Browse HRG

Summary
SymbolHRG
Namehistidine-rich glycoprotein
Aliases HRGP; HPRG; histidine-proline rich glycoprotein; thrombophilia due to elevated HRG; HPRGP; THPH11; histidine ......
Chromosomal Location3q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Secreted
Domain PF00031 Cystatin domain
Function

Plasma glycoprotein that binds a number of ligands such as heme, heparin, heparan sulfate, thrombospondin, plasminogen, and divalent metal ions. Binds heparin and heparin/glycosaminoglycans in a zinc-dependent manner. Binds heparan sulfate on the surface of liver, lung, kidney and heart endothelial cells. Binds to N-sulfated polysaccharide chains on the surface of liver endothelial cells. Inhibits rosette formation. Acts as an adapter protein and is implicated in regulating many processes such as immune complex and pathogen clearance, cell chemotaxis, cell adhesion, angiogenesis, coagulation and fibrinolysis. Mediates clearance of necrotic cells through enhancing the phagocytosis of necrotic cells in a heparan sulfate-dependent pathway. This process can be regulated by the presence of certain HRG ligands such as heparin and zinc ions. Binds to IgG subclasses of immunoglobins containing kappa and lambda light chains with different affinities regulating their clearance and inhibiting the formation of insoluble immune complexes. Tethers plasminogen to the cell surface. Binds T-cells and alters the cell morphology. Modulates angiogenesis by blocking the CD6-mediated antiangiongenic effect of thrombospondins, THBS1 and THBS2. Acts as a regulator of the vascular endothelial growth factor (VEGF) signaling pathway; inhibits endothelial cell motility by reducing VEGF-induced complex formation between PXN/paxillin and ILK/integrin-linked protein kinase and by promoting inhibition of VEGF-induced tyrosine phosphorylation of focal adhesion kinases and alpha-actinins in endothelial cells. Also plays a role in the regulation of tumor angiogenesis and tumor immune surveillance. Normalizes tumor vessels and promotes antitumor immunity by polarizing tumor-associated macrophages, leading to decreased tumor growth and metastasis.

> Gene Ontology
 
Biological Process GO:0001525 angiogenesis
GO:0001558 regulation of cell growth
GO:0001667 ameboidal-type cell migration
GO:0001952 regulation of cell-matrix adhesion
GO:0001954 positive regulation of cell-matrix adhesion
GO:0001974 blood vessel remodeling
GO:0002347 response to tumor cell
GO:0002418 immune response to tumor cell
GO:0002576 platelet degranulation
GO:0002831 regulation of response to biotic stimulus
GO:0002833 positive regulation of response to biotic stimulus
GO:0002834 regulation of response to tumor cell
GO:0002836 positive regulation of response to tumor cell
GO:0002837 regulation of immune response to tumor cell
GO:0002839 positive regulation of immune response to tumor cell
GO:0006887 exocytosis
GO:0007044 cell-substrate junction assembly
GO:0007045 cell-substrate adherens junction assembly
GO:0007160 cell-matrix adhesion
GO:0007162 negative regulation of cell adhesion
GO:0007596 blood coagulation
GO:0007599 hemostasis
GO:0009620 response to fungus
GO:0010466 negative regulation of peptidase activity
GO:0010543 regulation of platelet activation
GO:0010591 regulation of lamellipodium assembly
GO:0010593 negative regulation of lamellipodium assembly
GO:0010594 regulation of endothelial cell migration
GO:0010596 negative regulation of endothelial cell migration
GO:0010631 epithelial cell migration
GO:0010632 regulation of epithelial cell migration
GO:0010633 negative regulation of epithelial cell migration
GO:0010810 regulation of cell-substrate adhesion
GO:0010811 positive regulation of cell-substrate adhesion
GO:0010951 negative regulation of endopeptidase activity
GO:0015886 heme transport
GO:0016049 cell growth
GO:0016525 negative regulation of angiogenesis
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0030031 cell projection assembly
GO:0030032 lamellipodium assembly
GO:0030168 platelet activation
GO:0030193 regulation of blood coagulation
GO:0030194 positive regulation of blood coagulation
GO:0030195 negative regulation of blood coagulation
GO:0030308 negative regulation of cell growth
GO:0030336 negative regulation of cell migration
GO:0031345 negative regulation of cell projection organization
GO:0031589 cell-substrate adhesion
GO:0032102 negative regulation of response to external stimulus
GO:0032103 positive regulation of response to external stimulus
GO:0032956 regulation of actin cytoskeleton organization
GO:0032970 regulation of actin filament-based process
GO:0033627 cell adhesion mediated by integrin
GO:0033628 regulation of cell adhesion mediated by integrin
GO:0033629 negative regulation of cell adhesion mediated by integrin
GO:0034103 regulation of tissue remodeling
GO:0034105 positive regulation of tissue remodeling
GO:0034329 cell junction assembly
GO:0034330 cell junction organization
GO:0034332 adherens junction organization
GO:0034333 adherens junction assembly
GO:0035767 endothelial cell chemotaxis
GO:0035924 cellular response to vascular endothelial growth factor stimulus
GO:0038084 vascular endothelial growth factor signaling pathway
GO:0040013 negative regulation of locomotion
GO:0042730 fibrinolysis
GO:0043254 regulation of protein complex assembly
GO:0043534 blood vessel endothelial cell migration
GO:0043535 regulation of blood vessel endothelial cell migration
GO:0043537 negative regulation of blood vessel endothelial cell migration
GO:0043542 endothelial cell migration
GO:0044089 positive regulation of cellular component biogenesis
GO:0045055 regulated exocytosis
GO:0045216 cell-cell junction organization
GO:0045765 regulation of angiogenesis
GO:0045785 positive regulation of cell adhesion
GO:0045861 negative regulation of proteolysis
GO:0045926 negative regulation of growth
GO:0048041 focal adhesion assembly
GO:0048514 blood vessel morphogenesis
GO:0048771 tissue remodeling
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050817 coagulation
GO:0050818 regulation of coagulation
GO:0050819 negative regulation of coagulation
GO:0050820 positive regulation of coagulation
GO:0050832 defense response to fungus
GO:0050865 regulation of cell activation
GO:0050878 regulation of body fluid levels
GO:0050920 regulation of chemotaxis
GO:0050922 negative regulation of chemotaxis
GO:0051181 cofactor transport
GO:0051271 negative regulation of cellular component movement
GO:0051346 negative regulation of hydrolase activity
GO:0051493 regulation of cytoskeleton organization
GO:0051893 regulation of focal adhesion assembly
GO:0051894 positive regulation of focal adhesion assembly
GO:0051917 regulation of fibrinolysis
GO:0051918 negative regulation of fibrinolysis
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0060312 regulation of blood vessel remodeling
GO:0060326 cell chemotaxis
GO:0060491 regulation of cell projection assembly
GO:0061041 regulation of wound healing
GO:0061045 negative regulation of wound healing
GO:0090109 regulation of cell-substrate junction assembly
GO:0090130 tissue migration
GO:0090132 epithelium migration
GO:0090287 regulation of cellular response to growth factor stimulus
GO:0090288 negative regulation of cellular response to growth factor stimulus
GO:0090303 positive regulation of wound healing
GO:0097581 lamellipodium organization
GO:0098542 defense response to other organism
GO:1900046 regulation of hemostasis
GO:1900047 negative regulation of hemostasis
GO:1900048 positive regulation of hemostasis
GO:1900746 regulation of vascular endothelial growth factor signaling pathway
GO:1900747 negative regulation of vascular endothelial growth factor signaling pathway
GO:1901342 regulation of vasculature development
GO:1901343 negative regulation of vasculature development
GO:1901678 iron coordination entity transport
GO:1901888 regulation of cell junction assembly
GO:1901890 positive regulation of cell junction assembly
GO:1902547 regulation of cellular response to vascular endothelial growth factor stimulus
GO:1902548 negative regulation of cellular response to vascular endothelial growth factor stimulus
GO:1902743 regulation of lamellipodium organization
GO:1902744 negative regulation of lamellipodium organization
GO:1903034 regulation of response to wounding
GO:1903035 negative regulation of response to wounding
GO:1903036 positive regulation of response to wounding
GO:1903391 regulation of adherens junction organization
GO:1903393 positive regulation of adherens junction organization
GO:2000146 negative regulation of cell motility
GO:2000181 negative regulation of blood vessel morphogenesis
GO:2000504 positive regulation of blood vessel remodeling
GO:2001026 regulation of endothelial cell chemotaxis
GO:2001027 negative regulation of endothelial cell chemotaxis
Molecular Function GO:0001948 glycoprotein binding
GO:0004857 enzyme inhibitor activity
GO:0004866 endopeptidase inhibitor activity
GO:0004867 serine-type endopeptidase inhibitor activity
GO:0004869 cysteine-type endopeptidase inhibitor activity
GO:0005539 glycosaminoglycan binding
GO:0008201 heparin binding
GO:0019865 immunoglobulin binding
GO:0020037 heme binding
GO:0030414 peptidase inhibitor activity
GO:0043394 proteoglycan binding
GO:0043395 heparan sulfate proteoglycan binding
GO:0046906 tetrapyrrole binding
GO:0061134 peptidase regulator activity
GO:0061135 endopeptidase regulator activity
GO:1901681 sulfur compound binding
Cellular Component GO:0030141 secretory granule
GO:0031091 platelet alpha granule
GO:0031093 platelet alpha granule lumen
GO:0031983 vesicle lumen
GO:0034774 secretory granule lumen
GO:0036019 endolysosome
GO:0060205 cytoplasmic membrane-bounded vesicle lumen
GO:0072562 blood microparticle
GO:0099503 secretory vesicle
> KEGG and Reactome Pathway
 
