LOCUS       NM_009195               3826 bp    mRNA    linear   ROD 10-FEB-2025
DEFINITION  Mus musculus solute carrier family 12, member 4 (Slc12a4),
            transcript variant 2, mRNA.
ACCESSION   NM_009195
VERSION     NM_009195.3
KEYWORDS    RefSeq; RefSeq Select.
SOURCE      Mus musculus (house mouse)
  ORGANISM  Mus musculus
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
            Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE   1  (bases 1 to 3826)
  AUTHORS   Shmukler,B.E., Rivera,A., Nishimura,K., Hsu,A., Wohlgemuth,J.G.,
            Dlott,J.S., Michael Snyder,L., Brugnara,C. and Alper,S.L.
  TITLE     Erythroid-specific inactivation of Slc12a6/Kcc3 by EpoR
            promoter-driven Cre expression reduces K-Cl cotransport activity in
            mouse erythrocytes
  JOURNAL   Physiol Rep 10 (5), e15186 (2022)
   PUBMED   35274823
REFERENCE   2  (bases 1 to 3826)
  AUTHORS   Parichha,A., Suresh,V., Chatterjee,M., Kshirsagar,A.,
            Ben-Reuven,L., Olender,T., Taketo,M.M., Radosevic,V.,
            Bobic-Rasonja,M., Trnski,S., Holtzman,M.J., Jovanov-Milosevic,N.,
            Reiner,O. and Tole,S.
  TITLE     Constitutive activation of canonical Wnt signaling disrupts choroid
            plexus epithelial fate
  JOURNAL   Nat Commun 13 (1), 633 (2022)
   PUBMED   35110543
  REMARK    Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3826)
  AUTHORS   Shmukler,B.E., Rivera,A., Bhargava,P., Nishimura,K., Kim,E.H.,
            Hsu,A., Wohlgemuth,J.G., Morton,J., Snyder,L.M., De Franceschi,L.,
            Rust,M.B., Hubner,C.A., Brugnara,C. and Alper,S.L.
  TITLE     Genetic disruption of KCC cotransporters in a mouse model of
            thalassemia intermedia
  JOURNAL   Blood Cells Mol Dis 81, 102389 (2020)
   PUBMED   31835175
  REMARK    GeneRIF: the effect of genetic inactivation of K-Cl cotransporters
            KCC1 and KCC3 in a mouse model of beta-thalassemia intermedia;
            conclude that genetic inactivation of K-Cl cotransport can reverse
            red cell dehydration and partially attenuate the hematologic
            phenotype in a mouse model of beta-thalassemia.
REFERENCE   4  (bases 1 to 3826)
  AUTHORS   Perry,J.S.A., Morioka,S., Medina,C.B., Iker Etchegaray,J.,
            Barron,B., Raymond,M.H., Lucas,C.D., Onengut-Gumuscu,S., Delpire,E.
            and Ravichandran,K.S.
  TITLE     Interpreting an apoptotic corpse as anti-inflammatory involves a
            chloride sensing pathway
  JOURNAL   Nat Cell Biol 21 (12), 1532-1543 (2019)
   PUBMED   31792382
REFERENCE   5  (bases 1 to 3826)
  AUTHORS   Shmukler,B.E., Rivera,A., Bhargava,P., Nishimura,K., Hsu,A.,
            Kim,E.H., Trudel,M., Rust,M.B., Hubner,C.A., Brugnara,C. and
            Alper,S.L.
  TITLE     Combined genetic disruption of K-Cl cotransporters and Gardos
            channel KCNN4 rescues erythrocyte dehydration in the SAD mouse
            model of sickle cell disease
  JOURNAL   Blood Cells Mol Dis 79, 102346 (2019)
   PUBMED   31352162
  REMARK    GeneRIF: effect of genetic inactivation of KCC3 and KCC1 in the SAD
            mouse model of sickle red cell dehydration, finding decreased red
            cell density and improved hematological indices.
            Erratum:[Blood Cells Mol Dis. 2020 Mar;81:102390. doi:
            10.1016/j.bcmd.2019.102390.. PMID: 31931456]
REFERENCE   6  (bases 1 to 3826)
  AUTHORS   Casula,S., Shmukler,B.E., Wilhelm,S., Stuart-Tilley,A.K., Su,W.,
            Chernova,M.N., Brugnara,C. and Alper,S.L.
  TITLE     A dominant negative mutant of the KCC1 K-Cl cotransporter: both N-
            and C-terminal cytoplasmic domains are required for K-Cl
            cotransport activity
  JOURNAL   J Biol Chem 276 (45), 41870-41878 (2001)
   PUBMED   11551954
REFERENCE   7  (bases 1 to 3826)
  AUTHORS   Hubner,C.A., Stein,V., Hermans-Borgmeyer,I., Meyer,T., Ballanyi,K.
            and Jentsch,T.J.
