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Reviewed, UniProtKB/Swiss-Prot P51790 (CLCN3_HUMAN)

Last modified November 25, 2008. Version 77. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Chloride channel protein 3
      Short name=ClC-3
Gene names
Name: CLCN3
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length762 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. May play an important role in neuronal cell function through regulation of membrane excitability by protein kinase C. It could help neuronal cells to establish short-term memory.

Subunit structure

Homo- or heterodimer. Isoform 2 interacts with GOPC, PDZK1 and SLC9A3R1/EBP50.

Subcellular location

Isoform 1: Membrane; Multi-pass membrane protein. Early endosome membrane; Multi-pass membrane protein. Late endosome membrane; Multi-pass membrane protein. Note= Isoform 1 is localized mainly in early and late endosomes.

Isoform 2: Membrane; Multi-pass membrane protein. Early endosome membrane; Multi-pass membrane protein. Late endosome membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Note= Isoform 2 partially colocalized with isoform 1 but is mainly enriched in the Golgi.

Isoform 3: Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein. Note= Isoform 3 may also be found at the plasma membrane.

Tissue specificity

Expressed primarily in tissues derived from neuroectoderm. Within the brain, its expression is particularly evident in the hippocampus, olfactory cortex, and olfactory bulb. Highly expressed in aortic and coronary vascular smooth muscle cells, and aortic endothelial cells. Also expressed in tracheal and alveolar epithelial cells, and intima and media of the pulmonary vessels. Expressed in bronchus and colon (at protein level).

Domain

Isoform 2 contains a C-terminal PDZ-binding motif mediating the interaction with GOPC.

Post-translational modification

N-glycosylated.

Sequence similarities

Belongs to the chloride channel (TC 2.A.49) family. [View classification]

Contains 2 CBS domains.

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Ontologies

Keywords

   Biological processIon transport
Transport
   Cellular componentCell membrane
Endosome
Golgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
   DomainCBS domain
Repeat
Transmembrane
   LigandChloride
   Molecular functionChloride channel
Ionic channel
Voltage-gated channel
   PTMGlycoprotein

Gene Ontology (GO)

   Biological processchloride transport

Inferred from electronic annotation. Source: InterPro

endosomal lumen acidification Ref.6

Traceable author statement. Source: UniProtKB

   Cellular componentGolgi membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell surface Ref.6

Non-traceable author statement. Source: UniProtKB

early endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral to membrane Ref.6

Traceable author statement. Source: UniProtKB

late endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-KW

vesicle membrane Ref.6

Inferred from direct assay. Source: UniProtKB

   Molecular functionPDZ domain binding Ref.6

Inferred from direct assay. Source: UniProtKB

chloride ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein heterodimerization activity Ref.6

Inferred from direct assay. Source: UniProtKB

protein homodimerization activity Ref.6

Non-traceable author statement. Source: UniProtKB

voltage-gated chloride channel activity Ref.1

Traceable author statement. Source: ProtInc

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

GOPCQ9HD261EBI-349797,EBI-349832
PDZK1Q5T2W11EBI-349797,EBI-349819
SLC9A3R1O147451EBI-349797,EBI-349787

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P51790-1)

Also known as: ClC-3A;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Notes: Isoform 1 is localized mainly in early and late endosomes.
Isoform 2 (identifier: P51790-2)

Also known as: ClC-3B;

The sequence of this isoform differs from the canonical sequence as follows:
     734-762: RLLGIITKKDILRHMAQTANQDPASIMFN → IVLGIITKKN...EVYLLNSTTL
Notes: Isoform 2 partially colocalized with isoform 1 but is mainly enriched in the Golgi.
Isoform 3 (identifier: P51790-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MESEQLFHRGYYRNSYNSITSASSDEELLDGAGVIMDFQTSEDDNLLDGDTAVGTHYTM
Notes: Isoform 3 may also be found at the plasma membrane.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 762762Chloride channel protein 3
PRO_0000094438

