Q99PS8 · HRG_RAT
- ProteinHistidine-rich glycoprotein
- GeneHrg
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids525 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 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).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 439-440 | Cleavage; by plasmin | ||||
Sequence: RK |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameHistidine-rich glycoprotein
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ99PS8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-18 | |||||
Sequence: MKVLTTALLLVTLQCSHA | ||||||
Chain | PRO_0000408508 | 19-525 | Histidine-rich glycoprotein | |||
Sequence: LSPTNCDASKPLAEKVLDLINKGRRSGYTFQLLRVSDAHLDRVETATIYYLVLDVVESDCWVLSTKAQDECLPAMRTSEVVIGQCKVIATRYSNESQDLSVNGYNCTMRSVSSAYINTKDSPVLVDSFEDSEPYRKLARKALDKYKAENGDFASFRVERAERVIRMRGGERTSYFIEFSVRNCSTQHFPRHPPVFGLCRVVLTYSTEASDLETPEYTDLICEVFNTEDLKNRSDMKPHRGHEHPHCDKHLCKLSGPRDHHHTHKTHEIGCPPPPEGKDNSDRPPLQEGALPQMLPGHSGPSGTNRSHRPPHNHSCNEHPCHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGHHPHGDHPHGHHPHGHDFLDYGPCDPPSNSQELKGQYHRGHGPPHGHSRKRGPGKGLFPFHQRQIGYVYRLPPLNVGEVLTPPEANFPIFSLPNCNRPPQPEIRPFPQTASKSCPGKFEGKFPQVSNFFEHTPPK | ||||||
Disulfide bond | 24↔504 | |||||
Sequence: CDASKPLAEKVLDLINKGRRSGYTFQLLRVSDAHLDRVETATIYYLVLDVVESDCWVLSTKAQDECLPAMRTSEVVIGQCKVIATRYSNESQDLSVNGYNCTMRSVSSAYINTKDSPVLVDSFEDSEPYRKLARKALDKYKAENGDFASFRVERAERVIRMRGGERTSYFIEFSVRNCSTQHFPRHPPVFGLCRVVLTYSTEASDLETPEYTDLICEVFNTEDLKNRSDMKPHRGHEHPHCDKHLCKLSGPRDHHHTHKTHEIGCPPPPEGKDNSDRPPLQEGALPQMLPGHSGPSGTNRSHRPPHNHSCNEHPCHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGHHPHGDHPHGHHPHGHDFLDYGPCDPPSNSQELKGQYHRGHGPPHGHSRKRGPGKGLFPFHQRQIGYVYRLPPLNVGEVLTPPEANFPIFSLPNCNRPPQPEIRPFPQTASKSC | ||||||
Disulfide bond | 78↔89 | |||||
Sequence: CWVLSTKAQDEC | ||||||
Disulfide bond | 103↔124 | |||||
Sequence: CKVIATRYSNESQDLSVNGYNC | ||||||
Glycosylation | 112 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 123 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 145 | Phosphoserine | ||||
Sequence: S | ||||||
Glycosylation | 200 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 201↔414 | |||||
Sequence: CSTQHFPRHPPVFGLCRVVLTYSTEASDLETPEYTDLICEVFNTEDLKNRSDMKPHRGHEHPHCDKHLCKLSGPRDHHHTHKTHEIGCPPPPEGKDNSDRPPLQEGALPQMLPGHSGPSGTNRSHRPPHNHSCNEHPCHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGHHPHGDHPHGHHPHGHDFLDYGPC | ||||||
Disulfide bond | 216↔239 | |||||
Sequence: CRVVLTYSTEASDLETPEYTDLIC | ||||||
Glycosylation | 322 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 330 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 438 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
N-glycosylated.
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).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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.
Gene expression databases
Interaction
Subunit
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 ATP5F1A; 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).
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).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 19-122 | Cystatin 1 | ||||
Sequence: LSPTNCDASKPLAEKVLDLINKGRRSGYTFQLLRVSDAHLDRVETATIYYLVLDVVESDCWVLSTKAQDECLPAMRTSEVVIGQCKVIATRYSNESQDLSVNGY | ||||||
Region | 41-84 | Interaction with ATP5F1A | ||||
Sequence: GRRSGYTFQLLRVSDAHLDRVETATIYYLVLDVVESDCWVLSTK | ||||||
Domain | 135-240 | Cystatin 2 | ||||
Sequence: NTKDSPVLVDSFEDSEPYRKLARKALDKYKAENGDFASFRVERAERVIRMRGGERTSYFIEFSVRNCSTQHFPRHPPVFGLCRVVLTYSTEASDLETPEYTDLICE | ||||||
Compositional bias | 275-289 | Basic and acidic residues | ||||
Sequence: RDHHHTHKTHEIGCP | ||||||
Region | 275-445 | Disordered | ||||
Sequence: RDHHHTHKTHEIGCPPPPEGKDNSDRPPLQEGALPQMLPGHSGPSGTNRSHRPPHNHSCNEHPCHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGHHPHGDHPHGHHPHGHDFLDYGPCDPPSNSQELKGQYHRGHGPPHGHSRKRGPGK | ||||||
Compositional bias | 342-399 | Basic residues | ||||
Sequence: HPHGHHPHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGHHPHGDHPH | ||||||
Compositional bias | 430-445 | Basic residues | ||||
Sequence: GHGPPHGHSRKRGPGK |
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).
