UniProtKB - P51801 (CLCKB_HUMAN)
Protein
Chloride channel protein ClC-Kb
Gene
CLCNKB
Organism
Homo sapiens (Human)
Status
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
Miscellaneous
Compared with CLCNKA/BSND, CLCNKB/BSND is more sensitive to pH and less responsive to Ca2+.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 121 | ChlorideBy similarity | 1 | |
Metal bindingi | 259 | CalciumBy similarity | 1 | |
Metal bindingi | 261 | CalciumBy similarity | 1 | |
Metal bindingi | 278 | CalciumBy similarity | 1 | |
Metal bindingi | 281 | CalciumBy similarity | 1 | |
Binding sitei | 426 | Chloride; via amide nitrogenBy similarity | 1 |
GO - Molecular functioni
- metal ion binding Source: UniProtKB-KW
- voltage-gated chloride channel activity Source: GO_Central
GO - Biological processi
- chloride transport Source: GO_Central
- excretion Source: ProtInc
- ion transmembrane transport Source: Reactome
- regulation of ion transmembrane transport Source: UniProtKB-KW
Keywordsi
Molecular function | Chloride channel, Ion channel, Voltage-gated channel |
Biological process | Ion transport, Transport |
Ligand | Calcium, Chloride, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | P51801 |
Reactomei | R-HSA-2672351, Stimuli-sensing channels |
Names & Taxonomyi
Protein namesi | Recommended name: Chloride channel protein ClC-KbShort name: Chloride channel Kb Alternative name(s): ClC-K2 |
Gene namesi | Name:CLCNKB |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000184908.17 |
HGNCi | HGNC:2027, CLCNKB |
MIMi | 602023, gene |
neXtProti | NX_P51801 |
Subcellular locationi
Plasma membrane
Plasma Membrane
- integral component of plasma membrane Source: GO_Central
- plasma membrane Source: Reactome
Other locations
- chloride channel complex Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 50 | CytoplasmicBy similarityAdd BLAST | 50 | |
Transmembranei | 51 – 82 | HelicalBy similarityAdd BLAST | 32 | |
Transmembranei | 91 – 111 | HelicalBy similarityAdd BLAST | 21 | |
Intramembranei | 116 – 127 | HelicalBy similarityAdd BLAST | 12 | |
Transmembranei | 141 – 160 | HelicalBy similarityAdd BLAST | 20 | |
Transmembranei | 161 – 180 | HelicalBy similarityAdd BLAST | 20 | |
Intramembranei | 203 – 224 | HelicalBy similarityAdd BLAST | 22 | |
Transmembranei | 236 – 255 | HelicalBy similarityAdd BLAST | 20 | |
Transmembranei | 282 – 310 | HelicalBy similarityAdd BLAST | 29 | |
Transmembranei | 325 – 342 | HelicalBy similarityAdd BLAST | 18 | |
Intramembranei | 349 – 360 | HelicalBy similarityAdd BLAST | 12 | |
Transmembranei | 400 – 420 | HelicalBy similarityAdd BLAST | 21 | |
Transmembranei | 421 – 440 | HelicalBy similarityAdd BLAST | 20 | |
Intramembranei | 464 – 496 | HelicalBy similarityAdd BLAST | 33 | |
Transmembranei | 500 – 520 | HelicalBy similarityAdd BLAST | 21 | |
Topological domaini | 521 – 687 | CytoplasmicBy similarityAdd BLAST | 167 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_001624 | 124 | P → L in BARTS3. 1 PublicationCorresponds to variant dbSNP:rs121909131EnsemblClinVar. | 1 | |
Natural variantiVAR_001625 | 204 | A → T in BARTS3. 1 PublicationCorresponds to variant dbSNP:rs121909132Ensembl. | 1 | |
Natural variantiVAR_001626 | 349 | A → D in BARTS3. 1 PublicationCorresponds to variant dbSNP:rs121909134EnsemblClinVar. | 1 | |
Natural variantiVAR_001627 | 432 | Y → H in BARTS3. 1 PublicationCorresponds to variant dbSNP:rs121909135EnsemblClinVar. | 1 | |
Natural variantiVAR_001628 | 438 | R → C in BARTS3. 1 PublicationCorresponds to variant dbSNP:rs121909133EnsemblClinVar. | 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.
