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Q02252 (MMSA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial

Short name=MMSDH
Short name=Malonate-semialdehyde dehydrogenase [acylating]
EC=1.2.1.18
EC=1.2.1.27
Alternative name(s):
Aldehyde dehydrogenase family 6 member A1
Gene names
Name:ALDH6A1
Synonyms:MMSDH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length535 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 + H2O + NAD+ = propanoyl-CoA + HCO3- + NADH.

3-oxopropanoate + CoA + NAD(P)+ = acetyl-CoA + CO2 + NAD(P)H.

Subunit structure

Homotetramer.

Subcellular location

Mitochondrion.

Involvement in disease

Methylmalonate semialdehyde dehydrogenase deficiency (MMSDHD) [MIM:614105]: A metabolic disorder characterized by elevated beta-alanine, 3-hydroxypropionic acid, and both isomers of 3-amino and 3-hydroxyisobutyric acids in urine organic acids.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1

Sequence similarities

Belongs to the aldehyde dehydrogenase family.

Ontologies

Keywords
   Cellular componentMitochondrion
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainTransit peptide
   LigandNAD
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbranched-chain amino acid catabolic process

Traceable author statement. Source: Reactome

brown fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

cellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

thymine catabolic process

Inferred from mutant phenotype PubMed 23835272. Source: BHF-UCL

thymine metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

valine catabolic process

Inferred from mutant phenotype PubMed 23835272. Source: BHF-UCL

valine metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentmitochondrial matrix

Traceable author statement. Source: Reactome

mitochondrion

Non-traceable author statement Ref.8. Source: UniProtKB

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionfatty-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

poly(A) RNA binding

Inferred from direct assay PubMed 22658674. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q02252-1)

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: Q02252-2)

The sequence of this isoform differs from the canonical sequence as follows:
     104-116: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3333Mitochondrion By similarity
Chain34 – 535502Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial
PRO_0000007189

Regions

Nucleotide binding209 – 2135NAD Potential
Nucleotide binding261 – 2666NAD Potential

Sites

Active site3171Nucleophile By similarity
Binding site4171NAD Potential

Amino acid modifications

Modified residue471N6-acetyllysine; alternate By similarity
Modified residue471N6-succinyllysine; alternate By similarity
Modified residue521N6-acetyllysine; alternate By similarity
Modified residue521N6-succinyllysine; alternate By similarity
Modified residue551N6-acetyllysine; alternate By similarity
Modified residue551N6-succinyllysine; alternate By similarity
Modified residue761N6-acetyllysine; alternate By similarity
Modified residue761N6-succinyllysine; alternate By similarity
Modified residue871N6-acetyllysine By similarity
Modified residue1171N6-acetyllysine; alternate By similarity
Modified residue1171N6-succinyllysine; alternate By similarity
Modified residue1291N6-acetyllysine; alternate By similarity
Modified residue1291N6-succinyllysine; alternate By similarity
Modified residue2981N6-acetyllysine By similarity
Modified residue3301N6-acetyllysine By similarity
Modified residue3311N6-acetyllysine By similarity
Modified residue3641N6-acetyllysine; alternate By similarity
Modified residue3641N6-succinyllysine; alternate By similarity
Modified residue3761N6-acetyllysine; alternate By similarity
Modified residue3761N6-succinyllysine; alternate By similarity
Modified residue3911N6-succinyllysine By similarity
Modified residue5001N6-acetyllysine By similarity
Modified residue5171N6-succinyllysine By similarity

Natural variations

Alternative sequence104 – 11613Missing in isoform 2.
VSP_055067
Natural variant4461G → R in MMSDHD. Ref.1
VAR_010244

Experimental info

Sequence conflict1011R → C in BAG57539. Ref.4
Sequence conflict2121E → K in BAG57539. Ref.4
Sequence conflict4601Y → H in BAG57539. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 24, 2001. Version 2.
Checksum: 0786AF63897E7962

FASTA53557,840
        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 

« Hide

Isoform 2 [UniParc].

Checksum: FBAB6B1DA77B3ADB
Show »

FASTA52256,228

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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MMSDHD 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] (ISOFORM 1).
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] (ISOFORM 1).
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Amygdala.
[5]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.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. expand/collapse author list , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] (ISOFORM 1).
Tissue: Brain and Muscle.
[8]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 106-535 (ISOFORM 1).
Tissue: Liver.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ249994 mRNA. Translation: CAB76468.1.
AF159889 mRNA. Translation: AAF80380.1.
AF148505 mRNA. Translation: AAF04489.1.
AF148855 Genomic DNA. Translation: AAG29581.1.
AK312389 mRNA. Translation: BAG35306.1.
AK294243 mRNA. Translation: BAG57539.1.
AC005484 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW81159.1.
BC004909 mRNA. Translation: AAH04909.1.
BC032371 mRNA. Translation: AAH32371.1.
M93405 mRNA. Translation: AAA36328.1.
CCDSCCDS9826.1.
RefSeqNP_005580.1. NM_005589.3.
UniGeneHs.293970.
Hs.744472.

3D structure databases

ProteinModelPortalQ02252.
SMRQ02252. Positions 38-517.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110472. 1 interaction.
IntActQ02252. 2 interactions.
STRING9606.ENSP00000342564.

Chemistry

DrugBankDB00157. NADH.

PTM databases

PhosphoSiteQ02252.

Polymorphism databases

DMDM12643424.

2D gel databases

REPRODUCTION-2DPAGEIPI00024990.
UCD-2DPAGEQ02252.

Proteomic databases

MaxQBQ02252.
PaxDbQ02252.
PeptideAtlasQ02252.
PRIDEQ02252.

Protocols and materials databases

DNASU4329.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000350259; ENSP00000342564; ENSG00000119711.
ENST00000553458; ENSP00000450436; ENSG00000119711.
GeneID4329.
KEGGhsa:4329.
UCSCuc001xpo.3. human.

Organism-specific databases

CTD4329.
GeneCardsGC14M074527.
HGNCHGNC:7179. ALDH6A1.
HPAHPA029072.
HPA029073.
HPA029074.
HPA029075.
MIM603178. gene.
614105. phenotype.
neXtProtNX_Q02252.
Orphanet289307. Developmental delay due to methylmalonate semialdehyde dehydrogenase deficiency.
PharmGKBPA24703.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1012.
HOGENOMHOG000271507.
HOVERGENHBG105023.
InParanoidQ02252.
KOK00140.
OMAQVVEHCC.
OrthoDBEOG7J70F8.
PhylomeDBQ02252.
TreeFamTF105651.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ02252.
BgeeQ02252.
CleanExHS_ALDH6A1.
GenevestigatorQ02252.

Family and domain databases

Gene3D3.40.309.10. 1 hit.
3.40.605.10. 1 hit.
InterProIPR016161. Ald_DH/histidinol_DH.
IPR016163. Ald_DH_C.
IPR016160. Ald_DH_CS_CYS.
IPR016162. Ald_DH_N.
IPR015590. Aldehyde_DH_dom.
IPR010061. MeMal-semiAld_DH.
[Graphical view]
PANTHERPTHR11699:SF27. PTHR11699:SF27. 1 hit.
PfamPF00171. Aldedh. 1 hit.
[Graphical view]
SUPFAMSSF53720. SSF53720. 1 hit.
TIGRFAMsTIGR01722. MMSDH. 1 hit.
PROSITEPS00070. ALDEHYDE_DEHYDR_CYS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiAldehyde_dehydrogenase_6_family,_member_A1.
GenomeRNAi4329.
NextBio17035.
PROQ02252.
SOURCESearch...

Entry information

Entry nameMMSA_HUMAN
AccessionPrimary (citable) accession number: Q02252
Secondary accession number(s): B2R609 expand/collapse secondary AC list , B4DFS8, J3KNU8, Q9UKM8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 24, 2001
Last modified: July 9, 2014
This is version 150 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM