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 198 were found are listed after the table.

Point mutations at position F198 in PRIO_HUMAN

ProteinPRIO_HUMAN (P04156)    Gene: PRNP    (other point mutations)Swiss-Prot
Cross-reference table
Family page
PositionF198
General numbering (PrionDB) -
DomainNot determined
Family alignments Mammalian prion proteins
Prion proteins (PRP, PRNP)
Other point mutations at the same position Position 198 in Mammalian prion proteins family
Position 198 in Prion proteins (PRP, PRNP) family
Reference #1Mallucci GR, Campbell TA, Dickinson A, Beck J, Holt M, Plant G, de Pauw KW, Hakin RN, Clarke CE, Howell S, Davies-Jones GA, Lawden M, Smith CM, Ince P, Ironside JW, Bridges LR, Dean A, Weeks I, Collinge J
Brain 1999 Oct;122 ( Pt 10):1823-37.		Medline
Text sourceHTML full text
Point mutationF198S (True positive)
Reference #2Zuegg J, Gready JE
Biochemistry 1999 Oct 19;38(42):13862-76.		Medline
Text sourceHTML and PDF full texts
Point mutationF198S (True positive)
Reference #3Tagliavini F, Lievens PM, Tranchant C, Warter JM, Mohr M, Giaccone G, Perini F, Rossi G, Salmona M, Piccardo P, Ghetti B, Beavis RC, Bugiani O, Frangione B, Prelli F
J Biol Chem 2001 Feb 23;276(8):6009-15.		Medline
Text sourceHTML full text
Point mutationF198S (True positive)
Reference #4Piccardo P, Liepnieks JJ, William A, Dlouhy SR, Farlow MR, Young K, Nochlin D, Bird TD, Nixon RR, Ball MJ, DeCarli C, Bugiani O, Tagliavini F, Benson MD, Ghetti B
Am J Pathol 2001 Jun;158(6):2201-7.		Medline
Text sourceHTML full text
Point mutationF198S (True positive)
Reference #5Daniels M, Cereghetti GM, Brown DR
Eur J Biochem 2001 Dec;268(23):6155-64.		Medline
Text sourceabstract
Point mutationF198S (True positive)
Reference #6Mastrangelo P, Serpell L, Dafforn T, Lesk A, Fraser P, Westaway D
FEBS Lett 2002 Dec 4;532(1-2):21-6.		Medline
Text sourceHTML and PDF full texts
Point mutationF198S (True positive)
Reference #7Apetri AC, Surewicz K, Surewicz WK
J Biol Chem 2004 Apr 23;279(17):18008-14. Epub 2004 Feb 2.		Medline
Text sourceHTML full text
Point mutationF198S (True positive)
Reference #8Piccardo P, Seiler C, Dlouhy SR, Young K, Farlow MR, Prelli F, Frangione B, Bugiani O, Tagliavini F, Ghetti B
J Neuropathol Exp Neurol 1996 Nov;55(11):1157-63.		Medline
Text sourceabstract
Point mutationF198S (True positive)
Reference #9Hegde RS, Mastrianni JA, Scott MR, DeFea KA, Tremblay P, Torchia M, DeArmond SJ, Prusiner SB, Lingappa VR
Science 1998 Feb 6;279(5352):827-34.		Medline
Text sourceHTML full text
Point mutationF198S (Not yet checked)
Reference #10Parchi P, Chen SG, Brown P, Zou W, Capellari S, Budka H, Hainfellner J, Reyes PF, Golden GT, Hauw JJ, Gajdusek DC, Gambetti P
Proc Natl Acad Sci U S A 1998 Jul 7;95(14):8322-7.		Medline
Text sourceHTML full text
Point mutationF198S (Not yet checked)
Reference #11Riek R, Wider G, Billeter M, Hornemann S, Glockshuber R, Wuthrich K
Proc Natl Acad Sci U S A 1998 Sep 29;95(20):11667-72.		Medline
Text sourceHTML and PDF full texts
Point mutationF198S (True positive)
Reference #12Prusiner SB
Proc Natl Acad Sci U S A 1998 Nov 10;95(23):13363-83.		Medline
Text sourceHTML full text
Point mutationF198S (Not yet checked)

Relevant sentences

Reference #1 (Mallucci GR et al.): F198S
  • Homozygosity at PRNP codon 129 , where methionine or valine can be encoded , increases susceptibility to sporadic (Palmer et al. , 1991(image) ) , iatrogenic (Collinge et al. , 1991a(image) ) and variant CJD (Collinge et al. , 1996) ; it also reduces age at onset of disease in inherited prion disease with the 144 bp insertion (Poulter et al. , 1992(image) ) and in inherited prion disease F198S

Reference #2 (Zuegg J et al.): F198S
  • The amino acid residues in black boxes are mutation sites known to be associated with inherited forms of PrP diseases in humans [CJD , D178N:129V (3) , V180I (3) , T183A (3) , E200K (3) , R208H (3) , V210I (3) , and M232R (3) ; GSS , P102L (3) , P105L (3) , A117V (3) , Y145Stop (3) , H187R (14) , F198S (3) , D202N (13) , Q212P (13) , and Q217R (3) ; FFI , D178N:129M (3) ; schizophrenia , N171S (12) ] , while in light gray boxes residues involved in some polymorphisms influencing these diseases are shown [M129V (3) , E219K (11) ]

Reference #3 (Tagliavini F et al.): F198S
  • INTRODUCTION (image)TOP (image)ABSTRACT (image)INTRODUCTION (image)EXPERIMENTAL PROCEDURES (image)RESULTS (image)DISCUSSION (image)REFERENCES Gerstmann-Sträussler-Scheinker disease (GSS)1 is an adult-onset neurodegenerative disorder (1 , 2 ) that is inherited as an autosomal dominant trait and segregates with variant genotypes resulting from the combination of a pathogenic mutation (P102L , P105L , A117V , F198S , D202N , Q212P , and Q217R) and a common polymorphism at codon 129 (Met / Val) in the prion protein (PrP) gene (PRNP) (3-9 )

  • In previous studies we have determined the biochemical composition of amyloid fibrils extracted from brain tissue of patients with mutations F198S and Q217R in PRNP

  • As previously observed in the Indiana kindred of GSS with F198S mutation (32 ) , the relative abundance of the low molecular weight fragment was not dependent upon the extent of amyloid burden

  • Notably , the degree of protease resistance of this peptide was lower than that of other GSS mutant proteins since , unlike analogous fragments from patients with F198S and Q217R PrP variants , it was completely degraded in the presence of SDS

  • Similar to previous studies on GSS F198S and Q217R , this fragment was derived from the mutant allele since only Val was found at position 117 and 129 (18 )

  • The top diagram illustrates the polypeptide chain of mature human PrP with the octapeptide repeat region , the common Met / Val polymorphism at codon 129 , and the mutations A117V , F198S , and Q217R associated with GSS

  • The first four PrP fragments correspond to amyloid peptides isolated from four GSS patients with F198S , Q217R , and A117V (present case) mutation

Reference #4 (Piccardo P et al.): F198S
  • 2001 ; 158:2201-2207.) © 2001 American Society for Investigative Pathology ------------------------------------------------------------------------ Regular Article Prion Proteins with Different Conformations Accumulate in Gerstmann-Sträussler-Scheinker Disease Caused by A117V and F198S Mutations Pedro Piccardo *{dagger} , Juris J

  • Purified GSS amyloid is composed primarily of ~7-kd PrP peptides , whose N terminus corresponds to residues W81 and G88 to G90 in patients with the A117V mutation and to residue W81 in patients with the F198S mutation

  • The aim of this study was to characterize PrP in brain extracts , microsomal preparations , and purified fractions from A117V patients and to determine the N terminus of PrP sc species in both GSS A117V and F198S

  • Conversely , in all patients with GSS F198S , an ~8-kd PrP sc fragment was isolated having the major N terminus start at residue G74

  • The finding that patients with GSS A117V and F198S accumulate PrP sc fragments of different size and N-terminal sequence , suggests that these mutations generate two distinct PrP conformers

