LOCUS       NM_001270618            4621 bp    mRNA    linear   ROD 20-OCT-2024
DEFINITION  Rattus norvegicus solute carrier family 12 member 1 (Slc12a1),
            transcript variant 2, mRNA.
ACCESSION   NM_001270618
VERSION     NM_001270618.1
KEYWORDS    RefSeq; RefSeq Select.
SOURCE      Rattus norvegicus (Norway rat)
  ORGANISM  Rattus norvegicus
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
            Muroidea; Muridae; Murinae; Rattus.
REFERENCE   1  (bases 1 to 4621)
  AUTHORS   Wang,P., Zhu,G., Wu,Q., Shen,L., Liu,D., Wang,Z., Wang,W., Ren,Z.,
            Jia,Y., Liu,M., Xue,Y., Ji,D., Hu,Y., Yu,Y. and Wang,X.
  TITLE     Renal CD81 interacts with sodium potassium 2 chloride cotransporter
            and sodium chloride cotransporter in rats with
            lipopolysaccharide-induced preeclampsia
  JOURNAL   FASEB J 37 (4), e22834 (2023)
   PUBMED   36961378
  REMARK    GeneRIF: Renal CD81 interacts with sodium potassium 2 chloride
            cotransporter and sodium chloride cotransporter in rats with
            lipopolysaccharide-induced preeclampsia.
REFERENCE   2  (bases 1 to 4621)
  AUTHORS   Ares,G.R.
  TITLE     Ubiquitination of NKCC2 by the cullin-RING E3 ubiquitin ligase
            family in the thick ascending limb of the loop of Henle
  JOURNAL   Am J Physiol Renal Physiol 324 (3), F315-F328 (2023)
   PUBMED   36727946
  REMARK    GeneRIF: Ubiquitination of NKCC2 by the cullin-RING E3 ubiquitin
            ligase family in the thick ascending limb of the loop of Henle.
REFERENCE   3  (bases 1 to 4621)
  AUTHORS   Saez,F., Hong,N.J. and Garvin,J.L.
  TITLE     NADPH oxidase 4-derived superoxide mediates flow-stimulated NKCC2
            activity in thick ascending limbs
  JOURNAL   Am J Physiol Renal Physiol 314 (5), F934-F941 (2018)
   PUBMED   29672130
  REMARK    GeneRIF: Elevations in luminal flow enhance NaCl reabsorption in
            thick ascending limbs by stimulating NKCC2 via NOX4 activation and
            increased [Formula: see text]. NKCC2 activation is primarily the
            result of insertion of new transporters in the membrane.
REFERENCE   4  (bases 1 to 4621)
  AUTHORS   Blankenstein,K.I., Borschewski,A., Labes,R., Paliege,A., Boldt,C.,
            McCormick,J.A., Ellison,D.H., Bader,M., Bachmann,S. and Mutig,K.
  TITLE     Calcineurin inhibitor cyclosporine A activates renal Na-K-Cl
            cotransporters via local and systemic mechanisms
  JOURNAL   Am J Physiol Renal Physiol 312 (3), F489-F501 (2017)
   PUBMED   28003191
  REMARK    GeneRIF: Suggest complex effect of cyclosporine A to activate renal
            Nkcc2 requires concomitant stimulation by AVP.
REFERENCE   5  (bases 1 to 4621)
  AUTHORS   Brandoni,A. and Torres,A.M.
  TITLE     Renal Expression and Urinary Excretion of Na-K-2Cl Cotransporter in
            Obstructive Nephropathy
  JOURNAL   Biomed Res Int 2017, 7171928 (2017)
   PUBMED   28164127
  REMARK    GeneRIF: the upregulation in the expression of NKCC2 in apical
            membranes during the postobstructive phase of bilateral ureteral
            obstruction could contribute to improving the excretion of sodium
            and consequently also the excretion of potassium, osmolytes, and
            water.
REFERENCE   6  (bases 1 to 4621)
  AUTHORS   Masilamani,S., Wang,X., Kim,G.H., Brooks,H., Nielsen,J.,
            Nielsen,S., Nakamura,K., Stokes,J.B. and Knepper,M.A.