Related information in OMIMKeywords - Diseasei
Bartter syndrome, Deafness, Disease mutationOrganism-specific databases
DisGeNETi | 1188 |
MalaCardsi | CLCNKB |
MIMi | 607364, phenotype 613090, phenotype |
OpenTargetsi | ENSG00000184908 |
Orphaneti | 93605, Classic Bartter syndrome 358, Gitelman syndrome 89938, Infantile Bartter syndrome with sensorineural deafness |
PharmGKBi | PA26554 |
Miscellaneous databases
Pharosi | P51801, Tchem |
Chemistry databases
DrugCentrali | P51801 |
GuidetoPHARMACOLOGYi | 701 |
Polymorphism and mutation databases
BioMutai | CLCNKB |
DMDMi | 288558843 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000094459 | 1 – 687 | Chloride channel protein ClC-KbAdd BLAST | 687 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 193 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
jPOSTi | P51801 |
MassIVEi | P51801 |
PaxDbi | P51801 |
PeptideAtlasi | P51801 |
PRIDEi | P51801 |
ProteomicsDBi | 56400 [P51801-1] 64546 |
PTM databases
GlyGeni | P51801, 1 site |
iPTMneti | P51801 |
PhosphoSitePlusi | P51801 |
Expressioni
Tissue specificityi
Expressed predominantly in the kidney.1 Publication
Gene expression databases
Bgeei | ENSG00000184908, Expressed in adult mammalian kidney and 103 other tissues |
ExpressionAtlasi | P51801, baseline and differential |
Genevisiblei | P51801, HS |
Organism-specific databases
HPAi | ENSG00000184908, Tissue enhanced (kidney, salivary gland) |
Interactioni
Subunit structurei
Interacts with BSND. Forms heteromers with BSND in the thick ascending limb of Henle and more distal segments (By similarity).
By similarityProtein-protein interaction databases
IntActi | P51801, 1 interactor |
MINTi | P51801 |
STRINGi | 9606.ENSP00000364831 |
Miscellaneous databases
RNActi | P51801, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 551 – 609 | CBS 1PROSITE-ProRule annotationAdd BLAST | 59 | |
Domaini | 626 – 684 | CBS 2PROSITE-ProRule annotationAdd BLAST | 59 |
Sequence similaritiesi
Keywords - Domaini
CBS domain, Repeat, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0476, Eukaryota |
GeneTreei | ENSGT00940000158748 |
HOGENOMi | CLU_006904_4_0_1 |
InParanoidi | P51801 |
OMAi | YWRAFFS |
OrthoDBi | 1152704at2759 |
PhylomeDBi | P51801 |
TreeFami | TF300522 |
Family and domain databases
Gene3Di | 1.10.3080.10, 1 hit |
InterProi | View protein in InterPro IPR000644, CBS_dom IPR014743, Cl-channel_core IPR001807, Cl-channel_volt-gated IPR002250, Cl_channel-K |
Pfami | View protein in Pfam PF00571, CBS, 1 hit PF00654, Voltage_CLC, 1 hit |
PRINTSi | PR00762, CLCHANNEL PR01119, CLCHANNELKDY |
SMARTi | View protein in SMART SM00116, CBS, 2 hits |
SUPFAMi | SSF81340, SSF81340, 1 hit |
PROSITEi | View protein in PROSITE PS51371, CBS, 2 hits |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P51801-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A087X136 | A0A087X136_HUMAN | Chloride channel protein ClC-Kb | CLCNKB | 463 | Annotation score: | ||
Q5T5Q6 | Q5T5Q6_HUMAN | Chloride channel protein ClC-Kb | CLCNKB | 146 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 609 | S → P in BAG53595 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_033770 | 4 | F → L. Corresponds to variant dbSNP:rs34851419EnsemblClinVar. | 1 | |
