Target Information

Target General Information

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Target ID

T58266 (Former ID: TTDI03179)

Target Name

Ephrin type-A receptor 8 (EPHA8)

Synonyms

hEK3; Tyrosine-protein kinase receptor EEK; KIAA1459; EPH-like kinase 3; EPH- and ELK-related kinase; EK3; EEK

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Gene Name

EPHA8

Target Type

Literature-reported target

[1]

Function

The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system plays also a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth. Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.

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BioChemical Class

Kinase

UniProt ID

EPHA8_HUMAN

EC Number

EC 2.7.10.1

Sequence

MAPARGRLPPALWVVTAAAAAATCVSAARGEVNLLDTSTIHGDWGWLTYPAHGWDSINEV
DESFQPIHTYQVCNVMSPNQNNWLRTSWVPRDGARRVYAEIKFTLRDCNSMPGVLGTCKE
TFNLYYLESDRDLGASTQESQFLKIDTIAADESFTGADLGVRRLKLNTEVRSVGPLSKRG
FYLAFQDIGACLAILSLRIYYKKCPAMVRNLAAFSEAVTGADSSSLVEVRGQCVRHSEER
DTPKMYCSAEGEWLVPIGKCVCSAGYEERRDACVACELGFYKSAPGDQLCARCPPHSHSA
APAAQACHCDLSYYRAALDPPSSACTRPPSAPVNLISSVNGTSVTLEWAPPLDPGGRSDI
TYNAVCRRCPWALSRCEACGSGTRFVPQQTSLVQASLLVANLLAHMNYSFWIEAVNGVSD
LSPEPRRAAVVNITTNQAAPSQVVVIRQERAGQTSVSLLWQEPEQPNGIILEYEIKYYEK
DKEMQSYSTLKAVTTRATVSGLKPGTRYVFQVRARTSAGCGRFSQAMEVETGKPRPRYDT
RTIVWICLTLITGLVVLLLLLICKKRHCGYSKAFQDSDEEKMHYQNGQAPPPVFLPLHHP
PGKLPEPQFYAEPHTYEEPGRAGRSFTREIEASRIHIEKIIGSGDSGEVCYGRLRVPGQR
DVPVAIKALKAGYTERQRRDFLSEASIMGQFDHPNIIRLEGVVTRGRLAMIVTEYMENGS
LDTFLRTHDGQFTIMQLVGMLRGVGAGMRYLSDLGYVHRDLAARNVLVDSNLVCKVSDFG
LSRVLEDDPDAAYTTTGGKIPIRWTAPEAIAFRTFSSASDVWSFGVVMWEVLAYGERPYW
NMTNRDVISSVEEGYRLPAPMGCPHALHQLMLDCWHKDRAQRPRFSQIVSVLDALIRSPE
SLRATATVSRCPPPAFVRSCFDLRGGSGGGGGLTVGDWLDSIRMGRYRDHFAAGGYSSLG
MVLRMNAQDVRALGITLMGHQKKILGSIQTMRAQLTSTQGPRRHL

