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Gene Review

PLP2  -  proteolipid protein 2 (colonic epithelium...

Homo sapiens

Synonyms: A4, A4-LSB, A4LSB, Differentiation-dependent protein A4, Intestinal membrane A4 protein, ...
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Disease relevance of PLP2

  • This study is the first report of the identification and characterization of a cleavage site recognized by murine coronavirus PLP2 activity [1].
  • PCR, using primers Plp1 and Plp2, was evaluated for the detection of DNA from Bordetella pertussis in bacterial strains and in nasopharyngeal samples from patients with a cough lasting at least 7 days [2].
  • In this study, we have used frozen cortical tissue of HCHWA-D and AD patients to investigate the beta/A4 amyloid protein and the amyloid precursor protein (APP) in different types of plaques and congophilic angiopathy [3].
  • A human glioma cell line (Bu-17) was stably transfected with full-length cDNA encoding beta/A4 amyloid protein precursor (APP) [4].
  • Alterations of beta/A4 amyloid protein precursor (APP) were investigated immunohistochemically in the gerbil brain after transient global ischemia and subsequent reperfusion [5].

Psychiatry related information on PLP2

  • Beta A4 protein immunoreactivity in the neocortex and hippocampus of familial Alzheimer's disease (AD) including the case with the beta A4 amyloid precursor protein (APP) gene mutation in codon 717 (APP717 Val-->Ile) and sporadic cases of AD is described [6].

High impact information on PLP2

  • The A4 protein (or beta-protein) is a 42- or 43-amino-acid peptide present in the extracellular neuritic plaques in Alzheimer's disease and is derived from a membrane-bound amyloid protein precursor (APP) [7].
  • The replicase polyprotein of murine coronavirus is extensively processed by three proteinases, two papain-like proteinases (PLPs), termed PLP1 and PLP2, and a picornavirus 3C-like proteinase (3CLpro) [1].
  • We found that the construct extending from the putative PLP2 cleavage site at glycine 2840-alanine 2841 was most similar in size to the processed MP1 replicase product generated in a trans-cleavage assay [1].
  • To determine which amino acids are critical for PLP2 recognition and processing, we generated 14 constructs with amino acid substitutions upstream and downstream of the putative cleavage site and assessed the effects of the mutations in the PLP2 trans-cleavage assay [1].
  • Therefore, murine coronavirus PLP2 cleaves the replicase polyprotein between glycine 2840 and alanine 2841, and the critical determinants for PLP2 recognition and processing occupy the P6, P2, and P1 positions of the cleavage site [1].

Biological context of PLP2

  • Promoter-linked transfection experiments of progressively deleted A4 5'-flanking sequences fused to the bacterial cat reporter gene suggest the presence of one negative and two positive DNA elements within the first 371 bp of the A4 promoter (pA4) [8].
  • The region has an elevated GC content (>53%), and we identified CpG islands associated with the 5' ends of SYP, A4, and LMO6 [9].
  • One of the positive clones contained an open reading frame of 456bp, of which the nucleotide sequence was identical to that of proteolipid protein 2 (PLP2), also known as protein A4 [10].
  • The amino acid sequence deduced from the ORF reveals a polypeptide of 152 amino acids with a predicted molecular mass of 17,000 Da, a size confirmed by coupled in vitro transcription and translation directed by the full-length A4 cDNA [11].
  • Differential screening of a subtraction cDNA library enriched for sequences unique to HT29-18-C1, a highly differentiated subclone of HT29-18, resulted in the isolation of a differentiation-dependent cDNA clone, A4 [11].

Anatomical context of PLP2

  • Indirect immunofluorescence analysis revealed that PLP2/A4 was predominantly located in plasma membrane and colocalized with CCR1 in transfected human HEK293 cells [10].
  • We conclude that this protein may be involved in the differential regulation of A4 in these intestinal cell lines [8].
  • Gene A4 is transcriptionally activated upon enterocyte differentiation of the human colonic epithelial cell line HT29-18 and its highly differentiated subclone HT29-18-C1 [Oliva et al., Arch. Biochem. Biophys. 302 (1993) 183-192] [8].
  • Rates of % BC during PRE, PLP1, and PLP2 were also determined for locations (maxilla or mandible) and types (screw or press-fit) [12].
  • Northern blot analysis of RNA obtained from various rat tissues shows that the expression of the A4 gene is tissue-selective and is enriched in colonic mucosa [11].

Associations of PLP2 with chemical compounds

  • Protease inhibitor studies revealed that unlike 3CLpro activity, PLP2 activity is not sensitive to cysteine protease inhibitor E64d [13].
  • Contrasting multi-site genotypic distributions among discordant quantitative phenotypes: the APOA1/C3/A4/A5 gene cluster and cardiovascular disease risk factors [14].

