Target Information

Target General Information

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Target ID

T04499 (Former ID: TTDR00891)

Target Name

Kinase suppressor of Ras-1 (KSR1)

Synonyms

Kinase suppressor of Ras 1; KSR

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Gene Name

KSR1

Target Type

Literature-reported target

[1]

Function

Promotes phosphorylation of Raf family members and activation of downstream MAP kinases. Promotes activation of MAPK1 and/or MAPK3, both in response to EGF and to cAMP. Does not have kinase activity by itself. Scaffolding protein that is part of a multiprotein signaling complex.

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BioChemical Class

Kinase

UniProt ID

KSR1_HUMAN

Sequence

MDRAALRAAAMGEKKEGGGGGDAAAAEGGAGAAASRALQQCGQLQKLIDISIGSLRGLRT
KCAVSNDLTQQEIRTLEAKLVRYICKQRQCKLSVAPGERTPELNSYPRFSDWLYTFNVRP
EVVQEIPRDLTLDALLEMNEAKVKETLRRCGASGDECGRLQYALTCLRKVTGLGGEHKED
SSWSSLDARRESGSGPSTDTLSAASLPWPPGSSQLGRAGNSAQGPRSISVSALPASDSPT
PSFSEGLSDTCIPLHASGRLTPRALHSFITPPTTPQLRRHTKLKPPRTPPPPSRKVFQLL
PSFPTLTRSKSHESQLGNRIDDVSSMRFDLSHGSPQMVRRDIGLSVTHRFSTKSWLSQVC
HVCQKSMIFGVKCKHCRLKCHNKCTKEAPACRISFLPLTRLRRTESVPSDINNPVDRAAE
PHFGTLPKALTKKEHPPAMNHLDSSSNPSSTTSSTPSSPAPFPTSSNPSSATTPPNPSPG
QRDSRFNFPAAYFIHHRQQFIFPVPSAGHCWKCLLIAESLKENAFNISAFAHAAPLPEAA
DGTRLDDQPKADVLEAHEAEAEEPEAGKSEAEDDEDEVDDLPSSRRPWRGPISRKASQTS
VYLQEWDIPFEQVELGEPIGQGRWGRVHRGRWHGEVAIRLLEMDGHNQDHLKLFKKEVMN
YRQTRHENVVLFMGACMNPPHLAIITSFCKGRTLHSFVRDPKTSLDINKTRQIAQEIIKG
MGYLHAKGIVHKDLKSKNVFYDNGKVVITDFGLFGISGVVREGRRENQLKLSHDWLCYLA
PEIVREMTPGKDEDQLPFSKAADVYAFGTVWYELQARDWPLKNQAAEASIWQIGSGEGMK
RVLTSVSLGKEVSEILSACWAFDLQERPSFSLLMDMLEKLPKLNRRLSHPGHFWKSADIN
SSKVVPRFERFGLGVLESSNPKM

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Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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Ligand Name: Trametinib

Ligand Info

Structure Description

Crystal Structure of KSR1:MEK1 in complex with AMP-PNP, and allosteric MEK inhibitor Trametinib

PDB:7JUX

Method

X-ray diffraction

Resolution

3.34 Å

Mutation

[2]

PDB Sequence

SVYLQEWDIP

⁶⁰⁹

FEQVELGEPI

⁶¹⁹

GQGRWGRVHR

⁶²⁹

GRWHGEVAIR

⁶³⁹

LLEMDGHNQD

⁶⁴⁹

HLKLFKKEVM

⁶⁵⁹

NYRQTRHENV

⁶⁶⁹

VLFMGACMNP

⁶⁷⁹

PHLAIITSFC

⁶⁸⁹

KGRTLHSFVR

⁶⁹⁹

DPKTSLDINK

⁷⁰⁹

TRQIAQEIIK

⁷¹⁹

GMGYLHAKGI

⁷²⁹

VHKDLKSKNV

⁷³⁹

FYDNGKVVIT

⁷⁴⁹

DFGLFGISGV

⁷⁵⁹

VRENQLKLSH

⁷⁷³

DWLCYLAPEI

⁷⁸³

VREMTPGKDE

⁷⁹³

DQLPFSKAAD

⁸⁰³

VYAFGTVWYE

⁸¹³

LQARDWPLKN

⁸²³

QAAEASIWQI

⁸³³

GSGEGMKRVL

⁸⁴³

TSVSLGKEVS

⁸⁵³

EILSACWAFD

⁸⁶³

LQERPSFSLL

⁸⁷³

MDMLEKLP

Residue

Distance (Å)

ASN823

4.538

GLN824

4.245

Residue

Distance (Å)

ALA825

4.246

Ligand Name: AMP-PNP

Ligand Info

Structure Description

Crystal Structure of KSR1:MEK1 in complex with AMP-PNP

PDB:7JUW

Method

X-ray diffraction

Resolution

2.88 Å

Mutation

[2]

PDB Sequence

VYLQEWDIPF

⁶¹⁰

EQVELGEPIG

⁶²⁰

QGRWGRVHRG

⁶³⁰

RWHGEVAIRL

⁶⁴⁰

LEMDGHNQDH

⁶⁵⁰

LKLFKKEVMN

⁶⁶⁰

YRQTRHENVV

⁶⁷⁰

LFMGACMNPP

⁶⁸⁰

HLAIITSFCK

⁶⁹⁰

GRTLHSFVRD

⁷⁰⁰

PKTSLDINKT

⁷¹⁰

RQIAQEIIKG

⁷²⁰

MGYLHAKGIV

⁷³⁰

HKDLKSKNVF

⁷⁴⁰

YDNGKVVITD

⁷⁵⁰

FGLFGISGVV

⁷⁶⁰

RENQLKLSHD

⁷⁷⁴

WLCYLAPEIV

⁷⁸⁴

REMTPGKDED

⁷⁹⁴

QLPFSKAADV

⁸⁰⁴

YAFGTVWYEL

⁸¹⁴

QARDWPLKNQ

⁸²⁴

AAEASIWQIG

⁸³⁴

SGEGMKRVLT

⁸⁴⁴

SVSLGKEVSE

⁸⁵⁴

ILSACWAFDL

⁸⁶⁴

QERPSFSLLM

⁸⁷⁴

DMLEKLP

Residue

Distance (Å)

ILE619

3.162

GLY620

4.210

GLN621

3.842

GLY622

3.186

ARG623

2.769

TRP624

4.372

GLY625

4.718

VAL627

3.552

ALA637

3.813

ARG639

3.154

VAL670

4.159

THR686

3.812

Residue

Distance (Å)

SER687

3.120

PHE688

3.536

CYS689

3.099

THR693

4.389

ASP733

3.995

LYS735

3.776

LYS737

4.560

ASN738

3.834

PHE740

3.421

THR749

4.322

ASP750

3.353

PHE754

4.853

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Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Mixed lineage kinase 1 (MAP3K9)	PF00069 ; PF14604	27.119 (80/295)	3.03E-26
Apoptosis signal-regulating kinase 2 (MAP3K6)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	27.900 (89/319)	4.28E-18
SPS1/STE20-related protein kinase YSK4 (YSK4)	PF00069	24.436 (65/266)	8.49E-18
Fused homolog (STK36)	PF13646 ; PF00069	24.893 (58/233)	5.64E-17
Activin receptor type IB (ACVR1B)	PF01064 ; PF00069 ; PF08515 More >>	28.125 (63/224)	1.96E-15
Serine/threonine-protein kinase 33 (STK33)	PF00069	24.915 (73/293)	2.43E-15
Mitogen-activated protein kinase kinase kinase kinase 5 (MAP4K5)	PF00780 ; PF00069	25.822 (55/213)	2.49E-15
MEK kinase kinase 3 (MAP4K3)	PF00780 ; PF00069	26.818 (59/220)	5.16E-15
TRAF2 and NCK interacting kinase (TNIK)	PF00780 ; PF00069	24.820 (69/278)	5.45E-15
PAK-1 protein kinase (PAK1)	PF00786 ; PF00069	22.137 (58/262)	1.21E-14
Serine/threonine-protein kinase PAK 3 (PAK3)	PF00786 ; PF00069	22.137 (58/262)	1.73E-14
MEK kinase kinase 1 (MAP4K1)	PF00780 ; PF00069	24.885 (54/217)	1.96E-14
MEK kinase kinase 2 (MAP4K2)	PF00780 ; PF00069	25.688 (56/218)	2.97E-14
PAK-2 protein kinase (PAK2)	PF00786 ; PF00069	22.519 (59/262)	4.41E-14
Maternal embryonic leucine zipper kinase (MELK)	PF02149 ; PF00069	24.686 (59/239)	7.48E-14
Serine/threonine-protein kinase WNK1 (WNK1)	PF12202 ; PF00069	25.455 (70/275)	1.34E-13
Serine/threonine-protein kinase ULK2 (ULK2)	PF12063 ; PF00069	26.047 (56/215)	1.47E-13
TGF-beta receptor type I (TGFBR1)	PF01064 ; PF00069 ; PF08515 More >>	26.339 (59/224)	1.58E-13
Serine/threonine-protein kinase ULK1 (ULK1)	PF12063 ; PF00069	24.775 (55/222)	1.96E-13
Omphalocele kinase 1 (NUAK1)	PF00069	25.431 (59/232)	2.00E-13
Calcium/calmodulin-dependent protein kinase type 1B (PNCK)	PF00069	27.711 (46/166)	2.59E-13
Serine/threonine-protein kinase PAK 5 (PAK5)	PF00786 ; PF00069	24.413 (52/213)	2.68E-13
PAK-4 protein kinase (PAK4)	PF00786 ; PF00069	25.359 (53/209)	2.75E-13
Polo-like kinase 4 (PLK4)	PF00069 ; PF18190 ; PF18409 More >>	24.424 (53/217)	3.18E-13
Serine/threonine-protein kinase H1 (PSKH1)	PF00069	25.110 (57/227)	4.95E-13
Serine/threonine-protein kinase Nek5 (NEK5)	PF00069	21.708 (61/281)	5.35E-13
Misshapen-like kinase 1 (MINK1)	PF00780 ; PF00069	25.688 (56/218)	6.42E-13
Serine/threonine-protein kinase WNK4 (WNK4)	PF12202 ; PF00069	25.000 (65/260)	8.25E-13
Serine/threonine-protein kinase PAK 6 (PAK6)	PF00786 ; PF00069	24.138 (49/203)	8.26E-13
MEK kinase kinase 4 (MAP4K4)	PF00780 ; PF00069	27.473 (50/182)	8.90E-13
Serine/threonine-protein kinase Nek8 (NEK8)	PF00069 ; PF00415	23.048 (62/269)	9.76E-13
Bone morphogenetic protein receptor (BMPR2)	PF01064 ; PF00069	26.695 (63/236)	1.20E-12
Calcium/calmodulin-dependent protein kinase type 1D (CAMK1D)	PF00069	27.273 (45/165)	1.50E-12
Serine/threonine-protein kinase TAO2 (TAOK2)	PF00069	24.138 (63/261)	1.73E-12
Apoptosis signal-regulating kinase 1 (MAP3K5)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	24.380 (59/242)	2.22E-12
Oxidative stress responsive 1 (OXSR1)	PF12202 ; PF00069	22.337 (65/291)	2.38E-12
Cyclin-dependent kinase 5 (CDK5)	PF00069	25.490 (39/153)	2.43E-12
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	PF16579 ; PF00069	24.891 (57/229)	2.79E-12
Serine/threonine-protein kinase Nek4 (NEK4)	PF00069	23.311 (69/296)	2.82E-12
Serine/threonine-protein kinase Sgk2 (SGK2)	PF00069 ; PF00433	25.962 (54/208)	2.89E-12
Calcium/calmodulin-dependent protein kinase type 1G (CAMK1G)	PF00069	26.061 (43/165)	4.14E-12
Mitogen-activated protein kinase kinase kinase 15 (MAP3K15)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	22.761 (61/268)	5.04E-12
Checkpoint kinase-1 (CHK1)	PF00069	29.508 (54/183)	6.29E-12
WNK lysine-deficient protein kinase 3 (WNK3)	PF12202 ; PF00069	24.164 (65/269)	9.16E-12
MAPK/ERK kinase kinase 4 (MAP3K4)	PF19431 ; PF00069	24.060 (64/266)	1.49E-11
NUAK family SNF1-like kinase 2 (NUAK2)	PF00069	23.913 (55/230)	1.56E-11
Proto-oncogene serine/threonine-protein kinase mos (MOS)	PF00069	22.549 (69/306)	1.89E-11
Death-associated protein kinase 3 (DAPK3)	PF00069	24.583 (59/240)	2.53E-11
BMP-2-inducible protein kinase (BMP2K)	PF15282 ; PF00069	25.112 (56/223)	2.55E-11
MAPK/ERK kinase kinase 2 (MAP3K2)	PF00564 ; PF00069	23.932 (56/234)	2.64E-11
Serine/threonine-protein kinase Nek3 (NEK3)	PF00069	24.017 (55/229)	3.70E-11
Ste-20-related kinase (STK39)	PF12202 ; PF00069	24.215 (54/223)	4.36E-11
Leucine-rich repeat kinase 2 (LRRK2)	PF16095 ; PF12799 ; PF13855 ; PF00069 ; PF08477 More >>	25.225 (56/222)	4.74E-11
Serine/threonine-protein kinase 24 (STK24)	PF00069	25.743 (52/202)	5.26E-11
Serine/threonine-protein kinase Nek11 (NEK11)	PF00069	35.165 (32/91)	5.42E-11
Myosin light chain kinase 2 (MYLK2)	PF00069	23.776 (68/286)	5.47E-11
MST-1 protein kinase (STK4)	PF11629 ; PF00069	23.697 (50/211)	5.71E-11
MAPK/ERK kinase kinase 3 (MAP3K3)	PF00564 ; PF00069	23.308 (62/266)	5.83E-11
Serine/threonine-protein kinase NIM1 (NIM1K)	PF00069	23.611 (51/216)	8.61E-11
Tyrosine-protein kinase EIF2AK2 (p68)	PF00035 ; PF00069	23.967 (58/242)	1.12E-10
Putative 3-phosphoinositide-dependent protein kinase 2 (PDPK2P)	PF00069	26.291 (56/213)	1.12E-10
5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2)	PF16579 ; PF00069	24.017 (55/229)	1.61E-10
STE20-related serine/threonine-protein kinase (SLK)	PF00069 ; PF12474	24.057 (51/212)	1.71E-10
Testis-specific serine/threonine-protein kinase 4 (TSSK4)	PF00069	24.444 (55/225)	1.90E-10
Phosphorylase kinase testis gamma 2 (PHKG2)	PF00069	25.743 (52/202)	2.13E-10
Serine/threonine-protein kinase Sgk3 (SGK3)	PF00069 ; PF00433 ; PF00787 More >>	26.923 (56/208)	2.20E-10
Serine/threonine-protein kinase Sgk1 (SGK1)	PF00069 ; PF00433	25.481 (53/208)	2.26E-10
Serine/threonine-protein kinase MARK2 (MARK2)	PF02149 ; PF00069 ; PF00627 More >>	23.148 (50/216)	2.40E-10
Microtubule affinity regulating kinase 3 (MARK3)	PF02149 ; PF00069 ; PF00627 More >>	24.424 (53/217)	2.58E-10
TAO kinase 1 (TAOK1)	PF00069	23.194 (61/263)	2.58E-10
Nik-related protein kinase (NRK)	PF00780 ; PF00069	27.053 (56/207)	2.65E-10
Cyclin-dependent kinase 1 (CDK1)	PF00069	24.286 (51/210)	2.84E-10
Testis-specific serine/threonine-protein kinase 3 (TSSK3)	PF00069	22.264 (59/265)	2.91E-10
MAP/microtubule affinity-regulating kinase 4 (MARK4)	PF02149 ; PF00069 ; PF00627 More >>	23.188 (48/207)	2.98E-10
Serine/threonine-protein kinase 26 (STK26)	PF00069	24.752 (50/202)	3.10E-10
Receptor-interacting serine/threonine-protein kinase 3 (RIPK3)	PF00069 ; PF12721	24.179 (81/335)	3.25E-10
Aurora kinase C (AURKC)	PF00069	22.897 (49/214)	4.61E-10
Microtubule-associated serine/threonine-protein kinase 2 (MAST2)	PF08926 ; PF17820 ; PF00069 More >>	22.932 (61/266)	4.71E-10
Phosphoinositide dependent protein kinase-1 (PDPK1)	PF14593 ; PF00069	26.291 (56/213)	4.77E-10
Serine/threonine-protein kinase MAK (MAK)	PF00069	26.733 (54/202)	4.85E-10
Protein kinase C delta (PRKCD)	PF00130 ; PF00069 ; PF00433 More >>	27.751 (58/209)	5.24E-10
Salt-inducible kinase 2 (SIK2)	PF00069	25.000 (51/204)	5.88E-10
Stress-activated protein kinase 2b (p38 beta)	PF00069	22.831 (50/219)	6.63E-10
TAO kinase 3 (TAOK3)	PF00069	25.764 (59/229)	6.66E-10
Serine/threonine-protein kinase MARK1 (MARK1)	PF02149 ; PF00069 ; PF00627 More >>	23.148 (50/216)	6.83E-10
Cyclin-dependent kinase-like 2 (CDKL2)	PF00069	25.000 (50/200)	6.86E-10
SNF-related serine/threonine-protein kinase (SNRK)	PF00069	26.316 (55/209)	7.62E-10
Serine/threonine-protein kinase 3 (STK3)	PF11629 ; PF00069	23.451 (53/226)	8.06E-10
Aurora kinase A (AURKA)	PF00069	23.333 (56/240)	8.39E-10
Calcium/calmodulin-dependent protein kinase type 1 (CAMK1)	PF00069	27.879 (46/165)	8.91E-10
Serine/threonine-protein kinase NLK (NLK)	PF00069	26.009 (58/223)	9.31E-10
Ribosomal protein S6 kinase alpha-5 (RSK5)	PF00069 ; PF00433	27.126 (67/247)	1.15E-09
Polo-like kinase 1 (PLK1)	PF00069 ; PF00659	24.155 (50/207)	1.26E-09
