P51797 · CLCN6_HUMAN
- ProteinH(+)/Cl(-) exchange transporter 6
- GeneCLCN6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids869 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalytic activity
- 2 chloride(in) + H+(out) = 2 chloride(out) + H+(in)This reaction proceeds in the forward direction.
2 chloride (in)CHEBI:17996+ H+ (out)CHEBI:15378= 2 chloride (out)CHEBI:17996+ H+ (in)CHEBI:15378
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 157 | chloride (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Site | 200 | Mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking H+ and Cl- transport | ||||
Sequence: E | ||||||
Site | 267 | Mediates proton transfer from the protein to the inner aqueous phase | ||||
Sequence: E | ||||||
Binding site | 489 | chloride (UniProtKB | ChEBI) | ||||
Sequence: F | ||||||
Binding site | 576 | chloride (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 630-632 | ATP (UniProtKB | ChEBI) | ||||
Sequence: HHA | ||||||
Binding site | 849-852 | ATP (UniProtKB | ChEBI) | ||||
Sequence: TRHN |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endosome membrane | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | late endosome membrane | |
Cellular Component | lysosomal membrane | |
Cellular Component | membrane | |
Molecular Function | antiporter activity | |
Molecular Function | ATP binding | |
Molecular Function | chloride transmembrane transporter activity | |
Molecular Function | voltage-gated chloride channel activity | |
Biological Process | cell volume homeostasis | |
Biological Process | chloride transport | |
Biological Process | monoatomic ion transmembrane transport | |
Biological Process | response to mechanical stimulus | |
Biological Process | signal transduction |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameH(+)/Cl(-) exchange transporter 6
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP51797
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Features
Showing features for topological domain, transmembrane, intramembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-80 | Cytoplasmic | ||||
Sequence: MAGCRGSLCCCCRWCCCCGERETRTPEELTILGETQEEEDEILPRKDYESLDYDRCINDPYLEVLETMDNKKGRRYEAVK | ||||||
Transmembrane | 81-113 | Helical | ||||
Sequence: WMVVFAIGVCTGLVGLFVDFFVRLFTQLKFGVV | ||||||
Transmembrane | 128-150 | Helical | ||||
Sequence: LSLLELLGFNLTFVFLASLLVLI | ||||||
Intramembrane | 159-166 | Helical | ||||
Sequence: IPEVKCYL | ||||||
Transmembrane | 176-194 | Helical | ||||
Sequence: RLRTLLCKVLGVLFSVAGG | ||||||
Transmembrane | 200-217 | Helical | ||||
Sequence: EGPMIHSGSVVGAGLPQF | ||||||
Intramembrane | 241-253 | Helical | ||||
Sequence: FVSAGAAAGVAAA | ||||||
Intramembrane | 257-265 | Helical | ||||
Sequence: PIGGTLFSL | ||||||
Transmembrane | 277-294 | Helical | ||||
Sequence: TWKVLFCSMSATFTLNFF | ||||||
Transmembrane | 335-364 | Helical | ||||
Sequence: GFFVVMGVIGGLLGATFNCLNKRLAKYRMR | ||||||
Transmembrane | 371-392 | Helical | ||||
Sequence: KLVRVLESLLVSLVTTVVVFVA | ||||||