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length525
- Mass (Da)59,049
- Last updated2001-06-01 v1
- Checksum38290A631FAC7777
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0G2K3G0 | A0A0G2K3G0_RAT | Hrg | 536 |
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 6 | in Ref. 1; AAG28417 | ||||
Sequence: T → A | ||||||
Sequence conflict | 74 | in Ref. 1; AAG28417 and 2; BAB33093 | ||||
Sequence: V → I | ||||||
Sequence conflict | 93-98 | in Ref. 1; AAG28417 and 2; BAB33093 | ||||
Sequence: MRTSEV → RWTSEI | ||||||
Sequence conflict | 133-134 | in Ref. 1; AAG28417 and 2; BAB33093 | ||||
Sequence: YI → LS | ||||||
Sequence conflict | 143-145 | in Ref. 1; AAG28417 and 2; BAB33093 | ||||
Sequence: VDS → FDF | ||||||
Sequence conflict | 165 | in Ref. 1; AAG28417 and 2; BAB33093 | ||||
Sequence: A → E | ||||||
Sequence conflict | 172 | in Ref. 1; AAG28417 | ||||
Sequence: S → L | ||||||
Sequence conflict | 184 | in Ref. 1; AAG28417 and 2; BAB33093 | ||||
Sequence: M → G | ||||||
Sequence conflict | 191 | in Ref. 1; AAG28417 | ||||
Sequence: S → N | ||||||
Sequence conflict | 211 | in Ref. 1; AAG28417 | ||||
Sequence: P → L | ||||||
Sequence conflict | 215 | in Ref. 1; AAG28417 and 2; BAB33093 | ||||
Sequence: L → F | ||||||
Sequence conflict | 218-224 | in Ref. 1; AAG28417 and 2; BAB33093 | ||||
Sequence: VVLTYST → ALLSYSI | ||||||
Sequence conflict | 237-238 | in Ref. 1; AAG28417 and 2; BAB33093 | ||||
Sequence: LI → VT | ||||||
Sequence conflict | 242 | in Ref. 1; AAG28417 and 2; BAB33093 | ||||
Sequence: F → V | ||||||
Compositional bias | 275-289 | Basic and acidic residues | ||||
Sequence: RDHHHTHKTHEIGCP | ||||||
Sequence conflict | 329 | in Ref. 1; AAG28417 | ||||
Sequence: H → R | ||||||
Sequence conflict | 339-348 | in Ref. 1; AAG28417 and 2; BAB33093 | ||||
Sequence: Missing | ||||||
Compositional bias | 342-399 | Basic residues | ||||
Sequence: HPHGHHPHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGQHPHGHHPHGHHPHGDHPH | ||||||
Sequence conflict | 374 | in Ref. 1; AAG28417 | ||||
Sequence: H → R | ||||||
Sequence conflict | 381-385 | in Ref. 2; BAB33093 | ||||
Sequence: QHPHG → HHLHR | ||||||
Sequence conflict | 384 | in Ref. 1; AAG28417 | ||||
Sequence: H → R | ||||||
Sequence conflict | 421-425 | in Ref. 1; AAG28417 | ||||
Sequence: Missing | ||||||
Sequence conflict | 429 | in Ref. 1; AAG28417 | ||||
Sequence: R → Q | ||||||
Compositional bias | 430-445 | Basic residues | ||||
Sequence: GHGPPHGHSRKRGPGK | ||||||
Sequence conflict | 479 | in Ref. 2; BAB33093 | ||||
Sequence: I → S | ||||||
Sequence conflict | 494 | in Ref. 2; BAB33093 | ||||
Sequence: R → Q | ||||||
Sequence conflict | 510 | in Ref. 2; BAB33093 | ||||
Sequence: G → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF194029 EMBL· GenBank· DDBJ | AAG28417.1 EMBL· GenBank· DDBJ | mRNA | ||
AB055895 EMBL· GenBank· DDBJ | BAB33092.1 EMBL· GenBank· DDBJ | mRNA | ||
AB055896 EMBL· GenBank· DDBJ | BAB33093.1 EMBL· GenBank· DDBJ | mRNA | ||
BC089779 EMBL· GenBank· DDBJ | AAH89779.1 EMBL· GenBank· DDBJ | mRNA |