  TITLE     Disruption of KCC2 reveals an essential role of K-Cl cotransport
            already in early synaptic inhibition
  JOURNAL   Neuron 30 (2), 515-524 (2001)
   PUBMED   11395011
REFERENCE   8  (bases 1 to 3826)
  AUTHORS   Shmukler,B.E., Brugnara,C. and Alper,S.L.
  TITLE     Structure and genetic polymorphism of the mouse KCC1 gene
  JOURNAL   Biochim Biophys Acta 1492 (2-3), 353-361 (2000)
   PUBMED   11004507
REFERENCE   9  (bases 1 to 3826)
  AUTHORS   Su,W., Shmukler,B.E., Chernova,M.N., Stuart-Tilley,A.K., de
            Franceschi,L., Brugnara,C. and Alper,S.L.
  TITLE     Mouse K-Cl cotransporter KCC1: cloning, mapping, pathological
            expression, and functional regulation
  JOURNAL   Am J Physiol 277 (5), C899-C912 (1999)
   PUBMED   10564083
REFERENCE   10 (bases 1 to 3826)
  AUTHORS   Pellegrino,C.M., Rybicki,A.C., Musto,S., Nagel,R.L. and
            Schwartz,R.S.
  TITLE     Molecular identification and expression of erythroid K:Cl
            cotransporter in human and mouse erythroleukemic cells
  JOURNAL   Blood Cells Mol Dis 24 (1), 31-40 (1998)
   PUBMED   9516379
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            BY740705.1 and AK159274.1.
            
            On Dec 6, 2011 this sequence version replaced NM_009195.2.
            
            Transcript Variant: This variant (2) uses a different splice site
            in the 5' coding region, compared to variant 1. The resulting
            protein (isoform 2) is shorter than isoform 1 by two amino acids.
            
            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 :: AK159274.1, AK160072.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMN00849374,
                                           SAMN00849375 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-13                BY740705.1         2-14
            14-3826             AK159274.1         2-3814
FEATURES             Location/Qualifiers
     source          1..3826
                     /organism="Mus musculus"
                     /mol_type="mRNA"
                     /db_xref="taxon:10090"
                     /chromosome="8"
                     /map="8 53.06 cM"
     gene            1..3826
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /note="solute carrier family 12, member 4"
                     /db_xref="GeneID:20498"
                     /db_xref="MGI:MGI:1309465"
     exon            1..191
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     CDS             77..3334
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /note="isoform 2 is encoded by transcript variant 2; K-Cl
                     cotransporter KCC1; mKCC1; erythroid K-Cl cotransporter 1;
                     electroneutral potassium-chloride cotransporter 1; K-Cl
                     Co-transporter-1"
                     /codon_start=1
                     /product="solute carrier family 12 member 4 isoform 2"
                     /protein_id="NP_033221.1"
                     /db_xref="CCDS:CCDS22623.1"
                     /db_xref="GeneID:20498"
                     /db_xref="MGI:MGI:1309465"
                     /translation="MPHFTVVPVDGPRRGDYDNLEGLSWVDYGERAEREDSDGQGNHR
                     ENSPFLCPLDASRGNDYYDRNLALFEEELDIRPKVSSLLGKLVSYTNLTQGAKEHEEA
                     ESGEGGRRRAAKAPSMGTLMGVYLPCLQNIFGVILFLRLTWMVGTAGVLQALLIVLIC
                     CCCTLLTAISMSAIATNGVVPAGGSYFMISRSLGPEFGGAVGLCFYLGTTFAAAMYIL
                     GAIEILLTYIAPPAAIFYPSGTHDMSSATLNNMRVYGTIFLTLMTLVVFVGVKYVNKF
                     ASLFLACVIISILSIYAGGIKSIFDPPVFPVCMLGNRTLSRDQFDICAKTVVVDNETV
                     ATRLWTFFCHSPNLTADSCDPYFLLNNVTEIPGIPGAAAGVLQENLWSAYLEKGEVVE
                     KHGLPSTDTLGLKESLSLYVVADIATSFTVLVGIFFPSVTGIMAGSNRSGDLRDAQKS
                     IPVGTILAIVTTSLVYFSSVILFGACIEGVVLRDKYGDGVSRNLVVGTLAWPSPWVIV
