{"uniprot":"Q7RTY7","gene":"OVCH1","name":"Ovochymase-1","organism":"Homo sapiens (Human)","status":"dark","length":1134,"sequence":"MGLLASAGLLLLLVIGHPRSLGLKCGIRMVNMKSKEPAVGSRFFSRISSWRNSTVTGHPWQVSLKSDEHHFCGGSLIQEDRVVTAAHCLDSLSEKQLKNITVTSGEYSLFQKDKQEQNIPVSKIITHPEYNSREYMSPDIALLYLKHKVKFGNAVQPICLPDSDDKVEPGILCLSSGWGKISKTSEYSNVLQEMELPIMDDRACNTVLKSMNLPPLGRTMLCAGFPDWGMDACQGDSGGPLVCRRGGGIWILAGITSWVAGCAGGSVPVRNNHVKASLGIFSKVSELMDFITQNLFTGLDRGQPLSKVGSRYITKALSSVQEVNGSQRGKGILDMEKQVGCDHDYVSLRSSSGVLFNQRSLMEDDGKQNKRVCGKILPSPLLAETSEAMVPFVSDTEDSGSGFELTVTAVQKSEAGSGCGSLAILVEEGTNHSAKYPDLYPSNTRCHWFICAPEKHIIKLTFEDFAVKFSPNCIYDAVVIYGDSEEKHKLAKLCGMLTITSIFSSSNMTVIYFKSDGKNRLQGFKARFTILPSESLNKFEPKLPPQNNPVSTVKAILHDVCGIPPFSPQWLSRRIAGGEEACPHCWPWQVGLRFLGDYQCGGAIINPVWILTAAHCVQLKNNPLSWTIIAGDHDRNLKESTEQVRRAKHIIVHEDFNTLSYDSDIALIQLSSPLEYNSVVRPVCLPHSAEPLFSSEICAVTGWGSISADGGLASRLQQIQVHVLEREVCEHTYYSAHPGGITEKMICAGFAASGEKDFCQGDSGGPLVCRHENGPFVLYGIVSWGAGCVQPWKPGVFARVMIFLDWIQSKINGPASLQTNNKCKTLKQQLPPPTPSPDSASWPGCCSEAELEKPRGFFPTPRYLLDYRGRLECSWVLRVSASSMAKFTIEYLSLLGSPVCQDSVLIIYEERHSKRKTAGGLHGRRLYSMTFMSPGPLVRVTFHALVRGAFGISYIVLKVLGPKDSKITRLSQSSNREHLVPCEDVLLTKPEGIMQIPRNSHRTTMGCQWRLVAPLNHIIQLNIINFPMKPTTFVCHGHLRVYEGFGPGKKLIASFAGTLAMILTKDILKREKLNFINTYIMHIWENSVYDNVRSVGKRKQKKFASNLSYSMEAEKSRIQVPADLVPAKGSLSGS","function_summary":"A secreted human serine endopeptidase that assembles and activates protease-dependent immune complexes. It carries a trypsin-like catalytic core that performs proteolysis and multiple CUB modules that mediate high-avidity binding to extracellular assemblies. After secretory-pathway maturation, it operates in the extracellular space to cleave and activate latent precursors within complement pathways, thereby driving zymogen activation and orchestrating complement activation cascades.","plain_language":"OVCH1 has barely been studied. The model's best guess: A secreted human serine endopeptidase that assembles and activates protease-dependent immune complexes. It carries a trypsin-like catalytic core that performs proteolysis and multiple CUB modules that mediate high-avidity binding to extracellular assemblies.","uniprot_summary":"Probable serine-type endopeptidase.","go_terms":{"molecular_function":[{"id":"GO:0004252","label":"serine-type endopeptidase activity"},{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0006956","label":"complement activation"},{"id":"GO:0031638","label":"zymogen activation"}],"cellular_component":[{"id":"GO:0005794","label":"Golgi apparatus"}]},"interpro":[{"id":"IPR009003","name":"Peptidase S1, PA clan","type":"homologous_superfamily","start":40,"end":295},{"id":"IPR035914","name":"Spermadhesin, CUB domain superfamily","type":"homologous_superfamily","start":330,"end":414},{"id":"IPR035914","name":"Spermadhesin, CUB domain superfamily","type":"homologous_superfamily","start":415,"end":537},{"id":"IPR009003","name":"Peptidase S1, PA clan","type":"homologous_superfamily","start":557,"end":812},{"id":"IPR035914","name":"Spermadhesin, CUB domain superfamily","type":"homologous_superfamily","start":843,"end":955},{"id":"IPR035914","name":"Spermadhesin, CUB domain superfamily","type":"homologous_superfamily","start":987,"end":1062},{"id":"IPR001254","name":"Serine proteases, trypsin domain","type":"domain","start":38,"end":296},{"id":"IPR000859","name":"CUB domain","type":"domain","start":333,"end":410},{"id":"IPR000859","name":"CUB domain","type":"domain","start":419,"end":531},{"id":"IPR001254","name":"Serine proteases, trypsin domain","type":"domain","start":574,"end":812},{"id":"IPR000859","name":"CUB domain","type":"domain","start":846,"end":957},{"id":"IPR001314","name":"Peptidase S1A, chymotrypsin family","type":"family","start":601,"end":616},{"id":"IPR001314","name":"Peptidase S1A, chymotrypsin family","type":"family","start":660,"end":674},{"id":"IPR001314","name":"Peptidase S1A, chymotrypsin family","type":"family","start":756,"end":768},{"id":"IPR018114","name":"Serine protease-like, trypsin family, histidine active site","type":"active_site","start":83,"end":88},{"id":"IPR033116","name":"Serine proteases, trypsin family, serine active site","type":"active_site","start":231,"end":242},{"id":"IPR018114","name":"Serine protease-like, trypsin family, histidine active site","type":"active_site","start":611,"end":616}],"reasoning":"I begin by dissecting the InterPro architecture and its order along the sequence. The N-terminus carries a canonical trypsin-like serine protease core: IPR009003 (Peptidase S1, PA clan, residues 40–295) and IPR001254 (Serine proteases, trypsin domain, residues 38–296) define a chymotrypsin/trypsin fold that is characteristic of PA-clan endopeptidases. Catalytic chemistry is specified by IPR018114 (Serine protease-like, trypsin family, histidine active site, residues 83–88) and IPR033116 (Serine proteases, trypsin family, serine active site, residues 231–242), establishing a His–Asp–Ser catalytic triad that causes endopeptidase activity. This N-terminal protease module is followed by a long spacer that leads into a cluster of CUB domains: IPR035914 (Spermadhesin, CUB domain superfamily, residues 330–414), IPR035914 (residues 415–537), IPR035914 (residues 843–955), and IPR035914 (residues 987–1062), with discrete CUB modules annotated as IPR000859 (CUB domain, residues 333–410; 419–531; 846–957). CUB domains are extracellular interaction modules that target proteins to specific macromolecular assemblies and frequently mediate complement and protease complex assembly. A second protease-like region appears later: IPR009003 (PA clan, residues 557–812) and IPR001254 (Serine proteases, trypsin domain, residues 574–812) together with S1A-family signatures IPR001314 (Peptidase S1A, chymotrypsin family, residues 601–616; 660–674; 756–768) and catalytic annotations IPR018114 (histidine active site, residues 611–616) indicate a second trypsin-fold module. In many complement-associated proteases, such duplicated or tandem trypsin-like domains are present; however, one or both can be catalytically impaired while retaining binding and assembly functions. The presence of two trypsin-fold cores separated by CUB-rich linkers creates a bimodular scaffold that both catalyzes proteolysis and organizes multiprotein complexes.\n\nThis domain architecture dictates molecular function. The paired trypsin-fold cores and their conserved active-site motifs (IPR018114 and IPR033116) cause serine-type endopeptidase activity, aligning with GO:0004252 serine-type endopeptidase activity. The extensive CUB array and modular arrangement favor multivalent protein binding, supporting GO:0005515 protein binding as an intrinsic property necessary for assembling and positioning protease complexes.\n\nFrom function to process, a trypsin-like endopeptidase tethered by multiple CUB domains is a hallmark of complement-associated proteases that process zymogens. The architecture is tailored to cleave and activate complement components and related substrates, which places the protein squarely in complement-mediated immunity. Thus, the protease’s activity and assembly role drive GO:0006956 complement activation. The presence of two trypsin-like cores and CUB-mediated targeting also explains GO:0031638 zymogen activation: the enzyme both activates itself and orchestrates activation cascades by cleaving latent precursors.\n\nCellular location follows from biosynthetic routing and extracellular deployment. The CUB-rich and trypsin-fold architecture is characteristic of secreted or luminal proteins that traverse the secretory pathway. The annotation of secreted/extracellular space is consistent with this, and the trafficking route through the Golgi is expected for glycoprotein assembly and maturation, supporting GO:0005794 Golgi apparatus. After Golgi processing, the protein is released to the extracellular space where complement activation occurs.\n\nMechanistically, the N-terminal trypsin domain provides catalytic cleavage that triggers and coordinates zymogen activation within complement pathways, while the CUB modules and the second trypsin-like region create a high-avidity platform that binds complement components and regulators. I hypothesize that the protein forms a secreted protease-scaffold that binds and activates complement zymogens and their substrates in the extracellular milieu. Likely interaction partners include complement components and regulators that dock via CUB domains—such as C3/C4 precursors and their binding partners—along with assembly factors that chaperone complement complexes. This cooperative assembly explains how the enzyme both executes proteolysis and organizes higher-order immune complexes.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q7RTY7.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q7RTY7"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q7RTY7/entry","atlas":"/p/Q7RTY7"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}