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Aliases for HRG Gene

Aliases for HRG Gene

  • Histidine-Rich Glycoprotein 2 3
  • Histidine-Proline-Rich Glycoprotein 3 4
  • THPH11 3 6
  • HPRG 3 4
  • Histidine-Proline Rich Glycoprotein 2
  • Thrombophilia Due To Elevated HRG 2
  • HRGP 3

External Ids for HRG Gene

Previous GeneCards Identifiers for HRG Gene

  • GC03P183155
  • GC03P187640
  • GC03P187785
  • GC03P187704
  • GC03P187866
  • GC03P186378
  • GC03P183793

Summaries for HRG Gene

Entrez Gene Summary for HRG Gene

  • This histidine-rich glycoprotein contains two cystatin-like domains and is located in plasma and platelets. The physiological function has not been determined but it is known that the protein binds heme, dyes and divalent metal ions. The encoded protein also has a peptide that displays antimicrobial activity against C. albicans, E. coli, S. aureus, P. aeruginosa, and E. faecalis. It can inhibit rosette formation and interacts with heparin, thrombospondin and plasminogen. Two of the protein's effects, the inhibition of fibrinolysis and the reduction of inhibition of coagulation, indicate a potential prothrombotic effect. Mutations in this gene lead to thrombophilia due to abnormal histidine-rich glycoprotein levels. [provided by RefSeq, Nov 2014]

GeneCards Summary for HRG Gene

HRG (Histidine-Rich Glycoprotein) is a Protein Coding gene. Diseases associated with HRG include thrombophilia due to hrg deficiency and hereditary thrombophilia due to congenital histidine-rich glycoprotein deficiency. Among its related pathways are Hemostasis and Hemostasis. GO annotations related to this gene include heparin binding and serine-type endopeptidase inhibitor activity.

UniProtKB/Swiss-Prot for HRG Gene

  • 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 Wiki entry for HRG Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HRG Gene

Genomics for HRG Gene

Regulatory Elements for HRG Gene

Genomic Location for HRG Gene

Start:
186,660,216 bp from pter
End:
186,678,240 bp from pter
Size:
18,025 bases
Orientation:
Plus strand

Genomic View for HRG Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for HRG Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HRG Gene

Proteins for HRG Gene

  • Protein details for HRG Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P04196-HRG_HUMAN
    Recommended name:
    Histidine-rich glycoprotein
    Protein Accession:
    P04196
    Secondary Accessions:
    • B9EK35
    • D3DNU7

    Protein attributes for HRG Gene

    Size:
    525 amino acids
    Molecular mass:
    59578 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Interacts (via the HRR domain) with TPM1; the interaction appears to contribute to the antiangiogenic properties of the HRR domain. Interacts with THBS2; the interaction blocks the antiangiogenic effect of THBS2 with CD36 (By similarity). Interacts with THBS1 (via the TSP type I repeats); the interaction blocks the antiangiogenic effect of THBS1 with CD3. Interacts with PLG (via its Kringle domains); the interaction tethers PLG to the cell surface and enhances its activation. Interacts with HPSE; the interaction is enhanced at acidic pH, partially inhibits binding of HPSE to cell surface receptors and modulates its enzymatic activity. Interacts (via the HRR domain) with TMP1; the interaction partially mediates the antiangiogenic properties of HRG. Interacts with kappa and lambda light chains of IgG molecules. Interacts with ATP5A1; the interaction occurs on the surface of T-cells and alters their cell morphology in concert with CONA. Binds IgG molecules containing kappa and lambda light chains and inhibits the formation of insoluble immunoglobulin complexes. Interacts with F12; the interaction, which is enhanced in the presence of zinc ions and inhibited by heparin-binding to HRG, inhibits factor XII autoactivation and contact-initiated coagulation.

neXtProt entry for HRG Gene

Proteomics data for HRG Gene at MOPED

Post-translational modifications for HRG Gene

  • N-glycosylated.
  • Proteolytic cleavage produces several HRG fragments which are mostly disulfide-linked and, therefore, not released. Cleavage by plasmin is inhibited in the presence of heparin, zinc ions or in an acidic environment. Cleavage reduces binding of HRG to heparan sulfate, but enhances the ability of HRG to bind and tether plasminogen to the cell surface. On platelet activation, releases a 33 kDa antiangiogenic peptide which encompasses the HRR. Also cleaved in the C-terminal by plasmin.
  • Glycosylation at Asn63, Asn125, Asn344, and Asn345
  • Modification sites at PhosphoSitePlus

