SII-SWORD/CoKE huggingface dataset:
L-amino acid ligase, C-terminal domain 2 (LAL_C2)
Type: Domain

L-amino-acid ligases are ATP-grasp superfamily enzymes that catalyze the formation of an alpha-peptide bond between two l-amino acids in an ATP-dependent manner. They share a common structural architecture that consists of three domains referred to as the A-domain, B-domain and C-domain. The C domain can be further divided into the C1-subdomain and the C2-subdomain . This entry represents the C2 subdomain.
Mitochondrial membrane-anchored protein (MIX)
Type: Domain

MIX forms an all α-helical fold comprising seven α-helices that fold into a single domain. The distribution of helices is similar to a number of scaffold proteins, namely HEAT repeats, 14-3-3, and tetratricopeptide repeat proteins, suggesting that MIX mediates protein-protein interactions .
Thaumarchaeal output domain 1 (TackOD1)
Type: Domain

TackOD1 (Thaumarchaeal output domain 1) is a predicted metal-binding domain found in archaea and in some bacteria. It contains 11 highly conserved Cys residues, which form 5 CxxC motifs and an HxxC motif. In several instances, it is found in combination with the receiver domain (

) .
Tail specific protease, N-terminal domain (TSP_N)
Type: Domain

Tail specific proteases are involved in cleaving the C termini of specific protein substrates. The N-terminal domain of tail specific proteases has a novel fold composed of 10 α helices .
V-type ATP synthase subunit I, N-terminal (V_ATPase_I_N)
Type: Domain

Vacuolar H+-ATPase (V-ATPase) is a ubiquitous multi-subunit proton pump that acidifies a wide variety of intracellular compartments, which in turn affects many biological processes, including membrane trafficking, protein degradation and coupled transport of small molecules and pH homeostasis. Subunit 'a' of V0 (the functional domain responsible for proton transport) sector is highly conserved across eukaryotic species and exists in multiple isoforms. It is the largest subunit of V-ATPases and partitioned almost equally into an N-terminal cytosolic domain and a C-terminal integral membrane. Structure analysis of the N-terminal cytosolic domain from the Meiothermus ruber subunit 'I' homologue of subunit a shows that it is composed of a curved long central α-helix bundle capped on both ends by two lobes with similar α/β architecture .
Endo-alpha-N-acetylgalactosaminidase, N-terminal (GH101_N)
Type: Domain

This is the N-terminal domain found in Streptococcus pneumoniae endo-alpha-N-acetylgalactosaminidase (

) , a cell surface-anchored glycoside hydrolase from family GH101 involved in the breakdown of mucin type O-linked glycans. This is a twisted β-sandwich domain composed of two sheets of six and seven antiparallel β-strands. The domain appears to be missing the extended metal and carbohydrate-binding loops .
Dynamin-like helical domain (DLP_helical)
Type: Domain

This helical domain is found in bacterial proteins such as labile enterotoxin output A (LeoA), a large GTPase (64.2kDa) with a putative involvement in membrane vesicle (MV) secretion in Escherichia coli. The crystal structure of LeoA reveals a fold with all the hallmarks of a dynamin-like protein (DLP) .
Glutamine synthetase, C-terminal (Gln-synt_C)
Type: Domain

This domain is found in type III glutamine synthetase present in Bacteroides fragilis. Glutamine synthetase (GS) are large oligomeric enzymes that catalyze the condensation of ammonium and glutamate to form glutamine, the principal source of nitrogen for protein and nucleic acid synthesis. This domain is located in the C-terminal end of the protein .
UPF0242, C-terminal PAS-like domain (UPF0242_PAS)
Type: Domain

This domain is found at the C terminus of proteins of the uncharacterised family UPF0242. This domain is related to the PAS domain (

).
Acetyltransferase (GNAT) domain (Acetyltransf_19)
Type: Domain

This entry represents a likely acetyltransferase enzyme that is related to

.
Domain of unknown function DUF5627 (DUF5627)
Type: Domain

This is a domain of unknown function found in bacteria.
SNTX, thioredoxin-like domain (Thioredoxin_11)
Type: Domain

This domain is found in pore-forming toxin stonustoxin (SNTX), a lethal venom found in Synanceia horrida. Because of the thioredoxin-like nature of the domain, it is referred to as the THX domain. The THX domain is comprised of a five-stranded β-sheet and shares greatest structural similarity with Saccharomyces cerevisiae mitochondrial THX3. It is thought that THX domain plays a purely structural role .
MalK-like, OB fold domain (OB_MalK-like)
Type: Domain

This entry corresponds to one of two OB-fold domains found, among others, in the MalK transport protein.
PheRS DNA binding domain 2 (PheRS_DBD2)
Type: Domain

This is a DNA-binding fold domain found in Phenylalanyl-tRNA Synthetase N-terminal region. Mutational analysis indicate that DBD-1, 2 and 3 play critical roles in tRNA- Phe binding and recognition, i.e., from the drastic reduction of aminoacylation activity seen upon removal of the N-terminal domains. DBD-2 and DBD-3 constitute large insertions sequentially included between two neighbouring antiparallel strands of the DBD-1 domain .
5-3 exonuclease XRN1, DCP1-binding motif (XRN1_DBM)
Type: Domain

This domain is found in the 5'-3' exonuclease (XRN1) present in Drosophila melanogaster. XRN1 degrades deadenylated mRNA that has recently been decapped by decapping enzyme 2 (DCP2). DCP2 associates with decapping activators DCP1 and EDC4. The direct interaction between DCP1 and XRN1 couples mRNA decapping to 5' exonucleolytic degradation. This domain is responsible for binding to DCP1. In particular, the helical C-terminal region of the domain contributes to the binding affinity and the specificity of the interaction .
Argonaute, N domain (AGO_N)
Type: Domain

This is the N domain often found in the N-terminal region of Argonaute (AGO) present in Kluyveromyces polyspora. AGO forms part of the RNA-induced silencing complex that mediates the gene silencing pathway, RNA interference. The N domain blocks the nucleic acid-binding channel and prevents propagation of guide-target pairing beyond position 16 .
Ribosome-associated protein quality control protein P2, RNA-binding domain (RqcP2_RBD)
Type: Domain

This domain adopts an RRM like fold and is found in the B. subtilis Ribosome-associated protein quality control protein P2 (RqcP2, also known as YlmH). RqcP2 is a component of the ribosome quality control system (RQC), a ribosome-associated complex that mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes and their subsequent degradation .
TbRIF5 SNase domain 2 (RIF5_SNase_2)
Type: Domain

This domain can be found in the Trypanosoma brucei TbRIF5 protein, which could contribute to the processing of dsRNA targets .
Spindle pole body component 110, C-terminal (Spc110_C)
Type: Domain

This entry represents the C-terminal domain of Spc110 (spindle pole body component 110). Its N terminus is shown to bind to gamma-tubulin small complex (g-TuSC), while its C-terminal domain is essential for calmodulin-binding. The C terminus of Spc110 is anchored to the SPB via a conserved PACT domain .
Unkempt, zinc finger domain 1 (UNK_Znf_1)
Type: Domain

This is a CCCH zinc finger domain found in Unkempt N-terminal region.

Unkempt is an evolutionary conserved RNA-binding protein that regulates translation of its target genes and is required for the establishment of the early bipolar neuronal morphology . It carries six CCCH zinc fingers (Znfs) forming two compact clusters, Znf1-3 and Znf4-6, that recognize distinct trinucleotide RNA substrates. These clusters, recognize an unexpectedly short stretch of RNA sequence-only three consecutive ribonucleotides-with a varying degree of specificity. Znf1-3 binds to the UUA motif of RNA substrates .
EZH2, N-terminal domain (EZH2_N)
Type: Domain

Polycomb repressive complex 2 (PRC2) carries out the methylation of lysine 27 of histone H3, a hallmark of repressive chromatin. Three core subunits make up the catalytic core of PRC2; the SET domain containing EZH2, the zinc-finger containing SUZ12 and the WD40 repeat protein EED. The complex forms a compact arrangement of three lobes. This is the N-terminal domain of EZH2 .
RNase II-type exonuclease, C-terminal S1 domain (RNase_II_C_S1)
Type: Domain

This entry describes the C-terminal S1 domain found in type 2 RNase (DrII) exonucleases, such as DrR63 from Deinococcus radiodurans. Structure analysis of DrII indicates that it has an N-terminal HTH domain which interacts with a flexible loop that connects two β-strands from the conserved C-terminal S1 domain, forming a β-wing fold common in wHTH domains .
Hemagglutinin component HA-70, C-terminal (HA70_C)
Type: Domain

