{"uniprot":"Q8IX04","gene":"UEVLD","name":"Ubiquitin-conjugating enzyme E2 variant 3","organism":"Homo sapiens (Human)","status":"dark","length":471,"sequence":"MEFDCEGLRRLLGKYKFRDLTVEELRNVNVFFPHFKYSMDTYVFKDSSQKDLLNFTGTIPVMYQGNTYNIPIRFWILDSHPFAPPICFLKPTANMGILVGKHVDAQGRIYLPYLQNWSHPKSVIVGLIKEMIAKFQEELPMYSLSSSDEARQVDLLAYIAKITEGVSDTNSKSWANHENKTVNKITVVGGGELGIACTLAISAKGIADRLVLLDLSEGTKGATMDLEIFNLPNVEISKDLSASAHSKVVIFTVNSLGSSQSYLDVVQSNVDMFRALVPALGHYSQHSVLLVASQPVEIMTYVTWKLSTFPANRVIGIGCNLDSQRLQYIITNVLKAQTSGKEVWVIGEQGEDKVLTWSGQEEVVSHTSQVQLSNRAMELLRVKGQRSWSVGLSVADMVDSIVNNKKKVHSVSALAKGYYDINSEVFLSLPCILGTNGVSEVIKTTLKEDTVTEKLQSSASSIHSLQQQLKL","function_summary":"A cytoplasmic, bifunctional enzyme–scaffold that combines an N-terminal ubiquitin E2-variant platform with a C-terminal lactate dehydrogenase-like core. It assembles into oligomers and binds cadherin-associated complexes, positioning it at adhesion and cytoskeletal interfaces while catalyzing NAD(H)-dependent interconversion of pyruvate and lactate. Through this coupling of adhesion scaffolding and redox metabolism, it supports broader metabolic pathways and can be packaged into extracellular vesicles.","plain_language":"UEVLD has barely been studied. The model's best guess: A cytoplasmic, bifunctional enzyme–scaffold that combines an N-terminal ubiquitin E2-variant platform with a C-terminal lactate dehydrogenase-like core. It assembles into oligomers and binds cadherin-associated complexes, positioning it at adhesion and cytoskeletal interfaces while catalyzing NAD(H)-dependent interconversion of pyruvate and lactate.","uniprot_summary":"Probable lactate dehydrogenase.","go_terms":{"molecular_function":[{"id":"GO:0042802","label":"identical protein binding"},{"id":"GO:0045296","label":"cadherin binding"},{"id":"GO:0004457","label":"lactate dehydrogenase activity"}],"biological_process":[{"id":"GO:0006570","label":"tyrosine metabolic process"}],"cellular_component":[{"id":"GO:0070062","label":"extracellular exosome"}]},"interpro":[{"id":"IPR016135","name":"Ubiquitin-conjugating enzyme/RWD-like","type":"homologous_superfamily","start":1,"end":144},{"id":"IPR036291","name":"NAD(P)-binding domain superfamily","type":"homologous_superfamily","start":172,"end":316},{"id":"IPR015955","name":"Lactate dehydrogenase/glycoside hydrolase, family 4, C-terminal","type":"homologous_superfamily","start":317,"end":471},{"id":"IPR008883","name":"Ubiquitin E2 variant, N-terminal","type":"domain","start":2,"end":145},{"id":"IPR001236","name":"Lactate/malate dehydrogenase, N-terminal","type":"domain","start":184,"end":316},{"id":"IPR022383","name":"Lactate/malate dehydrogenase, C-terminal","type":"domain","start":320,"end":462},{"id":"IPR001557","name":"L-lactate/malate dehydrogenase","type":"family","start":184,"end":208},{"id":"IPR001557","name":"L-lactate/malate dehydrogenase","type":"family","start":290,"end":310},{"id":"IPR001557","name":"L-lactate/malate dehydrogenase","type":"family","start":314,"end":332},{"id":"IPR001557","name":"L-lactate/malate dehydrogenase","type":"family","start":344,"end":357}],"reasoning":"I begin by dissecting the InterPro architecture and its order along the sequence. The N-terminus (residues 1–144) is defined by IPR016135 (Ubiquitin-conjugating enzyme/RWD-like homologous superfamily) and reinforced by IPR008883 (Ubiquitin E2 variant, N-terminal domain, residues 2–145). This tandem strongly indicates an E2-variant scaffold rather than a catalytic ubiquitin-transfer enzyme; E2 variants typically lack the active-site cysteine and instead create protein–protein interaction platforms that regulate ubiquitin-like pathways and cytoskeletal/adhesion assemblies. This architecture predisposes the protein to multivalent binding and oligomerization, which causally supports GO:0042802 identical protein binding and GO:0045296 cadherin binding.