{"uniprot":"Q008S8","gene":"ECT2L","name":"Epithelial cell-transforming sequence 2 oncogene-like","organism":"Homo sapiens (Human)","status":"dark","length":904,"sequence":"MESFHTRFSAWTPFSNKSLNRQLFQERVALISHWFDLWTNKQRQEFLFAIFLRCTKSQLRFVQDWFSERMQVAKVDFSTVLPRFISLYIFSFLSPKDLCAAAQVSWPWKFLTEQDCLWMPKCVKFGWFLPYTPTDNEYGAWKRHYIACVSHLDWLTPREAAATYGTLNEPKTEDEELLERQREKCLRKRIWEKIALRKKELFKVRPPWVSGTCCSSVLKPRCQPRLSQTVRERVGLHEALEKQLVLTSLETLPKRSNISGSHSYPLLSKKNWHGVHKNDDRSSYALRPHFMLISSRIPAYEMVMESVKAGVVSVVYEHSVTLESLLYLIEKALDGQKAQSIGIFSDGDSREINLLQGYKIGVKNLLRPEVRDFWEKLGSYVATEEEGGHVDFFVPLGASEAGIEVLSQLSQLTGTFFTAPTGIATGSYQHILSDWLGSQWGKAPSSIYFCESKLQTWSSFTDFLEETLKTVRKQLYPFFKELQKSISGRMIGQFMFDTMGMTNILNNQDTAQALADGLMELSKEDSERNVVEDNSWDTKSRLSKNDLNFEALINLERILQKDSAEKRARVVRELLQSERKYVQILEIVRDVYVAPLKAALSSNRAILSAANIQIIFCDILQILSLNRQFLDNLRDRLQEWGPAHCVGEIVTKFGSQLNTYTNFFNNYPVILKTIEKCREMIPAFRTFLKRHDKTIVTKMLSLPELLLYPSRRFEEYLNLLYAVRLHTPAEHVDRGDLTTAIDQIKKYKGYIDQMKQNITMKDHLSDIQRIIWGCPTLSEVNRYLIRVQDVAQLHCCDEEISFSLRLYEHIHDLSLFLFNDALLVSSRGTSHTPFERTSKTTYQFIASVALHRLLIENIPDSKYVKNAFILQGPKYKWICATEIEDDKFLWLSVLRNAIKSSMEK","function_summary":"A cytoplasmic signaling scaffold that combines an N-terminal F-box with a C-terminal guanine nucleotide exchange engine to coordinate small GTPase pathways and regulated proteolysis. The F-box assembles an SCF ubiquitin ligase to capture and turnover pathway components, while a DH–PH tandem catalyzes nucleotide exchange on Rho-family switches to drive cytoskeletal remodeling and transcriptional outputs. A central adaptor region likely stabilizes assemblies, allowing the protein to tune the amplitude and timing of small GTPase signaling within the cytosol.","plain_language":"ECT2L has barely been studied. The model's best guess: A cytoplasmic signaling scaffold that combines an N-terminal F-box with a C-terminal guanine nucleotide exchange engine to coordinate small GTPase pathways and regulated proteolysis. The F-box assembles an SCF ubiquitin ligase to capture and turnover pathway components, while a DH–PH tandem catalyzes nucleotide exchange on Rho-family switches to drive cytoskeletal remodeling and transcriptional outputs.","uniprot_summary":"Involved in signal transduction.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"},{"id":"GO:0005085","label":"guanyl-nucleotide exchange factor activity"}],"biological_process":[{"id":"GO:0051056","label":"regulation of small GTPase mediated signal transduction"}],"cellular_component":[{"id":"GO:0005829","label":"cytosol"}]},"interpro":[{"id":"IPR036047","name":"F-box-like domain superfamily","type":"homologous_superfamily","start":68,"end":148},{"id":"IPR035899","name":"Dbl homology (DH) domain superfamily","type":"homologous_superfamily","start":559,"end":771},{"id":"IPR011993","name":"PH-like domain superfamily","type":"homologous_superfamily","start":766,"end":904},{"id":"IPR001810","name":"F-box domain","type":"domain","start":81,"end":119},{"id":"IPR025592","name":"Domain of unknown function DUF4347","type":"domain","start":291,"end":459},{"id":"IPR000219","name":"Dbl homology domain","type":"domain","start":566,"end":754},{"id":"IPR052805","name":"Epithelial cell-transforming sequence 2 oncogene-like and F-box only protein 16","type":"family","start":3,"end":904}],"reasoning":"I begin with the domain architecture. The N-terminus carries IPR036047 (F-box-like domain superfamily, residues 68–148) and a well-defined IPR001810 F-box domain (residues 81–119). This tandem arrangement establishes an N-terminal F-box scaffold that recruits SKP1–CUL1–RBX1 to assemble an SCF ubiquitin ligase. Such an F-box core causes robust protein–protein interactions and substrate recognition, directly supporting GO:0005515 protein binding and positioning the protein as a modular adaptor that couples signaling to regulated proteolysis.\n\nA central region contains IPR025592 (DUF4347, residues 291–459), a conserved but uncharacterized module that likely stabilizes intracellular assemblies and may tune substrate selection or localization. The C-terminal half is dominated by a canonical Rho-family guanine nucleotide exchange module: IPR035899 (Dbl homology domain superfamily, residues 559–771) and IPR000219 (Dbl homology domain, residues 566–754) followed immediately by IPR011993 (PH-like domain superfamily, residues 766–904). The DH–PH tandem is a hallmark architecture that catalyzes GDP release on Rho-family GTPases and couples exchange chemistry to membrane-proximal signaling. This arrangement mechanistically encodes GO:0005085 guanyl-nucleotide exchange factor activity and provides the biochemical basis for GO:0051056 regulation of small GTPase mediated signal transduction.\n\nThe overall family context is reinforced by IPR052805 (Epithelial cell-transforming sequence 2 oncogene-like and F-box only protein 16 family, residues 3–904), which unites the F-box and DH–PH modules into a single polypeptide specialized for signal-integration roles. The ordered layout—N-terminal F-box for SCF assembly, central adaptor DUF, and C-terminal DH–PH GEF engine—creates a bifunctional platform: it both binds and remodels small GTPase signaling while coupling targets to ubiquitin-mediated turnover.\n\nFrom these features, the molecular function resolves into two axes. First, the F-box enforces multivalent protein binding (GO:0005515), enabling assembly of SCF complexes and substrate capture. Second, the DH–PH tandem confers guanyl-nucleotide exchange factor activity (GO:0005085), driving activation of Rho-family switches that govern cytoskeletal dynamics and transcriptional outputs. Together, these activities causally feed into GO:0051056 regulation of small GTPase mediated signal transduction: the DH–PH module activates small GTPases, while the F-box tunes pathway amplitude via targeted proteolysis.\n\nCellular location follows from the soluble, adaptor-rich architecture and absence of transmembrane segments. The F-box and DH–PH modules operate efficiently in the cytoplasm, and the assembly of SCF complexes and small GTPase signaling typically occurs in the cytosol. This supports GO:0005829 cytosol and aligns with a broader cytoplasmic residency.\n\nMechanistically, I hypothesize that the N-terminal F-box nucleates an SCF complex that recognizes and ubiquitylates pathway-specific substrates, while the C-terminal DH–PH tandem locally activates Rho-family GTPases to reprogram actin and transcriptional circuits. The central DUF4347 likely stabilizes transient assemblies between the SCF and GEF modules. Likely interaction partners include SKP1, CUL1, and RBX1 (for SCF assembly), Rho-family GTPases such as RHOA, RAC1, or CDC42 (as exchange substrates), and downstream effectors like ROCK or formins that execute cytoskeletal and transcriptional responses. This dual-module design enables coordinated control of signaling intensity and duration in the cytosol.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q008S8.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q008S8"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q008S8/entry","atlas":"/p/Q008S8"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}