Nucleic Acids Research, 2000, Vol. 28, No. 1 231-234
© 2000 Oxford University Press
SMART: a web-based tool for the study of genetically mobile domains
1EMBL, Meyerhofstrasse1, 69012 Heidelberg, Germany, 2Max-Delbrück-Center, Berlin-Buch, Germany and 3MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK
Received September 30, 1999; Accepted October 4, 1999.
| ABSTRACT |
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SMART (a Simple Modular Architecture Research Tool) allows the identification and annotation of genetically mobile domains and the analysis of domain architectures (http://SMART.embl-heidelberg.de ). More than 400 domain families found in signalling, extracellular and chromatin-associated proteins are detectable. These domains are extensively annotated with respect to phyletic distributions, functional class, tertiary structures and functionally important residues. Each domain found in a non-redundant protein database as well as search parameters and taxonomic information are stored in a relational database system. User interfaces to this database allow searches for proteins containing specific combinations of domains in defined taxa.
| INTRODUCTION |
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The explosion of sequence data increases the need for computational sequence analysis tools that annotate novel genes with predicted functions. Function prediction, however, is fraught with potential pitfalls such as considerable sequence divergence, non-equivalent functions of homologues and non-identical multi-domain architectures (1). Detecting non-enzymatic regulatory domains is essential to predict a proteins cellular role, binding partners and subcellular localisation. Such domains are usually divergent in sequence and occur in contrasting multi-domain contexts. This leads to difficulties unravelling the evolution and function of multi-domain proteins. These problems are addressed by the SMART Web tool, which was first described by Schultz et al. (2) as a database for signalling domains. Here we report on the expansion of SMARTs domain coverage, its relational database system and the development of new Web tools for the analysis of mobile domains.
| THE SMART ALIGNMENT SET |
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Domain detection in SMART relies on multiple sequence alignments of representative family members (2). In the past year, we have improved the alignment construction method to achieve higher levels of reproducibility and have increased the number of domain families detectable by SMART. Older alignments have been updated to integrate new homology and structural findings. As a consequence, SMART alignments are of high quality and have been exploited in recent comparative genomics studies (e.g., 35).
Alignment construction protocol
The starting point for the construction of a multiple sequence alignment that optimally represents a domain family, is an alignment of divergent family members based on known tertiary structures, where possible, or from homologues identified in a PSI-BLAST (6) analysis. These alignments are optimised manually and, following construction of a hidden Markov model (HMM) (7), used to search current sequence databases. Each sequence of the alignment is also used as a query in a PSI-BLAST search. All sequences that are significantly similar [as detected by HMM (E < 0.01) or PSI-BLAST (E < 0.001) searches] are added to the alignment using the sequence versus HMM alignment method of HMMer. Alignments are checked manually for potential false positives or misassembled protein sequences derived from genomic sources. From this alignment, one of each sequence pair sharing >67% identity is deleted to reduce redundancy. The resulting alignment is used as a starting point for a subsequent round of searches. This iterative procedure is pursued until no new homologues are detected.
Increased coverage
Originally, SMART was intended as a tool for the analysis of domains involved in eukaryotic signal transduction (2) but was expanded to detect domains of extracellular proteins and bacterial two-component regulatory systems (8). In 1999, domains associated with DNA, RNA, chromatin and actin cytoskeleton functions have been added (see http://SMART.embl-heidelberg. de/changes.shtml for a list of all new added domains). In addition, new reported domain families that fall within the categories covered by SMART have been incorporated. These include extracellular GPS (9) and PSI (10) domains, intracellular signalling domains as ENTH (11) and GoLoco (12) as well as domains in splicing factors [e.g., FF (13) and PWI (14)]. During this process, additional, previously undetected members are often recognized, as for example ENTH domains in Saccharomyces cerevisiae and mammalian huntingtin interacting proteins or PWI domains in fungal proteins. As a result of this improvement in coverage, SMART now includes >400 domains.
