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FLASH GENE
Symbol HGS contributors: mct - updated : 11-07-2018
HGNC name hepatocyte growth factor-regulated tyrosine kinase substrate
HGNC id 4897
Location 17q25.3      Physical location : 79.651.019 - 79.669.145
Synonym name human growth factor-regulated tyrosine kinase substrate
Synonym symbol(s) HRS, ZFYVE8
DNA
TYPE functioning gene
STRUCTURE 18.13 kb     22 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
22 - 2926 - 777 - 1998 9630564
- splicing 2665 - 690 in brain 1998 9630564
missing an exon
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Reproductivefemale systemovary  highly
 male systemtestis   
Respiratoryrespiratory tractlarynx  highly
Skin/Tegumentskin   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoietic    
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticleukocyte
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • five zinc finger domain
  • an UIM (ubiquitin interaction motif) domain, necessary for EGF-stimulated tyrosine phosphorylation of HGS, and that couples receptor sorting to vesicle formation
  • an immunoreceptor based activation (coiled-coil) motif (ITAM)
  • a proline/glutamine rich region
  • a FYVE domain, required for HGS to reside in a microdomain of early endosomes, plays an essential role in its function
  • C-terminal region, which does not contain the UIM domain, can bind to interleukin-2 receptor beta (IL-2Rbeta)
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic
    text
  • colocalizing with NF2
  • localize to endosomal membranes
  • basic FUNCTION
  • regulation of protein trafficking mediated by endosome
  • inhibiting the cytokine cell growth function induced by STAM, NF2 interactor
  • early endosomal protein that plays a role in regulating the trafficking of growth factor-receptor complexes through early endosomes
  • essential for lysosomal targeting but dispensable for multivesicular body biogenesis and transport to late endosomes
  • plays potentially an important role in neural cell survival (
  • plays a key role in the regulation of the endocytic degradative transport of ubiquitinated receptor tyrosine kinases
  • regulates the FGFR2 degradative pathway, but not its juxtanuclear recycling transport
  • regulates the sorting of ligand-stimulated and unstimulated growth factor receptors on early endosomes
  • required for fascilitating the secretion of exosomes in dendritic cells (DCs)
  • involved in the regulation of antigen-presentation activity through the exosome secretion
  • having ability to influence both recycling and degradation and has been termed a “master regulator” of endocytosis (
  • USP8 and HGS function in the same pathway for CXCR4 trafficking
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • ESCRT-0 complex is composed of two subunits, HGS and STAM, both of which can engage ubiquitinylated substrates destined for lysosomal degradation
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • directly with the C terminus of NF2
  • PELP1-binding protein providing evidence of a physiologic interaction between HRS and PELP1
  • interacts with ubiquitylated cargoes through its ubiquitin-interacting-motif domain (UIM domain), and plays an essential early role in endosomal sorting
  • HGS and SNX3 functions in sorting and membrane invagination within multivesicular bodies
  • TRAK1 interacts with HGS, an essential component of the endosomal sorting and trafficking machinery
  • HGS interacts with SNX1 and regulates degradation of epidermal growth factor receptor, but also via the core complex component VPS35
  • become ubiquitinated by ITCH in response to CXCR4 activation
  • LITAF interacted and colocalized with endosomal sorting complex required for transport (ESCRT) components STAM, HGS, and TSG101 on early endosomes and functioned with the ESCRT machinery in the control of endosome-to-lysosome trafficking
  • cell & other
    REGULATION
    Other tyrosine phosphorylated
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    smooth muscle HGS deficiency leads to impaired esophageal motility
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS