S12A2_SQUAC
ID S12A2_SQUAC Reviewed; 1191 AA.
AC P55013;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 25-MAY-2022, entry version 99.
DE RecName: Full=Solute carrier family 12 member 2;
DE AltName: Full=Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1;
DE AltName: Full=NKCC;
DE AltName: Full=Na-K-CL symporter;
GN Name=SLC12A2; Synonyms=NKCC1;
OS Squalus acanthias (Spiny dogfish).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Chondrichthyes;
OC Elasmobranchii; Squalomorphii; Squaliformes; Squalidae; Squalus.
OX NCBI_TaxID=7797;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND PHOSPHORYLATION AT THR-189 AND THR-1114.
RC TISSUE=Rectal gland;
RX PubMed=8134373; DOI=10.1073/pnas.91.6.2201;
RA Xu J.-C., Lytle C., Zhu T.T., Payne J.A., Benz E. Jr., Forbush B. III;
RT "Molecular cloning and functional expression of the bumetanide-sensitive
RT Na-K-Cl cotransporter.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:2201-2205(1994).
CC -!- FUNCTION: Cation-chloride cotransporter which mediates the
CC electroneutral transport of chloride, potassium and/or sodium ions
CC across the membrane. Plays a vital role in the regulation of ionic
CC balance and cell volume. {ECO:0000269|PubMed:8134373}.
CC -!- ACTIVITY REGULATION: Inhibited by bumetanide.
CC {ECO:0000269|PubMed:8134373}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:A0A0G2KTI4}.
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000305|PubMed:8134373}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in rectal gland, brain, gill and
CC intestine. Also detected at lower levels in heart, kidney, and testis.
CC {ECO:0000269|PubMed:8134373}.
CC -!- SIMILARITY: Belongs to the SLC12A transporter family. {ECO:0000305}.
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DR EMBL; U05958; AAB60617.1; -; mRNA.
DR PIR; A53491; A53491.
DR AlphaFoldDB; P55013; -.
DR SMR; P55013; -.
DR TCDB; 2.A.30.1.5; the cation-chloride cotransporter (ccc) family.
DR iPTMnet; P55013; -.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0071944; C:cell periphery; IDA:ARUK-UCL.
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:0046873; F:metal ion transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0098659; P:inorganic cation import across plasma membrane; IDA:ARUK-UCL.
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; IPR013612; AA_permease_N.
DR InterPro; IPR002444; NKCC1.
DR InterPro; IPR018491; SLC12_C.
DR InterPro; IPR002443; SLC12A1/SLC12A2.
DR InterPro; IPR004842; SLC12A_fam.
DR PANTHER; PTHR11827; PTHR11827; 1.
DR PANTHER; PTHR11827:SF58; PTHR11827:SF58; 1.
DR Pfam; PF00324; AA_permease; 1.
DR Pfam; PF08403; AA_permease_N; 1.
DR Pfam; PF03522; SLC12; 1.
DR PRINTS; PR01207; NAKCLTRNSPRT.
DR PRINTS; PR01208; NAKCLTRSPRT1.
