{"uniprot":"P0DMP2","gene":"SRGAP2B","name":"SLIT-ROBO Rho GTPase-activating protein 2B","organism":"Homo sapiens (Human)","status":"dark","length":458,"sequence":"MTSPAKFKKDKEIIAEYDTQVKEIRAQLTEQMKCLDQQCELRVQLLQDLQDFFRKKAEIEMDYSRNLEKLAERFLAKTCSTKDQQFKKDQNVLSPVNCWNLLLNQVKRESRDHTTLSDIYLNNIIPRFVQVSEDSGRLFKKSKEVGQQLQDDLMKVLNELYSVMKTYHMYNADSISAQSKLKEAEKQEEKQIGKSVKQEDRQTPRSPDSTANVRIEEKHVRRSSVKKIEKMKEKRQAKYTENKLKAIKARNEYLLALEATNASVFKYYIHDLSDLIDCCDLGYHASLNRALRTFLSAELNLEQSKHEGLDAIENAVENLDATSDKQRLMEMYNNVFCPPMKFEFQPHMGDMASQLCAQQPVQSELLQRCQQLQSRLSTLKIENEEVKKTMEATLQTIQDIVTVEDFDVSDCFQYSNSMESVKSTVSETFMSKPSIAKRRANQQETEQFYFTVRECYGF","function_summary":"A human scaffolding protein that assembles membrane-proximal signaling complexes through an extended BAR superfamily core to control cytoskeletal organization and membrane remodeling. By building multivalent assemblies that tune Rho-dependent pathways and differentiation programs, it supports cardiomyocyte maturation. A soluble pool likely enters the nucleus to coordinate transcriptional programs that accompany cardiac muscle cell development, linking membrane-cytoskeleton dynamics to nuclear regulation.","plain_language":"SRGAP2B has barely been studied. The model's best guess: A human scaffolding protein that assembles membrane-proximal signaling complexes through an extended BAR superfamily core to control cytoskeletal organization and membrane remodeling. By building multivalent assemblies that tune Rho-dependent pathways and differentiation programs, it supports cardiomyocyte maturation.","uniprot_summary":"May be involved in cardiac muscle cell development.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0055013","label":"cardiac muscle cell development"}],"cellular_component":[{"id":"GO:0005654","label":"nucleoplasm"}]},"interpro":[{"id":"IPR027267","name":"AH/BAR domain superfamily","type":"homologous_superfamily","start":24,"end":347},{"id":"IPR001060","name":"FCH domain","type":"domain","start":22,"end":120},{"id":"IPR031160","name":"F-BAR domain","type":"domain","start":22,"end":324},{"id":"IPR051627","name":"SLIT-ROBO Rho GTPase-activating","type":"family","start":6,"end":455}],"reasoning":"I begin with the InterPro architecture. The N-terminal third contains IPR001060 (FCH domain, residues 22–120), which seeds membrane-remodeling scaffolds. This region is embedded within IPR031160 (F-BAR domain, residues 22–324) and encompassed by IPR027267 (AH/BAR domain superfamily, residues 24–347). F-BAR modules dimerize into crescent-shaped scaffolds that bind acidic membranes and impose or sense negative curvature, thereby organizing actin and endocytic machinery. The overall BAR superfamily signature extending to residue 347 indicates a long, membrane-proximal scaffold that nucleates multiprotein assemblies rather than catalyzing classical enzymatic reactions. The full-length sequence also falls within IPR051627 (SLIT-ROBO Rho GTPase-activating family, residues 6–455), a family that couples membrane-associated scaffolding to Rho-family signaling. Together, this ordered layout—an N-terminal FCH that feeds into an extended F-BAR core within the AH/BAR superfamily and a family linked to SLIT-ROBO pathways—creates a high-avidity platform for assembling and positioning signaling complexes. This architecture causes robust multivalent interactions with other proteins, supporting GO:0005515 protein binding as the primary molecular function.\n\nFrom this scaffolded molecular function, I infer the biological role. F-BAR scaffolds classically coordinate actin remodeling and endocytic events that shape cell morphology and migration. Membership in the SLIT-ROBO Rho GTPase-activating family ties the scaffold to pathways that regulate cytoskeletal dynamics and cell guidance cues. Such cytoskeletal and morphogenetic control is a prerequisite for specialized differentiation programs in muscle lineages. Consequently, this scaffolded signaling is well-suited to drive the developmental trajectory formalized as GO:0055013 cardiac muscle cell development, where precise control of actin organization and membrane remodeling underlies cardiomyocyte maturation.\n\nCellular placement follows from the same logic. BAR-domain assemblies often operate at membrane–cytoskeleton interfaces and can shuttle to soluble compartments. The presence of a large, soluble scaffold and the developmental role suggest a nuclear-accessible pool. The explicit nucleoplasmic label (GO:0005654 nucleoplasm) aligns with a model in which the scaffold transiently accumulates in the nucleus to coordinate transcriptional programs that accompany cardiomyocyte differentiation. A plausible cycle is nucleocytoplasmic shuttling: cytoplasmic membrane binding via the F-BAR core, followed by nuclear entry of a soluble fraction to modulate gene expression modules that reinforce cardiac muscle cell development.\n\nMechanistically, I hypothesize that the F-BAR platform recruits and positions Rho-family regulators and actin-assembly factors at membrane subdomains, shaping cortical actin and endocytic hotspots that feed forward into differentiation pathways. In parallel, a nucleoplasmic pool likely engages transcriptional regulators and chromatin-associated complexes to fine-tune cardiomyocyte gene programs. Likely partners include SLIT-ROBO pathway components and Rho GTPase modulators that dock onto BAR scaffolds, as well as nuclear co-regulators that couple cytoskeletal state to transcriptional output.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-P0DMP2.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/P0DMP2"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/P0DMP2/entry","atlas":"/p/P0DMP2"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}