Reviewed, UniProtKB/Swiss-Prot P51801 (CLCKB_HUMAN)

Names and origin

Protein names

Recommended name:
    Chloride channel protein ClC-Kb
      Short name=Chloride channel Kb
Alternative name(s):
    ClC-K2

Gene names

Name:

CLCNKB

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	687 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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	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.6
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. [View classification] Contains 2 CBS domains.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Bartter syndrome Disease mutation
Domain	CBS domain Repeat Transmembrane
Ligand	Chloride
Molecular function	Chloride channel Ionic channel Voltage-gated channel
PTM	Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	chloride transport Inferred from electronic annotation. Source: InterPro excretion Ref.6 Traceable author statement. Source: ProtInc
Cellular component	chloride channel complex Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	chloride ion binding Inferred from electronic annotation. Source: UniProtKB-KW voltage-gated chloride channel activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 687	687	Chloride channel protein ClC-Kb		PRO_0000094459
Regions
	Topological domain	1 – 49	49	Cytoplasmic Potential
	Transmembrane	50 – 69	20	1 Potential
	Transmembrane	91 – 114	24	2 Potential
	Transmembrane	138 – 159	22	3 Potential
	Transmembrane	169 – 188	20	4 Potential
	Transmembrane	200 – 224	25	5 Potential
	Transmembrane	239 – 257	19	6 Potential
	Transmembrane	282 – 302	21	7 Potential
	Transmembrane	325 – 348	24	8 Potential
	Transmembrane	398 – 417	20	9 Potential
	Transmembrane	420 – 438	19	10 Potential
	Transmembrane	466 – 487	22	11 Potential
	Transmembrane	495 – 514	20	12 Potential
	Topological domain	515 – 645	131	Cytoplasmic Potential
	Transmembrane	646 – 664	19	13 Potential
	Topological domain	665 – 687	23	Extracellular Potential
	Domain	551 – 609	59	CBS 1
	Domain	626 – 684	59	CBS 2
Amino acid modifications
	Glycosylation	679	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	4	1	F → L: dbSNP rs34851419.		VAR_033770
	Natural variant	27	1	R → L: dbSNP rs2015352. Ref.1 Ref.2		VAR_046797
	Natural variant	88	1	S → R: dbSNP rs5256.		VAR_014466
	Natural variant	104	1	V → I: dbSNP rs35530360.		VAR_033771
	Natural variant	124	1	P → L in BS3. Ref.6		VAR_001624
	Natural variant	126	1	V → L: dbSNP rs5258.		VAR_046798
	Natural variant	143	1	N → H: dbSNP rs5259.		VAR_014467
	Natural variant	204	1	A → T in BS3. Ref.6		VAR_001625
	Natural variant	214	1	A → G: dbSNP rs1889789. Ref.1 Ref.2		VAR_033772
	Natural variant	334	1	V → L: dbSNP rs5251.		VAR_014468
	Natural variant	349	1	A → D in BS3. Ref.6		VAR_001626
	Natural variant	395	1	R → W: dbSNP rs34255952.		VAR_046799
	Natural variant	419	1	I → V: dbSNP rs6650119.		VAR_033773
	Natural variant	432	1	Y → H in BS3. Ref.6		VAR_001627
	Natural variant	438	1	R → C in BS3. Ref.6		VAR_001628
	Natural variant	481	1	T → S: dbSNP rs12140311.		VAR_046800
	Natural variant	562	1	T → M: dbSNP rs5253. Ref.3		VAR_014469
	Natural variant	578	1	E → K: dbSNP rs2275166. Ref.3		VAR_024409
	Natural variant	660	1	S → L: dbSNP rs5255.		VAR_046801
Experimental info
	Sequence conflict	287	1	A → V in CAA83121. Ref.1
	Sequence conflict	287	1	A → V in AAB35898. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P51801-1 [UniParc]. Last modified October 14, 2008. Version 2. Checksum: 1D28BC04477684D0	FASTA	687	75,417
	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 DTPLEEVVKV VTSTDVAEYP LVESTESQIL VGIVRRAQLV 610 620 630 640 650 660 QALKAEPPSW APGHQQCLQD ILAAGCPTEP VTLKLSPETS LHEAHNLFEL LNLHSLFVTS 670 680 RGRAVGCVSW VEMKKAISNL TNPPAPK

References

	« Hide 'large scale' referencesShow '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 AND GLY-214. 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 AND GLY-214. 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. , 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], VARIANTS MET-562 AND LYS-578.
[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]	"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. , 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
EMBLGenBankDDBJ	Z30644 mRNA. Translation: CAA83121.1. S80315 mRNA. Translation: AAB35898.1. AL355994 Genomic DNA. Translation: CAI16140.1. U93879 Genomic DNA. Translation: AAB65149.1.
IPI	IPI00020881.
PIR	D57713.
RefSeq	NP_000076.2.
UniGene	Hs.352243
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	P51801.
PTM databases
PhosphoSite	P51801.
Genome annotation databases
Ensembl	ENST00000331579; ENSP00000332055; ENSG00000184908; Homo sapiens. [Genome view] ENST00000375667; ENSP00000364819; ENSG00000184908; Homo sapiens. [Genome view] ENST00000375668; ENSP00000364820; ENSG00000184908; Homo sapiens. [Genome view] ENST00000375679; ENSP00000364831; ENSG00000184908; Homo sapiens. [Genome view] ENST00000431772; ENSP00000389344; ENSG00000184908; Homo sapiens. [Genome view]
GeneID	1188.
KEGG	hsa:1188.
UCSC	uc001axw.2. human.
Organism-specific databases
GeneCards	GC01P016242.
H-InvDB	HIX0020336.
HGNC	HGNC:2027. CLCNKB.
MIM	602023. gene. 607364. phenotype.
Orphanet	112. Bartter syndrome. 358. Gitelman syndrome.
PharmGKB	PA26554.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P51801.
HOVERGEN	P51801.
Gene expression databases
ArrayExpress	P51801.
Bgee	P51801.
CleanEx	HS_CLCNKB.
Genevestigator	P51801.
GermOnline	ENSG00000184908. Homo sapiens.
Family and domain databases
InterPro	IPR014743. Cl-channel_core. IPR001807. Cl-channel_volt. IPR002250. Cl_channelKDY. IPR000644. Cysta_beta_synth_core. [Graphical view]
Gene3D	G3DSA:1.10.3080.10. Cl-channel_core. 1 hit.
PANTHER	PTHR11689. Cl-channel_volt. 1 hit.
Pfam	PF00571. CBS. 1 hit. PF00654. Voltage_CLC. 1 hit. [Graphical view]
PRINTS	PR00762. CLCHANNEL. PR01119. CLCHANNELKDY.
SMART	SM00116. CBS. 2 hits. [Graphical view]
PROSITE	PS51371. CBS. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

CLCKB_HUMAN

Accession

Primary (citable) accession number: P51801
Secondary accession number(s): Q5T5Q8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 14, 2008
Last modified:	October 13, 2009
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.