BSND_HUMAN
ID BSND_HUMAN Reviewed; 320 AA.
AC Q8WZ55; Q6NT28;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Barttin;
GN Name=BSND; Synonyms=BART;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS BARTS4A LEU-8;
RP TRP-8 AND SER-10.
RC TISSUE=Kidney;
RX PubMed=11687798; DOI=10.1038/ng752;
RA Birkenhaeger R., Otto E., Schuermann M.J., Vollmer M., Ruf E.-M.,
RA Maier-Lutz I., Beekmann F., Fekete A., Omran H., Feldmann D., Milford D.V.,
RA Jeck N., Konrad M., Landau D., Knoers N.V.A.M., Antignac C., Sudbrak R.,
RA Kispert A., Hildebrandt F.;
RT "Mutation of BSND causes Bartter syndrome with sensorineural deafness and
RT kidney failure.";
RL Nat. Genet. 29:310-314(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-98.
RX PubMed=11734858; DOI=10.1038/35107099;
RA Estevez R., Boettger T., Stein V., Birkenhaeger R., Otto E.,
RA Hildebrandt F., Jentsch T.J.;
RT "Barttin is a Cl- channel beta-subunit crucial for renal Cl-reabsorption
RT and inner ear K+ secretion.";
RL Nature 414:558-561(2001).
RN [4]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS
RP BARTS4A LEU-8; TRP-8 AND SER-10.
RX PubMed=12111250; DOI=10.1007/s00424-002-0819-8;
RA Waldegger S., Jeck N., Barth P., Peters M., Vitzthum H., Wolf K., Kurtz A.,
RA Konrad M., Seyberth H.W.;
RT "Barttin increases surface expression and changes current properties of
RT ClC-K channels.";
RL Pflugers Arch. 444:411-418(2002).
RN [5]
RP MUTAGENESIS OF TYR-98, AND CHARACTERIZATION OF VARIANTS BARTS4A LEU-8 AND
RP SER-10.
RX PubMed=12761627; DOI=10.1007/s00418-003-0535-2;
RA Hayama A., Rai T., Sasaki S., Uchida S.;
RT "Molecular mechanisms of Bartter syndrome caused by mutations in the BSND
RT gene.";
RL Histochem. Cell Biol. 119:485-493(2003).
RN [6]
RP VARIANT BARTS4A ARG-47.
RX PubMed=12574213; DOI=10.1210/jc.2002-021398;
RA Miyamura N., Matsumoto K., Taguchi T., Tokunaga H., Nishikawa T.,
RA Nishida K., Toyonaga T., Sakakida M., Araki E.;
RT "Atypical Bartter syndrome with sensorineural deafness with G47R mutation
RT of the beta-subunit for ClC-Ka and ClC-Kb chloride channels, barttin.";
RL J. Clin. Endocrinol. Metab. 88:781-786(2003).
RN [7]
RP PALMITOYLATION AT CYS-54 AND CYS-56, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF CYS-54 AND CYS-56.
RX PubMed=26013830; DOI=10.1074/jbc.m114.631705;
RA Steinke K.V., Gorinski N., Wojciechowski D., Todorov V., Guseva D.,
RA Ponimaskin E., Fahlke C., Fischer M.;
RT "Human CLC-K channels require palmitoylation of their accessory subunit
RT barttin to be functional.";
RL J. Biol. Chem. 290:17390-17400(2015).
CC -!- FUNCTION: Functions as a beta-subunit for CLCNKA and CLCNKB chloride
CC channels. In the kidney CLCNK/BSND heteromers mediate chloride
CC reabsorption by facilitating its basolateral efflux. In the stria,
CC CLCNK/BSND channels drive potassium secretion by recycling chloride for
CC the basolateral SLC12A2 cotransporter. {ECO:0000269|PubMed:11734858,
CC ECO:0000269|PubMed:12111250}.
CC -!- SUBUNIT: Interacts with CLCNK channels. Forms heteromers with CLCNKA in
CC the thin ascending limb of Henle and with CLCNKB in the thick ascending
CC limb and more distal segments (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q8WZ55; Q15848: ADIPOQ; NbExp=3; IntAct=EBI-7996695, EBI-10827839;
CC Q8WZ55; Q9BQE5: APOL2; NbExp=3; IntAct=EBI-7996695, EBI-4290634;
CC Q8WZ55; P53367: ARFIP1; NbExp=5; IntAct=EBI-7996695, EBI-2808808;
CC Q8WZ55; O95393: BMP10; NbExp=3; IntAct=EBI-7996695, EBI-3922513;
CC Q8WZ55; O14735: CDIPT; NbExp=3; IntAct=EBI-7996695, EBI-358858;
CC Q8WZ55; Q9Y5P4-2: CERT1; NbExp=3; IntAct=EBI-7996695, EBI-11156432;
CC Q8WZ55; P29400-2: COL4A5; NbExp=3; IntAct=EBI-7996695, EBI-12211159;
CC Q8WZ55; Q4VAQ0: COL8A2; NbExp=3; IntAct=EBI-7996695, EBI-10241815;
CC Q8WZ55; Q8N6G5: CSGALNACT2; NbExp=3; IntAct=EBI-7996695, EBI-10267100;
CC Q8WZ55; Q5VYK3: ECPAS; NbExp=3; IntAct=EBI-7996695, EBI-521451;
CC Q8WZ55; Q05329: GAD2; NbExp=3; IntAct=EBI-7996695, EBI-9304251;
CC Q8WZ55; O00291: HIP1; NbExp=3; IntAct=EBI-7996695, EBI-473886;
CC Q8WZ55; P24593: IGFBP5; NbExp=3; IntAct=EBI-7996695, EBI-720480;
CC Q8WZ55; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-7996695, EBI-10266796;
CC Q8WZ55; P13473-2: LAMP2; NbExp=3; IntAct=EBI-7996695, EBI-21591415;
CC Q8WZ55; Q9HB07: MYG1; NbExp=3; IntAct=EBI-7996695, EBI-709754;
CC Q8WZ55; Q96AL5: PBX3; NbExp=3; IntAct=EBI-7996695, EBI-741171;
CC Q8WZ55; Q9NRY7: PLSCR2; NbExp=3; IntAct=EBI-7996695, EBI-3937430;
CC Q8WZ55; Q59EV6: PPGB; NbExp=3; IntAct=EBI-7996695, EBI-14210385;
CC Q8WZ55; P43378: PTPN9; NbExp=3; IntAct=EBI-7996695, EBI-742898;
CC Q8WZ55; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-7996695, EBI-396669;
CC Q8WZ55; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-7996695, EBI-2623095;
CC Q8WZ55; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-7996695, EBI-10262251;
CC Q8WZ55; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-7996695, EBI-742688;
CC Q8WZ55; Q9UNK0: STX8; NbExp=3; IntAct=EBI-7996695, EBI-727240;
CC Q8WZ55; Q969Z0: TBRG4; NbExp=3; IntAct=EBI-7996695, EBI-702328;
CC Q8WZ55; Q8WY91: THAP4; NbExp=3; IntAct=EBI-7996695, EBI-726691;
CC Q8WZ55; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-7996695, EBI-2852148;
CC Q8WZ55; Q15836: VAMP3; NbExp=3; IntAct=EBI-7996695, EBI-722343;
CC Q8WZ55; O76024: WFS1; NbExp=3; IntAct=EBI-7996695, EBI-720609;
CC Q8WZ55; O95159: ZFPL1; NbExp=3; IntAct=EBI-7996695, EBI-718439;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}. Cytoplasm {ECO:0000250}. Note=A significant
CC amount also observed intracellularly. Staining in membranes of the
CC renal tubule and of potassium-secreting epithelia of the inner ear is
CC basolateral (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed primarily in kidney. Expressed in
CC specific nephron segments and in the stria vascularis of the inner ear.
CC {ECO:0000269|PubMed:11687798}.
