Methylglutaconyl-CoA hydratase, mitochondrial precursor

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Reviewed, UniProtKB/Swiss-Prot Q13825 (AUHM_HUMAN)

Last modified July 22, 2008. Version 76. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Methylglutaconyl-CoA hydratase, mitochondrial
    EC=4.2.1.18
Alternative name(s):
    AU-specific RNA-binding enoyl-CoA hydratase
      Short name=AU-binding protein/enoyl-CoA hydratase

Gene names

Name:

AUH

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	339 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Catalyzes the conversion of 3-methylglutaconyl-CoA to 3-hydroxy-3-methylglutaryl-CoA. Has very low enoyl-CoA hydratase activity. Was originally identified as RNA-binding protein that binds in vitro to clustered 5'-AUUUA-3' motifs.
Catalytic activity	(S)-3-hydroxy-3-methylglutaryl-CoA = trans-3-methylglutaconyl-CoA + H(2)O.
Pathway	Amino-acid degradation; L-leucine degradation; HMG-CoA from 3-isovaleryl-CoA: step 3/3.
Subunit structure	Homohexamer.
Subcellular location	MitochondrionBy similarity.
Involvement in disease	Defects in AUH are the cause of 3-methylglutaconic aciduria type 1 (MGA1) [MIM:250950]. MGA1 is an inborn error of leucine metabolism. It leads to an autosomal recessive syndrome with variable clinical phenotype, ranging from delayed speech development to severe psychomotor retardation, coma, failure to thrive, metabolic acidosis and dystonia. MGA1 can be distinguished from other forms of MGA by the pattern of metabolite excretion: 3-methylglutaconic acid levels are higher than those detected in other forms, whereas methylglutaric acid levels are usually only slightly elevated, and there is a high level of 3-hydroxyisovaleric acid excretion (not present in other MGA forms).
Sequence similarities	Belongs to the enoyl-CoA hydratase/isomerase family.

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Ontologies

Keywords
Biological process	Branched-chain amino acid catabolism
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Transit peptide
Ligand	RNA-binding
Molecular function	Lyase
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	mRNA catabolic process Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	enoyl-CoA hydratase activity Ref.1 Inferred from direct assay. Source: UniProtKB mRNA 3'-UTR binding Ref.1 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13825-1) 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: Q13825-2) The sequence of this isoform differs from the canonical sequence as follows: 140-168: Missing.
Notes: No experimental confirmation available.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Transit peptide

1 – 67

Mitochondrion

Chain

68 – 339

272

Methylglutaconyl-CoA hydratase, mitochondrial

Regions

Region

105 – 119

RNA-binding

Natural variations

Alternative sequence

140 – 168

Missing in isoform 2.

Natural variant

240

A → V in MGA1.

Experimental info

Mutagenesis

105

K → N: Abolishes RNA-binding; when associated with E-109 and Q-113

Mutagenesis

109

K → E: Abolishes RNA-binding; when associated with N-105 and Q-113

Mutagenesis

113

K → Q: Abolishes RNA-binding; when associated with N-105 and E-109

Secondary structure

339

Helix Strand Turn

Details...

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: E04FEB95933FB30B Show »	FASTA	339	35,609
10 20 30 40 50 60 MAAAVAAAPG ALGSLHAGGA RLVAACSAWL CPGLRLPGSL AGRRAGPAIW AQGWVPAAGG 70 80 90 100 110 120 PAPKRGYSSE MKTEDELRVR HLEEENRGIV VLGINRAYGK NSLSKNLIKM LSKAVDALKS 130 140 150 160 170 180 DKKVRTIIIR SEVPGIFCAG ADLKERAKMS SSEVGPFVSK IRAVINDIAN LPVPTIAAID 190 200 210 220 230 240 GLALGGGLEL ALACDIRVAA SSAKMGLVET KLAIIPGGGG TQRLPRAIGM SLAKELIFSA 250 260 270 280 290 300 RVLDGKEAKA VGLISHVLEQ NQEGDAAYRK ALDLAREFLP QGPVAMRVAK LAINQGMEVD 310 320 330 LVTGLAIEEA CYAQTIPTKD RLEGLLAFKE KRPPRYKGE « Hide
Isoform 2 [UniParc]. Checksum: 24B4C6983AFED47F Show »		310	32,508
10 20 30 40 50 60 MAAAVAAAPG ALGSLHAGGA RLVAACSAWL CPGLRLPGSL AGRRAGPAIW AQGWVPAAGG 70 80 90 100 110 120 PAPKRGYSSE MKTEDELRVR HLEEENRGIV VLGINRAYGK NSLSKNLIKM LSKAVDALKS 130 140 150 160 170 180 DKKVRTIIIR SEVPGIFCAA NLPVPTIAAI DGLALGGGLE LALACDIRVA ASSAKMGLVE 190 200 210 220 230 240 TKLAIIPGGG GTQRLPRAIG MSLAKELIFS ARVLDGKEAK AVGLISHVLE QNQEGDAAYR 250 260 270 280 290 300 KALDLAREFL PQGPVAMRVA KLAINQGMEV DLVTGLAIEE ACYAQTIPTK DRLEGLLAFK 310 EKRPPRYKGE « Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"AUH, a gene encoding an AU-specific RNA binding protein with intrinsic enoyl-CoA hydratase activity." Nakagawa J., Waldner H.P., Meyer-Monard S., Hofsteenge J., Jenoe P., Moroni C. Proc. Natl. Acad. Sci. U.S.A. 92:2051-2055(1995) [PubMed: 7892223] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 68-87; 213-215; 235-241; 251-268 AND 278-286, FUNCTION, RNA-BINDING. Tissue: Neuroblastoma.
[2]	"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] (ISOFORM 2). Tissue: Testis.
[3]	"3-methylglutaconic aciduria type I is caused by mutations in AUH." Ijlst L., Loupatty F.J., Ruiter J.P.N., Duran M., Lehnert W., Wanders R.J.A. Am. J. Hum. Genet. 71:1463-1466(2002) [PubMed: 12434311] [Abstract] Cited for: DISEASE, FUNCTION.
[4]	"Crystal structure of human AUH protein, a single-stranded RNA binding homolog of enoyl-CoA hydratase." Kurimoto K., Fukai S., Nureki O., Muto Y., Yokoyama S. Structure 9:1253-1263(2001) [PubMed: 11738050] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 75-339, HEXAMERIZATION, FUNCTION, MUTAGENESIS OF LYS-105; LYS-109 AND LYS-113.
[5]	"Mutations in the AUH gene cause 3-methylglutaconic aciduria type I." Ly T.B.N., Peters V., Gibson K.M., Liesert M., Buckel W., Wilcken B., Carpenter K., Ensenauer R., Hoffmann G.F., Mack M., Zschocke J. Hum. Mutat. 21:401-407(2003) [PubMed: 12655555] [Abstract] Cited for: VARIANT MGA1 VAL-240, FUNCTION.
+	Additional computationally mapped references.

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Web resources

GeneReviews

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Cross-references

Sequence databases

X79888 mRNA. Translation: CAA56260.1.
BC020722 mRNA. Translation: AAH20722.1.

PIR

I37195.

RefSeq

NP_001689.1.

UniGene

Hs.175905

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HZD	X-ray	2.20	A/B/C/D/E/F	68-339	[»]

ModBase

Search...

PTM databases

PhosphoSite

Q13825.

Genome annotation databases

Ensembl

ENSG00000148090. Homo sapiens. [Contig view]

GeneID

549.

KEGG

hsa:549.

Organism-specific databases

H-InvDB

HIX0000590.
HIX0018470.

HGNC

HGNC:890. AUH.

HPA

HPA004171.

MIM

250950. phenotype.
600529. gene.

Orphanet

67046. 3-methylglutaconic aciduria, type 1.

PharmGKB

PA25181.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q13825.

HOVERGEN

Q13825.

Enzyme and pathway databases

BioCyc

MetaCyc:MON-11820.

Reactome

REACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpress

Q13825.

CleanEx

HS_AUH.

GermOnline

ENSG00000148090. Homo sapiens.

Family and domain databases

InterPro

IPR001753. Crotonase_core.
[Graphical view]

Pfam

PF00378. ECH. 1 hit.
[Graphical view]

PROSITE

PS00166. ENOYL_COA_HYDRATASE. 1 hit.
[Graphical view]

ProDom

Q13825.
[Graphical view] [Entries sharing at least one domain]

BLOCKS

Search...

Other Resources

SOURCE

Search...

ProtoNet

Search...

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Entry information

Entry name

AUHM_HUMAN

Accession

Primary (citable) accession number: Q13825
Secondary accession number(s): Q8WUE4

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	November 1, 1996
Last modified:	July 22, 2008
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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