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3D Structure

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AlphaFold

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

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	32.281 (92/285)	2.26E-28
Receptor-interacting serine/threonine-protein kinase 3 (RIPK3)	PF00069 ; PF12721	30.450 (88/289)	1.12E-20
Ribosomal protein S6 kinase alpha-2 (RSK2)	PF00069 ; PF00433	29.707 (71/239)	2.87E-20
Serine/threonine-protein kinase Nek4 (NEK4)	PF00069	28.346 (72/254)	8.41E-20
Ribosomal protein S6 kinase alpha-1 (RSK1)	PF00069 ; PF00433	28.395 (69/243)	1.31E-19
Serine/threonine-protein kinase 26 (STK26)	PF00069	29.200 (73/250)	1.96E-19
SIK family kinase 3 (SIK3)	PF00069	31.276 (76/243)	2.63E-19
Ribosomal protein S6 kinase alpha-3 (RSK3)	PF00069 ; PF00433	28.870 (69/239)	3.43E-19
Salt-inducible kinase 2 (SIK2)	PF00069	29.876 (72/241)	3.97E-19
MST-1 protein kinase (STK4)	PF11629 ; PF00069	28.378 (84/296)	4.49E-19
Ribosomal protein S6 kinase alpha-6 (RSK6)	PF00069 ; PF00433	29.167 (70/240)	7.50E-19
Fused homolog (STK36)	PF13646 ; PF00069	26.941 (59/219)	7.92E-19
Serine/threonine-protein kinase Nek5 (NEK5)	PF00069	25.095 (66/263)	1.15E-18
Serine/threonine-protein kinase Nek11 (NEK11)	PF00069	26.066 (55/211)	1.39E-18
Omphalocele kinase 1 (NUAK1)	PF00069	27.074 (62/229)	5.55E-18
Microtubule affinity regulating kinase 3 (MARK3)	PF02149 ; PF00069 ; PF00627 More >>	27.459 (67/244)	5.71E-18
Salt-inducible kinase 1 (SIK1)	PF00069	27.869 (68/244)	7.16E-18
Putative serine/threonine-protein kinase SIK1B (SIK1B)	PF00069	27.869 (68/244)	7.41E-18
Serine/threonine-protein kinase PAK 5 (PAK5)	PF00786 ; PF00069	29.703 (60/202)	9.04E-18
Calcium/calmodulin-dependent protein kinase type 1G (CAMK1G)	PF00069	27.897 (65/233)	9.07E-18
Serine/threonine-protein kinase 3 (STK3)	PF11629 ; PF00069	27.208 (77/283)	9.42E-18
Serine/threonine-protein kinase MARK2 (MARK2)	PF02149 ; PF00069 ; PF00627 More >>	26.740 (73/273)	1.01E-17
NIMA-related kinase 7 (NEK7)	PF00069	24.407 (72/295)	1.01E-17
Calcium/calmodulin-dependent protein kinase type 1 (CAMK1)	PF00069	28.713 (58/202)	1.27E-17
Serine/threonine-protein kinase 24 (STK24)	PF00069	27.309 (68/249)	1.69E-17
Serine/threonine-protein kinase ULK1 (ULK1)	PF12063 ; PF00069	26.778 (64/239)	2.03E-17
Serine/threonine-protein kinase MARK1 (MARK1)	PF02149 ; PF00069 ; PF00627 More >>	25.818 (71/275)	2.54E-17
Inhibitor of nuclear factor kappa-B kinase alpha (IKKA)	PF18397 ; PF12179 ; PF00069 More >>	25.837 (54/209)	3.52E-17
Serine/threonine-protein kinase 33 (STK33)	PF00069	31.111 (56/180)	4.18E-17
Serine/threonine-protein kinase ULK2 (ULK2)	PF12063 ; PF00069	28.111 (61/217)	7.01E-17
NIMA-related kinase 2 (NEK2)	PF00069	26.136 (69/264)	8.73E-17
MAP/microtubule affinity-regulating kinase 4 (MARK4)	PF02149 ; PF00069 ; PF00627 More >>	28.251 (63/223)	2.13E-16
ERK activator kinase 7 (MAP2K7)	PF00069	27.941 (76/272)	2.30E-16
Serine/threonine-protein kinase PAK 6 (PAK6)	PF00786 ; PF00069	26.733 (54/202)	2.32E-16
Polo-like kinase 4 (PLK4)	PF00069 ; PF18190 ; PF18409 More >>	27.700 (59/213)	2.60E-16
Serine/threonine-protein kinase Nek8 (NEK8)	PF00069 ; PF00415	25.114 (55/219)	3.92E-16
Serine/threonine-protein kinase 25 (STK25)	PF00069	27.778 (75/270)	4.08E-16
PAK-4 protein kinase (PAK4)	PF00786 ; PF00069	29.208 (59/202)	5.80E-16
Serine/threonine-protein kinase ICK (CILK1)	PF00069	26.335 (74/281)	5.90E-16
Serine/threonine-protein kinase tousled-like 2 (TLK2)	PF00069	27.354 (61/223)	8.16E-16
Serine/threonine-protein kinase Nek9 (NEK9)	PF00069 ; PF00415	25.275 (69/273)	1.19E-15
NIMA-related kinase 6 (NEK6)	PF00069	23.488 (66/281)	1.82E-15
5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2)	PF16579 ; PF00069	29.469 (61/207)	1.95E-15
Serine/threonine-protein kinase MAK (MAK)	PF00069	26.549 (60/226)	1.96E-15
ERK activator kinase 5 (MAP2K5)	PF00564 ; PF00069	29.245 (62/212)	2.12E-15
PKC-delta-interacting protein kinase (RIPK4)	PF12796 ; PF00069	30.568 (70/229)	2.49E-15
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	PF16579 ; PF00069	28.986 (60/207)	2.86E-15
Apoptosis signal-regulating kinase 2 (MAP3K6)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	28.854 (73/253)	4.02E-15
NUAK family SNF1-like kinase 2 (NUAK2)	PF00069	25.957 (61/235)	5.33E-15
Serine/threonine-protein kinase H1 (PSKH1)	PF00069	30.233 (65/215)	5.49E-15
Aurora kinase C (AURKC)	PF00069	24.498 (61/249)	7.71E-15
Ste-20-related kinase (STK39)	PF12202 ; PF00069	24.638 (85/345)	8.59E-15
Bone morphogenetic protein receptor (BMPR2)	PF01064 ; PF00069	29.915 (70/234)	9.97E-15
Calcium/calmodulin-dependent protein kinase type 1D (CAMK1D)	PF00069	25.200 (63/250)	1.03E-14
Serine/threonine-protein kinase tousled-like 1 (TLK1)	PF00069	27.570 (59/214)	1.08E-14
Cyclin-dependent kinase 7 (CDK7)	PF00069	28.502 (59/207)	1.14E-14
Serine/threonine-protein kinase NIM1 (NIM1K)	PF00069	29.461 (71/241)	1.62E-14
Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE)	PF00069 ; PF18394 ; PF18396 More >>	27.854 (61/219)	2.10E-14
Myosin light chain kinase 2 (MYLK2)	PF00069	23.874 (53/222)	2.12E-14
Extracellular signal-regulated kinase 5 (ERK5)	PF00069	29.911 (67/224)	2.21E-14
IL-1 receptor-associated kinase 3 (IRAK3)	PF00531 ; PF00069	24.169 (80/331)	3.21E-14
Serine/threonine-protein kinase Nek3 (NEK3)	PF00069	22.835 (58/254)	4.56E-14
Serine/threonine-protein kinase PLK3 (PLK3)	PF00069 ; PF00659	26.984 (68/252)	5.06E-14
Serine/threonine-protein kinase TAO2 (TAOK2)	PF00069	29.907 (64/214)	7.88E-14
Oxidative stress responsive 1 (OXSR1)	PF12202 ; PF00069	25.442 (72/283)	8.25E-14
Apoptosis signal-regulating kinase 1 (MAP3K5)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	29.808 (62/208)	8.95E-14
Myosin light chain kinase 3 (MYLK3)	PF00069	27.189 (59/217)	9.56E-14
Protein kinase C theta (PRKCQ)	PF00130 ; PF00069 ; PF00433 More >>	25.100 (63/251)	1.10E-13
Proto-oncogene serine/threonine-protein kinase mos (MOS)	PF00069	25.993 (72/277)	1.23E-13
Checkpoint kinase-1 (CHK1)	PF00069	29.064 (59/203)	1.27E-13
BR serine/threonine kinase 1 (BRSK1)	PF00069	25.000 (55/220)	1.37E-13
Serine/threonine-protein kinase Sgk1 (SGK1)	PF00069 ; PF00433	25.692 (65/253)	1.40E-13
Serine/threonine-protein kinase D2 (PRKD2)	PF00130 ; PF00069	26.316 (55/209)	2.24E-13
PAK-2 protein kinase (PAK2)	PF00786 ; PF00069	27.228 (55/202)	2.32E-13
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	PF18397 ; PF12179 ; PF00069 More >>	24.286 (51/210)	2.71E-13
Activin receptor type IB (ACVR1B)	PF01064 ; PF00069 ; PF08515 More >>	26.349 (83/315)	3.74E-13
Putative serine/threonine-protein kinase PRKY (PRKY)	PF00069	27.711 (46/166)	3.96E-13
NIMA-related kinase 1 (NEK1)	PF00069	20.800 (52/250)	4.01E-13
BR serine/threonine kinase 2 (BRSK2)	PF00069	25.333 (57/225)	4.45E-13
Putative 3-phosphoinositide-dependent protein kinase 2 (PDPK2P)	PF00069	23.039 (47/204)	5.36E-13
Myosin light chain kinase family member 4 (MYLK4)	PF00069	25.688 (56/218)	5.73E-13
Death-associated protein kinase 1 (DAPK1)	PF00023 ; PF12796 ; PF13637 ; PF00531 ; PF00069 More >>	26.728 (58/217)	5.80E-13
Leucine-rich repeat kinase 2 (LRRK2)	PF16095 ; PF12799 ; PF13855 ; PF00069 ; PF08477 More >>	25.746 (69/268)	6.64E-13
Calcium/calmodulin-dependent protein kinase type 1B (PNCK)	PF00069	26.939 (66/245)	7.28E-13
Doublecortin-like kinase 2 (DCLK2)	PF03607 ; PF00069	28.205 (66/234)	7.70E-13
Extracellular signal-regulated kinase 2 (ERK2)	PF00069	28.856 (58/201)	8.74E-13
Leucine-rich repeat serine/threonine-protein kinase 1 (LRRK1)	PF12796 ; PF16095 ; PF00069 ; PF08477 More >>	25.378 (84/331)	8.77E-13
TAO kinase 1 (TAOK1)	PF00069	29.858 (63/211)	8.93E-13
Cyclin-dependent kinase 13 (CDK13)	PF12330 ; PF00069	24.893 (58/233)	1.01E-12
cAMP-dependent protein kinase catalytic subunit PRKX (PRKX)	PF00069	27.711 (46/166)	1.14E-12
Aurora kinase A (AURKA)	PF00069	26.207 (76/290)	1.26E-12
Protein kinase D (PRKD1)	PF00130 ; PF00169 ; PF00069 More >>	25.359 (53/209)	1.32E-12
Phosphoinositide dependent protein kinase-1 (PDPK1)	PF14593 ; PF00069	23.039 (47/204)	1.40E-12
PAK-1 protein kinase (PAK1)	PF00786 ; PF00069	26.961 (55/204)	1.42E-12
TAO kinase 3 (TAOK3)	PF00069	29.048 (61/210)	2.03E-12
Cyclin-dependent kinase 15 (CDK15)	PF00069	25.792 (57/221)	2.37E-12
Protein kinase C alpha (PRKCA)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	26.316 (60/228)	2.99E-12
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform (PHKG1)	PF00069	28.877 (54/187)	3.09E-12
Ribosomal protein S6 kinase alpha-5 (RSK5)	PF00069 ; PF00433	27.333 (41/150)	3.19E-12
Serine/threonine-protein kinase D3 (PRKD3)	PF00130 ; PF00169 ; PF00069 More >>	26.667 (56/210)	3.60E-12
Protein kinase C beta (PRKCB)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	28.750 (46/160)	3.76E-12
Serine/threonine-protein kinase PAK 3 (PAK3)	PF00786 ; PF00069	26.961 (55/204)	3.84E-12
Ribosomal protein S6 kinase beta-1 (S6K1)	PF00069 ; PF00433	25.000 (54/216)	4.25E-12
Dual specificity mitogen-activated protein kinase kinase 6 (MAP2K6)	PF00069	26.899 (85/316)	4.34E-12
Mitogen-activated protein kinase kinase kinase 15 (MAP3K15)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	28.641 (59/206)	4.80E-12
Doublecortin-like kinase 1 (DCLK1)	PF03607 ; PF00069	29.651 (51/172)	5.77E-12
Mitogen-activated protein kinase 15 (MAPK15)	PF00069	30.508 (54/177)	5.79E-12
Serine/threonine-protein kinase Sgk2 (SGK2)	PF00069 ; PF00433	25.000 (69/276)	5.92E-12
Testis-specific serine kinase 2 (TSSK2)	PF00069	25.417 (61/240)	6.91E-12
Cyclin-dependent kinase-like 4 (CDKL4)	PF00069	27.317 (56/205)	6.99E-12
Serine/threonine-protein kinase Nek10 (NEK10)	PF00069	23.504 (55/234)	7.66E-12
TGF-beta-stimulated factor 1 (STK16)	PF00069	26.971 (65/241)	7.71E-12
MAPK/ERK kinase kinase 1 (MAP3K1)	PF00069	28.125 (45/160)	7.80E-12
Serine/threonine-protein kinase H2 (PSKH2)	PF00069	28.019 (58/207)	8.05E-12
Cyclin-dependent kinase 3 (CDK3)	PF00069	28.000 (56/200)	8.22E-12
Protein kinase C epsilon (PRKCE)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	26.446 (64/242)	8.38E-12
Cyclin-dependent kinase 1 (CDK1)	PF00069	26.609 (62/233)	1.06E-11
Serine/threonine-protein kinase 32A (STK32A)	PF00069	24.823 (70/282)	1.24E-11
Cyclin-dependent kinase 12 (CDK12)	PF00069	23.721 (51/215)	1.28E-11
Stress-activated protein kinase JNK3 (JNK3)	PF00069	28.856 (58/201)	1.31E-11
Mitogen-activated protein kinase 13 (MAPK13)	PF00069	29.851 (60/201)	1.42E-11
SNF-related serine/threonine-protein kinase (SNRK)	PF00069	23.789 (54/227)	1.46E-11
MAPK-activated protein kinase 3 (MAPKAPK3)	PF00069	26.316 (60/228)	2.20E-11
Extracellular signal-regulated kinase 1 (ERK1)	PF00069	26.866 (54/201)	2.49E-11
RAC-gamma serine/threonine-protein kinase (AKT3)	PF00169 ; PF00069 ; PF00433 More >>	26.852 (58/216)	2.56E-11
Polo-like kinase 1 (PLK1)	PF00069 ; PF00659	25.397 (64/252)	2.58E-11
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	PF00069	27.306 (74/271)	2.62E-11
Protein kinase C delta (PRKCD)	PF00130 ; PF00069 ; PF00433 More >>	24.312 (53/218)	2.67E-11
SPS1/STE20-related protein kinase YSK4 (YSK4)	PF00069	24.521 (64/261)	2.74E-11
Cyclin-dependent kinase 2 (CDK2)	PF00069	25.214 (59/234)	3.18E-11
Tyrosine-protein kinase EIF2AK2 (p68)	PF00035 ; PF00069	22.430 (72/321)	3.48E-11
Cyclin-dependent kinase 11A (CDK11A)	PF00069	29.834 (54/181)	3.68E-11
Calcium/calmodulin-dependent protein kinase type II subunit beta (CAMK2B)	PF08332 ; PF00069	24.615 (48/195)	3.72E-11
