Reviewed, UniProtKB/Swiss-Prot Q02252 (MMSA_HUMAN)

Names and origin

Protein names

Recommended name:
    Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial
      Short name=MMSDH
      Short name=Malonate-semialdehyde dehydrogenase [acylating]
    EC=1.2.1.27
    EC=1.2.1.18
Alternative name(s):
    Aldehyde dehydrogenase family 6 member A1

Gene names

Name:	ALDH6A1
Synonyms:	MMSDH

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	535 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Plays a role in valine and pyrimidine metabolism. Binds fatty acyl-CoA.
Catalytic activity	2-methyl-3-oxopropanoate + CoA + H(2)O + NAD(+) = propanoyl-CoA + HCO(3)(-) + NADH. 3-oxopropanoate + CoA + NAD(P)(+) = acetyl-CoA + CO(2) + NAD(P)H.
Subunit structure	Homotetramer.
Subcellular location	Mitochondrion.
Involvement in disease	Defects in ALDH6A1 are the cause of methylmalonate semialdehyde dehydrogenase deficiency (MMSDH deficiency) [MIM:603178]. This is characterized by elevated beta-alanine, 3-hydroxypropionic acid, and both isomers of 3-amino and 3-hydroxyisobutyric acids in urine organic acids.
Sequence similarities	Belongs to the aldehyde dehydrogenase family.

Ontologies

Keywords
Cellular component	Mitochondrion
Disease	Disease mutation
Domain	Transit peptide
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Acetylation
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW thymine metabolic process Inferred from sequence or structural similarity. Source: UniProtKB valine metabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	mitochondrion Ref.5 Non-traceable author statement. Source: UniProtKB
Molecular function	acyl-CoA binding Inferred from sequence or structural similarity. Source: UniProtKB malonate-semialdehyde dehydrogenase (acetylating) activity Inferred from sequence or structural similarity. Source: UniProtKB methylmalonate-semialdehyde dehydrogenase (acylating) activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 33	33	Mitochondrion By similarity
	Chain	34 – 535	502	Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial		PRO_0000007189
Regions
	Nucleotide binding	209 – 213	5	NAD Potential
	Nucleotide binding	261 – 266	6	NAD Potential
Sites
	Active site	317	1	Nucleophile By similarity
	Binding site	417	1	NAD Potential
Amino acid modifications
	Modified residue	55	1	N6-acetyllysine By similarity
	Modified residue	117	1	N6-acetyllysine By similarity
	Modified residue	331	1	N6-acetyllysine By similarity
Natural variations
	Natural variant	446	1	G → R in MMSDH deficiency.		VAR_010244

