{"uniprot":"Q9Y5G3","gene":"PCDHGB1","name":"Protocadherin gamma-B1","organism":"Homo sapiens (Human)","status":"dark","length":927,"sequence":"MQRAREAEMMKSQVLFPFLLSLFCGAISQQIRYTIPEELANGSRVGKLAKDLGLSVRELPTRKLRVSAEDYFNVSLESGDLLVNGRIDREKICGRKLECALEFETVAENPMNVFHVVVVIQDINDNAPRFVAKGIDLEICESALPGVKFSLDSAQDADVEGNSLKLYTINPNQYFSLSTKESPDGSKYPVLLLEKPLDREHQSSHRLILTAMDGGDPPLSGTTHIWIRVTDANDNAPVFSQEVYRVSLQENVPWGTSVLRVMATDQDEGINAEITYAFLNSPISTSLFNLNPNTGDITTNGTLDFEETSRYVLSVEAKDGGVHTAHCNVQIEIVDENDNAPEVTFMSFSNQIPEDSDLGTVIALIKVRDKDSGQNGMVTCYTQEEVPFKLESTSKNYYKLVIAGALNREQTADYNVTIIATDKGKPALSSRTSITLHISDINDNAPVFHQASYVVHVSENNPPGASIAQVSASDPDLGPNGRVSYSILASDLEPRELLSYVSVSPQSGVVFAQRAFDHEQLRAFELTLQARDQGSPALSANVSLRVLVGDLNDNAPRVLYPALGPDGSALFDMVPRAAEPGYLVTKVVAVDADSGHNAWLSYHVLQASEPGLFSLGLRTGEVRTARALGDRDAARQRLLVAVRDGGQPPLSATATLHLIFADSLQEVLPDLSDRPEPSDPQTELQFYLVVALALISVLFLLAVILAIALRLRRSSSLDTEGCFQTGLCSKSGPGVPPNHSEGTLPYSYNLCIASHSAKTEFNSLNLTPEMAPPQDLLCDDPSMVVCASNEDHKIAYDPSLSSHQAPPNTDWRFSQAQRPGTSGSQNGDDTGTWPNNQFDTEMLQAMILASASEAADGSSTLGGGAGTMGLSARYGPQFTLQHVPDYRQNVYIPGSNATLTNAAGKRDGKAPAGGNGNKKKSGKKEKK","function_summary":"A single-pass type I membrane adhesion molecule that uses a calcium-stabilized cadherin ectodomain to mediate homophilic cell-cell adhesion and a cytoplasmic tail to recruit catenin complexes that couple junctions to the actin cytoskeleton and signaling pathways. It resides at the cell surface and adherens junctions, where it stabilizes intercellular cohesion, and it can be packaged into extracellular vesicles.","plain_language":"PCDHGB1 has barely been studied. The model's best guess: A single-pass type I membrane adhesion molecule that uses a calcium-stabilized cadherin ectodomain to mediate homophilic cell-cell adhesion and a cytoplasmic tail to recruit catenin complexes that couple junctions to the actin cytoskeleton and signaling pathways. It resides at the cell surface and adherens junctions, where it stabilizes intercellular cohesion, and it can be packaged into extracellular vesicles.","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 the formation of multicellular aggregates.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0007155","label":"cell adhesion"}],"cellular_component":[{"id":"GO:0070062","label":"extracellular exosome"}]},"interpro":[{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":29,"end":100},{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":124,"end":231},{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":233,"end":335},{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":337,"end":440},{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":437,"end":559},{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":552,"end":659},{"id":"IPR002126","name":"Cadherin-like","type":"domain","start":28,"end":130},{"id":"IPR013164","name":"Cadherin, N-terminal","type":"domain","start":30,"end":109},{"id":"IPR002126","name":"Cadherin-like","type":"domain","start":131,"end":239},{"id":"IPR002126","name":"Cadherin-like","type":"domain","start":239,"end":343},{"id":"IPR002126","name":"Cadherin-like","type":"domain","start":344,"end":558},{"id":"IPR002126","name":"Cadherin-like","type":"domain","start":574,"end":671},{"id":"IPR032455","name":"Cadherin, cytoplasmic C-terminal domain","type":"domain","start":683,"end":764},{"id":"IPR031904","name":"Cadherin, C-terminal catenin-binding domain","type":"domain","start":806,"end":927},{"id":"IPR020894","name":"Cadherin conserved site","type":"conserved_site","start":227,"end":237},{"id":"IPR020894","name":"Cadherin conserved site","type":"conserved_site","start":436,"end":446},{"id":"IPR020894","name":"Cadherin conserved site","type":"conserved_site","start":546,"end":556}],"reasoning":"I begin by dissecting the InterPro architecture and its order along the sequence. The N-terminal ectodomain is built from tandem cadherin-like repeats: IPR015919 (Cadherin-like superfamily) spans residues 29–100, 124–231, 233–335, 337–440, 552–659, and is complemented by specific cadherin modules IPR002126 (Cadherin-like domain) at 28–130, 131–239, 239–343, 344–558, and 574–671. Within these repeats lie two conserved calcium-binding motifs, IPR020894 (Cadherin conserved site) at 227–237 and 436–446, plus a third motif at 546–556. This tandem arrangement of cadherin repeats creates a rigid, calcium-stabilized extracellular rod that mediates homophilic adhesion. The extracellular block is followed by a single-pass transmembrane segment implied by the type I topology, and a cytoplasmic tail that contains IPR032455 (Cadherin, cytoplasmic C-terminal domain, 683–764) and IPR031904 (Cadherin, C-terminal catenin-binding domain, 806–927). This C-terminal architecture is the canonical docking platform for catenins and other cytoskeletal adaptors, coupling adhesion to the actin cytoskeleton and signaling hubs.\n\nThis domain layout dictates molecular function. The tandem cadherin repeats and conserved calcium-binding sites generate a Ca2+-stiffened adhesive surface that forms trans-dimers with cadherins on neighboring cells; the intracellular catenin-binding tail recruits cytoskeletal and signaling partners. Together, these features enforce multivalent protein interactions, aligning with GO:0005515 protein binding as the operative molecular function.\n\nFrom this molecular activity, the biological process follows directly. Calcium-stabilized cadherin ectodomains drive cell-cell adhesion by homophilic binding, which is the core of GO:0007155 cell adhesion. The extracellular cadherin array causes adhesive cohesion between adjacent cells, while the cytoplasmic catenin-binding domain consolidates junctional complexes and tunes adhesion dynamics.\n\nCellular location is dictated by topology and trafficking. The presence of an extensive extracellular cadherin ectodomain and a cytoplasmic tail defines a single-pass type I membrane protein that resides at the cell surface and concentrates at adherens junctions. The architecture and membrane insertion support a membrane assignment and are consistent with packaging into extracellular vesicles; thus, beyond being a membrane-resident adhesion molecule, it can be found in GO:0070062 extracellular exosome.\n\nMechanistically, the ectodomain’s calcium-bound repeats generate a rigid adhesive shaft that mediates homophilic cell-cell binding. The cytoplasmic tail recruits catenins via IPR031904, which nucleate complexes with α-, β-, and p120-catenins and actin-regulatory machinery, thereby stabilizing junctions and coupling adhesion to intracellular signaling. I therefore hypothesize that this protein forms trans-adhesive bridges with identical cadherin molecules on neighboring cells, while its intracellular tail assembles catenin–actin modules and occasionally traffics via exosome pathways.\n\nTo synthesize: the cadherin-like ectodomain array (IPR015919 and IPR002126 modules with conserved sites IPR020894) causes calcium-dependent homophilic adhesion; the cytoplasmic C-terminal catenin-binding domains (IPR032455 and IPR031904) cause junctional coupling to the cytoskeleton and signaling; together they enforce cell adhesion at the membrane and in exosome-associated contexts, matching GO:0005515, GO:0007155, and GO:0070062.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q9Y5G3.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q9Y5G3"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q9Y5G3/entry","atlas":"/p/Q9Y5G3"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}