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SERP1  -  stress-associated endoplasmic reticulum...

Homo sapiens

Synonyms: FLJ43424, RAMP4, Ribosome-attached membrane protein 4, Stress-associated endoplasmic reticulum protein 1
 
 
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Disease relevance of SERP1

  • Expression of SERP1 was enhanced in vitro by hypoxia and/or reoxygenation or other forms of stress, causing accumulation of unfolded proteins in endoplasmic reticulum (ER) stress, and in vivo by middle cerebral artery occlusion in rats [1].
  • Mutation of both copies of the SERP1 gene in myxoma virus results in a significant attenuation of the virus, such that more than 50% of infected animals are able to recover from the otherwise lethal infection [2].
  • Using myxoma virus and recombinant vaccinia virus constructs for experiments with tunicamycin and peptide N-glycosidase F, it is shown that the secreted SERP1 protein is modified by N-linked glycosylation [2].
  • Substitution of Serp-1 P2-P7 with Ala6 allowed for inhibition of urokinase but lost plasmin inhibition, unexpectedly inducing a diametrically opposed, proinflammatory response with mononuclear cell activation, thrombosis, and aneurysm formation (p < 0.03) [3].
  • The myxoma and malignant rabbit fibroma poxviruses are lethal tumorigenic viruses of rabbits whose virulence is modulated by the production of a virus-encoded secreted serine proteinase inhibitor, SERP-1 [4].
 

High impact information on SERP1

 

Chemical compound and disease context of SERP1

 

Biological context of SERP1

 

Anatomical context of SERP1

  • In basal conditions, the Sec61 complex in SERP1-/- microsomes was more cofractionated with ribosomes, compared with SERP1+/+ counterparts, in high-salt conditions [5].
  • Using monoclonal antibodies and human affinity-purified antibodies specific to the Plasmodium falciparum 126-kDa serine-rich protein, SERP, we found that these antibodies have no direct effect upon merozoite invasion at the concentrations tested but can cooperate with blood monocytes to strongly inhibit P. falciparum in vitro growth [11].
  • In the present work, we intend to determine the capacity of human lymphocytes to recognize subfragments of the serine-stretch protein SERP, a blood-stage antigen from Plasmodium falciparum [12].
  • Responses of T cells from sensitized donors to recombinant and synthetic peptides corresponding to sequences of the Plasmodium falciparum SERP antigen [12].
  • We cloned the asFP499 gene into a mammalian expression vector and showed that this protein was expressed in the human lymphoblast cell line Ramos RA1 and in the embryonic kidney 293T cell line (HEK 293T) [13].
 

Associations of SERP1 with chemical compounds

  • In the present study, examination of SERP-1 glycosylation-site mutants showed that the N-linked glycosylation of Asn(172) was essential for SERP-1 secretion, whereas mutation of Asn(99) decreased secretion efficiency, indicating that N-linked glycosylation plays an essential role in the processing and trafficking of SERP-1 [7].
 

Other interactions of SERP1

  • SERP-1 forms complexes with and inhibits the human fibrinolytic enzymes plasmin, urokinase, and two-chain tissue-type plasminogen activator (association rate constants 3.4 x 10(4), 4.3 x 10(4), and 3.6 x 10(4) M-1 s-1 respectively) [4].
  • SERP-1 acts as a substrate for and is cleaved by thrombin, porcine trypsin, human neutrophil elastase, porcine pancreatic elastase, thermolysin, subtilisin, bovine alpha-chymotrypsin, and factor Xa [4].
 

Analytical, diagnostic and therapeutic context of SERP1

  • Serp-1, a myxomaviral serpin, also targets the urokinase receptor, displaying profound anti-inflammatory and anti-atherogenic activity in a wide range of animal models [3].
  • Genomic DNA was extracted from the blood of six donors from different endemic areas of Brazil and West Africa. The SERP region encoding amino acids 630 to 781 was amplified by polymerase chain reaction (PCR) and sequenced [10].

