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Protein

Chloride channel protein ClC-Ka

Gene

CLCNKA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.

Activity 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

  • identical protein binding Source: IntAct
  • metal ion binding Source: UniProtKB-KW
  • voltage-gated chloride channel activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionChloride channel, Ion channel, Voltage-gated channel
Biological processIon transport, Transport
LigandCalcium, Chloride, Metal-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000186510.11
HGNCiHGNC:2026 CLCNKA
MIMi602024 gene
neXtProtiNX_P51800

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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 dbSNP:rs121909137EnsemblClinVar.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
ProteomicsDBi56399

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 Expressed in 80 organ(s), highest expression level in cortex of kidney
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

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-12538872,EBI-12538872

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107601, 1 interactor
DIPiDIP-29432N
IntActiP51800, 20 interactors
STRINGi9606.ENSP00000332771

Structurei

Secondary structure

1687
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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, 1 hit
InterProiView protein in InterPro
IPR000644 CBS_dom
IPR014743 Cl-channel_core
IPR001807 Cl-channel_volt-gated
IPR002250 Cl_channel-K
PfamiView protein in Pfam
PF00571 CBS, 1 hit
PF00654 Voltage_CLC, 1 hit
PRINTSiPR00762 CLCHANNEL
PR01119 CLCHANNELKDY
SMARTiView protein in SMART
SM00116 CBS, 1 hit
SUPFAMiSSF81340 SSF81340, 2 hits
PROSITEiView protein in PROSITE
PS51371 CBS, 2 hits

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 dbSNP:rs9442189Ensembl.1
Natural variantiVAR_03376845R → H. Corresponds to variant dbSNP:rs35932996Ensembl.1
Natural variantiVAR_03078467M → I1 PublicationCorresponds to variant dbSNP:rs17855678Ensembl.1
Natural variantiVAR_06307480W → C in BARTS4B; a patient also carrying a mutation in CLCNKB. 1 PublicationCorresponds to variant dbSNP:rs121909137EnsemblClinVar.1
Natural variantiVAR_01978783R → G1 PublicationCorresponds to variant dbSNP:rs10927887Ensembl.1
Natural variantiVAR_019788315Y → F1 PublicationCorresponds to variant dbSNP:rs12126269Ensembl.1
Natural variantiVAR_068971357H → Q1 PublicationCorresponds to variant dbSNP:rs79751787Ensembl.1
Natural variantiVAR_014465447A → T2 PublicationsCorresponds to variant dbSNP:rs1805152Ensembl.1
Natural variantiVAR_059209534R → W. Corresponds to variant dbSNP:rs12140223Ensembl.1
Natural variantiVAR_061095683P → L. Corresponds to variant dbSNP:rs12746751Ensembl.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 No translation available.
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

Similar proteinsi

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 No translation available.
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, 20 interactors
STRINGi9606.ENSP00000332771

Chemistry databases

DrugBankiDB04552 Niflumic Acid
GuidetoPHARMACOLOGYi700

PTM databases

iPTMnetiP51800
PhosphoSitePlusiP51800

Polymorphism and mutation databases

BioMutaiCLCNKA
DMDMi1705857

Proteomic databases

PaxDbiP51800
PeptideAtlasiP51800
PRIDEiP51800
ProteomicsDBi56399

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
EuPathDBiHostDB:ENSG00000186510.11
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

ReactomeiR-HSA-2672351 Stimuli-sensing channels

Miscellaneous databases

EvolutionaryTraceiP51800
GeneWikiiCLCNKA
GenomeRNAii1187
PROiPR:P51800
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000186510 Expressed in 80 organ(s), highest expression level in cortex of kidney
CleanExiHS_CLCNKA
GenevisibleiP51800 HS

Family and domain databases

Gene3Di1.10.3080.10, 1 hit
InterProiView protein in InterPro
IPR000644 CBS_dom
IPR014743 Cl-channel_core
IPR001807 Cl-channel_volt-gated
IPR002250 Cl_channel-K
PfamiView protein in Pfam
PF00571 CBS, 1 hit
PF00654 Voltage_CLC, 1 hit
PRINTSiPR00762 CLCHANNEL
PR01119 CLCHANNELKDY
SMARTiView protein in SMART
SM00116 CBS, 1 hit
SUPFAMiSSF81340 SSF81340, 2 hits
PROSITEiView protein in PROSITE
PS51371 CBS, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiCLCKA_HUMAN
AccessioniPrimary (citable) accession number: P51800
Secondary accession number(s): B4DPD3
, E7EPH6, Q5T5P8, Q5T5Q4, Q7Z6D1, Q86VT1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 12, 2018
This is version 168 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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