HRG_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: HRG_HUMAN
• UniProt AC: P04196
• Protein Name: Histidine-rich glycoprotein
• Gene Name: HRG
• Organism: Homo sapiens (Human).
• Sequence Length: 525
• Subcellular Localization: Secreted .
• Protein Description: 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: MKALIAALLLITLQYSCAVSPTDCSAVEPEAEKALDLINKRRRDGYLFQLLRIADAHLDRVENTTVYYLVLDVQESDCSVLSRKYWNDCEPPDSRRPSEIVIGQCKVIATRHSHESQDLRVIDFNCTTSSVSSALANTKDSPVLIDFFEDTERYRKQANKALEKYKEENDDFASFRVDRIERVARVRGGEGTGYFVDFSVRNCPRHHFPRHPNVFGFCRADLFYDVEALDLESPKNLVINCEVFDPQEHENINGVPPHLGHPFHWGGHERSSTTKPPFKPHGSRDHHHPHKPHEHGPPPPPDERDHSHGPPLPQGPPPLLPMSCSSCQHATFGTNGAQRHSHNNNSSDLHPHKHHSHEQHPHGHHPHAHHPHEHDTHRQHPHGHHPHGHHPHGHHPHGHHPHGHHPHCHDFQDYGPCDPPPHNQGHCCHGHGPPPGHLRRRGPGKGPRPFHCRQIGSVYRLPPLRKGEVLPLPEANFPSFPLPHHKHPLKPDNQPFPQSVSESCPGKFKSGFPQVSMFFTHTFPK

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
46	Phosphorylation	NKRRRDGYLFQLLRI HHHCCCCHHHHHHHH	14.50	-
63	N-linked_Glycosylation	AHLDRVENTTVYYLV HCHHHCCCEEEEEEE	37.89	16335952
67	Phosphorylation	RVENTTVYYLVLDVQ HCCCEEEEEEEEEEC	6.76	-
68	Phosphorylation	VENTTVYYLVLDVQE CCCEEEEEEEEEECH	5.98	-
125	N-linked_Glycosylation	DLRVIDFNCTTSSVS CEEEEEEECCCCHHH	20.62	8348977
125	N-linked_Glycosylation	DLRVIDFNCTTSSVS CEEEEEEECCCCHHH	20.62	8348977
128	Phosphorylation	VIDFNCTTSSVSSAL EEEEECCCCHHHHHH	22.62	-
165	Phosphorylation	ANKALEKYKEENDDF HHHHHHHHHHHCCCH	17.79	-
174	Phosphorylation	EENDDFASFRVDRIE HHCCCHHHHCHHEEE	17.36	-
202	N-linked_Glycosylation	FVDFSVRNCPRHHFP EEEEEECCCCCCCCC	37.68	-
202	N-linked_Glycosylation	FVDFSVRNCPRHHFP EEEEEECCCCCCCCC	37.68	8348977
233	Phosphorylation	VEALDLESPKNLVIN EEECCCCCCCCEEEE	48.77	24719451
271	O-linked_Glycosylation	HWGGHERSSTTKPPF CCCCCCCCCCCCCCC	29.11	OGP
271	Phosphorylation	HWGGHERSSTTKPPF CCCCCCCCCCCCCCC	29.11	24275569
273	O-linked_Glycosylation	GGHERSSTTKPPFKP CCCCCCCCCCCCCCC	39.83	OGP
274	O-linked_Glycosylation	GHERSSTTKPPFKPH CCCCCCCCCCCCCCC	43.43	OGP
283	Phosphorylation	PPFKPHGSRDHHHPH CCCCCCCCCCCCCCC	31.34	24275569
344	N-linked_Glycosylation	AQRHSHNNNSSDLHP HHCCCCCCCCCCCCC	44.32	16335952
345	N-linked_Glycosylation	QRHSHNNNSSDLHPH HCCCCCCCCCCCCCC	48.48	UniProtKB CARBOHYD
356	Phosphorylation	LHPHKHHSHEQHPHG CCCCCCCCCCCCCCC	28.56	27130503

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Oops, there are no upstream regulatory protein records of HRG_HUMAN !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of HRG_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
344	N-linked Glycosylation	340 (4)	H ⇒ R;L	rs2228243	Blood protein levels	28240269

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
FIBA_HUMAN	FGA	physical	9276466
PLS1_HUMAN	PLSCR1	physical	21988832
TNR1A_HUMAN	TNFRSF1A	physical	21988832
SPY1_HUMAN	SPRY1	physical	21988832
PRAF1_HUMAN	RABAC1	physical	21988832
ZN363_HUMAN	RCHY1	physical	21988832

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• 613116: Thrombophilia due to histidine-rich glycoprotein deficiency (THPH11)
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

N-linked Glycosylation

"Glycoproteomics analysis of human liver tissue by combination ofmultiple 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).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-125, AND MASSSPECTROMETRY.
PubMed: 19159218

"High affinity interaction between histidine-rich glycoprotein and thecell surface type ATP synthase on T-cells.";
Ohta T., Ikemoto Y., Usami A., Koide T., Wakabayashi S.;
Biochim. Biophys. Acta 1788:1099-1107(2009).
Cited for: INTERACTION WITH ATP5A1, FUNCTION, GLYCOSYLATION AT ASN-63, AND MASSSPECTROMETRY.
PubMed: 19285951

"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).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-63; ASN-125 AND ASN-344,AND MASS SPECTROMETRY.
PubMed: 16335952