  TITLE     Time course of renal Na-K-ATPase, NHE3, NKCC2, NCC, and ENaC
            abundance changes with dietary NaCl restriction
  JOURNAL   Am J Physiol Renal Physiol 283 (4), F648-F657 (2002)
   PUBMED   12217855
  REMARK    GeneRIF: there was no change in mRNA abundance, suggesting that the
            increase in protein in response to dietary NaCl restriction was not
            a result of altered gene transcription
REFERENCE   7  (bases 1 to 4621)
  AUTHORS   Kobayashi,K., Uchida,S., Mizutani,S., Sasaki,S. and Marumo,F.
  TITLE     Intrarenal and cellular localization of CLC-K2 protein in the mouse
            kidney
  JOURNAL   J Am Soc Nephrol 12 (7), 1327-1334 (2001)
   PUBMED   11423561
REFERENCE   8  (bases 1 to 4621)
  AUTHORS   Obermuller,N., Kunchaparty,S., Ellison,D.H. and Bachmann,S.
  TITLE     Expression of the Na-K-2Cl cotransporter by macula densa and thick
            ascending limb cells of rat and rabbit nephron
  JOURNAL   J Clin Invest 98 (3), 635-640 (1996)
   PUBMED   8698854
REFERENCE   9  (bases 1 to 4621)
  AUTHORS   Simon,D.B., Karet,F.E., Hamdan,J.M., DiPietro,A., Sanjad,S.A. and
            Lifton,R.P.
  TITLE     Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is
            caused by mutations in the Na-K-2Cl cotransporter NKCC2
  JOURNAL   Nat Genet 13 (2), 183-188 (1996)
   PUBMED   8640224
REFERENCE   10 (bases 1 to 4621)
  AUTHORS   Gamba,G., Miyanoshita,A., Lombardi,M., Lytton,J., Lee,W.S.,
            Hediger,M.A. and Hebert,S.C.
  TITLE     Molecular cloning, primary structure, and characterization of two
            members of the mammalian electroneutral sodium-(potassium)-chloride
            cotransporter family expressed in kidney
  JOURNAL   J Biol Chem 269 (26), 17713-17722 (1994)
   PUBMED   8021284
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            JAXUCZ010000003.1, BC087017.1 and FM059245.1.
            
            Transcript Variant: This variant (2) has an alternate exon of the
            same size replacing another exon compared to variant 1. The
            resulting isoform (2) has the same N- and C-termini and is the same
            length, but it has an internal region of alternate sequence
            compared to isoform 1.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: U10096.1, SRR26643287.8897.1
                                           [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-22                JAXUCZ010000003.1  132859590-132859611
            23-368              BC087017.1         65-410
            369-947             FM059245.1         1-579
            948-4621            BC087017.1         990-4663
FEATURES             Location/Qualifiers
     source          1..4621
                     /organism="Rattus norvegicus"
                     /mol_type="mRNA"
                     /strain="BN"
                     /db_xref="taxon:10116"
                     /chromosome="3"
                     /map="3q36"
     gene            1..4621
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /note="solute carrier family 12 member 1"
                     /db_xref="GeneID:25065"
                     /db_xref="RGD:3685"
     exon            1..22
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            23..623
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     CDS             216..3503
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /note="isoform 2 is encoded by transcript variant 2;
                     kidney-specific Na-K-Cl symporter; bumetanide-sensitive
                     sodium-(potassium)-chloride cotransporter 2; Solute
                     carrier family 12, member 1 (bumetanide-sensitive
                     sodium-[potassium]-chloride cotransporter); Na-K-2Cl
                     cotransporter 2; solute carrier family 12
                     (sodium/potassium/chloride transporters), member 1; solute
                     carrier family 12 (sodium/potassium/chloride transporter),
                     member 1; bumetanide-sensitive sodium-(potassium)-chloride
                     cotransporter 1"
                     /codon_start=1
                     /product="solute carrier family 12 member 1 isoform 2"
                     /protein_id="NP_001257547.1"
                     /db_xref="GeneID:25065"
                     /db_xref="RGD:3685"
                     /translation="MSVNIPSNSVPSGASRFQVHVINEGHGSGAAMSDSTDPPHYEET
                     SFGDEAQNRLKISFRPGNQECYENFLQTGETAKTDTTFHAYDSHTNTYYLQTFGHNTM
                     DAVPKIEYYRNTGSVSGPKVNRPSLQEIHEQLAKNVAVAPGSADRVANGDGMPGDEQA
                     ENKEEDVTGVVKFGWVKGVLVRCMLNIWGVMLFIRLSWIVGEAGIGLGVIIIGLSVVV
                     TTLTGISMSAICTNGVVRGGGAYYLISRSLGPEFGGSIGLIFAFANAVAVAMYVVGFA
                     ETVVDLLKESDSMMVDPTNDIRIIGSITVVILLGISVAGMEWEAKAQVILLVILLIAI
                     ANFFIGTVIPSNNEKKSRGFFNYQASIFAENFGPSFTEGEGFFSVFAIFFPAATGILA
                     GANISGDLEDPQDAIPRGTMLAIFITTVAYIGVAICVAACVVRDATGSMNDTVVSGMN
                     CNGSAACGLGYDFSRCQHEPCQYGLMNNFQVMSMVSGFGPLITAGIFSATLSSALASL
                     VSAPKVFQALCKDNIFKGLQFFAKGYGKNNEPLRGYFLTFVIAMAFILIAELNVIAPI
                     ISNFFLASYALINFSCFHASYAKSPGWRPAYGIYNMWVSLFGAILCCAVMFVINWWAA
                     VITYVIELFLYIYVTYKKPDVNWGSSTQALSYVSALDNALELTTVEDHVKNFRPQCIV
                     LTGGPMTRPALLDITHAFTKNSGLCICCEVFVGPRKLCVKEMNSGMAKKQAWLMKNKI
                     KAFYAAVAADCFRDGVRSLLQASGLGRMKPNTLVIGYKKNWRKAPLSELENYVGIIHD
                     AFDFEIGVVIVRISQGFDISPVLQVQDELEKLEQERLALEAAIKDNDCEEGKGGIRGL
                     FKKAGKLNITKPAPKKDSNISTIQSMHVGEFNQKLVEASAQFKKKQGKGTIDVWWLFD
                     DGGLTLLIPYILTLRKKWKDCKLRIYVGGKINRIEEEKISMASLLSKFRIKFADIHII
                     GDINIKPNKESWKVFEEMIEPYRLHESHKDLTTAEKLKRESPWKITDAELEAVKEKSY
                     RQVRLNELLQEHSRAANLIVLSLPVARKGSISDLLYMAWLEILTKNLPPVLLVRGNHK
                     NVLTFYS"
     exon            624..755
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            756..831
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            832..927
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            928..1067
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            1068..1178
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            1179..1290
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            1291..1418
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            1419..1503
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            1504..1655
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            1656..1763
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            1764..1887
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            1888..1989
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            1990..2145
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            2146..2245
