Protein: RNA-binding protein Nova-1 (Neuro-oncological ventral antigen 1) (Ventral neuron-specific protein 1) (Q9JKN6)
Organism: Mus musculus (Mouse)
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. Binding to 5'-YCAY-3' clusters results in a local and asymmetric action to regulate spliceosome assembly and alternative splicing in neurons. Binding to an exonic 5'-YCAY-3' cluster changed the protein complexes assembled on pre-mRNA, blocking U1 snRNP (small nuclear ribonucleoprotein) binding and exon inclusion, whereas binding to an intronic 5'-YCAY-3' cluster enhanced spliceosome assembly and exon inclusion. With NOVA1, they perform unique biological functions in different brain areas and cell types. Autoregulates its own expression by acting as a splicing repressor. Acts to activate the inclusion of exon E3A in the glycine receptor alpha-2 chain and of exon E9 in gamma-aminobutyric-acid receptor gamma-2 subunit via a distal downstream UCAU-rich intronic splicing enhancer. Acts to regulate a novel glycine receptor alpha-2 chain splice variant (alpha-2N) in developing spinal cord.
Subcellular location: Nucleus {ECO:0000269|PubMed:8558240}.
Sequence: MMAAAPIQQNGTHTGVPIDLDPPDSRKRPLEAPPEAGSTKRTNTGEDGQYFLKVLIPSYAAGSIIGKGGQTIVQLQKETGATIKLSKSKDFYPGTTERVCLIQGTIEALNAVHGFIAEKIREMPQNVAKTEPVSILQPQTTVNPDRIKQTLPSSPTTTKSSPSDPMTTSRANQVKIIVPNSTAGLIIGKGGATVKAIMEQSGAWVQLSQKPDGINLQERVVTVSGEPEQNRKAVELIIQKIQEDPQSGSCLNISYANVTGPVANSNPTGSPYANTAEVLPTAAAAAGLLGHANLAGVAAFPAVLSGFTGNDLVAITSALNTLASYGYNLNTLGLGLSQAAATGALAAAAASANPAAAAANLLATYASEASASGSTAGGTAGTFALGSLAAATAATNGYFGAASPLAASAILGTEKSTDGSKDVVEIAVPENLVGAILGKGGKTLVEYQELTGARIQISKKGEFVPGTRNRKVTITGTPAATQAAQYLITQRITYEQGVRAANPQKVG
InterPro domains: - IPR036612: K Homology domain, type 1 superfamily (homologous_superfamily) [47-495]
- IPR004087: K Homology domain (domain) [48-493]
- IPR047276: RNA-binding protein Nova-1/2, type I K Homology domain 2 (domain) [172-241]
- IPR047275: RNA-binding protein Nova-1/2, type I K Homology domain 1 (domain) [49-121]
- IPR004088: K Homology domain, type 1 (domain) [53-489]
- IPR047274: RNA-binding protein Nova-1/2, type I K Homology domain 3 (domain) [422-492]
Interaction partners: - Polypyrimidine tract-binding protein 2
- E3 ubiquitin-protein ligase UBR5
- ELAV-like protein 4
- Polypyrimidine tract-binding protein 1
- RNA binding protein fox-1 homolog 1
- RNA binding protein fox-1 homolog 2
- Serine/arginine repetitive matrix protein 4
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)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0032501 (multicellular organismal process), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0044237 (cellular metabolic process), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0046483 (heterocycle metabolic process), GO:0048731 (system development), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0016043 (cellular component organization), GO:0031323 (regulation of cellular metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0043170 (macromolecule metabolic process), GO:0022008 (neurogenesis), GO:0007399 (nervous system development), GO:0090304 (nucleic acid metabolic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0051252 (regulation of RNA metabolic process), GO:0006996 (organelle organization), GO:0030182 (neuron differentiation), GO:0010468 (regulation of gene expression), GO:0048666 (neuron development), GO:0016070 (RNA metabolic process), GO:0048699 (generation of neurons), GO:0043484 (regulation of RNA splicing), GO:1903311 (regulation of mRNA metabolic process), GO:0006396 (RNA processing), GO:0008380 (RNA splicing), 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:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)