LOCUS       NM_001650               5158 bp    mRNA    linear   PRI 09-OCT-2024
DEFINITION  Homo sapiens aquaporin 4 (AQP4), transcript variant 4, mRNA.
ACCESSION   NM_001650
VERSION     NM_001650.7
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 5158)
  AUTHORS   Braun,M., Sevao,M., Keil,S.A., Gino,E., Wang,M.X., Lee,J.,
            Haveliwala,M.A., Klein,E., Agarwal,S., Pedersen,T., Rhodes,C.H.,
            Jansson,D., Cook,D., Peskind,E., Perl,D.P., Piantino,J.,
            Schindler,A.G. and Iliff,J.J.
  TITLE     Macroscopic changes in aquaporin-4 underlie blast traumatic brain
            injury-related impairment in glymphatic function
  JOURNAL   Brain 147 (6), 2214-2229 (2024)
   PUBMED   38802114
  REMARK    GeneRIF: Macroscopic changes in aquaporin-4 underlie blast
            traumatic brain injury-related impairment in glymphatic function.
REFERENCE   2  (bases 1 to 5158)
  AUTHORS   De Bellis,M., Pisani,F., Mola,M.G., Rosito,S., Simone,L.,
            Buccoliero,C., Trojano,M., Nicchia,G.P., Svelto,M. and Frigeri,A.
  TITLE     Translational readthrough generates new astrocyte AQP4 isoforms
            that modulate supramolecular clustering, glial endfeet
            localization, and water transport
  JOURNAL   Glia 65 (5), 790-803 (2017)
   PUBMED   28206694
REFERENCE   3  (bases 1 to 5158)
  AUTHORS   Loughran,G., Chou,M.Y., Ivanov,I.P., Jungreis,I., Kellis,M.,
            Kiran,A.M., Baranov,P.V. and Atkins,J.F.
  TITLE     Evidence of efficient stop codon readthrough in four mammalian
            genes
  JOURNAL   Nucleic Acids Res 42 (14), 8928-8938 (2014)
   PUBMED   25013167
REFERENCE   4  (bases 1 to 5158)
  AUTHORS   De Bellis,M., Pisani,F., Mola,M.G., Basco,D., Catalano,F.,
            Nicchia,G.P., Svelto,M. and Frigeri,A.
  TITLE     A novel human aquaporin-4 splice variant exhibits a
            dominant-negative activity: a new mechanism to regulate water
            permeability
  JOURNAL   Mol Biol Cell 25 (4), 470-480 (2014)
   PUBMED   24356448
  REMARK    GeneRIF: The expression of AQP4-Delta4 may represent a new
            regulatory mechanism through which the cell-surface expression and
            therefore the activity of AQP4 can be physiologically modulated.
REFERENCE   5  (bases 1 to 5158)
  AUTHORS   Rossi,A., Pisani,F., Nicchia,G.P., Svelto,M. and Frigeri,A.
  TITLE     Evidences for a leaky scanning mechanism for the synthesis of the
            shorter M23 protein isoform of aquaporin-4: implication in
            orthogonal array formation and neuromyelitis optica antibody
            interaction
  JOURNAL   J Biol Chem 285 (7), 4562-4569 (2010)
   PUBMED   20007705
  REMARK    GeneRIF: In cells transiently transfected with AQP4-M1 coding
            sequence we observed besides AQP4-M1 the additional presence of the
            AQP4-M23 isoform associated with the formation of typical
            orthogonal arrays of particles.
REFERENCE   6  (bases 1 to 5158)
  AUTHORS   Beier,H. and Grimm,M.
  TITLE     Misreading of termination codons in eukaryotes by natural nonsense
            suppressor tRNAs
  JOURNAL   Nucleic Acids Res 29 (23), 4767-4782 (2001)
   PUBMED   11726686
  REMARK    Review article
REFERENCE   7  (bases 1 to 5158)
  AUTHORS   Umenishi,F. and Verkman,A.S.
  TITLE     Isolation and functional analysis of alternative promoters in the
            human aquaporin-4 water channel gene
  JOURNAL   Genomics 50 (3), 373-377 (1998)
   PUBMED   9676432
REFERENCE   8  (bases 1 to 5158)
  AUTHORS   Lu,M., Lee,M.D., Smith,B.L., Jung,J.S., Agre,P., Verdijk,M.A.,
            Merkx,G., Rijss,J.P. and Deen,P.M.
  TITLE     The human AQP4 gene: definition of the locus encoding two water
            channel polypeptides in brain
  JOURNAL   Proc Natl Acad Sci U S A 93 (20), 10908-10912 (1996)
   PUBMED   8855281
REFERENCE   9  (bases 1 to 5158)
  AUTHORS   Yang,B., Ma,T. and Verkman,A.S.
  TITLE     cDNA cloning, gene organization, and chromosomal localization of a
            human mercurial insensitive water channel. Evidence for distinct
            transcriptional units
  JOURNAL   J Biol Chem 270 (39), 22907-22913 (1995)
   PUBMED   7559426
REFERENCE   10 (bases 1 to 5158)
  AUTHORS   Min,R., Abbink,T.E.M. and van der Knaap,M.S.
  TITLE     Megalencephalic Leukoencephalopathy with Subcortical Cysts
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301707
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from HQ901095.1, AK222684.1,
            DT220791.1, DA244620.1, AC018371.10 and BU687682.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_001650.6.
            
            Summary: This gene encodes a member of the aquaporin family of
            intrinsic membrane proteins that function as water-selective
            channels in the plasma membranes of many cells. This protein is the
            predominant aquaporin found in brain and has an important role in
            brain water homeostasis. Alternatively spliced transcript variants
            encoding different isoforms have been described for this gene.
            Additional isoforms, resulting from the use of alternative in-frame
            translation initiation codons, have also been described. Recent
            studies provided evidence for translational readthrough in this
            gene, and expression of C-terminally extended isoforms via the use
            of an alternative in-frame translation termination codon. [provided
            by RefSeq, Jun 2018].
            
            Transcript Variant: This variant (1, also known as hMIWC2)
            represents the predominant transcript and encodes four isoforms,
            resulting from the use of two alternative in-frame translation
            initiation codons and two alternative in-frame translation
            termination codons. This RefSeq represents isoform M1, which
            results from the use of the upstream AUG start codon and the
            upstream UGA stop codon.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: SRR1660809.115395.1,
                                           SRR1660803.80948.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2147920, SAMEA2154665
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000383168.9/ ENSP00000372654.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-990               HQ901095.1         112-1101
            991-1432            AK222684.1         1040-1481
            1433-1902           DT220791.1         218-687
            1903-2107           DA244620.1         394-598
            2108-4598           AC018371.10        14081-16571
            4599-5158           BU687682.1         23-582              c
FEATURES             Location/Qualifiers
     source          1..5158
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="18"
                     /map="18q11.2"
     gene            1..5158
                     /gene="AQP4"
                     /gene_synonym="hAQP4; MIWC; MLC4; WCH4"
                     /note="aquaporin 4"
                     /db_xref="GeneID:361"
                     /db_xref="HGNC:HGNC:637"
                     /db_xref="MIM:600308"
     exon            1..50
                     /gene="AQP4"
                     /gene_synonym="hAQP4; MIWC; MLC4; WCH4"
                     /inference="alignment:Splign:2.1.0"
     CDS             19..990
                     /gene="AQP4"
                     /gene_synonym="hAQP4; MIWC; MLC4; WCH4"
                     /note="isoform M1 is encoded by transcript variant 4;
                     mercurial-insensitive water channel; aquaporin type4"
                     /codon_start=1
                     /product="aquaporin-4 isoform M1"
                     /protein_id="NP_001641.1"
                     /db_xref="CCDS:CCDS11889.1"
                     /db_xref="GeneID:361"
                     /db_xref="HGNC:HGNC:637"
                     /db_xref="MIM:600308"
                     /translation="MSDRPTARRWGKCGPLCTRENIMVAFKGVWTQAFWKAVTAEFLA
                     MLIFVLLSLGSTINWGGTEKPLPVDMVLISLCFGLSIATMVQCFGHISGGHINPAVTV
                     AMVCTRKISIAKSVFYIAAQCLGAIIGAGILYLVTPPSVVGGLGVTMVHGNLTAGHGL
                     LVELIITFQLVFTIFASCDSKRTDVTGSIALAIGFSVAIGHLFAINYTGASMNPARSF
                     GPAVIMGNWENHWIYWVGPIIGAVLAGGLYEYVFCPDVEFKRRFKEAFSKAAQQTKGS
                     YMEVEDNRSQVETDDLILKPGVVHVIDVDRGEEKKGKDQSGEVLSSV"
     exon            51..465
                     /gene="AQP4"
                     /gene_synonym="hAQP4; MIWC; MLC4; WCH4"
                     /inference="alignment:Splign:2.1.0"
     exon            466..630
                     /gene="AQP4"
                     /gene_synonym="hAQP4; MIWC; MLC4; WCH4"
                     /inference="alignment:Splign:2.1.0"
     exon            631..711
                     /gene="AQP4"
                     /gene_synonym="hAQP4; MIWC; MLC4; WCH4"
                     /inference="alignment:Splign:2.1.0"
     exon            712..5158
                     /gene="AQP4"
                     /gene_synonym="hAQP4; MIWC; MLC4; WCH4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5129..5134
                     /regulatory_class="polyA_signal_sequence"
                     /gene="AQP4"
                     /gene_synonym="hAQP4; MIWC; MLC4; WCH4"
                     /note="hexamer: AATAAA"
     polyA_site      5158
                     /gene="AQP4"
                     /gene_synonym="hAQP4; MIWC; MLC4; WCH4"
                     /note="major polyA site"
ORIGIN      
        1 actctggctg gggaaggcat gagtgacaga cccacagcaa ggcggtgggg taagtgtgga
       61 cctttgtgta ccagagagaa catcatggtg gctttcaaag gggtctggac tcaagctttc