Updating of alignments
In 1999 more than 40 alignments have been updated (see http://SMART.embl-heidelberg.de/changes.shtml for a list). For instance, in cases where the tertiary structure of a domain has been solved, we ensured that domain boundaries derived from sequence analysis are consistent with the three dimensional structure. The histidine kinase structures (1517), for example, revealed two structurally independent domains, namely A, which contains the phosphorylation site, and B, the catalytic core. The previous SMART histidine kinase alignment was therefore split into two domains, HisKA and HATPase_c, the latter includes heat shock protein 90 and DNA gyrase B homologues (18). Updates were also undertaken to ensure that newly-deposited sequences are suitably represented in the current SMART alignments. Recent identification of distant domain homologues such as SH3 (19) and VWA domains in prokaryotes (4) and VWA domains in integrin ß-subunits (20), have been incorporated into the SMART database. Updates of domain families have resulted in unexpected structural or functional predictions. For example, revisiting the SET domain family resulted in the prediction that some plant N-methyltransferases (21) contain this domain (unpublished data). This suggests that SET domain proteins may possess methyltransferase activities.
| DATA ACQUISITION AND INTEGRATION INTO A RELATIONAL DATABASE SYSTEM |
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SMART was designed to facilitate the study of domain evolution and multi-domain architectures by correlations with phyletic distributions. Consequently, it was essential that all members of a domain family complete with associated taxonomic information were recorded in an easy-to-retrieve format.
The SMART database
Information on >400 domain types in >54 000 different proteins is stored in SMART using a relational database management system (RDBMS; see http://www.PostgreSQL.org ). For each domain hit, boundaries, raw bit score and E-value are recorded. The protein accession code, description line, the sequence length and the species name are stored. To allow phylogenetic analyses, the full taxonomic description for each species derived from the NCBI Taxonomy database (see http://www.ncbi.nlm.nih.gov/Taxonomy/tax.html ) is also recorded. Each SMART domain is identified by a unique accession number, thus providing stable references for other domain databases and is linked to corresponding domains in Pfam (22) and PROSITE (23). By including into the database annotation, search parameters (see below) and cross-references to other domain databases, SMART has been converted into a relational database scheme, resulting also in increased system stability and easier maintenance (see Fig. 1 for the structure of the database).
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New searching method
To improve sensitivity of domain and repeat detection, SMARTs searching method has been changed to HMMs using the implementation of the HMMer2 program (7) (see http://hmmer. wustl.edu ). HMMer2 provides statistically sound E-values, giving a robust estimate of the significance of a domain hit. From a database search with a HMM derived from the SMART alignment, the highest per protein E-value of identified true positives (Ep) and the lowest per protein E-value of predicted true negatives (En) are stored within the SMART database. Similarly, for two or more repeats in a protein, the lowest E-value of a false positive repeat (Er) is stored. To ensure that the E-value thresholds are independent from the database size, the size of the protein database used when deriving the thresholds is also recorded. SMART will predict a domain homologue within any sequence, that has an E-value <Ep or else where Ep < E-value < En and E-value < 1.0. In cases where no repeat threshold is defined, all hits in a protein are reported, otherwise only those with E-values < Er are shown.
| THE SMART WEB SERVER: NEW FEATURES |
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SMART offers different Web interfaces to query the underlying RDBMS for particular domain architectures. This query can be limited to specific taxonomic groups. In addition, we have improved the output of basic SMART searches, to present results in a more coherent and concise format.
Architecture SMART and Alert SMART
Architecture SMART allows users to search for specific domain architectures using an AND/NOT logic. Searches can be restricted to any taxonomic group. Selecting for plant proteins with B41 domains, for example, reveals a single domain architecture consisting of MyTH4, B41 and C-terminal kinesin motor (KISc) domains (Fig. 2a). In metazoa, by contrast, B41 domains can be found in combination with 18 other domains. Restricting the search to metazoan proteins with both B41 and MyTH4 domains reveals two distinct domain architectures (Fig. 2a) both of which contain an N-terminal myosin-like ATPase motor domain (MYSc). Thus, in plants and in metazoans, the B41/MyTH4 domain pair is combined with motor domains, but in contrasting domain architectures.
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Users wishing to be kept informed by Email of sequences newly deposited in databases, that contain particular domains, should register their requirements using the alert SMART facility.
