LOCUS       NM_000688               2375 bp    mRNA    linear   PRI 20-SEP-2024
DEFINITION  Homo sapiens 5'-aminolevulinate synthase 1 (ALAS1), transcript
            variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_000688
VERSION     NM_000688.6
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 2375)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   2  (bases 1 to 2375)
  AUTHORS   Nomura,K., Kitagawa,Y., Aihara,M., Ohki,Y., Furuyama,K. and
            Hirokawa,T.
  TITLE     Heme-dependent recognition of 5-aminolevulinate synthase by the
            human mitochondrial molecular chaperone ClpX
  JOURNAL   FEBS Lett 595 (24), 3019-3029 (2021)
   PUBMED   34704252
  REMARK    GeneRIF: Heme-dependent recognition of 5-aminolevulinate synthase
            by the human mitochondrial molecular chaperone ClpX.
REFERENCE   3  (bases 1 to 2375)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   4  (bases 1 to 2375)
  AUTHORS   Lahiji,A.P., Anderson,K.E., Chan,A., Simon,A., Desnick,R.J. and
            Ramanujam,V.M.S.
  TITLE     5-Aminolevulinate dehydratase porphyria: Update on hepatic
            5-aminolevulinic acid synthase induction and long-term response to
            hemin
  JOURNAL   Mol Genet Metab 131 (4), 418-423 (2020)
   PUBMED   33199206
  REMARK    GeneRIF: 5-Aminolevulinate dehydratase porphyria: Update on hepatic
            5-aminolevulinic acid synthase induction and long-term response to
            hemin.
REFERENCE   5  (bases 1 to 2375)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   6  (bases 1 to 2375)
  AUTHORS   Cotter,P.D., Drabkin,H.A., Varkony,T., Smith,D.I. and Bishop,D.F.
  TITLE     Assignment of the human housekeeping delta-aminolevulinate synthase
            gene (ALAS1) to chromosome band 3p21.1 by PCR analysis of somatic
            cell hybrids
  JOURNAL   Cytogenet Cell Genet 69 (3-4), 207-208 (1995)
   PUBMED   7698013
REFERENCE   7  (bases 1 to 2375)
  AUTHORS   Bishop,D.F.
  TITLE     Two different genes encode delta-aminolevulinate synthase in
            humans: nucleotide sequences of cDNAs for the housekeeping and
            erythroid genes
  JOURNAL   Nucleic Acids Res 18 (23), 7187-7188 (1990)
   PUBMED   2263504
REFERENCE   8  (bases 1 to 2375)
  AUTHORS   May,B.K., Bhasker,C.R., Bawden,M.J. and Cox,T.C.
  TITLE     Molecular regulation of 5-aminolevulinate synthase. Diseases
            related to heme biosynthesis
  JOURNAL   Mol Biol Med 7 (5), 405-421 (1990)
   PUBMED   2095458
  REMARK    Review article
REFERENCE   9  (bases 1 to 2375)
  AUTHORS   Bishop,D.F., Henderson,A.S. and Astrin,K.H.
  TITLE     Human delta-aminolevulinate synthase: assignment of the
            housekeeping gene to 3p21 and the erythroid-specific gene to the X
            chromosome
  JOURNAL   Genomics 7 (2), 207-214 (1990)
   PUBMED   2347585
REFERENCE   10 (bases 1 to 2375)
  AUTHORS   Bawden,M.J., Borthwick,I.A., Healy,H.M., Morris,C.P., May,B.K. and
            Elliott,W.H.
  TITLE     Sequence of human 5-aminolevulinate synthase cDNA
  JOURNAL   Nucleic Acids Res 15 (20), 8563 (1987)
   PUBMED   3671094
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AU279391.1, BC011798.2, CD014147.1, X56351.1 and AI868691.1.
            
            On Nov 22, 2018 this sequence version replaced NM_000688.5.
            
            Summary: This gene encodes the mitochondrial enzyme which is
            catalyzes the rate-limiting step in heme (iron-protoporphyrin)
            biosynthesis. The enzyme encoded by this gene is the housekeeping
            enzyme; a separate gene encodes a form of the enzyme that is
            specific for erythroid tissue. The level of the mature encoded
            protein is regulated by heme: high levels of heme down-regulate the
            mature enzyme in mitochondria while low heme levels up-regulate. A
            pseudogene of this gene is located on chromosome 12. Alternative
            splicing results in multiple transcript variants encoding different
            isoforms. [provided by RefSeq, Jan 2015].
            
            Transcript Variant: This variant (1) represents the longest
            transcript. Variants 1, 2, and 3 encode the same protein.
            
            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 :: SRR3476690.314247.1,
                                           SRR1803615.95332.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000484952.6/
                                                  ENSP00000418779.1
            RefSeq Select criteria             :: based on conservation
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-96                AU279391.1         40-135
            97-823              BC011798.2         72-798
            824-1533            CD014147.1         763-1472            c
            1534-2067           X56351.1           1305-1838
            2068-2375           AI868691.1         7-314               c
FEATURES             Location/Qualifiers
     source          1..2375
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3p21.2"
     gene            1..2375
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /note="5'-aminolevulinate synthase 1"
                     /db_xref="GeneID:211"
                     /db_xref="HGNC:HGNC:396"
                     /db_xref="MIM:125290"
     exon            1..96
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /inference="alignment:Splign:2.1.0"
     exon            97..273
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /inference="alignment:Splign:2.1.0"
     exon            274..504
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /inference="alignment:Splign:2.1.0"
     CDS             306..2228
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /EC_number="2.3.1.37"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; 5-aminolevulinate synthase, nonspecific,
                     mitochondrial; migration-inducing protein 4; delta-ALA
                     synthase 1; 5-aminolevulinic acid synthase 1;
                     delta-aminolevulinate synthase 1; aminolevulinate, delta-,
                     synthase 1; 5-aminolevulinate synthase, non-specific,
                     mitochondrial"
                     /codon_start=1
                     /product="5-aminolevulinate synthase, non-specific,
                     mitochondrial isoform 1 precursor"
                     /protein_id="NP_000679.1"
                     /db_xref="CCDS:CCDS2847.1"
                     /db_xref="GeneID:211"
                     /db_xref="HGNC:HGNC:396"
                     /db_xref="MIM:125290"
                     /translation="MESVVRRCPFLSRVPQAFLQKAGKSLLFYAQNCPKMMEVGAKPA
                     PRALSTAAVHYQQIKETPPASEKDKTAKAKVQQTPDGSQQSPDGTQLPSGHPLPATSQ
                     GTASKCPFLAAQMNQRGSSVFCKASLELQEDVQEMNAVRKEVAETSAGPSVVSVKTDG
                     GDPSGLLKNFQDIMQKQRPERVSHLLQDNLPKSVSTFQYDRFFEKKIDEKKNDHTYRV
                     FKTVNRRAHIFPMADDYSDSLITKKQVSVWCSNDYLGMSRHPRVCGAVMDTLKQHGAG
                     AGGTRNISGTSKFHVDLERELADLHGKDAALLFSSCFVANDSTLFTLAKMMPGCEIYS
                     DSGNHASMIQGIRNSRVPKYIFRHNDVSHLRELLQRSDPSVPKIVAFETVHSMDGAVC
                     PLEELCDVAHEFGAITFVDEVHAVGLYGARGGGIGDRDGVMPKMDIISGTLGKAFGCV
                     GGYIASTSSLIDTVRSYAAGFIFTTSLPPMLLAGALESVRILKSAEGRVLRRQHQRNV
                     KLMRQMLMDAGLPVVHCPSHIIPVRVADAAKNTEVCDELMSRHNIYVQAINYPTVPRG
                     EELLRIAPTPHHTPQMMNYFLENLLVTWKQVGLELKPHSSAECNFCRRPLHFEVMSER
                     EKSYFSGLSKLVSAQA"
     exon            505..732
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /inference="alignment:Splign:2.1.0"
     exon            733..882
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /inference="alignment:Splign:2.1.0"
     exon            883..1105
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1106..1290
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1291..1470
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1471..1635
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1636..1904
