[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). TISSUE=Retina; DOI=10.1006/geno.1995.1015; PubMed=7665160 [NCBI, ExPASy, EBI, Israel, Japan] Borsani G., Rugarli E.I., Taglialatela M., Wong C., Ballabio A.; "Characterization of a human and murine gene (CLCN3) sharing similarities to voltage-gated chloride channels and to a yeast integral membrane protein."; Genomics 27:131-141(1995).
[2]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). TISSUE=Lens epithelium; DOI=10.1076/ceyr.17.7.708.5162; PubMed=9678416 [NCBI, ExPASy, EBI, Israel, Japan] Shepard A.R., Rae J.L.; "Ion transporters and receptors in cDNA libraries from lens and cornea epithelia."; Curr. Eye Res. 17:708-719(1998).
[3]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), GLYCOSYLATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLY-222. TISSUE=Colon tumor; DOI=10.1074/jbc.M009376200; PubMed=11274166 [NCBI, ExPASy, EBI, Israel, Japan] Huang P., Liu J., Di A., Robinson N.C., Musch M.W., Kaetzel M.A., Nelson D.J.; "Regulation of human CLC-3 channels by multifunctional Ca2+/calmodulin-dependent protein kinase."; J. Biol. Chem. 276:20093-20100(2001).
[4]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, INTERACTION WITH SLC9A3R1, DOMAIN, AND FUNCTION. DOI=10.1096/fj.01-0845fje; PubMed=11967229 [NCBI, ExPASy, EBI, Israel, Japan] Ogura T., Furukawa T., Toyozaki T., Yamada K., Zheng Y.-J., Katayama Y., Nakaya H., Inagaki N.; "ClC-3B, a novel ClC-3 splicing variant that interacts with EBP50 and facilitates expression of CFTR-regulated ORCC."; FASEB J. 16:863-865(2002).
[5]	TISSUE SPECIFICITY. TISSUE=Aortic endothelium, Fetal lung, and Vascular smooth muscle; DOI=10.1006/jmcc.1998.0901; PubMed=10198195 [NCBI, ExPASy, EBI, Israel, Japan] Lamb F.S., Clayton G.H., Liu B.-X., Smith R.L., Barna T.J., Schutte B.C.; "Expression of CLCN voltage-gated chloride channel genes in human blood vessels."; J. Mol. Cell. Cardiol. 31:657-666(1999).
[6]	INTERACTION WITH GOPC; PDZK1 AND SLC9A3R1, GLYCOSYLATION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. DOI=10.1074/jbc.M211050200; PubMed=12471024 [NCBI, ExPASy, EBI, Israel, Japan] Gentzsch M., Cui L., Mengos A., Chang X.-B., Chen J.-H., Riordan J.R.; "The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins."; J. Biol. Chem. 278:6440-6449(2003).

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: Homo- or heterodimer. Isoform 2 interacts with GOPC, PDZK1 and SLC9A3R1/EBP50.
INTERACTION:
Q9HD26:GOPC; NbExp=1; IntAct=EBI-349797, EBI-349832;
Q5T2W1:PDZK1; NbExp=1; IntAct=EBI-349797, EBI-349819;
O14745:SLC9A3R1; NbExp=1; IntAct=EBI-349797, EBI-349787;
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.
SUBCELLULAR LOCATION: 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.
SUBCELLULAR LOCATION: Isoform 3: Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein. Note=Isoform 3 may also be found at the plasma membrane.

ALTERNATIVE PRODUCTS: 3 named isoforms [FASTA] produced by alternative splicing.

Name	1
Synonyms	ClC-3A
Isoform ID	P51790-1
This is the isoform sequence displayed in this entry.

Name	2
Synonyms	ClC-3B
Isoform ID	P51790-2
Features which should be applied to build the isoform sequence: VSP_016073.

Name	3
Isoform ID	P51790-3
Features which should be applied to build the isoform sequence: VSP_016072.

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.
PTM: N-glycosylated.
SIMILARITY: Belongs to the chloride channel (TC 1.A.11) family [view classification].
SIMILARITY: Contains 2 CBS domains.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

X78520; CAA55281.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X78520; CAA55280.1; ALT_INIT; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF029346; AAB95161.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF172729; AAD51034.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB019542; BAC54560.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

I37240; I37240.

RefSeq

NP_001820.2; -.
NP_776297.2; -.

UniGene

Hs.481186

3D structure databases

SMR

P51790; 594-755.

ModBase

P51790.

Protein-protein interaction databases

IntAct

P51790; -.

PTM databases

PhosphoSite

P51790; -.

Organism-specific databases

HGNC:2021; CLCN3.

600580; gene. [NCBI / EBI]

PharmGKB

PA26548; -.

GeneCards

P51790.

Gene expression databases

ArrayExpress

P51790; -.

CleanEx

HS_CLCN3; -.

GermOnline

ENSG00000109572; Homo sapiens.

Ontologies

GO:0009986;	Cellular component: cell surface (non-traceable author statement from UniProtKB).
GO:0005769;	Cellular component: early endosome (inferred from direct assay from UniProtKB).
GO:0005794;	Cellular component: Golgi apparatus (inferred from direct assay from UniProtKB).
GO:0016021;	Cellular component: integral to membrane (traceable author statement from UniProtKB).
GO:0005770;	Cellular component: late endosome (inferred from direct assay from UniProtKB).
GO:0012506;	Cellular component: vesicle membrane (inferred from direct assay from UniProtKB).
GO:0030165;	Molecular function: PDZ domain binding (inferred from direct assay from UniProtKB).
GO:0046982;	Molecular function: protein heterodimerization activity (inferred from direct assay from UniProtKB).
GO:0042803;	Molecular function: protein homodimerization activity (non-traceable author statement from UniProtKB).
GO:0005247;	Molecular function: voltage-gated chloride channel activity (traceable author statement from ProtInc).
GO:0048388;	Biological process: endosomal lumen acidification (traceable author statement from UniProtKB).
GO:0006810;	Biological process: transport (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR014743; Cl-channel_core.
IPR001807; Cl-channel_volt.
IPR002245; Cl_channel3.
IPR000644; Cysta_beta_synth_core.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.3080.10; Cl-channel_core; 1.

PANTHER

PTHR11689; Cl-channel_volt; 1.

Pfam

PF00571; CBS; 1.
PF00654; Voltage_CLC; 1.
Pfam graphical view of domain structure.

PRINTS

PR00762; CLCHANNEL.
PR01114; CLCHANNEL3.

SMART

SM00116; CBS; 2.
SMART graphical view of domain structure.

PROSITE

PS51371; CBS; 2.
PROSITE graphical view of domain structure (profiles).

BLOCKS

P51790.

Genome annotation databases

Ensembl

ENSG00000109572; Homo sapiens. [Contig view]

GeneID

1182; -.

KEGG

hsa:1182; -.

Phylogenomic databases

HOVERGEN

P51790; -.

Other

CLCN3; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Alternative splicing; CBS domain; Cell membrane; Chloride; Chloride channel; Endosome; Glycoprotein; Golgi apparatus; Ion transport; Ionic channel; Membrane; Repeat; Transmembrane; Transport; Voltage-gated channel.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 762`	`762`	`Chloride channel protein 3.`	`PRO_0000094438`
`TRANSMEM`	`68 88`	`21`	`Potential.`
`TRANSMEM`	`154 174`	`21`	`Potential.`
`TRANSMEM`	`175 195`	`21`	`Potential.`
`TRANSMEM`	`202 222`	`21`	`Potential.`
`TRANSMEM`	`259 279`	`21`	`Potential.`
`TRANSMEM`	`285 305`	`21`	`Potential.`
`TRANSMEM`	`330 350`	`21`	`Potential.`
`TRANSMEM`	`365 385`	`21`	`Potential.`
`TRANSMEM`	`442 462`	`21`	`Potential.`
`TRANSMEM`	`467 487`	`21`	`Potential.`
`TRANSMEM`	`508 528`	`21`	`Potential.`
`TRANSMEM`	`536 556`	`21`	`Potential.`
`DOMAIN`	`602 666`	`65`	`CBS 1.`
`DOMAIN`	`699 756`	`58`	`CBS 2.`
`CARBOHYD`	`8 8`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`119 119`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`393 393`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`421 421`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`618 618`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`629 629`		`N-linked (GlcNAc...) (Potential).`
`VAR_SEQ`	`1 1`		`M -> MESEQLFHRGYYRNSYNSITSASSDEELLDGAGVIMDFQT` `SEDDNLLDGDTAVGTHYTM (in isoform 3).`	`VSP_016072`
`VAR_SEQ`	`734 762`		`RLLGIITKKDILRHMAQTANQDPASIMFN -> IVLGIITKKNILEHLEQLKQHVEPLAPPWHYNKKRYPPAY` `GPDGKPRPRFNNVQLNLTDEEREETEEEVYLLNSTTL (in isoform 2).`	`VSP_016073`
`MUTAGEN`	`222 222`		`G->E: Changes channel selectivity from I(-)>Cl(-) to Cl(-)>I(-).`
`CONFLICT`	`589 590`		`Missing (in Ref. 2 and 3).`

Sequence information

Length: 762 AA [This is the length of the unprocessed precursor]

Molecular weight: 84793 Da [This is the MW of the unprocessed precursor]

CRC64: 8FCF0E132001B9C0 [This is a checksum on the sequence]

        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

P51790 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools