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 02-SEP-2026, entry version 104. 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). RN [10] RP FUNCTION, INTERACTION WITH CBLN2, AND SUBCELLULAR LOCATION. RX PubMed=34135511; DOI=10.1038/s41586-021-03661-6; RA Dai J., Patzke C., Liakath-Ali K., Seigneur E., Suedhof T.C.; RT "GluD1 is a signal transduction device disguised as an ionotropic RT receptor."; RL Nature 595:261-265(2021). 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). Functions as part of a trans-synaptic CC complex by binding to cerebellins and postsynaptic GRID1. This CC interaction helps regulate the activity of NMDA and AMPA receptors at CC hippocampal synapses without affecting synapse formation. NRXN1B-CBLN2- CC GRID1 complex transduce presynaptic signals into postsynaptic NMDAR CC response (PubMed:34135511). {ECO:0000250|UniProtKB:Q63373, CC ECO:0000269|PubMed:30100184, ECO:0000269|PubMed:34135511}. 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, PubMed:34135511). Interacts with CBLN1; interaction is CC CBLN1 hexamer form-dependent; CBLN1-binding is calcium-independent; CC isoform 1b does not interact with CBLN1 (PubMed:21410790, CC PubMed:22220752, PubMed:29782851). Interacts with CLSTN3 CC (PubMed:24613359, 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, ECO:0000269|PubMed:34135511}. CC -!- INTERACTION: CC P0DI97; Q9R171: Cbln1; NbExp=4; IntAct=EBI-2794440, EBI-2794140; CC -!- SUBCELLULAR LOCATION: Presynaptic cell membrane CC {ECO:0000269|PubMed:34135511}; Single-pass type I membrane protein CC {ECO:0000255}. 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_001346959.2. [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 iPTMnet; P0DI97; -. DR SwissPalm; P0DI97; -. DR PeptideAtlas; P0DI97; -. DR ProteomicsDB; 293750; -. [P0DI97-1] DR ABCD; P0DI97; 1 sequenced antibody. DR Antibodypedia; 30173; 313 antibodies from 37 providers. DR DNASU; 18189; -. DR Ensembl; ENSMUST00000174337.8; ENSMUSP00000133724.3; ENSMUSG00000024109.19. DR GeneID; 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; 6275838at2759; -. DR BioGRID-ORCS; 18189; 2 hits in 78 CRISPR screens. 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; NAS:ComplexPortal. DR GO; GO:0098978; C:glutamatergic synapse; NAS:ComplexPortal. 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:0005886; C:plasma membrane; NAS:ComplexPortal. 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:0031982; C:vesicle; IDA:BHF-UCL. 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:0004888; F:transmembrane signaling receptor activity; IDA:BHF-UCL. DR GO; GO:0098990; P:AMPA selective glutamate receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0016339; P:calcium-dependent cell-cell adhesion; IDA:BHF-UCL. DR GO; GO:0090125; P:cell-cell adhesion involved in synapse maturation; NAS:ComplexPortal. DR GO; GO:0021707; P:cerebellar granule cell differentiation; IGI:BHF-UCL. 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; IDA:BHF-UCL. 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: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:0048812; P:neuron projection morphogenesis; NAS:ComplexPortal. DR GO; GO:0097114; P:NMDA glutamate receptor clustering; IDA:BHF-UCL. DR GO; GO:0098989; P:NMDA selective glutamate receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IDA:BHF-UCL. 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:1903078; P:positive regulation of protein localization to plasma membrane; IDA:BHF-UCL. 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: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:0007165; P:signal transduction; IDA:BHF-UCL. DR GO; GO:0007416; P:synapse assembly; NAS:ComplexPortal. DR GO; GO:0060074; P:synapse maturation; NAS:ComplexPortal. DR GO; GO:0097091; P:synaptic vesicle clustering; IDA:BHF-UCL. DR CDD; cd00110; LamG; 1. DR FunFam; 2.60.120.200:FF:000003; neurexin-1 isoform X1; 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; IPR050372; Neurexin-related_CASP. 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. 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 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 //