RILM: a web‐based resource to aid comparative and functional analysis of the insulin and IGF‐1 receptor family

The metazoan receptors for insulin (INSR), insulin‐like growth factor 1 (IGF1R), and other insulin‐like molecules are transmembrane tyrosine kinases involved in the regulation of cell size, cell proliferation, development, signaling of nutritional and environmental conditions, and aging. Historically, mutations in the human insulin receptor have been studied because such changes often lead to severe insulin resistance. More recently, amino acid sequence alterations in the insulin receptor‐like receptors of Drosophila melanogaster and Caenorhabditis elegans, as well as in the mouse insulin receptor have been the focus of attention. These modifications can have profound effects on growth, body size, metabolism, and aging. To integrate the many findings on insulin/IGF1 receptor structure and function across species we have created “Receptors for Insulin and Insulin‐like Molecules” (RILM), a curated computer‐based resource that displays residue‐by‐residue information on sequence homology, three‐dimensional structure, structure/function annotation, and documented mutations. The resource includes data obtained from sequence and structure analysis tools, primary database resources, and published reports. The information is integrated via a structure‐based multiple sequence alignment of diverse members of the family. RILM was designed to provide easy access to multiple data types that could prove useful in the analysis of the effect of mutations on protein structure and ligand binding within this receptor family. RILM is available at www.biochem.ucl.ac.uk/RILM. Hum Mutat 28(7), 660–668, 2007. © 2007 Wiley‐Liss, Inc.

[1]  M. Piggott Highlights of Australian Chemistry: Crystal Structure of the Insulin Receptor Ectodomain , 2006 .

[2]  M. Lawrence,et al.  Structure of the insulin receptor ectodomain reveals a folded-over conformation , 2006, Nature.

[3]  N. Mckern,et al.  The first three domains of the insulin receptor differ structurally from the insulin-like growth factor 1 receptor in the regions governing ligand specificity , 2006, Proceedings of the National Academy of Sciences.

[4]  Fabrice Armougom,et al.  Expresso: automatic incorporation of structural information in multiple sequence alignments using 3D-Coffee , 2006, Nucleic Acids Res..

[5]  Peng Yue,et al.  SNPs3D: Candidate gene and SNP selection for association studies , 2006, BMC Bioinformatics.

[6]  I. Hisatome,et al.  Mutation at cleavage site of insulin-like growth factor receptor in a short-stature child born with intrauterine growth retardation. , 2005, The Journal of clinical endocrinology and metabolism.

[7]  R. Baserga The insulin-like growth factor-I receptor as a target for cancer therapy , 2005, Expert opinion on therapeutic targets.

[8]  Modesto Orozco,et al.  PMUT: a web-based tool for the annotation of pathological mutations on proteins , 2005, Bioinform..

[9]  Sean D. Mooney,et al.  MutDB services: interactive structural analysis of mutation data , 2005, Nucleic Acids Res..

[10]  Sean D. Mooney,et al.  Bioinformatics approaches and resources for single nucleotide polymorphism functional analysis , 2005, Briefings Bioinform..

[11]  C. Kenyon The Plasticity of Aging: Insights from Long-Lived Mutants , 2005, Cell.

[12]  B. Groner,et al.  The insulin like growth factor-1 receptor (IGF-1R) as a drug target: novel approaches to cancer therapy. , 2004, Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society.

[13]  S. Brunak,et al.  Improved prediction of signal peptides: SignalP 3.0. , 2004, Journal of molecular biology.

[14]  Geoffrey J. Barton,et al.  The Jalview Java alignment editor , 2004, Bioinform..

[15]  L. Kuo,et al.  Structure of apo, unactivated insulin-like growth factor-1 receptor kinase at 1.5 A resolution. , 2003, Acta crystallographica. Section D, Biological crystallography.

[16]  Matthias Blüher,et al.  Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue , 2003, Science.

[17]  Martin Holzenberger,et al.  IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice , 2003, Nature.

[18]  J. Whittaker,et al.  Structural biology of insulin and IGF1 receptors: implications for drug design , 2002, Nature Reviews Drug Discovery.

[19]  Christopher T. Saunders,et al.  Evaluation of structural and evolutionary contributions to deleterious mutation prediction. , 2002, Journal of molecular biology.

[20]  P. Bork,et al.  Human non-synonymous SNPs: server and survey. , 2002, Nucleic acids research.

[21]  W. S. Valdar,et al.  Scoring residue conservation , 2002, Proteins.

[22]  M. Kasuga,et al.  [Mutations in the insulin receptor gene]. , 2002, Nihon rinsho. Japanese journal of clinical medicine.

[23]  Michael S Avidan,et al.  Regulation of Hypoxic Death in C. elegans by the Insulin/IGF Receptor Homolog DAF-2 , 2002, Science.

[24]  L. Dimeglio,et al.  Genotype-phenotype correlation in inherited severe insulin resistance. , 2002, Human molecular genetics.

[25]  Ourania Horaitis,et al.  Time for a unified system of mutation description and reporting: a review of locus-specific mutation databases. , 2002, Genome research.

[26]  M. Orozco,et al.  Characterization of disease-associated single amino acid polymorphisms in terms of sequence and structure properties. , 2002, Journal of molecular biology.

[27]  Y. Kido,et al.  Distinct and overlapping functions of insulin and IGF-I receptors. , 2001, Endocrine reviews.

[28]  A. Pautsch,et al.  Crystal structure of bisphosphorylated IGF-1 receptor kinase: insight into domain movements upon kinase activation. , 2001, Structure.

[29]  S. Henikoff,et al.  Predicting deleterious amino acid substitutions. , 2001, Genome research.

[30]  M. Tatar,et al.  A Mutant Drosophila Insulin Receptor Homolog That Extends Life-Span and Impairs Neuroendocrine Function , 2001, Science.

[31]  D. Chasman,et al.  Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation. , 2001, Journal of molecular biology.

[32]  Warren C. Lathe,et al.  Prediction of deleterious human alleles. , 2001, Human molecular genetics.

[33]  E. Hafen,et al.  An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control , 2001, Current Biology.

[34]  W. Müller,et al.  Origin of insulin receptor-like tyrosine kinases in marine sponges. , 1999, The Biological bulletin.

[35]  C. Yip,et al.  Quaternary structure of the insulin-insulin receptor complex. , 1999, Science.

[36]  K. Siddle,et al.  Single-molecule imaging of human insulin receptor ectodomain and its Fab complexes. , 1999, Journal of structural biology.

[37]  D. Riddle,et al.  Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. , 1998, Genetics.

[38]  N. Mckern,et al.  Crystal structure of the first three domains of the type-1 insulin-like growth factor receptor , 1998, Nature.

[39]  J. Thompson,et al.  The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. , 1997, Nucleic acids research.

[40]  N. Mckern,et al.  The Disulfide Bonds in the C-terminal Domains of the Human Insulin Receptor Ectodomain* , 1997, The Journal of Biological Chemistry.

[41]  S. Hubbard Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog , 1997, The EMBO journal.

[42]  Koutarou D. Kimura,et al.  daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. , 1997, Science.

[43]  S. J. Taylor,et al.  Insulin-like growth factor I receptor signaling in transformation by src oncogenes , 1997, Molecular and cellular biology.

[44]  C. Sander,et al.  Positioning hydrogen atoms by optimizing hydrogen‐bond networks in protein structures , 1996, Proteins.

[45]  B. Lamothe,et al.  Targeted disruption of the insulin receptor gene in the mouse results in neonatal lethality. , 1996, The EMBO journal.

[46]  R. Garofalo,et al.  The Drosophila insulin receptor is required for normal growth. , 1996, Endocrinology.

[47]  M. Billeter,et al.  MOLMOL: a program for display and analysis of macromolecular structures. , 1996, Journal of molecular graphics.

[48]  M. Frasch,et al.  The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. , 1995, The EMBO journal.

[49]  S. Hubbard,et al.  Crystal structure of the tyrosine kinase domain of the human insulin receptor , 1994, Nature.

[50]  D. Coppola,et al.  Effect of a null mutation of the insulin-like growth factor I receptor gene on growth and transformation of mouse embryo fibroblasts , 1994, Molecular and cellular biology.

[51]  Simeon I. Taylor,et al.  Two mutations in a conserved structural motif in the insulin receptor inhibit normal folding and intracellular transport of the receptor. , 1994, The Journal of biological chemistry.

[52]  C. Kenyon,et al.  A C. elegans mutant that lives twice as long as wild type , 1993, Nature.

[53]  J. Baker,et al.  Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r) , 1993, Cell.

[54]  N. Niikawa,et al.  Ring chromosome 15 involving deletion of the insulin-like growth factor 1 receptor gene in a patient with features of Silver-Russell syndrome. , 1993, Clinical dysmorphology.

[55]  L. Schäffer,et al.  Identification of a disulfide bridge connecting the alpha-subunits of the extracellular domain of the insulin receptor. , 1992, Biochemical and biophysical research communications.

[56]  E. Bonora,et al.  Detection of Mutations in Insulin Receptor Gene by Denaturing Gradient Gel Electrophoresis , 1992, Diabetes.

[57]  V. P. Knutson,et al.  Cellular trafficking and processing of the insulin receptor 1 , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[58]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[59]  L. Liotta,et al.  The type I insulin-like growth factor receptor is a motility receptor in human melanoma cells. , 1989, The Journal of biological chemistry.

[60]  P. Shier,et al.  Primary structure of a putative receptor for a ligand of the insulin family. , 1989, The Journal of biological chemistry.

[61]  G. Bell,et al.  Alternative splicing of human insulin receptor messenger RNA. , 1989, Biochemical and biophysical research communications.

[62]  T. Olson,et al.  Post-translational changes in tertiary and quaternary structure of the insulin proreceptor. Correlation with acquisition of function. , 1988, The Journal of biological chemistry.

[63]  W. Kabsch,et al.  Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical features , 1983, Biopolymers.

[64]  C. Kahn,et al.  Biosynthesis and glycosylation of the insulin receptor. Evidence for a single polypeptide precursor of the two major subunits. , 1983, The Journal of biological chemistry.

[65]  D. Riddle,et al.  Positive selection of Caenorhabditis elegans mutants with increased stress resistance and longevity. , 2003, Genetics.

[66]  C. Yip,et al.  Mechanism of transmembrane signaling: insulin binding and the insulin receptor. , 2000, Biochemistry.

[67]  M. Elmlinger,et al.  Cloning and sequencing of the complete cDNA encoding the human insulin receptor related receptor. , 1999, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[68]  H. Werner,et al.  The insulin-like growth factor-I receptor signaling pathways are important for tumorigenesis and inhibition of apoptosis. , 1997, Critical reviews in oncogenesis.

[69]  Mark D. Johnson,et al.  Early neonatal death in mice homozygous for a null allele of the insulin receptor gene , 1996, Nature Genetics.

[70]  D. Accili,et al.  Homozygosity for a null allele of the insulin receptor gene in a patient with leprechaunism , 1995, Human mutation.

[71]  Piotr Mikolajczyk,et al.  A+A+C , 1964 .