Reviewed, UniProtKB/Swiss-Prot Q13825 (AUHM_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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.

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. Ref.1 Ref.5 Ref.7 Ref.8
Catalytic activity	(S)-3-hydroxy-3-methylglutaryl-CoA = trans-3-methylglutaconyl-CoA + H2O.
Pathway	Amino-acid degradation; L-leucine degradation; (S)-3-hydroxy-3-methylglutaryl-CoA from 3-isovaleryl-CoA: step 3/3.
Subunit structure	Homohexamer. Ref.7
Subcellular location	Mitochondrion By 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). Ref.5 Ref.8
Sequence similarities	Belongs to the enoyl-CoA hydratase/isomerase family.

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 Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	branched chain family amino acid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW 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 methylglutaconyl-CoA hydratase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

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.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 67

67

Mitochondrion Ref.1

Chain

68 – 339

272

Methylglutaconyl-CoA hydratase, mitochondrial

PRO_0000007415

Regions

Region

105 – 119

15

RNA-binding

Natural variations

Alternative sequence

140 – 168

29

Missing in isoform 2.

VSP_008336

Natural variant

240

1

A → V in MGA1. Ref.8

VAR_016911

Experimental info

Mutagenesis

105

1

K → N: Abolishes RNA-binding; when associated with E-109 and Q-113. Ref.7

Mutagenesis

109

1

K → E: Abolishes RNA-binding; when associated with N-105 and Q-113. Ref.7

Mutagenesis

113

1

K → Q: Abolishes RNA-binding; when associated with N-105 and E-109. Ref.7

Secondary structure

1

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339

Helix Strand Turn

Details...

Beta strand

76 – 81

6

Helix

84 – 86

3

Beta strand

89 – 94

6

Helix

97 – 99

3

Helix

107 – 120

14

Beta strand

125 – 133

9

Beta strand

135 – 138

4

Helix

143 – 146

4

Helix

151 – 169

19

Beta strand

175 – 184

10

Helix

186 – 193

8

Beta strand

194 – 200

7

Beta strand

204 – 206

3

Helix

209 – 212

4

Helix

220 – 228

9

Helix

230 – 239

10

Beta strand

242 – 244

3

Helix

245 – 250

6

Beta strand

255 – 258

4

Helix

266 – 276

11

Turn

277 – 280

4

Helix

283 – 297

15

Helix

301 – 313

13

Turn

314 – 317

4

Helix

319 – 328

10

Turn

329 – 331

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: E04FEB95933FB30B	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
	Isoform 2. Checksum: 24B4C6983AFED47F	FASTA	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

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]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	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].
[4]	"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.
[5]	"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.
[6]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[7]	"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.
[8]	"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.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X79888 mRNA. Translation: CAA56260.1.
AL158071, AL353645, AL513353 Genomic DNA. Translation: CAH72265.1.
AL158071, AL353645, AL513353 Genomic DNA. Translation: CAH72266.1.
AL513353, AL158071, AL353645 Genomic DNA. Translation: CAH72310.1.
AL513353, AL158071, AL353645 Genomic DNA. Translation: CAH72311.1.
AL353645, AL158071, AL513353 Genomic DNA. Translation: CAH73894.1.
AL353645, AL158071, AL513353 Genomic DNA. Translation: CAH73895.1.
CH471089 Genomic DNA. Translation: EAW62794.1.
CH471089 Genomic DNA. Translation: EAW62795.1.
BC020722 mRNA. Translation: AAH20722.1.

IPI

IPI00017802.
IPI00102904.

PIR

I37195.

RefSeq

NP_001689.1.

UniGene

Hs.175905

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HZD	X-ray	2.20	A/B/C/D/E/F	68-339	[»]
2ZQQ	X-ray	2.20	A/B/C/D/E/F	68-339	[»]
2ZQR	X-ray	2.50	A/B/C/D/E/F	68-339	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q13825.

PTM databases

PhosphoSite

Q13825.

Proteomic databases

PRIDE

Q13825.

Genome annotation databases

Ensembl

ENST00000375731; ENSP00000364883; ENSG00000148090; Homo sapiens. [Genome view]

GeneID

549.

KEGG

hsa:549.

UCSC

uc004arf.2. human.
uc004arg.2. human.

Organism-specific databases

CTD

549.

GeneCards

GC09M093015.

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...

Phylogenomic databases

eggNOG

prNOG14641.

HOGENOM

HBG748731.

HOVERGEN

Q13825.

InParanoid

Q13825.

OMA

KERVKMN.

OrthoDB

EOG9W9MPT.

PhylomeDB

Q13825.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-11820.

BRENDA

4.2.1.18. 247.

Reactome

REACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpress

Q13825.

Bgee

Q13825.

CleanEx

HS_AUH.

Genevestigator

Q13825.

GermOnline

ENSG00000148090. Homo sapiens.

Family and domain databases

InterPro

IPR001753. Crotonase_core.
IPR018376. Enoyl-CoA_hyd/isom_CS.
[Graphical view]

Pfam

PF00378. ECH. 1 hit.
[Graphical view]

PROSITE

PS00166. ENOYL_COA_HYDRATASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

2269.

SOURCE

Search...

Entry information

Entry name

AUHM_HUMAN

Accession

Primary (citable) accession number: Q13825
Secondary accession number(s): B1ALV7, B1ALV8, Q8WUE4

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	November 1, 1996
Last modified:	February 9, 2010
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.