Natural variantiVAR_046797 | 27 | R → L2 PublicationsCorresponds to variant dbSNP:rs2015352EnsemblClinVar. | 1 | |
Natural variantiVAR_014466 | 88 | S → R. Corresponds to variant dbSNP:rs5256EnsemblClinVar. | 1 | |
Natural variantiVAR_033771 | 104 | V → I. Corresponds to variant dbSNP:rs35530360EnsemblClinVar. | 1 | |
Natural variantiVAR_001624 | 124 | P → L in BARTS3. 1 PublicationCorresponds to variant dbSNP:rs121909131EnsemblClinVar. | 1 | |
Natural variantiVAR_014467 | 143 | N → H. Corresponds to variant dbSNP:rs5259Ensembl. | 1 | |
Natural variantiVAR_001625 | 204 | A → T in BARTS3. 1 PublicationCorresponds to variant dbSNP:rs121909132Ensembl. | 1 | |
Natural variantiVAR_033772 | 214 | A → G2 PublicationsCorresponds to variant dbSNP:rs1889789EnsemblClinVar. | 1 | |
Natural variantiVAR_069104 | 287 | A → V3 PublicationsCorresponds to variant dbSNP:rs7367494EnsemblClinVar. | 1 | |
Natural variantiVAR_014468 | 334 | V → L. Corresponds to variant dbSNP:rs5251Ensembl. | 1 | |
Natural variantiVAR_001626 | 349 | A → D in BARTS3. 1 PublicationCorresponds to variant dbSNP:rs121909134EnsemblClinVar. | 1 | |
Natural variantiVAR_046799 | 395 | R → W. Corresponds to variant dbSNP:rs34255952Ensembl. | 1 | |
Natural variantiVAR_033773 | 419 | I → V. Corresponds to variant dbSNP:rs6650119EnsemblClinVar. | 1 | |
Natural variantiVAR_001627 | 432 | Y → H in BARTS3. 1 PublicationCorresponds to variant dbSNP:rs121909135EnsemblClinVar. | 1 | |
Natural variantiVAR_001628 | 438 | R → C in BARTS3. 1 PublicationCorresponds to variant dbSNP:rs121909133EnsemblClinVar. | 1 | |
Natural variantiVAR_046800 | 481 | T → S. Corresponds to variant dbSNP:rs12140311EnsemblClinVar. | 1 | |
Natural variantiVAR_014469 | 562 | M → T2 PublicationsCorresponds to variant dbSNP:rs5253EnsemblClinVar. | 1 | |
Natural variantiVAR_024409 | 578 | K → E2 PublicationsCorresponds to variant dbSNP:rs2275166EnsemblClinVar. | 1 | |
Natural variantiVAR_046801 | 660 | S → L. Corresponds to variant dbSNP:rs5255EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_045965 | 1 – 49 | MEEFV…RLGED → MPCPPLLSVPVRAAGEQDRW VREEVTWGGGPTVTGGWGWR AHLRSVSPP in isoform 2. 1 PublicationAdd BLAST | 49 | |
Alternative sequenceiVSP_045966 | 50 – 218 | Missing in isoform 2. 1 PublicationAdd BLAST | 169 | |
Alternative sequenceiVSP_045967 | 616 | Missing in isoform 2. 1 Publication | 1 |
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 No translation available. U93879 Genomic DNA Translation: AAB65149.1 |
CCDSi | CCDS168.1 [P51801-1] CCDS57974.1 [P51801-2] |
PIRi | D57713 |
RefSeqi | NP_000076.2, NM_000085.4 [P51801-1] NP_001159417.2, NM_001165945.2 [P51801-2] |
Genome annotation databases
Ensembli | ENST00000375667; ENSP00000364819; ENSG00000184908 [P51801-2] ENST00000375679; ENSP00000364831; ENSG00000184908 [P51801-1] |
GeneIDi | 1188 |
KEGGi | hsa:1188 |
UCSCi | uc001axx.6, human [P51801-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
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 No translation available. U93879 Genomic DNA Translation: AAB65149.1 |
