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Protein

Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial

Gene

ALDH6A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionOxidoreductase
LigandNAD

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000119711.12
HGNCiHGNC:7179 ALDH6A1
MIMi603178 gene
neXtProtiNX_Q02252

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs72552258EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

Chemistry databases

DrugBankiDB00157 NADH

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-2DPAGEiIPI00024990
UCD-2DPAGEiQ02252

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, 19 interactors
IntActiQ02252, 3 interactors
MINTiQ02252
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
GeneTreeiENSGT00910000144256
HOGENOMiHOG000271507
HOVERGENiHBG105023
InParanoidiQ02252
KOiK00140
OMAiSQWKEED
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
InterProiView protein in InterPro
IPR016161 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
PANTHERiPTHR43866 PTHR43866, 1 hit
PfamiView protein in Pfam
PF00171 Aldedh, 1 hit
SUPFAMiSSF53720 SSF53720, 1 hit
TIGRFAMsiTIGR01722 MMSDH, 1 hit
PROSITEiView protein in PROSITE
PS00070 ALDEHYDE_DEHYDR_CYS, 1 hit

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 dbSNP:rs72552258EnsemblClinVar.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

Similar proteinsi

Entry informationi

Entry nameiMMSA_HUMAN
AccessioniPrimary (citable) accession number: Q02252
Secondary accession number(s): B2R609
, B4DFS8, J3KNU8, Q9UKM8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 24, 2001
Last modified: May 23, 2018
This is version 185 of the entry and version 2 of the sequence. See 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

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