LOCUS       NM_000670               2002 bp    mRNA    linear   PRI 07-APR-2024
DEFINITION  Homo sapiens alcohol dehydrogenase 4 (class II), pi polypeptide
            (ADH4), transcript variant 3, mRNA.
ACCESSION   NM_000670
VERSION     NM_000670.5
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 2002)
  AUTHORS   Karunakara,S.H., Puttahanumantharayappa,L.D., Sannappa Gowda,N.G.,
            Shiragannavar,V.D. and Santhekadur,P.K.
  TITLE     Novel Insights into MEG3/miR664a-3p/ADH4 Axis and Its Possible Role
            in Hepatocellular Carcinoma from an in Silico Perspective
  JOURNAL   Genes (Basel) 13 (12), 2254 (2022)
   PUBMED   36553522
  REMARK    GeneRIF: Novel Insights into MEG3/miR664a-3p/ADH4 Axis and Its
            Possible Role in Hepatocellular Carcinoma from an in Silico
            Perspective.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2002)
  AUTHORS   Cui,J., Peng,W., Yi,T., Gao,P., Zhou,M. and Zhu,T.
  TITLE     No significant association between SNPs in the CLOCK and ADH4 genes
            and susceptibility to cluster headaches: A systematic review and
            meta-analysis
  JOURNAL   Ann Hum Genet 86 (4), 159-170 (2022)
   PUBMED   35437765
  REMARK    GeneRIF: No significant association between SNPs in the CLOCK and
            ADH4 genes and susceptibility to cluster headaches: A systematic
            review and meta-analysis.
REFERENCE   3  (bases 1 to 2002)
  AUTHORS   Luo,J., Hou,Y., Ma,W., Xie,M., Jin,Y., Xu,L., Li,C., Wang,Y.,
            Chen,J., Chen,W., Zheng,Y. and Yu,D.
  TITLE     A novel mechanism underlying alcohol dehydrogenase expression:
            hsa-miR-148a-3p promotes ADH4 expression via an AGO1-dependent
            manner in control and ethanol-exposed hepatic cells
  JOURNAL   Biochem Pharmacol 189, 114458 (2021)
   PUBMED   33556337
  REMARK    GeneRIF: A novel mechanism underlying alcohol dehydrogenase
            expression: hsa-miR-148a-3p promotes ADH4 expression via an
            AGO1-dependent manner in control and ethanol-exposed hepatic cells.
REFERENCE   4  (bases 1 to 2002)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   5  (bases 1 to 2002)
  AUTHORS   Papasavva,M., Katsarou,M.S., Vikelis,M., Mitropoulou,E.,
            Dermitzakis,E.V., Papakonstantinou,S., Arvaniti,C.,
            Mitsikostas,D.D., Gozes,I., Tsatsakis,A.M. and Drakoulis,N.
  TITLE     Analysis of HCRTR2, GNB3, and ADH4 Gene Polymorphisms in a
            Southeastern European Caucasian Cluster Headache Population
  JOURNAL   J Mol Neurosci 70 (3), 467-474 (2020)
   PUBMED   31768945
  REMARK    GeneRIF: Analysis of HCRTR2, GNB3, and ADH4 Gene Polymorphisms in a
            Southeastern European Caucasian Cluster Headache Population.
REFERENCE   6  (bases 1 to 2002)
  AUTHORS   Edman,K. and Maret,W.
  TITLE     Alcohol dehydrogenase genes: restriction fragment length
            polymorphisms for ADH4 (pi-ADH) and ADH5 (chi-ADH) and construction
            of haplotypes among different ADH classes
  JOURNAL   Hum Genet 90 (4), 395-401 (1992)
   PUBMED   1362387
REFERENCE   7  (bases 1 to 2002)
  AUTHORS   von Bahr-Lindstrom,H., Jornvall,H. and Hoog,J.O.
  TITLE     Cloning and characterization of the human ADH4 gene
  JOURNAL   Gene 103 (2), 269-274 (1991)
   PUBMED   1889753
REFERENCE   8  (bases 1 to 2002)
  AUTHORS   Hoog,J.O., von Bahr-Lindstrom,H., Heden,L.O., Holmquist,B.,
            Larsson,K., Hempel,J., Vallee,B.L. and Jornvall,H.
  TITLE     Structure of the class II enzyme of human liver alcohol
            dehydrogenase: combined cDNA and protein sequence determination of
            the pi subunit
  JOURNAL   Biochemistry 26 (7), 1926-1932 (1987)
   PUBMED   3036213
REFERENCE   9  (bases 1 to 2002)
  AUTHORS   Mardh,G., Dingley,A.L., Auld,D.S. and Vallee,B.L.