Finding proteins with similar domain architecture
SMART can search for all proteins that have an identical domain architecture as the query (having all the domains of the query protein in the same collinear order) or an identical domain composition (at least one of all domain types of the query protein, irrespective of order). Identification of proteins with identical, or near-identical, domain architectures as the query may improve predictions of protein, as opposed to domain, functions. This feature also reveals, using a taxonomic breakdown, the phyletic distribution of the architecture. In addition, it allows the detection of very divergent members of domain families that are not detectable by standard sequence searching methods. The Caenorhabditis elegans protein K08B12.5 (gi 1938422), for example, is predicted by SMART to contain the following domains: S_TKc, S_TK_X, C1, CNH and PBD (Fig. 2b). Searching for proteins that contain each of these domains in identical order demonstrates, that all such proteins possess a PH domain between the C1 and CNH domains (Fig. 2b). This suggests, that further investigation might also reveal a divergent PH domain in K08B12.5.
Improved representation of results
SMART analysis of a query sequence reveals not only domains, but also intrinsic features such as signal sequences (24), transmembrane helices (25), coiled coil regions (26) and compositionally biased regions (27). In the last year, methods for the prediction of GPI anchors (28) and for improved repeat detection (M.A.Andrade, EMBL, Heidelberg, unpublished data) have been added. To provide a comprehensive overview of these features, all predictions are merged into a single line output (Fig. 2c). The following priority list is used to resolve overlapping predictions based on the perceived prediction accuracy: Domain > Signal > TM > Coils > Seg. All predictions are also provided in a tabular format.
| FUTURE PERSPECTIVES |
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SMART detects domains from sequences with relatively high selectivity and specificity. Domain families that contain extremely divergent representatives are deliberately targeted for inclusion in this database due to problems in their detection using other methods. Future work will focus on increasing the types of mobile domains detected and on improved functional predictions within single families.
| ACKNOWLEDGEMENTS |
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The authors would like to thank colleagues from the EMBL group for lively discussions and help, in particular B. Eisenhaber for linking the GPI prediction and M. A. Andrade for providing repeater to SMART. J.S., T.D. and P.B. are supported by the DFG and by the EC (grant 01KW9602/6) as well as by the BMBF grants MEDSEQ and TARGID. C.P.P. is supported by the Medical Research Council, UK.
| FOOTNOTES |
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* To whom correspondence should be addressed at: EMBL, Meyerhofstrasse 1, 69012 Heidelberg, Germany. Tel: +49 6221 387526; Fax: +49 6221 387517; Email: bork@embl-heidelberg.de
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M. Boccellino, G. Camussi, A. Giovane, L. Ferro, V. Calderaro, C. Balestrieri, and L. Quagliuolo Platelet-Activating Factor Regulates Cadherin-Catenin Adhesion System Expression and {beta}-Catenin Phosphorylation during Kaposi's Sarcoma Cell Motility Am. J. Pathol., May 1, 2005; 166(5): 1515 - 1522. [Abstract] [Full Text] [PDF] |
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N. M. Springer and S. M. Kaeppler Evolutionary Divergence of Monocot and Dicot Methyl-CpG-Binding Domain Proteins Plant Physiology, May 1, 2005; 138(1): 92 - 104. [Abstract] [Full Text] [PDF] |
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H. A. M. Lauzon, P. B. Jamieson, P. J. Krell, and B. M. Arif Gene organization and sequencing of the Choristoneura fumiferana defective nucleopolyhedrovirus genome J. Gen. Virol., April 1, 2005; 86(4): 945 - 961. [Abstract] [Full Text] [PDF] |
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M. A. Nunn, A. Sharma, G. C. Paesen, S. Adamson, O. Lissina, A. C. Willis, and P. A. Nuttall Complement Inhibitor of C5 Activation from the Soft Tick Ornithodoros moubata J. Immunol., February 15, 2005; 174(4): 2084 - 2091. [Abstract] [Full Text] [PDF] |
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S. Hahner, M. Fassnacht, F. Hammer, M. Schammann, D. Weismann, I. A. Hansen, and B. Allolio Evidence against a role of human airway trypsin-like protease - the human analogue of the growth-promoting rat adrenal secretory protease - in adrenal tumourigenesis Eur. J. Endocrinol., January 1, 2005; 152(1): 143 - 153. [Abstract] [Full Text] [PDF] |
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A. Merino-Trigo, M. C. Kerr, F. Houghton, A. Lindberg, C. Mitchell, R. D. Teasdale, and P. A. Gleeson Sorting nexin 5 is localized to a subdomain of the early endosomes and is recruited to the plasma membrane following EGF stimulation J. Cell Sci., December 15, 2004; 117(26): 6413 - 6424. [Abstract] [Full Text] [PDF] |
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A. M. Hinsby, J. V. Olsen, and M. Mann Tyrosine Phosphoproteomics of Fibroblast Growth Factor Signaling: A ROLE FOR INSULIN RECEPTOR SUBSTRATE-4 J. Biol. Chem., November 5, 2004; 279(45): 46438 - 46447. [Abstract] [Full Text] [PDF] |
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B. Boesten and U. B. Priefer The C-terminal receiver domain of the Rhizobium leguminosarum bv. viciae FixL protein is required for free-living microaerobic induction of the fnrN promoter Microbiology, November 1, 2004; 150(11): 3703 - 3713. [Abstract] [Full Text] [PDF] |
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J.-R. Hong, G.-H. Lin, C. J.-F. Lin, W.-p. Wang, C.-C. Lee, T.-L. Lin, and J.-L. Wu Phosphatidylserine receptor is required for the engulfment of dead apoptotic cells and for normal embryonic development in zebrafish Development, November 1, 2004; 131(21): 5417 - 5427. [Abstract] [Full Text] [PDF] |
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R. L. Goforth, E. C. Peterson, J. Yuan, M. J. Moore, A. D. Kight, M. B. Lohse, J. Sakon, and R. L. Henry Regulation of the GTPase Cycle in Post-translational Signal Recognition Particle-based Protein Targeting Involves cpSRP43 J. Biol. Chem., October 8, 2004; 279(41): 43077 - 43084. [Abstract] [Full Text] [PDF] |
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J. G. Valenzuela, M. Garfield, E. D. Rowton, and V. M. Pham Identification of the most abundant secreted proteins from the salivary glands of the sand fly Lutzomyia longipalpis, vector of Leishmania chagasi J. Exp. Biol., October 1, 2004; 207(21): 3717 - 3729. [Abstract] [Full Text] [PDF] |
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B. Noh, S.-H. Lee, H.-J. Kim, G. Yi, E.-A. Shin, M. Lee, K.-J. Jung, M. R. Doyle, R. M. Amasino, and Y.-S. Noh Divergent Roles of a Pair of Homologous Jumonji/Zinc-Finger-Class Transcription Factor Proteins in the Regulation of Arabidopsis Flowering Time PLANT CELL, October 1, 2004; 16(10): 2601 - 2613. [Abstract] [Full Text] [PDF] |
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D. Drecktrah, L. A. Knodler, and O. Steele-Mortimer Modulation and Utilization of Host Cell Phosphoinositides by Salmonella spp. Infect. Immun., August 1, 2004; 72(8): 4331 - 4335. [Full Text] [PDF] |
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Z. Shan, H. Xu, X. Shi, Y. Yu, H. Yao, X. Zhang, Y. Bai, C. Gao, P. E. J. Saris, and M. Qiao Identification of two new genes involved in twitching motility in Pseudomonas aeruginosa Microbiology, August 1, 2004; 150(8): 2653 - 2661. [Abstract] [Full Text] [PDF] |
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A. V. Smirnova and M. S. Ullrich Topological and deletion analysis of CorS, a Pseudomonas syringae sensor kinase Microbiology, August 1, 2004; 150(8): 2715 - 2726. [Abstract] [Full Text] [PDF] |
