SII-SWORD/CoKE huggingface dataset:
TerB, N-terminal (TerB_N)
Type: Domain

This entry represents the N-terminal domain of TerB, and TerB-C containing proteins . It has a predominantly α-helical structure and contains an absolutely conserved glutamate . The presence of a conserved acidic residue suggests that it might chelate metal like TerB . These proteins occur in an two-gene operon containing an AAA+ ATPase and SF-II DNA helicase suggesting a role in stress stress response or phage defense .
Major capsid protein ORF017-like (ORF017-like)
Type: Family

This entry, previously known as DUF4043, represents a group of proteins from tailed bacteriophages and prophages mainly found in proteobacteria and firmicutes, including Major capsid protein from Pseudomonas phage KPP25 (ORF017,

), Major capsid protein from Ralstonia phage GP4 and Major structural protein ORF14 from Helicobacter pylori . There is a single completely conserved residue G that may be functionally important.
Phage integrase SAM-like domain (SAM-like_dom)
Type: Domain

This domain was originally identified by clustering human gut metagenomic sequences . It appears related to the N-terminal domain of phage integrases.
Protein of unknown function DUF4044 (DUF4044)
Type: Family

This family of proteins is functionally uncharacterised. There is a single completely conserved residue M that may be functionally important.
Coiled-coil domain-containing protein 28 (CCDC28)
Type: Family

This entry includes CCDC28A and CCDC28B. CCDC28B modulates mTORC2 complex assembly and function, possibly enhances AKT1 phosphorylation .
Antitoxin SocA-like, Panacea domain (SocA_Panacea)
Type: Domain

This entry represents a domain found centrally in Antitoxin SocA from Caulobacter vibrioides. SocA is the antitoxin component of an atypical type II toxin-antitoxin (TA) system which neutralises the toxic activity of toxin SocB by acting as an adapter to promote its degradation by the protease ClpXP . The Panacea domain is also found in similar proteins from bacteria, archaea and tailed bacteriophages that form a complex with their cognate toxins in a way normally observed in Type II TA systems .
Domain of unknown function DUF4064 (DUF4064)
Type: Domain

This presumed domain is functionally uncharacterised.
Domain of unknown function DUF4070 (DUF4070)
Type: Domain

This is a bacterial domain often found at the C terminus of radical SAM methylases.
Putative glycosyl hydrolase domain DUF4015 (DUF4015)
Type: Domain

This domain is related to known glycosyl hydrolase domains, suggesting it is involved in carbohydrate breakdown.
Protein of unknown function DUF4075 (DUF4075)
Type: Family

This family of proteins is functionally uncharacterised. Some members are annotated as putative mature parasite-infected erythrocyte surface antigen protein from Bacillus spp.
Apiosidase-like, catalytic domain (Apiosidase-like_cat_dom)
Type: Domain

This entry represents the catalytic domain of endo-apiosidase (GH140,

) and related proteins some of which form part of the rhamnogalacturonan-II (RG-II) degradome. This domain adopts an (α/β)8-barrel that harbours the aspartate and glutamate residues essential for the catalytic activity .
Domain of unknown function DUF4077 (DUF4077)
Type: Domain

This functionally uncharacterised domain is found in the N-terminal region of sequences annotated as methyl-accepting chemotaxis proteins from Bacillus spp.
Stress response protein NST1 (NST1)
Type: Family

NST1 is a family of proteins that seem to be involved, directly or indirectly, in the salt sensitivity of some cellular functions in yeast. It does this without affecting sodium accumulation. It negatively affects salt-tolerance through an interaction with the splicing factor Msl1p. This interaction stresses the importance of efficient RNA processing under salt stress conditions .
Domain of unknown function DUF4041 (DUF4041)
Type: Domain

This presumed domain is functionally uncharacterised. It is often found in association with a putative DNA-binding domain.
Domain of unknown function DUF4074 (DUF4074)
Type: Domain

This functionally uncharacterised domain is found at the C-terminal of a number of metazoan homeobox proteins.
Domain of unknown function DUF4214 (DUF4214)
Type: Domain

This domain of unknown function is found on a variety of different proteins, including transferases and allergen V5/Tpx-1 related proteins.
Domain of unknown function DUF4042 (DUF4042)
Type: Domain

This presumed domain is functionally uncharacterised.
Protein of unknown function DUF4144 (DUF4144)
Type: Family

The function of these proteins is not known.
Domain of unknown function DUF4145 (DUF4145)
Type: Domain

This domain is found in a variety of restriction endonuclease enzymes. The exact function of this domain is uncertain.
MOFRL-associated domain (MOFRL_assoc_dom)
Type: Domain

This domain is frequently found at the N terminus of proteins that carrying the MOFRL domain (

), some of which are glycerate kinases . However, proteins matched by this entry do not have flavodoxin-like domain (

) or restriction-enzyme-like fold (

), which can be found in other type of glycerate kinases (

).
Wall-associated receptor kinase, galacturonan-binding domain (WAK_GUB)
Type: Domain

Wall-associated kinases (WAKs) are transmembrane proteins containing a cytoplasmic serine/threonine kinase domain and an extracellular domain in contact with the pectin fraction of the plant cell wall . The cysteine-rich galacturonan-binding domain is located near the N-terminal end of the extracellular domain and binds to the cell-wall pectins .
Domain of unknown function DUF4080 (DUF4080)
Type: Domain

This presumed domain is found at the C terminus of a number of sequences annotated as radical SAM methylthiotransferases. The domain is functionally uncharacterised. It was found by clustering human gut metagenomic sequences .
Domain of unknown function DUF4081 (DUF4081)
Type: Domain

This functionally uncharacterised domain is often found N-terminal to the GNAT acetyltransferase domain (

).
Protein of unknown function DUF4153 (DUF4153)
Type: Family

This family consists of putative membrane proteins.
Type III secretion system protein (T3SS_LEE_assoc)
Type: Family

This is a family of bacterial putative type III secretion apparatus proteins associated with the locus of enterocyte effacement (LEE).
YfiR/HmsC-like (YfiR/HmsC-like)
Type: Family

YfiR has been shown to regulate YfiN, a diguanylate cyclase and a bifunctional protein that produces c-di-GMP in response to reductive stress and then dynamically relocates to the division site to arrest cell division in response to envelope stress in Escherichia coli. YfiR may serve as a periplasmic redox sensor that regulates YfiN activity in response to reducing conditions .
Protein of unknown function DUF4156 (DUF4156)
Type: Family

The function of this family is unknown but some members are annotated as putative lipoprotein outer membrane proteins.
eCIS core domain (eCIS_core_dom)
Type: Domain

This entry represents a domain found in a group of prokaryotic proteins that was previously known as DUF4157. This domain has been recently identified as a highly conserved eCIS (extracellular Contractile Injection System) core domain . eCIS is a cell-free toxin-delivery system that evolved from a bacteriophage tail and is prevalent in prokaryotes. This eCIS core DUF4157 domain contains an HEXXH motif that is characteristic of many families of metallopeptidases and a putative metal-binding site for a divalent cation such as zinc. Proteobacterial members of this family are thought to be related to the type VI secretion system (T6SS). This region is responsible for the toxicity of the protein in the bacterial periplasm . eCIS-associated toxins carry DUF4157 domains in their N terminus or are found adjacent to genes with this domain .

eCIS core DUF4157 domain containing proteins were identified in Halogeometricum borinquese, two of which, Hbor_02990 and Hbor_38900, were found to be toxic and closely associated with a downstream 'immunity' partner that seemed to prevent toxicity when expressed in tandem with their respective toxin . Another two of these proteins, Hbor_01880 and Hbor_38720, were not found to be toxic in H. volcanii, both genes are closely associated with a downstream gene, potentially indicating that they may be toxic against another target organism.
Domain of unknown function DUF4158 (DUF4158)
Type: Domain

