Cytochrome P450 2U1
Developmental stage
Expressed in fetal thymus.
Function
A cytochrome P450 monooxygenase involved in the metabolism of arachidonic acid and its conjugates (PubMed:14660610, PubMed:24563460). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:14660610, PubMed:24563460). Acts as an omega and omega-1 hydroxylase for arachidonic acid and possibly for other long chain fatty acids. May modulate the arachidonic acid signaling pathway and play a role in other fatty acid signaling processes (PubMed:14660610, PubMed:24563460). May down-regulate the biological activities of N-arachidonoyl-serotonin, an endocannabinoid that has anti-nociceptive effects through inhibition of fatty acid amide hydrolase FAAH, TRPV1 receptor and T-type calcium channels. Catalyzes C-2 oxidation of the indole ring of N-arachidonoyl-serotonin forming a less active product 2-oxo-N-arachidonoyl-serotonin (PubMed:24563460).
Involvement in disease
Spastic paraplegia 56, autosomal recessive, with or without pseudoxanthoma elasticum
SPG56
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations. In SPG56, upper limbs are often also affected. Some SPG56 patients may have a subclinical axonal neuropathy; others also have pseudoxanthoma elasticum.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Lipid metabolism; arachidonate metabolism.
Sequence Similarities
Belongs to the cytochrome P450 family.
Tissue Specificity
Widely expressed with stronger expression in thymus, heart and cerebellum.
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Microsome membrane
- Multi-pass membrane protein
- Mitochondrion inner membrane
- Multi-pass membrane protein
Alternative names
Cytochrome P450 2U1, Long-chain fatty acid omega-monooxygenase, CYP2U1