\n\nThe central and C-terminal halves assemble a classical dehydrogenase core. IPR036291 (NAD(P)-binding domain superfamily, residues 172–316) and the paired IPR001236 (Lactate/malate dehydrogenase, N-terminal domain, residues 184–316) together with IPR022383 (Lactate/malate dehydrogenase, C-terminal domain, residues 320–462) create the bipartite fold typical of LDH/MDH enzymes. Multiple family-level signatures—IPR001557 (L-lactate/malate dehydrogenase family, residues 184–208; 290–310; 314–332; 344–335)—confirm this enzymatic identity and span the canonical catalytic core. The C-terminal region is further consolidated by IPR015955 (Lactate dehydrogenase/glycoside hydrolase family 4, C-terminal homologous superfamily, residues 317–471), which stabilizes the oligomeric assembly and substrate-binding groove. This ordered LDH/MDH architecture directly causes GO:0004457 lactate dehydrogenase activity by binding NAD(H) and catalyzing reversible interconversion of pyruvate and lactate.\n\nFrom molecular function to process, the LDH-like core situates the protein in central carbon metabolism. The explicit lactate dehydrogenase activity links to cytosolic redox buffering and pyruvate–lactate cycling. The presence of cadherin-binding and oligomerization tendencies, together with an E2-variant N-terminus, provides a mechanistic bridge to adhesion complexes and cytoskeletal interfaces. This scaffolding role can couple metabolic state to adhesion and signaling hubs. The supplied biological process label, GO:0006570 tyrosine metabolic process, can be rationalized mechanistically: adhesion/cytoskeletal assemblies and redox enzymes often intersect with tyrosine pathway enzymes and tyrosine phosphorylation cascades; by organizing cadherin-associated complexes and tuning NAD(H) pools, the protein can modulate flux and signaling in tyrosine-related metabolism.\n\nCellular localization follows from the soluble, enzyme-rich architecture and adhesion coupling. The absence of transmembrane segments and the soluble dehydrogenase fold argue for a cytoplasmic residency, consistent with a cytosolic metabolic scaffold. The GO cellular component leaf GO:0070062 extracellular exosome can be reconciled by noting that many cytosolic metabolic/scaffold proteins are selectively packaged into exosomes; cadherin-associated assemblies and oligomeric LDH-like complexes are frequently detected in extracellular vesicles.\n\nIntegrating these lines of evidence yields a mechanistic hypothesis: an N-terminal E2-variant platform nucleates oligomerization and cadherin/cytoskeleton interactions, while the central–C-terminal LDH-like core provides NAD(H)-dependent catalytic and binding activities. This dual architecture causes a bifunctional behavior—metabolic enzyme activity coupled to adhesion/scaffold functions—positioned in the cytoplasm and trafficked via exosomes. Likely interaction partners include cadherins and catenins at adhesion sites, actin-associated adaptors, and ubiquitin-like pathway regulators; oligomerization with itself (identical protein binding) stabilizes higher-order assemblies that tune lactate/pyruvate balance and interface with tyrosine-related metabolic signaling.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8IX04.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8IX04"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8IX04/entry","atlas":"/p/Q8IX04"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}