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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P49768: Variant p.Met233Leu

Presenilin-1
Gene: PSEN1
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Variant information Variant position: help 233
Type of variant: help LP/P [Disclaimer]
Residue change: help From Methionine (M) to Leucine (L) at position 233 (M233L, p.Met233Leu).
Physico-chemical properties: help Similar physico-chemical property. Both residues are medium size and hydrophobic.
BLOSUM score: help 2
Variant description: help In AD3; slightly decreased protease activity with APP resulting in altered amyloid-beta production and mildly increased amyloid-beta 42/amyloid-beta 40 ratio.
Other resources: help


Sequence information Variant position: help 233
Protein sequence length: help 467
Location on the sequence: help IHWKGPLRLQQAYLIMISAL M ALVFIKYLPEWTAWLILAVI
Sequence annotation in neighborhood: help
TypePositionsDescription
Chain 1 – 298 Presenilin-1 NTF subunit
Transmembrane 221 – 241 Helical
Alternative sequence 185 – 467 Missing. In isoform 4.
Mutagenesis 214 – 214 H -> D. Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Mutagenesis 219 – 219 L -> F. Decreased protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Mutagenesis 223 – 223 Q -> R. Abolishes protease activity with APP.
Mutagenesis 226 – 226 L -> F. Increases protease activity with APP.
Mutagenesis 230 – 230 S -> I. Abolishes protease activity with APP.
Mutagenesis 238 – 238 I -> M. Abolishes protease activity with APP.
Mutagenesis 239 – 239 K -> N. Abolishes protease activity with APP.
Mutagenesis 245 – 245 T -> P. Abolishes protease activity with APP.
Mutagenesis 248 – 248 L -> R. Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Helix 219 – 239



Literature citations
DGGE method for the mutational analysis of the coding and proximal promoter regions of the Alzheimer's disease presenilin-1 gene: two novel mutations.
Aldudo J.; Bullido M.J.; Valdivieso F.;
Hum. Mutat. 14:433-439(1999)
Cited for: VARIANTS AD3 LEU-233; ARG-282 AND THR-409; VARIANT GLY-318; Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations.
Rogaeva E.A.; Fafel K.C.; Song Y.Q.; Medeiros H.; Sato C.; Liang Y.; Richard E.; Rogaev E.I.; Frommelt P.; Sadovnick A.D.; Meschino W.; Rockwood K.; Boss M.A.; Mayeux R.; St George-Hyslop P.;
Neurology 57:621-625(2001)
Cited for: VARIANTS AD3 GLN-35; VAL-79; CYS-115; ASN-116; THR-143; ILE-146; LEU-146; VAL-146; TYR-156 DELINS PHE-THR-TYR; ARG-163; LEU-177; SER-177; PRO-178; ALA-206; SER-206; GLU-209; LEU-213; ARG-222; THR-231; LEU-233; PRO-235; PHE-261; ARG-274; ARG-352 INS; ILE-354; GLN-358; TYR-365; VAL-394; PHE-418; GLU-431; PHE-435 AND VAL-439; VARIANT GLY-318; Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Abeta42 and Abeta40 peptides by gamma-secretase.
Sun L.; Zhou R.; Yang G.; Shi Y.;
Proc. Natl. Acad. Sci. U.S.A. 114:E476-E485(2017)
Cited for: CHARACTERIZATION OF VARIANTS AD3 GLN-35; VAL-79; LEU-82; PRO-85; LEU-89; SER-92; MET-94; PHE-96; LEU-97; HIS-115; ASN-116; ASP-120; LYS-120; ARG-134; ASP-135; VAL-139; THR-143; LEU-146; ILE-147; VAL-153; ASN-154; ARG-163; TYR-163; PRO-166; PRO-169; PHE-170; PRO-171; TRP-173; MET-174; LEU-177; PRO-178; VAL-183; ASP-184; ALA-206; SER-206; ARG-209; VAL-209; LEU-213; ARG-217; ARG-222; PHE-229; THR-231; LEU-233; THR-233; ARG-235; PRO-235; VAL-235; ILE-237; GLU-246; SER-250; VAL-260; PHE-261; PHE-262; ARG-263; LEU-264; SER-266; SER-267; GLY-269; VAL-271; ARG-274; VAL-275; ALA-280; GLY-280; ARG-282; VAL-285; VAL-286; ILE-354; GLN-358; GLU-378; VAL-378; VAL-381; ALA-384; ILE-390; VAL-392; VAL-394; THR-396; SER-405; THR-409; TYR-410; PHE-418; PRO-426; GLU-431; PHE-435; SER-436 AND VAL-439; CHARACTERIZATION OF VARIANT CMD1U GLY-333; MUTAGENESIS OF THR-99; PHE-105; ARG-108; LEU-113; PRO-117; GLU-123; HIS-131; ALA-136; ILE-143; LEU-150; TRP-165; ILE-168; PHE-176; GLU-184; ILE-202; SER-212; HIS-214; LEU-219; GLN-223; LEU-226; SER-230; ILE-238; LYS-239; THR-245; LEU-248; TYR-256; VAL-272; GLU-273; ARG-278; PRO-284; THR-291; ARG-352; SER-365; ARG-377; PHE-386; VAL-391; VAL-412; LEU-420; LEU-424; ALA-434 AND ILE-437;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.