SII-SWORD/CoKE huggingface dataset:
LTXXQ motif family protein (LTXXQ)
Type: Family

This family summarizes bacterial proteins related to CpxP, a periplasmic protein that forms part of a two-component system which acts as a global modulator of cell-envelope stress in Gram-negative bacteria. CpxP aids in combating extracytoplasmic protein-mediated toxicity, and may also be involved in the response to alkaline pH . Functioning as a dimer, it inhibits activation of the kinase CpxA, but also plays a vital role in the quality control system of P pili. It has been suggested that CpxP directly interacts with CpxA via its concave polar surface . Another member of this family, Spy, is also a periplasmic protein that may be involved in the response to stress . The homology between CpxP and Spy suggests similar functions. A characteristic 5-residue sequence motif LTXXQ is found repeated twice in many members of this family .
G-box binding protein, multifunctional mosaic region (MFMR)
Type: Domain

This region is often found to the N terminus of the basic-leucine zipper domain (

). It is between 150 and 200 amino acids in length. The N-terminal half of this domain is rich in proline residues and has been termed the PRD (proline rich domain) , whereas the C-terminal half is more polar and has been called the MFMR (multifunctional mosaic region). According to their motif composition, proteins containing this domain can be classified into three sub-families called A, B and C . It has been suggested that some of these motifs may be involved in mediating protein-protein interactions . The MFMR region contains a nuclear localisation signal in bZIP opaque and GBF-2 . The MFMR also contains a transregulatory activity in TAF-1. The MFMR in CPRF-2 contains cytoplasmic retention signals .
Carnosine N-methyltransferase (CARME)
Type: Family

This family includes Carnosine N-methyltransferase (

), conserved from yeast to human, that catalyses the formation of anserine (beta-alanyl-N(Pi)-methyl-L-histidine) from carnosine. Anserine, a methylated derivative of carnosine (beta-alanyl-L-histidine), is an abundant constituent of vertebrate skeletal muscles. It also methylates other L-histidine-containing di- and tripeptides such as Gly-Gly-His, Gly-His and homocarnosine (GABA-His) .

Carnosine N-methyltransferase unmet from Drosophila melanogaster, acts as a sensor to signal methionine availability to the mTORC1 signaling pathway . It associates with the GATOR2 complex in the absence of methionine to inhibit mTORC1 signalling, but dissociates in the presence of the methionine derivative S-adenosyl-L-methionine; S-adenosyl-L-homocysteine binding does not induce dissociation . It is required for mTORC1 pathway response to methionine starvation .
Prokaryotic N-terminal methylation site (N_methyl_site)
Type: PTM

This short motif directs methylation of the conserved phenylalanine residue. It is most often found at the N terminus of pilins and other proteins involved in secretion (see

,

,

and

).
Nif11 domain (Nif11)
Type: Domain

This domain is found mainly in the Cyanobacteria and in Proteobacteria such as the nitrogen-fixing bacterium Azotobacter vinelandii. It is found in Nif11, a protein described in Azotobacter as linked to nitrogen fixation . It also constitutes a leader peptide in Nif11-derived peptides (N11P), which are thought to be post-translationally modified microcins derived from a putative nitrogen-fixing protein . N11P sequences have a classic leader peptide cleavage motif, usually Gly-Gly, which marks the end of family-wide similarity area and the beginning of a low-complexity region rich in Cys, Gly and Ser .
8-oxoguanine DNA glycosylase, N-terminal (OGG_N)
Type: Domain

The presence of 8-oxoguanine residues in DNA can give rise to G-C to T-A transversion mutations. This enzyme is found in archaeal, bacterial and eukaryotic species, and is specifically responsible for the process which leads to the removal of 8-oxoguanine residues. It has DNA glycosylase activity (

) and DNA lyase activity (

) . The region featured in this family is the N-terminal domain, which is organised into a single copy of a TBP-like fold. The domain contributes residues to the 8-oxoguanine binding pocket .
PA-IL-like (PA-IL)
Type: Family

The members of this family are similar to the galactophilic lectin-1 expressed by Pseudomonas aeruginosa (PA-IL,

). Lectins recognising specific carbohydrates found on the surface of host cells are known to be involved in the initiation of infections by this organism. The protein is thought to be organised into an extensive network of β-sheets, as is the case with many other lectins .
Transcriptional repressor PaaX-like, N-terminal (PaaX-like_N)
Type: Domain

