Syntenin-1 Explained

Syntenin-1 is a protein that in humans is encoded by the SDCBP gene.^[1]

Function

The protein encoded by this gene was initially identified as a molecule linking syndecan-mediated signaling to the cytoskeleton. The syntenin protein contains tandemly repeated PDZ domains that bind the cytoplasmic, C-terminal domains of a variety of transmembrane proteins. This protein may also affect cytoskeletal-membrane organization, cell adhesion, protein trafficking, and the activation of transcription factors. The protein is primarily localized to membrane-associated adherens junctions and focal adhesions but is also found at the endoplasmic reticulum and nucleus. Alternative splicing results in multiple transcript variants encoding different isoforms.^[2]

Interactions

SDCBP has been shown to interact with:

• EFNB1,^[3]
• GRIK1,^[4]
• GRIK2,^{[4] [5]}
• Interleukin 5 receptor alpha subunit,^[6]
• Merlin,^[7]
• RAB5A,
• SOX4,^[6]
• TRAF6,^[8]
• ULK1.^[9] and
• ERICH2^[10]

Further reading

• Bass MD, Humphries MJ . Cytoplasmic interactions of syndecan-4 orchestrate adhesion receptor and growth factor receptor signalling. . Biochem. J. . 368 . Pt 1 . 1–15 . 2002 . 12241528 . 1222989 . 10.1042/BJ20021228 .
• Harrod TR, Justement LB . Evaluating function of transmembrane protein tyrosine phosphatase CD148 in lymphocyte biology. . Immunol. Res. . 26 . 1–3 . 153–66 . 2003 . 12403354 . 10.1385/IR:26:1-3:153 . 26502472 .
• Sarkar D, Boukerche H, Su ZZ, Fisher PB . mda-9/syntenin: recent insights into a novel cell signaling and metastasis-associated gene. . Pharmacol. Ther. . 104 . 2 . 101–15 . 2005 . 15518882 . 10.1016/j.pharmthera.2004.08.004 .
• Letter: The condition of psychiatry. . N. Engl. J. Med. . 292 . 18 . 982 . 1975 . 1117941 . 10.1056/NEJM197505012921826 .
• Lin JJ, Jiang H, Fisher PB . Melanoma differentiation associated gene-9, mda-9, is a human gamma interferon responsive gene. . Gene . 207 . 2 . 105–10 . 1998 . 9511750 . 10.1016/S0378-1119(97)00562-3 .
• Torres R, Firestein BL, Dong H, Staudinger J, Olson EN, Huganir RL, Bredt DS, Gale NW, Yancopoulos GD . PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands. . Neuron . 21 . 6 . 1453–63 . 1999 . 9883737 . 10.1016/S0896-6273(00)80663-7 . 15441813 . free .
• Lin D, Gish GD, Songyang Z, Pawson T . The carboxyl terminus of B class ephrins constitutes a PDZ domain binding motif. . J. Biol. Chem. . 274 . 6 . 3726–33 . 1999 . 9920925 . 10.1074/jbc.274.6.3726 . free .
• Fernández-Larrea J, Merlos-Suárez A, Ureña JM, 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. . Mol. Cell . 3 . 4 . 423–33 . 1999 . 10230395 . 10.1016/S1097-2765(00)80470-0 . free .
• Fialka I, Steinlein P, Ahorn H, Böck G, Burbelo PD, Haberfellner M, Lottspeich F, Paiha K, Pasquali C, Huber LA . Identification of syntenin as a protein of the apical early endocytic compartment in Madin-Darby canine kidney cells. . J. Biol. Chem. . 274 . 37 . 26233–9 . 1999 . 10473577 . 10.1074/jbc.274.37.26233 . free .
• Grootjans JJ, Reekmans G, Ceulemans H, David G . Syntenin-syndecan binding requires syndecan-synteny and the co-operation of both PDZ domains of syntenin. . J. Biol. Chem. . 275 . 26 . 19933–41 . 2000 . 10770943 . 10.1074/jbc.M002459200 . free .
• Koroll M, Rathjen FG, 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 . 14 . 10646–54 . 2001 . 11152476 . 10.1074/jbc.M010647200 . free .
• Zimmermann P, Tomatis D, Rosas M, Grootjans J, Leenaerts I, Degeest G, Reekmans G, Coomans C, David G . Characterization of syntenin, a syndecan-binding PDZ protein, as a component of cell adhesion sites and microfilaments. . Mol. Biol. Cell . 12 . 2 . 339–50 . 2001 . 11179419 . 30947 . 10.1091/mbc.12.2.339 .
• Jannatipour M, Dion P, Khan S, Jindal H, Fan X, Laganière J, Chishti AH, Rouleau GA . Schwannomin isoform-1 interacts with syntenin via PDZ domains. . J. Biol. Chem. . 276 . 35 . 33093–100 . 2001 . 11432873 . 10.1074/jbc.M105792200 . free .
• Geijsen N, Uings IJ, Pals C, Armstrong J, McKinnon M, Raaijmakers JA, Lammers JW, Koenderman L, Coffer PJ . Cytokine-specific transcriptional regulation through an IL-5Ralpha interacting protein. . Science . 293 . 5532 . 1136–8 . 2001 . 11498591 . 10.1126/science.1059157 . 28003281 .
• Hirbec H, Perestenko O, Nishimune A, Meyer G, Nakanishi S, Henley JM, Dev KK . The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs. . J. Biol. Chem. . 277 . 18 . 15221–4 . 2002 . 11891216 . 10.1074/jbc.C200112200 . 13732968 . free .
• Koo TH, Lee JJ, Kim EM, Kim KW, Kim HD, Lee JH . Syntenin is overexpressed and promotes cell migration in metastatic human breast and gastric cancer cell lines. . Oncogene . 21 . 26 . 4080–8 . 2002 . 12037664 . 10.1038/sj.onc.1205514 . free .
• Biederer T, Sara Y, Mozhayeva M, Atasoy D, Liu X, Kavalali ET, Südhof TC . SynCAM, a synaptic adhesion molecule that drives synapse assembly. . Science . 297 . 5586 . 1525–31 . 2002 . 12202822 . 10.1126/science.1072356 . 2002Sci...297.1525B . 14529914 .

