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Gene Review

PDZK1  -  PDZ domain containing 1

Homo sapiens

Synonyms: CAP70, CFTR-associated protein of 70 kDa, CLAMP, NHERF-3, NHERF3, ...
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Disease relevance of PDZK1


High impact information on PDZK1

  • In the first cytosolic loop, the affected region is embedded between a putative G protein binding sequence and the site of phospholipid sensitivity, and in the COOH-terminal tail, splicing affects pump regulation by calmodulin, phosphorylation, and differential interaction with PDZ domain-containing anchoring and signaling proteins [6].
  • SLC9A3R1 is a PDZ domain-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family and is implicated in diverse aspects of epithelial membrane biology and immune synapse formation in T cells [7].
  • Linking at least two CFTR molecules via cytoplasmic C-terminal binding by either multivalent CAP70 or a bivalent monoclonal antibody potentiates the CFTR chloride channel activity [8].
  • We have identified a novel hydrophilic CFTR binding protein, CAP70, which is also concentrated on the apical surfaces [8].
  • The Checkpoint Clamp Activates Mec1 Kinase during Initiation of the DNA Damage Checkpoint [9].

Biological context of PDZK1


Anatomical context of PDZK1


Associations of PDZK1 with chemical compounds

  • Taken together, the present study indicates the novel role of PDZK1 in regulating the functional activity of URAT1-mediated urate transport in the apical membrane of renal proximal tubules [14].
  • A mutant SR-BI (SR-BIdel509) that lacked only the leucine in the PDZ-interacting domain failed to interact with PDZK1 in vitro, while showing normal selective uptake function in nonpolarized cells [15].
  • PDZK1 directly regulates the function of organic cation/carnitine transporter OCTN2 [10].
  • Transfection of PDZK1 increased the uptake of glycylsarcosine by PEPT2, whereas such stimulation was not observed for PEPT2 with the last four amino acids deleted [16].
  • Alanine-scanning mutation in PEPT2 revealed the presence of a consensus sequence (-T-X-L) that is responsible for the PDZK1 interaction [16].

Physical interactions of PDZK1

  • In an effort to elucidate the role of this interaction in vivo, the PDZK1-interacting domain of SR-BI was identified and mutated and expressed liver-specifically in mice [15].
  • Results obtained by various in vitro analyses suggested that MAP17 interacts with the fourth domain of PDZK1 but not with other PDZ proteins localized in proximal tubular brush borders [17].
  • PDZK1 directly interacts with PEPT2, exerting functional regulation of its transporting activity [16].
  • The CFTR associated protein CAP70 interacts with the apical Cl-/HCO3- exchanger DRA in rabbit small intestinal mucosa [18].
  • Our discoveries provide insight into the specific interaction of the GOPC PDZ domain with the C-terminal peptide of Nlg and also provide a general insight about the possible binding mode of the interaction of Nlg with other PDZ domain-containing proteins [19].

Co-localisations of PDZK1

  • Immunohistochemical analysis indicated that OCTN1 was colocalized with PDZK1 on cell-surface, whereas colocalization with PDZK1-E195K was partially observed in cytoplasmic region [20].

Regulatory relationships of PDZK1

  • Here we show that PDZK1 controls in a tissue-specific and post-transcriptional fashion the expression of SR-BI in vivo [21].
  • Furthermore, we clarified the mechanism of enhanced glycylsarcosine (Gly-Sar) transport activity in PEPT2-expressing HEK293 cells after the PDZK1 coexpression [22].

Other interactions of PDZK1

  • Unexpectedly, we found that hepatic overexpression of SPAP in mice resulted in liver deficiency of PDZK1 [23].
  • Coimmunoprecipitation studies revealed that the wild-type URAT1, but not its mutant lacking the PDZ-motif, directly interacts with PDZK1 [14].
  • Bcr (breakpoint cluster region) protein binds to PDZ-domains of scaffold protein PDZK1 and vesicle coat protein Mint3 [24].
  • The interaction was recapitulated in HEK cells transfected with DRA and PDZK1, the human orthologue of CAP70 [18].
  • A corresponding transcriptional mapping using oligonucleotide arrays extracted three up-regulated genes (IRTA2, PDZK1, and S100A6) within the smallest region of overlapping in amplifications [3].

