PMADS

Id:	acc3540
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:	H4
Disease Info:
Drug:	gefitinib
Drug Info:	"Gefitinib is an oral, selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used in the treatment of certain types of non - small cell lung cancer."
Effect:	modulate
Effect Info:	"Gefitinib induces glioma cell death by promoting the phosphorylation of IRE1, apoptosis signal-regulating kinase-1 (Ask1), and c-Jun N-terminal kinase (JNK)."
Note:
Score:	4.0
Pubmed(PMID):	33920356
Sentence Index:	33920356_7-8
Sentence:	"Three branches of ER stress, namely Activating Transcription Factor-6 (ATF6), Protein Kinase R (PKR)-Like ER Kinase (PERK), and Inositol-Requiring Enzyme 1 (IRE1), were activated by gefitinib, along with the elevation of intracellular free Ca2+, Reactive Oxygen Species (ROS), and NADPH Oxidase2/4 (NOX2/4). Specifically, elevated IRE1 phosphorylation, Tumor Necrosis Factor (TNF) Receptor-Associated Factor-2 (TRAF2) expression, Apoptosis Signal-Regulating Kinase-1 (Ask1) phosphorylation, c-Jun N-Terminal Kinase (JNK) phosphorylation, and Noxa expression appeared in gefitinib-treated glioma cells."

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