HRG_BOVIN
ID HRG_BOVIN Reviewed; 396 AA.
AC P33433;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 25-MAY-2022, entry version 107.
DE RecName: Full=Histidine-rich glycoprotein;
DE AltName: Full=Histidine-proline-rich glycoprotein;
DE Short=HPRG;
DE Flags: Fragments;
GN Name=HRG;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP PROTEIN SEQUENCE, PROTEOLYTIC PROCESSING, GLYCOSYLATION AT ASN-70; ASN-91;
RP ASN-122 AND ASN-220, AND DISULFIDE BONDS.
RX PubMed=8348977; DOI=10.1016/0014-5793(93)80945-q;
RA Soerensen C.B., Krogh-Pedersen H., Petersen T.E.;
RT "Determination of the disulphide bridge arrangement of bovine histidine-
RT rich glycoprotein.";
RL FEBS Lett. 328:285-290(1993).
CC -!- FUNCTION: Plasma glycoprotein that binds a number of ligands such as
CC heme, heparin, heparan sulfate, thrombospondin, plasminogen, and
CC divalent metal ions. Inhibits rosette formation. Acts as an adapter
CC protein and implicated in regulating many processes such as immune
CC complex and pathogen clearance, cell adhesion, angiogenesis,
CC coagulation and fibrinolysis. Mediates clearance of necrotic cells
CC through enhancing the phagocytosis of necrotic cells in a heparan
CC sulfate-dependent pathway. This process can be regulated by the
CC presence of certain HRG ligands such as heparin and zinc ions. Binds to
CC IgG subclasses of immunoglobins containing kappa and lambda light
CC chains with different affinities regulating their clearance and
CC inhibiting the formation of insoluble immune complexes. Tethers
CC plasminogen to the cell surface. Binds T-cells and alters the cell
CC morphology. Modulates angiogenesis by blocking the CD6-mediated
CC antiangiongenic effect of thrombospondins, THBS1 and THBS2 (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts (via the HRR domain) with TPM1; the interaction
CC appears to contribute to the antiangiogenic properties of the HRR
CC domain. Interacts with THBS1 (via the TSP type I repeats); the
CC interaction blocks the antiangiogenic effect of THBS1 with CD36 (By
CC similarity). Interacts with PLG (via its Kringle domains); the
CC interaction tethers PLG to the cell surface and enhances its
CC activation. Interacts with THBS2; the interaction blocks the
CC antiangiogenic effect of THBS2 with CD36. Interacts with HPSE; the
CC interaction is enhanced at acidic pH, partially inhibits binding of
CC HPSE to cell surface receptors and modulates its enzymatic activity.
CC Interacts (via the HRR domain) with TMP1; the interaction partially
CC mediates the antiangiogenic properties of HRG. Interacts with kappa and
CC lambda light chains of IgG molecules. Interacts with ATP5F1A; the
CC interaction occurs on the surface of T-cells and alters their cell
CC morphology in concert with CONA. Binds IgG molecules containing kappa
CC and lambda light chains and inhibits the formation of insoluble
CC immunoglobulin complexes. Interacts with F12; the interaction, which is
CC enhanced in the presence of zinc ions and inhibited by heparin-binding
CC to HRG, inhibits factor XII autoactivation and contact-initiated
CC coagulation (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- DOMAIN: The His-rich (HRR) region contains approximately 12 tandem
CC internal repeats of the 5-residue G[H/P][H/P]PH consensus sequence. HRR
CC binds heparan sulfate and possesses antiangiogenic, antibacterial and
CC antifungal properties through binding Candida cells, and preferentially
CC lysing the ergosterol-containing liposomes at low pH. The tandem
CC repeats also bind divalent metal ions and heme (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: The cystatin domains can also bind heparan sulfate. Binding is
CC enhanced in the presence of zinc ions (By similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:8348977}.
CC -!- PTM: Proteolytic cleavage produces several HRG fragments which are
CC mostly disulfide-linked and, therefore, not released. On platelet
CC activation, may release a 33 kDa antiangiogenic peptide which
CC encompasses the HRR (By similarity). {ECO:0000250}.
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DR AlphaFoldDB; P33433; -.
DR SMR; P33433; -.
DR iPTMnet; P33433; -.
DR PeptideAtlas; P33433; -.
DR PRIDE; P33433; -.
DR eggNOG; ENOG502S50D; Eukaryota.
DR InParanoid; P33433; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0036019; C:endolysosome; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; ISS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR GO; GO:0019865; F:immunoglobulin binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; ISS:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0050832; P:defense response to fungus; ISS:UniProtKB.
DR GO; GO:0042730; P:fibrinolysis; IEA:UniProtKB-KW.
DR GO; GO:0015886; P:heme transport; IBA:GO_Central.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0033629; P:negative regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:2001027; P:negative regulation of endothelial cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0051918; P:negative regulation of fibrinolysis; IBA:GO_Central.
DR GO; GO:0010593; P:negative regulation of lamellipodium assembly; ISS:UniProtKB.
DR GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030168; P:platelet activation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:2000504; P:positive regulation of blood vessel remodeling; ISS:UniProtKB.
DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; ISS:UniProtKB.
DR GO; GO:0002839; P:positive regulation of immune response to tumor cell; ISS:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0030193; P:regulation of blood coagulation; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0010543; P:regulation of platelet activation; ISS:UniProtKB.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; ISS:UniProtKB.
DR InterPro; IPR046350; Cystatin_sf.
DR SUPFAM; SSF54403; SSF54403; 1.
PE 1: Evidence at protein level;
KW Blood coagulation; Copper; Direct protein sequencing; Disulfide bond;
KW Fibrinolysis; Glycoprotein; Hemostasis; Heparin-binding; Phosphoprotein;
KW Reference proteome; Repeat; Secreted; Zinc.
FT CHAIN 1..396
FT /note="Histidine-rich glycoprotein"
FT /id="PRO_0000207164"
FT DOMAIN 1..102
FT /note="Cystatin 1"
FT DOMAIN 103..169
FT /note="Cystatin 2"
FT REGION 176..322
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 229..244
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 251..267
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 268..282
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..318
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 230..231
FT /note="Cleavage"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99PS8"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine; partial"
FT /evidence="ECO:0000269|PubMed:8348977"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8348977"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8348977"
FT CARBOHYD 220
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8348977"
FT DISULFID 7..375
FT /evidence="ECO:0000269|PubMed:8348977"
FT DISULFID 56..67
FT /evidence="ECO:0000269|PubMed:8348977"
FT DISULFID 77..92
FT /evidence="ECO:0000269|PubMed:8348977"
FT DISULFID 123..297
FT /evidence="ECO:0000269|PubMed:8348977"
FT DISULFID 137..160
FT /evidence="ECO:0000269|PubMed:8348977"
FT DISULFID 212..242
FT /evidence="ECO:0000269|PubMed:8348977"
FT VARIANT 86
FT /note="S -> R"
FT VARIANT 309
FT /note="S -> Q"
FT VARIANT 322
FT /note="H -> Y"
FT NON_CONS 52..53
FT /evidence="ECO:0000305"
FT NON_CONS 71..72
FT /evidence="ECO:0000305"
FT NON_CONS 78..79
FT /evidence="ECO:0000305"
FT NON_CONS 103..104
FT /evidence="ECO:0000305"
FT NON_CONS 163..164
FT /evidence="ECO:0000305"
FT NON_CONS 263..264
FT /evidence="ECO:0000305"
FT NON_CONS 303..304
FT /evidence="ECO:0000305"
SQ SEQUENCE 396 AA; 44471 MW; 128A8223499DE6FC CRC64;
AVNPTGCDAV EPVAVRALDL INKGRDGYLF QLLRVADAHL DKVESIAVYY LVESDCPVLS
RKHWDDCELN VTVIGQCKLA GPEDLSVNDF NCTTSSVSSA LTNMRARGGE GTSYFLDFSV
RNCSSHHFPR HHIFGFCRAD LFYDVEASDL ETPKDIVTNC EVFHRRFSAV QHHLGRPFHS
GEHEHSPAGR PPFKPSGSKD HGHPHESYNF RCPPPLEHKN HSDSPPFQAR APLPFPPPGL
RCPHPPFGTK GNHRPPHDHS SDEHHPHGHH PHGHHPHGHH PHGHHPPDND FYDHGPCDPP
PHRPPPRHSK ERGPGKGHFR FHWRPTGYIH RLPSLKKGEV LPLPEANFPS FSLPNHNNPL
QPEIQAFPQS ASESCPGTFN IKFLHISKFF AYTLPK
