PMADS

Id:	acc1529
Group:	2sens
Protein:	ASK-1
Gene Symbol:	MAP3K5
Protein Id:	Q99683
Protein Name:	M3K5_HUMAN
PTM:	phosphorylation
Site:	Thr845
Site Sequence:	TETFTGTLQYMAPEIIDKGPR
Disease Category:	Cancer
Disease:	Glioma
Disease Subtype:
Disease Cellline:	U87
Disease Info:
Drug:	temozolomide(TMZ)
Drug Info:	"Temozolomide (TMZ) is an alkylating chemotherapeutic agent primarily used in the treatment of glioblastoma multiforme, functioning by inhibiting DNA synthesis in cancer cells through methylation of guanine residues, and is often administered in combination with radiotherapy."
Effect:	increase
Effect Info:	ASK-1 dephosphorylation induces TMZ resistance
Note:	site unclear
Score:	5.0
Pubmed(PMID):	36951032
Sentence Index:	36951032_7-8
Sentence:	"ASK-1 phosphorylation, but not protein expression, was higher in U87 and U251 cells than in TMZ-resistant glioma cells exposed to TMZ. The addition of the ASK-1 inhibitor selonsertib (SEL) resulted in the dephosphorylation of ASK-1 in U87 and U251 cells after the TMZ challenge."

Sequence & Structure:

MSTEADEGITFSVPPFAPSGFCTIPEGGICRRGGAAAVGEGEEHQLPPPPPGSFWNVESAAAPGIGCPAATSSSSATRGRGSSVGGGSRRTTVAYVINEASQGQLVVAESEALQSLREACETVGATLETLHFGKLDFGETTVLDRFYNADIAVVEMSDAFRQPSLFYHLGVRESFSMANNIILYCDTNSDSLQSLKEIICQKNTMCTGNYTFVPYMITPHNKVYCCDSSFMKGLTELMQPNFELLLGPICLPLVDRFIQLLKVAQASSSQYFRESILNDIRKARNLYTGKELAAELARIRQRVDNIEVLTADIVINLLLSYRDIQDYDSIVKLVETLEKLPTFDLASHHHVKFHYAFALNRRNLPGDRAKALDIMIPMVQSEGQVASDMYCLVGRIYKDMFLDSNFTDTESRDHGASWFKKAFESEPTLQSGINYAVLLLAAGHQFESSFELRKVGVKLSSLLGKKGNLEKLQSYWEVGFFLGASVLANDHMRVIQASEKLFKLKTPAWYLKSIVETILIYKHFVKLTTEQPVAKQELVDFWMDFLVEATKTDVTVVRFPVLILEPTKIYQPSYLSINNEVEEKTISIWHVLPDDKKGIHEWNFSASSVRGVSISKFEERCCFLYVLHNSDDFQIYFCTELHCKKFFEMVNTITEEKGRSTEEGDCESDLLEYDYEYDENGDRVVLGKGTYGIVYAGRDLSNQVRIAIKEIPERDSRYSQPLHEEIALHKHLKHKNIVQYLGSFSENGFIKIFMEQVPGGSLSALLRSKWGPLKDNEQTIGFYTKQILEGLKYLHDNQIVHRDIKGDNVLINTYSGVLKISDFGTSKRLAGINPCTETFTGTLQYMAPEIIDKGPRGYGKAADIWSLGCTIIEMATGKPPFYELGEPQAAMFKVGMFKVHPEIPESMSAEAKAFILKCFEPDPDKRACANDLLVDEFLKVSSKKKKTQPKLSALSAGSNEYLRSISLPVPVLVEDTSSSSEYGSVSPDTELKVDPFSFKTRAKSCGERDVKGIRTLFLGIPDENFEDHSAPPSPEEKDSGFFMLRKDSERRATLHRILTEDQDKIVRNLMESLAQGAEEPKLKWEHITTLIASLREFVRSTDRKIIATTLSKLKLELDFDSHGISQVQVVLFGFQDAVNKVLRNHNIKPHWMFALDSIIRKAVQTAITILVPELRPHFSLASESDTADQEDLDVEDDHEEQPSNQTVRRPQAVIEDAVATSGVSTLSSTVSHDSQSAHRSLNVQLGRMKIETNRLLEELVRKEKELQALLHRAIEEKDQEIKHLKLKSQPIEIPELPVFHLNSSGTNTEDSELTDWLRVNGADEDTISRFLAEDYTLLDVLYYVTRDDLKCLRLRGGMLCTLWKAIIDFRNKQT

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
MAP3K5	SELONSERTIB	Mitogen-activated protein kinase kinase kinase 5 inhibitor	3	Terminated	non-alcoholic steatohepatitis	ClinicalTrials ClinicalTrials
MAP3K5	SELONSERTIB	Mitogen-activated protein kinase kinase kinase 5 inhibitor	2	Completed	diabetic nephropathy	ClinicalTrials ClinicalTrials
MAP3K5	SELONSERTIB	Mitogen-activated protein kinase kinase kinase 5 inhibitor	2	Completed	pulmonary arterial hypertension	ClinicalTrials
MAP3K5	SELONSERTIB	Mitogen-activated protein kinase kinase kinase 5 inhibitor	2	Completed	non-alcoholic fatty liver disease	ClinicalTrials ClinicalTrials
MAP3K5	SELONSERTIB	Mitogen-activated protein kinase kinase kinase 5 inhibitor	2	Completed	non-alcoholic steatohepatitis	ClinicalTrials ClinicalTrials
MAP3K5	SELONSERTIB	Mitogen-activated protein kinase kinase kinase 5 inhibitor	2	Completed	Hepatitis, Alcoholic	ClinicalTrials
MAP3K5	SELONSERTIB	Mitogen-activated protein kinase kinase kinase 5 inhibitor	1	Completed	diabetic nephropathy	ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

Protein Tractability:

source: Open Targets

Small molecule

Antibody

PROTAC

Other modalities

Approved Drug

Advanced Clinical

Phase 1 Clinical

Structure with Ligand

High-Quality Ligand

High-Quality Pocket

Med-Quality Pocket

Druggable Family

Approved Drug

Advanced Clinical

Phase 1 Clinical

UniProt loc high conf

GO CC high conf

UniProt loc med conf

UniProt SigP or TMHMM

GO CC med conf

Human Protein Atlas loc

Approved Drug

Advanced Clinical

Phase 1 Clinical

Literature

UniProt Ubiquitination

Database Ubiquitination

Half-life Data

Small Molecule Binder

Approved Drug

Advanced Clinical

Phase 1 Clinical

PTM Intensity:

source: CPTAC

No intensity data of this site,
show all other sites!

MAP3K5-Ser1004
Cancer	Intensity
BRCA	-0.449
COAD
HGSC
ccRCC
GBM	-0.271
HNSC
LUAD	-0.492
LUSC	-0.566
non_ccRCC
PDAC	1.778
UCEC

MAP3K5-Ser1029
Cancer	Intensity
BRCA	-1.51
COAD	0.551
HGSC	2.262
ccRCC	-0.289
GBM	-0.01
HNSC	-0.474
LUAD	-0.081
LUSC	-0.894
non_ccRCC	0.015
PDAC	0.43
UCEC

MAP3K5-Ser1033
Cancer	Intensity
BRCA	-0.734
COAD	-0.572
HGSC	2.632
ccRCC	-0.254
GBM	-0.494
HNSC	-0.618
LUAD	-0.352
LUSC	-0.339
non_ccRCC	0.43
PDAC	0.302
UCEC

MAP3K5-Ser1072
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.707
GBM
HNSC
LUAD
LUSC
non_ccRCC	-0.707
PDAC
UCEC

