SII-SWORD/CoKE huggingface dataset:
REase associating with pPIWI, RE domain (pPIWI_RE_REase)
Type: Domain

This entry represents the restriction endonuclease (REase) domain found in a conserved three-gene island that also contains a DinG-type helicase and the pPIWI_RE module. This three gene island is predicted to form a conflict system which targets R-loop formation of invasive plasmids during plasmid replication .
CD-NTase-associated protein 16, NUDIX domain (Cap16_NUDIX)
Type: Domain

This entry represents the NUDIX domain found in CD-NTase-associated protein 16 (Cap16), an effector protein of a CBASS antivirus system which provides immunity against bacteriophages [. It responds to antiviral nucleotide second messenger signaling and induce cell death, similarly to Cap15 and Cap14 .
Bacterial archaeo-eukaryotic release factor family 8 (Bact_RF_family8)
Type: Domain

This entry represents a domain found in a bacterial family under the archaeo-eukaryotic release factor superfamily. It is likely to play roles in biological conflicts or regulation under stress conditions at the ribosome .
YdcK Beta solenoid repeat (B_solenoid_ydck_rpt)
Type: Repeat

The crystal structure of YDCK from Salmonella cholerae includes a β-solenoid repeat. This entry includes a single repeat unit of YDCK repeat.
TTHB210-like domain (TTHB210-like_dom)
Type: Domain

This domain is found in TTHB210 protein present in Thermus thermophilus. TTHB210 is a Sigma-E factor regulated gene product that forms a homodecamer. This domain is chain G and can be classified with chains A, C, E and I based on its folds .
Domain of unknown function DUF5631 (DUF5631)
Type: Domain

This is an α helical domain found at the C-terminal region of the hypothetical protein Rv3899c from Mycobacterium tuberculosis which is conserved across mycobacteria .
Nicking enzyme C-terminal middle helical domain (NES_C_h)
Type: Domain

This domain is found in nicking enzyme in S. aureus. NES initiates and terminates the transfer of plasmids that variously confer resistance to a range of drugs, including vancomycin and gentamicin. This domain is found in the C-terminal region of NES. The C-terminal region is required for conjugation and significantly impacts the catalytic activity of the N-terminal relaxase .
Nucleotide modification associated domain 5 (Nmad5)
Type: Domain

This entry represents an α+β fold domain associated with DNA base modifying genes in prokaryotes. It is likely to be involved in modified DNA base biosynthesis .
SMODS-associated and fused to various effectors (SAVED)
Type: Domain

This entry represents a sensor domain, sensing nucleotides or nucleotide derivatives generated by SMODS and other nucleotide synthetase domains . This domain has been recently characterised in CD-NTase-associated protein 4 (Cap4), the founding member of a major family of downstream receptors that specifically respond to nucleotide second messenger signals in CBASS (cyclic oligonucleotide-based antiphage signaling system) immunity, a bacterial system that provides immunity against bacteriophage . SAVED exhibits divergence in its nucleotide binding pocket which enables the recognition of a wide range of CD-NTase products such as bacterial second messengers with alternative ring size, nucleobase, and 3'-5' or 2'-5' phosphodiester linkages . The sensing of ligands by SAVED activates effectors that are essential for CBASS-mediated protection of bacteria from phage infection.
Bacterial archaeo-eukaryotic release factor family 7 (Bact_RF_family7)
Type: Family

This entry represetns the bacterial family that is under the the archaeo-eukaryotic release factor superfamily. It is likely to play roles in biological conflicts or regulation under stress conditions at the ribosome. Consistent with this, many members of the family associate on the genome with HPF-like ribosome hibernation factor .
SabA, N-terminal extracellular adhesion domain (SabA_N_adhesion)
Type: Domain

This is the N-terminal extracellular adhesion domain of Sialic acid binding adhesin (SabA) present in Helicobacter pylori. The N-terminal domain of SabA functions as a sugar-binding adhesion domain with conserved disulfide bonds. Notably, these amino acid residues are not only conserved among SabA orthologs but also between SabA and BabA .
Macroglobulin domain MG4 (MG4)
Type: Domain

This domain is MG4 found in thioester-containing proteins (TEPs) such as Alpha-2-macroglobulin, complement C3 and C5 and complement-like proteins .
Tc toxin complex TcA, C-terminal TcB-binding domain (TcA_TcB_BD)
Type: Domain

This domain is found in the C-terminal region of the Tc toxin TcA, present in Photorhabdus luminescens. Tc Toxin complexes bind to the cell surface, are endocytosed and perforate the host endosomal membrane by forming channels that translocate toxic enzymes into the host. This domain is responsible for binding to toxin TcB. Binding of TcA to TcB/TcC opens the β-propeller gate .
Luciferase domain (Luciferase_dom)
Type: Domain

This entry describes the luciferase domain found in fungi. This entry also includes uncharacterised bacterial sequences.

Fungal luciferase is part of the gene cluster that mediates the fungal bioluminescence cycle . It may use the fungal luciferin 3-hydroxyhispidin as a substrate to produce an endoperoxide as a high-energy intermediate with decomposition that yields oxyluciferin (also known as caffeoylpyruvate) and light emission. The fungal bioluminescence cycle begins with the hispidin synthetase that catalyses the formation of hispidin which is further hydroxylated by the hispidin-3-hydroxylase, yielding the fungal luciferin 3-hydroxyhispidin. The luciferase then produces an endoperoxide as a high-energy intermediate with decomposition that yields oxyluciferin and light emission. Oxyluciferin can be recycled to caffeic acid by caffeoylpyruvate hydrolase .
Sorting nexin-17/31, FERM domain (SNX17/31_FERM)
Type: Domain

This domain can be found at C terminus of sorting nexin 17 (SNX17) and sorting nexin 31 (SNX31). SNX17 localizes to early endosomes where it directly binds NPX(Y/F) motifs in the target receptors to mediate their rates of endocytic internalization, recycling, or degradation. The domain is known as terminal band 4.1/ezrin/radixin/moesin (FERM) domain. The FERM domain binds directly to the common motif, NPX(Y/F), in the cytoplasmic region of its target proteins .
Restriction enzyme adenine methylase associated (RAMA)
Type: Domain

This entry represents an α+β fold domain associated with restriction enzymes across prokaryotes and fused to JAB deubiquitinases, and chromatin proteins in a wide range of eukaryotes. The domain is predicted to function as a modified-DNA reader domain .
Phosphodiesterase 4 upstream conserved regions (UCR) (PDE4_UCR)
Type: Domain

This is the upstream conserved region (UCR) found in Phosphodiesterase 4 (PDE4) enzymes. PDE4 is a contributor to intracellular signalling and an important drug target. The four members of this enzyme family (PDE4A to -D) are functional dimers in which each subunit contains two upstream conserved regions (UCR), UCR1 and -2, which precede the C-terminal catalytic domain. Due to alternative promoters/start sites and variable mRNA splicing, transcription from the four PDE4 genes results in the expression of more than 25 different isoforms of PDE4. Each isoform has a unique N-terminal region that determines its specific subcellular localization by mediating interactions with scaffolding proteins. The isoforms are further classified into long, short, and supershort forms based on the presence or absence of two upstream conserved regions (UCRs, known as UCR1 and UCR2). Long splice variants contain both UCR1 and UCR2, short variants lack UCR1, and the supershort forms of PDE4 additionally lack part of UCR2. The extent to which UCRs are present determines critical functional differences between the isoforms. Phosphorylation by protein kinase A (PKA) at a conserved site on UCR1 activates all long PDE4 isoforms. Mutation and deletion studies have shown that long forms of PDE4 are dimeric, with key dimerization interactions mediated by UCR1 and UCR2, and that the C-terminal half of UCR2 could play a negative regulatory role .
Aminoarabinose transferase, C-terminal (Arnt_C)
Type: Domain

ArnT is a member of the GT-C family of glycosyltransferases, and it has a similar fold to a bacterial oligosaccharyltransferase (OST) from Campylobacter lari (PglB) and to an archaeal OST from Archaeoglobus fulgidus (AglB). This entry represents the C-terminal periplasmic domain of Arnt proteins .
ORF 12 gene product, N-terminal (ORF_12_N)
Type: Domain

This is the N-terminal domain of Streptomyces clavuligerus ORF 12 gene product, which is directly involved in biosynthesis of Clavulanic acid (CA). The N-terminal domain consists of one four-stranded antiparallel β-sheet surrounded by four α-helices and folds similarly to steroid isomerases and polyketide cyclases (PKTC). However, the N-terminal domain has no apparent polar-lined active-site pocket or conserved catalytic residues analogous to those of either the steroid isomerases or PKTCs. ORF 12 has 2 binding sites, CA is able to bind both to an active site and between the two domains. The active site pocket is lined by residues from both the N- and the C-terminal domains (His88, Ser173, Thr209, Ser234, Ser278, Met383, Phe374, Ala376 and Phe385). The C-2 carboxylate of CA is positioned deep in the pocket, making electrostatic interactions with Lys375, Arg418 and Lys89. Lys89 is located in strand beta-2 of the N-terminal domain and may also be involved in the beta-lactam core-binding region, including the residues Lys89 as well as Arg418 .
Mind bomb, SH3 repeat domain (SH3_15)
Type: Domain

The REP domain of Mind bomb which serves as the substrate recognition domain for a second, membrane-distal epitope of the Notch ligand (C-box). Although the first Mib repeat of REP may play a dominant role in ligand binding, the two repeats appear to cooperate in the engagement of the Jag1 tail. Mind bomb (Mib) proteins are large, multi-domain E3 ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. The structure and functional analysis, show that Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membrane proximal region and the other near the C terminus. REP domains have a five-stranded anti-parallel twisted β sheet topology similar to that of SH3 domains .
Midasin, AAA lid domain 7 (AAA_lid_7)
Type: Domain

This entry represents the α helical AAA+ lid domain that is found to the C terminus of AAA domains. This lid domain is found in midasin proteins.

Midasin (MDN1, REA1) is a is a member of the AAA(+) family of ATPases. It is a nuclear chaperone required for maturation and nuclear export of pre-60S ribosome subunits .
MyBP-C, tri-helix bundle domain (MyBP-C_THB)
Type: Domain

This domain can be found in the myosin-binding motif (m-domain) region present in myosin-binding protein C (MyBP-C). MyBP-C is a sarcomeric assembly protein necessary for the regulation of sarcomere structure and function . The MyBP-C family of proteins consists mainly of modules with immunoglobulin (Ig) or fibronectin folds . This domain exhibits a three-helix bundle fold and there is a known actin-binding motif, LK(R/K)XK positioned in the third helix (alpha3), similar to that found in villin and related proteins .
Knl1, C-terminal RWD domain (Knl1_RWD_C)
Type: Domain

This domain is found in Knl1, a sub-unit of the KMN network, present in Homo sapiens. The KMN network is the core of the outer kinetochore which is responsible for microtubule binding/stabilization and controls the spindle assembly checkpoint. This domain is the second of two RING finger, WD repeat, DEAD-like helicase (RWD) domains. The tandem RWD domains mediate kinetochore targeting of the microtubule-binding subunits by interacting with the Mis12 complex. The Mis12 complex is a KMN sub-complex that tethers directly onto the underlying chromatin layer .
Centromere-binding protein ParB, C-terminal (ParB_C)
Type: Domain

This entry represents the C-terminal DNA-binding domain found in centromere-binding protein ParB, which is required for stable segregation. The C-terminal domain has a ribbon-helix helix (RHH) motif with a C-terminal loop (residues 119-128) following helix alpha-2. The domain forms a dimer with the C-terminal of the beta chain .
Cas12a, RuvC nuclease domain (RuvC_1)
Type: Domain

This is a RuvC nuclease domain found in type V CRISPR-associated protein Cas12a (Cpf1). These proteins carry out endoribonuclease activity for processing its own guide RNAs and RNA-guided DNase activity for target DNA cleavage. The C-terminal region of Cas12a carries the RUVC domain, NUC domain and the arginine-rich bridge helix (BH). Both the NUC and BH domains are nested in the RuvC domain. Mutations in the RuvC domain impair cleavage of both strands in a target DNA duplex, while a mutation in the Nuc domain impaired target strand cleavage only. This indicates that the DNA nuclease active sites are located at the interface of the RuvC and Nuc domains and that cleavage of the non-target DNA strand by the RuvC domain is a prerequisite for target strand cleavage by the Nuc domain .
RapA2, cadherin-like domain (RapA2_cadherin-like)
Type: Domain

This entry reprsents the cadherin-like domains found in RapA2, a calcium-binding lectin that interacts specifically in a calcium-dependent manner with the acidic exopolysaccharide (EPS) and capsular polysaccharide produced by R.leguminosarum .
Uncharacterized protein ZSWIM9 (ZSWIM9)
Type: Family

This is a family of proteins of unknown function predominantly found in chordates, including the uncharacterised protein ZSWIM9 from human.
Origin recognition complex subunit 3, winged helix C-terminal (ORC_WH_C)
Type: Domain

This is the C-terminal winged-helix (WH) DNA-binding domain of the origin recognition complex subunit 3 present in Drosophila melanogaster. The WH domain is responsible for recognizing origin sequences .
Glucose ABC transporter, C-terminal (GlcV_C)
Type: Domain

This is the C-terminal domain found at the ATPase subunit of the glucose ABC transporter from Sulfolobus solfataricus. Overall, the C-terminal domain (residues 243-353) contains only β-strands, which form an elongated barrel-shaped structure composed of two parts. This entry represents the upper part which includes a three-stranded anti-parallel β-sheets and two small anti-parallel β-strands. The overall structure of this domain is very similar to that of the C-terminal domain of MalK from T. litoralis however, the function of the C-terminal domain in GlcV is not clear .
VioE domain (VioE_dom)
Type: Domain

This domain can be found in VioE from Chromobacterium violaceum. VioE plays a key role in the biosynthesis of violacein. Violacein has potential medical applications as an antibacterial, anti-tryptanocidal, anti-ulcerogenic and as an anti-cancer drug. VioE forms a homodimer with a chiefly hydrophobic interface between the two VioE monomers. The fact that VioE adopts a fold normally associated with lipoprotein carrier proteins may be due to VioE for binding the hydrophobic polyethylene glycol .
Rubisco accumulation factor 1, C-terminal (Raf1_C)
Type: Domain

This is the C-terminal domain, also known as the beta domain, of Rubsico Assembly Chaperone protein (Raf1). Raf1 is necessary for rubisco to catalyze the rate-limiting step of carbon fixation through carboxylating the five-carbon sugar substrate ribulose-1,5-bisphosphate. The beta domains primary function is dimerization, which is critical for Raf1 to achieve the necessary avidity for complex formation with RbcL (the large complex sub-unbit of Rubsico) assembly intermediates. The beta domain is also involved, to a small extent, in binding to RbcL with use of the lustiness near the beta domain's conserved top surface .
Midline-1, COS domain (Midline-1_COS)
Type: Domain

This entry represents the COS domain found in the C-I subfamily of the tripartite motif (TRIM) family of E3 ubiquitin ligases.

The C-1 subfamily includes MID1 (TRIM18), MID2 (TRIM1), TRIM9, TNL (TRIM67), TRIM36 and TRIFIC (TRIM46) . The C-I subfamily contains C-terminal FNIII and B30.2 domains which are associated with microtubules . C-I subfamily members also contain a relatively conserved region of approximately 60 amino acids, termed the C-terminal subgroup One Signature (COS) domain .
Gp37/Dip protein (Dip)
Type: Family

This protein is found in the giant phage phi KZ. This protein has been shown to bind to RNAse E of the host P. aeruginosa and to inhibit the RNA degradation machinery of the bacterium .
Large polyvalent protein-associated domain 13 (LPD13)
Type: Domain

This is an alpha and beta domain that is found in polyvalent proteins of both conjugative elements and phages/prophages .
Hemagglutinin I (HA1)
Type: Domain

This domain can be found in hemagglutinin I (HA1) from Physarum polycephalum. Although the physiological function of the secreted HA1 remains to be established, HA1 recognizes cell wall polysaccharides of E. coli. The β-sandwich fold of HA1, composed of two up and down β-sheets, is conserved among other legume lectin-like proteins. The up and down β-sheet region is a minimal carbohydrate recognition domain .
Protein of unknown function DUF5554 (DUF5554)
Type: Family

This is a family of unknown function found in primates.
Protein of unknown function DUF5553 (DUF5553)
Type: Family

This is a family of unknown function found in primates.
Primase X (PriX)
Type: Domain

This domain is found in non-catalytic subunit of the archaeal eukaryotic-type primase, PriX. Detailed sequence analysis combined with structural analysis of a truncated PriX protein from the hyperthermophilic archaeon Sulfolobus solfataricus shows that, PriX is essential for the survival of the organism and that it is homologous to the C-terminal domain of archaeal and eukaryotic large primase subunits PriL. Highly conserved PriX homologues are present in many members of the phylum Crenarchaeota .
Type III secretion system ExsE (T3SS_ExsE)
Type: Domain

This domain is found in ExsE present in Pseudomonas aeruginosa. ExsE forms part of the ExsACDE signaling cascade which acts as an important regulatory switch that ensures timely expression of the Type III secretion system (T3SS) and so plays a critical role in facilitating infection. Prior to host-cell contact, the T3SS is inactive and ExsE and Type III Secretion Chaperone (ExsC) form a stable complex. ExsC forms a compact homodimer and ExsE wraps around one face of this dimer .
L-serine kinase SerK, C-terminal domain (SerK_C)
Type: Domain

This domain is found in the C-terminal region of free serine kinase (SerK) in the hyperthermophilic archaeon Thermococcus kodakarensis (TK0378). SerK converts ADP and l-serine (Ser) into AMP and O-phospho-l-serine (Sep), which is a precursor of l-cysteine. The domain is not conserved in the ParB/Srx family. The differences between SerK and the other members of the ParB/Srx family is concentrated in the C-terminal region, which may include residues involved in the Sep binding . Members of this group are mainly found in archaea.
Histidine kinase DraK, N-terminal domain (DraK_HK_N)
Type: Domain

This is the N-terminal domain found in DraK Histidine Kinase (HK) present in Streptomyces coelicolor (SCO3062). Activation of the DraK HK leads to autophosphorylation of its kinase domain in the cytoplasm and subsequent transphosphorylation of DraR promoting blue-pigmented polyketide actinorhodin (ACT) production. The N-terminal domain is known as the sensor (or input) domain and undergoes a conformational change resulting in phosphorylation of a conserved histidine in its cytoplasmic kinase domain .
Cyclic nucleotide phosphodiesterase, C-terminal domain (CNP_C)
Type: Domain

This is the C-temrinal domain found in Listeria monocytogenes, Lmo2642 cyclic nucleotide phosphodiesterase. The auxiliary C-terminal domain, consists of five α-helices forming a long helical bundle, and is connected to the catalytic domain (

) by two loop segments. It is suggested that this auxiliary domain of Lmo2642 might confer functional specificity to the protein through the interactions with unknown factors or involving the substrate recognition .
HEN1, double-stranded RNA binding domain 2 (HEN1_dsRBD2)
Type: Domain

This domain is found in HEN1 proteins from Arabidopsis. Structural characterization revealed that small RNA substrate binds to two double-stranded RNA (dsRNA)-specific binding domains, dsRBD1 and dsRBD2. This entry relates to dsRBD2 which together with dsRBD1 forms a strong grip on the duplex region of the small RNA substrate, and these interactions help position the other duplex terminus towards the MTase domain (

) .
HopA1 effector protein (HopA1)
Type: Family

This family includes the HopA1 effector protein from Pseudomonas syringae. Structurally this protein has an α + β fold . The effector protein HopA1 was shown to affect the EDS1 complex by binding EDS1 directly and activating the immune response signaling pathway.
Fibrillin 1, unique N-terminal domain (Fibrillin_U_N)
Type: Domain

This is the N-terminal domain of human fibrillin-1. Fibrillin is a primary constituent of microfibrils in the extracellular matrix of many elastic and non-elastic connective tissues. This domain, known as the fibrillin unique N-terminal (FUN) domain, constitutes the minimal interaction site for the fibrillin C terminus. The FUN domain has homologues in the human proteins LTBP-1L/2 and VWCE, which are also associated with a C-terminal EGF-like domain .
SopB, HTH domain (SoPB_HTH)
Type: Domain

This domain is found in centromere-binding protein (SopB). SopB displays an intriguing range of DNA-binding properties essential for partition; it binds the centromere to form a partition complex, which recruits NTPase (SopA), and it also inhibits SopA polymerization. The domain has a helix-turn-helix (HTH) structure and is thought to be the specific DNA-binding domain mainly through residues from the recognition helix, alpha 3, of the HTH. The domain has show structural similarity to the DNA-binding domains of P1 ParB and KorB .
Protein of of unknown function DUF5551 (DUF5551)
Type: Family

This is a family of unknown function found mainly in primates.
Trypsin inhibitor (Tryp_inh)
Type: Domain

This is domain is found in trypsin inhibitor 1, 2 and 3 found in Chenopodiaceae. Structure analysis of S. oleracea trypsin inhibitor III (SOTI-III), in complex with bovine pancreatic trypsin, shows a knottin-like cystine-bridge topology .
Lantibiotic immunity protein Spa1, C-terminal (Spa1_C)
Type: Domain

This is the C-terminal domain found in SpaI from Bacillus subtilis. SpaI is an immunity lipoprotein that protects the Gram-positive bacteria against their own lantibiotics, in this case subtilin. SpaI together with the ABC transporter SpaFEG protects the membrane from subtilin insertion .
Carbohydrate binding module 65 domain 1 (CBM65_1)
Type: Domain

This domain is found in the non-catalytic carbohydrate binding module 65B (CMB65B) from Eubacterium cellulosolvens. CBMs are present in plant cell wall degrading enzymes and are responsible for targeting, which enhances catalysis. CBM65s display higher affinity for oligosaccharides, such as cellohexaose, and particularly polysaccharides than cellotetraose, which fully occupies the core component of the substrate binding cleft. The concave surface presented by β-sheet 2 comprises the beta-glucan binding site in CBM65s. C6 of all the backbone glucose moieties makes extensive hydrophobic interactions with the surface tryptophans of CBM65s. Three out of the four surface Trp are highly conserved. The conserved metal ion site typical of CBMs is absent in this CBM65 family .
IL-40-like, Ig domain (IL-40-like_Ig)
Type: Domain

This Ig domain is found in tandem in IL-40 (also known as C17orf99), which is found across mammalian species . It is a B cell-associated cytokine that plays important roles in humoral immune responses and may also play a role in B cell development. It is expressed in bone marrow and fetal liver and its expression is also induced in peripheral B cells upon activation . This domain is also found in many proteins from animals, apart from mammals.