The fukutin protein family – predicted enzymes modifying cell-surface molecules
نویسندگان
چکیده
Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive disorder that is observed predominantly in Japanese populations [1]. Recently, the cause of this syndrome was discovered to be lesions in the gene encoding the protein fukutin; these lesions involve retroposon insertion and point mutations, which result in a truncated protein [2]. Consistent with the phenotypic patterns of the disease, the fukutin mRNA has been found in skeletal muscles, heart, brain and pancreas [2]. Fukutin contains a signal peptide and is localized to the Golgi and secretory granules [2]. Here, we report on a detailed computer analysis of the fukutin protein sequence, resulting in the prediction that it is an enzyme that modifies cell-surface glycoproteins or glycolipids. A gapped BLASTP [3] search of the non-redundant (NR) database at the National Center for Biotechnology Information using the fukutin sequence as the query revealed significant hits (with evalues < 10–9) not only to Caenorhabditis elegans proteins, such as T07D3.4 and T07A5.1, but also to the uncharacterized protein RP688 from the intracellular parasitic bacterium Rickettsia prowazekii (e < 10–4). The RP688 sequence was used for further analysis of this protein family by iteratively searching the NR database using the PSI-BLAST program, which was run with the cut-off of e = 0.001 [3]. At convergence, not only fukutin and its C. elegans homologs, but also bacterial proteins involved in polysaccharide/phosphorylcholine modification and a yeast protein involved in mannosyl phosphorylation of oligosaccharides were retrieved from the database. Reverse searches with these sequences retrieved the original members of the fukutin family without any false positives. Fukutin, therefore, belongs to a family of proteins associated with the modification of the cell surface. A multiple alignment of the fukutin protein family was constructed using Gibbs sampling, as implemented in PROBE [4], in conjunction with the –m4 option of PSI-BLAST (Figure 1). The alignment shows prominent conservation in an amino-terminal block, followed by a weakly conserved carboxy-terminal region. The most notable feature of the amino-terminal region is the presence of the strictly conserved signature G[TS]hhGhhx4hhxaxxDxD (in single-letter amino acid code and in which ‘h’ is a hydrophobic amino acid, ‘a’ is an aromatic amino acid and ‘x’ denotes any amino acid). A pattern search with this motif recovers from the NR database the fukutin family in its entirety without any false positives. The carboxy-terminal region contains a motif with a conserved aspartate residue flanked by hydrophobic residues (Figure 1). Secondary structure prediction using the PHD program [5] suggests a compact α/β fold for the fukutin domain (Figure 1). LicD2 from Streptococcus pneumoniae is involved in the addition R836 Current Biology Vol 9 No 22
منابع مشابه
Pathogenic interactions between Helicobacter pylori adhesion protein HopQ and human cell surface adhesion molecules CEACAMs in gastric epithelial cells
Objective(s): The present paper aims to review the studies describing the interactions between HopQ and CEACAMs along with possible mechanisms responsible for pathogenicity of Helicobacter pylori.Materials and Methods: The literature was searched on “PubMed” using different key words including Helicobacter pylori, CEACAM and gastric.<br ...
متن کاملProteoglycans and neuronal migration in the cerebral cortex during development and disease
Chondroitin sulfate proteoglycans and heparan sulfate proteoglycans are major constituents of the extracellular matrix and the cell surface in the brain. Proteoglycans bind with many proteins including growth factors, chemokines, axon guidance molecules, and cell adhesion molecules through both the glycosaminoglycan and the core protein portions. The functions of proteoglycans are flexibly regu...
متن کاملZebrafish Fukutin family proteins link the unfolded protein response with dystroglycanopathies
Allelic mutations in putative glycosyltransferase genes, fukutin and fukutin-related protein (fkrp), lead to a wide range of muscular dystrophies associated with hypoglycosylation of α-dystroglycan, commonly referred to as dystroglycanopathies. Defective glycosylation affecting dystroglycan-ligand interactions is considered to underlie the disease pathogenesis. We have modelled dystroglycanopat...
متن کاملPreparation of heavy chain polyclonal antibody against zinc transporter SLC39A6 and its diagnostic application
Background: SLC39A6 Protein (solute carrier family 39) or LIV-1 is a zinc transporter protein that is overexpressed in positive estrogen cancers such as breast cancer. The LIV-1 protein transfer zinc into the cytoplasm through the plasma membrane. Today it is known that just as a decrease in the concentration of zinc in the cell can cause cancer, an excessive increase in the concentration of zi...
متن کاملP-201: The Role of P53 Family Members in Infertility
Background: P53, p63, and p73 transcription factors which are belong to The p53 family, are conserved during evolution. They have important roles in many molecular and cellular functions, including tumor suppression, the development of epithelial cell layers, and the development of central nervous system and immune system. Studies show these molecules also have role in maintaining the genomic i...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Current Biology
دوره 9 شماره
صفحات -
تاریخ انتشار 1999