Reviewed,
UniProtKB/Swiss-Prot P51790 (CLCN3_HUMAN)
Last modified
November 25, 2008.
Version 77.
History...
Clusters with 100%,
90%,
50% identity |
Documents (3) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: Chloride channel protein 3 Short name=ClC-3 | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 762 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
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. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| GOPC | Q9HD26 | 1 | EBI-349797,EBI-349832 | |
| PDZK1 | Q5T2W1 | 1 | EBI-349797,EBI-349819 | |
| SLC9A3R1 | O14745 | 1 | EBI-349797,EBI-349787 |
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. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 762 | 762 | Chloride channel protein 3 | PRO_0000094438 | |||||
Regions | |||||||||
| Transmembrane | 68 – 88 | 21 | Potential | ||||||
| Transmembrane | 154 – 174 | 21 | Potential | ||||||
| Transmembrane | 175 – 195 | 21 | Potential | ||||||
| Transmembrane | 202 – 222 | 21 | Potential | ||||||
| Transmembrane | 259 – 279 | 21 | Potential | ||||||
| Transmembrane | 285 – 305 | 21 | Potential | ||||||
| Transmembrane | 330 – 350 | 21 | Potential | ||||||
| Transmembrane | 365 – 385 | 21 | Potential | ||||||
| Transmembrane | 442 – 462 | 21 | Potential | ||||||
| Transmembrane | 467 – 487 | 21 | Potential | ||||||
| Transmembrane | 508 – 528 | 21 | Potential | ||||||
| Transmembrane | 536 – 556 | 21 | Potential | ||||||
| Domain | 602 – 666 | 65 | CBS 1 | ||||||
| Domain | 699 – 756 | 58 | CBS 2 | ||||||
Amino acid modifications | |||||||||
| Glycosylation | 8 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 119 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 393 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 421 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 618 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 629 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 | 1 | M → MESEQLFHRGYYRNSYNSIT SASSDEELLDGAGVIMDFQT SEDDNLLDGDTAVGTHYTM in isoform 3. | VSP_016072 | |||||
| Alternative sequence | 734 – 762 | 29 | RLLGI…SIMFN → IVLGIITKKNILEHLEQLKQ HVEPLAPPWHYNKKRYPPAY GPDGKPRPRFNNVQLNLTDE EREETEEEVYLLNSTTL in isoform 2. | VSP_016073 | |||||
Experimental info | |||||||||
| Mutagenesis | 222 | 1 | G → E: Changes channel selectivity from I(-)>Cl(-) to Cl(-)>I(-) | ||||||
| Sequence conflict | 589 – 590 | 2 | Missing Ref.2 Ref.3 | ||||||
Sequences
| ||||||||||||||||||||||||||||||
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. |
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. | |
| PIR | I37240. |
| RefSeq | NP_001820.2. NP_776297.2. |
| UniGene | Hs.481186 |
3D structure databases | |
| SMR | P51790. Positions 594-755. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P51790. |
PTM databases | |
| PhosphoSite | P51790. |
Genome annotation databases | |
| Ensembl | ENSG00000109572. Homo sapiens. [Contig view] |
| GeneID | 1182. |
| KEGG | hsa:1182. |
Organism-specific databases | |
| HGNC | HGNC:2021. CLCN3. |
| MIM | 600580. gene. |
| PharmGKB | PA26548. |
| GenAtlas | Search... |
| GeneCards | Search... |
Phylogenomic databases | |
| HOVERGEN | P51790. |
Gene expression databases | |
| ArrayExpress | P51790. |
| CleanEx | HS_CLCN3. |
| GermOnline | ENSG00000109572. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR014743. Cl-channel_core. IPR001807. Cl-channel_volt. IPR002245. Cl_channel3. IPR000644. Cysta_beta_synth_core. [Graphical view] |
| Gene3D | G3DSA:1.10.3080.10. Cl-channel_core. 1 hit. |
| PANTHER | PTHR11689. Cl-channel_volt. 1 hit. |
| Pfam | PF00571. CBS. 1 hit. PF00654. Voltage_CLC. 1 hit. [Graphical view] |
| PRINTS | PR00762. CLCHANNEL. PR01114. CLCHANNEL3. |
| SMART | SM00116. CBS. 2 hits. [Graphical view] |
| PROSITE | PS51371. CBS. 2 hits. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 4884. |
| SOURCE | Search... |
Entry information
| Entry name | CLCN3_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P51790 Secondary accession number(s): O14918, Q86Z21 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
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 |

Clusters with


