Q8TDX5 (ACMSD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
2-amino-3-carboxymuconate-6-semialdehyde decarboxylase
EC=4.1.1.45

Alternative name(s):
Picolinate carboxylase

Gene names

Name:

ACMSD

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	336 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.5
Catalytic activity	2-amino-3-(3-oxoprop-1-en-1-yl)but-2-enedioate = 2-aminomuconate semialdehyde + CO2. Ref.1
Pathway	Secondary metabolite metabolism; quinolate metabolism.
Subunit structure	Monomer. Ref.5
Sequence similarities	Belongs to the ACMSD family.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Ligand	Metal-binding Zinc
Molecular function	Decarboxylase Lyase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	quinolinate metabolic process Inferred from direct assay Ref.1. Source: UniProtKB tryptophan catabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	aminocarboxymuconate-semialdehyde decarboxylase activity Inferred from direct assay Ref.1. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.1 (identifier: Q8TDX5-1)

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.

Isoform 2 (identifier: Q8TDX5-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 336

336

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

PRO_0000190979

Sites

Metal binding

6

1

Zinc

Metal binding

8

1

Zinc

Metal binding

174

1

Zinc

Metal binding

291

1

Zinc

Binding site

47

1

Substrate Probable

Amino acid modifications

Modified residue

116

1

Phosphothreonine By similarity

Natural variations

Alternative sequence

1 – 58

58

Missing in isoform 2.

VSP_050622

Alternative sequence

59 – 83

25

RIREM…MFSYW → MGKSSEWCERIAGIQKFVLE KWTKK in isoform 2.

VSP_050623

Secondary structure

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336

Helix Strand Turn

Details...

Beta strand

3 – 8

6

Helix

17 – 21

5

Beta strand

27 – 33

7

Beta strand

36 – 41

6

Beta strand

44 – 50

7

Helix

51 – 53

3

Helix

56 – 66

11

Beta strand

70 – 74

5

Helix

77 – 80

4

Helix

86 – 106

21

Turn

108 – 110

3

Beta strand

111 – 115

5

Helix

122 – 134

13

Beta strand

139 – 147

9

Helix

155 – 157

3

Helix

158 – 167

10

Beta strand

170 – 174

5

Helix

182 – 184

3

Helix

189 – 192

4

Helix

194 – 208

15

Helix

211 – 214

4

Beta strand

220 – 223

4

Helix

224 – 226

3

Helix

229 – 242

14

Helix

244 – 247

4

Beta strand

248 – 250

3

Helix

255 – 258

4

Beta strand

261 – 265

5

Helix

271 – 281

11

Beta strand

285 – 287

3

Helix

303 – 306

4

Helix

313 – 320

8

Helix

322 – 328

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: 892B01D2A77C35A5	FASTA	336	38,035
	10 20 30 40 50 60 MKIDIHSHIL PKEWPDLKKR FGYGGWVQLQ HHSKGEAKLL KDGKVFRVVR ENCWDPEVRI 70 80 90 100 110 120 REMDQKGVTV QALSTVPVMF SYWAKPEDTL NLCQLLNNDL ASTVVSYPRR FVGLGTLPMQ 130 140 150 160 170 180 APELAVKEME RCVKELGFPG VQIGTHVNEW DLNAQELFPV YAAAERLKCS LFVHPWDMQM 190 200 210 220 230 240 DGRMAKYWLP WLVGMPAETT IAICSMIMGG VFEKFPKLKV CFAHGGGAFP FTVGRISHGF 250 260 270 280 290 300 SMRPDLCAQD NPMNPKKYLG SFYTDALVHD PLSLKLLTDV IGKDKVILGT DYPFPLGELE 310 320 330 PGKLIESMEE FDEETKNKLK AGNALAFLGL ERKQFE
	Isoform 2 [UniParc]. Checksum: 4F7B961D6B0C9185	FASTA	278	31,213
	10 20 30 40 50 60 MGKSSEWCER IAGIQKFVLE KWTKKAKPED TLNLCQLLNN DLASTVVSYP RRFVGLGTLP 70 80 90 100 110 120 MQAPELAVKE MERCVKELGF PGVQIGTHVN EWDLNAQELF PVYAAAERLK CSLFVHPWDM 130 140 150 160 170 180 QMDGRMAKYW LPWLVGMPAE TTIAICSMIM GGVFEKFPKL KVCFAHGGGA FPFTVGRISH 190 200 210 220 230 240 GFSMRPDLCA QDNPMNPKKY LGSFYTDALV HDPLSLKLLT DVIGKDKVIL GTDYPFPLGE 250 260 270 LEPGKLIESM EEFDEETKNK LKAGNALAFL GLERKQFE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: Brain.
[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]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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 Liver.
[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 DHAP, FUNCTION, SUBUNIT, ZINC-BINDING SITES.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00064913.
IPI00152656.

RefSeq

NP_612199.2. NM_138326.2.

UniGene

Hs.655728.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WM1	X-ray	2.01	A	1-336	[»]

ProteinModelPortal

Q8TDX5.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8TDX5. 1 interaction.

MINT

MINT-1479806.

STRING

9606.ENSP00000348459.

PTM databases

PhosphoSite

Q8TDX5.

Polymorphism databases

DMDM

37999723.

Proteomic databases

PaxDb

Q8TDX5.

PRIDE

Q8TDX5.

Protocols and materials databases

DNASU

130013.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000283054; ENSP00000283054; ENSG00000153086.
ENST00000356140; ENSP00000348459; ENSG00000153086.
ENST00000392928; ENSP00000376659; ENSG00000153086.

GeneID

130013.

KEGG

hsa:130013.

UCSC

uc002ttz.3. human.
uc002tua.3. human.

Organism-specific databases

CTD

130013.

GeneCards

GC02P135596.

H-InvDB

HIX0019780.

HGNC

HGNC:19288. ACMSD.

HPA

HPA010533.
HPA011179.

MIM

608889. gene.

neXtProt

NX_Q8TDX5.

PharmGKB

PA134973312.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2159.

HOGENOM

HOG000254105.

HOVERGEN

HBG050450.

InParanoid

Q8TDX5.

KO

K03392.

OMA

WDLNAQE.

OrthoDB

EOG4V9TQW.

Enzyme and pathway databases

BioCyc

MetaCyc:HS14455-MONOMER.

BRENDA

4.1.1.45. 2681.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00270.

Gene expression databases

ArrayExpress

Q8TDX5.

Bgee

Q8TDX5.

CleanEx

HS_ACMSD.

Genevestigator

Q8TDX5.

GermOnline

ENSG00000153086. Homo sapiens.

Family and domain databases

InterPro

IPR006992. Amidohydro_2.
[Graphical view]

Pfam

PF04909. Amidohydro_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8TDX5.

GenomeRNAi

130013.

NextBio

82680.

SOURCE

Search...

Entry information

Entry name

ACMSD_HUMAN

Accession

Primary (citable) accession number: Q8TDX5
Secondary accession number(s): Q3B7X3, Q53SR5, Q96KY2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 24, 2003
Last sequence update:	June 1, 2002
Last modified:	May 29, 2013
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.