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Protein

Chloride channel protein ClC-Ka

Gene

CLCNKA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. May be important in urinary concentrating mechanisms.

Enzyme regulationi

Activated by extracellular calcium and inhibited by extracellular protons.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi259Calcium1 Publication1
Metal bindingi261Calcium1 Publication1
Metal bindingi278Calcium1 Publication1
Metal bindingi281Calcium1 Publication1

GO - Molecular functioni

GO - Biological processi

  • chloride transmembrane transport Source: GO_Central
  • excretion Source: ProtInc
  • ion transmembrane transport Source: Reactome
  • transport Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Chloride channel, Ion channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Transport

Keywords - Ligandi

Calcium, Chloride, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:G66-31526-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Chloride channel protein ClC-Ka
Short name:
Chloride channel Ka
Alternative name(s):
ClC-K1
Gene namesi
Name:CLCNKA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:2026. CLCNKA.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei52 – 72HelicalSequence analysisAdd BLAST21
Transmembranei161 – 181HelicalSequence analysisAdd BLAST21
Transmembranei202 – 222HelicalSequence analysisAdd BLAST21
Transmembranei236 – 256HelicalSequence analysisAdd BLAST21
Transmembranei282 – 302HelicalSequence analysisAdd BLAST21
Transmembranei329 – 349HelicalSequence analysisAdd BLAST21
Transmembranei396 – 416HelicalSequence analysisAdd BLAST21
Transmembranei417 – 437HelicalSequence analysisAdd BLAST21
Transmembranei452 – 472HelicalSequence analysisAdd BLAST21
Transmembranei486 – 506HelicalSequence analysisAdd BLAST21
Topological domaini507 – 687CytoplasmicSequence analysisAdd BLAST181

GO - Cellular componenti

  • chloride channel complex Source: UniProtKB-KW
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Bartter syndrome 4B, neonatal, with sensorineural deafness (BARTS4B)2 Publications
The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Loss-of-function of both CLCNKA and CLCNKB results in the disease phenotype (PubMed:18310267).1 Publication
Disease descriptionA digenic form of Bartter syndrome, an autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. BARTS4B is associated with sensorineural deafness.
See also OMIM:613090
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06307480W → C in BARTS4B; a patient also carrying a mutation in CLCNKB. 1 PublicationCorresponds to variant rs121909137dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi259E → N: Calcium insensitive. 1 Publication1
Mutagenesisi261E → Q: Calcium insensitive. 1 Publication1
Mutagenesisi278D → N: Calcium insensitive. 1 Publication1
Mutagenesisi281E → D: Calcium insensitive. 1 Publication1

Keywords - Diseasei

Bartter syndrome, Deafness, Disease mutation

Organism-specific databases

DisGeNETi1187.
MalaCardsiCLCNKA.
MIMi613090. phenotype.
OpenTargetsiENSG00000186510.
Orphaneti89938. Infantile Bartter syndrome with sensorineural deafness.
PharmGKBiPA26553.

Chemistry databases

DrugBankiDB04552. Niflumic Acid.
GuidetoPHARMACOLOGYi700.

Polymorphism and mutation databases

BioMutaiCLCNKA.
DMDMi1705857.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000944551 – 687Chloride channel protein ClC-KaAdd BLAST687

Proteomic databases

PaxDbiP51800.
PeptideAtlasiP51800.
PRIDEiP51800.

PTM databases

iPTMnetiP51800.
PhosphoSitePlusiP51800.

Expressioni

Tissue specificityi

Expressed predominantly in the kidney. All nephron segments expressing BSND also express CLCNK proteins.1 Publication

Gene expression databases

BgeeiENSG00000186510.
CleanExiHS_CLCNKA.
GenevisibleiP51800. HS.

Organism-specific databases

HPAiHPA057717.

Interactioni

Subunit structurei

Homodimer (PubMed:17562318). Interacts with BSND. Forms heteromers with BSND in the thin ascending limb of Henle (By similarity).By similarity1 Publication

Protein-protein interaction databases

BioGridi107601. 1 interactor.
DIPiDIP-29432N.
IntActiP51800. 9 interactors.
STRINGi9606.ENSP00000332771.

Structurei

Secondary structure

1687
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi547 – 550Combined sources4
Helixi564 – 572Combined sources9
Beta strandi577 – 583Combined sources7
Turni585 – 587Combined sources3
Beta strandi589 – 595Combined sources7
Helixi596 – 604Combined sources9
Helixi618 – 623Combined sources6
Helixi641 – 650Combined sources10
Beta strandi654 – 660Combined sources7
Beta strandi663 – 669Combined sources7
Helixi670 – 681Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2PFIX-ray1.60A/B533-687[»]
ProteinModelPortaliP51800.
SMRiP51800.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51800.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini551 – 609CBS 1PROSITE-ProRule annotationAdd BLAST59
Domaini626 – 684CBS 2PROSITE-ProRule annotationAdd BLAST59

Sequence similaritiesi

Contains 2 CBS domains.PROSITE-ProRule annotation

Keywords - Domaini

CBS domain, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0476. Eukaryota.
COG0038. LUCA.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000231297.
HOVERGENiHBG005332.
InParanoidiP51800.
KOiK05017.
OMAiPCPHIRR.
OrthoDBiEOG091G01RJ.
PhylomeDBiP51800.
TreeFamiTF300522.

Family and domain databases

Gene3Di1.10.3080.10. 2 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002250. Cl_channel-K.
[Graphical view]
PfamiPF00571. CBS. 1 hit.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01119. CLCHANNELKDY.
SMARTiSM00116. CBS. 1 hit.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 2 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P51800-1) [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
MEELVGLREG FSGDPVTLQE LWGPCPHIRR AIQGGLEWLK QKVFRLGEDW
60 70 80 90 100
YFLMTLGVLM ALVSYAMNFA IGCVVRAHQW LYREIGDSHL LRYLSWTVYP
110 120 130 140 150
VALVSFSSGF SQSITPSSGG SGIPELKTML AGVILEDYLD IKNFGAKVVG
160 170 180 190 200
LSCTLATGST LFLGKVGPFV HLSVMIAAYL GRVRTTTIGE PENKSKQNEM
210 220 230 240 250
LVAAAAVGVA TVFAAPFSGV LFSIEVMSSH FSVRDYWRGF FAATCGAFIF
260 270 280 290 300
RLLAVFNSEQ ETITSLYKTS FRVDVPFDLP EIFFFVALGG ICGVLSCAYL
310 320 330 340 350
FCQRTFLSFI KTNRYSSKLL ATSKPVYSAL ATLLLASITY PPGVGHFLAS
360 370 380 390 400
RLSMKQHLDS LFDNHSWALM TQNSSPPWPE ELDPQHLWWE WYHPRFTIFG
410 420 430 440 450
TLAFFLVMKF WMLILATTIP MPAGYFMPIF ILGAAIGRLL GEALAVAFPE
460 470 480 490 500
GIVTGGVTNP IMPGGYALAG AAAFSGAVTH TISTALLAFE LTGQIVHALP
510 520 530 540 550
VLMAVLAANA IAQSCQPSFY DGTIIVKKLP YLPRILGRNI GSHHVRVEHF
560 570 580 590 600
MNHSITTLAK DTPLEEVVKV VTSTDVTEYP LVESTESQIL VGIVQRAQLV
610 620 630 640 650
QALQAEPPSR APGHQQCLQD ILARGCPTEP VTLTLFSETT LHQAQNLFKL
660 670 680
LNLQSLFVTS RGRAVGCVSW VEMKKAISNL TNPPAPK
Length:687
Mass (Da):75,285
Last modified:October 1, 1996 - v1
Checksum:iE97C6928470A4460
GO
Isoform 2 (identifier: P51800-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     77-119: Missing.

Note: No experimental confirmation available.
Show »
Length:644
Mass (Da):70,458
Checksum:i0ADDA2F448320E16
GO
Isoform 3 (identifier: P51800-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     615-615: Missing.

Note: No experimental confirmation available.
Show »
Length:686
Mass (Da):75,157
Checksum:iDF721CCFE6735ED2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti28I → V in BAG60545 (PubMed:14702039).Curated1
Sequence conflicti451G → D in BAG60545 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0486958R → H.Corresponds to variant rs9442189dbSNPEnsembl.1
Natural variantiVAR_03376845R → H.Corresponds to variant rs35932996dbSNPEnsembl.1
Natural variantiVAR_03078467M → I.1 PublicationCorresponds to variant rs17855678dbSNPEnsembl.1
Natural variantiVAR_06307480W → C in BARTS4B; a patient also carrying a mutation in CLCNKB. 1 PublicationCorresponds to variant rs121909137dbSNPEnsembl.1
Natural variantiVAR_01978783R → G.1 PublicationCorresponds to variant rs10927887dbSNPEnsembl.1
Natural variantiVAR_033769287A → V.Corresponds to variant rs34188929dbSNPEnsembl.1
Natural variantiVAR_019788315Y → F.1 PublicationCorresponds to variant rs12126269dbSNPEnsembl.1
Natural variantiVAR_068971357H → Q.1 PublicationCorresponds to variant rs79751787dbSNPEnsembl.1
Natural variantiVAR_014465447A → T.2 PublicationsCorresponds to variant rs1805152dbSNPEnsembl.1
Natural variantiVAR_059209534R → W.Corresponds to variant rs12140223dbSNPEnsembl.1
Natural variantiVAR_061095683P → L.Corresponds to variant rs12746751dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04470077 – 119Missing in isoform 2. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_045795615Missing in isoform 3. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z30643 mRNA. Translation: CAA83120.1.
AK298285 mRNA. Translation: BAG60545.1.
AK225550 mRNA. No translation available.
AL355994 Genomic DNA. Translation: CAI16137.1.
AL355994 Genomic DNA. Translation: CAI16138.1.
BC048282 mRNA. Translation: AAH48282.1.
BC053869 mRNA. Translation: AAH53869.1.
U93878 Genomic DNA. Translation: AAB65148.1.
CCDSiCCDS167.1. [P51800-1]
CCDS41269.1. [P51800-3]
CCDS57973.1. [P51800-2]
PIRiC57713.
RefSeqiNP_001036169.1. NM_001042704.1. [P51800-3]
NP_001244068.1. NM_001257139.1. [P51800-2]
NP_004061.3. NM_004070.3. [P51800-1]
UniGeneiHs.591533.