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /inference="alignment:Splign:2.1.0"
     exon            1905..2067
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /inference="alignment:Splign:2.1.0"
     exon            2068..2375
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2316..2321
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /note="hexamer: ATTAAA"
     regulatory      2333..2338
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /note="hexamer: AGTAAA"
     polyA_site      2340
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /note="major polyA site"
     regulatory      2353..2358
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /note="hexamer: AATAAA"
     polyA_site      2358
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
                     /note="major polyA site"
     polyA_site      2375
                     /gene="ALAS1"
                     /gene_synonym="ALAS; ALAS-H; ALAS3; ALASH; MIG4"
ORIGIN      
        1 aggctgctcc cggacaaggg caacgagcgt ttcgtttgga cttctcgact tgagtgcccg
       61 cctccttcgc cgccgcctct gcagtcctca gcgcagttat gcccagttct tcccgctgtg
      121 gggacacgac cacggaggaa tccttgcttc agggactcgg gaccctgctg gaccccttcc
      181 tcgggtttag gggatgtggg gaccaggaga aagtcaggat ccctaagagt cttccctgcc
      241 tggatggatg agtggcttct tctccaccta gattctttcc acaggagcca gcatacttcc
      301 tgaacatgga gagtgttgtt cgccgctgcc cattcttatc ccgagtcccc caggcctttc
      361 tgcagaaagc aggcaaatct ctgttgttct atgcccaaaa ctgccccaag atgatggaag
      421 ttggggccaa gccagcccct cgggcattgt ccactgcagc agtacactac caacagatca
      481 aagaaacccc tccggccagt gagaaagaca aaactgctaa ggccaaggtc caacagactc
      541 ctgatggatc ccagcagagt ccagatggca cacagcttcc gtctggacac cccttgcctg
      601 ccacaagcca gggcactgca agcaaatgcc ctttcctggc agcacagatg aatcagagag
      661 gcagcagtgt cttctgcaaa gccagtcttg agcttcagga ggatgtgcag gaaatgaatg
      721 ccgtgaggaa agaggttgct gaaacctcag caggccccag tgtggttagt gtgaaaaccg
      781 atggagggga tcccagtgga ctgctgaaga acttccagga catcatgcaa aagcaaagac
      841 cagaaagagt gtctcatctt cttcaagata acttgccaaa atctgtttcc acttttcagt
      901 atgatcgttt ctttgagaaa aaaattgatg agaaaaagaa tgaccacacc tatcgagttt
      961 ttaaaactgt gaaccggcga gcacacatct tccccatggc agatgactat tcagactccc
     1021 tcatcaccaa aaagcaagtg tcagtctggt gcagtaatga ctacctagga atgagtcgcc
     1081 acccacgggt gtgtggggca gttatggaca ctttgaaaca acatggtgct ggggcaggtg
     1141 gtactagaaa tatttctgga actagtaaat tccatgtgga cttagagcgg gagctggcag
     1201 acctccatgg gaaagatgcc gcactcttgt tttcctcgtg ctttgtggcc aatgactcaa
     1261 ccctcttcac cctggctaag atgatgccag gctgtgagat ttactctgat tctgggaacc
     1321 atgcctccat gatccaaggg attcgaaaca gccgagtgcc aaagtacatc ttccgccaca
     1381 atgatgtcag ccacctcaga gaactgctgc aaagatctga cccctcagtc cccaagattg
     1441 tggcatttga aactgtccat tcaatggatg gggcggtgtg cccactggaa gagctgtgtg
     1501 atgtggccca tgagtttgga gcaatcacct tcgtggatga ggtccacgca gtggggcttt
     1561 atggggctcg aggcggaggg attggggatc gggatggagt catgccaaaa atggacatca
     1621 tttctggaac acttggcaaa gcctttggtt gtgttggagg gtacatcgcc agcacgagtt
     1681 ctctgattga caccgtacgg tcctatgctg ctggcttcat cttcaccacc tctctgccac
     1741 ccatgctgct ggctggagcc ctggagtctg tgcggatcct gaagagcgct gagggacggg
     1801 tgcttcgccg ccagcaccag cgcaacgtca aactcatgag acagatgcta atggatgccg
     1861 gcctccctgt tgtccactgc cccagccaca tcatccctgt gcgggttgca gatgctgcta
     1921 aaaacacaga agtctgtgat gaactaatga gcagacataa catctacgtg caagcaatca
     1981 attaccctac ggtgccccgg ggagaagagc tcctacggat tgcccccacc cctcaccaca
     2041 caccccagat gatgaactac ttccttgaga atctgctagt cacatggaag caagtggggc
     2101 tggaactgaa gcctcattcc tcagctgagt gcaacttctg caggaggcca ctgcattttg
     2161 aagtgatgag tgaaagagag aagtcctatt tctcaggctt gagcaagttg gtatctgctc
     2221 aggcctgagc atgacctcaa ttatttcact taaccccagg ccattatcat atccagatgg
     2281 tcttcagagt tgtctttata tgtgaattaa gttatattaa attttaatct atagtaaaaa
     2341 catagtcctg gaaataaatt cttgcttaaa tggtg
//
