Table 1 SYDE interactors. (Upper panel) The putative domains in linear motifs predicted to mediate SYDE interaction were selected. It is assumed that if the known binding protein is the same class of protein-family or presents the domain or motif known to interact with a predicted SYDE linear motif the molecule is considered to be the putative interactor binding site (SLiM: short linear motif23). The consensus motifs were examined by ELM database and the selected sequence patterns localized in SYDE1 and SYDE2 are indicated according to several literatures listed in the references. (Lower panel) The SYDE1, SYDE2, and Drosophila Syd1 (DmSyd1) interactors are indicated by categorizing from the literatures as follows: domain architecture obtained from InterPro database, the experimental condition, and interacting region which is experimentally validated (–: not determined). AP-MS affinity purification-mass spectrometry, FLAP fluorescence recovery after photobleaching, Y2H yeast two-hybrid system: coIP: immunoprecipitation. *Predicted nuclear export signal is indicated by NES database28.
Protein | Predicted interactor | Domain architecture | Signaling pathway | Method | Score (ELM) | Predicted SYDE1 or SYDE2 interacting region |
|---|---|---|---|---|---|---|
SYDE1 | ATG8 (GABARAP) | ATG8, LIR domain | Autophagic pathway | ELM: LIG_LIR_Gen155 | 3.60e−03 | Y_LIR sequence 9TFSRL13 |
SYDE1 | Ruk/CIN85 | SH3 domain | Synaptic endocytosis | ELM:LIG_SH3_3 68 | 1.32e−02 | 207DSSVGGP213 233GDSPERP239 641PEVVTRP647 |
SYDE1 | YWHAZ | 14-3-3 | Neuronal differentiation | ELM: LIG_14-3-3 14-3-3 binding motif53 | 4.48e−03 | Arg containing phospho-motif 177RRRLSLR183 |
SYDE1 | Cyclin B/CDK1 | cyclin | Neuronal differentiation | ELM: DOC_Cyclin_RxL S/T-X-(X)-R/K motif54 (peptide library) | 4.21e−03 | RxL docking motif 166RLSIKMKKLPE175 |
SYDE1 | P38α, p38β | kinase | Neuronal homeostasis | ELM: DOC_MAPK Classical D motif specificity52 | 4.32e−03 | 617RPKRQPPLHL626 |
SYDE1 | Casein kinase Iγ | kinase | Endocytosis synaptic vesicles | ELM: MOD_CK1_1, D2P2 Palmitoylation-dependent phosphorylation49 | 1.70e−02 | 645SPPSNRY651 |
SYDE1 | Casein kinase II | kinase | Dendritic spine formation | ELM: MOD_CK2_1, D2P2, PROSITE25 | 1.46e−02 | pS/pT-D/E-X-D/E motif 678VTGSDSEDE686 (SYDE1) |
SYDE1 | RhoB | RhoGTPase domain | Synaptic plasticity | Docking by Swarmdock36 | – | RhoGAP |
SYDE2 | Pin1 | WW domain | Regulation of NMDA receptor | ELM: LIG_WW3 | 5.67e−04 | S/T-P motif 60SPPRS64 |
SYDE2 | Smek1 | Ser/Thr phosphatase4 regulatory subunit (EVH domain) | Neuronal differentiation | ELM: DOC_PP4 PP4 binding motif60 | 1.37e−03 | FxxP motif, SLiM region 158FRDP161 |
SYDE2 | Grb2 | kinase | Cerebral cortical development | ELM: LIG_SH2_Grb2 Consensus pYxN motif by pull-down experiment50 | 3.18e−04 | SH2 domain binding motif 551YINS554 |
SYDE2 | Fbw7 | SCF ubiquitin ligase complex, WD-40 motif | Neuronal differentiation | ELM: DEG_SCF_FBW7 Alignment of degron motifs63 ɸXɸɸɸTPPxS (ɸ: hydrophobic) | 7.14e−04 | TPxxS phospho-dependent degron 552INSPDNTPSLS562 |
SYDE2 | Calcineurin | Ser/Thr phosphatase | Ca2+-dependent synaptic plasticity | ELM: DOC_PP2B_LxvP141 πɸLxVP, SLiM region | 2.30e−03 | 179SFLRPP184 |
SYDE2 | Crk, Src | Kinase | ELM:LIG_SH3_3 | 1.32e −02 | 56RQQVSPP62 | |
SYDE1,2 | Crk | Kinase | ELM:LIG_SH2_Crk/Nck, putative phosphorylation and conserved binding motif59 | 1.52e−03 | SH2 domain binding motif 112YNPIP116 (SYDE1) 372YNPIP376 (SYDE2) | |
SYDE1,2 | GSK3 | Kinase | Regulation of synaptic clustering | ELM: MOD_GSK3_1, D2P2, conserved putative phosphorylation motif with DmRhoGAP100F58 | 2.68e−02 | 228GYLSDGDS235 (SYDE1) 619GYLSDGDS626(SYDE2) |
SYDE1,2 | RhoA | RhoGTPase domain | Regulation of dendritogenesis | Docking by Swarmdock36 | – | RhoGAP |
Protein | Interactor | Domain architecture | Signaling pathway | Experimental condition | Ref | Interacting region |
|---|---|---|---|---|---|---|
SYDE1 | Munc18 | Sec1-like domain | Presynaptic differentiation | coIP | Disordered domain | |
SYDE1 | Liprinα2 | Coiled-coil, SAM domain | Presynaptic differentiation | coIP | Disordered domain | |
SYDE1 | Ruk/CIN85 | SH3 domain | Control of Rho-family GTPases | Pull-down, LC–MS/MS | – | |
SYDE1 | XPO1 | ImportinβN domain, Nuclear export (exportin1, XPO1 domain) | Nuclear export to the cytoplasm | High through-put AP-MS, putative nuclear export signals* | L536RLVSS541* L713KDFDALILDLERELS728* | |
SYDE1 | ARHGAP28 | RhoGAP domain | RhoGAP activity, Actin filament | coIP, High through-put AP-MS | – | |
SYDE2 | PLEKHG3 | DH domain, PH domain | RhoGEF activity | High through-put AP-MS | – | |
SYDE2 | calcineurin | Serine/Threonine phosphatase | Activity-dependent dendritogenesis | Pull-down, ITC | SYDE2 232–289 235RVLSVP240 | |
DmSyd1 | Mtl | Small GTPase Rho | Rho-GTPase activity | Pull-down | RhoGAP | |
DmSyd1 | Rac1, Rac2 | Small GTPase Rho | Rho-GTPase activity | Pull-down | RhoGAP | |
DmSyd1 | RhoA, RhoL | Small GTPase Rho | Rho-GTPase activity | Pull-down | RhoGAP | |
DmSyd1 | Cdc42 | Small GTPase Rho | Rho-GTPase activity | Pull-down | RhoGAP | |
DmSyd1 | Neurexin-1 | lamininG domain, Syndecan/Neurexin domain | Neurexin-1 recruitment to active zones Postsynaptic GluR2 localization | Y2H, Co-IP, FLAP | PDZ | |
DmSyd1 | Bruchpilot (ELKS-related protein) | ELKS/CAST domain, coiled-coil | Presynaptic active zone organization Postsynaptic GluR2 localization | Y2H, coIP-MS/MS | PDZ, C-terminal (1-320aa, 1301-1844aa) |