  TITLE     Human class II (pi) alcohol dehydrogenase has a redox-specific
            function in norepinephrine metabolism
  JOURNAL   Proc Natl Acad Sci U S A 83 (23), 8908-8912 (1986)
   PUBMED   3466164
REFERENCE   10 (bases 1 to 2002)
  AUTHORS   Lange,L.G., Sytkowski,A.J. and Vallee,B.L.
  TITLE     Human liver alcohol dehydrogenase: purification, composition, and
            catalytic features
  JOURNAL   Biochemistry 15 (21), 4687-4693 (1976)
   PUBMED   9982
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AP002026.2 and AC019131.7.
            
            On Feb 27, 2020 this sequence version replaced NM_000670.4.
            
            Summary: This gene encodes class II alcohol dehydrogenase 4 pi
            subunit, which is a member of the alcohol dehydrogenase family.
            Members of this enzyme family metabolize a wide variety of
            substrates, including ethanol, retinol, other aliphatic alcohols,
            hydroxysteroids, and lipid peroxidation products. Class II alcohol
            dehydrogenase is a homodimer composed of 2 pi subunits. It exhibits
            a high activity for oxidation of long-chain aliphatic alcohols and
            aromatic alcohols and is less sensitive to pyrazole. This gene is
            localized to chromosome 4 in the cluster of alcohol dehydrogenase
            genes. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (3) differs in the 5' UTR and
            lacks an exon in the 5' coding region, which results in use of an
            alternate start codon compared to variant 1. It encodes isoform 2,
            which is shorter than and has a novel N-terminus 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 :: BC022319.1, AK290835.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2162895 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000265512.12/ ENSP00000265512.7
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-93                AP002026.2         70186-70278         c
            94-195              AP002026.2         68660-68761         c
            196-337             AP002026.2         67522-67663         c
            338-425             AP002026.2         65042-65129         c
            426-657             AP002026.2         62447-62678         c
            658-918             AP002026.2         57485-57745         c
            919-1054            AP002026.2         53190-53325         c
            1055-1193           AP002026.2         52575-52713         c
            1194-2002           AC019131.7         206928-207736       c
FEATURES             Location/Qualifiers
     source          1..2002
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4q23"
     gene            1..2002
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /note="alcohol dehydrogenase 4 (class II), pi polypeptide"
                     /db_xref="GeneID:127"
                     /db_xref="HGNC:HGNC:252"
                     /db_xref="MIM:103740"
     exon            1..93
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /inference="alignment:Splign:2.1.0"
     CDS             76..1218
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /EC_number="1.1.1.105"
                     /note="isoform 2 is encoded by transcript variant 3;
                     aldehyde reductase; alcohol dehydrogenase class II pi
                     chain; epididymis secretory protein Li 4;
                     all-trans-retinol dehydrogenase [NAD(+)] ADH4; alcohol
                     dehydrogenase 2"
                     /codon_start=1
                     /product="all-trans-retinol dehydrogenase [NAD(+)] ADH4
                     isoform 2"
                     /protein_id="NP_000661.2"
                     /db_xref="CCDS:CCDS34032.1"
                     /db_xref="GeneID:127"
                     /db_xref="HGNC:HGNC:252"
                     /db_xref="MIM:103740"
                     /translation="MGTKGKVIKCKAAIAWEAGKPLCIEEVEVAPPKAHEVRIQIIAT
                     SLCHTDATVIDSKFEGLAFPVIVGHEAAGIVESIGPGVTNVKPGDKVIPLYAPLCRKC
                     KFCLSPLTNLCGKISNLKSPASDQQLMEDKTSRFTCKGKPVYHFFGTSTFSQYTVVSD
