Reviewed,
UniProtKB/Swiss-Prot Q02252 (MMSA_HUMAN)
Last modified
November 25, 2008.
Version 88.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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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 |
| ||||
| 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 | |
| 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 processInferred from sequence or structural similarity. Source: UniProtKB valine metabolic processInferred 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) activityInferred from sequence or structural similarity. Source: UniProtKB methylmalonate-semialdehyde dehydrogenase (acylating) activityInferred 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
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References
| « Hide '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 | |
|---|---|
| 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 |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 14 Human chromosome 14: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


