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Protein

Chloride transport protein 6

Gene

Clcn6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Chloride transport protein, initially identified as voltage-gated chloride channel. The presence of the conserved gating glutamate residues suggests that is functions as antiporter.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei157 – 1571ChlorideBy similarity
Sitei200 – 2001Mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking H(+) and Cl(-) transportBy similarity
Sitei267 – 2671Mediates proton transfer from the protein to the inner aqueous phaseBy similarity
Binding sitei490 – 4901Chloride; via amide nitrogenBy similarity
Binding sitei577 – 5771ChlorideBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi631 – 6333ATPBy similarity
Nucleotide bindingi850 – 8534ATPBy similarity

GO - Molecular functioni

  1. antiporter activity Source: UniProtKB-KW
  2. ATP binding Source: UniProtKB-KW
  3. voltage-gated chloride channel activity Source: InterPro

GO - Biological processi

  1. response to mechanical stimulus Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Transport

Keywords - Ligandi

ATP-binding, Chloride, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_346473. Stimuli-sensing channels.

Protein family/group databases

TCDBi2.A.49.3.4. the chloride carrier/channel (clc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Chloride transport protein 6
Alternative name(s):
Chloride channel protein 6
Short name:
ClC-6
Gene namesi
Name:Clcn6
Synonyms:Clc6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1347049. Clcn6.

Subcellular locationi

  1. Endosome membrane 1 Publication; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8080CytoplasmicBy similarityAdd
BLAST
Transmembranei81 – 11333HelicalBy similarityAdd
BLAST
Transmembranei128 – 15023HelicalBy similarityAdd
BLAST
Intramembranei159 – 1668HelicalBy similarity
Transmembranei176 – 19419HelicalBy similarityAdd
BLAST
Transmembranei200 – 21718HelicalBy similarityAdd
BLAST
Intramembranei241 – 25313HelicalBy similarityAdd
BLAST
Intramembranei257 – 2659HelicalBy similarity
Transmembranei277 – 29418HelicalBy similarityAdd
BLAST
Transmembranei335 – 36430HelicalBy similarityAdd
BLAST
Transmembranei371 – 39222HelicalBy similarityAdd
BLAST
Transmembranei463 – 48220HelicalBy similarityAdd
BLAST
Transmembranei488 – 51225HelicalBy similarityAdd
BLAST
Intramembranei520 – 53415HelicalBy similarityAdd
BLAST
Intramembranei535 – 5373Note=Loop between two helicesBy similarity
Intramembranei538 – 54912HelicalBy similarityAdd
BLAST
Intramembranei550 – 5534Note=Loop between two helicesBy similarity
Transmembranei554 – 57219HelicalBy similarityAdd
BLAST
Topological domaini573 – 870298CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. endosome membrane Source: UniProtKB-SubCell
  2. integral component of membrane Source: UniProtKB-KW
  3. lysosomal membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Reduced pain sensitivity and moderate behavioral abnormalities, but have normal fertility and are generally not very different from wild-type.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 870870Chloride transport protein 6PRO_0000094450Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi410 – 4101N-linked (GlcNAc...)Sequence Analysis
Glycosylationi423 – 4231N-linked (GlcNAc...)Sequence Analysis
Glycosylationi433 – 4331N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

N-glycosylated on several asparagine residues.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiO35454.
PaxDbiO35454.
PRIDEiO35454.

PTM databases

PhosphoSiteiO35454.

Expressioni

Tissue specificityi

Detected in whole brain and in hippocampus neurons (at protein level). Detected in brain, trigeminus, dorsal root ganglion, spinal cord, eye, kidney, testis, skeletal muscle, thymus and pancreas. Isoform ClC-6c is expressed only in kidney.2 Publications

Gene expression databases

BgeeiO35454.
CleanExiMM_CLCN6.
ExpressionAtlasiO35454. baseline.
GenevestigatoriO35454.

Interactioni

Protein-protein interaction databases

IntActiO35454. 1 interaction.
MINTiMINT-4090929.

Structurei

3D structure databases

ProteinModelPortaliO35454.
SMRiO35454. Positions 87-579, 780-862.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini606 – 66358CBS 1PROSITE-ProRule annotationAdd
BLAST
Domaini808 – 86962CBS 2PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi156 – 1605Selectivity filter part_1By similarity
Motifi198 – 2025Selectivity filter part_2By similarity
Motifi488 – 4925Selectivity filter part_3By similarity

Sequence similaritiesi

Contains 2 CBS domains.PROSITE-ProRule annotation

Keywords - Domaini

CBS domain, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0038.
HOGENOMiHOG000231081.
HOVERGENiHBG050985.
InParanoidiO35454.
KOiK05015.