This is the C-terminal domain found in hemagglutinin component such as HA70 from Clostridium botulinum. HA is a component of the large botulinum neurotoxin complex and is critical for its oral toxicity. HA plays multiple roles in toxin penetration in the gastrointestinal tract, including protection from the digestive environment, binding to the intestinal mucosal surface, and disruption of the epithelial barrier . HA consists of three different proteins, designated HA70 (also known as HA3), HA33 (HA1), and HA17 (HA2) based on molecular mass . HA70 consists of three domains (D1-3). The D1 and D2 domains, which adopt similar structures, mediate the trimerization of HA70 with each protomer. The D3 domain, sitting at the tip of the trimer, is composed of two similar jelly-roll-like β-sandwich structures . Furthermore, crystal structures of HA70 in a complex with alpha2,3-or alpha2,6-SiaLac (alpha2,6-sialyllactose), show that alpha2,3-and alpha2,6-SiaLac bound to the same region in the D3 domain of HA70. This domain is the D3 domain found in HA3/HA70 which has been shown to be involved in binding to carbohydrate of glycoproteins from epithelial cells in the infection process .
60S ribosome subunit biogenesis protein NIP7, pre-PUA domain (NIP7_N)
Type: Domain

Human 60S ribosome subunit biogenesis protein NIP7 homologue (also known as KD93) is essential in the accurate processing of pre-rRNA . The overall fold of KD93 consists of two interlinked α/β domains. The C-terminal domain resembles the PUA domain of some RNA modification enzymes, especially that of archaeosine tRNA-ribosyltransferase (ArcTGT), suggesting a possible molecular function related to RNA binding .

This entry represents the N-terminal, pre-PUA domain of NIP7 and its homologues from eukaryotes, and UPF0113 proteins from archaea, whose function is unknown.
Pilin PilJ, C-terminal (PilJ_C)
Type: Domain

This is the C-terminal domain of PilJ, a Type IV pilin found in Gram-positive Clostridium difficile. Incorporation of PilJ into pili exposes the C-terminal domain of PilJ to create a novel interaction surface. This C-terminal domain is not observed in other Type IV pilin proteins .
Agglutinin, C-terminal (Agglutinin_C)
Type: Domain

This entry represents the C-terminal domain of the alpha chain found in Marasmius Oreades lectin protein (MOA) which binds specifically with Gal.alpha(1,3)Gal-containing sugar epitopes. The enzymatic activity of the MOA may be associated with this domain. The domain has an α/β-fold, which features a central six-stranded, mostly anti-parallel, β-sheet flanked by three α-helices, and a short two-stranded β-sheet .
tRNA methyltransferase 5a/b, N-terminal (Trm5a/b_N)
Type: Domain

This is the N-terminal domain of tRNA methyltransferase 5a (Trm5a, also known as Taw22) from Pyrococcus abyssi and Tmr5b from Methanocaldococcus jannaschii. These proteins catalyse the methyl transfer from S-adenosyl methionine (AdoMet) to N1 of G37 . This domain, also known as the D1 domain, contacts the tertiary core (elbow) region of the tRNA L shape in a ternary complex of the enzyme with tRNA and AdoMet .
Cucumopine synthase, C-terminal helical bundle domain (Cucumopine_C)
Type: Domain

McbB from Marinactinospora thermotolerans is an enzyme that catalyzes the Pictet-Spengler (PS) reaction of L-tryptophan and oxaloacetaldehyde to produce the betaC scaffold of marinacarbolines. This is the C-terminal domain composed of 5 bundled α helices. It is weakly similar to the signal transduction histidine-protein kinase BarA from E. coli and the DNA endonuclease I-MsoI from Monomastix sp .
Fanconi-associated nuclease 1, SAP domain, bacteria (FAN1_SAP_bact)
Type: Domain

This domain is found in Fanconi-anemia-associated nuclease 1 (FAN1) present in Pseudomonas aeruginosa. FAN1 is a nuclease associated with Fanconi anemia (FA), an autosomal recessive genetic disorder caused by defects in FA genes responsible for processing DNA inter-strand cross-links (ICLs). The domain, known as the SAP domain, helps to augment the overall protein DNA interaction by interacting with the 3' and 5' ends of the template strand. Support of the pre-nick segment binding is crucial as multiple mutations in this domain resulted in hypersensitivity to a cross-linking agent in the SAP domain of Caenorhabditis elegans' FAN1. The helix-hairpin-helix of the SAP recognize three consecutive phosphate groups (C19, A20 and A21) at the 3' end of the template via the basic residues K116, K135 and K117 .
Domain of unknown function DUF5632 (DUF5632)
Type: Domain

This an α-β-α domain found at the N-terminal region of Rv3899c, a hypothetical protein from Mycobacterium tuberculosis which is conserved across mycobacteria .
Glycoside hydrolase family 2, domain 5 (Glyco_hydro2_dom5)
Type: Domain

This domain is found in dimeric beta-D-galactosidase from Paracoccus sp. 32d, which contributes to stabilization of the functional dimer. It is suggested that the location of this domain 5, may be one of the factors responsible for the creation of a functional dimer and cold-adaptation of this enzyme .
piRNA-mediated silencing protein C19orf84 (C19orf84)
Type: Family

