{"uniprot":"Q8N8L6","gene":"ARL10","name":"ADP-ribosylation factor-like protein 10","organism":"Homo sapiens (Human)","status":"dark","length":244,"sequence":"MAPRPLGPLVLALGGAAAVLGSVLFILWKTYFGRGRERRWDRGEAWWGAEAARLPEWDEWDPEDEEDEEPALEELEQREVLVLGLDGAGKSTFLRVLSGKPPLEGHIPTWGFNSVRLPTKDFEVDLLEIGGSQNLRFYWKEFVSEVDVLVFVVDSADRLRLPWARQELHKLLDKDPDLPVVVVANKQDLSEAMSMGELQRELGLQAIDNQREVFLLAASIAPAGPTFEEPGTVHIWKLLLELLS","function_summary":"A small regulatory GTPase that cycles between GTP- and GDP-bound states to control effector binding and signaling assemblies. By shuttling between cytosol and membrane-proximal compartments, it concentrates at the endoplasmic reticulum and the mitochondrial outer membrane, where it organizes complexes that enhance inflammatory signaling. Through this nucleotide-driven switch mechanism, it promotes assembly of pathways that activate the I-kappaB kinase cascade and downstream transcriptional responses.","plain_language":"ARL10 has barely been studied. The model's best guess: A small regulatory GTPase that cycles between GTP- and GDP-bound states to control effector binding and signaling assemblies. By shuttling between cytosol and membrane-proximal compartments, it concentrates at the endoplasmic reticulum and the mitochondrial outer membrane, where it organizes complexes that enhance inflammatory signaling.","uniprot_summary":"May be involved in signal transduction.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0043123","label":"positive regulation of I-kappaB kinase/NF-kappaB signaling"}],"cellular_component":[{"id":"GO:0005783","label":"endoplasmic reticulum"},{"id":"GO:0005741","label":"mitochondrial outer membrane"}]},"interpro":[{"id":"IPR027417","name":"P-loop containing nucleoside triphosphate hydrolase","type":"homologous_superfamily","start":76,"end":231},{"id":"IPR042951","name":"ADP-ribosylation factor-like protein 10","type":"family","start":1,"end":244},{"id":"IPR006689","name":"Small GTPase superfamily, ARF/SAR type","type":"family","start":64,"end":243}],"reasoning":"I begin with the InterPro architecture. The sequence is dominated by IPR042951 (ADP-ribosylation factor-like protein 10 family, residues 1–244), which frames the entire polypeptide as an ARL10-class small GTPase. Nested within this, IPR006689 (Small GTPase superfamily, ARF/SAR type, residues 64–243) specifies the ARF/SAR lineage that uses nucleotide-dependent conformational switching to regulate membrane-associated pathways. Centrally, IPR027417 (P-loop containing nucleoside triphosphate hydrolase homologous superfamily, residues 76–231) provides the Walker-motif NTPase core that binds and hydrolyzes GTP. The ordered layout—an N-terminal ARL10-defining envelope, followed by an ARF/SAR-type small GTPase module and a P-loop NTPase engine—causes a classic molecular switch: GTP binding and hydrolysis cycle between active and inactive states that modulate effector binding and membrane association.\n\nThis switch architecture dictates molecular function. The P-loop NTPase core and ARF/SAR signatures establish a small GTPase that transduces signals via regulated protein–protein interfaces. Such switches operate by recruiting or releasing effectors; therefore, protein binding (GO:0005515) is an intrinsic readout of the active/inactive cycle and is reinforced by the broad ARF/SAR scaffold that presents effector surfaces.\n\nFrom this molecular function, I infer the biological process. ARL10-class GTPases often tune stress and inflammatory signaling by coupling membrane trafficking and organelle interfaces. A nucleotide-controlled effector hub at endomembranes and mitochondria can potentiate pathways that culminate in NF-kappaB activation. By stabilizing assemblies that favor IKK complex engagement and transcriptional responses, the switch architecture supports positive regulation of I-kappaB kinase/NF-kappaB signaling (GO:0043123). The causal chain is: GTPase cycling assembles signaling-competent complexes; these complexes bias IKK toward activation; NF-kappaB transcriptional outputs rise.\n\nCellular location follows from both the domain logic and the localization evidence. Small ARF/SAR-type GTPases typically sample cytosolic pools and membrane-proximal compartments. Here, the presence at the endoplasmic reticulum (GO:0005783) and the mitochondrial outer membrane (GO:0005741) positions the switch at ER–mitochondria contact sites. This dual residency provides a mechanistic basis: ER association supplies trafficking and stress-sensing inputs, while the mitochondrial outer membrane offers a platform for apoptotic and inflammatory signaling crosstalk. The soluble nature of the switch and its cycling behavior are consistent with a cytoplasmic pool that dynamically engages these membranes.\n\nPutting these strands together, I propose a mechanism in which the ARL10-family switch alternates between GTP- and GDP-bound states to choreograph effector binding at ER and mitochondrial surfaces. In its active state, it likely captures adaptors and kinases that feed into the IKK axis, thereby amplifying NF-kappaB signaling. At ER–mitochondria junctions, it may coordinate apoptotic priming and calcium flux that secondarily enhance IKK activity.\n\nThis model suggests specific interaction partners. At the ER, ARF/SAR-type GTPases often engage soluble and membrane-associated effectors; candidate partners include Sec7-domain and other ARF-cycle regulators that tune membrane recruitment. At mitochondria, outer-membrane import and scaffold systems (e.g., TOM complex components and BCL-2 family adaptors) provide platforms that can couple to inflammatory signaling. To drive NF-kappaB, transient assemblies with the IKK complex and upstream adaptors are expected. Together, these interactions arise naturally from the GTPase switch architecture and the dual ER/mitochondrial localization.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8N8L6.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8N8L6"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8N8L6/entry","atlas":"/p/Q8N8L6"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}