Target Information

Target General Information

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Target ID

T94366

Target Name

Hsp90 co-chaperone Cdc37 (CDC37)

Synonyms

p50Cdc37; Hsp90 co-chaperone Cdc37, N-terminally processed; Hsp90 chaperone protein kinase-targeting subunit; CDC37A

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Gene Name

CDC37

Target Type

Literature-reported target

[1]

Function

Inhibits HSP90AA1 ATPase activity. Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity.

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UniProt ID

CDC37_HUMAN

Sequence

MVDYSVWDHIEVSDDEDETHPNIDTASLFRWRHQARVERMEQFQKEKEELDRGCRECKRK
VAECQRKLKELEVAEGGKAELERLQAEAQQLRKEERSWEQKLEEMRKKEKSMPWNVDTLS
KDGFSKSMVNTKPEKTEEDSEEVREQKHKTFVEKYEKQIKHFGMLRRWDDSQKYLSDNVH
LVCEETANYLVIWCIDLEVEEKCALMEQVAHQTIVMQFILELAKSLKVDPRACFRQFFTK
IKTADRQYMEGFNDELEAFKERVRGRAKLRIEKAMKEYEEEERKKRLGPGGLDPVEVYES
LPEELQKCFDVKDVQMLQDAISKMDPTDAKYHMQRCIDSGLWVPNSKASEAKEGEEAGPG
DPLLEAVPKTGDEKDVSV

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3D Structure

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PDB

HIT2.0 ID

T89A2U

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: L-serine-O-phosphate

Ligand Info

Structure Description

Structure of the RAF1-HSP90-CDC37 complex (RHC-I)

PDB:7Z38

Method

Electron microscopy

Resolution

3.16 Å

Mutation

[2]

PDB Sequence

VDYSVWDHIE

¹¹

VDDEDETHPN

²²

IDTASLFRWR

³²

HQARVERMEQ

⁴²

FQKEKEELDR

⁵²

GCRECKRKVA

⁶²

ECQRKLKELE

⁷²

VAEGGKAELE

⁸²

RLQAEAQQLR

⁹²

KEERSWEQKL

¹⁰²

EEMRKKEKSM

¹¹²

PWNVDTLSKD

¹²²

GFSKSMVNTK

¹³²

PEKTEEDSEE

¹⁴²

VREQKHKTFV

¹⁵²

EKYEKQIKHF

¹⁶²

GMLRRWDDSQ

¹⁷²

KYLSDNVHLV

¹⁸²

CEETANYLVI

¹⁹²

WCIDLEVEEK

²⁰²

CALMEQVAHQ

²¹²

TIVMQFILEL

²²²

AKSLKVDPRA

²³²

CFRQFFTKIK

²⁴²

TADRQYMEGF

²⁵²

NDELEAFKER

²⁶²

VRGRAKLRIE

²⁷²

Residue

Distance (Å)

GLU11

3.668

VAL12

1.331

ASP14

1.327

ASP15

2.778

PHE29

4.086

Residue

Distance (Å)

ARG32

2.737

HIS33

2.610

ARG36

2.697

ASN115

4.672

VAL116

3.985

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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

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
PI3K-Akt signaling pathway	hsa04151	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy

Degree	10	Degree centrality	1.07E-03	Betweenness centrality	1.81E-04
Closeness centrality	2.40E-01	Radiality	1.42E+01	Clustering coefficient	3.56E-01
Neighborhood connectivity	4.91E+01	Topological coefficient	1.34E-01	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target