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    ACMSD aminocarboxymuconate semialdehyde decarboxylase [ Homo sapiens (human) ]

    Gene ID: 130013, updated on 2-Nov-2024

    Summary

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    Official Symbol
    ACMSDprovided by HGNC
    Official Full Name
    aminocarboxymuconate semialdehyde decarboxylaseprovided by HGNC
    Primary source
    HGNC:HGNC:19288
    See related
    Ensembl:ENSG00000153086 MIM:608889; AllianceGenome:HGNC:19288
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Summary
    The neuronal excitotoxin quinolinate is an intermediate in the de novo synthesis pathway of NAD from tryptophan, and has been implicated in the pathogenesis of several neurodegenerative disorders. Quinolinate is derived from alpha-amino-beta-carboxy-muconate-epsilon-semialdehyde (ACMS). ACMSD (ACMS decarboxylase; EC 4.1.1.45) can divert ACMS to a benign catabolite and thus prevent the accumulation of quinolinate from ACMS.[supplied by OMIM, Oct 2004]
    Expression
    Biased expression in kidney (RPKM 17.3), liver (RPKM 10.7) and 1 other tissue See more
    Orthologs
    mouse all
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    Genomic context

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    See ACMSD in Genome Data Viewer
    Location:
    2q21.3
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (134838616..134902034)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (135278873..135342322)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (135596186..135659604)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene VDAC2 pseudogene 4 Neighboring gene chromosome 18 open reading frame 32 pseudogene Neighboring gene MPRA-validated peak3872 silencer Neighboring gene microRNA 5590 Neighboring gene CCNT2 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16566 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:135675361-135676034 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16567 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11979 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16568 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16569 Neighboring gene cyclin T2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11980 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:135732781-135733282 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:135733283-135733782 Neighboring gene mitogen-activated protein kinase kinase kinase 19 Neighboring gene MPRA-validated peak3873 silencer

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. A kynurenine pathway enzyme aminocarboxymuconate-semialdehyde decarboxylase may be involved in treatment-resistant depression, and baseline inflammation status of patients predicts treatment response: a pilot study. Yilmaz NS, et al. J Neural Transm (Vienna), 2022 Dec. PMID 36334154
    2. Phthalate esters enhance quinolinate production by inhibiting alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD), a key enzyme of the tryptophan pathway. Fukuwatari T, et al. Toxicol Sci, 2004 Oct. PMID 15229365
    3. An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation. Brundin L, et al. Transl Psychiatry, 2016 Aug 2. PMID 27483383, Free PMC Article
    4. The ACMSD gene, involved in tryptophan metabolism, is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism. Martí-Massó JF, et al. J Mol Med (Berl), 2013 Dec. PMID 23955123, Free PMC Article
    5. Tissue expression and biochemical characterization of human 2-amino 3-carboxymuconate 6-semialdehyde decarboxylase, a key enzyme in tryptophan catabolism. Pucci L, et al. FEBS J, 2007 Feb. PMID 17288562

    See all (23) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Limits production of the glutamatergic excitotoxin quinolinate, by diverting it to picolinate; inhibited by phthalates, by virtue of their structural similarity to nicotinate.
      Title: Phthalate esters enhance quinolinate production by inhibiting alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD), a key enzyme of the tryptophan pathway.
    2. A kynurenine pathway enzyme aminocarboxymuconate-semialdehyde decarboxylase may be involved in treatment-resistant depression, and baseline inflammation status of patients predicts treatment response: a pilot study.
      Title: A kynurenine pathway enzyme aminocarboxymuconate-semialdehyde decarboxylase may be involved in treatment-resistant depression, and baseline inflammation status of patients predicts treatment response: a pilot study.
    3. This study shows that ACMSD is a key regulator of mammalian dietary niacin requirements and NAD(+) metabolism.
      Title: Alpha-Amino-Beta-Carboxy-Muconate-Semialdehyde Decarboxylase Controls Dietary Niacin Requirements for NAD(+) Synthesis.
    4. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters.
      Title: An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation.
    5. The crystal structures of the human enzyme in its native catalytically active state, a substrate analogue-bound form and a selected active site mutant form with one of the putative substrate binding residues altered, are reported.
      Title: Human α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD): a structural and mechanistic unveiling.
    6. ACMSD is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism. ACMSD mutation contributes to the development of Familial cortical myoclonic tremor and epilepsy.
      Title: The ACMSD gene, involved in tryptophan metabolism, is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism.
    7. Data report a crystal structure of human ACMSD in complex with the glycolytic intermediate 1,3-dihydroxyacetonephosphate (DHAP),suggesting a regulatory link between NAD synthesis and glycolysis.
      Title: The crystal structure of human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase in complex with 1,3-dihydroxyacetonephosphate suggests a regulatory link between NAD synthesis and glycolysis.
    8. identification and expression of cDNA
      Title: Identification and expression of a cDNA encoding human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD). A key enzyme for the tryptophan-niacine pathway and "quinolinate hypothesis".
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    An atlas of genetic influences on human blood metabolites.
    EBI GWAS Catalog
    Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies.
    EBI GWAS Catalog
    Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    NOT enables aminocarboxymuconate-semialdehyde decarboxylase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables aminocarboxymuconate-semialdehyde decarboxylase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables hydrolase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in negative regulation of quinolinate biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in picolinic acid biosynthetic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of 'de novo' NAD biosynthetic process from tryptophan TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in secondary metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in tryptophan catabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    2-amino-3-carboxymuconate-6-semialdehyde decarboxylase
    Names
    picolinate carboxylase
    NP_001294912.1
    NP_612199.2
    XP_005263643.1
    XP_005263645.1
    XP_005263647.1
    XP_011508894.1
    XP_016858814.1
    XP_016858815.1
    XP_047299289.1
    XP_054196473.1
    XP_054196474.1
    XP_054196475.1
    XP_054196476.1
    XP_054196477.1
    XP_054196478.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001307983.2 → NP_001294912.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform 2

