NOVA2_MOUSE
ID NOVA2_MOUSE Reviewed; 492 AA.
AC A0A1W2P872; D3YVV7;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=RNA-binding protein Nova-2;
GN Name=Nova2 {ECO:0000312|MGI:MGI:104296};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP INTERACTION WITH PTBP2.
RX PubMed=10829067; DOI=10.1073/pnas.110128397;
RA Polydorides A.D., Okano H.J., Yang Y.Y.L., Stefani G., Darnell R.B.;
RT "A brain-enriched polypyrimidine tract-binding protein antagonizes the
RT ability of Nova to regulate neuron-specific alternative splicing.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:6350-6355(2000).
RN [3]
RP FUNCTION.
RX PubMed=14615540; DOI=10.1126/science.1090095;
RA Ule J., Jensen K.B., Ruggiu M., Mele A., Ule A., Darnell R.B.;
RT "CLIP identifies Nova-regulated RNA networks in the brain.";
RL Science 302:1212-1215(2003).
RN [4]
RP FUNCTION.
RX PubMed=16041372; DOI=10.1038/ng1610;
RA Ule J., Ule A., Spencer J., Williams A., Hu J.S., Cline M., Wang H.,
RA Clark T., Fraser C., Ruggiu M., Zeeberg B.R., Kane D., Weinstein J.N.,
RA Blume J., Darnell R.B.;
RT "Nova regulates brain-specific splicing to shape the synapse.";
RL Nat. Genet. 37:844-852(2005).
RN [5] {ECO:0007744|PubMed:21183079}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, ALTERNATIVE SPLICING, TISSUE SPECIFICITY,
RP AND DEVELOPMENTAL STAGE.
RX PubMed=27223325; DOI=10.7554/elife.14371;
RA Saito Y., Miranda-Rottmann S., Ruggiu M., Park C.Y., Fak J.J., Zhong R.,
RA Duncan J.S., Fabella B.A., Junge H.J., Chen Z., Araya R., Fritzsch B.,
RA Hudspeth A.J., Darnell R.B.;
RT "NOVA2-mediated RNA regulation is required for axonal pathfinding during
RT development.";
RL Elife 5:0-0(2016).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=30638744; DOI=10.1016/j.neuron.2018.12.019;
RA Saito Y., Yuan Y., Zucker-Scharff I., Fak J.J., Jereb S., Tajima Y.,
RA Licatalosi D.D., Darnell R.B.;
RT "Differential NOVA2-Mediated Splicing in Excitatory and Inhibitory Neurons
RT Regulates Cortical Development and Cerebellar Function.";
RL Neuron 101:707-720.e5(2019).
CC -!- FUNCTION: Functions to regulate alternative splicing in neurons by
CC binding pre-mRNA in a sequence-specific manner to activate exon
CC inclusion or exclusion. It binds specifically to the sequences 5'-YCAY-
CC 3' and regulates splicing in only a subset of regulated exons
CC (PubMed:14615540). Binding to an exonic 5'-YCAY-3' cluster changes the
CC protein complexes assembled on pre-mRNA, blocking U1 snRNP binding and
CC exon inclusion, whereas binding to an intronic 5'-YCAY-3' cluster
CC enhances spliceosome assembly and exon inclusion (PubMed:16041372).
CC With NOVA1, they perform unique biological functions in different brain
CC areas and cell types. Uniquely regulates alternative splicing events of
CC a series of axon guidance related genes during cortical development,
CC being essential for central nervous system development by regulating
CC neural networks wiring (PubMed:27223325, PubMed:16041372). Regulates
CC differentially alternative splicing on the same transcripts expressed
CC in different neurons. This includes functional differences in
CC transcripts expressed in cortical and cerebellar excitatory versus
CC inhibitory neurons where is required for, respectively, development of
CC laminar structure and motor coordination and synapse formation. Also
CC the regulation the regulation of intron retention can sequester the
CC trans-acting splicing factor PTBP2, acting as a variable cis-acting
CC scaffolding platform for PTBP2 across various natural conditions
CC (PubMed:30638744). {ECO:0000269|PubMed:14615540,
CC ECO:0000269|PubMed:16041372, ECO:0000269|PubMed:27223325,
CC ECO:0000269|PubMed:30638744}.
CC -!- SUBUNIT: Interacts with PTBP2; the interaction is direct.
CC {ECO:0000269|PubMed:10829067}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:30638744}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=NOVA2 {ECO:0000303|PubMed:27223325};
CC IsoId=A0A1W2P872-1; Sequence=Displayed;
CC Name=2; Synonyms=SuperNOVA2 {ECO:0000303|PubMed:27223325};
CC IsoId=A0A1W2P872-2; Sequence=VSP_061137;
CC -!- TISSUE SPECIFICITY: Expressed in brain cortex (PubMed:27223325).
CC Expression is enriched in excitatory neuronal-linage (PubMed:30638744).
CC {ECO:0000269|PubMed:27223325, ECO:0000269|PubMed:30638744}.
CC -!- DEVELOPMENTAL STAGE: Expression level is progressively up-regulated
CC during neural differentiation from neural progenitor cells at 12.5 dpc
CC to 18.5 dpc. {ECO:0000269|PubMed:27223325}.
CC -!- DOMAIN: The third KH domain (KH3) recognizes specifically 5'-YCAY-3'.
CC {ECO:0000269|PubMed:14615540}.
CC -!- DISRUPTION PHENOTYPE: Knockouts are born indistinguishable from
CC littermates but failed to thrive, demonstrating progressive motor
CC dysfunction and overt motor weakness, and they die an average of 14-18
CC days after birth. They have agenesis of the corpus callosum, and axonal
CC outgrowth defects specific to ventral motoneuron axons and efferent
CC innervation of the cochlea (PubMed:27223325). Conditional knockouts in
CC excitatory neurons die between three and four weeks old and show
CC disorganized cortical and hippocampal CA1 and CA3 laminar structure.
CC Conditional knockouts in inhibitory neurons show no neuronal migration
CC or position abnormality. They display reduced thickness of CA1 stratum
CC lacunosum-moleculare (SLM) and dentate gyrus molecular layer
CC (PubMed:30638744). Conditional knockouts in Purkinje cells have
CC progressive motor discoordination and cerebellar atrophy. They show a
CC marked defect in dendritic morphology, Purkinje cells degeneration,
CC loss of synaptic layer thickness accompanied by neuritic swelling and
CC reduced spine density (PubMed:30638744). {ECO:0000269|PubMed:27223325,
CC ECO:0000269|PubMed:30638744}.
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DR EMBL; AC153651; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC170864; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS20882.2; -. [A0A1W2P872-1]
DR RefSeq; NP_001025048.2; NM_001029877.3. [A0A1W2P872-1]
DR SMR; A0A1W2P872; -.
DR STRING; 10090.ENSMUSP00000134257; -.
DR ProteomicsDB; 318904; -.
DR ProteomicsDB; 361151; -.
DR Antibodypedia; 18063; 167 antibodies from 25 providers.
DR DNASU; 384569; -.
DR Ensembl; ENSMUST00000032571; ENSMUSP00000032571; ENSMUSG00000030411. [A0A1W2P872-2]
DR Ensembl; ENSMUST00000220302; ENSMUSP00000151939; ENSMUSG00000030411. [A0A1W2P872-1]
DR GeneID; 384569; -.
DR KEGG; mmu:384569; -.
DR UCSC; uc012fau.1; mouse.
DR CTD; 4858; -.
DR MGI; MGI:104296; Nova2.
DR VEuPathDB; HostDB:ENSMUSG00000030411; -.
DR eggNOG; KOG2191; Eukaryota.
DR GeneTree; ENSGT00940000161740; -.
DR HOGENOM; CLU_022670_1_1_1; -.
DR OMA; QNRALKG; -.
DR OrthoDB; 1167935at2759; -.
DR ChiTaRS; Nova2; mouse.
DR Proteomes; UP000000589; Chromosome 7.
DR Bgee; ENSMUSG00000030411; Expressed in cortical plate and 131 other tissues.
DR ExpressionAtlas; A0A1W2P872; baseline and differential.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:MGI.
DR GO; GO:1990825; F:sequence-specific mRNA binding; ISO:MGI.
DR GO; GO:0021954; P:central nervous system neuron development; IMP:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IEA:InterPro.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IGI:YuBioLab.
DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IMP:UniProtKB.
DR GO; GO:1902667; P:regulation of axon guidance; IMP:UniProtKB.
DR GO; GO:0051252; P:regulation of RNA metabolic process; IGI:MGI.
DR Gene3D; 3.30.1370.10; -; 3.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR033087; Nova-2.
DR PANTHER; PTHR10288:SF162; PTHR10288:SF162; 1.
DR Pfam; PF00013; KH_1; 3.
DR SMART; SM00322; KH; 3.
DR SUPFAM; SSF54791; SSF54791; 3.
DR PROSITE; PS50084; KH_TYPE_1; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Isopeptide bond; mRNA processing; mRNA splicing;
KW Neurogenesis; Nucleus; Reference proteome; Repeat; RNA-binding;
KW Ubl conjugation.
FT CHAIN 1..492
FT /note="RNA-binding protein Nova-2"
FT /id="PRO_0000453422"
FT DOMAIN 32..99
FT /note="KH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 130..196
FT /note="KH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 406..473
FT /note="KH 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT MOTIF 10..26
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT CROSSLNK 112
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9UNW9"
FT VAR_SEQ 1
FT /note="M -> MRMMAAGAVHGLFTASAAPQPPPPPPPPPPPQPQPPQQPSPPPQQPP
FT PPPQPPQQQQPPPQAPPM (in isoform 2)"
FT /id="VSP_061137"
SQ SEQUENCE 492 AA; 49067 MW; 870EB04F537D3D59 CRC64;
MEPEAPDSRK RPLETPPEVV CTKRSNTGEE GEYFLKVLIP SYAAGSIIGK GGQTIVQLQK
ETGATIKLSK SKDFYPGTTE RVCLVQGTAE ALNAVHSFIA EKVREIPQAM TKPEVVNILQ
PQTTMNPDRA KQAKLIVPNS TAGLIIGKGG ATVKAVMEQS GAWVQLSQKP EGINLQERVV
TVSGEPEQVH KAVSAIVQKV QEDPQSSSCL NISYANVAGP VANSNPTGSP YASPADVLPA
AAAASAAAAS GLLGPAGLAG VGAFPAALPA FSGTDLLAIS TALNTLASYG YNTNSLSLGL
NSAAASGVLA AVAAGANPAA AAAANLLASY AGDAGAGPGA GAAPPPPPPP GALGSFALAA
AANGYLGAGA GGAAGAGGAP LVAAAAAAGA AGGFLTAEKL AAESAKELVE IAVPENLVGA
ILGKGGKTLV EYQELTGARI QISKKGEFLP GTRNRRVTIT GSPAATQAAQ YLISQRVTYE
QGVRASNPQK VG
