Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol HHAT contributors: mct - updated : 22-06-2018
HGNC name hedgehog acyltransferase
HGNC id 18270
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • ten transmembrane domains
  • two reentrant loops with the critical His and Asp residues on opposite sides of the endoplasmic reticulum membrane
  • HOMOLOGY
    Homologene
    FAMILY small subfamily of membrane-bound O-acyltransferase proteins
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • acting within the secretory pathway to catalyze N-terminal palmitoylation of 'hedgehog'
  • in the developing testis, HHAT is not required for Sertoli cell commitment but plays a role in proper testis cord formation and the differentiation of fetal Leydig cells
  • is the enzyme in the endoplasmic reticulum that palmitoylates Hedgehog proteins, is a member of a small subfamily of membrane-bound O-acyltransferase proteins that acylate secreted proteins, and is an important drug target in cancer
  • HHAT regulated the proliferation of both SHH responsive and non-responsive ESR1 positive cells, suggesting a SHH independent function for HHAT
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • covalent attachment of palmitate to the N-terminal cysteine of SHH is catalyzed by Hedgehog acyltransferase (Hhat) and is critical for proper signaling
  • is a multipass transmembrane enzyme that mediates the covalent attachment of the 16-carbon fatty acid palmitate to the N-terminal cysteine of Sonic Hedgehog (SHH)
  • PORCN, HHAT and GHRL have been shown to acylate specific proteins or peptides
  • palmitoylation of the secreted signaling protein sonic hedgehog (SHH) by the enzyme hedgehog acyltransferase (HHAT) is required for functional signaling
  • cell & other
    REGULATION
    Other is palmitoylated on multiple cytosolic cysteines that maintain protein structure within the membrane
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    leads to syndromic 46,XY disorder of sex development by impeding Hedgehog protein palmitoylation and signaling
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • HHAT as a potential candidate in the etiology and pathogenesis of Holoprosencephaly (HPE) and its associated disorders
  • Marker
    Therapy target
    ANIMAL & CELL MODELS
  • in mice, Hhat loss-of-function leads to holoprosencephaly together with acrania and agnathia