CPLX1 complexin 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CPLX1provided by HGNC
Official Full Name: complexin 1provided by HGNC
Primary source: HGNC:HGNC:2309
See related: Ensembl:ENSG00000168993 MIM:605032
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CPX1; CPX-I; EIEE63
Summary: Proteins encoded by the complexin/synaphin gene family are cytosolic proteins that function in synaptic vesicle exocytosis. These proteins bind syntaxin, part of the SNAP receptor. The protein product of this gene binds to the SNAP receptor complex and disrupts it, allowing transmitter release. [provided by RefSeq, Jul 2008]
Expression: Biased expression in brain (RPKM 19.8), fat (RPKM 3.8) and 5 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 4p16.3

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	4	NC_000004.12 (784957..826157, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (778745..819945, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

data define CPLX1 as a PD risk factor and provide functional insights into the role and regulation of blood SNCA levels. The new blood biomarkers of PARK4 in this Turkish family might become useful for PD prediction
Title: Blood RNA biomarkers in prodromal PARK4 and rapid eye movement sleep behavior disorder show role of complexin 1 loss for risk of Parkinson's disease.
Homozygous CPLX1 variants were identified in three patients with severe infantile myoclonic epilepsy and ID.
Title: Variants in CPLX1 in two families with autosomal-recessive severe infantile myoclonic epilepsy and ID.
This study demonstrated that complexin-I influence cognitive function in early and late stages of Alzheimer's disease.
Title: Presynaptic proteins complexin-I and complexin-II differentially influence cognitive function in early and late stages of Alzheimer's disease.
Study showed for the first time that neuro-Behcet's disease and Behcet's disease patients are inclined to display the GG genotype of the CPLX1 rs936551 polymorphism and to exhibit increased CPLX1 expression levels
Title: Increased complexin-1 and decreased miR-185 expression levels in Behçet's disease with and without neurological involvement.
Collectively these results demonstrate that CPX-1 is a secreted collagen-binding glycoprotein and provide a foundation for future studies investigating the function of CPX-1.
Title: Carboxypeptidase X-1 (CPX-1) is a secreted collagen-binding glycoprotein.
Studies indicate the role of the small regulatory factor complexin in Ca(2+)-dependent vesicle fusion and exocytosis.
Title: Complexins: small but capable.
Data support the the trans insertion model for complexin clamping.
Title: Re-visiting the trans insertion model for complexin clamping.
Together with synaptotagmin 1, complexin synchronizes and stimulates rapid fusion of accumulated docked vesicles in response to physiological Ca(2+) concentrations.
Title: Complexin arrests a pool of docked vesicles for fast Ca2+-dependent release.
The 'central helix' of complexin is anchored to one SNARE complex, while its 'accessory helix' extends away at ~45 degrees and bridges to a second complex, occupying the vacant v-SNARE binding site to inhibit fusion.
Title: Complexin cross-links prefusion SNAREs into a zigzag array.
The crystal structure of complexin bound to a prefusion SNAREpin mimetic shows that the accessory helix extends away from the SNAREpin in an 'open' conformation, binding another SNAREpin and inhibiting its assembly, to clamp fusion.
Title: A conformational switch in complexin is required for synaptotagmin to trigger synaptic fusion.

