Target Information

Target General Information

Target ID

T71492 (Former ID: TTDR01013)

Target Name

PDZ domain containing-protein (PDZK1)

Synonyms

Sodium-hydrogen exchanger regulatory factor 3; PDZD1; PDZ domain-containing protein 1; NaPi-Cap1; Na/Pi cotransporter C-terminal-associated protein 1; Na(+)/H(+) exchanger regulatory factor 3; Na(+)/H(+) exchange regulatory cofactor NHE-RF3; NHERF3; NHERF-3; Multi-PDZ domain containing adaptor protein; CFTR-associated protein of 70 kDa; CAP70

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Gene Name

PDZK1

Target Type

Literature-reported target

[1]

Function

May be involved in the coordination of a diverse range of regulatory processes for ion transport and second messenger cascades. In complex with SLC9A3R1, may cluster proteins that are functionally dependent in a mutual fashion and modulate the trafficking and the activity of the associated membrane proteins. May play a role in the cellular mechanisms associated with multidrug resistance through its interaction with ABCC2 and PDZK1IP1. May potentiate the CFTR chloride channel activity. Required for normal cell-surface expression of SCARB1. Plays a role in maintaining normal plasma cholesterol levels via its effects on SCARB1. Plays a role in the normal localization and function of the chloride-anion exchanger SLC26A6 to the plasma membrane in the brush border of the proximal tubule of the kidney. May be involved in the regulation of proximal tubular Na(+)-dependent inorganic phosphate cotransport therefore playing an important role in tubule function. A scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains.

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UniProt ID

NHRF3_HUMAN

Sequence

MTSTFNPRECKLSKQEGQNYGFFLRIEKDTEGHLVRVVEKCSPAEKAGLQDGDRVLRING
VFVDKEEHMQVVDLVRKSGNSVTLLVLDGDSYEKAVKTRVDLKELGQSQKEQGLSDNILS
PVMNGGVQTWTQPRLCYLVKEGGSYGFSLKTVQGKKGVYMTDITPQGVAMRAGVLADDHL
IEVNGENVEDASHEEVVEKVKKSGSRVMFLLVDKETDKRHVEQKIQFKRETASLKLLPHQ
PRIVEMKKGSNGYGFYLRAGSEQKGQIIKDIDSGSPAEEAGLKNNDLVVAVNGESVETLD
HDSVVEMIRKGGDQTSLLVVDKETDNMYRLAHFSPFLYYQSQELPNGSVKEAPAPTPTSL
EVSSPPDTTEEVDHKPKLCRLAKGENGYGFHLNAIRGLPGSFIKEVQKGGPADLAGLEDE
DVIIEVNGVNVLDEPYEKVVDRIQSSGKNVTLLVCGKKAYDYFQAKKIPIVSSLADPLDT
PPDSKEGIVVESNHDSHMAKERAHSTASHSSSNSEDTEM

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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). 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 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).

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

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein (PREX2)	PF00610 ; PF00169 ; PF00621 More >>	24.324 (54/222)	4.49E-05
DEP domain-containing protein 6 (DEPTOR)	PF00610	32.353 (22/68)	1.00E-03


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.

Degree	5	Degree centrality	5.37E-04	Betweenness centrality	8.26E-04
Closeness centrality	1.95E-01	Radiality	1.34E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	5.80E+00	Topological coefficient	2.00E-01	Eccentricity	12
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Target Regulators

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Target-interacting Proteins

Target-interacting Proteins Info

References

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REF 1

Targeted disruption of the PDZK1 gene in mice causes tissue-specific depletion of the high density lipoprotein receptor scavenger receptor class B ... J Biol Chem. 2003 Dec 26;278(52):52820-5.

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