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Binds to 5'-YCAY-3' repeats, with a minimum of 2 to 3 repeats necessary for high-affinity binding. Mediates both exon inclusion and exclusion, depending upon the position of its binding site within the pre-mRNA (PubMed:10811881). Binding to 5'-YCAY-3' clusters results in a local and asymmetric action to regulate spliceosome assembly. Binding to an exonic 5'-YCAY-3' cluster changes the protein complexes assembled on pre-mRNA, blocking U1 small nuclear ribonucleoprotein (snRNP) binding and inhibiting exon inclusion, whereas binding to an intronic 5'-YCAY-3' repeat enhances spliceosome assembly and favors exon inclusion (By similarity). Regulates the splicing of gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2) and glycine receptor subunit alpha-2 (GLRA2) pre-mRNAs, among others (By similarity). Autoregulates its own splicing. Binds to its own exon 4 and directs its exclusion, thus leading to NOVA1 isoform 3 production (By similarity). May affect the splicing of many genes involved in vocal behavior (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JKN6"}],"value":"Directly interacts with PTBP2; this interaction inhibits NOVA-dependent activation of exon inclusion in glycine receptor subunit alpha-2 (GLRA2) pre-mRNA, when PTBP2 also binds to pre-mRNA"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P51513","intActId":"EBI-726123"},"interactantTwo":{"uniProtKBAccession":"P18507","geneName":"GABRG2","intActId":"EBI-9008430"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P51513","intActId":"EBI-726123"},"interactantTwo":{"uniProtKBAccession":"P50406","geneName":"HTR6","intActId":"EBI-1182222"},"numberOfExperiments":9,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JKN6"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["P51513-4"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"synonyms":[{"value":"Tumor"}],"isoformIds":["P51513-2"],"sequenceIds":["VSP_060047","VSP_060048"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["P51513-5"],"sequenceIds":["VSP_060046"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8398153"}],"value":"Expressed in cerebellum, brain stem, hippocampus, and frontal cortex"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10811881"}],"value":"The KH domain consists of approximately 70 amino acids and includes a conserved hydrophobic core, an invariant Gly-X-X-Gly motif, and an additional variable segment. The third KH domain (KH3) binds a hairpin loop containing the 5'-YCAY-3' motif on target pre-mRNAs. RNA binding by KH3 requires residues C-terminal to the KH domain"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39966351"}],"value":"Valine at position 197 is unique to modern humans. Other mammalian species, including Neanderthals and Denisovans, have a isoleucine at this position. The variant p.Val197Ile is extremely rare in humans, with only one allele reported in gnomAD v4.1.0. When tested in transgenic mice, p.Ile197Val allele does not affect development, brain size, nor fertility and does not alter motor performance, but affects vocalization patterns in pups and adults. It has been proposed that this variant may have contributed to the development of neural systems involved in more complex vocal communication in modern humans"}],"commentType":"POLYMORPHISM"},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"8558240"}],"value":"Trigger of a neurological autoimmnue disorder, called paraneoplastic opsoclonus-myoclonus ataxia (POMA), that can cause extreme motor dysfunction. This disorder develops when tumor cells ectopically express NOVA1, that is normally restricted to the nervous system, triggering an anti-tumor immune response that breaches the blood-brain barrier, leading to autoimmune neurologic disease. 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