{"uniprot":"Q6ZP01","gene":"RBM44","name":"RNA-binding protein 44","organism":"Homo sapiens (Human)","status":"dark","length":1051,"sequence":"MQATAVVETASGKGYHSNGGNLQKDKPSNPKKENLLLSSNGCDEVKLTFPDDDWNSSTLEQRANNKEISNIDKMDLLEPFFSVSQDTNTESTQFQSSELEDSTDYAFLNKTYSIPYSESKLKKESLTPLSSELDPEVQKKEEVFFNILEHQDKTVGLERIYNISDANYRESAEDTQKHDTDEDSQQEYHSAEEQEYISNHLSFDQTKALDISNPEVVELGNSGYEVKCASNVEDNRVNSGSGSIISFDSLDVYGQEESLHVSKFQNSVMLREYHDLKHEKYKEQETNSMYHTVFDGSVLRSNSPGNQESQSKSGSLSPQKVLKMKIYTENMKSQINEGKDFCGNKIVENKILLHLENPSTLPQDKALETLLQPCKDCQTSWTSVFDDSIISACGYYESLQNTADSALDFSAMLPKIAVRDNQAIEDNTSLKVAHSSTTKKTCFHNIGEMCTKSLTDAASCTVTINQTVDVSTDFRACFTTSRATSARPSVVSTSSNTEITMMNKKRPDEWQNEKQKSVACSTDWSYSEDCIDTQMAITKGSGKSLSVDSLKPNGNFLNKDFLELRKACGITDLKKHPEREFQLFKDTEKDLPSMCCQKIMQRAIKAELHLLNVHYQMCRRHCCDIYKLVMENREGLNMNLSSNSAKKELGSALLSLLGDLKVRYVTLKEKIHKGIPLEELPPLSLESKLLSTFSTFASRLMKKETHVFSEADAEQDNQRAHDVDVSSNLKKTLSQMSLSSDNSHATQNISPKKDDFKNGDINADFSQLKLGDKDCRHYQETSEDWSDAKESLTGVDVSGTQGNQVEQDTWNLDLTGEMKNVEPSQRDKGYLIHVGGLCPSVSEADLRSHFQKYQVSEISIYDSTNYRYASLAFTKNSDAKIAVKEMNGIEINGKSVNVWPVKILGEYTSPLSSKNGNRISSNNLEKSTNKQIHSEFSISRLPRTRPRQLGSEQDSEVFPSDQGVKKNCKQIESAKLLPDTPVQFIPPNTLNLRSFTKIIKRLAELHPEVSRDHIINALQEVRIRHKGFLNGLSITTIVEMTSSLLKNSASS","function_summary":"A cytoplasmic scaffold that uses an RNA-recognition core and a C-terminal helical assembly module to organize macromolecular complexes controlling spindle formation and chromosome segregation. By assembling ribonucleoprotein and adaptor networks, it promotes spindle and centrosome functions, stabilizes microtubule–kinetochore attachments, and supports metaphase plate congression. It dynamically partitions between cytosol and nuclear speckles and concentrates on spindle-associated assemblies during mitosis.","plain_language":"RBM44 has barely been studied. The model's best guess: A cytoplasmic scaffold that uses an RNA-recognition core and a C-terminal helical assembly module to organize macromolecular complexes controlling spindle formation and chromosome segregation. By assembling ribonucleoprotein and adaptor networks, it promotes spindle and centrosome functions, stabilizes microtubule–kinetochore attachments, and supports metaphase plate congression.","uniprot_summary":"Involved in mitotic spindle assembly and chromosome segregation.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0090235","label":"regulation of metaphase plate congression"},{"id":"GO:0007051","label":"spindle organization"},{"id":"GO:0032388","label":"positive regulation of intracellular transport"},{"id":"GO:0090068","label":"positive regulation of cell cycle process"},{"id":"GO:0045787","label":"positive regulation of cell cycle"},{"id":"GO:0051988","label":"regulation of attachment of spindle microtubules to kinetochore"},{"id":"GO:0000070","label":"mitotic sister chromatid segregation"},{"id":"GO:0090169","label":"regulation of spindle assembly"},{"id":"GO:0008104","label":"protein localization"}],"cellular_component":[{"id":"GO:0005829","label":"cytosol"},{"id":"GO:0016607","label":"nuclear speck"}]},"interpro":[{"id":"IPR012677","name":"Nucleotide-binding alpha-beta plait domain superfamily","type":"homologous_superfamily","start":767,"end":899},{"id":"IPR035979","name":"RNA-binding domain superfamily","type":"homologous_superfamily","start":823,"end":902},{"id":"IPR000504","name":"RNA recognition motif domain","type":"domain","start":830,"end":899},{"id":"IPR056870","name":"TTC3/DZIP3/RBM44-like, helical domain","type":"domain","start":994,"end":1045}],"reasoning":"I begin with the InterPro architecture and its order along the polypeptide. A central nucleotide-binding alpha-beta plait domain superfamily signature, IPR012677 (residues 767–899), overlaps with an RNA-binding domain superfamily, IPR035979 (823–902), and is capped by a canonical RNA recognition motif, IPR000504 (830–899). This tightly clustered C-terminal module establishes an RRM-centered RNA-binding core that typically mediates sequence- and structure-specific interactions with RNA and RNA–protein assemblies. Downstream, a distinct helical scaffold appears as IPR056870 (TTC3/DZIP3/RBM44-like, helical domain; residues 994–1045). Helical repeat modules in TTC3/DZIP3-like proteins often create elongated coiled-coil platforms that recruit and organize cytoskeletal and centrosomal factors. The ordered layout—RRM-based RNA-binding core followed by a helical assembly scaffold—causally supports two capabilities: high-affinity macromolecular binding and assembly of higher-order complexes.\n\nFrom this architecture, the primary molecular function resolves as multivalent macromolecular binding. The RRM and RNA-binding superfamily signatures explain broad GO:0005515 protein binding by providing a versatile platform that stabilizes ribonucleoprotein assemblies and protein partners. The helical TTC3/DZIP3-like region extends this binding capacity toward cytoskeletal and centrosomal complexes, enabling avid interactions that are characteristic of scaffolds.\n\nThis binding toolkit drives several mitotic processes. The helical scaffold is well-suited to organize and stabilize spindle apparatus components, directly enabling GO:0007051 spindle organization and GO:0090169 regulation of spindle assembly. By positioning and stabilizing microtubule-attachment modules at kinetochores and spindle poles, the architecture promotes GO:0051988 regulation of attachment of spindle microtubules to kinetochore and supports GO:0090235 regulation of metaphase plate congression. The same scaffolded assemblies enhance fidelity of chromosome segregation, aligning with GO:0000070 mitotic sister chromatid segregation and GO:0045787 positive regulation of cell cycle. The capacity to recruit and retain partners at centrosomes is captured by GO:0071539 protein localization to centrosome, while the RRM-centered binding hub and helical repeats together explain GO:0032388 positive regulation of intracellular transport by coordinating cargo and motor assemblies along microtubules.\n\nCellular localization follows from these functions and modules. The soluble nature of the RRM/helical scaffold supports a cytosolic pool consistent with GO:0005829 cytosol. The RRM module commonly participates in nuclear ribonucleoprotein dynamics; transient residence in RNA-processing territories explains localization to GO:0016607 nuclear speck. During mitosis, the helical TTC3/DZIP3-like domain drives redistribution to spindle structures and centrosomes, consistent with a dynamic cytoplasmic–nuclear cycle.\n\nMechanistically, I hypothesize that the RRM-centered core nucleates RNA- and adaptor-rich assemblies that tune spindle and kinetochore function, while the TTC3/DZIP3-like helical tail anchors these assemblies to centrosomes and spindle microtubules. Likely interaction partners include tubulin heterodimers and microtubule-associated proteins that shape spindle architecture; plus kinetochore and centrosomal adaptors that mediate microtubule attachments and centrosome targeting. Through these assemblies, the protein stabilizes spindle formation, ensures proper metaphase plate congression, and promotes accurate sister chromatid segregation.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q6ZP01.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q6ZP01"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q6ZP01/entry","atlas":"/p/Q6ZP01"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}