MAP3K5-Ser1240
Cancer	Intensity
BRCA
COAD
HGSC	1.923
ccRCC	-0.384
GBM	-1.659
HNSC	-0.05
LUAD	-0.216
LUSC	-0.178
non_ccRCC	0.566
PDAC	-0.003
UCEC

MAP3K5-Ser82
Cancer	Intensity
BRCA
COAD	-1.76
HGSC	1.532
ccRCC	0.335
GBM	-0.159
HNSC
LUAD	-0.381
LUSC	0.517
non_ccRCC
PDAC	-0.084
UCEC

MAP3K5-Ser83
Cancer	Intensity
BRCA
COAD
HGSC	1.935
ccRCC	-0.109
GBM	-0.583
HNSC
LUAD	-0.798
LUSC	0.066
non_ccRCC
PDAC	-0.511
UCEC

MAP3K5-Ser952
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.722
GBM	1.082
HNSC	-0.895
LUAD	0.026
LUSC	0.55
non_ccRCC	-1.485
PDAC
UCEC

MAP3K5-Ser955
Cancer	Intensity
BRCA
COAD
HGSC	-1.148
ccRCC
GBM	0.684
HNSC
LUAD
LUSC	0.464
non_ccRCC
PDAC
UCEC

MAP3K5-Ser958
Cancer	Intensity
BRCA
COAD	-0.462
HGSC	-0.855
ccRCC	0.182
GBM	1.658
HNSC
LUAD	-0.522
LUSC
non_ccRCC
PDAC
UCEC

MAP3K5-Ser977
Cancer	Intensity
BRCA
COAD	0.104
HGSC	-1.72
ccRCC	0.381
GBM
HNSC	0.866
LUAD	0.368
LUSC
non_ccRCC
PDAC
UCEC

MAP3K5-Ser978
Cancer	Intensity
BRCA
COAD	-0.509
HGSC	-1.528
ccRCC	0.281
GBM	1.514
HNSC	0.178
LUAD	0.064
LUSC
non_ccRCC
PDAC
UCEC

MAP3K5-Ser979
Cancer	Intensity
BRCA
COAD	-1.468
HGSC
ccRCC	-0.052
GBM	1.344
HNSC	0.189
LUAD	-0.014
LUSC
non_ccRCC
PDAC
UCEC

MAP3K5-Ser980
Cancer	Intensity
BRCA
COAD	-1.463
HGSC
ccRCC	0.175
GBM
HNSC	0.659
LUAD	0.629
LUSC
non_ccRCC
PDAC
UCEC

MAP3K5-Ser984
Cancer	Intensity
BRCA
COAD	0.122
HGSC	-1.983
ccRCC	0.2
GBM	0.791
HNSC	0.502
LUAD	0.368
LUSC
non_ccRCC
PDAC
UCEC

MAP3K5-Ser997
Cancer	Intensity
BRCA
COAD
HGSC	2.345
ccRCC	-0.798
GBM	-0.139
HNSC	-0.168
LUAD	-0.676
LUSC	-0.597
non_ccRCC	0.032
PDAC	0
UCEC

MAP3K5-Thr1059
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.829
GBM	0.83
HNSC
LUAD	-1.53
LUSC	-0.435
non_ccRCC	0.307
PDAC
UCEC

MAP3K5-Thr976
Cancer	Intensity
BRCA
COAD
HGSC	-1.489
ccRCC	0.375
GBM
HNSC	0.66
LUAD	0.455
LUSC
non_ccRCC
PDAC
UCEC

MAP3K5-Tyr961
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

MAP3K5-Tyr982
Cancer	Intensity
BRCA
COAD	-1.692
HGSC
ccRCC	0.116
GBM	0.647
HNSC	0.835
LUAD	0.094
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
S	967	D	Alzheimer's disease	Phosphorylation	24985705
S	1033	D	Hepatitis	Phosphorylation	35438255
S	83	U	Hepatitis	Phosphorylation	30205811
S	83	U	Non-alcoholic fatty liver disease	Phosphorylation	30205811

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb