ID NRX1B_MOUSE Reviewed; 468 AA. AC P0DI97; DT 21-SEP-2011, integrated into UniProtKB/Swiss-Prot. DT 21-SEP-2011, sequence version 1. DT 27-MAR-2024, entry version 94. DE RecName: Full=Neurexin-1-beta {ECO:0000305}; DE AltName: Full=Neurexin I-beta; DE Flags: Precursor; GN Name=Nrxn1 {ECO:0000312|MGI:MGI:1096391}; 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]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [2] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; 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 [3] RP INTERACTION WITH CBLN1, AND MUTAGENESIS OF ASP-137 AND ASN-238. RX PubMed=21410790; DOI=10.1111/j.1460-9568.2011.07638.x; RA Matsuda K., Yuzaki M.; RT "Cbln family proteins promote synapse formation by regulating distinct RT neurexin signaling pathways in various brain regions."; RL Eur. J. Neurosci. 33:1447-1461(2011). RN [4] RP INTERACTION WITH CBLN1; CBLN2 AND CBLN4. RX PubMed=22220752; DOI=10.1111/j.1471-4159.2012.07648.x; RA Wei P., Pattarini R., Rong Y., Guo H., Bansal P.K., Kusnoor S.V., RA Deutch A.Y., Parris J., Morgan J.I.; RT "The Cbln family of proteins interact with multiple signaling pathways."; RL J. Neurochem. 121:717-729(2012). RN [5] RP INTERACTION WITH CLSTN3. RX PubMed=24613359; DOI=10.1016/j.celrep.2014.02.010; RA Um J.W., Pramanik G., Ko J.S., Song M.Y., Lee D., Kim H., Park K.S., RA Suedhof T.C., Tabuchi K., Ko J.; RT "Calsyntenins function as synaptogenic adhesion molecules in concert with RT neurexins."; RL Cell Rep. 6:1096-1109(2014). RN [6] RP ALTERNATIVE PROMOTER USAGE (ISOFORM 6), AND ALTERNATIVE SPLICING. RX PubMed=25737549; DOI=10.1073/pnas.1502849112; RA Yan Q., Weyn-Vanhentenryck S.M., Wu J., Sloan S.A., Zhang Y., Chen K., RA Wu J.Q., Barres B.A., Zhang C.; RT "Systematic discovery of regulated and conserved alternative exons in the RT mammalian brain reveals NMD modulating chromatin regulators."; RL Proc. Natl. Acad. Sci. U.S.A. 112:3445-3450(2015). RN [7] RP INTERACTION WITH CBLN1; CBLN2 AND CBLN4. RX PubMed=29782851; DOI=10.1016/j.brainres.2018.05.022; RA Rong Y., Bansal P.K., Wei P., Guo H., Correia K., Parris J., Morgan J.I.; RT "Glycosylation of Cblns attenuates their receptor binding."; RL Brain Res. 1694:129-139(2018). RN [8] RP FUNCTION, GLYCOSYLATION AT SER-346, AND MUTAGENESIS OF SER-346 AND RP 362-SER-SER-363. RX PubMed=30100184; DOI=10.1016/j.cell.2018.07.002; RA Zhang P., Lu H., Peixoto R.T., Pines M.K., Ge Y., Oku S., Siddiqui T.J., RA Xie Y., Wu W., Archer-Hartmann S., Yoshida K., Tanaka K.F., Aricescu A.R., RA Azadi P., Gordon M.D., Sabatini B.L., Wong R.O.L., Craig A.M.; RT "Heparan Sulfate Organizes Neuronal Synapses through Neurexin RT Partnerships."; RL Cell 174:1450-1464(2018). RN [9] RP INTERACTION WITH CLSTN3. RX PubMed=32434929; DOI=10.1074/jbc.ra120.013077; RA Kim H., Kim D., Kim J., Lee H.Y., Park D., Kang H., Matsuda K., RA Sterky F.H., Yuzaki M., Kim J.Y., Choi S.Y., Ko J., Um J.W.; RT "Calsyntenin-3 interacts with both alpha- and beta-neurexins in the RT regulation of excitatory synaptic innervation in specific Schaffer RT collateral pathways."; RL J. Biol. Chem. 295:9244-9262(2020). CC -!- FUNCTION: Neuronal cell surface protein involved in cell recognition CC and cell adhesion by forming intracellular junctions through binding to CC neuroligins (By similarity). Plays a role in formation of synaptic CC junctions (PubMed:30100184). {ECO:0000250|UniProtKB:Q63373, CC ECO:0000269|PubMed:30100184}. CC -!- SUBUNIT: The cytoplasmic C-terminal region binds to CASK. Binds NLGN1, CC NLGN2 and NLGN3, DAG1 (alpha-dystroglycan) and alpha-latrotoxin. CC Binding to neuroligins is calcium-dependent, and the binding preference CC ranks as follow: NLGN1 > NLGN4 >> NLGN3 > NLGN2 (By similarity). CC Interacts with CBLN2 and more weakly with CBLN4 (PubMed:22220752, CC PubMed:29782851). Interacts with CBLN1; interaction is CBLN1 hexamer CC form-dependent; CBLN1-binding is calcium-independent; isoform 1b does CC not interact with CBLN1 (PubMed:21410790, PubMed:22220752, CC PubMed:29782851). Interacts with CLSTN3 (PubMed:24613359, CC PubMed:32434929). {ECO:0000250|UniProtKB:Q63373, CC ECO:0000269|PubMed:21410790, ECO:0000269|PubMed:22220752, CC ECO:0000269|PubMed:24613359, ECO:0000269|PubMed:29782851, CC ECO:0000269|PubMed:32434929}. CC -!- INTERACTION: CC P0DI97; Q9R171: Cbln1; NbExp=4; IntAct=EBI-2794440, EBI-2794140; CC -!- SUBCELLULAR LOCATION: Presynaptic cell membrane CC {ECO:0000250|UniProtKB:Q63373}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q63373}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=7; CC Comment=A number of isoforms, alpha-type and beta-type are produced CC by alternative promoter usage. Beta-type isoforms differ from alpha- CC type isoforms in their N-terminus.; CC Name=1b; CC IsoId=P0DI97-1; Sequence=Displayed; CC Name=1a; CC IsoId=Q9CS84-1; Sequence=External; CC Name=2a; Synonyms=Alpha-2B; CC IsoId=Q9CS84-2; Sequence=External; CC Name=3a; Synonyms=Alpha-2C; CC IsoId=Q9CS84-3; Sequence=External; CC Name=4a; CC IsoId=Q9CS84-4; Sequence=External; CC Name=5a; CC IsoId=Q9CS84-5; Sequence=External; CC Name=6; CC IsoId=Q9CS84-6; Sequence=External; CC -!- PTM: O-glycosylated; contains heparan sulfate. Heparan sulfate CC attachment is required for synapse development by mediating CC interactions with neuroligins. {ECO:0000269|PubMed:30100184}. CC -!- SIMILARITY: Belongs to the neurexin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CH466537; EDL38657.1; -; Genomic_DNA. DR CCDS; CCDS84341.1; -. [P0DI97-1] DR RefSeq; NP_001333888.1; NM_001346959.1. [P0DI97-1] DR AlphaFoldDB; P0DI97; -. DR SMR; P0DI97; -. DR ComplexPortal; CPX-4083; NLGN1(-SSA-SSB) - NRXN1-beta(-SS4) complex. DR ComplexPortal; CPX-4122; NLGN1(+SSA+SSB) - NRXN1-beta(-SS4) complex. DR CORUM; P0DI97; -. DR IntAct; P0DI97; 2. DR SwissPalm; P0DI97; -. DR PaxDb; 10090-ENSMUSP00000134402; -. DR PeptideAtlas; P0DI97; -. DR ProteomicsDB; 293750; -. [P0DI97-1] DR ABCD; P0DI97; 1 sequenced antibody. DR Antibodypedia; 30173; 334 antibodies from 37 providers. DR DNASU; 18189; -. DR Ensembl; ENSMUST00000174337.8; ENSMUSP00000133724.3; ENSMUSG00000024109.19. [P0DI97-1] DR GeneID; 18189; -. DR KEGG; mmu:18189; -. DR AGR; MGI:1096391; -. DR CTD; 9378; -. DR MGI; MGI:1096391; Nrxn1. DR VEuPathDB; HostDB:ENSMUSG00000024109; -. DR eggNOG; KOG3514; Eukaryota. DR GeneTree; ENSGT00940000154292; -. DR HOGENOM; CLU_025785_1_0_1; -. DR OrthoDB; 2999458at2759; -. DR TreeFam; TF334142; -. DR BioGRID-ORCS; 18189; 2 hits in 78 CRISPR screens. DR ChiTaRS; Nrxn1; mouse. DR Proteomes; UP000000589; Chromosome 17. DR Bgee; ENSMUSG00000024109; Expressed in medial dorsal nucleus of thalamus and 180 other cell types or tissues. DR ExpressionAtlas; P0DI97; baseline and differential. DR GO; GO:0044295; C:axonal growth cone; IDA:BHF-UCL. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0030139; C:endocytic vesicle; ISS:BHF-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0060076; C:excitatory synapse; NAS:ComplexPortal. DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0060077; C:inhibitory synapse; NAS:ComplexPortal. DR GO; GO:0031594; C:neuromuscular junction; NAS:ComplexPortal. DR GO; GO:0098984; C:neuron to neuron synapse; NAS:ComplexPortal. DR GO; GO:0043025; C:neuronal cell body; IDA:BHF-UCL. DR GO; GO:0031965; C:nuclear membrane; IDA:BHF-UCL. DR GO; GO:0005730; C:nucleolus; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL. DR GO; GO:0048787; C:presynaptic active zone membrane; IDA:SynGO. DR GO; GO:0042734; C:presynaptic membrane; IDA:BHF-UCL. DR GO; GO:0098635; C:protein complex involved in cell-cell adhesion; EXP:ComplexPortal. DR GO; GO:0032991; C:protein-containing complex; IPI:MGI. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO. DR GO; GO:0031982; C:vesicle; IDA:BHF-UCL. DR GO; GO:0033130; F:acetylcholine receptor binding; IDA:MGI. DR GO; GO:0005246; F:calcium channel regulator activity; IGI:MGI. DR GO; GO:0005509; F:calcium ion binding; ISO:MGI. DR GO; GO:0048306; F:calcium-dependent protein binding; IDA:BHF-UCL. DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:BHF-UCL. DR GO; GO:0097109; F:neuroligin family protein binding; IPI:BHF-UCL. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI. DR GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:BHF-UCL. DR GO; GO:0005105; F:type 1 fibroblast growth factor receptor binding; ISO:MGI. DR GO; GO:0030534; P:adult behavior; ISO:MGI. DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW. DR GO; GO:0016339; P:calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; IDA:BHF-UCL. DR GO; GO:0090125; P:cell-cell adhesion involved in synapse maturation; NAS:ComplexPortal. DR GO; GO:0071277; P:cellular response to calcium ion; ISO:MGI. DR GO; GO:0021707; P:cerebellar granule cell differentiation; IGI:BHF-UCL. DR GO; GO:0007268; P:chemical synaptic transmission; IGI:MGI. DR GO; GO:0045184; P:establishment of protein localization; IDA:BHF-UCL. DR GO; GO:0046847; P:filopodium assembly; IMP:CACAO. DR GO; GO:0097112; P:gamma-aminobutyric acid receptor clustering; IDA:BHF-UCL. DR GO; GO:0097116; P:gephyrin clustering involved in postsynaptic density assembly; IDA:BHF-UCL. DR GO; GO:0097117; P:guanylate kinase-associated protein clustering; IDA:BHF-UCL. DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IDA:BHF-UCL. DR GO; GO:0007612; P:learning; ISO:MGI. DR GO; GO:0099558; P:maintenance of synapse structure; NAS:ComplexPortal. DR GO; GO:0051490; P:negative regulation of filopodium assembly; IDA:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI. DR GO; GO:0097118; P:neuroligin clustering involved in postsynaptic membrane assembly; IDA:BHF-UCL. DR GO; GO:0007158; P:neuron cell-cell adhesion; IDA:BHF-UCL. DR GO; GO:0042551; P:neuron maturation; IDA:BHF-UCL. DR GO; GO:0031175; P:neuron projection development; ISO:MGI. DR GO; GO:0048812; P:neuron projection morphogenesis; NAS:ComplexPortal. DR GO; GO:0007269; P:neurotransmitter secretion; IGI:MGI. DR GO; GO:0097114; P:NMDA glutamate receptor clustering; IDA:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI. DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IDA:BHF-UCL. DR GO; GO:0045743; P:positive regulation of fibroblast growth factor receptor signaling pathway; ISO:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI. DR GO; GO:1900075; P:positive regulation of neuromuscular synaptic transmission; NAS:ComplexPortal. DR GO; GO:0010976; P:positive regulation of neuron projection development; NAS:ComplexPortal. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:MGI. DR GO; GO:0010739; P:positive regulation of protein kinase A signaling; ISO:MGI. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IDA:BHF-UCL. DR GO; GO:0051965; P:positive regulation of synapse assembly; IGI:MGI. DR GO; GO:0090129; P:positive regulation of synapse maturation; IDA:MGI. DR GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; NAS:ComplexPortal. DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IDA:BHF-UCL. DR GO; GO:0097119; P:postsynaptic density protein 95 clustering; IDA:BHF-UCL. DR GO; GO:0097104; P:postsynaptic membrane assembly; IDA:BHF-UCL. DR GO; GO:0099054; P:presynapse assembly; IDA:SynGO. DR GO; GO:0097105; P:presynaptic membrane assembly; IDA:BHF-UCL. DR GO; GO:0035418; P:protein localization to synapse; IDA:BHF-UCL. DR GO; GO:0090126; P:protein-containing complex assembly involved in synapse maturation; IDA:BHF-UCL. DR GO; GO:0097120; P:receptor localization to synapse; IDA:BHF-UCL. DR GO; GO:2000311; P:regulation of AMPA receptor activity; IDA:BHF-UCL. DR GO; GO:2000310; P:regulation of NMDA receptor activity; IDA:BHF-UCL. DR GO; GO:0099151; P:regulation of postsynaptic density assembly; IDA:SynGO. DR GO; GO:0099150; P:regulation of postsynaptic specialization assembly; IDA:SynGO. DR GO; GO:1905606; P:regulation of presynapse assembly; IDA:SynGO. DR GO; GO:0098693; P:regulation of synaptic vesicle cycle; IDA:SynGO. DR GO; GO:0150036; P:regulation of trans-synaptic signaling by endocannabinoid, modulating synaptic transmission; IDA:SynGO. DR GO; GO:0007165; P:signal transduction; IDA:BHF-UCL. DR GO; GO:0035176; P:social behavior; ISO:MGI. DR GO; GO:0007416; P:synapse assembly; IDA:SynGO. DR GO; GO:0060074; P:synapse maturation; NAS:ComplexPortal. DR GO; GO:0099560; P:synaptic membrane adhesion; IDA:SynGO. DR GO; GO:0097091; P:synaptic vesicle clustering; IDA:BHF-UCL. DR GO; GO:0042297; P:vocal learning; ISO:MGI. DR GO; GO:0071625; P:vocalization behavior; ISO:MGI. DR CDD; cd00110; LamG; 1. DR Gene3D; 2.60.120.200; -; 1. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR001791; Laminin_G. DR InterPro; IPR003585; Neurexin-like. DR InterPro; IPR027789; Syndecan/Neurexin_dom. DR PANTHER; PTHR15036:SF51; NEUREXIN-1; 1. DR PANTHER; PTHR15036; PIKACHURIN-LIKE PROTEIN; 1. DR Pfam; PF02210; Laminin_G_2; 1. DR Pfam; PF01034; Syndecan; 1. DR SMART; SM00294; 4.1m; 1. DR SMART; SM00282; LamG; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR PROSITE; PS50025; LAM_G_DOMAIN; 1. DR Genevisible; P0DI97; MM. PE 1: Evidence at protein level; KW Alternative promoter usage; Alternative splicing; Angiogenesis; Calcium; KW Cell adhesion; Cell membrane; Cell projection; Glycoprotein; KW Heparan sulfate; Membrane; Metal-binding; Phosphoprotein; Proteoglycan; KW Reference proteome; Repeat; Signal; Synapse; Transmembrane; KW Transmembrane helix. FT SIGNAL 1..46 FT /evidence="ECO:0000255" FT CHAIN 47..468 FT /note="Neurexin-1-beta" FT /id="PRO_0000412630" FT TRANSMEM 393..413 FT /note="Helical" FT /evidence="ECO:0000255" FT DOMAIN 87..285 FT /note="Laminin G-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122" FT REGION 201..230 FT /note="Essential for interaction with CBLN1; modulates FT interaction affinity with NLGN1, NLGN2 and NLGN3; prevents FT interaction with DAG1/alpha-dystroglycan; modulates FT interaction with alpha-latrotoxin" FT /evidence="ECO:0000250|UniProtKB:P58400, FT ECO:0000250|UniProtKB:Q63373" FT REGION 350..381 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 435..468 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 435..451 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 452..468 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 137 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q63373" FT BINDING 154 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q63373" FT BINDING 236 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q63373" FT BINDING 238 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q63373" FT MOD_RES 450 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P58400" FT MOD_RES 451 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P58400" FT MOD_RES 454 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P58400" FT CARBOHYD 346 FT /note="O-linked (Xyl...) (heparan sulfate) serine" FT /evidence="ECO:0000269|PubMed:30100184" FT MUTAGEN 137 FT /note="D->A: Loss of NLGN1-binding. No effect on FT CBLN1-binding." FT /evidence="ECO:0000269|PubMed:21410790" FT MUTAGEN 238 FT /note="N->A: Loss of NLGN1-binding. No effect on FT CBLN1-binding." FT /evidence="ECO:0000269|PubMed:21410790" FT MUTAGEN 346 FT /note="S->A: Abolishes heparan sulfate attachment. Does not FT affect cell surface location." FT /evidence="ECO:0000269|PubMed:30100184" FT MUTAGEN 362..363 FT /note="SS->AA: No effect on heparan sulfate attachment." FT /evidence="ECO:0000269|PubMed:30100184" SQ SEQUENCE 468 AA; 50223 MW; F118A9053BAB4E21 CRC64; MYQRMLRCGA DLGSPGGGSG GGAGGRLALI WIVPLTLSGL LGVAWGASSL GAHHIHHFHG SSKHHSVPIA IYRSPASLRG GHAGTTYIFS KGGGQITYKW PPNDRPSTRA DRLAIGFSTV QKEAVLVRVD SSSGLGDYLE LHIHQGKIGV KFNVGTDDIA IEESNAIIND GKYHVVRFTR SGGNATLQVD SWPVIERYPA GNNDNERLAI ARQRIPYRLG RVVDEWLLDK GRQLTIFNSQ ATIIIGGKEQ GQPFQGQLSG LYYNGLKVLN MAAENDANIA IVGNVRLVGE VPSSMTTEST ATAMQSEMST SIMETTTTLA TSTARRGKPP TKEPISQTTD DILVASAECP SDDEDIDPCE PSSGGLANPT RVGGREPYPG SAEVIRESSS TTGMVVGIVA AAALCILILL YAMYKYRNRD EGSYHVDESR NYISNSAQSN GAVVKEKQPS SAKSANKNKK NKDKEYYV //