LOCUS       NM_000048               2140 bp    mRNA    linear   PRI 11-OCT-2024
DEFINITION  Homo sapiens argininosuccinate lyase (ASL), transcript variant 2,
            mRNA.
ACCESSION   NM_000048
VERSION     NM_000048.4
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 2140)
  AUTHORS   Kho,J., Polak,U., Jiang,M.M., Odom,J.D., Hunter,J.V., Ali,S.M.,
            Burrage,L.C., Nagamani,S.C., Pautler,R.G., Thompson,H.P.,
            Urayama,A., Jin,Z. and Lee,B.
  TITLE     Argininosuccinate lyase deficiency causes blood-brain barrier
            disruption via nitric oxide-mediated dysregulation of claudin
            expression
  JOURNAL   JCI Insight 8 (17), e168475 (2023)
   PUBMED   37490345
  REMARK    GeneRIF: Argininosuccinate lyase deficiency causes blood-brain
            barrier disruption via nitric oxide-mediated dysregulation of
            claudin expression.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2140)
  AUTHORS   Kido,J., Matsumoto,S., Sugawara,K., Sawada,T. and Nakamura,K.
  TITLE     Variants associated with urea cycle disorders in Japanese patients:
            Nationwide study and literature review
  JOURNAL   Am J Med Genet A 185 (7), 2026-2036 (2021)
   PUBMED   33851512
  REMARK    GeneRIF: Variants associated with urea cycle disorders in Japanese
            patients: Nationwide study and literature review.
REFERENCE   3  (bases 1 to 2140)
  AUTHORS   Nagamani,S.C.S., Ali,S., Izem,R., Schady,D., Masand,P.,
            Shneider,B.L., Leung,D.H. and Burrage,L.C.
  TITLE     Biomarkers for liver disease in urea cycle disorders
  JOURNAL   Mol Genet Metab 133 (2), 148-156 (2021)
   PUBMED   33846069
  REMARK    GeneRIF: Biomarkers for liver disease in urea cycle disorders.
REFERENCE   4  (bases 1 to 2140)
  AUTHORS   Zheng,Z., Lin,Y., Lin,W., Zhu,L., Jiang,M., Wang,W. and Fu,Q.
  TITLE     Clinical and genetic analysis of five Chinese patients with urea
            cycle disorders
  JOURNAL   Mol Genet Genomic Med 8 (7), e1301 (2020)
   PUBMED   32410394
  REMARK    GeneRIF: Clinical and genetic analysis of five Chinese patients
            with urea cycle disorders.
REFERENCE   5  (bases 1 to 2140)
  AUTHORS   Nagamani,S.C.S., Erez,A. and Lee,B.
  TITLE     Argininosuccinate Lyase Deficiency
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   21290785
REFERENCE   6  (bases 1 to 2140)
  AUTHORS   Ah Mew,N., Simpson,K.L., Gropman,A.L., Lanpher,B.C., Chapman,K.A.
            and Summar,M.L.
  TITLE     Urea Cycle Disorders Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301396
REFERENCE   7  (bases 1 to 2140)
  AUTHORS   Stone,R.L., Aimi,J., Barshop,B.A., Jaeken,J., Van den Berghe,G.,
            Zalkin,H. and Dixon,J.E.
  TITLE     A mutation in adenylosuccinate lyase associated with mental
            retardation and autistic features
  JOURNAL   Nat Genet 1 (1), 59-63 (1992)
   PUBMED   1302001
REFERENCE   8  (bases 1 to 2140)
  AUTHORS   Abramson,R.D., Barbosa,P., Kalumuck,K. and O'Brien,W.E.
  TITLE     Characterization of the human argininosuccinate lyase gene and
            analysis of exon skipping
  JOURNAL   Genomics 10 (1), 126-132 (1991)
   PUBMED   2045097
REFERENCE   9  (bases 1 to 2140)
  AUTHORS   Barbosa,P., Cialkowski,M. and O'Brien,W.E.
  TITLE     Analysis of naturally occurring and site-directed mutations in the
            argininosuccinate lyase gene
  JOURNAL   J Biol Chem 266 (8), 5286-5290 (1991)
   PUBMED   1705937
REFERENCE   10 (bases 1 to 2140)
  AUTHORS   Naylor,S.L., Klebe,R.J. and Shows,T.B.