CCDSi | CCDS168.1 [P51801-1] CCDS57974.1 [P51801-2] |
PIRi | D57713 |
RefSeqi | NP_000076.2, NM_000085.4 [P51801-1] NP_001159417.2, NM_001165945.2 [P51801-2] |
3D structure databases
SMRi | P51801 |
ModBasei | Search... |
Protein-protein interaction databases
IntActi | P51801, 1 interactor |
MINTi | P51801 |
STRINGi | 9606.ENSP00000364831 |
Chemistry databases
DrugCentrali | P51801 |
GuidetoPHARMACOLOGYi | 701 |
PTM databases
GlyGeni | P51801, 1 site |
iPTMneti | P51801 |
PhosphoSitePlusi | P51801 |
Polymorphism and mutation databases
BioMutai | CLCNKB |
DMDMi | 288558843 |
Proteomic databases
jPOSTi | P51801 |
MassIVEi | P51801 |
PaxDbi | P51801 |
PeptideAtlasi | P51801 |
PRIDEi | P51801 |
ProteomicsDBi | 56400 [P51801-1] 64546 |
Protocols and materials databases
Antibodypediai | 14485, 132 antibodies |
Genome annotation databases
Ensembli | ENST00000375667; ENSP00000364819; ENSG00000184908 [P51801-2] ENST00000375679; ENSP00000364831; ENSG00000184908 [P51801-1] |
GeneIDi | 1188 |
KEGGi | hsa:1188 |
UCSCi | uc001axx.6, human [P51801-1] |
Organism-specific databases
CTDi | 1188 |
DisGeNETi | 1188 |
EuPathDBi | HostDB:ENSG00000184908.17 |
GeneCardsi | CLCNKB |
HGNCi | HGNC:2027, CLCNKB |
HPAi | ENSG00000184908, Tissue enhanced (kidney, salivary gland) |
MalaCardsi | CLCNKB |
MIMi | 602023, gene 607364, phenotype 613090, phenotype |
neXtProti | NX_P51801 |
OpenTargetsi | ENSG00000184908 |
Orphaneti | 93605, Classic Bartter syndrome 358, Gitelman syndrome 89938, Infantile Bartter syndrome with sensorineural deafness |
PharmGKBi | PA26554 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0476, Eukaryota |
GeneTreei | ENSGT00940000158748 |
HOGENOMi | CLU_006904_4_0_1 |
InParanoidi | P51801 |
OMAi | YWRAFFS |
OrthoDBi | 1152704at2759 |
PhylomeDBi | P51801 |
TreeFami | TF300522 |
Enzyme and pathway databases
PathwayCommonsi | P51801 |
Reactomei | R-HSA-2672351, Stimuli-sensing channels |
Miscellaneous databases
BioGRID-ORCSi | 1188, 5 hits in 842 CRISPR screens |
ChiTaRSi | CLCNKB, human |
GeneWikii | CLCNKB |
GenomeRNAii | 1188 |
Pharosi | P51801, Tchem |
PROi | PR:P51801 |
RNActi | P51801, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000184908, Expressed in adult mammalian kidney and 103 other tissues |
ExpressionAtlasi | P51801, baseline and differential |
Genevisiblei | P51801, HS |
Family and domain databases
Gene3Di | 1.10.3080.10, 1 hit |
InterProi | View protein in InterPro IPR000644, CBS_dom IPR014743, Cl-channel_core IPR001807, Cl-channel_volt-gated IPR002250, Cl_channel-K |
Pfami | View protein in Pfam PF00571, CBS, 1 hit PF00654, Voltage_CLC, 1 hit |
PRINTSi | PR00762, CLCHANNEL PR01119, CLCHANNELKDY |
SMARTi | View protein in SMART SM00116, CBS, 2 hits |
SUPFAMi | SSF81340, SSF81340, 1 hit |
PROSITEi | View protein in PROSITE PS51371, CBS, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CLCKB_HUMAN | |
Accessioni | P51801Primary (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: | December 2, 2020 | |
This is version 184 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- 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 - 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