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P51801 (CLCKB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Chloride channel protein ClC-Kb
Short name=Chloride channel Kb
Alternative name(s):
ClC-K2
Gene names
Name:CLCNKB
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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. Ref.5

Subunit structure

Interacts with BSND. Forms heteromers with BSND in the thick ascending limb of Henle and more distal segments By similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Expressed predominantly in the kidney. Ref.5

Involvement in disease

Defects in CLCNKB are the cause of Bartter syndrome type 3 (BS3) [MIM:607364]; also known as classic Bartter syndrome. It is an autosomal recessive form of often severe intravascular volume depletion due to renal salt-wasting associated with low blood pressure, hypokalemic alkalosis, hypercalciuria, and normal serum magnesium levels. Ref.8

Defects in CLCNKB are a cause of Bartter syndrome type 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. Ref.6 Ref.7

Miscellaneous

Compared with CLCNKA/BSND, CLCNKB/BSND is more sensitive to pH and less responsive to Ca2+.

Sequence similarities

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

Contains 2 CBS domains.

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DiseaseBartter syndrome
Deafness
Disease mutation
   DomainCBS domain
Repeat
Transmembrane
Transmembrane helix
   LigandChloride
   Molecular functionChloride channel
Ionic channel
Voltage-gated channel
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological processexcretion

Traceable author statement. Source: ProtInc

   Cellular componentchloride channel complex

Inferred from electronic annotation. Source: UniProtKB-KW

integral to plasma membrane

Traceable author statement. Source: ProtInc

   Molecular functionvoltage-gated chloride channel activity

Traceable author statement. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 687687Chloride channel protein ClC-Kb
PRO_0000094459

Regions

Topological domain1 – 5050Cytoplasmic Potential
Transmembrane51 – 7121Helical; Potential
Transmembrane94 – 11421Helical; Potential
Transmembrane161 – 18121Helical; Potential
Transmembrane202 – 22221Helical; Potential
Transmembrane236 – 25621Helical; Potential
Transmembrane282 – 30221Helical; Potential
Transmembrane325 – 34521Helical; Potential
Transmembrane396 – 41621Helical; Potential
Transmembrane417 – 43721Helical; Potential
Transmembrane452 – 47221Helical; Potential
Transmembrane486 – 50621Helical; Potential
Domain551 – 60959CBS 1
Domain626 – 68459CBS 2

Amino acid modifications

Glycosylation6791N-linked (GlcNAc...) Potential

Natural variations

Natural variant41F → L.
Corresponds to variant rs34851419 [ dbSNP | Ensembl ].
VAR_033770
Natural variant271R → L. Ref.1 Ref.2
Corresponds to variant rs2015352 [ dbSNP | Ensembl ].
VAR_046797
Natural variant881S → R.
Corresponds to variant rs5256 [ dbSNP | Ensembl ].
VAR_014466
Natural variant1041V → I.
Corresponds to variant rs35530360 [ dbSNP | Ensembl ].
VAR_033771
Natural variant1241P → L in BS3. Ref.8
VAR_001624
Natural variant1261V → L.
Corresponds to variant rs5258 [ dbSNP | Ensembl ].
VAR_046798
Natural variant1431N → H.
Corresponds to variant rs5259 [ dbSNP | Ensembl ].
VAR_014467
Natural variant2041A → T in BS3. Ref.8
VAR_001625
Natural variant2141A → G. Ref.1 Ref.2
Corresponds to variant rs1889789 [ dbSNP | Ensembl ].
VAR_033772
Natural variant3341V → L.
Corresponds to variant rs5251 [ dbSNP | Ensembl ].
VAR_014468
Natural variant3491A → D in BS3. Ref.8
VAR_001626
Natural variant3951R → W.
Corresponds to variant rs34255952 [ dbSNP | Ensembl ].
VAR_046799
Natural variant4191I → V.
Corresponds to variant rs6650119 [ dbSNP | Ensembl ].
VAR_033773
Natural variant4321Y → H in BS3. Ref.8
VAR_001627
Natural variant4381R → C in BS3. Ref.8
VAR_001628
Natural variant4811T → S.
Corresponds to variant rs12140311 [ dbSNP | Ensembl ].
VAR_046800
Natural variant5621M → T. Ref.1 Ref.2
Corresponds to variant rs5253 [ dbSNP | Ensembl ].
VAR_014469
Natural variant5781K → E. Ref.1 Ref.2
Corresponds to variant rs2275166 [ dbSNP | Ensembl ].
VAR_024409
Natural variant6601S → L.
Corresponds to variant rs5255 [ dbSNP | Ensembl ].
VAR_046801

Experimental info

Sequence conflict2871A → V in CAA83121. Ref.1
Sequence conflict2871A → V in AAB35898. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P51801 [UniParc].

Last modified February 9, 2010. Version 3.
Checksum: 4D28BC19DDD5D412

FASTA68775,446
        10         20         30         40         50         60 
MEEFVGLREG SSGNPVTLQE LWGPCPRIRR GIRGGLEWLK QKLFRLGEDW YFLMTLGVLM 

        70         80         90        100        110        120 
ALVSCAMDLA VESVVRAHQW LYREIGDSHL LRYLSWTVYP VALVSFSSGF SQSITPSSGG 

       130        140        150        160        170        180 
SGIPEVKTML AGVVLEDYLD IKNFGAKVVG LSCTLACGST LFLGKVGPFV HLSVMMAAYL 

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

       250        260        270        280        290        300 
FAATCGAFMF RLLAVFNSEQ ETITSLYKTS FRVDVPFDLP EIFFFVALGG LCGILGSAYL 

       310        320        330        340        350        360 
FCQRIFFGFI RNNRFSSKLL ATSKPVYSAL ATLVLASITY PPSAGRFLAS RLSMKQHLDS 

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

       430        440        450        460        470        480 
MPAGYFMPIF VYGAAIGRLF GETLSFIFPE GIVAGGITNP IMPGGYALAG AAAFSGAVTH 

       490        500        510        520        530        540 
TISTALLAFE VTGQIVHALP VLMAVLAANA IAQSCQPSFY DGTVIVKKLP YLPRILGRNI 

       550        560        570        580        590        600 
GSHRVRVEHF MNHSITTLAK DMPLEEVVKV VTSTDVAKYP LVESTESQIL VGIVRRAQLV 

       610        620        630        640        650        660 
QALKAEPPSW APGHQQCLQD ILAAGCPTEP VTLKLSPETS LHEAHNLFEL LNLHSLFVTS 

       670        680 
RGRAVGCVSW VEMKKAISNL TNPPAPK

« Hide

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: 8041726] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-27; GLY-214; THR-562 AND GLU-578.
Tissue: Kidney.
[2]"Cloning, tissue distribution, and intrarenal localization of ClC chloride channels in human kidney."
Takeuchi Y., Uchida S., Marumo F., Sasaki S.
Kidney Int. 48:1497-1503(1995) [PubMed: 8544406] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-27; GLY-214; THR-562 AND GLU-578.
Tissue: Kidney.
[3]"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: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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.
[5]"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: 11734858] [Abstract]
Cited for: FUNCTIONAL CHARACTERIZATION, TISSUE SPECIFICITY.
[6]"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: 15044642] [Abstract]
Cited for: INVOLVEMENT IN BS4B.
[7]"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: 18310267] [Abstract]
Cited for: INVOLVEMENT IN BS4B.
[8]"Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III."
Simon D.B., Bindra R.S., Mansfield T.A., Nelson-Williams C., Mendonca E., Stone R., Schurman S., Nayir A., Alpay H., Bakkaloglu A., Rodriguez-Soriano J., Morales J.M., Sanjad S.A., Taylor C.M., Pilz D., Brem A., Trachtman H., Griswold W. expand/collapse author list , Richard G.A., John E., Lifton R.P.
Nat. Genet. 17:171-178(1997) [PubMed: 9326936] [Abstract]
Cited for: VARIANTS BS3 LEU-124; THR-204; ASP-349; HIS-432 AND CYS-438.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		Z30644 mRNA. Translation: CAA83121.1.
S80315 mRNA. Translation: AAB35898.1.
AL355994 Genomic DNA. Translation: CAI16140.1.
U93879 Genomic DNA. Translation: AAB65149.1.
IPIIPI00020881.
PIRD57713.
RefSeqNP_000076.2. NM_000085.3.
UniGeneHs.352243.

3D structure databases

ProteinModelPortalP51801.
SMRP51801. Positions 48-687.
ModBaseSearch...

Protein-protein interaction databases

STRINGP51801.

Polymorphism databases

DMDM288558843.

Proteomic databases

PRIDEP51801.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000375679; ENSP00000364831; ENSG00000184908.
GeneID1188.
KEGGhsa:1188.

Organism-specific databases

CTD1188.
GeneCardsGC01P016370.
H-InvDBHIX0020336.
HGNCHGNC:2027. CLCNKB.
MIM602023. gene.
607364. phenotype.
613090. phenotype.
neXtProtNX_P51801.
Orphanet93605. Classic Bartter syndrome.
358. Gitelman syndrome.
89938. Infantile Bartter syndrome with deafness.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG17923.
GeneTreeENSGT00550000074179.
HOGENOMHBG755253.
HOVERGENHBG005332.
InParanoidP51801.
OMAVSCAYLF.
OrthoDBEOG4KD6KM.
PhylomeDBP51801.

Gene expression databases

ArrayExpressP51801.
BgeeP51801.
CleanExHS_CLCNKB.
GenevestigatorP51801.
GermOnlineENSG00000184908. Homo sapiens.

Family and domain databases

InterProIPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002250. Cl_channel-K.
IPR000644. Cysta_beta_synth_core.
[Graphical view]
Gene3DG3DSA:1.10.3080.10. Cl-channel_core. 2 hits.
KOK05018.
PANTHERPTHR11689. Cl-channel_volt. 1 hit.
PfamPF00571. CBS. 2 hits.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSPR00762. CLCHANNEL.
PR01119. CLCHANNELKDY.
SMARTSM00116. CBS. 2 hits.
[Graphical view]
SUPFAMSSF81340. Cl-channel_core. 1 hit.
PROSITEPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

SOURCESearch...

Entry information

Entry nameCLCKB_HUMAN
AccessionPrimary (citable) accession number: P51801
Secondary accession number(s): Q5T5Q8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 9, 2010
Last modified: January 25, 2012
This is version 113 of the entry and version 3 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

Human chromosome 1

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

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