SII-SWORD/CoKE huggingface dataset:
Glycine cleavage system H-protein/Simiate (GCV_H/Fam206)
Type: Family

This is a family of glycine cleavage H-proteins, part of the glycine cleavage system (GCS) found in bacteria, archaea, and the mitochondria of eukaryotes. GCS is a multienzyme complex consisting of 4 different components (P-, H-, T- and L-proteins) which catalyzes the oxidative cleavage of glycine . The H-protein shuttles the methylamine group of glycine from the P-protein (glycine dehydrogenase) to the T-protein (aminomethyltransferase) via a lipoyl group, attached to a completely conserved lysine residue .

This enty includes Abitram proteins. Abitram (also known as Simiate) functions in transcription regulation . Furthermore, it associates with both G- and F-Actin and affects actin polymerization and actin turnover, influencing filopodia dynamics and arborization of neurons .
PdxS/SNZ N-terminal domain (PdxS/SNZ_N)
Type: Domain

The family of pyridoxal 5'-phosphate synthase subunits, known as the PdxS/SNZ family, occur in organisms in four kingdoms and form one of the most highly conserved families . A PdxS/SNZ protein has a classic (β/α)8-barrel fold, consisting of eight parallel β-strands alternating with eight α helices. PdxS subunits form two hexameric rings . Proteins are involved in vitamin B6 biosynthesis.

The term vitamin B6 is used to refer collectively to the compound pyridoxine and its vitameric forms, pyridoxal, pyridoxamine, and their phosphorylated derivatives. Vitamin B6 is required by all organisms and plays an essential role as a co-factor for enzymatic reactions. Plants, fungi, bacteria, archaebacteria, and protists synthetize vitamin B6. Animals and some highly specialised obligate pathogens obtain it nutritionally. Vitamin B6 has two distinct biosynthetic pathways, which do not coexist in any organism. The pdxA/pdxJ pathway, that has been extensively characterised in Escherichia coli, is found in the gamma subdivision of the proteobacteria. A second pathway of vitamin B6 synthesis involving the pdxS/SNZ and pdxT/SNO protein families, which are completely unrelated in sequence to the pdxA/pdxJ proteins, is found in plants, fungi, protists, archaebacteria and most bacteria .

PdxS/SNZ and pdxT/SNO proteins form a complex which serves as a glutamine amidotransferase to supply ammonia as a source of the ring nitrogen of vitamin B6 . PdxT/SNO and pdxS/SNZ appear to encode respectively the glutaminase subunit, which produces ammonia from glutamine, and the synthase subunit, which combines ammonia with five- and three-carbon phosphosugars to form vitamin B6 .

This entry represents the N-terminal domain of the pyridoxal 5'-phosphate synthase subunit PdxS/SNZ.
Flagellum site-determining protein YlxH/ Fe-S cluster assembling factor NBP35 (YlxH/NBP35)
Type: Family

This entry represents members of the MRP/Nbp35 class of iron-sulfur (FeS) cluster scaffolds, such as Nbp35 and Cfd1, that function to assemble nascent FeS clusters for transfer to FeS-requiring enzymes. They have been identified as ATPases . This family also contains FleN/FlhG, which regulates aspects of flagellar assembly, placement and number . FleN/FlhG activates the SRP-GTPase FlhF .
Pre-mRNA-splicing regulator WTAP (WTAP)
Type: Family

Pre-mRNA-splicing regulator WTAP (Wilms' tumor 1-associating protein) is a regulatory subunit of the WMM N6-methyltransferase complex, a multiprotein complex that mediates N6-methyladenosine (m6A) formation, which acts as an epitranscriptomic marker . It plays a role in the efficiency of mRNA splicing and processing, and mRNA stability . In Drosophila, the homologous protein pfemale-lethal(2)D has been implicated in alternative splicing regulation of genes involved in sexual determination and is required for eye development . FKBP12-interacting protein of 37kDa (AtFIP37, At3g54170), the homologue from Arabidopsis, may also have a role in splicing events . AtFIP37 interacts with mRNA adenosine methylase (MTA, encoded by At4g10760) in vitro and in vivo .
pGP3 C-terminal domain (pGP3_C)
Type: Domain

This domain is found in Chlamydia virulence proteins which are thought to be required for growth within mammalian cells . The C-terminal domain shows distant homology to the TNF superfamily .
Systemic RNA interference defective protein 5 (Sid-5)
Type: Family

In the nematode Caenorhabditis elegans, RNA interference (RNAi) silencing signals are efficiently taken up from the environment and transported between cells and tissues . SID-5 is a C. elegans endosome-associated protein that promotes the transport of RNAi silencing signals between cells .
Integrin beta N-terminal (Integrin_beta_N)
Type: Domain

This short disulphide rich domain is found at the N terminus of integrin beta chains.
Negative modulator of initiation of replication SeqA, N-terminal (SeqA_N)
Type: Domain

The binding of SeqA protein to hemimethylated GATC sequences is important in the negative modulation of chromosomal initiation at oriC, and in the formation of SeqA foci necessary for Escherichia coli chromosome segregation . SeqA tetramers are able to aggregate or multimerise in a reversible, concentration-dependent manner . Apart from its function in the control of DNA replication, SeqA may also be a specific transcription factor .

This family represents the N-terminal domain of SeqA: a short domain that is reported to mediate the dimerisation of SeqA .
MCM OB domain (MCM_OB)
Type: Domain

This OB-fold domain is found within MCM (mini-chromosome maintenance) proteins, which are components if the MCM complex involved in chromosome replication . This domain, found at the N terminus, contains an insertion at the zinc binding motif .
Polycomb group protein, RNA binding region (SCML2_RBR)
Type: Domain

This entry represents the RNA-binding region of human SCML2/4, also found in other Polycomb-group proteins from the Scm (Sex comb on midleg) subfamily. Members of this group are found in vertebrates.

Sex comb on midleg-like protein 2 (SCML2) is a mammalian Polycomb-group protein, which associates with the Polycomb repressive complex-1 (PRC1) that is essential for the epigenetic regulation of gene expression. Isoform SCML2A has been shown to bind to PRC1 via its SPM domain and to interact with ncRNAs through a novel RNA-binding region (RBR). The RBR is necessary for targeting of SCML2A to chromatin and PRC1 recruitment, suggesting a role for ncRNAs in regulating SCML2 function .

Sex comb on midleg-like protein 4 (SCML4), which is thought to have a similar function, has been associated with coronary artery disease .
SD-repeat containing protein, B domain (Sdr_B)
Type: Domain

SD-repeat containing (Sdr) proteins are surface proteins that play an important role in Staphylococcus aureus adhesion and pathogenesis . They are characterised by the presence of a structural region, named R region, mainly composed of repeating Ser-Asp dipeptides. The Sdr family members share a conserved structural organisation. They all start with a short N-terminal signal sequence followed by an A region for ligand binding, the characteristic R region of variable length, an LPXTG cell wall-anchoring motif, a hydrophobic membrane region, and sometimes a cytoplasmic tail. In addition, SdrC, SdrE and SdrD have several additional B domains inserted between region A and R. The B domain often exists as a series of repeats which may act as a spacer .

This entry represents the B domain found in some Sdr family members.
Restriction endonuclease BfiI C-terminal domain (BfiI_C)
Type: Domain

This entry represents the C-terminal domain of novel type IIs restriction endonuclease BfiI and similar proteins.

Type II restriction endonucleases are components of restriction modification (RM) systems that protect bacteria and archaea against invading foreign DNA. They usually function as homodimers or homotetramers that cleave DNA at defined sites of 4 to 8 bp in length, and they require Mg2+, not ATP or GTP, for catalysis. Unlike all other restriction enzymes known to date, BfiI is unique in cleaving DNA at fixed positions downstream of an asymmetric sequence in the absence of Mg2+ . BfiI consists of two discrete domains with distinct functions: an N-terminal catalytic domain with non-specific nuclease activity and dimerization function that is more closely related to Nuc, an EDTA-resistant nuclease from the phospholipase D (PLD) superfamily ; and a C-terminal domain that specifically recognizes its target sequences, 5'-ACTGGG-3' . BfiI presumably evolved through domain fusion of a DNA recognition domain to the catalytic Nuc-like domain from the PLD superfamily . BfiI forms a functionally active homodimer which has two DNA-binding surfaces located at the C-terminal domains but only one active site, located at the dimer interface between the two N-terminal catalytic domains .
Tail tubular protein Gp11 (Tail_Gp11)
Type: Family

This family includes the tail tubular Gp11 protein from bacteriophage T7. In Podoviridae the virus tail is attached to the head through the tail adaptor protein. The location of Gp11 in the tail, together with its oligomerization change upon assembly (between monomer and dodecamer), suggests that Gp11 could act as an adaptor protein .
Hydin adenylate kinase-like domain (Hydin_ADK)
Type: Domain

This domain found in the Hydin protein is homologous to adenylate kinases .
Transcription termination factor FttA, KH domain (TffA_KH)
Type: Domain

This entry represents the KH domain found at the N terminus of transcription termination factor FttA and similar archaeal proteins .

FttA is a single-stranded endoribonuclease (endoRNase) that mediates cleavage at the RNA exit channel of RNA polymerase (RNAP); the 5'-3' exonuclease activity of this protein degrades the nascent RNA released from RNAP. It terminates transcription on the whole genome, a process that is linked to FttA-mediated RNA cleavage and does not require NTP hydrolysis . It also has weak activity 5'-3' exodeoxyribonuclease activity on ssDNA .
Exosome complex exonuclease RRP44, S1 domain (RRP44_S1)
Type: Domain

This domain corresponds to the S1 domain found at the C terminus of ribonucleases such as yeast Rrp44 . It displays a characteristic OB fold.
Rrp44-like cold shock domain (Rrp44_CSD1)
Type: Domain

Rrp44 (also known as Dis3) constitutes the only active nuclease of the yeast exosome core . The structure of Rrp44 consists of CSD1, CSD2, RNB, and S1 domains. The two N-terminal cold shock domains (CSD1 and CSD2) and the C-terminal S1 domain all display characteristic OB folds . This entry represents CSD1.
UPA domain (UPA)
Type: Domain

The UPA domain is conserved in UNC5, PIDD, and ankyrins. From the structures of UNC5 and ankyrin, the UPA domain has been shown to have a β sandwich structure .
CBX family C-terminal motif (CBX7_C)
Type: Conserved_site

CBX7 and RING1B are components of a Polycomb group (PcG) multiprotein PRC1-like complex which maintains many genes, including Hox genes, transcriptionally repressed during development, signalling and cancer by recognizing trimethylated lysines on histones . This motif is found at the C terminus of CBX7 where it binds the RAWUL domain of the RING1B protein .
Yaf2/RYBP C-terminal binding motif (YAF2_RYBP)
Type: Conserved_site

This motif is found in the C-terminal region of the Yaf2 and RYBP proteins, which are homologous parts of the PRC1 complex .

RYBP is a zinc finger protein with an essential role during embryonic development, which binds transcriptional factors, Polycomb products, and mediators of apoptosisis . RYBP also binds ubiquitin and Cbx proteins via the C-terminal docking module . RYBP is natively unstructured until it binds to the C-terminal region of the Polycomb protein Ring1B or to DNA . Yaf2 binds to MYC and inhibits MYC-mediated transactivation .
Protein of unknown function (DUF5137) (DUF5137)
Type: Family

This is a family of uncharacterised yeast proteins.
COMMD1 N-terminal domain (COMMD1_N)
Type: Domain

COMM (copper metabolism gene MURR1) domain proteins constitute a family initially identified as interacting partners of COMMD1 (previously known as MURR1), the prototype member of this protein family. COMMD1 is a multifunctional protein that has been shown to participate in two apparently distinct activities, regulation of the transcription factor NF-kappa-B and control of copper metabolism. The family is defined by the presence of a C-terminal motif termed COMM domain, which functions as an interface for protein-protein interactions. The proteins designated as COMMD or COMM domain containing 1-10 are extensively conserved in multicellular eukaryotic organisms .

This helical domain is found at the N terminus of COMMD1. This domain adopts an α-helical structure unlike any other helical protein .
Viral cysteine endopeptidase C107 (Peptidase_C107)
Type: Family

This is a family of viral cysteine endopeptidases that process RNA polyproteins (MEROPS family C107). Processing sites have been identified in the mesonivirus . The endopeptidase is described as "3C-like" and probably has a trypsin-like fold. Site directed mutagenesis suggest that residues His-1434 and Cys-1539 form the catalytic dyad .
Cuticle protein CPCFC (CPCFC)
Type: Domain

This entry contains cuticle proteins with a CX(5)C motif, although some members have a CX(7)C motif. In Anopheles gambiae, mRNA for this protein is most abundant immediately following ecdysis in larvae, pupae and adults, and is localised primarily in epidermis that secretes hard cuticle, sclerites, setae, head capsules, appendages and spermatheca. EM immunolocalisation studies have shown that the protein is present in the endocuticle of legs and antennae. CPCFC is found throughout the Hexapoda and in several classes of Crustacea .
Domain of unknown function DUF5300 (DUF5300)
Type: Domain

This domain is found in a small group of proteins found in Clostridia, which is functionally uncharacterised. Proteins in this family are around 130 amino acids in length. Based on NMR structure

, it forms a β-sandwich structure consisting of two 4-stranded antiparallel β-strands. The structure is very similar to glutamine glutamyltransferases (

] and peptide transporters (

).
Domain of unknown function DUF5301 (DUF5301)
Type: Domain

This entry represents a domain found in a small family of proteins from firmicutes that is functionally uncharacterised. Based on NMR structure

, it forms an α/β structure with a six-stranded antiparallel β-sheet planked by a single α-helix. The only protein with similar structures is a putative lipoprotein (

).
Tse2 immunity protein Tsi2 (Tsi2)
Type: Family

Tsi2 is an essential protein in Pseudomonas aeruginosa, providing protection from the activity of Tse2, most likely by directly interacting with Tse2 . Tse2 is a toxin transported via the type VI secretion system and is targeted towards other bacteria in the environment . This entry includes Tsi2 homologues found in Gammaproteobacteria.
SidM, Rab1-activation domain, Legionella pneumophila (DrrA_GEF_Leg_pneum)
Type: Domain

Effector protein DrrA (also known as SidM) of Legionella pneumophila, an intracellular pathogen, is a potent guanine nucleotide-exchange factor (GEF) specific for the host Rab1 GTPase . It competes with endogenous exchange factors to recruit and activate Rab1 on plasma membrane-derived organelle, therefore effectively hijacking the host's vesicle trafficking to avoid phagosome-lysosome fusion .
Pichia pastoris 6-phosphofructokinase, gamma subunit (PpPFK_gamma)
Type: Family

Pichia pastoris 6-phosphofructokinase (PpPfk) is the most complex and probably largest (1 MDa) eukaryotic Pfk . It forms a dodecamer of four α-β-γ trimers . The gamma subunit is unique, in contrast to other eukaryotic ATP-dependent 6-phosphofructokinases, and participates in oligomerization of the alpha and beta chains . It is not essential for enzymatic activity, but it modulates the allosteric behavior of the enzyme .
TTHB210-like (TTHB210-like)
Type: Family

