InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: HRG

Summary

InnateDB Protein

IDBP-69041.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

HRG

Protein Name

histidine-rich glycoprotein

Synonyms

HPRG; HRGP; THPH11;

Species

Homo sapiens

Ensembl Protein

ENSP00000232003

InnateDB Gene

IDBG-69039 (HRG)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:11134179, ECO:0000269PubMed:12235005, ECO:0000269PubMed:14744774, ECO:0000269PubMed:15220341, ECO:0000269PubMed:15313924, ECO:0000269PubMed:16436387, ECO:0000269PubMed:16489009, ECO:0000269PubMed:19285951, ECO:0000269PubMed:19535045, ECO:0000269PubMed:19712047, ECO:0000269PubMed:19903770, ECO:0000269PubMed:20573803, ECO:0000269PubMed:21215706, ECO:0000269PubMed:21304106}.

Subcellular Localization

Secreted {ECO:0000269PubMed:21215706}.

Disease Associations

Thrombophilia due to histidine-rich glycoprotein deficiency (THPH11) [MIM:613116]: A hemostatic disorder characterized by a tendency to thrombosis. {ECO:0000269PubMed:11057869, ECO:0000269PubMed:9414276}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in macrophages and in malignant cells. Expressed by the liver and secreted in plasma (at protein level). {ECO:0000269PubMed:14744774, ECO:0000269PubMed:19903770, ECO:0000269PubMed:21215706}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 11 experimentally validated interaction(s) in this database.

Experimentally validated
Total	11 [view]
Protein-Protein	11 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004867	serine-type endopeptidase inhibitor activity
GO:0004869	cysteine-type endopeptidase inhibitor activity
GO:0005102	receptor binding
GO:0005515	protein binding
GO:0008201	heparin binding
GO:0008270	zinc ion binding
GO:0019865	immunoglobulin binding
GO:0020037	heme binding
GO:0043395	heparan sulfate proteoglycan binding
GO:0046872	metal ion binding

Biological Process

GO:0001525	angiogenesis
GO:0002576	platelet degranulation
GO:0002839	positive regulation of immune response to tumor cell
GO:0006935	chemotaxis
GO:0007162	negative regulation of cell adhesion
GO:0007596	blood coagulation
GO:0008285	negative regulation of cell proliferation
GO:0010468	regulation of gene expression
GO:0010543	regulation of platelet activation
GO:0010593	negative regulation of lamellipodium assembly
GO:0010951	negative regulation of endopeptidase activity
GO:0014070	response to organic cyclic compound
GO:0015886	heme transport
GO:0016525	negative regulation of angiogenesis
GO:0030168	platelet activation
GO:0030193	regulation of blood coagulation
GO:0030308	negative regulation of cell growth
GO:0032956	regulation of actin cytoskeleton organization
GO:0033629	negative regulation of cell adhesion mediated by integrin
GO:0034395	regulation of transcription from RNA polymerase II promoter in response to iron
GO:0042730	fibrinolysis
GO:0043065	positive regulation of apoptotic process
GO:0043254	regulation of protein complex assembly
GO:0043537	negative regulation of blood vessel endothelial cell migration
GO:0045087	innate immune response (InnateDB)
GO:0050730	regulation of peptidyl-tyrosine phosphorylation
GO:0050832	defense response to fungus
GO:0051894	positive regulation of focal adhesion assembly
GO:0051918	negative regulation of fibrinolysis
GO:0097037	heme export
GO:1900747	negative regulation of vascular endothelial growth factor signaling pathway
GO:2000504	positive regulation of blood vessel remodeling
GO:2001027	negative regulation of endothelial cell chemotaxis

Cellular Component

GO:0005576	extracellular region
GO:0005886	plasma membrane
GO:0031093	platelet alpha granule lumen
GO:0031982	vesicle
GO:0036019	endolysosome
GO:0061474	phagolysosome membrane
GO:0070062	extracellular vesicular exosome
GO:0072562	blood microparticle