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Q99PS8 (HRG_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified September 21, 2011. Version 55. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·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
Histidine-rich glycoprotein 1
Short name=HRG1
Gene names
Name:Hrg
Synonyms:Hrg1
OrganismRattus norvegicus (Rat)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

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

Subunit structure

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.

Subcellular location

Secreted Ref.1.

Tissue specificity

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

Domain

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.

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

Post-translational modification

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.

Sequence similarities

Contains 2 cystatin domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 525507Histidine-rich glycoprotein
PRO_0000408508

Regions

Domain19 – 122104Cystatin 1
Domain135 – 240106Cystatin 2
Region41 – 8444Interaction with ATP5A1 By similarity
Compositional bias267 – 31246Pro-rich
Compositional bias337 – 497161His/Pro-rich (HRR)
Compositional bias462 – 49736Pro-rich

Sites

Site439 – 4402Cleavage; by plasmin By similarity

Amino acid modifications

Glycosylation1121N-linked (GlcNAc...) Potential
Glycosylation1231N-linked (GlcNAc...) Potential
Glycosylation2001N-linked (GlcNAc...) Potential
Glycosylation3221N-linked (GlcNAc...) Potential
Glycosylation3301N-linked (GlcNAc...) Potential
Disulfide bond24 ↔ 504 By similarity
Disulfide bond78 ↔ 89 By similarity
Disulfide bond103 ↔ 124 By similarity
Disulfide bond201 ↔ 414 By similarity
Disulfide bond216 ↔ 239 By similarity

Experimental info

Sequence conflict61T → A in AAG28417. Ref.1
Sequence conflict741V → I in AAG28417. Ref.1
Sequence conflict741V → I in BAB33093. Ref.2
Sequence conflict93 – 986MRTSEV → RWTSEI in AAG28417. Ref.1
Sequence conflict93 – 986MRTSEV → RWTSEI in BAB33093. Ref.2
Sequence conflict133 – 1342YI → LS in AAG28417. Ref.1
Sequence conflict133 – 1342YI → LS in BAB33093. Ref.2
Sequence conflict143 – 1453VDS → FDF in AAG28417. Ref.1
Sequence conflict143 – 1453VDS → FDF in BAB33093. Ref.2
Sequence conflict1651A → E in AAG28417. Ref.1
Sequence conflict1651A → E in BAB33093. Ref.2
Sequence conflict1721S → L in AAG28417. Ref.1
Sequence conflict1841M → G in AAG28417. Ref.1
Sequence conflict1841M → G in BAB33093. Ref.2
Sequence conflict1911S → N in AAG28417. Ref.1
Sequence conflict2111P → L in AAG28417. Ref.1
Sequence conflict2151L → F in AAG28417. Ref.1
Sequence conflict2151L → F in BAB33093. Ref.2
Sequence conflict218 – 2247VVLTYST → ALLSYSI in AAG28417. Ref.1
Sequence conflict218 – 2247VVLTYST → ALLSYSI in BAB33093. Ref.2
Sequence conflict237 – 2382LI → VT in AAG28417. Ref.1
Sequence conflict237 – 2382LI → VT in BAB33093. Ref.2
Sequence conflict2421F → V in AAG28417. Ref.1
Sequence conflict2421F → V in BAB33093. Ref.2
Sequence conflict3291H → R in AAG28417. Ref.1
Sequence conflict339 – 34810Missing in AAG28417. Ref.1
Sequence conflict339 – 34810Missing in BAB33093. Ref.2
Sequence conflict3741H → R in AAG28417. Ref.1
Sequence conflict381 – 3855QHPHG → HHLHR in BAB33093. Ref.2
Sequence conflict3841H → R in AAG28417. Ref.1
Sequence conflict421 – 4255Missing in AAG28417. Ref.1
Sequence conflict4291R → Q in AAG28417. Ref.1
Sequence conflict4791I → S in BAB33093. Ref.2
Sequence conflict4941R → Q in BAB33093. Ref.2
Sequence conflict5101G → S in BAB33093. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q99PS8 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 38290A631FAC7777

FASTA52559,049
        10         20         30         40         50         60 
MKVLTTALLL VTLQCSHALS PTNCDASKPL AEKVLDLINK GRRSGYTFQL LRVSDAHLDR 

        70         80         90        100        110        120 
VETATIYYLV LDVVESDCWV LSTKAQDECL PAMRTSEVVI GQCKVIATRY SNESQDLSVN 

       130        140        150        160        170        180 
GYNCTMRSVS SAYINTKDSP VLVDSFEDSE PYRKLARKAL DKYKAENGDF ASFRVERAER 

       190        200        210        220        230        240 
VIRMRGGERT SYFIEFSVRN CSTQHFPRHP PVFGLCRVVL TYSTEASDLE TPEYTDLICE 

       250        260        270        280        290        300 
VFNTEDLKNR SDMKPHRGHE HPHCDKHLCK LSGPRDHHHT HKTHEIGCPP PPEGKDNSDR 

       310        320        330        340        350        360 
PPLQEGALPQ MLPGHSGPSG TNRSHRPPHN HSCNEHPCHG QHPHGHHPHG QHPHGHHPHG 

       370        380        390        400        410        420 
QHPHGHHPHG QHPHGHHPHG QHPHGHHPHG HHPHGDHPHG HHPHGHDFLD YGPCDPPSNS 

       430        440        450        460        470        480 
QELKGQYHRG HGPPHGHSRK RGPGKGLFPF HQRQIGYVYR LPPLNVGEVL TPPEANFPIF 

       490        500        510        520 
SLPNCNRPPQ PEIRPFPQTA SKSCPGKFEG KFPQVSNFFE HTPPK

« Hide

References

« Hide 'large scale' references
[1]"Murine histidine-rich glycoprotein: cloning, characterization and cellular origin."
Hulett M.D., Parish C.R.
Immunol. Cell Biol. 78:280-287(2000) [PubMed: 10849117] [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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF194029 mRNA. Translation: AAG28417.1.
AB055895 mRNA. Translation: BAB33092.1.
AB055896 mRNA. Translation: BAB33093.1.
BC089779 mRNA. Translation: AAH89779.1.
IPIIPI00201347.
RefSeqNP_596919.1. NM_133428.1.
UniGeneRn.16100.

3D structure databases

ProteinModelPortalQ99PS8.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ99PS8.

Proteomic databases

PRIDEQ99PS8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000047595; ENSRNOP00000049290; ENSRNOG00000001809.
GeneID171016.
KEGGrno:171016.
UCSCNM_133428. rat.

Organism-specific databases

CTD3273.
RGD619808. Hrg.

Phylogenomic databases

GeneTreeENSGT00440000039583.
HOVERGENHBG004597.
InParanoidQ99PS8.
OMAIQPFPQS.

Gene expression databases

ArrayExpressQ99PS8.
GenevestigatorQ99PS8.

Family and domain databases

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

Other

NextBio621505.

Entry information

Entry nameHRG_RAT
AccessionPrimary (citable) accession number: Q99PS8
Secondary accession number(s): D3ZJN0, Q99PS7, Q9ESB2
Entry history
Integrated into UniProtKB/Swiss-Prot: May 31, 2011
Last sequence update: June 1, 2001
Last modified: September 21, 2011
This is version 55 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

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