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P51800 (CLCKA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Chloride channel protein ClC-Ka

Short name=Chloride channel Ka
Alternative name(s):
ClC-K1
Gene names
Name:CLCNKA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length687 AA.
Sequence statusComplete.
Protein existenceEvidence 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 be important in urinary concentrating mechanisms.

Subunit structure

Homodimer. Interacts with BSND. Forms heteromers with BSND in the thin ascending limb of Henle By similarity. Ref.10

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Expressed predominantly in the kidney. All nephron segments expressing BSND also express CLCNK proteins. Ref.7

Involvement in disease

Bartter syndrome 4B (BS4B) [MIM:613090]: A digenic, 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. Bartter syndrome type 4B is associated with sensorineural deafness.
Note: 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 (Ref.8). Ref.8 Ref.11

Sequence similarities

Belongs to the chloride channel (TC 2.A.49) family. CLCNKA subfamily. [View classification]

Contains 2 CBS domains.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P51800-1)

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.
Isoform 2 (identifier: P51800-2)

The sequence of this isoform differs from the canonical sequence as follows:
     77-119: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: P51800-3)

The sequence of this isoform differs from the canonical sequence as follows:
     615-615: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 687687Chloride channel protein ClC-Ka
PRO_0000094455

Regions

Transmembrane52 – 7221Helical; Potential
Transmembrane161 – 18121Helical; Potential
Transmembrane202 – 22221Helical; Potential
Transmembrane236 – 25621Helical; Potential
Transmembrane282 – 30221Helical; Potential
Transmembrane329 – 34921Helical; Potential
Transmembrane396 – 41621Helical; Potential
Transmembrane417 – 43721Helical; Potential
Transmembrane452 – 47221Helical; Potential
Transmembrane486 – 50621Helical; Potential
Topological domain507 – 687181Cytoplasmic Potential
Domain551 – 60959CBS 1
Domain626 – 68459CBS 2

Sites

Metal binding2591Calcium
Metal binding2611Calcium
Metal binding2781Calcium
Metal binding2811Calcium

Natural variations

Alternative sequence77 – 11943Missing in isoform 2.
VSP_044700
Alternative sequence6151Missing in isoform 3.
VSP_045795
Natural variant81R → H.
Corresponds to variant rs9442189 [ dbSNP | Ensembl ].
VAR_048695
Natural variant451R → H.
Corresponds to variant rs35932996 [ dbSNP | Ensembl ].
VAR_033768
Natural variant671M → I. Ref.5
Corresponds to variant rs17855678 [ dbSNP | Ensembl ].
VAR_030784
Natural variant801W → C in BS4B; a patient also carrying a mutation in CLCNKB. Ref.11
VAR_063074
Natural variant831R → G. Ref.3
Corresponds to variant rs10927887 [ dbSNP | Ensembl ].
VAR_019787
Natural variant2871A → V.
Corresponds to variant rs34188929 [ dbSNP | Ensembl ].
VAR_033769
Natural variant3151Y → F. Ref.5
Corresponds to variant rs12126269 [ dbSNP | Ensembl ].
VAR_019788
Natural variant3571H → Q. Ref.3
Corresponds to variant rs79751787 [ dbSNP | Ensembl ].
VAR_068971
Natural variant4471A → T. Ref.2 Ref.3
Corresponds to variant rs1805152 [ dbSNP | Ensembl ].
VAR_014465
Natural variant5341R → W.
Corresponds to variant rs12140223 [ dbSNP | Ensembl ].
VAR_059209
Natural variant6831P → L.
Corresponds to variant rs12746751 [ dbSNP | Ensembl ].
VAR_061095

Experimental info

Sequence conflict281I → V in BAG60545. Ref.2
Sequence conflict4511G → D in BAG60545. Ref.2

Secondary structure

..................... 687
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: E97C6928470A4460

FASTA68775,285
        10         20         30         40         50         60 
MEELVGLREG FSGDPVTLQE LWGPCPHIRR AIQGGLEWLK QKVFRLGEDW YFLMTLGVLM 

        70         80         90        100        110        120 
ALVSYAMNFA IGCVVRAHQW LYREIGDSHL LRYLSWTVYP VALVSFSSGF SQSITPSSGG 

       130        140        150        160        170        180 
SGIPELKTML AGVILEDYLD IKNFGAKVVG LSCTLATGST LFLGKVGPFV HLSVMIAAYL 

       190        200        210        220        230        240 
GRVRTTTIGE PENKSKQNEM LVAAAAVGVA TVFAAPFSGV LFSIEVMSSH FSVRDYWRGF 

       250        260        270        280        290        300 
FAATCGAFIF RLLAVFNSEQ ETITSLYKTS FRVDVPFDLP EIFFFVALGG ICGVLSCAYL 

       310        320        330        340        350        360 
FCQRTFLSFI KTNRYSSKLL ATSKPVYSAL ATLLLASITY PPGVGHFLAS RLSMKQHLDS 

       370        380        390        400        410        420 
LFDNHSWALM TQNSSPPWPE ELDPQHLWWE WYHPRFTIFG TLAFFLVMKF WMLILATTIP 

       430        440        450        460        470        480 
MPAGYFMPIF ILGAAIGRLL GEALAVAFPE GIVTGGVTNP IMPGGYALAG AAAFSGAVTH 

       490        500        510        520        530        540 
TISTALLAFE LTGQIVHALP VLMAVLAANA IAQSCQPSFY DGTIIVKKLP YLPRILGRNI 

       550        560        570        580        590        600 
GSHHVRVEHF MNHSITTLAK DTPLEEVVKV VTSTDVTEYP LVESTESQIL VGIVQRAQLV 

       610        620        630        640        650        660 
QALQAEPPSR APGHQQCLQD ILARGCPTEP VTLTLFSETT LHQAQNLFKL LNLQSLFVTS 

       670        680 
RGRAVGCVSW VEMKKAISNL TNPPAPK 

« Hide

Isoform 2 [UniParc].

Checksum: 0ADDA2F448320E16
Show »

FASTA64470,458
Isoform 3 [UniParc].

Checksum: DF721CCFE6735ED2
Show »

FASTA68675,157

References

« Hide 'large scale' references
[1]"Two highly homologous members of the ClC chloride channel family in both rat and human kidney."
Kieferle S., Fong P., Bens M., Vandewalle A., Jentsch T.
Proc. Natl. Acad. Sci. U.S.A. 91:6943-6947(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Kidney.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT THR-447.
Tissue: Kidney.
[3]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANTS GLY-83; GLN-357 AND THR-447.
Tissue: Kidney.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANTS ILE-67 AND PHE-315.
Tissue: Colon.
[6]"Refined chromosomal localization of six human CLCN chloride ion channel genes."
Schutte B.C., Malik M.I., Fingert J., Barna T.J., Stone E., Lamb F.S.
Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 153-203.
[7]"Barttin is a Cl- channel beta-subunit crucial for renal Cl-reabsorption and inner ear K+ secretion."
Estevez R., Boettger T., Stein V., Birkenhaeger R., Otto E., Hildebrandt F., Jentsch T.J.
Nature 414:558-561(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Molecular analysis of digenic inheritance in Bartter syndrome with sensorineural deafness."
Nozu K., Inagaki T., Fu X.J., Nozu Y., Kaito H., Kanda K., Sekine T., Igarashi T., Nakanishi K., Yoshikawa N., Iijima K., Matsuo M.
J. Med. Genet. 45:182-186(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN BS4B.
[9]"Dissecting a regulatory calcium-binding site of CLC-K kidney chloride channels."
Gradogna A., Fenollar-Ferrer C., Forrest L.R., Pusch M.
J. Gen. Physiol. 140:681-696(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: CALCIUM-BINDING SITES.
[10]"The structure of the cytoplasmic domain of the chloride channel ClC-Ka reveals a conserved interaction interface."
Markovic S., Dutzler R.
Structure 15:715-725(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 533-687, SUBUNIT.
[11]"Salt wasting and deafness resulting from mutations in two chloride channels."
Schlingmann K.P., Konrad M., Jeck N., Waldegger P., Reinalter S.C., Holder M., Seyberth H.W., Waldegger S.
N. Engl. J. Med. 350:1314-1319(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BS4B CYS-80.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRC57713.
RefSeqNP_001036169.1. NM_001042704.1.
NP_001244068.1. NM_001257139.1.
NP_004061.3. NM_004070.3.
UniGeneHs.591533.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2PFIX-ray1.60A/B533-687[»]
ProteinModelPortalP51800.
SMRP51800. Positions 52-687.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-29432N.
STRING9606.ENSP00000332771.

Chemistry

DrugBankDB04552. Niflumic Acid.
GuidetoPHARMACOLOGY700.

PTM databases

PhosphoSiteP51800.

Polymorphism databases

DMDM1705857.

Proteomic databases

PaxDbP51800.
PRIDEP51800.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000331433; ENSP00000332771; ENSG00000186510. [P51800-1]
ENST00000375692; ENSP00000364844; ENSG00000186510. [P51800-3]
ENST00000420078; ENSP00000410353; ENSG00000186510. [P51800-3]
ENST00000439316; ENSP00000414445; ENSG00000186510. [P51800-2]
GeneID1187.
KEGGhsa:1187.
UCSCuc001axu.3. human. [P51800-1]
uc001axv.3. human.

Organism-specific databases

CTD1187.
GeneCardsGC01P016345.
HGNCHGNC:2026. CLCNKA.
MIM602024. gene.
613090. phenotype.
neXtProtNX_P51800.
Orphanet89938. Infantile Bartter syndrome with deafness.
PharmGKBPA26553.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0038.
HOGENOMHOG000231297.
HOVERGENHBG005332.
InParanoidP51800.
KOK05017.
OMAVGHFLAS.
OrthoDBEOG77WWCD.
PhylomeDBP51800.
TreeFamTF300522.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

BgeeP51800.
CleanExHS_CLCNKA.
GenevestigatorP51800.

Family and domain databases

Gene3D1.10.3080.10. 2 hits.
InterProIPR000644. CBS_dom.
IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002250. Cl_channel-K.
[Graphical view]
PfamPF00571. CBS. 1 hit.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSPR00762. CLCHANNEL.
PR01119. CLCHANNELKDY.
SMARTSM00116. CBS. 1 hit.
[Graphical view]
SUPFAMSSF81340. SSF81340. 2 hits.
PROSITEPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP51800.
GeneWikiCLCNKA.
GenomeRNAi1187.
NextBio4912.
PROP51800.
SOURCESearch...

Entry information

Entry nameCLCKA_HUMAN
AccessionPrimary (citable) accession number: P51800
Secondary accession number(s): B4DPD3 expand/collapse secondary AC list , E7EPH6, Q5T5P8, Q5T5Q4, Q7Z6D1, Q86VT1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM