SII-SWORD/CoKE huggingface dataset:
PspA/VIPP1 (PspA_VIPP1)
Type: Family

In Gram-negative organisms, PspA is part of the multi-gene Phage shock protein (Psp) response system that mitigates envelope damage by preventing proton leakage across a damaged membrane, thereby maintaining proton motive force . In Mycobacterium tuberculosis, PspA has been shown to integrate envelope stress-sensing and envelope-preserving functions . It also regulates lipid droplet homeostasis and nonreplicating persistence (NRP) in M. tuberculosis . The PspA homologue in plants, inner membrane-associated protein of 30 kDa (IM30), also known as vesicle-inducing protein in plastids 1 (VIPP1), plays a critical role in thylakoid biogenesis, essential for photosynthesis .
tRNA (pseudouridine(54)-N(1))-methyltransferase, TrmY (TrmY)
Type: Family

Proteins in this entry belong to the TrmY family (under the methyltransferase superfamily).
Archaeal TrmY specifically catalyses the N1-methylation of pseudouridine at position 54 (Psi54) in tRNAs .
SpoVT-AbrB domain (SpoVT-AbrB_dom)
Type: Domain

The SpoVT-AbrB domain is a DNA-binding domain found in a large protein superfamily , which includes:

Bacterial antibiotic resistance protein B (AbrB), a transition-state regulator.

Bacterial SpoVT, a late sporulation factor that modulates forespore-specific sigma G-dependent transcription.

Bacterial PrlF, an antitoxin component of a toxin-antitoxin (TA) module.

Bacterial transcription factors (antitoxins) of plasmid maintenance systems (VapB, MvpT, VppA ,VagC, PemI, MazE, ChpS).

Bacterial transcriptional regulator MraZ, involved in the expression of the division and cell wall (dcw) cluster. It contains two copies of the SpoVT-AbrB domain.

Bacterial endoribonuclease SymE.

Sulfolobus solfataricus repressor-like proteins SSo7c3 and SSo7c4.

The SpoVT-AbrB domain contains four β strands and one α helix and can be described as a pair of β hairpins linked by the α helix .
Domain of unknown function DUF362 (DUF362)
Type: Domain

This domain is found in some iron-sulphur proteins.
Putative heavy-metal chelation domain (DUF364)
Type: Domain

This domain of unknown function has a PLP-dependent transferase-like fold. Its genomic context suggests that it may have a role in anaerobic vitamin B12 biosynthesis. This domain is often found at the C terminus of proteins containing DUF4213 (

). The structure of UniProtKB

, PDB:3l5o, suggests that the protein has an enolase N-terminal-like fold and this Rossmann-like C-terminal domain. Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The protein may be playing a role in heavy-metal chelation .
Protein of unknown function DUF366 (DUF366)
Type: Family

This is an archaeal family of unknown function.
Undecaprenyl phosphate translocase-like (VCA0040-like)
Type: Family

This entry represents a group of prokaryotic proteins associated with transmembrane transport of undecaprenyl phosphate lipids, which is required for the biogenesis of microbial cell surface polymers, including

from Vibrio cholerae (VCA0040) . Members of this family usually have between 6 and 9 predicted transmembrane segments.
GTP-dependent dephospho-CoA kinase (GTP-dep_dephospho-CoA_kin)
Type: Family

Dephospho-coenzyme A kinase (DPCK) catalyzes the ATP-dependent phosphorylation of dephospho-CoA, the final step in coenzyme A (CoA) biosynthesis. This entry represents a group of DPCKs, including TK1697 from T. kodakarensis .
Mycobacterial 4 TMS phage holin, superfamily IV (Phage_holin_4_2)
Type: Family

These proteins are predicted transmembrane proteins with probably four transmembrane spans. The 1.E.40 is represented by the mycobacterial 4 phage holin, but it also contains many cyanobacterial. proteobacterial and firmicute proteins. Holins are encoded within the genomes of Gram-positive and Gram-negative bacteria as well as in those of the bacteriophage of these organisms. The primary function of holins appears to be transport of murein hydrolases across the cytoplasmic membrane to the cell wall where these enzymes hydrolyse the cell wall polymer as a prelude to cell lysis. When chromosomally encoded the enzymes are therefore autolysins. Holins may also facilitate leakage of electrolytes and nutrients from the cell cytoplasm, thereby promoting cell death. Some may catalyse export of nucleases .
Class III signal peptide motif (Class3_signal_pept_motif)
Type: Conserved_site

This entry represents the class III signal peptide motif QXSXEXXXL found at the N-terminal in major and minor structural pili proteins in archaea. The Q residue is the +1 residue of the signal peptidase cleavage site . Two proteins containing this motif are cleaved by a type IV pilin-like signal peptidase.

The archaeal flagellum is the best-studied cell surface organelle in the domain Archaea; it resembles the bacterial type IV pilus system while also possessing certain archaeon-specific traits. It is usually composed of multiple flagellin subunits. The pili are composed mainly of glycoprotein subunits (major and minor structural pili proteins) with apparent molecular masses of 17 and 15 kDa, which are essential for pili formation, with the exception of EpdA which is not essential for pili formation .
Ferrous iron transporter FeoA-like domain (Fe-transptr_FeoA-like)
Type: Domain

This entry represents the core domain of the ferrous iron (Fe2+) transport protein FeoA found in bacteria. This domain also occurs at the C terminus in related proteins. This suggests that this domain may be metal-binding. In most cases this is likely to be either iron or manganese.

The transporter Feo is composed of three proteins: FeoA a small, soluble SH3-domain protein probably located in the cytosol which is composed of a β-barrel with two α-helices ; FeoB, a large protein with a cytosolic N-terminal G-protein domain and a C-terminal integral inner-membrane domain containing two 'Gate' motifs which likely functions as the Fe2+ permease; and FeoC, a small protein apparently functioning as an [Fe-S]-dependent transcriptional repressor . Feo allows the bacterial cell to acquire iron from its environment.
Phage shock protein, PspC, N-terminal (Phageshock_PspC_N)
Type: Domain

This domain is found in Phage shock protein C (PspC) that is thought to be a transcriptional regulator. The presumed domain is 60 amino acid residues in length.
Extracellular matrix regulatory protein A-like (RemA-like)
Type: Family

This family of mostly uncharacterised proteins includes the extracellular matrix regulatory protein A (RemA) from
Bacillus subtilis
. RemA is required for biosynthesis of the extracellular matrix and biofilm formation . It binds to DNA at multiple sites upstream of the promoters of the operons eps and tapA-sipW-tasA, which are required for the synthesis of the extracellular matrix components, extracellular polysaccharide and TasA amyloid proteins. SinR negatively regulates eps operon expression by occluding RemA binding . Structure of RemA homologue from Geobacillus thermodenitrificans revealed that it forms an unique octameric ring with the potential to form a 16-meric superstructure and suggests that RemA can wrap DNA around its ring-like structure .
Stage V sporulation protein G (SpoVG)
Type: Family

This entry represents the stage V sporulation protein G (SpoVG). It is essential for sporulation and specific to stage V sporulation in Bacillus megaterium and Bacillus subtilis . In B. subtilis, expression decreases after 30-60 minutes of cold shock .
Protein of unknown function DUF371 (DUF371)
Type: Family

This is an archaeal family of unknown function.
Domain of unknown function DUF374 (DUF374)
Type: Domain

This is a bacterial domain of unknown function.
D-arabinono-1,4-lactone oxidase, C-terminal domain (ALO_C)
Type: Domain

This domain is found at the C-terminal of the fungal protein D-arabinono-1,4-lactone oxidase

, which is involved in the final step of the biosynthesis pathway of D-erythroascorbic acid, an important antioxidant and one of the virulence factors .

