NRXN1

Neurexin 1
PDB rendering based on 1c4r.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3B3Q​
Identifiers
Symbols	NRXN1 ; Hs.22998; PTHSL2; SCZD17
External IDs	OMIM: 600565 HomoloGene: 21005 GeneCards: NRXN1 Gene
Gene ontology Molecular function • receptor activity • transmembrane signaling receptor activity • receptor binding • calcium channel regulator activity • calcium ion binding • protein binding • acetylcholine receptor binding • metal ion binding • calcium-dependent protein binding • cell adhesion molecule binding • neuroligin family protein binding Cellular component • endoplasmic reticulum • plasma membrane • integral component of plasma membrane • cell surface • integral component of membrane • cell junction • endocytic vesicle • nuclear membrane • vesicle • presynaptic membrane • neuronal cell body • protein complex • axonal growth cone Biological process • angiogenesis • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules • neuron cell-cell adhesion • signal transduction • synaptic transmission • neurotransmitter secretion • axon guidance • synapse assembly • learning • calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules • cerebellar granule cell differentiation • neuronal signal transduction • extracellular matrix organization • adult behavior • social behavior • protein localization to synapse • vocal learning • establishment of protein localization • neuromuscular process controlling balance • negative regulation of filopodium assembly • positive regulation of synapse assembly • positive regulation of synaptic transmission, glutamatergic • prepulse inhibition • regulation of insulin secretion involved in cellular response to glucose stimulus • vocalization behavior • positive regulation of establishment of protein localization to plasma membrane • protein complex assembly involved in synapse maturation • positive regulation of synapse maturation • synaptic vesicle clustering • postsynaptic membrane assembly • presynaptic membrane assembly • gamma-aminobutyric acid receptor clustering • NMDA glutamate receptor clustering • gephyrin clustering involved in postsynaptic density assembly • guanylate kinase-associated protein clustering • neuroligin clustering involved in postsynaptic membrane assembly • postsynaptic density protein 95 clustering • receptor localization to synapse • regulation of N-methyl-D-aspartate selective glutamate receptor activity • regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity • positive regulation of excitatory postsynaptic potential • regulation of grooming behavior Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9378	18189
Ensembl	ENSG00000179915	ENSMUSG00000024109
UniProt	P58400	Q9CS84
RefSeq (mRNA)	NM_001135659	NM_020252
RefSeq (protein)	NP_001129131	NP_064648
Location (UCSC)	Chr 2: 49.92 – 51.03 Mb	Chr 17: 90.03 – 91.09 Mb
PubMed search

Neurexin-1-alpha is a protein that in humans is encoded by the NRXN1 gene.^[1]

Neurexins are a family of proteins that function in the vertebrate nervous system as cell adhesion molecules and receptors. They are encoded by several unlinked genes of which two, NRXN1 and NRXN3, are among the largest known human genes. Three of the genes (NRXN1-3) utilize two alternate promoters and include numerous alternatively spliced exons to generate thousands of distinct mRNA transcripts and protein isoforms. The majority of transcripts are produced from the upstream promoter and encode alpha-neurexin isoforms; a much smaller number of transcripts are produced from the downstream promoter and encode beta-neurexin isoforms. The alpha-neurexins contain epidermal growth factor-like (EGF-like) sequences and laminin G domains, and have been shown to interact with neurexophilins. The beta-neurexins lack EGF-like sequences and contain fewer laminin G domains than alpha-neurexins.^[1]

Genomics

The gene is found in a single copy on the short arm of chromosome 2 (2p16.3). The gene is 1,112,187 bases in length, is located on the Crick (minus) strand and encodes a protein of 1,477 amino acids (molecular weight 161.883 kDa).

Mutation of this gene that interrupt its expression have been associated with Schizophrenia, autism, and intellectual disability (NRXN1 mutations and brain disorders).

Interactions

NRXN1 has been shown to interact with NLGN1.^[2][3]

References

1. "Entrez Gene: NRXN1 neurexin 1".
2. Comoletti, Davide; Flynn Robyn; Jennings Lori L; Chubykin Alexander; Matsumura Takehito; Hasegawa Hana; Südhof Thomas C; Taylor Palmer (Dec 2003). "Characterization of the interaction of a recombinant soluble neuroligin-1 with neurexin-1beta". J. Biol. Chem. (United States) 278 (50): 50497–50505. doi:10.1074/jbc.M306803200. ISSN 0021-9258. PMID 14522992.
3. Ichtchenko, K; Nguyen T; Südhof T C (Feb 1996). "Structures, alternative splicing, and neurexin binding of multiple neuroligins". J. Biol. Chem. (UNITED STATES) 271 (5): 2676–2682. doi:10.1074/jbc.271.5.2676. ISSN 0021-9258. PMID 8576240.

Further reading

• Missler M, Südhof TC (1998). "Neurexins: three genes and 1001 products". Trends Genet. 14 (1): 20–26. doi:10.1016/S0168-9525(97)01324-3. PMID 9448462.
• Nakajima D, Okazaki N, Yamakawa H, et al. (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Res. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
• Ushkaryov YA, Petrenko AG, Geppert M, Südhof TC (1992). "Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin". Science 257 (5066): 50–56. doi:10.1126/science.1621094. PMID 1621094.
• Ichtchenko K, Nguyen T, Südhof TC (1996). "Structures, alternative splicing, and neurexin binding of multiple neuroligins". J. Biol. Chem. 271 (5): 2676–2682. doi:10.1074/jbc.271.5.2676. PMID 8576240.
• Petrenko AG, Ullrich B, Missler M, et al. (1996). "Structure and evolution of neurexophilin". J. Neurosci. 16 (14): 4360–9. PMID 8699246.
• Hata Y, Butz S, Südhof TC (1996). "CASK: a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins". J. Neurosci. 16 (8): 2488–94. PMID 8786425.
• Perin MS (1996). "Mirror image motifs mediate the interaction of the COOH terminus of multiple synaptotagmins with the neurexins and calmodulin". Biochemistry 35 (43): 13808–13816. doi:10.1021/bi960853x. PMID 8901523.
• Nguyen T, Südhof TC (1997). "Binding properties of neuroligin 1 and neurexin 1beta reveal function as heterophilic cell adhesion molecules". J. Biol. Chem. 272 (41): 26032–26039. doi:10.1074/jbc.272.41.26032. PMID 9325340.
• Nagase T, Ishikawa K, Miyajima N, et al. (1998). "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res. 5 (1): 31–39. doi:10.1093/dnares/5.1.31. PMID 9628581.
• Missler M, Hammer RE, Südhof TC (1999). "Neurexophilin binding to alpha-neurexins. A single LNS domain functions as an independently folding ligand-binding unit". J. Biol. Chem. 273 (52): 34716–34723. doi:10.1074/jbc.273.52.34716. PMID 9856994.
• Kleiderlein JJ, Nisson PE, Jessee J, et al. (1999). "CCG repeats in cDNAs from human brain". Hum. Genet. 103 (6): 666–673. doi:10.1007/s004390050889. PMID 9921901.
• Biederer T, Südhof TC (2001). "Mints as adaptors. Direct binding to neurexins and recruitment of munc18". J. Biol. Chem. 275 (51): 39803–39806. doi:10.1074/jbc.C000656200. PMID 11036064.
• Koroll M, Rathjen FG, Volkmer H (2001). "The neural cell recognition molecule neurofascin interacts with syntenin-1 but not with syntenin-2, both of which reveal self-associating activity". J. Biol. Chem. 276 (14): 10646–10654. doi:10.1074/jbc.M010647200. PMID 11152476.
• Fukuda M, Mikoshiba K (2001). "Characterization of KIAA1427 protein as an atypical synaptotagmin (Syt XIII)". Biochem. J. 354 (Pt 2): 249–57. doi:10.1042/0264-6021:3540249. PMC 1221650. PMID 11171101.
• Fukuda M, Mikoshiba K (2001). "Synaptotagmin-like protein 1-3: a novel family of C-terminal-type tandem C2 proteins". Biochem. Biophys. Res. Commun. 281 (5): 1226–1233. doi:10.1006/bbrc.2001.4512. PMID 11243866.
• Rowen L, Young J, Birditt B, et al. (2002). "Analysis of the human neurexin genes: alternative splicing and the generation of protein diversity". Genomics 79 (4): 587–597. doi:10.1006/geno.2002.6734. PMID 11944992.
• Tabuchi K, Südhof TC (2002). "Structure and evolution of neurexin genes: insight into the mechanism of alternative splicing". Genomics 79 (6): 849–859. doi:10.1006/geno.2002.6780. PMID 12036300.
• Nakayama M, Kikuno R, Ohara O (2003). "Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs". Genome Res. 12 (11): 1773–1784. doi:10.1101/gr.406902. PMC 187542. PMID 12421765.