{"uniprot":"Q6ZVE7","gene":"GOLT1A","name":"Vesicle transport protein GOT1A","organism":"Homo sapiens (Human)","status":"dark","length":132,"sequence":"MISITEWQKIGVGITGFGIFFILFGTLLYFDSVLLAFGNLLFLTGLSLIIGLRKTFWFFFQRHKLKGTSFLLGGVVIVLLRWPLLGMFLETYGFFSLFKGFFPVAFGFLGNVCNIPFLGALFRRLQGTSSMV","function_summary":"A multi-pass membrane scaffold in human cells that organizes vesicle docking and fusion along the early secretory pathway. By assembling and stabilizing trafficking machinery at perinuclear ER–Golgi stations, it promotes cargo flow between the endoplasmic reticulum and Golgi cisternae and the trans-Golgi network. This assembly role supports efficient membrane delivery that can enhance inflammatory signaling cascades, consistent with its perinuclear enrichment and membrane-embedded architecture.","plain_language":"GOLT1A has barely been studied. The model's best guess: A multi-pass membrane scaffold in human cells that organizes vesicle docking and fusion along the early secretory pathway. By assembling and stabilizing trafficking machinery at perinuclear ER–Golgi stations, it promotes cargo flow between the endoplasmic reticulum and Golgi cisternae and the trans-Golgi network.","uniprot_summary":"May be involved in vesicle-mediated transport.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0043123","label":"positive regulation of I-kappaB kinase/NF-kappaB signaling"}],"cellular_component":[{"id":"GO:0005783","label":"endoplasmic reticulum"},{"id":"GO:0005635","label":"nuclear envelope"},{"id":"GO:0005802","label":"trans-Golgi network"},{"id":"GO:0000137","label":"Golgi cis cisterna"}]},"interpro":[{"id":"IPR045176","name":"Protein transport protein Got1","type":"family","start":1,"end":131},{"id":"IPR007305","name":"Vesicle transport protein, Got1/SFT2-like","type":"family","start":15,"end":110}],"reasoning":"I begin with the InterPro architecture. The sequence is dominated by two overlapping family signatures that span essentially the entire polypeptide: IPR045176 (Protein transport protein Got1 family, residues 1–131) and IPR007305 (Vesicle transport protein, Got1/SFT2-like family, residues 15–110). This tandem of Got1/Sft2-like family profiles defines a compact, multi-pass membrane module that lacks catalytic motifs and instead forms a small helical bundle specialized for vesicle trafficking. The N-to-C arrangement—full-length Got1 family coverage followed by an internal Sft2-like core—creates a membrane-embedded scaffold that binds other trafficking factors rather than performing enzymatic chemistry. Such an architecture causally supports a molecular function centered on multivalent protein binding (GO:0005515), because membrane-tethered adaptors in the Got1/Sft2 lineage assemble and stabilize fusion machinery.\n\nFrom this binding-centric membrane scaffold, I infer the biological role. Got1/Sft2-like proteins organize vesicle docking and fusion steps that move cargo between the endoplasmic reticulum and Golgi. By stabilizing SNARE assemblies and coordinating vesicle tethering, this architecture drives vesicle-mediated transport and Golgi-directed trafficking. This trafficking nexus can feed forward into signaling pathways: membrane-delivered receptors and adaptors modulate inflammatory cascades. Thus, a membrane scaffold that promotes efficient ER-to-Golgi and intra-Golgi traffic can positively regulate I-kappaB kinase/NF-kappaB signaling (GO:0043123) by ensuring timely delivery and turnover of pathway components at perinuclear secretory stations.\n\nThe cellular geography follows directly from the trafficking role and the membrane-embedded architecture. The protein is a multi-pass membrane component that concentrates at the Golgi apparatus and its cisternae, consistent with localization to the Golgi cis cisterna (GO:0000137) and the trans-Golgi network (GO:0005802). Its role in early secretory pathway flow also places it at the endoplasmic reticulum (GO:0005783), and the continuity of the ER with the nuclear envelope explains presence at the nuclear envelope (GO:0005635). Together, these compartments form a perinuclear secretory hub where this scaffold operates.\n\nMechanistically, I hypothesize that the protein forms a membrane-anchored platform that binds and organizes vesicle fusion machinery. By stabilizing cognate SNAREs and associated tethering complexes, it promotes vesicle docking and fusion along the ER–Golgi axis. This assembly function predicts transient interactions with ER–Golgi tethers and SNAREs, and it explains how perturbations in this hub could modulate NF-kappaB signaling through altered trafficking and receptor supply. Likely partners include ER–Golgi tethering factors and Golgi SNAREs that collectively choreograph cargo flow and signal transduction at perinuclear membranes.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q6ZVE7.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q6ZVE7"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q6ZVE7/entry","atlas":"/p/Q6ZVE7"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}