{"uniprot":"Q96K37","gene":"SLC35E1","name":"Solute carrier family 35 member E1","organism":"Homo sapiens (Human)","status":"dark","length":410,"sequence":"MAAAAVGAGHGAGGPGAASSSGGAREGARVAALCLLWYALSAGGNVVNKVILSAFPFPVTVSLCHILALCAGLPPLLRAWRVPPAPPVSGPGPSPHPSSGPLLPPRFYPRYVLPLAFGKYFASVSAHVSIWKVPVSYAHTVKATMPIWVVLLSRIIMKEKQSTKVYLSLIPIISGVLLATVTELSFDMWGLVSALAATLCFSLQNIFSKKVLRDSRIHHLRLLNILGCHAVFFMIPTWVLVDLSAFLVSSDLTYVYQWPWTLLLLAVSGFCNFAQNVIAFSILNLVSPLSYSVANATKRIMVITVSLIMLRNPVTSTNVLGMMTAILGVFLYNKTKYDANQQARKHLLPVTTADLSSKERHRSPLEKPHNGLLFPQHGDYQYGRNNILTDHFQYSRQSYPNSYSLNRYDV","function_summary":"A multi-pass membrane transporter in human cells that resides at the Golgi and uses an alternating-access antiport mechanism to exchange small, often phosphorylated metabolites across the membrane. By tuning the lumenal milieu and precursor pools at the ER–Golgi interface, it supports vesicle formation and cargo flow through the early secretory pathway. Its membrane-embedded architecture and transient protein contacts position it as a transport-driven modulator of Golgi trafficking.","plain_language":"SLC35E1 has barely been studied. The model's best guess: A multi-pass membrane transporter in human cells that resides at the Golgi and uses an alternating-access antiport mechanism to exchange small, often phosphorylated metabolites across the membrane. By tuning the lumenal milieu and precursor pools at the ER–Golgi interface, it supports vesicle formation and cargo flow through the early secretory pathway.","uniprot_summary":"Probable transporter.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0006888","label":"endoplasmic reticulum to Golgi vesicle-mediated transport"}],"cellular_component":[{"id":"GO:0005794","label":"Golgi apparatus"}]},"interpro":[{"id":"IPR037185","name":"Multidrug transporter EmrE superfamily","type":"homologous_superfamily","start":103,"end":181},{"id":"IPR004853","name":"Sugar phosphate transporter domain","type":"domain","start":29,"end":333},{"id":"IPR050186","name":"Triose Phosphate/Phosphate Translocator","type":"family","start":32,"end":341}],"reasoning":"I begin with the InterPro architecture. The core of the protein is defined by IPR004853 (Sugar phosphate transporter domain, residues 29–333), which is the hallmark of the drug/metabolite transporter fold that mediates alternating-access exchange of small, often phosphorylated solutes across membranes. This transporter core is further specified by IPR050186 (Triose Phosphate/Phosphate Translocator family, residues 32–341), a family whose members catalyze strict counter-exchange of phosphate-containing metabolites rather than net uptake. Embedded within this scaffold is IPR037185 (Multidrug transporter EmrE superfamily, residues 103–181), a homologous superfamily that enforces a multi-pass membrane architecture optimized for secondary-active antiport. The ordered layout—an EmrE-like transmembrane core nested within a sugar-phosphate transporter domain and classified as a triose phosphate/phosphate translocator—causally dictates a multi-pass membrane transporter that operates by alternating access and obligate antiport.\n\nThis architecture determines molecular function. The EmrE-like fold and TPT family membership together cause transmembrane transporter activity that exchanges small anionic metabolites without hydrolysis. Such transporters often require transient protein contacts for trafficking and assembly, which supports GO:0005515 protein binding as an intrinsic property of a membrane-resident complex-forming transporter.\n\nFrom function to process, a phosphate/sugar-phosphate exchanger in the early secretory pathway would directly influence lumenal composition and vesicle dynamics. By tuning the balance of phosphorylated sugars and inorganic phosphate in the Golgi-ER interface, the transporter can modulate luminal pH buffering and glycosylation precursor pools, thereby facilitating vesicle budding and cargo flow. This mechanistic role aligns with GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport.\n\nCellular location follows from both topology and pathway coupling. The multi-pass transporter fold and the TPT family identity require a membrane environment, and the functional tie to early secretory traffic points to the Golgi apparatus. This is consistent with a residence at the Golgi apparatus (GO:0005794) and with a multi-pass membrane localization.\n\nMechanistically, I hypothesize that the protein forms a counter-exchange module that couples cytosolic and luminal pools of phosphate-bearing metabolites to sustain Golgi homeostasis. By transiently binding trafficking factors, it could scaffold or regulate COPII/COPI vesicle cycles. Likely interaction partners include Golgi-resident small GTPases and coat components that sense or respond to luminal status—such as ARF1 and COPI subunits—providing a conduit between metabolite exchange and vesicle flow.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q96K37.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q96K37"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q96K37/entry","atlas":"/p/Q96K37"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}