Protein kinase C eta type (PRKCH)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	25.664 (58/226)	1.34E-09
MAP kinase p38 (MAPK12)	PF00069	25.121 (52/207)	1.58E-09
Cyclin-dependent kinase 3 (CDK3)	PF00069	23.923 (50/209)	1.66E-09
Serine/threonine-protein kinase ULK4 (ULK4)	PF00069	26.087 (60/230)	1.69E-09
Microtubule-associated serine/threonine-protein kinase 4 (MAST4)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	24.291 (60/247)	1.79E-09
Serine/threonine-protein kinase 35 (STK35)	PF00069	21.961 (56/255)	1.82E-09
Protein kinase G1 (PRKG1)	PF00027 ; PF16808 ; PF00069 More >>	26.761 (57/213)	1.85E-09
Serine/threonine-protein kinase ICK (CILK1)	PF00069	26.733 (54/202)	2.00E-09
Microtubule-associated serine/threonine-protein kinase 3 (MAST3)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	23.887 (59/247)	2.00E-09
Serine/threonine-protein kinase 10 (STK10)	PF00069 ; PF12474	22.749 (48/211)	2.07E-09
RAC-beta serine/threonine-protein kinase (AKT2)	PF00169 ; PF00069 ; PF00433 More >>	24.091 (53/220)	2.54E-09
Serine/threonine-protein kinase/endoribonuclease IRE2 (ERN2)	PF00069 ; PF06479	26.087 (54/207)	2.72E-09
STE20-related kinase adapter protein beta (STRADB)	PF00069	23.077 (51/221)	2.78E-09
RAC-gamma serine/threonine-protein kinase (AKT3)	PF00169 ; PF00069 ; PF00433 More >>	25.877 (59/228)	3.01E-09
CaM kinase-like vesicle-associated protein (CAMKV)	PF00069	24.859 (44/177)	3.14E-09
Ribosomal protein S6 kinase alpha-6 (RSK6)	PF00069 ; PF00433	25.000 (60/240)	3.38E-09
Ribosomal protein S6 kinase alpha-4 (RPS6KA4)	PF00069 ; PF00433	24.715 (65/263)	3.81E-09
Serine/threonine-protein kinase PLK3 (PLK3)	PF00069 ; PF00659	27.673 (44/159)	4.13E-09
SIK family kinase 3 (SIK3)	PF00069	22.368 (51/228)	4.19E-09
Serine/threonine-protein kinase H2 (PSKH2)	PF00069	26.519 (48/181)	4.27E-09
Activin receptor type IIA (ACVR2A)	PF01064 ; PF00069	24.920 (78/313)	5.93E-09
NIMA-related kinase 1 (NEK1)	PF00069	24.413 (52/213)	6.23E-09
Myosin light chain kinase 3 (MYLK3)	PF00069	24.510 (50/204)	6.87E-09
Hormonally up-regulated neu tumor-associated kinase (HUNK)	PF00069	25.000 (37/148)	6.91E-09
Serine/threonine-protein kinase SBK2 (SBK2)	PF00069	24.904 (65/261)	7.72E-09
Cyclin-dependent kinase 2 (CDK2)	PF00069	23.113 (49/212)	8.65E-09
Death-associated protein kinase 2 (DAPK2)	PF00069	23.673 (58/245)	9.03E-09
Serine/threonine-protein kinase WNK2 (WNK2)	PF12202 ; PF00069	25.210 (90/357)	9.03E-09
BR serine/threonine kinase 2 (BRSK2)	PF00069	22.467 (51/227)	9.71E-09
MAPK/ERK kinase kinase 1 (MAP3K1)	PF00069	20.896 (56/268)	9.73E-09
Ribosomal protein S6 kinase-related protein (RSKR)	PF00069	29.609 (53/179)	1.14E-08
Salt-inducible kinase 1 (SIK1)	PF00069	23.671 (49/207)	1.20E-08
Putative serine/threonine-protein kinase SIK1B (SIK1B)	PF00069	23.671 (49/207)	1.28E-08
Serine/threonine-protein kinase D3 (PRKD3)	PF00130 ; PF00169 ; PF00069 More >>	23.105 (64/277)	1.32E-08
Polo-like kinase 2 (PLK2)	PF00069 ; PF00659	25.610 (42/164)	1.43E-08
Microtubule-associated serine/threonine-protein kinase 1 (MAST1)	PF08926 ; PF17820 ; PF00069 More >>	22.727 (45/198)	1.53E-08
Serine/threonine-protein kinase 25 (STK25)	PF00069	23.500 (47/200)	1.54E-08
Myosin light chain kinase family member 4 (MYLK4)	PF00069	24.171 (51/211)	1.63E-08
Cyclin-dependent kinase 9 (CDK9)	PF00069	24.490 (36/147)	2.08E-08
Protein kinase C theta (PRKCQ)	PF00130 ; PF00069 ; PF00433 More >>	24.138 (56/232)	2.13E-08
Inhibitor of nuclear factor kappa-B kinase alpha (IKKA)	PF18397 ; PF12179 ; PF00069 More >>	25.455 (56/220)	2.58E-08
Rhodopsin kinase GRK7 (GRK7)	PF00069 ; PF00615	24.201 (53/219)	2.62E-08
Myosin light kinase (MYLK)	PF16620 ; PF00041 ; PF07679 ; PF00069 More >>	24.186 (52/215)	2.77E-08
Cyclin-dependent kinase 10 (CDK10)	PF00069	27.211 (40/147)	2.82E-08
Titin (TTN)		21.888 (51/233)	3.76E-08
Ribosomal protein S6 kinase beta-1 (S6K1)	PF00069 ; PF00433	25.703 (64/249)	5.21E-08
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform (PHKG1)	PF00069	26.136 (46/176)	5.30E-08
Serine/threonine-protein kinase Nek10 (NEK10)	PF00069	21.986 (62/282)	5.67E-08
BR serine/threonine kinase 1 (BRSK1)	PF00069	20.721 (46/222)	5.67E-08
Protein kinase D (PRKD1)	PF00130 ; PF00169 ; PF00069 More >>	23.746 (71/299)	6.06E-08
Ribosomal protein S6 kinase alpha-1 (RSK1)	PF00069 ; PF00433	25.405 (47/185)	6.52E-08
Ribosomal protein S6 kinase alpha-2 (RSK2)	PF00069 ; PF00433	24.490 (60/245)	6.57E-08
Protein kinase C gamma (PRKCG)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	33.043 (38/115)	6.76E-08
Ribosomal protein S6 kinase alpha-3 (RSK3)	PF00069 ; PF00433	24.324 (45/185)	8.45E-08
Extracellular signal-regulated kinase 5 (ERK5)	PF00069	22.093 (57/258)	8.55E-08
Protein kinase C epsilon (PRKCE)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	22.189 (75/338)	8.65E-08
NIMA-related kinase 2 (NEK2)	PF00069	22.884 (73/319)	8.69E-08
Myosin-IIIb (MYO3B)	PF00612 ; PF00063 ; PF00069 More >>	22.615 (64/283)	8.99E-08
Cyclin-dependent kinase 16 (CDK16)	PF12330 ; PF00069	19.913 (46/231)	9.87E-08
STE20-related kinase adapter protein alpha (STRADA)	PF00069	22.917 (55/240)	1.00E-07
Cyclin-dependent kinase 17 (CDK17)	PF12330 ; PF00069	20.792 (42/202)	1.01E-07
Protein kinase C iota (PRKCI)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	24.907 (67/269)	1.46E-07
Stress-activated protein kinase 2a (p38 alpha)	PF00069	23.394 (51/218)	1.55E-07
Serine/threonine-protein kinase D2 (PRKD2)	PF00130 ; PF00069	22.477 (49/218)	1.73E-07
Protein kinase C beta (PRKCB)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	32.143 (36/112)	1.76E-07
Serine/threonine-protein kinase STK11 (STK11)	PF00069	22.043 (41/186)	1.87E-07
Doublecortin-like kinase 2 (DCLK2)	PF03607 ; PF00069	24.051 (57/237)	2.19E-07
Cyclin-dependent kinase 13 (CDK13)	PF12330 ; PF00069	23.333 (49/210)	2.22E-07
TGF-beta-stimulated factor 1 (STK16)	PF00069	23.529 (60/255)	3.12E-07
ERK activator kinase 7 (MAP2K7)	PF00069	24.845 (40/161)	3.59E-07
Cyclin-dependent kinase-like 5 (CDKL5)	PF00069	22.886 (46/201)	3.64E-07
Cyclin-dependent kinase 7 (CDK7)	PF00069	23.333 (49/210)	3.69E-07
Doublecortin-like kinase 1 (DCLK1)	PF03607 ; PF00069	22.848 (69/302)	4.20E-07
Serine/threonine-protein kinase 32C (STK32C)	PF00069	20.601 (48/233)	4.52E-07
Eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4)	PF12745 ; PF00069 ; PF05773 ; PF13393 More >>	24.324 (36/148)	4.78E-07
Striated muscle preferentially expressed protein kinase (SPEG)	PF07679 ; PF00069 ; PF16650 More >>	23.669 (40/169)	5.39E-07
Citron Rho-interacting kinase (CIT)	PF00780 ; PF00169 ; PF00069 More >>	23.789 (54/227)	6.11E-07
Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMK2A)	PF08332 ; PF00069	24.576 (58/236)	6.47E-07
CaM-kinase IV kinase (CAMKK1)	PF00069	27.711 (46/166)	6.73E-07
NF-kappa-B-activating kinase (TBK1)	PF00069 ; PF18394 ; PF18396 More >>	24.664 (55/223)	6.86E-07
Aurora kinase B (AURKB)	PF00069	21.212 (49/231)	7.89E-07
Calmodulin-dependent kinase II (CAMKK2)	PF00069	26.190 (44/168)	9.54E-07
Serine/threonine-protein kinase greatwall (MASTL)	PF00069	21.569 (33/153)	9.60E-07
Unc-51 like kinase 3 (ULK3)	PF04212 ; PF00069	21.675 (44/203)	9.62E-07
Death-associated protein kinase 1 (DAPK1)	PF00023 ; PF12796 ; PF13637 ; PF00531 ; PF00069 More >>	23.438 (45/192)	1.06E-06
Serine/threonine-protein kinase 17B (STK17B)	PF00069	29.496 (41/139)	1.06E-06
Serine/threonine-protein kinase MRCK gamma (CDC42BPG)	PF00130 ; PF00780 ; PF08826 ; PF00069 More >>	24.506 (62/253)	1.15E-06
Protein kinase C alpha (PRKCA)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	31.250 (35/112)	1.16E-06
Cyclin-dependent kinase 15 (CDK15)	PF00069	21.986 (31/141)	1.17E-06
Calcium/calmodulin-dependent protein kinase type IV (CAMK4)	PF00069	23.445 (49/209)	1.25E-06
Testis-specific serine/threonine-protein kinase 6 (TSSK6)	PF00069	25.339 (56/221)	1.33E-06
Protein kinase C zeta (PRKCZ)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	22.222 (60/270)	1.53E-06
cAMP-dependent protein kinase catalytic subunit PRKX (PRKX)	PF00069	25.481 (53/208)	1.58E-06
Homeodomain-interacting protein kinase 4 (HIPK4)	PF00069	24.554 (55/224)	1.69E-06
Dual-specificity tyrosine-phosphorylation regulated kinase 1B (DYRK1B)	PF00069	24.312 (53/218)	2.13E-06
Cyclin-dependent kinase 12 (CDK12)	PF00069	23.333 (49/210)	2.35E-06
Cyclin-dependent kinase 18 (CDK18)	PF00069	20.779 (48/231)	2.45E-06
MAP kinase signal-integrating kinase 2 (MKNK2)	PF00069	22.275 (47/211)	2.85E-06
Cyclin-dependent kinase-like 3 (CDKL3)	PF00069	21.724 (63/290)	3.07E-06
Putative serine/threonine-protein kinase PRKY (PRKY)	PF00069	29.496 (41/139)	3.26E-06
Serine/threonine-protein kinase SBK1 (SBK1)	PF00069	20.000 (48/240)	3.75E-06
Ribosomal protein S6 kinase beta-2 (RPS6KB2)	PF00069 ; PF00433	23.320 (59/253)	4.02E-06
Obscurin (OBSCN)	PF00041 ; PF07679 ; PF00612 ; PF00069 ; PF00621 More >>	21.622 (40/185)	4.14E-06
Calcium/calmodulin-dependent protein kinase type II subunit beta (CAMK2B)	PF08332 ; PF00069	22.034 (52/236)	4.44E-06
Cyclin-dependent kinase 14 (CDK14)	PF00069	23.611 (34/144)	4.45E-06
Serine/threonine-protein kinase Nek9 (NEK9)	PF00069 ; PF00415	18.552 (41/221)	4.61E-06
Leucine-rich repeat serine/threonine-protein kinase 1 (LRRK1)	PF12796 ; PF16095 ; PF00069 ; PF08477 More >>	24.242 (56/231)	4.77E-06
Activin receptor type IIB (ACVR2B)	PF01064 ; PF00069	24.051 (57/237)	6.26E-06
Serine/threonine-protein kinase cot (COT)	PF00069	22.699 (37/163)	7.52E-06
Myosin-IIIa (MYO3A)	PF00612 ; PF00063 ; PF00069 More >>	23.345 (67/287)	8.48E-06
cAMP-dependent protein kinase catalytic subunit alpha (PRKACA)	PF00069	25.417 (61/240)	8.68E-06
Protein kinase G2 (PRKG2)	PF00027 ; PF00069	24.312 (53/218)	8.70E-06
Cyclin-dependent kinase 4 (CDK4)	PF00069	24.684 (39/158)	9.21E-06
Serine/threonine-protein kinase MRCK beta (CDC42BPB)	PF00130 ; PF00780 ; PF08826 ; PF15796 ; PF00069 More >>	21.642 (58/268)	9.29E-06
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	PF18397 ; PF12179 ; PF00069 More >>	23.611 (51/216)	1.01E-05
Serine/threonine-protein kinase tousled-like 2 (TLK2)	PF00069	23.005 (49/213)	1.03E-05
Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D)	PF08332 ; PF00069	23.305 (55/236)	1.04E-05
ERK activator kinase 5 (MAP2K5)	PF00564 ; PF00069	22.283 (41/184)	1.29E-05
Stress-activated protein kinase JNK3 (JNK3)	PF00069	23.232 (46/198)	1.45E-05
Eukaryotic translation initiation factor 2-alpha kinase 1 (EIF2AK1)	PF00069	45.833 (22/48)	1.63E-05
Cytoplasmic DRAK1 (STK17A)	PF00069	24.603 (31/126)	1.65E-05
cAMP-dependent protein kinase catalytic subunit gamma (PRKACG)	PF00069	24.000 (66/275)	1.98E-05
Wee1-like protein kinase 2 (WEE2)	PF00069	25.455 (42/165)	2.14E-05
Serine/threonine-protein kinase NIK (MAP3K14)	PF00069	23.295 (41/176)	2.17E-05
cAMP-dependent protein kinase catalytic subunit beta (PRKACB)	PF00069	25.641 (60/234)	2.18E-05
Mitogen-activated protein kinase 15 (MAPK15)	PF00069	24.277 (42/173)	2.98E-05
Dual specificity protein kinase TTK (MPS1)	PF00069	18.974 (37/195)	2.99E-05
Mitogen-activated protein kinase 13 (MAPK13)	PF00069	22.768 (51/224)	3.30E-05
Stress-activated protein kinase JNK1 (JNK1)	PF00069	25.000 (37/148)	3.32E-05
Cyclin-dependent kinase 11B (CDK11B)	PF00069	23.039 (47/204)	3.33E-05
Cyclin-dependent kinase 6 (CDK6)	PF00069	20.266 (61/301)	3.62E-05
Cyclin-dependent kinase 20 (CDK20)	PF00069	26.794 (56/209)	3.93E-05
Dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A)	PF00069	24.242 (56/231)	4.04E-05
Cyclin-dependent kinase-like 4 (CDKL4)	PF00069	20.705 (47/227)	4.24E-05
Anti-mullerian hormone II receptor (AMHR2)	PF00069	20.354 (46/226)	4.42E-05
CDC42 binding protein kinase alpha (DMPK-like alpha)	PF00130 ; PF00780 ; PF08826 ; PF15796 ; PF00069 ; PF00433 More >>	20.248 (49/242)	4.80E-05
Homeodomain-interacting protein kinase 1 (HIPK1)	PF00069	24.686 (59/239)	5.10E-05
MAPK-activated protein kinase 2 (MAPKAPK2)	PF00069	29.078 (41/141)	5.60E-05
Calcium/calmodulin-dependent protein kinase type II subunit gamma (CAMK2G)	PF08332 ; PF00069	23.077 (54/234)	6.15E-05
Extracellular signal-regulated kinase 1 (ERK1)	PF00069	23.529 (48/204)	6.66E-05
Cyclin-dependent kinase 11A (CDK11A)	PF00069	22.967 (48/209)	7.14E-05
Homeodomain interacting protein kinase 2 (HIPK2)	PF00069	23.849 (57/239)	7.33E-05
NIMA-related kinase 7 (NEK7)	PF00069	18.978 (52/274)	7.36E-05