Sequences

	Sequence		Length	Mass (Da)
	Q02252-1 [UniParc]. Last modified January 24, 2001. Version 2. Checksum: 0786AF63897E7962	FASTA	535	57,840
	10 20 30 40 50 60 MAALLAAAAV RARILQVSSK VKSSPTWYSA SSFSSSVPTV KLFIGGKFVE SKSDKWIDIH 70 80 90 100 110 120 NPATNEVIGR VPQATKAEMD AAIASCKRAF PAWADTSVLS RQQVLLRYQQ LIKENLKEIA 130 140 150 160 170 180 KLITLEQGKT LADAEGDVFR GLQVVEHACS VTSLMMGETM PSITKDMDLY SYRLPLGVCA 190 200 210 220 230 240 GIAPFNFPAM IPLWMFPMAM VCGNTFLMKP SERVPGATML LAKLLQDSGA PDGTLNIIHG 250 260 270 280 290 300 QHEAVNFICD HPDIKAISFV GSNKAGEYIF ERGSRHGKRV QANMGAKNHG VVMPDANKEN 310 320 330 340 350 360 TLNQLVGAAF GAAGQRCMAL STAVLVGEAK KWLPELVEHA KNLRVNAGDQ PGADLGPLIT 370 380 390 400 410 420 PQAKERVCNL IDSGTKEGAS ILLDGRKIKV KGYENGNFVG PTIISNVKPN MTCYKEEIFG 430 440 450 460 470 480 PVLVVLETET LDEAIQIVNN NPYGNGTAIF TTNGATARKY AHLVDVGQVG VNVPIPVPLP 490 500 510 520 530 MFSFTGSRSS FRGDTNFYGK QGIQFYTQLK TITSQWKEED ATLSSPAVVM PTMGR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular characterization of methylmalonate semialdehyde dehydrogenase deficiency." Chambliss K.L., Gray R.G.F., Rylance G., Pollitt R.J., Gibson K.M. J. Inherit. Metab. Dis. 23:497-504(2000) [PubMed: 10947204] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT MMSDH DEFICIENCY ARG-446. Tissue: Liver and Lymphocyte.
[2]	"Molecular basis of human MMSDH deficiency: gene organization and mutation analysis." Ding J.H., Yang B.Z., Wilkinson J., Roe C.R. Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Skin.
[3]	"The structure and organization of the methylmalonic semialdehyde dehydrogenase (MMSDH) gene." Ding J.H., Yang B.Z., Wilkinson J.K., Roe C.R. Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Muscle.
[5]	"CoA-dependent methylmalonate-semialdehyde dehydrogenase, a unique member of the aldehyde dehydrogenase superfamily. cDNA cloning, evolutionary relationships, and tissue distribution." Kedishvili N.Y., Popov K.M., Rougraff P.M., Zhao Y., Crabb D.W., Harris R.A. J. Biol. Chem. 267:19724-19729(1992) [PubMed: 1527093] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 106-535. Tissue: Liver.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ249994 mRNA. Translation: CAB76468.1. AF159889 mRNA. Translation: AAF80380.1. AF148505 mRNA. Translation: AAF04489.1. AF148855 Genomic DNA. Translation: AAG29581.1. BC004909 mRNA. Translation: AAH04909.1. BC032371 mRNA. Translation: AAH32371.1. M93405 mRNA. Translation: AAA36328.1.
RefSeq	NP_005580.1.
UniGene	Hs.293970
3D structure databases
HSSP	HSSP built from PDB template 1O9J based on UniProtKB Q28399.
ModBase	Search...
PTM databases
PhosphoSite	Q02252.
2-D gel databases
REPRODUCTION-2DPAGE	IPI00024990.
Proteomic databases
PeptideAtlas	Q02252.
Genome annotation databases
Ensembl	ENSG00000119711. Homo sapiens. [Contig view]
GeneID	4329.
KEGG	hsa:4329.
NMPDR	fig|9606.3.peg.9864.
Organism-specific databases
H-InvDB	HIX0011806.
HGNC	HGNC:7179. ALDH6A1.
MIM	603178. gene+phenotype.
PharmGKB	PA24703.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q02252.
HOVERGEN	Q02252.
Enzyme and pathway databases
Reactome	REACT_13. Metabolism of amino acids.
Gene expression databases
ArrayExpress	Q02252.
CleanEx	HS_ALDH6A1.
GermOnline	ENSG00000119711. Homo sapiens.
Family and domain databases
InterPro	IPR016160. Ald_DHase_CS. IPR016162. Ald_DHase_N. IPR015590. Aldehyde_DHase. IPR010061. MeMal-semiAld_DHase. [Graphical view]
Gene3D	G3DSA:3.40.605.10. Aldehyde_dehydrogenase_N. 1 hit.
PANTHER	PTHR11699. Aldehyde_dehyd. 1 hit. PTHR11699:SF27. MMSDH. 1 hit.
Pfam	PF00171. Aldedh. 1 hit. [Graphical view]
TIGRFAMs	TIGR01722. MMSDH. 1 hit.
PROSITE	PS00070. ALDEHYDE_DEHYDR_CYS. 1 hit. PS00687. ALDEHYDE_DEHYDR_GLU. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00157. NADH.
LinkHub	Q02252.
NextBio	17035.
SOURCE	Search...

Entry information

Entry name

MMSA_HUMAN

Accession

Primary (citable) accession number: Q02252
Secondary accession number(s): Q9UKM8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	January 24, 2001
Last modified:	November 25, 2008
This is version 88 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)