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Protein

Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial

Gene

ALDH6A1

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

Functioni

Plays a role in valine and pyrimidine metabolism. Binds fatty acyl-CoA.

Catalytic activityi

2-methyl-3-oxopropanoate + CoA + H2O + NAD+ = propanoyl-CoA + HCO3- + NADH.
3-oxopropanoate + CoA + NAD(P)+ = acetyl-CoA + CO2 + NAD(P)H.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei317NucleophilePROSITE-ProRule annotation1
Binding sitei417NADSequence analysis1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi209 – 213NADSequence analysis5
Nucleotide bindingi261 – 266NADSequence analysis6

GO - Molecular functioni

GO - Biological processi

  • branched-chain amino acid catabolic process Source: Reactome
  • brown fat cell differentiation Source: Ensembl
  • thymine catabolic process Source: BHF-UCL
  • thymine metabolic process Source: UniProtKB
  • valine catabolic process Source: BHF-UCL
  • valine metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

NAD

Enzyme and pathway databases

BioCyciZFISH:HS04328-MONOMER.
BRENDAi1.2.1.18. 2681.
1.2.1.27. 2681.
ReactomeiR-HSA-70895. Branched-chain amino acid catabolism.

Names & Taxonomyi

Protein namesi
Recommended name:
Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial (EC:1.2.1.18, EC:1.2.1.27)
Short name:
MMSDH
Short name:
Malonate-semialdehyde dehydrogenase [acylating]
Alternative name(s):
Aldehyde dehydrogenase family 6 member A1
Gene namesi
Name:ALDH6A1
Synonyms:MMSDH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:7179. ALDH6A1.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: UniProtKB
  • nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Methylmalonate semialdehyde dehydrogenase deficiency (MMSDHD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA metabolic disorder characterized by elevated beta-alanine, 3-hydroxypropionic acid, and both isomers of 3-amino and 3-hydroxyisobutyric acids in urine organic acids.
See also OMIM:614105
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010244446G → R in MMSDHD. 1 PublicationCorresponds to variant rs72552258dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi4329.
MalaCardsiALDH6A1.
MIMi614105. phenotype.
OpenTargetsiENSG00000119711.
Orphaneti289307. Developmental delay due to methylmalonate semialdehyde dehydrogenase deficiency.
PharmGKBiPA24703.

Polymorphism and mutation databases

DMDMi12643424.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 33MitochondrionBy similarityAdd BLAST33
ChainiPRO_000000718934 – 535Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrialAdd BLAST502

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei47N6-acetyllysine; alternateBy similarity1
Modified residuei47N6-succinyllysine; alternateBy similarity1
Modified residuei52N6-acetyllysine; alternateBy similarity1
Modified residuei52N6-succinyllysine; alternateBy similarity1
Modified residuei55N6-acetyllysine; alternateBy similarity1
Modified residuei55N6-succinyllysine; alternateBy similarity1
Modified residuei76N6-acetyllysine; alternateBy similarity1
Modified residuei76N6-succinyllysine; alternateBy similarity1
Modified residuei87N6-acetyllysineBy similarity1
Modified residuei117N6-acetyllysine; alternateBy similarity1
Modified residuei117N6-succinyllysine; alternateBy similarity1
Modified residuei129N6-acetyllysine; alternateBy similarity1
Modified residuei129N6-succinyllysine; alternateBy similarity1
Modified residuei262PhosphoserineCombined sources1
Modified residuei298N6-acetyllysineBy similarity1
Modified residuei330N6-acetyllysineBy similarity1
Modified residuei331N6-acetyllysineBy similarity1
Modified residuei364N6-acetyllysine; alternateBy similarity1
Modified residuei364N6-succinyllysine; alternateBy similarity1
Modified residuei376N6-acetyllysine; alternateBy similarity1
Modified residuei376N6-succinyllysine; alternateBy similarity1
Modified residuei380PhosphoserineCombined sources1
Modified residuei391N6-succinyllysineBy similarity1
Modified residuei500N6-acetyllysineBy similarity1
Modified residuei517N6-succinyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ02252.
MaxQBiQ02252.
PaxDbiQ02252.
PeptideAtlasiQ02252.
PRIDEiQ02252.

