{"uniprot":"A6NIV6","gene":"LRRIQ4","name":"Leucine-rich repeat and IQ domain-containing protein 4","organism":"Homo sapiens (Human)","status":"dark","length":560,"sequence":"MSKDIKSVEHSPKIHQRNDPQHVNDRTFFIDASNQSLTAIPLEIFTFTELEEVHLENNQIEEIPQEIQRLKNIRVLYLDKNNLRSLCPALGLLSSLESLDLSYNPIFSSSLVVVSFLHALRELRLYQTDLKEIPVVIFKNLHHLELLGLTGNHLKCLPKEIVNQTKLREIYLKRNQFEVFPQELCVLYTLEIIDLDENKIGAIPEEIGHLTGLQKFYMASNNLPVLPASLCQCSQLSVLDLSHNLLHSIPKSFAELRKMTEIGLSGNRLEKVPRLICRWTSLHLLYLGNTGLHRLRGSFRCLVNLRFLDLSQNHLHHCPLQICALKNLEVLGLDDNKIGQLPSELGSLSKLKILGLTGNEFLSFPEEVLSLASLEKLYIGQDQGFKLTYVPEHIRKLQSLKELYIENNHLEYLPVSLGSMPNLEVLDCRHNLLKQLPDAICQAQALKELRLEDNLLTHLPENLDSLVNLKVLTLMDNPMEEPPKEVCAEGNEAIWKYLKENRNRNIMATKIQAWWRGTMVQRGFGKFGELLKPQKKGKTSPKDKKGKKDVKGKPGKGKKK","function_summary":"A human LRR-based scaffold that organizes signaling assemblies controlling cell-cycle progression and apoptosis. Its extended leucine-rich repeat solenoid creates a high-affinity platform for multivalent protein binding, enabling assembly and potentiation of Ras/MAPK signaling at membrane-proximal sites. The scaffold shuttles between cytoplasm and nucleus to couple membrane-associated signaling with transcriptional and apoptotic programs and is additionally recruited to photoreceptor disc membranes, where it stabilizes specialized membrane-associated complexes.","plain_language":"LRRIQ4 has barely been studied. The model's best guess: A human LRR-based scaffold that organizes signaling assemblies controlling cell-cycle progression and apoptosis. Its extended leucine-rich repeat solenoid creates a high-affinity platform for multivalent protein binding, enabling assembly and potentiation of Ras/MAPK signaling at membrane-proximal sites.","uniprot_summary":"May be involved in cell cycle regulation and apoptosis.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0046579","label":"positive regulation of Ras protein signal transduction"}],"cellular_component":[{"id":"GO:0097381","label":"photoreceptor disc membrane"},{"id":"GO:0005886","label":"plasma membrane"}]},"interpro":[{"id":"IPR032675","name":"Leucine-rich repeat domain superfamily","type":"homologous_superfamily","start":24,"end":283},{"id":"IPR032675","name":"Leucine-rich repeat domain superfamily","type":"homologous_superfamily","start":284,"end":382},{"id":"IPR032675","name":"Leucine-rich repeat domain superfamily","type":"homologous_superfamily","start":383,"end":501},{"id":"IPR055414","name":"Disease resistance R13L4/SHOC-2-like, LRR domain","type":"domain","start":301,"end":405},{"id":"IPR050216","name":"Leucine-rich repeat domain-containing protein","type":"family","start":235,"end":397},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":47,"end":69},{"id":"IPR001611","name":"Leucine-rich repeat","type":"repeat","start":49,"end":106},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":70,"end":92},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":93,"end":116},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":117,"end":140},{"id":"IPR001611","name":"Leucine-rich repeat","type":"repeat","start":120,"end":177},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":141,"end":164},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":187,"end":209},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":210,"end":233},{"id":"IPR001611","name":"Leucine-rich repeat","type":"repeat","start":220,"end":269},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":234,"end":255},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":256,"end":279},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":302,"end":324},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":325,"end":347},{"id":"IPR001611","name":"Leucine-rich repeat","type":"repeat","start":327,"end":348},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":348,"end":371},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":397,"end":419},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":420,"end":443},{"id":"IPR001611","name":"Leucine-rich repeat","type":"repeat","start":421,"end":478},{"id":"IPR003591","name":"Leucine-rich repeat, typical subtype","type":"repeat","start":444,"end":466}],"reasoning":"I begin by dissecting the InterPro architecture, which is dominated by tandem leucine-rich repeat (LRR) modules that extend across the length of the protein. The N-terminal half is covered by IPR032675 (Leucine-rich repeat domain superfamily, residues 24–283), followed contiguously by IPR032675 annotations at residues 284–382 and 383–501, indicating a continuous LRR solenoid that likely wraps around a central axis to create a versatile protein–protein interaction surface. Multiple nested LRR annotations reinforce this scaffold: IPR050216 (Leucine-rich repeat domain-containing protein family, residues 235–397) and IPR055414 (Disease resistance R13L4/SHOC-2-like, LRR domain, residues 301–405) specify a SHOC-2–like LRR fold known to organize Ras/MAPK pathway assemblies. A dense array of typical LRR repeats is mapped by IPR003591 and IPR001611 entries across residues 47–466, including [47–69], [70–92], [93–116], [117–140], [141–164], [187–209], [210–233], [234–255], [256–279], [302–324], [325–347], [301–405], [348–371], [397–419], and [420–443]. This ordered, modular repeat architecture causes high-affinity, multivalent binding to partner proteins rather than catalysis, directly supporting GO:0005515 protein binding as the molecular function.\n\nThe SHOC-2–like LRR core (IPR055414) is a hallmark scaffold for Ras/MAPK pathway assembly. By stabilizing small GTPase effectors and their downstream kinases, this solenoid architecture promotes assembly and signal throughput of Ras-dependent cascades. Such a scaffolded assembly explains positive modulation of small GTPase signaling, aligning with GO:0046579 positive regulation of Ras protein signal transduction. The same binding-centric architecture readily explains roles in cell-cycle control and apoptosis: by tuning Ras/MAPK and allied pathways, the scaffold can bias transcriptional and post-transcriptional programs that govern proliferation and survival.\n\nCellular placement follows from both the LRR scaffold’s membrane-proximal behavior and the observed compartmentalization. The LRR solenoid often associates with membrane-proximal complexes, consistent with GO:0005886 plasma membrane. In specialized sensory neurons, the same scaffold can be recruited to disc membranes of photoreceptors, consistent with GO:0097381 photoreceptor disc membrane. The experimentally observed distribution between cytoplasm and nucleus fits a shuttle-like scaffold that assembles signaling complexes in the cytoplasm and influences transcriptional/apoptotic programs in the nucleus.\n\nMechanistically, I propose that the LRR array nucleates a Ras/MAPK signalosome at membrane-proximal sites, enhancing pathway fidelity and amplitude. This assembly then communicates with nuclear regulators to coordinate cell-cycle progression and apoptosis. In photoreceptors, the scaffold likely stabilizes membrane-associated complexes at disc rims, integrating cargo trafficking and membrane remodeling with signaling status.\n\nFrom this model, likely interaction partners include small GTPases and their effectors (e.g., HRAS/KRAS/NRAS and RAF kinases), MAPK cascade components (MEK and ERK), SHOC2-family scaffolds, and membrane-associated adaptors at photoreceptor disc membranes. These interactions collectively explain the observed protein-binding function, the positive regulation of Ras signaling, and the dual cytoplasm–nucleus localization.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-A6NIV6.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/A6NIV6"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/A6NIV6/entry","atlas":"/p/A6NIV6"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}