CC -!- PTM: Palmitoylation is necessary for activation of plasma membrane-
CC inserted CLC-K/barttin channels. {ECO:0000269|PubMed:26013830}.
CC -!- DISEASE: Bartter syndrome 4A, neonatal, with sensorineural deafness
CC (BARTS4A) [MIM:602522]: A form of Bartter syndrome, an autosomal
CC recessive disorder characterized by impaired salt reabsorption in the
CC thick ascending loop of Henle with pronounced salt wasting, hypokalemic
CC metabolic alkalosis, and varying degrees of hypercalciuria. BARTS4A is
CC associated with sensorineural deafness. {ECO:0000269|PubMed:11687798,
CC ECO:0000269|PubMed:12111250, ECO:0000269|PubMed:12574213,
CC ECO:0000269|PubMed:12761627}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BC069510; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY034632; AAK57750.1; -; mRNA.
DR EMBL; BC069510; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS602.1; -.
DR RefSeq; NP_476517.1; NM_057176.2.
DR AlphaFoldDB; Q8WZ55; -.
DR BioGRID; 113582; 68.
DR IntAct; Q8WZ55; 36.
DR MINT; Q8WZ55; -.
DR STRING; 9606.ENSP00000360312; -.
DR TCDB; 8.A.53.1.1; the clc-k accessory subunit, barttin, (barttin) family.
DR iPTMnet; Q8WZ55; -.
DR PhosphoSitePlus; Q8WZ55; -.
DR SwissPalm; Q8WZ55; -.
DR BioMuta; BSND; -.
DR DMDM; 54035724; -.
DR MassIVE; Q8WZ55; -.
DR PaxDb; Q8WZ55; -.
DR PeptideAtlas; Q8WZ55; -.
DR PRIDE; Q8WZ55; -.
DR ProteomicsDB; 75220; -.
DR Antibodypedia; 33230; 176 antibodies from 25 providers.
DR DNASU; 7809; -.
DR Ensembl; ENST00000651561.1; ENSP00000498282.1; ENSG00000162399.9.
DR GeneID; 7809; -.
DR KEGG; hsa:7809; -.
DR MANE-Select; ENST00000651561.1; ENSP00000498282.1; NM_057176.3; NP_476517.1.
DR UCSC; uc001cye.4; human.
DR CTD; 7809; -.
DR DisGeNET; 7809; -.
DR GeneCards; BSND; -.
DR HGNC; HGNC:16512; BSND.
DR HPA; ENSG00000162399; Tissue enriched (kidney).
DR MalaCards; BSND; -.
DR MIM; 602522; phenotype.
DR MIM; 606412; gene.
DR neXtProt; NX_Q8WZ55; -.
DR OpenTargets; ENSG00000162399; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR Orphanet; 89938; Bartter syndrome type 4.
DR PharmGKB; PA134911659; -.
DR VEuPathDB; HostDB:ENSG00000162399; -.
DR eggNOG; ENOG502S3DP; Eukaryota.
DR GeneTree; ENSGT00390000008549; -.
DR HOGENOM; CLU_078815_0_0_1; -.
DR InParanoid; Q8WZ55; -.
DR OMA; FYAMGSV; -.
DR OrthoDB; 1577809at2759; -.
DR PhylomeDB; Q8WZ55; -.
DR TreeFam; TF335975; -.
DR PathwayCommons; Q8WZ55; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; Q8WZ55; -.
DR BioGRID-ORCS; 7809; 17 hits in 1059 CRISPR screens.
DR GeneWiki; BSND; -.
DR GenomeRNAi; 7809; -.
DR Pharos; Q8WZ55; Tbio.
DR PRO; PR:Q8WZ55; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8WZ55; protein.
DR Bgee; ENSG00000162399; Expressed in adult mammalian kidney and 13 other tissues.
DR ExpressionAtlas; Q8WZ55; baseline and differential.
DR Genevisible; Q8WZ55; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0005254; F:chloride channel activity; IEA:Ensembl.