2D gel databases

REPRODUCTION-2DPAGEIPI00024990.
UCD-2DPAGEQ02252.

PTM databases

iPTMnetiQ02252.
PhosphoSitePlusiQ02252.
SwissPalmiQ02252.

Expressioni

Gene expression databases

BgeeiENSG00000119711.
CleanExiHS_ALDH6A1.
ExpressionAtlasiQ02252. baseline and differential.
GenevisibleiQ02252. HS.

Organism-specific databases

HPAiHPA029072.
HPA029073.
HPA029074.
HPA029075.

Interactioni

Subunit structurei

Homotetramer.

Protein-protein interaction databases

BioGridi110472. 17 interactors.
IntActiQ02252. 3 interactors.
STRINGi9606.ENSP00000450436.

Structurei

3D structure databases

ProteinModelPortaliQ02252.
SMRiQ02252.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the aldehyde dehydrogenase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2449. Eukaryota.
ENOG410XNP1. LUCA.
GeneTreeiENSGT00850000132298.
HOGENOMiHOG000271507.
HOVERGENiHBG105023.
InParanoidiQ02252.
KOiK00140.
OMAiSNVKPNM.
OrthoDBiEOG091G06SO.
PhylomeDBiQ02252.
TreeFamiTF105651.

Family and domain databases

CDDicd07085. ALDH_F6_MMSDH. 1 hit.
Gene3Di3.40.309.10. 1 hit.
3.40.605.10. 1 hit.
InterProiIPR016161. 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]
PANTHERiPTHR11699:SF183. PTHR11699:SF183. 1 hit.
PfamiPF00171. Aldedh. 1 hit.
[Graphical view]
SUPFAMiSSF53720. SSF53720. 1 hit.
TIGRFAMsiTIGR01722. MMSDH. 1 hit.
PROSITEiPS00070. ALDEHYDE_DEHYDR_CYS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: Q02252-1) [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
MAALLAAAAV RARILQVSSK VKSSPTWYSA SSFSSSVPTV KLFIGGKFVE
60 70 80 90 100
SKSDKWIDIH NPATNEVIGR VPQATKAEMD AAIASCKRAF PAWADTSVLS
110 120 130 140 150
RQQVLLRYQQ LIKENLKEIA KLITLEQGKT LADAEGDVFR GLQVVEHACS
160 170 180 190 200
VTSLMMGETM PSITKDMDLY SYRLPLGVCA GIAPFNFPAM IPLWMFPMAM
210 220 230 240 250
VCGNTFLMKP SERVPGATML LAKLLQDSGA PDGTLNIIHG QHEAVNFICD
260 270 280 290 300
HPDIKAISFV GSNKAGEYIF ERGSRHGKRV QANMGAKNHG VVMPDANKEN
310 320 330 340 350
TLNQLVGAAF GAAGQRCMAL STAVLVGEAK KWLPELVEHA KNLRVNAGDQ
360 370 380 390 400
PGADLGPLIT PQAKERVCNL IDSGTKEGAS ILLDGRKIKV KGYENGNFVG
410 420 430 440 450
PTIISNVKPN MTCYKEEIFG PVLVVLETET LDEAIQIVNN NPYGNGTAIF
460 470 480 490 500
TTNGATARKY AHLVDVGQVG VNVPIPVPLP MFSFTGSRSS FRGDTNFYGK
510 520 530
QGIQFYTQLK TITSQWKEED ATLSSPAVVM PTMGR
Length:535
Mass (Da):57,840
Last modified:January 24, 2001 - v2
Checksum:i0786AF63897E7962
GO
Isoform 2 (identifier: Q02252-2) [UniParc]FASTAAdd to basket

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

Show »
Length:522
Mass (Da):56,228
Checksum:iFBAB6B1DA77B3ADB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti101R → C in BAG57539 (PubMed:14702039).Curated1
Sequence conflicti212E → K in BAG57539 (PubMed:14702039).Curated1
Sequence conflicti460Y → H in BAG57539 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010244446G → R in MMSDHD. 1 PublicationCorresponds to variant rs72552258dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_055067104 – 116Missing in isoform 2. 1 PublicationAdd BLAST13

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS61501.1. [Q02252-2]
CCDS9826.1. [Q02252-1]
RefSeqiNP_001265522.1. NM_001278593.1. [Q02252-2]
NP_005580.1. NM_005589.3. [Q02252-1]
UniGeneiHs.293970.
Hs.744472.

Genome annotation databases

EnsembliENST00000350259; ENSP00000342564; ENSG00000119711. [Q02252-2]
ENST00000553458; ENSP00000450436; ENSG00000119711. [Q02252-1]
GeneIDi4329.
KEGGihsa:4329.
UCSCiuc001xpo.5. human. [Q02252-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS61501.1. [Q02252-2]
CCDS9826.1. [Q02252-1]
RefSeqiNP_001265522.1. NM_001278593.1. [Q02252-2]
NP_005580.1. NM_005589.3. [Q02252-1]
UniGeneiHs.293970.
Hs.744472.

3D structure databases

ProteinModelPortaliQ02252.
SMRiQ02252.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110472. 17 interactors.
IntActiQ02252. 3 interactors.
STRINGi9606.ENSP00000450436.

PTM databases

iPTMnetiQ02252.
PhosphoSitePlusiQ02252.
SwissPalmiQ02252.

Polymorphism and mutation databases

DMDMi12643424.

2D gel databases

REPRODUCTION-2DPAGEIPI00024990.
UCD-2DPAGEQ02252.

Proteomic databases

EPDiQ02252.
MaxQBiQ02252.
PaxDbiQ02252.
PeptideAtlasiQ02252.
PRIDEiQ02252.

Protocols and materials databases

DNASUi4329.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000350259; ENSP00000342564; ENSG00000119711. [Q02252-2]
ENST00000553458; ENSP00000450436; ENSG00000119711. [Q02252-1]
GeneIDi4329.
KEGGihsa:4329.
UCSCiuc001xpo.5. human. [Q02252-1]

Organism-specific databases

CTDi4329.
DisGeNETi4329.
GeneCardsiALDH6A1.
HGNCiHGNC:7179. ALDH6A1.
HPAiHPA029072.
HPA029073.
HPA029074.
HPA029075.
MalaCardsiALDH6A1.
MIMi603178. gene.
614105. phenotype.
neXtProtiNX_Q02252.
OpenTargetsiENSG00000119711.
Orphaneti289307. Developmental delay due to methylmalonate semialdehyde dehydrogenase deficiency.
PharmGKBiPA24703.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2449. Eukaryota.
ENOG410XNP1. LUCA.
GeneTreeiENSGT00850000132298.
HOGENOMiHOG000271507.
HOVERGENiHBG105023.
InParanoidiQ02252.
KOiK00140.
OMAiSNVKPNM.
OrthoDBiEOG091G06SO.
PhylomeDBiQ02252.
TreeFamiTF105651.

Enzyme and pathway databases

BioCyciZFISH:HS04328-MONOMER.
BRENDAi1.2.1.18. 2681.
1.2.1.27. 2681.
ReactomeiR-HSA-70895. Branched-chain amino acid catabolism.

Miscellaneous databases

GeneWikiiAldehyde_dehydrogenase_6_family,_member_A1.
GenomeRNAii4329.
PROiQ02252.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000119711.
CleanExiHS_ALDH6A1.
ExpressionAtlasiQ02252. baseline and differential.
GenevisibleiQ02252. HS.

Family and domain databases

CDDicd07085. ALDH_F6_MMSDH. 1 hit.
Gene3Di3.40.309.10. 1 hit.
3.40.605.10. 1 hit.
InterProiIPR016161. 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]
PANTHERiPTHR11699:SF183. PTHR11699:SF183. 1 hit.
PfamiPF00171. Aldedh. 1 hit.
[Graphical view]
SUPFAMiSSF53720. SSF53720. 1 hit.
TIGRFAMsiTIGR01722. MMSDH. 1 hit.
PROSITEiPS00070. ALDEHYDE_DEHYDR_CYS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMMSA_HUMAN
AccessioniPrimary (citable) accession number: Q02252
Secondary accession number(s): B2R609
, B4DFS8, J3KNU8, Q9UKM8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 24, 2001
Last modified: November 2, 2016
This is version 176 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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 one 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.