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P04196

- HRG_HUMAN

UniProt

P04196 - HRG_HUMAN

Protein

Histidine-rich glycoprotein

Gene

HRG

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 153 (01 Oct 2014)
      Sequence version 1 (20 Mar 1987)
      Previous versions | rss
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    Functioni

    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.14 Publications

    Cofactori

    Zinc.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei439 – 4402Cleavage; by plasminBy similarity

    GO - Molecular functioni

    1. cysteine-type endopeptidase inhibitor activity Source: InterPro
    2. heme binding Source: UniProtKB
    3. heparan sulfate proteoglycan binding Source: UniProtKB
    4. heparin binding Source: UniProtKB
    5. immunoglobulin binding Source: UniProtKB
    6. metal ion binding Source: UniProtKB
    7. protein binding Source: UniProtKB
    8. receptor binding Source: UniProtKB
    9. serine-type endopeptidase inhibitor activity Source: Ensembl
    10. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. angiogenesis Source: UniProtKB-KW
    2. blood coagulation Source: Reactome
    3. chemotaxis Source: UniProtKB-KW
    4. defense response to fungus Source: UniProtKB
    5. fibrinolysis Source: Reactome
    6. negative regulation of angiogenesis Source: UniProtKB
    7. negative regulation of blood vessel endothelial cell migration Source: UniProtKB
    8. negative regulation of cell adhesion Source: UniProtKB
    9. negative regulation of cell adhesion mediated by integrin Source: UniProtKB
    10. negative regulation of cell growth Source: UniProtKB
    11. negative regulation of cell proliferation Source: UniProtKB
    12. negative regulation of endothelial cell chemotaxis Source: UniProtKB
    13. negative regulation of fibrinolysis Source: Ensembl
    14. negative regulation of lamellipodium assembly Source: UniProtKB
    15. negative regulation of vascular endothelial growth factor signaling pathway Source: UniProtKB
    16. platelet activation Source: UniProtKB
    17. platelet degranulation Source: Reactome
    18. positive regulation of apoptotic process Source: UniProtKB
    19. positive regulation of blood vessel remodeling Source: UniProtKB
    20. positive regulation of focal adhesion assembly Source: UniProtKB
    21. positive regulation of immune response to tumor cell Source: UniProtKB
    22. regulation of actin cytoskeleton organization Source: UniProtKB
    23. regulation of blood coagulation Source: UniProtKB
    24. regulation of gene expression Source: UniProtKB
    25. regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
    26. regulation of platelet activation Source: UniProtKB
    27. regulation of protein complex assembly Source: UniProtKB

    Keywords - Biological processi

    Angiogenesis, Blood coagulation, Chemotaxis, Fibrinolysis, Hemostasis

    Keywords - Ligandi

    Copper, Heparin-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_641. Dissolution of Fibrin Clot.

    Protein family/group databases

    MEROPSiI25.022.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Histidine-rich glycoprotein
    Alternative name(s):
    Histidine-proline-rich glycoprotein
    Short name:
    HPRG
    Gene namesi
    Name:HRG
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:5181. HRG.

    Subcellular locationi

    Secreted 1 Publication

    GO - Cellular componenti

    1. blood microparticle Source: UniProt
    2. extracellular region Source: UniProtKB
    3. extracellular vesicular exosome Source: UniProt
    4. plasma membrane Source: Reactome
    5. platelet alpha granule lumen Source: Reactome

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Thrombophilia due to histidine-rich glycoprotein deficiency (THPH11) [MIM:613116]: A hemostatic disorder characterized by a tendency to thrombosis.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti103 – 1031G → E in THPH11; HRG Tokushima 1; results in increased intracellular degradation and reduced protein secretion. 1 Publication
    VAR_063000
    Natural varianti241 – 2411C → R in THPH11; HRG Tokushima 2; results in increased intracellular degradation and reduced protein secretion. 1 Publication
    VAR_063001

    Keywords - Diseasei

    Disease mutation, Thrombophilia

    Organism-specific databases

    MIMi613116. phenotype.
    Orphaneti217467. Hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency.
    PharmGKBiPA29455.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 18181 PublicationAdd
    BLAST
    Chaini19 – 525507Histidine-rich glycoproteinPRO_0000006709Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi24 ↔ 504By similarity
    Glycosylationi63 – 631N-linked (GlcNAc...)2 Publications
    Disulfide bondi78 ↔ 89By similarity
    Disulfide bondi105 ↔ 126By similarity
    Glycosylationi125 – 1251N-linked (GlcNAc...)2 Publications
    Disulfide bondi203 ↔ 417By similarity
    Disulfide bondi218 ↔ 241By similarity
    Glycosylationi344 – 3441N-linked (GlcNAc...)1 Publication
    Glycosylationi345 – 3451N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    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.3 Publications
    N-glycosylated.3 Publications

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiP04196.
    PeptideAtlasiP04196.
    PRIDEiP04196.

    2D gel databases

    SWISS-2DPAGEP04196.

    PTM databases

    PhosphoSiteiP04196.

    Expressioni

    Tissue specificityi

    Expressed in macrophages and in malignant cells. Expressed by the liver and secreted in plasma (at protein level).3 Publications

    Gene expression databases

    BgeeiP04196.
    CleanExiHS_HRG.
    GenevestigatoriP04196.

    Organism-specific databases

    HPAiHPA050269.
    HPA054598.

    Interactioni

    Subunit structurei

    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.By similarity8 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    RCHY1Q96PM53EBI-3915012,EBI-947779
    SPy_2034Q99XU04EBI-3915012,EBI-8852705From a different organism.

    Protein-protein interaction databases

    BioGridi109509. 8 interactions.
    DIPiDIP-47264N.
    IntActiP04196. 11 interactions.
    STRINGi9606.ENSP00000232003.

    Structurei

    3D structure databases

    ProteinModelPortaliP04196.
    SMRiP04196. Positions 141-254.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini19 – 136118Cystatin 1Add
    BLAST
    Domaini137 – 254118Cystatin 2Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni41 – 8444Interaction with ATP5A1Add
    BLAST
    Regioni348 – 38235Necessary for endothelial cell focal adhesions and anti-angiogenic activitiesAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi276 – 32146Pro-richAdd
    BLAST
    Compositional biasi350 – 497148His/Pro-rich (HRR)Add
    BLAST

    Domaini

    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.

    Sequence similaritiesi

    Contains 2 cystatin domains.Curated

    Keywords - Domaini

    Repeat, Signal

    Phylogenomic databases

    eggNOGiNOG75740.
    HOGENOMiHOG000090255.
    HOVERGENiHBG004597.
    InParanoidiP04196.
    OMAiRTNYYVD.
    OrthoDBiEOG7HXCSK.
    PhylomeDBiP04196.
    TreeFamiTF333729.

    Family and domain databases

    InterProiIPR000010. Prot_inh_cystat.
    [Graphical view]
    PfamiPF00031. Cystatin. 1 hit.
    [Graphical view]
    SMARTiSM00043. CY. 2 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P04196-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKALIAALLL ITLQYSCAVS PTDCSAVEPE AEKALDLINK RRRDGYLFQL    50
    LRIADAHLDR VENTTVYYLV LDVQESDCSV LSRKYWNDCE PPDSRRPSEI 100
    VIGQCKVIAT RHSHESQDLR VIDFNCTTSS VSSALANTKD SPVLIDFFED 150
    TERYRKQANK ALEKYKEEND DFASFRVDRI ERVARVRGGE GTGYFVDFSV 200
    RNCPRHHFPR HPNVFGFCRA DLFYDVEALD LESPKNLVIN CEVFDPQEHE 250
    NINGVPPHLG HPFHWGGHER SSTTKPPFKP HGSRDHHHPH KPHEHGPPPP 300
    PDERDHSHGP PLPQGPPPLL PMSCSSCQHA TFGTNGAQRH SHNNNSSDLH 350
    PHKHHSHEQH PHGHHPHAHH PHEHDTHRQH PHGHHPHGHH PHGHHPHGHH 400
    PHGHHPHCHD FQDYGPCDPP PHNQGHCCHG HGPPPGHLRR RGPGKGPRPF 450
    HCRQIGSVYR LPPLRKGEVL PLPEANFPSF PLPHHKHPLK PDNQPFPQSV 500
    SESCPGKFKS GFPQVSMFFT HTFPK 525
    Length:525
    Mass (Da):59,578
    Last modified:March 20, 1987 - v1
    Checksum:iA2B124D6CE93114F
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti79 – 791S → L.
    Corresponds to variant rs4516605 [ dbSNP | Ensembl ].
    VAR_048856
    Natural varianti103 – 1031G → E in THPH11; HRG Tokushima 1; results in increased intracellular degradation and reduced protein secretion. 1 Publication
    VAR_063000
    Natural varianti118 – 1181D → G.
    Corresponds to variant rs3733008 [ dbSNP | Ensembl ].
    VAR_020488
    Natural varianti180 – 1801I → T.
    Corresponds to variant rs10770 [ dbSNP | Ensembl ].
    VAR_022080
    Natural varianti204 – 2041P → S.
    Corresponds to variant rs9898 [ dbSNP | Ensembl ].
    VAR_014528
    Natural varianti241 – 2411C → R in THPH11; HRG Tokushima 2; results in increased intracellular degradation and reduced protein secretion. 1 Publication
    VAR_063001
    Natural varianti340 – 3401H → R.
    Corresponds to variant rs2228243 [ dbSNP | Ensembl ].
    VAR_020489
    Natural varianti436 – 4361G → R.
    Corresponds to variant rs2229331 [ dbSNP | Ensembl ].
    VAR_024427
    Natural varianti448 – 4481R → C.
    Corresponds to variant rs1042445 [ dbSNP | Ensembl ].
    VAR_024428
    Natural varianti493 – 4931N → I.
    Corresponds to variant rs1042464 [ dbSNP | Ensembl ].
    VAR_024429

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS3280.1.
    PIRiA01287. KGHUGH.
    RefSeqiNP_000403.1. NM_000412.3.
    UniGeneiHs.1498.

    Genome annotation databases

    EnsembliENST00000232003; ENSP00000232003; ENSG00000113905.
    GeneIDi3273.
    KEGGihsa:3273.
    UCSCiuc003fqq.3. human.

    Polymorphism databases

    DMDMi123523.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS3280.1.
    PIRi A01287. KGHUGH.
    RefSeqi NP_000403.1. NM_000412.3.
    UniGenei Hs.1498.

    3D structure databases

    ProteinModelPortali P04196.
    SMRi P04196. Positions 141-254.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109509. 8 interactions.
    DIPi DIP-47264N.
    IntActi P04196. 11 interactions.
    STRINGi 9606.ENSP00000232003.

    Protein family/group databases

    MEROPSi I25.022.

    PTM databases

    PhosphoSitei P04196.

    Polymorphism databases

    DMDMi 123523.

    2D gel databases

    SWISS-2DPAGE P04196.

    Proteomic databases

    PaxDbi P04196.
    PeptideAtlasi P04196.
    PRIDEi P04196.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000232003 ; ENSP00000232003 ; ENSG00000113905 .
    GeneIDi 3273.
    KEGGi hsa:3273.
    UCSCi uc003fqq.3. human.

    Organism-specific databases

    CTDi 3273.
    GeneCardsi GC03P186378.
    HGNCi HGNC:5181. HRG.
    HPAi HPA050269.
    HPA054598.
    MIMi 142640. gene.
    613116. phenotype.
    neXtProti NX_P04196.
    Orphaneti 217467. Hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency.
    PharmGKBi PA29455.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG75740.
    HOGENOMi HOG000090255.
    HOVERGENi HBG004597.
    InParanoidi P04196.
    OMAi RTNYYVD.
    OrthoDBi EOG7HXCSK.
    PhylomeDBi P04196.
    TreeFami TF333729.

    Enzyme and pathway databases

    Reactomei REACT_641. Dissolution of Fibrin Clot.

    Miscellaneous databases

    GeneWikii HRG_(gene).
    GenomeRNAii 3273.
    NextBioi 12999.
    PROi P04196.
    SOURCEi Search...

    Gene expression databases

    Bgeei P04196.
    CleanExi HS_HRG.
    Genevestigatori P04196.

    Family and domain databases

    InterProi IPR000010. Prot_inh_cystat.
    [Graphical view ]
    Pfami PF00031. Cystatin. 1 hit.
    [Graphical view ]
    SMARTi SM00043. CY. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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. 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. 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.

    Entry informationi

    Entry nameiHRG_HUMAN
    AccessioniPrimary (citable) accession number: P04196
    Secondary accession number(s): B9EK35, D3DNU7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 20, 1987
    Last sequence update: March 20, 1987
    Last modified: October 1, 2014
    This is version 153 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 3
      Human chromosome 3: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3