{"uniprot":"Q6UXH9","gene":"PAMR1","name":"Inactive serine protease PAMR1","organism":"Homo sapiens (Human)","status":"dark","length":720,"sequence":"MELGCWTQLGLTFLQLLLISSLPREYTVINEACPGAEWNIMCRECCEYDQIECVCPGKREVVGYTIPCCRNEENECDSCLIHPGCTIFENCKSCRNGSWGGTLDDFYVKGFYCAECRAGWYGGDCMRCGQVLRAPKGQILLESYPLNAHCEWTIHAKPGFVIQLRFVMLSLEFDYMCQYDYVEVRDGDNRDGQIIKRVCGNERPAPIQSIGSSLHVLFHSDGSKNFDGFHAIYEEITACSSSPCFHDGTCVLDKAGSYKCACLAGYTGQRCENLLEERNCSDPGGPVNGYQKITGGPGLINGRHAKIGTVVSFFCNNSYVLSGNEKRTCQQNGEWSGKQPICIKACREPKISDLVRRRVLPMQVQSRETPLHQLYSAAFSKQKLQSAPTKKPALPFGDLPMGYQHLHTQLQYECISPFYRRLGSSRRTCLRTGKWSGRAPSCIPICGKIENITAPKTQGLRWPWQAAIYRRTSGVHDGSLHKGAWFLVCSGALVNERTVVVAAHCVTDLGKVTMIKTADLKVVLGKFYRDDDRDEKTIQSLQISAIILHPNYDPILLDADIAILKLLDKARISTRVQPICLAASRDLSTSFQESHITVAGWNVLADVRSPGFKNDTLRSGVVSVVDSLLCEEQHEDHGIPVSVTDNMFCASWEPTAPSDICTAETGGIAAVSFPGRASPEPRWHLMGLVSWSYDKTCSHRLSTAFTKVLPFKDWIERNMK","function_summary":"A secreted human serine endopeptidase that assembles into extracellular complexes via modular CUB, calcium-binding EGF-like, and CCP/Sushi domains to capture substrates and organize pericellular assemblies. Its C-terminal trypsin-like catalytic core executes targeted proteolysis that modulates extracellular and secretory pathway pathways, thereby shaping cellular responses to xenobiotic exposure. The N-terminal binding modules drive avid protein interactions and calcium-tuned targeting, while the protease domain executes precise cleavage events in the extracellular space and associated complexes.","plain_language":"PAMR1 has barely been studied. The model's best guess: A secreted human serine endopeptidase that assembles into extracellular complexes via modular CUB, calcium-binding EGF-like, and CCP/Sushi domains to capture substrates and organize pericellular assemblies. Its C-terminal trypsin-like catalytic core executes targeted proteolysis that modulates extracellular and secretory pathway pathways, thereby shaping cellular responses to xenobiotic exposure.","uniprot_summary":"Probable serine protease.","go_terms":{"molecular_function":[{"id":"GO:0004252","label":"serine-type endopeptidase activity"},{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0071466","label":"cellular response to xenobiotic stimulus"}],"cellular_component":[{"id":"GO:0005615","label":"extracellular space"},{"id":"GO:0032991","label":"protein-containing complex"}]},"interpro":[{"id":"IPR035914","name":"Spermadhesin, CUB domain superfamily","type":"homologous_superfamily","start":123,"end":239},{"id":"IPR035976","name":"Sushi/SCR/CCP superfamily","type":"homologous_superfamily","start":280,"end":350},{"id":"IPR009003","name":"Peptidase S1, PA clan","type":"homologous_superfamily","start":414,"end":720},{"id":"IPR000859","name":"CUB domain","type":"domain","start":128,"end":236},{"id":"IPR000742","name":"EGF-like domain","type":"domain","start":235,"end":272},{"id":"IPR001881","name":"EGF-like calcium-binding domain","type":"domain","start":235,"end":272},{"id":"IPR000436","name":"Sushi/SCR/CCP domain","type":"domain","start":278,"end":344},{"id":"IPR000436","name":"Sushi/SCR/CCP domain","type":"domain","start":387,"end":444},{"id":"IPR001254","name":"Serine proteases, trypsin domain","type":"domain","start":445,"end":720},{"id":"IPR051659","name":"Serine Protease S1 Domain-Containing Protein","type":"family","start":2,"end":720},{"id":"IPR001314","name":"Peptidase S1A, chymotrypsin family","type":"family","start":490,"end":505},{"id":"IPR001314","name":"Peptidase S1A, chymotrypsin family","type":"family","start":556,"end":570},{"id":"IPR001314","name":"Peptidase S1A, chymotrypsin family","type":"family","start":658,"end":670}],"reasoning":"I begin by dissecting the domain architecture. The N-terminal third is dominated by modular binding and targeting domains: IPR035914 (Spermadhesin, CUB domain superfamily, residues 123–239) contains a canonical IPR000859 CUB domain (128–236), followed immediately by an IPR000742 EGF-like domain (235–272) that is annotated as IPR001881 EGF-like calcium-binding domain (235–272), and then an IPR035976 Sushi/SCR/CCP superfamily segment (280–350) that includes a defined IPR000436 Sushi/SCR/CCP domain (278–344). This sequence of CUB–EGF(Ca2+)-like–CCP/Sushi modules is a hallmark of secreted extracellular proteins that mediate high-affinity, calcium-tuned substrate capture and assembly into larger complexes. The CUB and CCP/Sushi modules cause avid protein binding and extracellular matrix association, while the calcium-binding EGF-like unit stabilizes domain–domain interfaces and confers Ca2+-dependent targeting.\n\nThe C-terminal half transitions into a catalytic apparatus. IPR009003 (Peptidase S1, PA clan homologous superfamily, 414–720) and IPR001254 (Serine proteases, trypsin domain, 445–720) define a trypsin-like serine protease fold. Multiple family-level signatures reinforce this chemistry: IPR001314 (Peptidase S1A, chymotrypsin family, 490–505), IPR001314 (556–570), and IPR001314 (658–670) collectively mark conserved S1A motifs that organize the catalytic triad and substrate-binding pocket. The overall architecture is captured by IPR051659 (Serine Protease S1 Domain-Containing Protein family, 2–720), which spans nearly the full length and indicates a secreted protease scaffold. This ordered layout—N-terminal extracellular targeting modules feeding into a C-terminal S1A catalytic core—causally establishes serine-type endopeptidase activity and multivalent protein binding.\n\nFrom these features, I infer molecular function. The S1A/trypsin domain (IPR001254; IPR009003) and S1A family motifs (IPR001314) specify GO:0004252 serine-type endopeptidase activity. The CUB, EGF-like, and CCP/Sushi modules create avid extracellular interactions, supporting GO:0005515 protein binding as an intrinsic property of the targeting region. The calcium-binding EGF-like domain further stabilizes substrate engagement and complex formation, reinforcing both binding and proteolysis.\n\nThis protease’s biological role follows from its extracellular design and secretory nature. Secreted trypsin-like proteases with modular targeting domains typically remodel extracellular proteins, activate latent factors, or process cargo within secretory pathways. Such processing can tune cellular responses to exogenous compounds and toxins. Therefore, the enzyme’s proteolysis and assembly into complexes provide a mechanistic route to GO:0071466 cellular response to xenobiotic stimulus: by activating or inactivating extracellular cues and secreted mediators, it modulates pathways that buffer xenobiotic exposure.\n\nCellular location is dictated by the signal implied by the extracellular modules and the secreted designation. The CUB–EGF–CCP architecture is classically non-cytosolic, and the presence of a soluble trypsin-like domain argues for a luminal/extracellular route. Thus, I place the protein in the GO:0005615 extracellular space and as part of GO:0032991 protein-containing complexes. The modular binding domains drive assembly into higher-order complexes, consistent with the latter cellular component term.\n\nMechanistically, I hypothesize that the N-terminal CUB and CCP/Sushi modules nucleate complexes with extracellular matrix proteins and complement receptor systems, positioning the C-terminal S1A protease domain to selectively cleave target substrates. Likely partners include glycoproteins and adhesion molecules captured via CUB/EGF/CCP interactions, as well as secreted or pericellular substrates whose processing tunes xenobiotic-response pathways. In secretory compartments and at the cell surface, this architecture enables Ca2+-stabilized substrate capture followed by precise endoproteolysis that modulates extracellular signaling and cargo handling.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q6UXH9.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q6UXH9"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q6UXH9/entry","atlas":"/p/Q6UXH9"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}