                     INLAKIDDDANLERVCLLGCGFSTGYGAAINNAKVTPGSTCAVFGLGGVGLSAVMGCK
                     AAGASRIIGIDINSEKFVKAKALGATDCLNPRDLHKPIQEVIIELTKGGVDFALDCAG
                     GSETMKAALDCTTAGWGSCTFIGVAAGSKGLTIFPEELIIGRTINGTFFGGWKSVDSI
                     PKLVTDYKNKKFNLDALVTHTLPFDKISEAFDLMNQGKSVRTILIF"
     exon            94..195
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /inference="alignment:Splign:2.1.0"
     exon            196..337
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /inference="alignment:Splign:2.1.0"
     exon            338..425
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /inference="alignment:Splign:2.1.0"
     exon            426..657
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /inference="alignment:Splign:2.1.0"
     exon            658..918
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /inference="alignment:Splign:2.1.0"
     exon            919..1054
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /inference="alignment:Splign:2.1.0"
     exon            1055..1193
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /inference="alignment:Splign:2.1.0"
     exon            1194..2002
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1838..1843
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /note="hexamer: AATAAA"
     polyA_site      1865
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /note="major polyA site"
     regulatory      1974..1979
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
                     /note="hexamer: AATAAA"
     polyA_site      2002
                     /gene="ADH4"
                     /gene_synonym="ADH-2; HEL-S-4"
ORIGIN      
        1 acggaactcc ctgggtagga gtttgaagct ttcttaactc agaaagaaac ttccaacaca
       61 gtttcccaaa gaaaaatggg caccaagggc aaagttatta aatgcaaagc agccatcgcc
      121 tgggaagcag gcaagcccct ttgcattgaa gaggttgaag tagctccccc caaggctcat
      181 gaagttcgca ttcagatcat tgctacctct ctgtgccata ctgatgccac tgttatcgat
      241 tctaaatttg agggcctagc tttcccagtg atcgttggcc atgaggctgc aggtattgtg
      301 gaaagtattg ggccaggagt gaccaacgtc aaaccaggtg acaaagtaat tccactttat
      361 gcacctctat gtagaaaatg caagttttgt ctgagtccac tcacaaattt gtgtgggaaa
      421 atcagtaatc tcaaaagtcc tgctagtgat caacaactaa tggaagacaa aaccagcagg
      481 tttacctgca aaggaaaacc agtttaccat ttctttggaa ccagtacatt ctctcagtac
      541 actgtggtgt cagatatcaa tcttgccaaa atagatgatg atgcaaattt agagagagtt
      601 tgtctgcttg gatgtgggtt ttcaactggc tatggggctg caatcaacaa tgccaaggtc
      661 acccctggtt cgacttgtgc tgtctttggc ctaggaggtg tgggtctttc tgctgtaatg
      721 ggttgtaaag cagcaggagc ttccagaatc ataggtattg acatcaacag tgagaagttt
      781 gtgaaggcta aagccctggg agccactgac tgcctcaatc ctagagactt acataaaccg
      841 atccaggaag ttatcattga attgaccaag ggaggtgtgg attttgccct tgactgtgca
      901 ggtggatctg aaaccatgaa agcagccctg gactgtacaa ccgcaggctg gggatcatgt
      961 actttcattg gagtagctgc tggtagcaaa ggattgacta tttttccaga ggagctaata
     1021 atcggccgta ctataaatgg aacattcttt ggtggttgga aaagtgtaga ttctatccca
     1081 aagctggtca ctgactataa gaataagaaa ttcaatctgg atgcactggt gacccatacc
     1141 ctgccttttg acaaaatcag tgaggcattt gacctaatga accaaggaaa aagcgtccga
     1201 acaatcctca tcttttgaag atgccaggag caattcagaa tactatctga ttgaatgtga
     1261 acctgcctgg ttaatttatt acctgatttg atgaaccaag gaaagccatg agtttaaaca
     1321 aatatttaca tttaatatgg gaacataaaa gagctttaaa tattatagac tttgtacctg
     1381 ttatatatat gaatattccc tatgttaaat aataataata actagtgttt atgaatagaa
     1441 tcatatcatc tttagaaatt gtttaaaatt agttctggga agttgaaagt ggggaatgaa
     1501 gagataataa ataaaactag attggccata tgtttataat ttttttagat tgggtaatga
     1561 atacatggag tttcattata cttttctctc cacttttgtc tatgttgaaa attttctggg
     1621 agctaaatga tgagaacaca tggacacatg atggggaaca acacacactg gggcctgttg
     1681 agggcaggga gtcggcagag agagagcatc aggaagaata gctaatggat gctgggcttc
     1741 atacctgggt gatgagatga tctgtgcagc aaagcaccat ggtacatgtt tacctatgta
     1801 acaaacctgc acatcctgca catgtaccct ggaacttaat aaaagttgga aatttttaaa
     1861 aagaatgaat aagacctggt atttgatagc acaacaggga gactatagtc aacagcaatt
     1921 taattgtata ttttaatatg actaaaagag tataatggat tgtttgtaac acaaataaat
     1981 gcttgaggag atggacaccc ca
//
