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Protein

2-amino-3-carboxymuconate-6-semialdehyde decarboxylase

Gene

ACMSD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Converts alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS) to alpha-aminomuconate semialdehyde (AMS). ACMS can be converted non-enzymatically to quinolate (QA), a key precursor of NAD, and a potent endogenous excitotoxin of neuronal cells which is implicated in the pathogenesis of various neurodegenerative disorders. In the presence of ACMSD, ACMS is converted to AMS, a benign catabolite. ACMSD ultimately controls the metabolic fate of tryptophan catabolism along the kynurenine pathway.1 Publication

Catalytic activityi

2-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate = 2-aminomuconate semialdehyde + CO2.1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi6 – 61Zinc
Metal bindingi8 – 81Zinc
Binding sitei47 – 471SubstrateCurated
Metal bindingi174 – 1741Zinc
Metal bindingi291 – 2911Zinc

GO - Molecular functioni

  1. aminocarboxymuconate-semialdehyde decarboxylase activity Source: UniProtKB
  2. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. cellular nitrogen compound metabolic process Source: Reactome
  2. quinolinate metabolic process Source: UniProtKB
  3. small molecule metabolic process Source: Reactome
  4. tryptophan catabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Decarboxylase, Lyase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS14455-MONOMER.
BRENDAi4.1.1.45. 2681.
ReactomeiREACT_916. Tryptophan catabolism.
UniPathwayiUPA00270.

Names & Taxonomyi

Protein namesi
Recommended name:
2-amino-3-carboxymuconate-6-semialdehyde decarboxylase (EC:4.1.1.45)
Alternative name(s):
Picolinate carboxylase
Gene namesi
Name:ACMSD
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Unplaced

Organism-specific databases

HGNCiHGNC:19288. ACMSD.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: UniProtKB
  2. extracellular vesicular exosome Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134973312.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 3363362-amino-3-carboxymuconate-6-semialdehyde decarboxylasePRO_0000190979Add
BLAST

Proteomic databases

PaxDbiQ8TDX5.
PRIDEiQ8TDX5.

PTM databases

PhosphoSiteiQ8TDX5.

Expressioni

Gene expression databases

BgeeiQ8TDX5.
CleanExiHS_ACMSD.
GenevestigatoriQ8TDX5.

Organism-specific databases

HPAiHPA010533.
HPA011179.

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

BioGridi126217. 1 interaction.
IntActiQ8TDX5. 1 interaction.
MINTiMINT-1479806.
STRINGi9606.ENSP00000348459.

Structurei

Secondary structure

1
336
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi3 – 86Combined sources
Helixi17 – 215Combined sources
Beta strandi27 – 337Combined sources
Beta strandi36 – 416Combined sources
Beta strandi44 – 507Combined sources
Helixi51 – 533Combined sources
Helixi56 – 6611Combined sources
Beta strandi70 – 745Combined sources
Helixi77 – 804Combined sources
Helixi86 – 10621Combined sources
Turni108 – 1103Combined sources
Beta strandi111 – 1155Combined sources
Helixi122 – 13413Combined sources
Beta strandi139 – 1479Combined sources
Helixi155 – 1573Combined sources
Helixi158 – 16710Combined sources
Beta strandi170 – 1745Combined sources
Helixi182 – 1854Combined sources
Helixi189 – 1924Combined sources
Helixi194 – 20714Combined sources
Turni208 – 2103Combined sources
Helixi211 – 2144Combined sources
Beta strandi220 – 2234Combined sources
Helixi224 – 2263Combined sources
Helixi229 – 24214Combined sources
Helixi244 – 2474Combined sources
Beta strandi248 – 2503Combined sources
Helixi255 – 2584Combined sources
Beta strandi261 – 2655Combined sources
Helixi271 – 28111Combined sources
Beta strandi285 – 2873Combined sources
Helixi303 – 3075Combined sources
Helixi313 – 3208Combined sources
Helixi322 – 3287Combined sources
Helixi332 – 3343Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2WM1X-ray2.01A1-336[»]
4IGMX-ray2.39A/B/C/D/E/F1-332[»]
4IGNX-ray2.33A/B/C/D/E/F1-332[»]
4IH3X-ray2.49A/B/C/D/E/F1-332[»]
4OFCX-ray1.99A/B/C/D/E/F1-335[»]
ProteinModelPortaliQ8TDX5.
SMRiQ8TDX5. Positions 1-332.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8TDX5.

Family & Domainsi

Sequence similaritiesi

Belongs to the ACMSD family.Curated

Phylogenomic databases

eggNOGiCOG2159.
GeneTreeiENSGT00490000043417.
HOGENOMiHOG000254105.
HOVERGENiHBG050450.
InParanoidiQ8TDX5.
KOiK03392.
OMAiGFNMRPD.
OrthoDBiEOG7WDN2Q.
PhylomeDBiQ8TDX5.
TreeFamiTF313232.

Family and domain databases

InterProiIPR006992. Amidohydro_2.
[Graphical view]
PfamiPF04909. Amidohydro_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q8TDX5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKIDIHSHIL PKEWPDLKKR FGYGGWVQLQ HHSKGEAKLL KDGKVFRVVR
60 70 80 90 100
ENCWDPEVRI REMDQKGVTV QALSTVPVMF SYWAKPEDTL NLCQLLNNDL
110 120 130 140 150
ASTVVSYPRR FVGLGTLPMQ APELAVKEME RCVKELGFPG VQIGTHVNEW
160 170 180 190 200
DLNAQELFPV YAAAERLKCS LFVHPWDMQM DGRMAKYWLP WLVGMPAETT
210 220 230 240 250
IAICSMIMGG VFEKFPKLKV CFAHGGGAFP FTVGRISHGF SMRPDLCAQD
260 270 280 290 300
NPMNPKKYLG SFYTDALVHD PLSLKLLTDV IGKDKVILGT DYPFPLGELE
310 320 330
PGKLIESMEE FDEETKNKLK AGNALAFLGL ERKQFE
Length:336
Mass (Da):38,035
Last modified:June 1, 2002 - v1
Checksum:i892B01D2A77C35A5
GO
Isoform 2Curated (identifier: Q8TDX5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-58: Missing.
     59-83: RIREMDQKGVTVQALSTVPVMFSYW → MGKSSEWCERIAGIQKFVLEKWTKK

Note: No experimental confirmation available.Curated

Show »
Length:278
Mass (Da):31,213
Checksum:i4F7B961D6B0C9185
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5858Missing in isoform 2. 1 PublicationVSP_050622Add
BLAST
Alternative sequencei59 – 8325RIREM…MFSYW → MGKSSEWCERIAGIQKFVLE KWTKK in isoform 2. 1 PublicationVSP_050623Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB071418 mRNA. Translation: BAB86938.1.
AC016725 Genomic DNA. Translation: AAY14997.1.
CH471058 Genomic DNA. Translation: EAX11650.1.
CH471058 Genomic DNA. Translation: EAX11651.1.
CH471058 Genomic DNA. Translation: EAX11652.1.
BC016018 mRNA. Translation: AAH16018.1.
BC107420 mRNA. Translation: AAI07421.1.
CCDSiCCDS2173.2. [Q8TDX5-1]
RefSeqiNP_612199.2. NM_138326.2. [Q8TDX5-1]
XP_005263644.1. XM_005263587.2. [Q8TDX5-2]
XP_005263645.1. XM_005263588.2. [Q8TDX5-2]
UniGeneiHs.655728.

