UniProtKB - Q16836 (HCDH_HUMAN)
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Protein
Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial
Gene
HADH
Organism
Homo sapiens (Human)
Status
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.
: fatty acid beta-oxidation Pathwayi
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 57 | NAD2 Publications | 1 | |
Binding sitei | 73 | Coenzyme A | 1 | |
Binding sitei | 80 | Coenzyme A | 1 | |
Binding sitei | 122 | NAD2 Publications | 1 | |
Binding sitei | 127 | NAD2 Publications | 1 | |
Binding sitei | 149 | Coenzyme A | 1 | |
Binding sitei | 149 | NAD2 Publications | 1 | |
Sitei | 170 | Important for catalytic activityCurated | 1 | |
Binding sitei | 173 | NAD2 Publications | 1 | |
Binding sitei | 305 | NAD2 Publications | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 34 – 39 | NAD2 Publications | 6 |
GO - Molecular functioni
- 3-hydroxyacyl-CoA dehydrogenase activity Source: Reactome
- NAD+ binding Source: InterPro
GO - Biological processi
- fatty acid beta-oxidation Source: Reactome
- negative regulation of insulin secretion Source: Ensembl
- response to activity Source: Ensembl
- response to drug Source: Ensembl
- response to insulin Source: Ensembl
Keywordsi
Molecular function | Oxidoreductase |
Biological process | Fatty acid metabolism, Lipid metabolism |
Ligand | NAD |
Enzyme and pathway databases
BioCyci | MetaCyc:HS06563-MONOMER. |
BRENDAi | 1.1.1.35. 2681. |
Reactomei | R-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-RKi | Q16836. |
UniPathwayi | UPA00659. |
Chemistry databases
SwissLipidsi | SLP: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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000138796.15. |
HGNCi | HGNC:4799. HADH. |
MIMi | 601609. gene. |
neXtProti | NX_Q16836. |
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:231530Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_024079 | 40 | A → T in HADH deficiency. 1 PublicationCorresponds to variant dbSNP:rs137853101Ensembl. | 1 | |
Natural variantiVAR_024080 | 57 | D → E in HADH deficiency. 1 PublicationCorresponds to variant dbSNP:rs137853102Ensembl. | 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:609975Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_024081 | 258 | P → L in HHF4; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs137853103Ensembl. | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 3033. |
GeneReviewsi | HADH. |
MalaCardsi | HADH. |
MIMi | 231530. phenotype. 609975. phenotype. |
OpenTargetsi | ENSG00000138796. |
Orphaneti | 71212. Hyperinsulinism due to short chain 3-hydroxylacyl-CoA dehydrogenase deficiency. |
PharmGKBi | PA29173. |
Chemistry databases
DrugBanki | DB03612. 3-Hydroxybutyryl-Coenzyme A. DB03059. Acetoacetyl-Coenzyme A. DB00157. NADH. |
Polymorphism and mutation databases
BioMutai | HADH. |
DMDMi | 311033442. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 12 | MitochondrionAdd BLAST | 12 | |
ChainiPRO_0000007406 | 13 – 314 | Hydroxyacyl-coenzyme A dehydrogenase, mitochondrialAdd BLAST | 302 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 80 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 81 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 81 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 87 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 87 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 125 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 136 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 136 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 179 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 185 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 185 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 192 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 192 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 202 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 202 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 206 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 212 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 212 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 241 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 241 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 312 | N6-acetyllysine; alternateCombined sources | 1 | |
Modified residuei | 312 | N6-succinyllysine; alternateBy similarity | 1 |
Post-translational modificationi
Succinylation at Lys-81, adjacent to a coenzyme A binding site. Desuccinylated by SIRT5 (By similarity).By similarity
Keywords - PTMi
AcetylationProteomic databases
EPDi | Q16836. |
MaxQBi | Q16836. |
PeptideAtlasi | Q16836. |
PRIDEi | Q16836. |
TopDownProteomicsi | Q16836-1. [Q16836-1] |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00298406. |
UCD-2DPAGEi | Q16836. |
PTM databases
iPTMneti | Q16836. |
PhosphoSitePlusi | Q16836. |
Expressioni
Tissue specificityi
Expressed in liver, kidney, pancreas, heart and skeletal muscle.
Gene expression databases
Bgeei | ENSG00000138796. |
CleanExi | HS_HADH. |
ExpressionAtlasi | Q16836. baseline and differential. |
Genevisiblei | Q16836. HS. |
Organism-specific databases
HPAi | HPA039588. HPA043888. |
Interactioni
Subunit structurei
Homodimer.2 Publications
Protein-protein interaction databases
BioGridi | 109283. 23 interactors. |
IntActi | Q16836. 4 interactors. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Helixi | 1 – 11 | Combined sources | 11 | |
Helixi | 14 – 22 | Combined sources | 9 | |
Beta strandi | 29 – 33 | Combined sources | 5 | |
Helixi | 37 – 48 | Combined sources | 12 | |
Beta strandi | 52 – 56 | Combined sources | 5 | |
Helixi | 60 – 79 | Combined sources | 20 | |
Beta strandi | 82 – 84 | Combined sources | 3 | |
Helixi | 86 – 98 | Combined sources | 13 | |
Beta strandi | 100 – 104 | Combined sources | 5 | |
Helixi | 106 – 109 | Combined sources | 4 | |
Helixi | 110 – 112 | Combined sources | 3 | |
Beta strandi | 114 – 118 | Combined sources | 5 | |
Helixi | 124 – 134 | Combined sources | 11 | |
Turni | 135 – 137 | Combined sources | 3 | |
Beta strandi | 143 – 146 | Combined sources | 4 | |
Beta strandi | 149 – 151 | Combined sources | 3 | |
Helixi | 153 – 157 | Combined sources | 5 | |
Helixi | 163 – 165 | Combined sources | 3 | |
Beta strandi | 166 – 171 | Combined sources | 6 | |
Turni | 175 – 177 | Combined sources | 3 | |
Beta strandi | 180 – 184 | Combined sources | 5 | |
Helixi | 191 – 203 | Combined sources | 13 | |
Beta strandi | 207 – 211 | Combined sources | 5 | |
Turni | 215 – 218 | Combined sources | 4 | |
Helixi | 219 – 235 | Combined sources | 17 | |
Helixi | 241 – 252 | Combined sources | 12 | |
Helixi | 258 – 265 | Combined sources | 8 | |
Helixi | 267 – 279 | Combined sources | 13 | |
Turni | 280 – 283 | Combined sources | 4 | |
Helixi | 285 – 287 | Combined sources | 3 | |
Helixi | 291 – 298 | Combined sources | 8 | |
Turni | 304 – 307 | Combined sources | 4 | |
Beta strandi | 308 – 312 | Combined sources | 5 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1F0Y | X-ray | 1.80 | A/B | 13-314 | [»] | |
1F12 | X-ray | 2.40 | A/B | 13-314 | [»] | |
1F14 | X-ray | 2.30 | A/B | 13-314 | [»] | |
1F17 | X-ray | 2.30 | A/B | 13-314 | [»] | |
1IL0 | X-ray | 2.20 | A/B | 13-314 | [»] | |
1LSJ | X-ray | 2.50 | A/B | 13-314 | [»] | |
1LSO | X-ray | 2.60 | A/B | 13-314 | [»] | |
1M75 | X-ray | 2.30 | A/B | 13-314 | [»] | |
1M76 | X-ray | 2.15 | A/B | 13-314 | [»] | |
2HDH | X-ray | 2.20 | A/B | 24-314 | [»] | |
3HAD | X-ray | 2.00 | A/B | 13-314 | [»] | |
3RQS | X-ray | 2.00 | A/B | 1-314 | [»] | |
ProteinModelPortali | Q16836. | |||||
SMRi | Q16836. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q16836. |
Family & Domainsi
Sequence similaritiesi
Belongs to the 3-hydroxyacyl-CoA dehydrogenase family.Curated
Keywords - Domaini
Transit peptidePhylogenomic databases
GeneTreei | ENSGT00880000137923. |
HOGENOMi | HOG000141498. |
HOVERGENi | HBG000832. |
InParanoidi | Q16836. |
KOi | K00022. |
PhylomeDBi | Q16836. |
TreeFami | TF300886. |
Family and domain databases
Gene3Di | 1.10.1040.10. 1 hit. |
InterProi | View 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. |
Pfami | View protein in Pfam PF00725. 3HCDH. 1 hit. PF02737. 3HCDH_N. 1 hit. |
PIRSFi | PIRSF000105. HCDH. 1 hit. |
SUPFAMi | SSF48179. SSF48179. 1 hit. SSF51735. SSF51735. 1 hit. |
PROSITEi | View protein in PROSITE PS00067. 3HCDH. 1 hit. |
s (3)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basket
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.
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Isoform 2 (identifier: Q16836-2) | |||||
Sequence conflicti | 41 | L → P in AAB58153 (Ref. 2) Curated | 1 | ||
Sequence conflicti | 56 | R → H in AAB58153 (Ref. 2) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_024079 | 40 | A → T in HADH deficiency. 1 PublicationCorresponds to variant dbSNP:rs137853101Ensembl. | 1 | |
Natural variantiVAR_024080 | 57 | D → E in HADH deficiency. 1 PublicationCorresponds to variant dbSNP:rs137853102Ensembl. | 1 | |
Natural variantiVAR_026764 | 86 | L → P4 PublicationsCorresponds to variant dbSNP:rs4956145Ensembl. | 1 | |
Natural variantiVAR_055701 | 152 | Q → H1 PublicationCorresponds to variant dbSNP:rs1051519Ensembl. | 1 | |
Natural variantiVAR_024081 | 258 | P → L in HHF4; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs137853103Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_016551 | 1 | M → MGRAGLEAPPPPCGVTGTPG ARGLQGRVGPRPQSLAFRGC LPRASSLPGSPRCRRRCHTM in isoform 2. 1 Publication | 1 | |
Alternative sequenceiVSP_016552 | 236 | R → RDFQTCGDSNSGLGFSLK in isoform 2 and isoform 3. 1 Publication | 1 |
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. |
CCDSi | CCDS3678.1. [Q16836-1] CCDS54790.1. [Q16836-3] |
PIRi | JC4879. |
RefSeqi | NP_001171634.2. NM_001184705.2. NP_005318.3. NM_005327.4. |
UniGenei | Hs.438289. |
Genome annotation databases
Ensembli | ENST00000309522; ENSP00000312288; ENSG00000138796. [Q16836-1] ENST00000603302; ENSP00000474560; ENSG00000138796. [Q16836-3] |
GeneIDi | 3033. |
KEGGi | hsa:3033. |
UCSCi | uc003hyq.4. human. [Q16836-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | HCDH_HUMAN | |
Accessioni | Q16836Primary (citable) accession number: Q16836 Secondary accession number(s): J3KQ17 Q4W5B4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | November 2, 2010 | |
Last modified: | March 28, 2018 | |
This is version 195 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |