Q6NVY1 (HIBCH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
3-hydroxyisobutyryl-CoA hydrolase, mitochondrial
EC=3.1.2.4

Alternative name(s):
3-hydroxyisobutyryl-coenzyme A hydrolase
Short name=HIB-CoA hydrolase
Short name=HIBYL-CoA-H

Gene names

Name:

HIBCH

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	386 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	Hydrolyzes 3-hydroxyisobutyryl-CoA (HIBYL-CoA), a saline catabolite. Has high activity toward isobutyryl-CoA. Could be an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Also hydrolyzes 3-hydroxypropanoyl-CoA. Ref.1
Catalytic activity	3-hydroxy-2-methylpropanoyl-CoA + H2O = CoA + 3-hydroxy-2-methylpropanoate. Ref.1
Pathway	Amino-acid degradation; L-valine degradation.
Subcellular location	Mitochondrion By similarity.
Tissue specificity	Highly expressed in liver and kidney, also detected in heart, muscle and brain (at protein level). Not detected in lung. Ref.1
Involvement in disease	Defects in HIBCH are the cause of HIBCH deficiency (HIBCHD) [MIM:250620]; also known as deficiency of beta-hydroxyisobutyryl CoA deacylase or methacrylic aciduria. The enzyme defect results in accumulation of methacrylyl-CoA, a highly reactive compound, which readily undergoes addition reactions with free sulfhydryl groups. Affected individuals showed delayed development of motor skills, hypotonia, initial poor feeding, and a deterioration in neurological function during first stages of life. Ref.9
Sequence similarities	Belongs to the enoyl-CoA hydratase/isomerase family.
Sequence caution	The sequence AAC52114.1 differs from that shown. Reason: Erroneous initiation. The sequence AAH05190.2 differs from that shown. Reason: Erroneous initiation. The sequence AAY24178.1 differs from that shown. Reason: Erroneous initiation. The sequence BAD96699.1 differs from that shown. Reason: Erroneous initiation. The sequence BAD96743.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Branched-chain amino acid catabolism
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Molecular function	Hydrolase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	branched chain family amino acid catabolic process Traceable author statement. Source: Reactome
Cellular component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular function	3-hydroxyisobutyryl-CoA hydrolase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q6NVY1-1)

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: Q6NVY1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     338-385: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 32

32

Mitochondrion By similarity

Chain

33 – 386

354

3-hydroxyisobutyryl-CoA hydrolase, mitochondrial

PRO_0000284929

Sites

Binding site

121

1

Substrate

Binding site

146

1

Substrate; via amide nitrogen

Binding site

169

1

Substrate

Binding site

177

1

Substrate

Amino acid modifications

Modified residue

92

1

N6-acetyllysine Ref.6

Natural variations

Alternative sequence

338 – 385

48

Missing in isoform 2.

VSP_024780

Natural variant

46

1

T → A. Ref.2 Ref.4 Ref.5
Corresponds to variant rs1058180 [ dbSNP | Ensembl ].

VAR_031869

Natural variant

122

1

Y → C in HIBCHD. Ref.9

VAR_031870

Experimental info

Sequence conflict

41

1

E → G in AAH67822. Ref.5

Sequence conflict

83

1

L → V in AAC52114. Ref.1

Sequence conflict

111

1

Q → R in BAD96699. Ref.2

Sequence conflict

184 – 198

15

LPRLQ…FLALT → FATTPRKTWLLPCIN in AAC52114. Ref.1

Sequence conflict

369

1

E → K in BAD96699. Ref.2

Secondary structure

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386

Helix Strand Turn

Details...

