LOCUS       NM_000031               3129 bp    mRNA    linear   PRI 03-APR-2024
DEFINITION  Homo sapiens aminolevulinate dehydratase (ALAD), transcript variant
            2, mRNA.
ACCESSION   NM_000031
VERSION     NM_000031.6
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 3129)
  AUTHORS   Palir,N., Stajnko,A., Snoj Tratnik,J., Mazej,D., Briski,A.S.,
            France-Stiglic,A., Rosolen,V., Mariuz,M., Giordani,E., Barbone,F.,
            Horvat,M. and Falnoga,I.
  TITLE     ALAD and APOE polymorphisms are associated with lead and mercury
            levels in Italian pregnant women and their newborns with adequate
            nutritional status of zinc and selenium
  JOURNAL   Environ Res 220, 115226 (2023)
   PUBMED   36621546
  REMARK    GeneRIF: ALAD and APOE polymorphisms are associated with lead and
            mercury levels in Italian pregnant women and their newborns with
            adequate nutritional status of zinc and selenium.
REFERENCE   2  (bases 1 to 3129)
  AUTHORS   Qader,A., Rehman,K. and Akash,M.S.H.
  TITLE     Genetic susceptibility of delta-ALAD associated with lead (Pb)
            intoxication: sources of exposure, preventive measures, and
            treatment interventions
  JOURNAL   Environ Sci Pollut Res Int 28 (33), 44818-44832 (2021)
   PUBMED   34244947
  REMARK    GeneRIF: Genetic susceptibility of delta-ALAD associated with lead
            (Pb) intoxication: sources of exposure, preventive measures, and
            treatment interventions.
            Review article
REFERENCE   3  (bases 1 to 3129)
  AUTHORS   Perini,J.A., Silva,M.C., Vasconcellos,A.C.S., Viana,P.V.S.,
            Lima,M.O., Jesus,I.M., Kempton,J.W., Oliveira,R.A.A., Hacon,S.S.
            and Basta,P.C.
  TITLE     Genetic Polymorphism of Delta Aminolevulinic Acid Dehydratase
            (ALAD) Gene and Symptoms of Chronic Mercury Exposure in Munduruku
            Indigenous Children within the Brazilian Amazon
  JOURNAL   Int J Environ Res Public Health 18 (16), 8746 (2021)
   PUBMED   34444495
  REMARK    GeneRIF: Genetic Polymorphism of Delta Aminolevulinic Acid
            Dehydratase (ALAD) Gene and Symptoms of Chronic Mercury Exposure in
            Munduruku Indigenous Children within the Brazilian Amazon.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 3129)
  AUTHORS   Liu,G., Sil,D., Maio,N., Tong,W.H., Bollinger,J.M. Jr., Krebs,C.
            and Rouault,T.A.
  TITLE     Heme biosynthesis depends on previously unrecognized acquisition of
            iron-sulfur cofactors in human amino-levulinic acid dehydratase
  JOURNAL   Nat Commun 11 (1), 6310 (2020)
   PUBMED   33298951
  REMARK    GeneRIF: Heme biosynthesis depends on previously unrecognized
            acquisition of iron-sulfur cofactors in human amino-levulinic acid
            dehydratase.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3129)
  AUTHORS   Gevaert,K., Goethals,M., Martens,L., Van Damme,J., Staes,A.,
            Thomas,G.R. and Vandekerckhove,J.
  TITLE     Exploring proteomes and analyzing protein processing by mass
            spectrometric identification of sorted N-terminal peptides
  JOURNAL   Nat Biotechnol 21 (5), 566-569 (2003)
   PUBMED   12665801
REFERENCE   6  (bases 1 to 3129)
  AUTHORS   Dawson,S.J. and White,L.A.
  TITLE     Treatment of Haemophilus aphrophilus endocarditis with
            ciprofloxacin
  JOURNAL   J Infect 24 (3), 317-320 (1992)
   PUBMED   1602151
REFERENCE   7  (bases 1 to 3129)
  AUTHORS   Ishida,N., Fujita,H., Fukuda,Y., Noguchi,T., Doss,M., Kappas,A. and
            Sassa,S.
  TITLE     Cloning and expression of the defective genes from a patient with
            delta-aminolevulinate dehydratase porphyria
  JOURNAL   J Clin Invest 89 (5), 1431-1437 (1992)
   PUBMED   1569184
REFERENCE   8  (bases 1 to 3129)
  AUTHORS   Astrin,K.H., Kaya,A.H., Wetmur,J.G. and Desnick,R.J.
  TITLE     RsaI polymorphism in the human delta-aminolevulinate dehydratase
            gene at 9q34
  JOURNAL   Nucleic Acids Res 19 (15), 4307 (1991)
   PUBMED   1678509
REFERENCE   9  (bases 1 to 3129)
  AUTHORS   Wetmur,J.G., Bishop,D.F., Cantelmo,C. and Desnick,R.J.
  TITLE     Human delta-aminolevulinate dehydratase: nucleotide sequence of a
            full-length cDNA clone
  JOURNAL   Proc Natl Acad Sci U S A 83 (20), 7703-7707 (1986)
   PUBMED   3463993
REFERENCE   10 (bases 1 to 3129)
  AUTHORS   Roels,H.A., Buchet,J.P., Lauwerys,R.R. and Sonnet,J.
  TITLE     Comparison of in vivo effect of inorganic lead and cadmium on
            glutathione reductase system and delta-aminolevulinate dehydratase
            in human erythrocytes
  JOURNAL   Br J Ind Med 32 (3), 181-192 (1975)
   PUBMED   1156566
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA805310.1, AK290490.1,
            AK131490.1, BC000977.3 and BU625796.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 20, 2018 this sequence version replaced NM_000031.5.
            
            Summary: The ALAD enzyme is composed of 8 identical subunits and
            catalyzes the condensation of 2 molecules of delta-aminolevulinate
            to form porphobilinogen (a precursor of heme, cytochromes and other
            hemoproteins). ALAD catalyzes the second step in the porphyrin and
            heme biosynthetic pathway; zinc is essential for enzymatic
            activity. ALAD enzymatic activity is inhibited by lead and a defect
            in the ALAD structural gene can cause increased sensitivity to lead
            poisoning and acute hepatic porphyria. Alternative splicing of this
            gene results in multiple transcript variants encoding different
            isoforms. [provided by RefSeq, Dec 2015].
            
            Transcript Variant: This variant (2) lacks a segment of the coding
            region and initiates translation from an alternate start codon,
            compared to variant 1. The resulting isoform (b) has a distinct
            N-terminus, compared to isoform a.
            
            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 :: SRR1803617.172413.1,
                                           SRR1660805.72089.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            CDS uses downstream in-frame AUG :: experimental evidence
                                                (PMID:12665801)
            MANE Ensembl match               :: ENST00000409155.8/
                                                ENSP00000386284.3
            RefSeq Select criteria           :: based on conservation,
                                                expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-545               DA805310.1         18-562
            546-1236            AK290490.1         712-1402
            1237-3090           AK131490.1         1430-3283
            3091-3124           BC000977.3         3069-3102
            3125-3129           BU625796.1         18-22               c
FEATURES             Location/Qualifiers
     source          1..3129
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="9"
                     /map="9q32"
     gene            1..3129
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /note="aminolevulinate dehydratase"
                     /db_xref="GeneID:210"
                     /db_xref="HGNC:HGNC:395"
                     /db_xref="MIM:125270"
     exon            1..73
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /inference="alignment:Splign:2.1.0"
     exon            74..261
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /inference="alignment:Splign:2.1.0"
     CDS             149..1141
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /EC_number="4.2.1.24"
                     /note="isoform b is encoded by transcript variant 2;
                     porphobilinogen synthase; aminolevulinate, delta-,
                     dehydratase; testicular tissue protein Li 95;
                     delta-aminolevulinic acid dehydratase"
                     /codon_start=1
                     /product="delta-aminolevulinic acid dehydratase isoform b"
                     /protein_id="NP_000022.3"
                     /db_xref="CCDS:CCDS6794.2"
                     /db_xref="GeneID:210"
                     /db_xref="HGNC:HGNC:395"
                     /db_xref="MIM:125270"
                     /translation="MQPQSVLHSGYFHPLLRAWQTATTTLNASNLIYPIFVTDVPDDI
                     QPITSLPGVARYGVKRLEEMLRPLVEEGLRCVLIFGVPSRVPKDERGSAADSEESPAI
                     EAIHLLRKTFPNLLVACDVCLCPYTSHGHCGLLSENGAFRAEESRQRLAEVALAYAKA
                     GCQVVAPSDMMDGRVEAIKEALMAHGLGNRVSVMSYSAKFASCFYGPFRDAAKSSPAF
                     GDRRCYQLPPGARGLALRAVDRDVREGADMLMVKPGMPYLDIVREVKDKHPDLPLAVY
                     HVSGEFAMLWHGAQAGAFDLKAAVLEAMTAFRRAGADIIITYYTPQLLQWLKEE"
     exon            262..312
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /inference="alignment:Splign:2.1.0"
     exon            313..409
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /inference="alignment:Splign:2.1.0"
     exon            410..545
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /inference="alignment:Splign:2.1.0"
     exon            546..629
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /inference="alignment:Splign:2.1.0"
     exon            630..718
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /inference="alignment:Splign:2.1.0"
     exon            719..774
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /inference="alignment:Splign:2.1.0"
     exon            775..862
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /inference="alignment:Splign:2.1.0"
     exon            863..949
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /inference="alignment:Splign:2.1.0"
     exon            950..1079
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /inference="alignment:Splign:2.1.0"
     exon            1080..3129
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3104..3109
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /note="hexamer: AATAAA"
     polyA_site      3129
                     /gene="ALAD"
                     /gene_synonym="ALADH; PBGS"
                     /note="major polyA site"
ORIGIN      
        1 acgcggtctg tgggagaccg gagcgggaga cagcggtgac aggagcagcg gccgggagcc
       61 cttagggagg cagacagagc ctgcagccaa tgccccagga gccctcggtt ccaaccaact
      121 gatgcccctg tgcccactgg cccacgccat gcagccccag tccgttctgc acagcggcta
      181 cttccaccca ctacttcggg cctggcagac agccaccacc accctcaatg cctccaacct
      241 catctacccc atctttgtca cggatgttcc tgatgacata cagcctatca ccagcctccc
      301 aggagtggcc aggtatggtg tgaagcggct ggaagagatg ctgaggccct tggtggaaga
      361 gggcctacgc tgtgtcttga tctttggcgt ccccagcaga gttcccaagg acgagcgggg
      421 ttccgcagct gactccgagg agtccccagc tattgaggca atccatctgt tgaggaagac
      481 cttccccaac ctcctggtgg cctgtgatgt ctgcctgtgt ccctacacct cccatggtca
      541 ctgcgggctc ctgagtgaaa acggagcatt ccgggctgag gagagccgcc agcggctggc
      601 tgaggtggca ttggcgtatg ccaaggcagg atgtcaggtg gtagccccgt cggacatgat
      661 ggatggacgc gtggaagcca tcaaagaggc cctgatggca catggacttg gcaacagggt
      721 atcggtgatg agctacagtg ccaaatttgc ttcctgtttc tatggccctt tccgggatgc
      781 agctaagtca agcccagctt ttggggaccg ccgctgctac cagctgcccc ctggagcacg
      841 aggcctggct ctccgagctg tggaccggga tgtacgggaa ggagctgaca tgctcatggt
      901 gaagccggga atgccctacc tggacatcgt gcgggaggta aaggacaagc accctgacct
      961 ccctctcgcc gtgtaccacg tctctggaga gtttgccatg ctgtggcatg gagcccaggc
     1021 cggggcattt gatctcaagg ctgccgtact ggaggccatg actgccttcc gcagagcagg
     1081 tgctgacatc atcatcacct actacacacc gcagctgctg cagtggctga aggaggaatg
     1141 atggagacag tgccaggccc aagaactaga actttaaaac gttcccgggg cctcagacaa
     1201 gtgaaaacca aagtaaatgc tgcttttaga actgtgccct catgccctct tcctgctcac
     1261 atgctagcgg ggcccagcag ccctgggtgg ttttgccagc atgctaactc ttgtaactcg
     1321 cagctgcatc ctatgagctc tcccaagctt ccccgcccct cccctgggtc agccgtgagg
     1381 cccacctttg ccaccctcag ctctttcctc tggtgtggct tcagcttgaa agcaacctgg
     1441 agtcgggggc acagcctttg gggcctggct gggagagggt cttggagcat taggggaaga
     1501 agagagcagt gggatcttgg ggcctgagaa gccttggaac gcttctggca gcagagctgg
     1561 gtgtgggaat gaggcctaga tcgatatccc tgggttagag ttgaaatttg ccgcaattcc
     1621 actggaaggc atttcccacg aggccagagg ttgccaggct gcctgaggtc tcctattcta
     1681 ctctgaacca taaacccaga gaagaattac tcattaacca gcataaatac tgcctgagga
     1741 tcaaaactca gaggcaaaga gggagttcct gactgctaga ggtgccacca ccacaaacac
     1801 tttttattca ggagatactt tttgagaatc tctgctctgt tcctaggttc agtgctgggt
     1861 cctgggaata cagcaggaca gacctcagct tatctcttca tagaaattat acaaagagaa
     1921 ttggggagac agctaagaag aaaacaaaga aataaagcag ttacaaattg tgataagtgc
     1981 tttgaaggaa agaaggggtc tgagacaaca acagggaagg ggcctctctt gaaacagtag
     2041 ttgggaagga ggcagacatg caccagtgat gtggtgacag gtgctctgaa ggaggtcacc
     2101 aggacctgac ctctttgaag gatcagaaaa tacttccctg aaggactgac atttgagcct
     2161 agacctgaag ggtgagccat caagctaaga caattgggga agagcattcc agggagaggg
     2221 aggagttgtg caaaggccct ggggctcctt ctagctggag gaatgcaagg ctagcttgtc
     2281 tggagcactg agaggatggc ctgaactgag tggagagaga cagaccagga ccaaaccatg
     2341 cagaggtcaa gggccacatt caccttttca gagtgactca atcaaatttg tagtttgtaa
     2401 aagtatttta acagctctgc ggcaaagtgc aaatgaaaag tcttgatggc atggactgga
     2461 gcggggacag tggggatgga gaaaggggaa tggattgtgg atgtgtttag aaggtagatt
     2521 cgatgtgaag gatgaatctg gcttgacctt ctgggtggct gatgggccat ttactgagat
     2581 ggggcagcct ggaagaggaa cagaagcagg gtcggggtgg agggagaata ctaaacttag
     2641 cttgagacat tttgcaataa ggaagctata tctagagtgc ttatgtgact cacctaaggc
     2701 cactcaacaa gtttgtggca gaactggatt agaactgcac agaaaacagc caagctggga
     2761 tttgaaccca tgtagtccaa ctccaaggcc tctgccccta accactgtgc cataccacct
     2821 cccaataatc aacagcaaaa ttataggtct aacaatgttt tatagacacc cctccattta
     2881 tgtgatgggt ttgcatcctg ataaacccat cataagttga aaatatgatc ataagttgaa
     2941 aatatgatca taagtcaaaa atgtatttaa tatacctaac ctaccaaaca tcatagctta
     3001 gcctagcctg ccttaaacat gctcagaaca cttacattag cctacagtgg gcaaaactat
     3061 ccaacacaaa atctatattg taataaagtt gtaaagaatt ttgaataaaa attcaatatt
     3121 tgaagtaca
//
