Hrg histidine-rich glycoprotein [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Hrgprovided by MGI
Official Full Name: histidine-rich glycoproteinprovided by MGI
Primary source: MGI:MGI:2146636
See related: Ensembl:ENSMUSG00000022877 AllianceGenome:MGI:2146636
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: Hprg; Hrgp; D16jh2; D18020
Summary: Enables serine-type endopeptidase inhibitor activity. Involved in several processes, including negative regulation of blood vessel endothelial cell migration; positive regulation of blood vessel remodeling; and positive regulation of immune response to tumor cell. Acts upstream of or within several processes, including heme export; negative regulation of fibrinolysis; and regulation of transcription from RNA polymerase II promoter in response to iron. Located in endolysosome and phagolysosome membrane. Human ortholog(s) of this gene implicated in thrombophilia due to HRG deficiency and thrombosis. Orthologous to human HRG (histidine rich glycoprotein). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Restricted expression toward liver adult (RPKM 112.7) See more
Orthologs: human all
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Genomic context

Location:: 16 B1; 16 13.79 cM

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	16	NC_000082.7 (22769822..22780409)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	16	NC_000082.6 (22951072..22961659)

Chromosome 16 - NC_000082.7 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?

Histidine-rich glycoprotein in metabolic dysfunction-associated steatohepatitis-related disease progression and liver carcinogenesis.
Title: Histidine-rich glycoprotein in metabolic dysfunction-associated steatohepatitis-related disease progression and liver carcinogenesis.
Other HBPs such as alpha 2-HS glycoprotein (AHSG) and histidine-rich glycoprotein (HRG) need further investigation for potential applications in the management of Acute pancreatitis (AP) . Pancreas HBPs are extracellular and so easily accessible and are potential drug targets in AP, whereas plasma HBPs represent potential biomarkers for AP.
Title: The heparin-binding proteome in normal pancreas and murine experimental acute pancreatitis.
HRG binds to alpha2 integrin through low-affinity interactions in a heparin sulfate-independent manner, thereby blocking endothelial cells adhesion to collagen I.
Title: Histidine-rich glycoprotein blocks collagen-binding integrins and adhesion of endothelial cells through low-affinity interaction with α2 integrin.
Mice deficient in HRG have normal hemostasis, but demonstrate accelerated thrombosis via the contact system.
Title: Arterial thrombosis is accelerated in mice deficient in histidine-rich glycoprotein.
mononuclear phagocytes have specific binding sites for HRG and that these cells are essential for uptake of HRG from blood and distribution of HRG in tissues. Thus, inflammatory cells mediate the effect of HRG on tumor growth and metastatic spread.
Title: Histidine-rich glycoprotein uptake and turnover is mediated by mononuclear phagocytes.
Results show that HRG is a novel transcriptional target gene of FXR in human hepatoma cells, human upcyteVR primary hepatocytes and 3D human liver microtissues in vitro and in mouse liver in vivo.
Title: The nuclear bile acid receptor FXR controls the liver derived tumor suppressor histidine-rich glycoprotein.
HRG-deficiency promotes tumor progression via enhanced platelet activity. HRG is a potent tumor suppressor, with capacity to attenuate the angiogenic switch, tumor growth, EMT and subsequent metastatic spread, by regulating platelet activity.
Title: HRG regulates tumor progression, epithelial to mesenchymal transition and metastasis via platelet-induced signaling in the pre-tumorigenic microenvironment.
CD36-mediated anti-angiogenic activity has context-dependent role in the tumor microenvironment in the presence of TSP-1 while HRG modulates this activity.
Title: Context dependent role of the CD36--thrombospondin--histidine-rich glycoprotein axis in tumor angiogenesis and growth.
HRG loss influences macrophage gene regulation, leading to excessive stimulation of tumor angiogenesis, suppression of tumor immune response, and increased tumor growth and metastatic spread
Title: Genetic deficiency in plasma protein HRG enhances tumor growth and metastasis by exacerbating immune escape and vessel abnormalization.
the identification and characterization of a novel peptide, VTIP-peptide (VTIP-P), which binds and enhances the activation of CREM/CREB
Title: Identification and characterization of a novel peptide interacting with cAMP-responsive elements binding and cAMP-responsive elements modulator in mouse liver.

Submit: New GeneRIF Correction See all GeneRIFs (15)

Variation

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Alleles

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

Targeted (2) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI265597 (e-PCR)
- UniSTS:160542

D18020 (e-PCR)
- UniSTS:124761

D16Mit2 (e-PCR), detects polymorphism
- UniSTS:127835

AW413091 (e-PCR)
- UniSTS:180879

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables cysteine-type endopeptidase inhibitor activity	IEA Inferred from Electronic Annotation more info
enables heme binding	ISO Inferred from Sequence Orthology more info
enables heparan sulfate proteoglycan binding	ISO Inferred from Sequence Orthology more info
enables heparin binding	IBA Inferred from Biological aspect of Ancestor more info
enables heparin binding	ISO Inferred from Sequence Orthology more info
enables immunoglobulin binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase inhibitor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables signaling receptor binding	ISO Inferred from Sequence Orthology more info
enables zinc ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables zinc ion binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within blood coagulation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in cytolysis by host of symbiont cells	ISO Inferred from Sequence Orthology more info
involved_in defense response to fungus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to fungus	ISO Inferred from Sequence Orthology more info
acts_upstream_of fibrinolysis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within hemostasis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of angiogenesis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of blood vessel endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell adhesion	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell adhesion mediated by integrin	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell growth	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of endothelial cell chemotaxis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of fibrinolysis	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within negative regulation of fibrinolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of lamellipodium assembly	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of vascular endothelial growth factor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in platelet activation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of blood vessel remodeling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of blood vessel remodeling	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of focal adhesion assembly	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of immune response to tumor cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of immune response to tumor cell	ISO Inferred from Sequence Orthology more info
involved_in regulation of actin cytoskeleton organization	ISO Inferred from Sequence Orthology more info
involved_in regulation of blood coagulation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of blood coagulation	ISO Inferred from Sequence Orthology more info
involved_in regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in regulation of peptidyl-tyrosine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in regulation of platelet activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of platelet activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein-containing complex assembly	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in cell surface	ISO Inferred from Sequence Orthology more info
located_in collagen-containing extracellular matrix	HDA more info	PubMed
is_active_in extracellular region	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular region	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: histidine-rich glycoprotein

Names: histidine-proline-rich glycoprotein

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_053176.2 → NP_444406.2 histidine-rich glycoprotein precursor

See identical proteins and their annotated locations for NP_444406.2

Status: VALIDATED

Source sequence(s)

AI182388, AI196096, AI303163, CB593922, CB946752

Consensus CDS

CCDS49800.1

UniProtKB/Swiss-Prot

Q6YK32, Q6YKA2, Q99PS5, Q99PS6, Q9ESB3

UniProtKB/TrEMBL

A0A0R4J039

Related

ENSMUSP00000023590.9, ENSMUST00000023590.9

Conserved Domains (1) summary

cl09238
Location:30 → 131

CY; Cystatin-like domain; Cystatins are a family of cysteine protease inhibitors that occur mainly as single domain proteins. However some extracellular proteins such as kininogen, His-rich glycoprotein and fetuin also contain these domains.