Beta strand

37 – 39

3

Beta strand

49 – 51

3

Helix

54 – 56

3

Helix

62 – 77

16

Beta strand

84 – 87

4

Helix

100 – 107

8

Helix

114 – 127

14

Beta strand

135 – 139

5

Beta strand

156 – 159

4

Helix

169 – 171

3

Helix

183 – 186

4

Helix

194 – 197

4

Helix

206 – 209

4

Beta strand

214 – 216

3

Helix

219 – 221

3

Helix

222 – 231

10

Helix

237 – 250

14

Turn

253 – 256

4

Helix

262 – 264

3

Helix

265 – 271

7

Beta strand

274 – 276

3

Helix

277 – 287

11

Helix

290 – 299

10

Helix

304 – 315

12

Helix

322 – 337

16

Turn

341 – 343

3

Helix

347 – 351

5

Helix

364 – 366

3

Helix

369 – 376

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2007. Version 2. Checksum: 11B0632ED1DF2FFA	FASTA	386	43,482
	10 20 30 40 50 60 MGQREMWRLM SRFNAFKRTN TILHHLRMSK HTDAAEEVLL EKKGCTGVIT LNRPKFLNAL 70 80 90 100 110 120 TLNMIRQIYP QLKKWEQDPE TFLIIIKGAG GKAFCAGGDI RVISEAEKAK QKIAPVFFRE 130 140 150 160 170 180 EYMLNNAVGS CQKPYVALIH GITMGGGVGL SVHGQFRVAT EKCLFAMPET AIGLFPDVGG 190 200 210 220 230 240 GYFLPRLQGK LGYFLALTGF RLKGRDVYRA GIATHFVDSE KLAMLEEDLL ALKSPSKENI 250 260 270 280 290 300 ASVLENYHTE SKIDRDKSFI LEEHMDKINS CFSANTVEEI IENLQQDGSS FALEQLKVIN 310 320 330 340 350 360 KMSPTSLKIT LRQLMEGSSK TLQEVLTMEY RLSQACMRGH DFHEGVRAVL IDKDQSPKWK 370 380 PADLKEVTEE DLNNHFKSLG SSDLKF
	Isoform 2 [UniParc]. Checksum: 747FD3FC0745E844	FASTA	338	38,012
	10 20 30 40 50 60 MGQREMWRLM SRFNAFKRTN TILHHLRMSK HTDAAEEVLL EKKGCTGVIT LNRPKFLNAL 70 80 90 100 110 120 TLNMIRQIYP QLKKWEQDPE TFLIIIKGAG GKAFCAGGDI RVISEAEKAK QKIAPVFFRE 130 140 150 160 170 180 EYMLNNAVGS CQKPYVALIH GITMGGGVGL SVHGQFRVAT EKCLFAMPET AIGLFPDVGG 190 200 210 220 230 240 GYFLPRLQGK LGYFLALTGF RLKGRDVYRA GIATHFVDSE KLAMLEEDLL ALKSPSKENI 250 260 270 280 290 300 ASVLENYHTE SKIDRDKSFI LEEHMDKINS CFSANTVEEI IENLQQDGSS FALEQLKVIN 310 320 330 KMSPTSLKIT LRQLMEGSSK TLQEVLTMEY RLSQACMF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure and tissue-specific expression of human beta-hydroxyisobutyryl-coenzyme A hydrolase." Hawes J.W., Jaskiewicz J., Shimomura Y., Huang B., Bunting J., Harper E.T., Harris R.A. J. Biol. Chem. 271:26430-26434(1996) [PubMed: 8824301] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY. Tissue: Brain.
[2]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-46. Tissue: Small intestine.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-46.
[5]	"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], VARIANT ALA-46. Tissue: Testis.
[6]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-92, MASS SPECTROMETRY.
[7]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"Crystal structure of human beta-hydroxyisobutyryl-COA hydrolase in complex with quercetin." Structural genomics consortium (SGC) Submitted (JAN-2008) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 32-386 IN COMPLEX WITH 3-HYDROXY-2-METHYLPROPANOIC ACID AND QUERCETIN.
[9]	"Mutations in the gene encoding 3-hydroxyisobutyryl-CoA hydrolase results in progressive infantile neurodegeneration." Loupatty F.J., Clayton P.T., Ruiter J.P.N., Ofman R., Ijlst L., Brown G.K., Thorburn D.R., Harris R.A., Duran M., Desousa C., Krywawych S., Heales S.J.R., Wanders R.J.A. Am. J. Hum. Genet. 80:195-199(2007) [PubMed: 17160907] [Abstract] Cited for: VARIANT HIBCHD CYS-122.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U66669 mRNA. Translation: AAC52114.1. Different initiation.
AK222979 mRNA. Translation: BAD96699.1. Different initiation.
AK223023 mRNA. Translation: BAD96743.1. Different initiation.
AC092178 Genomic DNA. Translation: AAY24178.1. Different initiation.
AC010679 Genomic DNA. Translation: AAX93234.1.
CH471058 Genomic DNA. Translation: EAX10873.1.
CH471058 Genomic DNA. Translation: EAX10875.1.
BC005190 mRNA. Translation: AAH05190.2. Different initiation.
BC067822 mRNA. Translation: AAH67822.1.

IPI

IPI00377161.
IPI00419802.

RefSeq

NP_055177.2. NM_014362.3.
NP_932164.1. NM_198047.2.

UniGene

Hs.656685.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3BPT	X-ray	1.50	A	32-386	[»]

ProteinModelPortal

Q6NVY1.

SMR

Q6NVY1. Positions 32-386.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q6NVY1. 2 interactions.

STRING

Q6NVY1.

PTM databases

PhosphoSite

Q6NVY1.

Polymorphism databases

DMDM

146324905.

2D gel databases

REPRODUCTION-2DPAGE

IPI00419802.

Proteomic databases

PeptideAtlas

Q6NVY1.

PRIDE

Q6NVY1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000359678; ENSP00000352706; ENSG00000198130.

GeneID

26275.

KEGG

hsa:26275.

NMPDR

fig|9606.3.peg.19056.

UCSC

uc002uru.1. human.
uc002urv.1. human.

Organism-specific databases

CTD

26275.

GeneCards

GC02M191054.

H-InvDB

HIX0002677.

HGNC

HGNC:4908. HIBCH.

HPA

HPA036540.

MIM

250620. phenotype.
610690. gene.

neXtProt

NX_Q6NVY1.

Orphanet

88639. Neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency.

PharmGKB

PA29281.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04305.

GeneTree

ENSGT00570000079226.

HOVERGEN

HBG054809.

InParanoid

Q6NVY1.

PhylomeDB

Q6NVY1.

Enzyme and pathway databases

BRENDA

3.1.2.4. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q6NVY1.

Bgee

Q6NVY1.

CleanEx

HS_HIBCH.

Genevestigator

Q6NVY1.

Family and domain databases

InterPro

IPR001753. Crotonase_core.
[Graphical view]

KO

K05605.

Pfam

PF00378. ECH. 1 hit.
[Graphical view]

PROSITE

PS00166. ENOYL_COA_HYDRATASE. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

48577.

SOURCE

Search...

Entry information

Entry name

HIBCH_HUMAN

Accession

Primary (citable) accession number: Q6NVY1
Secondary accession number(s): D3DPI4 , Q53GA8, Q53GF2, Q53RF7, Q53TC6, Q92931, Q9BS94

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 2007
Last sequence update:	May 1, 2007
Last modified:	January 25, 2012
This is version 73 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.