This entry describes the N-terminal region of Transcriptional repressor PaaX from Escherichia coli and similar bacterial proteins. PaaX is involved in metabolism of phenylacetic acid . The gene product has been shown to bind to the promoter sites and repress their transcription .
Peptidase S11, D-Ala-D-Ala carboxypeptidase A, C-terminal (Peptidase_S11_C)
Type: Domain

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

This entry contains proteins that are annotated as penicillin-binding protein 5 and 6. These belong to MEROPS peptidase family S11 (D-Ala-D-Ala carboxypeptidase A family, clan SE). Penicillin-binding protein 5 expressed by Escherichia coli functions as a D-alanyl-D-alanine carboxypeptidase. It is composed of two domains that are oriented at approximately right angles to each other. The N-terminal domain (

) is the catalytic domain. The C-terminal domain, this entry, is organised into a sandwich of two anti-parallel β-sheets, and has a relatively hydrophobic surface as compared to the N-terminal domain. Its precise function is unknown; it may mediate interactions with other cell wall-synthesising enzymes, thus allowing the protein to be recruited to areas of active cell wall synthesis. It may also function as a linker domain that positions the active site in the catalytic domain closer to the peptidoglycan layer, to allow it to interact with cell wall peptides .
GPI inositol-deacylase PGAP1-like alpha/beta domain (PGAP1-ab_dom-like)
Type: Domain

This domain is found in GPI inositol-deacylase PGAP1 and related proteins. It is found toward the N terminus and it is a lipase domain with a typical α/β/α hydrolase architecture .

PGAP1 is an endoplasmic reticulum membrane protein with a catalytic serine-containing motif that is conserved in a number of lipases. PGAP1 functions as a GPI inositol-deacylase; this deacylation is important not only for the efficient transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi body but also for efficient degradation of misfolded GPI-anchored proteins in the ER .
PHA accumulation regulator DNA-binding, N-terminal (PHA_DNA-bd_N)
Type: Domain

This domain is found at the N terminus of the polyhydroxyalkanoate (PHA) synthesis regulators. These regulators have been shown to directly bind DNA and PHA . The invariant nature of this domain compared to the C-terminal

domain(s) suggests that it contains the DNA-binding function.
TonB-dependent receptor, plug domain (Plug_dom)
Type: Domain

This entry represents the plug domain, which has been shown to be an independently folding subunit of the TonB-dependent receptors . It acts as the channel gate, blocking the pore until the channel is bound by a ligand. At this point it undergoes conformational changes and opens the channel.

In
Escherichia coli
the TonB protein interacts with outer membrane receptor proteins that carry out high-affinity binding and energy-dependent uptake of specific substrates into the periplasmic space . These substrates are either poorly permeable through the porin channels or are encountered at very low concentrations. In the absence of TonB, these receptors bind their substrates but do not carry out active transport. TonB-dependent regulatory systems consist of six components: a specialised outer membrane-localized TonB-dependent receptor (TonB-dependent transducer) that interacts with its energizing TonB-ExbBD protein complex, a cytoplasmic membrane-localized anti-sigma factor and an extracytoplasmic function (ECF)-subfamily sigma factor . The TonB complex senses signals from outside the bacterial cell and transmits them via two membranes into the cytoplasm, leading to transcriptional activation of target genes. The proteins that are currently known or presumed to interact with TonB include BtuB , CirA, FatA, FcuT, FecA , FhuA , FhuE, FepA , FptA, HemR, IrgA, IutA, PfeA, PupA and Tbp1. The TonB protein also interacts with some colicins. Most of these proteins contain a short conserved region at their N terminus .
Protein serine/threonine phosphatase 2C, C-terminal (PP2C_C)
Type: Domain

Protein phosphatase 2C (PP2C, also known as Protein phosphatase 1) is involved in regulating cellular responses to stress in various eukaryotes. It consists of two domains: an N-terminal catalytic domain and a C-terminal domain characteristic of mammalian PP2Cs. This domain consists of three antiparallel α helices, one of which packs against two corresponding α-helices of the N-terminal domain. The C-terminal domain does not seem to play a role in catalysis, but it may provide protein substrate specificity due to the cleft that is created between it and the catalytic domain .
Plasmid pRiA4b, Orf3-like domain (Plasmid_pRiA4b_Orf3-like)
Type: Domain

