Representation of a prediction of the amino acids in tertiary structures of homologues that overlay in three dimensions. Alignments held by SMART are mostly based on published observations (see domain annotations for details), but are updated and edited manually.
Alignment block
Ungapped alignments that usually represent a single secondary structure.
Bits scores
Alignment scores are reported by HMMer and BLAST as bits scores. The likelihood that the query sequence is a bona fide homologue of the database sequence is compared to the likelihood that the sequence was instead generated by a "random" model. Taking the logarithm (to base 2) of this likelihood ratio gives the bits score.
BLAST, Basic local alignment search tool.
An excellent database searching tool developed at the National Center for Biotechnology Information (NCBI) ([1], [2], [3], [4]). SMART uses NCBI-BLAST for detection of outlier homologues and homologues of known structure. WU-BLAST is used for nrdb searches with user supplied sequences.
Cellular Role
Chromatin is the tangled fibrous complex of DNA and protein within a eukaryotic nucleus
Interaction (with the environment)
Molecules that sense cellular environmental change, such as osmolarity, light flux, acidity, ion concentration etc
Enzymes that catalyze reactions in living cells that transform organic molecules
The process of making an identical copy of a section of duplex (double-stranded) DNA, using existing DNA as a template for the synthesis of new DNA strands
Proteins that participate in a pathway that is initiated by a molecular stimulus and terminated by a cellular response
Transporters (permeases) are proteins that straddle the cell membrane and carry specific nutrients, ions, etc. across the membrane
The process in which the genetic code carried by messenger RNA directs the synthesis of proteins from amino acids
The synthesis of an RNA copy from a sequence of DNA (a gene); the first step in gene expression
Coiled coils
Intimately-associated bundles of long alpha-helices ([1], [2], [3]). Coiled coils are detected in SMART using the method of Lupas et al. ([4], COILS home). Coiled coils predictions are indicated on the second line in SMART's graphical output.
Conserved structural entities with distinctive secondary structure content and an hydrophobic core. In small disulphide-rich and Zn2+-binding or Ca2+- binding domains the hydrophobic core may be provided by cystines and metal ions, respectively. Homologous domains with common functions usually show sequence similarities.
Domain composition
Proteins with the same domain composition have at least one copy of each of domains of the query.
Domain organisation
Proteins having all the domains as the query in the same order (Additional domains are allowed).
A WWW-based system that allows easy retrieval of sequence, structure, molecular biology and literature data (Entrez). SMART's domain annotation pages contain links to the Entrez system thereby providing extensive literature, structure and sequence information.
This represents the number of sequences with a score greater-than, or equal to, X, expected absolutely by chance. The E-value connects the score ("X") of an alignment between a user-supplied sequence and a database sequence, generated by any algorithm, with how many alignments with similar or greater scores that would be expected from a search of a random sequence database of equivalent size. Since version 2.0 E-values are calculated using Hidden Markov Models, leading to more accurate estimates than before.
Extracellular Domains
Domain families that are most prevalent in proteins outside of the cytoplasm and the nucleus.
A position in an alignment that represents a deletion within one sequence relative to another. Gap penalties are requirements for alignment algorithms in order to reduce excessively-gapped regions. Gaps in alignments represent insertions that usually occur in protruding loops or beta-bulges within protein structures.
Genomic database
Protein database used in SMART's 'Genomic' mode. It contains data from completely sequenced genomes only. Ensembl data is used for Metazoan genomes and Swiss-Prot for others. A complete list of genomes in the database is avaliable.
HMM, Hidden Markov model
HMMs are statistical models of the sequence consensus of an homologous family (see the docu). A particular class of HMMs has been shown to be equivalent to generalised profiles (8867839). Applications of HMMs to sequence analysis are nicely provided by HMMer and SAM.
HMM consensus
The HMM consensus is a 'one line summary' of the corresponding HMM. The amino acid shown for the consensus is the highest probability amino acid at that position according to the HMM. Capital letters mean "highly conserved" residues (probability > 0.5 for protein models). (modified from the HMMer User's Guide)
The HMMer package ([1], [2]) provides multiple alignment and database searching capabilities.
There are several programs in the package (see the docu) including one (hmmfs) that searches databases for non-overlapping LOCAL similarities (i.e. that match across at least part of the HMM), and another (hmmls) that searches databases for non-overlapping GLOBAL similarities (i.e. that match across the full HMM). These correspond approximately to profile-based searches using negative and positive profiles, respectively (see WiseTools). Database searches using hmmls or hmmfs provide alignment scores as bits scores.
Evolutionary descent from a common ancestor due to gene duplication.
Intracellular Domains
Domain families that are most prevalent in proteins within the cytoplasm.
Numbers of domains that are thought from SwissProt annotations to be present in different cellular compartments (cytoplasm, extracellular space, nucleus, and membrane-associated) are shown in annotation pages.
Sequence motifs are short conserved regions of polypeptides. Sets of sequence motifs need not necessarily represent homologues.
NRDB, non-redundant database
A database that contains no identical pairs of sequences. It can contain multiple sequences originating from the same gene (fragments, alternative splicing products...). SMART in 'Standard' mode uses such database.
Open reading frame.
Outlier homologues
These are often difficult to detect using HMM methodology. A complementary approach to their detection is to query a database of sequences taken from multiple sequence alignments, using BLAST.
Selecting this option will also activate searches against sequence databases derived from proteins of known structure. A simple BLAST search of the PDB is performed, together with a search of RPS_Blast profiles derived from SCOP. These profiles were kindly provided by Steffen Schmidt (see Schmidt et al. J. Chem. Inf. Comput. Sci. 2002 (42) 405-7).
This represents a probability that, given a database of a particular size, random sequences score higher than a value X. P-values are generated by the BLAST algorithm that has been integrated into SMART.
PDB, protein data bank
PDB is an archive of experimentally-determined three-dimensional structures (Brookhaven nat. Labs or EBI). Domain families represented in SMART and in the PDB are annotated as being of known structure; links are provided in SMART to the PDB via PDBsum and MMDB. PDBsum links can be used to access a variety of sequence-based and structure-based tools, whereas MMDB provides access to literature information and structure similarities.
Pfam is a database of protein domain families represented as (i) multiple alignments, and (ii) HMM-profiles ([1], [2]). Pfam WWW servers allow comparison of user-supplied sequences with the Pfam database (Sanger Center and Washington Univ.).
SMART contains a facility to search the Pfam collection using HMMer.
Prokaryotic domains
SMART now also searches for domains found in two component regulatory systems. These can be found mainly in Prokaryotes, but a few were also found in eukaryotes like yeast and plants.
A profile is a table of position-specific scores and gap penalties, representing an homologous family, that may be used to search sequence databases (Ref.: [1], [2], [3]).
In CLUSTAL-W-derived profiles those sequences that are more distantly related are assigned higher weights ([4], [5], [6]). Issues in profile-based database searching are discussed in Bork & Gibson (1996) [7].
An excellent WWW server that allows a user to compare a protein or DNA sequence against a database of profiles (located at the ISREC).
This is a dictionary of protein sites and motif patterns. Some SMART domain annotations contain links to PROSITE.
Schnipsel database; domain sequence database
"Schnipsel" is a German word meaning 'snippet' or 'fragment'. The schnipsel database consists of the sequences off all domains found with SMART in NRDB. Outliers of a family often cannot be detected by a profile, yet are detectable by pairwise similarity to one or more established members of a sequence family. So, searching against the schnipsel database gives complementary information to the profile searches.
Searched domains
In the first version of SMART, only eukaryotic signalling domains could be searched. In 1998 we have extended this set by prokaryotic signalling and extracellular domains. In the input page you can choose wether you only want to search cytoplasmic (prokaryotic + eukaryotic), extracellular or all domains.
Secondary Literature
The secondary literature is derived by the following procedure. For each of the hand selected papers referenced by a domain, 100 neighbouring papers are retrieved using Medline. If one of these neighbouring papers is referenced from more than two original papers, it is included into the secondary literature list.
Seed Alignment
Alignment that contains only one of each pair of homologues that are represented in a CLUSTALW-derived phylogenetic tree linked by a branch of length less than a distance of 0.2 (see the related article).
A program of Wootton & Federhen [1] that detects regions of the query sequence that have low compositional complexity [2].
Sequence ID or ACC
Sequence identifiers or accession codes may be entered via the SMART homepage to initiate a query. You can use either Uniprot or Ensembl sequence identifiers.
Signalling Domains
The original set of domains used in SMART were collected as those that satisfied one or both of two criteria:
  1. cytoplasmic domains that possess kinase, phosphatase, ubiquitin ligase or phospholipase enzymatic activities or those that stimulate GTPase-activation or guanine nucleotide exchange
  2. cytoplasmic domains that occur in at least two proteins with different domain organisations, of which one also contains a domain that satisfies criterion 1
These domains mostly mediate or regulate the transduction of an extracellular signal towards the nucleus resulting in the initiation of a cellular response. More recently, prokaryotic two-component signalling domains have been added to the SMART set.
This program predicts the presence and location of signal peptide cleavage sites in amino acid sequences (SignalP home page).
SMART, Simple Modular Architecture Research Tool
Our main goal in providing this tool is to allow automatic identification and annotation of domains in user-supplied protein sequences.
Numbers of domains present in a variety of selected taxa (animal, archaea, bacteria, fungi, plants and protozoa) are shown in annotation pages.
The SwissProt database is an extensively annotated and non-redundant collection of protein sequences. SwissProt annotations have been mined for SMART-derived annotations of alignments.
This program predicts the location and topology of transmembrane helices (TMHMM2).
For each of the domains found by SMART a combination of thresholds is used to distinguish between true and false hits. The different thresholds are described in the SMART paper.
A package that is based on database searches using profiles. Profiles may be generated using PairWise, and then compared with sequence databases using SearchWise. Scores are generated for alignments that match the whole of the profile (using a "positive" profile) or else that match at least part of the profile (using a "negative" profile). Only the top-scoring optimal alignment of each sequence is reported; hence, SMART relies on re-iterating the search for new repeats until none are reported that score above threshold. Score thresholds have been set manually that are considered to represent a score just above the top-scoring true negative. Additional thresholds have been estimated for domains that are repeated in single polypeptides. A more recent package allows comparison of DNA sequences at the level of their conceptual translations, regardless of sequence error and introns (see Wise2).