SII-SWORD/CoKE huggingface dataset:
Cold-shock domain, conserved site (CSD_CS)
Type: Conserved_site

The cold-shock domain (CSD) is an ancient β-barrel fold of about 70 amino acids that binds single-stranded nucleic acids (both RNA and DNA). CSD- containing proteins have been found in all three domains of life and function in a variety of processes that are related, for the most part, to post- translational gene regulation. CSDs were first found in bacterial cold-shock proteins (CSPs). CSPs are small, abundant proteins that are essentially composed of one CSD. Some members of this family are strongly induced after cold shock and are involved in adaptation to low temperatures, while others function during normal growth conditions. Bacterial CSPs bind to single- stranded nucleic acids and function as RNA chaperones, rescuing RNAs trapped in unproductive folding states. This general molecular function enables CSPs to participate in the regulation of practically any step of gene expression involving RNA, including transcription, translation, and RNA turnover. Since their discovery in bacterial CSPs, CSDs have been found in many other bacterial and eukaryotic proteins. In multicellular organisms, CSDs are usually embedded in larger proteins .

The CSD adopts a five-stranded antiparallel β-barrel structure, which is similar to the oligonucleotide/oligosaccharide fold (OB-fold). Many CSDs contain the motifs [YF]-G-F-I and [VF]-[VF]-H, which are known as the ribonucleoprotein (RNP)-1 and RNP-2 motifs and include most of the residues involved in the interaction with nucleic acids. RNP-1 and RNP-2 are located in strands beta2 and beta3, respectively .

This conserved region is located at the N-terminal. The beginning of this region is highly similar to the RNP-1 RNA-binding motif .
Squalene/phytoene synthase, conserved site (Squalene/phytoene_synthase_CS)
Type: Conserved_site

Squalene synthase

(farnesyl-diphosphate farnesyltransferase)(SQS) and phytoene synthase

(PSY) share a number of functional similarities. These similarities are also reflected at the level of their primary structure . In particular three well conserved regions are shared by SQS and PSY; they could be involved in substrate binding and/or the catalytic mechanism. SQS catalyses the conversion of two molecules of farnesyl diphosphate (FPP) into squalene. It is the first committed step in the cholesterol biosynthetic pathway. The reaction carried out by SQS is catalysed in two separate steps: the first is a head-to-head condensation of the two molecules of FPP to form presqualene diphosphate; this intermediate is then rearranged in a NADP-dependent reduction, to form squalene:

2 FPP ->presqualene diphosphate + NADP ->squalene

SQS is found in eukaryotes. In yeast it is encoded by the ERG9 gene, in mammals by the FDFT1 gene. SQS seems to be membrane-bound.

PSY catalyses the conversion of two molecules of geranylgeranyl diphosphate (GGPP)into phytoene. It is the second step in the biosynthesis of carotenoids from isopentenyl diphosphate. The reaction carried out by PSY is catalysed in two separate steps: the first is a head-to-head condensation of the two molecules of GGPP to form prephytoene diphosphate; this intermediate is then rearranged to form phytoene:

2 GGPP ->prephytoene diphosphate ->phytoene

PSY is found in all organisms that synthesise carotenoids: plants and photosynthetic bacteria as well as some non-photosynthetic bacteria and fungi. In bacteria PSY is encoded by the gene crtB. In plants PSY is localised in the chloroplast.

Both SQS and PSY share a number of functional similarities which are also reflected at the level of their primary structure. In particular, three well conserved regions are shared by SQS and PSY, which could be involved in substrate binding and/or the catalytic mechanism. This entry contains the second and third conserved regions located in the central part of these enzymes.
Nerve growth factor conserved site (Nerve_growth_factor_CS)
Type: Conserved_site

This entry covers the central region of the proteins and include two of the six cysteines involved in disulphide bonds.

During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells . Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF or beta-NGF), a vertebrate protein that stimulates division and differentiation of sympathetic and embryonic sensory neurons . NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown ; it has also been found in several snake venoms .

NGF is a protein of about 120 residues that is cleaved from a larger precursor molecule. It contains six cysteines all involved in intrachain disulphide bonds. A schematic representation of the structure of NGF is shown below:

+------------------------+
| |
| |
xxxxxxCxxxxxxxxxxxxxxxxxxxxxCxxxxCxxxxxCxxxxxxxxxxxxxCxCxxxx
| | | |
+--------------------------|-----+ |
+---------------------+

'C': conserved cysteine involved in a disulphide bond.

This entry also contains NGF-related proteins such as neutrophin 3, which promotes the survival of visceral and proprioceptive sensory neurons, and brain-derived neurotrophin, which promotes the survival of neuronal populations that are located either in the central nervous system or directly connected to it .
Gliding motility associated protein GldN (Gliding_motility_assoc_GldN)
Type: Family

Members of this protein family are exclusive to the Bacteroidetes phylum (previously Cytophaga-Flavobacteria-Bacteroides). GldN is a protein linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) and Cytophaga hutchinsonii. Knockouts of GldN abolish the gliding phenotype . Gliding motility appears closely linked to chitin utilization in the model species C. johnsonae. Bacteroidetes with members of this protein also include those which are not believed to express the gliding phenotype, such as Prevotella intermedia and Porphyromonas gingivalis (Bacteroides gingivalis).
CRISPR-associated protein, Csx14 (CRISPR-assoc_prot_Csx14)
Type: Family

This entry is found in Cas proteins from a variety of bacterial and archaeal species, including Pelotomaculum thermopropionicum (strain DSM 13744/JCM 10971/SI), Thermoanaerobacter tengcongensis MB4, Roseiflexus sp. (strain RS-1), Thermoplasma volcanium, Picrophilus torridus, and Methanospirillum hungatei. The function of these proteins is unknown.

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
GldD-like (GldD-like)
Type: Family

This entry represents the GldD lipoprotein family, found in members of the Bacteroidetes lineage, including species such as Cytophaga johnsonae, which exhibit a poorly understood form of rapid gliding motility, as well as species that lack this capability. GldD is a post-translationally modified lipoprotein and an essential component of the bacterial gliding motility machinery. In C. johnsonae, mutation of the GldD gene disrupts both gliding motility and chitin utilisation, underscoring its functional importance . Although GldD is critical for surface motility, its precise molecular role remains to be fully elucidated.
CRISPR-associated protein Cas1, ECOLI subtype (CRISPR-assoc_Cas1_ECOLI)
Type: Family

This entry describes the Cas1 protein particular to the ECOLI subtype of CRISPR/Cas system.

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
Gliding motility-associated protein, GldL (Motility-assoc_prot_GldL)
Type: Family

This protein family, GldL, is named for the member from Cytophaga johnsonae (Flavobacterium johnsoniae), which is required for a type of rapid gliding motility found in certain members of the Bacteriodetes . However, members of this protein family are found also in several members of the Bacteriodetes that appear not to be motile
GldB-like (GldB-like)
Type: Family

This entry represents the GldB protein family, which is found in various members of the Bacteroidetes lineage, including species such as Cytophaga johnsonae , known for exhibiting a poorly understood form of rapid gliding motility, as well as other species that lack this phenotype . GldB is an essential component of the bacterial gliding motility machinery in *F. johnsoniae* and related organisms. It is believed to be anchored to the cell membrane and to function as part of a larger motility complex, though its precise molecular role remains unresolved. GldB operates in coordination with other Gld proteins to facilitate the distinct form of bacterial surface locomotion termed gliding motility. While distantly related to zincin-type proteins, GldB lacks the conserved zinc-binding motif characteristic of that family.
Gliding motility-associated protein, GldC (Motility-assoc_prot_GldC)
Type: Family

Members of this protein family are exclusive to the Bacteroidetes phylum (previously Cytophaga-Flavobacteria-Bacteroides) . GldC is a protein linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) and Cytophaga hutchinsonii. Knockouts of GldC do not abolish the gliding phenotype but do impair it. Gliding motility appears closely linked to chitin utilization in the model species C. johnsonae. Bacteroidetes with members of this protein family appear to have all of the genes associated with gliding motility.
CRISPR-associated protein Cas1, NMENI subtype (CRISPR-assoc_Cas1_NMENI)
Type: Family

This entry describes the Cas1 variant of the NMENI subtype of CRISPR/Cas system.

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
CRISPR-associated protein Cas1, DVULG subtype (CRISPR-assoc_Cas1_DVULG)
Type: Family

This entry describes the Cas1 protein particular to the DVULG subtype of CRISPR/Cas system. This is also known as Cas1 Type I-C .

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes . CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).
CRISPR-associated protein Cas1, YPEST subtype (CRISPR-assoc_Cas1_YPEST-subtyp)
Type: Family

This entry describes the Cas1 protein particular to the YPEST subtype of CRISPR/Cas system. This is also known as Cas1 Type I-F .

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
CRISPR-associated protein Cas1, HMARI/TNEAP subtype (CRISPR-assoc_Cas1_HMARI/TNEAP)
Type: Family

This entry describes a Cas1 subgroup that includes Cas1 proteins of the related HMARI and TNEAP subtypes of CRISPR/Cas system.

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
Gliding motility-associated protein GldM (Motility-assoc_prot_GldM)
Type: Family

This protein family, GldM, is named for the member from Cytophaga johnsonae (Flavobacterium johnsoniae), which is required for a type of rapid gliding motility found in certain members of the Bacteriodetes . However, members of this protein family are found also in several members of the Bacteriodetes that appear not to be motile. The best conserved region, toward the N terminus, is centred on a highly hydrobobic probable transmembrane helix. Two paralogs are found in Cytophaga hutchinsonii.
Gliding motility-associated ABC transporter permease protein GldF (Motility-assoc_ABC_perm_GldF)
Type: Family

Members of this protein family are exclusive to the Bacteroidetes phylum. GldF is believed to be a ABC transporter permease protein (along with ATP-binding subunit, GldA and a substrate-binding subunit, GldG) and is linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) and Cytophaga hutchinsonii. Knockouts of GldF abolish the gliding phenotype . Gliding motility appears closely linked to chitin utilization in the model species C. johnsonae. Bacteroidetes with members of this protein family appear to have all of the genes associated with gliding motility.
Type IX secretion system membrane protein, PorP/SprF family (PorP/SprF_Bacteroidetes)
Type: Family

This entry describes a protein family unique to, and greatly expanded in, the Bacteriodetes. Species in this lineage include several, such as Cytophaga hutchinsonii and Cytophaga johnsonae (Flavobacterium johnsoniae), that exhibit a poorly understood rapid gliding phenotype. Several members of this protein family are found in operons with other genes whose loss leads to a loss of the rapid gliding phenotype .
Gliding motility-associated protein GldE (Motility-assoc_prot_GldE)
Type: Family

Members of this protein family are exclusive to the Bacteroidetes phylum (previously Cytophaga-Flavobacteria-Bacteroides). GldC is a protein linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) and Cytophaga hutchinsonii. GldE was discovered because of its adjacency to GldD in C. johnsonae. Over expression of GldE partially suppresses the effects of a GldB point mutant suggesting that GldB and GldE interact . Gliding motility appears closely linked to chitin utilization in the model species C. johnsonae. Not all Bacteroidetes with members of this protein family appear to have all of the genes associated with gliding motility and in fact some do not appear to have the gliding phenotype.
Gliding-associated putative ABC transporter substrate-binding GldG (Motility-assoc_ABC-rel_GldG)
Type: Family

Members of this protein family are exclusive to the Bacteroidetes phylum (previously Cytophaga-Flavobacteria-Bacteroides). GldG is a protein linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) and Cytophaga hutchinsonii. Knockouts of GldG abolish the gliding phenotype . GldG, along with GldA and GldF are believed to compose an ABC transporter and are observed as an operon. Gliding motility appears closely linked to chitin utilization in the model species C. johnsonae. Bacteroidetes with members of this protein family appear to have all of the genes associated with gliding motility.
Gliding motility-associated ABC transporter ATP-binding subunit GldA (Motility-assoc_ABC_GldA)
Type: Family

Members of this protein family are exclusive to the Bacteroidetes phylum (previously Cytophaga-Flavobacteria-Bacteroides). GldA is an ABC transporter ATP-binding protein (

) linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) and Cytophaga hutchinsonii. Knockouts of GldA abolish the gliding phenotype . Gliding motility appears closely linked to chitin utilization in the model species C. johnsonae. Bacteroidetes with members of this protein family appear to have all of the genes associated with gliding motility.
Gliding motility-associated lipoprotein GldJ (Glid_motil-assoc_lipo_GldJ)
Type: Family

Members of this protein family are exclusive to the Bacteroidetes phylum (previously Cytophaga-Flavobacteria-Bacteroides). GldJ is a lipoprotein linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) . Knockouts of GldJ abolish the gliding phenotype. GldJ is homologous to GldK. There is a GldJ homologue in Cytophaga hutchinsonii and several other species that has a different, shorter architecture and is represented by

. Gliding motility appears closely linked to chitin utilization in the model species C. johnsonae. Bacteroidetes with members of this protein family appear to have all of the genes associated with gliding motility.
Gliding motility-associated lipoprotein GldK (Glid_motil-assoc_lipo_GldK)
Type: Family

Members of this protein family are exclusive to the Bacteroidetes phylum (previously Cytophaga-Flavobacteria-Bacteroides). GldK is a lipoprotein linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) . Knockouts of GldK abolish the gliding phenotype. GldK is homologous to GldJ . There is a GldK homologue in Cytophaga hutchinsonii and several other species that has a different, shorter architecture and is represented by

. Gliding motility appears closely linked to chitin utilisation in the model species C. johnsonae. Bacteroidetes with members of this protein family appear to have all of the genes associated with gliding motility.
Gliding motility-associated lipoprotein GldK, short form (Glid_motil-assoc_GldK_short)
Type: Family

Members of this protein family are exclusive to the Bacteroidetes phylum (previously Cytophaga-Flavobacteria-Bacteroides). GldK is a lipoprotein linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) . Knockouts of GldK abolish the gliding phenotype. GldK is homologous to GldJ . This entry represents a GldK homologue in Cytophaga hutchinsonii and several other species that has a different, shorter architecture than that found in C. johnsonae and related species (represented by

). Gliding motility appears closely linked to chitin utilisation in the model species C. johnsonae. Bacteroidetes with members of this protein family appear to have all of the genes associated with gliding motility.
Gliding motility-associated lipoprotein GldJ-short (Glid_motil-assoc_GldJ-short)
Type: Family

Members of this protein family are exclusive to the Bacteroidetes phylum (previously Cytophaga-Flavobacteria-Bacteroides). GldJ is a lipoprotein linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) . Knockouts of GldJ abolish the gliding phenotype. GldJ is homologous to GldK. This model represents the GldJ homologue in Cytophaga hutchinsonii and several other species which is of shorter architecture than that found in C. johnsonae and is represented by

. Gliding motility appears closely linked to chitin utilisation in the model species C. johnsonae. Bacteroidetes with members of this protein family appear to have all of the genes associated with gliding motility.
Gliding motility-associated, peptidyl-prolyl isomerase, GldI (Motility-assoc_PPIase_GldI)
Type: Family

Members of this protein family are exclusive to the Bacteroidetes phylum (previously Cytophaga-Flavobacteria-Bacteroides). GldI is a FKBP-type peptidyl-prolyl cis-trans isomerase (

) linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) and Cytophaga hutchinsonii. Knockout of this gene abolishes the gliding phenotype . Gliding motility appears closely linked to chitin utilization in the model species C. johnsonae. This family is only found in Bacteroidetes containing the suite of genes proposed to confer the gliding motility phenotype.
Selenium metabolism protein YedF (Se_metab_YedF)
Type: Family

Members of this protein family are about 200 amino acids in size, and include the uncharacterised YedF protein of Escherichia coli. This family shares an N-terminal domain, modelled by

, with the sulphurtransferase TusA (also called SirA). The C-terminal domain includes a typical redox-active disulphide motif, CGXC. This protein family found only among those genomes that also carry the selenium donor protein SelD, and its connection to selenium metabolism is indicated by the method of partial phylogenetic profiling vs. SelD. Its gene is typically found next to selD. Members of this family are found even when selenocysteine and selenouridine biosynthesis pathways are, except for SelD, completely absent, as in Enterococcus faecalis. Its role in selenium metabolism is unclear, but may include either detoxification or a role in labile selenoprotein biosynthesis.
Diaminopropionate ammonia-lyase, subgroup (DiNH2propionate_NH3-lyase_sub)
Type: Family

Members of this protein family are the homodimeric, pyridoxal phosphate enzyme diaminopropionate ammonia-lyase, which adds water to remove two amino groups, leaving pyruvate . The structure of E. coli diaminopropionate ammonia-lyase has been revealed .
O-phosphoseryl-tRNA(Sec) selenium transferase (Sec-tRNA_Se_transferase)
Type: Family

In the archaea and eukaryotes, the conversion of the mischarged serine to selenocysteine (Sec) on its tRNA is accomplished in two steps. This enzyme, O-phosphoseryl-tRNA(Sec) selenium transferase, acts second, after a phosphophorylation step catalysed by a homologue of the bacterial SelA protein. It converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec), which is required for selenoprotein biosynthesis .
2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-acetyltransferase, DapH (DapH)
Type: Family

This enzyme catalyses the transfer of an acetyl group from acetyl-CoA to tetrahydrodipicolinate and is part of the diaminopimelate pathway of lysine biosynthesis. An alternate name is tetrahydrodipicolinate N-acetyltransferase.
Release factor glutamine methyltransferase (RF_methyltr_PrmC)
Type: Family

Members of this protein family are HemK, a protein once thought to be involved in heme biosynthesis but now recognised to be a protein-glutamine methyltransferase that modifies the peptide chain release factors . All members of the seed alignment are encoded next to the release factor 1 gene (prfA) and confirmed by phylogenetic analysis. However, the family is diverse enough that even many members of the seed alignment do not score above the seed alignment, which was set high enough to exclude all instances of PrmB.
2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase, actinobacteria (DapD_actinobacteria)
Type: Family

This enzyme is part of the diaminopimelate pathway of lysine biosynthesis . This entry represents a clade of the enzyme specific to Actinobacteria. The alternate name for this is enzyme is tetrahydrodipicolinate N-succinyltransferase.
2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase, gammaproteobacteria (DapD_gammaproteobac)
Type: Family

2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase (DapD) is involved in the succinylated branch of the "lysine biosynthesis via diaminopimelate (DAP)" pathway (

). This entry represents the gammaproteobacteria family of DapD sequences, which is the most closely related to the actinobacterial DapD family represented by

. All of the genes evaluated for the seed of this model are found in genomes where the downstream desuccinylase is present, but known DapD genes are absent. Additionally, many of the genes identified by this model are found proximal to genes involved in this lysine biosynthesis pathway.