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SMART, A Simple Modular Architecture Research Tool: Identification Of Signaling Domains.

J. Schultz, F. Milpetz, P. Bork, C. Ponting
Published 1998 · Biology, Computer Science, Medicine

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Accurate multiple alignments of 86 domains that occur in signaling proteins have been constructed and used to provide a Web-based tool (SMART: simple modular architecture research tool) that allows rapid identification and annotation of signaling domain sequences. The majority of signaling proteins are multidomain in character with a considerable variety of domain combinations known. Comparison with established databases showed that 25% of our domain set could not be deduced from SwissProt and 41% could not be annotated by Pfam. SMART is able to determine the modular architectures of single sequences or genomes; application to the entire yeast genome revealed that at least 6.7% of its genes contain one or more signaling domains, approximately 350 greater than previously annotated. The process of constructing SMART predicted (i) novel domain homologues in unexpected locations such as band 4.1-homologous domains in focal adhesion kinases; (ii) previously unknown domain families, including a citron-homology domain; (iii) putative functions of domain families after identification of additional family members, for example, a ubiquitin-binding role for ubiquitin-associated domains (UBA); (iv) cellular roles for proteins, such predicted DEATH domains in netrin receptors further implicating these molecules in axonal guidance; (v) signaling domains in known disease genes such as SPRY domains in both marenostrin/pyrin and Midline 1; (vi) domains in unexpected phylogenetic contexts such as diacylglycerol kinase homologues in yeast and bacteria; and (vii) likely protein misclassifications exemplified by a predicted pleckstrin homology domain in a Candida albicans protein, previously described as an integrin.
This paper references
R. Quatrano (1998)
A phosphotyrosine interaction domain
P. Bork (1995)
Proteins regulating Ras and its relatives
M. Boguski (1993)
The death domain motif found in Fas (Apo‐1) and TNF receptor is present in proteins involved in apoptosis and axonal guidance
K. Hofmann (1995)
A workbench for multiple alignment construction and analysis
G. Schuler (1991)
Proc. Natl. Acad. Sci. USA 95
Paper Colloquium (1998)
K Ozaki (1996)
Protein Eng
R B Russell (1994)
The N-terminal pleckstrin, coiled-coil, and IQ domains of the exchange factor Ras-GRF act cooperatively to facilitate activation by calcium.
R. Buchsbaum (1996)
The multiplicity of domains in proteins.
R. Doolittle (1995)
Proc. Natl. Acad. Sci. USA 93
C Gale (1996)
Detection of conserved segments in proteins: iterative scanning of sequence databases with alignment blocks.
R. Tatusov (1994)
J. Biol. Chem
I Knezevic (1996)
The International FMF Consortium
Nucleic Acids Res
T K Attwood (1997)
Protein Sci
C P Ponting (1996)
Maximum Discrimination Hidden Markov Models of Sequence Consensus
S. Eddy (1995)
The death domain: a module shared by proteins with diverse cellular functions.
E. Feinstein (1995)
A candidate gene for familial Mediterranean fever
The French Fmf Consortium (1997)
A duplicated catalytic motif in a new superfamily of phosphohydrolases and phospholipid synthases that includes poxvirus envelope proteins.
E. Koonin (1996)
Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptors
E. Leonardo (1997)
SPRY domains in ryanodine receptors (Ca(2+)-release channels).
C. Ponting (1997)
Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22
N. Quaderi (1997)
Trends Biochem. Sci
P Bork (1997)
J. Biol. Chem
C R Loomis (1985)
Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever
I. Aksentijevich (1997)
J. Cell. Biol
M D Schaller (1995)
Extending the C2 domain family: C2s in PKCs δ, ϵ,η,θ, phospholipases, GAPs, and perforin
C.P. Pointing (1996)
CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.
J. Thompson (1994)
Trends Biochem. Sci
G D Fasman (1990)
Schultz et al
B. Rost (1998)
PH domain: the first anniversary.
T. Gibson (1994)
Structure and distribution of modules in extracellular proteins.
P. Bork (1996)
Direct Binding of the Platelet Integrin αIIbβ3 (GPIIb-IIIa) to Talin
I. Knezevic (1996)
Mol. Cell. Biol
R Buchsbaum (1996)
Chromosomal deletion complexes in mice by radiation of embryonic stem cells
Y. You (1997)
Cloning and expression of a gene encoding an integrin-like protein in Candida albicans.
