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Q6NVY1 (HIBCH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length386 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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

HIBCH deficiency (HIBCHD) [MIM:250620]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. 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

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3232Mitochondrion By similarity
Chain33 – 3863543-hydroxyisobutyryl-CoA hydrolase, mitochondrial
PRO_0000284929

Sites

Binding site1211Substrate
Binding site1461Substrate; via amide nitrogen
Binding site1691Substrate
Binding site1771Substrate

Amino acid modifications

Modified residue551N6-acetyllysine; alternate By similarity
Modified residue551N6-succinyllysine; alternate By similarity
Modified residue921N6-acetyllysine; alternate Ref.6
Modified residue921N6-succinyllysine; alternate By similarity
Modified residue2211N6-acetyllysine; alternate By similarity
Modified residue2211N6-succinyllysine; alternate By similarity
Modified residue2571N6-succinyllysine By similarity
Modified residue2971N6-acetyllysine; alternate By similarity
Modified residue2971N6-succinyllysine; alternate By similarity
Modified residue3011N6-succinyllysine By similarity
Modified residue3531N6-acetyllysine; alternate By similarity
Modified residue3531N6-succinyllysine; alternate By similarity
Modified residue3601N6-acetyllysine By similarity
Modified residue3651N6-acetyllysine By similarity
Modified residue3771N6-succinyllysine By similarity

Natural variations

Alternative sequence338 – 38548Missing in isoform 2.
VSP_024780
Natural variant461T → A. Ref.2 Ref.4 Ref.5
Corresponds to variant rs1058180 [ dbSNP | Ensembl ].
VAR_031869
Natural variant1221Y → C in HIBCHD. Ref.9
VAR_031870

Experimental info

Sequence conflict411E → G in AAH67822. Ref.5
Sequence conflict831L → V in AAC52114. Ref.1
Sequence conflict1111Q → R in BAD96699. Ref.2
Sequence conflict184 – 19815LPRLQ…FLALT → FATTPRKTWLLPCIN in AAC52114. Ref.1
Sequence conflict3691E → K in BAD96699. Ref.2

Secondary structure

................................................................ 386
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2007. Version 2.
Checksum: 11B0632ED1DF2FFA

FASTA38643,482
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 747FD3FC0745E844
Show »

FASTA33838,012

References

« Hide '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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-92, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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] [Europe PMC] [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] [Europe PMC] [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.
RefSeqNP_055177.2. NM_014362.3.
NP_932164.1. NM_198047.2.
UniGeneHs.656685.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3BPTX-ray1.50A32-386[»]
ProteinModelPortalQ6NVY1.
SMRQ6NVY1. Positions 32-386.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117658. 4 interactions.
IntActQ6NVY1. 2 interactions.
STRING9606.ENSP00000352706.

PTM databases

PhosphoSiteQ6NVY1.

Polymorphism databases

DMDM146324905.

2D gel databases

REPRODUCTION-2DPAGEIPI00419802.

Proteomic databases

PaxDbQ6NVY1.
PeptideAtlasQ6NVY1.
PRIDEQ6NVY1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000359678; ENSP00000352706; ENSG00000198130. [Q6NVY1-1]
ENST00000392332; ENSP00000376144; ENSG00000198130. [Q6NVY1-2]
GeneID26275.
KEGGhsa:26275.
UCSCuc002uru.3. human. [Q6NVY1-1]
uc002urv.3. human. [Q6NVY1-2]

Organism-specific databases

CTD26275.
GeneCardsGC02M191054.
HGNCHGNC:4908. HIBCH.
HPAHPA036540.
HPA036541.
MIM250620. phenotype.
610690. gene.
neXtProtNX_Q6NVY1.
Orphanet88639. Neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency.
PharmGKBPA29281.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1024.
HOVERGENHBG054809.
InParanoidQ6NVY1.
KOK05605.
PhylomeDBQ6NVY1.
TreeFamTF314329.

Enzyme and pathway databases

BRENDA3.1.2.4. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKQ6NVY1.
UniPathwayUPA00362.

Gene expression databases

ArrayExpressQ6NVY1.
BgeeQ6NVY1.
CleanExHS_HIBCH.
GenevestigatorQ6NVY1.

Family and domain databases

Gene3D1.10.12.10. 1 hit.
InterProIPR014748. Crontonase_C.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ6NVY1.
GenomeRNAi26275.
NextBio48577.
PROQ6NVY1.
SOURCESearch...

Entry information

Entry nameHIBCH_HUMAN
AccessionPrimary (citable) accession number: Q6NVY1
Secondary accession number(s): D3DPI4 expand/collapse secondary AC list , Q53GA8, Q53GF2, Q53RF7, Q53TC6, Q92931, Q9BS94
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: May 1, 2007
Last modified: April 16, 2014
This is version 93 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM