Hgs HGF-regulated tyrosine kinase substrate [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Hgsprovided by MGI
Official Full Name: HGF-regulated tyrosine kinase substrateprovided by MGI
Primary source: MGI:MGI:104681
See related: Ensembl:ENSMUSG00000025793 AllianceGenome:MGI:104681
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: tn; Hgr; Hrs; ZFYVE8
Summary: Enables identical protein binding activity and ubiquitin-dependent protein binding activity. Predicted to be involved in several processes, including lysosomal transport; negative regulation of signal transduction; and positive regulation of exosomal secretion. Predicted to act upstream of or within protein transport. Located in cytoplasm. Is expressed in several structures, including central nervous system; genitourinary system; olfactory epithelium; retina layer; and spleen. Orthologous to human HGS (hepatocyte growth factor-regulated tyrosine kinase substrate). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in testis adult (RPKM 102.6), adrenal adult (RPKM 78.0) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 11 E2; 11 84.16 cM

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	11	NC_000077.7 (120358431..120374810)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	11	NC_000077.6 (120467605..120483984)

Chromosome 11 - NC_000077.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability.
Title: Hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability.
The knockdown of Syk and Hrs enhances TLR3-mediated antiviral response in the form of IFN-beta, IL-6, and CXCL8 secretion.
Title: Syk and Hrs Regulate TLR3-Mediated Antiviral Response in Murine Astrocytes.
Findings find that Hrs is indispensable for the autophagic clearance of neurodegeneration-related proteins and for the survival of hippocampal neurons in mammals. In particular, the work provides the novel insight that the loss of Hrs results in insufficient autophagic clearance and enhanced ER stress, thereby triggering JNK activation and subsequent apoptotic and necroptotic neuronal cell death.
Title: ESCRT-0 dysfunction compromises autophagic degradation of protein aggregates and facilitates ER stress-mediated neurodegeneration via apoptotic and necroptotic pathways.
HGS expression in the nervous system is developmentally regulated.HGS is required for motor neuron function.
Title: Motor and Sensory Deficits in the teetering Mice Result from Mutation of the ESCRT Component HGS.
Smooth Muscle Hgs Deficiency Leads to Impaired Esophageal Motility.
Title: Smooth Muscle Hgs Deficiency Leads to Impaired Esophageal Motility.
ESCRT-0 protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is targeted to endosomes independently of signal-transducing adaptor molecule (STAM) and the complex formation with STAM promotes its endosomal dissociation.
Title: ESCRT-0 protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is targeted to endosomes independently of signal-transducing adaptor molecule (STAM) and the complex formation with STAM promotes its endosomal dissociation.
These results indicate that Hrs plays important roles during peripheral development and physiological functions of B lymphocytes.
Title: Hepatocyte growth factor regulated tyrosine kinase substrate in the peripheral development and function of B-cells.
A new mechanism to modify BMP signaling by Hgs during early mouse development.
Title: Hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs) is involved in BMP signaling through phosphorylation of SMADS and TAK1 in early mouse embryo.
Hrs is a master molecule that controls in part the degradation of STAM1 and the accumulation of ubiquitinated proteins
Title: Hrs, a mammalian master molecule in vesicular transport and protein sorting, suppresses the degradation of ESCRT proteins signal transducing adaptor molecule 1 and 2.
Data suggest that Hrs regulates the KGFR degradative pathway, but not its juxtanuclear recycling transport, and that Hrs recruitment to the receptor, but not its ligand-induced phosphorylation, could be required for its function.
Title: Hrs regulates the endocytic sorting of the fibroblast growth factor receptor 2b.

Submit: New GeneRIF Correction See all GeneRIFs (21)

Phenotypes

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Associated conditions

Description	Tests
teetering GeneReviews: Not available

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Spontaneous (1)
Transgenic (1)
Targeted (7) 1 citation
Endonuclease-mediated (3)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC102191P1 (e-PCR)
- UniSTS:270086

PMC316760P1 (e-PCR)
- UniSTS:273044

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin-like protein ligase binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin-modified protein reader activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in endocytic recycling	IBA Inferred from Biological aspect of Ancestor more info
involved_in endosome to lysosome transport	ISO Inferred from Sequence Orthology more info
involved_in membrane invagination	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of angiogenesis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of platelet-derived growth factor receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of receptor signaling pathway via JAK-STAT	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of vascular endothelial growth factor receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of exosomal secretion	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in protein localization to membrane	ISO Inferred from Sequence Orthology more info
involved_in protein targeting to lysosome	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein transport	IEA Inferred from Electronic Annotation more info
involved_in receptor internalization	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of MAP kinase activity	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
part_of ESCRT-0 complex	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	ISO Inferred from Sequence Orthology more info
is_active_in early endosome	IBA Inferred from Biological aspect of Ancestor more info
located_in early endosome	ISO Inferred from Sequence Orthology more info
located_in endosome	ISO Inferred from Sequence Orthology more info
located_in lysosome	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in secretory granule	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: hepatocyte growth factor-regulated tyrosine kinase substrate

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001159328.1 → NP_001152800.1 hepatocyte growth factor-regulated tyrosine kinase substrate isoform 1

See identical proteins and their annotated locations for NP_001152800.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AK046299, AK145031, BY315543, CJ294093

Consensus CDS

CCDS49005.1

UniProtKB/TrEMBL

B1ATZ1, Q3TLL4, Q3UMA3

Related

ENSMUSP00000101809.3, ENSMUST00000106203.9

Conserved Domains (6) summary

cd03569
Location:4 → 145

VHS_Hrs_Vps27p; VHS domain family, Hrs and Vps27p subfamily; composed of Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and its yeast homolog Vps27p (vacuolar protein sorting). The VHS domain, an essential part of Hrs/Vps27p, has a superhelical ...

cd15720
Location:159 → 219

FYVE_Hrs; FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins

pfam07223
Location:518 → 736

DUF1421; Protein of unknown function (DUF1421)

pfam12210
Location:406 → 500

Hrs_helical; Hepatocyte growth factor-regulated tyrosine kinase substrate

cd16269
Location:530 → 541

GBP_C; coiled coil [structural motif]

cl20817
Location:485 → 559

GBP_C; Guanylate-binding protein, C-terminal domain
NM_008244.3 → NP_032270.3 hepatocyte growth factor-regulated tyrosine kinase substrate isoform 2

See identical proteins and their annotated locations for NP_032270.3

Status: VALIDATED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site, compared to variant 1. This difference results in a protein (isoform 2) that is one amino acid shorter than isoform 1.

Source sequence(s)

AK046299, AK145031, BY315543, CJ294093

Consensus CDS

CCDS88297.1

UniProtKB/Swiss-Prot

Q61691, Q8BQW3, Q99LI8

UniProtKB/TrEMBL

Q3TLL4

Related

ENSMUSP00000101811.3, ENSMUST00000106205.9

Conserved Domains (6) summary

cd03569
Location:4 → 145

VHS_Hrs_Vps27p; VHS domain family, Hrs and Vps27p subfamily; composed of Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and its yeast homolog Vps27p (vacuolar protein sorting). The VHS domain, an essential part of Hrs/Vps27p, has a superhelical ...

cd15720
Location:159 → 219

FYVE_Hrs; FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins

pfam07223
Location:517 → 735

DUF1421; Protein of unknown function (DUF1421)

pfam12210
Location:405 → 499

Hrs_helical; Hepatocyte growth factor-regulated tyrosine kinase substrate

cd16269
Location:529 → 540

GBP_C; coiled coil [structural motif]

cl20817
Location:484 → 558

GBP_C; Guanylate-binding protein, C-terminal domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000077.7 Reference GRCm39 C57BL/6J

Range

120358431..120374810

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006532270.3 → XP_006532333.2 hepatocyte growth factor-regulated tyrosine kinase substrate isoform X1

UniProtKB/TrEMBL

Q3TLL4

Conserved Domains (6) summary

TIGR03185
Location:205 → 544

DNA_S_dndD; DNA sulfur modification protein DndD

cd15720
Location:159 → 219

FYVE_Hrs; FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins

cd03569
Location:6 → 143

VHS_Hrs; VHS (Vps27/Hrs/STAM) domain of Hepatocyte growth factor-regulated tyrosine kinase substrate, Hrs

pfam05672
Location:498 → 565

MAP7; MAP7 (E-MAP-115) family

pfam09770
Location:545 → 699

PAT1; Topoisomerase II-associated protein PAT1

pfam12210
Location:413 → 507

Hrs_helical; Hepatocyte growth factor-regulated tyrosine kinase substrate
XM_006532274.4 → XP_006532337.2 hepatocyte growth factor-regulated tyrosine kinase substrate isoform X5

UniProtKB/TrEMBL

Q3TLL4

Conserved Domains (6) summary

TIGR03185
Location:205 → 544

DNA_S_dndD; DNA sulfur modification protein DndD

cd15720
Location:159 → 219

FYVE_Hrs; FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins

cd03569
Location:6 → 143

VHS_Hrs; VHS (Vps27/Hrs/STAM) domain of Hepatocyte growth factor-regulated tyrosine kinase substrate, Hrs

pfam05672
Location:498 → 565

MAP7; MAP7 (E-MAP-115) family

pfam09770
Location:545 → 699

PAT1; Topoisomerase II-associated protein PAT1

pfam12210
Location:413 → 507

Hrs_helical; Hepatocyte growth factor-regulated tyrosine kinase substrate
XM_006532271.3 → XP_006532334.2 hepatocyte growth factor-regulated tyrosine kinase substrate isoform X2

UniProtKB/TrEMBL

Q3TLL4

Conserved Domains (6) summary

TIGR03185
Location:205 → 543

DNA_S_dndD; DNA sulfur modification protein DndD

cd15720
Location:159 → 219

FYVE_Hrs; FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins

cd03569
Location:6 → 143

VHS_Hrs; VHS (Vps27/Hrs/STAM) domain of Hepatocyte growth factor-regulated tyrosine kinase substrate, Hrs

pfam05672
Location:497 → 564

MAP7; MAP7 (E-MAP-115) family

pfam09770
Location:544 → 698

PAT1; Topoisomerase II-associated protein PAT1

pfam12210
Location:412 → 506

Hrs_helical; Hepatocyte growth factor-regulated tyrosine kinase substrate
XM_006532272.3 → XP_006532335.2 hepatocyte growth factor-regulated tyrosine kinase substrate isoform X3

UniProtKB/TrEMBL

Q3TLL4

Conserved Domains (6) summary

TIGR03185
Location:205 → 537

DNA_S_dndD; DNA sulfur modification protein DndD

cd15720
Location:159 → 219

FYVE_Hrs; FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins

cd03569
Location:6 → 143

VHS_Hrs; VHS (Vps27/Hrs/STAM) domain of Hepatocyte growth factor-regulated tyrosine kinase substrate, Hrs

pfam05672
Location:491 → 558

MAP7; MAP7 (E-MAP-115) family

pfam09770
Location:538 → 692

PAT1; Topoisomerase II-associated protein PAT1

pfam12210
Location:406 → 500

Hrs_helical; Hepatocyte growth factor-regulated tyrosine kinase substrate
XM_006532273.3 → XP_006532336.2 hepatocyte growth factor-regulated tyrosine kinase substrate isoform X4

UniProtKB/TrEMBL

Q3TLL4

Conserved Domains (6) summary

TIGR03185
Location:205 → 536

DNA_S_dndD; DNA sulfur modification protein DndD

cd15720
Location:159 → 219

FYVE_Hrs; FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins

cd03569
Location:6 → 143

VHS_Hrs; VHS (Vps27/Hrs/STAM) domain of Hepatocyte growth factor-regulated tyrosine kinase substrate, Hrs

pfam05672
Location:490 → 557

MAP7; MAP7 (E-MAP-115) family

pfam09770
Location:537 → 691

PAT1; Topoisomerase II-associated protein PAT1

pfam12210
Location:405 → 499

Hrs_helical; Hepatocyte growth factor-regulated tyrosine kinase substrate
XM_030245590.1 → XP_030101450.1 hepatocyte growth factor-regulated tyrosine kinase substrate isoform X6

UniProtKB/TrEMBL

Q3TLL4

Conserved Domains (6) summary

TIGR03185
Location:207 → 546

DNA_S_dndD; DNA sulfur modification protein DndD

cd15720
Location:161 → 221

FYVE_Hrs; FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins

cd03569
Location:15 → 145

VHS_Hrs; VHS (Vps27/Hrs/STAM) domain of Hepatocyte growth factor-regulated tyrosine kinase substrate, Hrs

pfam05672
Location:500 → 567

MAP7; MAP7 (E-MAP-115) family

pfam09770
Location:547 → 701

PAT1; Topoisomerase II-associated protein PAT1

pfam12210
Location:415 → 509

Hrs_helical; Hepatocyte growth factor-regulated tyrosine kinase substrate