                     VGSFFSTCGAGLQSLTGAPRLLQAIAKDNIIPFLRVFGHGKANGEPTWALLLTALIAE
                     LGILIASLDMVAPILSMFFLMCYLFVNLACAVQTLLRTPNWRPRFKYYHWTLSFLGMS
                     LCLALMFVSSWYYALVAMLIAGMIYKYIEYQGAEKEWGDGIRGLSLSAARYALLRLEE
                     GPPHTKNWRPQLLVLLKLDEDLHVKYPRLLTFASQLKAGKGLTIVGSVIQGSFLESYG
                     EAQAAEQTIKNMMDIEKVKGFCQVVVASKVREGLAHLIQSCGLGGMRHNSVVLGWPYG
                     WRQSEDPRAWKTFIDTVRCTTAAHLALLVPKNIAFYPSNHERYLDGHIDVWWIVHDGG
                     MLMLLPFLLRQHKVWKKCRMRIFTVAQMDDNSIQMKKDLAIFLYHLRLEAEVEVVEMH
                     NSDISAYTYERTLMMEQRSQMLRQMRLTKTERDREAQLVKDRHSALRLESLYSDEEEE
                     SVAGADKIQMTWTRDKYMAEPWDPSHAPDNFRELVHIKPDQSNVRRMHTAVKLNEVIV
                     TRSHDARLVLLNMPGPPKNSEGDENYMEFLEVLTEGLERVLLVRGGGREVITIYS"
     exon            192..286
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            287..418
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            419..565
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            566..620
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            621..751
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            752..993
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            994..1208
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1209..1373
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1374..1472
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1473..1530
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1531..1705
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1706..1824
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1825..1923
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            1924..2043
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            2044..2148
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            2149..2317
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            2318..2513
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            2514..2683
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            2684..2815
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            2816..2923
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            2924..3108
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            3109..3242
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     exon            3243..3826
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3801..3806
                     /regulatory_class="polyA_signal_sequence"
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /note="hexamer: AATAAA"
     polyA_site      3824
                     /gene="Slc12a4"
                     /gene_synonym="KCC1; RBCKCC1"
                     /note="major polyA site"
ORIGIN      
        1 gagcgggcgg ggcgggccag cctggggcgg cggggactgc cggctggagg ccgggaccgc
       61 gggccaagcg cgcgcgatgc ctcacttcac cgtggtgccg gtggacgggc cgcgacgcgg
      121 cgactatgac aacctcgagg ggctcagttg ggtggactac ggcgagcgcg ccgagcggga
      181 agactcggac ggacagggta accacagaga gaatagccct ttcctttgcc ctttggacgc
      241 ctccagagga aatgactact atgaccggaa cttggcactg tttgaggagg agctggacat
      301 ccgcccaaag gtgtcatctc tcctgggcaa gcttgtcagc tataccaacc tcacccaagg
      361 agccaaggag cacgaggagg ctgagagtgg agaaggtggc cgacggagag ctgccaaggc
      421 tcccagcatg ggcacactca tgggagtgta cctgccctgc ctgcagaata tctttggggt
      481 catcctcttc ctgcggctga cctggatggt gggcacagct ggtgtgctgc aggctctcct
      541 cattgtcctc atctgctgct gctgtaccct gctgacagcc atctccatga gcgccattgc
      601 caccaacggc gtggttccag ctggtggctc gtacttcatg atttcccgct ctttgggacc
      661 agaattcgga ggtgctgtgg gcctgtgctt ctacctgggg acgacatttg cagcagccat
      721 gtatatccta ggggccattg agatcttgct gacctacatt gctccgccag ctgccatctt
      781 ttacccatcg ggcacccatg acatgtcaag cgccaccttg aataacatga gagtgtatgg
      841 gaccattttc ctgactctga tgaccctagt ggtgtttgtc ggtgtcaagt acgtgaacaa
      901 gtttgcctcg ctcttcctgg cctgcgtgat catctccatc ctttccattt acgcgggagg
      961 catcaagtcc atttttgacc ctcccgtgtt tccggtgtgt atgctgggca ataggaccct
     1021 gtctcgggac cagtttgaca tctgtgccaa gacagtcgtg gtggacaatg agacagtggc
     1081 cacccggctg tggactttct tctgccacag ccccaacctt actgctgact cctgtgaccc
     1141 ctacttcctg ctcaacaatg tgacagagat tcctggcata cctggggcag ctgctggtgt
     1201 gctccaggag aacctctgga gcgcttacct ggagaagggg gaggtcgtgg agaagcatgg
     1261 gctgccgtcc acagacaccc tcggcctaaa ggagagcctg tccctgtatg tggtggctga
     1321 catcgccacg tccttcaccg tgctggttgg catctttttc ccttctgtga caggcatcat
     1381 ggctggttca aaccgctccg gggatctccg tgacgcccag aagtctatcc cagtggggac
     1441 cattctggcc attgttacca cttcgctggt gtacttcagc agtgtgatcc tcttcggtgc
     1501 ctgcatcgag ggtgtggtac tccgggacaa gtacggtgat ggcgtcagca ggaacctggt
     1561 ggtgggcacc ctggcctggc cttcgccttg ggtcatcgtg gttggctcct tcttctcaac
     1621 atgtggggct ggtctccaga gcctcactgg ggcgccacgt ttactgcaag ccattgccaa
     1681 ggataacatc atccccttcc tccgggtgtt tggccatggg aaagcaaacg gtgaaccgac
     1741 gtgggccctc ctcctgacag cgctcatcgc tgagctgggc atcctgattg cttcccttga
     1801 catggtggcc cccattctgt ccatgttctt tctgatgtgt tacctctttg taaacttggc
     1861 ctgtgccgtg cagacacttc tgaggacccc caactggcgg ccccggttca agtactatca
     1921 ctggacattg tctttcctag gcatgagtct ctgcctggct cttatgtttg tctcctcctg
     1981 gtactatgcc ctagtggcca tgctcatcgc aggcatgatc tacaagtaca tcgagtacca
     2041 aggggccgag aaggagtggg gcgatgggat ccgaggcctg tccctgagtg cggcacgcta
     2101 tgcactgctg aggctggagg aagggcctcc tcacaccaag aactggcggc ctcagctcct
     2161 ggtgctgctt aagttagacg aagatcttca tgtgaagtac ccccggctcc tcaccttcgc
     2221 ctcccagctg aaggccggga agggcctgac aatcgttggc tctgtcatcc agggcagctt
     2281 tctggagagc tatggtgaag cccaggccgc tgagcagacc atcaagaaca tgatggacat
     2341 tgagaaagtc aaaggcttct gccaggtagt ggtggccagc aaggttcgag agggactggc
     2401 ccacctcatc cagtcttgcg gcctgggcgg catgagacac aactccgtgg tgctgggctg
     2461 gccctatggc tggcgacaga gtgaggaccc acgtgcctgg aagaccttta ttgacactgt
     2521 gcgctgcacc acagctgccc acctggccct gctggtgcca aagaacatag ctttctaccc
     2581 cagcaaccac gagcgctacc tggatggcca tatcgacgtg tggtggatcg tgcatgatgg
     2641 aggcatgctt atgctgctgc cctttctgct gcgccagcat aaggtttgga agaagtgccg
     2701 gatgcgcatt ttcaccgtgg cccagatgga tgacaacagc atccagatga agaaggatct
     2761 ggccatcttc ctgtatcacc tccgcctgga agctgaagtg gaggtggtag agatgcacaa
     2821 cagtgacatc tctgcctata cctatgagcg gacactgatg atggagcagc ggtctcagat
     2881 gctgcggcag atgaggttga ccaaaactga gcgggatcga gaggcccagc tggtaaagga
     2941 caggcactcg gctcttaggc tggagagcct ctactccgac gaggaggaag agtctgtggc
     3001 aggggccgac aagatccaga tgacgtggac cagagacaag tacatggctg agccctggga
     3061 ccccagccac gcccctgaca acttccggga gctggtgcac attaagccgg accagtccaa
     3121 cgtgcggcgc atgcacactg ctgtgaagct caacgaggtc attgtcacgc gctcccacga
     3181 tgcccgtctg gttttgctga acatgcctgg cccccctaag aacagcgagg gcgacgagaa
     3241 ctacatggaa ttccttgaag tcctaaccga gggccttgaa cgggtgttgt tggtgcgtgg
     3301 cggcggccgg gaagtcatca ccatctattc ctgagccccg atggagtctt gtggcctgga
     3361 gttggggtgt ctaggacaac agtgcccggc cttgcaccta cttgccagtt ctgctttgcc
     3421 cagccttgct ttggaccagc tctgctacgt ctccagggaa accaagcttg ggccttgcag
     3481 tggaaatgga tccgagggcc caggggaccc tggtggattt agggactgtc ccctcccata
     3541 ctccaataga ggcctatcct gactagagaa gactggtgag ggttgatacg ggatttgaat
     3601 tcccagatgg gcccacaagt gctatttatt gtatatttat tgtttggatg tcatcatttc
     3661 agaaagggga agaggggcac agtaagaggg ggagctgagc tgggcctgcc tgcaggaaga
     3721 cctggcccag gctgctgtgg gcagaggccc tcatcaagcc aagtggaatg gagccggcca
     3781 agctgagcct gacttttttc aataaaacat tgtgtacttc tgggcc
//
