ACMSD aminocarboxymuconate semialdehyde decarboxylase [Homo sapiens (human)] - Gene

Summary

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

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_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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".

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Cda11f02 (e-PCR)
- UniSTS:23601

RH102026 (e-PCR)
- UniSTS:96360

SHGC-36425 (e-PCR)
- UniSTS:62426

WI-14557 (e-PCR)
- UniSTS:24795

SHGC-145418 (e-PCR)
- UniSTS:174565

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

EC 4.1.1.45

NP_612199.2

EC 4.1.1.45

XP_005263643.1

EC 4.1.1.45

XP_005263645.1

EC 4.1.1.45

XP_005263647.1

EC 4.1.1.45

XP_011508894.1

EC 4.1.1.45

XP_016858814.1

EC 4.1.1.45

XP_016858815.1

EC 4.1.1.45

XP_047299289.1

EC 4.1.1.45

XP_054196473.1

EC 4.1.1.45

XP_054196474.1

EC 4.1.1.45

XP_054196475.1

EC 4.1.1.45

XP_054196476.1

EC 4.1.1.45

XP_054196477.1

EC 4.1.1.45

XP_054196478.1

EC 4.1.1.45

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)

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
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

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

134838616..134902034

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

NC_060926.1 Alternate T2T-CHM13v2.0

Range

135278873..135342322

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

A0A0S2Z681
XM_054340503.1 → XP_054196478.1 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X4
XM_054340500.1 → XP_054196475.1 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X2

UniProtKB/TrEMBL

A0A0S2Z681
XM_054340501.1 → XP_054196476.1 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X2

UniProtKB/TrEMBL

A0A0S2Z681
XM_054340498.1 → XP_054196473.1 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X1
XM_054340502.1 → XP_054196477.1 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase isoform X3