{"uniprot":"Q9H106","gene":"SIRPD","name":"Signal-regulatory protein delta","organism":"Homo sapiens (Human)","status":"dark","length":197,"sequence":"MPIPASPLHPPLPSLLLYLLLELAGVTHVFHVQQTEMSQTVSTGESIILSCSVPNTLPNGPVLWFKGTGPNRKLIYNFKQGNFPRVKEIGDTTKPGNTDFSTRIREISLADAGTYYCVKFIKGRAIKEYQSGRGTQVFVTEQNPRPPKNRPAGRAGSRAHHDAHTCLSALPERNSTNYFVQPCCCLRLLGLTGLLSK","function_summary":"A cell-surface immunoglobulin-like receptor that uses an extracellular Ig platform to bind ligands and initiate signaling at the plasma membrane. By coupling ligand recognition to intracellular pathways, it promotes cell recognition and signal transduction that mobilize antibacterial defenses. Its single-pass type I architecture positions an extracellular recognition module to detect cues consistent with pattern-recognition, thereby triggering membrane-proximal signaling cascades that coordinate innate immune responses.","plain_language":"SIRPD has barely been studied. The model's best guess: A cell-surface immunoglobulin-like receptor that uses an extracellular Ig platform to bind ligands and initiate signaling at the plasma membrane. By coupling ligand recognition to intracellular pathways, it promotes cell recognition and signal transduction that mobilize antibacterial defenses.","uniprot_summary":"May be involved in immune system processes.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0008037","label":"cell recognition"},{"id":"GO:0007165","label":"signal transduction"},{"id":"GO:0009617","label":"response to bacterium"},{"id":"GO:0002221","label":"pattern recognition receptor signaling pathway"}],"cellular_component":[{"id":"GO:0005886","label":"plasma membrane"}]},"interpro":[{"id":"IPR013783","name":"Immunoglobulin-like fold","type":"homologous_superfamily","start":31,"end":152},{"id":"IPR036179","name":"Immunoglobulin-like domain superfamily","type":"homologous_superfamily","start":32,"end":148},{"id":"IPR007110","name":"Immunoglobulin-like domain","type":"domain","start":13,"end":117},{"id":"IPR013106","name":"Immunoglobulin V-set domain","type":"domain","start":34,"end":140},{"id":"IPR003599","name":"Immunoglobulin domain subtype","type":"domain","start":36,"end":140},{"id":"IPR051755","name":"Immunoglobulin-like Cell Surface Receptor","type":"family","start":7,"end":157}],"reasoning":"I begin with the InterPro architecture. The ectodomain is defined by multiple immunoglobulin signatures: IPR007110 (Immunoglobulin-like domain, residues 13–117) sits within a larger Ig scaffold captured by IPR013783 (Immunoglobulin-like fold homologous superfamily, residues 31–152) and IPR036179 (Immunoglobulin-like domain superfamily, residues 32–148). Within this scaffold, the N-terminal half carries a V-set module, IPR013106 (Immunoglobulin V-set domain, residues 34–140), further refined by IPR003599 (Immunoglobulin domain subtype, residues 36–140). The entire extracellular region is classified by IPR051755 (Immunoglobulin-like Cell Surface Receptor family, residues 7–157), which typifies single-pass type I receptors that bind ligands via Ig-like domains and signal across the membrane. The ordered layout—an N-terminal signal sequence leading into tandem Ig-like domains and a single transmembrane segment—creates a rigid extracellular recognition platform coupled to a cytoplasmic signaling tail.\n\nThis Ig-based ectodomain causes high-affinity, avidity-driven protein binding at the cell surface, consistent with GO:0005515 protein binding as the molecular function. The V-set domain architecture is optimized for ligand capture and cell–cell or cell–pathogen recognition rather than enzymatic catalysis, reinforcing a binding/sensing role.\n\nFrom this binding capacity, the biological role follows. Ig-like cell-surface receptors commonly mediate cell recognition and initiate signaling cascades. The extracellular Ig platform supports GO:0008037 cell recognition by enabling selective adhesion and ligand detection. The membrane-proximal signaling capacity and Ig receptor family identity align with GO:0007165 signal transduction: ligand engagement by the Ig ectodomain triggers intracellular pathways through the single-pass receptor core. In innate immunity, such receptors often act as soluble or membrane-associated pattern-recognition modules; this architecture supports GO:0002221 pattern recognition receptor signaling pathway by enabling detection and relay of extracellular danger signals. Together, these activities drive GO:0009617 response to bacterium, as recognition and signaling at the surface initiate antibacterial programs.\n\nThe cellular context is dictated by the topology. The presence of a single-pass type I receptor family signature (IPR051755) and the Ig ectodomain imply a luminal/extracellular N-terminus and cytosolic C-terminus, placing the protein at the cell surface. This supports GO:0005886 plasma membrane as the cellular component and aligns with a membrane localization.\n\nMechanistically, the Ig ectodomain forms a recognition hub that binds extracellular ligands or microbial patterns, while the transmembrane and cytosolic regions couple to intracellular effectors. I hypothesize that the receptor clusters with Src-family kinases and adaptor modules to propagate signals that modulate phagocytic and inflammatory pathways. Likely partners include membrane-proximal signaling adaptors and kinases that assemble at Ig-like receptor cytoplasmic tails, enabling rapid activation of innate immune signaling and bactericidal responses.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q9H106.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q9H106"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q9H106/entry","atlas":"/p/Q9H106"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}