SII-SWORD/CoKE huggingface dataset:
Vacuolar membrane protease, C-terminal domain (PFF1_C)
Type: Domain

This entry includes fungal vacuolar membrane proteases, such as PFF1 from yeast, which may be involved in vacuolar sorting and osmoregulation . It is an homologue of human ERMP1 .

According to AlphaFold structure predictions, these proteins consist of a M28 peptidase domain (

) at the N-terminal, a central transmembrane domain (

) and a C-terminal domain with an elongated β-sandwich-like fold, similar to the Mu homology domain (MHD) (

). This entry represents the C-terminal MHD-like domain of PFF1 and its fungal homologues.
Vacuolar membrane protease, transmembrane domain (PFF1_TM)
Type: Domain

This entry includes fungal vacuolar membrane proteases, such as PFF1 from yeast, which may be involved in vacuolar sorting and osmoregulation . It is the homologue of human ERMP1 .

According to AlphaFold structure predictions, these proteins consist of a M28 peptidase domain (

) at the N-terminal, a central transmembrane domain (TM) and a C-terminal domain with an elongated β-sandwich-like fold (

), similar to the Mu homology domain (MHD) (

). This entry represents the TM domain of PFF1 and its fungal homologues.
Thioredoxin-like reductase Rv2466c-like (Rv2466c-like)
Type: Family

This entry represents a family of proteins mainly found in actinomycetes, including thioredoxin-like reductase Rv2466c from Mycobacterium tuberculosis. Rv2466c is a key oxidoreductase that mediates the reductive activation of TP053, a thienopyrimidine derivative that kills replicating and non-replicating M.tuberculosis. This enzyme transforms nitro-containing compounds to their corresponding amine and uses as a cofactor, a low molecular weight sugar thiol, mycothiol. This protein adopts a thioredoxin-like fold and forms a unique homodimer in which the C-terminal β-strand is swapped between the thioredoxin domains of each subunit . Rv2466c undergoes significant conformational changes upon formation of its oxidised state .
SO2946-like, C-terminal domain (SO2946-like_C)
Type: Domain

This entry represents the C-terminal domain of SO2946 from Shewanella oneidensis (

). This protein consists of a short helical N-terminal domain and a large C-terminal domain with the jelly-roll topology, identified as a putative carbohydrate-binding module .
Telomere end-binding protein alpha subunit-like, OB2 domain (TEBP-like_OB2)
Type: Domain

This entry represents the second OB-fold domain (OB2) of the telomere end-binding protein (TEBP) alpha subunit. Similar to the first OB-fold domain (OB1), this domain binds to ssDNA .
Type ISP restriction-modification enzyme, coupler domain (ISP_coupler)
Type: Domain

Type ISP restriction-modification (RM) enzymes cleave random DNA between distant target sites when two enzymes collide following convergent ATP-driven translocation. This entry represents the all-helical coupler domain of type ISP RM enzymes, which links the ATPase to the MTase and the C-terminal TRD (target recognition domain) domains and seems to play a key role in transferring conformational strain during initiation .
Baseplate hub protein gp44/GpP-like, second domain (Gp44/GpP-like_2nd)
Type: Domain

This domain is found in baseplate hub protein gp44 from Escherichia phage Mu, GpP from Shewanella oneidensis (

) and similar proteins found in tailed bacteriophages and bacterial prophages. This domain is located C-terminal to

and N-terminal to

.
Baseplate hub protein gp44/GpP-like, C-terminal (Gp44/GpP-like_C)
Type: Domain

This domain is found in baseplate hub protein gp44 from Escherichia phage Mu, Mu phage baseplate assembly protein GpP from Shewanella oneidensis (

) and similar sequences found in tailed bacteriophages and prophages from proteobacteria. It is normally found associated with

.
BDI_1685-like, C-terminal domain (BDI_1685-like_C)
Type: Domain

This domain is found at the C-terminal end of BDI_1685 from Parabacteroides distasonis (

) and similar bacterial sequences. This domain is usually found associated with

.
GPR128, N-terminal domain (GPR128_N)
Type: Domain

GRP128, also known as Adhesion G-protein coupled receptor G7 (AGRG7), is an orphan receptor of the adhesion family (subclass B2) that belongs to class B GPCRs. Expression of GPR128 was detected in the mouse intestinal mucosa and is thought to be involved in energy balance . This entry represents the N-terminal domain of GPR128, which, according to structure prediction and comparison using Foldseek, it adopts a fold similar to the hormone receptor domain (HormR,

) which is usually found preceding the stalk region of the GAIN domain in cell-adhesion GPCRs .
GPR128, GAIN subdomain A (GPR128_GAIN_subdom_A)
Type: Domain

GRP128, also known as Adhesion G-protein coupled receptor G7 (AGRG7), is an orphan receptor of the adhesion family (subclass B2) that belongs to class B GPCRs. Expression of GPR128 was detected in the mouse intestinal mucosa and is thought to be involved in energy balance . It consists of an N-terminal HormR-like domain (

), followed by the GAIN domain which consists of a stalk (comprising subdomains A and B,

) and a GPS motif . This entry represents the GAIN subdomain A of the stalk from GPR128 GAIN domain, which is all α-helical .

