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Protein

Chloride channel protein ClC-Kb

Gene

CLCNKB

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi259CalciumBy similarity1
Metal bindingi261CalciumBy similarity1
Metal bindingi278CalciumBy similarity1
Metal bindingi281CalciumBy similarity1

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:G66-32518-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Chloride channel protein ClC-Kb
Short name:
Chloride channel Kb
Alternative name(s):
ClC-K2
Gene namesi
Name:CLCNKB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:2027. CLCNKB.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 50CytoplasmicSequence analysisAdd BLAST50
Transmembranei51 – 71HelicalSequence analysisAdd BLAST21
Transmembranei94 – 114HelicalSequence analysisAdd BLAST21
Transmembranei161 – 181HelicalSequence analysisAdd BLAST21
Transmembranei202 – 222HelicalSequence analysisAdd BLAST21
Transmembranei236 – 256HelicalSequence analysisAdd BLAST21
Transmembranei282 – 302HelicalSequence analysisAdd BLAST21
Transmembranei325 – 345HelicalSequence analysisAdd BLAST21
Transmembranei396 – 416HelicalSequence analysisAdd BLAST21
Transmembranei417 – 437HelicalSequence analysisAdd BLAST21
Transmembranei452 – 472HelicalSequence analysisAdd BLAST21
Transmembranei486 – 506HelicalSequence analysisAdd BLAST21

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

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Bartter syndrome 3 (BARTS3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:607364
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_001624124P → L in BARTS3. 1 PublicationCorresponds to variant rs121909131dbSNPEnsembl.1
Natural variantiVAR_001625204A → T in BARTS3. 1 PublicationCorresponds to variant rs121909132dbSNPEnsembl.1
Natural variantiVAR_001626349A → D in BARTS3. 1 PublicationCorresponds to variant rs121909134dbSNPEnsembl.1
Natural variantiVAR_001627432Y → H in BARTS3. 1 PublicationCorresponds to variant rs121909135dbSNPEnsembl.1
Natural variantiVAR_001628438R → C in BARTS3. 1 PublicationCorresponds to variant rs121909133dbSNPEnsembl.1
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

Keywords - Diseasei

Bartter syndrome, Deafness, Disease mutation

Organism-specific databases

DisGeNETi1188.
MalaCardsiCLCNKB.
MIMi607364. phenotype.
613090. phenotype.
OpenTargetsiENSG00000184908.
Orphaneti93605. Classic Bartter syndrome.
358. Gitelman syndrome.
89938. Infantile Bartter syndrome with sensorineural deafness.
PharmGKBiPA26554.

Chemistry databases

GuidetoPHARMACOLOGYi701.

Polymorphism and mutation databases

BioMutaiCLCNKB.
DMDMi288558843.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000944591 – 687Chloride channel protein ClC-KbAdd BLAST687

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi679N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP51801.
PeptideAtlasiP51801.
PRIDEiP51801.

PTM databases

iPTMnetiP51801.
PhosphoSitePlusiP51801.

Expressioni

Tissue specificityi

Expressed predominantly in the kidney.1 Publication

Gene expression databases

BgeeiENSG00000184908.
CleanExiHS_CLCNKB.
ExpressionAtlasiP51801. baseline and differential.
GenevisibleiP51801. HS.

Organism-specific databases

HPAiHPA057717.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi107602. 1 interactor.
IntActiP51801. 1 interactor.
MINTiMINT-7969230.
STRINGi9606.ENSP00000364831.

Structurei

3D structure databases

ProteinModelPortaliP51801.
SMRiP51801.
ModBaseiSearch...
MobiDBiSearch...