C. Gale (1996)
Syst. Zool
W M Fitch (1970)
AC Tose (1993)
Comput. Appl. Biosci
B Rost (1994)
J. Cell. Biol
A J Otsuka (1995)
Applying motif and profile searches.
P. Bork (1996)
Analysis of compositionally biased regions in sequence databases.
J. Wootton (1996)
Trends Biochem. Sci
C P Ponting (1997)
J. Cell Sci
D Ilic (1997)
Recent enhancements to the Blocks Database servers
J. Henikoff (1997)
Distinguishing homologous from analogous proteins.
W. Fitch (1970)
Trends Biochem. Sci
T J Gibson (1994)
Nucleic Acids Res
J G Henikoff (1997)
Trends Biochem. Sci
K Hofmann (1996)
Trends Biochem. Sci
E V Koonin (1996)
A novel partner for the GTP‐bound forms of rho and rac
P. Madaule (1995)
Nucleic Acids Res
A Bairoch (1997)
Protein Sci
C P Ponting (1996)
The prediction of transmembrane protein sequences and their conformation: an evaluation.
G. Fasman (1990)
Novel developments with the PRINTS protein fingerprint database
T. Attwood (1997)
A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: Identification of duplicated repeats and potential active site residues
C. Ponting (1996)
Annu. Rev. Biochem
R F Doolittle (1995)
Trends Biochem. Sci
C W V Hogue (1996)
Nat. Genet
N A Quaderi (1997)
M. Saraste (2000)
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
S. Altschul (1997)
An ankyrin-related gene (unc-44) is necessary for proper axonal guidance in Caenorhabditis elegans
A. J. Otsuka (1995)
Q. Rev. Biophys
P Bork (1996)
Nucleic Acids Res
E Birney (1996)
Pleckstrin's repeat performance: a novel domain in G-protein signaling?
C. Ponting (1996)
A dynamic look at structures: WWW-Entrez and the Molecular Modeling Database.
C. W. Hogue (1996)
Pfam: A comprehensive database of protein domain families based on seed alignments
E. L. Sonnhammer (1997)
Proc. Natl. Acad. Sci. USA 91
R L Tatusov (1994)
p62, a Phosphotyrosine-independent Ligand of the SH2 Domain of p56lck, Belongs to a New Class of Ubiquitin-binding Proteins*
R. Vadlamudi (1996)
Cytoplasmic signalling domains: the next generation.
P. Bork (1997)
sn-1,2-Diacylglycerol kinase of Escherichia coli. Purification, reconstitution, and partial amino- and carboxyl-terminal analysis.
Carson R. Loomis (1985)
PairWise and SearchWise: finding the optimal alignment in a simultaneous comparison of a protein profile against all DNA translation frames.
E. Birney (1996)
Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains
M. Schaller (1995)
The PROSITE database, its status in 1997
A. Bairoch (1997)
A mechanism for regulation of the adhesion-associated protein tyrosine kinase pp125FAK
A. Richardson (1996)
J. Biol. Chem
R K Vadlamudi (1996)
Trends Biochem. Sci
E Feinstein (1995)
Proc. Natl. Acad. Sci. USA 94
A R Mushegian (1997)
Searching protein sequence libraries: comparison of the sensitivity and selectivity of the Smith-Waterman and FASTA algorithms.
W. Pearson (1991)
Comput. Biol
S R Eddy (1995)
Nucleic Acids Res
S F Altschul (1997)
Nat. Genet
The French (1997)
Predicting coiled coils from protein sequences
A. Lupas (1991)
PHD - an automatic mail server for protein secondary structure prediction
B. Rost (1994)
Rom1p and Rom2p are GDP/GTP exchange proteins (GEPs) for the Rho1p small GTP binding protein in Saccharomyces cerevisiae.
K. Ozaki (1996)
The UBA domain: a sequence motif present in multiple enzyme classes of the ubiquitination pathway.
K. Hofmann (1996)
Nucleic Acids Res
J D Thompson (1994)
Protein Sci
D T Haynie (1996)
Trends Biochem. Sci
C P Ponting (1996)
Focal adhesion kinase: at the crossroads of signal transduction.
D. Ilic (1997)
The mouse rostral cerebellar malformation gene encodes an UNC-5-like protein
S. Ackerman (1997)
Positionally cloned human disease genes: patterns of evolutionary conservation and functional motifs.
A. Mushegian (1997)
The N‐terminal domains of tensin and auxilin are phosphatase homologues
D. T. Haynie (1996)
Presence of an SH2 domain in the actin-binding protein tensin.
S. Davis (1991)

This paper is referenced by
Posttranslational hydroxylation of ankyrin repeats in IκB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH)
M. Cockman (2006)
Three Isoforms of Synaptic Scaffolding Molecule and Their Characterization
K. Hirao (2000)
Structure and lipid transport mechanism of a StAR-related domain
Y. Tsujishita (2000)
Domain repertoires as a tool to derive protein recognition rules
A. Zucconi (2000)
Cloning and characterization of human and mouse SNRK sucrose non-fermenting protein (SNF-1)-related kinases.
N. Kertesz (2002)
Interaction of HIV-1 Integrase with DNA Repair Protein hRad18*
L. Mulder (2002)
The MADF-BESS domain factor Dip3 potentiates synergistic activation by Dorsal and Twist.
V. Bhaskar (2002)
Identification of a novel type of cGMP phosphodiesterase that is defective in the chemotactic stmF mutants.
M. Meima (2002)
Identification and Characterization of Scp15, a Protein from Streptomyces coelicolor A3(2) Inducing Neurites in PC12 Cells
S. Nakashima (2003)
Mechanism of multiple lysine methylation by the SET domain enzyme Rubisco LSMT
R. Trievel (2003)
Protein–DNA Interactions: The Story so Far and a New Method for Prediction
S. Jones (2003)
Genome sequence and comparative analysis of the solvent-producing bacterium Clostridium acetobutylicum.
J. Nölling (2001)
Characterization of C. elegans RING finger protein 1, a binding partner of ubiquitin-conjugating enzyme 1.
Emily A. Crowe (2004)
Evolution of the multifunctional protein tyrosine phosphatase family.
Birgit Pils (2004)
Biochemische und molekularbiologische Charakterisierung von RAIP, einem neuen ER-lokalisierten proapoptotischen Protein
Erik Braziulis (2004)
MUSCLE: a multiple sequence alignment method with reduced time and space complexity
R. Edgar (2004)
Analysis of the Role of Ubiquitin-interacting Motifs in Ubiquitin Binding and Ubiquitylation*[boxs]
Stephanie L H Miller (2004)
PAS domain of the Aer redox sensor requires C-terminal residues for native-fold formation and flavin adenine dinucleotide binding.
S. Herrmann (2004)
Automated Genome-Wide Protein Domain Exploration
Bhanu Rekepalli (2007)
Conservation of the TRAPPII-specific subunits of a Ypt/Rab exchanger complex
R. Cox (2006)
A leucine-rich repeat protein is required for growth promotion and enhanced seed production mediated by the endophytic fungus Piriformospora indica in Arabidopsis thaliana.
Bationa Shahollari (2007)
Comparative and phylogenetic analysis of α-l-fucosidase genes
J. Intra (2007)
Genes encoding putative Takeout/juvenile hormone binding proteins in the honeybee (Apis mellifera) and modulation by age and juvenile hormone of the takeout-like gene GB19811.
Tzachi Hagai (2007)
Flavodoxin:quinone reductase (FqrB): a redox partner of pyruvate:ferredoxin oxidoreductase that reversibly couples pyruvate oxidation to NADPH production in Helicobacter pylori and Campylobacter jejuni.
M. St Maurice (2007)
Expression, purification and DNA-binding activities of two putative ModE proteins of Herbaspirillum seropedicae (Burkholderiales, Oxalobacteraceae)
André L. F. Souza (2008)
The role of cell signaling in poxvirus tropism: the case of the M-T5 host range protein of myxoma virus.
Steven J. Werden (2008)
Ankyrin for methylated lysines
M. Brent (2008)
The leptospiral antigen Lp49 is a two-domain protein with putative protein binding function.
P. O. Giuseppe (2008)
Comprehensive survey and classification of homeobox genes in the genome of amphioxus, Branchiostoma floridae
N. Takatori (2008)
Caenorhabditis elegans Gelsolin-like Protein 1 Is a Novel Actin Filament-severing Protein with Four Gelsolin-like Repeats*
T. Klaavuniemi (2008)
Evolution of primary microcephaly genes and the enlargement of primate brains.
C. Ponting (2005)
MATH domain proteins represent a novel protein family in Arabidopsis thaliana, and at least one member is modified in roots during the course of a plant–microbe interaction
R. Oelmüller (2005)
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