{"uniprot":"Q96KW2","gene":"POM121L2","name":"POM121-like protein 2","organism":"Homo sapiens (Human)","status":"dark","length":1035,"sequence":"MGSFLSKLELSPSSPAQVRTDLPERPTKRRPPQPLHQVHRVQFVHRAHPAPRYRPVRRRPNLDPANPTTWLANEAWRRFPMKKSQNSPLGPLPSDWWESYLKRTIWSLRHPRPIWSPVTIRITPPDQRVPPSTSPEDVIALAGLPPSEELADPCSKETVLRALRECRKGKGRLEEPLFPESLDSKRRSPETRPSAFKPLMKNGTLTSFVPRPGPLKRSLHSWGSDHSLTKRPNCSSMSSLASIYRGGTLSSKRNAIGSSYSSCRNFSDPWKRSVPSVSFETPEWPIKKEKSCHRPSSPVPLVSDFESLGGSESSGQQNQKIPQLPSSPENLVSEIPPPQLGYAVSDENLTLGKKAELQVSNNAGEDTTEVNTDPFPETWLAIQPSLSLALPSSETDLTQGANPQLENLRKMQKSLGPLASPQSTGEATSVAHSPLKTPSLPTPPGCSQSELLPGTSPDSKPTATFILLTPTSPTLPVTDTTWPPSTSQADRSPMPPDPPAPPTIQSTLLGMVSSPTSHLSASAPPDATSAHLMLKPILGPLHNSEIGSSSYSRISVTAAASSISSLSTIQGTLTPTFKPIFGSIDPLKTTPMIAPFSSKQTPPPFTHASTHHFHGLVKATSVVMSTTLASTSKDSVFKPPLDFGVVNVTSAVGNTYSVPSTCDTFLLGTAQAFRADFTPATGFIFPPHHHPTIPTVHTVTMFTQVLSSVVQISPRSSTANFRGMGSPLPASALVSTNWLASTPSISNLTPAITSPLGSSSRPPFPLSQGANPQPAFGATNGQKQGPSQPALMPSVSSSFLFGSSAVALPTPMPTPAQPAFISTTQSALGCLTPSASTSQTPASTWSGIGGIPAGFPISQASTTGFRIVIQTHQSGAFGSVFGSRAPQPFTFGGFVTPMDCDESGIIMTGPDMSPTSGAFSIGALPSGTTNTMIPFGKGWSQNTEGLPSHRTAFSLGRGSISARKTMAPIAQNTPVPGQAKAGSSVGFGMPFPPAQGSVGRGPFRSSASSFSIGAKSKTPKNREKGHSRRHHAYKK","function_summary":"A human nuclear pore complex scaffold that resides in the nucleus and nucleoplasm and uses multivalent binding surfaces to organize transport machinery. By assembling and stabilizing export-competent complexes at the nuclear pore, it promotes directional protein export from the nucleus through a non-enzymatic, scaffold-driven mechanism that coordinates transport receptors and Ran-cycle factors at the nucleoplasmic face of the pore.","plain_language":"POM121L2 has barely been studied. The model's best guess: A human nuclear pore complex scaffold that resides in the nucleus and nucleoplasm and uses multivalent binding surfaces to organize transport machinery. By assembling and stabilizing export-competent complexes at the nuclear pore, it promotes directional protein export from the nucleus through a non-enzymatic, scaffold-driven mechanism that coordinates transport receptors and Ran-cycle factors at the nucleoplasmic face of the pore.","uniprot_summary":"Component of the nuclear pore complex (NPC), a complex structure supported by the nuclear envelope and responsible for the trafficking of macromolecules between the nucleus and the cytoplasm.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0006611","label":"protein export from nucleus"}],"cellular_component":[{"id":"GO:0005654","label":"nucleoplasm"}]},"interpro":[{"id":"IPR026054","name":"Nuclear pore complex protein","type":"family","start":2,"end":1023}],"reasoning":"I begin with the InterPro architecture: IPR026054 (Nuclear pore complex protein family) spans residues 2–1023, essentially covering the entire polypeptide. A full-length family signature of this kind defines a nucleoporin that forms part of the nuclear pore complex (NPC). Such nucleoporin-family architectures typically encode extended, low-complexity and repeat-rich scaffolds that assemble into higher-order NPC structures and create selective permeability barriers. This pervasive nucleoporin signature dictates a non-enzymatic, multivalent binding role—consistent with GO:0005515 protein binding—where extensive interaction surfaces organize transport factors and other nucleoporins.\n\nFrom this scaffolded nucleoporin identity, the molecular function resolves as multivalent protein binding that assembles and regulates transport machinery rather than catalyzing reactions. The NPC family architecture causes selective macromolecular exchange by providing docking platforms for karyopherins and Ran-cycle components. This binding-centric mechanism naturally feeds into nuclear transport pathways, specifically the pathway formalized as GO:0006611 protein export from nucleus. By furnishing binding sites and structural context, the protein promotes vectorial transit of cargo-export complexes back to the cytoplasm.\n\nThe cellular context follows directly. Nucleoporins reside at the nuclear envelope but are enriched on the nucleoplasmic face of the NPC and within the perinuclear space. This places the protein in the nucleus and nucleoplasm, aligning with GO:0005654 nucleoplasm and the experimentally observed nuclear localization. The absence of transmembrane enzymatic cores and the dominance of a nucleoporin family profile argue for a soluble, peripherally associated NPC scaffold that projects into the nucleoplasm.\n\nMechanistically, I infer that the protein forms part of an NPC-associated platform that captures export-competent complexes assembled by the export receptor and modulated by the Ran GTPase cycle. It likely binds transport receptors and FG-repeat nucleoporins to choreograph cargo handoff and directionality. In this role, it would transiently engage karyopherins and Ran pathway components to bias assembly/disassembly steps that culminate in efficient nuclear export.\n\nGiven this framework, I hypothesize interaction with central channel and cytoplasmic filament nucleoporins that create the transport conduit (e.g., NUP62- and NUP98-centered assemblies), as well as with transport receptors and cofactors that drive export. Likely partners include the export receptor (CRM1/XPO1), Ran GTPase and its regulators, and cytoplasmic filament nucleoporins that interface with the export machinery. Together, these contacts would stabilize export-competent complexes and couple them to the NPC’s selective barrier.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q96KW2.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q96KW2"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q96KW2/entry","atlas":"/p/Q96KW2"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}