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Protein

Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial

Gene

HADH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays an essential role in the mitochondrial beta-oxidation of short chain fatty acids. Exerts it highest activity toward 3-hydroxybutyryl-CoA.

Catalytic activityi

(S)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH.

Pathwayi: fatty acid beta-oxidation

This protein is involved in the pathway fatty acid beta-oxidation, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway fatty acid beta-oxidation and in Lipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei57NAD2 Publications1
Binding sitei73Coenzyme A1
Binding sitei80Coenzyme A1
Binding sitei122NAD2 Publications1
Binding sitei127NAD2 Publications1
Binding sitei149Coenzyme A1
Binding sitei149NAD2 Publications1
Sitei170Important for catalytic activityCurated1
Binding sitei173NAD2 Publications1
Binding sitei305NAD2 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi34 – 39NAD2 Publications6

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processFatty acid metabolism, Lipid metabolism
LigandNAD

Enzyme and pathway databases

BioCyciMetaCyc:HS06563-MONOMER
BRENDAi1.1.1.35 2681
ReactomeiR-HSA-77310 Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA
R-HSA-77346 Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA
R-HSA-77348 Beta oxidation of octanoyl-CoA to hexanoyl-CoA
R-HSA-77350 Beta oxidation of hexanoyl-CoA to butanoyl-CoA
R-HSA-77352 Beta oxidation of butanoyl-CoA to acetyl-CoA
SABIO-RKiQ16836
UniPathwayi
UPA00659

Chemistry databases

SwissLipidsiSLP:000001250

Names & Taxonomyi

Protein namesi
Recommended name:
Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (EC:1.1.1.35)
Short name:
HCDH
Alternative name(s):
Medium and short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase
Short-chain 3-hydroxyacyl-CoA dehydrogenase
Gene namesi
Name:HADH
Synonyms:HAD, HADHSC, SCHAD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000138796.15
HGNCiHGNC:4799 HADH
MIMi601609 gene
neXtProtiNX_Q16836

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

3-alpha-hydroxyacyl-CoA dehydrogenase deficiency (HADH deficiency)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive, metabolic disorder with various clinical presentations including hypoglycemia, hepatoencephalopathy, myopathy or cardiomyopathy, and in some cases sudden death.
See also OMIM:231530
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02407940A → T in HADH deficiency. 1 PublicationCorresponds to variant dbSNP:rs137853101EnsemblClinVar.1
Natural variantiVAR_02408057D → E in HADH deficiency. 1 PublicationCorresponds to variant dbSNP:rs137853102EnsemblClinVar.1
Familial hyperinsulinemic hypoglycemia 4 (HHF4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionMost common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. HHF4 should be easily recognizable by analysis of acylcarnitine species and that this disorder responds well to treatment with diazoxide. It provides the first 'experiment of nature' that links impaired fatty acid oxidation to hyperinsulinism and that provides support for the concept that a lipid signaling pathway is implicated in the control of insulin secretion.
See also OMIM:609975
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_024081258P → L in HHF4; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs137853103EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3033
GeneReviewsiHADH
MalaCardsiHADH
MIMi231530 phenotype
609975 phenotype
OpenTargetsiENSG00000138796
Orphaneti71212 Hyperinsulinism due to short chain 3-hydroxylacyl-CoA dehydrogenase deficiency
PharmGKBiPA29173

Chemistry databases

DrugBankiDB03612 3-Hydroxybutyryl-Coenzyme A
DB03059 Acetoacetyl-Coenzyme A
DB00157 NADH

Polymorphism and mutation databases

BioMutaiHADH
DMDMi311033442

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 12MitochondrionAdd BLAST12
ChainiPRO_000000740613 – 314Hydroxyacyl-coenzyme A dehydrogenase, mitochondrialAdd BLAST302

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei80N6-succinyllysineBy similarity1
Modified residuei81N6-acetyllysine; alternateBy similarity1
Modified residuei81N6-succinyllysine; alternateBy similarity1
Modified residuei87N6-acetyllysine; alternateBy similarity1
Modified residuei87N6-succinyllysine; alternateBy similarity1
Modified residuei125N6-acetyllysineBy similarity1
Modified residuei136N6-acetyllysine; alternateBy similarity1
Modified residuei136N6-succinyllysine; alternateBy similarity1
Modified residuei179N6-acetyllysineBy similarity1
Modified residuei185N6-acetyllysine; alternateCombined sources1
Modified residuei185N6-succinyllysine; alternateBy similarity1
Modified residuei192N6-acetyllysine; alternateBy similarity1
Modified residuei192N6-succinyllysine; alternateBy similarity1
Modified residuei202N6-acetyllysine; alternateCombined sources1
Modified residuei202N6-succinyllysine; alternateBy similarity1
Modified residuei206N6-succinyllysineBy similarity1
Modified residuei212N6-acetyllysine; alternateBy similarity1
Modified residuei212N6-succinyllysine; alternateBy similarity1
Modified residuei241N6-acetyllysine; alternateCombined sources1
Modified residuei241N6-succinyllysine; alternateBy similarity1
Modified residuei312N6-acetyllysine; alternateCombined sources1
Modified residuei312N6-succinyllysine; alternateBy similarity1

Post-translational modificationi

Succinylation at Lys-81, adjacent to a coenzyme A binding site. Desuccinylated by SIRT5 (By similarity).By similarity

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ16836
MaxQBiQ16836
PeptideAtlasiQ16836
PRIDEiQ16836
ProteomicsDBi61096
61097 [Q16836-2]
TopDownProteomicsiQ16836-1 [Q16836-1]

2D gel databases

REPRODUCTION-2DPAGEiIPI00298406
UCD-2DPAGEiQ16836

PTM databases

iPTMnetiQ16836
PhosphoSitePlusiQ16836

Expressioni

Tissue specificityi

Expressed in liver, kidney, pancreas, heart and skeletal muscle.

Gene expression databases

BgeeiENSG00000138796 Expressed in 233 organ(s), highest expression level in parietal pleura
CleanExiHS_HADH
ExpressionAtlasiQ16836 baseline and differential
GenevisibleiQ16836 HS

Organism-specific databases

HPAiHPA039588
HPA043888

Interactioni

Subunit structurei

Homodimer.2 Publications

Protein-protein interaction databases

BioGridi109283, 23 interactors
IntActiQ16836, 5 interactors

Structurei

Secondary structure

1314
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ16836
SMRiQ16836
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16836

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

GeneTreeiENSGT00880000137923
HOGENOMiHOG000141498
HOVERGENiHBG000832
InParanoidiQ16836
KOiK00022
PhylomeDBiQ16836
TreeFamiTF300886

Family and domain databases

Gene3Di1.10.1040.10, 1 hit
InterProiView protein in InterPro
IPR022694 3-OHacyl-CoA_DH
IPR006180 3-OHacyl-CoA_DH_CS
IPR006176 3-OHacyl-CoA_DH_NAD-bd
IPR006108 3HC_DH_C
IPR008927 6-PGluconate_DH-like_C_sf
IPR013328 6PGD_dom2
IPR036291 NAD(P)-bd_dom_sf
PfamiView protein in Pfam
PF00725 3HCDH, 1 hit
PF02737 3HCDH_N, 1 hit
PIRSFiPIRSF000105 HCDH, 1 hit
SUPFAMiSSF48179 SSF48179, 1 hit
SSF51735 SSF51735, 1 hit
PROSITEiView protein in PROSITE
PS00067 3HCDH, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 12 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q16836-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MAFVTRQFMR SVSSSSTASA SAKKIIVKHV TVIGGGLMGA GIAQVAAATG
60 70 80 90 100
HTVVLVDQTE DILAKSKKGI EESLRKVAKK KFAENLKAGD EFVEKTLSTI
110 120 130 140 150
ATSTDAASVV HSTDLVVEAI VENLKVKNEL FKRLDKFAAE HTIFASNTSS
160 170 180 190 200
LQITSIANAT TRQDRFAGLH FFNPVPVMKL VEVIKTPMTS QKTFESLVDF
210 220 230 240 250
SKALGKHPVS CKDTPGFIVN RLLVPYLMEA IRLYERGDAS KEDIDTAMKL
260 270 280 290 300
GAGYPMGPFE LLDYVGLDTT KFIVDGWHEM DAENPLHQPS PSLNKLVAEN
310
KFGKKTGEGF YKYK
Length:314
Mass (Da):34,294
Last modified:November 2, 2010 - v3
Checksum:i0C6F7C01BBCE646A
GO
Isoform 2 (identifier: Q16836-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGRAGLEAPPPPCGVTGTPGARGLQGRVGPRPQSLAFRGCLPRASSLPGSPRCRRRCHTM
     236-236: R → RDFQTCGDSNSGLGFSLK

Show »
Length:390
Mass (Da):42,140
Checksum:i3C20D80AAC4EB142
GO
Isoform 3 (identifier: Q16836-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     236-236: R → RDFQTCGDSNSGLGFSLK

Note: No experimental confirmation available.
Show »
Length:331
Mass (Da):36,051
Checksum:i11B5646AD077A666
GO

