P51800 (CLCKA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Chloride channel protein ClC-Ka
Short name=Chloride channel Ka

Alternative name(s):
ClC-K1

Gene names

Name:

CLCNKA

Organism

Homo sapiens (Human)

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.
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.
Subunit structure	Interacts with BSND. Forms heteromers with BSND in the thin ascending limb of Henle By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Expressed predominantly in the kidney. All nephron segments expressing BSND also express CLCNK proteins. Ref.5
Involvement in disease	Defects in CLCNKA 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.7 Ref.8
Sequence similarities	Belongs to the chloride channel (TC 2.A.49) family. CLCNKA subfamily. [View classification] Contains 2 CBS domains.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Bartter syndrome Deafness Disease mutation
Domain	CBS domain Repeat Transmembrane Transmembrane helix
Ligand	Chloride
Molecular function	Chloride channel Ionic channel Voltage-gated channel
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	excretion Traceable author statement. Source: ProtInc
Cellular component	chloride channel complex Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	voltage-gated chloride channel activity 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-Ka

PRO_0000094455

Regions

Transmembrane

52 – 72

21

Helical; Potential

Transmembrane

161 – 181

21

Helical; Potential

Transmembrane

202 – 222

21

Helical; Potential

Transmembrane

236 – 256

21

Helical; Potential

Transmembrane

282 – 302

21

Helical; Potential

Transmembrane

329 – 349

21

Helical; Potential

Transmembrane

396 – 416

21

Helical; Potential

Transmembrane

417 – 437

21

Helical; Potential

Transmembrane

452 – 472

21

Helical; Potential

Transmembrane

486 – 506

21

Helical; Potential

Domain

551 – 609

59

CBS 1

Domain

626 – 684

59

CBS 2

Amino acid modifications

Modified residue

660

1

Phosphoserine Ref.6

Natural variations

Natural variant

8

1

R → H.
Corresponds to variant rs9442189 [ dbSNP | Ensembl ].

VAR_048695

Natural variant

45

1

R → H.
Corresponds to variant rs35932996 [ dbSNP | Ensembl ].

VAR_033768

Natural variant

67

1

M → I. Ref.3
Corresponds to variant rs17855678 [ dbSNP | Ensembl ].

VAR_030784

Natural variant

80

1

W → C in BS4B; a patient also carrying a mutation in CLCNKB. Ref.8

VAR_063074

Natural variant

83

1

R → G.
Corresponds to variant rs10927887 [ dbSNP | Ensembl ].

VAR_019787

Natural variant

287

1

A → V.
Corresponds to variant rs34188929 [ dbSNP | Ensembl ].

VAR_033769

Natural variant

315

1

Y → F. Ref.3
Corresponds to variant rs12126269 [ dbSNP | Ensembl ].

VAR_019788

Natural variant

447

1

A → T.
Corresponds to variant rs1805152 [ dbSNP | Ensembl ].

VAR_014465

Natural variant

534

1

R → W.
Corresponds to variant rs12140223 [ dbSNP | Ensembl ].

VAR_059209

Natural variant

683

1

P → L.
Corresponds to variant rs12746751 [ dbSNP | Ensembl ].

VAR_061095

Experimental info

Sequence conflict

615

1

Missing in AAH53869. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

687

Helix Strand Turn

Details...

Helix

547 – 550

4

Helix

564 – 572

9

Beta strand

577 – 583

7

Turn

585 – 587

3

Beta strand

589 – 595

7

Helix

596 – 604

9

Helix

618 – 623

6

Helix

641 – 650

10

Beta strand

654 – 660

7

Beta strand

663 – 669

7

Helix

670 – 681

12

Sequences

	Sequence		Length	Mass (Da)
	P51800 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: E97C6928470A4460	FASTA	687	75,285
	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

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]. Tissue: Kidney.
[2]	"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].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ILE-67 AND PHE-315. Tissue: Colon.
[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: TISSUE SPECIFICITY.
[6]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-660, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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]	"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: VARIANT BS4B CYS-80.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z30643 mRNA. Translation: CAA83120.1.
AL355994 Genomic DNA. Translation: CAI16137.1.
BC048282 mRNA. Translation: AAH48282.1.
BC053869 mRNA. Translation: AAH53869.1.
U93878 Genomic DNA. Translation: AAB65148.1.

IPI

IPI00020879.

PIR

C57713.

RefSeq

NP_001036169.1. NM_001042704.1.
NP_004061.3. NM_004070.3.

UniGene

Hs.352243.
Hs.591533.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2PFI	X-ray	1.60	A/B	533-687	[»]

ProteinModelPortal

P51800.

SMR

P51800. Positions 48-687.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29432N.

STRING

P51800.

Polymorphism databases

DMDM

1705857.

Proteomic databases

PRIDE

P51800.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000331433; ENSP00000332771; ENSG00000186510.

GeneID

1187.

KEGG

hsa:1187.

UCSC

uc001axu.1. human.

Organism-specific databases

CTD

1187.

GeneCards

GC01P016345.

H-InvDB

HIX0056769.

HGNC

HGNC:2026. CLCNKA.

MIM

602024. gene.
613090. phenotype.

neXtProt

NX_P51800.

Orphanet

89938. Infantile Bartter syndrome with deafness.

PharmGKB

PA26553.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17923.

GeneTree

ENSGT00550000074179.

HOGENOM

HBG755253.

HOVERGEN

HBG005332.

InParanoid

P51800.

OMA

TNRFSSK.

PhylomeDB

P51800.

Gene expression databases

ArrayExpress

P51800.

Bgee

P51800.

CleanEx

HS_CLCNKA.

Genevestigator

P51800.

GermOnline

ENSG00000186510. Homo sapiens.

Family and domain databases

InterPro

IPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt-gated.
IPR002250. Cl_channel-K.
IPR000644. Cysta_beta_synth_core.
[Graphical view]

Gene3D

G3DSA:1.10.3080.10. Cl-channel_core. 2 hits.

KO

K05017.

PANTHER

PTHR11689. Cl-channel_volt. 1 hit.

Pfam

PF00571. CBS. 2 hits.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]

PRINTS

PR00762. CLCHANNEL.
PR01119. CLCHANNELKDY.

SMART

SM00116. CBS. 1 hit.
[Graphical view]

SUPFAM

SSF81340. Cl-channel_core. 1 hit.

PROSITE

PS51371. CBS. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB04552. Niflumic Acid.

NextBio

4912.

SOURCE

Search...

Entry information

Entry name

CLCKA_HUMAN

Accession

Primary (citable) accession number: P51800
Secondary accession number(s): Q5T5P8, Q7Z6D1, Q86VT1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 25, 2012
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.