{"uniprot":"O15037","gene":"KHNYN","name":"Protein KHNYN","organism":"Homo sapiens (Human)","status":"dark","length":678,"sequence":"MPTWGARPASPDRFAVSAEAENKVREQQPHVERIFSVGVSVLPKDCPDNPHIWLQLEGPKENASRAKEYLKGLCSPELQDEIHYPPKLHCIFLGAQGFFLDCLAWSTSAHLVPRAPGSLMISGLTEAFVMAQSRVEELAERLSWDFTPGPSSGASQCTGVLRDFSALLQSPGDAHREALLQLPLAVQEELLSLVQEASSGQGPGALASWEGRSSALLGAQCQGVRAPPSDGRESLDTGSMGPGDCRGARGDTYAVEKEGGKQGGPREMDWGWKELPGEEAWEREVALRPQSVGGGARESAPLKGKALGKEEIALGGGGFCVHREPPGAHGSCHRAAQSRGASLLQRLHNGNASPPRVPSPPPAPEPPWHCGDRGDCGDRGDVGDRGDKQQGMARGRGPQWKRGARGGNLVTGTQRFKEALQDPFTLCLANVPGQPDLRHIVIDGSNVAMVHGLQHYFSSRGIAIAVQYFWDRGHRDITVFVPQWRFSKDAKVRESHFLQKLYSLSLLSLTPSRVMDGKRISSYDDRFMVKLAEETDGIIVSNDQFRDLAEESEKWMAIIRERLLPFTFVGNLFMVPDDPLGRNGPTLDEFLKKPARTQGSSKAQHPSRGFAEHGKQQQGREEEKGSGGIRKTRETERLRRQLLEVFWGQDHKVDFILQREPYCRDINQLSEALLSLNF","function_summary":"A modular RNA-binding and RNA-degrading factor that concentrates in cytoplasmic ribonucleoprotein granules and exchanges with the nucleoplasm. It uses tandem RNA-recognition modules to capture target transcripts, a catalytic center to cleave them, and a C-terminal adaptor to engage ubiquitylated partners. By assembling and remodeling RNA–protein complexes in decay hubs, it suppresses viral RNA accumulation and tunes cellular responses to UV-induced stress.","plain_language":"KHNYN has barely been studied. The model's best guess: A modular RNA-binding and RNA-degrading factor that concentrates in cytoplasmic ribonucleoprotein granules and exchanges with the nucleoplasm. It uses tandem RNA-recognition modules to capture target transcripts, a catalytic center to cleave them, and a C-terminal adaptor to engage ubiquitylated partners.","uniprot_summary":"May be involved in cytoplasmic RNA degradation.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0045071","label":"negative regulation of viral genome replication"},{"id":"GO:0034644","label":"cellular response to UV"}],"cellular_component":[{"id":"GO:0005654","label":"nucleoplasm"},{"id":"GO:0000932","label":"P-body"}]},"interpro":[{"id":"IPR036612","name":"K Homology domain, type 1 superfamily","type":"homologous_superfamily","start":58,"end":141},{"id":"IPR056629","name":"N4BP1, first type I KH-domain","type":"domain","start":12,"end":75},{"id":"IPR056630","name":"N4BP1, second type I KH-domain","type":"domain","start":76,"end":196},{"id":"IPR021869","name":"Ribonuclease Zc3h12a-like, NYN domain","type":"domain","start":437,"end":589},{"id":"IPR056578","name":"N4BP1, C-terminal UBA domain","type":"domain","start":630,"end":675},{"id":"IPR051101","name":"ZC3H12/N4BP1 Ribonuclease and Regulator","type":"family","start":349,"end":623}],"reasoning":"I begin with the InterPro architecture. The N-terminus carries two tandem RNA-recognition modules: IPR056629 (N4BP1, first type I KH-domain, residues 12–75) followed immediately by IPR056630 (N4BP1, second type I KH-domain, residues 76–196). These are encompassed by IPR036612 (K Homology domain, type 1 superfamily, residues 58–141), reinforcing that the N-terminal half is a high-affinity RNA-binding platform that selects and organizes single-stranded RNA substrates. The central-to-C-terminal half transitions into ribonuclease machinery: IPR021869 (Ribonuclease Zc3h12a-like, NYN domain, residues 437–589) sits within IPR051101 (ZC3H12/N4BP1 Ribonuclease and Regulator family, residues 349–623), defining a metal-dependent endoribonuclease core that executes RNA cleavage. The extreme C-terminus bears IPR056578 (N4BP1, C-terminal UBA domain, residues 630–675), a ubiquitin-associated module that recruits ubiquitylated partners and couples RNA decay to ubiquitin signaling. The ordered layout—tandem KH RNA-binding domains, followed by a NYN catalytic center, capped by a UBA adaptor—creates a modular RNA-targeting and processing machine.\n\nThis architecture dictates molecular function. The paired KH domains cause selective RNA engagement and assembly of ribonucleoprotein complexes, while the NYN domain provides endoribonuclease activity that commits bound transcripts to decay. The UBA tail confers avid protein binding to ubiquitylated factors and scaffolds larger assemblies. Together these features necessitate GO:0005515 protein binding as a core capability, arising from KH-mediated RNA–protein interfaces and UBA-driven ubiquitin interactions.\n\nFrom these molecular activities, the biological processes follow. Endoribonuclease action and RNA triage in cytoplasmic RNA granules suppress replication of RNA viruses by degrading or sequestering their RNAs, aligning with GO:0045071 negative regulation of viral genome replication. The same RNA decay and signaling functions integrate with stress-responsive pathways; UV exposure triggers RNA surveillance and translational arrest, consistent with GO:0034644 cellular response to UV. The KH–NYN–UBA chain enables rapid remodeling of RNA–protein assemblies during stress, thereby tuning antiviral and UV-response circuits.\n\nCellular location is implied by the assembly logic. KH-driven RNA binding and NYN-mediated cleavage are hallmarks of cytoplasmic RNA decay hubs, placing the protein in GO:0000932 P-body. Dynamic exchange with nuclear RNA processing pathways and stress granules rationalizes nucleoplasmic residency (GO:0005654 nucleoplasm), where RNA maturation and signaling intersect with cytoplasmic decay.\n\nMechanistically, the protein likely binds target RNAs via its KH tandem, concentrates them in P-bodies, and uses the NYN center to cleave selected transcripts. The UBA domain recruits ubiquitylated RNA-binding factors and decay machinery, coupling RNA turnover to ubiquitin pathways. This assembly suppresses viral RNA accumulation and tunes UV-induced RNA surveillance. I hypothesize interactions with P-body scaffolds and decay factors—such as DDX6, EDC4, LSM1–7, DCP1/2, and GW182/TNRC6—to coordinate selective RNA repression and turnover, and with ubiquitin pathway adaptors that dock via the UBA tail to enforce antiviral and stress-responsive RNA control.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-O15037.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/O15037"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/O15037/entry","atlas":"/p/O15037"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}