Genome annotation databases

EnsembliENST00000331433; ENSP00000332771; ENSG00000186510. [P51800-1]
ENST00000375692; ENSP00000364844; ENSG00000186510. [P51800-3]
ENST00000439316; ENSP00000414445; ENSG00000186510. [P51800-2]
GeneIDi1187.
KEGGihsa:1187.
UCSCiuc001axu.4. human. [P51800-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z30643 mRNA. Translation: CAA83120.1.
AK298285 mRNA. Translation: BAG60545.1.
AK225550 mRNA. No translation available.
AL355994 Genomic DNA. Translation: CAI16137.1.
AL355994 Genomic DNA. Translation: CAI16138.1.
BC048282 mRNA. Translation: AAH48282.1.
BC053869 mRNA. Translation: AAH53869.1.
U93878 Genomic DNA. Translation: AAB65148.1.
CCDSiCCDS167.1. [P51800-1]
CCDS41269.1. [P51800-3]
CCDS57973.1. [P51800-2]
PIRiC57713.
RefSeqiNP_001036169.1. NM_001042704.1. [P51800-3]
NP_001244068.1. NM_001257139.1. [P51800-2]
NP_004061.3. NM_004070.3. [P51800-1]
UniGeneiHs.591533.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2PFIX-ray1.60A/B533-687[»]
ProteinModelPortaliP51800.
SMRiP51800.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107601. 1 interactor.
DIPiDIP-29432N.
IntActiP51800. 9 interactors.
STRINGi9606.ENSP00000332771.

Chemistry databases

DrugBankiDB04552. Niflumic Acid.
GuidetoPHARMACOLOGYi700.

PTM databases

iPTMnetiP51800.
PhosphoSitePlusiP51800.

Polymorphism and mutation databases

BioMutaiCLCNKA.
DMDMi1705857.

Proteomic databases

PaxDbiP51800.
PeptideAtlasiP51800.
PRIDEiP51800.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000331433; ENSP00000332771; ENSG00000186510. [P51800-1]
ENST00000375692; ENSP00000364844; ENSG00000186510. [P51800-3]
ENST00000439316; ENSP00000414445; ENSG00000186510. [P51800-2]
GeneIDi1187.
KEGGihsa:1187.
UCSCiuc001axu.4. human. [P51800-1]

Organism-specific databases

CTDi1187.
DisGeNETi1187.
GeneCardsiCLCNKA.
HGNCiHGNC:2026. CLCNKA.
HPAiHPA057717.
MalaCardsiCLCNKA.
MIMi602024. gene.
613090. phenotype.
neXtProtiNX_P51800.
OpenTargetsiENSG00000186510.
Orphaneti89938. Infantile Bartter syndrome with sensorineural deafness.
PharmGKBiPA26553.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0476. Eukaryota.
COG0038. LUCA.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000231297.
HOVERGENiHBG005332.
InParanoidiP51800.
KOiK05017.
OMAiPCPHIRR.
OrthoDBiEOG091G01RJ.
PhylomeDBiP51800.
TreeFamiTF300522.

Enzyme and pathway databases

BioCyciZFISH:G66-31526-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Miscellaneous databases

EvolutionaryTraceiP51800.
GeneWikiiCLCNKA.
GenomeRNAii1187.
PROiP51800.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000186510.
CleanExiHS_CLCNKA.
GenevisibleiP51800. HS.

Family and domain databases

Gene3Di1.10.3080.10. 2 hits.
InterProiIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002250. Cl_channel-K.
[Graphical view]
PfamiPF00571. CBS. 1 hit.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSiPR00762. CLCHANNEL.
PR01119. CLCHANNELKDY.
SMARTiSM00116. CBS. 1 hit.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 2 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCLCKA_HUMAN
AccessioniPrimary (citable) accession number: P51800
Secondary accession number(s): B4DPD3
, E7EPH6, Q5T5P8, Q5T5Q4, Q7Z6D1, Q86VT1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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 one 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.