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 CDK5

Gene summary

Basic gene Info.	Gene symbol	CDK5
	Gene name	cyclin-dependent kinase 5
	Synonyms	PSSALRE
	Cytomap	UCSC genome browser: 7q36
	Type of gene	protein-coding
	RefGenes	NM_001164410.1, NM_004935.3,
	Description	TPKII catalytic subunitcell division protein kinase 5cyclin-dependent-like kinase 5protein kinase CDK5 splicingserine/threonine-protein kinase PSSALREtau protein kinase II catalytic subunit
	Modification date	20141207
dbXrefs	MIM : 123831
	HGNC : HGNC
	Ensembl : ENSG00000164885
	HPRD : 00449
Protein	UniProt: Q00535 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_CDK5
	BioGPS: 1020
Pathway	NCI Pathway Interaction Database: CDK5
	KEGG: CDK5
	REACTOME: CDK5
	Pathway Commons: CDK5
Context	iHOP: CDK5
	ligand binding site mutation search in PubMed: CDK5
	UCL Cancer Institute: CDK5
Assigned class in mutLBSgeneDB	B: This gene belongs to targetable_mutLBSgenes.

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

GO ID	GO Term	PubMed ID
GO:0016310	phosphorylation	20357208
GO:0018105	peptidyl-serine phosphorylation	21145489
GO:0048709	oligodendrocyte differentiation	18042622
GO:1901215	negative regulation of neuron death	24548080

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Ligand binding site mutations for CDK5

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
A31	A31T	BLCA	1
G11	G11W	COAD	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 CDK5

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
A31	A31T	-0.92595543
G11	G11W	-0.64470398

(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 CDK5 from PDB

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Differential gene expression and gene-gene network for CDK5

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 CDK5 and the right PPI network was created from samples without mutations in the LBS of CDK5. 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 CDK5

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0031117	Peripheral Nervous System Diseases	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for CDK5

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
Experimental	DB02052	Indirubin-3'-Monoxime	Small molecule
Experimental	DB02116	Olomoucine	Small molecule
Experimental	DB02950	Hymenialdisine	Small molecule
Experimental	DB03428	SU9516	Small molecule
Experimental\|investigational	DB03496	Flavopiridol	Small molecule
Experimental	DB04014	Alsterpaullone	Small molecule
Experimental	DB07364	6-PHENYL[5H]PYRROLO[2,3-B]PYRAZINE	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of CDK5 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
ALH		ALOISINE A	1ung	A	A31
ALH		ALOISINE A	1ung	B	A31
IXM		INDIRUBIN-3'-MONOXIME	1unh	A	A31
IXM		INDIRUBIN-3'-MONOXIME	1unh	B	A31
3O0		4-AMINOTHIAZOLE	3o0g	B	A31
Z3R		4-(1,3-BENZOTHIAZOL-2-YL)THIOPHENE-2- SULFONAMIDE	4au8	A	A31
Z3R		4-(1,3-BENZOTHIAZOL-2-YL)THIOPHENE-2- SULFONAMIDE	4au8	B	A31
RRC		ROSCOVITINE	1unl	A	G11 A31

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Conservation information for LBS of CDK5

