Alternative titles; symbols
HGNC Approved Gene Symbol: SDCBP
Cytogenetic location: 8q12.1 Genomic coordinates (GRCh38) : 8:58,553,261-58,582,858 (from NCBI)
The syndecans (e.g., SDC1; 186355) are transmembrane proteoglycans that place structurally heterogeneous heparan sulfate chains at the cell surface and a highly conserved polypeptide in the cytoplasm. Versatile heparan sulfate moieties support various processes of molecular recognition, signaling, and trafficking. Grootjans et al. (1997) reported the identification of a protein that binds to the cytoplasmic domains of the syndecans in yeast 2-hybrid screens and other assays. This protein, designated syntenin, contains a tandem repeat of PDZ domains that reacts with the FYA (phe-tyr-ala) C-terminal amino acid sequence of the syndecans. Proteins produced by fusion of green fluorescent protein and syntenin colocalized to plasma membranes and intracellular vesicles with syndecans. Cells that overexpress the fusion protein showed numerous cell surface extensions, suggesting effects of syntenin on cytoskeleton-membrane organization. Grootjans et al. (1997) proposed that syntenin may function as an adaptor that couples syndecans to cytoskeletal proteins or cytosolic downstream signal-effectors.
Fernandez-Larrea et al. (1999) used the 2-hybrid screen to identify pro-TGF-alpha (190170) cytoplasmic domain-binding proteins, which they referred to as TACIPs (pro-TGF-alpha cytoplasmic domain-interacting proteins), involved in the trafficking of pro-TGF-alpha. They cloned 2 such proteins, TACIP1 and TACIP18, both of which showed a lack of interaction with a pro-TGF-alpha C-terminal mutant that does not reach the cell surface. TACIP1 and TACP18 are identical to the PDZ proteins alpha-1-syntrophin (601017) and syntenin, respectively. Fernandez-Larrea et al. (1999) noted that TACIP18/syntenin had also been identified as melanoma differentiation-associated gene-9, or MDA9, by Lin et al. (1998).
Using Northern blot analysis, Borrell-Pages et al. (2000) detected a 2.4-kb TACIP18 transcript in all 8 human tissues examined. RNA dot blot analysis revealed widespread and variable TACIP18 expression, with highest content in placenta. Expression of TACIP18 was generally higher in fetal tissues than in adult counterparts.
PDZ domains are known to bind to the C terminus of a variety of transmembrane proteins. Accordingly, Fernandez-Larrea et al. (1999) demonstrated that the PDZ domains of TACIP1 and TACIP18 are responsible for the interaction with the cytoplasmic domain of pro-TGF-alpha. Analysis of a panel of pro-TGF-alpha C-terminal mutants showed that mutations that prevented the binding to TACIP1, but not to TACIP18, did not disrupt the transport of pro-TGF-alpha to the cell surface in vivo. Furthermore, the cytoplasmic domain of syndecan-2 (142460), which is also known to bind TACIP18, efficiently replaces that of pro-TGF-alpha, since pro-TGF-alpha/syndecan chimeric molecules were transported to the cell surface with normal kinetics. Mutations that prevented the binding of TACIP18 to the cytoplasmic domain of syndecans also interfered with the normal trafficking of pro-TGF-alpha/syndecan chimeras, further supporting a role for TACIP18 in the trafficking of pro-TGF-alpha. Unlike the majority of PDZ proteins, which localize near the plasma membrane, TACIP18 localizes early in the secretory pathway. In vivo, TACIP18 specifically interacted with immature pro-TGF-alpha in a perinuclear area that colocalizes with endoplasmic reticulum markers.
The interleukin-5 (IL5; 147850) receptor consists of the IL5-specific alpha subunit (IL5RA; 147851) and the signal-transducing beta-subunit, CFS2RB (138981), which is shared with IL3 (147740) and GMCSF (138960). Using a yeast 2-hybrid screen of a granulocyte cDNA library with the cytoplasmic domain of IL5RA as bait, Geijsen et al. (2001) identified an interaction of IL5RA with syntenin. GST pull-down, BIAcore, coimmunoprecipitation, and deletion mutant analyses confirmed an association of syntenin with the last 15 C-terminal residues of IL5RA; syntenin did not interact with CFS2RB. Within this 15-residue stretch of IL5RA, the C-terminal phenylalanine is critical. Deletion of either of the 2 tandem PDZ domains of syntenin, which are known to interact with C-terminal peptide sequences, abrogated the IL5RA-syntenin interaction. A second 2-hybrid screen identified the mouse transcriptional factor Sox4 (184430) as a binding partner for syntenin but not for IL5RA. The syntenin-Sox4 interaction occurs outside of the PDZ domains of syntenin. Luciferase reporter analysis and fluorescence microscopy showed that IL5, but not IL3, induces cytoplasmic and nuclear expression of syntenin and, in a syntenin- and cytoplasmic IL5RA-dependent manner, of Sox4. Geijsen et al. (2001) concluded that syntenin acts as an adaptor molecule in the IL5RA-mediated activation of SOX4. They also noted that mice lacking either Il5ra or Sox4 have defects in B-cell development.
