SII-SWORD/CoKE huggingface dataset:
Domain of unknown function DUF5640 (DUF5640)
Type: Domain

This domain is composed of eight antiparallel β strands and carries a G-X-W motif in the N-terminal region. The conserved glycine-X-tryptophan (G-X-W) motif is characteristic for the lipocalin family .
Nup54, C-terminal interacting domain (Nup54_C)
Type: Domain

The mammalian nuclear pore complex (NPC) conducts nucleocytoplasmic transport and contains multiple copies of nucleoporins (nups). This is the C-terminal interacting domain found on Nup54. Nup45 is a splice variant of Nup58 with an identical α-helical region. Nup54 along with Nup62 and Nup58 are essential for nuclear transport. The C-terminal part of the α-helical region of Nup54 interacts with a C-terminal part of the α-helical region of Nup58. Interestingly, this region appears in two distinct conformations: a single helix and a helix-loop-helix, termed 'straight' and 'bent'. Whereas the straight conformer consists of a 34 residues long α helix (residues 460-493), the bent conformer is composed of two α helices, each 13 residues long, connected by a central loop (N helix, residues 460-472; C helix, residues 477-489) .
Sulfhydryl oxidase, flavin adenine dinucleotide (FAD) binding domain (QSOX_FAD-bd_dom)
Type: Domain

This is a flavin adenine dinucleotide (FAD) binding domain found in Quiescin sulfhydryl oxidases (QSOX) (

). QSOX is a multi-domain disulfide catalyst that is localized primarily to the Golgi apparatus and secreted fluids and has attracted attention due to its over-production in tumors. Structural studies indicate that the closure of the Trx1 domain over the FAD-binding site may enhance the active-site chemistry for disulfide formation .
TraI, N-terminal subdomain (TraI_N)
Type: Domain

This is a subdomain found in TraI present in E. coli. Tra1 is a conjugative relaxase that forms part of the Type IV secretion system. This subdomain, referred to as 2A, is located in N-terminal region of the translocation signal (TSA) domain. TSA is known to reside in a larger ssDNA-binding domain .
Domain of unknown function DUF5618 (DUF5618)
Type: Domain

This is a domain of unknown function found mostly in bacteria.
Major vault protein repeat domain 3 (Vault_3)
Type: Domain

This domain is found in the major vault protein.

The major vault protein is the major polypeptide component of a large cellular ribonuclear protein complex found in the cytoplasm of eukaryotic cells (known as vaults). Several roles for vaults have been proposed. Vault proteins have been associated with development of multi-drug resistance . They have also being implicated in the regulation of several cellular processes including transport mechanisms, signal transmission and immune responses .
Domain of unknown function DUF5600 (DUF5600)
Type: Domain

This domain can be found in EH-domain-containing ATPase 2 (EHD2) present in Mus musculus. The domain is helical in nature and has extensive contacts with the G-domain .
5'-3' exoribonuclease 1, D1 domain (XRN1_D1)
Type: Domain

This domain can be found in 5' to 3' exoribonuclease 1 (XRN1) which belong to a family of conserved enzymes in eukaryotes and have important functions in transcription, RNA metabolism, and RNA interference. Xrn1 in fungi and animals is primarily cytosolic and is involved in degradation of decapped mRNAs, nonsense mediated decay, microRNA decay and is essential for proper development. The Xrn1 homologue in Drosophila, known as Pacman, is required for male fertility . This domain (D1) along with 3 other domains, make up a 510-residue segment following the conserved regions found in XRNs but they are only present in XRN1 and are absent in Rat1/XRN2. The amino acid sequences of these four domains contain an excess of basic residues, suggesting that these domains might help in binding the RNA substrate. Mutational studies carried out in D1 domain show that the mutant forms had dramatically reduced nuclease activity towards ssDNA substrate indicating that domain D1 is required for Xrn1 nuclease activity .
Histone chaperone Rtt106, N-terminal domain (Rtt106_N)
Type: Domain

This is the N-terminal domain of Rtt106 in Saccharomyces cerevisiae. Rtt106 is a histone chaperone that contributes to the deposition of newly synthesized acetylated Histone 3 Lysine 56 (H3K56ac) carrying H3-H4 complex on replicating DNA. The N-terminal domain of Rtt106 homodimerizes and interacts with H3-H4 independently of acetylation .
SUN coiled coil domain 2 (Sun_CC2)
Type: Domain

LINC complexes are formed by coupling of KASH (Klarsicht, ANC-1, and Syne/Nesprin Homology) and SUN (Sad1 and UNC-84) proteins from the inner and outer nuclear membranes (INM and ONM, respectively). The formation of LINC complexes by KASH and SUN proteins at the nuclear envelope (NE) establishes the physical linkage between the cytoskeleton and nuclear lamina, which is instrumental for the mechanical force transmission from the cytoplasm to the nuclear interior, and is essential for cellular processes such as nuclear positioning and migration, centrosome-nucleus anchorage, and chromosome dynamics. SUN2 possesses two coiled-coil domains (CC1 and CC2). These coiled-coil domains are also believed to act as rigid spacers to delineate the distance between the ONM and INM of the NE. Furthermore, the two coiled-coil domains of SUN2 have been indicated to be able to directly modulate SUN domain activity and regulate the subsequent interactions between the SUN and KASH domains. CC2 forms a three-helix bundle to lock the SUN domain in an inactive conformation acting as an inhibitory component. Structure-based sequence analysis demonstrated that several Gly residues are located in the flexible linker regions between the three helices which would ideally provide the breaks/turns in CC2 for three-helix bundle formation. The last helix alpha3 of CC2 (that is immediately connected to the SUN domain) has been shown to be an essential segment for promoting SUN domain trimerization in the SUN-KASH complex structure .
IL-7Ralpha, fibronectin type III domain (FN3_7)
Type: Domain

This domain is found in Interleukin-7 receptor subunit alpha (IL-7Ralpha), which together IL-7 form a complex crucial to several signalling cascades leading to the development and homeostasis of T and B cells. IL-7Ralpha carries a 219 residue ectodomain on the N-terminal region which is crucial for T and B-cell development. Mutations in the IL-7Ralpha ectodomain inhibits T and B cell development, resulting in patients with a form of severe combined immunodeficiency (SCID). The ectodomain folds into two fibronectin type III (FNIII) domains connected by a 310-helical linker. This entry comprises the first of the two FNIII domains, D1. In the D1 domain of IL-7Ralpha, a disulfide bond (C22R-C37R) conserved among cytokine receptor class I (CRH I) family members bridges two β strands .
Barnase-EndoU-ColicinE5/D-RelE like (PBECR5)
Type: Domain

Polyvalent proteins are predicted to be transmitted by genomic parasites such as conjugative elements, plasmids, and phages during the initial phase of infection along with their DNA. They are typified by the presence of multiple domains with disparate activities .

This entry represents a predicted endoRNase of the Barnase-EndoU-ColicinE5/D-RelE like nuclease fold found in polyvalent proteins of phages and conjugative elements. The predicted active site contains a conserved histidine and threonine residues .
Maltokinase N-terminal cap domain (Mak_N_cap)
Type: Domain

Glycogen is a central energy storage molecule in bacteria and the metabolic pathways associated with its biosynthesis and degradation are crucial for maintaining cellular energy homeostasis. In mycobacteria, the GlgE pathway involves the combined action of trehalose synthase (TreS), maltokinase (Mak) and maltosyltransferase (GlgE). The N-terminal lobe can be divided into two subdomains: a cap N-terminal subdomain comprising the first 88 amino acid residues. This entry is for the cap N-terminal domain found in mycobacterial maltokinase (Mak), (