  TITLE     Argininosuccinic aciduria: assignment of the argininosuccinate
            lyase gene to the pter to q22 region of human chromosome 7 by
            bioautography
  JOURNAL   Proc Natl Acad Sci U S A 75 (12), 6159-6162 (1978)
   PUBMED   282632
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BX328836.2, BC008195.1,
            AC068533.7 and AI469765.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_000048.3.
            
            Summary: This gene encodes a member of the lyase 1 family. The
            encoded protein forms a cytosolic homotetramer and primarily
            catalyzes the reversible hydrolytic cleavage of argininosuccinate
            into arginine and fumarate, an essential step in the liver in
            detoxifying ammonia via the urea cycle. Mutations in this gene
            result in the autosomal recessive disorder argininosuccinic
            aciduria, or argininosuccinic acid lyase deficiency. A
            nontranscribed pseudogene is also located on the long arm of
            chromosome 22. Alternatively spliced transcript variants encoding
            different isoforms have been described. [provided by RefSeq, Jul
            2008].
            
            Transcript Variant: This variant (2) differs in the 5' UTR compared
            to variant 1. Variants 1 and 2 encode the same 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 :: SRR1803612.193225.1,
                                           SRR7410570.272416.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000304874.14/ ENSP00000307188.9
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-8                 BX328836.2         51-58
            9-1518              BC008195.1         1-1510
            1519-1708           AC068533.7         65346-65535         c
            1709-1907           AI469765.1         26-224              c
            1908-2140           AC068533.7         64914-65146         c
FEATURES             Location/Qualifiers
     source          1..2140
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q11.21"
     gene            1..2140
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /note="argininosuccinate lyase"
                     /db_xref="GeneID:435"
                     /db_xref="HGNC:HGNC:746"
                     /db_xref="MIM:608310"
     exon            1..38
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            39..93
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     CDS             82..1476
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /EC_number="4.3.2.1"
                     /note="isoform 1 is encoded by transcript variant 2;
                     argininosuccinase; arginosuccinase"
                     /codon_start=1
                     /product="argininosuccinate lyase isoform 1"
                     /protein_id="NP_000039.2"
                     /db_xref="CCDS:CCDS5531.1"
                     /db_xref="GeneID:435"
                     /db_xref="HGNC:HGNC:746"
                     /db_xref="MIM:608310"
                     /translation="MASESGKLWGGRFVGAVDPIMEKFNASIAYDRHLWEVDVQGSKA
                     YSRGLEKAGLLTKAEMDQILHGLDKVAEEWAQGTFKLNSNDEDIHTANERRLKELIGA
                     TAGKLHTGRSRNDQVVTDLRLWMRQTCSTLSGLLWELIRTMVDRAEAERDVLFPGYTH
                     LQRAQPIRWSHWILSHAVALTRDSERLLEVRKRINVLPLGSGAIAGNPLGVDRELLRA
                     ELNFGAITLNSMDATSERDFVAEFLFWASLCMTHLSRMAEDLILYCTKEFSFVQLSDA
                     YSTGSSLMPQKKNPDSLELIRSKAGRVFGRCAGLLMTLKGLPSTYNKDLQEDKEAVFE
                     VSDTMSAVLQVATGVISTLQIHQENMGQALSPDMLATDLAYYLVRKGMPFRQAHEASG
                     KAVFMAETKGVALNQLSLQELQTISPLFSGDVICVWDYGHSVEQYGALGGTARSSVDW
                     QIRQVRALLQAQQA"
     exon            94..288
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            289..372
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            373..429
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            430..527
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            528..605
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            606..683
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            684..736
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            737..799
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            800..914
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            915..999
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            1000..1059
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            1060..1143
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            1144..1224
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            1225..1331
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     exon            1332..2140
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1498..1503
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /note="hexamer: AATAAA"
     polyA_site      1518
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /note="major polyA site"
     regulatory      1722..1727
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /note="hexamer: AATAAA"
     regulatory      1727..1732
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /note="hexamer: AACAAA"
     polyA_site      1740
                     /gene="ASL"
                     /gene_synonym="ASAL"
     polyA_site      1756
                     /gene="ASL"
                     /gene_synonym="ASAL"
     regulatory      1887..1892
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /note="hexamer: AATAAA"
     regulatory      1891..1896
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /note="hexamer: AATAAA"
     regulatory      1902..1907
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ASL"
                     /gene_synonym="ASAL"
                     /note="hexamer: AATAAA"
     polyA_site      1903
                     /gene="ASL"
                     /gene_synonym="ASAL"
     polyA_site      1912
                     /gene="ASL"
                     /gene_synonym="ASAL"
     polyA_site      1926
                     /gene="ASL"
                     /gene_synonym="ASAL"
ORIGIN      
        1 agtggcgggc gcgacactat ccgtgcggcc aggcggagac ccggaggacc gaagcttccg
       61 gacgacgagg aaccgcccaa catggcctcg gagagtggga agctttgggg tggccggttt
      121 gtgggtgcag tggaccccat catggagaag ttcaacgcgt ccattgccta cgaccggcac
      181 ctttgggagg tggatgttca aggcagcaaa gcctacagca ggggcctgga gaaggcaggg
      241 ctcctcacca aggccgagat ggaccagata ctccatggcc tagacaaggt ggctgaggag
      301 tgggcccagg gcaccttcaa actgaactcc aatgatgagg acatccacac agccaatgag
      361 cgccgcctga aggagctcat tggtgcaacg gcagggaagc tgcacacggg acggagccgg
      421 aatgaccagg tggtcacaga cctcaggctg tggatgcggc agacctgctc cacgctctcg
      481 ggcctcctct gggagctcat taggaccatg gtggatcggg cagaggcgga acgtgatgtt
      541 ctcttcccgg ggtacaccca tttgcagagg gcccagccca tccgctggag ccactggatt
      601 ctgagccacg ccgtggcact gacccgagac tctgagcggc tgctggaggt gcggaagcgg
      661 atcaatgtcc tgcccctggg gagtggggcc attgcaggca atcccctggg tgtggaccga
      721 gagctgctcc gagcagaact caactttggg gccatcactc tcaacagcat ggatgccact
      781 agtgagcggg actttgtggc cgagttcctg ttctgggctt cgctgtgcat gacccatctc
      841 agcaggatgg ccgaggacct catcctctac tgcaccaagg aattcagctt cgtgcagctc
      901 tcagatgcct acagcacggg aagcagcctg atgccccaga agaaaaaccc cgacagtttg
      961 gagctgatcc ggagcaaggc tgggcgtgtg tttgggcggt gtgccgggct cctgatgacc
     1021 ctcaagggac ttcccagcac ctacaacaaa gacttacagg aggacaagga agctgtgttt
     1081 gaagtgtcag acactatgag tgccgtgctc caggtggcca ctggcgtcat ctctacgctg
     1141 cagattcacc aagagaacat gggacaggct ctcagccccg acatgctggc cactgacctt
     1201 gcctattacc tggtccgcaa agggatgcca ttccgccagg cccacgaggc ctccgggaaa
     1261 gctgtgttca tggccgagac caagggggtc gccctcaacc agctgtcact gcaggagctg
     1321 cagaccatca gccccctgtt ctcgggcgac gtgatctgcg tgtgggacta cgggcacagt
     1381 gtggagcagt atggtgccct gggcggcact gcgcgctcca gcgtcgactg gcagatccgc
     1441 caggtgcggg cgctactgca ggcacagcag gcctaggtcc tcccacacct gccccctaat
     1501 aaagtgggcg cgagaggagg ctgctgtgtg tttcctgccc cagcctggct ccctcgttgc
     1561 tgggctttcg gggctggcca gtggggacag tcagggactg gagaggcagg gcagggtggc
     1621 ctgtaatccc agcactttgg aagggcaagg tgcgaggatg cttgaggcca ggagtttgac
     1681 acagcctggg caacacaggg agacccccat ctctactcaa taataaaaca aatagcctgg
     1741 cgtggtggcc catgcatata gtcccagcta cttgtaaggc tgaggtgaga ggacacttgt
     1801 gcccaggagt ggaggctgca gtgagctatg atcacgccac tgcattccag cctggataac
     1861 agagtgagaa cctatctcta aaaataaata aataaacgaa aaataaatgg aagcggagaa
     1921 aactgggcaa gggcaatgag agtcgtagac gggaagggaa gagggggctc ccatcatagc
     1981 ctctgctctg tccaggcccc atccccttca gacagggtat cacagtgacc tcctaggcca
     2041 ggagcgatgg ctcacgcctg taatcctagc attttgggag gcctgggcaa caggaagact
     2101 ccaactacca tattaaaaaa aacatgaatg aaagcaaaaa
//
