Human Gene NRXN1 (ENST00000625672.2) from GENCODE V38
  Description: Homo sapiens neurexin 1 (NRXN1), transcript variant alpha5, mRNA. (from RefSeq NM_001330082)
RefSeq Summary (NM_001330078): This gene encodes a single-pass type I membrane protein that belongs to the neurexin family. Neurexins are cell-surface receptors that bind neuroligins to form Ca(2+)-dependent neurexin/neuroligin complexes at synapses in the central nervous system. This complex is required for efficient neurotransmission and is involved in the formation of synaptic contacts. Three members of this gene family have been studied in detail and are estimated to generate over 3,000 variants through the use of two alternative promoters (alpha and beta) and extensive alternative splicing in each family member. Recently, a third promoter (gamma) was identified for this gene in the 3' region. Mutations in this gene are associated with Pitt-Hopkins-like syndrome-2 and may contribute to susceptibility to schizophrenia. [provided by RefSeq, Aug 2016]. Sequence Note: The RefSeq transcript and protein were derived from genomic sequence to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on alignments.
Gencode Transcript: ENST00000625672.2
Gencode Gene: ENSG00000179915.24
Transcript (Including UTRs)
   Position: hg38 chr2:49,918,505-51,028,456 Size: 1,109,952 Total Exon Count: 21 Strand: -
Coding Region
   Position: hg38 chr2:49,921,944-51,028,273 Size: 1,106,330 Coding Exon Count: 21 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-09-27 09:51:20

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:49,918,505-51,028,456)mRNA (may differ from genome)Protein (1496 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
LynxMGIneXtProtOMIMPubMedReactome
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: NRX1A_HUMAN
DESCRIPTION: RecName: Full=Neurexin-1-alpha; AltName: Full=Neurexin I-alpha; Flags: Precursor;
FUNCTION: Cell surface protein involved in cell-cell-interactions, excytosis of secretory granules and regulation of signal transmission. Function is isoform-specific. Alpha-type isoforms have a long N-terminus with six laminin G-like domains and play an important role in synaptic signal transmission. Alpha-type isoforms play a role in the regulation of calcium channel activity and Ca(2+)-triggered neurotransmitter release at synapses and at neuromuscular junctions. They play an important role in Ca(2+)- triggered exocytosis of secretory granules in pituitary gland. They may effect their functions at synapses and in endocrine cells via their interactions with proteins from the exocytotic machinery. Likewise, alpha-type isoforms play a role in regulating the activity of postsynaptic NMDA receptors, a subtype of glutamate-gated ion channels. Both alpha-type and beta-type isoforms may play a role in the formation or maintenance of synaptic junctions via their calcium-dependent interactions (via the extracellular domains) with neuroligin family members, CBLN1 or CBLN2. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Alpha-type isoforms were first identified as receptors for alpha-latroxin from spider venom (By similarity).
SUBUNIT: Interacts (via laminin G-like domain 2 and/or laminin G- like domain 6) with NLGN1 forming a heterotetramer, where one NLGN1 dimer interacts with one NRXN1 dimer. Interacts (via laminin G-like domain 2 and/or laminin G-like domain 6) with NLGN1, NLGN2, NLGN3, NLGN4X and NLGN4Y; these interactions are calcium- dependent. Interacts (via laminin G-like domain 2) with NXPH1 and NXPH3. Interacts with CBLN1 and CBLN2. Interacts with LRRTM1, LRRTM2, LRRTM3 and LRRTM4 (By similarity). Alpha-type isoforms (neurexin-1-alpha) interact (via laminin G-like domain 2 and/or laminin G-like domain 6) with DAG1 (via alpha-dystroglycan chain). Alpha-type isoforms interact with alpha-latroxin from spider venom. The cytoplasmic C-terminal region binds to CASK, CASKIN1 and APBA1. Interacts with SYT13 and SYTL1 (By similarity).
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein (Probable). Cell junction, synapse (Probable). Note=Localized on the pre-synaptic membrane (By similarity).
TISSUE SPECIFICITY: Brain.
PTM: N-glycosylated (By similarity).
PTM: O-glycosylated (By similarity).
SIMILARITY: Belongs to the neurexin family.
SIMILARITY: Contains 3 EGF-like domains.
SIMILARITY: Contains 6 laminin G-like domains.
SEQUENCE CAUTION: Sequence=BAA25504.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;

-  MalaCards Disease Associations
  MalaCards Gene Search: NRXN1
Diseases sorted by gene-association score: pitt-hopkins-like syndrome 2* (1019), schizophrenia 17* (575), pitt-hopkins-like syndrome* (369), pitt-hopkins syndrome (14), astigmatism (7), autism spectrum disorder (6), schizophrenia (4), pervasive developmental disorder (2), autistic disorder (1), nicotine dependence, protection against (1), disease of mental health (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 15.14 RPKM in Brain - Cerebellar Hemisphere
Total median expression: 116.91 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -49.80183-0.272 Picture PostScript Text
3' UTR -716.503439-0.208 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR008985 - ConA-like_lec_gl_sf
IPR013320 - ConA-like_subgrp
IPR000742 - EG-like_dom
IPR000152 - EGF-type_Asp/Asn_hydroxyl_site
IPR001791 - Laminin_G
IPR003585 - Neurexin-like

Pfam Domains:
PF02210 - Laminin G domain

ModBase Predicted Comparative 3D Structure on Q9ULB1
FrontTopSide
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGI     
Protein Sequence     
Alignment     

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005246 calcium channel regulator activity
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0033130 acetylcholine receptor binding
GO:0038023 signaling receptor activity
GO:0046872 metal ion binding
GO:0050839 cell adhesion molecule binding
GO:0097109 neuroligin family protein binding