Multiple alignments for Q00535 in multiple species

LBS	AA sequence	# species	Species
A31	THEIVALKRVR	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
A31	TGVYVALKEVK	2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
A31	SGEIVALKRVR	1	Caenorhabditis elegans
A31	TMEIVALKRVR	1	Drosophila melanogaster
A31	TGEIVALKVIR	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
A31	TGLYVALKEVK	1	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056)
C83	LVFEFCDQDLK	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
C83	LVFEFMDNDLK	3	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056), Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
C83	LVFEYCDQDLK	1	Caenorhabditis elegans
C83	LVFEHCDQDLK	1	Drosophila melanogaster
C83	LVFEYMEKDLK	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D144	ELKLADFGLAR	6	Homo sapiens, Drosophila melanogaster, Rattus norvegicus, Bos taurus, Mus musculus, Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D144	QLKLGDFGLAR	3	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056), Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
D144	TLKLADFGLAR	1	Caenorhabditis elegans
D84	VFEFCDQDLKK	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
D84	VFEFMDNDLKK	3	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056), Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
D84	VFEYCDQDLKK	1	Caenorhabditis elegans
D84	VFEHCDQDLKK	1	Drosophila melanogaster
D84	VFEYMEKDLKK	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D86	EFCDQDLKKYF	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
D86	EFMDNDLKKFM	2	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
D86	EYCDQDLKKFF	1	Caenorhabditis elegans
D86	EHCDQDLKKYF	1	Drosophila melanogaster
D86	EYMEKDLKKYM	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D86	EFMDNDLKKYM	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
E12	LEKIGEGTYGT	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
E12	MEKIGEGTYGT	2	Caenorhabditis elegans, Drosophila melanogaster
E12	LEKLGEGTYAH	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
E12	LERLGNGTYAT	1	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056)
E12	LEKLGNGTYAT	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
E12	LEKVGNGTYAT	1	Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
E81	LTLVFEFCDQD	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
E81	LTLVFEFMDND	3	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056), Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
E81	LTLVFEYCDQD	1	Caenorhabditis elegans
E81	LTLVFEHCDQD	1	Drosophila melanogaster
E81	LMLVFEYMEKD	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
F80	KLTLVFEFCDQ	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
F80	KLTLVFEFMDN	3	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056), Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
F80	KLTLVFEYCDQ	1	Caenorhabditis elegans
F80	KLTLVFEHCDQ	1	Drosophila melanogaster
F80	KLMLVFEYMEK	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
F82	TLVFEFCDQDL	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
F82	TLVFEFMDNDL	3	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056), Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
F82	TLVFEYCDQDL	1	Caenorhabditis elegans
F82	TLVFEHCDQDL	1	Drosophila melanogaster
F82	MLVFEYMEKDL	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G11	KLEKIGEGTYG	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
G11	KMEKIGEGTYG	2	Caenorhabditis elegans, Drosophila melanogaster
G11	RLEKLGEGTYA	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G11	QLERLGNGTYA	1	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056)
G11	QLEKLGNGTYA	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G11	QLEKVGNGTYA	1	Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
I10	EKLEKIGEGTY	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
I10	DKMEKIGEGTY	2	Caenorhabditis elegans, Drosophila melanogaster
I10	QRLEKLGEGTY	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
I10	KQLERLGNGTY	1	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056)
I10	KQLEKLGNGTY	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
I10	KQLEKVGNGTY	1	Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
K89	DQDLKKYFDSC	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
K89	DQDLKKFFDSL	1	Caenorhabditis elegans
K89	DQDLKKYFDSL	1	Drosophila melanogaster
K89	EKDLKKYMDTY	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
K89	DNDLKKFMDSR	1	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056)
K89	DNDLKKYMDSR	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
K89	DNDLKKFMDNR	1	Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
L133	KPQNLLINRNG	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
L133	KPQNLLINTNG	1	Caenorhabditis elegans
L133	KPQNLLINKNG	1	Drosophila melanogaster
L133	KPQNLLINSRG	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
L133	KPQNLLINNKG	1	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056)
L133	KPQNLLINKRG	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L133	KPQNLLINNRG	1	Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
N131	DLKPQNLLINR	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
N131	DLKPQNLLINK	2	Drosophila melanogaster, Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
N131	DLKPQNLLINN	2	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
N131	DLKPQNLLINT	1	Caenorhabditis elegans
N131	DLKPQNLLINS	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Q130	RDLKPQNLLIN	10	Homo sapiens, Caenorhabditis elegans, Drosophila melanogaster, Rattus norvegicus, Bos taurus, Mus musculus, Schizosaccharomyces pombe (strain 972 / ATCC 24843), Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056), Saccharomyces cere
Q85	FEFCDQDLKKY	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
Q85	FEFMDNDLKKF	2	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
Q85	FEYCDQDLKKF	1	Caenorhabditis elegans
Q85	FEHCDQDLKKY	1	Drosophila melanogaster
Q85	FEYMEKDLKKY	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Q85	FEFMDNDLKKY	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V18	GTYGTVFKAKN	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
V18	GTYATVYKGLN	3	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056), Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)
V18	GTYGTVFKARN	1	Caenorhabditis elegans
V18	GTYGTVFKGRN	1	Drosophila melanogaster
V18	GTYAHVYKGQN	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V64	KHKNIVRLHDV	4	Homo sapiens, Rattus norvegicus, Bos taurus, Mus musculus
V64	KHENIVRLYDV	2	Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056), Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V64	KHRNVVRLYDV	1	Caenorhabditis elegans
V64	KHKNIVRLIDV	1	Drosophila melanogaster
V64	RHPNIMSLSDV	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V64	KHDNIVRLFDV	1	Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37)