P04196 (HRG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histidine-rich glycoprotein

Alternative name(s):
Histidine-proline-rich glycoprotein
Short name=HPRG

Gene names

Name:

HRG

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	525 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Angiogenesis Blood coagulation Chemotaxis Fibrinolysis Hemostasis
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation Thrombophilia
Domain	Repeat Signal
Ligand	Copper Heparin-binding Metal-binding Zinc
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW 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 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: Compara 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 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_component	extracellular region Inferred from direct assay PubMed 18797515. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome platelet alpha granule lumen Traceable author statement. Source: Reactome
Molecular_function	cell surface binding Inferred from direct assay Ref.14Ref.17. Source: UniProtKB cysteine-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 serine-type endopeptidase inhibitor activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from direct assay Ref.13Ref.17Ref.26. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RCHY1	Q96PM5	3	EBI-3915012,EBI-947779

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Ref.6
	Chain	19 – 525	507	Histidine-rich glycoprotein		PRO_0000006709
Regions
	Domain	19 – 136	118	Cystatin 1
	Domain	137 – 254	118	Cystatin 2
	Region	41 – 84	44	Interaction with ATP5A1
	Region	348 – 382	35	Necessary for endothelial cell focal adhesions and anti-angiogenic activities
	Compositional bias	276 – 321	46	Pro-rich
	Compositional bias	350 – 497	148	His/Pro-rich (HRR)
Sites
	Site	439 – 440	2	Cleavage; by plasmin By similarity
Amino acid modifications
	Glycosylation	63	1	N-linked (GlcNAc...) Ref.15 Ref.19
	Glycosylation	125	1	N-linked (GlcNAc...) Ref.15 Ref.22
	Glycosylation	344	1	N-linked (GlcNAc...) Ref.15
	Glycosylation	345	1	N-linked (GlcNAc...) Potential
	Disulfide bond	24 ↔ 504		By similarity
	Disulfide bond	78 ↔ 89		By similarity
	Disulfide bond	105 ↔ 126		By similarity
	Disulfide bond	203 ↔ 417		By similarity
	Disulfide bond	218 ↔ 241		By similarity
Natural variations
	Natural variant	79	1	S → L. Corresponds to variant rs4516605 [ dbSNP | Ensembl ].		VAR_048856
	Natural variant	103	1	G → E in THPH11; HRG Tokushima 1; results in increased intracellular degradation and reduced protein secretion. Ref.28		VAR_063000
	Natural variant	118	1	D → G. Corresponds to variant rs3733008 [ dbSNP | Ensembl ].		VAR_020488
	Natural variant	180	1	I → T. Corresponds to variant rs10770 [ dbSNP | Ensembl ].		VAR_022080
	Natural variant	204	1	P → S. Corresponds to variant rs9898 [ dbSNP | Ensembl ].		VAR_014528
	Natural variant	241	1	C → R in THPH11; HRG Tokushima 2; results in increased intracellular degradation and reduced protein secretion. Ref.29		VAR_063001
	Natural variant	340	1	H → R. Corresponds to variant rs2228243 [ dbSNP | Ensembl ].		VAR_020489
	Natural variant	436	1	G → R. Corresponds to variant rs2229331 [ dbSNP | Ensembl ].		VAR_024427
	Natural variant	448	1	R → C. Corresponds to variant rs1042445 [ dbSNP | Ensembl ].		VAR_024428
	Natural variant	493	1	N → I. Corresponds to variant rs1042464 [ dbSNP | Ensembl ].		VAR_024429

Sequences

	Sequence		Length	Mass (Da)
	P04196 [UniParc]. Last modified March 20, 1987. Version 1. Checksum: A2B124D6CE93114F	FASTA	525	59,578
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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, 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, MASS SPECTROMETRY. 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, 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. , 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.
IPI	IPI00022371.
PIR	KGHUGH. A01287.
RefSeq	NP_000403.1. NM_000412.2.
UniGene	Hs.1498.
3D structure databases
ProteinModelPortal	P04196.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-47264N.
IntAct	P04196. 7 interactions.
STRING	9606.ENSP00000232003.
Protein family/group databases
MEROPS	I25.022.
PTM databases
PhosphoSite	P04196.
Polymorphism databases
DMDM	123523.
2D gel databases
SWISS-2DPAGE	P04196.
Proteomic databases
PaxDb	P04196.
PeptideAtlas	P04196.
PRIDE	P04196.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000232003; ENSP00000232003; ENSG00000113905.
GeneID	3273.
KEGG	hsa:3273.
UCSC	uc003fqq.3. human.
Organism-specific databases
CTD	3273.
GeneCards	GC03P186378.
HGNC	HGNC:5181. HRG.
MIM	142640. gene. 613116. phenotype.
neXtProt	NX_P04196.
Orphanet	217467. Hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency.
PharmGKB	PA29455.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG75740.
HOGENOM	HOG000090255.
HOVERGEN	HBG004597.
InParanoid	P04196.
OMA	HEHHPHG.
OrthoDB	EOG4WDDC3.
PhylomeDB	P04196.
Enzyme and pathway databases
Reactome	REACT_604. Hemostasis.
Gene expression databases
Bgee	P04196.
CleanEx	HS_HRG.
Genevestigator	P04196.
GermOnline	ENSG00000113905. Homo sapiens.
Family and domain databases
InterPro	IPR000010. Prot_inh_cystat. [Graphical view]
Pfam	PF00031. Cystatin. 1 hit. [Graphical view]
SMART	SM00043. CY. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	3273.
NextBio	12999.
SOURCE	Search...

Entry information

Entry name

HRG_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 141 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.