L-gulonolactone oxidase transforms L-gulono-1,4-lactone to L-xylo-hexulonolactone, which spontaneously isomerizes to L-ascorbate. This enzyme can be found in a range of organisms from chordates and plants to Mycobacteria .

Alditol oxidase from Streptomyces coelicolor also belong to this family. It performs selective oxidation of the terminal primary hydroxyl group of several alditols .
Las1 (Las1)
Type: Family

Las1 is an endoribonuclease responsible for cleavage at the C2 site during pre-rRNA processing . It interacts with Grc3 polynucleotide kinase and is required for ribosome synthesis . Las1-mediated C2 cleavage depends on the functional integrity of the associated Grc3 phosphotransferase, while phosphorylation of the 26S pre-rRNA by Grc3 relies on a functionally competent Las1 nuclease .
Ribonuclease P subunit, Rpr2/Snm1/Rpp21 (Rpr2/Snm1/Rpp21)
Type: Family

This entry contains ribonuclease P (Rnp) proteins from eukaryotes and archaea. Rnp is a ubiquitous ribozyme that catalyzes a Mg2 -dependent hydrolysis to remove the 5'-leader sequence of precursor tRNA (pre-tRNA) . Archaeal and eukaryotic RNase P consist of a single RNA and archaeal RNase P has four or five proteins, while eukaryotic RNase P consists of 9 or 10 proteins. Eukaryotic and archaeal RNase P RNAs cooperatively function with protein subunits in catalysis .

Human RNase P is composed of a singular protein Pop1 and three subcomplexes, the Rpp20-Rpp25 heterodimer, Pop5-Rpp14-(Rpp30)2-Rpp40 heteropentamer, and Rpp21-Rpp29-Rpp38 heterotrimer. Although both Pop5 and Rpp14 have similar protein structure, they share a very limited sequence similarity. Moreover, the C-terminal fragments after the conserved β sheets in Pop5 and Rpp14 exhibit distinct structural features that mediate interactions with Pop1 and Rpp40, respectively .

In the hyperthermophilic archaeon Pyrococcus horikoshii OT3, RNase P is composed of the RNase P RNA (pRNA) and five proteins (PhoPop5, PhoRpp38, PhoRpp21, PhoRpp29, and PhoRpp30) .

This entry includes Rpp21 from animals, Snm1/Rpr2 from yeasts and RNP4 from archaea . Snm1 is a subunit of RNase MRP (mitochondrial RNA processing), a ribonucleoprotein endoribonuclease that has roles in both mitochondrial DNA replication and nuclear 5.8S rRNA processing. Snm1 is an RNA binding protein that binds the MRP RNA specifically . This subunit possibly binds the precursor tRNA .
Protein of unknown function DUF365 (DUF365)
Type: Family

This is an archaeal family of unknown function.
16S/18S rRNA aminocarboxypropyltransferase Tsr3, C-terminal (Tsr3_C)
Type: Domain

This domain can be found in the eukaryotic ribosome biogenesis protein Tsr3, which is involved in ribosomal RNA biogenesis . This domain is also found in the C terminus of Tsr3 homologues from archaea. It is usually associated with a putative metal-binding region in RNase L inhibitor, RLI (

).

Tsr3 from fungi and animals are responsible for 18S rRNA hypermodification. The Crystal structure of archaeal Tsr3 homologues revealed the same fold as in SPOUT-class RNA-methyltransferases but a distinct SAM binding mode. This unique SAM binding mode explains why Tsr3 transfers the acp and not the methyl group of SAM to its substrate. Structurally, Tsr3 therefore represents a novel class of acp transferase enzymes .
Archaeal transcription elongation factor Spt4 (Spt4_arch)
Type: Family

This entry represents Spt4 from Sulfolobus acidocaldarius (also known as RpoE2) and similar sequences mainly found in archaea. Spt4, of about 64 amino acids, forms a heterodimer with Spt5. The Spt4/5 heterodimer is considered a transcription elongation factor, responsible for making the archaeal DNA-directed RNA polymerase (RNAP) processive .

DNA-directed RNA polymerases, also known as DNA-dependent RNA polymerases, are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. Eukaryotes have three different DNA-directed RNA polymerases (RNAPs), Pol I, II, and III, whereas Archaea and Bacteria have single enzymes.

RNAPs are multisubunit enzymes. Archaeal RNAP is closely related to eukaryotic RNAP II , which consists of 12 subunits. Archaeal RNAP has an additional subunit, Rpo13, with no orthologue in the eukaryotic enzyme .
Domain of unknown function DUF382 (DUF382)
Type: Domain

This domain is specific to the human splicing factor 3b subunit 2 and its orthologs.
Dihydroneopterin aldolase MtpD, C-terminal domain (MtpD_C)
Type: Domain

This domain contains a strongly conserved YPLM motif and it is found at the C terminus of archaeal specific 7,8-dihydroneopterin aldolase (DHNA) MtpD, an enzyme involved in the synthesis of 6-hydroxymethyl-7,8-dihydropterin diphosphate (6-HMDP) . 6-HMDP is the precursor of the pterin containing moiety of the essential C1-carriers tetrahydrofolate and tetrahydromethanopterin.
Na+/H+ antiporter MnhB subunit-related protein (MnhB)
Type: Domain

This domain is found a subunit of the Na
+
/H
+
antiporter , as well as in the bacterial NADH dehydrogenase subunit. Usually four transmembrane regions are found in this domain.
Uncharacterised protein family UPF0280 (UPF0280)
Type: Family

This family consists of bacterial and archaeal proteins. MA1715 from the archaeon Methanosarcina acetivorans is required for optimal growth with sulfide as the sole sulfur source and has been shown to support both cysteine and homocysteine biosynthesis . The protein is thought to capture environmental sulfide, catalyse its oxidation to sulfane, and then deliver this sulfane sulfur to specific target proteins. Two key recipients of this sulfur transfer are SepCysS and MA1821, which use it for cysteine and homocysteine biosynthesis respectively . The presence of persulfides on the active-site cysteine residues of these target proteins provides evidence for this sulfur transfer mechanism. A similar system is seen with MJ1681, another protein containing cysteine persulfides that is involved in the production of 2-mercaptoethanesulfonic acid .
Mannoside phosphorylase (Mannoside_phosphorylase)
Type: Family

This family of glycosyl hydrolases include 4-O-beta-D-mannosyl-D-glucose phosphorylase (RaMP1) and beta-1,4-mannooligosaccharide phosphorylase (RaMP2). The first one converts 4-O-beta-D-mannopyranosyl-D-glucopyranose (Man-Glc) to mannose 1-phosphate (Man1P) and glucose, while the second one catalyses the phosphorolysis of beta-1,4-mannooligosaccharides longer than beta-1,4-mannobiose to mannose 1-phosphate (Man1P) and shorter mannooligosaccharides. Both are involved in a mannan catabolic pathway which feeds into glycolysis .
DNA polymerase alpha/delta/epsilon, subunit B (DNA_pol_a/d/e_bsu)
Type: Domain

DNA polymerase epsilon is essential for cell viability and chromosomal DNA replication in budding yeast. In addition, DNA polymerase epsilon may be involved in DNA repair and cell-cycle checkpoint control. The enzyme consists of at least four subunits in mammalian cells as well as in yeast. The largest subunit of DNA polymerase epsilon is responsible for polymerase activity. In mouse, the DNA polymerase epsilon subunit B is the second largest subunit of the DNA polymerase. A part of the N-terminal was found to be responsible for the interaction with SAP18. Experimental evidence suggests that this subunit may recruit histone deacetylase to the replication fork to modify the chromatin structure .
Nucleoporin, Nup133/Nup155-like, C-terminal (Nucleoporin_Nup133/Nup155_C)
Type: Domain

