Details for: PDZK1

Gene ID: 5174

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PDZK1

Ensembl ID: ENSG00000174827

Description: PDZ domain containing 1

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • epithelial cell of proximal tubule CL0002306
    CSI 11.98
    rCSI 29.25%
    PRS 91.01
  • enteroendocrine cell CL0000164
    CSI 6.36
    rCSI 8.69%
    PRS 93.51
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 4.61
    rCSI 6.53%
    PRS 94.22
  • epithelial cell of proximal tubule segment 3 CL4030011
    CSI 4.16
    rCSI 33.05%
    PRS 91.35
  • midzonal region hepatocyte CL0019028
    CSI 3.98
    rCSI 9.33%
    PRS 92.51
  • renal principal cell CL0005009
    CSI 3.17
    rCSI 8.24%
    PRS 94.77
  • group 3 innate lymphoid cell CL0001071
    CSI 3.05
    rCSI 2.29%
    PRS 97
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.8
    rCSI 7.3%
    PRS 96.74
  • pancreatic A cell CL0000171
    CSI 2.78
    rCSI 2.91%
    PRS 96.16
  • enterocyte CL0000584
    CSI 2.75
    rCSI 4.44%
    PRS 92.83
  • intestinal epithelial cell CL0002563
    CSI 2.66
    rCSI 2.78%
    PRS 93.71
  • intrahepatic cholangiocyte CL0002538
    CSI 2.55
    rCSI 6.13%
    PRS 95.08
  • periportal region hepatocyte CL0019026
    CSI 2.48
    rCSI 9.64%
    PRS 92.25
  • M cell of gut CL0000682
    CSI 2.47
    rCSI 2.63%
    PRS 96.16
  • luminal epithelial cell of mammary gland CL0002326
    CSI 2.17
    rCSI 3.95%
    PRS 97.55
  • hepatocyte CL0000182
    CSI 2.16
    rCSI 3.87%
    PRS 93.87
  • colonocyte CL1000347
    CSI 2.15
    rCSI 3.08%
    PRS 93.78
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.08
    rCSI 5.28%
    PRS 92.15
  • centrilobular region hepatocyte CL0019029
    CSI 1.97
    rCSI 5.15%
    PRS 91.73
  • enteroendocrine cell of small intestine CL0009006
    CSI 1.88
    rCSI 4.13%
    PRS 95.94
  • parietal epithelial cell CL1000452
    CSI 1.71
    rCSI 4.56%
    PRS 92.49
  • renal interstitial pericyte CL1001318
    CSI 1.69
    rCSI 4.65%
    PRS 94.36
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.67
    rCSI 4.31%
    PRS 93.97
  • pancreatic ductal cell CL0002079
    CSI 1.63
    rCSI 3.17%
    PRS 95.96
  • podocyte CL0000653
    CSI 1.49
    rCSI 6.63%
    PRS 95.44
  • basket cell CL0000118
    CSI 1.14
    rCSI 7.15%
    PRS 80.89
  • enterocyte of epithelium of small intestine CL1000334
    CSI 0.43
    rCSI 6.72%
    PRS 95.7