  • 3 GSS is caused by mutations P102L , P105L , A117V , G131V , F198S , D202N , Q212P , and Q217R in PRNP

  • 10 -13 , 14 , 15 Previous studies showed that the amyloid subunit in GSS F198S is a 7-kd peptide with an N terminus at residue G81.16 Similar studies in patients from one American and one Alsatian family with GSS A117V revealed that the 7-kd amyloid protein had a major N-terminal cleavage site at residue G81 and G88 to G90.17 -18 In addition , we have reported on the presence of PrP sc isoforms of ~27 to 29 , 18 to 19 , and 8 kd in brain extracts and microsomal fractions of patients from the Indiana kindred with GSS F198S

  • To explore this possibility , we determined the N-terminal cleavage sites of the PrP fragments that accumulate in GSS A117V and GSS F198S

  • Materials and Methods (image)Top (image)Abstract (image)Introduction (image)Materials and Methods (image)Results (image)Discussion (image)References The experiments were performed using brain tissue from individuals carrying PRNP mutations A117V and F198S

  • The Clinical , Genetic , and Pathological Information for Five GSS A117V Patients and One Asymptomatic A117V Mutation Carrier ; and for Two GSS F198S Patients is Summarized Biochemical Assays Tissue was obtained from six subjects with PRNP A117V

  • Tissue was obtained from the frontal cortex and cerebellum of a patient of the Indiana kindred (GSS F198S) heterozygous for the M / V polymorphism at codon 129

  • Determination of the N-Terminal Cleavage Site of PrP Fragments in Patients with GSS A117V and GSS F198S To characterize the primary structure of the 7-kd PrP sc fragment , partially purified and PK-treated PrP obtained from the frontal cortex of patients with GSS A117V (ie , patients 1 to 5) was analyzed using Edman chemistry , after resolution of fragments by gel electrophoresis (see Materials and Methods)

  • Patients with GSS F198S and GSS A117V accumulate PrP sc fragments that can be cleaved by PK to generate peptides of different mobility (ie , the small fragment is 7 kd in GSS A117V and 8 kd in GSS F198S) in gel electrophoresis

  • To explore this possibility , we analyzed the 8-kd PrP sc fragment obtained from the frontal cortex of two patients with GSS F198S (Figure 5)(image)

  • This indicates PK cleavage in the second PrP octarepeat region for GSS F198S , different from the PK cleavage site for GSS A117V

  • To analyze the possibility that different PrP conformers might be present in different brain areas , we determined the N-terminal sequence of PrP sc purified from the caudate nucleus (an area with absent or small amounts of amyloid) , and the cerebellum (a region with abundant amyloid) in a homozygous 129 V patient with GSS F198S

  • Studies on amyloid fractions have previously shown that patients with GSS F198S accumulate amyloid peptides of ~11 kd spanning residues 58 to 150

  • 32 Further analysis showed that the smallest amyloid subunit in GSS F198S and GSS Q217R corresponds to a 7-kd fragment comprising residues W81 to Y150 and W81 to E146 , respectively.16 In addition , preliminary data on a patient of an American family with GSS A117V showed a similar fibrillogenic fragment with a ragged N terminus corresponding to W81 , G82 , and Q83 and the C terminus at E146.17 Thus , patients with these GSS variants may accumulate amyloid subunits of similar size and primary structure , despite the different genotypes and phenotypic presentations

  • Therefore , to expand our studies we purified PrP sc from patients of the Indiana kindred with GSS F198S and determined the N-terminal cleavage site of the ~8-kd fragment isolated from areas with and without amyloid accumulation

  • In view of the fact that the smallest amyloidogenic fragment has a mobility of ~7 kd and N terminus at W81 and PrPsc peptides of ~8 kd have an N terminus at G74 , we speculate that sequential proteolytic cleavage of a precursor PrP sc fragment generates fibrillogenic peptides in GSS F198S

  • In conclusion , the data obtained in the GSS variants analyzed in this study demonstrate that N- and C-truncated PrP isoforms of different size and N-termini , accumulate in GSS A117V and GSS F198S