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Y.-X. Tao and R. A. Johns NEURONAL PDZ DOMAINS: A Promising New Molecular Target for Inhaled Anesthetics? Mol. Interv., August 1, 2004; 4(4): 215 - 221. [Abstract] [Full Text] [PDF] |
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C. T. Pappas, J. Sram, O. V. Moskvin, P. S. Ivanov, R. C. Mackenzie, M. Choudhary, M. L. Land, F. W. Larimer, S. Kaplan, and M. Gomelsky Construction and Validation of the Rhodobacter sphaeroides 2.4.1 DNA Microarray: Transcriptome Flexibility at Diverse Growth Modes J. Bacteriol., July 15, 2004; 186(14): 4748 - 4758. [Abstract] [Full Text] [PDF] |
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M. Foster-Cuevas, G. J. Wright, M. J. Puklavec, M. H. Brown, and A. N. Barclay Human Herpesvirus 8 K14 Protein Mimics CD200 in Down-Regulating Macrophage Activation through CD200 Receptor J. Virol., July 15, 2004; 78(14): 7667 - 7676. [Abstract] [Full Text] [PDF] |
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M. Garate, Z. Cao, E. Bateman, and N. Panjwani Cloning and Characterization of a Novel Mannose-binding Protein of Acanthamoeba J. Biol. Chem., July 9, 2004; 279(28): 29849 - 29856. [Abstract] [Full Text] [PDF] |
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H. A. M. Lauzon, C. J. Lucarotti, P. J. Krell, Q. Feng, A. Retnakaran, and B. M. Arif Sequence and Organization of the Neodiprion lecontei Nucleopolyhedrovirus Genome J. Virol., July 1, 2004; 78(13): 7023 - 7035. [Abstract] [Full Text] [PDF] |
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M. Pagni, V. Ioannidis, L. Cerutti, M. Zahn-Zabal, C. V. Jongeneel, and L. Falquet MyHits: a new interactive resource for protein annotation and domain identification Nucleic Acids Res., July 1, 2004; 32(suppl_2): W332 - W335. [Abstract] [Full Text] [PDF] |
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M. Vanstraelen, J. A. Torres Acosta, L. De Veylder, D. Inze, and D. Geelen A Plant-Specific Subclass of C-Terminal Kinesins Contains a Conserved A-Type Cyclin-Dependent Kinase Site Implicated in Folding and Dimerization Plant Physiology, July 1, 2004; 135(3): 1417 - 1429. [Abstract] [Full Text] [PDF] |
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Y. Imamura, T. Katahira, and D. Kitamura Identification and Characterization of a Novel BASH N Terminus-associated Protein, BNAS2 J. Biol. Chem., June 18, 2004; 279(25): 26425 - 26432. [Abstract] [Full Text] [PDF] |
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A. Sharma, M. Isogai, T. Yamamoto, K. Sakaguchi, J. Hashimoto, and S. Komatsu A Novel Interaction between Calreticulin and Ubiquitin-Like Nuclear Protein in Rice Plant Cell Physiol., June 15, 2004; 45(6): 684 - 692. [Abstract] [Full Text] [PDF] |
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D. M. Hodzic, D. B. Yeater, L. Bengtsson, H. Otto, and P. D. Stahl Sun2 Is a Novel Mammalian Inner Nuclear Membrane Protein J. Biol. Chem., June 11, 2004; 279(24): 25805 - 25812. [Abstract] [Full Text] [PDF] |
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M. Kim, H. Yang, S.-K. Kim, P. A. Reche, R. S. Tirabassi, R. E. Hussey, Y. Chishti, J. G. Rheinwald, T. J. Morehead, T. Zech, et al. Biochemical and Functional Analysis of Smallpox Growth Factor (SPGF) and Anti-SPGF Monoclonal Antibodies J. Biol. Chem., June 11, 2004; 279(24): 25838 - 25848. [Abstract] [Full Text] [PDF] |
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M. A. Olayioye, P. Hoffmann, T. Pomorski, J. Armes, R. J. Simpson, B. E. Kemp, G. J. Lindeman, and J. E. Visvader The Phosphoprotein StarD10 Is Overexpressed in Breast Cancer and Cooperates with ErbB Receptors in Cellular Transformation Cancer Res., May 15, 2004; 64(10): 3538 - 3544. [Abstract] [Full Text] [PDF] |
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B. Li, L. Zhuang, and B. Trueb Zyxin Interacts with the SH3 Domains of the Cytoskeletal Proteins LIM-nebulette and Lasp-1 J. Biol. Chem., May 7, 2004; 279(19): 20401 - 20410. [Abstract] [Full Text] [PDF] |
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S.-H. Shiu, W. M. Karlowski, R. Pan, Y.-H. Tzeng, K. F. X. Mayer, and W.-H. Li Comparative Analysis of the Receptor-Like Kinase Family in Arabidopsis and Rice PLANT CELL, May 1, 2004; 16(5): 1220 - 1234. [Abstract] [Full Text] [PDF] |
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S.-H. Shiu and W.-H. Li Origins, Lineage-Specific Expansions, and Multiple Losses of Tyrosine Kinases in Eukaryotes Mol. Biol. Evol., May 1, 2004; 21(5): 828 - 840. [Abstract] [Full Text] [PDF] |
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J. J. Burden, X.-M. Sun, A. B. G. Garcia, and A. K. Soutar Sorting Motifs in the Intracellular Domain of the Low Density Lipoprotein Receptor Interact with a Novel Domain of Sorting Nexin-17 J. Biol. Chem., April 16, 2004; 279(16): 16237 - 16245. [Abstract] [Full Text] [PDF] |
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I. A. Hansen, M. Fassnacht, S. Hahner, F. Hammer, M. Schammann, S. R. Meyer, A. B. Bicknell, and B. Allolio The Adrenal Secretory Serine Protease AsP Is a Short Secretory Isoform of the Transmembrane Airway Trypsin-Like Protease Endocrinology, April 1, 2004; 145(4): 1898 - 1905. [Abstract] [Full Text] [PDF] |
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B. A. Weir and M. P. Yaffe Mmd1p, a Novel, Conserved Protein Essential for Normal Mitochondrial Morphology and Distribution in the Fission Yeast Schizosaccharomyces pombe Mol. Biol. Cell, April 1, 2004; 15(4): 1656 - 1665. [Abstract] [Full Text] [PDF] |
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R. C. Edgar MUSCLE: multiple sequence alignment with high accuracy and high throughput Nucleic Acids Res., March 19, 2004; 32(5): 1792 - 1797. [Abstract] [Full Text] [PDF] |
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H. Qin, A. Percival-Smith, C. Li, C. Y. H. Jia, G. Gloor, and S. S.-C. Li A Novel Transmembrane Protein Recruits Numb to the Plasma Membrane during Asymmetric Cell Division J. Biol. Chem., March 19, 2004; 279(12): 11304 - 11312. [Abstract] [Full Text] [PDF] |
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K. Ishiguro and R. Xavier Homer-3 regulates activation of serum response element in T cells via its EVH1 domain Blood, March 15, 2004; 103(6): 2248 - 2256. [Abstract] [Full Text] [PDF] |
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M. B. Howard, N. A. Ekborg, L. E. Taylor II, R. M. Weiner, and S. W. Hutcheson Chitinase B of "Microbulbifer degradans" 2-40 Contains Two Catalytic Domains with Different Chitinolytic Activities J. Bacteriol., March 1, 2004; 186(5): 1297 - 1303. [Abstract] [Full Text] [PDF] |
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B. K. Zolman and B. Bartel An Arabidopsis indole-3-butyric acid-response mutant defective in PEROXIN6, an apparent ATPase implicated in peroxisomal function PNAS, February 10, 2004; 101(6): 1786 - 1791. [Abstract] [Full Text] [PDF] |
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J.-L. Imler and L. Zheng Biology of Toll receptors: lessons from insects and mammals J. Leukoc. Biol., January 1, 2004; 75(1): 18 - 26. [Abstract] [Full Text] [PDF] |
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J. Gates, G. Lam, J. A. Ortiz, R. Losson, and C. S. Thummel rigor mortis encodes a novel nuclear receptor interacting protein required for ecdysone signaling during Drosophila larval development Development, January 1, 2004; 131(1): 25 - 36. [Abstract] [Full Text] [PDF] |
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Y. Mudgil, S.-H. Shiu, S. L. Stone, J. N. Salt, and D. R. Goring A Large Complement of the Predicted Arabidopsis ARM Repeat Proteins Are Members of the U-Box E3 Ubiquitin Ligase Family Plant Physiology, January 1, 2004; 134(1): 59 - 66. [Abstract] [Full Text] [PDF] |
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C. Vogel, S. A. Teichmann, and C. Chothia The immunoglobulin superfamily in Drosophila melanogaster and Caenorhabditis elegans and the evolution of complexity Development, December 22, 2003; 130(25): 6317 - 6328. [Abstract] [Full Text] [PDF] |
