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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Amino Acid Motifs

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Disease relevance of Amino Acid Motifs


High impact information on Amino Acid Motifs

  • These studies illustrate that Notch-like EGF and discoidin/C domains, protein motifs that facilitate a variety of cellular interactions, participate in gamete recognition as well [6].
  • We have identified and characterized a novel family of mouse genes that share a protein motif, the T-box, with the prototypical T locus [7].
  • Although there is no obvious sequence similarity between HCF and other known proteins, HCF contains eight repeats of a new 26 amino acid motif. cDNAs encoding HCF predict a large open reading frame of 2035 codons [8].
  • In addition, both brm and SNF2 contain a 77 amino acid motif that is found in other Drosophila, yeast, and human regulatory proteins and may be characteristic of a new family of regulatory proteins [9].
  • SH2 regions are protein motifs capable of binding target protein sequences that contain a phosphotyrosine [10].

Chemical compound and disease context of Amino Acid Motifs

  • A highly conserved protein motif characteristic of Class II aminoacyl tRNA synthetases was found to align with a region of Escherichia coli asparagine synthetase A. The alignment was most striking for aspartyl tRNA synthetase, an enzyme with catalytic similarities to asparagine synthetase [11].
  • An aspartic acid at amino acid 108 is required to rescue infectious virus after transfection of a poliovirus cDNA containing a CGDD but not SGDD amino acid motif in 3Dpol [12].
  • The N-terminal metal binding extension of the Cu,Zn superoxide dismutase from Haemophilus ducreyi is constituted by a histidine-rich region followed by a methione-rich sequence which shows high similarity with protein motifs involved in the binding of Cu(I) [13].
  • Immunoblot analysis with the antipeptide antibody revealed cross-reactivity with native toxin, a recombinant protein containing the toxin A repeats, and a glucan-binding protein from Streptococcus mutans whose primary structure has repeating amino acid motifs similar to those of the synthetic peptide [14].
  • Orthologues of the putative S. aureus NAD(+)-dependent DNA ligase could be identified in the genomes of Bacillus stearothermophilus and other gram-positive bacteria and confirmed the presence of four conserved amino acid motifs, including motif I, KXDG with lysine 112, which is believed to be the proposed site of adenylation [15].

Biological context of Amino Acid Motifs


Anatomical context of Amino Acid Motifs


Associations of Amino Acid Motifs with chemical compounds

  • Synthetic ras peptides encompassing the common activating substitution of leucine for glutamine at position 61 were constructed with an amino acid motif appropriate for binding to the H-2Kb murine class I MHC molecule [26].
  • The introduction of alanine-scanning mutations within this membrane-proximal region did not prevent endoproteolytic release, indicating that a specific amino acid motif was not an absolute requirement for cleavage [27].
  • Analysis of the cytoplasmic domain of L-MAG identifies amino acid motifs at tyrosine 35 and tyrosine 65 which meet the criteria for "tyrosine internalization signals" that direct transmembrane glycoproteins into the endocytic pathway [28].
  • These interactions are dependent on the presence of the conserved amino acid motif WSPCSVTCG within the sequences of the constructs and are completely inhibited by several sulfated glycoconjugates as well as by suramin, a polysulfonated drug with anti-protozoan activity [29].
  • The granulin/epithelin protein motif has an unusual structure consisting of a parallel stack of beta-hairpins stapled together by six disulphide bonds [30].

Gene context of Amino Acid Motifs

  • However, most of the cooperative interactions arise from the YPWM amino-acid motif of Ultrabithorax-located amino-terminally to its homeodomain-which forms a reverse turn and inserts into a hydrophobic pocket on the Extradenticle homeodomain surface [31].
  • The amino acid motif QKRAA, when expressed on HLA-DRB1, carries susceptibility to develop rheumatoid arthritis [32].
  • Some members possess a death domain, a protein motif that functions to transmit apoptotic signals, whereas others, such as CD40, do not [33].
  • This interaction involves a conserved amino acid motif, which is critical for the silencing activity of TIF1beta but not TIF1alpha [34].
  • Bcd-dependent translational repression involves a portion of the PEST motif of Bcd, a conserved protein motif best known for its function in protein degradation [35].

Analytical, diagnostic and therapeutic context of Amino Acid Motifs


  1. Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. Reyes, G.R., Purdy, M.A., Kim, J.P., Luk, K.C., Young, L.M., Fry, K.E., Bradley, D.W. Science (1990) [Pubmed]
  2. NMR solution structure of a dsRNA binding domain from Drosophila staufen protein reveals homology to the N-terminal domain of ribosomal protein S5. Bycroft, M., Grünert, S., Murzin, A.G., Proctor, M., St Johnston, D. EMBO J. (1995) [Pubmed]
  3. Cloning and characterization of a p53 and DNA damage down-regulated gene PIQ that codes for a novel calmodulin-binding IQ motif protein and is up-regulated in gastrointestinal cancers. Luo, X., He, Q., Huang, Y., Sheikh, M.S. Cancer Res. (2005) [Pubmed]
  4. Characterization and mapping of the pyrophosphorolytic activity of the phage phi 29 DNA polymerase. Involvement of amino acid motifs highly conserved in alpha-like DNA polymerases. Blasco, M.A., Bernad, A., Blanco, L., Salas, M. J. Biol. Chem. (1991) [Pubmed]
  5. Encephalitogenic epitopes of myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein for experimental allergic encephalomyelitis induction in Biozzi ABH (H-2Ag7) mice share an amino acid motif. Amor, S., O'Neill, J.K., Morris, M.M., Smith, R.M., Wraith, D.C., Groome, N., Travers, P.J., Baker, D. J. Immunol. (1996) [Pubmed]
  6. Identification of mouse sperm SED1, a bimotif EGF repeat and discoidin-domain protein involved in sperm-egg binding. Ensslin, M.A., Shur, B.D. Cell (2003) [Pubmed]
  7. An ancient family of embryonically expressed mouse genes sharing a conserved protein motif with the T locus. Bollag, R.J., Siegfried, Z., Cebra-Thomas, J.A., Garvey, N., Davison, E.M., Silver, L.M. Nat. Genet. (1994) [Pubmed]
  8. The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein. Wilson, A.C., LaMarco, K., Peterson, M.G., Herr, W. Cell (1993) [Pubmed]
  9. brahma: a regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2. Tamkun, J.W., Deuring, R., Scott, M.P., Kissinger, M., Pattatucci, A.M., Kaufman, T.C., Kennison, J.A. Cell (1992) [Pubmed]
  10. Three-dimensional solution structure of the src homology 2 domain of c-abl. Overduin, M., Rios, C.B., Mayer, B.J., Baltimore, D., Cowburn, D. Cell (1992) [Pubmed]
  11. A relationship between asparagine synthetase A and aspartyl tRNA synthetase. Hinchman, S.K., Henikoff, S., Schuster, S.M. J. Biol. Chem. (1992) [Pubmed]
  12. An aspartic acid at amino acid 108 is required to rescue infectious virus after transfection of a poliovirus cDNA containing a CGDD but not SGDD amino acid motif in 3Dpol. Walker, D.E., McPherson, D., Jablonski, S.A., McPherson, S., Morrow, C.D. J. Virol. (1995) [Pubmed]
  13. X-ray absorption investigation of a unique protein domain able to bind both copper(I) and copper(II) at adjacent sites of the N-terminus of Haemophilus ducreyi Cu,Zn superoxide dismutase. D'Angelo, P., Pacello, F., Mancini, G., Proux, O., Hazemann, J.L., Desideri, A., Battistoni, A. Biochemistry (2005) [Pubmed]
  14. Antigenic cross-reactivity and functional inhibition by antibodies to Clostridium difficile toxin A, Streptococcus mutans glucan-binding protein, and a synthetic peptide. Wren, B.W., Russell, R.R., Tabaqchali, S. Infect. Immun. (1991) [Pubmed]
  15. Cloning and functional characterization of an NAD(+)-dependent DNA ligase from Staphylococcus aureus. Kaczmarek, F.S., Zaniewski, R.P., Gootz, T.D., Danley, D.E., Mansour, M.N., Griffor, M., Kamath, A.V., Cronan, M., Mueller, J., Sun, D., Martin, P.K., Benton, B., McDowell, L., Biek, D., Schmid, M.B. J. Bacteriol. (2001) [Pubmed]
  16. Crystal structure of a Pumilio homology domain. Wang, X., Zamore, P.D., Hall, T.M. Mol. Cell (2001) [Pubmed]
  17. The L6 gene for flax rust resistance is related to the Arabidopsis bacterial resistance gene RPS2 and the tobacco viral resistance gene N. Lawrence, G.J., Finnegan, E.J., Ayliffe, M.A., Ellis, J.G. Plant Cell (1995) [Pubmed]
  18. Two distinct gene subfamilies within the family of cysteine protease genes. Karrer, K.M., Peiffer, S.L., DiTomas, M.E. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  19. A strategy for making synthetic peptide vaccines. Ogasawara, K., Naruse, H., Itoh, Y., Gotohda, T., Arikawa, J., Kida, H., Good, R.A., Onoé, K. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  20. Cloning and chromosomal mapping of a human immunodeficiency virus 1 "TATA" element modulatory factor. Garcia, J.A., Ou, S.H., Wu, F., Lusis, A.J., Sparkes, R.S., Gaynor, R.B. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  21. Functional characterization of a signal transducing motif present in the T cell antigen receptor zeta chain. Irving, B.A., Chan, A.C., Weiss, A. J. Exp. Med. (1993) [Pubmed]
  22. Constitutive expression of calreticulin in osteoblasts inhibits mineralization. St-Arnaud, R., Prud'homme, J., Leung-Hagesteijn, C., Dedhar, S. J. Cell Biol. (1995) [Pubmed]
  23. dishevelled is required during wingless signaling to establish both cell polarity and cell identity. Theisen, H., Purcell, J., Bennett, M., Kansagara, D., Syed, A., Marsh, J.L. Development (1994) [Pubmed]
  24. Gene structure and cDNA sequence identify the beaded filament protein CP49 as a highly divergent type I intermediate filament protein. Hess, J.F., Casselman, J.T., FitzGerald, P.G. J. Biol. Chem. (1996) [Pubmed]
  25. Mice lacking the integrin beta5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state. Lane, N.E., Yao, W., Nakamura, M.C., Humphrey, M.B., Kimmel, D., Huang, X., Sheppard, D., Ross, F.P., Teitelbaum, S.L. J. Bone Miner. Res. (2005) [Pubmed]
  26. Lysis of ras oncogene-transformed cells by specific cytotoxic T lymphocytes elicited by primary in vitro immunization with mutated ras peptide. Peace, D.J., Smith, J.W., Chen, W., You, S.G., Cosand, W.L., Blake, J., Cheever, M.A. J. Exp. Med. (1994) [Pubmed]
  27. Structural requirements regulate endoproteolytic release of the L-selectin (CD62L) adhesion receptor from the cell surface of leukocytes. Chen, A., Engel, P., Tedder, T.F. J. Exp. Med. (1995) [Pubmed]
  28. Endocytic depletion of L-MAG from CNS myelin in quaking mice. Bö, L., Quarles, R.H., Fujita, N., Bartoszewicz, Z., Sato, S., Trapp, B.D. J. Cell Biol. (1995) [Pubmed]
  29. Thrombospondin related anonymous protein (TRAP) of Plasmodium falciparum binds specifically to sulfated glycoconjugates and to HepG2 hepatoma cells suggesting a role for this molecule in sporozoite invasion of hepatocytes. Müller, H.M., Reckmann, I., Hollingdale, M.R., Bujard, H., Robson, K.J., Crisanti, A. EMBO J. (1993) [Pubmed]
  30. The hairpin stack fold, a novel protein architecture for a new family of protein growth factors. Hrabal, R., Chen, Z., James, S., Bennett, H.P., Ni, F. Nat. Struct. Biol. (1996) [Pubmed]
  31. Structure of a DNA-bound Ultrabithorax-Extradenticle homeodomain complex. Passner, J.M., Ryoo, H.D., Shen, L., Mann, R.S., Aggarwal, A.K. Nature (1999) [Pubmed]
  32. A function for the QKRAA amino acid motif: mediating binding of DnaJ to DnaK. Implications for the association of rheumatoid arthritis with HLA-DR4. Auger, I., Roudier, J. J. Clin. Invest. (1997) [Pubmed]
  33. The effects of malignant transformation on susceptibility of human urothelial cells to CD40-mediated apoptosis. Bugajska, U., Georgopoulos, N.T., Southgate, J., Johnson, P.W., Graber, P., Gordon, J., Selby, P.J., Trejdosiewicz, L.K. J. Natl. Cancer Inst. (2002) [Pubmed]
  34. Interaction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family. Nielsen, A.L., Ortiz, J.A., You, J., Oulad-Abdelghani, M., Khechumian, R., Gansmuller, A., Chambon, P., Losson, R. EMBO J. (1999) [Pubmed]
  35. Sequence interval within the PEST motif of Bicoid is important for translational repression of caudal mRNA in the anterior region of the Drosophila embryo. Niessing, D., Dostatni, N., Jäckle, H., Rivera-Pomar, R. EMBO J. (1999) [Pubmed]
  36. Microinjection of anti-coilin antibodies affects the structure of coiled bodies. Almeida, F., Saffrich, R., Ansorge, W., Carmo-Fonseca, M. J. Cell Biol. (1998) [Pubmed]
  37. Processing of the Ebola virus glycoprotein by the proprotein convertase furin. Volchkov, V.E., Feldmann, H., Volchkova, V.A., Klenk, H.D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  38. Molecular cloning of translocation t(1;14)(q21;q32) defines a novel gene (BCL9) at chromosome 1q21. Willis, T.G., Zalcberg, I.R., Coignet, L.J., Wlodarska, I., Stul, M., Jadayel, D.M., Bastard, C., Treleaven, J.G., Catovsky, D., Silva, M.L., Dyer, M.J. Blood (1998) [Pubmed]
  39. Identification of the regulatory site in smooth muscle calponin that is phosphorylated by protein kinase C. Nakamura, F., Mino, T., Yamamoto, J., Naka, M., Tanaka, T. J. Biol. Chem. (1993) [Pubmed]
  40. Human TCR as antigen: homologies and potentially cross-reactive HLA-DR2-restricted epitopes within the AV and BV CDR2 loops. Vandenbark, A.A., Culbertson, N., Finn, T., Barnes, D., Buenafe, A., Burrows, G.G., Law, S., Chou, Y.K., Offner, H. Crit. Rev. Immunol. (2000) [Pubmed]
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