Regions

Transmembrane68 – 8821 Potential
Transmembrane154 – 17421 Potential
Transmembrane175 – 19521 Potential
Transmembrane202 – 22221 Potential
Transmembrane259 – 27921 Potential
Transmembrane285 – 30521 Potential
Transmembrane330 – 35021 Potential
Transmembrane365 – 38521 Potential
Transmembrane442 – 46221 Potential
Transmembrane467 – 48721 Potential
Transmembrane508 – 52821 Potential
Transmembrane536 – 55621 Potential
Domain602 – 66665CBS 1
Domain699 – 75658CBS 2

Amino acid modifications

Glycosylation81N-linked (GlcNAc...) Potential
Glycosylation1191N-linked (GlcNAc...) Potential
Glycosylation3931N-linked (GlcNAc...) Potential
Glycosylation4211N-linked (GlcNAc...) Potential
Glycosylation6181N-linked (GlcNAc...) Potential
Glycosylation6291N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence11M → MESEQLFHRGYYRNSYNSIT SASSDEELLDGAGVIMDFQT SEDDNLLDGDTAVGTHYTM in isoform 3.
VSP_016072
Alternative sequence734 – 76229RLLGI…SIMFN → IVLGIITKKNILEHLEQLKQ HVEPLAPPWHYNKKRYPPAY GPDGKPRPRFNNVQLNLTDE EREETEEEVYLLNSTTL in isoform 2.
VSP_016073

Experimental info

Mutagenesis2221G → E: Changes channel selectivity from I(-)>Cl(-) to Cl(-)>I(-)
Sequence conflict589 – 5902Missing Ref.2 Ref.3

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (ClC-3A) [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 8FCF0E132001B9C0

FASTA76284,793
        10         20         30         40         50         60 
MTNGGSINSS THLLDLLDEP IPGVGTYDDF HTIDWVREKC KDRERHRRIN SKKKESAWEM 

        70         80         90        100        110        120 
TKSLYDAWSG WLVVTLTGLA SGALAGLIDI AADWMTDLKE GICLSALWYN HEQCCWGSNE 

       130        140        150        160        170        180 
TTFEERDKCP QWKTWAELII GQAEGPGSYI MNYIMYIFWA LSFAFLAVSL VKVFAPYACG 

       190        200        210        220        230        240 
SGIPEIKTIL SGFIIRGYLG KWTLMIKTIT LVLAVASGLS LGKEGPLVHV ACCCGNIFSY 

       250        260        270        280        290        300 
LFPKYSTNEA KKREVLSAAS AAGVSVAFGA PIGGVLFSLE EVSYYFPLKT LWRSFFAALV 

       310        320        330        340        350        360 
AAFVLRSINP FGNSRLVLFY VEYHTPWYLF ELFPFILLGV FGGLWGAFFI RANIAWCRRR 

       370        380        390        400        410        420 
KSTKFGKYPV LEVIIVAAIT AVIAFPNPYT RLNTSELIKE LFTDCGPLES SSLCDYRNDM 

       430        440        450        460        470        480 
NASKIVDDIP DRPAGIGVYS AIWQLCLALI FKIIMTVFTF GIKVPSGLFI PSMAIGAIAG 

       490        500        510        520        530        540 
RIVGIAVEQL AYYHHDWFIF KEWCEVGADC ITPGLYAMVG AAACLGGVTR MTVSLVVIVF 

       550        560        570        580        590        600 
ELTGGLEYIV PLMAAVMTSK WVGDAFGREG IYEAHIRLNG YPFLDAKEEF EFTHTTLAAD 

       610        620        630        640        650        660 
VMRPRRNDPP LAVLTQDNMT VDDIENMINE TSYNGFPVIM SKESQRLVGF ALRRDLTIAI 

       670        680        690        700        710        720 
ESARKKQEGI VGSSRVCFAQ HTPSLPAESP RPLKLRSILD MSPFTVTDHT PMEIVVDIFR 

       730        740        750        760 
KLGLRQCLVT HNGRLLGIIT KKDILRHMAQ TANQDPASIM FN

« Hide

Isoform 2 (ClC-3B) [UniParc].

Checksum: B41D68E9981F9877
Show »

81090,559
Isoform 3 [UniParc].

Checksum: 7C713581F0EDBDC6
Show »

82091,243

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References

[1]"Characterization of a human and murine gene (CLCN3) sharing similarities to voltage-gated chloride channels and to a yeast integral membrane protein."
Borsani G., Rugarli E.I., Taglialatela M., Wong C., Ballabio A.
Genomics 27:131-141(1995) [PubMed: 7665160] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Retina.
[2]"Ion transporters and receptors in cDNA libraries from lens and cornea epithelia."
Shepard A.R., Rae J.L.
Curr. Eye Res. 17:708-719(1998) [PubMed: 9678416] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Tissue: Lens epithelium.
[3]"Regulation of human CLC-3 channels by multifunctional Ca2+/calmodulin-dependent protein kinase."
Huang P., Liu J., Di A., Robinson N.C., Musch M.W., Kaetzel M.A., Nelson D.J.
J. Biol. Chem. 276:20093-20100(2001) [PubMed: 11274166] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), GLYCOSYLATION, SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-222.
Tissue: Colon tumor.
[4]"ClC-3B, a novel ClC-3 splicing variant that interacts with EBP50 and facilitates expression of CFTR-regulated ORCC."
Ogura T., Furukawa T., Toyozaki T., Yamada K., Zheng Y.-J., Katayama Y., Nakaya H., Inagaki N.
FASEB J. 16:863-865(2002) [PubMed: 11967229] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, INTERACTION WITH SLC9A3R1, DOMAIN, FUNCTION.
[5]"Expression of CLCN voltage-gated chloride channel genes in human blood vessels."
Lamb F.S., Clayton G.H., Liu B.-X., Smith R.L., Barna T.J., Schutte B.C.
J. Mol. Cell. Cardiol. 31:657-666(1999) [PubMed: 10198195] [Abstract]
Cited for: TISSUE SPECIFICITY.
Tissue: Aortic endothelium, Fetal lung and Vascular smooth muscle.
[6]"The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins."
Gentzsch M., Cui L., Mengos A., Chang X.-B., Chen J.-H., Riordan J.R.
J. Biol. Chem. 278:6440-6449(2003) [PubMed: 12471024] [Abstract]
Cited for: INTERACTION WITH GOPC; PDZK1 AND SLC9A3R1, GLYCOSYLATION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

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Cross-references

Sequence databases

X78520 mRNA. Translation: CAA55281.1.
X78520 mRNA. Translation: CAA55280.1. Different initiation.
AF029346 mRNA. Translation: AAB95161.1.
AF172729 mRNA. Translation: AAD51034.1.
AB019542 mRNA. Translation: BAC54560.1.
PIRI37240.
RefSeqNP_001820.2.
NP_776297.2.
UniGeneHs.481186

3D structure databases

SMRP51790. Positions 594-755.
ModBaseSearch...

Protein-protein interaction databases

IntActP51790.

PTM databases

PhosphoSiteP51790.

Genome annotation databases

EnsemblENSG00000109572. Homo sapiens. [Contig view]
GeneID1182.
KEGGhsa:1182.

Organism-specific databases

HGNCHGNC:2021. CLCN3.
MIM600580. gene.
PharmGKBPA26548.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOVERGENP51790.

Gene expression databases

ArrayExpressP51790.
CleanExHS_CLCN3.
GermOnlineENSG00000109572. Homo sapiens.

Family and domain databases

InterProIPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt.
IPR002245. Cl_channel3.
IPR000644. Cysta_beta_synth_core.
[Graphical view]
Gene3DG3DSA:1.10.3080.10. Cl-channel_core. 1 hit.
PANTHERPTHR11689. Cl-channel_volt. 1 hit.
PfamPF00571. CBS. 1 hit.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSPR00762. CLCHANNEL.
PR01114. CLCHANNEL3.
SMARTSM00116. CBS. 2 hits.
[Graphical view]
PROSITEPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio4884.
SOURCESearch...

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Entry information

Entry nameCLCN3_HUMAN
AccessionPrimary (citable) accession number: P51790
Secondary accession number(s): O14918, Q86Z21
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 25, 2008
This is version 77 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents