Gene Report

Basic Information

Approved Symbol	HGS
Approved Name	hepatocyte growth factor-regulated tyrosine kinase substrate
Symbol Alias	Hrs, ZFYVE8, Vps27
Location	17q25
Position	chr17:79668713-79669151 (+)
External Links	Entrez Gene: 9146 Ensembl: ENSG00000185359 UCSC: uc002kbg.3 HGNC ID: 4897
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between HGS and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
Hepatocyte growth factor-regulated tyrosine kinase substrate	Tochigi, 2008	patients and normal controls		Genes differentially expressed in major depression Genes differentially expressed in major depression

Positive relationships between HGS and other components at different levels (count: 0)

Positive relationship network of HGS in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between HGS and MDD (count: 0)

Negative relationships between HGS and other components at different levels (count: 0)

HGS related SNPs in MK4MDD (count: 0)

HGS related proteins in MK4MDD (count: 0)

HGS related GO terms (count: 29)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0005829	cytosol	cellular component	TAS
GO:0042059	negative regulation of epidermal growth factor receptor signaling pathway	biological process	TAS
GO:0010628	positive regulation of gene expression	biological process	IMP[18767904]
GO:0006622	protein targeting to lysosome	biological process	IMP[18767904]
GO:0005515	protein binding	molecular function	IPI[10861283\|12802020\|15611048\|16084064\|16189514\|18675823\|20150893\|22458338\|25416956]
GO:0043231	intracellular membrane-bounded organelle	cellular component	IDA
GO:0005768	endosome	cellular component	IDA[15611048]
GO:0033565	ESCRT-0 complex	cellular component	TAS[20588296]
GO:0070062	extracellular exosome	cellular component	IDA[19056867]
GO:0005769	early endosome	cellular component	IDA[10861283]
GO:0007165	signal transduction	biological process	TAS[9407053]
GO:0006892	post-Golgi vesicle-mediated transport	biological process	TAS
GO:0046426	negative regulation of JAK-STAT cascade	biological process	IDA[12444102]
GO:0061024	membrane organization	biological process	TAS
GO:0008285	negative regulation of cell proliferation	biological process	TAS[9407053]
GO:0006914	autophagy	biological process	TAS[20588296]
GO:0043405	regulation of MAP kinase activity	biological process	IMP[17714434]
GO:0031901	early endosome membrane	cellular component	IEA
GO:1903543	positive regulation of exosomal secretion	biological process	IMP[24105262]
GO:0019904	protein domain specific binding	molecular function	IPI[11984006]
GO:0010324	membrane invagination	biological process	IMP[18767904]
GO:0042176	regulation of protein catabolic process	biological process	TAS[15611048]
GO:0016197	endosomal transport	biological process	NAS[10861283]; TAS
GO:0032585	multivesicular body membrane	cellular component	IEA
GO:0005737	cytoplasm	cellular component	IDA
GO:0046872	metal ion binding	molecular function	IEA
GO:0036258	multivesicular body assembly	biological process	TAS[20588296]
GO:0072657	protein localization to membrane	biological process	IMP[18767904]
GO:0007173	epidermal growth factor receptor signaling pathway	biological process	TAS

HGS related KEGG pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04144	endocytosis	Endocytosis	Endocytosis is a mechanism for cells to remove ligands, nutr...... Endocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins entering through clathrin-dependent endocytosis (CDE) have sequences in their cytoplasmic domains that bind to the APs (adaptor-related protein complexes) and enable their rapid removal from the PM. In addition to APs and clathrin, there are numerous accessory proteins including dynamin. Depending on the various proteins that enter the endosome membrane, these cargoes are sorted to distinct destinations. Some cargoes, such as nutrient receptors, are recycled back to the PM. Ubiquitylated membrane proteins, such as activated growth-factor receptors, are sorted into intraluminal vesicles and eventually end up in the lysosome lumen via multivesicular endosomes (MVEs). There are distinct mechanisms of clathrin-independent endocytosis (CIE) depending upon the cargo and the cell type. More...

HGS related BioCarta pathways (count: 0)

HGS related Reactome pathways (count: 2)