Notes and References

1. Grootjans JJ, Zimmermann P, Reekmans G, Smets A, Degeest G, Dürr J, David G . Syntenin, a PDZ protein that binds syndecan cytoplasmic domains . Proc Natl Acad Sci USA . 94 . 25 . 13683–8 . January 1998 . 9391086 . 28366 . 10.1073/pnas.94.25.13683 . 1997PNAS...9413683G . free .
2. Web site: Entrez Gene: SDCBP syndecan binding protein (syntenin).
3. Lin D, Gish GD, Songyang Z, Pawson T . The carboxyl terminus of B class ephrins constitutes a PDZ domain binding motif . J. Biol. Chem. . 274 . 6 . 3726–33 . February 1999 . 9920925 . 10.1074/jbc.274.6.3726. free .
4. Hirbec H, Francis JC, Lauri SE, Braithwaite SP, Coussen F, Mulle C, Dev KK, Coutinho V, Meyer G, Isaac JT, Collingridge GL, Henley JM, Couthino V . Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP . Neuron . 37 . 4 . 625–38 . February 2003 . 12597860 . 3314502 . 10.1016/s0896-6273(02)01191-1.
5. Hirbec H, Perestenko O, Nishimune A, Meyer G, Nakanishi S, Henley JM, Dev KK . The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs . J. Biol. Chem. . 277 . 18 . 15221–4 . May 2002 . 11891216 . 10.1074/jbc.C200112200 . free . 2262/89271 . free .
6. Geijsen N, Uings IJ, Pals C, Armstrong J, McKinnon M, Raaijmakers JA, Lammers JW, Koenderman L, Coffer PJ . Cytokine-specific transcriptional regulation through an IL-5Ralpha interacting protein . Science . 293 . 5532 . 1136–8 . August 2001 . 11498591 . 10.1126/science.1059157 . 28003281 .
7. Jannatipour M, Dion P, Khan S, Jindal H, Fan X, Laganière J, Chishti AH, Rouleau GA . Schwannomin isoform-1 interacts with syntenin via PDZ domains . J. Biol. Chem. . 276 . 35 . 33093–100 . August 2001 . 11432873 . 10.1074/jbc.M105792200 . free .
8. Chen F, Du Y, Zhang Z, Chen G, Zhang M, Shu HB, Zhai Z, Chen D . Syntenin negatively regulates TRAF6-mediated IL-1R/TLR4 signaling . Cell. Signal. . 20 . 4 . 666–74 . April 2008 . 18234474 . 10.1016/j.cellsig.2007.12.002 . 28812149 .
9. Tomoda T, Kim JH, Zhan C, Hatten ME . Role of Unc51.1 and its binding partners in CNS axon outgrowth . Genes Dev. . 18 . 5 . 541–58 . March 2004 . 15014045 . 374236 . 10.1101/gad.1151204 .
10. Web site: Results - mentha: the interactome browser. mentha.uniroma2.it. 2017-05-04.