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P04196 (HRG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histidine-rich glycoprotein
Alternative name(s):
Histidine-proline-rich glycoprotein
Short name=HPRG
Gene names
Name:HRG
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length525 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.23 Ref.25 Ref.26 Ref.27

Cofactor

Zinc. Ref.17

Subunit 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. Ref.8 Ref.9 Ref.12 Ref.14 Ref.18 Ref.19 Ref.24 Ref.26

Subcellular location

Secreted Ref.27.

Tissue specificity

Expressed in macrophages and in malignant cells. Expressed by the liver and secreted in plasma (at protein level). Ref.11 Ref.23 Ref.27

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. Ref.10

The cystatin domains can also bind heparan sulfate. Binding is enhanced in the presence of zinc ions. Ref.10

Post-translational modification

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. Ref.11 Ref.18 Ref.23

N-glycosylated. Ref.19

Involvement in disease

Thrombophilia due to histidine-rich glycoprotein deficiency (THPH11) [MIM:613116]: A hemostatic disorder characterized by a tendency to thrombosis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.28 Ref.29

Sequence similarities

Contains 2 cystatin domains.

Ontologies

Keywords
   Biological processAngiogenesis
Blood coagulation
Chemotaxis
Fibrinolysis
Hemostasis
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Thrombophilia
   DomainRepeat
Signal
   LigandCopper
Heparin-binding
Metal-binding
Zinc
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

blood coagulation

Traceable author statement. Source: Reactome

chemotaxis

Inferred from electronic annotation. Source: UniProtKB-KW

defense response to fungus

Inferred from direct assay PubMed 18797515. Source: UniProtKB

fibrinolysis

Traceable author statement. Source: Reactome

negative regulation of angiogenesis

Inferred from direct assay Ref.11Ref.17Ref.16Ref.23. Source: UniProtKB

negative regulation of blood vessel endothelial cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell adhesion

Inferred from direct assay Ref.11. Source: UniProtKB

negative regulation of cell adhesion mediated by integrin

Inferred from direct assay Ref.16. Source: UniProtKB

negative regulation of cell growth

Inferred from direct assay Ref.27. Source: UniProtKB

negative regulation of cell proliferation

Inferred from direct assay Ref.11. Source: UniProtKB

negative regulation of endothelial cell chemotaxis

Inferred from direct assay Ref.11Ref.17Ref.16. Source: UniProtKB

negative regulation of fibrinolysis

Inferred from electronic annotation. Source: Ensembl

negative regulation of lamellipodium assembly

Inferred from direct assay Ref.16. Source: UniProtKB

negative regulation of vascular endothelial growth factor signaling pathway

Inferred from direct assay Ref.16. Source: UniProtKB

platelet activation

Inferred from direct assay Ref.23. Source: UniProtKB

platelet degranulation

Traceable author statement. Source: Reactome

positive regulation of apoptotic process

Inferred from direct assay Ref.11. Source: UniProtKB

positive regulation of blood vessel remodeling

Inferred from direct assay Ref.27. Source: UniProtKB

positive regulation of focal adhesion assembly

Inferred from direct assay Ref.11Ref.17. Source: UniProtKB

positive regulation of immune response to tumor cell

Inferred from direct assay Ref.27. Source: UniProtKB

regulation of actin cytoskeleton organization

Inferred from direct assay Ref.16. Source: UniProtKB

regulation of blood coagulation

Inferred from direct assay Ref.26PubMed 6740558. Source: UniProtKB

regulation of gene expression

Inferred from direct assay Ref.27. Source: UniProtKB

regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.16. Source: UniProtKB

regulation of platelet activation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of protein complex assembly

