Q8WZ55 (BSND_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Barttin

Gene names

Name:	BSND
Synonyms:	BART

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	320 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions as a beta-subunit for CLCNKA and CLCNKB chloride channels. In the kidney CLCNK/BSND heteromers mediate chloride reabsorption by facilitating its basolateral efflux. In the stria, CLCNK/BSND channels drive potassium secretion by recycling chloride for the basolateral SLC12A2 cotransporter. Ref.3 Ref.4
Subunit structure	Interacts with CLCNK channels. Forms heteromers with CLCNKA in the thin ascending limb of Henle and with CLCNKB in the thick ascending limb and more distal segments By similarity. Ref.3 Ref.4
Subcellular location	Cell membrane; Multi-pass membrane protein By similarity. Cytoplasm By similarity. Note: A significant amount also observed intracellularly. Staining in membranes of the renal tubule and of potassium-secreting epithelia of the inner ear is basolateral By similarity. Ref.3 Ref.4
Tissue specificity	Expressed primarily in kidney. Expressed in specific nephron segments and in the stria vascularis of the inner ear. Ref.1
Involvement in disease	Defects in BSND are the cause of Bartter syndrome type 4A (BS4A) [MIM:602522]; also known as infantile Bartter syndrome with sensorineural deafness. BS refers to a group of autosomal recessive disorders characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. BS4A is associated with sensorineural deafness. Ref.1 Ref.4 Ref.5 Ref.6
Sequence caution	The sequence BC069510 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Disease	Bartter syndrome Deafness Disease mutation
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	chloride transport Inferred from sequence or structural similarity. Source: GOC
Cellular component	basolateral plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB protein complex Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 320	320	Barttin		PRO_0000064999
Regions
	Topological domain	1 – 5	5	Cytoplasmic Potential
	Transmembrane	6 – 26	21	Helical; Potential
	Topological domain	27 – 32	6	Extracellular Potential
	Transmembrane	33 – 53	21	Helical; Potential
	Topological domain	54 – 320	267	Cytoplasmic Potential
Natural variations
	Natural variant	8	1	R → L in BS4A; completely abolishes CLCNKA activation; mutated protein fails to increase surface expression of CLCNKA; intracellular localization; probably retained in the ER. Ref.1 Ref.4 Ref.5		VAR_019783
	Natural variant	8	1	R → W in BS4A; completely abolishes CLCNKA activation. Ref.1 Ref.4		VAR_019784
	Natural variant	10	1	G → S in BS4A; increases CLCNKA currents over those obtained with wild-type; still activates CLCNKA to an extent similar to that of wild-type; intracellular but some plasma membrane localization as well. Ref.1 Ref.4 Ref.5		VAR_019785
	Natural variant	43	1	V → I. Corresponds to variant rs34561376 [ dbSNP | Ensembl ].		VAR_061564
	Natural variant	47	1	G → R in BS4A; atypical; might be due to a less severe loss of function. Ref.6		VAR_019786
Experimental info
	Mutagenesis	98	1	Y → A: Stimulation of CLCNKA and CLCNKB currents enhanced; intense localization in the plasma membrane with no intracellular localization observed. Ref.3 Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q8WZ55 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: DED232CAF85AE5AA	FASTA	320	35,197
	10 20 30 40 50 60 MADEKTFRIG FIVLGLFLLA LGTFLMSHDR PQVYGTFYAM GSVMVIGGII WSMCQCYPKI 70 80 90 100 110 120 TFVPADSDFQ GILSPKAMGL LENGLAAEMK SPSPQPPYVR LWEEAAYDQS LPDFSHIQMK 130 140 150 160 170 180 VMSYSEDHRS LLAPEMGQPK LGTSDGGEGG PGDVQAWMEA AVVIHKGSDE SEGERRLTQS 190 200 210 220 230 240 WPGPLACPQG PAPLASFQDD LDMDSSEGSS PNASPHDREE ACSPQQEPQG CRCPLDRFQD 250 260 270 280 290 300 FALIDAPTLE DEPQEGQQWE IALPNNWQRY PRTKVEEKEA SDTGGEEPEK EEEDLYYGLP 310 320 DGAGDLLPDK ELGFEPDTQG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure." Birkenhaeger R., Otto E., Schuermann M.J., Vollmer M., Ruf E.-M., Maier-Lutz I., Beekmann F., Fekete A., Omran H., Feldmann D., Milford D.V., Jeck N., Konrad M., Landau D., Knoers N.V.A.M., Antignac C., Sudbrak R., Kispert A., Hildebrandt F. Nat. Genet. 29:310-314(2001) [PubMed: 11687798] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANTS BS4A LEU-8; TRP-8 AND SER-10. Tissue: Kidney.
[2]	"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].
[3]	"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: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-98.
[4]	"Barttin increases surface expression and changes current properties of ClC-K channels." Waldegger S., Jeck N., Barth P., Peters M., Vitzthum H., Wolf K., Kurtz A., Konrad M., Seyberth H.W. Pflugers Arch. 444:411-418(2002) [PubMed: 12111250] [Abstract] Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS BS4A LEU-8; TRP-8 AND SER-10.
[5]	"Molecular mechanisms of Bartter syndrome caused by mutations in the BSND gene." Hayama A., Rai T., Sasaki S., Uchida S. Histochem. Cell Biol. 119:485-493(2003) [PubMed: 12761627] [Abstract] Cited for: MUTAGENESIS OF TYR-98, CHARACTERIZATION OF VARIANTS BS4A LEU-8 AND SER-10.
[6]	"Atypical Bartter syndrome with sensorineural deafness with G47R mutation of the beta-subunit for ClC-Ka and ClC-Kb chloride channels, barttin." Miyamura N., Matsumoto K., Taguchi T., Tokunaga H., Nishikawa T., Nishida K., Toyonaga T., Sakakida M., Araki E. J. Clin. Endocrinol. Metab. 88:781-786(2003) [PubMed: 12574213] [Abstract] Cited for: VARIANT BS4A ARG-47.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY034632 mRNA. Translation: AAK57750.1. BC069510 mRNA. No translation available.
IPI	IPI00103841.
RefSeq	NP_476517.1. NM_057176.2.
UniGene	Hs.151291.
3D structure databases
ProteinModelPortal	Q8WZ55.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4536104.
STRING	Q8WZ55.
PTM databases
PhosphoSite	Q8WZ55.
Polymorphism databases
DMDM	54035724.
Proteomic databases
PRIDE	Q8WZ55.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000371265; ENSP00000360312; ENSG00000162399.
GeneID	7809.
KEGG	hsa:7809.
NMPDR	fig|9606.3.peg.1235.
UCSC	uc001cye.1. human.
Organism-specific databases
CTD	7809.
GeneCards	GC01P055464.
H-InvDB	HIX0028661.
HGNC	HGNC:16512. BSND.
MIM	602522. phenotype. 606412. gene.
neXtProt	NX_Q8WZ55.
Orphanet	90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB. 89938. Infantile Bartter syndrome with deafness.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00390000008549.
HOGENOM	HBG126312.
HOVERGEN	HBG050739.
InParanoid	Q8WZ55.
OMA	EAAYDQS.
OrthoDB	EOG4T4CW5.
PhylomeDB	Q8WZ55.
Gene expression databases
ArrayExpress	Q8WZ55.
Bgee	Q8WZ55.
CleanEx	HS_BSND.
Genevestigator	Q8WZ55.
GermOnline	ENSG00000162399. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other
NextBio	30203.
SOURCE	Search...

Entry information

Entry name

BSND_HUMAN

Accession

Primary (citable) accession number: Q8WZ55
Secondary accession number(s): Q6NT28

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	March 1, 2002
Last modified:	January 25, 2012
This is version 74 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.