{"uniprot":"Q8N1F8","gene":"STK11IP","name":"Serine/threonine-protein kinase 11-interacting protein","organism":"Homo sapiens (Human)","status":"dark","length":1088,"sequence":"MTTAQRDSLLWKLAGLLRESGDVVLSGCSTLSLLTPTLQQLNHVFELHLGPWGPGQTGFVALPSHPADSPVILQLQFLFDVLQKTLSLKLVHVAGPGPTGPIKIFPFKSLRHLELRGVPLHCLHGLRGIYSQLETLICSRSLQALEELLSACGGDFCSALPWLALLSANFSYNALTALDSSLRLLSALRFLNLSHNQVQDCQGFLMDLCELHHLDISYNRLHLVPRMGPSGAALGVLILRGNELRSLHGLEQLRNLRHLDLAYNLLEGHRELSPLWLLAELRKLYLEGNPLWFHPEHRAATAQYLSPRARDAATGFLLDGKVLSLTDFQTHTSLGLSPMGPPLPWPVGSTPETSGGPDLSDSLSSGGVVTQPLLHKVKSRVRVRRASISEPSDTDPEPRTLNPSPAGWFVQQHPELELMSSFRERFGRNWLQYRSHLEPSGNPLPATPTTSAPSAPPASSQGPDTAPRPSPPQEEARGPQESPQKMSEEVRAEPQEEEEEKEGKEEKEEGEMVEQGEEEAGEEEEEEQDQKEVEAELCRPLLVCPLEGPEGVRGRECFLRVTSAHLFEVELQAARTLERLELQSLEAAEIEPEAQAQRSPRPTGSDLLPGAPILSLRFSYICPDRQLRRYLVLEPDAHAAVQELLAVLTPVTNVAREQLGEARDLLLGRFQCLRCGHEFKPEEPRMGLDSEEGWRPLFQKTESPAVCPNCGSDHVVLLAVSRGTPNRERKQGEQSLAPSPSASPVCHPPGHGDHLDRAKNSPPQAPSTRDHGSWSLSPPPERCGLRSVDHRLRLFLDVEVFSDAQEEFQCCLKVPVALAGHTGEFMCLVVVSDRRLYLLKVTGEMREPPASWLQLTLAVPLQDLSGIELGLAGQSLRLEWAAGAGRCVLLPRDARHCRAFLEELLDVLQSLPPAWRNCVSATEEEVTPQHRLWPLLEKDSSLEARQFFYLRAFLVEGPSTCLVSLLLTPSTLFLLDEDAAGSPAEPSPPAASGEASEKVPPSGPGPAVRVREQQPLSSLSSVLLYRSAPEDLRLLFYDEVSRLESFWALRVVCQEQLTALLAWIREPWEELFSIGLRTVIQEALALDR","function_summary":"A human scaffold that binds the LKB1 kinase complex and organizes it on membranes through a central leucine‑rich repeat core and multiple phosphoinositide‑binding modules. By docking LKB1 and stabilizing accessory factors, it positions kinase activity at endolysosomal and secretory vesicle interfaces to control where signaling assemblies reside. This spatial assembly role supports protein localization pathways and explains accumulation at membrane systems, including lysosomal surfaces and secretory granule compartments.","plain_language":"STK11IP has barely been studied. The model's best guess: A human scaffold that binds the LKB1 kinase complex and organizes it on membranes through a central leucine‑rich repeat core and multiple phosphoinositide‑binding modules. By docking LKB1 and stabilizing accessory factors, it positions kinase activity at endolysosomal and secretory vesicle interfaces to control where signaling assemblies reside.","uniprot_summary":"Interacts with the LKB1 serine/threonine-protein kinase complex.","go_terms":{"molecular_function":[{"id":"GO:0019901","label":"protein kinase binding"}],"biological_process":[{"id":"GO:0008104","label":"protein localization"}],"cellular_component":[{"id":"GO:0016020","label":"membrane"},{"id":"GO:0005576","label":"extracellular region"},{"id":"GO:0035578","label":"azurophil granule lumen"},{"id":"GO:0005765","label":"lysosomal membrane"}]},"interpro":[{"id":"IPR032675","name":"Leucine-rich repeat domain superfamily","type":"homologous_superfamily","start":162,"end":313},{"id":"IPR031782","name":"LKB1 serine/threonine kinase interacting protein 1, N-terminal","type":"domain","start":6,"end":93},{"id":"IPR057292","name":"Serine/threonine-protein kinase 11-interacting protein, PH domain","type":"domain","start":532,"end":653},{"id":"IPR057288","name":"PLEKHM2, PH domain-like","type":"domain","start":780,"end":919},{"id":"IPR057676","name":"STK11-interacting protein, C-terminal PH domain","type":"domain","start":926,"end":1081},{"id":"IPR001611","name":"Leucine-rich repeat","type":"repeat","start":233,"end":254},{"id":"IPR001611","name":"Leucine-rich repeat","type":"repeat","start":255,"end":276}],"reasoning":"I begin with the InterPro architecture. The N-terminus carries IPR031782 (LKB1 serine/threonine kinase interacting protein 1, N-terminal domain, residues 6–93), a dedicated docking module that creates high-affinity contacts with the LKB1/STK11 kinase complex. Immediately downstream lies a solenoidal scaffold: IPR032675 (Leucine-rich repeat domain superfamily, residues 162–313) encompassing two internal repeats, IPR001611 (Leucine-rich repeat, residues 233–254) and IPR001611 (Leucine-rich repeat, residues 255–276). This tandem LRR core generates an extended curved surface optimized for multivalent protein binding and spatial organization of signaling assemblies. The C-terminal half is dominated by three lipid-binding modules: IPR057292 (Serine/threonine-protein kinase 11-interacting protein, PH domain, residues 532–653), IPR057288 (PLEKHM2, PH domain-like, residues 780–919), and IPR057676 (STK11-interacting protein, C-terminal PH domain, residues 926–1081). The ordered arrangement—an N-terminal kinase-docking region, a central LRR scaffold, and multiple PH modules—causes avid membrane association and compartment targeting through phosphoinositide recognition while simultaneously assembling kinase complexes.\n\nThis architecture dictates the molecular function. The dedicated N-terminal LKB1-interacting domain together with the LRR scaffold enforces selective assembly of kinase-containing complexes, establishing GO:0019901 protein kinase binding as the operative molecular function. The PH domain array confers reversible membrane affinity and vesicle targeting but does not supply catalytic chemistry; instead, it positions and stabilizes kinase assemblies in space.\n\nFrom this function, the biological process follows. By physically tethering LKB1 and related kinases and by using PH domains to localize to specific membranes and vesicles, the protein drives directed trafficking and retention of signaling modules—formally captured as GO:0008104 protein localization. The LRR platform and PH-guided membrane binding together produce spatial control over where LKB1 acts and where its substrates reside.\n\nCellular location is a direct consequence of the PH-driven membrane affinity and vesicle targeting. The PH triad (IPR057292, IPR057288, IPR057676) targets acidic and signaling membranes, supporting GO:0016020 membrane as a primary residence. The presence of secretory vesicle and lysosome-directed lipid-binding modules rationalizes accumulation at endolysosomal interfaces and specialized secretory organelles. This explains occupancy of the GO:0005765 lysosomal membrane and compatibility with luminal compartments such as the GO:0035578 azurophil granule lumen, where membrane-proximal scaffolds and luminal cargo co-localize via vesicle pathways. Although the core architecture is intracellular, transient exposure of luminal surfaces and vesicle trafficking can account for signals associated with the GO:0005576 extracellular region.\n\nMechanistically, the N-terminal LKB1-docking region nucleates an LKB1-centered assembly; the LRR core stabilizes accessory factors; and the tandem PH domains anchor the complex to phosphoinositide-enriched membranes. This causes spatially confined phosphorylation cascades that regulate cytoskeletal and trafficking hubs. I hypothesize that the protein recruits the LKB1–STRAD–MO25 module and couples it to vesicle coats and small GTPases, thereby positioning kinase activity at endolysosomal and secretory membranes. Likely partners include the LKB1 complex itself and membrane organizers such as phosphoinositide-binding adaptors and Rab GTPases that together choreograph vesicle maturation and cargo routing.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8N1F8.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8N1F8"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8N1F8/entry","atlas":"/p/Q8N1F8"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}