E). The N-terminal cap subdomain and the C-terminal lobe are predominantly acidic, the intermediate subdomain is enriched in positively charged residues. A structural search with only the first 88 amino acid residues of Mak, corresponding to the N-terminal cap subdomain of maltokinases, unveiled a resemblance with proteins displaying the cystatin fold and a remote similarity with the N-terminal domain of the serine/threonine protein kinase GCN2. Conservation of the cap subdomain in maltokinases (including the bifunctional TreS-Mak enzymes), in particular of the residues in the proximity of the P-loop, together with the potential flexibility of this region, are compatible with regulatory functions for this subdomain. Hence it is hypothesised that the N-terminal cap subdomain plays a central role in modulation of Mak enzymatic activity .
Gammaproteobacterial serine protease (Serine_protease)
Type: Family

This family includes serine proteases such as L. pneumophila effector Lpg1137 . Lpg1137, is a serine protease that targets the mitochondria-associated ER membrane (MAM) and degrades STX17 (syntaxin 17), a SNARE implicated in macroautophagy/autophagy as well as mitochondria dynamics and membrane trafficking in fed cells. Lpg1137 has a sequence (-Gly-Leu-Ser68-Gly-Gly-) that matches the consensus sequence for the active site of serine proteases (Gly-X-Ser-X-Gly/Ala, where X is any residue). It exhibits proteolytic activity toward STX17 in vitro, whereas an active site mutant in which Ser68 is replaced by Ala does not. Expressed Lpg1137 localizes to the MAM and mitochondria, in addition to the cytosol, and binds to STX17 .
Phosphoglucose isomerase, N-terminal (PG_isomerase_N)
Type: Domain

This domain is found in the N-terminal region of glucose-6-phosphate isomerase-like protein, just before the phospho-glucose isomerase C-terminal SIS domain.
RK-1-like defensin (Defensin_RK-1)
Type: Domain

This entry includes RK-1, a defensin like peptide from rabbit kidney . It also includes some rat alpha defensins.
EXOG, C-terminal (Exog_C)
Type: Domain

This is the C-terminal domain found in EndoG-like mitochondrial endo/exonuclease (EXOG) proteins in higher eukaryotes. Evolutionary conserved mitochondrial nucleases are involved in programmed cell death and normal cell proliferation in lower and higher eukaryotes. It has been proposed that during metazoan evolution duplication of an ancestral nuclease gene could have generated the paralogous EndoG-and EXOG-protein subfamilies in higher eukaryotes, thereby maintaining the full endo/exonuclease activity found in mitochondria of lower eukaryotes .
Cell-traversal protein for ookinetes and sporozoites (CelTOS)
Type: Domain

Cell-traversal protein for ookinetes and sporozoites (CelTOS) is a conserved protein that is essential for traversal of malaria parasites in both the mosquito vector and human host and is therefore critical for malaria transmission and disease pathogenesis. It specifically binds phosphatidic acid commonly present within the inner leaflet of plasma membranes, and potently disrupts liposomes composed of phosphatidic acid by forming pores. CelTOS resembles class I viral membrane fusion glycoproteins and a bacterial pore-forming toxin with roles in membrane binding and disruption. CelTOS forms an α helical dimer that resembles a tuning fork. Structure analysis indicate that it has a distinct structural architecture with two subdomains that independently resemble membrane binding and/or disrupting proteins and could simultaneously act during disruption .
DNA polymerase II intein domain IV (PI-TkoII_IV)
Type: Domain

This domain can be found in the hyperthermophilic archaeon Thermococcus kodakaraensis Pol-2 intein. It is suggested to be a potential DNA binding domain .
Morc, S5 domain 2-like (Morc_S5)
Type: Domain

This domain is found in MORC proteins in eukaryotes and possesses a structure similar to the second domain of ribosomal S5 proteins. Arabidopsis microrchidia (MORC) ATPase family proteins are conserved among plants and animals and are involved in transcriptional silencing. In Arabidopsis, MORC6/DMS11 was reported to function in the condensation of pericentromeric heterochromatin, thereby facilitating transcriptional silencing . Further studies demonstrate that MORC6 and its homologs MORC1 and MORC2 form a complex which associates with SUVH9, required for Pol V occupancy in the RdDM (RNA-directed DNA methylation) pathway.
Copper(I)-binding protein CorA (Cu_bind_CorA)
Type: Domain

This domain is found in CorA present in Methylomicrobium album. CorA is a copper repressible surface associated copper(I)-binding protein. CorA can bind one copper ion per protein molecule. The overall fold of CorA is similar to M. capsulatus protein MopE, including the unique copper(I)-binding site and most of the secondary structure elements .
Domain of unknown function DUF5625 (DUF5625)
Type: Domain

This is a domain of unknown function found in proteobacteria.
Protein of unknown function DUF5550 (DUF5550)
Type: Family

This is a family of unknown function found in primates.
Acetyl-coA carboxylase zinc finger domain (Znf-ACC)
Type: Domain

Acetyl-coA carboxylase (ACC) is a central metabolic enzyme that catalyzes the committed step in fatty acid biosynthesis: biotin-dependent conversion of acetyl-coA to malonyl-coA . In bacteria this protein contains a small zinc finger domain.
ZBTB21, zinc finger domain (Znf_C2H2_6)
Type: Domain

This is a C2H2 type zinc finger domain which can be found in Zinc finger and BTB domain-containing protein 21 (ZBTB21).
Flap endonuclease GEN, chromatin organization modifier domain (GEN_chromo)
Type: Domain

Chromodomains serve as chromatin-targeting modules, general protein interaction elements as well as dimerization sites. They are found in many chromatin-associated proteins that bind modified histone tails for chromatin targeting. Chromodomains often recognize modified lysines through their aromatic cage thus targeting proteins to chromatin. Family members such as GEN1 carry a chomodomain which directly contacts DNA and its truncation severely hampers GEN1's catalytic activity. The chromodomain allows GEN1 to correctly position itself against DNA molecules, and without the chromodomain, GEN1's ability to cut DNA was severely impaired. The GEN1 chromodomain was found to be distantly related to the CDY chromodomains and chromobox proteins, particularly to the chromo-shadow domains of CBX1, CBX3 and CBX5. Furthermore, it is conserved from yeast (Yen1) to humans with the only exception being the Caenorhabditis elegans GEN1, which has a much smaller protein size of 443 amino acids compared to yeast Yen1 (759 aa) or human GEN1 (908 aa) .
Allene oxide cyclase barrel-like domain (AOC-like)
Type: Domain

This is an allene oxide cyclase barrel like domain found in spirotetronate cyclases such as AbyU, a Diels-Alderase enzyme. It is comprised of two eight-stranded antiparallel β-barrels .

Proteins containing this domain include PyrI4 from Streptomyces rugosporus. PyrI4 is a spiro-conjugate synthase involved in the biosynthesis of the spirotetramate antibiotics pyrroindomycins .
CEL-III, C-terminal (CEL_III_C)
Type: Domain

This is the C-terminal domain found in CEL-III protein which is a lectin that exhibits both hemolytic and hemagglutinating activity. The domain is responsible for oligomerization and insertion of CEL-III into the erythrocyte membrane. The domain is composed of eight stranded β sandwich and two α helices, the latter changes conformation upon binding to the cell surface carbohydrates .
Toll-like receptor 3 trans-membrane domain (TLR3_TMD)
Type: Domain

Toll-like receptor (TLR) 3 is an endosomal TLR that mediates immune responses against viral infections upon activation by its ligand double-stranded RNA, a replication intermediate of most viruses. TLR3 is expressed widely in the body and activates both the innate and adaptive immune systems . This entry represents the Toll-like receptor 3 trans-membrane domain which has been shown to form dimers and trimers with different surfaces for helix-helix interaction .
Bdellovibrio, beta-sandwich (BD_b_sandwich)
Type: Domain

This entry represents a β-sandwich domain exclusively found at the N-terminal of CHROMO domains in many Bdellovibrio proteins .
DipZ, thioredoxin-like C-terminal domain (Thioredoxin_10)
Type: Domain

This is the C-terminal thioredoxin like domain found in DipZ/Rv2874 in the pathogenic bacterium Mycobacterium tuberculosis . Structure analysis of Rv2874-C shows the presence of a C-terminal domain formed by the 128 residues Thr568-Gly695. These residues form a jelly-roll structure in which two antiparallel β-sheets sandwich a hydrophobic core. This domain is combined with a second domain with a carbohydrate-binding module (CBM) fold .
Tse2 ADP-ribosyltransferase toxin (ADPRTs_Tse2)
Type: Domain

Tse2 from P. aeruginosa has structural features similar to ADP-ribosylating toxins. It is a cytoactive toxin secreted by a type six secretion apparatus of Pseudomonas aeruginosa and found mostly in gamma proteobacteria. It naturally attacks a target in the cytoplasm of bacterial cells. Structural analysis shows similarity between Tse2 and nicotinamide adenine dinucleotide (NAD)-dependent enzymes from bacteria, notably the mono-ADP-ribosyltransferase toxins (ADPRTs). Furthermore, it revealed that the Tse2 active site is occluded upon binding the cognate immunity protein Tsi2. The abrogation of toxicity for the R14A, S80A, and H122A mutant Tse2 proteins indicates the importance of these amino acids in the mechanism of Tse2 toxicity and, given their conservation with NAD-reactive enzymes, also supports their assignment as being involved in a catalytic reaction .
Plexin, TIG domain 1 (TIG1_plexin)
Type: Domain

This entry represents an TIG or IPT domain (Ig domain shared by Plexins and Transcription factors) found in plexins .
ARHGEF1-like, PH domain (PH_16)
Type: Domain

This pleckstrin homology (PH) domain is found in some Rho guanine nucleotide exchange factors, such as ARHGEF18 (p114RhoGEF) and ARHGEF1 (p115-RhoGEF) .
5-hmdU DNA kinase 2 (HMUD2)
Type: Family

5-hmdU DNA kinase 2 from phages which phosphorylates 5-hydroxymethyluracil (5hmdU) into 5-phosphomethyl-2'-deoxyuridine (5-PmdU) on DNA as a step in the pathway leading to thymidine hypermodifications in the viral genome which probably prevent degradation of viral genome by the host restriction-modification antiviral defense system .
Mcm6, C-terminal winged-helix domain (Mcm6_C)
Type: Domain

The minichromosome maintenance (Mcm) complex is the replicative helicase in eukaryotic species, that plays essential roles in the initiation and elongation phases of DNA replication. During late M and early G(1), the Mcm complex is loaded onto chromatin to form prereplicative complex in a Cdt1-dependent manner. This entry represents the C-terminal domain of human Mcm6 which is the Cdt1 binding domain (CBD). The structure of CBD exhibits a typical winged helix fold that is generally involved in protein-nucleic acid interaction. The CBD failed to interact with DNA in experiments . The CBD-Cdt1 interaction involves the helix-turn-helix motif of CBD .
Homing endonuclease associated repeat (HNH_repeat)
Type: Repeat

Homing endonucleases are found in bacteria and viruses and catalyze the hydrolysis of genomic DNA within the cells that synthesize them . This entry represents a 60 residue repeat of unknown function found associated with homing endonuclease domains.
HEPN like, Abia C-terminal domain (HEPN_AbiA_CTD)
Type: Domain

This entry represents a domain found in the AbiA-CTD-like HEPN nuclease that is fused to reverse transcriptase and is in operon with R-M system .
FtsK alpha domain (FtsK_alpha)
Type: Domain