This entry, previously known as DUF5549, represents the piRNA-mediated silencing protein C19orf84 and related proteins found in mammals. C19orf84 is essential for orchestrating piRNA-directed DNA methylation . C19orf84 interacts with SPOCD1 and mediates the in vivo association of SPOCD1 with the de novo methylation machinery. DNMT3C, the DNA methyltransferase responsible for transposon methylation, associates with SPOCD1 and C19ORF84 .
Actin-like protein, N-terminal (ALP_N)
Type: Domain

This is the N-terminal domain found in archaeal actin homologue Ta0583 found in thermophilic archaeon Thermoplasma acidophilum. Structural analysis indicate that the fold of Ta0583 contains the core structure of actin indicating that it belongs to the actin/Hsp70 superfamily of ATPases. Furthermore, Ta0583 co-crystallised with ADP shows that the nucleotide binds at the interface between the subdomains of Ta0583 in a manner similar to that of actin. It has been suggested that Ta0583 might function in the cellular organisation of T. acidophilum .

Other family members include ParM, another actin-like protein found in Staphylococcus aureus. Crystal structure coordinates revealed that this protein is most structurally related to the chromosomally encoded Actin-like proteins (Alp) Ta0583 from the archaea Thermoplasma acidophilum. Furthermore, biophysical analyses have suggested that ParM filaments undergo a treadmilling-like mechanism of motion in vitro similar to that of F-actin. The recruitment of ParM to the segrosome complex, was shown to be required for the conversion of static ParM filaments to a dynamic form proficient for active segregation and facilitated by the C terminus of ParR .
Snf8/Vps36 family (Snf8/Vps36)
Type: Family

This family includes Snf8 and Vps36. Vps36 is involved in Golgi to endosome trafficking. Snf8 is a component of the endosomal sorting complex required for transport II (ESCRT-II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs .
RNA ligase 2, C-terminal (Rnl2_C)
Type: Domain

This is the C-terminal domain of RNA ligase 2 (Rnl2). The C-terminal domain consists of a four-helix bundle. The C-terminal domain is thought to be critical for binding the Rnl2 to adenylylated nicked duplex. This is known as step 2 of the ligation pathway .
SNRNP25, ubiquitin-like domain (SNRNP25_ubiquitin)
Type: Domain

This domain has a ubiquitin-like fold found in a diverse range of proteins including RNP25 . RNP25 is a component of the U11/U12 snRNPs that are part of the U12-type spliceosome. It contains a conserved ubiquitin-like (Ubl) domain with a β-grasp Ubl fold, a common structure involved in protein-protein interactions .
HTH-type transcriptional regulator AlkX, C-terminal, Actinobacteria (AlkX_C)
Type: Domain

This is the C-terminal tetracycline repressor domain found in HTH-type transcriptional regulator AlkX and similar sequences from actinobacteria. It represses the expression of the alkB-rubAB operon, which encodes the alkane hydroxylase AlkB and the rubredoxins RubA and RubB . AlkX can bind to the promoter region of mmpS1 and mmpL3 and to the intragenic region of mmpL11, suggesting that it may participate in the regulatory network that controls the expression of MmpL lipid transporters . Similar to other TetR family regulators, these proteins are α-helical dimeric proteins consisting of a smaller N-terminal DNA-binding domain and a larger C-terminal regulatory domain .
ArsA, HSP20-like domain (ArsA_HSP20-like)
Type: Domain

This domain is found at the C terminus of ArsA-like proteins. This domain is related to HSP20 (

).
Nucleotide modification associated domain 4 (Nmad4)
Type: Domain

This entry represents an α+β fold domain typically associated with DNA methylases. It may be involved in modified nucleotide biosynthesis .
Integron cassette protein VCH_CASS1 chain (VCH_CASS14)
Type: Domain

This domain is a chain that forms part of the integron cassette protein VCH_CASS14 present in Vibrio cholerae. In each monomer lies a deep binding pocket for small molecule substrates formed by helices alpha-1 and alpha-2 and residues from the central four strands of the β-sheet. The pocket is extensively lined with hydrophobic side chains .
Pre-nudix hydrolase domain (Pre-Nudix)
Type: Domain

This domain is found just before the N-terminal region of nucleoside diphosphate-linked moiety (Nudix) hydrolases (

). Nudix hydrolases catalyze the hydrolysis of nucleoside diphosphates which are often toxic metabolic intermediates and signalling molecules .
Cas9, alpha-helical lobe domain (Cas9_alpha-helical_lobe)
Type: Domain

This entry represents the α-helical lobe domain found in Cas9, a endonuclease that cleaves linear or circular dsDNA target complementary to the spacer. Cas9 adopts a bilobed architecture composed of a nuclease lobe containing juxtaposed RuvC and HNH nuclease domains and a variable α-helical lobe likely to be involved in nucleic acid binding. Amino acid residues located in both the nuclease and α-helical lobe clefts are highly conserved within type II-A Cas9 proteins .
Protein of unknown function DUF5560 (DUF5560)
Type: Family

This is a family of unknown function found mostly in primates.
Avirulence Effector AvrLm4-7 (AvrLm4-7)
Type: Domain

AvrLm4-7 is found in Leptosphaeria maculans, an ascomycete fungus in the dothideomycete group which is responsible for stem canker (blackleg) of Brassica napus (oilseed rape, OSR) and other crucifers. AvrLm4-7 is one of six avirulence genes which encodes a small secreted protein strongly over-expressed at the onset of plant infection. This gene confers a dual recognition specificity by two distinct resistance genes of OSR, Rlm4 and Rlm7 and loss of AvrLm4 avirulence was demonstrated to be associated with a strong fitness cost. Structure and functional analysis of AvrLm4-7 protein show that it contains the motifs RAWG and RYRE, part of a well-structured protein region held together by disulfide bridges. Mutations in the RAWG motif or in the RYRE motif (especially mutations in both motifs) almost abolished the translocation of AvrLm4-7 into cells. Furthermore, loss of recognition of AvrLm4-7 by Rlm4 is caused by the mutation of a single glycine to an arginine residue located in a loop of the protein .
Integrin beta, epidermal growth factor-like domain 1 (EGF_integrin_1)
Type: Domain

This is the first EGF-like domain found in several integrin beta subunits. This domain lacks one disulphide (C2-C4) relative to the integrin EGF 2, 3, and 4 domains; this allows the C-terminal end of EGF1 to flex remarkably relative to its N-terminal end .

EGF-like domains in beta subunits contain three disulphide groups with the same connectivity as in other EGF domains. The disulphide bonds function as critical "locks" for integrin inactivity, with bond disruption enabling activation . Each EGF-like domain contains three β strands, with the first two antiparallel strands (A and B) forming a major β sheet found in classical EGF domains. Strand C is hydrogen bonded to strand D, which is contributed in part by the consecutive domain, with strands C and D forming a minor β sheet-like conformation .

Integrin beta subunits consist of an extracellular domain with a head region, a stalk/leg section, a transmembrane domain, and a cytoplasmic tail. The head region contains a β-I-like domain inserted into a hybrid domain, connected to a plexin-semaphorin-integrin (PSI) [

]. C-terminal to the PSI domain is an A-domain, which has been predicted to adopt a Rossmann fold similar to that of the alpha subunit, but with additional loops between the second and third β strands. This domain is referred to as VWA [

]. Many VWA domains bind metal ions via a noncontiguous sequence motif called metal ion-dependent adhesion site (MIDAS) . This is followed by a β-subunit stalk/leg section that contains four cysteine-rich integrin epidermal growth factor-like (I-EGF) modules [

], [

],

]. Finally, this is followed by the β-ankle TM domain [

] and a cytoplasmic tail [

] .

Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton, and activate many intracellular signalling pathways . An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a VWA domain inserted within the integrin domain at the N-terminal.

Most integrins recognise relatively short peptide motifs and, in general, require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits . There are at least 18 types of alpha and 8 types of beta subunits recognised in humans . Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule . Each association of alpha and beta subunits has its binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activates or inhibits another.
26S proteasome regulatory subunit RPN2, C-terminal (RPN2_C)
Type: Domain

This is the C-terminal domain found in S. cerevisiae Rpn2 (26S proteasome regulatory subunit RPN2) as well as other eukaryotic species. A study revealed that the C-terminal 52 residues of the Rpn2 C-terminal domain are responsible for mediating interactions with the ubiquitin-binding subunit Rpn13. Furthermore, the extreme C-terminal 20 or 21 residues of Rpn2 (926-945 or 925-945) of S. cerevisiae, were shown to be equally effective at binding Rpn13. Multiple sequence alignments indicate that Rpn2 orthologues are highly conserved in this C-terminal region and share characteristic acidic, aromatic, and proline residues, suggesting a common function. In the structure of Rpn2 from S. cerevisiae , this region is exposed and disordered, and is thus accessible for associating with Rpn13. The Rpn2 binding surface of human Rpn13 has been mapped by nuclear magnetic resonance titration to one surface of its Pru domain .