ID   NKCL_MANSE              Reviewed;        1060 AA.
AC   Q25479;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   25-MAY-2022, entry version 83.
DE   RecName: Full=Bumetanide-sensitive sodium-(potassium)-chloride cotransporter;
DE   AltName: Full=Na-K-CL symporter;
OS   Manduca sexta (Tobacco hawkmoth) (Tobacco hornworm).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Lepidoptera; Glossata; Ditrysia; Bombycoidea;
OC   Sphingidae; Sphinginae; Sphingini; Manduca.
OX   NCBI_TaxID=7130;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Malpighian tubule;
RX   PubMed=7550244; DOI=10.1016/0965-1748(95)00049-2;
RA   Reagan J.D.;
RT   "Molecular cloning of a putative Na(+)-K(+)-2Cl-cotransporter from the
RT   Malpighian tubules of the tobacco hornworm, Manduca sexta.";
RL   Insect Biochem. Mol. Biol. 25:875-880(1995).
CC   -!- FUNCTION: Electrically silent transporter system. Mediates sodium and
CC       chloride reabsorption. Plays a vital role in the regulation of ionic
CC       balance and cell volume.
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- SIMILARITY: Belongs to the SLC12A transporter family. {ECO:0000305}.
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DR   EMBL; U17344; AAA75600.1; -; mRNA.
DR   PIR; T30823; T30823.
DR   AlphaFoldDB; Q25479; -.
DR   SMR; Q25479; -.
DR   TCDB; 2.A.30.1.9; the cation-chloride cotransporter (ccc) family.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0015377; F:cation:chloride symporter activity; IEA:InterPro.
DR   GO; GO:0006813; P:potassium ion transport; IEA:UniProtKB-KW.
DR   GO; GO:0006814; P:sodium ion transport; IEA:UniProtKB-KW.
DR   InterPro; IPR004841; AA-permease/SLC12A_dom.
DR   InterPro; IPR018491; SLC12_C.
DR   InterPro; IPR002443; SLC12A1/SLC12A2.
DR   InterPro; IPR004842; SLC12A_fam.
DR   PANTHER; PTHR11827; PTHR11827; 1.
DR   Pfam; PF00324; AA_permease; 1.
DR   Pfam; PF03522; SLC12; 1.
DR   PRINTS; PR01207; NAKCLTRNSPRT.
DR   TIGRFAMs; TIGR00930; 2a30; 1.
PE   2: Evidence at transcript level;
KW   Chloride; Glycoprotein; Ion transport; Membrane; Potassium;
KW   Potassium transport; Sodium; Sodium transport; Symport; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..1060
FT                   /note="Bumetanide-sensitive sodium-(potassium)-chloride
FT                   cotransporter"
FT                   /id="PRO_0000178022"
FT   TOPO_DOM        1..122
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        123..143
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        154..174
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        175..197
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        198..218
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        250..270
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        271..275
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        276..296
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        332..352
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        353..367
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        368..388
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        432..452
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        453..497
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        498..518
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        563..583
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        584..642
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        643..663
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        882..902
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        903..1060
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        396
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        404
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        419
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        816
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   1060 AA;  117393 MW;  4C39D1F0B645FFEF CRC64;
     MNDENRFNVS AVEGESKKNG IHMGANIITR PLRSSVENVE RGVAPNSQSE GWHHESGWKR
     RRSLAQLTRE ALPRMENYRN SKRALKRPSL GELHGDHLIT EEDEKDQNHR DTKSPTPAVG
     IKLGWIQGVF IPCLLNIWGV MLFLRLSWVV SQAGIGLSLV IIAISAIVCV ITTLSMSAIC
     TNGEVKGGGI YYIISRSLGP EFGASVGIIF AFANAVAASM NTIGFCDSLN DLLRSNGLKI
     TEDPINDVRI VGTVALLVMC IICAIGMDWE SKAQNFLIAI IVGAMVDFVV GTIMGPKDNS
     EIAKGFVGLS SATFVENFKS DFRFSEKLDQ NFFSVFAIFF PSVTGIQAGA NISGDLKDPA
     SAIPKGTLLA LLISMVSYTL MVLFAGGGAL RDASGNITDL LIVNGTVTDY SSVSLCALNN
     TCEYGLHNSY SVMQLMSAWG PFIYGGCWAA TLSTALTNLL SVPRLIQALG VDRIYPGLIF
     FSKPYGRHGE PYRGYVLTFF VSLLFLLIAD LNTIAPLISN FYLASYALIN FCTFHRALVR
     PLGWRPTFRY YNMWLSLAGF LMCVAIMLLV HWVMSLVTFA IFFTLYLIVH YRRPDVNWGS
     STQAQMYKTA LSSAHALART GEHVKNYWPQ LLVLAGRPQA RPALVDLGNL ISKAGSLMIV
     GDISQEKLSY KVRSARARSD DEWLRGRKVR AFCSRVHGFS FEPGARALVQ GSGVGRLAPN
     VLLMGYKSDW TTCPANDLVS YFNVLHTAFE NRLAVAIVRV SGGLDYSAVV SEGAEEGAAG
     SLTATSSSGE LRVRRDGLIM HADSDLDIRD TQPKHNLSNL LTLTTSRSFT ISECKEKDKK
     KKERKPNDMH RQIVYNTASG LELSKFQLAQ MSLFQKKQES GTLDVWWLYD DGGLTILLPY
     IISQRSAWAN CKLRIFALAN RLHEMELEER NMANLLAKFR IDYSSLTMVQ DITDPPQPET
     KALFDETIKK FTEESASPDC RISDMELQTL AVKTNRQLRL RELLLANSKD ARLVVMSLPM
     PRKGSISAPL YMAWLEMMSR DLPPMLFVRG NHTSVLTFYS