Submit: New GeneRIF Correction See all GeneRIFs (16)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
4p partial monosomy syndrome MedGen: C1956097 OMIM: 194190 GeneReviews: Wolf-Hirschhorn Syndrome	Compare labs
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 63 MedGen: C4693810 OMIM: 617976 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Acetylcholine Neurotransmitter Release Cycle, organism-specific biosystem (from REACTOME)
Acetylcholine Neurotransmitter Release Cycle, organism-specific biosystemAcetylcholine neurotransmitter release cycle involves syntheis of choline, loading of clathrin scultpted synaptic vesicles, docking and priming of the acetyl choline loaded synaptic vesicles and then...
Dopamine Neurotransmitter Release Cycle, organism-specific biosystem (from REACTOME)
Dopamine Neurotransmitter Release Cycle, organism-specific biosystemDopamine neurotransmitter cycle occurs in dopaminergic neurons. Dopamine is synthesized and loaded into the clathrin sculpted monoamine transport vesicles. The vesicles are docked, primed and fused w...
GABA synthesis, release, reuptake and degradation, organism-specific biosystem (from REACTOME)
GABA synthesis, release, reuptake and degradation, organism-specific biosystemGABA is a major inhibitory neurotransmitter in the mammalian central nervous system. GABA modulates neuronal excitability throughout the nervous system. Disruption of GABA neurotransmission leads to ...
Glutamate Neurotransmitter Release Cycle, organism-specific biosystem (from REACTOME)
Glutamate Neurotransmitter Release Cycle, organism-specific biosystemCommunication at the synapse involves the release of glutamate from the presynaptic neuron and its binding to glutamate receptors on the postsynaptic cell to generate a series of events that lead to ...
Neuronal System, organism-specific biosystem (from REACTOME)
Neuronal System, organism-specific biosystemThe human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication a...
Neurotransmitter Release Cycle, organism-specific biosystem (from REACTOME)
Neurotransmitter Release Cycle, organism-specific biosystemNeurotransmitter is stored in the synaptic vesicle in the pre-synaptic terminal prior to its release in the synaptic cleft upon depolarization of the pre-synaptic membrane. The release of the neurotr...
Norepinephrine Neurotransmitter Release Cycle, organism-specific biosystem (from REACTOME)
Norepinephrine Neurotransmitter Release Cycle, organism-specific biosystemNoradrenalin release cycle consists of reacidification of the empty clathrin sculpted monoamine transport vesicle, loading of dopamine into reacidified clathrin coated monamine transport vesicle, con...
Serotonin Neurotransmitter Release Cycle, organism-specific biosystem (from REACTOME)
Serotonin Neurotransmitter Release Cycle, organism-specific biosystemSerotonin is synthesized in the serotonergic neurons in the central nervous system and the enterochrommaffin cells of the gastroinetstinal system. Serotonin is loaded into the clathrin sculpted monoa...
Synaptic Vesicle Pathway, organism-specific biosystem (from WikiPathways)
Synaptic Vesicle Pathway, organism-specific biosystemPathway depicting synaptic transmission of neurotransmitters from the presynaptic nerve terminal to the synaptic cleft upon depolarization. Synaptotagmin mediated transport along the nerve cell cytos...
Synaptic vesicle cycle, organism-specific biosystem (from KEGG)
Synaptic vesicle cycle, organism-specific biosystemCommunication between neurons is mediated by the release of neurotransmitter from synaptic vesicles (SVs). At the nerve terminal, SVs cycle through repetitive episodes of exocytosis and endocytosis. ...
Synaptic vesicle cycle, conserved biosystem (from KEGG)
Synaptic vesicle cycle, conserved biosystemCommunication between neurons is mediated by the release of neurotransmitter from synaptic vesicles (SVs). At the nerve terminal, SVs cycle through repetitive episodes of exocytosis and endocytosis. ...
Transmission across Chemical Synapses, organism-specific biosystem (from REACTOME)
Transmission across Chemical Synapses, organism-specific biosystemChemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron,...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH78792 (e-PCR)
- UniSTS:67922

RH18288 (e-PCR)
- UniSTS:41332

D4S1270 (e-PCR)
- UniSTS:67705

Homology

Homologs of the CPLX1 gene: The CPLX1 gene is conserved in Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 197 organisms have orthologs with human gene CPLX1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
SNARE binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
neurotransmitter transporter activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
syntaxin-1 binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
chemical synaptic transmission	TAS Traceable Author Statement more info	PubMed
exocytic insertion of neurotransmitter receptor to postsynaptic membrane	IEA Inferred from Electronic Annotation more info
exocytosis	TAS Traceable Author Statement more info	PubMed
insulin secretion	IEA Inferred from Electronic Annotation more info
regulation of exocytosis	TAS Traceable Author Statement more info	PubMed
regulation of neurotransmitter secretion	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of synaptic vesicle fusion to presynaptic active zone membrane	IEA Inferred from Electronic Annotation more info
synaptic vesicle exocytosis	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
SNARE complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Schaffer collateral - CA1 synapse	IEA Inferred from Electronic Annotation more info
calyx of Held	IEA Inferred from Electronic Annotation more info
cytosol	TAS Traceable Author Statement more info
dendrite	IEA Inferred from Electronic Annotation more info
glutamatergic synapse	IEA Inferred from Electronic Annotation more info
neuronal cell body	IEA Inferred from Electronic Annotation more info
postsynapse	IEA Inferred from Electronic Annotation more info
synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex	IEA Inferred from Electronic Annotation more info
synaptobrevin 2-SNAP-25-syntaxin-3-complexin complex	TAS Traceable Author Statement more info	PubMed
terminal bouton	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: complexin-1

Names: CPX I; complexin I; synaphin 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.