Syntenin-1 (SDCBP)
The protein contains 298 amino acids for an estimated molecular weight of 32444 Da.
Multifunctional adapter protein involved in diverse array of functions including trafficking of transmembrane proteins, neuro and immunomodulation, exosome biogenesis, and tumorigenesis (PubMed:26291527). Positively regulates TGFB1-mediated SMAD2/3 activation and TGFB1-induced epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types. May increase TGFB1 signaling by enhancing cell-surface expression of TGFR1 by preventing the interaction between TGFR1 and CAV1 and subsequent CAV1-dependent internalization and degradation of TGFR1 (PubMed:25893292). In concert with SDC1/4 and PDCD6IP, regulates exosome biogenesis (PubMed:22660413). Regulates migration, growth, proliferation, and cell cycle progression in a variety of cancer types (PubMed:26539120). In adherens junctions may function to couple syndecans to cytoskeletal proteins or signaling components. Seems to couple transcription factor SOX4 to the IL-5 receptor (IL5RA) (PubMed:11498591). May also play a role in vesicular trafficking (PubMed:11179419). Seems to be required for the targeting of TGFA to the cell surface in the early secretory pathway (PubMed:10230395). (updated: Oct. 25, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs11550282 | |
| dbSNP:rs1127509 |
Biological Process
Actin cytoskeleton organization
Axon guidance
Chemical synaptic transmission
Ephrin receptor signaling pathway
Intracellular signal transduction
Negative regulation of proteasomal ubiquitin-dependent protein catabolic process
Negative regulation of receptor internalization
Neutrophil degranulation
Positive regulation of cell growth
Positive regulation of cell migration
Positive regulation of cell population proliferation
Positive regulation of epithelial to mesenchymal transition
Positive regulation of exosomal secretion
Positive regulation of extracellular exosome assembly
Positive regulation of JNK cascade
Positive regulation of pathway-restricted SMAD protein phosphorylation
Positive regulation of phosphorylation
Positive regulation of transforming growth factor beta receptor signaling pathway
Protein targeting to membrane
Ras protein signal transduction
Regulation of mitotic cell cycle
Regulation of necroptotic process
Substrate-dependent cell migration, cell extension
Cellular Component
Adherens junction
Azurophil granule lumen
Blood microparticle
Cytoplasm
Cytoskeleton
Cytosol
Endoplasmic reticulum membrane
Extracellular exosome
Extracellular region
Extracellular space
Extracellular vesicle
Focal adhesion
Interleukin-5 receptor complex
Intracellular membrane-bounded organelle
Melanosome
Membrane
Membrane raft
Nuclear membrane
Nucleoplasm
Nucleus
Plasma membrane
Synapse
Vesicle
The reference OMIM entry for this protein is 602217
Syndecan-binding protein; sdcbp
Syntenin
Pro-tgf-alpha cytoplasmic domain-interacting protein 18; tacip18
Melanoma differentiation-associated gene 9; mda9
CLONING
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).GENE FUNCTION
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, ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602217 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed