Q02252 (MMSA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial
Short name=MMSDH
Short name=Malonate-semialdehyde dehydrogenase [acylating]
EC=1.2.1.18
EC=1.2.1.27

Alternative name(s):
Aldehyde dehydrogenase family 6 member A1

Gene names

Name:	ALDH6A1
Synonyms:	MMSDH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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 + 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 component	Mitochondrion
Disease	Disease mutation
Domain	Transit peptide
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	branched-chain amino acid catabolic process Traceable author statement. Source: Reactome brown fat cell differentiation Inferred from electronic annotation. Source: Compara thymine metabolic process Inferred from sequence or structural similarity. Source: UniProtKB valine metabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	mitochondrial matrix Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA
Molecular_function	fatty-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 MMSDHD. Ref.1		VAR_010244

Sequences

	Sequence		Length	Mass (Da)
	Q02252 [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], 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]. 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]	"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. , 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]. Tissue: Amygdala.
[5]	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. , 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].
[6]	"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]. Tissue: Brain and Muscle.
[7]	"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. Tissue: Liver.
[8]	"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. CH471061 Genomic DNA. Translation: EAW81159.1. BC004909 mRNA. Translation: AAH04909.1. BC032371 mRNA. Translation: AAH32371.1. M93405 mRNA. Translation: AAA36328.1.
IPI	IPI00024990.
RefSeq	NP_005580.1. NM_005589.2.
UniGene	Hs.293970.
3D structure databases
ProteinModelPortal	Q02252.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q02252. 2 interactions.
STRING	9606.ENSP00000342564.
PTM databases
PhosphoSite	Q02252.
Polymorphism databases
DMDM	12643424.
2D gel databases
REPRODUCTION-2DPAGE	IPI00024990.
UCD-2DPAGE	Q02252.
Proteomic databases
PaxDb	Q02252.
PeptideAtlas	Q02252.
PRIDE	Q02252.
Protocols and materials databases
DNASU	4329.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000553458; ENSP00000450436; ENSG00000119711.
GeneID	4329.
KEGG	hsa:4329.
UCSC	uc001xpo.3. human.
Organism-specific databases
CTD	4329.
GeneCards	GC14M074527.
HGNC	HGNC:7179. ALDH6A1.
HPA	HPA029072. HPA029073. HPA029074. HPA029075.
MIM	603178. gene. 614105. phenotype.
neXtProt	NX_Q02252.
Orphanet	289307. Developmental delay due to methylmalonate semialdehyde dehydrogenase deficiency.
PharmGKB	PA24703.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1012.
HOGENOM	HOG000271507.
HOVERGEN	HBG105023.
InParanoid	Q02252.
KO	K00140.
OMA	IASCKRA.
OrthoDB	EOG4HHP25.
PhylomeDB	Q02252.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q02252.
Bgee	Q02252.
CleanEx	HS_ALDH6A1.
Genevestigator	Q02252.
GermOnline	ENSG00000119711. Homo sapiens.
Family and domain databases
Gene3D	3.40.309.10. 1 hit. 3.40.605.10. 1 hit.
InterPro	IPR016161. Ald_DH/histidinol_DH. IPR016163. Ald_DH_C. IPR016160. Ald_DH_CS. IPR016162. Ald_DH_N. IPR015590. Aldehyde_DH_dom. IPR010061. MeMal-semiAld_DH. [Graphical view]
PANTHER	PTHR11699:SF27. PTHR11699:SF27. 1 hit.
Pfam	PF00171. Aldedh. 1 hit. [Graphical view]
SUPFAM	SSF53720. Aldehyde_DH/Histidinol_DH. 1 hit.
TIGRFAMs	TIGR01722. MMSDH. 1 hit.
PROSITE	PS00070. ALDEHYDE_DEHYDR_CYS. 1 hit. PS00687. ALDEHYDE_DEHYDR_GLU. False negative. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00157. NADH.
GenomeRNAi	4329.
NextBio	17035.
SOURCE	Search...

Entry information

Entry name

MMSA_HUMAN

Accession

Primary (citable) accession number: Q02252
Secondary accession number(s): B2R609, Q9UKM8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	January 24, 2001
Last modified:	May 1, 2013
This is version 138 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.