KEGG -
Reactome R-HSA-75205: Dissolution of Fibrin Clot
R-HSA-109582: Hemostasis
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-114608: Platelet degranulation
R-HSA-76005: Response to elevated platelet cytosolic Ca2+
Summary
SymbolHRG
Namehistidine-rich glycoprotein
Aliases HRGP; HPRG; histidine-proline rich glycoprotein; thrombophilia due to elevated HRG; HPRGP; THPH11; histidine ......
Chromosomal Location3q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between HRG and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between HRG and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
22374984Fibrosarcoma; Pancreatic carcinomaPromote immunity (infiltration)Compared with wild-type mice, fibrosarcomas in hrg(-/-) mice were more hypoxic, necrotic, and less perfused, indicating enhanced vessel abnormalization. HRG deficiency was associated with a suppressed antitumor immune response, with both increased infiltration of M2 marker-expressing macrophages and decreased infiltration of dendritic cells and cytotoxic T cells.
Summary
SymbolHRG
Namehistidine-rich glycoprotein
Aliases HRGP; HPRG; histidine-proline rich glycoprotein; thrombophilia due to elevated HRG; HPRGP; THPH11; histidine ......
Chromosomal Location3q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of HRG in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolHRG
Namehistidine-rich glycoprotein
Aliases HRGP; HPRG; histidine-proline rich glycoprotein; thrombophilia due to elevated HRG; HPRGP; THPH11; histidine ......
Chromosomal Location3q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of HRG in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14121.0680.186
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.0070.996
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)871.8750.0897
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.2160.736
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.4060.771
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.0270.987
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.9280.399
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.7240.715
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.8230.658
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.2530.887
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.8930.398
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2720.482
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of HRG in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 414250250.222
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.74.1-0.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.75.1-1.41
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.509.50.492
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86250250.473
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.33.71.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22139.109.10.519
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolHRG
Namehistidine-rich glycoprotein
Aliases HRGP; HPRG; histidine-proline rich glycoprotein; thrombophilia due to elevated HRG; HPRGP; THPH11; histidine ......
Chromosomal Location3q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HRG. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolHRG
Namehistidine-rich glycoprotein
Aliases HRGP; HPRG; histidine-proline rich glycoprotein; thrombophilia due to elevated HRG; HPRGP; THPH11; histidine ......
Chromosomal Location3q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HRG. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HRG.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolHRG
Namehistidine-rich glycoprotein
Aliases HRGP; HPRG; histidine-proline rich glycoprotein; thrombophilia due to elevated HRG; HPRGP; THPH11; histidine ......
Chromosomal Location3q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HRG. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolHRG
Namehistidine-rich glycoprotein
Aliases HRGP; HPRG; histidine-proline rich glycoprotein; thrombophilia due to elevated HRG; HPRGP; THPH11; histidine ......
Chromosomal Location3q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of HRG expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolHRG
Namehistidine-rich glycoprotein
Aliases HRGP; HPRG; histidine-proline rich glycoprotein; thrombophilia due to elevated HRG; HPRGP; THPH11; histidine ......
Chromosomal Location3q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between HRG and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolHRG
Namehistidine-rich glycoprotein
Aliases HRGP; HPRG; histidine-proline rich glycoprotein; thrombophilia due to elevated HRG; HPRGP; THPH11; histidine ......
Chromosomal Location3q27
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting HRG collected from DrugBank database.
> Drugs from DrugBank database
 

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