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            2246..2357
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            2358..2498
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            2499..2605
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            2606..2688
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            2689..2832
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            2833..2964
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            2965..3076
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            3077..3163
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            3164..3299
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            3300..3367
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
     exon            3368..4607
                     /gene="Slc12a1"
                     /gene_synonym="BSC1; Nkcc2"
                     /inference="alignment:Splign:2.1.0"
ORIGIN      
        1 cagaaggcgg ctgaatggga ggcagctttg ggaatcattc tgaagattac atgggagacc
       61 acatatcaac attacagcag gaatccagct atcgggtcgt ctagatccaa aaccaagtgc
      121 tcggtattgt aaccctacga ttctctattt tgaagcagaa gtaggttaaa acaccaacca
      181 ctgtaaaata ggtagttcaa agtagatttt ggaagatgtc agtcaacatc ccttccaact
      241 cagtgcccag tggtgccagt cgtttccaag tccatgttat aaatgagggc catggcagtg
      301 gtgcagccat gagtgacagc acggaccccc cacattatga agagacctct ttcggggatg
      361 aagcccaaaa cagactgaaa atcagcttta ggcctgggaa tcaggagtgc tatgaaaatt
      421 ttctccaaac tggagagact gctaaaacag acaccacgtt tcacgcctat gactctcaca
      481 caaacacata ttacctacaa acctttggcc acaacaccat ggacgccgtc cccaagattg
      541 agtactaccg caacaccggc agtgtgagcg ggcccaaggt caaccggccg agcctgcagg
      601 agatccacga gcagctagct aagaatgtgg ctgtggcccc tggttcagct gacagggttg
      661 ctaatggaga tgggatgcct ggagatgagc aagcagaaaa caaggaagaa gacgtgactg
      721 gtgttgtgaa gtttggatgg gtgaaaggtg tgctggtgag gtgcatgctg aacatctggg
      781 gagtcatgct cttcattcgc ctctcctgga ttgtaggaga agcgggaatt ggtctgggag
      841 tcatcatcat tggcctgagc gtggtagtga caacactcac aggtatctct atgtctgcta
      901 tttgcacaaa cggagtggtg agaggaggtg gagcctacta cctgatttcc cggagcttag
      961 ggcctgagtt cggtgggtca ataggcttga tttttgcttt cgccaatgca gtggctgtcg
     1021 ctatgtatgt ggtggggttc gcggagactg tggtagacct tcttaaggag agtgattcaa
     1081 tgatggtgga tccaaccaat gacatccgaa taatcggttc catcacggtg gtgattcttc
     1141 tagggatctc agtagctggg atggagtggg aagctaaggc tcaagtgatt ctcctggtca
     1201 ttctactcat tgctatcgca aacttcttca ttggaactgt catcccatcc aacaacgaga
     1261 agaaatccag aggcttcttc aactaccaag catctatatt tgcggaaaac tttgggccaa
     1321 gcttcacaga gggagaaggc ttcttctcgg tctttgctat ctttttccca gctgctactg
     1381 ggattcttgc tggtgccaac atctctggag acctggagga tccccaggac gccatcccca
     1441 gagggaccat gctggccatt ttcatcacca ccgtcgccta cataggtgtt gctatttgcg
     1501 tagctgcctg tgtggtccga gacgccactg ggagcatgaa cgacactgtc gtttctggga
     1561 tgaattgcaa tgggtccgca gcctgcggac tgggctacga cttctcaaga tgtcagcatg
     1621 agccatgcca gtatgggttg atgaacaatt ttcaggtcat gagcatggtg tccgggttcg
     1681 gccccctcat caccgcaggg atcttttcgg caacactgtc ttcggcccta gcctccctcg
     1741 tcagtgcacc caaagtattc caggctctgt gcaaggacaa catcttcaaa ggacttcagt
     1801 tcttcgcaaa gggctatggg aaaaacaacg agcccctgag agggtacttc ctcacttttg
     1861 tgatagccat ggcattcatt ctcatcgccg agctgaacgt cattgcacct atcatatcca
     1921 acttcttcct ggcctcatat gcgcttatta atttctcctg cttccatgcc tcgtatgcca
     1981 aatcgccagg atggaggccg gcatatggga tttacaacat gtgggtatct ctcttcggag
     2041 ccattttgtg ctgtgcagtc atgtttgtca tcaactggtg ggcggctgtc atcacctatg
     2101 tcattgagct cttcctctat atctatgtga cttataagaa gccagatgtg aactggggct
     2161 cctccacaca ggctctgtcc tacgtgagcg ctttagacaa tgctctggaa ttaaccacag
     2221 tggaagacca tgtgaaaaac ttcagacccc agtgcattgt cttaacagga ggacccatga
     2281 caagacctgc tctcctggac ataacccatg cctttacgaa gaatagtggc ctctgtatct
     2341 gctgcgaagt cttcgtggga cctcgcaagc tgtgtgttaa agagatgaac agtggcatgg
     2401 ctaaaaagca ggcctggctg atgaagaaca aaatcaaggc tttttatgct gcggtggcgg
     2461 cagactgctt cagggacggt gtgcggagtc tccttcaggc ctcaggcctg gggagaatga
     2521 agccaaacac tctagtgatt ggatacaaaa agaactggag gaaagctccc ttgtctgagc
     2581 ttgagaatta cgtgggaatc atacatgacg cctttgactt tgagattggt gtagtcatag
     2641 tcagaatcag ccaagggttt gacatctctc cagttctcca ggtacaagat gaactggaga
     2701 aactggaaca ggagagactg gctctggagg ccgcaatcaa agacaacgac tgtgaggagg
     2761 gcaagggggg catccgaggc ttgtttaaga aggccggcaa actgaacatt accaagccgg
     2821 cccctaaaaa agacagcaac atcagcacca tccagtcgat gcacgtcggg gagttcaatc
     2881 agaagctggt agaagccagc gctcagttta aaaagaaaca gggaaaaggc acgatcgatg
     2941 tttggtggtt atttgatgat ggagggttga cactgcttat cccatatatc ttgactctca
     3001 gaaagaaatg gaaagactgt aagttaagaa tctatgttgg aggaaaaatc aaccgcattg
     3061 aagaggaaaa aatttcaatg gcttctcttc tcagcaaatt taggataaaa tttgcagaca
     3121 ttcatataat tggagacatc aacattaagc caaacaaaga gagctggaaa gtctttgaag
     3181 agatgattga accttatagg ctccacgaaa gccacaaaga tttgaccact gctgagaaat
     3241 taaaaagaga aagtccatgg aaaattacag atgcagaact ggaagcagtc aaggaaaaga
     3301 gttaccgcca agttcgactg aacgagctgt tacaggagca ttccagagcc gccaacctca
     3361 tcgtattgag ccttccagtg gcgagaaaag gatctatttc ggatttgttg tacatggcgt
     3421 ggttagaaat cctgaccaag aacctccctc ctgtgctact ggttagagga aatcacaaga
     3481 atgtcctgac attttactct taaagcgcga gggatgagaa atgttgtacc ttggtgtccg
     3541 aataattaca aaacgtgtct ggtactttgt gttttaaaac ctcatctatg aatatacaaa
     3601 cctctggaga ctatcccacc tgattctaca taaatttcat cttttttaaa aaagttatta
     3661 ttaatgagag ttttttccca ccagttttaa aaacatcgaa aacatttttc ccttgtcgct
     3721 ggtgaataag aaattaataa gagctggctg acatgcttgc aggatgtgct aatgtagatg
     3781 agctccaggc aaacgcaatc tcttgtttcc gtggattctt ctgcatggcc ccgtgcaggc
     3841 cacaggccca tagcgggctc tctttaagtt gttattgaca gactggtgtg gtgaaagcag
     3901 gcggctatca tagggaaaga cacactgggt cagtggcctg attctgcttg gcctcctgag
     3961 aagtttgtgg agatttaaaa atcaatatcc ggaaactgta agaaggacta gagtctacaa
     4021 agtgttcaaa gcagttacct aaattaaggt ttatttaatg cagccgataa taagcttaac
     4081 ctctgatcac acgtagcttg cattcgctgc tagccagagg tacactaggt aggtgagcaa
     4141 agacacatgt tccacttaga cgaaatagag tcccaacata caaatatcaa ttgtcttcct
     4201 ggttaaatgt tttgaaattt ctaccttaat actactttat cttttttctc tgattaagtg
     4261 gtttgcatag acgaaataaa aatagacgat ctcattgaaa aataatctca caggtttcca
     4321 atccactact aaaaatatat ccagatccta catttattta ctttctctat atacaggtat
     4381 atgggtttta tagaataaca aggatataag tggagaaact tgtaaaattt taaaacacag
     4441 gtgttgattt ttcttcttgt tcgtgtgtgt ataatattta atcacagaaa aaatgcttat
     4501 atgataaatg gcttggtttt ggttttgttg gcatattttg actgttctgg ggaagcttgt
     4561 ggggggcaaa tcaacctgaa ataaaattct actaaaaaaa aaaaaaaaaa aaaaaaaaaa
     4621 a
//