Members of this entry are similar to the protein product of ORF-3 (

) found on plasmid pRiA4 in the bacterium Agrobacterium rhizogenes. This plasmid is responsible for tumorigenesis at wound sites of plants infected by this bacterium, but the ORF-3 product does not seem to be involved in the pathogenetic process . Other proteins found in this entry are annotated as being putative TnpR resolvases (

,

), but no further evidence was found to back this. Moreover, another member of this entry is described as a probable lexA repressor (

) and in fact carries a LexA DNA binding domain (

), but no references were found to expand on this.
Protein OS9-like domain (OS9-like_dom)
Type: Domain

This entry represents a domain found in the OS9 protein, which is a lectin that functions in endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD) .
Purine catabolism PurC-like domain (PucR_dom)
Type: Domain

This domain is found in the purine catabolism regulatory protein expressed by Bacillus subtilis (PucR,

).

PucR is thought to be a transcriptional regulator of genes involved in the purine degradation pathway, and may contain a LysR-like DNA-binding domain . It is similar to LysR-type regulators in that it represses its own expression . The other members of this family are also putative regulatory proteins.
Reovirus RNA-dependent RNA polymerase lambda 3 (RdRP_5)
Type: Family

The sequences in this family are similar to the reoviral minor core protein lambda 3 (

), which functions as a RNA-dependent RNA polymerase within the protein capsid. It is organised into 3 domains. The N- and C-terminal domains create a "cage" which encloses a conserved central catalytic domain within a hollow centre. This catalytic domain is arranged to form finger, palm and thumb subdomains. Unlike other RNA polymerases, such as HIV reverse transcriptase and T7 RNA polymerase, the lambda 3 protein binds template and substrate with only localised rearrangements, and catalytic activity can occur with little structural change. However, the structure of the catalytic complex is similar to that of other polymerase catalytic complexes with known structure .
RED-like, N-terminal (RED_N)
Type: Domain

This domain contains sequences that are similar to the N-terminal region of Red protein (

). This and related proteins contain a RED repeat which consists of a number of RE and RD sequence elements . The region in question has several conserved NLS sequences and a putative trimeric coiled-coil region , suggesting that these proteins are expressed in the nucleus . Protein RED (also known as IK) is found in the nucleus and is a component of the spliceosome . It is also associated with the spindle pole where it co-localizes with and interacts with the spindle assembly checkpoint protein MAD1 during metaphase and anaphase. Depletion of RED shortens the mitotic cycle and MAD1 is incorrectly localized .
Protein of unknown function DUF3294 (DUF3294)
Type: Family

This family was annotated as mitochondrial ribosomal protein Mrp8, based on the presumed similarity of the S.cerevisiae protein to an E.coli mitochondrial ribosomal protein. However, this similarity is spurious, and the function is not known.
RTP801-like (RTP801-like)
Type: Family

RTP801, also known as REDD1, is the protein product of a hypoxia-inducible factor 1 (HIF-1)- responsive gene and is thought to be involved in various cellular processes . Both RTP801 and RTP801-like (REDD2) work downstream of AKT and upstream of TSC2 to inhibit mTOR, a serine/threonine kinase that plays an essential role in cell growth control . Two members of this family expressed by Drosophila melanogaster, Scylla (

) and Charybde (

), are designated as Hox targets .
SUN domain (SUN_dom)
Type: Domain

Sad1/UNC-84 (SUN)-domain proteins are inner nuclear membrane (INM) proteins that are part of bridging complexes linking cytoskeletal elements with the nucleoskeleton. Originally identified based on an ~150-amino acid region of homology between the C terminus of the Schizosaccharomyces pombe Sad1 protein and the Caenorhabditis elegans UNC-84 protein, SUN proteins are present in the proteomes of most eucaryotes. In addition to the SUN domain, these proteins contain a transmembrane sequence and at least one coiled-coil domain and localise to the inner nuclear envelope. SUN proteins are anchored in the inner nuclear envelope by their transmembrane segment and oriented in the membrane such that the C-terminal SUN domain is located in the space between the inner and outer nuclear membrane. Here, the SUN domain can interact with the C- terminal tail of an outer nuclear envelope protein that binds to the cytoskeleton, including the centrosome .