Analytical, diagnostic and therapeutic context of PDZK1


  1. 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. Kocher, O., Comella, N., Gilchrist, A., Pal, R., Tognazzi, K., Brown, L.F., Knoll, J.H. Lab. Invest. (1999) [Pubmed]
  2. PDZK1 and GREB1 are estrogen-regulated genes expressed in hormone-responsive breast cancer. Ghosh, M.G., Thompson, D.A., Weigel, R.J. Cancer Res. (2000) [Pubmed]
  3. Overexpression of PDZK1 within the 1q12-q22 amplicon is likely to be associated with drug-resistance phenotype in multiple myeloma. Inoue, J., Otsuki, T., Hirasawa, A., Imoto, I., Matsuo, Y., Shimizu, S., Taniwaki, M., Inazawa, J. Am. J. Pathol. (2004) [Pubmed]
  4. Activated in prostate cancer: a PDZ domain-containing protein highly expressed in human primary prostate tumors. Chaib, H., Rubin, M.A., Mucci, N.R., Li, L., Taylor JMG, n.u.l.l., Day, M.L., Rhim, J.S., Macoska, J.A. Cancer Res. (2001) [Pubmed]
  5. Selective PDZ protein-dependent stimulation of phosphatidylinositol 3-kinase by the adenovirus E4-ORF1 oncoprotein. Frese, K.K., Lee, S.S., Thomas, D.L., Latorre, I.J., Weiss, R.S., Glaunsinger, B.A., Javier, R.T. Oncogene (2003) [Pubmed]
  6. Role of alternative splicing in generating isoform diversity among plasma membrane calcium pumps. Strehler, E.E., Zacharias, D.A. Physiol. Rev. (2001) [Pubmed]
  7. A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis. Helms, C., Cao, L., Krueger, J.G., Wijsman, E.M., Chamian, F., Gordon, D., Heffernan, M., Daw, J.A., Robarge, J., Ott, J., Kwok, P.Y., Menter, A., Bowcock, A.M. Nat. Genet. (2003) [Pubmed]
  8. Accessory protein facilitated CFTR-CFTR interaction, a molecular mechanism to potentiate the chloride channel activity. Wang, S., Yue, H., Derin, R.B., Guggino, W.B., Li, M. Cell (2000) [Pubmed]
  9. The Checkpoint Clamp Activates Mec1 Kinase during Initiation of the DNA Damage Checkpoint. Majka, J., Niedziela-Majka, A., Burgers, P.M. Mol. Cell (2006) [Pubmed]
  10. PDZK1 directly regulates the function of organic cation/carnitine transporter OCTN2. Kato, Y., Sai, Y., Yoshida, K., Watanabe, C., Hirata, T., Tsuji, A. Mol. Pharmacol. (2005) [Pubmed]
  11. Interaction with PDZK1 is required for expression of organic anion transporting protein 1A1 on the hepatocyte surface. Wang, P., Wang, J.J., Xiao, Y., Murray, J.W., Novikoff, P.M., Angeletti, R.H., Orr, G.A., Lan, D., Silver, D.L., Wolkoff, A.W. J. Biol. Chem. (2005) [Pubmed]
  12. Identification and partial characterization of PDZK1: a novel protein containing PDZ interaction domains. Kocher, O., Comella, N., Tognazzi, K., Brown, L.F. Lab. Invest. (1998) [Pubmed]
  13. Targeted disruption of the PDZK1 gene by homologous recombination. Kocher, O., Pal, R., Roberts, M., Cirovic, C., Gilchrist, A. Mol. Cell. Biol. (2003) [Pubmed]
  14. The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus. Anzai, N., Miyazaki, H., Noshiro, R., Khamdang, S., Chairoungdua, A., Shin, H.J., Enomoto, A., Sakamoto, S., Hirata, T., Tomita, K., Kanai, Y., Endou, H. J. Biol. Chem. (2004) [Pubmed]
  15. A carboxyl-terminal PDZ-interacting domain of scavenger receptor B, type I is essential for cell surface expression in liver. Silver, D.L. J. Biol. Chem. (2002) [Pubmed]
  16. Screening of the interaction between xenobiotic transporters and PDZ proteins. Kato, Y., Yoshida, K., Watanabe, C., Sai, Y., Tsuji, A. Pharm. Res. (2004) [Pubmed]
  17. Interactions of MAP17 with the NaPi-IIa/PDZK1 protein complex in renal proximal tubular cells. Pribanic, S., Gisler, S.M., Bacic, D., Madjdpour, C., Hernando, N., Sorribas, V., Gantenbein, A., Biber, J., Murer, H. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  18. The CFTR associated protein CAP70 interacts with the apical Cl-/HCO3- exchanger DRA in rabbit small intestinal mucosa. Rossmann, H., Jacob, P., Baisch, S., Hassoun, R., Meier, J., Natour, D., Yahya, K., Yun, C., Biber, J., Lackner, K.J., Fiehn, W., Gregor, M., Seidler, U., Lamprecht, G. Biochemistry (2005) [Pubmed]
  19. Solution structure of GOPC PDZ domain and its interaction with the C-terminal motif of neuroligin. Li, X., Zhang, J., Cao, Z., Wu, J., Shi, Y. Protein Sci. (2006) [Pubmed]
  20. Mutation in an Adaptor Protein PDZK1 Affects Transport Activity of Organic Cation Transporter OCTNs and Oligopeptide Transporter PEPT2. Sugiura, T., Kato, Y., Kubo, Y., Tsuji, A. Drug Metab. Pharmacokinet. (2006) [Pubmed]
  21. Targeted disruption of the PDZK1 gene in mice causes tissue-specific depletion of the high density lipoprotein receptor scavenger receptor class B type I and altered lipoprotein metabolism. Kocher, O., Yesilaltay, A., Cirovic, C., Pal, R., Rigotti, A., Krieger, M. J. Biol. Chem. (2003) [Pubmed]
  22. The PDZ domain protein PDZK1 interacts with human peptide transporter PEPT2 and enhances its transport activity. Noshiro, R., Anzai, N., Sakata, T., Miyazaki, H., Terada, T., Shin, H.J., He, X., Miura, D., Inui, K., Kanai, Y., Endou, H. Kidney Int. (2006) [Pubmed]
  23. Identification of small PDZK1-associated protein, DD96/MAP17, as a regulator of PDZK1 and plasma high density lipoprotein levels. Silver, D.L., Wang, N., Vogel, S. J. Biol. Chem. (2003) [Pubmed]
  24. Bcr (breakpoint cluster region) protein binds to PDZ-domains of scaffold protein PDZK1 and vesicle coat protein Mint3. Malmberg, E.K., Andersson, C.X., Gentzsch, M., Chen, J.H., Mengos, A., Cui, L., Hansson, G.C., Riordan, J.R. J. Cell. Sci. (2004) [Pubmed]
  25. PDZK1: I. a major scaffolder in brush borders of proximal tubular cells. Gisler, S.M., Pribanic, S., Bacic, D., Forrer, P., Gantenbein, A., Sabourin, L.A., Tsuji, A., Zhao, Z.S., Manser, E., Biber, J., Murer, H. Kidney Int. (2003) [Pubmed]
  26. Organic cation/carnitine transporter OCTN2 (Slc22a5) is responsible for carnitine transport across apical membranes of small intestinal epithelial cells in mouse. Kato, Y., Sugiura, M., Sugiura, T., Wakayama, T., Kubo, Y., Kobayashi, D., Sai, Y., Tamai, I., Iseki, S., Tsuji, A. Mol. Pharmacol. (2006) [Pubmed]
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