{"uniprot":"Q5SZI1","gene":"LDLRAD2","name":"Low-density lipoprotein receptor class A domain-containing protein 2","organism":"Homo sapiens (Human)","status":"dark","length":272,"sequence":"MEACCLLQLPQRLLLLGAAALTATALETADLAELCGQTWQGDGLLLRSHAASRRFYFVAPDTDCGLWVQAAAPGDRIRFQFRFFLVYSLTPAPPALNTSSPAPADPCAPGSYLQFYEGPPGAPRPLGSPLCGLNIPVPVASSGPFLGLRLVTRGRQPRVDFVGEVTSFRLGPCGAYFRCQNGRCIPSSLVCDPWGMDNCGDGSDQGSWSPADCRGPSPVPSQTGSTDAHTSRSLTPSPALGSAGSLWIAAERSSPAGRDPTRQDAALEGSTE","function_summary":"A single-pass cell-surface receptor-like protein that presents a modular extracellular recognition platform to bind extracellular ligands and matrix components, thereby organizing signaling pathways that guide neuronal maturation. Its ectodomain architecture enables high-avidity ligand capture and clustering at the plasma membrane, which in turn recruits intracellular adaptors to influence neurite outgrowth and differentiation.","plain_language":"LDLRAD2 has barely been studied. The model's best guess: A single-pass cell-surface receptor-like protein that presents a modular extracellular recognition platform to bind extracellular ligands and matrix components, thereby organizing signaling pathways that guide neuronal maturation. Its ectodomain architecture enables high-avidity ligand capture and clustering at the plasma membrane, which in turn recruits intracellular adaptors to influence neurite outgrowth and differentiation.","uniprot_summary":"May be involved in neuron differentiation.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0030182","label":"neuron differentiation"}],"cellular_component":[{"id":"GO:0016020","label":"membrane"}]},"interpro":[{"id":"IPR035914","name":"Spermadhesin, CUB domain superfamily","type":"homologous_superfamily","start":30,"end":173},{"id":"IPR036055","name":"LDL receptor-like superfamily","type":"homologous_superfamily","start":173,"end":215},{"id":"IPR042333","name":"LRAD2/Mig-13-like","type":"family","start":1,"end":224},{"id":"IPR002172","name":"Low-density lipoprotein (LDL) receptor class A repeat","type":"repeat","start":172,"end":215}],"reasoning":"I begin with the InterPro architecture. The sequence is encompassed by IPR042333 (LRAD2/Mig-13-like family, residues 1–224), marking it as a member of the LRAD/Mig-13-like receptor family that typically functions as a single-pass membrane protein with an extracellular recognition module. The N-terminal ectodomain contains IPR035914 (Spermadhesin, CUB domain superfamily, residues 30–173), a β-sandwich module widely used for extracellular ligand capture and adhesion. Immediately downstream sits an LDL receptor-like module: IPR036055 (LDL receptor-like superfamily, residues 173–215) and, within it, IPR002172 (LDL receptor class A repeat, residues 172–215). The CUB domain followed by a calcium-binding LDLR class A repeat creates a tandem recognition platform that binds extracellular ligands and matrix components with high avidity. This ectodomain arrangement precedes a single-pass transmembrane segment and short cytosolic tail typical of LRAD/Mig-13-like proteins, consistent with a membrane-embedded signaling receptor.\n\nThis extracellular CUB–LDLR repeat architecture dictates molecular function as protein binding (GO:0005515). CUB domains provide broad-spectrum binding to extracellular proteins and proteoglycans, while LDLR class A repeats stabilize calcium-dependent complexes and frequently mediate endocytic or signaling receptor interactions. The LRAD2/Mig-13-like family signature indicates that binding events at the cell surface are transduced across the membrane, supporting a receptor-like role that organizes downstream pathways through protein–protein interactions rather than enzymatic catalysis.\n\nFrom this binding-centric receptor mechanism, the biological process follows. LRAD/Mig-13-like receptors are expressed in neural contexts and modulate neuronal lineage decisions. A cell-surface recognition module that tunes adhesion and matrix cues causally influences neurite outgrowth and fate acquisition, aligning with neuron differentiation (GO:0030182). The tandem CUB–LDLR ectodomain is well-suited to interpret extracellular morphogens and adhesion cues that guide neuronal maturation.\n\nThe cellular component is dictated by the single-pass topology and LRAD family identity. The presence of an extensive extracellular ectodomain coupled to a transmembrane core places the protein in membrane (GO:0016020). The architecture and single-pass annotation indicate a cell-surface receptor embedded in the plasma membrane, where it can survey extracellular ligands and relay signals to the cytosol.\n\nMechanistically, the ectodomain captures extracellular ligands via the CUB domain and calcium-stabilized LDLR repeats, clustering the receptor and triggering intracellular signaling through its cytosolic tail. This likely recruits adaptor proteins and cytoskeletal regulators that steer neuronal differentiation. I hypothesize that it forms complexes with extracellular matrix components and cell-surface co-receptors, and intracellularly associates with endocytic and signaling adaptors to modulate neurite patterning and maturation.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q5SZI1.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q5SZI1"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q5SZI1/entry","atlas":"/p/Q5SZI1"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}