EMAIL THIS PAGE TO A FRIEND

Molecular and cellular biology

Age-related macular degeneration-associated silent polymorphisms in HtrA1 impair its ability to antagonize insulin-like growth factor 1.


PMID 23478260

Abstract

Synonymous single nucleotide polymorphisms (SNPs) within a transcript's coding region produce no change in the amino acid sequence of the protein product and are therefore intuitively assumed to have a neutral effect on protein function. We report that two common variants of high-temperature requirement A1 (HTRA1) that increase the inherited risk of neovascular age-related macular degeneration (NvAMD) harbor synonymous SNPs within exon 1 of HTRA1 that convert common codons for Ala34 and Gly36 to less frequently used codons. The frequent-to-rare codon conversion reduced the mRNA translation rate and appeared to compromise HtrA1's conformation and function. The protein product generated from the SNP-containing cDNA displayed enhanced susceptibility to proteolysis and a reduced affinity for an anti-HtrA1 antibody. The NvAMD-associated synonymous polymorphisms lie within HtrA1's putative insulin-like growth factor 1 (IGF-1) binding domain. They reduced HtrA1's abilities to associate with IGF-1 and to ameliorate IGF-1-stimulated signaling events and cellular responses. These observations highlight the relevance of synonymous codon usage to protein function and implicate homeostatic protein quality control mechanisms that may go awry in NvAMD.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

05-172
Anti-IGF-I Antibody, clone Sm1.2, Anti-IGF-I Antibody, clone Sm1.2 is an antibody against IGF-I for use in IH, IP, NEUT & WB.
T6763 Trypsin Acetylated from bovine pancreas, Type V-S, ≥8,500 BAEE units/mg protein (biuret)
T1005
Trypsin from bovine pancreas, Type XI, lyophilized powder, ≥6,000 BAEE units/mg protein
T8658
Trypsin from bovine pancreas, suitable for protein sequencing, lyophilized powder
T7309
Trypsin from bovine pancreas, ≥2,500 USP units/mg solid, meets USP testing specifications
T9935
Trypsin from bovine pancreas, essentially salt-free, lyophilized powder, ≥9,000 BAEE units/mg protein, BioReagent, suitable for cell culture
T9201
Trypsin from bovine pancreas, powder, ≥7,500 BAEE units/mg solid
T6424 Trypsin from human pancreas, salt-free, lyophilized powder, vial of ≥1,000 BAEE units
T7409 Trypsin from porcine pancreas, lyophilized powder, Type II-S, 1,000-2,000 units/mg dry solid
T5266 Trypsin from porcine pancreas, lyophilized powder, γ-irradiated, BioXtra, suitable for cell culture, 1,000-2,000 BAEE units/mg solid
T7168 Trypsin from porcine pancreas, tablet, 1 mg tablet
93614 Trypsin from porcine pancreas, ≥10000 U/mg
93615 Trypsin from porcine pancreas, ~1500 U/mg
85450C Trypsin Powder, Porcine 1:250, Gamma irradiated by SER-TAIN Process, dry powder
T3568 TrypZean® bovine, recombinant, expressed in corn, lyophilized powder, ≥3,350 units/mg solid (USP)