Computationally mapped potential isoform sequencesi

There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MSE2A0A0A0MSE2_HUMAN
Hydroxyacyl-coenzyme A dehydrogenas...
HADH
317Annotation score:
E9PF18E9PF18_HUMAN
Hydroxyacyl-coenzyme A dehydrogenas...
HADH
390Annotation score:
A0A0D9SFP2A0A0D9SFP2_HUMAN
Hydroxyacyl-coenzyme A dehydrogenas...
HADH
318Annotation score:
A0A1W2PQV5A0A1W2PQV5_HUMAN
Hydroxyacyl-coenzyme A dehydrogenas...
HADH
245Annotation score:
A0A1W2PNM1A0A1W2PNM1_HUMAN
Hydroxyacyl-coenzyme A dehydrogenas...
HADH
267Annotation score:
A0A1W2PQ78A0A1W2PQ78_HUMAN
Hydroxyacyl-coenzyme A dehydrogenas...
HADH
176Annotation score:
A0A1W2PP40A0A1W2PP40_HUMAN
Hydroxyacyl-coenzyme A dehydrogenas...
HADH
145Annotation score:
A0A1W2PQC2A0A1W2PQC2_HUMAN
Hydroxyacyl-coenzyme A dehydrogenas...
HADH
165Annotation score:
A0A1W2PRT2A0A1W2PRT2_HUMAN
Hydroxyacyl-coenzyme A dehydrogenas...
HADH
183Annotation score:
A0A1W2PQ55A0A1W2PQ55_HUMAN
Hydroxyacyl-coenzyme A dehydrogenas...
HADH
100Annotation score:
There are more potential isoformsShow all

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Isoform 2 (identifier: Q16836-2)
Sequence conflicti41L → P in AAB58153 (Ref. 2) Curated1
Sequence conflicti56R → H in AAB58153 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02407940A → T in HADH deficiency. 1 PublicationCorresponds to variant dbSNP:rs137853101EnsemblClinVar.1
Natural variantiVAR_02408057D → E in HADH deficiency. 1 PublicationCorresponds to variant dbSNP:rs137853102EnsemblClinVar.1
Natural variantiVAR_02676486L → P4 PublicationsCorresponds to variant dbSNP:rs4956145Ensembl.1
Natural variantiVAR_055701152Q → H1 PublicationCorresponds to variant dbSNP:rs1051519EnsemblClinVar.1
Natural variantiVAR_024081258P → L in HHF4; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs137853103EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0165511M → MGRAGLEAPPPPCGVTGTPG ARGLQGRVGPRPQSLAFRGC LPRASSLPGSPRCRRRCHTM in isoform 2. 1 Publication1
Alternative sequenceiVSP_016552236R → RDFQTCGDSNSGLGFSLK in isoform 2 and isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X96752 mRNA Translation: CAA65528.1
AF001902 mRNA Translation: AAB54008.1
AF001903 mRNA Translation: AAB54009.1
AF001904 Genomic DNA Translation: AAB58153.1
AF095703 Genomic DNA Translation: AAD13581.1
AC114733 Genomic DNA Translation: AAY41050.1
AC118062 Genomic DNA No translation available.
BC000306 mRNA Translation: AAH00306.1
CCDSiCCDS3678.1 [Q16836-1]
CCDS54790.1 [Q16836-3]
PIRiJC4879
RefSeqiNP_001171634.2, NM_001184705.2
NP_005318.3, NM_005327.4
UniGeneiHs.438289

Genome annotation databases

EnsembliENST00000309522; ENSP00000312288; ENSG00000138796 [Q16836-1]
ENST00000603302; ENSP00000474560; ENSG00000138796 [Q16836-3]
GeneIDi3033
KEGGihsa:3033
UCSCiuc003hyq.4 human [Q16836-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X96752 mRNA Translation: CAA65528.1
AF001902 mRNA Translation: AAB54008.1
AF001903 mRNA Translation: AAB54009.1
AF001904 Genomic DNA Translation: AAB58153.1
AF095703 Genomic DNA Translation: AAD13581.1
AC114733 Genomic DNA Translation: AAY41050.1
AC118062 Genomic DNA No translation available.
BC000306 mRNA Translation: AAH00306.1
CCDSiCCDS3678.1 [Q16836-1]
CCDS54790.1 [Q16836-3]
PIRiJC4879
RefSeqiNP_001171634.2, NM_001184705.2
NP_005318.3, NM_005327.4
UniGeneiHs.438289