Other Protein References for HRG Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for HRG Gene

Domains for HRG Gene

Protein Domains for HRG Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for HRG Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P04196

UniProtKB/Swiss-Prot:

HRG_HUMAN :
  • P04196
Domain:
  • The His/Pro-rich (HRR) region contains approximately 12 tandem internal repeats of the 5-residue G[H/P][H/P]PH consensus sequence. HRR binds heparan sulfate and possesses antiangiogenic, antibacterial and antifungal properties through binding Candida cells, and preferentially lysing the ergosterol-containing liposomes at low pH. The tandem repeats also bind divalent metal ions and heme
  • The cystatin domains can also bind heparan sulfate. Binding is enhanced in the presence of zinc ions
  • Contains 2 cystatin domains.
genes like me logo Genes that share domains with HRG: view

No data available for Gene Families for HRG Gene

Function for HRG Gene

Molecular function for HRG Gene

GENATLAS Biochemistry:
histidine-rich glycoprotein (plasma),binding plasminogen and heparin,cystatin (cysteine proteinase inhibitor) superfamily,interacting with plasma proteins involved in blood coagulation and fibronolysis
UniProtKB/Swiss-Prot 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 (GO) - Molecular Function for HRG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004867 serine-type endopeptidase inhibitor activity IEA --
GO:0004869 cysteine-type endopeptidase inhibitor activity IEA --
GO:0005102 receptor binding IDA 16436387
GO:0005515 protein binding IPI 11134179
GO:0008201 heparin binding IDA 16436387
genes like me logo Genes that share ontologies with HRG: view

Phenotypes for HRG Gene

genes like me logo Genes that share phenotypes with HRG: view

Animal Models for HRG Gene

MGI Knock Outs for HRG:

Animal Model Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for HRG

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targeting and HOMER Transcription for HRG Gene

Localization for HRG Gene

Subcellular locations from UniProtKB/Swiss-Prot for HRG Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for HRG Gene COMPARTMENTS Subcellular localization image for HRG gene
Compartment Confidence
extracellular 5
plasma membrane 4

Gene Ontology (GO) - Cellular Components for HRG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005886 plasma membrane TAS --
GO:0031093 platelet alpha granule lumen TAS --
GO:0031982 vesicle --
GO:0036019 endolysosome IEA --
genes like me logo Genes that share ontologies with HRG: view

Pathways for HRG Gene

genes like me logo Genes that share pathways with HRG: view

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

Gene Ontology (GO) - Biological Process for HRG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis IEA --
GO:0002576 platelet degranulation TAS --
GO:0002839 positive regulation of immune response to tumor cell IDA 21215706
GO:0006935 chemotaxis IEA --
GO:0007162 negative regulation of cell adhesion IDA 14744774
genes like me logo Genes that share ontologies with HRG: view

Compounds for HRG Gene

(1) HMDB Compounds for HRG Gene

Compound Synonyms Cas Number PubMed IDs
Heme
  • (protoporphyrinato)iron
14875-96-8

(22) Novoseek inferred chemical compound relationships for HRG Gene

Compound -log(P) Hits PubMed IDs
kininogen 78.1 11
heparin 60 61
fibrinogen 58.6 19
heparan sulfate 54.5 11
dermatan sulfate 52.2 7
genes like me logo Genes that share compounds with HRG: view

Transcripts for HRG Gene

mRNA/cDNA for HRG Gene

Unigene Clusters for HRG Gene

Histidine-rich glycoprotein:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for HRG

Primer Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for HRG Gene

No ASD Table

Relevant External Links for HRG Gene

GeneLoc Exon Structure for
HRG
ECgene alternative splicing isoforms for
HRG

Expression for HRG Gene

mRNA expression in normal human tissues for HRG Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HRG Gene

This gene is overexpressed in Liver (52.5).

Protein differential expression in normal tissues for HRG Gene

This gene is overexpressed in Synovial fluid (15.9), Serum (15.7), Plasma (15.1), and Monocytes (8.2).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for HRG Gene

SOURCE GeneReport for Unigene cluster for HRG Gene Hs.1498

mRNA Expression by UniProt/SwissProt for HRG Gene

P04196-HRG_HUMAN
Tissue specificity: Expressed in macrophages and in malignant cells. Expressed by the liver and secreted in plasma (at protein level).
genes like me logo Genes that share expressions with HRG: view

Expression partners for HRG Gene

In Situ Assay Products

Orthologs for HRG Gene

This gene was present in the common ancestor of chordates.

