Protein: RNA-binding protein Nova-2 (Astrocytic NOVA1-like RNA-binding protein) (Neuro-oncological ventral antigen 2) (Q9UNW9)
Organism: Homo sapiens (Human)
Function: Functions to regulate alternative splicing in neurons by binding pre-mRNA in a sequence-specific manner to activate exon inclusion or exclusion. It binds specifically to the sequences 5'-YCAY-3' and regulates splicing in only a subset of regulated exons. Binding to an exonic 5'-YCAY-3' cluster changes the protein complexes assembled on pre-mRNA, blocking U1 snRNP binding and exon inclusion, whereas binding to an intronic 5'-YCAY-3' cluster enhances spliceosome assembly and exon inclusion. With NOVA1, they perform unique biological functions in different brain areas and cell types. Uniquely regulates alternative splicing events of a series of axon guidance related genes during cortical development, being essential for central nervous system development by regulating neural networks wiring. Regulates differentially alternative splicing on the same transcripts expressed in different neurons. This includes functional differences in transcripts expressed in cortical and cerebellar excitatory versus inhibitory neurons where is required for, respectively, development of laminar structure and motor coordination and synapse formation. Also the regulation the regulation of intron retention can sequester the trans-acting splicing factor PTBP2, acting as a variable cis-acting scaffolding platform for PTBP2 across various natural conditions (By similarity).
Subcellular location: Nucleus {ECO:0000250|UniProtKB:A0A1W2P872}.
Sequence: MEPEAPDSRKRPLETPPEVVCTKRSNTGEEGEYFLKVLIPSYAAGSIIGKGGQTIVQLQKETGATIKLSKSKDFYPGTTERVCLVQGTAEALNAVHSFIAEKVREIPQAMTKPEVVNILQPQTTMNPDRAKQAKLIVPNSTAGLIIGKGGATVKAVMEQSGAWVQLSQKPEGINLQERVVTVSGEPEQVHKAVSAIVQKVQEDPQSSSCLNISYANVAGPVANSNPTGSPYASPADVLPAAAAASAAAASGLLGPAGLAGVGAFPAALPAFSGTDLLAISTALNTLASYGYNTNSLGLGLNSAAASGVLAAVAAGANPAAAAAANLLASYAGEAGAGPAGGAAPPPPPPPGALGSFALAAAANGYLGAGAGGGAGGGGGPLVAAAAAAGAAGGFLTAEKLAAESAKELVEIAVPENLVGAILGKGGKTLVEYQELTGARIQISKKGEFLPGTRNRRVTITGSPAATQAAQYLISQRVTYEQGVRASNPQKVG
InterPro domains: - IPR036612: K Homology domain, type 1 superfamily (homologous_superfamily) [31-480]
- IPR004087: K Homology domain (domain) [31-478]
- IPR047276: RNA-binding protein Nova-1/2, type I K Homology domain 2 (domain) [131-200]
- IPR047275: RNA-binding protein Nova-1/2, type I K Homology domain 1 (domain) [33-104]
- IPR004088: K Homology domain, type 1 (domain) [36-474]
- IPR047274: RNA-binding protein Nova-1/2, type I K Homology domain 3 (domain) [409-477]
Interaction partners: - Polypyrimidine tract-binding protein 2
- Protein FAM107B
- RNA-binding protein Nova-1
- Heterogeneous nuclear ribonucleoproteins C1/C2
- Voltage-gated potassium channel regulatory subunit KCNF1
- Sodium channel protein type 1 subunit alpha
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0097159 (organic cyclic compound binding), GO:1901363 (heterocyclic compound binding), GO:0003676 (nucleic acid binding), GO:0003723 (RNA binding), GO:0003729 (mRNA binding), GO:0003730 (mRNA 3'-UTR binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0044237 (cellular metabolic process), GO:0071704 (organic substance metabolic process), GO:0019222 (regulation of metabolic process), GO:0044238 (primary metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0043170 (macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0051252 (regulation of RNA metabolic process), GO:0090304 (nucleic acid metabolic process), GO:0010467 (gene expression), GO:0010468 (regulation of gene expression), GO:0043484 (regulation of RNA splicing), GO:0016070 (RNA metabolic process), GO:1903311 (regulation of mRNA metabolic process), GO:0006396 (RNA processing), GO:0050684 (regulation of mRNA processing), GO:0048024 (regulation of mRNA splicing, via spliceosome), GO:0000381 (regulation of alternative mRNA splicing, via spliceosome)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)