Zimmermann et al. (2002) showed that the PDZ domains of several proteins bind phosphatidylinositol 4,5-bisphosphate (PIP2). High-affinity binding of syntenin to PIP2-containing lipid layers required both of its PDZ domains. Competition and mutagenesis experiments revealed that the protein- and the PIP2-binding sites in the PDZ domains overlap. Overlay assays indicated that the 2 PDZ domains of syntenin cooperate in binding to cognate peptides and PIP2. Experiments on living cells demonstrated PIP2-dependent and peptide-dependent modes of plasma membrane association of the PDZ domains of syntenin. These observations suggested that local changes in phosphoinositide concentration control the association of PDZ proteins with their target receptors at the plasma membrane.
Using yeast 2-hybrid and coprecipitation analysis, Koroll et al. (2001) found that rat syntenin-1 and the long isoform of human syntenin-2 (SDCBP2; 617358) homodimerized and heterodimerized. Yeast 2-hybrid analysis showed that the second PDZ domain of syntenin-1 bound to C-terminal tails of several transmembrane proteins, including neurofascin (NFASC; 609145), pro-TGF-alpha, syndecan-3 (SDC3; 186357), ephrin B2 (EFNB2; 600527), ephrin receptor EPHA7 (602190), and neurexin I (NRXN1; 600565).
Gross (2014) mapped the SDCBP gene to chromosome 8q12.1 based on an alignment of the SDCBP sequence (GenBank AF000652) with the genomic sequence (GRCh38).
Borrell-Pages, M., Fernandez-Larrea, J., Borroto, A., Rojo, F., Baselga, J., Arribas, J. The carboxy-terminal cysteine of the tetraspanin L6 antigen is required for its interaction with SITAC, a novel PDZ protein. Molec. Biol. Cell 11: 4217-4225, 2000. [PubMed: 11102519] [Full Text: https://doi.org/10.1091/mbc.11.12.4217]
Fernandez-Larrea, J., Merlos-Suarez, A., Urena, J. M., Baselga, J., Arribas, J. A role for a PDZ protein in the early secretory pathway for the targeting of proTGF-alpha to the cell surface. Molec. Cell 3: 423-433, 1999. [PubMed: 10230395] [Full Text: https://doi.org/10.1016/s1097-2765(00)80470-0]
Geijsen, N., Uings, I. J., Pals, C., Armstrong, J., McKinnon, M., Raaijmakers, J. A. M., Lammers, J.-W. J., Koenderman, L., Coffer, P. J. Cytokine-specific transcriptional regulation through an IL-5R-alpha interacting protein. Science 293: 1136-1138, 2001. [PubMed: 11498591] [Full Text: https://doi.org/10.1126/science.1059157]
Grootjans, J. J., Zimmermann, P., Reekmans, G., Smets, A., Degeest, G., Durr, J., David, G. Syntenin, a PDZ protein that binds syndecan cytoplasmic domains. Proc. Nat. Acad. Sci. 94: 13683-13688, 1997. [PubMed: 9391086] [Full Text: https://doi.org/10.1073/pnas.94.25.13683]
Gross, M. B. Personal Communication. Baltimore, Md. 8/29/2014.
Koroll, M., Rathjen, F. G., Volkmer, H. The neural cell recognition molecule neurofascin interacts with syntenin-1 but not with syntenin-2, both of which reveal self-associating activity. J. Biol. Chem. 276: 10646-10654, 2001. [PubMed: 11152476] [Full Text: https://doi.org/10.1074/jbc.M010647200]
Lin, J. J., Jiang, H., Fisher, P. B. Melanoma differentiation associated gene-9, mda-9, is a human gamma interferon responsive gene. Gene 207: 105-110, 1998. [PubMed: 9511750] [Full Text: https://doi.org/10.1016/s0378-1119(97)00562-3]
Zimmermann, P., Meerschaert, K., Reekmans, G., Leenaerts, I., Small, J. V., Vandekerckhove, J., David, G., Gettermans, J. PIP2-PDZ domain binding controls the association of syntenin with the plasma membrane. Molec. Cell 9: 1215-1225, 2002. [PubMed: 12086619] [Full Text: https://doi.org/10.1016/s1097-2765(02)00549-x]