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.
InParanoidiP51801.
KOiK05018.
OMAiCQRIFFG.
OrthoDBiEOG091G01RJ.
PhylomeDBiP51801.
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. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 2 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P51801-1) [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
MEEFVGLREG SSGNPVTLQE LWGPCPRIRR GIRGGLEWLK QKLFRLGEDW
60 70 80 90 100
YFLMTLGVLM ALVSCAMDLA VESVVRAHQW LYREIGDSHL LRYLSWTVYP
110 120 130 140 150
VALVSFSSGF SQSITPSSGG SGIPEVKTML AGVVLEDYLD IKNFGAKVVG
160 170 180 190 200
LSCTLACGST LFLGKVGPFV HLSVMMAAYL GRVRTTTIGE PENKSKQNEM
210 220 230 240 250
LVAAAAVGVA TVFAAPFSGV LFSIEVMSSH FSVWDYWRGF FAATCGAFMF
260 270 280 290 300
RLLAVFNSEQ ETITSLYKTS FRVDVPFDLP EIFFFVALGG LCGILGSAYL
310 320 330 340 350
FCQRIFFGFI RNNRFSSKLL ATSKPVYSAL ATLVLASITY PPSAGRFLAS
360 370 380 390 400
RLSMKQHLDS LFDNHSWALM TQNSSPPWPE ELDPQHLWWE WYHPRFTIFG
410 420 430 440 450
TLAFFLVMKF WMLILATTIP MPAGYFMPIF VYGAAIGRLF GETLSFIFPE
460 470 480 490 500
GIVAGGITNP IMPGGYALAG AAAFSGAVTH TISTALLAFE VTGQIVHALP
510 520 530 540 550
VLMAVLAANA IAQSCQPSFY DGTVIVKKLP YLPRILGRNI GSHRVRVEHF
560 570 580 590 600
MNHSITTLAK DMPLEEVVKV VTSTDVAKYP LVESTESQIL VGIVRRAQLV
610 620 630 640 650
QALKAEPPSW APGHQQCLQD ILAAGCPTEP VTLKLSPETS LHEAHNLFEL
660 670 680
LNLHSLFVTS RGRAVGCVSW VEMKKAISNL TNPPAPK
Length:687
Mass (Da):75,446
Last modified:February 9, 2010 - v3
Checksum:i4D28BC19DDD5D412
GO
Isoform 2 (identifier: P51801-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: MEEFVGLREG...KQKLFRLGED → MPCPPLLSVP...RAHLRSVSPP
     50-218: Missing.
     616-616: Missing.

Note: No experimental confirmation available.
Show »
Length:517
Mass (Da):56,998
Checksum:iC2F9D66B22BBD4B1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti609S → P in BAG53595 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0337704F → L.Corresponds to variant rs34851419dbSNPEnsembl.1
Natural variantiVAR_04679727R → L.2 PublicationsCorresponds to variant rs2015352dbSNPEnsembl.1
Natural variantiVAR_01446688S → R.Corresponds to variant rs5256dbSNPEnsembl.1
Natural variantiVAR_033771104V → I.Corresponds to variant rs35530360dbSNPEnsembl.1
Natural variantiVAR_001624124P → L in BARTS3. 1 PublicationCorresponds to variant rs121909131dbSNPEnsembl.1
Natural variantiVAR_046798126V → L.Corresponds to variant rs5258dbSNPEnsembl.1
Natural variantiVAR_014467143N → H.Corresponds to variant rs5259dbSNPEnsembl.1
Natural variantiVAR_001625204A → T in BARTS3. 1 PublicationCorresponds to variant rs121909132dbSNPEnsembl.1
Natural variantiVAR_033772214A → G.2 PublicationsCorresponds to variant rs1889789dbSNPEnsembl.1
Natural variantiVAR_069104287A → V.3 PublicationsCorresponds to variant rs34188929dbSNPEnsembl.1
Natural variantiVAR_014468334V → L.Corresponds to variant rs5251dbSNPEnsembl.1
Natural variantiVAR_001626349A → D in BARTS3. 1 PublicationCorresponds to variant rs121909134dbSNPEnsembl.1
Natural variantiVAR_046799395R → W.Corresponds to variant rs34255952dbSNPEnsembl.1
Natural variantiVAR_033773419I → V.Corresponds to variant rs6650119dbSNPEnsembl.1
Natural variantiVAR_001627432Y → H in BARTS3. 1 PublicationCorresponds to variant rs121909135dbSNPEnsembl.1
Natural variantiVAR_001628438R → C in BARTS3. 1 PublicationCorresponds to variant rs121909133dbSNPEnsembl.1
Natural variantiVAR_046800481T → S.Corresponds to variant rs12140311dbSNPEnsembl.1
Natural variantiVAR_014469562M → T.2 PublicationsCorresponds to variant rs5253dbSNPEnsembl.1
Natural variantiVAR_024409578K → E.2 PublicationsCorresponds to variant rs2275166dbSNPEnsembl.1
Natural variantiVAR_046801660S → L.Corresponds to variant rs5255dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0459651 – 49MEEFV…RLGED → MPCPPLLSVPVRAAGEQDRW VREEVTWGGGPTVTGGWGWR AHLRSVSPP in isoform 2. 1 PublicationAdd BLAST49
Alternative sequenceiVSP_04596650 – 218Missing in isoform 2. 1 PublicationAdd BLAST169
Alternative sequenceiVSP_045967616Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z30644 mRNA. Translation: CAA83121.1.
S80315 mRNA. Translation: AAB35898.1.
AK098217 mRNA. Translation: BAG53595.1.
AL355994 Genomic DNA. Translation: CAI16140.1.
AL355994 Genomic DNA. Translation: CAI16141.1.
U93879 Genomic DNA. Translation: AAB65149.1.
CCDSiCCDS168.1. [P51801-1]
CCDS57974.1. [P51801-2]
PIRiD57713.
RefSeqiNP_000076.2. NM_000085.4. [P51801-1]
NP_001159417.2. NM_001165945.2. [P51801-2]
UniGeneiHs.352243.