This is the C-terminal half of a family of nucleoporin proteins. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells, and mediate bidirectional nucleocytoplasmic transport, especially of mRNA and proteins. Two nucleoporin classes are known: one is characterised by the FG repeat and the other is represented by this family, which lacks any repeats. RNA undergoing nuclear export first encounters the basket of the nuclear pore and many nucleoporins are accessible on the basket side of the pore .
Actin-related protein 2/3 complex subunit 2 (ARPC2)
Type: Family

Arp2/3 binds to pre-existing actin filaments and nucleates new daughter filaments, and thus becomes incorporated into the dynamic actin network at the leading edge of motile cells and other actin-based protrusive structures . In order to nucleate filaments, Arp2/3 must bind to a member of the N-WASp/SCAR family protein . Arp2 and Arp3 are thought to be brought together after activation, forming an actin-like nucleus for actin monomers to bind and create a new actin filament. In the absence of an activating protein, Arp2/3 shows very little nucleation activity. Recent research has focused on the binding and hydrolysis of ATP by Arp2 and Arp3 , and crystal structures of the Arp2/3 complex have been solved .

The human complex consists of Arp2/3 complex composed of ARP2, ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC. This family represents the ARPC2/p34-ARC subunit.
Exocyst complex component Sec8, N-terminal (Sec8_exocyst_N)
Type: Domain

Sec8 is a component of the exocyst complex, composed of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84, which mediates the tethering of post-Golgi secretory vesicles to the plasma membrane. The exocyst promotes the assembly of SNARE complex for membrane fusion and it is also involved in many cellular processes such as cell polarization, primary ciliogenesis, cytokinesis, pathogen invasion, tumorigenesis and metastasis . Subunits of the exocyst have a rod structure which is a shared feature for the Complex Associated with Tethering Containing Helical Rods (CATCHRs) proteins, such as those of the Conserved Oligomeric Golgi complex (COG) and Golgi-Associated Retrograde Protein complex (GARP), consisting of a N-terminal long coiled-coil followed by a region of anti-parallel short helical bundle units .

This entry represents the conserved coiled-coil region at the N-terminal of Sec8 proteins, which interacts with Sec6 and form an antiparallel zipper. This zipper then interacts with that formed between Sec3-Sec5, to assemble in a four-helical bundle .
Cdc23 (APC8)
Type: Domain

The anaphase-promoting complex is composed of eight protein subunits, including BimE (APC1), CDC27 (APC3), CDC16 (APC6), and CDC23 (APC8). This entry is for CDC23.
Up-frameshift suppressor 2, C-terminal (Upf2/Nmd2_C)
Type: Domain

This entry represents the C-terminal domain found in Up-frameshift suppressor 2 (also known as Nonsense-mediated mRNA decay protein 2). Transcripts harbouring premature signals for translation termination are recognised and rapidly degraded by eukaryotic cells through a pathway known as nonsense-mediated mRNA decay. In Saccharomyces cerevisiae, three trans-acting factors (Upf1 to Upf3) are required for nonsense-mediated mRNA decay .
Transport protein particle (TRAPP) component (TRAPP_component)
Type: Family

TRAPP plays a key role in the targeting and/or fusion of ER-to-Golgi transport vesicles with their acceptor compartment. TRAPP is a large multimeric protein that contains at least 10 subunits. This family contains many TRAPP family proteins. The Bet3 subunit is one of the better characterised TRAPP proteins and has a dimeric structure with hydrophobic channels. The channel entrances are located on a putative membrane-interacting surface that is distinctively flat, wide and decorated with positively charged residues. Bet3 is proposed to localise TRAPP to the Golgi .
TolB, N-terminal (TolB_N)
Type: Domain