Family and domain databases

Gene3Di1.10.3080.10. 2 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002248. Cl_channel-6.
[Graphical view]
PfamiPF00571. CBS. 1 hit.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01117. CLCHANNEL6.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 2 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform ClC-6a (identifier: O35454-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAGCRGSVCC CCRWCCCCGE RESRTPEELT ILGETQEEED EILPRKDYES
60 70 80 90 100
LDYDRCINDP YLEVLETMDN KKGRRYEAVK WMVVFAIGVC TGLVGLFVDF
110 120 130 140 150
SVRLFTQLKF GVVQTSVEEC SQKGCLALSL LELLGFNLTF VFLASLLVLI
160 170 180 190 200
EPVAAGSGIP EIKCYLNGVK VPGIVRLRTL LCKVFGVLFS VSGGLFVGKE
210 220 230 240 250
GPMIHSGAVV GAGLPQFQSI SLRKIQFNFP YFRSDRDKRD FVSAGAAAGV
260 270 280 290 300
AAAFGAPIGG TLFSLEEGSS FWNQGLTWKV LFCSMSATFT LNFFRSGIQF
310 320 330 340 350
GSWGSFQLPG LLNFGEFKCS DSDKKCHLWT AMDLGFFVVM GVIGGLLGAT
360 370 380 390 400
FNCLNKRLAK YRMRNVHPKP KLVRVLESLL VSLVTTVVVF VASMVLGECR
410 420 430 440 450
QMSSTSQTGN GSFQLQVTSE DVNSTIKAFF CPNDTYNDMA TLFFNSQESA
460 470 480 490 500
ILQLFHQDGT FSPVTLALFF ILYFLLACWT FGTSVPSGLF VPSLLCGAAF
510 520 530 540 550
GRLVANVLKS YIGLGHLYSG TFALIGAAAF LGGVVRMTIS LTVILIESTN
560 570 580 590 600
EITYGLPIMV TLMVAKWTGD LFNKGIYDVH IGLRGVPLLE WETDVEMDKL
610 620 630 640 650
RASDIMEPNL TYVYPHTRIQ SLVSILRTTV HHAFPVVTEN RGNEKEFMKG
660 670 680 690 700
NQLISNNIKF KKSSILTRAG EQRKRGQSMK SYPSSELRNV CDEHVASEEP
710 720 730 740 750
AEKEDLLQQM LERRYTPYPN LYPDQSPSED WTMEERFRPL TFHGLVLRSQ
760 770 780 790 800
LVTLLVRGVC YSESQSSASQ PRLSYAEMAE DYPRYPDIHD LDLTLLNPRM
810 820 830 840 850
IVDVTPYMNP SPFTVSPNTH VSQVFNLFRT MGLRHLPVVN AVGEIVGIIT
860 870
RHNLTNEFLQ ARLRQHYQTL
Length:870
Mass (Da):96,980
Last modified:January 1, 1998 - v1
Checksum:i872C090069188749
GO
Isoform ClC-6c (identifier: O35454-2)

Sequence is not available
Length:
Mass (Da):

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030106
, AF030101, AF030102, AF030103, AF030104, AF030105 Genomic DNA. Translation: AAC17702.1.
CCDSiCCDS18928.1. [O35454-1]
RefSeqiNP_036059.1. NM_011929.2. [O35454-1]
UniGeneiMm.89987.

Genome annotation databases

EnsembliENSMUST00000030879; ENSMUSP00000030879; ENSMUSG00000029016. [O35454-1]
GeneIDi26372.
KEGGimmu:26372.
UCSCiuc008vtr.1. mouse. [O35454-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030106
, AF030101, AF030102, AF030103, AF030104, AF030105 Genomic DNA. Translation: AAC17702.1.
CCDSiCCDS18928.1. [O35454-1]
RefSeqiNP_036059.1. NM_011929.2. [O35454-1]
UniGeneiMm.89987.

3D structure databases

ProteinModelPortaliO35454.
SMRiO35454. Positions 87-579, 780-862.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO35454. 1 interaction.
MINTiMINT-4090929.

Chemistry

ChEMBLiCHEMBL2176794.

Protein family/group databases

TCDBi2.A.49.3.4. the chloride carrier/channel (clc) family.

PTM databases

PhosphoSiteiO35454.

Proteomic databases

MaxQBiO35454.
PaxDbiO35454.
PRIDEiO35454.

Protocols and materials databases

DNASUi26372.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030879; ENSMUSP00000030879; ENSMUSG00000029016. [O35454-1]
GeneIDi26372.
KEGGimmu:26372.
UCSCiuc008vtr.1. mouse. [O35454-1]

Organism-specific databases

CTDi1185.
MGIiMGI:1347049. Clcn6.

Phylogenomic databases

eggNOGiCOG0038.
HOGENOMiHOG000231081.
HOVERGENiHBG050985.
InParanoidiO35454.
KOiK05015.

Enzyme and pathway databases

ReactomeiREACT_346473. Stimuli-sensing channels.

Miscellaneous databases

NextBioi304269.
PROiO35454.
SOURCEiSearch...

Gene expression databases

BgeeiO35454.
CleanExiMM_CLCN6.
ExpressionAtlasiO35454. baseline.
GenevestigatoriO35454.

Family and domain databases

Gene3Di1.10.3080.10. 2 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002248. Cl_channel-6.
[Graphical view]
PfamiPF00571. CBS. 1 hit.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01117. CLCHANNEL6.
SMARTiSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 2 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. Kornak U., Boesl M.R., Jentsch T.J.
    Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Alternative splicing of ClC-6 (a member of the ClC chloride-channel family) transcripts generates three truncated isoforms one of which, ClC-6c, is kidney-specific."
    Eggermont J., Buyse G., Voets T., Tytgat J., De Smedt H., Droogmans G., Nilius B.
    Biochem. J. 325:269-276(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, ALTERNATIVE SPLICING.
    Tissue: Chronic myeloid leukemia cell.
  3. Cited for: FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.

Entry informationi

Entry nameiCLCN6_MOUSE
AccessioniPrimary (citable) accession number: O35454
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: April 1, 2015
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The presence of conserved gating glutamate residues is typical for family members that function as antiporters (By similarity).By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.