Some proteins known to contain a SUN domain are listed below:

Fission yeast spindle pole body-associated protein Sad1.

Yeast spindle pole body assembly component MPS3, essential for nuclear division and fusion.

Yeast uncharacterised protein SLP1.

Caenorhabditis nuclear migration and anchoring protein UNC-84.

Caenorhabditis SUN domain-containing protein 1 (sun-1), involved in centrosome attachment to the nucleus.

Mammalian sperm-associated antigen 4 protein (SPAG4), may assist the organisation and assembly of outer dense fibres (ODFs), a specific structure of the sperm tail.

Mammalian sperm-associated antigen 4-like protein (SPAG4L).

Mammalian SUN1.

Mammalian SUN2.

Mammalian SUN3.

Klaroid protein from Drosophila melanogaster .
Ribosomal RNA methyltransferase, SPB1-like, C-terminal (rRNA_MeTfrase_SPB1-like_C)
Type: Domain

This domain is found at the C terminus SPB1-like proteins. This domain interacts with the meandering tail of Erb1 and its removal is required to form the pre-mature inter-subunit surface of the Arx1/Nog2 particle .

SPB1 is an adoMet-dependent rRNA methyltransferase required for proper assembly of pre-ribosomal particles during the biogenesis of the 60S ribosomal subunit . In Saccharomyces cerevisiae, it specifically methylates the guanosine in position 2922 of the 25S rRNA at the stage of 27S pre-rRNA maturation . It interacts with the snoRNA-associated proteins Nop1 and Nop58 .
Spen paralogue and orthologue SPOC, C-terminal (SPOC_C)
Type: Domain

Spen (split end) proteins regulate the expression of key transcriptional effectors in diverse signalling pathways. They are large proteins characterised by N-terminal RNA-binding motifs and a highly conserved C-terminal SPOC (Spen paralog and ortholog C-terminal) domain. The function of the SPOC domain is unknown, but the SPOC domain of the SHARP Spen protein has been implicated in the interaction of SHARP with the SMRT/NcoR corepressor, where SHARP plays an essential role in the repressor complex .

The SPOC domain is folded into a single compact domain consisting of a β-barrel with seven strands framed by six α helices. A number of deep grooves and clefts in the surface, plus two nonpolar loops, render the SPOC domain well suited to protein-protein interactions; most of the conserved residues occur on the protein surface rather than in the core. Other proteins containing a SPOC domain include Drosophila Split ends, which promotes sclerite development in the head and restricts it in the thorax, and mouse MINT (homologue of SHARP), which is involved in skeletal and neuronal development via its repression of Msx2.
ORF D-335-like (ORF_D-335)
Type: Domain

The sequences featured in this family are similar to a probable integrase (

) expressed by the SSV1 virus of the archaeon Sulfolobus shibatae. This protein may be necessary for the integration of the virus into the host genome by a process of site-specific recombination .
Chromosome segregation in meiosis protein 3 (Csm3)
Type: Domain

This entry represents a domain found in a group of proteins, including Csm3 from budding yeasts, Swi3 from fission yeasts and TIPIN from animals. They are involved in DNA replication and the maintenance of replication fork stability .
TfuA-like, core (TfuA_core)
Type: Domain

This domain consists of a group of sequences that are similar to the core of TfuA protein (

). TfuA plays a crucial dual role in peptide backbone thioamidation, functioning as both a hydrolase and a protein interaction mediator. It catalyses the hydrolysis of ThiS-COSH using a Ser/Lys catalytic pair to generate sulfide, while also enhancing YcaO's affinity for peptide substrates by approximately 8-fold. Structurally, TfuA has a unique di-domain architecture consisting of a main α/β fold domain which contains the catalytic residues and ThiS binding pocket, and a 4-helical bundle insertion which mediates interactions with YcaO. TfuA shares some local structural similarities with periplasmic solute-binding proteins and alpha/beta hydrolases. The coordinated action of these domains enables TfuA to work with YcaO as a thioamide synthetase, facilitating peptide modifications in archaea and bacteria .
TipAS antibiotic-recognition domain (TipAS_dom)
Type: Domain

TipAL is a bacterial transcriptional regulator of the MerR family. The tipA gene can be expressed as a long form, TipAL, and a short form, TipAS, which constitutes the C-terminal part of TipAL. TipAS forms the antibiotic-recognition domain . This domain, which has an α-helical globin-like fold, is also found at the C terminus of other MerR family transcription factors, including Mta, a central regulator of multidrug resistance in Bacillus subtilis , and SkgA from Caulobacter crescentus .
TMEM120A/B (TMEM120A/B)
Type: Family

This entry represents a group of transmembrane proteins including TACAN (also known as TMEM120A) and TMEM120B. TMEM120A is involved in mechanosensation and plays an essential role in lipid metabolism and adipocyte differentiation . It was first described as an ion channel that contributes to sensing mechanical pain , however, several studies show that TMEM120A does not exhibit mechanosensitive channel activity and display no typical ion channel structural characteristics . TMEM120A is structurally similar to a lipid-modifying enzyme, ELOVL7, and contains a bound coenzyme A molecule, which suggests it might function as an enzyme in lipid metabolism . Therefore, if TMEM120A is an enzyme rather than an ion channel is still in debate. TMEM120A and TMEM120B may be required for efficient adipogenesis .
ShET2 enterotoxin, N-terminal (Toxin_15_N)
Type: Domain

This domain is present in the N-terminal region of the ShET2 enterotoxin produced by Shigella flexneri (

) and Escherichia coli (

). This protein was found to confer toxigenicity in Ussing chamber assays, and the N-terminal region was found to be important for its enterotoxic effect. The N-terminal domain is a cysteine-type peptidase with a Cys/His/Asp catalytic triad that cleaves within the receptor-interacting protein homotypic interaction motifs found within host adaptor proteins such as receptor-interacting serine/threonine protein kinases RIPK1 and RIPK3, TIR-domain-containing adapter-inducing interferon beta and Z-DNA-binding protein 1, inactivating them and thus inhibiting necroptosis and inflammatory signalling . The toxin is injected into the host cell by the type III secretion system .

Most proteins containing this domain are annotated as putative enterotoxins, but one member (

) is a regulator of acetyl CoA synthetase, and another two members (

and

) are annotated as ankyrin-like regulatory proteins and contain Ank repeats (

).
Clostridium neurotoxin, receptor binding N-terminal (Toxin_rcpt-bd_N)
Type: Domain

The Clostridium neurotoxin family is composed of tetanus neurotoxin and seven serotypes of botulinum neurotoxin. These toxins act as inhibitors of neurotransmitter release .

The structure of the botulinum neurotoxin reveals a four domain protein. The N-terminal catalytic domain (

), the central translocation domain and two receptor binding domains . This domain is the N-terminal receptor binding domain, which is comprised of two seven-stranded β-sheets sandwiched together to form a jelly role motif . The role of this domain in receptor binding appears to be indirect.
Nucleoprotein, TPR/MLP1-2 domain (Nucleoprot-TPR/MLP1-2_dom)
Type: Domain

This domain is found in several proteins, including TPR protein and yeast myosin-like protein 1 (MLP1) and MPL2.

TPR and MLP1/2 share several features; for example, they have coiled-coil regions and are associated with nuclear pores . TPR is thought to be a component of nuclear pore complex-attached intranuclear filaments , and is implicated in nuclear protein import . Moreover, its N-terminal region is involved in the activation of oncogenic kinases, possibly by mediating the dimerisation of kinase domains or by targeting these kinases to the nuclear pore complex . MLP1 acts as a docking platform for heterogeneous nuclear ribonucleoproteins that are required for mRNA export .
TraC-like (TraC)
Type: Family

The members of this family are sequences that are similar to TraC (

) from Rhizobium etli. The gene encoding this protein is one of a group of genes found on plasmid p42a of Rhizobium etli (strain CFN 42/ATCC 51251) that are thought to be involved in the process of plasmid self-transmission. Mobilisation of plasmid p42a is of importance as it is required for transfer of plasmid p42d, the symbiotic plasmid which carries most of the genes required for nodulation and nitrogen fixation by this symbiotic bacterium. The predicted protein products of p42a are similar to known transfer proteins of Agrobacterium tumefaciens plasmid pTiC58 .