ID	Name	Description
Gene mapped Reactome pathways
REACT_12484	egfr downregulation	Regulation of receptor tyrosine kinase (RTK) activity is imp...... Regulation of receptor tyrosine kinase (RTK) activity is implicated in the control of almost all cellular functions. One of the best understood RTKs is epidermal growth factor receptor (EGFR). Growth factors can bind to EGFR and activate it to initiate signalling cascades within the cell. EGFRs can also be recruited to clathrin-coated pits which can be internalised into endocytic vesicles. From here, EGFRs can either be recycled back to the plasma membrane or directed to lysosomes for destruction.This provides a mechanism by which EGFR signalling is negatively regulated and controls the strength and duration of EGFR-induced signals. It also prevents EGFR hyperactivation as commonly seen in tumorigenesis. The proto-oncogene Cbl can negatively regulate EGFR signalling. The Cbl family of RING-type ubiquitin ligases are able to poly-ubiquitinate EGFR, an essential step in EGFR degradation. All Cbl proteins have a unique domain that recognises phosphorylated tyrosine residues on activated EGFRs. They also direct the ubiquitination and degradation of activated EGFRs by recruiting ubiquitin-conjugation enzymes. Cbl proteins function by specifically targeting activated EGFRs and mediating their down-regulation, thus providing a means by which signaling processes can be negatively regulated. Cbl also promotes receptor internalization via it's interaction with an adaptor protein, CIN85 (Cbl-interacting protein of 85kDa). CIN85 binds to Cbl via it's SH3 domain and is enhanced by the EGFR-induced tyrosine phosphorylation of Cbl. The proline-rich region of CIN85 interacts with endophilins which are regulatory components of clathrin-coated vesicles (CCVs). Endophilins bind to membranes and induce membrane curvature, in conjunction with other proteins involved in CCV formation. The rapid recruitment of endophilin to the activated receptor complex by CIN85 is the mechanism which controls receptor internalization. More...
REACT_9417	signaling by_egfr	The epidermal growth factor receptor (EGFR) is one member of...... The epidermal growth factor receptor (EGFR) is one member of the ErbB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands leads to autophosphorylation of tyrosine residues on the receptor and subsequent activation of signal transduction pathways that are involved in regulating cellular proliferation, differentiation, and survival. Ligand binding with EGFR results in receptor homo- or heterodimerization at the cell surface. Trans-autophosphorylation of the EGFR tyrosine kinase domains occurs and the phosphorylated tyrosine kinase residues serve as binding sites for the recruitment of signal transducers and activators of intracellular substrates, such as Ras, which then stimulate an intracellular signal transduction cascade. More...

HGS related interactors from protein-protein interaction data in HPRD (count: 49)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
HGS	UBB	No	in vitro	16429130
HGS	KRT18	No	yeast 2-hybrid	16189514
HGS	EGFR	No	in vitro	12953068
HGS	LYST	No	in vitro;yeast 2-hybrid	11984006
HGS	CCDC33	No	yeast 2-hybrid	16189514
HGS	SMAD2	No	in vitro;in vivo	11094085
HGS	PELP1	No	in vitro;in vivo;yeast 2-hybrid	16352611
HGS	UBA52	No	in vitro	11916981
HGS	LDOC1	No	yeast 2-hybrid	16189514
HGS	VPS37D	No	yeast 2-hybrid	15218037
HGS	PIK3R1	Yes	in vitro	10970851
HGS	UBC	No	in vitro	12207904
HGS	EXOC7	No	yeast 2-hybrid	16189514
HGS	TOM1L1	No	yeast 2-hybrid	15611048
HGS	UBQLN4	No	yeast 2-hybrid	16713569
HGS	DLG4	Yes	in vivo;yeast 2-hybrid	12151521
HGS	NEDD4	No	in vitro;in vivo	12230472
HGS	GFI1B	No	yeast 2-hybrid	16713569
HGS	UBQLN1	No	yeast 2-hybrid	16189514
HGS	NF2	No	in vitro;in vivo;yeast 2-hybrid	10861283 , 11285248
HGS	STAM	No	in vivo	9407053
HGS	HAP1	No	in vitro;in vivo;yeast 2-hybrid	12021262
HGS	CEP55	No	in vitro	17853893
HGS	VPS37C	No	in vitro;yeast 2-hybrid	15509564
HGS	USHBP1	No	yeast 2-hybrid	16189514
HGS	MET	No	in vivo	8380735
HGS	TADA2A	No	yeast 2-hybrid	16189514
HGS	MAP3K7	No	in vitro;in vivo	11397816
HGS	UBE2I	No	yeast 2-hybrid	16189514
HGS	NMI	No	yeast 2-hybrid	16189514
HGS	SNAP25	Yes	yeast 2-hybrid	10825299
HGS	TSG101	No	in vivo	12802020 , 12900395
HGS	SCAMP3	No	in vivo	19158374
HGS	EHMT2	Yes	yeast 2-hybrid	16189514
HGS	SNX1	No	in vivo	11110793
HGS	STAM2	No	yeast 2-hybrid	16189514
HGS	EPS15	No	in vitro;in vivo	10514494 , 12551915 , 10809762
HGS	MED7	No	yeast 2-hybrid	16189514
HGS	EXOC8	No	yeast 2-hybrid	16189514
HGS	GKAP1	No	yeast 2-hybrid	16189514
HGS	SMAD3	No	in vitro;in vivo	11094085
HGS	BEGAIN	No	yeast 2-hybrid	16189514
HGS	C1orf190	No	yeast 2-hybrid	16189514
HGS	KRT19	No	yeast 2-hybrid	16189514
HGS	DAZAP2	No	yeast 2-hybrid	16189514
HGS	MIF4GD	No	yeast 2-hybrid	16189514
HGS	PAK1	No	in vivo	11397816
HGS	CLTC	No	in vitro;yeast 2-hybrid	11532964
HGS	VPS37A	No	in vitro;in vivo;yeast 2-hybrid	15240819 , 15509564

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped Reactome pathways