Disease relevance of GIPC1

• Expression of GIPC1 mRNA was down-regulated in 12 out of 14 cases of primary kidney tumors, 10 out of 18 cases of primary colorectal tumors, 3 out of 8 cases of primary gastric cancer, 3 out of 3 cases of primary prostate cancer [1].
• GIPC1 and GIPC2 mRNAs are expressed together in OKAJIMA, TMK1, MKN45 and KATO-III cells derived from diffuse-type of gastric cancer, and are up-regulated in several cases of primary gastric cancer [2].
• On the other hand, GIPC1 mRNA was almost undetectable in leukemia/lymphoma cell lines HL-60, Raji, and Daudi [1].
• GIPC1 mRNA was relatively highly expressed in gastric cancer cell lines OKAJIMA, TMK1, MKN28, MKN45, MKN74, KATO-III, pancreatic cancer cell line AsPC-1, colorectal cancer cell line SW480, and lung cancer cell line A549 [1].
• In this report we show that TIP-2/GIPC interacts with the E6 protein of human papillomavirus type 18 (HPV-18) [3].

High impact information on GIPC1

• Similar defects in basal synaptic transmission as well as presynaptic properties were observed in Myo6 and GIPC1 mutant mice [4].
• Binding of internalized receptors to the PDZ domain of GIPC/synectin recruits myosin VI to endocytic vesicles [5].
• By immunofluorescence, endogenous and GFP-tagged GIPC show both a diffuse and punctate cytoplasmic distribution in HeLa cells reflecting, respectively, the existence of soluble and membrane-associated pools [6].
• APPL1 was isolated as a binding partner for the TrkA-interacting protein GIPC1 from rat brain lysate by mass spectrometry [7].
• APPL1 Associates with TrkA and GIPC1 and Is Required for Nerve Growth Factor-Mediated Signal Transduction [7].

Biological context of GIPC1

• Because GIPC1 induces increased expression of TGFbeta type III receptor at the cell surface and enhanced responsiveness to TGFbeta, down-regulation of GIPC1 mRNA in tumors might promote cellular proliferation through interference of TGFbeta signaling [1].
• Therefore, GIPC1, GIPC2 and GIPC3 might play key roles in carcinogenesis and embryogenesis through modulation of growth factor signaling and cell adhesion [2].
• Both GIPC2 gene on human chromosome 1 and GIPC1 gene on human chromosome 19p13.1 were found to consist of 6 exons [8].
• In this study, we identified a novel GIPC1-related gene in human genome by using bioinformatics, and isolated GIPC2 cDNAs by using cDNA-PCR [8].
• In agreement with this observation, silencing of E6 by RNA interference in HeLa cells causes an increase in the intracellular TIP-2/GIPC level [3].

Anatomical context of GIPC1

• Expression of human GIPC1 in normal tissues, cancer cell lines, and primary tumors [1].
• Expression level of GIPC1 mRNA was relatively lower in bone marrow and peripheral blood leukocytes [1].
• Dynamic translocation of GAIP to the plasma membrane and coassembly in a protein complex in which GIPC was a required component was dictated by D2R activation and physical interactions [9].
• In line with this activity of TIP-2/GIPC, we observed that depletion of this protein in HeLa cells hampers induction of the Id3 gene by TGF-beta treatment and also diminishes the antiproliferative effect of this cytokine [3].
• Our data suggest that GIPC/SEMCAP-1 plays a role in biosynthetic sorting of proteins, specifically gp75, to melanosomes [10].

Associations of GIPC1 with chemical compounds

• The alpha(6) integrin and TIP-2/GIPC co-localize in retraction fibers in carcinoma cells plated on laminin, a finding suggesting a functional interaction in vivo [11].
• Interactions of GIPC with dopamine D2, D3 but not D4 receptors define a novel mode of regulation of G protein-coupled receptors [12].
• Using the yeast two-hybrid system and an in vitro glutathione S-transferase fusion protein-binding assay, the binding of GIPC to the CYTO was shown to involve a newly identified class I PDZ-binding domain in the CD93 carboxyl terminus [13].
• Gel filtration, sucrose gradient centrifugation and chemical cross-linking showed that whereas bulk of cytosolic GIPC was present as monomer, oligomers with an estimated molecular mass corresponding to GIPC homotrimer were readily detectable in the membrane fraction [14].
• Using functional complementation and a yeast mutant deficient in ammonium (NH4+) transport (Deltamep1-3), three wheat (Triticum aestivum) TIP2 aquaporin homologues were isolated that restored the ability of the mutant to grow when 2 mM NH4+ was supplied as the sole nitrogen source [15].

Physical interactions of GIPC1

• Using the beta1-adrenergic receptor carboxyl terminus as bait, we identified the novel beta1-adrenergic receptor-binding partner GIPC in a yeast two-hybrid screen of a human heart cDNA library [16].
• GIPC binds to the human lutropin receptor (hLHR) through an unusual PDZ domain binding motif, and it regulates the sorting of the internalized human choriogonadotropin and the density of cell surface hLHR [17].
• In precipitation assays, GST-GIPC specifically binds megalin [18].
• 5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis [19].

Other interactions of GIPC1

• GIPC1 and GIPC2 show 62.0% total-amino-acid identity [2].
• GIPC1 and GIPC3 show 59.9% total-amino-acid identity [2].
• PDZ domain protein GIPC interacts with the cytoplasmic tail of melanosomal membrane protein gp75 (tyrosinase-related protein-1) [10].
• CD93 interacts with the PDZ domain-containing adaptor protein GIPC: implications in the modulation of phagocytosis [13].
• Isolation of endosomal fractions by high-resolution centrifugation determined that APPL1, GIPC1, and phosphorylated TrkA are enriched in the same fractions [7].

Analytical, diagnostic and therapeutic context of GIPC1

• Molecular cloning and characterization of human GIPC2, a novel gene homologous to human GIPC1 and Xenopus Kermit [8].
• Pull-down and immunoprecipitation assays confirmed this interaction and showed that it is dependent on the PDZ domain of GIPC and the C-terminal tetrapeptide of the hLHR [17].
• GAIP is found by immunoelectron microscopy in CCPs, and GIPC is found in CCPs and apical tubules of endocytic compartments in the renal brush border [18].
• Immunogold electron microscopy showed that GIPC is present in clusters near vesicles [14].
• Assignment of PDZ domain-containing protein GIPC gene (C19orf3) to human chromosome band 19p13.1 by in situ hybridization and radiation hybrid mapping [20].

References