Alternative titles; symbols
HGNC Approved Gene Symbol: SDC2
Cytogenetic location: 8q22.1 Genomic coordinates (GRCh38): 8:96,493,813-96,611,790 (from NCBI)
SDC2 is a BAR domain-containing protein involved in recycling endosome (RE) biogenesis (Giridharan et al., 2013).
By polyacrylamide gel electrophoresis of cell surface-associated heparan sulfate proteoglycans after heparitinase treatment, Lories et al. (1987) demonstrated the presence of core proteins with an apparent molecular weight of 125,000, 90,000, 64,000, 48,000 and 35,000. The 90-kD and the 48-kD core proteins share the epitope of the monoclonal antibody 6G12, which Marynen et al. (1989) used in the isolation of the cDNA from a human lung fibroblast expression library. Southern blot analysis indicated the presence of 1 or a limited number of genes corresponding to the 48/90-kD cDNA.
The transmembrane heparan sulfate proteoglycan for which cDNAs were cloned from human lung fibroblasts by Marynen et al. (1989) is also called fibroglycan or syndecan-2 (David et al., 1992). It is located in the same region as the MYC gene. As pointed out by Spring et al. (1994), 4 members of the syndecan family show a remarkable physical relationship with 4 members of the MYC gene family.
By Southern hybridization to a panel of human-mouse somatic cell hybrid DNA and by in situ hybridization, Marynen et al. (1989) showed that the heparan sulfate proteoglycan core protein maps to 8q22-q24. (Heparan sulfate proteoglycan of basement membrane (HSPG2; 142461) maps to chromosome 1.)
Gross (2021) mapped the SDC2 gene to chromosome 8q22.1 based on an alignment of the SDC2 sequence (GenBank BC030133) with the genomic sequence (GRCh38).
Bobardt et al. (2003) demonstrated that syndecans, including SDC2, can function as in trans HIV receptors via binding of HIV-1 gp120 to the syndecan heparan sulfate chains. Flow cytometric analysis demonstrated SDC expression on endothelial cells. HIV bound to SDC on endothelial cell lines maintained its infectivity for at least 1 week, compared with less than 1 day for unbound virus. Bobardt et al. (2003) suggested that SDC-rich endothelial cells lining the vasculature can provide a microenvironment that boosts HIV replication in T cells.
Using yeast 2-hybrid experiments, coimmunoprecipitation assays, and in vitro pull-down assays, Ethell et al. (2000) demonstrated that mouse synbindin (TRAPPC4; 610971) interacted directly with rat syndecan-2. Yeast 2-hybrid analysis also showed that synbindin interacted with rat syndecan-4 (SDC4; 600017). Mutation analysis showed that the interaction required the PDZ-like domain of synbindin and the EFYA motif in the C-terminal domain of Sdc2. Primary rat hippocampal neurons transfected with synbindin and Sdc2 expressed the proteins in clusters along dendritic spines. Sdc2 lacking the EFYA motif formed clusters that lacked synbindin, suggesting synbindin clustering was dependent on Sdc2. Synbindin coimmunoprecipitated with Sdc2 from synaptic membrane fractions. Ethell et al. (2000) suggested that SDC2 induces dendritic spine formation by recruiting intracellular vesicles toward postsynaptic sites through interaction with synbindin.
Coles et al. (2011) reported that RPTP-sigma, also known as PTPRS (601576), acts bimodally in sensory neuron extension, mediating CSPG (155760) inhibition and HSPG growth promotion. Crystallographic analyses of a shared HSPG-CSPG binding site revealed a conformational plasticity that can accommodate diverse glycosaminoglycans with comparable affinities. Heparan sulfate and analogs induced RPTP-sigma ectodomain oligomerization in solution, which was inhibited by chondroitin sulfate. RPTP-sigma and HSPGs colocalize in puncta on sensory neurons in culture, whereas CSPGs occupy the extracellular matrix. Coles et al. (2011) concluded that their results lead to a model where proteoglycans can exert opposing effects on neuronal extension by competing to control the oligomerization of a common receptor.
Using immunoprecipitation analysis in HeLa cells, Giridharan et al. (2013) demonstrated that the SH3 domain of SYND2 interacted directly with 2 of the 14 proline-rich domains of MICALL1 (619563). SYND2 colocalized with MICALL1 and EHD1 (605888) at tubular REs, with SYND2 and MICALL1 displaying similar dynamics of association with tubular membranes. Knockdown analysis showed that interaction between MICALL1 and SYND2 was required for their localization to tubular REs, whereas EHD1 stabilized interaction between MICALL1 and SYND2 on recycling tubules. A lipid overlay assay revealed that MICALL1 and SYND2 bound to phosphatidic acid in membranes of REs for localization and for RE tubule biogenesis. Further analysis demonstrated that MICALL and SYND2 were capable of generating tubules from phosphatidic acid-containing membranes.
Ishikawa-Brush et al. (1997) found that the 3-prime end of the SDC2 gene was located approximately 30 kb proximal to the translocation breakpoint in a 27-year-old female patient with a balanced translocation 46,X,t(X;8)(p22.13;q22.1) associated with multiple exostoses and autism (Bolton et al., 1995). The breakpoint of the X chromosome was located in the first intron of the gastrin-releasing peptide receptor gene (GRPR; 305670) and a possible causal relationship to autism (209850) was posited. Since one of the biologic functions of the SDC2 gene product is related to aggregating cells in the formation of bone, the authors suggested interference with its function as a mechanism of the multiple exostoses. There is precedence for a position effect; translocation occurring in the 3-prime end of the PAX6 gene (607108) as far away as approximately 100 kb appeared to be disruptive to the gene and was associated with aniridia.
In a cohort of 330 individuals with systemic sclerosis (see 181750), Banka et al. (2015) observed a statistical association between a c.211T-A transversion in the SDC2 gene, resulting in a ser71-to-thr (S71T) missense polymorphism (rs1042381), and protection against disease. The minor allele frequency was 0.122 in patients compared to 0.167 in 308 local controls and 0.182 in the Exome Variant Server database (odds ratio of 0.52, p less than 1 x 10(-5)). The gene was chosen for study based on its putative expression in connective tissue.
Banka, S., Cain, S. A., Carim, S., Daly, S. B., Urquhart, J. E., Erdem, G., Harris, J., Bottomley, M., Donnai, D., Kerr, B., Kingston, H., Superti-Furga, A., Unger, S., Ennis, H., Worthington, J., Herrick, A. L., Merry, C. L. R., Yue, W. W., Kielty, C. M., Newman, W. G. Leri's pleonosteosis, a congenital rheumatic disease, results from microduplication at 8q22.1 encompassing GDF6 and SDC2 and provides insight into systemic sclerosis pathogenesis. Ann. Rheum. Dis. 74: 1249-1256, 2015. [PubMed: 24442880] [Full Text: https://doi.org/10.1136/annrheumdis-2013-204309]
Bobardt, M. D., Saphire, A. C. S., Hung, H.-C., Yu, X., Van der Schueren, B., Zhang, Z., David, G., Gallay, P. A. Syndecan captures, protects, and transmits HIV to T lymphocytes. Immunity 18: 27-39, 2003. [PubMed: 12530973] [Full Text: https://doi.org/10.1016/s1074-7613(02)00504-6]
Bolton, P., Powell, J., Rutter, M., Buckle, V., Yates, J. R. W., Ishikawa-Brush, Y., Monaco, A. P. Autism, mental retardation, multiple exostoses and short stature in a female with 46,X,t(X;8)(p22.13;q22.1). Psychiat. Genet. 5: 51-55, 1995. [PubMed: 7551962] [Full Text: https://doi.org/10.1097/00041444-199522000-00001]
Coles, C. H., Shen, Y., Tenney, A. P., Siebold, C., Sutton, G. C., Lu, W., Gallagher, J. T., Jones, E. Y., Flanagan, J. G., Aricescu, A. R. Proteoglycan-specific molecular switch for RPTP-sigma clustering and neuronal extension. Science 332: 484-488, 2011. [PubMed: 21454754] [Full Text: https://doi.org/10.1126/science.1200840]
David, G., van der Schueren, B., Marynen, P., Cassiman, J.-J., van den Berghe, H. Molecular cloning of amphiglycan, a novel integral membrane heparan sulfate proteoglycan expressed by epithelial and fibroblastic cells. J. Cell Biol. 118: 961-969, 1992. [PubMed: 1500433] [Full Text: https://doi.org/10.1083/jcb.118.4.961]
Ethell, I. M., Hagihara, K., Miura, Y., Irie, F., Yamaguchi, Y. Synbindin, a novel syndecan-2-binding protein in neuronal dendritic spines. J. Cell Biol. 151: 53-67, 2000. [PubMed: 11018053] [Full Text: https://doi.org/10.1083/jcb.151.1.53]
Giridharan, S. S. P., Cai, B., Vitale, N., Naslavsky, N., Caplan, S. Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis. Molec. Biol. Cell 24: 1776-1790, 2013. [PubMed: 23596323] [Full Text: https://doi.org/10.1091/mbc.E13-01-0026]
Gross, M. B. Personal Communication. Baltimore, Md. 10/12/2021.
Ishikawa-Brush, Y., Powell, J. F., Bolton, P., Miller, A. P., Francis, F., Willard, H. F., Lehrach, H., Monaco, A. P. Autism and multiple exostoses associated with an X;8 translocation occurring within the GRPR gene and 3-prime to the SDC2 gene. Hum. Molec. Genet. 6: 1241-1250, 1997. [PubMed: 9259269] [Full Text: https://doi.org/10.1093/hmg/6.8.1241]
Lories, V., De Boeck, H., David, G., Cassiman, J. J., Van den Berghe, H. Heparan sulfate proteoglycans of human lung fibroblasts: structural heterogeneity of the core proteins of the hydrophobic cell-associated forms. J. Biol. Chem. 262: 854-859, 1987. [PubMed: 2948951]
Marynen, P., Zhang, J., Cassiman, J.-J., David, G. The gene for the 48kDa and the 90kDa core proteins of cell surface-associated heparan sulphate proteoglycan of human lung fibroblast maps to chromosome 8q2. (Abstract) Cytogenet. Cell Genet. 51: 1040, 1989.
Marynen, P., Zhang, J., Cassiman, J.-J., Van den Berghe, H., David, G. Partial primary structure of the 48- and 90-kilodalton core proteins of cell surface-associated heparan sulfate proteoglycans of lung fibroblasts: prediction of an integral membrane domain and evidence for multiple distinct core proteins at the cell surface of human lung fibroblasts. J. Biol. Chem. 264: 7017-7024, 1989. [PubMed: 2523388]
Spring, J., Goldberger, O. A., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., Bernfield, M. Mapping of the syndecan genes in the mouse: linkage with members of the Myc gene family. Genomics 21: 597-601, 1994. [PubMed: 7959737] [Full Text: https://doi.org/10.1006/geno.1994.1319]