Tbio NRXN1 Neurexin-1

Protein Summary

Description

Cell surface protein involved in cell-cell-interactions, exocytosis 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-latrotoxin from spider venom (By similarity). 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]

Uniprot Accession IDs

• Q9ULB1
• A7KRL9
• O60323
• Q53TJ9
• Q53TQ1
• Q5HYI0
• Q9C079
• Q9C080
• Q9C081
• Q9H3M2
• Q9UDM6

Gene Name

• NRXN1

Ensembl ID

• ENST00000404971
• ENSP00000385142
• ENSG00000179915
• ENST00000406316
• ENSP00000384311
• ENST00000625672
• ENSP00000485887

Symbol

• KIAA0578
• PTHSL2
• SCZD17
• Hs.22998

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0
biological term	0
cell line	0
cell type or tissue	0
cellular component	0

Related Tools

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 326.37   (req: < 5)

Gene RIFs: 72   (req: <= 3)

Antibodies: 248   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 326.37   (req: >= 5)

Gene RIFs: 72   (req: > 3)

Antibodies: 248   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 32

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

GWAS Traits (28)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
self reported educational attainment	EFO_0004784	4	8	16		97.1
self reported educational attainment	EFO_0004784	4	8	16		97.1
chronotype measurement	EFO_0008328	3	6	6	1.1	96.7
chronotype measurement	EFO_0008328	3	6	6	1.1	96.7
body mass index	EFO_0004340	3	3	6		96.6

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
self reported educational attainment	EFO_0004784	16		97.1
self reported educational attainment	EFO_0004784	16		97.1
chronotype measurement	EFO_0008328	6	1.1	96.7
chronotype measurement	EFO_0008328	6	1.1	96.7
body mass index	EFO_0004340	6		96.6

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Orthologs (5)

1 – 5 of 5

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Mouse	neurexin I	MGI:1096391	18189
Horse	neurexin 1	VGNC:20895	100052908
Chicken	neurexin 1	CGNC:49297	395398
Zebrafish	neurexin 1a	ZDB-GENE-070206-1	565531
C. elegans	NeuReXin related		179503

Species	Name	OMA	EggNOG	Inparanoid
Mouse	neurexin I
Horse	neurexin 1
Chicken	neurexin 1
Zebrafish	neurexin 1a
C. elegans	NeuReXin related

Protein Structure (0 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

AF-Q9ULB1-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

Pathways (6)

Reactome (5)

KEGG (1)

Extracellular matrix organization (R-HSA-1474244)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Extracellular matrix organization	297 targets	R-HSA-1474244
Reactome	Neurexins and neuroligins	60 targets	R-HSA-6794361
Reactome	Neuronal System	398 targets	R-HSA-112316
Reactome	Non-integrin membrane-ECM interactions	43 targets	R-HSA-3000171
Reactome	Protein-protein interactions at synapses	91 targets	R-HSA-6794362

Name	Explore in Pharos	Explore in Source
Extracellular matrix organization	297 targets	R-HSA-1474244
Neurexins and neuroligins	60 targets	R-HSA-6794361
Neuronal System	398 targets	R-HSA-112316
Non-integrin membrane-ECM interactions	43 targets	R-HSA-3000171
Protein-protein interactions at synapses	91 targets	R-HSA-6794362

Gene Ontology Terms (47)

Functions (6)

Components (15)

Processes (26)

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10

1 – 6 of 6

GO Term	Evidence	Assigned by
acetylcholine receptor binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
calcium channel regulator activity	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
calcium ion binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
cell adhesion molecule binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
neuroligin family protein binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
signaling receptor activity	Traceable Author Statement (TAS)	ProtInc

Protein-Protein Interactions (277)

Explore Interacting Targets

1 – 10 of 277

• See Interactions on String-DB

NLGN3

Tbio

Family: Enzyme

Novelty: 0.00819625

Score: 0.998

Data Source: STRINGDB

NLGN1

Tbio

Family: Enzyme

Novelty: 0.0097512

Score: 0.998

Data Source: STRINGDB

NLGN4X

Tbio

Family: Enzyme

Novelty: 0.01004489

Score: 0.997

Data Source: STRINGDB

NLGN2

Tbio

Family: Enzyme

Novelty: 0.01613168

Score: 0.997

Data Source: STRINGDB

CASK

Tchem

Family: Kinase

Novelty: 0.00856437

Score: 0.987

Data Source: STRINGDB

LRRTM2

Tbio

Novelty: 0.08084156

Score: 0.985

Data Source: STRINGDB

LRRTM1

Tbio

Novelty: 0.0409182

Score: 0.983

Data Source: STRINGDB

LRRTM3

Tbio

Novelty: 0.18633527

Score: 0.975

Data Source: STRINGDB

SHANK2

Tbio

Novelty: 0.00710548

Score: 0.975

Data Source: STRINGDB

SYT1

Tbio

Novelty: 0.00176103

Score: 0.974

Data Source: STRINGDB

Publication Statistics

PubMed Score  326.37

PubMed score by year

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PubTator Score  113.61

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

Alternative promoter usage
Alternative splicing
Calcium
Cell adhesion
Cell junction
Cell membrane
Complete proteome
Disulfide bond
EGF-like domain
Glycoprotein

GWAS Trait Find Similar Targets

albuminuria
body height
body mass index
chronotype measurement
intelligence
lifestyle measurement
mathematical ability
risk-taking behaviour
schizophrenia
self reported educational attainment

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
limbs/digits/tail phenotype
nervous system phenotype
respiratory system phenotype