{"uniprot":"H3BQB6","gene":"STMND1","name":"Stathmin domain-containing protein 1","organism":"Homo sapiens (Human)","status":"dark","length":276,"sequence":"MGCGPSQPAEDRRRVRAPKKGWKEEFKADVSVPHTGENCSPRMEAALTKNTVDIAEGLEQVQMGSLPGTISENSPSPSERNRRVNSDLVTNGLINKPQSLESRERQKSSDILEELIVQGIIQSHSKVFRNGESYDVTLTTTEKPLRKPPSRLKKLKIKKQVKDFTMKDIEEKMEAAEERRKTKEEEIRKRLRSDRLLPSANHSDSAELDGAEVAFAKGLQRVRSAGFEPSDLQGGKPLKRKKSKCDATLIDRNESDESFGVVESDMSYNQADDIVY","function_summary":"A soluble regulator that concentrates at the centrosome and in the cytosol to control microtubule dynamics and relay cytoskeletal state to nuclear programs. By assembling transient complexes with tubulin and centrosomal scaffolds, it tunes microtubule assembly near the organizing center and thereby enhances transcriptional outputs driven by RNA polymerase II through centrosome-to-nucleus signaling.","plain_language":"STMND1 has barely been studied. The model's best guess: A soluble regulator that concentrates at the centrosome and in the cytosol to control microtubule dynamics and relay cytoskeletal state to nuclear programs. By assembling transient complexes with tubulin and centrosomal scaffolds, it tunes microtubule assembly near the organizing center and thereby enhances transcriptional outputs driven by RNA polymerase II through centrosome-to-nucleus signaling.","uniprot_summary":"Probable regulator of microtubule synthesis.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0045944","label":"positive regulation of transcription by RNA polymerase II"}],"cellular_component":[{"id":"GO:0005829","label":"cytosol"},{"id":"GO:0005813","label":"centrosome"}]},"interpro":[{"id":"IPR036002","name":"Stathmin superfamily","type":"homologous_superfamily","start":148,"end":191},{"id":"IPR000956","name":"Stathmin family","type":"family","start":51,"end":244}],"reasoning":"I begin with the InterPro architecture. The core of the polypeptide is defined by IPR000956 (Stathmin family, residues 51–244), a hallmark of stathmin-like proteins that bind and remodel microtubules through a conserved, largely helical scaffold. Nested within this, the C-terminal region carries IPR036002 (Stathmin superfamily, residues 148–191), reinforcing that the central-to-C-terminal block forms the canonical stathmin fold. This ordered arrangement—an extended stathmin-family core with a conserved superfamily segment toward the C-terminus—creates a soluble, non-enzymatic module optimized for multivalent protein interactions rather than catalysis. Such stathmin architectures typically present acidic, flexible surfaces that capture tubulin heterodimers and regulatory partners, which causally supports a primary molecular function of protein binding (GO:0005515).\n\nFrom this binding-centric scaffold, I infer the biological role. Stathmin-like modules tune microtubule dynamics by sequestering tubulin and biasing catastrophe/rescue equilibria; this dynamic control feeds into higher-order cell-cycle and transcriptional programs. The explicit localization to the centrosome (GO:0005813) and cytosol (GO:0005829) positions the protein at microtubule-organizing centers and in the soluble phase where assembly-disassembly cycles are orchestrated. Centrosomal residency provides a conduit between cytoskeletal state and nuclear programs. This coupling explains participation in positive regulation of transcription by RNA polymerase II (GO:0045944): by modulating microtubule availability and signaling flux from centrosomes, the protein can enhance transcriptional outputs that depend on cytoskeleton-to-nucleus crosstalk.\n\nCellular location follows directly from the architecture and function. The soluble stathmin fold lacks transmembrane features and is consistent with cytosolic pools (GO:0005829). Its enrichment at the centrosome (GO:0005813) arises because stathmin-like factors concentrate where microtubules are nucleated and remodeled, enabling tight spatial control of tubulin flux and downstream signaling.\n\nMechanistically, I hypothesize that the protein forms transient complexes with tubulin heterodimers and centrosomal scaffolds to tune microtubule assembly near the microtubule-organizing center. This assembly-state control propagates to transcriptional pathways via centrosome-to-nucleus signaling and cytoskeleton-sensitive coactivator recruitment, thereby positively regulating RNA polymerase II-driven transcription. Likely interaction partners include α/β-tubulin dimers and centrosomal organizers (e.g., pericentrin and CEP proteins), as well as kinases that modulate stathmin-family activity through phosphorylation-dependent switching between cytosolic and centrosomal pools.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-H3BQB6.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/H3BQB6"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/H3BQB6/entry","atlas":"/p/H3BQB6"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}