{"uniprot":"C9JG80","gene":"NPIPB4","name":"Nuclear pore complex-interacting protein family member B4","organism":"Homo sapiens (Human)","status":"dark","length":1138,"sequence":"MVKLSIVLTPQFLSHDQGQLTKELQQHVKSVTCPCEYLRKVINTLADHHHRGTDFGGSPWLHVIIAFPTSYKVVITLWIVYLWVSLLKTIFWSRNGHDGSTDVQQRAWRSNRRRQEGLRSICMHTKKRVSSFRGNKIVLKDVITLRRHVETKVRAKIRKRKVTTKINHHDKINGKRKTARKQKMFQRAQELRRRAEDYHKCKIPPSARKALCNWVRMAAAEHRHSSGLPYWPYLTAETLKNRMGHQPPPPTQQHSITDNSLSLKTPPECLLTPLPPSADDNLKTPPECVLTPLPPSADDNLKTPPECVLTPLPPSADDNLKTPPECLLTPLPPSADDKLKTPPECLLTPLPPSALPSAPPSADDNLKTRAECLLHPLPPSADDNLKTPSERQLTPLPPSAPPSADDNIKTPAERLRGPLPPSADDNLKTPSERQLTPLPPSAPPSADDNIKTPAERLRGPLPPSADDNLKTPSERQLTPLPPSAPPSADDNIKTPAERLRGPLPPSADDNLKTPSERQLTPLPPSAPPSADDNIKTPAERLRGPLPPSADDNLKTPSERQLTPLPPSAPPSADDNIKTPAERLRGPLPPSADDNLKTPSERQLTPLPPSAPPSADDNIKTPAFHPQRMIISRHLPSVSSLPFHPQLHPQQMIISRYLLSVCGFRFHHQPMIISRHLPSVSSLPFHPQLHPQQMIISRHLPSVCGGRFHPQRMIISRHLPSVSSLPFHPQLHPQQMIISRHLPSVCGGRFHPQRMIISRHLPSVSSLPFHPQLHPQQMIISRHLPSVCGGRFHPQRMIISRHLPSVSSLPFHPQLHPQQMIISRHLPSVCGGRFHPQRMIISRHLPSVSSLPFHPQLHPQQMIISRHLPSVCGERLRGPLPPSADDNLKTPSERQLTPLPPSAPPSADDNIKTPAERLRGPLPPSADDNLKTPSERQLTPLPPSAPPSADDNIKTPAERLRGPLPPSADDNLKTPSERQLTPLPPSAPPSADDNIKTPAERLRGPLPPSADDNLKTPPLATQEAEAEKPRKPKRQRAAEMEPPPEPKRRRVGDVEPSRKPKRRRAADVEPSSPEPKRRRVGDVEPSRKPKRRRAADVEPSSPEPKRRRVGDVEPSRKPKRRRAADVEPSLPEPKRRRLS","function_summary":"A soluble nuclear scaffold that associates with nuclear pore–proximal assemblies to organize multivalent protein complexes in the nucleoplasm. By coupling nucleocytoplasmic transport and nuclear regulatory machinery, it likely coordinates transport-linked gene-expression programs that are especially critical during late germ cell differentiation, thereby contributing to spermatid development.","plain_language":"NPIPB4 has barely been studied. The model's best guess: A soluble nuclear scaffold that associates with nuclear pore–proximal assemblies to organize multivalent protein complexes in the nucleoplasm. By coupling nucleocytoplasmic transport and nuclear regulatory machinery, it likely coordinates transport-linked gene-expression programs that are especially critical during late germ cell differentiation, thereby contributing to spermatid development.","uniprot_summary":"May be involved in spermatogenesis.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0007286","label":"spermatid development"}],"cellular_component":[{"id":"GO:0005654","label":"nucleoplasm"}]},"interpro":[{"id":"IPR054697","name":"Nuclear pore complex interacting protein, N-terminal","type":"domain","start":41,"end":253},{"id":"IPR009443","name":"Nuclear pore complex interacting protein","type":"family","start":2,"end":335},{"id":"IPR048893","name":"Nuclear pore complex-interacting protein B13-like, MII repeat","type":"repeat","start":622,"end":788}],"reasoning":"I begin with the InterPro architecture. The N-terminus carries IPR054697 (Nuclear pore complex interacting protein, N-terminal domain, residues 41–253), embedded within a broader family signature IPR009443 (Nuclear pore complex interacting protein family, residues 2–335). This tandem of a defined N-terminal module nested in a family envelope indicates a conserved scaffold specialized for binding nuclear pore-associated partners rather than catalysis. Far downstream, a second module appears as IPR048893 (Nuclear pore complex-interacting protein B13-like, MII repeat, residues 622–788). MII repeats are repeat elements that typically mediate avid, multivalent protein–protein interactions and often tune subcellular targeting. The ordered layout—an NPC-interacting N-terminal binding platform followed by a distal repeat-mediated interaction cassette—creates a bipartite scaffold that concentrates binding capacity and positions the protein within nuclear pathways.\n\nThis architecture dictates molecular function as protein binding (GO:0005515). The absence of catalytic motifs and the presence of two interaction-centric modules argue that the protein operates as a soluble adaptor that organizes complexes rather than executing enzymatic chemistry. The N-terminal NPC-interacting domain provides specificity toward nuclear pore-associated assemblies, while the C-terminal MII repeat amplifies binding avidity and selectivity, together causing robust, multivalent complex formation.\n\nFrom this binding-centric function, I infer the biological process. NPC-interacting scaffolds commonly regulate nucleocytoplasmic transport, chromatin-associated assemblies, and transcriptional programs that drive cell-type specification. The explicit association with nuclear pore complexes naturally links to developmental pathways. In germ cells, nuclear transport and chromatin remodeling are pivotal; thus, a scaffold that stabilizes NPC-proximal assemblies is well positioned to influence spermatid development (GO:0007286). By coordinating transport and gene-expression modules in late germ cell stages, the protein can modulate the transitions required for spermiogenesis.\n\nCellular location follows directly from the soluble, scaffold-like architecture and NPC association. The lack of transmembrane segments and the presence of nuclear-targeting interaction domains point to a soluble nuclear pool. This supports a nucleoplasmic residence (GO:0005654), consistent with a role interfacing with nuclear pore-proximal assemblies and chromatin-associated complexes inside the nucleus.\n\nMechanistically, I hypothesize that the N-terminal NPC-interacting domain nucleates assemblies adjacent to the nuclear pore, while the MII repeat stabilizes higher-order complexes that couple transport to transcriptional or chromatin states. In germ cells, this coupling would fine-tune cargo flux and gene-regulatory landscapes necessary for spermatid maturation. Likely partners include nucleoporins and transport adaptors at the pore, as well as testis-enriched chromatin and RNA-processing factors that together orchestrate spermatid development within the nucleoplasm.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-C9JG80.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/C9JG80"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/C9JG80/entry","atlas":"/p/C9JG80"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}