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PDZK1](/details-gene/5174) (PDZ domain containing 1) is a protein-coding gene located on chromosome 1q21.1. It functions primarily as a scaffolding or adaptor protein, utilizing its four PDZ domains to organize and localize other proteins, particularly at the plasma membrane. Also known as Na+/H+ exchange regulatory cofactor NHE-RF3, it plays a critical role in regulating transmembrane transport of ions and other solutes. Expression data indicates that **Overall**, [PDZK1](/details-gene/5174) is most significantly expressed in specialized epithelial cells, with the highest significance observed in the [epithelial cell of proximal tubule](/details-cell/CL0002306) of the kidney. Its prominent role in tissues with high transport activity, such as the kidney, intestine, and liver, underscores its function in maintaining cellular homeostasis through the spatial organization of membrane-associated protein complexes. ## Cellular Roles and Expression Landscape The expression profile of [PDZK1](/details-gene/5174) highlights its essential function in epithelial cells specialized for absorption and secretion. **Overall**, the gene shows the highest significance in the [epithelial cell of proximal tubule](/details-cell/CL0002306) (CSI: 11.98), a cell type characterized by a dense brush border and high rates of molecular transport. This pattern is consistent across other functionally related cell types, including [enteroendocrine cell](/details-cell/CL0000164) (CSI: 6.36), [enterocyte](/details-cell/CL0000584) (CSI: 2.75), and [hepatocytes](/details-cell/CL0019028) (CSI: 3.98), suggesting a conserved role in organizing transport machinery in polarized epithelial tissues. The gene's significance extends to other renal and intestinal cell types such as [kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111) and [M cell of gut](/details-cell/CL0000682), further solidifying its identity as a key structural component in tissues that form a barrier and facilitate exchange with the external environment. This highly specific expression pattern in transport-heavy epithelia suggests a specialized function that is less critical in other lineages. ## Pathways and Molecular Function The molecular function of [PDZK1](/details-gene/5174) is centered on its role as a protein-membrane adaptor. Gene Ontology annotations confirm its involvement in `Pdz domain binding` ([GO:0030165](/details-go/GO:0030165)), `protein-membrane adaptor activity` ([GO:0043495](/details-go/GO:0043495)), and `protein binding` ([GO:0005515](/details-go/GO:0005515)). These functions enable it to act as a molecular scaffold, recruiting and stabilizing protein complexes at specific subcellular locations. Consistent with its expression in kidney and intestinal cells, [PDZK1](/details-gene/5174) is localized to the `apical plasma membrane` ([GO:0016324](/details-go/GO:0016324)), `brush border` ([GO:0005903](/details-go/GO:0005903)), and `microvillus membrane` ([GO:0031528](/details-go/GO:0031528)). Its biological processes are directly tied to this localization, where it facilitates the `positive regulation of cation transmembrane transport` ([GO:1904064](/details-go/GO:1904064)) and `protein localization to plasma membrane` ([GO:0072659](/details-go/GO:0072659)). Research has confirmed its role in organizing renal brush border ion exchangers ([Link](https://pubmed.ncbi.nlm.nih.gov/16141316/)) and its interaction with transporters like the cystic fibrosis transmembrane conductance regulator (CFTR) and the multidrug resistance-associated protein (MRP2) ([Link](https://doi.org/10.1016/s0092-8674(00)00096-9); [Link](https://pubmed.ncbi.nlm.nih.gov/10496535/)). ## Research Directions Evidence suggests that the role of [PDZK1](/details-gene/5174) extends beyond normal physiology into pathology. For instance, its upregulation has been noted in carcinomas, where it may contribute to tumor progression by interacting with and stabilizing multidrug resistance proteins like MRP2 ([Link](https://pubmed.ncbi.nlm.nih.gov/10496535/)). This creates a clear link between its scaffolding function and clinically relevant outcomes like chemoresistance. Based on its established functions and expression patterns, several testable hypotheses can be proposed: 1. Upregulation of [PDZK1](/details-gene/5174) in hepatocellular or colorectal carcinoma cells enhances chemoresistance by increasing the stability and membrane localization of ABC transporters like MRP2, thereby promoting drug efflux. 2. Genetic variants in [PDZK1](/details-gene/5174) that impair its PDZ domain binding capacity are associated with inherited renal transport disorders, such as Fanconi syndrome, due to the destabilization of apical transporters in proximal tubule cells. 3. In the intestine, [PDZK1](/details-gene/5174) acts as a master regulator of nutrient absorption by scaffolding not only ion exchangers but also key nutrient transporters like the sodium-coupled monocarboxylate transporters SMCT1/2 ([Link](https://doi.org/10.1007/s12576-018-00658-1)), and its disruption could contribute to malabsorption syndromes. To test the first hypothesis regarding chemoresistance, a key experiment could be designed. To test the role of [PDZK1](/details-gene/5174) in chemoresistance, one could perform a CRISPR-Cas9 knockout of the gene in a relevant carcinoma cell line (e.g., HepG2) that endogenously expresses both [PDZK1](/details-gene/5174) and MRP2. The knockout and wild-type control cells would then be treated with a known MRP2 substrate, such as cisplatin or doxorubicin. The impact on cell survival would be measured using viability assays, while MRP2 protein levels and localization would be assessed by western blotting and immunofluorescence, respectively. A significant increase in drug sensitivity in the [PDZK1](/details-gene/5174) knockout cells would validate its role in mediating resistance. As an intracellular scaffolding protein without enzymatic activity, [PDZK1](/details-gene/5174) presents a challenging direct therapeutic target. However, its function is mediated through specific protein-protein interactions. Therefore, a promising therapeutic strategy would be the development of small-molecule inhibitors designed to disrupt the binding between a specific PDZ domain on [PDZK1](/details-gene/5174) and its partner protein (e.g., MRP2). Such an approach would represent an **inhibition** strategy, aiming to functionally antagonize the scaffolding effect of [PDZK1](/details-gene/5174) and potentially re-sensitize resistant tumors to conventional chemotherapy.

Genular Protein ID: 3060900525

Symbol: NHRF3_HUMAN

Name: Na(+)/H(+) exchange regulatory cofactor NHE-RF3

UniProtKB Accession Codes:

Q5T2W1 B4DPB9 E7EU02 O60450 Q5T5P6 Q9BQ41

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 19 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 6 PDBsum 6 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 4 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9461128

Title: Identification and partial characterization of PDZK1: a novel protein containing PDZ interaction domains.

PubMed ID: 9461128

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 10496535

Title: PDZK1, a novel PDZ domain-containing protein up-regulated in carcinomas and mapped to chromosome 1q21, interacts with cMOAT (MRP2), the multidrug resistance-associated protein.

PubMed ID: 10496535

PubMed ID: 11051556

Title: Accessory protein facilitated CFTR-CFTR interaction, a molecular mechanism to potentiate the chloride channel activity.

PubMed ID: 11051556

DOI: 10.1016/s0092-8674(00)00096-9

PubMed ID: 15494376

Title: Bcr (breakpoint cluster region) protein binds to PDZ-domains of scaffold protein PDZK1 and vesicle coat protein Mint3.

PubMed ID: 15494376

DOI: 10.1242/jcs.01472

PubMed ID: 15766278

Title: The CFTR associated protein CAP70 interacts with the apical Cl-/HCO3-exchanger DRA in rabbit small intestinal mucosa.

PubMed ID: 15766278

DOI: 10.1021/bi048828b

PubMed ID: 16141316

Title: Role of PDZK1 in membrane expression of renal brush border ion exchangers.

PubMed ID: 16141316

DOI: 10.1073/pnas.0506578102

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 30604288

Title: Identification of the multivalent PDZ protein PDZK1 as a binding partner of sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8) and SMCT2 (SLC5A12).

PubMed ID: 30604288

DOI: 10.1007/s12576-018-00658-1

Sequence Information:

  • Length: 519
  • Mass: 57129
  • Checksum: 98BF707F87CD77A6
  • Sequence:
    • MTSTFNPREC KLSKQEGQNY GFFLRIEKDT EGHLVRVVEK CSPAEKAGLQ DGDRVLRING 
VFVDKEEHMQ VVDLVRKSGN SVTLLVLDGD SYEKAVKTRV DLKELGQSQK EQGLSDNILS 
PVMNGGVQTW TQPRLCYLVK EGGSYGFSLK TVQGKKGVYM TDITPQGVAM RAGVLADDHL 
IEVNGENVED ASHEEVVEKV KKSGSRVMFL LVDKETDKRH VEQKIQFKRE TASLKLLPHQ 
PRIVEMKKGS NGYGFYLRAG SEQKGQIIKD IDSGSPAEEA GLKNNDLVVA VNGESVETLD 
HDSVVEMIRK GGDQTSLLVV DKETDNMYRL AHFSPFLYYQ SQELPNGSVK EAPAPTPTSL 
EVSSPPDTTE EVDHKPKLCR LAKGENGYGF HLNAIRGLPG SFIKEVQKGG PADLAGLEDE 
DVIIEVNGVN VLDEPYEKVV DRIQSSGKNV TLLVCGKKAY DYFQAKKIPI VSSLADPLDT 
PPDSKEGIVV ESNHDSHMAK ERAHSTASHS SSNSEDTEM