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1F0YX-ray1.80A/B13-314[»]
1F12X-ray2.40A/B13-314[»]
1F14X-ray2.30A/B13-314[»]
1F17X-ray2.30A/B13-314[»]
1IL0X-ray2.20A/B13-314[»]
1LSJX-ray2.50A/B13-314[»]
1LSOX-ray2.60A/B13-314[»]
1M75X-ray2.30A/B13-314[»]
1M76X-ray2.15A/B13-314[»]
2HDHX-ray2.20A/B24-314[»]
3HADX-ray2.00A/B13-314[»]
3RQSX-ray2.00A/B1-314[»]
ProteinModelPortaliQ16836
SMRiQ16836
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109283, 23 interactors
IntActiQ16836, 5 interactors

Chemistry databases

DrugBankiDB03612 3-Hydroxybutyryl-Coenzyme A
DB03059 Acetoacetyl-Coenzyme A
DB00157 NADH
SwissLipidsiSLP:000001250

PTM databases

iPTMnetiQ16836
PhosphoSitePlusiQ16836

Polymorphism and mutation databases

BioMutaiHADH
DMDMi311033442

2D gel databases

REPRODUCTION-2DPAGEiIPI00298406
UCD-2DPAGEiQ16836

Proteomic databases

EPDiQ16836
MaxQBiQ16836
PeptideAtlasiQ16836
PRIDEiQ16836
ProteomicsDBi61096
61097 [Q16836-2]
TopDownProteomicsiQ16836-1 [Q16836-1]

Protocols and materials databases

DNASUi3033
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000309522; ENSP00000312288; ENSG00000138796 [Q16836-1]
ENST00000603302; ENSP00000474560; ENSG00000138796 [Q16836-3]
GeneIDi3033
KEGGihsa:3033
UCSCiuc003hyq.4 human [Q16836-1]

Organism-specific databases

CTDi3033
DisGeNETi3033
EuPathDBiHostDB:ENSG00000138796.15
GeneCardsiHADH
GeneReviewsiHADH
HGNCiHGNC:4799 HADH
HPAiHPA039588
HPA043888
MalaCardsiHADH
MIMi231530 phenotype
601609 gene
609975 phenotype
neXtProtiNX_Q16836
OpenTargetsiENSG00000138796
Orphaneti71212 Hyperinsulinism due to short chain 3-hydroxylacyl-CoA dehydrogenase deficiency
PharmGKBiPA29173
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00880000137923
HOGENOMiHOG000141498
HOVERGENiHBG000832
InParanoidiQ16836
KOiK00022
PhylomeDBiQ16836
TreeFamiTF300886

Enzyme and pathway databases

UniPathwayi
UPA00659

BioCyciMetaCyc:HS06563-MONOMER
BRENDAi1.1.1.35 2681
ReactomeiR-HSA-77310 Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA
R-HSA-77346 Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA
R-HSA-77348 Beta oxidation of octanoyl-CoA to hexanoyl-CoA
R-HSA-77350 Beta oxidation of hexanoyl-CoA to butanoyl-CoA
R-HSA-77352 Beta oxidation of butanoyl-CoA to acetyl-CoA
SABIO-RKiQ16836

Miscellaneous databases

ChiTaRSiHADH human
EvolutionaryTraceiQ16836
GeneWikiiHydroxyacyl-Coenzyme_A_dehydrogenase
GenomeRNAii3033
PROiPR:Q16836
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138796 Expressed in 233 organ(s), highest expression level in parietal pleura
CleanExiHS_HADH
ExpressionAtlasiQ16836 baseline and differential
GenevisibleiQ16836 HS

Family and domain databases

Gene3Di1.10.1040.10, 1 hit
InterProiView protein in InterPro
IPR022694 3-OHacyl-CoA_DH
IPR006180 3-OHacyl-CoA_DH_CS
IPR006176 3-OHacyl-CoA_DH_NAD-bd
IPR006108 3HC_DH_C
IPR008927 6-PGluconate_DH-like_C_sf
IPR013328 6PGD_dom2
IPR036291 NAD(P)-bd_dom_sf
PfamiView protein in Pfam
PF00725 3HCDH, 1 hit
PF02737 3HCDH_N, 1 hit
PIRSFiPIRSF000105 HCDH, 1 hit
SUPFAMiSSF48179 SSF48179, 1 hit
SSF51735 SSF51735, 1 hit
PROSITEiView protein in PROSITE
PS00067 3HCDH, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHCDH_HUMAN
AccessioniPrimary (citable) accession number: Q16836
Secondary accession number(s): J3KQ17
, O00324, O00397, O00753, Q4W5B4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 2, 2010
Last modified: September 12, 2018
This is version 198 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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