{"uniprot":"P01715","gene":"IGLV3-1","name":"Immunoglobulin lambda variable 3-1","organism":"Homo sapiens (Human)","status":"dark","length":115,"sequence":"MAWIPLFLGVLAYCTGSVASYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTAH","function_summary":"A kappa-type light-chain variable region that pairs with a heavy-chain variable region to create the antigen-binding site of antibodies. It operates in two states: at the cell surface as part of the membrane-bound B-cell receptor that initiates clonal expansion and differentiation, and after secretion as a soluble effector that circulates and can be packaged into extracellular vesicles. By driving high-affinity antigen recognition through a β-sandwich immunoglobulin fold and stabilizing hypervariable loops, it underpins humoral immunity and can indirectly influence filtration physiology in the kidney via immune-modulatory actions.","plain_language":"IGLV3-1 has barely been studied. The model's best guess: A kappa-type light-chain variable region that pairs with a heavy-chain variable region to create the antigen-binding site of antibodies. It operates in two states: at the cell surface as part of the membrane-bound B-cell receptor that initiates clonal expansion and differentiation, and after secretion as a soluble effector that circulates and can be packaged into extracellular vesicles.","uniprot_summary":"V region of the variable domain of immunoglobulin light chains that participates in the antigen recognition. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by an adaptive immune response essential for the defense system of multicellular organisms.","go_terms":{"molecular_function":[{"id":"GO:0042802","label":"identical protein binding"}],"biological_process":[{"id":"GO:0003094","label":"glomerular filtration"}],"cellular_component":[{"id":"GO:0070062","label":"extracellular exosome"},{"id":"GO:0005886","label":"plasma membrane"}]},"interpro":[{"id":"IPR013783","name":"Immunoglobulin-like fold","type":"homologous_superfamily","start":11,"end":115},{"id":"IPR036179","name":"Immunoglobulin-like domain superfamily","type":"homologous_superfamily","start":23,"end":112},{"id":"IPR007110","name":"Immunoglobulin-like domain","type":"domain","start":5,"end":115},{"id":"IPR013106","name":"Immunoglobulin V-set domain","type":"domain","start":24,"end":112},{"id":"IPR003599","name":"Immunoglobulin domain subtype","type":"domain","start":26,"end":115},{"id":"IPR050150","name":"Immunoglobulin Variable Light Chain","type":"family","start":18,"end":108}],"reasoning":"I begin with the InterPro architecture, which is uniformly immunoglobulin-like across the length of the polypeptide. IPR007110 (Immunoglobulin-like domain, residues 5–115) and IPR013783 (Immunoglobulin-like fold, residues 11–115) define a β-sandwich scaffold typical of antibody variable domains. This scaffold is refined by IPR036179 (Immunoglobulin-like domain superfamily, residues 23–112), and more specifically typed by IPR013106 (Immunoglobulin V-set domain, residues 24–112) and IPR003599 (Immunoglobulin domain subtype, residues 26–115). The family-level assignment IPR050150 (Immunoglobulin Variable Light Chain, residues 18–108) resolves the module as a kappa-type light-chain variable region. The ordered layout—an N-terminal signal-compatible Ig-like domain spanning nearly the entire sequence—establishes a single V-set immunoglobulin variable domain that pairs with a heavy-chain variable region to form the antigen-binding site.\n\nThis V-set architecture causes high-affinity antigen recognition through complementarity-determining regions housed in the Ig-like fold. The molecular function is therefore dominated by specific antigen binding; in GO terms, this is captured by GO:0005515 protein binding and further mechanistically explained by the V-set β-sandwich that stabilizes hypervariable loops. The same β-sandwich also mediates homotypic and heterotypic contacts among immunoglobulin assemblies; this supports GO:0042802 identical protein binding, as light-chain variable domains can self-associate or assemble symmetric higher-order complexes during biosynthesis and secretion.\n\nFrom this molecular function, the biological process follows: antigen recognition by the membrane-bound B-cell receptor initiates clonal expansion and differentiation, culminating in high-affinity antibody production and secretion. Secreted antibodies shape organ physiology beyond immunity. In particular, glomerular filtration depends on tightly regulated protein–protein and protein–matrix interactions in the renal filtrate pathway; antibodies and soluble immune complexes modulate this milieu, providing a mechanistic route to GO:0003094 glomerular filtration as an affected process.\n\nCellular localization is dictated by the two operational states of immunoglobulin modules. As part of the B-cell receptor complex, the light-chain variable region resides at the cell surface, consistent with GO:0005886 plasma membrane. Upon differentiation to plasma cells, the same module is secreted and can be packaged into extracellular vesicles, aligning with GO:0070062 extracellular exosome. The soluble, secreted state coheres with the experimentally observed secreted localization.\n\nMechanistically, the light-chain variable domain pairs with a heavy-chain variable domain to form the antigen-binding site; antigen engagement at the membrane triggers intracellular signaling via the BCR complex. In the secreted state, identical protein binding likely reflects assembly and stabilization of multimeric immunoglobulin complexes and transient homotypic clustering that enhance avidity and trafficking. I therefore hypothesize interactions with heavy-chain variable domains (to form the Fab), with membrane-anchoring components of the BCR, and with extracellular partners that include antigens and vesicle biogenesis machinery. Together, these interactions enable antigen recognition at the plasma membrane and immune modulation that can influence filtration physiology in the kidney.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-P01715.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/P01715"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/P01715/entry","atlas":"/p/P01715"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}