Format

Send to:

Choose Destination

CLCN3 chloride voltage-gated channel 3 [ Homo sapiens (human) ]

Gene ID: 1182, updated on 5-Aug-2018

Summary

Official Symbol
CLCN3provided by HGNC
Official Full Name
chloride voltage-gated channel 3provided by HGNC
Primary source
HGNC:HGNC:2021
See related
Ensembl:ENSG00000109572 MIM:600580; Vega:OTTHUMG00000160973
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
CLC3; ClC-3
Summary
This gene encodes a member of the voltage-gated chloride channel (ClC) family. The encoded protein is present in all cell types and localized in plasma membranes and in intracellular vesicles. It is a multi-pass membrane protein which contains a ClC domain and two additional C-terminal CBS (cystathionine beta-synthase) domains. The ClC domain catalyzes the selective flow of Cl- ions across cell membranes, and the CBS domain may have a regulatory function. This protein plays a role in both acidification and transmitter loading of GABAergic synaptic vesicles, and in smooth muscle cell activation and neointima formation. This protein is required for lysophosphatidic acid (LPA)-activated Cl- current activity and fibroblast-to-myofibroblast differentiation. The protein activity is regulated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in glioma cells. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]
Expression
Ubiquitous expression in brain (RPKM 27.7), colon (RPKM 19.9) and 25 other tissues See more
Orthologs

Genomic context

See CLCN3 in Genome Data Viewer
Location:
4q33
Exon count:
16
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 4 NC_000004.12 (169620521..169723187)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (170541672..170644338)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105377529 Neighboring gene NIMA related kinase 1 Neighboring gene uncharacterized LOC107986240 Neighboring gene histone PARylation factor 1

Genomic regions, transcripts, and products

Expression

  • 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 Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Pathways from BioSystems

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • DKFZp564I0463

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
PDZ domain binding IDA
Inferred from Direct Assay
more info
PubMed 
antiporter activity IEA
Inferred from Electronic Annotation
more info
 
chloride channel activity IDA
Inferred from Direct Assay
more info
PubMed 
chloride channel activity TAS
Traceable Author Statement
more info
PubMed 
chloride ion binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein heterodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
protein homodimerization activity NAS
Non-traceable Author Statement
more info
PubMed 
solute:proton antiporter activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
voltage-gated chloride channel activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
volume-sensitive chloride channel activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
Process Evidence Code Pubs
chloride transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
endosomal lumen acidification TAS
Traceable Author Statement
more info
PubMed 
negative regulation of cell volume IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of pH TAS
Traceable Author Statement
more info
PubMed 
synaptic vesicle lumen acidification IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Component Evidence Code Pubs
Golgi apparatus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Golgi apparatus IDA
Inferred from Direct Assay
more info
PubMed 
Golgi membrane IEA
Inferred from Electronic Annotation
more info
 
cell surface NAS
Non-traceable Author Statement
more info
PubMed 
cytoplasmic vesicle IDA
Inferred from Direct Assay
more info
PubMed 
early endosome IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
early endosome IDA
Inferred from Direct Assay
more info
PubMed 
early endosome membrane IEA
Inferred from Electronic Annotation
more info
 
endosome IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
external side of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
integral component of membrane TAS
Traceable Author Statement
more info
PubMed 
integral component of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
late endosome IDA
Inferred from Direct Assay
more info
PubMed 
late endosome membrane IEA
Inferred from Electronic Annotation
more info
 
membrane HDA PubMed 
phagocytic vesicle IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
secretory granule IDA
Inferred from Direct Assay
more info
PubMed 
specific granule IDA
Inferred from Direct Assay
more info
PubMed 
synaptic vesicle IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
synaptic vesicle IDA
Inferred from Direct Assay
more info
PubMed 
transport vesicle membrane IEA
Inferred from Electronic Annotation
more info
 
vesicle membrane IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
H(+)/Cl(-) exchange transporter 3
Names
chloride channel 3
chloride channel protein 3
chloride channel, voltage-sensitive 3
chloride transporter ClC-3

NCBI Reference Sequences (RefSeq)

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.

Genomic

  1. NG_029731.1 RefSeqGene

    Range
    5001..107667
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001243372.1NP_001230301.1  H(+)/Cl(-) exchange transporter 3 isoform a

    See identical proteins and their annotated locations for NP_001230301.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (a) lacks an in-frame exon in the middle coding region, compared to variant b. The resulting isoform (a) lacks an internal segment, compared to isoform b.
    Source sequence(s)
    AA780395, AC106878, AK304362, DA102505
    Consensus CDS
    CCDS58932.1
    UniProtKB/Swiss-Prot
    P51790
    Related
    ENSP00000353857.3, OTTHUMP00000219505, ENST00000360642.7, OTTHUMT00000363289
    Conserved Domains (2) summary
    cd03684
    Location:136615
    ClC_3_like; ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has ...
    cd04591
    Location:638776
    CBS_pair_EriC_assoc_euk_bac; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains in the EriC CIC-type chloride channels in eukaryotes and bacteria. These ion channels are proteins with a seemingly simple task of allowing the passive flow of ...
  2. NM_001243374.1NP_001230303.1  H(+)/Cl(-) exchange transporter 3 isoform c

    See identical proteins and their annotated locations for NP_001230303.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (c) lacks two exons from the 5' end but has an alternate 5' exon, compared to variant b. The resulting isoform (c) has a shorter and distinct N-terminus, compared to isoform b.
    Source sequence(s)
    AA780395, AC106878, AK127483, AK304362, BP284718
    Consensus CDS
    CCDS75208.1
    UniProtKB/Swiss-Prot
    P51790
    UniProtKB/TrEMBL
    B3KXK0
    Related
    ENSP00000478336.1, ENST00000613795.4
    Conserved Domains (2) summary
    cd03684
    Location:109615
    ClC_3_like; ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has ...
    cd04591
    Location:638776
    CBS_pair_EriC_assoc_euk_bac; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains in the EriC CIC-type chloride channels in eukaryotes and bacteria. These ion channels are proteins with a seemingly simple task of allowing the passive flow of ...
  3. NM_001829.3NP_001820.2  H(+)/Cl(-) exchange transporter 3 isoform b

    See identical proteins and their annotated locations for NP_001820.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (b) represents the predominant transcript and encodes isoform b.
    Source sequence(s)
    AA780395, AC106878, BC136510, BX647119, DA102505
    Consensus CDS
    CCDS34101.1
    UniProtKB/Swiss-Prot
    P51790
    Related
    ENSP00000424603.1, OTTHUMP00000219460, ENST00000513761.5, OTTHUMT00000363210
    Conserved Domains (2) summary
    cd03684
    Location:136642
    ClC_3_like; ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has ...
    cd04591
    Location:665803
    CBS_pair_EriC_assoc_euk_bac; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains in the EriC CIC-type chloride channels in eukaryotes and bacteria. These ion channels are proteins with a seemingly simple task of allowing the passive flow of ...
  4. NM_173872.3NP_776297.2  H(+)/Cl(-) exchange transporter 3 isoform e

    See identical proteins and their annotated locations for NP_776297.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (e) has an additional exon in the 3' coding region, which results in frame-shift, compared to variant b. The resulting isoform (e) has a longer and distinct C-terminus, compared to isoform b.
    Source sequence(s)
    AA780395, AB019542, AC106878, AK304362, DA102505
    Consensus CDS
    CCDS34100.1
    UniProtKB/Swiss-Prot
    P51790
    Related
    ENSP00000261514.5, OTTHUMP00000219503, ENST00000347613.8, OTTHUMT00000363287
    Conserved Domains (2) summary
    cd03684
    Location:136642
    ClC_3_like; ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has ...
    cd04591
    Location:665803
    CBS_pair_EriC_assoc_euk_bac; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains in the EriC CIC-type chloride channels in eukaryotes and bacteria. These ion channels are proteins with a seemingly simple task of allowing the passive flow of ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p12 Primary Assembly

    Range
    169620521..169723187
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005262726.3XP_005262783.1  H(+)/Cl(-) exchange transporter 3 isoform X1

    Conserved Domains (4) summary
    COG0517
    Location:629774
    CBS; CBS domain [Signal transduction mechanisms]
    cd03684
    Location:109615
    ClC_3_like; ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has ...
    cd04591
    Location:638776
    CBS_pair_EriC_assoc_euk_bac; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains in the EriC CIC-type chloride channels in eukaryotes and bacteria. These ion channels are proteins with a seemingly simple task of allowing the passive flow of ...
    pfam00654
    Location:194595
    Voltage_CLC; Voltage gated chloride channel
  2. XM_011531586.2XP_011529888.1  H(+)/Cl(-) exchange transporter 3 isoform X2

    Conserved Domains (4) summary
    COG0517
    Location:621766
    CBS; CBS domain [Signal transduction mechanisms]
    cd03684
    Location:101607
    ClC_3_like; ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has ...
    cd04591
    Location:630768
    CBS_pair_EriC_assoc_euk_bac; This cd contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domains in the EriC CIC-type chloride channels in eukaryotes and bacteria. These ion channels are proteins with a seemingly simple task of allowing the passive flow of ...
    pfam00654
    Location:186587
    Voltage_CLC; Voltage gated chloride channel
Support Center