MultifacetedProtDB - Bologna Biocomputing Group

EC number	EC number description
1.1.1.211	Oxidoreductases; Acting on the CH-OH group of donors; With NAD+ or NADP+ as acceptor; long-chain-3-hydroxyacyl-CoA dehydrogenase
2.3.1.-	Transferases; Acyltransferases; Transferring groups other than aminoacyl groups;
4.2.1.17	Lyases; Carbon-oxygen lyases; Hydro-lyases; enoyl-CoA hydratase

Structure

PDB	Resolution (Å)	PDB name
5ZQZ	4.2	Structure of human mitochondrial trifunctional protein, tetramer
5ZRV	7.7	Structure of human mitochondrial trifunctional protein, octamer
6DV2	3.6	Crystal Structure of Human Mitochondrial Trifunctional Protein

GO term

GO ontology	GO term	GO description
Biological Process	GO:0035965	cardiolipin acyl-chain remodeling
Biological Process	GO:0006635	fatty acid beta-oxidation
Biological Process	GO:0032868	response to insulin
Biological Process	GO:0009410	response to xenobiotic stimulus
Molecular Function	GO:0003857	3-hydroxyacyl-CoA dehydrogenase activity
Molecular Function	GO:0070403	NAD+ binding
Molecular Function	GO:0003985	acetyl-CoA C-acetyltransferase activity
Molecular Function	GO:0004300	enoyl-CoA hydratase activity
Molecular Function	GO:0000062	fatty-acyl-CoA binding
Molecular Function	GO:0016509	long-chain-3-hydroxyacyl-CoA dehydrogenase activity
Molecular Function	GO:0044877	protein-containing complex binding
Cellular Component	GO:0016507	mitochondrial fatty acid beta-oxidation multienzyme complex
Cellular Component	GO:0005743	mitochondrial inner membrane
Cellular Component	GO:0042645	mitochondrial nucleoid
Cellular Component	GO:0005739	mitochondrion

InterPro / Pfam

InterPro	InterPro name
IPR001753	Enoyl-CoA hydratase/isomerase
IPR006108	3-hydroxyacyl-CoA dehydrogenase, C-terminal
IPR006176	3-hydroxyacyl-CoA dehydrogenase, NAD binding
IPR006180	3-hydroxyacyl-CoA dehydrogenase, conserved site
IPR008927	6-phosphogluconate dehydrogenase-like, C-terminal domain superfamily
IPR012803	Fatty acid oxidation complex, alpha subunit, mitochondrial
IPR018376	Enoyl-CoA hydratase/isomerase, conserved site
IPR029045	ClpP/crotonase-like domain superfamily
IPR036291	NAD(P)-binding domain superfamily

Pfam	Pfam name
PF00378	Enoyl-CoA hydratase/isomerase
PF00725	3-hydroxyacyl-CoA dehydrogenase, C-terminal domain
PF02737	3-hydroxyacyl-CoA dehydrogenase, NAD binding domain

Reactome

Reactome	Reactome Name	Node type	Reactome Root	Reactome Root Name
R-HSA-1482798	Acyl chain remodeling of CL	Leaf	R-HSA-1430728	Metabolism
R-HSA-77285	Beta oxidation of myristoyl-CoA to lauroyl-CoA	Leaf	R-HSA-1430728	Metabolism
R-HSA-77288	mitochondrial fatty acid beta-oxidation of unsaturated fatty acids	Leaf	R-HSA-1430728	Metabolism
R-HSA-77305	Beta oxidation of palmitoyl-CoA to myristoyl-CoA	Leaf	R-HSA-1430728	Metabolism
R-HSA-77310	Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA	Leaf	R-HSA-1430728	Metabolism
R-HSA-77346	Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA	Leaf	R-HSA-1430728	Metabolism
R-HSA-77348	Beta oxidation of octanoyl-CoA to hexanoyl-CoA	Leaf	R-HSA-1430728	Metabolism
R-HSA-77350	Beta oxidation of hexanoyl-CoA to butanoyl-CoA	Leaf	R-HSA-1430728	Metabolism

Subcellular location

Location	ECO term	Pubmed
Mitochondrion	ECO:0000269	PubMed:29915090
Mitochondrion inner membrane	ECO:0000269	PubMed:29915090

Interactor | Variant | Drug

Phenotype

HPO ID	HPO name
HP:0000007	Autosomal recessive inheritance
HP:0000488	Retinopathy
HP:0000512	Abnormal electroretinogram
HP:0000532	Abnormal chorioretinal morphology
HP:0000533	Chorioretinal atrophy
HP:0000545	Myopia
HP:0000572	Visual loss
HP:0000577	Exotropia
HP:0000580	Pigmentary retinopathy
HP:0000613	Photophobia
HP:0000662	Nyctalopia
HP:0000829	Hypoparathyroidism
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001259	Coma
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001324	Muscle weakness
HP:0001396	Cholestasis
HP:0001508	Failure to thrive
HP:0001518	Small for gestational age
HP:0001531	Failure to thrive in infancy
HP:0001560	Abnormality of the amniotic fluid
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001639	Hypertrophic cardiomyopathy
HP:0001644	Dilated cardiomyopathy
HP:0001653	Mitral regurgitation
HP:0001699	Sudden death
HP:0001712	Left ventricular hypertrophy
HP:0001761	Pes cavus
HP:0001789	Hydrops fetalis
HP:0001939	Abnormality of metabolism/homeostasis
HP:0001943	Hypoglycemia
HP:0001985	Hypoketotic hypoglycemia
HP:0001987	Hyperammonemia
HP:0002033	Poor suck
HP:0002093	Respiratory insufficiency
HP:0002240	Hepatomegaly
HP:0002359	Frequent falls
HP:0002476	Primitive reflex
HP:0002611	Cholestatic liver disease
HP:0002878	Respiratory failure
HP:0002901	Hypocalcemia
HP:0002910	Elevated hepatic transaminase
HP:0002913	Myoglobinuria
HP:0003128	Lactic acidosis
HP:0003198	Myopathy
HP:0003201	Rhabdomyolysis
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003324	Generalized muscle weakness
HP:0003326	Myalgia
HP:0003394	Muscle spasm
HP:0003487	Babinski sign
HP:0003546	Exercise intolerance
HP:0003551	Difficulty climbing stairs
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0003756	Skeletal myopathy
HP:0005180	Tricuspid regurgitation
HP:0006555	Diffuse hepatic steatosis
HP:0007067	Distal peripheral sensory neuropathy
HP:0007141	Sensorimotor neuropathy
HP:0007340	Lower limb muscle weakness
HP:0007703	Abnormality of retinal pigmentation
HP:0008110	Equinovarus deformity
HP:0008138	Equinus calcaneus
HP:0008872	Feeding difficulties in infancy
HP:0009063	Progressive distal muscle weakness
HP:0009830	Peripheral neuropathy
HP:0011675	Arrhythmia
HP:0011808	Decreased patellar reflex
HP:0011968	Feeding difficulties
HP:0025145	Rigors
HP:0030051	Tip-toe gait
HP:0030856	Posterior staphyloma
HP:0031956	Elevated circulating aspartate aminotransferase concentration
HP:0045045	Elevated circulating acylcarnitine concentration
HP:0100626	Chronic hepatic failure
HP:0100950	Decreased 3-hydroxyacyl-CoA dehydrogenase level

Tissue and cell type

Tissue	Cell type	Expression level	Reliability
adrenal gland	glandular cells	High	Approved
appendix	glandular cells	Medium	Approved
bone marrow	hematopoietic cells	Medium	Approved
breast	glandular cells	Medium	Approved
breast	myoepithelial cells	Medium	Approved
bronchus	respiratory epithelial cells	Medium	Approved
caudate	glial cells	Medium	Approved
caudate	neuronal cells	Medium	Approved
cerebellum	cells in molecular layer	Low	Approved
cerebral cortex	endothelial cells	Medium	Approved
cerebral cortex	glial cells	Low	Approved
cerebral cortex	neuronal cells	Low	Approved
cerebral cortex	neuropil	Low	Approved
cervix	glandular cells	Low	Approved
cervix	squamous epithelial cells	Medium	Approved
colon	endothelial cells	Low	Approved
colon	glandular cells	High	Approved
colon	peripheral nerve/ganglion	Low	Approved
duodenum	glandular cells	High	Approved
endometrium 1	cells in endometrial stroma	Low	Approved
endometrium 1	glandular cells	Medium	Approved
endometrium 2	cells in endometrial stroma	Medium	Approved
endometrium 2	glandular cells	Medium	Approved
epididymis	glandular cells	Low	Approved
esophagus	squamous epithelial cells	Medium	Approved
fallopian tube	glandular cells	Low	Approved
gallbladder	glandular cells	Medium	Approved
heart muscle	cardiomyocytes	Medium	Approved
hippocampus	glial cells	Medium	Approved
hippocampus	neuronal cells	Low	Approved
kidney	cells in tubules	Medium	Approved
liver	hepatocytes	Medium	Approved
lung	macrophages	Medium	Approved
lymph node	non-germinal center cells	Low	Approved
nasopharynx	respiratory epithelial cells	Medium	Approved
oral mucosa	squamous epithelial cells	Medium	Approved
ovary	follicle cells	Medium	Approved
ovary	ovarian stroma cells	Low	Approved
pancreas	exocrine glandular cells	Medium	Approved
pancreas	pancreatic endocrine cells	Low	Approved
parathyroid gland	glandular cells	Medium	Approved
placenta	decidual cells	Low	Approved
placenta	trophoblastic cells	Low	Approved
prostate	glandular cells	Medium	Approved
rectum	glandular cells	Medium	Approved
salivary gland	glandular cells	Medium	Approved
seminal vesicle	glandular cells	Medium	Approved
skeletal muscle	myocytes	Medium	Approved
skin 1	Langerhans	Medium	Approved
skin 1	fibroblasts	Low	Approved
skin 2	epidermal cells	Medium	Approved
small intestine	glandular cells	High	Approved
smooth muscle	smooth muscle cells	Medium	Approved
soft tissue 1	chondrocytes	Medium	Approved
soft tissue 1	fibroblasts	Medium	Approved
soft tissue 2	fibroblasts	Medium	Approved
spleen	cells in red pulp	Low	Approved
spleen	cells in white pulp	Low	Approved
stomach 1	glandular cells	High	Approved
stomach 2	glandular cells	High	Approved
testis	Leydig cells	High	Approved
testis	elongated or late spermatids	Low	Approved
thyroid gland	glandular cells	Medium	Approved
tonsil	germinal center cells	Medium	Approved
tonsil	non-germinal center cells	Low	Approved
urinary bladder	urothelial cells	Medium	Approved
vagina	squamous epithelial cells	Medium	Approved

Disease

Disease name	MONDO ID	ICD10	ICD10 chapter	OMIM	Orphanet
mitochondrial trifunctional protein deficiency	MONDO:0012172	G71	chapter6, Diseases of the nervous system	OMIM:609015	Orphanet:746
long chain 3-hydroxyacyl-coa dehydrogenase deficiency	MONDO:0012173	E71	chapter4, Endocrine, nutritional and metabolic diseases	OMIM:609016	Orphanet:5
acute fatty liver of pregnancy	MONDO:0016573	O26	chapter15, Pregnancy, childbirth and the puerperium		Orphanet:243367

Summary of P40939

Gene: HADHA, HADH
Protein: Trifunctional enzyme subunit alpha, mitochondrial

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Summary of P40939

Gene: HADHA, HADH Protein: Trifunctional enzyme subunit alpha, mitochondrial

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Gene: HADHA, HADH
Protein: Trifunctional enzyme subunit alpha, mitochondrial