The ~320-residue GAIN domain is an ancient domain that exists in primitive ancestor organisms, and is conserved in all aGPCRs and all PKD1-related proteins. Functionally, the GAIN domain is both necessary and sufficient for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment. In contrast to most other autoproteolytic domains that cause the release of the cleaved mature protein, autoproteolysis of the GAIN domain does not lead to the dissociation of the cleaved extracellular sequences containing the GAIN domain from the membrane-embedded regions of the protein. The GAIN domain forms a tightly associated heterodimer upon proteolysis. Cleavage at the GAIN domain is not a feature that all GAIN domain-containing receptors possess and the GAIN domain likely has other functions (such as interacting with ligands or transmembrane helices) in addition to the autoproteolysis function.
GPR128, GAIN subdomain B (GPR128_GAIN_subdom_B)
Type: Domain

GRP128, also known as Adhesion G-protein coupled receptor G7 (AGRG7), is an orphan receptor of the adhesion family (subclass B2) that belongs to class B GPCRs. Expression of GPR128 was detected in the mouse intestinal mucosa and is thought to be involved in energy balance . It consists of an N-terminal HormR-like domain (

), followed by the GAIN domain which consists of a stalk (consisting of subdomains A (

) and B) and a GPS motif (

) , followed by a C-terminal transmembrane region (

). This entry represents subdomain B of the stalk from GPR128 GAIN domain.

The ~320-residue GAIN domain is an ancient domain that exists in primitive ancestor organisms, and is conserved in all aGPCRs and all PKD1-related proteins. Functionally, the GAIN domain is both necessary and sufficient for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment. In contrast to most other autoproteolytic domains that cause the release of the cleaved mature protein, autoproteolysis of the GAIN domain does not lead to the dissociation of the cleaved extracellular sequences containing the GAIN domain from the membrane-embedded regions of the protein. The GAIN domain forms a tightly associated heterodimer upon proteolysis. Cleavage at the GAIN domain is not a feature that all GAIN domain-containing receptors possess and the GAIN domain likely has other functions (such as interacting with ligands or transmembrane helices) in addition to the autoproteolysis function.
Transcriptional regulator MlrA-like, C-terminal domain (MlrA-like_C)
Type: Domain

The HTH transcription regulator MlrA belongs to the MerR superfamily of transcription regulators that promote expression of several stress regulon genes by re configuring the spacer between the -35 and -10 promoter elements. MlrA it is also known as YehV, and has been shown to control cell-cell aggregation by co-regulating the expression of curli and extracellular matrix production in Escherichia coli and Salmonella typhimurium . MlrA is part of a signalling cascade that regulates curli biosynthesis . These proteins have dissimilar C-terminal domains that bind specific coactivator molecules. This entry represents the C-terminal domain, which is structurally similar to a B12 binding domain (

).

This group also includes the MerR-type HTH-type transcriptional repressor BluR from Escherichia coli, which controls the expression of several small proteins that may play a role in biofilm maturation .
Transcriptional regulator MlrA-like, helical domain (MlrA-like_helical)
Type: Domain

The HTH transcription regulator MlrA belongs to the MerR superfamily of transcription regulators that promote expression of several stress regulon genes by re configuring the spacer between the -35 and -10 promoter elements. MlrA it is also known as YehV, and has been shown to control cell-cell aggregation by co-regulating the expression of curli and extracellular matrix production in Escherichia coli and Salmonella typhimurium . MlrA is part of a signalling cascade that regulates curli biosynthesis . These proteins have dissimilar C-terminal domains that may bind specific coactivator molecules. This entry represents an helical domain, similar to the B12-binding module cap domain (

).

This group also includes the MerR-type HTH-type transcriptional repressor BluR from Escherichia coli, which controls the expression of several small proteins that may play a role in biofilm maturation .
Teichoic acid transporter subunit TagH, SH3-like domain (TagH_SH3-like)
Type: Domain

This domain is found in TagH from Staphylococcus epidermidis (

), the ATPase subunit of the two-component transporter TagGH, which is involved in the synthesis of bacterial polysaccharides-wall teichoic acids. This entry represents the middle SH3-like subdomain that consists of a twisted antiparallel β-sheet and two β-hairpins tightly packed forming a barrel structure . It is usually found C-terminal to

and N-terminal to

.
Teichoic acid transporter subunit TagH, C-terminal domain (TagH_C)
Type: Domain

TagH from Staphylococcus epidermidis (

) is the ATPase subunit of the two-component transporter TagGH involved in the synthesis of bacterial polysaccharides-wall teichoic acids. This entry represents the C-terminal of TagH that adopts an α/β structure consisting of a central antiparallel mixed β-sheet packed on one side with helices . It is anticipated that this domain is involved in the binding to negatively charged polymer. It is usually found C-terminal to

.
Amylase-binding protein AbpA (AbpA-like)
Type: Family

Amylase binding streptococci only colonise hosts that produce amylase in their saliva. In Streptococcus gordonii, amylase binding is mediated by amylase-binding protein A (AbpA). This protein folds into an elongated structure that consists of two domains: an N-terminal helical domain and a small C-terminal α/β domain consisting of a three-stranded β-sheet packed with α-helix . The helical domain has been shown to be responsible for the amylase binding, while the C-terminal domain interacts with SrtB.
ATR1, N-terminal domain (ATR1_N)
Type: Domain

Host-adapted plant pathogens secrete numerous effectors into the host extracellular spaces or inside cells. The A. thaliana TNL receptor RPP1 confers strain-specific immunity through recognition of H.arabidopsidis effector ATR1. ATR1 consists of two α-helical domains that are involved in interactions with the receptor. The ATR1 N-terminal domain interacts with both, the C-terminal jelly roll/Ig-like domain (C-JID) and the LRRs of the RPP1 receptor . This entry represents the N-terminal domain.
Cas12a, PI domain (Cas12a_PI)
Type: Domain

This entry represents the PI (PAM-interacting) domain found in Cpf1, also known as CRISPR-associated endonuclease Cas12a. The CRISPR-Cpf1 system is a class 2 CRISPR-Cas system that mediates robust DNA interference. Cpf1 differ from Cas9 in many aspects, including the guide RNAs and substrate specificity. The Cpf1-crRNA complex cleaves a target double-stranded DNA containing a short T-rich PAM motif on the 5' end of the non-target strand. The PAM motif is recognised by the Cpf1 PI (PAM-interacting) domain. This domain folds into an array of four helices and along with the helix-loop-helix motif in the REC1 domain, it channels the PAM strand into a cavity leading to the nuclease site .
NigD-like, OB domain (NigD-like_OB)
Type: Domain

This entry represents an OB fold domain found in NigD and related proteins from bacteria.
Quiescin sulphydryl oxidase, pseudo-Erv domain (QSOX_pErv)
Type: Domain

Quiescin sulphydryl oxidase (QSOX) family of enzymes is the only known example of conserved concatenation of disulphide-generating and disulphide-transferring modules within a single polypeptide. Formation and transfer of disulphide bonds in QSOX are mediated by redox-active cysteine pairs in a canonical Cys-X-X-Cys pattern. One of these pair is in the N-terminal thioredoxin-like domain (Trx1). Another is in the C-terminal flavin adenine dinucleotide (FAD)-binding domain (Erv) related to the mitochondrial enzyme Erv1. The middle domain, the so-called pseudo-Erv domain, bridges the Trx1 and Erv domains and is structurally similar to the Erv domain .
DUF3829-like, C-terminal domain (DUF3829-like_C)
Type: Domain

This domain is found at the C-terminal end of uncharacterised DUF3829-like proteins. It is often found associated to

. Its function is unknown. It shows four α-helices.
SAS-6, C-terminal coiled coil (SAS-6_C_CC)
Type: Domain

This domain is found at the C-terminal end of Spindle assembly abnormal protein 6 (Sas-6). Sas-6 is a central scaffolding component of the centrioles ensuring their nine-fold symmetry. Sas-6 forms a dimer through this domain to then further homo-oligomerise to form a ring structure from which the CC domains emanate as spokes .
Acyl-CoA dehydrogenase 11-like C-terminal domain (ACDH-11_C)
Type: Domain

Acyl-CoA dehydrogenase 11 (ACDH-11) sequesters C11/C12-chain fatty acids and prevents these fatty acids from activating nuclear hormone receptors and driving fat-7 expression. This enzyme consists of four domains, of which the C-terminal folds into a four-helical up-and-down bundle .
Mixed lineage kinase domain-like, N-terminal domain (MLKL_N)
Type: Domain

Mixed-lineage kinase domain-like (MLKL) is crucial for necroptosis, permeabilising membranes via its N-terminal domain upon phosphorylation of its kinase-like domain by RIP3. The MLKL N-terminal domain forms a four-helical up-and-down bundle that is sufficient to induce liposome leakage and a fifth C-terminal helix that inhibits this activity .
Degenerin mec-4/10, cytosolic domain (Mec-4/10_cyt)
Type: Domain

This entry represents the cytosolic domain found in Degenerin mec-4 and mec-10, the pore-forming subunits of the sensory mechanotransduction complex that mediates touch sensation .
RNA-directed RNA polymerase, C-terminal (RdRP_C)
Type: Domain

This domain is found at the C-terminal of RNA-directed RNA polymerase (RdRP). This protein adopts a closed cage-like structure consisting of a central polymerase domain sandwiched between N-terminal and C-terminal bracelet domains. This domain adopts a predominantly α-helical configuration .
Type six secretion immunity 3 domain (Tsi3)
Type: Domain

This entry represents the Tsi3 domain. Tsi3 immunity protein prevents early activation of toxin Tse3. Three loops of Tsi3 deeply insert into the groove of Tse3, fully blocking its active site. This interaction serves as the structural basis for Tse3 inactivation .
VP17, central beta-barrel (VP17_central_barrel)
Type: Domain

This entry represents the central β-barrel of VP17, the large major capsid protein of of bacteriophage P23-77 .
RNA-directed RNA polymerase, N-terminal (RdRP_N)
Type: Domain

This domain is found at the N terminus of RNA-directed RNA polymerase (RdRP) found in reoviruses. This protein adopts a closed cage-like structure consisting of a central polymerase domain sandwiched between the N-terminal and the C-terminal bracelet domains. This domain adopts a predominantly α-helical configuration .
MCM3 winged helix domain (MCM3_WHD)
Type: Domain

This entry represents the C-terminal winged helix domain found in yeast DNA replication licensing factor MCM3. This protein acts as a component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells .
Csm6 6H domain (Csm6_6H)
Type: Domain

This entry represents the six-helix domain (6H) of CRISPR system endoribonuclease Csm6 from Thermus termophilus and related sequences . Csm6 is a ssRNA-specific endoribonuclease that provides an auxiliary RNA-targeting interference mechanism in type III-A CRISPR-Cas systems, working together with the RNA- and DNA-targeting endonuclease activities of the Csm effector complex. Csm6 consists of a CARF domain at the N-terminal, a 6H central domain and the HEPN domain (

) at the C-terminal .
CRISPR-associated endonuclease C2c1, wedge domain, second region (C2c1_WED-II)
Type: Domain

This entry represents the second region of the wedge domain (WED-II) of CRISPR-associated endonuclease C2c1 (also known as Cas12b). It adopts an oligonucleotide-binding (OB) fold with eight β-stranded distorted β-sheets flanked by two α-helices and one β-hairpin .

C2c1 is a class 2 type V-B effector protein that was shown to be active for target DNA cleavage in vivo and in vitro. In contrast to Cpf1, this enzyme cleavage activity requires both crRNA and tracrRNA. The structure of C2c1 consists of an α-helical recognition (REC) lobe, including Helical-I and Helical-II, and a NUC lobe, including OBD, RuvC, and two Nuc domains .
CRISPR-associated endonuclease C2c1, Nuc-II domain (C2c1_Nuc-II)
Type: Domain

This entry represents the C-terminal second Nuc (Nuc-II) domain of C2c1 CRISPR-Cas endonuclease (also known as Cas12b). This domain folds into an open five-stranded β-barrel and an α-helix. Nuc-II is essential for cleavage activity.

C2c1 is a class 2 type V-B effector protein that was shown to be active for target DNA cleavage in vivo and in vitro. In contrast to Cpf1, this enzyme cleavage activity requires both crRNA and tracrRNA. The structure of C2c1 consists of an α-helical recognition (REC) lobe, including Helical-I and Helical-II, and a NUC lobe, including OBD, RuvC, and two Nuc domains .
C2c1 CRISPR-Cas endonuclease, RuvC-like domain (C2c1_RuvC-like)
Type: Domain

This entry represents the RuvC-like domain of C2c1 CRISPR-Cas endonuclease (also known as Cas12b).