References

  1. Stress-associated endoplasmic reticulum protein 1 (SERP1)/Ribosome-associated membrane protein 4 (RAMP4) stabilizes membrane proteins during stress and facilitates subsequent glycosylation. Yamaguchi, A., Hori, O., Stern, D.M., Hartmann, E., Ogawa, S., Tohyama, M. J. Cell Biol. (1999) [Pubmed]
  2. SERP1, a serine proteinase inhibitor encoded by myxoma virus, is a secreted glycoprotein that interferes with inflammation. Macen, J.L., Upton, C., Nation, N., McFadden, G. Virology (1993) [Pubmed]
  3. Identification of myxomaviral serpin reactive site loop sequences that regulate innate immune responses. Dai, E., Viswanathan, K., Sun, Y.M., Li, X., Liu, L.Y., Togonu-Bickersteth, B., Richardson, J., Macaulay, C., Nash, P., Turner, P., Nazarian, S.H., Moyer, R., McFadden, G., Lucas, A.R. J. Biol. Chem. (2006) [Pubmed]
  4. Inhibition of plasmin, urokinase, tissue plasminogen activator, and C1S by a myxoma virus serine proteinase inhibitor. Lomas, D.A., Evans, D.L., Upton, C., McFadden, G., Carrell, R.W. J. Biol. Chem. (1993) [Pubmed]
  5. Deletion of SERP1/RAMP4, a component of the endoplasmic reticulum (ER) translocation sites, leads to ER stress. Hori, O., Miyazaki, M., Tamatani, T., Ozawa, K., Takano, K., Okabe, M., Ikawa, M., Hartmann, E., Mai, P., Stern, D.M., Kitao, Y., Ogawa, S. Mol. Cell. Biol. (2006) [Pubmed]
  6. Transplant vasculopathy: viral anti-inflammatory serpin regulation of atherogenesis. Lucas, A., Dai, E., Liu, L., Guan, H., Nash, P., McFadden, G., Miller, L. J. Heart Lung Transplant. (2000) [Pubmed]
  7. Post-translational modification of the myxoma-virus anti-inflammatory serpin SERP-1 by a virally encoded sialyltransferase. Nash, P., Barry, M., Seet, B.T., Veugelers, K., Hota, S., Heger, J., Hodgkinson, C., Graham, K., Jackson, R.J., McFadden, G. Biochem. J. (2000) [Pubmed]
  8. Amelioration of antigen induced arthritis in rabbits treated with a secreted viral serine proteinase inhibitor. Maksymowych, W.P., Nation, N., Nash, P., Macen, J., Lucas, A., McFadden, G., Russell, A.S. J. Rheumatol. (1996) [Pubmed]
  9. Serpins, the vasculature, and viral therapeutics. Richardson, J., Viswanathan, K., Lucas, A. Front. Biosci. (2006) [Pubmed]
  10. A recombinant hybrid protein as antigen for an anti-blood stage malaria vaccine: a study on the conservation of a protective component. Knapp, B., Nau, U., Scherf, A. Mem. Inst. Oswaldo Cruz (1992) [Pubmed]
  11. Plasmodium falciparum serine repeat protein, a new target of monocyte-dependent antibody-mediated parasite killing. Soe, S., Singh, S., Camus, D., Horii, T., Druilhe, P. Infect. Immun. (2002) [Pubmed]
  12. Responses of T cells from sensitized donors to recombinant and synthetic peptides corresponding to sequences of the Plasmodium falciparum SERP antigen. Roussilhon, C., Hundt, E., Agrapart, M., Stüber, W., Knapp, B., Dubois, P., Ballet, J.J. Immunol. Lett. (1990) [Pubmed]
  13. Identification of a functional nuclear export signal in the green fluorescent protein asFP499. Mustafa, H., Strasser, B., Rauth, S., Irving, R.A., Wark, K.L. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
 
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