Q2LAM0 · FA2H_RAT
- ProteinFatty acid 2-hydroxylase
- GeneFa2h
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids372 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the hydroxylation of free fatty acids at the C-2 position to produce 2-hydroxy fatty acids, which are building blocks of sphingolipids and glycosphingolipids common in neural tissue and epidermis (Probable). FA2H is stereospecific for the production of (R)-2-hydroxy fatty acids (By similarity).
Plays an essential role in the synthesis of galactosphingolipids of the myelin sheath (PubMed:17901466).
Responsible for the synthesis of sphingolipids and glycosphingolipids involved in the formation of epidermal lamellar bodies critical for skin permeability barrier (By similarity).
Participates in the synthesis of glycosphingolipids and a fraction of type II wax diesters in sebaceous gland, specifically regulating hair follicle homeostasis. Involved in the synthesis of sphingolipids of plasma membrane rafts, controlling lipid raft mobility and trafficking of raft-associated proteins (By similarity).
Plays an essential role in the synthesis of galactosphingolipids of the myelin sheath (PubMed:17901466).
Responsible for the synthesis of sphingolipids and glycosphingolipids involved in the formation of epidermal lamellar bodies critical for skin permeability barrier (By similarity).
Participates in the synthesis of glycosphingolipids and a fraction of type II wax diesters in sebaceous gland, specifically regulating hair follicle homeostasis. Involved in the synthesis of sphingolipids of plasma membrane rafts, controlling lipid raft mobility and trafficking of raft-associated proteins (By similarity).
Catalytic activity
- a 1,2-saturated fatty acid + 2 Fe(II)-[cytochrome b5] + 2 H+ + O2 = a (R)-2-hydroxy fatty acid + 2 Fe(III)-[cytochrome b5] + H2OThis reaction proceeds in the forward direction.
- 2 Fe(II)-[cytochrome b5] + 2 H+ + hexadecanoate + O2 = (R)-2-hydroxyhexadecanoate + 2 Fe(III)-[cytochrome b5] + H2OThis reaction proceeds in the forward direction.
- 2 Fe(II)-[cytochrome b5] + 2 H+ + O2 + octadecanoate = (R)-2-hydroxyoctadecanoate + 2 Fe(III)-[cytochrome b5] + H2OThis reaction proceeds in the forward direction.
- docosanoate + 2 Fe(II)-[cytochrome b5] + 2 H+ + O2 = 2-hydroxydocosanoate + 2 Fe(III)-[cytochrome b5] + H2OThis reaction proceeds in the forward direction.
- 2 Fe(II)-[cytochrome b5] + 2 H+ + O2 + tetracosanoate = (R)-2-hydroxytetracosanoate + 2 Fe(III)-[cytochrome b5] + H2OThis reaction proceeds in the forward direction.
Cofactor
Note: Binds 2 Zn2+ ions per subunit that likely form a catalytic dimetal center.
Pathway
Lipid metabolism; fatty acid metabolism.
Sphingolipid metabolism; galactosylceramide biosynthesis.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 43 | Fe (UniProtKB | ChEBI) of heme (UniProtKB | ChEBI); axial binding residue | ||||
Sequence: H | ||||||
Binding site | 69 | Fe (UniProtKB | ChEBI) of heme (UniProtKB | ChEBI); axial binding residue | ||||
Sequence: H | ||||||
Binding site | 234 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 239 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 257 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 260 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 261 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 315 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 319 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 336 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 339 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 340 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | membrane | |
Molecular Function | fatty acid alpha-hydroxylase activity | |
Molecular Function | heme binding | |
Molecular Function | iron ion binding | |
Biological Process | central nervous system myelin maintenance | |
Biological Process | ceramide biosynthetic process | |
Biological Process | establishment of skin barrier | |
Biological Process | fatty acid biosynthetic process | |
Biological Process | fatty acid metabolic process | |
Biological Process | galactosylceramide biosynthetic process | |
Biological Process | glucosylceramide biosynthetic process | |
Biological Process | lipid modification | |
Biological Process | peripheral nervous system myelin maintenance | |
Biological Process | plasma membrane raft organization | |
Biological Process | regulation of acinar cell proliferation | |
Biological Process | regulation of hair cycle | |
Biological Process | regulation of sebum secreting cell proliferation | |
Biological Process | sebaceous gland cell differentiation |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameFatty acid 2-hydroxylase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ2LAM0
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Microsome membrane ; Multi-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 168-188 | Helical | ||||
Sequence: VWYSVPIIWVPLVLYLSWSYY | ||||||
Transmembrane | 213-233 | Helical | ||||
Sequence: SVFIGLFVLGMLIWTLVEYLI | ||||||
Transmembrane | 268-288 | Helical | ||||
Sequence: SRLVFPPVPASVVVAFFYVFL | ||||||
Transmembrane | 290-310 | Helical | ||||
Sequence: LILPEAVAGILFAGGLLGYVL |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000312352 | 1-372 | Fatty acid 2-hydroxylase | |||
Sequence: MAPAPPPAASFTSAEVQRRLAAGACWVRRGASLYDLTGFVRHHPGGEQLLLARAGQDISADLDGPPHKHSDNARRWLEQYYVGELRADPQDPTENGAGAPAETQKTDAAIEPQFKVVDWDKDLVDWQKPLLWQVGHLGEKYDEWVHQPVARPIRLFHSDLIEAFSKTVWYSVPIIWVPLVLYLSWSYYRTLTQDNIRLFASFTRDYSLVVPESVFIGLFVLGMLIWTLVEYLIHRFLFHMKPPSNSHYLIMLHFVMHGQHHKAPFDGSRLVFPPVPASVVVAFFYVFLRLILPEAVAGILFAGGLLGYVLYDMTHYYLHFGSPHKGSYLYNMKAHHVKHHFEYQKSGFGISTKLWDYFFHTLIPEEADPKMQ |
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected in oligodendrocytes (at protein level). Detected in sciatic nerve.
Induction
Up-regulated in sciatic nerve during myelination. Up-regulated in differentiating cultured Schwann cells.
Developmental stage
Detected at low levels in sciatic nerve from newborns. Levels increase strongly during the first 3 weeks, and decrease thereafter to reach a low, constitutive level in 4 week olds. Expressed at a low, constitutive level in adults.
Gene expression databases
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 8-86 | Cytochrome b5 heme-binding | ||||
Sequence: AASFTSAEVQRRLAAGACWVRRGASLYDLTGFVRHHPGGEQLLLARAGQDISADLDGPPHKHSDNARRWLEQYYVGELR | ||||||
Domain | 219-361 | Fatty acid hydroxylase | ||||
Sequence: FVLGMLIWTLVEYLIHRFLFHMKPPSNSHYLIMLHFVMHGQHHKAPFDGSRLVFPPVPASVVVAFFYVFLRLILPEAVAGILFAGGLLGYVLYDMTHYYLHFGSPHKGSYLYNMKAHHVKHHFEYQKSGFGISTKLWDYFFHT |
Domain
The histidine box domains may contain the active site and/or be involved in metal ion binding.
The N-terminal cytochrome b5 heme-binding domain is essential for catalytic activity.
Sequence similarities
Belongs to the sterol desaturase family. SCS7 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length372
- Mass (Da)42,673
- Last updated2007-12-04 v2
- ChecksumAC02C568DF1BF7A6
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
DQ339484 EMBL· GenBank· DDBJ | ABC71132.1 EMBL· GenBank· DDBJ | mRNA | ||
CO396956 EMBL· GenBank· DDBJ | - | mRNA | No translation available. |