Hormonally up-regulated neu tumor-associated kinase (HUNK)	PF00069	27.523 (60/218)	3.93E-11
Cyclin-dependent kinase 11B (CDK11B)	PF00069	29.444 (53/180)	3.97E-11
cAMP-dependent protein kinase catalytic subunit gamma (PRKACG)	PF00069	25.126 (50/199)	4.06E-11
Stress-activated protein kinase JNK1 (JNK1)	PF00069	28.079 (57/203)	4.21E-11
Aurora kinase B (AURKB)	PF00069	24.803 (63/254)	4.22E-11
Cyclin-dependent kinase-like 1 (CDKL1)	PF00069	30.693 (62/202)	4.32E-11
IL-1 receptor-associated kinase 1 (IRAK1)	PF00531 ; PF00069	22.874 (78/341)	4.66E-11
MAPK/ERK kinase kinase 4 (MAP3K4)	PF19431 ; PF00069	26.636 (57/214)	4.68E-11
STE20-related serine/threonine-protein kinase (SLK)	PF00069 ; PF12474	26.047 (56/215)	5.62E-11
Stress-activated protein kinase JNK2 (JNK2)	PF00069	27.861 (56/201)	5.65E-11
Cyclin-dependent kinase 5 (CDK5)	PF00069	25.946 (48/185)	5.67E-11
Serine/threonine-protein kinase WNK1 (WNK1)	PF12202 ; PF00069	27.624 (50/181)	5.72E-11
TGF-beta receptor type I (TGFBR1)	PF01064 ; PF00069 ; PF08515 More >>	25.301 (63/249)	6.94E-11
Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMK2A)	PF08332 ; PF00069	25.128 (49/195)	7.00E-11
Maternal embryonic leucine zipper kinase (MELK)	PF02149 ; PF00069	25.980 (53/204)	7.09E-11
Ribosomal protein S6 kinase beta-2 (RPS6KB2)	PF00069 ; PF00433	24.597 (61/248)	7.72E-11
Polo-like kinase 2 (PLK2)	PF00069 ; PF00659	23.016 (58/252)	8.06E-11
Serine/threonine-protein kinase NLK (NLK)	PF00069	37.234 (35/94)	9.21E-11
Death-associated protein kinase 3 (DAPK3)	PF00069	24.885 (54/217)	9.69E-11
Protein kinase C gamma (PRKCG)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	28.671 (41/143)	9.92E-11
NF-kappa-B-activating kinase (TBK1)	PF00069 ; PF18394 ; PF18396 More >>	27.230 (58/213)	1.14E-10
MAPK/ERK kinase kinase 3 (MAP3K3)	PF00564 ; PF00069	30.675 (50/163)	1.14E-10
Cyclin-dependent kinase-like 3 (CDKL3)	PF00069	27.363 (55/201)	1.35E-10
Death-associated protein kinase 2 (DAPK2)	PF00069	25.346 (55/217)	1.36E-10
Cyclin-dependent kinase 9 (CDK9)	PF00069	25.000 (54/216)	1.60E-10
RAC-beta serine/threonine-protein kinase (AKT2)	PF00169 ; PF00069 ; PF00433 More >>	26.210 (65/248)	1.70E-10
Cyclin-dependent kinase 20 (CDK20)	PF00069	26.901 (46/171)	1.91E-10
TRAF2 and NCK interacting kinase (TNIK)	PF00780 ; PF00069	25.000 (67/268)	2.02E-10
Cyclin-dependent kinase-like 2 (CDKL2)	PF00069	27.451 (56/204)	2.11E-10
Citron Rho-interacting kinase (CIT)	PF00780 ; PF00169 ; PF00069 More >>	25.108 (58/231)	2.24E-10
Cyclin-dependent kinase-like 5 (CDKL5)	PF00069	26.442 (55/208)	2.27E-10
RAC-alpha serine/threonine-protein kinase (AKT1)	PF00169 ; PF00069 ; PF00433 More >>	27.309 (68/249)	2.31E-10
MAPK-activated protein kinase 2 (MAPKAPK2)	PF00069	26.282 (41/156)	2.47E-10
Unc-51 like kinase 3 (ULK3)	PF04212 ; PF00069	25.909 (57/220)	2.61E-10
MAP kinase p38 (MAPK12)	PF00069	27.363 (55/201)	2.68E-10
Stress-activated protein kinase 2a (p38 alpha)	PF00069	28.502 (59/207)	2.82E-10
WNK lysine-deficient protein kinase 3 (WNK3)	PF12202 ; PF00069	26.519 (48/181)	3.05E-10
Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D)	PF08332 ; PF00069	23.963 (52/217)	3.19E-10
Doublecortin-like kinase 3 (DCLK3)	PF00069	26.141 (63/241)	3.63E-10
Ribosomal protein S6 kinase-related protein (RSKR)	PF00069	32.051 (50/156)	3.69E-10
Serine/threonine-protein kinase 10 (STK10)	PF00069 ; PF12474	25.234 (54/214)	3.70E-10
Serine/threonine-protein kinase Sgk3 (SGK3)	PF00069 ; PF00433 ; PF00787 More >>	24.498 (61/249)	3.93E-10
Calcium/calmodulin-dependent protein kinase type IV (CAMK4)	PF00069	26.776 (49/183)	4.07E-10
Cyclin-dependent kinase 14 (CDK14)	PF00069	24.227 (47/194)	4.10E-10
Calcium/calmodulin-dependent protein kinase type II subunit gamma (CAMK2G)	PF08332 ; PF00069	24.103 (47/195)	4.47E-10
Phosphorylase kinase testis gamma 2 (PHKG2)	PF00069	25.957 (61/235)	4.61E-10
MEK kinase kinase 3 (MAP4K3)	PF00780 ; PF00069	24.913 (72/289)	4.67E-10
Cyclin-dependent kinase 4 (CDK4)	PF00069	27.211 (40/147)	4.70E-10
Testis-specific serine/threonine-protein kinase 1 (TSSK1B)	PF00069	27.749 (53/191)	4.90E-10
Mitogen-activated protein kinase 4 (MAPK4)	PF00069	27.225 (52/191)	5.16E-10
Cytoplasmic DRAK1 (STK17A)	PF00069	25.610 (42/164)	5.28E-10
Protein kinase C iota (PRKCI)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	24.224 (78/322)	5.36E-10
Serine/threonine-protein kinase WNK2 (WNK2)	PF12202 ; PF00069	28.177 (51/181)	6.28E-10
CaM-kinase IV kinase (CAMKK1)	PF00069	29.878 (49/164)	6.67E-10
ERK activator kinase 2 (MEK2)	PF00069	27.500 (55/200)	7.11E-10
Cyclin-dependent kinase 6 (CDK6)	PF00069	26.368 (53/201)	7.72E-10
cAMP-dependent protein kinase catalytic subunit beta (PRKACB)	PF00069	25.854 (53/205)	9.73E-10
Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3)	PF00069	28.417 (79/278)	1.03E-09
Stress-activated protein kinase 2b (p38 beta)	PF00069	27.619 (58/210)	1.08E-09
Cyclin-dependent kinase 10 (CDK10)	PF00069	28.358 (57/201)	1.11E-09
STE20-related kinase adapter protein alpha (STRADA)	PF00069	25.792 (57/221)	1.13E-09
Protein kinase C eta type (PRKCH)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	24.434 (54/221)	1.15E-09
cAMP-dependent protein kinase catalytic subunit alpha (PRKACA)	PF00069	25.490 (52/204)	1.24E-09
CDC42 binding protein kinase alpha (DMPK-like alpha)	PF00130 ; PF00780 ; PF08826 ; PF15796 ; PF00069 ; PF00433 More >>	25.652 (59/230)	1.38E-09
Cyclin-dependent kinase 18 (CDK18)	PF00069	24.742 (48/194)	1.39E-09
Microtubule-associated serine/threonine-protein kinase 3 (MAST3)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	27.817 (79/284)	1.55E-09
MEK kinase kinase 1 (MAP4K1)	PF00780 ; PF00069	25.292 (65/257)	1.71E-09
Yet another novel kinase 2 (STK32B)	PF00069	24.000 (54/225)	1.74E-09
Cyclin-dependent kinase 17 (CDK17)	PF12330 ; PF00069	23.618 (47/199)	1.80E-09
Serine/threonine-protein kinase WNK4 (WNK4)	PF12202 ; PF00069	27.108 (90/332)	1.98E-09
MAPK/ERK kinase kinase 2 (MAP3K2)	PF00564 ; PF00069	27.570 (59/214)	2.29E-09
Testis-specific serine/threonine-protein kinase 6 (TSSK6)	PF00069	27.586 (56/203)	2.36E-09
Testis-specific serine/threonine-protein kinase 3 (TSSK3)	PF00069	25.532 (60/235)	2.95E-09
Cyclin-dependent kinase 16 (CDK16)	PF12330 ; PF00069	24.878 (51/205)	3.42E-09
ERK activator kinase 1 (MEK1)	PF00069	28.395 (46/162)	3.51E-09
Glycogen synthase kinase-3 alpha (GSK-3A)	PF00069	28.780 (59/205)	3.73E-09
Microtubule-associated serine/threonine-protein kinase 4 (MAST4)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	25.523 (61/239)	4.19E-09
Protein kinase N1 (PKN1)	PF02185 ; PF00069 ; PF00433 More >>	27.650 (60/217)	4.24E-09
Myosin-IIIa (MYO3A)	PF00612 ; PF00063 ; PF00069 More >>	24.164 (65/269)	4.69E-09
Ribosomal protein S6 kinase alpha-4 (RPS6KA4)	PF00069 ; PF00433	25.862 (60/232)	6.82E-09
STE20-related kinase adapter protein beta (STRADB)	PF00069	26.667 (52/195)	7.57E-09
Microtubule-associated serine/threonine-protein kinase 2 (MAST2)	PF08926 ; PF17820 ; PF00069 More >>	24.336 (55/226)	8.06E-09
Myosin-IIIb (MYO3B)	PF00612 ; PF00063 ; PF00069 More >>	24.549 (68/277)	9.13E-09
Protein kinase G1 (PRKG1)	PF00027 ; PF16808 ; PF00069 More >>	25.701 (55/214)	1.42E-08
Titin (TTN)		28.293 (58/205)	1.53E-08
Calmodulin-dependent kinase II (CAMKK2)	PF00069	27.219 (46/169)	1.60E-08
Microtubule-associated serine/threonine-protein kinase 1 (MAST1)	PF08926 ; PF17820 ; PF00069 More >>	26.068 (61/234)	1.67E-08
Misshapen-like kinase 1 (MINK1)	PF00780 ; PF00069	26.728 (58/217)	1.81E-08
Serine/threonine-protein kinase Chk2 (RAD53)	PF00498 ; PF00069	26.389 (57/216)	2.14E-08
