Search Results

Overview

Uniprot IDQ02318
Protein NameSterol 26-hydroxylase, mitochondrial
Gene NameCYP27A1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
134 RNDMELWKEHRDQHD
39 PAALPSDKATGAPGA
498 ARLIQKYKVVLAPET
509 APETGELKSVARIVL
520 RIVLVPNKKVGLQFL
521 IVLVPNKKVGLQFLQ

Function

Cytochrome P450 monooxygenase that catalyzes regio- and stereospecific hydroxylation of cholesterol and its derivatives. Hydroxylates (with R stereochemistry) the terminal methyl group of cholesterol side-chain in a three step reaction to yield at first a C26 alcohol, then a C26 aldehyde and finally a C26 acid (PubMed:12077124, PubMed:21411718, PubMed:28190002, PubMed:9660774). Regulates cholesterol homeostasis by catalyzing the conversion of excess cholesterol to bile acids via both the 'neutral' (classic) and the 'acid' (alternative) pathways (PubMed:11412116, PubMed:1708392, PubMed:2019602, PubMed:7915755, PubMed:9186905, PubMed:9660774, PubMed:9790667). May also regulate cholesterol homeostasis via generation of active oxysterols, which act as ligands for NR1H2 and NR1H3 nuclear receptors, modulating the transcription of genes involved in lipid metabolism (PubMed:12077124, PubMed:9660774). Catalyzes the conversion of 7-ketocholesterol (7-oxocholesterol) into 7-keto,27-hydroxycholesterol, a precursor of 7-keto,27-hydroxycholesterol, an active oxysterol that activates smoothened (SMO) and the smoothened signaling pathway (By similarity). Plays a role in cholestanol metabolism in the cerebellum. Similarly to cholesterol, hydroxylates cholestanol and may facilitate sterol diffusion through the blood-brain barrier to the systemic circulation for further degradation (PubMed:28190002). Also hydroxylates retinal 7-ketocholesterol, a noxious oxysterol with pro-inflammatory and pro-apoptotic effects, and may play a role in its elimination from the retinal pigment epithelium (PubMed:21411718). May play a redundant role in vitamin D biosynthesis. Catalyzes 25-hydroxylation of vitamin D3 that is required for its conversion to a functionally active form (PubMed:15465040)

Protein Sequence

10 MAALGCARLR 20 WALRGAGRGL 30 CPHGARAKAA 40 IPAALPSDKA 50 TGAPGAGPGV 60 RRRQRSLEEI 70 PRLGQLRFFF 80 QLFVQGYALQ 90 LHQLQVLYKA 100 KYGPMWMSYL 110 GPQMHVNLAS 120 APLLEQVMRQ 130 EGKYPVRNDM 140 ELWKEHRDQH 150 DLTYGPFTTE 160 GHHWYQLRQA 170 LNQRLLKPAE 180 AALYTDAFNE 190 VIDDFMTRLD 200 QLRAESASGN 210 QVSDMAQLFY 220 YFALEAICYI 230 LFEKRIGCLQ 240 RSIPEDTVTF 250 VRSIGLMFQN 260 SLYATFLPKW 270 TRPVLPFWKR 280 YLDGWNAIFS 290 FGKKLIDEKL 300 EDMEAQLQAA 310 GPDGIQVSGY 320 LHFLLASGQL 330 SPREAMGSLP 340 ELLMAGVDTT 350 SNTLTWALYH 360 LSKDPEIQEA 370 LHEEVVGVVP 380 AGQVPQHKDF 390 AHMPLLKAVL 400 KETLRLYPVV 410 PTNSRIIEKE 420 IEVDGFLFPK 430 NTQFVFCHYV 440 VSRDPTAFSE 450 PESFQPHRWL 460 RNSQPATPRI 470 QHPFGSVPFG 480 YGVRACLGRR 490 IAELEMQLLL 500 ARLIQKYKVV 510 LAPETGELKS 520 VARIVLVPNK 530 KVGLQFLQRQ C

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005743 mitochondrial inner membrane
Cellular Component GO:0005759 mitochondrial matrix
Cellular Component GO:0005739 mitochondrion
Molecular Function GO:0047748 cholestanetetraol 26-dehydrogenase activity
Molecular Function GO:0031073 cholesterol 26-hydroxylase activity
Molecular Function GO:0020037 heme binding
Molecular Function GO:0005506 iron ion binding
Molecular Function GO:0008395 steroid hydroxylase activity
Molecular Function GO:0030343 vitamin D3 25-hydroxylase activity
Biological Process GO:0006699 bile acid biosynthetic process
Biological Process GO:0036378 calcitriol biosynthetic process from calciol
Biological Process GO:0006707 cholesterol catabolic process
Biological Process GO:0008203 cholesterol metabolic process
Biological Process GO:0016125 sterol metabolic process

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.