{"uniprot":"Q9Y5F1","gene":"PCDHB12","name":"Protocadherin beta-12","organism":"Homo sapiens (Human)","status":"dark","length":795,"sequence":"MENGGAGTLQIRQVLLFFVLLGMSQAGSETGNFLVMEELQSGSFVGNLAKTLGLEVSELSSRGARVVSNDNKECLQLDTNTGDLLLREMLDREELCGSNEPCVLYFQVLMKNPTQFLQIELQVRDINDHSPVFLEKEMLLEIPENSPVGAVFLLESAKDLDVGINAVKSYTINPNSHFHVKIRVNPDNRKYPELVLDKALDYEERPELSFILTALDGGSPPRSGTALVRVVVVDINDNSPEFEQAFYEVKILENSILGSLVVTVSAWDLDSGTNSELSYTFSHASEDIRKTFEINQKSGDITLTAPLDFEAIESYSIIIQATDGGGLFGKSTVRIQVMDVNDNAPEITVSSITSPIPENTPETVVMVFRIRDRDSGDNGKMVCSIPEDIPFVLKSSVNNYYTLETERPLDRESRAEYNITITVTDLGTPRLKTEHNITVLVSDVNDNAPAFTQTSYALFVRENNSPALHIGSISATDRDSGTNAQVNYSLLPSQDPHLPLASLVSINADNGHLFALRSLDYEALQGFQFRVGATDHGSPALSSEALVRVLVLDANDNSPFVLYPLQNGSAPCTELVPWAAEPGYLVTKVVAVDGDSGQNAWLSYQLLKATEPGLFGVWAHNGEVRTARLLSERDAAKHRLVVLVKDNGEPPRSATATLHVLLVDGFSQPYLPLPEAAPAQAQADSLTVYLVVALASVSSLFLFSVLLFVAVRLCRRSRAAPVGRCSVPEGPFPGHLVDVSGTGTLSQSYHYEVCVTGGSRSNKFKFLKPIIPNFLPQSTGSEVEENPPFQNNLGF","function_summary":"A single-pass cell-surface adhesion molecule that presents a multi-repeat extracellular cadherin ectodomain to mediate calcium-stabilized cell-cell adhesion and a cytoplasmic tail that couples adhesion to intracellular signaling and cytoskeletal organization. By assembling adhesive interfaces at the plasma membrane and relaying them to intracellular scaffolds, it supports cell adhesion and contributes to neural tissue patterning and development through regulated junction formation and signaling.","plain_language":"PCDHB12 has barely been studied. The model's best guess: A single-pass cell-surface adhesion molecule that presents a multi-repeat extracellular cadherin ectodomain to mediate calcium-stabilized cell-cell adhesion and a cytoplasmic tail that couples adhesion to intracellular signaling and cytoskeletal organization. By assembling adhesive interfaces at the plasma membrane and relaying them to intracellular scaffolds, it supports cell adhesion and contributes to neural tissue patterning and development through regulated junction formation and signaling.","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"},{"id":"GO:0007399","label":"nervous system development"}],"cellular_component":[{"id":"GO:0005886","label":"plasma membrane"}]},"interpro":[{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":32,"end":108},{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":127,"end":234},{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":230,"end":444},{"id":"IPR015919","name":"Cadherin-like superfamily","type":"homologous_superfamily","start":439,"end":664},{"id":"IPR013164","name":"Cadherin, N-terminal","type":"domain","start":32,"end":112},{"id":"IPR002126","name":"Cadherin-like","type":"domain","start":54,"end":133},{"id":"IPR002126","name":"Cadherin-like","type":"domain","start":134,"end":242},{"id":"IPR002126","name":"Cadherin-like","type":"domain","start":242,"end":347},{"id":"IPR002126","name":"Cadherin-like","type":"domain","start":348,"end":561},{"id":"IPR002126","name":"Cadherin-like","type":"domain","start":580,"end":671},{"id":"IPR032455","name":"Cadherin, cytoplasmic C-terminal domain","type":"domain","start":685,"end":768},{"id":"IPR020894","name":"Cadherin conserved site","type":"conserved_site","start":230,"end":240},{"id":"IPR020894","name":"Cadherin conserved site","type":"conserved_site","start":335,"end":345},{"id":"IPR020894","name":"Cadherin conserved site","type":"conserved_site","start":439,"end":449},{"id":"IPR020894","name":"Cadherin conserved site","type":"conserved_site","start":549,"end":559}],"reasoning":"I begin by dissecting the InterPro architecture and its order along the sequence. The N-terminus carries IPR013164 (Cadherin, N-terminal, residues 32–112), immediately followed and reinforced by multiple cadherin-like modules: IPR002126 (Cadherin-like domain) appears repeatedly—[54–133], [134–242], [242–347], [348–561], and [580–671]—together forming a canonical extracellular cadherin ectodomain. This ectodomain is further bracketed by cadherin superfamily signatures that span most of the extracellular region: IPR015919 (Cadherin-like superfamily) at [32–108], [127–234], [230–444], and [439–664]. The presence of several cadherin conserved sites—IPR020894 (Cadherin conserved site) at [230–240], [335–345], [439–449], and [549–559]—marks calcium-coordination motifs that rigidify cadherin repeats and enable calcium-dependent adhesion. After the long ectodomain, IPR032455 (Cadherin, cytoplasmic C-terminal domain, residues 685–768) defines a cytosolic tail specialized for intracellular coupling to signaling and cytoskeletal adaptors. The overall topology therefore resolves as a single-pass type I membrane protein with an N-terminal extracellular adhesive region and a C-terminal cytoplasmic signaling module.\n\nThis cadherin ectodomain architecture causes calcium-stabilized homophilic and heterophilic adhesion by presenting multiple cadherin repeats that bind one another across cell surfaces. The conserved cadherin sites coordinate Ca2+, which stiffens the ectodomain and prevents its unfolding during mechanical stress; this rigidity is essential for adhesion and directly supports the molecular function formalized as GO:0005515 protein binding. The cytoplasmic C-terminal domain recruits intracellular partners that translate adhesive state into cytoskeletal and transcriptional responses, reinforcing a primary role in multivalent protein interactions.\n\nFrom this molecular function, the biological processes follow. Calcium-dependent adhesion is the core driver of GO:0007155 cell adhesion, as the ectodomain mediates cell-cell contacts and the cytoplasmic tail organizes junctional complexes. In neural tissues, cadherin-mediated adhesion instructs tissue patterning and circuit assembly; thus the same adhesive and signaling logic naturally extends to GO:0007399 nervous system development, where regulated adhesion and downstream signaling guide neurite outgrowth and synapse formation.\n\nThe cellular context is dictated by the topology. The extensive extracellular cadherin array and the single-pass arrangement place the protein at the cell surface, consistent with a type I orientation and the GO:0005886 plasma membrane. The cytoplasmic C-terminal domain anchors intracellular interactions at membrane-proximal junctions, consolidating a plasma-membrane residency.\n\nMechanistically, the ectodomain forms calcium-stiffened adhesive interfaces that nucleate junctions; the cytoplasmic tail then couples to adaptor proteins to modulate actin and signaling pathways. I hypothesize that extracellularly it engages in homophilic cadherin binding and heterophilic contacts with other cadherins, while intracellularly it recruits catenins and PDZ-domain scaffolds. These assemblies would transmit mechanical cues into biochemical signals, tuning adhesion strength and transcriptional programs that underpin neural development and broader cell-adhesion processes.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q9Y5F1.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q9Y5F1"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q9Y5F1/entry","atlas":"/p/Q9Y5F1"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}