Genome annotation databases

GeneIDi130013.
KEGGihsa:130013.
UCSCiuc002ttz.3. human. [Q8TDX5-1]
uc002tua.3. human. [Q8TDX5-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB071418 mRNA. Translation: BAB86938.1.
AC016725 Genomic DNA. Translation: AAY14997.1.
CH471058 Genomic DNA. Translation: EAX11650.1.
CH471058 Genomic DNA. Translation: EAX11651.1.
CH471058 Genomic DNA. Translation: EAX11652.1.
BC016018 mRNA. Translation: AAH16018.1.
BC107420 mRNA. Translation: AAI07421.1.
CCDSiCCDS2173.2. [Q8TDX5-1]
RefSeqiNP_612199.2. NM_138326.2. [Q8TDX5-1]
XP_005263644.1. XM_005263587.2. [Q8TDX5-2]
XP_005263645.1. XM_005263588.2. [Q8TDX5-2]
UniGeneiHs.655728.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2WM1X-ray2.01A1-336[»]
4IGMX-ray2.39A/B/C/D/E/F1-332[»]
4IGNX-ray2.33A/B/C/D/E/F1-332[»]
4IH3X-ray2.49A/B/C/D/E/F1-332[»]
4OFCX-ray1.99A/B/C/D/E/F1-335[»]
ProteinModelPortaliQ8TDX5.
SMRiQ8TDX5. Positions 1-332.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126217. 1 interaction.
IntActiQ8TDX5. 1 interaction.
MINTiMINT-1479806.
STRINGi9606.ENSP00000348459.

PTM databases

PhosphoSiteiQ8TDX5.

Proteomic databases

PaxDbiQ8TDX5.
PRIDEiQ8TDX5.

Protocols and materials databases

DNASUi130013.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi130013.
KEGGihsa:130013.
UCSCiuc002ttz.3. human. [Q8TDX5-1]
uc002tua.3. human. [Q8TDX5-2]

Organism-specific databases

CTDi130013.
GeneCardsiGC02P135596.
H-InvDBHIX0019780.
HGNCiHGNC:19288. ACMSD.
HPAiHPA010533.
HPA011179.
MIMi608889. gene.
neXtProtiNX_Q8TDX5.
PharmGKBiPA134973312.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2159.
GeneTreeiENSGT00490000043417.
HOGENOMiHOG000254105.
HOVERGENiHBG050450.
InParanoidiQ8TDX5.
KOiK03392.
OMAiGFNMRPD.
OrthoDBiEOG7WDN2Q.
PhylomeDBiQ8TDX5.
TreeFamiTF313232.

Enzyme and pathway databases

UniPathwayiUPA00270.
BioCyciMetaCyc:HS14455-MONOMER.
BRENDAi4.1.1.45. 2681.
ReactomeiREACT_916. Tryptophan catabolism.

Miscellaneous databases

EvolutionaryTraceiQ8TDX5.
GenomeRNAii130013.
NextBioi82680.
PROiQ8TDX5.
SOURCEiSearch...

Gene expression databases

BgeeiQ8TDX5.
CleanExiHS_ACMSD.
GenevestigatoriQ8TDX5.

Family and domain databases

InterProiIPR006992. Amidohydro_2.
[Graphical view]
PfamiPF04909. Amidohydro_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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'."
    Fukuoka S., Ishiguro K., Yanagihara K., Tanabe A., Egashira Y., Sanada H., Shibata K.
    J. Biol. Chem. 277:35162-35167(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY.
    Tissue: Brain1 Publication.
  2. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Kidney and LiverImported.
  5. "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."
    Garavaglia S., Perozzi S., Galeazzi L., Raffaelli N., Rizzi M.
    FEBS J. 276:6615-6623(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) IN COMPLEX WITH ZINC IONS AND DHAP, FUNCTION, SUBUNIT, ZINC-BINDING SITES.

Entry informationi

Entry nameiACMSD_HUMAN
AccessioniPrimary (citable) accession number: Q8TDX5
Secondary accession number(s): Q3B7X3, Q53SR5, Q96KY2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: June 1, 2002
Last modified: March 4, 2015
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.