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Protein

Histidine-rich glycoprotein

Gene

Hrg

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plasma glycoprotein that binds a number of ligands such as heme, heparin, heparan sulfate, thrombospondin, plasminogen, and divalent metal ions. Inhibits rosette formation. Acts as an adapter protein and implicated in regulating many processes such as immune complex and pathogen clearance, 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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Blood coagulation, Fibrinolysis, Hemostasis

Keywords - Ligandi

Copper, Heparin-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-114608. Platelet degranulation.
R-RNO-75205. 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
Histidine-rich glycoprotein 1
Short name:
HRG1
Gene namesi
Name:Hrg
Synonyms:Hrg1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 11

Organism-specific databases

RGDi619808. Hrg.

Subcellular locationi

  • Secreted 1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence analysisAdd
BLAST
Chaini19 – 525507Histidine-rich glycoproteinPRO_0000408508Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi24 ↔ 504By similarity
Disulfide bondi78 ↔ 89By similarity
Disulfide bondi103 ↔ 124By similarity
Glycosylationi112 – 1121N-linked (GlcNAc...)Sequence analysis
Glycosylationi123 – 1231N-linked (GlcNAc...)Sequence analysis
Modified residuei145 – 1451PhosphoserineCombined sources
Glycosylationi200 – 2001N-linked (GlcNAc...)Sequence analysis
Disulfide bondi201 ↔ 414By similarity
Disulfide bondi216 ↔ 239By similarity
Glycosylationi322 – 3221N-linked (GlcNAc...)Sequence analysis
Glycosylationi330 – 3301N-linked (GlcNAc...)Sequence analysis
Modified residuei438 – 4381PhosphoserineCombined sources

Post-translational modificationi

N-glycosylated.By similarity
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 (By similarity).By similarity

Sites

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

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ99PS8.
PRIDEiQ99PS8.

PTM databases

iPTMnetiQ99PS8.

Expressioni

Tissue specificityi

Expressed in liver, blood plasma, serum and in platelets. Also present in fibrin clots, wound fluid from acute wounds and chronic leg ulcers.1 Publication

Gene expression databases

ExpressionAtlasiQ99PS8. baseline and differential.
GenevisibleiQ99PS8. RN.

Interactioni

Subunit structurei

Interacts with THBS1 (via the TSP type I repeats); the interaction blocks the antiangiogenic effect of THBS1 with CD36. 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 similarity). Interacts with PLG (via its Kringle domains); the interaction tethers PLG to the cell surface and enhances its activation. 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).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000049290.

Structurei

3D structure databases

ProteinModelPortaliQ99PS8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini19 – 122104Cystatin 1Add
BLAST
Domaini135 – 240106Cystatin 2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni41 – 8444Interaction with ATP5A1By similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi267 – 31246Pro-richAdd
BLAST
Compositional biasi337 – 497161His/Pro-rich (HRR)Add
BLAST
Compositional biasi462 – 49736Pro-richAdd
BLAST

Domaini

The His-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 (By similarity).By similarity
The cystatin domains can also bind heparan sulfate. Binding is enhanced in the presence of zinc ions (By similarity).By similarity

Sequence similaritiesi

Contains 2 cystatin domains.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

GeneTreeiENSGT00730000111384.
HOGENOMiHOG000090255.
HOVERGENiHBG004597.
InParanoidiQ99PS8.
OMAiPMILPSF.
OrthoDBiEOG7HXCSK.
PhylomeDBiQ99PS8.
TreeFamiTF333729.

Family and domain databases

InterProiIPR000010. Cystatin_dom.
[Graphical view]
SMARTiSM00043. CY. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q99PS8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKVLTTALLL VTLQCSHALS PTNCDASKPL AEKVLDLINK GRRSGYTFQL
60 70 80 90 100
LRVSDAHLDR VETATIYYLV LDVVESDCWV LSTKAQDECL PAMRTSEVVI
110 120 130 140 150
GQCKVIATRY SNESQDLSVN GYNCTMRSVS SAYINTKDSP VLVDSFEDSE
160 170 180 190 200
PYRKLARKAL DKYKAENGDF ASFRVERAER VIRMRGGERT SYFIEFSVRN
210 220 230 240 250
CSTQHFPRHP PVFGLCRVVL TYSTEASDLE TPEYTDLICE VFNTEDLKNR
260 270 280 290 300
SDMKPHRGHE HPHCDKHLCK LSGPRDHHHT HKTHEIGCPP PPEGKDNSDR
310 320 330 340 350
PPLQEGALPQ MLPGHSGPSG TNRSHRPPHN HSCNEHPCHG QHPHGHHPHG
360 370 380 390 400
QHPHGHHPHG QHPHGHHPHG QHPHGHHPHG QHPHGHHPHG HHPHGDHPHG
410 420 430 440 450
HHPHGHDFLD YGPCDPPSNS QELKGQYHRG HGPPHGHSRK RGPGKGLFPF
460 470 480 490 500
HQRQIGYVYR LPPLNVGEVL TPPEANFPIF SLPNCNRPPQ PEIRPFPQTA
510 520
SKSCPGKFEG KFPQVSNFFE HTPPK
Length:525
Mass (Da):59,049
Last modified:June 1, 2001 - v1
Checksum:i38290A631FAC7777
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 61T → A in AAG28417 (PubMed:10849117).Curated
Sequence conflicti74 – 741V → I in AAG28417 (PubMed:10849117).Curated
Sequence conflicti74 – 741V → I in BAB33093 (Ref. 2) Curated
Sequence conflicti93 – 986MRTSEV → RWTSEI in AAG28417 (PubMed:10849117).Curated
Sequence conflicti93 – 986MRTSEV → RWTSEI in BAB33093 (Ref. 2) Curated
Sequence conflicti133 – 1342YI → LS in AAG28417 (PubMed:10849117).Curated
Sequence conflicti133 – 1342YI → LS in BAB33093 (Ref. 2) Curated
Sequence conflicti143 – 1453VDS → FDF in AAG28417 (PubMed:10849117).Curated
Sequence conflicti143 – 1453VDS → FDF in BAB33093 (Ref. 2) Curated
Sequence conflicti165 – 1651A → E in AAG28417 (PubMed:10849117).Curated
Sequence conflicti165 – 1651A → E in BAB33093 (Ref. 2) Curated
Sequence conflicti172 – 1721S → L in AAG28417 (PubMed:10849117).Curated
Sequence conflicti184 – 1841M → G in AAG28417 (PubMed:10849117).Curated
Sequence conflicti184 – 1841M → G in BAB33093 (Ref. 2) Curated
Sequence conflicti191 – 1911S → N in AAG28417 (PubMed:10849117).Curated
Sequence conflicti211 – 2111P → L in AAG28417 (PubMed:10849117).Curated
Sequence conflicti215 – 2151L → F in AAG28417 (PubMed:10849117).Curated
Sequence conflicti215 – 2151L → F in BAB33093 (Ref. 2) Curated
Sequence conflicti218 – 2247VVLTYST → ALLSYSI in AAG28417 (PubMed:10849117).Curated
Sequence conflicti218 – 2247VVLTYST → ALLSYSI in BAB33093 (Ref. 2) Curated
Sequence conflicti237 – 2382LI → VT in AAG28417 (PubMed:10849117).Curated
Sequence conflicti237 – 2382LI → VT in BAB33093 (Ref. 2) Curated
Sequence conflicti242 – 2421F → V in AAG28417 (PubMed:10849117).Curated
Sequence conflicti242 – 2421F → V in BAB33093 (Ref. 2) Curated
Sequence conflicti329 – 3291H → R in AAG28417 (PubMed:10849117).Curated
Sequence conflicti339 – 34810Missing in AAG28417 (PubMed:10849117).Curated
Sequence conflicti339 – 34810Missing in BAB33093 (Ref. 2) Curated
Sequence conflicti374 – 3741H → R in AAG28417 (PubMed:10849117).Curated
Sequence conflicti381 – 3855QHPHG → HHLHR in BAB33093 (Ref. 2) Curated
Sequence conflicti384 – 3841H → R in AAG28417 (PubMed:10849117).Curated
Sequence conflicti421 – 4255Missing in AAG28417 (PubMed:10849117).Curated
Sequence conflicti429 – 4291R → Q in AAG28417 (PubMed:10849117).Curated
Sequence conflicti479 – 4791I → S in BAB33093 (Ref. 2) Curated
Sequence conflicti494 – 4941R → Q in BAB33093 (Ref. 2) Curated
Sequence conflicti510 – 5101G → S in BAB33093 (Ref. 2) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF194029 mRNA. Translation: AAG28417.1.
AB055895 mRNA. Translation: BAB33092.1.
AB055896 mRNA. Translation: BAB33093.1.
BC089779 mRNA. Translation: AAH89779.1.
RefSeqiNP_596919.1. NM_133428.2.
UniGeneiRn.16100.

Genome annotation databases

EnsembliENSRNOT00000047595; ENSRNOP00000049290; ENSRNOG00000001809.
GeneIDi171016.
KEGGirno:171016.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF194029 mRNA. Translation: AAG28417.1.
AB055895 mRNA. Translation: BAB33092.1.
AB055896 mRNA. Translation: BAB33093.1.
BC089779 mRNA. Translation: AAH89779.1.
RefSeqiNP_596919.1. NM_133428.2.
UniGeneiRn.16100.

3D structure databases

ProteinModelPortaliQ99PS8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000049290.

Protein family/group databases

MEROPSiI25.022.

PTM databases

iPTMnetiQ99PS8.

Proteomic databases

PaxDbiQ99PS8.
PRIDEiQ99PS8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000047595; ENSRNOP00000049290; ENSRNOG00000001809.
GeneIDi171016.
KEGGirno:171016.

Organism-specific databases

CTDi3273.
RGDi619808. Hrg.

Phylogenomic databases

GeneTreeiENSGT00730000111384.
HOGENOMiHOG000090255.
HOVERGENiHBG004597.
InParanoidiQ99PS8.
OMAiPMILPSF.
OrthoDBiEOG7HXCSK.
PhylomeDBiQ99PS8.
TreeFamiTF333729.

Enzyme and pathway databases

ReactomeiR-RNO-114608. Platelet degranulation.
R-RNO-75205. Dissolution of Fibrin Clot.

Miscellaneous databases

PROiQ99PS8.

Gene expression databases

ExpressionAtlasiQ99PS8. baseline and differential.
GenevisibleiQ99PS8. RN.

Family and domain databases

InterProiIPR000010. Cystatin_dom.
[Graphical view]
SMARTiSM00043. CY. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Murine histidine-rich glycoprotein: cloning, characterization and cellular origin."
    Hulett M.D., Parish C.R.
    Immunol. Cell Biol. 78:280-287(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    Strain: Lewis.
  2. "Molecular diversity of mammalian histidine-rich glycoprotein."
    Wakabayashi S., Takahashi K., Hirokado Y., Togo Y., Izumi S., Ohashi T., Sato N., Hirata D., Tsuchida N., Koide T.
    Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Liver.
  3. "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: Liver.
  4. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145 AND SER-438, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiHRG_RAT
AccessioniPrimary (citable) accession number: Q99PS8
Secondary accession number(s): D3ZJN0, Q99PS7, Q9ESB2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 31, 2011
Last sequence update: June 1, 2001
Last modified: July 6, 2016
This is version 88 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.