Transmembrane | 462-481 | Helical | ||||
Sequence: PVTLALFFVLYFLLACWTYG | ||||||
Transmembrane | 487-511 | Helical | ||||
Sequence: GLFVPSLLCGAAFGRLVANVLKSYI | ||||||
Intramembrane | 519-533 | Helical | ||||
Sequence: GTFALIGAAAFLGGV | ||||||
Intramembrane | 534-536 | Note=Loop between two helices | ||||
Sequence: VRM | ||||||
Intramembrane | 537-548 | Helical | ||||
Sequence: TISLTVILIEST | ||||||
Intramembrane | 549-552 | Note=Loop between two helices | ||||
Sequence: NEIT | ||||||
Transmembrane | 553-571 | Helical | ||||
Sequence: YGLPIMVTLMVAKWTGDFF | ||||||
Topological domain | 572-869 | Cytoplasmic | ||||
Sequence: NKGIYDIHVGLRGVPLLEWETEVEMDKLRASDIMEPNLTYVYPHTRIQSLVSILRTTVHHAFPVVTENRGNEKEFMKGNQLISNNIKFKKSSILTRAGEQRKRSQSMKSYPSSELRNMCDEHIASEEPAEKEDLLQQMLERRYTPYPNLYPDQSPSEDWTMEERFRPLTFHGLILRSQLVTLLVRGVCYSESQSSASQPRLSYAEMAEDYPRYPDIHDLDLTLLNPRMIVDVTPYMNPSPFTVSPNTHVSQVFNLFRTMGLRHLPVVNAVGEIVGIITRHNLTYEFLQARLRQHYQTI |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Neurodegeneration, childhood-onset, with hypotonia, respiratory insufficiency, and brain imaging abnormalities (CONRIBA)
- Note
- DescriptionAn autosomal dominant, progressive, neurodegenerative disorder characterized by severe global developmental delay, impaired intellectual development, poor or absent speech, hypotonia, impaired motor development, respiratory insufficiency, and feeding difficulties. Most patients have visual defects, including cortical visual blindness, nystagmus, and esotropia. Brain imaging shows abnormalities affecting the brainstem, cerebellum, and corticospinal tracts. Disease onset is in infancy or early childhood.
- See alsoMIM:619173
Natural variants in CONRIBA
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_085384 | 553 | Y>C | in CONRIBA; strongly slowed gating and increased current amplitudes; dbSNP:rs1644918844 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 157 | Increases the nitrate/chloride conductance ratio. | ||||
Sequence: S → P | ||||||
Natural variant | VAR_023051 | 198 | in dbSNP:rs198400 | |||
Sequence: E → G | ||||||
Mutagenesis | 200 | Abolishes proton transport, but not chloride transport. Strongly increases anion current; when associated with S-576. | ||||
Sequence: E → A | ||||||
Mutagenesis | 267 | Loss of proton and chloride transport. | ||||
Sequence: E → A | ||||||
Mutagenesis | 410 | Abolishes N-glycosylation; when associated with A-422 and A-432. | ||||
Sequence: N → A | ||||||
Mutagenesis | 422 | Abolishes N-glycosylation; when associated with A-410 and A-432. | ||||
Sequence: N → A | ||||||
Mutagenesis | 432 | Abolishes N-glycosylation; when associated with A-410 and A-422. | ||||
Sequence: N → A | ||||||
Natural variant | VAR_085384 | 553 | in CONRIBA; strongly slowed gating and increased current amplitudes; dbSNP:rs1644918844 | |||
Sequence: Y → C | ||||||
Mutagenesis | 576 | Strongly increases anion current; when associated with A-200. | ||||
Sequence: Y → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 960 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000094449 | 1-869 | H+/Cl- exchange transporter 6 | |||
Sequence: MAGCRGSLCCCCRWCCCCGERETRTPEELTILGETQEEEDEILPRKDYESLDYDRCINDPYLEVLETMDNKKGRRYEAVKWMVVFAIGVCTGLVGLFVDFFVRLFTQLKFGVVQTSVEECSQKGCLALSLLELLGFNLTFVFLASLLVLIEPVAAGSGIPEVKCYLNGVKVPGIVRLRTLLCKVLGVLFSVAGGLFVEKEGPMIHSGSVVGAGLPQFQSISLRKIQFNFPYFRSDRDKRDFVSAGAAAGVAAAFGAPIGGTLFSLEEGSSFWNQGLTWKVLFCSMSATFTLNFFRSGIQFGSWGSFQLPGLLNFGEFKCSDSDKKCHLWTAMDLGFFVVMGVIGGLLGATFNCLNKRLAKYRMRNVHPKPKLVRVLESLLVSLVTTVVVFVASMVLGECRQMSSSSQIGNDSFQLQVTEDVNSSIKTFFCPNDTYNDMATLFFNPQESAILQLFHQDGTFSPVTLALFFVLYFLLACWTYGISVPSGLFVPSLLCGAAFGRLVANVLKSYIGLGHIYSGTFALIGAAAFLGGVVRMTISLTVILIESTNEITYGLPIMVTLMVAKWTGDFFNKGIYDIHVGLRGVPLLEWETEVEMDKLRASDIMEPNLTYVYPHTRIQSLVSILRTTVHHAFPVVTENRGNEKEFMKGNQLISNNIKFKKSSILTRAGEQRKRSQSMKSYPSSELRNMCDEHIASEEPAEKEDLLQQMLERRYTPYPNLYPDQSPSEDWTMEERFRPLTFHGLILRSQLVTLLVRGVCYSESQSSASQPRLSYAEMAEDYPRYPDIHDLDLTLLNPRMIVDVTPYMNPSPFTVSPNTHVSQVFNLFRTMGLRHLPVVNAVGEIVGIITRHNLTYEFLQARLRQHYQTI | ||||||
Glycosylation | 410 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 422 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 432 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 773 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Structure
Family & Domains
Features
Showing features for motif, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 156-160 | Selectivity filter part_1 | ||||
Sequence: GSGIP | ||||||
Motif | 198-202 | Selectivity filter part_2 | ||||
Sequence: EKEGP | ||||||
Motif | 487-491 | Selectivity filter part_3 | ||||
Sequence: GLFVP | ||||||
Domain | 605-662 | CBS 1 | ||||
Sequence: MEPNLTYVYPHTRIQSLVSILRTTVHHAFPVVTENRGNEKEFMKGNQLISNNIKFKKS | ||||||
Domain | 807-868 | CBS 2 | ||||
Sequence: MNPSPFTVSPNTHVSQVFNLFRTMGLRHLPVVNAVGEIVGIITRHNLTYEFLQARLRQHYQT |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 6 isoforms produced by Alternative splicing.
P51797-1
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.
- Name1
- SynonymsA, Clc-6a
- Length869
- Mass (Da)97,289
- Last updated2010-11-02 v2
- ChecksumD625F0C2189EB6F7
P51797-2
- Name2
- SynonymsB, ClC-6b, D2-A1
P51797-3
- Name3
- SynonymsC, ClC-6c, D1-A1
P51797-4
- Name4
- SynonymsD, ClC-6d, D1-A2
P51797-5
- Name5
- Differences from canonical
- 844-869: IVGIITRHNLTYEFLQARLRQHYQTI → VSEAPALPPPLREDPLARCCLCTQASHQKRRHPTRRGECGPTLALNPARLPCTRDPFPCLPADGTSVPLAVLSSQSRASTRLCLPPEMLLFTPYHWCSLVLHLRRDLRIR
P51797-6
- Name6
- Differences from canonical
- 50-71: Missing
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A3B3IRY0 | A0A3B3IRY0_HUMAN | CLCN6 | 498 |
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 19 | in Ref. 6; BAG57898 | ||||
Sequence: G → S | ||||||
Alternative sequence | VSP_047169 | 50-71 | in isoform 6 | |||
Sequence: Missing | ||||||
Sequence conflict | 92 | in Ref. 6; BAG57898 | ||||
Sequence: G → D | ||||||
Alternative sequence | VSP_001047 | 237-308 | in isoform 4 | |||
Sequence: DKRDFVSAGAAAGVAAAFGAPIGGTLFSLEEGSSFWNQGLTWKVLFCSMSATFTLNFFRSGIQFGSWGSFQL → SGCWSCCSFRGANRGYLVQSRGGFVLLEPRAHVESALLFHVCHLHPQLLPFWDSVWKLGFLPAPWIAELWRV | ||||||
Alternative sequence | VSP_001043 | 237-320 | in isoform 2 | |||
Sequence: DKRDFVSAGAAAGVAAAFGAPIGGTLFSLEEGSSFWNQGLTWKVLFCSMSATFTLNFFRSGIQFGSWGSFQLPGLLNFGEFKCS → YGKRQERLCISRSGCWSCCSFRGANRGYLVQSRGGFVLLEPRAHVESALLFHVCHLHPQLLPFWDSVWKLGFLPAPWIAELWRV | ||||||
Alternative sequence | VSP_001048 | 309-869 | in isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_001045 | 319-353 | in isoform 3 | |||
Sequence: CSDSDKKCHLWTAMDLGFFVVMGVIGGLLGATFNC → SLREPPCVSGNHRGGVCGLDGVRRMPTDVLFESNR | ||||||
Alternative sequence | VSP_001044 | 321-869 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_001046 | 354-869 | in isoform 3 | |||
Sequence: Missing | ||||||
Sequence conflict | 442 | in Ref. 6; BAG57898 | ||||
Sequence: F → S | ||||||
Alternative sequence | VSP_017188 | 844-869 | in isoform 5 | |||
Sequence: IVGIITRHNLTYEFLQARLRQHYQTI → VSEAPALPPPLREDPLARCCLCTQASHQKRRHPTRRGECGPTLALNPARLPCTRDPFPCLPADGTSVPLAVLSSQSRASTRLCLPPEMLLFTPYHWCSLVLHLRRDLRIR |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X83378 EMBL· GenBank· DDBJ | CAA58292.1 EMBL· GenBank· DDBJ | mRNA | ||
X96391 EMBL· GenBank· DDBJ | CAA65255.1 EMBL· GenBank· DDBJ | mRNA | ||
X99472 EMBL· GenBank· DDBJ | CAA67835.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X99473 EMBL· GenBank· DDBJ | CAA67836.1 EMBL· GenBank· DDBJ | mRNA | ||
X99474 EMBL· GenBank· DDBJ | CAA67837.1 EMBL· GenBank· DDBJ | mRNA | ||
X99475 EMBL· GenBank· DDBJ | CAA67838.1 EMBL· GenBank· DDBJ | mRNA | ||
AF009257 EMBL· GenBank· DDBJ | AAB69287.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF009247 EMBL· GenBank· DDBJ | AAB69287.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF009248 EMBL· GenBank· DDBJ | AAB69287.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF009249 EMBL· GenBank· DDBJ | AAB69287.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF009250 EMBL· GenBank· DDBJ | AAB69287.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF009251 EMBL· GenBank· DDBJ | AAB69287.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF009252 EMBL· GenBank· DDBJ | AAB69287.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF009253 EMBL· GenBank· DDBJ | AAB69287.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF009254 EMBL· GenBank· DDBJ | AAB69287.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF009255 EMBL· GenBank· DDBJ | AAB69287.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF009256 EMBL· GenBank· DDBJ | AAB69287.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
D28475 EMBL· GenBank· DDBJ | BAA05836.4 EMBL· GenBank· DDBJ | mRNA | ||
AK289999 EMBL· GenBank· DDBJ | BAF82688.1 EMBL· GenBank· DDBJ | mRNA | ||
AK294764 EMBL· GenBank· DDBJ | BAG57898.1 EMBL· GenBank· DDBJ | mRNA | ||
AL021155 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL953897 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471130 EMBL· GenBank· DDBJ | EAW71715.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC117420 EMBL· GenBank· DDBJ | AAI17421.1 EMBL· GenBank· DDBJ | mRNA | ||
BC117424 EMBL· GenBank· DDBJ | AAI17425.1 EMBL· GenBank· DDBJ | mRNA |