Overview
| Uniprot ID | P04196 |
|---|
| Protein Name | Histidine-rich glycoprotein |
|---|
| Gene Name | HRG |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 84 |
DCSVLSRKYWNDCEP |
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
Protein Sequence
10
MKALIAALLL
20
ITLQYSCAVS
30
PTDCSAVEPE
40
AEKALDLINK
50
RRRDGYLFQL
60
LRIADAHLDR
70
VENTTVYYLV
80
LDVQESDCSV
90
LSRKYWNDCE
100
PPDSRRPSEI
110
VIGQCKVIAT
120
RHSHESQDLR
130
VIDFNCTTSS
140
VSSALANTKD
150
SPVLIDFFED
160
TERYRKQANK
170
ALEKYKEEND
180
DFASFRVDRI
190
ERVARVRGGE
200
GTGYFVDFSV
210
RNCPRHHFPR
220
HPNVFGFCRA
230
DLFYDVEALD
240
LESPKNLVIN
250
CEVFDPQEHE
260
NINGVPPHLG
270
HPFHWGGHER
280
SSTTKPPFKP
290
HGSRDHHHPH
300
KPHEHGPPPP
310
PDERDHSHGP
320
PLPQGPPPLL
330
PMSCSSCQHA
340
TFGTNGAQRH
350
SHNNNSSDLH
360
PHKHHSHEQH
370
PHGHHPHAHH
380
PHEHDTHRQH
390
PHGHHPHGHH
400
PHGHHPHGHH
410
PHGHHPHCHD
420
FQDYGPCDPP
430
PHNQGHCCHG
440
HGPPPGHLRR
450
RGPGKGPRPF
460
HCRQIGSVYR
470
LPPLRKGEVL
480
PLPEANFPSF
490
PLPHHKHPLK
500
PDNQPFPQSV
510
SESCPGKFKS
520
GFPQVSMFFT
HTFPK
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0072562 |
blood microparticle |
| Cellular Component |
GO:0009986 |
cell surface |
| Cellular Component |
GO:0070062 |
extracellular exosome |
| Cellular Component |
GO:0031012 |
extracellular matrix |
| Cellular Component |
GO:0005576 |
extracellular region |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Cellular Component |
GO:0031093 |
platelet alpha granule lumen |
| Molecular Function |
GO:0004869 |
cysteine-type endopeptidase inhibitor activity |
| Molecular Function |
GO:0020037 |
heme binding |
| Molecular Function |
GO:0043395 |
heparan sulfate proteoglycan binding |
| Molecular Function |
GO:0008201 |
heparin binding |
| Molecular Function |
GO:0019865 |
immunoglobulin binding |
| Molecular Function |
GO:0046872 |
metal ion binding |
| Molecular Function |
GO:0004867 |
serine-type endopeptidase inhibitor activity |
| Molecular Function |
GO:0005102 |
signaling receptor binding |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0001525 |
angiogenesis |
| Biological Process |
GO:0061844 |
antimicrobial humoral immune response mediated by antimicrobial peptide |
| Biological Process |
GO:0006935 |
chemotaxis |
| Biological Process |
GO:0051838 |
cytolysis by host of symbiont cells |
| Biological Process |
GO:0050832 |
defense response to fungus |
| Biological Process |
GO:0042730 |
fibrinolysis |
| Biological Process |
GO:0016525 |
negative regulation of angiogenesis |
| Biological Process |
GO:0043537 |
negative regulation of blood vessel endothelial cell migration |
| Biological Process |
GO:0007162 |
negative regulation of cell adhesion |
| Biological Process |
GO:0033629 |
negative regulation of cell adhesion mediated by integrin |
| Biological Process |
GO:0030308 |
negative regulation of cell growth |
| Biological Process |
GO:0008285 |
negative regulation of cell population proliferation |
| Biological Process |
GO:2001027 |
negative regulation of endothelial cell chemotaxis |
| Biological Process |
GO:0051918 |
negative regulation of fibrinolysis |
| Biological Process |
GO:0010593 |
negative regulation of lamellipodium assembly |
| Biological Process |
GO:1900747 |
negative regulation of vascular endothelial growth factor signaling pathway |
| Biological Process |
GO:0030168 |
platelet activation |
| Biological Process |
GO:0043065 |
positive regulation of apoptotic process |
| Biological Process |
GO:2000504 |
positive regulation of blood vessel remodeling |
| Biological Process |
GO:0051894 |
positive regulation of focal adhesion assembly |
| Biological Process |
GO:0002839 |
positive regulation of immune response to tumor cell |
| Biological Process |
GO:0032956 |
regulation of actin cytoskeleton organization |
| Biological Process |
GO:0030193 |
regulation of blood coagulation |
| Biological Process |
GO:0010468 |
regulation of gene expression |
| Biological Process |
GO:0010543 |
regulation of platelet activation |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.