The exact function of this domain is not clear, but it frequently occurs at the N terminus of transposase Tn3 family proteins.
Domain of unknown function DUF4159 (DUF4159)
Type: Domain

This is a domain of unknown function found in bacteria.
Domain of unknown function DUF4094 (DUF4094)
Type: Domain

This domain is found in a number of proteins, including eleven beta-1,3-galactosyltransferases paralogues from Arabidopsis thaliana. Beta-1,3-galactosyltransferase transfers galactose from UDP-galactose to substrates with a terminal glycosyl residue . This domain is found in N-terminal domain of the beta-1,3-galactosyltransferase.
Beta-galactosidase jelly roll domain (BetaGal_jelly_roll_dom)
Type: Domain

This domain is found in beta-galactosidase enzymes, mainly from the glycosyl hydrolase 35 family. It has a jelly roll fold .
Daunorubicin resistance ATP-binding protein DrrA1-3-like, C-terminal domain (DrrA1-3-like_C)
Type: Domain

This domain is found at the C-terminal end of Daunorubicin resistance ATP-binding protein DrrA1-3 from Streptomyces coeruleorubidus, Multidrug efflux system ATP-binding protein Rv1218c from Mycobacterium tuberculosis, some putative ABC transporter proteins and related prokaryotic sequences. DrrA1-3 are part of the ABC transporter complex DrrA3B3 involved in daunorubicin efflux . Rv1218c is probably part of the ABC transporter complex Rv1217c-Rv1218c involved in the resistance to a wide range of structurally unrelated drugs .
Deacetylase PdaC (PdaC)
Type: Domain

This domain forms an α/β-two layer sandwich. It is found in the
Bacillus subtilis
proteins anti-sigma-V factor RsiV, which downregulates SigV activity , and peptidoglycan-N-acetylmuramic acid deacetylase PdaC, which catalyσes the deacetylation of N-acetylmuramic acid which makes the peptidoglycan resistant to lysozyme .
ALIX V-shaped domain (ALIX_V_dom)
Type: Domain

The binding of the LYPxL motif of late HIV p6Gag and EIAV p9Gag to this domain is necessary for viral budding. In ALIX, a component of the ESCRT pathway, this domain is central between an N-terminal Bro1 domain (

) and a C-terminal proline-rich domain. The ALIX central domain is formed by two three-helix bundles disposed in a V shape . Retroviruses thus used this domain to hijack the ESCRT system of the cell .
UCH repeated domain (UCH_repeat_domain)
Type: Domain

This is a repeated domain found in de-ubiquitinating proteins. It's exact function is not known, although it is likely to be involved in the binding of the Ubps in the complex with Rsp5 and Rup1 .
Probable zinc-binding domain (Zn-bnd_dom_prob)
Type: Domain

This entry represents a probable zinc-binding domain with two CxxC sequence motifs.
FIIND domain (FIIND_dom)
Type: Domain

This entry contains the whole FIIND domain

composed by the ZU5 sub-domain

and the UPA sub-domain

.

The so-called function-to-find (FIIND) domain was initially identified in two proteins: NLRP1 (also known as NALP1, CARD7, NAC, DEFCAP) and CARD8 (also known as TUCAN, Cardinal) . NLRP1 is a member of the Nod-like receptor (NLR) protein superfamily and is involved in apoptosis and inflammation; to date, it remains the only NLR protein known to possess a FIIND domain. The domain is likewise present in CARD8, where, as in NLRP1, it is followed by a C-terminal CARD domain. Both proteins are reported to form an "inflammasome", a macromolecular complex capable of processing caspase-1 and activating pro-IL1β . The FIIND domain comprises two subdomains: ZU5 (found in the tight-junction protein ZO-1 and the netrin receptor UNC5) and UPA (conserved in UNC5, the death-domain-containing protein PIDD, and proteins of the ankyrin family). Notably, the FIIND domain is found in only a small subset of the animal kingdom, including primates, rodents (mouse, rat), carnivores (e.g., dog), and a few other species such as horses. Early studies describing NLRP1 did not initially recognise FIIND as a distinct domain, mistakenly identifying it as part of the adjacent leucine-rich repeat (LRR) domain . The discovery of CARD8 later revealed that its N-terminal region shared significant sequence identity with an uncharacterised region in NLRP1 . Before receiving its current designation, the FIIND domain was referred to as the NALP1-associated domain (NAD) .
KTSC domain (KTSC_dom)
Type: Domain

This short domain is named after lysine tRNA synthetase C-terminal domain. It is found at the C terminus of some lysyl tRNA synthetases and also as a single domain protein in bacterial proteins. The domain is about 60 amino acids in length and contains a reasonably conserved YXY motif in the centre of the sequence. The function of this domain is unknown, but it could be an RNA binding domain.
Protein of unknown function DUF4164 (DUF4164)
Type: Family

This protein family of unknown function contains several conserved LE/LD sequence pairs.
Domain of unknown function DUF4166 (DUF4166)
Type: Domain

This domain of unknown function is found in bacterial proteins, such as the uncharacterised protein YndH from Bacillus subtilis.
Domain of unknown function DUF4216 (DUF4216)
Type: Domain

The function of this domain is not known. It is found in a number of putative transposases.
ATP-dependent rRNA helicase SPB4-like, C-terminal extension (SPB4-like_CTE)
Type: Domain

This short domain is found towards the C-terminal of many eukaryotic helicases, including some DEAD box helicases such as ATP-dependent rRNA helicase SPB4 from Saccharomyces cerevisiae. The DEAD box helicases are involved in various aspects of RNA metabolism, including nuclear transcription, pre mRNA splicing, ribosome biogenesis, nucleocytoplasmic transport, translation, RNA decay and organellar gene expression. SPB4 is organised into four domains: dual RecA domains (D1 and D2,

and

), a C-terminal extension (CTE, represented by this entry) and a C-terminal tail (CTT). This domain packs closely onto the catalytic core of Spb4 and engages the four nucleotides immediately 5' to those within the RNA binding pocket. It shows a mainly α-helical structure .
Domain of unknown function DUF4219 (DUF4219)
Type: Domain

This domain is very short and is found at the N-terminal of many Gag-pol polyproteins from retrotransposons and related sequences. There is a highly conserved YxxWxxxM sequence motif.
Domain of unknown function DUF4220 (DUF4220)
Type: Domain

This presumed domain is functionally uncharacterised.
Protein of unknown function DUF4221 (DUF4221)
Type: Family

This protein family contains highly conserved asparagine and cysteine residues. The function is not known.
Protein of unknown function DUF4222 (DUF4222)
Type: Family

These short proteins are largely found in enteric bacteria and are likely to be of phage origin. Their molecular function is unknown.
Protein of unknown function DUF4223 (DUF4223)
Type: Family

This family of proteins is functionally uncharacterised. Proteins in this family are approximately 60 amino acids in length and are predicted to be to be lipoproteins.
Domain of unknown function DUF4224 (DUF4224)
Type: Domain

This presumed domain is functionally uncharacterised. Proteins carrying this domain are thought to be of phage origin.
Protein of unknown function DUF4225 (DUF4225)
Type: Family

This family of proteins is functionally uncharacterised.
Protein of unknown function DUF4227 (DUF4227)
Type: Family

This family of proteins is functionally uncharacterised.
PADRE domain (PADRE_dom)
Type: Family

This entry represents the Pathogen and abiotic stress response, cadmium tolerance, disordered region-containing (PADRE) domain, which is specifically found in plants. PADRE typically occurs in small single-domain proteins with a bipartite architecture. PADRE contains conserved sequence motifs at the N-terminal, and its C-terminal includes an intrinsically disordered region with multiple phosphorylation sites. This domain is associated with plant defense upon diverse stress stimulus and has a role in disease resistance to fungi .
Protein of unknown function DUF4229 (DUF4229)
Type: Family

This family of proteins is functionally uncharacterised.
Protein of unknown function DUF4230 (DUF4230)
Type: Family

This family of proteins is functionally uncharacterised.
Protein of unknown function DUF4231 (DUF4231)
Type: Family

This family of proteins is functionally uncharacterised.
Domain of unknown function DUF4232 (DUF4232)
Type: Domain

This entry represents a domain of unknown function found in uncharacterised bacterial proteins, many of which are thought to be lipoproteins. This domain may adopt a Ig-like fold.
Protein of unknown function DUF4233 (DUF4233)
Type: Family

This family consists of functionally uncharacterised integral membrane proteins.
Domain of unknown function DUF4234 (DUF4234)
Type: Domain

This presumed domain is functionally uncharacterised.
Protein of unknown function DUF4235 (DUF4235)
Type: Family

This family of integral membrane proteins is functionally uncharacterised.
Domain of unknown function DUF4236 (DUF4236)
Type: Domain

This presumed domain is functionally uncharacterised.
Tuberculosis necrotizing toxin (TNT)
Type: Domain

This is the C-terminal domain of CpnT secreted by Mycobacterium tuberculosis (Mtb). It induces necrosis of infected cells to evade immune responses. Mtb utilizes the protein CpnT to kill human macrophages by secreting its C-terminal domain (CTD), named tuberculosis necrotizing toxin (TNT), that induces necrosis. It acts as a NAD+ glycohydrolase which hydrolyzes the essential cellular coenzyme NAD+ in the cytosol of infected macrophages resulting in necrotic cell death . CpnT transports its toxic CTD from the cell surface of M. tuberculosis by proteolytic cleavage, where the toxin is cleaved to induce host cell death .

Structural analysis determined that the TNT core contains only six β-strands as opposed to seven found in all known NAD+-utilizing toxins, and is significantly smaller, with only two short α-helices and two 3/10 helices. Furthermore, the putative NAD+ binding pocket identified Q822, Y765 and R757 as residues possibly involved in NAD+-binding and hydrolysis based on similar positions of catalytic amino acids of ADP-ribosylating toxins. Glutamine 822 residue was detected to be highly conserved among TNT homologues .
Protein of unknown function DUF4238 (DUF4238)
Type: Family

This family of proteins is functionally uncharacterised.
Protein of unknown function DUF4239 (DUF4239)
Type: Family

This family of proteins is functionally uncharacterised. It is distantly related to bestrophin proteins. Structure prediction suggests that these proteins can form homopentamers as Bestrophin proteins do. These proteins may function as chloride channels. This domain is sometimes found at the C terminus in large RHS proteins suggesting that it may function as a toxin.
Domain of unknown function DUF4240 (DUF4240)
Type: Domain

The function of this domain is not known.
Protein of unknown function DUF4241 (DUF4241)
Type: Family

This family of proteins is functionally uncharacterised.
SCO4226-like (SCO4226-like)
Type: Family

This entry represents a family of proteins found in prokaryotes, including SCO4226 from Streptomyces coelicolor (

). This protein adopts a dimeric configuration able to bind four nickel ions, with each monomer showing a typical ferredoxin-like fold with five β-strands packing against two α-helices. It may play a role in cellular nickel homeostasis, detoxification, and/or nickel utilization in specialized cytoplasmic compartment .
Questin oxidase-like (Questin_oxidase-like)
Type: Family

This family consists of oxidoreductases involved in the synthesis of different polyketides and derivatives. Questin oxidase GedK from Aspergillus terreus catalyses the ring cleavage of the anthraquinone questin to form benzophenone desmethylsulochrin . It is part of the gene cluster that mediates the biosynthesis of geodin, an intermediate in the biosynthesis of other natural products . MdpL from Emericella nidulans is part of the gene cluster that mediates the biosynthesis of monodictyphenone . TpcI from Neosartorya fumigata is part of the gene cluster that mediates the biosynthesis of trypacidin, a mycotoxin with antiprotozoal activity and that plays a role in the infection process .

This entry also includes ptaJ from Pestalotiopsis fici, AflY from Aspergillus parasiticus, CPUR_05427 from the phytopathogenic Claviceps purpurea, AgnL3 from Paecilomyces divaricatus and NotM from Aspergillus sp.. PtaJ is part of the gene cluster that mediates the biosynthesis of pestheic acid, a diphenyl ether which is a biosynthetic precursor of the unique chloropupukeananes . AflY is part of the gene cluster that mediates the biosynthesis of aflatoxins, the most toxic and carcinogenic compounds among the known mycotoxins . CPUR_05427 is part of the ergochrome gene cluster that is responsible for the typical purple-black color of the sclerotia containing the toxic ergot alkaloids . AgnL3 is part of the gene cluster that mediates the biosynthesis of agnestins, dihydroxy-xanthone metabolites . NotM is part of the gene cluster that mediates the biosynthesis of notoamide that is a fungal indole alkaloid .
Protein of unknown function DUF4244 (DUF4244)
Type: Family

This family of proteins is functionally uncharacterised. There is a conserved EYA sequence motif.
Protein of unknown function DUF4245 (DUF4245)
Type: Family

This family of proteins is functionally uncharacterised.
Protein of unknown function DUF4246 (DUF4246)
Type: Family

This family of proteins is functionally uncharacterised.
Protein of unknown function DUF4247 (DUF4247)
Type: Family

This family of proteins is functionally uncharacterised.
Protein of unknown function DUF4248 (DUF4248)
Type: Family

This family of proteins is functionally uncharacterised.
Protein of unknown function DUF4099 (DUF4099)
Type: Family

This family of uncharacterised proteins was found by clustering human gut metagenomic sequences .
Plastid division protein CDP1-like, IMS domain (CDP1-like_IMS)
Type: Domain

This domain corresponds to the C-terminal intermembrane space (IMS) region from Plastid division protein CDP1, Protein ACCUMULATION AND REPLICATION OF CHLOROPLASTS 6 (ARC6) and its paralogue PARC6 .

This group of proteins function as key components of the plastid division machinery, which is responsible for the constriction and division of plastids, including chloroplasts and non-green plastids . It includes proteins such as FtsZ, ARC6, DRP5B, and MinE. ARC6 and PARC6 are essential for the chloroplast replication process , which implies the assembly and constriction of the tubulin-like FtsZ ring on the stromal surface of the inner envelope membrane (IEM) and the dynamin-like ARC5 ring on the cytosolic surface of the outer envelope membrane (OEM). They are also involved in stromule biogenesis and may contribute to plant gravitropism. ARC6 facilitates FtsZ ring assembly and promotes the recruitment of MCD1, which is essential for forming the chloroplast Z-ring. CDP1, on the other hand, is required for the localisation of PDV1 and the correct formation of the FtsZ ring in non-green plastids .

ARC6 is evolutionarily related to the cyanobacterial cell division protein Ftn2/ZipN , having similar structures. This domain from ARC6 and PARC6 interacts with PDV2 and PDV1 respectively. PDV proteins recruit dynamin-like ARC5 ring to the chloroplast surface and mediate its constriction. .
Protein of unknown function DUF4249 (DUF4249)
Type: Family

This family of proteins is functionally uncharacterised. There are two completely conserved residues (C and G) that may be functionally important.
Protein of unknown function DUF4250 (DUF4250)
Type: Family

This family of proteins is functionally uncharacterised. There are two completely conserved residues (N and R) that may be functionally important.
Protein of unknown function DUF4251 (DUF4251)
Type: Family

This family of proteins is functionally uncharacterised.