Target Information

Target General Information

Target ID

T92078 (Former ID: TTDI01962)

Target Name

Dihydropyrimidinase related protein 2 (DPYSL2)

Synonyms

Unc33like phosphoprotein 2; Unc-33-like phosphoprotein 2; ULIP2; ULIP-2; N2A3; Dihydropyrimidinaserelated protein 2; Dihydropyrimidinase-related protein 2; DRP2; DRP-2; Collapsin response mediator protein 2; CRMP2; CRMP-2

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Gene Name

DPYSL2

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Epilepsy/seizure [ICD-11: 8A61-8A6Z]

Function

Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. May play a role in endocytosis. Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration.

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UniProt ID

DPYL2_HUMAN

Sequence

MSYQGKKNIPRITSDRLLIKGGKIVNDDQSFYADIYMEDGLIKQIGENLIVPGGVKTIEA
HSRMVIPGGIDVHTRFQMPDQGMTSADDFFQGTKAALAGGTTMIIDHVVPEPGTSLLAAF
DQWREWADSKSCCDYSLHVDISEWHKGIQEEMEALVKDHGVNSFLVYMAFKDRFQLTDCQ
IYEVLSVIRDIGAIAQVHAENGDIIAEEQQRILDLGITGPEGHVLSRPEEVEAEAVNRAI
TIANQTNCPLYITKVMSKSSAEVIAQARKKGTVVYGEPITASLGTDGSHYWSKNWAKAAA
FVTSPPLSPDPTTPDFLNSLLSCGDLQVTGSAHCTFNTAQKAVGKDNFTLIPEGTNGTEE
RMSVIWDKAVVTGKMDENQFVAVTSTNAAKVFNLYPRKGRIAVGSDADLVIWDPDSVKTI
SAKTHNSSLEYNIFEGMECRGSPLVVISQGKIVLEDGTLHVTEGSGRYIPRKPFPDFVYK
RIKARSRLAELRGVPRGLYDGPVCEVSVTPKTVTPASSAKTSPAKQQAPPVRNLHQSGFS
LSGAQIDDNIPRRTTQRIVAPPGGRANITSLG

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3D Structure

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PDB

HIT2.0 ID

T54RPK

Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

Lacosamide

Drug Info

Approved

Convulsion

[1], [2]

Mode of Action

[+] 1 Modes of Action

Modulator

[+] 1 Modulator drugs

Lacosamide

Drug Info

[1]

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: 1beta-Hydroxyalantolactone

Ligand Info

Structure Description

CYS179 and CYS504 of CRMP2 were covalently binded by a Sesquiterpene lactone

PDB:7X68

Method

X-ray diffraction

Resolution

1.80 Å

Mutation

[3]

PDB Sequence

DRLLIKGGKI

²⁴

VNDDQSFYAD

³⁴

IYMEDGLIKQ

⁴⁴

IGENLIVPGG

⁵⁴

VKTIEAHSRM

⁶⁴

VIPGGIDVHT

⁷⁴

RFQMPDQGMT

⁸⁴

SADDFFQGTK

⁹⁴

AALAGGTTMI

¹⁰⁴

IDHVVPEPGT

¹¹⁴

SLLAAFDQWR

¹²⁴

EWADSKSCCD

¹³⁴

YSLHVDISEW

¹⁴⁴

HKGIQEEMEA

¹⁵⁴

LVKDHGVNSF

¹⁶⁴

LVYMAFKDRF

¹⁷⁴

QLTDCQIYEV

¹⁸⁴

LSVIRDIGAI

¹⁹⁴

AQVHAENGDI

²⁰⁴

IAEEQQRILD

²¹⁴

LGITGPEGHV

²²⁴

LSRPEEVEAE

²³⁴

AVNRAITIAN

²⁴⁴

QTNCPLYITK

²⁵⁴

VMSKSSAEVI

²⁶⁴

AQARKKGTVV

²⁷⁴

YGEPITASLG

²⁸⁴

TDGSHYWSKN

²⁹⁴

WAKAAAFVTS

³⁰⁴

PPLSPDPTTP

³¹⁴

DFLNSLLSCG

³²⁴

DLQVTGSAHC

³³⁴

TFNTAQKAVG

³⁴⁴

KDNFTLIPEG

³⁵⁴

TNGTEERMSV

³⁶⁴

IWDKAVVTGK

³⁷⁴

MDENQFVAVT

³⁸⁴

STNAAKVFNL

³⁹⁴

YPRKGRIAVG

⁴⁰⁴

SDADLVIWDP

⁴¹⁴

DSVKTISAKT

⁴²⁴

HNSSLEYNIF

⁴³⁴

EGMECRGSPL

⁴⁴⁴

VVISQGKIVL

⁴⁵⁴

EDGTLHVTEG

⁴⁶⁴

SGRYIPRKPF

⁴⁷⁴

PDFVYKRIKA

⁴⁸⁴

RSRLAELRGV

⁴⁹⁴

PRGLYDGPVC

⁵⁰⁴

Residue

Distance (Å)

CYS179

1.621

GLU183

3.986

Residue

Distance (Å)

CYS504

1.596

GLU505

3.658

Click to View More Binding Site Information of This Target with Different Ligands

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

There is no similarity protein (E value < 0.005) for this target


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	7	Degree centrality	7.52E-04	Betweenness centrality	3.98E-04
Closeness centrality	2.17E-01	Radiality	1.38E+01	Clustering coefficient	4.76E-02
Neighborhood connectivity	1.54E+01	Topological coefficient	1.57E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

Co-Targets

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Co-Targets

Co-Targets Info

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

References

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REF 1

2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7472).

REF 3

CYS179 and CYS504 of CRMP2 were covalently binded by a Sesquiterpene lactone

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