C2c1 is a class 2 type V-B effector protein that was shown to be active for target DNA cleavage in vivo and in vitro. In contrast to Cpf1, this enzyme cleavage activity requires both crRNA and tracrRNA. The structure of C2c1 consists of an α-helical recognition (REC) lobe, including Helical-I and Helical-II, and a NUC lobe, including OBD, RuvC, and two Nuc domains .
CRISPR-associated endonuclease C2c1, second helical domain (C2c1_helical_2nd)
Type: Domain

This entry represents the second helical domain (REC2) from CRISPR-associated endonuclease C2c1 (also known as Cas12b). This domain, together with the first helical domain (helical-I or REC1) (

) forms the α-recognition (REC) lobe, which recognises a 20bp guide:target heteroduplex in RNAs .

C2c1 is a class 2 type V-B effector protein that was shown to be active for target DNA cleavage in vivo and in vitro. In contrast to Cpf1, this enzyme cleavage activity requires both crRNA and tracrRNA. The structure of C2c1 consists of an α-helical recognition (REC) lobe, including Helical-I and Helical-II, and a NUC lobe, including OBD, RuvC, and two Nuc domains .
CRISPR-associated endonuclease C2c1, first helical domain (C2c1_helical_1st)
Type: Domain

This entry represents the first helical domain (REC1) of CRISPR-associated endonuclease C2c1 (also known as Cas12b). This domain, together with the second helical domain (

) forms the α-recognition (REC) lobe, which recognises a 20bp guide:target heteroduplex in RNAs .

C2c1 is a class 2 type V-B effector protein that was shown to be active for target DNA cleavage in vivo and in vitro. In contrast to Cpf1, this enzyme cleavage activity requires both crRNA and tracrRNA. The structure of C2c1 consists of an α-helical recognition (REC) lobe, including Helical-I and Helical-II, and a NUC lobe, including OBD, RuvC, and two Nuc domains .
Surface cell antigen Sca2 helical repeat (Sca2)
Type: Repeat

Sca2 (surface cell antigen 2) is the only bacterial protein known to promote both actin filament nucleation and profilin-dependent elongation, mimicking eukaryotic formins to assemble actin comet tails for Rickettsia motility. Sca2's functional mimicry of formins is achieved through a unique mechanism. Unlike formins, Sca2 is monomeric, but has N- and C-terminal repeat domains (NRD and CRD) that interact with each other for processive barbed-end elongation. The crystal structure of NRD reveals a previously undescribed fold, consisting of helix-loop-helix repeats arranged into an overall crescent shape .
ExsA-like, N-terminal regulatory domain (ExsA-like_N)
Type: Domain

This entry represents the ExsA regulatory domain which mediates the ExsD binding. The structure of this domain closely resembles those of the regulatory domains of AraC and ToxT, having typical cupin-like fold .

ExsA is an AraC-type transcriptional activator protein that is regulated through protein-protein interactions rather than small molecule ligands. Prior to infection, ExsA is inhibited through a direct interaction with the anti-activator ExsD. Upon host cell contact, this interaction is disrupted by the anti-antiactivator protein ExsC .

This domain is also found in Virulence regulon transcriptional activator VirF which is the transcriptional activator of the Yersinia virulence regulon and in the Thermoregulatory protein LcrF which is the transcriptional activator of the thermally regulated virulent yopE gene .
FKBP26, IF domain (FKBP26_IF)
Type: Domain

This domain is centrally located in Long-type peptidyl-prolyl cis-trans isomerase from Methanocaldococcus jannaschii (FKBP26) and similar archaeal sequences. FKBP26 catalyses the cis-trans isomerisation of peptidyl prolyl bonds and exhibits chaperone-like activity. The latter activity requires a 50-residue insertion (IF domain, for 'Insert-in-Flap', this entry) in the catalytic FKBP domain (

). It resembles a fractured four-stranded β-barrel with the first and second strands connected by a helix that partially covers the fracture. It shows a highly hydrophobic surface .
Glucokinase regulatory protein, second SIS domain (GKRP_SIS_2)
Type: Domain

Glucokinase regulatory protein (GKRP) binds glucokinase (GK) mainly through hydrophobic interactions, functioning as an allosteric switch in blood glucose control by the liver . GKRP is trilobal in shape, consisting of two topologically identical sugar isomerase (SIS) domains capped by an α-helical lid domain (

). This entry represents the second SIS domain from GKRP .
HdrB-like C-terminal domain (HdrB-like_C)
Type: Domain

This entry represents a domain found at the C-terminal of poorly characterised bacterial proteins similar to HdrB from Helicobacter sp.