PrionDB: Extraction of mutation data from the literature

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This data was extracted from Medline abstracts and full texts (when available) in an automated manner.

The table below describes different point mutations at a given position and provides links to other documents. The sentence(s) where the point mutations in PRIO_HUMAN at position 199 were found are listed after the table.

Point mutations at position T199 in PRIO_HUMAN

ProteinPRIO_HUMAN (P04156)    Gene: PRNP    (other point mutations)Swiss-Prot
Cross-reference table
Family page
PositionT199
General numbering (PrionDB) -
DomainNot determined
Family alignments Mammalian prion proteins
Prion proteins (PRP, PRNP)
Other point mutations at the same position Position 199 in Mammalian prion proteins family
Position 199 in Prion proteins (PRP, PRNP) family
Reference #1Capellari S, Parchi P, Russo CM, Sanford J, Sy MS, Gambetti P, Petersen RB
Am J Pathol 2000 Aug;157(2):613-22.		Medline
Text sourceHTML full text
Point mutationT199A (True positive)
Reference #2DeArmond SJ, Sanchez H, Yehiely F, Qiu Y, Ninchak-Casey A, Daggett V, Camerino AP, Cayetano J, Rogers M, Groth D, Torchia M, Tremblay P, Scott MR, Cohen FE, Prusiner SB
Neuron 1997 Dec;19(6):1337-48.		Medline
Text sourceHTML full text
Point mutationT199A (Not yet checked)

Relevant sentences

Reference #1 (Capellari S et al.): T199A
  • Moreover , cell lines with PrP mutated at codon 181 or 199 , either combined or not with the E200K mutation (N181Q / 129M ; N181Q / 129M / E200K ; T199A / 129M ; T199A / 129M / E200K) , were constructed

  • Second , we used N181Q and T199A glycosylation knock-out mutants with or without the E200K substitution , and demonstrated a difference in mobility between the PrP M and PrP C I forms only in the 181-glycan knock-out (N181Q) mutant (Figure 2C)(image)

Reference #2 (DeArmond SJ et al.): T199A
  • When the second glycosylation site was mutated , the levels of SHaPrPC(T199A) were about the same as wild-type SHaPrPC ; however , SHaPrPC(T199A) appeared to be distributed to all neuronal compartments including the cell body , dendritic tree , and axons in the white matter (Figure 2 C)

  • Mutations in the Asn-Linked Glycosylation Consensus Sites Alter the Distribution of PrP in the Brains of Tg Mice Histoblots show the distribution of wild-type and mutant PrPC proteins in the hippocampus of Tg mice expressing (A) wild-type SHaPrPC , (B) SHaPrPC(T183A) , (C) SHaPrPC(T199A) , and (D) SHaPrP(T183A , T199A)

  • Of the three different mutant PrPs , only Tg (SHaPrP-T199A) mice were found to support PrPSc formation

  • We found that Sc237 scrapie prions but not the 139H strain transmitted to two Tg mouse lines expressing mutant SHaPrPC(T199A) (Table 1 ) (F

  • The level of expression of wild-type SHaPrPC and SHaPrPC(T199A) in the Tg mouse lines was estimated by comparing serially diluted dot blots of 10% brain homogenates from uninfected Tg mouse and Syrian hamster brains (Table 1 )

  • The concentrations of mutant SHaPrPC in Tg(SHaPrP-T199A)315 / Prnp0 / 0 and Tg(SHaPrP-T199A)317 / Prnp0 / 0 mice were similar to the amount of wild-type SHaPrPC expressed in the Tg(SHaPrP)81 / Prnp0 / 0 mouse line

  • Wild-Type SHaPrP View this table: [In this window] [In new window] Two lines of Tg(SHaPrP-T199A)Prnp0 / 0 mice were inoculated with Sc237 and 139H strains of prions

  • In contrast , Tg(SHaPrP)81 / Prnp0 / 0 mice expressing levels of wild-type SHaPrPC comparable to those in Tg(SHaPrP-T199A)Prnp0 / 0 mice exhibited incubation times of 50 days

  • The apparent slow conversion of mutant PrPC into PrPSc in Tg(SHaPrP-T199A)Prnp0 / 0 mice contrasts with the more rapid conversion of unglycosylated PrPC into PrPSc in scrapie-infected neuroblastoma cells (Taraboulos et al. 1990(image) The neuroanatomic distribution of mutant SHaPrPSc (T199A) deposition in Tg(SHaPrP-T199A)315 / Prnp0 / 0 and Tg(SHaPrP-T199A)317 / Prnp0 / 0 mice and the distribution of wild-type SHaPrPSc deposition in the Tg(SHaPrP)7 / Prnp0 / 0 and Tg(SHaPrP)81 / Prnp0 / 0 mouse lines were compared (Scott et al. 1989(image) wild-type SHaPrPSc in Tg(SHaPrP)7 / Prnp0 / 0 and in Tg(SHaPrP)81 / Prnp0 / 0 mice were similar , and the distributions of mutant SHaPrPSc in Tg(SHaPrP-T199A)315 / Prnp0 / 0 and in Tg(SHaPrP-T199A)317 / Prnp0 / 0 mice were similar ; however , the distributions of wild-type SHaPrPSc and mutant SHaPrPSc were markedly different (Figure 3 )

  • Finally , amyloid plaques composed of protease-resistant wild-type SHaPrPSc could be identified in both Tg(SHaPrP)7 / Prnp0 / 0 and Tg(SHaPrP)81 / Prnp0 / 0 mice by their amyloid-like deposits were identified in Tg(SHaPrP-T199A)315 / Prnp0 / 0 or Tg(SHaPrP-T199A)317 / Prnp0 / 0 mice

  • Regional Deposition of Wild-Type SHaPrPSc and Mutant SHaPrPSc(T199A) in Tg Mice Inoculated with the Sc237 Scrapie Prions Previously Passaged in Syrian Hamsters Histoblots of coronal brain sections through the thalamus and hippocampus were immunostained for protease-resistant PrPSc

  • (A and B) Deposition of wild-type SHaPrPSc in the brains of Tg(SHaPrP)7 / Prnp0 / 0 and Tg(SHaPrP)81 / Prnp0 / 0 mice and (C and D) mutant SHaPrPSc(T199A) in Tg(SHaPrP-T199A)315 / Prnp0 / 0 and Tg(SHaPrP-T199A)317 / Prnp0 / 0 mice

  • (E) Tg(SHaPrP-T199A)317 / Prnp0 / 0 mice inoculated with the 139H prion strain did not develop signs of scrapie , and no protease-resistant PrP accumulated in their brains ; only weak , nonspecific staining is seen

  • Similarly , no immunostaining was found in Tg(SHaPrP-T199A)315 / Prnp0 / 0 mice inoculated with 139H (not shown)

  • Relatively fewer charge isomers were seen when one of the two consensus sites was mutated to produce either SHaPrPC(T183A) or SHaPrPC(T199A) (Figure 4 B , Figure 4 C , Figure 4 F , and Figure 4 G)

  • (B and F) Mutant SHaPrPC(T199A) in hippocampus and cerebellum

  • (D) Mutant SHaPrPC(T183A , T199A) in hippocampus

  • View larger version: [In this window] [In new window] In both the hippocampus and cerebellum , more charge isomers with a wider pH range were found with mutation of the second Asn-linked glycosylation consensus site (T199A) (Figure 4 B and Figure 4 F) than with mutation of the first site (T183A) (Figure 4 C and Figure 4 G)

  • Mutation of the second consensus site (T199A) resulted in a shift toward neutral pH for the PrP charge isomers expressed in the the cerebellum compared to those in the hippocampus (Figure 4 B and Figure 4 F)

  • These results suggest that the first oligosaccharide linked to N181 is more sialylated than the one covalently bound to N197 ; furthermore , the higher concentration of PrPC(T199A) may reflect increased stability compared to PrPC(T183A)

  • Presumably , the retention of PrPC(T183A) in the cell body prevented it from trafficking to CLDs on the cell surface , where PrPSc formation is thought to occur (Gorodinsky and the finding that Tg(SHaPrP-T183A)Prnp0 / 0 mice were resistant to prions , while Tg(SHaPrP-T199A)Prnp0 / 0 mice developed scrapie but only after greatly prolonged incubation times (Table 1 )

  • Mutation of the second glycosylation site produced a PrPC(T199A) of which only a portion was abnormally sorted by the pyramidal neurons of the hippocampus , since both the cell bodies and the surrounding neuropil contained PrPC(T199A) (Figure 2 C)

  • Whether the abnormal trafficking of PrPC(T199A) or an aberrant conformation is responsible for the slowed formation of PrPSc in Tg(SHaPrP-T199A)Prnp0 / 0 mice requires further investigation

  • It is notable that the pattern of PrPSc accumulation in Tg(SHaPrP-T199A)Prnp0 / 0 mice was highly restricted compared to that in wild-type mice in spite of the greatly prolonged incubation times (Table 1 ; Figure 3 )

  • The three resulting mutant SHaPrPs were designated SHaPrP(T183A) , SHaPrP(T199A) , and SHaPrP(T183A , T199A)

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F.Horn (priondbcmbi.ru.nl), 22-Aug-2005