TolB is a periplasmic protein from Escherichia coli that is part of the Tol-dependent translocation system involving group A and E colicins that is used to penetrate and kill cells . TolB has two domains, an α-helical N-terminal domain that shares structural similarity with the C-terminal domain of transfer RNA ligases, and a β-propeller C-terminal domain (

) that shares structural similarity with numerous members of the prolyl oligopeptidase family and, to a lesser extent, to class B metallo-beta-lactamases . The N-terminal domain is essential for Tol function and colicin toxicity .
CCR4-Not complex component, Not1, C-terminal (CCR4-Not_Not1_C)
Type: Domain

The Ccr4-Not complex is a global regulator of gene expression that is conserved from yeast to human. It affects genes positively and negatively and is thought to regulate transcription factor IID function. In Saccharomyces cerevisiae, it exists in two prominent forms and consists of at least nine core subunits: the five Not proteins (Not1 to Not5), Caf1, Caf40, Caf130 and Ccr4 . The Ccr4-Not complex regulates many different cellular functions, including RNA degradation and transcription initiation. It may be a regulatory platform that senses nutrient levels and stress . Caf1 and Ccr4, are directly involved in mRNA deadenylation, and Caf1p is associated with Dhh1, a putative RNA helicase thought to be a component of the decapping complex . Pop2, a component of the Ccr4-Not complex, functions as a deadenylase .

The Ccr4-Not complex is a global regulator of transcription that affects genes positively and negatively and is thought to regulate transcription factor TFIID .
Radical SAM (rSAM)
Type: Domain

The Radical SAM domain is organised in a fold related to the β-barrel or TIM barrel, in which β-strands are arranged in a barrel-like array, with peripheral helices intervening between β-strands. The [4Fe-4S] clusters and substrates are bound within the barrels, as is typical of TIM barrel enzymes .

Radical SAM proteins are found in all domains of life and share an unusual Fe-S cluster associated with generation of a free radical by reductive cleavage of SAM and often provide an anaerobic or oxygen-independent mechanism that is found as an aerobic reaction in other proteins. Radical SAM proteins catalyse diverse reactions, including unusual methylations, isomerisation, sulphur insertion, ring formation, anaerobic oxidation and protein radical formation. These proteins function in DNA precursor, vitamin, cofactor, antibiotic and herbicide biosynthesis and in biodegradation pathways .

Radical SAM proteins share several common features, notably three strictly conserved cysteine residues generally included in the CxxxCxxC motif. These critical cysteines coordinate the unusual [4Fe-4S]2+/1+ cluster, while SAM serves as ligand for the fourth iron atom and acts as a cofactor or a cosubstrate . The radical SAM enzymes biochemically characterised to date have in common the cleavage of the [4Fe-4S]1+-SAM complex to [4Fe-4S]2+-Met and the 5'-deoxyadenosyl radical, which abstracts a hydrogen atom from the substrate to initiate a radical mechanism .
Ssl1-like (Ssl1-like)
Type: Domain

Ssl1-like proteins are 40kDa subunits of the transcription factor II H complex. This domain is often found associated with the C2H2 type Zn-finger.
Replication factor-A protein 1, N-terminal (Rep_factor-A_N)
Type: Domain

Replication factor-a protein 1 (RPA1) forms a multiprotein complex with RPA2 and RPA3 that binds single-stranded DNA and functions in the recognition of DNA damage for nucleotide excision repair. The complex binds to single-stranded DNA sequences participating in DNA replication in addition to those mediating transcriptional repression and activation, and stimulates the activity of cognate strand exchange protein Sep1. It cooperates with T-AG and DNA topoisomerase I to unwind template DNA containing the Simian Virus 40 origin of replication .
Mei2-like, C-terminal RNA recognition motif (Mei2-like_Rrm_C)
Type: Domain

This RNA recognition motif 2 is found in meiosis protein mei2 and mei2-like proteins . It is found C-terminal to the RNA-binding region RNP-1 (

).