Orthologs for HRG Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia HRG 35
  • 78.73 (n)
  • 65.71 (a)
HRG 36
  • 64 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia HRG 35
  • 98.67 (n)
  • 96.76 (a)
HRG 36
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Hrg 16
Hrg 36
  • 60 (a)
OneToOne
dog
(Canis familiaris)
Mammalia HRG 36
  • 58 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia HRG 36
  • 41 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia HRG 36
  • 39 (a)
OneToOne
chicken
(Gallus gallus)
Aves HRG 36
  • 32 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia HRG 36
  • 30 (a)
OneToOne
Species with no ortholog for HRG:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for HRG Gene

ENSEMBL:
Gene Tree for HRG (if available)
TreeFam:
Gene Tree for HRG (if available)

Paralogs for HRG Gene

Selected SIMAP similar genes for HRG Gene using alignment to 1 proteins:

Pseudogenes.org Pseudogenes for HRG Gene

genes like me logo Genes that share paralogs with HRG: view

No data available for Paralogs for HRG Gene

Variants for HRG Gene

Sequence variations from dbSNP and Humsavar for HRG Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type MAF
rs9898 - 186,672,838(+) ACTGC(C/T)CCAGA reference, missense
rs10770 - 186,671,770(+) CCGAA(C/T)CGAGA missense, reference
rs1042445 - 186,677,647(+) GACCC(C/T)GTCCC reference, missense
rs1042464 - 186,677,783(+) AGACA(A/T)TCAGC reference, missense
rs1126720 -- 186,666,148(+) ATCAA(C/T)AAAAG synonymous-codon, reference

Structural Variations from Database of Genomic Variants (DGV) for HRG Gene

Variant ID Type Subtype PubMed ID
nsv508974 CNV Insertion 20534489
dgv1541e1 CNV Complex 17122850
nsv878068 CNV Gain 21882294
essv25049 CNV CNV 17122850
nsv436928 CNV Loss 16327808
esv29238 CNV Loss 19812545
nsv516553 CNV Loss 19592680
nsv818196 CNV Loss 17921354
essv23735 CNV CNV 17122850
nsv437901 CNV Loss 16468122

Relevant External Links for HRG Gene

HapMap Linkage Disequilibrium report
HRG
Human Gene Mutation Database (HGMD)
HRG

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HRG Gene

Disorders for HRG Gene

(1) OMIM Diseases for HRG Gene (142640)

UniProtKB/Swiss-Prot

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

(13) Novoseek inferred disease relationships for HRG Gene

Disease -log(P) Hits PubMed IDs
thrombophilia 51.4 6
protein c deficiency 49.5 1
corneal neovascularization 41.1 1
thrombosis 24.6 6
hyperhomocysteinemia 17 1

Genatlas disease for HRG Gene

thrombophilia,with low histidine-rich glycoprotein level

Relevant External Links for HRG

Genetic Association Database (GAD)
HRG
Human Genome Epidemiology (HuGE) Navigator
HRG
genes like me logo Genes that share disorders with HRG: view

No data available for University of Copenhagen DISEASES for HRG Gene

Publications for HRG Gene

  1. Evidence for the absence of intron H of the histidine-rich glycoprotein (HRG) gene: genetic mapping and in situ localization of HRG to chromosome 3q28-q29. (PMID: 8188234) Hennis B.C. … Kluft C. (Genomics 1994) 3 4 23
  2. HRG Tokushima: molecular and cellular characterization of histidine- rich glycoprotein (HRG) deficiency. (PMID: 9414276) Shigekiyo T. … Koide T. (Blood 1998) 3 4 23
  3. Differential binding of histidine-rich glycoprotein (HRG) to human IgG subclasses and IgG molecules containing kappa and lambda light chains. (PMID: 10514432) Gorgani N.N. … Altin J.G. (J. Biol. Chem. 1999) 3 4 23
  4. Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1. (PMID: 11134179) Simantov R. … Silverstein R.L. (J. Clin. Invest. 2001) 3 4 23
  5. The anti-angiogenic His/Pro-rich fragment of histidine-rich glycoprotein binds to endothelial cell heparan sulfate in a Zn2+- dependent manner. (PMID: 16436387) Vanwildemeersch M. … Spillmann D. (J. Biol. Chem. 2006) 3 4 23

Products for HRG Gene

Sources for HRG Gene

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