FtsK is a DNA translocase that coordinates chromosome segregation and cell division in bacteria . In addition to its role as activator of XerCD site-specific recombination, FtsK can translocate double-stranded DNA (dsDNA) rapidly and directionally and reverse direction . FtsK can be split into three domains called alpha (this entry), beta and gamma. The alpha and beta domains contain the core ATPase machinery of the DNA translocase .
Cdc13, OB4 dimerization domain (Cdc13_OB4_dimer)
Type: Domain

This domain is found in Cdc13 proteins in budding yeasts. The Cdc13-Stn1-Ten1 complex is crucial for telomere protection. This domain is the C-terminal OB4 domain and is responsible for dimerization. Dimerization of Cdc13 is important for high-affinity DNA binding .
N-acetylglucosamine binding protein A domain 2 (GbpA_2)
Type: Domain

This domain can be found in N-acetylglucosamine binding protein (GbpA) from Vibrio cholerae, a bacterial pathogen that colonizes the chitinous exoskeleton of zooplankton as well as the human gastrointestinal tract. GbpA binds to GlcNAc oligosaccharides. Structural comparison show that there are distant structural similarities between domain 2 of GbpA and the beta-domain of the flagellin protein p5. It is suggested that this domain interacts with the bacterial surface, and functions to project an alginate binding domain of the protein from the cell surface .
SHIRT domain (SHIRT)
Type: Domain

The SHIRT domain is found in a range of presumed bacterial adhesin proteins.
RNF31, C-terminal (RNF31_C)
Type: Domain

This is the C-terminal domain of RNF31 (also known as HOIP) from humans. HOIP is a component of the linear ubiquitin chain assembly complex (LUBAC), which synthesizes the linear ubiquitin chains that help control innate immunity and inflammation . This region has an RBR domain which catalyzes the transfer of ubiquitin onto a substrate .
Protein of unknown function DUF5546 (DUF5546)
Type: Family

This is a family of unknown function found in primates.
SpaA-like, prealbumin fold domain subgroup 1 (SpaA_PFL_dom_1)
Type: Domain

This entry contains a prealbumin-like fold domain from a wide variety of bacterial surface proteins. This entry corresponds to domain 1 and domain 3 of SpaA from Corynebacterium diphtheriae . It is also present in Collagen adhesin and Trypsin-resistant surface T6 protein from Streptococci species. Some members of this family contain an isopeptide bond.

This domain is also found in eukaryotic proteins including Nodal modulators .
Phosphoinositide phosphatase, C-terminal (PI_PP_C)
Type: Domain

This domain is found in the C-terminal region of effector protein SidP present in Legionella longbeachae. SidP functions as a PI-3-phosphatase specifically hydrolyzing PI(3)P and PI(3,5)P2. This C-terminal domain is rich with glutamate residues .
TbRIF5 SNase domain 1 (RIF5_SNase_1)
Type: Domain

This domain can be found in the Trypanosoma brucei TbRIF5 protein, which could contribute to the processing of dsRNA targets .
Glycoside hydrolase family 5, C-terminal domain (GH5_C)
Type: Domain

This is the C-terminal domain found in endo-glycoceramidases (EGC) and glucosylceramidase (an EGC homologue) , membrane-associated family 5 glycosidases. The C-terminal domain assumes a β-sandwich fold, which resembles that of many carbohydrate-binding modules .
Pallilysin, beta barrel domain (Pallilysin)
Type: Domain

The Treponema pallidum protein, Tp0751 (also known as pallilysin), possesses adhesive properties and has been previously reported to mediate attachment to the host extracellular matrix components laminin, fibronectin, and fibrinogen. Tp0751 adopts an eight-stranded β-barrel with a profile of short conserved regions consistent with a non-canonical lipocalin fold. Lipocalins, along with fatty acid-binding proteins and avidins, are members of the calycin superfamily, which is defined by the distinct features of a central β-barrel and a key structural signature consisting of three short conserved regions (SCR1, SCR2, and SCR3). However, Tp0751 does not contain all three conserved regions, hence it is considered an outlier to canonical lipocalins. In SCR1, there is a GxW motif .