      See identical proteins and their annotated locations for NP_001294912.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) contains an alternate exon in its 5' UTR. This variant represents translation initiation at an alternate start codon compared to variant 1; the 5'-most initiation codon, as used in variant 1, is associated with a truncated ORF that would render the transcript a candidate for nonsense-mediated decay (NMD). Leaky scanning may allow translation initiation at the alternate start codon to encode an isoform (2) that has a shorter and distinct N-terminus, compared to isoform 1.
      Source sequence(s)
      AK125008, BC016018
      Consensus CDS
      CCDS77464.1
      UniProtKB/TrEMBL
      A0A0S2Z681
      Related
      ENSP00000376659.1, ENST00000392928.5
      Conserved Domains (1) summary
      pfam04909
      Location:26 → 272
      Amidohydro_2; Amidohydrolase

    2. NM_138326.3 → NP_612199.2  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform 1

      See identical proteins and their annotated locations for NP_612199.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      BC016018, BC107420, BG428338
      Consensus CDS
      CCDS2173.2
      UniProtKB/Swiss-Prot
      Q3B7X3, Q53SR5, Q8TDX5, Q96KY2
      UniProtKB/TrEMBL
      Q6ZV40
      Related
      ENSP00000348459.5, ENST00000356140.10
      Conserved Domains (1) summary
      pfam04909
      Location:45 → 330
      Amidohydro_2; Amidohydrolase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      134838616..134902034
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011510592.3 → XP_011508894.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X2

      See identical proteins and their annotated locations for XP_011508894.1

      UniProtKB/TrEMBL
      A0A0S2Z681
      Conserved Domains (1) summary
      pfam04909
      Location:26 → 272
      Amidohydro_2; Amidohydrolase

    2. XM_047443333.1 → XP_047299289.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X4

    3. XM_017003325.2 → XP_016858814.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X2

      UniProtKB/TrEMBL
      A0A0S2Z681
      Conserved Domains (1) summary
      pfam04909
      Location:26 → 272
      Amidohydro_2; Amidohydrolase

    4. XM_005263588.5 → XP_005263645.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X2

      See identical proteins and their annotated locations for XP_005263645.1

      UniProtKB/TrEMBL
      A0A0S2Z681
      Conserved Domains (1) summary
      pfam04909
      Location:26 → 272
      Amidohydro_2; Amidohydrolase

    5. XM_005263586.5 → XP_005263643.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X1

      Conserved Domains (1) summary
      pfam04909
      Location:3 → 281
      Amidohydro_2; Amidohydrolase

    6. XM_017003326.2 → XP_016858815.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X2

      UniProtKB/TrEMBL
      A0A0S2Z681
      Conserved Domains (1) summary
      pfam04909
      Location:26 → 272
      Amidohydro_2; Amidohydrolase

    7. XM_005263590.5 → XP_005263647.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X3

      Conserved Domains (1) summary
      pfam04909
      Location:14 → 261
      Amidohydro_2; Amidohydrolase

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      135278873..135342322
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054340499.1 → XP_054196474.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X2

      UniProtKB/TrEMBL
      A0A0S2Z681

    2. XM_054340503.1 → XP_054196478.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X4

    3. XM_054340500.1 → XP_054196475.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X2

      UniProtKB/TrEMBL
      A0A0S2Z681

    4. XM_054340501.1 → XP_054196476.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X2

      UniProtKB/TrEMBL
      A0A0S2Z681

    5. XM_054340498.1 → XP_054196473.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X1

    6. XM_054340502.1 → XP_054196477.1  2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8TDX5.1 GenPept UniProtKB/Swiss-Prot:Q8TDX5

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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