Target Information

Target General Information

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Target ID

T18474 (Former ID: TTDI03176)

Target Name

Ephrin type-A receptor 5 (EPHA5)

Synonyms

hEK7; EPH-like kinase 7; EPH homology kinase 1; EK7; EHK1; EHK-1; Brain-specific kinase; BSK

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Gene Name

EPHA5

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. Among GPI-anchored ephrin-A ligands, EFNA5 most probably constitutes the cognate/functional ligand for EPHA5. Functions as an axon guidance molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal and hippocamposeptal pathways. Together with EFNA5 plays also a role in synaptic plasticity in adult brain through regulation of synaptogenesis. In addition to its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion. 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

EPHA5_HUMAN

EC Number

EC 2.7.10.1

Sequence

MRGSGPRGAGRRRPPSGGGDTPITPASLAGCYSAPRRAPLWTCLLLCAALRTLLASPSNE
VNLLDSRTVMGDLGWIAFPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISN
EGASRIFIELKFTLRDCNSLPGGLGTCKETFNMYYFESDDQNGRNIKENQYIKIDTIAAD
ESFTELDLGDRVMKLNTEVRDVGPLSKKGFYLAFQDVGACIALVSVRVYYKKCPSVVRHL
AVFPDTITGADSSQLLEVSGSCVNHSVTDEPPKMHCSAEGEWLVPIGKCMCKAGYEEKNG
TCQVCRPGFFKASPHIQSCGKCPPHSYTHEEASTSCVCEKDYFRRESDPPTMACTRPPSA
PRNAISNVNETSVFLEWIPPADTGGRKDVSYYIACKKCNSHAGVCEECGGHVRYLPRQSG
LKNTSVMMVDLLAHTNYTFEIEAVNGVSDLSPGARQYVSVNVTTNQAAPSPVTNVKKGKI
AKNSISLSWQEPDRPNGIILEYEIKYFEKDQETSYTIIKSKETTITAEGLKPASVYVFQI
RARTAAGYGVFSRRFEFETTPVFAASSDQSQIPVIAVSVTVGVILLAVVIGVLLSGSCCE
CGCGRASSLCAVAHPSLIWRCGYSKAKQDPEEEKMHFHNGHIKLPGVRTYIDPHTYEDPN
QAVHEFAKEIEASCITIERVIGAGEFGEVCSGRLKLPGKRELPVAIKTLKVGYTEKQRRD
FLGEASIMGQFDHPNIIHLEGVVTKSKPVMIVTEYMENGSLDTFLKKNDGQFTVIQLVGM
LRGISAGMKYLSDMGYVHRDLAARNILINSNLVCKVSDFGLSRVLEDDPEAAYTTRGGKI
PIRWTAPEAIAFRKFTSASDVWSYGIVMWEVVSYGERPYWEMTNQDVIKAVEEGYRLPSP
MDCPAALYQLMLDCWQKERNSRPKFDEIVNMLDKLIRNPSSLKTLVNASCRVSNLLAEHS
PLGSGAYRSVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIM
NSLQEMKVQLVNGMVPL

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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	34.286 (96/280)	1.89E-29
Fused homolog (STK36)	PF13646 ; PF00069	27.778 (70/252)	1.60E-21
Serine/threonine-protein kinase Nek5 (NEK5)	PF00069	26.718 (70/262)	1.55E-20
Receptor-interacting serine/threonine-protein kinase 3 (RIPK3)	PF00069 ; PF12721	30.249 (85/281)	2.14E-20
Serine/threonine-protein kinase Nek4 (NEK4)	PF00069	28.740 (73/254)	2.47E-20
Serine/threonine-protein kinase 24 (STK24)	PF00069	27.957 (78/279)	5.53E-20
Serine/threonine-protein kinase 26 (STK26)	PF00069	28.854 (73/253)	1.35E-19
Serine/threonine-protein kinase 33 (STK33)	PF00069	29.694 (68/229)	1.45E-19
NIMA-related kinase 7 (NEK7)	PF00069	25.094 (67/267)	4.98E-19
Serine/threonine-protein kinase ULK2 (ULK2)	PF12063 ; PF00069	27.734 (71/256)	8.18E-19
MST-1 protein kinase (STK4)	PF11629 ; PF00069	31.658 (63/199)	9.65E-19
Microtubule affinity regulating kinase 3 (MARK3)	PF02149 ; PF00069 ; PF00627 More >>	28.689 (70/244)	1.05E-18
Serine/threonine-protein kinase Nek11 (NEK11)	PF00069	25.081 (77/307)	1.69E-18
Serine/threonine-protein kinase MARK2 (MARK2)	PF02149 ; PF00069 ; PF00627 More >>	28.689 (70/244)	1.95E-18
Serine/threonine-protein kinase Nek9 (NEK9)	PF00069 ; PF00415	27.338 (76/278)	1.98E-18
Serine/threonine-protein kinase MARK1 (MARK1)	PF02149 ; PF00069 ; PF00627 More >>	27.757 (73/263)	3.71E-18
MAP/microtubule affinity-regulating kinase 4 (MARK4)	PF02149 ; PF00069 ; PF00627 More >>	29.707 (71/239)	4.25E-18
Serine/threonine-protein kinase 3 (STK3)	PF11629 ; PF00069	30.693 (62/202)	4.61E-18
Omphalocele kinase 1 (NUAK1)	PF00069	26.556 (64/241)	6.46E-18
Serine/threonine-protein kinase Nek8 (NEK8)	PF00069 ; PF00415	25.714 (72/280)	6.84E-18
Polo-like kinase 4 (PLK4)	PF00069 ; PF18190 ; PF18409 More >>	28.968 (73/252)	1.11E-17
Serine/threonine-protein kinase PAK 5 (PAK5)	PF00786 ; PF00069	31.373 (64/204)	1.17E-17
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	PF16579 ; PF00069	30.808 (61/198)	1.58E-17
Ribosomal protein S6 kinase alpha-2 (RSK2)	PF00069 ; PF00433	28.125 (63/224)	1.71E-17
Serine/threonine-protein kinase 25 (STK25)	PF00069	26.032 (82/315)	1.88E-17
Calcium/calmodulin-dependent protein kinase type 1G (CAMK1G)	PF00069	26.000 (65/250)	3.84E-17
Calcium/calmodulin-dependent protein kinase type 1 (CAMK1)	PF00069	26.991 (61/226)	4.29E-17
Ribosomal protein S6 kinase alpha-3 (RSK3)	PF00069 ; PF00433	28.636 (63/220)	5.44E-17
Ribosomal protein S6 kinase alpha-1 (RSK1)	PF00069 ; PF00433	27.442 (59/215)	5.94E-17
Serine/threonine-protein kinase PAK 6 (PAK6)	PF00786 ; PF00069	26.636 (57/214)	1.28E-16
NIMA-related kinase 6 (NEK6)	PF00069	25.000 (58/232)	1.44E-16
Ribosomal protein S6 kinase alpha-6 (RSK6)	PF00069 ; PF00433	27.523 (60/218)	1.70E-16
SIK family kinase 3 (SIK3)	PF00069	28.309 (77/272)	1.76E-16
Myosin light chain kinase 2 (MYLK2)	PF00069	26.941 (59/219)	1.96E-16
Cyclin-dependent kinase 7 (CDK7)	PF00069	29.293 (58/198)	1.98E-16
PKC-delta-interacting protein kinase (RIPK4)	PF12796 ; PF00069	30.268 (79/261)	2.39E-16
Putative serine/threonine-protein kinase SIK1B (SIK1B)	PF00069	26.923 (70/260)	2.61E-16
Serine/threonine-protein kinase ICK (CILK1)	PF00069	28.151 (67/238)	2.77E-16
Salt-inducible kinase 1 (SIK1)	PF00069	26.923 (70/260)	2.84E-16
Salt-inducible kinase 2 (SIK2)	PF00069	31.034 (72/232)	3.25E-16
Serine/threonine-protein kinase ULK1 (ULK1)	PF12063 ; PF00069	28.440 (62/218)	4.24E-16
Serine/threonine-protein kinase MAK (MAK)	PF00069	28.571 (82/287)	4.37E-16
NUAK family SNF1-like kinase 2 (NUAK2)	PF00069	27.642 (68/246)	4.61E-16
Serine/threonine-protein kinase NIM1 (NIM1K)	PF00069	29.921 (76/254)	7.29E-16
5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2)	PF16579 ; PF00069	28.636 (63/220)	8.17E-16
Extracellular signal-regulated kinase 5 (ERK5)	PF00069	29.808 (62/208)	1.01E-15
Myosin light chain kinase 3 (MYLK3)	PF00069	28.972 (62/214)	1.24E-15
Extracellular signal-regulated kinase 2 (ERK2)	PF00069	30.846 (62/201)	2.22E-15
Serine/threonine-protein kinase PLK3 (PLK3)	PF00069 ; PF00659	27.650 (60/217)	2.74E-15
Putative 3-phosphoinositide-dependent protein kinase 2 (PDPK2P)	PF00069	25.616 (52/203)	3.34E-15
Extracellular signal-regulated kinase 1 (ERK1)	PF00069	30.846 (62/201)	4.03E-15
Inhibitor of nuclear factor kappa-B kinase alpha (IKKA)	PF18397 ; PF12179 ; PF00069 More >>	26.667 (56/210)	4.05E-15
NIMA-related kinase 2 (NEK2)	PF00069	24.904 (65/261)	4.65E-15
Cyclin-dependent kinase 13 (CDK13)	PF12330 ; PF00069	26.106 (59/226)	4.75E-15
NIMA-related kinase 1 (NEK1)	PF00069	25.907 (50/193)	4.95E-15
PAK-4 protein kinase (PAK4)	PF00786 ; PF00069	28.704 (62/216)	5.19E-15
Polo-like kinase 2 (PLK2)	PF00069 ; PF00659	26.482 (67/253)	5.54E-15
Phosphoinositide dependent protein kinase-1 (PDPK1)	PF14593 ; PF00069	25.616 (52/203)	6.25E-15
Activin receptor type IB (ACVR1B)	PF01064 ; PF00069 ; PF08515 More >>	26.821 (81/302)	6.96E-15
Ribosomal protein S6 kinase beta-1 (S6K1)	PF00069 ; PF00433	25.461 (69/271)	7.57E-15
Serine/threonine-protein kinase D2 (PRKD2)	PF00130 ; PF00069	25.339 (56/221)	8.56E-15
Ste-20-related kinase (STK39)	PF12202 ; PF00069	24.823 (70/282)	9.62E-15
Oxidative stress responsive 1 (OXSR1)	PF12202 ; PF00069	25.267 (71/281)	1.73E-14
Myosin light chain kinase family member 4 (MYLK4)	PF00069	27.228 (55/202)	1.87E-14
Serine/threonine-protein kinase Nek3 (NEK3)	PF00069	23.171 (57/246)	1.92E-14
Polo-like kinase 1 (PLK1)	PF00069 ; PF00659	28.241 (61/216)	2.31E-14
Cyclin-dependent kinase 2 (CDK2)	PF00069	28.571 (56/196)	2.56E-14
Aurora kinase C (AURKC)	PF00069	26.768 (53/198)	3.19E-14
Protein kinase D (PRKD1)	PF00130 ; PF00169 ; PF00069 More >>	24.670 (56/227)	4.31E-14
ERK activator kinase 5 (MAP2K5)	PF00564 ; PF00069	28.409 (50/176)	4.91E-14
Cyclin-dependent kinase 3 (CDK3)	PF00069	28.571 (56/196)	5.48E-14
Serine/threonine-protein kinase 32A (STK32A)	PF00069	26.126 (58/222)	6.29E-14
Aurora kinase A (AURKA)	PF00069	27.602 (61/221)	6.46E-14
Calcium/calmodulin-dependent protein kinase type 1D (CAMK1D)	PF00069	24.901 (63/253)	7.35E-14
IL-1 receptor-associated kinase 3 (IRAK3)	PF00531 ; PF00069	25.267 (71/281)	8.10E-14
Apoptosis signal-regulating kinase 1 (MAP3K5)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	29.808 (62/208)	8.90E-14
Serine/threonine-protein kinase H1 (PSKH1)	PF00069	27.232 (61/224)	9.21E-14
Tyrosine-protein kinase EIF2AK2 (p68)	PF00035 ; PF00069	22.870 (51/223)	9.48E-14
Serine/threonine-protein kinase D3 (PRKD3)	PF00130 ; PF00169 ; PF00069 More >>	25.217 (58/230)	1.16E-13
Cyclin-dependent kinase 12 (CDK12)	PF00069	25.229 (55/218)	1.20E-13
Protein kinase C alpha (PRKCA)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	27.650 (60/217)	1.47E-13
Leucine-rich repeat serine/threonine-protein kinase 1 (LRRK1)	PF12796 ; PF16095 ; PF00069 ; PF08477 More >>	27.917 (67/240)	1.53E-13
Death-associated protein kinase 1 (DAPK1)	PF00023 ; PF12796 ; PF13637 ; PF00531 ; PF00069 More >>	28.182 (62/220)	1.73E-13
Serine/threonine-protein kinase NLK (NLK)	PF00069	29.756 (61/205)	1.83E-13
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	PF18397 ; PF12179 ; PF00069 More >>	23.232 (69/297)	2.12E-13
SNF-related serine/threonine-protein kinase (SNRK)	PF00069	23.193 (77/332)	2.16E-13
Mitogen-activated protein kinase 13 (MAPK13)	PF00069	29.224 (64/219)	2.28E-13
Ribosomal protein S6 kinase alpha-5 (RSK5)	PF00069 ; PF00433	28.667 (43/150)	2.30E-13
Mitogen-activated protein kinase 15 (MAPK15)	PF00069	28.431 (58/204)	2.50E-13
Putative serine/threonine-protein kinase PRKY (PRKY)	PF00069	26.866 (54/201)	2.69E-13
Cyclin-dependent kinase 17 (CDK17)	PF12330 ; PF00069	26.368 (53/201)	4.56E-13
Dual specificity mitogen-activated protein kinase kinase 6 (MAP2K6)	PF00069	27.798 (77/277)	4.61E-13
Stress-activated protein kinase 2b (p38 beta)	PF00069	27.426 (65/237)	7.29E-13
MAP kinase p38 (MAPK12)	PF00069	26.061 (86/330)	8.45E-13
Serine/threonine-protein kinase tousled-like 2 (TLK2)	PF00069	25.794 (65/252)	8.88E-13
ERK activator kinase 7 (MAP2K7)	PF00069	28.462 (74/260)	9.87E-13
MAPK/ERK kinase kinase 1 (MAP3K1)	PF00069	25.352 (54/213)	1.01E-12
Protein kinase C delta (PRKCD)	PF00130 ; PF00069 ; PF00433 More >>	24.390 (50/205)	1.29E-12
cAMP-dependent protein kinase catalytic subunit PRKX (PRKX)	PF00069	26.866 (54/201)	1.39E-12
Serine/threonine-protein kinase TAO2 (TAOK2)	PF00069	28.000 (63/225)	1.43E-12
Protein kinase C theta (PRKCQ)	PF00130 ; PF00069 ; PF00433 More >>	24.091 (53/220)	1.47E-12
Hormonally up-regulated neu tumor-associated kinase (HUNK)	PF00069	26.523 (74/279)	1.62E-12
MAPK/ERK kinase kinase 4 (MAP3K4)	PF19431 ; PF00069	29.694 (68/229)	1.82E-12
Apoptosis signal-regulating kinase 2 (MAP3K6)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	28.326 (66/233)	1.83E-12
Cyclin-dependent kinase 1 (CDK1)	PF00069	25.296 (64/253)	1.88E-12
TGF-beta receptor type I (TGFBR1)	PF01064 ; PF00069 ; PF08515 More >>	26.351 (78/296)	2.10E-12
Testis-specific serine kinase 2 (TSSK2)	PF00069	25.954 (68/262)	2.10E-12
STE20-related serine/threonine-protein kinase (SLK)	PF00069 ; PF12474	27.907 (60/215)	2.11E-12
Ribosomal protein S6 kinase beta-2 (RPS6KB2)	PF00069 ; PF00433	25.103 (61/243)	2.12E-12
TAO kinase 1 (TAOK1)	PF00069	25.392 (81/319)	2.22E-12
Stress-activated protein kinase 2a (p38 alpha)	PF00069	26.923 (56/208)	2.29E-12
Cyclin-dependent kinase-like 2 (CDKL2)	PF00069	30.102 (59/196)	2.67E-12
Cyclin-dependent kinase 14 (CDK14)	PF00069	24.742 (48/194)	2.88E-12
Death-associated protein kinase 3 (DAPK3)	PF00069	26.728 (58/217)	3.53E-12
Mitogen-activated protein kinase kinase kinase 15 (MAP3K15)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	27.670 (57/206)	4.09E-12
Yet another novel kinase 2 (STK32B)	PF00069	25.210 (60/238)	4.68E-12
Bone morphogenetic protein receptor (BMPR2)	PF01064 ; PF00069	28.251 (63/223)	4.89E-12
BR serine/threonine kinase 1 (BRSK1)	PF00069	24.400 (61/250)	5.05E-12
Cyclin-dependent kinase 9 (CDK9)	PF00069	26.923 (56/208)	5.28E-12
Cyclin-dependent kinase 18 (CDK18)	PF00069	24.103 (47/195)	5.35E-12
Serine/threonine-protein kinase tousled-like 1 (TLK1)	PF00069	26.316 (60/228)	5.45E-12
Proto-oncogene serine/threonine-protein kinase mos (MOS)	PF00069	25.632 (71/277)	5.86E-12
Doublecortin-like kinase 1 (DCLK1)	PF03607 ; PF00069	28.507 (63/221)	6.50E-12
Checkpoint kinase-1 (CHK1)	PF00069	28.230 (59/209)	6.57E-12
cAMP-dependent protein kinase catalytic subunit gamma (PRKACG)	PF00069	23.770 (58/244)	7.21E-12
Serine/threonine-protein kinase Sgk3 (SGK3)	PF00069 ; PF00433 ; PF00787 More >>	27.317 (56/205)	8.87E-12
Cyclin-dependent kinase 15 (CDK15)	PF00069	23.881 (48/201)	9.32E-12
Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE)	PF00069 ; PF18394 ; PF18396 More >>	27.230 (58/213)	9.76E-12
Cyclin-dependent kinase 5 (CDK5)	PF00069	25.676 (57/222)	9.88E-12
Leucine-rich repeat kinase 2 (LRRK2)	PF16095 ; PF12799 ; PF13855 ; PF00069 ; PF08477 More >>	23.616 (64/271)	1.02E-11
PAK-2 protein kinase (PAK2)	PF00786 ; PF00069	25.118 (53/211)	1.03E-11
Death-associated protein kinase 2 (DAPK2)	PF00069	27.727 (61/220)	1.07E-11
Stress-activated protein kinase JNK1 (JNK1)	PF00069	29.353 (59/201)	1.11E-11
Calcium/calmodulin-dependent protein kinase type 1B (PNCK)	PF00069	25.630 (61/238)	1.12E-11
Unc-51 like kinase 3 (ULK3)	PF04212 ; PF00069	23.984 (59/246)	1.13E-11
Serine/threonine-protein kinase WNK1 (WNK1)	PF12202 ; PF00069	26.957 (62/230)	1.21E-11
Cyclin-dependent kinase 16 (CDK16)	PF12330 ; PF00069	24.615 (48/195)	1.28E-11
Stress-activated protein kinase JNK3 (JNK3)	PF00069	28.856 (58/201)	1.31E-11
Cyclin-dependent kinase 11B (CDK11B)	PF00069	29.000 (58/200)	1.63E-11
Cyclin-dependent kinase 11A (CDK11A)	PF00069	29.353 (59/201)	1.71E-11
Serine/threonine-protein kinase PAK 3 (PAK3)	PF00786 ; PF00069	24.820 (69/278)	2.13E-11
Testis-specific serine/threonine-protein kinase 1 (TSSK1B)	PF00069	26.592 (71/267)	2.15E-11
Cyclin-dependent kinase-like 3 (CDKL3)	PF00069	23.864 (63/264)	2.21E-11
STE20-related kinase adapter protein alpha (STRADA)	PF00069	26.087 (60/230)	2.26E-11
PAK-1 protein kinase (PAK1)	PF00786 ; PF00069	25.234 (54/214)	2.33E-11
BR serine/threonine kinase 2 (BRSK2)	PF00069	24.167 (58/240)	2.57E-11
Testis-specific serine/threonine-protein kinase 3 (TSSK3)	PF00069	26.563 (68/256)	2.61E-11
Serine/threonine-protein kinase 10 (STK10)	PF00069 ; PF12474	26.389 (57/216)	2.76E-11
Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMK2A)	PF08332 ; PF00069	23.478 (54/230)	2.78E-11
Serine/threonine-protein kinase Sgk2 (SGK2)	PF00069 ; PF00433	25.856 (68/263)	2.81E-11
MEK kinase kinase 3 (MAP4K3)	PF00780 ; PF00069	29.703 (60/202)	3.31E-11
Serine/threonine-protein kinase Sgk1 (SGK1)	PF00069 ; PF00433	26.341 (54/205)	3.36E-11
Cyclin-dependent kinase 6 (CDK6)	PF00069	26.383 (62/235)	3.72E-11
Serine/threonine-protein kinase H2 (PSKH2)	PF00069	25.893 (58/224)	4.03E-11
TAO kinase 3 (TAOK3)	PF00069	25.723 (80/311)	4.28E-11
SPS1/STE20-related protein kinase YSK4 (YSK4)	PF00069	23.622 (60/254)	4.33E-11
MAPK/ERK kinase kinase 3 (MAP3K3)	PF00564 ; PF00069	27.014 (57/211)	4.52E-11
Citron Rho-interacting kinase (CIT)	PF00780 ; PF00169 ; PF00069 More >>	25.660 (68/265)	4.97E-11
ERK activator kinase 1 (MEK1)	PF00069	28.866 (56/194)	5.06E-11
Protein kinase C epsilon (PRKCE)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	25.439 (58/228)	5.49E-11
TGF-beta-stimulated factor 1 (STK16)	PF00069	25.207 (61/242)	5.53E-11
TRAF2 and NCK interacting kinase (TNIK)	PF00780 ; PF00069	27.103 (58/214)	6.28E-11
Cyclin-dependent kinase-like 4 (CDKL4)	PF00069	26.699 (55/206)	6.30E-11
ERK activator kinase 2 (MEK2)	PF00069	27.500 (55/200)	7.77E-11
Stress-activated protein kinase JNK2 (JNK2)	PF00069	28.141 (56/199)	8.58E-11
Cytoplasmic DRAK1 (STK17A)	PF00069	27.950 (45/161)	9.67E-11
MEK kinase kinase 1 (MAP4K1)	PF00780 ; PF00069	25.188 (67/266)	9.94E-11
Maternal embryonic leucine zipper kinase (MELK)	PF02149 ; PF00069	26.506 (66/249)	1.17E-10
Cyclin-dependent kinase 20 (CDK20)	PF00069	25.581 (44/172)	1.19E-10
Protein kinase C eta type (PRKCH)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	25.463 (55/216)	1.30E-10
Testis-specific serine/threonine-protein kinase 6 (TSSK6)	PF00069	24.335 (64/263)	1.38E-10
Serine/threonine-protein kinase 32C (STK32C)	PF00069	24.675 (57/231)	1.39E-10
WNK lysine-deficient protein kinase 3 (WNK3)	PF12202 ; PF00069	28.571 (54/189)	1.61E-10
Serine/threonine-protein kinase Nek10 (NEK10)	PF00069	23.741 (66/278)	1.93E-10
Doublecortin-like kinase 2 (DCLK2)	PF03607 ; PF00069	25.541 (59/231)	2.22E-10
Calcium/calmodulin-dependent protein kinase type IV (CAMK4)	PF00069	27.869 (51/183)	2.41E-10
Cyclin-dependent kinase 4 (CDK4)	PF00069	26.442 (55/208)	2.45E-10
Protein kinase C gamma (PRKCG)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	24.034 (56/233)	2.89E-10
RAC-gamma serine/threonine-protein kinase (AKT3)	PF00169 ; PF00069 ; PF00433 More >>	27.039 (63/233)	3.04E-10
Aurora kinase B (AURKB)	PF00069	24.885 (54/217)	3.04E-10
Misshapen-like kinase 1 (MINK1)	PF00780 ; PF00069	28.037 (60/214)	3.07E-10
Protein kinase C beta (PRKCB)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	24.424 (53/217)	3.44E-10
Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3)	PF00069	29.630 (72/243)	3.84E-10
Mitogen-activated protein kinase 6 (MAPK6)	PF00069	28.718 (56/195)	4.63E-10
cAMP-dependent protein kinase catalytic subunit alpha (PRKACA)	PF00069	25.403 (63/248)	4.79E-10
Cyclin-dependent kinase-like 5 (CDKL5)	PF00069	26.804 (52/194)	4.80E-10
MAPK-activated protein kinase 3 (MAPKAPK3)	PF00069	24.242 (56/231)	5.30E-10
Activin receptor type IIA (ACVR2A)	PF01064 ; PF00069	27.014 (57/211)	5.59E-10
G protein-coupled receptor kinase 4 (GRK4)	PF00069 ; PF00615	26.339 (59/224)	6.47E-10
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform (PHKG1)	PF00069	26.738 (50/187)	8.28E-10
IL-1 receptor-associated kinase 1 (IRAK1)	PF00531 ; PF00069	25.106 (59/235)	1.01E-09
NF-kappa-B-activating kinase (TBK1)	PF00069 ; PF18394 ; PF18396 More >>	26.267 (57/217)	1.02E-09
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	PF00069	27.925 (74/265)	1.06E-09
Titin (TTN)		28.497 (55/193)	1.07E-09
RAC-beta serine/threonine-protein kinase (AKT2)	PF00169 ; PF00069 ; PF00433 More >>	23.108 (58/251)	1.17E-09
Calcium/calmodulin-dependent protein kinase type II subunit beta (CAMK2B)	PF08332 ; PF00069	22.927 (47/205)	1.17E-09
Mitogen-activated protein kinase 4 (MAPK4)	PF00069	26.738 (50/187)	1.22E-09
G protein-coupled receptor kinase 5 (GRK5)	PF00069 ; PF00615	26.214 (54/206)	1.33E-09
Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D)	PF08332 ; PF00069	23.556 (53/225)	1.51E-09
G protein-coupled receptor kinase 6 (GRK6)	PF00069 ; PF00615	25.664 (58/226)	1.61E-09
MEK kinase kinase 4 (MAP4K4)	PF00780 ; PF00069	28.169 (60/213)	1.80E-09
MAPK/ERK kinase kinase 2 (MAP3K2)	PF00564 ; PF00069	25.283 (67/265)	2.62E-09
cAMP-dependent protein kinase catalytic subunit beta (PRKACB)	PF00069	24.664 (55/223)	2.64E-09
MEK kinase kinase 2 (MAP4K2)	PF00780 ; PF00069	26.154 (51/195)	2.83E-09
Ribosomal protein S6 kinase-related protein (RSKR)	PF00069	28.477 (43/151)	3.04E-09
Glycogen synthase kinase-3 alpha (GSK-3A)	PF00069	28.293 (58/205)	3.47E-09
Cyclin-dependent kinase-like 1 (CDKL1)	PF00069	27.041 (53/196)	4.39E-09
CDC42 binding protein kinase alpha (DMPK-like alpha)	PF00130 ; PF00780 ; PF08826 ; PF15796 ; PF00069 ; PF00433 More >>	26.540 (56/211)	4.66E-09
Doublecortin-like kinase 3 (DCLK3)	PF00069	23.980 (47/196)	5.12E-09
Microtubule-associated serine/threonine-protein kinase 2 (MAST2)	PF08926 ; PF17820 ; PF00069 More >>	25.221 (57/226)	5.19E-09
Phosphorylase kinase testis gamma 2 (PHKG2)	PF00069	25.946 (48/185)	6.20E-09
Calcium/calmodulin-dependent protein kinase type II subunit gamma (CAMK2G)	PF08332 ; PF00069	21.739 (50/230)	6.42E-09
Cyclin-dependent kinase 10 (CDK10)	PF00069	25.472 (54/212)	6.77E-09
CaM-kinase IV kinase (CAMKK1)	PF00069	28.571 (46/161)	8.22E-09
Myosin-IIIa (MYO3A)	PF00612 ; PF00063 ; PF00069 More >>	24.164 (65/269)	8.40E-09
Serine/threonine-protein kinase WNK2 (WNK2)	PF12202 ; PF00069	28.729 (52/181)	8.61E-09
Mitogen-activated protein kinase kinase kinase kinase 5 (MAP4K5)	PF00780 ; PF00069	26.131 (52/199)	9.29E-09
MAPK-activated protein kinase 2 (MAPKAPK2)	PF00069	26.452 (41/155)	9.33E-09
Serine/threonine-protein kinase MRCK beta (CDC42BPB)	PF00130 ; PF00780 ; PF08826 ; PF15796 ; PF00069 More >>	24.893 (58/233)	1.07E-08
Serine/threonine-protein kinase 17B (STK17B)	PF00069	23.963 (52/217)	1.24E-08
Microtubule-associated serine/threonine-protein kinase 4 (MAST4)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	24.742 (72/291)	1.24E-08
Serine/threonine kinase-like domain-containing protein STKLD1 (STKLD1)	PF00069	35.955 (32/89)	1.32E-08
Serine/threonine-protein kinase WNK4 (WNK4)	PF12202 ; PF00069	28.272 (54/191)	1.49E-08
Microtubule-associated serine/threonine-protein kinase 3 (MAST3)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	26.519 (48/181)	1.82E-08
Serine/threonine-protein kinase pim-1 (PIM1)	PF00069	24.561 (70/285)	1.85E-08
Serine/threonine-protein kinase MRCK gamma (CDC42BPG)	PF00130 ; PF00780 ; PF08826 ; PF00069 More >>	24.345 (65/267)	2.08E-08
Serine/threonine-protein kinase pim-2 (PIM2)	PF00069	29.560 (47/159)	2.23E-08
Microtubule-associated serine/threonine-protein kinase 1 (MAST1)	PF08926 ; PF17820 ; PF00069 More >>	29.221 (45/154)	2.29E-08
Myosin-IIIb (MYO3B)	PF00612 ; PF00063 ; PF00069 More >>	27.027 (60/222)	2.72E-08
MAPK/MAK/MRK overlapping kinase (MOK)	PF00069	28.000 (56/200)	2.75E-08
Serine/threonine-protein kinase STK11 (STK11)	PF00069	25.366 (52/205)	2.88E-08
RAC-alpha serine/threonine-protein kinase (AKT1)	PF00169 ; PF00069 ; PF00433 More >>	26.522 (61/230)	3.33E-08
Protein kinase C iota (PRKCI)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	21.724 (63/290)	3.49E-08
Serine/threonine-protein kinase Chk2 (RAD53)	PF00498 ; PF00069	26.293 (61/232)	3.83E-08
Ribosomal protein S6 kinase alpha-4 (RPS6KA4)	PF00069 ; PF00433	26.115 (41/157)	3.84E-08
Calmodulin-dependent kinase II (CAMKK2)	PF00069	25.229 (55/218)	4.25E-08
Homeodomain-interacting protein kinase 4 (HIPK4)	PF00069	25.410 (62/244)	4.60E-08
Protein kinase G2 (PRKG2)	PF00027 ; PF00069	22.925 (58/253)	4.81E-08
PDZ binding kinase (PBK)	PF00069	23.413 (59/252)	5.06E-08
Glycogen synthase kinase-3 beta (GSK-3B)	PF00069	28.365 (59/208)	6.04E-08
Testis-specific serine/threonine-protein kinase 4 (TSSK4)	PF00069	18.650 (58/311)	6.25E-08
CaM kinase-like vesicle-associated protein (CAMKV)	PF00069	23.431 (56/239)	8.38E-08
Protein kinase G1 (PRKG1)	PF00027 ; PF16808 ; PF00069 More >>	24.299 (52/214)	8.61E-08
TBC domain-containing protein kinase-like protein (TBCK)	PF00069 ; PF00566 ; PF00581 More >>	23.154 (69/298)	9.34E-08
STE20-related kinase adapter protein beta (STRADB)	PF00069	24.242 (64/264)	9.36E-08
Rhodopsin kinase GRK7 (GRK7)	PF00069 ; PF00615	26.066 (55/211)	9.40E-08
Cyclin-dependent kinase 19 (CDK19)	PF00069	25.000 (52/208)	1.02E-07
Endoplasmic reticulum to nucleus signaling 1 (ERN1)	PF00069 ; PF06479	25.949 (41/158)	1.23E-07
Eukaryotic translation initiation factor 2-alpha kinase 1 (EIF2AK1)	PF00069	28.571 (40/140)	1.39E-07
Nik-related protein kinase (NRK)	PF00780 ; PF00069	23.729 (56/236)	1.54E-07
Striated muscle preferentially expressed protein kinase (SPEG)	PF07679 ; PF00069 ; PF16650 More >>	23.497 (43/183)	1.68E-07
Activin receptor type IIB (ACVR2B)	PF01064 ; PF00069	29.078 (41/141)	2.00E-07
Membrane-associated kinase (PKMYT1)	PF00069	26.977 (58/215)	2.21E-07
NDR2 protein kinase (STK38L)	PF00069 ; PF00433	24.219 (62/256)	2.40E-07
PRKR-like endoplasmic reticulum kinase (PERK)	PF00069	28.571 (28/98)	2.55E-07
Serine/threonine-protein kinase greatwall (MASTL)	PF00069	26.667 (40/150)	2.85E-07
Protein kinase N3 (PKN3)	PF02185 ; PF00069 ; PF00433 More >>	24.900 (62/249)	2.86E-07
Peripheral plasma membrane protein CASK (CASK)	PF00625 ; PF02828 ; PF00595 ; PF00069 ; PF00018 More >>	25.472 (54/212)	3.78E-07
Serine/threonine-protein kinase ULK4 (ULK4)	PF00069	24.255 (57/235)	3.95E-07
Rho-associated protein kinase 2 (ROCK2)	PF00069 ; PF08912	25.446 (57/224)	4.33E-07
Rho-associated protein kinase 1 (ROCK1)	PF00069 ; PF08912	25.561 (57/223)	4.46E-07
Beta-adrenergic receptor kinase 2 (ADRBK2)	PF00169 ; PF00069 ; PF00615 More >>	23.744 (52/219)	4.49E-07
Protein kinase C zeta (PRKCZ)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	21.860 (47/215)	5.93E-07
Serine/threonine-protein kinase cot (COT)	PF00069	26.897 (39/145)	6.40E-07
NDR1 protein kinase (STK38)	PF00069 ; PF00433	24.111 (61/253)	6.55E-07
Interleukin-1 receptor-associated kinase-like 2 (IRAK2)	PF00531 ; PF00069	25.980 (53/204)	7.05E-07
Protein kinase N1 (PKN1)	PF02185 ; PF00069 ; PF00433 More >>	25.806 (56/217)	8.87E-07
Serine/threonine-protein kinase NIK (MAP3K14)	PF00069	26.291 (56/213)	1.14E-06
Beta-adrenergic receptor kinase 1 (ADRBK1)	PF00169 ; PF00069 ; PF00615 More >>	23.744 (52/219)	1.23E-06
Homeodomain-interacting protein kinase 3 (HIPK3)	PF00069	26.957 (62/230)	1.83E-06
PAS domain-containing serine/threonine-protein kinase (PASK)	PF13426 ; PF00069	25.822 (55/213)	3.14E-06
Serine/threonine-protein kinase PDIK1L (PDIK1L)	PF00069	24.701 (62/251)	3.55E-06
Cyclin-dependent kinase 8 (CDK8)	PF00069	23.034 (41/178)	3.94E-06
PIM-3 protein kinase (PIM3)	PF00069	23.958 (69/288)	4.63E-06
Anti-mullerian hormone II receptor (AMHR2)	PF00069	23.451 (53/226)	4.71E-06
Dual-specificity tyrosine-phosphorylation regulated kinase 3 (DYRK3)	PF00069	25.483 (66/259)	5.66E-06
Large tumor suppressor homolog 2 (LATS2)	PF00069 ; PF00433	21.348 (57/267)	6.31E-06
Serine/threonine-protein kinase LATS1 (LATS1)	PF00069 ; PF00627	25.806 (40/155)	7.28E-06
Serine/threonine-protein kinase Kist (UHMK1)	PF00069 ; PF00076	29.114 (46/158)	8.35E-06
Tau-tubulin kinase 2 (TTBK2)	PF00069	21.304 (49/230)	8.86E-06
Serine/threonine-protein kinase SBK2 (SBK2)	PF00069	27.136 (54/199)	1.57E-05
Homeodomain interacting protein kinase 2 (HIPK2)	PF00069	27.039 (63/233)	1.90E-05
MAPK-activated protein kinase 5 (MAPKAPK5)	PF00069	25.140 (45/179)	1.93E-05
Protein kinase N2 (PKN2)	PF02185 ; PF00069 ; PF00433 More >>	26.570 (55/207)	2.06E-05
Eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4)	PF12745 ; PF00069 ; PF05773 ; PF13393 More >>	26.056 (37/142)	2.83E-05
Serine/threonine-protein kinase/endoribonuclease IRE2 (ERN2)	PF00069 ; PF06479	32.609 (45/138)	3.05E-05
Rhodopsin kinase GRK1 (GRK1)	PF00069 ; PF00615	23.153 (47/203)	4.67E-05
Homeodomain-interacting protein kinase 1 (HIPK1)	PF00069	26.609 (62/233)	5.68E-05
Myotonin-protein kinase (DMPK)	PF08826 ; PF00069	24.299 (52/214)	7.26E-05
Cyclin-G-associated kinase (GAK)	PF00069 ; PF10409	20.938 (67/320)	8.65E-05
Triple functional domain protein (TRIO)	PF00650 ; PF07679 ; PF00169 ; PF00069 ; PF00621 ; PF16609 ; PF00018 ; PF00435 More >>	23.902 (49/205)	1.62E-04
SCY1-like protein 2 (SCYL2)	PF00069	27.642 (34/123)	2.40E-04
Dual specificity protein kinase TTK (MPS1)	PF00069	21.429 (60/280)	3.76E-04
Wee1-like protein kinase 2 (WEE2)	PF00069	26.490 (40/151)	4.89E-04
Wee1-like protein kinase (WEE1)	PF00069	28.467 (39/137)	6.92E-04
MAP kinase signal-integrating kinase 2 (MKNK2)	PF00069	22.222 (50/225)	7.04E-04
Sugen kinase 110 (SBK3)	PF00069	25.641 (40/156)	1.00E-03
Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3 (ARAP3)	PF01412 ; PF00169 ; PF00788 ; PF00620 ; PF07647 More >>	29.091 (16/55)	1.00E-03
Diacylglycerol kinase delta (DGKD)	PF00130 ; PF00609 ; PF00781 ; PF00169 ; PF07647 More >>	31.944 (23/72)	1.00E-03
Diacylglycerol kinase eta (DGKH)	PF00130 ; PF00609 ; PF00781 ; PF00169 ; PF07647 More >>	27.273 (18/66)	2.00E-03
Tau-tubulin kinase (TTBK1)	PF00069	20.444 (46/225)	3.00E-03
Serine/threonine-protein kinase 35 (STK35)	PF00069	26.429 (37/140)	4.00E-03
Serine/threonine-protein kinase PINK1, mitochondrial (PINK1)	PF00069	26.220 (43/164)	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	Pathway Map
Axon guidance	hsa04360	Affiliated Target
Class: Organismal Systems => Development and regeneration	Pathway Hierarchy

Degree	3	Degree centrality	3.22E-04	Betweenness centrality	1.30E-06
Closeness centrality	1.84E-01	Radiality	1.31E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	1.00E+01	Topological coefficient	5.63E-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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Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

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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