TTHB210 is an uncharacterised protein found in Thermus thermophilus, and is controlled by the sigma(E) /anti-sigma(E) regulatory system. It is one of the five proteins of the extracytoplasmic function (ECF) sigma factor sigma(E)-regulated gene products whose physiological functions have not been determined. Its crystallographic structure reveals a novel homodecamer, although it is a dimer in solution .
ssDNA-binding protein ThermoDBP (ThermoDBP)
Type: Domain

ThermoDBP is a single-stranded DNA-binding protein (SSB) protein of the Thermoproteales. SSB proteins are essential for the genome maintenance of all known cellular organisms. Many SSBs contain an OB fold domain, albeit with low sequence conservation, and OB fold-containing SSB proteins have been detected in all three domains of life. However, the Thermoproteales SSB protein, ThermoDBP, lacks the OB fold and binds specifically to ssDNA with low sequence specificity. Its three-dimensional structure resembles that of the Hut operon positive regulatory protein HutP .
Antitoxin VbhA-like (VbhA-like)
Type: Domain

VbhA is the antitoxin to VbhT. VbhT is a toxin of the mammalian pathogen Bartonella schoenbuchensis responsible for the disruptive adenylation of host proteins . VbhT is composed of an N-terminal FIC domain and a C-terminal BID domain. VbhT also induces FIC-domain-mediated growth arrest in bacteria. It is inhibited by this antitoxin which binds to block the ATP binding site of the VbhT FIC domain . The antitoxin is related to an N-terminal domain in several Fic family proteins .
Gal11, coactivator domain (Gal11_coact)
Type: Domain

GAL11/MED15 (mediator of RNA polymerase II transcription subunit 15) acts in the general regulation of GAL structural genes and is required for full expression for several genes in this pathway, including GALs 1,7, and 10 in Saccharomyces cerevisiae . GAL11 function is dependent on GCN4 functionality and binds GCN4 in a degenerate manner with multiple orientations found at the GCN4-GAL11 interface . This entry represents an activator-binding domain of GAL11. The tertiary structure of this domain has been solved and shows a four-helix fold with a small shallow hydrophobic cleft at its centre into which three Gcn4 aromatic/aliphatic residues are inserted .
Lectin Bc2l-C, N-terminal domain, betaproteobacteria (Bc2l-C_N_b-proteobact)
Type: Domain

Lectin BC2L-C of Burkholderia cenocepacia is one of several lectins produced by this pathogen. BC2L-C has been shown to bind fucosylated human histo-blood group epitopes H-type 1, Lewis B, and Lewis Y. The C-terminal domain resembles BC2L-A, a calcium dependent mannose-binding protein. This entry describes the N-terminal domain, which trimerizes and binds alpha-MeSeFuc in pockets between the monomeric units. The N-terminal domain has a similar structure to tumour necrosis factor (TNF) .
Pesticin, translocation and receptor binding domain (Pesticin_N_RB)
Type: Domain

Pesticin (Pst) is a anti-bacterial toxin produced by Yersinia pestis that acts through uptake by the target related bacteria and the hydrolysis of peptidoglycan in the periplasm. Pst contains an N-terminal translocation domain, an intermediate receptor binding domain, and a phage-lysozyme like C-terminal activity domain. The N-terminal domain is further divided into the TonB box (which binds TonB), the T (translocation domain) and the R (receptor binding domain) . Bacteriocins such as pesticin are produced by Gram-negative bacteria to attack related bacteria stains. Pst is transported to the periplasm via FyuA, an outer-membrane receptor of Y. pestis and E. coli, where it hydrolyzes peptidoglycan via the cleavage of N-acetylmuramic acid and C4 of N-acetylglucosamine . Disruption of the peptidoglycan layer renders the bacteria vulnerable to lysis via osmotic pressure .

This domain covers the N-terminal translocation and the receptor binding regions.
Cellophane-induced protein 1 (Cin1)
Type: Domain

Cin1 (cellulose induced protein 1) repeat protein of Venturia inaequalis, the fungus responsible for scab disease of apple, includes eight cysteine-rich repeats and is greatly upregulated within the plant and on cellophane membranes. The crystal structure reveals a pair of disulfide bridges in each repeat. The repeats have been described as adopting a beads-on-a-string organization. Cin1 function is undetermined, however the α-helical structure may be involved in protein-protein or protein-carbohydrate interactions in the extracellular matrix .
Cytochrome oxidase Caa3-type, subunit IV (Caa3-IV)
Type: Domain

Cytochrome c oxidase, a haem copper oxidase superfamily member, is the final step in the electron-transport chain, linking O
2
reduction to transmembrane pumping in mitochondria and aerobic prokaryotes. Cytochrome c oxidase (aka Complex IV) catalyzes the reduction of O
2
to 2H
2
O, and acts downstream of Complexes I-III: NADH-Q oxidoreductase, succinate-Q reductase, and Q-cytochrome c oxidoreductase. In Thermus thermophilus caa3-oxidase is comprised of subunit (SU) I/III, a fusion of classical SU I and SU III, and IIc as well SU IV, which is composed of two connected transmembrane helices that interface with SU I/III .
Uncharacterised protein Clospo_01618-like domain (Clospo_01618-like_dom)
Type: Domain

This domain is found in Lipoprotein from Clostridium sporogenes (Clospo_01618) and similar proteins from firmicutes. It shows a two-layered α/β configuration. It displays structural similarity to the N-terminal domain of YycH, which plays a role in signal transduction and is found immediately downstream of the essential histidine kinase YycG. YycG forms a two-component system together with its cognate response regulator YycF. YycH functions as a modulator of YycG activity, possibly by interacting with YchI. All three molecules (YchG, YchH, and YchI) have been characterised as membrane proteins, and they may be able to form homodimers .
Putative lipoprotein BA_2398-like (BA_2398-like)
Type: Family

This uncharacterised protein family is found in Bacilli and Gammaproteobacteria.
L-lysine epsilon-oxidase (LodA)
Type: Family

L-lysine epsilon-oxidase is responsible for oxidative deamination of L-lysine, producing L-2-aminoadipate-6-semialdehyde . Hydrogen peroxide is a side-product of this enzymatic reaction, which requires the cofactor CTQ (cysteine tryptophylquinone) . CTQ most likely forms a Schiff base with the free amino acid substrate. The protein is also called marinocine, for its broad-spectrum antibacterial activity; the latter is most likely caused by hydrogen peroxide synthesis . The dimerization interface observed in the available 3D structure does not seem to be conserved. Homologues of LodA have been detected in various Gram-negative bacteria, and they appear to be associated with the formation of biofilms .
Uncharacterised protein, LodA-like (LodA-like)
Type: Domain

This domain is found in uncharacterised proteins similar to L-lysine epsilon-oxidase from Marinomonas mediterranea (see

). However, proteins containing this domain, such as Marme_1655, have been shown to possess glycine oxidase (GO) activity instead of lysine oxidase activity .
CdiA toxin, EC869-like (CdiA_EC869-like)
Type: Domain

This entry represents the C-terminal toxin domain of CdiA effector proteins. Despite sharing little sequence identity, the toxin domains are structurally similar and have homology to endonucleases. The EC869 toxin is a Zn(2+)-dependent DNase capable of completely degrading the genomes of target cells .

Contact-dependent growth inhibition (CDI) toxins are expressed by Gram-negative bacteria as part of a mechanism to inhibit the growth of neighbouring bacteria . CDI is mediated by the CdiB/CdiA two-partner secretion system. CdiA secretion is dependent on the outer membrane protein CdiB. The growth inhibitory activity resides within the C-terminal region of CdiA. Upon binding to a receptor on the surface of target bacteria, the CDI toxin is delivered .