DR TIGRFAMs; TIGR00930; 2a30; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Chloride; Disulfide bond; Glycoprotein; Ion transport;
KW Membrane; Phosphoprotein; Potassium; Potassium transport; Sodium;
KW Sodium transport; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1191
FT /note="Solute carrier family 12 member 2"
FT /id="PRO_0000178025"
FT TOPO_DOM 1..258
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TRANSMEM 259..285
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT INTRAMEM 259..271
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT INTRAMEM 272..279
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT INTRAMEM 280..285
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TOPO_DOM 286..293
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TRANSMEM 294..315
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TOPO_DOM 316..333
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TRANSMEM 334..369
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TOPO_DOM 370..378
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TRANSMEM 379..396
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TOPO_DOM 397..401
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TRANSMEM 402..426
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TOPO_DOM 427..458
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TRANSMEM 459..479
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT INTRAMEM 459..470
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT INTRAMEM 471..472
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT INTRAMEM 473..479
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TOPO_DOM 480..486
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TRANSMEM 487..514
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TOPO_DOM 515..572
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TRANSMEM 573..605
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TOPO_DOM 606..626
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TRANSMEM 627..641
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TOPO_DOM 642..643
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TRANSMEM 644..670
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TOPO_DOM 671..684
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TRANSMEM 685..703
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TOPO_DOM 704
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TRANSMEM 705..724
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT TOPO_DOM 725..1191
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT REGION 1..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 929..972
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..166
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 936..950
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 951..969
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 189
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:8134373"
FT MOD_RES 1114
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:8134373"
FT CARBOHYD 523
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 535
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 546
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 536..541
FT /evidence="ECO:0000250|UniProtKB:P55011"
FT DISULFID 550..555
FT /evidence="ECO:0000250|UniProtKB:P55011"
SQ SEQUENCE 1191 AA; 129775 MW; BA7BB9815431500C CRC64;
MEPAFPASSA GVQSQSGPEP GAGQQEPPPP ATPLRPVASQ SRFQVDLVTE GGGGGDGQKG
QTAAQPAAAA KDKDRGDGGA AAPSPASPAA AAEPPAAAAE EAKGRFRVNF VDPASDEPPL
SSQQQPPPPS SASSAHGGHQ PPSESMNGYP QNGDTMMSEG SLHSSGTGAH HYYDTHTNTY
YLRTFGHNTI DAVPRIDHYR HTVAQLGEKL IRPSLAELHD ELDKEPFEDG YVNGEESSPA
EEAVSKHVAD NKGVVKFGWI KGVLVRCMLN IWGVMLFIRL SWIVGHAGIG LALLVIGTAT
VVTTITGLST SAITTNGFVR GGGAYYLISR SLGPEFGGAI GLIFAFANAV AVAMYVVGFA
ETVRDLLVEH NALMIDEMSD IRIIGSVTIV VLFGISVAGM EWEAKAQIVL LGILLLAIVN
FTVGTFIPAN DKRAKGFFNY RGEIFSENFV PDFRDGEDFF SVFAIFFPAA TGILAGANIS
GDLADPQLAI PKGTLLAILI TTIVYAGAAV SVGSCIVREA TGNLTDAIIP GTVTNCTNVA
CKLGFNFSSC ATNKCSYGLM NDFQVMSLVS GFGPLITAGI FSATLSSALA SLVSAPKIFQ
ALCKDNIYPG LHVFSVGYGK NNEPLRGYVL TFFIGLGFIL IAELNVIAPI ISNFFLASYA
LINFSVFHAS LAKSPGWRPA FRFYNMWISL IGAILCCGVM FVINWWAALL TNVIVLALYI
YVTYKKPDVN WGSSTQALTY LNALQHAIRL TGVEDHVKNF RPQCLLMTGA PTSRPALLHL
VHAFTKNVGL VVCGHVHTGP RRQALKEIST DQAKYQRWLI KNKMKAFYAP VYAEDLREGT
QFLLQAVGLG RMRPNTLVFG FKKDWRQALM KDVENYINAI HDAFDYQYGV VVIRLKEGFN
ISHLQAQEEL CTSQEKSAHP KDIVVNLEHS DADSSKPSSK SVSETNSPAV CQDQKDEEDD
GKASTQPLLK KEVKDPSVPL NMTDQKLLQA SSQFQKKQGK GTIDVWWLFD DGGLTLLIPY
LLTTKKKWKD CKIRVFIGGK INRIDHDRRT MATLLSKFRI DFSDITVLGD MNTKPSKDNI
TAFEEMIEPF RLHEDDKEQE ASEKMKEEEP WRITDNELEI YRMKTYRQIR LNELLRENSG
TANLIVMSLP VARKGAVSSA LYMAWIETLS KDLPPILLVR GNHQSVLTFY S