Protein kinase N3 (PKN3)	PF02185 ; PF00069 ; PF00433 More >>	25.926 (70/270)	2.63E-08
Protein kinase G2 (PRKG2)	PF00027 ; PF00069	24.638 (51/207)	2.66E-08
Serine/threonine-protein kinase STK11 (STK11)	PF00069	25.943 (55/212)	3.02E-08
MEK kinase kinase 2 (MAP4K2)	PF00780 ; PF00069	24.876 (50/201)	3.08E-08
Rho-associated protein kinase 2 (ROCK2)	PF00069 ; PF08912	24.554 (55/224)	3.31E-08
Activin receptor type IIA (ACVR2A)	PF01064 ; PF00069	28.931 (46/159)	3.47E-08
Mitogen-activated protein kinase 6 (MAPK6)	PF00069	27.149 (60/221)	5.35E-08
Serine/threonine kinase-like domain-containing protein STKLD1 (STKLD1)	PF00069	34.737 (33/95)	5.58E-08
Serine/threonine-protein kinase MRCK beta (CDC42BPB)	PF00130 ; PF00780 ; PF08826 ; PF15796 ; PF00069 More >>	23.810 (60/252)	5.70E-08
Anti-mullerian hormone II receptor (AMHR2)	PF00069	25.284 (89/352)	6.67E-08
Serine/threonine-protein kinase MRCK gamma (CDC42BPG)	PF00130 ; PF00780 ; PF08826 ; PF00069 More >>	27.155 (63/232)	8.00E-08
Peripheral plasma membrane protein CASK (CASK)	PF00625 ; PF02828 ; PF00595 ; PF00069 ; PF00018 More >>	24.194 (45/186)	9.39E-08
Nik-related protein kinase (NRK)	PF00780 ; PF00069	25.974 (60/231)	9.59E-08
Glycogen synthase kinase-3 beta (GSK-3B)	PF00069	26.829 (55/205)	9.79E-08
Rho-associated protein kinase 1 (ROCK1)	PF00069 ; PF08912	26.009 (58/223)	1.03E-07
Serine/threonine-protein kinase 32C (STK32C)	PF00069	24.444 (55/225)	1.34E-07
G protein-coupled receptor kinase 6 (GRK6)	PF00069 ; PF00615	23.041 (50/217)	1.44E-07
MEK kinase kinase 4 (MAP4K4)	PF00780 ; PF00069	26.728 (58/217)	1.79E-07
Endoplasmic reticulum to nucleus signaling 1 (ERN1)	PF00069 ; PF06479	23.502 (51/217)	2.07E-07
Serine/threonine-protein kinase NIK (MAP3K14)	PF00069	30.986 (44/142)	2.58E-07
PRKR-like endoplasmic reticulum kinase (PERK)	PF00069	28.571 (28/98)	2.96E-07
NDR2 protein kinase (STK38L)	PF00069 ; PF00433	23.849 (57/239)	3.07E-07
PDZ binding kinase (PBK)	PF00069	22.925 (58/253)	3.91E-07
MAPK-activated protein kinase 5 (MAPKAPK5)	PF00069	25.143 (44/175)	4.44E-07
Triple functional domain protein (TRIO)	PF00650 ; PF07679 ; PF00169 ; PF00069 ; PF00621 ; PF16609 ; PF00018 ; PF00435 More >>	27.536 (57/207)	4.89E-07
Serine/threonine-protein kinase cot (COT)	PF00069	27.397 (40/146)	5.01E-07
Protein kinase N2 (PKN2)	PF02185 ; PF00069 ; PF00433 More >>	27.650 (60/217)	5.10E-07
Interleukin-1 receptor-associated kinase-like 2 (IRAK2)	PF00531 ; PF00069	27.500 (44/160)	5.33E-07
Protein kinase C zeta (PRKCZ)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	21.739 (55/253)	5.55E-07
Homeodomain-interacting protein kinase 4 (HIPK4)	PF00069	25.941 (62/239)	6.07E-07
Mitogen-activated protein kinase kinase kinase kinase 5 (MAP4K5)	PF00780 ; PF00069	24.091 (53/220)	6.51E-07
Striated muscle preferentially expressed protein kinase (SPEG)	PF07679 ; PF00069 ; PF16650 More >>	24.138 (42/174)	7.68E-07
Cyclin-dependent kinase 19 (CDK19)	PF00069	23.387 (58/248)	9.01E-07
Membrane-associated kinase (PKMYT1)	PF00069	27.389 (43/157)	9.78E-07
Eukaryotic translation initiation factor 2-alpha kinase 1 (EIF2AK1)	PF00069	26.582 (42/158)	1.46E-06
G protein-coupled receptor kinase 5 (GRK5)	PF00069 ; PF00615	23.301 (48/206)	1.50E-06
Serine/threonine-protein kinase SBK2 (SBK2)	PF00069	28.856 (58/201)	1.70E-06
Homeodomain interacting protein kinase 2 (HIPK2)	PF00069	26.496 (62/234)	1.84E-06
Serine/threonine-protein kinase Kist (UHMK1)	PF00069 ; PF00076	27.500 (66/240)	2.63E-06
NDR1 protein kinase (STK38)	PF00069 ; PF00433	24.153 (57/236)	2.64E-06
PAS domain-containing serine/threonine-protein kinase (PASK)	PF13426 ; PF00069	23.952 (40/167)	3.02E-06
Activin receptor type IIB (ACVR2B)	PF01064 ; PF00069	25.389 (49/193)	3.15E-06
Serine/threonine-protein kinase/endoribonuclease IRE2 (ERN2)	PF00069 ; PF06479	27.485 (47/171)	3.72E-06