      121 tggaaagcag tcacagcgga atttctggcc atgcttattt ttgttctcct cagcctggga
      181 tccaccatca actggggtgg aacagaaaag cctttaccgg tcgacatggt tctcatctcc
      241 ctttgctttg gactcagcat tgcaaccatg gtgcagtgct ttggccatat cagcggtggc
      301 cacatcaacc ctgcagtgac tgtggccatg gtgtgcacca ggaagatcag catcgccaag
      361 tctgtcttct acatcgcagc ccagtgcctg ggggccatca ttggagcagg aatcctctat
      421 ctggtcacac ctcccagtgt ggtgggaggc ctgggagtca ccatggttca tggaaatctt
      481 accgctggtc atggtctcct ggttgagttg ataatcacat ttcaattggt gtttactatc
      541 tttgccagct gtgattccaa acggactgat gtcactggct caatagcttt agcaattgga
      601 ttttctgttg caattggaca tttatttgca atcaattata ctggtgccag catgaatccc
      661 gcccgatcct ttggacctgc agttatcatg ggaaattggg aaaaccattg gatatattgg
      721 gttgggccca tcataggagc tgtcctcgct ggtggccttt atgagtatgt cttctgtcca
      781 gatgttgaat tcaaacgtcg ttttaaagaa gccttcagca aagctgccca gcaaacaaaa
      841 ggaagctaca tggaggtgga ggacaacagg agtcaggtag agacggatga cctgattcta
      901 aaacctggag tggtgcatgt gattgacgtt gaccggggag aggagaagaa ggggaaagac
      961 caatctggag aggtattgtc ttcagtatga ctagaagatc gcactgaaag cagacaagac
     1021 tccttagaac tgtcctcaga tttccttcca cccattaagg aaacagattt gttataaatt
     1081 agaaatgtgc aggtttgttg tttcatgtca tattactcag tctaaacaat aaatatttca
     1141 taatttacaa aggaggaacg gaagaaacct attgtgaatt ccaaatctaa aaaaagaaat
     1201 atttttaaaa tgttcttaag caaatatata cctattttat ctagttacct ttcattaaca
     1261 accaatttta accgtgtgtc aagatttggt taagtcttgc ctgacagaac tcaaagacac
     1321 gtctatcagc ttattccttc tctactggaa tattggtata gtcaattctt atttgaatat
     1381 ttattctatt aaactgagtt taacaatggc aaaatacagt atgtcacagt catgcacatt
     1441 caagagagaa aatataacaa gttcttttat gagcaatccc ttatgcatag actaccttgg
     1501 caaaagagca ttagcaagtg tcactgctca tcagttactt ccttccattt atatcacaaa
     1561 tacccaagtt tcaattctaa cttcatttca tggtatttct tcctcctcaa tgcccaaggt
     1621 aatgtgggac taaagcccag aaatttgaaa agaatattca gaaatccttc ccaaatcata
     1681 agggcaccta ttgagattca agacaagcag actcgtaaaa tcttgtagag gcagaggcaa
     1741 agttatcatc atacaaaaat cacaaacaaa aaggagatct gtattcgggt atcaaacggt
     1801 tgatctgttt tcagtgcaca ccctcaaatg caccacacca gttttacgat ctaagctttt
     1861 aaccccttta ccactttgct tatttttaaa aaatttattg gcaaaactgg ggattttgtt
     1921 tgtaactttg gttatctata tttaaacatt agctgagaca tatttttgat aacaagaact
     1981 tagctagttg agtcctggct ttttgttgat tattaagctg tgttcactct agaaggtgta
     2041 aaggccctgt cccaatctct gctctctcac ttctcgtgac atttgttgat aatctttact
     2101 gcaagtgtaa tgatatttga gtgaattaaa atgcatgaca gacaaggtac aacatggttg
     2161 cagaataaaa gggtgaggac atcagatcac tctgtattca aagcttacta gacgaacaat
     2221 ctttcatttc tggatatatt gtagctaacc caacacattt ttaaactatt tttgttactg
     2281 actcacttac ttgtcaaaat aattggtttt tctgtcctgc tttgcctttt gtcactagaa
     2341 tgttctccag aaaccccagt ttctgtcatc ttaactgtct agtctagccg ttaacttaga
     2401 caaagaagtg caaatgtcaa tttcactaaa caaaagctat tagaagtaaa gcagaaacct
     2461 atcactgcaa ggagtgactt gtaaataact gatgatcaag ggctgtcttc tctcaagcat
     2521 ggttccaact ctgtgtcact ttttagcgtt aatggcagtt gtgtgtctgt ggcagtgaga
     2581 taatggacca ctattaaacc tgattctctt cggtgctagg aaagagtgat gtgtgagatt
     2641 cccagagagt cgtcacacca gtgttatgcc tgggagtgcc actggcatac cgcaggtgcc
     2701 taaatcccag gcccctttct cagggggcgt ggccacacca cacactgcgc cagtgacaca
     2761 tagttacttc ctggctggga cggcacctat agaaactagg gtacaaatct cccaaagatg
     2821 gtttgcaccg tcatttcaaa tgtttgcaca atataccact tagaggctta aaatcagggt
     2881 ggttcagttc aaaaggtaat atcaaccgtc agcaaacatg tcagtttaaa aataagttcg
     2941 gttaacaagg aagtgttaag cagatttttt gaatacactt acaatatact ggcttataat
     3001 catttttatt ctgccatatg gtttatttca tatacactca cttttacact cacttccaat
     3061 tatagcattc aataagttac ggttaaagaa aagtgaatgg tgtttttgta atttgttttc
     3121 tagtagctag cagagagcct ggcacatagt atgtattcaa aacaagtgtg ttaattaata
     3181 aaaatatata aatctcattt gagatttaag aatataaata attttctttt aatctttatt
     3241 ttgctcaata tttaatagga agtatgattt caaggactac taaaggaagg caatatacat
     3301 gtgaaaacca taaaatacat tttttgcatt ctactatttt taggggcatg aaatgaatga
     3361 aagctttagc acttttttgc ccctacatat gagacaacat attttgtatt tcactcaagg
     3421 ctctgccagt aaaaagtaat gaaattgtac ctttctaatg acatctatgc agcaggggtc
     3481 tatcgccttg tggatggcac caaattatcc aagtgtatta ggagactggg gcttttttct
     3541 ttaatccctt cttattaatg aagtgcatag tgctgctccc aggagaccac tgctgacaga
     3601 tacacagaga agagatcaga gaggaaaaac tgggaagaca taaatgaatt atacccagcc
     3661 atgaaacaat gccaactgtc tcttccctaa ggaagagtac aagtacccta aaattgaaag
     3721 gtggtcccta cactgaaaac gcacatagtt tgtcaaaagt gtacaaaagg gaaagagtct
     3781 tattttaagc tttcaggctt tcttaaaaac ttggggacca gaatttcaat gtatgtttcc
     3841 attgttgaag ataacatttt cttcaaagag ccttaacctt ttgtactgga aggaaatatt
     3901 ttctggactt aagtagttgc ctaaatttaa gattcctaca ctttatttct gccattgatg
     3961 cttttcctaa acccttatac tatcttttta ttatctgagc cttttcctaa tgcagctcat
     4021 aggtgctagc tagagctgct gctcagtatt gaagacttta caaggagatt agaaatcttt
     4081 ggaaaacata tgtgatgaaa ttgagctata tgatttatca gagatctgat tccaaagagc
     4141 acagaatact gttctcagac catgaaacca gacaacacat gtattggttt aaactcgata
     4201 atgacaggaa aattccaaac tagagcagta aattcaaatg gtaagatgaa tcctagaagg
     4261 cctctgattg cagcatgttg acaccaacct cacgttacga acaattcaca gagaatttgc
     4321 ctttgtggca actgaagatg gaagtctggg gggcacagac aaccttatca aacaatataa
     4381 aagccaatat aaattctcat aagcactata gaatttgcaa attcagaaca ttttatacct
     4441 aaaagtaatt ctgtctttcc taaagtgttt ttaacatgaa aattagtagg aagatgtggt
     4501 tactatttgg aaagtgtaat gtaacaaaac tctcttttgt taccacaaat tttgtgagtt
     4561 tagtactcta cagattgccc cataagagca gtagcttttg aaactcataa ttctctgaaa
     4621 taaatgaaag acatttaatt caaggatcaa aaattgtggc catctttgca aatgactacc
     4681 tatagcctgt gaaaatacat ttcaaaaaat gttatgtgca atgaacacta aatttaagag
     4741 cagttacagt gtgactcact catgtttaaa aaaaatcgaa gagctaaaaa atacgtctaa
     4801 tttatgtaac ccattggaat gtatttctag gttctcttca ggattaatta aataaacatg
     4861 caatttatga aaacatataa acaattattt atcactttta tgacccaaat cacaataaaa
     4921 ttgtcattta ggataaactg gggagaatag actgaacata tggttatatt cacagttatt
     4981 tattaactta aatgttattc caacattaga gctaatgtta aaaagattta aactgtaacg
     5041 tctaatattt ggaataatat attaaagtat tagcactgtg gttgattttc ttgaattatg
     5101 ttgcatcttg tactactaag cttgtgaaaa taaacatttg gatgttttaa aaggtaaa
//
