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FLASH GENE
Symbol FA2H contributors: mct/shn - updated : 17-04-2013
HGNC name fatty acid 2-hydroxylase
HGNC id 21197
Corresponding disease
SDWHD spasticity, dystonia, and white matter degeneration
SPG35 spastic paraplegia 35
Location 16q23.1      Physical location : 74.746.857 - 74.808.729
Synonym name
  • fatty acid hydroxylase domain containing 1
  • fatty acid alpha-hydroxylase
  • fatty acid hydroxylase
  • spastic paraplegia 35 (autosomal recessive)
  • Synonym symbol(s) FAAH, FAXDC1, FLJ25287, SCS7, FAH1, SPG35
    EC.number 1.-.-.-
    DNA
    TYPE functioning gene
    STRUCTURE 61.87 kb     7 Exon(s)
    MAPPING cloned Y linked N status provisional
    Map cen - D16S3018 - D16S3115 - FA2H - D16S3051 - D16S3118 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 2442 43 372 - - 15337768
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly Homo sapiensAdultNM_024306
     stomach   highly Mus musculusAdultNM_178086
    Endocrinepancreas   lowly Homo sapiensAdultNM_024306
    Nervousbrain   highly Homo sapiensAdultNM_024306
     brain   moderately Mus musculusAdultNM_178086
    Reproductivemale systemtestis  highly Mus musculusAdultNM_178086
     male systemtestis  moderately Homo sapiensAdultNM_024306
     male systemprostate  moderately Homo sapiensAdultNM_024306
    Skin/Tegumentskin   highly Mus musculusAdultNM_178086
    Urinarykidney   lowly Mus musculusAdultNM_178086
     kidney   lowly Homo sapiensAdultNM_024306
    cell lineage expressed in cultured human keratinocytes and human epidermis
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal cytochrome b5 domain and four potential transmembrane domains
  • a iron-binding histidine motif conserved among membrane-bound desaturases/hydroxylases
  • a sterol desaturase domain at residues 210367
  • conjugated HemoP
    HOMOLOGY
    interspecies homolog to yeast ceramide 2-hydroxylase gene (FAH1)
    ortholog to Fa2h, Mus musculus
    ortholog to Fa2h, Rattus norvegicus
    ortholog to FA2H, Pan troglodytes
    ortholog to fa2h, Danio rerio
    Homologene
    FAMILY
  • cytochrome b5 family
  • SCS7 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,microsome
    text EGFP-FA2H fusion protein co-localized with calnexin, indicating that the enzyme resides in the endoplasmic reticulum
    basic FUNCTION
  • catalyzes the 2-hydroxylation of myelin galactolipids, galactosylceramide, and its sulfated form, sulfatide
  • membrane bound hemoprotein which function as an electron carrier for membrane bound oxygenase
  • involved in the formation of myelin 2-hydroxy galactosylceramides and -sulfatides
  • accounts for 2-hydroxyceramide/2-hydroxyglucosylceramide synthesis in epidermis and is required for epidermal permeability barrier formation
  • catalyze the initial step of straight chain fatty acid alpha-oxidation (Guo 2010)
  • role in adipocyte lipogenesis possibly by modulation of raft fluidity and level of SLC2A4 (Guo 2010)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism energetic
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
    cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SDWHD , SPG35
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • FA2H-siRNA in cultured human keratinocytes suppressed 2-hydroxylase activity and decreased 2-hydroxyceramide/2-hydroxyglucosylceramide levels in keratinocytes and contained abnormal epidermal lamellar bodies and did not form the normal extracellular lamellar membranes
  • FA2H-deficient (FA2H(-/-)) mice lacked 2-hydroxylated sphingolipids in the brain and in peripheral nerves while nonhydroxylated galactosylceramide is increased
  • 18-month-old FA2H(-/-) mice, however, exhibited scattered axonal and myelin sheath degeneration in the spinal cord and an even more pronounced loss of stainability of myelin sheaths in sciatic nerves