texas Health Science Center at Houston
Site Policies | State of Texas