  • The results show that octarepeats 3 and 4 are an integral part of the 8-kd peptide present in GSS F198S , but not in the 7-kd fragments detected in patients with GSS A117V

Reference #5 (Daniels M et al.): F198S
  • Human mutations E200K and F198S were found to enhance toxicity of PrP121-231 to PrP-knockout neurones and E200K enhanced toxicity to wild-type neurones

Reference #6 (Mastrangelo P et al.): F198S
  • Since the remaining GSS mutations (G131V , H178R , F198S , D202N , Q212P and Q217R) do not result in the creation of amino acid residues that are also conserved in Dpl , the hypothesis that GSS PRNP alleles result in PrPC molecules more Dpl-like than wt PrPC was rejected

Reference #7 (Apetri AC et al.): F198S
  • All variants containing mutations linked to familial prion diseases (P102L , D178N with 129M and 129V polymorphism , V180I , F198S , E200K , R208H , V210I , and Q217R) were constructed on the background of W99F / Y218W huPrP-(90-231) (21 ) by site-directed mutagenesis using appropriate primers and the QuikChange kit (Stratagene)

  • Fig. 2 shows representative equilibrium unfolding curves for the wild-type huPrP-(90-231) and the F198S variant

  • Urea-induced equilibrium unfolding for wild-type huPrP-(90-231) (circles) and the F198S variant (triangles)

  • The results of such experiments for two huPrP-(90-231) variants , F198S and V210I , are shown in Fig. 5

  • The control experiments described above were especially important for the F198S variant because the latter protein was reported to undergo time-dependent conversion to an oligomeric scrapie-like form (35 )

  • The effect of protein concentration on refolding kinetics of huPrP-(90-231) variants F198S and V210I

  • In the case of the F198S variant , the estimated population of the I state is as high as 1:350

Reference #8 (Piccardo P et al.): F198S
  • A GSS disease variant with mutation at codon 198 (F198S) has been studied in a large Indiana kindred

  • In the present paper , we analyzed proteinase-K (PK)-resistant PrP in 7 patients with GSS F198S disease

  • Our findings suggest that brain extracts from GSS F198S disease contain 3 prominent nonglycosylated PK-resistant PrP fragments forming a pattern not previously described in other prion diseases , which may in part explain the pathology of this GSS disease variant.

Reference #9 (Hegde RS et al.): F198S
  • Prion Proteins with Different Conformations Accumulate in Gerstmann-Straussler-Scheinker Disease Caused by A117V and F198S Mutations

Reference #10 (Parchi P et al.): F198S
  • In contrast , purified amyloid preparations from GSS affected subjects carrying the Y145STOP , F198S , A117V , or Q217R mutations were shown to contain PrP-res fragments of 11 and 7 kDa with ragged N and C termini (6 , 7 )

  • Of interest , a 19-kDa PrP-res fragment , although supposedly not glycosylated , has been detected in GSS F198S (25 )

  • The presence of a type 1 PrP-res in GSS P102L and of a type 2 PrP-res in GSS F198S would be consistent with the fact that , as shown for sporadic CJD , valine at codon 129 , which is invariably linked to the F198S mutation , favors the formation of PrP-res type 2 whereas methionine , which cosegregates with the P102L mutation , usually is associated with PrP-res type 1 (5 )

  • Ghetti Prion Proteins with Different Conformations Accumulate in Gerstmann-Straussler-Scheinker Disease Caused by A117V and F198S Mutations Am

Reference #11 (Riek R et al.): F198S
  • Close-ups of individual mutation sites: (a) D178N and T183A , (b) Q217R , (c) F198S , and (d) V180I and V210I

  • (c) The orange transparent surface represents the empty space that would be left after the amino acid replacement F198S in the absence of any subsequent structural rearrangement

Reference #12 (Prusiner S et al.): F198S
  • Surewicz Disease-associated F198S Mutation Increases the Propensity of the Recombinant Prion Protein for Conformational Conversion to Scrapie-like Form J

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