Genome annotation databases

EnsembliENST00000375667; ENSP00000364819; ENSG00000184908. [P51801-2]
ENST00000375679; ENSP00000364831; ENSG00000184908. [P51801-1]
GeneIDi1188.
KEGGihsa:1188.
UCSCiuc001axx.6. human. [P51801-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z30644 mRNA. Translation: CAA83121.1.
S80315 mRNA. Translation: AAB35898.1.
AK098217 mRNA. Translation: BAG53595.1.
AL355994 Genomic DNA. Translation: CAI16140.1.
AL355994 Genomic DNA. Translation: CAI16141.1.
U93879 Genomic DNA. Translation: AAB65149.1.
CCDSiCCDS168.1. [P51801-1]
CCDS57974.1. [P51801-2]
PIRiD57713.
RefSeqiNP_000076.2. NM_000085.4. [P51801-1]
NP_001159417.2. NM_001165945.2. [P51801-2]
UniGeneiHs.352243.

3D structure databases

ProteinModelPortaliP51801.
SMRiP51801.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107602. 1 interactor.
IntActiP51801. 1 interactor.
MINTiMINT-7969230.
STRINGi9606.ENSP00000364831.

Chemistry databases

GuidetoPHARMACOLOGYi701.

PTM databases

iPTMnetiP51801.
PhosphoSitePlusiP51801.

Polymorphism and mutation databases

BioMutaiCLCNKB.
DMDMi288558843.

Proteomic databases

PaxDbiP51801.
PeptideAtlasiP51801.
PRIDEiP51801.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375667; ENSP00000364819; ENSG00000184908. [P51801-2]
ENST00000375679; ENSP00000364831; ENSG00000184908. [P51801-1]
GeneIDi1188.
KEGGihsa:1188.
UCSCiuc001axx.6. human. [P51801-1]

Organism-specific databases

CTDi1188.
DisGeNETi1188.
GeneCardsiCLCNKB.
H-InvDBHIX0020336.
HGNCiHGNC:2027. CLCNKB.
HPAiHPA057717.
MalaCardsiCLCNKB.
MIMi602023. gene.
607364. phenotype.
613090. phenotype.
neXtProtiNX_P51801.
OpenTargetsiENSG00000184908.
Orphaneti93605. Classic Bartter syndrome.
358. Gitelman syndrome.
89938. Infantile Bartter syndrome with sensorineural deafness.
PharmGKBiPA26554.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0476. Eukaryota.
COG0038. LUCA.
GeneTreeiENSGT00760000119109.
HOGENOMiHOG000231297.
HOVERGENiHBG005332.
InParanoidiP51801.
KOiK05018.
OMAiCQRIFFG.
OrthoDBiEOG091G01RJ.
PhylomeDBiP51801.
TreeFamiTF300522.

Enzyme and pathway databases

BioCyciZFISH:G66-32518-MONOMER.
ReactomeiR-HSA-2672351. Stimuli-sensing channels.

Miscellaneous databases

ChiTaRSiCLCNKB. human.
GeneWikiiCLCNKB.
GenomeRNAii1188.
PROiP51801.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000184908.
CleanExiHS_CLCNKB.
ExpressionAtlasiP51801. baseline and differential.
GenevisibleiP51801. 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. 2 hits.
[Graphical view]
SUPFAMiSSF81340. SSF81340. 2 hits.
PROSITEiPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCLCKB_HUMAN
AccessioniPrimary (citable) accession number: P51801
Secondary accession number(s): B3KUY3, Q5T5Q7, Q5T5Q8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 9, 2010
Last modified: November 2, 2016
This is version 155 of the entry and version 3 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

Miscellaneous

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

Keywords - Technical termi

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. 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.