Biological Process:
GO:0007155 cell adhesion
GO:0007158 neuron cell-cell adhesion
GO:0007165 signal transduction
GO:0007268 chemical synaptic transmission
GO:0007269 neurotransmitter secretion
GO:0007411 axon guidance
GO:0007416 synapse assembly
GO:0007612 learning
GO:0030534 adult behavior
GO:0035176 social behavior
GO:0042297 vocal learning
GO:0050885 neuromuscular process controlling balance
GO:0051965 positive regulation of synapse assembly
GO:0051968 positive regulation of synaptic transmission, glutamatergic
GO:0060134 prepulse inhibition
GO:0061178 regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0071625 vocalization behavior
GO:0090129 positive regulation of synapse maturation
GO:0097104 postsynaptic membrane assembly
GO:0097116 gephyrin clustering involved in postsynaptic density assembly
GO:0097118 neuroligin clustering involved in postsynaptic membrane assembly
GO:0097119 postsynaptic density protein 95 clustering
GO:0099560 synaptic membrane adhesion
GO:2000463 positive regulation of excitatory postsynaptic potential
GO:2000821 regulation of grooming behavior

Cellular Component:
GO:0005730 nucleolus
GO:0005783 endoplasmic reticulum
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030054 cell junction
GO:0031965 nuclear membrane
GO:0031982 vesicle
GO:0032991 macromolecular complex
GO:0042734 presynaptic membrane
GO:0043025 neuronal cell body
GO:0045202 synapse


-  Descriptions from all associated GenBank mRNAs
  AB011150 - Homo sapiens mRNA for KIAA0578 protein, partial cds.
AB035356 - Homo sapiens mRNA for neurexin I-alpha protein, complete cds.
EF539882 - Homo sapiens NRXN1-alpha mRNA, complete cds, alternatively spliced.
AF064842 - Homo sapiens map 2q30-p32; 202.6 cR from top repeat region, complete sequence.
BC125179 - Homo sapiens neurexin 1, mRNA (cDNA clone IMAGE:40121982), partial cds.
BC125180 - Homo sapiens neurexin 1, mRNA (cDNA clone IMAGE:40121989), complete cds.
AB383911 - Synthetic construct DNA, clone: pF1KSDA0578, Homo sapiens NRXN1 gene for neurexin-1-alpha precursor, complete cds, without stop codon, in Flexi system.
AK093260 - Homo sapiens cDNA FLJ35941 fis, clone TESTI2011680, highly similar to Homo sapiens mRNA for neurexin I-alpha protein.
BX647616 - Homo sapiens mRNA; cDNA DKFZp313P2036 (from clone DKFZp313P2036).
AK295773 - Homo sapiens cDNA FLJ57994 complete cds, highly similar to Neurexin-1-alpha precursor.
BC046631 - Homo sapiens neurexin 1, mRNA (cDNA clone IMAGE:4815048), complete cds.
AK124726 - Homo sapiens cDNA FLJ42736 fis, clone BRAWH2015866, highly similar to Homo sapiens mRNA for neurexin I-alpha protein.
JD446195 - Sequence 427219 from Patent EP1572962.
JD302183 - Sequence 283207 from Patent EP1572962.
JD050380 - Sequence 31404 from Patent EP1572962.
JD097201 - Sequence 78225 from Patent EP1572962.
JD113407 - Sequence 94431 from Patent EP1572962.
JD313508 - Sequence 294532 from Patent EP1572962.
JD281054 - Sequence 262078 from Patent EP1572962.
JD259761 - Sequence 240785 from Patent EP1572962.
AF087975 - Homo sapiens full length insert cDNA clone YW18F07.
JD472056 - Sequence 453080 from Patent EP1572962.
JD526426 - Sequence 507450 from Patent EP1572962.
JD052326 - Sequence 33350 from Patent EP1572962.
JD087600 - Sequence 68624 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04514 - Cell adhesion molecules (CAMs)

Reactome (by CSHL, EBI, and GO)

Protein Q9ULB1 (Reactome details) participates in the following event(s):

R-HSA-2426263 Dystroglycan binds NRXN1
R-HSA-6794346 NRXNs bind NLGNs
R-HSA-6794348 NRXNs bind SYTs
R-HSA-6794352 NRXNs binds CASK tripartite complex
R-HSA-6794353 NRXNs binds MUNC18
R-HSA-6797974 LRRTMs bind NRXNs
R-HSA-6794345 NLGNs binds PSD-95 subfamily members
R-HSA-6797568 NRXNs bind CASK:Protein 4.1
R-HSA-6794338 GKAPs bind PSD-95 members
R-HSA-6794357 SHANK proteins bind GKAPs
R-HSA-6794344 HOMER binds SHANK proteins
R-HSA-6797554 ABP1 binds SHANK proteins
R-HSA-3000171 Non-integrin membrane-ECM interactions
R-HSA-6794361 Neurexins and neuroligins
R-HSA-1474244 Extracellular matrix organization
R-HSA-6794362 Protein-protein interactions at synapses
R-HSA-112316 Neuronal System

-  Other Names for This Gene
  Alternate Gene Symbols: A7KRL9, ENST00000625672.1, KIAA0578, NM_001330082, NRX1A_HUMAN, O60323, Q53TJ9, Q53TQ1, Q9C079, Q9C080, Q9C081, Q9H3M2, Q9UDM6, Q9ULB1, uc002rxb.1, uc002rxb.2, uc002rxb.3, uc002rxb.4, uc002rxb.5
UCSC ID: ENST00000625672.2
RefSeq Accession: NM_001330078
Protein: Q9ULB1 (aka NRX1A_HUMAN or NX1A_HUMAN)
CCDS: CCDS46282.1, CCDS54360.1, CCDS82449.1, CCDS82450.1, CCDS82451.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.