{"uniprot":"A6H8M9","gene":"CDHR4","name":"Cadherin-related family member 4","organism":"Homo sapiens (Human)","status":"dark","length":788,"sequence":"MVLLRLLVFLFAPVVSDLCSLPCFINVSESQGPGTVLQFLSFNCSSYTPTPTLELLNVQPPTTFFNPPSLARWQGTYVGKLTLSSSAQLDALMVNHYKVQLKFTCGNHVMEGSLSVDVQRDLSHIQCAGQFASPAGEMIQVPETVTPGARLYTLLLPGLELHGAQMSIISAQDLPHFPGPFSINEQGWLQAPSQGLLGQAQKVFQLQISVSFGQRQSCQGMVIVKVLPVPSSQVSFLEQAQNITIPENLAPGSEVVQVQARGVDLRYEILSPVPSPLFSIGRADGVVRTTTPLELARTSGTAVSRLQVKAFEQGQLWASAKLNLTMNVQLVNLWPPRCLPALLVSQIPETAPVGTVLNTLTCEDPDSVGATLDYKLWFRSSSNPASLCLYDRVLEVNATLDCDTPGACFQHAASILVLDGGQPQMTTEVPVLVMVTPINEFSPACAPRTFRVQEDAAPHTLLGSVVGTDMDYPHDNIEYYTSGGPTTFAVDRLSGEVHLLGPLDYEQQRLYRLTVLVIDHGQDQNPNHHLSGSCTITIEVEDVNDHAPECEPPFQELTIYAPLGRSVEVTKMSCQIPQEPQRLIYSYSIVGGNSQNRFILQGAILVHSDLVLGPFWPEQPRTYELLICVADAGPSTPHLSTTATIIVHLVPRRASTVATSTHRTTVPSTMTPMLVTDTEAFWQPQPWFVVVLTATGALLLLALGWLLGRLLQGLAQLLQAPSKPAQALLLNSIQGTEGSIEGFLEAPKMEMSQAPSSVMSLHFDGRAQDSRTGRDYLFNTHTGARRWL","function_summary":"A single-pass plasma membrane adhesion molecule whose extracellular region comprises tandem cadherin-like repeats that bind calcium to stabilize a rigid adhesive scaffold. This architecture promotes cell-cell cohesion by forming high-avidity adhesive interfaces and recruiting intracellular junctional complexes through its cytosolic tail. By assembling and stabilizing adhesion assemblies at the cell surface, it supports epithelial cohesion and junctional organization and modulates signaling pathways that respond to cell contact.","plain_language":"CDHR4 has barely been studied. The model's best guess: A single-pass plasma membrane adhesion molecule whose extracellular region comprises tandem cadherin-like repeats that bind calcium to stabilize a rigid adhesive scaffold. This architecture promotes cell-cell cohesion by forming high-avidity adhesive interfaces and recruiting intracellular junctional complexes through its cytosolic tail.","uniprot_summary":"Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to cell-body approximation.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0007155","label":"cell adhesion"}],"cellular_component":[{"id":"GO:0005886","label":"plasma membrane"}]},"interpro":[{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":236,"end":328},{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":335,"end":436},{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":438,"end":543},{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":544,"end":649},{"id":"IPR002126","name":"Cadherin-like","type":"domain","start":237,"end":338},{"id":"IPR002126","name":"Cadherin-like","type":"domain","start":338,"end":449},{"id":"IPR002126","name":"Cadherin-like","type":"domain","start":444,"end":554},{"id":"IPR050971","name":"Cadherin domain-containing protein","type":"family","start":306,"end":649},{"id":"IPR020894","name":"Cadherin conserved site","type":"conserved_site","start":538,"end":548}],"reasoning":"I begin with the InterPro architecture. The ectodomain is built from multiple cadherin-like repeats: IPR002126 (Cadherin-like domain) spans residues 237–338, followed contiguously by IPR002126 annotations at 338–449 and 444–554, and capped by a broader cadherin-like superfamily coverage IPR015919 across 236–328, 335–436, 544–649, and 438–543. This tandem arrangement of cadherin repeats forms a rigid, calcium-stabilized extracellular scaffold that mediates adhesive contacts. The presence of IPR050971 (Cadherin domain-containing protein family, residues 306–649) consolidates the identity of a cadherin-domain-containing adhesion molecule. A hallmark calcium-coordination motif is indicated by IPR020894 (Cadherin conserved site, residues 538–548), which typically stabilizes inter-repeat interfaces and confers calcium-dependent adhesion. Together, this extracellular cadherin array implies a single-pass type I topology with an N-terminal signal sequence and a short cytosolic tail that recruits intracellular partners.\n\nThis cadherin ectodomain architecture dictates molecular function. The tandem cadherin repeats create adhesive surfaces that bind other proteins—both extracellularly (homophilic or heterophilic cadherin interactions) and intracellularly (tail-mediated complexes)—thereby enforcing GO:0005515 protein binding as the operative molecular function. Calcium-stabilized cadherin folds cause high-avidity binding that nucleates larger adhesion assemblies.\n\nFrom this function, the biological process follows. Cadherin-mediated adhesion is the canonical driver of cell-cell cohesion; thus the architecture causally supports GO:0007155 cell adhesion. By forming adhesive junctional complexes, the protein organizes epithelial contacts and modulates barrier properties and signaling at cell interfaces.\n\nThe cellular context is determined by the single-pass type I membrane organization and cadherin ectodomain. Such molecules embed in the plasma membrane, consistent with GO:0005886 plasma membrane, where they assemble adherens junctions and related cell-cell contact sites. The extracellular cadherin array projects into the intercellular space, while the cytosolic tail couples to junctional scaffolds.\n\nMechanistically, the ectodomain’s calcium-stiffened repeats generate a high-affinity adhesive platform that clusters at cell-cell contacts. The cytosolic tail likely recruits catenin-like adaptors and junctional scaffolds, translating extracellular adhesion into intracellular architecture. I therefore hypothesize interactions with classical adhesion machinery: extracellular homophilic/heterophilic cadherins; intracellular β-catenin and p120-catenin complexes; α-catenin and actin-associated adaptors. These assemblies would stabilize epithelial adhesion and tune downstream signaling pathways that respond to cell contact and tissue integrity.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-A6H8M9.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/A6H8M9"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/A6H8M9/entry","atlas":"/p/A6H8M9"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}