Target Information

Target General Information

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Target ID

T73908 (Former ID: TTDI02557)

Target Name

Wnt-7a protein (WNT7A)

Synonyms

Protein Wnt-7a

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Gene Name

WNT7A

Target Type

Literature-reported target

[1]

Function

Plays an important role in embryonic development, including dorsal versus ventral patterning during limb development, skeleton development and urogenital tract development. Required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation. Required for normal, sexually dimorphic development of the Mullerian ducts, and for normal fertility in both sexes. Required for normal neural stem cell proliferation in the hippocampus dentate gyrus. Required for normal progress through the cell cycle in neural progenitor cells, for self-renewal of neural stem cells, and for normal neuronal differentiation and maturation. Promotes formation of synapses via its interaction with FZD5. Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway.

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UniProt ID

WNT7A_HUMAN

Sequence

MNRKARRCLGHLFLSLGMVYLRIGGFSSVVALGASIICNKIPGLAPRQRAICQSRPDAII
VIGEGSQMGLDECQFQFRNGRWNCSALGERTVFGKELKVGSREAAFTYAIIAAGVAHAIT
AACTQGNLSDCGCDKEKQGQYHRDEGWKWGGCSADIRYGIGFAKVFVDAREIKQNARTLM
NLHNNEAGRKILEENMKLECKCHGVSGSCTTKTCWTTLPQFRELGYVLKDKYNEAVHVEP
VRASRNKRPTFLKIKKPLSYRKPMDTDLVYIEKSPNYCEEDPVTGSVGTQGRACNKTAPQ
ASGCDLMCCGRGYNTHQYARVWQCNCKFHWCCYVKCNTCSERTEMYTCK

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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

Drug Binding Sites of Target

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Ligand Name: Palmitoleic acid

Ligand Info

Structure Description

STRUCTURE OF THE WNT DEACYLASE NOTUM IN COMPLEX WITH O-PALMITOLEOYL SERINE - CRYSTAL FORM IX - 1.5A

PDB:4UZQ

Method

X-ray diffraction

Resolution

1.50 Å

Mutation

Yes

[2]

PDB Sequence

Residue

Distance (Å)

SER206

1.344

Residue

Distance (Å)

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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 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 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 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 Pathway Affiliation

Biological Network Descriptors

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

KEGG Pathway	Pathway ID	Affiliated Target
mTOR signaling pathway	hsa04150	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Wnt signaling pathway	hsa04310	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Hippo signaling pathway	hsa04390	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Signaling pathways regulating pluripotency of stem cells	hsa04550	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
Melanogenesis	hsa04916	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy

Degree	4	Degree centrality	4.30E-04	Betweenness centrality	4.41E-06
Closeness centrality	1.92E-01	Radiality	1.33E+01	Clustering coefficient	3.33E-01
Neighborhood connectivity	2.05E+01	Topological coefficient	3.75E-01	Eccentricity	13
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Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

References

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REF 1

Wnt7a predicts poor prognosis, and contributes to growth and metastasis in tongue squamous cell carcinoma. Oncol Rep. 2019 Mar;41(3):1749-1758.

REF 2

Notum deacylates Wnt proteins to suppress signalling activity. Nature. 2015 Mar 12;519(7542):187-192.

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