Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

HGS

contributors: mct - updated : 11-07-2018

HGNC name	hepatocyte growth factor-regulated tyrosine kinase substrate
HGNC id	4897

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004712 22 - 2926 NP_004703 - 777 - 1998 9630564 HRSI2 - splicing 2665 - 690 in brain 1998 9630564 missing an exon

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Reproductive female system ovary     highly   male system testis       Respiratory respiratory tract larynx     highly Skin/Tegument skin       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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