Cyclin-G-associated kinase (GAK)	PF00069 ; PF10409	20.884 (52/249)	1.06E-04
Cyclin-dependent kinase 19 (CDK19)	PF00069	22.018 (48/218)	1.15E-04
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	PF00069	23.144 (53/229)	1.20E-04
Membrane-associated kinase (PKMYT1)	PF00069	26.619 (37/139)	1.22E-04
Homeodomain-interacting protein kinase 3 (HIPK3)	PF00069	27.564 (43/156)	1.30E-04
Glycogen synthase kinase-3 alpha (GSK-3A)	PF00069	22.897 (49/214)	1.66E-04
Rhodopsin kinase GRK1 (GRK1)	PF00069 ; PF00615	33.333 (36/108)	1.91E-04
Glycogen synthase kinase-3 beta (GSK-3B)	PF00069	23.832 (51/214)	2.30E-04
Cyclin-dependent kinase-like 1 (CDKL1)	PF00069	21.429 (51/238)	2.41E-04
Serine/threonine-protein kinase 32A (STK32A)	PF00069	20.548 (45/219)	2.84E-04
Stress-activated protein kinase JNK2 (JNK2)	PF00069	24.516 (38/155)	2.84E-04
PAS domain-containing serine/threonine-protein kinase (PASK)	PF13426 ; PF00069	23.129 (34/147)	2.96E-04
G protein-coupled receptor kinase 6 (GRK6)	PF00069 ; PF00615	30.357 (34/112)	3.26E-04
MAPK-activated protein kinase 3 (MAPKAPK3)	PF00069	25.194 (65/258)	4.19E-04
Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE)	PF00069 ; PF18394 ; PF18396 More >>	21.739 (45/207)	4.46E-04
Mitogen-activated protein kinase 4 (MAPK4)	PF00069	26.852 (29/108)	4.58E-04
Mitogen-activated protein kinase 6 (MAPK6)	PF00069	26.549 (30/113)	5.03E-04
PRKR-like endoplasmic reticulum kinase (PERK)	PF00069	21.918 (32/146)	5.31E-04
IL-1 receptor-associated kinase 1 (IRAK1)	PF00531 ; PF00069	23.529 (52/221)	5.75E-04
Beta-adrenergic receptor kinase 1 (ADRBK1)	PF00169 ; PF00069 ; PF00615 More >>	24.490 (36/147)	6.36E-04
Serine/threonine-protein kinase Chk2 (RAD53)	PF00498 ; PF00069	28.030 (37/132)	7.18E-04
Interleukin-1 receptor-associated kinase-like 2 (IRAK2)	PF00531 ; PF00069	24.306 (35/144)	7.83E-04
Endoplasmic reticulum to nucleus signaling 1 (ERN1)	PF00069 ; PF06479	26.061 (43/165)	7.86E-04
Wee1-like protein kinase (WEE1)	PF00069	21.469 (38/177)	8.33E-04
Beta-adrenergic receptor kinase 2 (ADRBK2)	PF00169 ; PF00069 ; PF00615 More >>	24.490 (36/147)	1.00E-03
NIMA-related kinase 6 (NEK6)	PF00069	20.115 (35/174)	1.00E-03
NDR2 protein kinase (STK38L)	PF00069 ; PF00433	26.168 (28/107)	1.00E-03
Peripheral plasma membrane protein CASK (CASK)	PF00625 ; PF02828 ; PF00595 ; PF00069 ; PF00018 More >>	23.111 (52/225)	2.00E-03
Casein kinase I epsilon (CSNK1E)	PF00069	20.629 (59/286)	2.00E-03
NDR1 protein kinase (STK38)	PF00069 ; PF00433	26.415 (28/106)	3.00E-03
Tribbles homolog 1 (TRIB1)	PF00069	24.855 (43/173)	3.00E-03
Cyclin-dependent kinase 8 (CDK8)	PF00069	25.455 (28/110)	4.00E-03
MAPK/MAK/MRK overlapping kinase (MOK)	PF00069	22.424 (37/165)	4.00E-03
Myotonin-protein kinase (DMPK)	PF08826 ; PF00069	24.752 (50/202)	4.00E-03
Yet another novel kinase 2 (STK32B)	PF00069	30.556 (33/108)	4.00E-03
Testis-specific serine kinase 2 (TSSK2)	PF00069	20.000 (44/220)	4.00E-03
Serine/threonine-protein kinase Kist (UHMK1)	PF00069 ; PF00076	20.468 (35/171)	5.00E-03
CDC7-related kinase (CDC7)	PF00069	32.787 (20/61)	5.00E-03
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Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
Ras signaling pathway	hsa04014	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
C-type lectin receptor signaling pathway	hsa04625	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Degree	12	Degree centrality	1.29E-03	Betweenness centrality	2.98E-04
Closeness centrality	2.35E-01	Radiality	1.41E+01	Clustering coefficient	3.33E-01
Neighborhood connectivity	4.13E+01	Topological coefficient	1.33E-01	Eccentricity	11
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Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins Info

References

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REF 1

Deficiency of kinase suppressor of Ras1 prevents oncogenic ras signaling in mice. Cancer Res. 2003 Jul 15;63(14):4232-8.

REF 2

Structural basis for the action of the drug trametinib at KSR-bound MEK. Nature. 2020 Dec;588(7838):509-514.

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