{"uniprot":"Q9Y4E6","gene":"WDR7","name":"WD repeat-containing protein 7","organism":"Homo sapiens (Human)","status":"dark","length":1490,"sequence":"MAGNSLVLPIVLWGRKAPTHCISAVLLTDDGATIVTGCHDGQICLWDLSVELQINPRALLFGHTASITCLSKACASSDKQYIVSASESGEMCLWDVSDGRCIEFTKLACTHTGIQFYQFSVGNQREGRLLCHGHYPEILVVDATSLEVLYSLVSKISPDWISSMSIIRSHRTQEDTVVALSVTGILKVWIVTSEISDMQDTEPIFEEESKPIYCQNCQSISFCAFTQRSLLVVCSKYWRVFDAGDYSLLCSGPSENGQTWTGGDFVSSDKVIIWTENGQSYIYKLPASCLPASDSFRSDVGKAVENLIPPVQHILLDRKDKELLICPPVTRFFYGCREYFHKLLIQGDSSGRLNIWNISDTADKQGSEEGLAMTTSISLQEAFDKLNPCPAGIIDQLSVIPNSNEPLKVTASVYIPAHGRLVCGREDGSIVIVPATQTAIVQLLQGEHMLRRGWPPHRTLRGHRNKVTCLLYPHQVSARYDQRYLISGGVDFSVIIWDIFSGEMKHIFCVHGGEITQLLVPPENCSARVQHCICSVASDHSVGLLSLREKKCIMLASRHLFPIQVIKWRPSDDYLVVGCSDGSVYVWQMDTGALDRCVMGITAVEILNACDEAVPAAVDSLSHPAVNLKQAMTRRSLAALKNMAHHKLQTLATNLLASEASDKGNLPKYSHNSLMVQAIKTNLTDPDIHVLFFDVEALIIQLLTEEASRPNTALISPENLQKASGSSDKGGSFLTGKRAAVLFQQVKETIKENIKEHLLDDEEEDEEIMRQRREESDPEYRSSKSKPLTLLEYNLTMDTAKLFMSCLHAWGLNEVLDEVCLDRLGMLKPHCTVSFGLLSRGGHMSLMLPGYNQPACKLSHGKTEVGRKLPASEGVGKGTYGVSRAVTTQHLLSIISLANTLMSMTNATFIGDHMKKGPTRPPRPSTPDLSKARGSPPTSSNIVQGQIKQVAAPVVSARSDADHSGSDPPSAPALHTCFLVNEGWSQLAAMHCVMLPDLLGLDKFRPPLLEMLARRWQDRCLEVREAAQALLLAELRRIEQAGRKEAIDAWAPYLPQYIDHVISPGVTSEAAQTITTAPDASGPEAKVQEEEHDLVDDDITTGCLSSVPQMKKISTSYEERRKQATAIVLLGVIGAEFGAEIEPPKLLTRPRSSSQIPEGFGLTSGGSNYSLARHTCKALTFLLLQPPSPKLPPHSTIRRTAIDLIGRGFTVWEPYMDVSAVLMGLLELCADAEKQLANITMGLPLSPAADSARSARHALSLIATARPPAFITTIAKEVHRHTALAANTQSQQNMHTTTLARAKGEILRVIEILIEKMPTDVVDLLVEVMDIIMYCLEGSLVKKKGLQECFPAICRFYMVSYYERNHRIAVGARHGSVALYDIRTGKCQTIHGHKGPITAVAFAPDGRYLATYSNTDSHISFWQMNTSLLGSIGMLNSAPQLRCIKTYQVPPVQPASPGSHNALKLARLIWTSNRNVILMAHDGKEHRFMV","function_summary":"A large human nuclear scaffold built from multiple WD-repeat beta-propellers and an intervening alpha-solenoid that assembles multivalent protein complexes in the nucleoplasm. By providing high-capacity binding surfaces rather than catalytic activity, it organizes chromatin-associated and transcriptional assemblies that guide hematopoietic progenitor cell differentiation. Its modular architecture enables avid, cooperative partner recruitment, positioning it as a hub that stabilizes nuclear assemblies controlling lineage specification.","plain_language":"WDR7 has barely been studied. The model's best guess: A large human nuclear scaffold built from multiple WD-repeat beta-propellers and an intervening alpha-solenoid that assembles multivalent protein complexes in the nucleoplasm. By providing high-capacity binding surfaces rather than catalytic activity, it organizes chromatin-associated and transcriptional assemblies that guide hematopoietic progenitor cell differentiation.","uniprot_summary":"Involved in hematopoietic progenitor cell differentiation.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0002244","label":"hematopoietic progenitor cell differentiation"}],"cellular_component":[{"id":"GO:0005654","label":"nucleoplasm"}]},"interpro":[{"id":"IPR015943","name":"WD40/YVTN repeat-like-containing domain superfamily","type":"homologous_superfamily","start":7,"end":237},{"id":"IPR011047","name":"Quinoprotein alcohol dehydrogenase-like superfamily","type":"homologous_superfamily","start":57,"end":594},{"id":"IPR015943","name":"WD40/YVTN repeat-like-containing domain superfamily","type":"homologous_superfamily","start":402,"end":734},{"id":"IPR015943","name":"WD40/YVTN repeat-like-containing domain superfamily","type":"homologous_superfamily","start":1356,"end":1451},{"id":"IPR036322","name":"WD40-repeat-containing domain superfamily","type":"homologous_superfamily","start":1359,"end":1481},{"id":"IPR057848","name":"WDR72-like, alpha-solenoid domain","type":"domain","start":1014,"end":1049},{"id":"IPR049916","name":"WD repeat-containing protein 72-like","type":"family","start":5,"end":1490},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":5,"end":49},{"id":"IPR019775","name":"WD40 repeat, conserved site","type":"conserved_site","start":34,"end":48},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":53,"end":95},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":208,"end":242},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":453,"end":546},{"id":"IPR019775","name":"WD40 repeat, conserved site","type":"conserved_site","start":485,"end":499},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":549,"end":597},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":1383,"end":1426}],"reasoning":"I begin by dissecting the InterPro architecture and its order along the polypeptide. The N-terminus carries multiple WD40-related signatures that define beta-propeller scaffolds: IPR001680 (WD40 repeat, residues 5–49) and IPR019775 (WD40 repeat, conserved site, residues 34–48) seed the first propeller blade; IPR001680 and IPR019775 repeats appear again at IPR001680 (residues 53–95), IPR001680 (residues 208–242), IPR001680 (residues 453–546), and IPR001680 (residues 549–597), reinforced by IPR019775 (residues 485–499). Two broad WD40/YVTN repeat-like superfamilies bracket the N-terminal and central regions—IPR015943 (residues 7–237) and IPR015943 (residues 402–734)—indicating an extended beta-propeller landscape. A central IPR011047 (Quinoprotein alcohol dehydrogenase-like superfamily, residues 57–594) further supports a large beta-helix/solenoid fold that commonly serves as a non-catalytic scaffold rather than an enzyme core in metazoan proteins. Midway through the sequence, IPR057848 (WDR72-like, alpha-solenoid domain, residues 1014–1049) introduces an alpha-solenoid segment that typically couples beta-propellers to elongated helical scaffolds, enhancing multivalent assembly. The C-terminal region is enriched for additional beta-propeller-like modules: IPR015943 (residues 1356–1451) and IPR036322 (WD40-repeat-containing domain superfamily, residues 1359–1481) together with IPR001680 (residues 1383–1426) confirm a late-stage propeller platform. The entire protein is classified by IPR049916 (WD repeat-containing protein 72-like family, residues 5–1490), consistent with a large, multidomain scaffold.\n\nThis ordered array of WD40 repeats and intervening solenoids causes a multivalent, non-enzymatic binding surface rather than catalytic chemistry. Such architectures create rigid yet adaptable platforms that nucleate and stabilize large assemblies. This directly supports GO:0005515 protein binding as the molecular function: the repeated beta-propeller modules and alpha-solenoid jointly generate high-affinity, avidity-driven interaction hubs.\n\nFrom this binding-centric foundation, I infer the biological role by considering where and how such scaffolds operate. The presence of nucleoplasmic localization (GO:0005654 nucleoplasm) situates the assemblies in the nuclear interior rather than membranes or cytoskeleton. Nuclear scaffolds commonly coordinate chromatin-associated complexes and transcriptional regulators. The developmental context—hematopoietic progenitor cell differentiation (GO:0002244)—fits a nuclear scaffold that modulates lineage-specific transcription and chromatin states. A WD-repeat platform in the nucleoplasm can recruit chromatin remodelers, histone-modifying enzymes, and lineage-determining transcription factors to enforce hematopoietic programs.\n\nCellular localization follows naturally from the architecture and function. The absence of transmembrane segments and the abundance of soluble beta-propeller/solenoid modules argue for a soluble nuclear protein. This aligns with nucleoplasm residency and explains how the scaffold organizes nuclear macromolecular assemblies.\n\nMechanistically, I hypothesize that the N-terminal and central beta-propellers (residues 5–242 and 402–734) nucleate core assemblies, while the alpha-solenoid (residues 1014–1049) extends binding reach and spatial reach, and the C-terminal propeller cluster (residues 1356–1481) fine-tunes partner specificity. In the nucleoplasm, this architecture likely captures chromatin-associated complexes and lineage regulators to bias progenitor cells toward hematopoietic differentiation. Candidate partners include chromatin remodelers and histone-modifying assemblies (e.g., NuRD and CHD complexes), as well as lineage-specifying transcription factors and mediator/adaptor modules that require WD-repeat scaffolding. Together, these features define a nuclear, multivalent scaffold that binds proteins to orchestrate hematopoietic progenitor cell differentiation within the nucleoplasm.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q9Y4E6.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q9Y4E6"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q9Y4E6/entry","atlas":"/p/Q9Y4E6"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}