DR GO; GO:0017081; F:chloride channel regulator activity; IBA:GO_Central.
DR GO; GO:0006821; P:chloride transport; IBA:GO_Central.
DR InterPro; IPR029181; Barttin.
DR PANTHER; PTHR28399; PTHR28399; 1.
DR Pfam; PF15462; Barttin; 1.
PE 1: Evidence at protein level;
KW Bartter syndrome; Cell membrane; Cytoplasm; Deafness; Disease variant;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..320
FT /note="Barttin"
FT /id="PRO_0000064999"
FT TOPO_DOM 1..5
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 27..32
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 33..53
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 54..320
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 167..233
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 250..320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..285
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VIM4"
FT MOD_RES 168
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VIM4"
FT LIPID 54
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:26013830"
FT LIPID 56
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:26013830"
FT VARIANT 8
FT /note="R -> L (in BARTS4A; completely abolishes CLCNKA
FT activation; mutated protein fails to increase surface
FT expression of CLCNKA; intracellular localization; probably
FT retained in the ER; dbSNP:rs74315288)"
FT /evidence="ECO:0000269|PubMed:11687798,
FT ECO:0000269|PubMed:12111250, ECO:0000269|PubMed:12761627"
FT /id="VAR_019783"
FT VARIANT 8
FT /note="R -> W (in BARTS4A; completely abolishes CLCNKA
FT activation; dbSNP:rs74315285)"
FT /evidence="ECO:0000269|PubMed:11687798,
FT ECO:0000269|PubMed:12111250"
FT /id="VAR_019784"
FT VARIANT 10
FT /note="G -> S (in BARTS4A; increases CLCNKA currents over
FT those obtained with wild-type; still activates CLCNKA to an
FT extent similar to that of wild-type; intracellular but some
FT plasma membrane localization as well; dbSNP:rs74315287)"
FT /evidence="ECO:0000269|PubMed:11687798,
FT ECO:0000269|PubMed:12111250, ECO:0000269|PubMed:12761627"
FT /id="VAR_019785"
FT VARIANT 43
FT /note="V -> I (in dbSNP:rs34561376)"
FT /id="VAR_061564"
FT VARIANT 47
FT /note="G -> R (in BARTS4A; atypical; dbSNP:rs74315289)"
FT /evidence="ECO:0000269|PubMed:12574213"
FT /id="VAR_019786"
FT MUTAGEN 54
FT /note="C->S: 38% reduction in palmitoylation. Abolishes
FT palmitoylation; when associated with S-56."
FT /evidence="ECO:0000269|PubMed:26013830"
FT MUTAGEN 56
FT /note="C->S: 74% reduction in palmitoylation. Abolishes
FT palmitoylation; when associated with S-54."
FT /evidence="ECO:0000269|PubMed:26013830"
FT MUTAGEN 98
FT /note="Y->A: Stimulation of CLCNKA and CLCNKB currents
FT enhanced; intense localization in the plasma membrane with
FT no intracellular localization observed."
FT /evidence="ECO:0000269|PubMed:11734858,
FT ECO:0000269|PubMed:12761627"
SQ SEQUENCE 320 AA; 35197 MW; DED232CAF85AE5AA CRC64;
MADEKTFRIG FIVLGLFLLA LGTFLMSHDR PQVYGTFYAM GSVMVIGGII WSMCQCYPKI
TFVPADSDFQ GILSPKAMGL LENGLAAEMK SPSPQPPYVR LWEEAAYDQS LPDFSHIQMK
VMSYSEDHRS LLAPEMGQPK LGTSDGGEGG PGDVQAWMEA AVVIHKGSDE SEGERRLTQS
WPGPLACPQG PAPLASFQDD LDMDSSEGSS PNASPHDREE ACSPQQEPQG CRCPLDRFQD
FALIDAPTLE DEPQEGQQWE IALPNNWQRY PRTKVEEKEA SDTGGEEPEK EEEDLYYGLP
DGAGDLLPDK ELGFEPDTQG