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S. Moskalenko, C. Tong, C. Rosse, G. Mirey, E. Formstecher, L. Daviet, J. Camonis, and M. A. White Ral GTPases Regulate Exocyst Assembly through Dual Subunit Interactions J. Biol. Chem., December 19, 2003; 278(51): 51743 - 51748. [Abstract] [Full Text] [PDF] |
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L. E. MacConaill, G. F. Fitzgerald, and D. van Sinderen Investigation of Protein Export in Bifidobacterium breve UCC2003 Appl. Envir. Microbiol., December 1, 2003; 69(12): 6994 - 7001. [Abstract] [Full Text] [PDF] |
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K.-C. Kim, L. Geng, and S. Huang Inactivation of a Histone Methyltransferase by Mutations in Human Cancers Cancer Res., November 15, 2003; 63(22): 7619 - 7623. [Abstract] [Full Text] [PDF] |
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T. Amano, S. Yamasaki, N. Yagishita, K. Tsuchimochi, H. Shin, K.-i. Kawahara, S. Aratani, H. Fujita, L. Zhang, R. Ikeda, et al. Synoviolin/Hrd1, an E3 ubiquitin ligase, as a novel pathogenic factor for arthropathy Genes & Dev., October 1, 2003; 17(19): 2436 - 2449. [Abstract] [Full Text] [PDF] |
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J. Pei, N. V. Dokholyan, E. I. Shakhnovich, and N. V. Grishin Using protein design for homology detection and active site searches PNAS, September 30, 2003; 100(20): 11361 - 11366. [Abstract] [Full Text] [PDF] |
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R. I. Herzog, C. Liu, S. G. Waxman, and T. R. Cummins Calmodulin Binds to the C Terminus of Sodium Channels Nav1.4 and Nav1.6 and Differentially Modulates Their Functional Properties J. Neurosci., September 10, 2003; 23(23): 8261 - 8270. [Abstract] [Full Text] [PDF] |
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N. Ariel, A. Zvi, K. S. Makarova, T. Chitlaru, E. Elhanany, B. Velan, S. Cohen, A. M. Friedlander, and A. Shafferman Genome-Based Bioinformatic Selection of Chromosomal Bacillus anthracis Putative Vaccine Candidates Coupled with Proteomic Identification of Surface-Associated Antigens Infect. Immun., August 1, 2003; 71(8): 4563 - 4579. [Abstract] [Full Text] [PDF] |
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F. Pessler and N. Hernandez Flexible DNA Binding of the BTB/POZ-domain Protein FBI-1 J. Biol. Chem., August 1, 2003; 278(31): 29327 - 29335. [Abstract] [Full Text] [PDF] |
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F. T.S. Nogueira, V. E. De Rosa Jr., M. Menossi, E. C. Ulian, and P. Arruda RNA Expression Profiles and Data Mining of Sugarcane Response to Low Temperature Plant Physiology, August 1, 2003; 132(4): 1811 - 1824. [Abstract] [Full Text] [PDF] |
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L. E. MacConaill, D. Butler, M. O'Connell-Motherway, G. F. Fitzgerald, and D. van Sinderen Identification of Two-Component Regulatory Systems in Bifidobacterium infantis by Functional Complementation and Degenerate PCR Approaches Appl. Envir. Microbiol., July 1, 2003; 69(7): 4219 - 4226. [Abstract] [Full Text] [PDF] |
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D. E. GOLL, V. F. THOMPSON, H. LI, W. WEI, and J. CONG The Calpain System Physiol Rev, July 1, 2003; 83(3): 731 - 801. [Abstract] [Full Text] [PDF] |
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Y.-S. Noh and R. M. Amasino PIE1, an ISWI Family Gene, Is Required for FLC Activation and Floral Repression in Arabidopsis PLANT CELL, July 1, 2003; 15(7): 1671 - 1682. [Abstract] [Full Text] [PDF] |
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M. B. Howard, N. A. Ekborg, L. E. Taylor, R. M. Weiner, and S. W. Hutcheson Genomic Analysis and Initial Characterization of the Chitinolytic System of Microbulbifer degradans Strain 2-40 J. Bacteriol., June 1, 2003; 185(11): 3352 - 3360. [Abstract] [Full Text] [PDF] |
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