Tau-tubulin kinase 2 (TTBK2)	PF00069	21.014 (58/276)	3.85E-06
Homeodomain-interacting protein kinase 3 (HIPK3)	PF00069	25.490 (52/204)	4.31E-06
Rhodopsin kinase GRK7 (GRK7)	PF00069 ; PF00615	23.333 (49/210)	4.68E-06
Eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4)	PF12745 ; PF00069 ; PF05773 ; PF13393 More >>	28.440 (31/109)	5.18E-06
Serine/threonine-protein kinase LATS1 (LATS1)	PF00069 ; PF00627	21.790 (56/257)	6.55E-06
Serine/threonine-protein kinase 17B (STK17B)	PF00069	21.348 (38/178)	7.40E-06
Homeodomain-interacting protein kinase 1 (HIPK1)	PF00069	25.214 (59/234)	8.41E-06
Beta-adrenergic receptor kinase 2 (ADRBK2)	PF00169 ; PF00069 ; PF00615 More >>	23.963 (52/217)	1.16E-05
Serine/threonine-protein kinase greatwall (MASTL)	PF00069	30.769 (28/91)	1.24E-05
Dual specificity protein kinase TTK (MPS1)	PF00069	22.593 (61/270)	1.25E-05
TBC domain-containing protein kinase-like protein (TBCK)	PF00069 ; PF00566 ; PF00581 More >>	26.036 (44/169)	1.32E-05
CaM kinase-like vesicle-associated protein (CAMKV)	PF00069	26.190 (44/168)	1.33E-05
Cyclin-dependent kinase 8 (CDK8)	PF00069	23.757 (43/181)	1.39E-05
Testis-specific serine/threonine-protein kinase 4 (TSSK4)	PF00069	20.161 (50/248)	2.91E-05
Tau-tubulin kinase (TTBK1)	PF00069	20.141 (57/283)	3.12E-05
Large tumor suppressor homolog 2 (LATS2)	PF00069 ; PF00433	22.348 (59/264)	3.23E-05
Serine/threonine-protein kinase pim-2 (PIM2)	PF00069	24.057 (51/212)	3.95E-05
G protein-coupled receptor kinase 4 (GRK4)	PF00069 ; PF00615	20.982 (47/224)	5.69E-05
Beta-adrenergic receptor kinase 1 (ADRBK1)	PF00169 ; PF00069 ; PF00615 More >>	24.771 (54/218)	8.50E-05
Serine/threonine-protein kinase ULK4 (ULK4)	PF00069	23.013 (55/239)	1.15E-04
Myotonin-protein kinase (DMPK)	PF08826 ; PF00069	23.767 (53/223)	1.30E-04
Serine/threonine-protein kinase SBK1 (SBK1)	PF00069	27.119 (64/236)	1.41E-04
MAP kinase signal-integrating kinase 2 (MKNK2)	PF00069	26.000 (39/150)	1.61E-04
Rhodopsin kinase GRK1 (GRK1)	PF00069 ; PF00615	30.337 (27/89)	2.52E-04
Wee1-like protein kinase (WEE1)	PF00069	24.407 (72/295)	4.90E-04
Cyclin-G-associated kinase (GAK)	PF00069 ; PF10409	18.983 (56/295)	5.14E-04
Sugen kinase 110 (SBK3)	PF00069	27.160 (44/162)	6.00E-04
Serine/threonine-protein kinase pim-1 (PIM1)	PF00069	29.592 (29/98)	6.78E-04
Dual-specificity tyrosine-phosphorylation regulated kinase 3 (DYRK3)	PF00069	25.714 (63/245)	1.00E-03
PIM-3 protein kinase (PIM3)	PF00069	32.653 (32/98)	1.00E-03
Casein kinase II alpha (CSNK2A1)	PF00069	21.778 (49/225)	1.00E-03
LRRN4 C-terminal-like protein (LRRN4CL)		35.821 (24/67)	2.00E-03
Serine/threonine-protein kinase PDIK1L (PDIK1L)	PF00069	21.687 (54/249)	2.00E-03
Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3 (ARAP3)	PF01412 ; PF00169 ; PF00788 ; PF00620 ; PF07647 More >>	31.034 (18/58)	2.00E-03
Serine/threonine-protein kinase 40 (STK40)	PF00069	23.490 (35/149)	2.00E-03
Casein kinase II subunit alpha 3 (CSNK2A3)	PF00069	21.364 (47/220)	4.00E-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	Pathway Map
Axon guidance	hsa04360	Affiliated Target
Class: Organismal Systems => Development and regeneration	Pathway Hierarchy

Degree	2	Degree centrality	2.15E-04	Betweenness centrality	2.56E-06
Closeness centrality	1.95E-01	Radiality	1.34E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	1.60E+01	Topological coefficient	5.00E-01	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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References

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REF 1

Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J Med Chem. 2009 Oct 22;52(20):6433-46.

REF 2

Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47.

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