Inferred from direct assay Ref.16. Source: UniProtKB

   Cellular_componentblood microparticle

Inferred from direct assay PubMed 22516433. Source: UniProt

extracellular region

Inferred from direct assay PubMed 18797515. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

plasma membrane

Traceable author statement. Source: Reactome

platelet alpha granule lumen

Traceable author statement. Source: Reactome

   Molecular_functioncysteine-type endopeptidase inhibitor activity

Inferred from electronic annotation. Source: InterPro

heme binding

Inferred from direct assay Ref.7. Source: UniProtKB

heparan sulfate proteoglycan binding

Inferred from direct assay Ref.13Ref.17. Source: UniProtKB

heparin binding

Inferred from direct assay Ref.17Ref.26. Source: UniProtKB

immunoglobulin binding

Inferred from direct assay Ref.8. Source: UniProtKB

metal ion binding

Inferred from direct assay Ref.7. Source: UniProtKB

receptor binding

Inferred from direct assay Ref.17. Source: UniProtKB

serine-type endopeptidase inhibitor activity

Inferred from electronic annotation. Source: Ensembl

zinc ion binding

Inferred from direct assay Ref.13Ref.17Ref.26. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RCHY1Q96PM53EBI-3915012,EBI-947779

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Ref.6
Chain19 – 525507Histidine-rich glycoprotein
PRO_0000006709

Regions

Domain19 – 136118Cystatin 1
Domain137 – 254118Cystatin 2
Region41 – 8444Interaction with ATP5A1
Region348 – 38235Necessary for endothelial cell focal adhesions and anti-angiogenic activities
Compositional bias276 – 32146Pro-rich
Compositional bias350 – 497148His/Pro-rich (HRR)

Sites

Site439 – 4402Cleavage; by plasmin By similarity

Amino acid modifications

Glycosylation631N-linked (GlcNAc...) Ref.15 Ref.19
Glycosylation1251N-linked (GlcNAc...) Ref.15 Ref.22
Glycosylation3441N-linked (GlcNAc...) Ref.15
Glycosylation3451N-linked (GlcNAc...) Potential
Disulfide bond24 ↔ 504 By similarity
Disulfide bond78 ↔ 89 By similarity
Disulfide bond105 ↔ 126 By similarity
Disulfide bond203 ↔ 417 By similarity
Disulfide bond218 ↔ 241 By similarity

Natural variations

Natural variant791S → L.
Corresponds to variant rs4516605 [ dbSNP | Ensembl ].
VAR_048856
Natural variant1031G → E in THPH11; HRG Tokushima 1; results in increased intracellular degradation and reduced protein secretion. Ref.28
VAR_063000
Natural variant1181D → G.
Corresponds to variant rs3733008 [ dbSNP | Ensembl ].
VAR_020488
Natural variant1801I → T.
Corresponds to variant rs10770 [ dbSNP | Ensembl ].
VAR_022080
Natural variant2041P → S.
Corresponds to variant rs9898 [ dbSNP | Ensembl ].
VAR_014528
Natural variant2411C → R in THPH11; HRG Tokushima 2; results in increased intracellular degradation and reduced protein secretion. Ref.29
VAR_063001
Natural variant3401H → R.
Corresponds to variant rs2228243 [ dbSNP | Ensembl ].
VAR_020489
Natural variant4361G → R.
Corresponds to variant rs2229331 [ dbSNP | Ensembl ].
VAR_024427
Natural variant4481R → C.
Corresponds to variant rs1042445 [ dbSNP | Ensembl ].
VAR_024428
Natural variant4931N → I.
Corresponds to variant rs1042464 [ dbSNP | Ensembl ].
VAR_024429

Sequences

Sequence LengthMass (Da)Tools
P04196 [UniParc].

Last modified March 20, 1987. Version 1.
Checksum: A2B124D6CE93114F

FASTA52559,578
        10         20         30         40         50         60 
MKALIAALLL ITLQYSCAVS PTDCSAVEPE AEKALDLINK RRRDGYLFQL LRIADAHLDR 

        70         80         90        100        110        120 
VENTTVYYLV LDVQESDCSV LSRKYWNDCE PPDSRRPSEI VIGQCKVIAT RHSHESQDLR 

       130        140        150        160        170        180 
VIDFNCTTSS VSSALANTKD SPVLIDFFED TERYRKQANK ALEKYKEEND DFASFRVDRI 

       190        200        210        220        230        240 
ERVARVRGGE GTGYFVDFSV RNCPRHHFPR HPNVFGFCRA DLFYDVEALD LESPKNLVIN 

       250        260        270        280        290        300 
CEVFDPQEHE NINGVPPHLG HPFHWGGHER SSTTKPPFKP HGSRDHHHPH KPHEHGPPPP 

       310        320        330        340        350        360 
PDERDHSHGP PLPQGPPPLL PMSCSSCQHA TFGTNGAQRH SHNNNSSDLH PHKHHSHEQH 

       370        380        390        400        410        420 
PHGHHPHAHH PHEHDTHRQH PHGHHPHGHH PHGHHPHGHH PHGHHPHCHD FQDYGPCDPP 

       430        440        450        460        470        480 
PHNQGHCCHG HGPPPGHLRR RGPGKGPRPF HCRQIGSVYR LPPLRKGEVL PLPEANFPSF 

       490        500        510        520 
PLPHHKHPLK PDNQPFPQSV SESCPGKFKS GFPQVSMFFT HTFPK 

« Hide

References

« Hide 'large scale' references
[1]"Amino acid sequence of human histidine-rich glycoprotein derived from the nucleotide sequence of its cDNA."
Koide T., Foster D.C., Yoshitake S., Davie E.W.
Biochemistry 25:2220-2225(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]Wakabayashi S., Takahashi K., Tokunaga F., Koide T.
Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[5]"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."
Hennis B.C., Frants R.R., Bakker E., Vossen R.H., van der Poort E.W., Blonden L.A., Cox S., Khan P.M., Spurr N.K., Kluft C.
Genomics 19:195-197(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 214-247.
[6]"Plasma protein map: an update by microsequencing."
Hughes G.J., Frutiger S., Paquet N., Ravier F., Pasquali C., Sanchez J.-C., James R., Tissot J.-D., Bjellqvist B., Hochstrasser D.F.
Electrophoresis 13:707-714(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 19-27.
Tissue: Plasma.
[7]"Human serum histidine-rich glycoprotein. I. Interactions with heme, metal ions and organic ligands."
Morgan W.T.
Biochim. Biophys. Acta 535:319-333(1978) [PubMed] [Europe PMC] [Abstract]
Cited for: HEME- AND METAL-BINDING.
[8]"Differential binding of histidine-rich glycoprotein (HRG) to human IgG subclasses and IgG molecules containing kappa and lambda light chains."
Gorgani N.N., Parish C.R., Altin J.G.
J. Biol. Chem. 274:29633-29640(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IMMUNOGLOBULIN G SUBCLASSES.
[9]"Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1."
Simantov R., Febbraio M., Crombie R., Asch A.S., Nachman R.L., Silverstein R.L.
J. Clin. Invest. 107:45-52(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH THBS1, FUNCTION.
[10]"Histidine-proline-rich glycoprotein has potent antiangiogenic activity mediated through the histidine-proline-rich domain."
Juarez J.C., Guan X., Shipulina N.V., Plunkett M.L., Parry G.C., Shaw D.E., Zhang J.C., Rabbani S.A., McCrae K.R., Mazar A.P., Morgan W.T., Donate F.
Cancer Res. 62:5344-5350(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF HIS/PRO-RICH DOMAIN.
[11]"A fragment of histidine-rich glycoprotein is a potent inhibitor of tumor vascularization."
Olsson A.K., Larsson H., Dixelius J., Johansson I., Lee C., Oellig C., Bjork I., Claesson-Welsh L.
Cancer Res. 64:599-605(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A NEGATIVE REGULATOR OF ANGIOGENESIS, PROTEOLYTIC PROCESSING, TISSUE SPECIFICITY.
[12]"Peptides derived from the histidine-proline domain of the histidine-proline-rich glycoprotein bind to tropomyosin and have antiangiogenic and antitumor activities."
Donate F., Juarez J.C., Guan X., Shipulina N.V., Plunkett M.L., Tel-Tsur Z., Shaw D.E., Morgan W.T., Mazar A.P.
Cancer Res. 64:5812-5817(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF THE HIS/PRO-RICH REGION, INTERACTION WITH TPM1.
[13]"Histidine-rich glycoprotein binds to cell-surface heparan sulfate via its N-terminal domain following Zn2+ chelation."
Jones A.L., Hulett M.D., Parish C.R.
J. Biol. Chem. 279:30114-30122(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: HEPARAN SULFATE-BINDING, METAL-BINDING.
[14]"Plasminogen is tethered with high affinity to the cell surface by the plasma protein, histidine-rich glycoprotein."
Jones A.L., Hulett M.D., Altin J.G., Hogg P., Parish C.R.
J. Biol. Chem. 279:38267-38276(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLG, FUNCTION.
[15]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-63; ASN-125 AND ASN-344.
Tissue: Plasma.
[16]"Minimal active domain and mechanism of action of the angiogenesis inhibitor histidine-rich glycoprotein."
Dixelius J., Olsson A.K., Thulin A., Lee C., Johansson I., Claesson-Welsh L.
Cancer Res. 66:2089-2097(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF THE HIS/PRO-RICH REGION AS A NEGATIVE REGULATOR OF ANGIOGENESIS.
[17]"The anti-angiogenic His/Pro-rich fragment of histidine-rich glycoprotein binds to endothelial cell heparan sulfate in a Zn2+-dependent manner."
Vanwildemeersch M., Olsson A.K., Gottfridsson E., Claesson-Welsh L., Lindahl U., Spillmann D.
J. Biol. Chem. 281:10298-10304(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF THE HIS/PRO-RICH REGION AS A NEGATIVE REGULATOR OF ANGIOGENESIS, COFACTOR, ZINC-BINDING, HEPARIN- AND HEPARAN SULFATE-BINDING.
[18]"Regulation of histidine-rich glycoprotein (HRG) function via plasmin-mediated proteolytic cleavage."
Poon I.K., Olsson A.K., Hulett M.D., Parish C.R.
Biochem. J. 424:27-37(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING, HEPARAN SULFATE-BINDING, INTERACTION WITH PLG, FUNCTION.
[19]"High affinity interaction between histidine-rich glycoprotein and the cell surface type ATP synthase on T-cells."
Ohta T., Ikemoto Y., Usami A., Koide T., Wakabayashi S.
Biochim. Biophys. Acta 1788:1099-1107(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATP5A1, FUNCTION, GLYCOSYLATION AT ASN-63, IDENTIFICATION BY MASS SPECTROMETRY.
[20]"Histidine-rich glycoprotein and concanavalin A synergistically stimulate the phosphatidylinositol 3-kinase-independent signaling pathway in leukocytes leading to increased cell adhesion and changes in cell morphology."
Ohta T., Ikemoto Y., Saeki K., Koide T., Wakabayashi S.
Cell. Immunol. 259:5-12(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[21]"Probing the Cu(2+) and Zn(2+) binding affinity of histidine-rich glycoprotein."
Jancso A., Kolozsi A., Gyurcsik B., Nagy N.V., Gajda T.
J. Inorg. Biochem. 103:1634-1643(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: METAL-BINDING.
[22]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-125.
Tissue: Liver.
[23]"Activated platelets provide a functional microenvironment for the antiangiogenic fragment of histidine-rich glycoprotein."
Thulin A., Ringvall M., Dimberg A., Karehed K., Vaisanen T., Vaisanen M.R., Hamad O., Wang J., Bjerkvig R., Nilsson B., Pihlajaniemi T., Akerud H., Pietras K., Jahnen-Dechent W., Siegbahn A., Olsson A.K.
Mol. Cancer Res. 7:1792-1802(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PROTEOLYTIC PROCESSING, IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY.
[24]"Histidine-rich glycoprotein binds heparanase and regulates its enzymatic activity and cell surface interactions."
Poon I.K., Yee D.Y., Jones A.L., Wood R.J., Davis D.S., Freeman C., Parish C.R., Hulett M.D.
Int. J. Biochem. Cell Biol. 42:1507-1516(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HPSE.
[25]"Histidine-rich glycoprotein functions cooperatively with cell surface heparan sulfate on phagocytes to promote necrotic cell uptake."
Poon I.K., Parish C.R., Hulett M.D.
J. Leukoc. Biol. 88:559-569(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, HEPARIN- AND HEPARAN SULFATE-BINDING.
[26]"Histidine-rich glycoprotein binds factor XIIa with high affinity and inhibits contact-initiated coagulation."
Macquarrie J.L., Stafford A.R., Yau J.W., Leslie B.A., Vu T.T., Fredenburgh J.C., Weitz J.I.
Blood 117:4134-4141(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH F12, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION.
[27]"HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF."
Rolny C., Mazzone M., Tugues S., Laoui D., Johansson I., Coulon C., Squadrito M.L., Segura I., Li X., Knevels E., Costa S., Vinckier S., Dresselaer T., Akerud P., De Mol M., Salomaki H., Phillipson M., Wyns S. expand/collapse author list , Larsson E., Buysschaert I., Botling J., Himmelreich U., Van Ginderachter J.A., De Palma M., Dewerchin M., Claesson-Welsh L., Carmeliet P.
Cancer Cell 19:31-44(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A TUMOR SUPPRESSOR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[28]"HRG Tokushima: molecular and cellular characterization of histidine-rich glycoprotein (HRG) deficiency."
Shigekiyo T., Yoshida H., Matsumoto K., Azuma H., Wakabayashi S., Saito S., Fujikawa K., Koide T.
Blood 91:128-133(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THPH11 GLU-103, CHARACTERIZATION OF VARIANT THPH11 GLU-103.
[29]"Histidine-rich glycoprotein (HRG) Tokushima 2: novel HRG deficiency, molecular and cellular characterization."
Shigekiyo T., Yoshida H., Kanagawa Y., Satoh K., Wakabayashi S., Matsumoto T., Koide T.
Thromb. Haemost. 84:675-679(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THPH11 ARG-241, CHARACTERIZATION OF VARIANT THPH11 ARG-241.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M13149 mRNA. Translation: AAA52694.1.
AB005803 Genomic DNA. Translation: BAA21613.1.
CH471052 Genomic DNA. Translation: EAW78183.1.
CH471052 Genomic DNA. Translation: EAW78184.1.
BC069574 mRNA. Translation: AAH69574.1.
BC150591 mRNA. Translation: AAI50592.1.
Z17218 Genomic DNA. Translation: CAA78925.1.
PIRKGHUGH. A01287.
RefSeqNP_000403.1. NM_000412.3.
UniGeneHs.1498.

3D structure databases

ProteinModelPortalP04196.
SMRP04196. Positions 22-76, 154-206.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109509. 8 interactions.
DIPDIP-47264N.
IntActP04196. 8 interactions.
STRING9606.ENSP00000232003.

Protein family/group databases

MEROPSI25.022.

PTM databases

PhosphoSiteP04196.

Polymorphism databases

DMDM123523.

2D gel databases

SWISS-2DPAGEP04196.

Proteomic databases

PaxDbP04196.
PeptideAtlasP04196.
PRIDEP04196.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000232003; ENSP00000232003; ENSG00000113905.
GeneID3273.
KEGGhsa:3273.
UCSCuc003fqq.3. human.

Organism-specific databases

CTD3273.
GeneCardsGC03P186378.
HGNCHGNC:5181. HRG.
HPAHPA050269.
HPA054598.
MIM142640. gene.
613116. phenotype.
neXtProtNX_P04196.
Orphanet217467. Hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency.
PharmGKBPA29455.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG75740.
HOGENOMHOG000090255.
HOVERGENHBG004597.
InParanoidP04196.
OMARTNYYVD.
OrthoDBEOG7HXCSK.
PhylomeDBP04196.
TreeFamTF333729.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.

Gene expression databases

BgeeP04196.
CleanExHS_HRG.
GenevestigatorP04196.

Family and domain databases

InterProIPR000010. Prot_inh_cystat.
[Graphical view]
PfamPF00031. Cystatin. 1 hit.
[Graphical view]
SMARTSM00043. CY. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHRG_(gene).
GenomeRNAi3273.
NextBio12999.
PROP04196.
SOURCESearch...

Entry information

Entry nameHRG_HUMAN
AccessionPrimary (citable) accession number: P04196
Secondary accession number(s): B9EK35, D3DNU7
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: March 20, 1987
Last modified: April 16, 2014
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM