Details for: PDZK1IP1

Gene ID: 10158

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: PDZK1IP1

Ensembl ID: ENSG00000162366

Description: PDZK1 interacting protein 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 25.81
    rCSI 23.3%
    PRS 91.57
  • epithelial cell of proximal tubule CL0002306
    CSI 21.89
    rCSI 53.46%
    PRS 87.3
  • kidney epithelial cell CL0002518
    CSI 21.87
    rCSI 41.74%
    PRS 98.03
  • epithelial cell of lung CL0000082
    CSI 18.5
    rCSI 15.34%
    PRS 93.49
  • respiratory basal cell CL0002633
    CSI 16.76
    rCSI 17.36%
    PRS 93.83
  • pancreatic acinar cell CL0002064
    CSI 16.23
    rCSI 21.57%
    PRS 94.84
  • innate lymphoid cell CL0001065
    CSI 14.79
    rCSI 30.53%
    PRS 86.89
  • secretory cell CL0000151
    CSI 14.1
    rCSI 14.71%
    PRS 91.73
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 11.72
    rCSI 14.2%
    PRS 74.58
  • erythrocyte CL0000232
    CSI 11.68
    rCSI 26.5%
    PRS 90.53
  • mucous neck cell CL0000651
    CSI 11.54
    rCSI 16.63%
    PRS 94.66
  • serous secreting cell CL0000313
    CSI 10.72
    rCSI 54.21%
    PRS 95.47
  • fallopian tube secretory epithelial cell CL4030006
    CSI 9.26
    rCSI 8.92%
    PRS 91.4
  • mucus secreting cell CL0000319
    CSI 9.21
    rCSI 14.62%
    PRS 95.88
  • multi-ciliated epithelial cell CL0005012
    CSI 8.76
    rCSI 8.74%
    PRS 87.61
  • respiratory suprabasal cell CL4033048
    CSI 8.58
    rCSI 11%
    PRS 93.8
  • acinar cell CL0000622
    CSI 8.43
    rCSI 12.37%
    PRS 96.42
  • M cell of gut CL0000682
    CSI 8.27
    rCSI 8.78%
    PRS 94.28
  • goblet cell CL0000160
    CSI 7.78
    rCSI 7.35%
    PRS 90.56
  • intestine goblet cell CL0019031
    CSI 7.57
    rCSI 6.72%
    PRS 90.5
  • bronchial goblet cell CL1000312
    CSI 7.25
    rCSI 28.96%
    PRS 94.96
  • transit amplifying cell of colon CL0009011
    CSI 7.19
    rCSI 8.45%
    PRS 92.53
  • colon epithelial cell CL0011108
    CSI 7.01
    rCSI 7.34%
    PRS 90.52
  • renal interstitial pericyte CL1001318
    CSI 6.92
    rCSI 19.06%
    PRS 90.73
  • pancreatic ductal cell CL0002079
    CSI 6.01
    rCSI 11.69%
    PRS 93.67
  • nasal mucosa goblet cell CL0002480
    CSI 5.79
    rCSI 6.72%
    PRS 92.71
  • epithelial cell of lower respiratory tract CL0002632
    CSI 5.73
    rCSI 4.44%
    PRS 94.46
  • suprabasal keratinocyte CL4033013
    CSI 5.67
    rCSI 9.26%
    PRS 65.9
  • respiratory hillock cell CL4030023
    CSI 5.64
    rCSI 10.06%
    PRS 95.38
  • squamous epithelial cell CL0000076
    CSI 5.61
    rCSI 13.31%
    PRS 89.69
  • mammary gland epithelial cell CL0002327
    CSI 5.43
    rCSI 19.07%
    PRS 95.58
  • megakaryocyte CL0000556
    CSI 5.1
    rCSI 22.11%
    PRS 93.14
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 5.08
    rCSI 7.21%
    PRS 91.2
  • intrahepatic cholangiocyte CL0002538
    CSI 4.81
    rCSI 11.55%
    PRS 92.31
  • colonocyte CL1000347
    CSI 4.73
    rCSI 6.78%
    PRS 90.74
  • epithelial cell CL0000066
    CSI 4.49
    rCSI 6.9%
    PRS 81.38
  • mononuclear phagocyte CL0000113
    CSI 4.05
    rCSI 8.91%
    PRS 94.77
  • club cell CL0000158
    CSI 3.94
    rCSI 5.77%
    PRS 88.84
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 3.83
    rCSI 9.99%
    PRS 94.31
  • type L enteroendocrine cell CL0002279
    CSI 3.64
    rCSI 6.84%
    PRS 93.73
  • ciliated epithelial cell CL0000067
    CSI 3.41
    rCSI 3%
    PRS 84.97
  • basal cell of epidermis CL0002187
    CSI 3.37
    rCSI 5.97%
    PRS 65.9
  • cytotoxic T cell CL0000910
    CSI 3.29
    rCSI 18.87%
    PRS 91.02
  • enterocyte CL0000584
    CSI 3.29
    rCSI 5.3%
    PRS 89.91
  • platelet CL0000233
    CSI 3.27
    rCSI 13.58%
    PRS 88.87
  • serous secreting cell of bronchus submucosal gland CL4033005
    CSI 3.25
    rCSI 18.5%
    PRS 93.31
  • luminal epithelial cell of mammary gland CL0002326
    CSI 3.17
    rCSI 5.77%
    PRS 96.15
  • parietal epithelial cell CL1000452
    CSI 3.03
    rCSI 8.09%
    PRS 88.5
  • renal alpha-intercalated cell CL0005011
    CSI 3
    rCSI 4.02%
    PRS 95.01
  • tracheal goblet cell CL1000329
    CSI 2.98
    rCSI 6.51%
    PRS 94.18
  • conjunctival epithelial cell CL1000432
    CSI 2.74
    rCSI 4.19%
    PRS 91.64
  • kidney proximal convoluted tubule epithelial cell CL1000838
    CSI 2.67
    rCSI 28.36%
    PRS 84.29
  • colon goblet cell CL0009039
    CSI 2.61
    rCSI 6.2%
    PRS 93.69
  • myofibroblast cell CL0000186
    CSI 2.6
    rCSI 3.6%
    PRS 89.73
  • duct epithelial cell CL0000068
    CSI 2.6
    rCSI 3.81%
    PRS 95.27
  • acinar cell of salivary gland CL0002623
    CSI 2.45
    rCSI 57.19%
    PRS 96.44
  • lung secretory cell CL1000272
    CSI 2.23
    rCSI 5.53%
    PRS 93.57
  • transit amplifying cell CL0009010
    CSI 2.15
    rCSI 3.28%
    PRS 95.31
  • foveolar cell of stomach CL0002179
    CSI 2.12
    rCSI 4.5%
    PRS 93.94
  • lung ciliated cell CL1000271
    CSI 2.06
    rCSI 2.38%
    PRS 87.98
  • respiratory goblet cell CL0002370
    CSI 2.04
    rCSI 22.22%
    PRS 94.67
  • melanocyte of skin CL1000458
    CSI 1.99
    rCSI 2.71%
    PRS 65.72
  • keratinocyte CL0000312
    CSI 1.95
    rCSI 1.64%
    PRS 92.27
  • epithelial cell of proximal tubule segment 3 CL4030011
    CSI 1.78
    rCSI 14.13%
    PRS 88.58
  • tracheobronchial serous cell CL0019001
    CSI 1.52
    rCSI 6.58%
    PRS 94.3
  • glandular epithelial cell CL0000150
    CSI 1.42
    rCSI 3.74%
    PRS 97.28
  • epithelial cell of esophagus CL0002252
    CSI 1.31
    rCSI 12.9%
    PRS 91.26
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.28
    rCSI 3.44%
    PRS 94.18
  • luminal cell of prostate epithelium CL0002340
    CSI 1.27
    rCSI 6.83%
    PRS 95.44
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.22
    rCSI 3.14%
    PRS 90.62
  • helper T cell CL0000912
    CSI 1.04
    rCSI 1.47%
    PRS 88.24
  • transit amplifying cell of small intestine CL0009012
    CSI 0.79
    rCSI 3.47%
    PRS 95.01
  • intestinal crypt stem cell of colon CL0009043
    CSI 0.56
    rCSI 4.24%
    PRS 96.03
  • peptic cell CL0000155
    CSI 0.47
    rCSI 4.62%
    PRS 95.31
  • paneth cell of colon CL0009009
    CSI 0.37
    rCSI 3.59%
    PRS 94.84

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)

Loading network (please wait)...

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 [PDZK1IP1](/details-gene/10158), also known as PDZK1 interacting protein 1 or MAP17, is a protein-coding gene located on human chromosome 1. It functions as a membrane-associated protein involved in [protein binding (GO:0005515)](https://www.ebi.ac.uk/QuickGO/term/GO:0005515) and is localized to the [membrane (GO:0016020)](https://www.ebi.ac.uk/QuickGO/term/GO:0016020) and [extracellular exosomes (GO:0070062)](https://www.ebi.ac.uk/QuickGO/term/GO:0070062). Expression data reveals its significance in two distinct biological domains: it is a highly prominent marker in specialized epithelial cells, particularly those of the kidney proximal tubule involved in solute transport, and it is also significantly expressed in specific hematopoietic lineages, most notably in [megakaryocyte-erythroid progenitor cells](/details-cell/CL0000050). Research has also implicated [PDZK1IP1](/details-gene/10158) in oncogenesis, as it is reportedly upregulated in various human carcinomas ([Link](https://pubmed.ncbi.nlm.nih.gov/9815914/)). ## Cellular Roles and Expression Landscape The expression profile of [PDZK1IP1](/details-gene/10158) highlights its specialized roles in distinct cellular contexts. **Overall**, the gene shows a striking significance in epithelial cells with high transport or secretory activity, as well as in a key hematopoietic progenitor population. Its most significant expression is observed in the kidney, specifically within the [epithelial cell of proximal tubule](/details-cell/CL0002306) (CSI: 21.89) and [kidney epithelial cell](/details-cell/CL0002518) (CSI: 21.87). This is consistent with its function as MAP17, a known regulatory subunit of the SGLT2 glucose transporter, which is critical for glucose reabsorption in this nephron segment ([Link](https://doi.org/10.1038/s41586-021-04212-9)). The pattern extends to a broad range of other secretory and specialized epithelial cells, including [epithelial cell of lung](/details-cell/CL0000082) (CSI: 18.50), [pancreatic acinar cell](/details-cell/CL0002064) (CSI: 16.23), and various mucus-secreting cell types, suggesting a conserved role in membrane-associated processes across diverse secretory tissues. Concurrently, [PDZK1IP1](/details-gene/10158) demonstrates a notable role in hematopoiesis. It is the top-ranked marker in the [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 25.81) and is also significant in mature [erythrocytes](/details-cell/CL0000232) (CSI: 11.68). This strong association suggests a potential function in the development, membrane integrity, or function of the red blood cell and platelet lineages. The gene also shows relevance in subsets of the immune system, such as [innate lymphoid cells](/details-cell/CL0001065) and [CD8-positive, alpha-beta memory T cells, CD45RO-positive](/details-cell/CL0001203), although its significance in these cells is less pronounced compared to its epithelial and erythroid roles. ## Pathways and Molecular Function The primary annotated molecular function of [PDZK1IP1](/details-gene/10158) is [protein binding (GO:0005515)](https://www.ebi.ac.uk/QuickGO/term/GO:0005515). This is experimentally supported by its identification as an interactor of PDZK1 ([Link](https://pubmed.ncbi.nlm.nih.gov/9461128/)) and its structural and functional association with the SGLT2 transporter ([Link](https://doi.org/10.1038/s41586-021-04212-9)). Its localization to the cell [membrane (GO:0016020)](https://www.ebi.ac.uk/QuickGO/term/GO:0016020) is consistent with its role as a transporter subunit and is central to its function in the highly active epithelial cells of the kidney and other secretory tissues. Furthermore, its annotation to [extracellular exosome (GO:0070062)](https://www.ebi.ac.uk/QuickGO/term/GO:0070062) suggests a role in intercellular communication. This function may be particularly relevant in the context of cancer, as exosomal transfer of proteins can modulate the tumor microenvironment. This aligns with early findings that identified [PDZK1IP1](/details-gene/10158) as being upregulated in carcinomas and capable of modulating tumor growth ([Link](https://pubmed.ncbi.nlm.nih.gov/8701988/)). ## Research Directions Early research has established a connection between [PDZK1IP1](/details-gene/10158) (MAP17) and cancer, noting its upregulation in carcinomas and its ability to influence cell replication ([Link](https://pubmed.ncbi.nlm.nih.gov/8701988/)). The gene's dual identity as a membrane protein and an exosomal component, combined with its highly specific expression pattern, provides a foundation for several testable hypotheses. 1. **Hypothesis on Oncogenic Function:** Given its upregulation in tumors and its presence in exosomes, overexpression of [PDZK1IP1](/details-gene/10158) in cancer cells may promote disease progression by altering the protein cargo of secreted exosomes, thereby influencing signaling pathways in recipient cells within the tumor microenvironment. 2. **Hypothesis on Hematopoietic Role:** The high significance of [PDZK1IP1](/details-gene/10158) in [megakaryocyte-erythroid progenitor cells](/details-cell/CL0000050) suggests it plays a previously underappreciated role in hematopoiesis. It may be essential for membrane stabilization or solute transport required during the terminal differentiation of erythrocytes and the formation of platelets. **Experimental Proposal:** To test the hypothesis regarding its role in hematopoiesis, a loss-of-function study could be performed. CRISPR-Cas9 could be used to knock out [PDZK1IP1](/details-gene/10158) in primary human CD34+ hematopoietic stem and progenitor cells. These modified cells, alongside wild-type controls, would then be cultured under conditions that promote differentiation towards the erythroid and megakaryocytic lineages. The impact of the knockout could be assessed by quantifying the efficiency of differentiation via flow cytometry for lineage-specific markers (e.g., CD235a for erythroblasts, CD41/CD61 for megakaryocytes) and by conducting colony-forming unit (CFU-E, CFU-Mk) assays. **Therapeutic Potential:** The properties of [PDZK1IP1](/details-gene/10158) make it a potentially valuable therapeutic target, particularly in oncology. As a membrane protein that is selectively upregulated on the surface of carcinoma cells, it represents an attractive candidate for targeted inhibition. This could be pursued through antibody-based therapies, such as antibody-drug conjugates (ADCs) that deliver a cytotoxic payload specifically to tumor cells expressing the protein, or through engineered cell therapies like CAR-T cells designed to recognize and eliminate [PDZK1IP1](/details-gene/10158)-positive cancer cells.

Genular Protein ID: 1880018349

Symbol: PDZ1I_HUMAN

Name: PDZK1-interacting protein 1

UniProtKB Accession Codes:

Q13113 Q6ICT9 Q96EI1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 EMDB 9 Ensembl 2 GO 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 10 PDBsum 10 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9815914

Title: Identification of a novel gene, selectively up-regulated in human carcinomas, using the differential display technique.

PubMed ID: 9815914

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: 8701988

Title: Identification and partial characterization of a novel membrane-associated protein (MAP17) up-regulated in human carcinomas and modulating cell replication and tumor growth.

PubMed ID: 8701988

PubMed ID: 9461128

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

PubMed ID: 9461128

PubMed ID: 34880493

Title: Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter.

PubMed ID: 34880493

DOI: 10.1038/s41586-021-04212-9

Sequence Information:

  • Length: 114
  • Mass: 12227
  • Checksum: 7DEB64C3AF78CB18
  • Sequence:
    • MSALSLLILG LLTAVPPASC QQGLGNLQPW MQGLIAVAVF LVLVAIAFAV NHFWCQEEPE 
PAHMILTVGN KADGVLVGTD GRYSSMAASF RSSEHENAYE NVPEEEGKVR STPM