Other interactions of PLP2

  • Mammalian two-hybrid and coimmunoprecipitation analyses demonstrated the association of PLP2/A4 with CCR1 [10].

Analytical, diagnostic and therapeutic context of PLP2


  1. Identification of the murine coronavirus MP1 cleavage site recognized by papain-like proteinase 2. Kanjanahaluethai, A., Jukneliene, D., Baker, S.C. J. Virol. (2003) [Pubmed]
  2. Evaluation of PCR for diagnosis of Bordetella pertussis and Bordetella parapertussis infections. Lind-Brandberg, L., Welinder-Olsson, C., Lagergård, T., Taranger, J., Trollfors, B., Zackrisson, G. J. Clin. Microbiol. (1998) [Pubmed]
  3. Distribution of beta/A4 protein and amyloid precursor protein in hereditary cerebral hemorrhage with amyloidosis-Dutch type and Alzheimer's disease. Rozemuller, A.J., Roos, R.A., Bots, G.T., Kamphorst, W., Eikelenboom, P., Van Nostrand, W.E. Am. J. Pathol. (1993) [Pubmed]
  4. Protease inhibitors generate cytotoxic fragments from Alzheimer amyloid protein precursor in cDNA-transfected glioma cells. Hayashi, Y., Kashiwagi, K., Yoshikawa, K. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  5. Regional accumulation of amyloid beta/A4 protein precursor in the gerbil brain following transient cerebral ischemia. Wakita, H., Tomimoto, H., Akiguchi, I., Ohnishi, K., Nakamura, S., Kimura, J. Neurosci. Lett. (1992) [Pubmed]
  6. Beta A4 protein deposition in familial Alzheimer's disease with the mutation in codon 717 of the beta A4 amyloid precursor protein gene and sporadic Alzheimer's disease. Cairns, N.J., Chadwick, A., Lantos, P.L., Levy, R., Rossor, M.N. Neurosci. Lett. (1993) [Pubmed]
  7. The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexin-II. Oltersdorf, T., Fritz, L.C., Schenk, D.B., Lieberburg, I., Johnson-Wood, K.L., Beattie, E.C., Ward, P.J., Blacher, R.W., Dovey, H.F., Sinha, S. Nature (1989) [Pubmed]
  8. Promoter regulation of a differentially expressed gene in the human colonic epithelial cell lines HT29-18 and HT29-18-C1. Oliva, M.M., Cortese, J.F., Yang, V.W. Gene (1995) [Pubmed]
  9. Sequence-based exon prediction around the synaptophysin locus reveals a gene-rich area containing novel genes in human proximal Xp. Fisher, S.E., Ciccodicola, A., Tanaka, K., Curci, A., Desicato, S., D'urso, M., Craig, I.W. Genomics (1997) [Pubmed]
  10. PLP2/A4 interacts with CCR1 and stimulates migration of CCR1-expressing HOS cells. Lee, S.M., Shin, H., Jang, S.W., Shim, J.J., Song, I.S., Son, K.N., Hwang, J., Shin, Y.H., Kim, H.H., Lee, C.K., Ko, J., Na, D.S., Kwon, B.S., Kim, J. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  11. Isolation and characterization of a differentiation-dependent gene in the human colonic cell line HT29-18. Oliva, M.M., Wu, T.C., Yang, V.W. Arch. Biochem. Biophys. (1993) [Pubmed]
  12. Longitudinal radiographic study of crestal bone levels adjacent to non-submerged dental implants. Pham, A.N., Fiorellini, J.P., Paquette, D., Williams, R.C., Weber, H.P. The Journal of oral implantology. (1994) [Pubmed]
  13. Identification of mouse hepatitis virus papain-like proteinase 2 activity. Kanjanahaluethai, A., Baker, S.C. J. Virol. (2000) [Pubmed]
  14. Contrasting multi-site genotypic distributions among discordant quantitative phenotypes: the APOA1/C3/A4/A5 gene cluster and cardiovascular disease risk factors. Payseur, B.A., Clark, A.G., Hixson, J., Boerwinkle, E., Sing, C.F. Genet. Epidemiol. (2006) [Pubmed]
  15. Quantitative changes in the amyloid beta A4 precursor protein in Alzheimer cerebrospinal fluid. Prior, R., Mönning, U., Schreiter-Gasser, U., Weidemann, A., Blennow, K., Gottfries, C.G., Masters, C.L., Beyreuther, K. Neurosci. Lett. (1991) [Pubmed]
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