SII-SWORD/CoKE huggingface dataset:
Gram-positive pilin backbone subunit 2, Cna-B-like domain (GramPos_pilinBB)
Type: Domain

This entry represents one of the major backbone units of Gram-positive pili, such as those from S.pneumoniae . There are three major pilin subunits that form the polymeric backbone of the pilin from S. pneumoniae, constructed of three transthyretin-like, CnaB, domains along with a crucial N-terminal domain, D1. The three Cna-B like domains are stabilised by internal Lys-Asn isopeptdie bonds, Gram-positive pili are formed from a single chain of covalently linked subunit proteins (pilins), usually comprising an adhesin at the distal tip, a major pilin that forms the polymer shaft and a minor pilin that mediates cell wall anchoring at the base .

Trypsin-resistant surface T6 protein N-terminal exhibits features of a typical signal sequence and the C-terminal segment is homologue to the membrane anchor region of other gram-positive surface proteins . The T6 pilin lysine, essential for polymerization, is located in a novel VAKS motif that is structurally homologous to the canonical YPKN pilin lysine in other three- and four-domain Gram-positive pilins. Structurally, T6 has also a conserved pilin core whose surface is decorated with variable loops and extensions .
Sam68, tyrosine-rich domain (Sam68-YY)
Type: Domain

This entry represents a tyrosine-rich domain found in Sam68, also known as KH domain-containing, RNA-binding, signal transduction-associated protein. Sam68 regulates TCF-1 alternative splicing. It is a crucial binding-partner of the APC-Arm domain that forms a superhelix with a positively charged groove, the surface-residues of which groove form numerous interactions with this domain to fix it in a bent conformation. APC-Arm is the armadillo repeat domain of the tumour-suppressor protein adenomatous polyposis coli or APC. APC plays plays important roles in Wnt signalling and other cellular processes .
Pathogenicity island component CagD (CagD)
Type: Family

CagD is a tightly conserved family of proteins found in the pathogenic strains of Helicobacter species. It is one of some 30 proteins, produced from the genomic insert termed the pathogenicity island, required for the type IV secretion system - T4SS - that delivers CagA oncoprotein toxin into the host cell. CagD is a covalent dimer in which each monomer folds as a single domain composed of five β-strands and three α-helices. CagD partially associates with the inner membrane, where it may be exposed to the periplasmic space; this may indicate that CagD is released into the supernatant during host cell infection in order then to bind to the host cell surface, or to be incorporated into the pilus structure .
RPRD1A/B, C-terminal domain (RPRD1A/B_C)
Type: Domain

Regulation of nuclear pre-mRNA domain-containing protein 1A/B (RPRD1A/B, RPRD1B is also known as CREPT, cell-cycle alteration and expression-elevated protein in tumour) belong to a family of eukaryotic transcriptional regulators that promote the binding of RNA-polymerase to the CYCLIN D1, CCDN1, promoter and other genes involved in the cell-cycle . It promotes the formation of a chromatin loop in the CYCLIN D1 gene, and is preferentially expressed in a range of different human tumours .

This entry represents the C-terminal coiled-coil domain which mediates the formation of homo and heterodimers .
Protein of unknown function DUF4858 (DUF4858)
Type: Family

This family consists of uncharacterised proteins around 190 residues in length and is mainly found in various Bacteroides species. The function of this family is unknown.
Domain of unknown function DUF4859 (DUF4859)
Type: Domain

This domain is mainly found in proteins from various Bacteroides and Prevotella species. Its function is unknown.
Protein of unknown function DUF4860 (DUF4860)
Type: Family

This family consists of uncharacterised proteins around 160 residues in length and is mainly found in various Firmicutes. The function of this family is unknown.
MITD1, C-terminal phospholipase D-like domain (MITD1_C)
Type: Domain

This entry represents the C-terminal domain of the MIT domain-containing proteins. It contains an unanticipated phospholipase d fold (PLD fold) that binds avidly to phosphoinositide-containing membranes .
Protein of unknown function DUF4861 (DUF4861)
Type: Family

This family consists of uncharacterised proteins around 400 residues in length and is mainly found in various Bacteroides species. The function of this family is unknown.
Methyl-CpG-binding domain protein 2/3, p55-binding region (MBD2/MBD3_p55-bd)
Type: Domain

This entry represents a second MBD domain of methyl-CpG-binding domain proteins 2 and 3. This region has been implicated in binding the RbAp46/48 (retinoblastoma protein-associated protein) homologue p55, which is one of the components of the MBD2-NuRD complex. The MBD2-NuRD complex is a nucleosome remodelling and deacetylation complex .

Methylation at CpG dinucleotide, the most common DNA modification in eukaryotes, has been correlated with gene silencing associated with various phenomena such as genomic imprinting, transposon and chromosome X inactivation, differentiation, and cancer. Effects of DNA methylation are mediated through proteins which bind to symmetrically methylated CpGs. Such proteins contain a specific domain of ~70 residues, the methyl-CpG-binding domain (MBD), which is linked to additional domains associated with chromatin, such as the bromodomain, the AT hook motif, the SET domain, or the PHD finger. MBD-containing proteins appear to act as structural proteins, which recruit a variety of histone deacetylase (HDAC) complexes and chromatin remodelling factors, leading to chromatin compaction and, consequently, to transcriptional repression. The MBD of MeCP2, MBD1, MBD2, MBD4 and BAZ2 mediates binding to DNA, in case of MeCP2, MBD1 and MBD2 preferentially to methylated CpG. In case of human MBD3 and SETDB1 the MBD has been shown to mediate protein-protein interactions .
Protein of unknown function DUF4862 (DUF4862)
Type: Family

This family consists of uncharacterised proteins around 300 residues in length and is mainly found in various high GC Gram-positive bacteria, but also in several pathogenic and non-pathogenic enterobacteria (Salmonella, E. coli). The function of this family is not clear.
4-hydroxylaminobenzoate lyase (PnbB)
Type: Family

This family, previously known as DUF4863, represents 4-hydroxylaminobenzoate lyase (PnbB) and related proteins mainly found in various proteobacteria, but also several fungal species. PnbB catalyses the conversion of 4-hydroxylaminobenzoate to 3,4-dihydroxybenzoate (protocatechuate) and ammonium. This enzyme is involved in the degradation of nitroaromatic compounds .
Transcriptional repressor p66, coiled-coil MBD2-interaction domain (P66_CC)
Type: Domain

This entry represents a short coiled-coil interaction region found in the transcriptional repressors P66alpha and P66beta. P66alpha and P66beta form complex with MBDs (methyl-binding domain-containing proteins) via a coiled-coil region on each. The MBD2-NuRD complex recognizes methylated DNA and silences expression of associated genes through histone deacetylase and nucleosome remodeling functions .
Protein of unknown function DUF4864 (DUF4864)
Type: Family

This family consists of uncharacterised proteins around 120 residues in length and is mainly found in bacteria and archaea.
E3 ubiquitin-protein ligase HECW1/2, N-terminal (HECW_N)
Type: Domain

This entry represents a domain found in E3 ubiquitin-protein ligases HECW1 and HECW2 that lies upstream of the C2 domain. Its function is not clearly understood, but it might be to determine the substrate spectrum of the ligase .
Protein of unknown function DUF4865 (DUF4865)
Type: Family

This family consists of uncharacterised proteins around 180 residues in length found in bacteria. The function of this family is not clear.
Nbr1, FW domain (Nbr1_FW)
Type: Domain

This entry represents the FW domain found in Nbr1 and similar eukaryotic proteins, including JOKA2 from Solanum tuberosum. In the fungus Chaetomium thermophilum it has been shown to bind the alpha-mannosidase Ams1, a cargo of selective autophagy in both budding yeast and fission yeast, and delivers Ams1 to the vacuole by autophagy in heterologous fission yeast. The FW domain has also been shown to interact with the microtubule-associated protein MAP1B . Structurally, the FW domain adopts an immunoglobulin-like β-sandwich structure and recognises the quaternary structure of the Ams1 tetramer .

Nbr1 (next to BRCA1) is an ubiquitin-binding autophagy adapter that participates in different processes including host defense or intracellular homeostasis . Nbr1-like molecules contain an N-terminal PB1 domain, one (animals, plants) or more (fungi) ZZ domains, an FW domain, and a C-terminal UBA domain .

JOKA2 activates ATG8CL-mediated selective autophagy, and contributes to defense against the fungal pathogen Phytophtora infestans .
Putative mobile pathogenicity island (SAPI)
Type: Family

This entry represents a group of putative Staphylococcus pathogenicity island proteins. SAPIs (S. aureus pathogenicity islands) are responsible for many superantigen-related diseases in humans as they carry two or more superantigens .
Arf GTPase-activating protein GIT1/2, coiled-coil domain (GIT1/2_CC)
Type: Domain

This entry represents the coiled-coil region of GIT (G protein-coupled receptor kinase-interacting) proteins. This coiled-coil region is the surface that associates with the equivalent binding-region on beta-PIX, or p21-activated kinase-interacting exchange factor proteins. Both GIT and PIX complex together to form a scaffold for the formation of multi-protein assemblies. On its own the GIT-CC region assembles into a parallel two-stranded CC in the asymmetric unit. Similarly the PIX coiled-coil region assembles into a trimer. At least in vitro the two regions associate together into a stable heteropentameric complex that consists of one PIX trimer and one GIT dimer .
Ubiquitin-protein ligase E3A, N-terminal zinc-binding domain (AZUL)
Type: Domain

The AZUL or amino-terminal zinc-binding domain of ubiquitin E3a ligase (Ube3A) is found in eukaryotes, and is an unusual zinc-finger domain. The final cysteine is usually mutated in Angelman syndrome patients. It is likely that AZUL plays a role in Ube3A substrate-recognition .
FOXP, coiled-coil domain (FOXP-CC)
Type: Domain

This coiled-coil domain, approximately 60-70 residues in length, is mainly found in Forkhead box proteins from animals . It modulates the dimeric associations of FOXP transcription factors. Several mutations found in this domain have been linked to the IPEX syndrome (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome) .
SATB, CUT1-like DNA-binding domain (CUTL)
Type: Domain

The CUTL domain is part of the N-terminal region of SATB proteins, special AT-rich sequence-binding proteins that are global chromatin organisers and gene expression regulators essential for T-cell development and breast cancer tumour growth and metastasis. This domain carries a DNA-binding region .
Interleukin-17 receptor, fibronectin-III-like domain 1 (IL17R_fnIII_D1)
Type: Domain

The five IL-17 receptors (IL17RA-IL17RE) exhibit considerable sequence divergence between one another, but all appear to contain extracellular domains composed of fibronectin type-III (FnIII) domains, and cytoplasmic SEF/IL-17R (SEFIR) domains that show loose homology to Toll/IL-1R (TLR) domains.

This is the first of two fibronectin-type domains on interleukin-17 receptor proteins A and B . These two fibronectin-type domains are linked and together bind two molecules of IL-17 at one of its receptor-binding interfaces. This allows the other interface to bind to another receptor, thus allowing the IL-17 family of homodimeric cytokines to coordinate two different receptors .
Protein of unknown function DUF4866 (DUF4866)
Type: Family

This family consists of uncharacterised proteins around 250 residues in length and is mainly found in various human gut Firmicutes species and abundant in human gut metagenomic datasets. The function of this family is unknown.
Protein of unknown function DUF4867 (DUF4867)
Type: Family

This family consists of uncharacterised proteins around 220 residues in length and is mainly found in various human gut Firmicutes and a few eubacteria species. It is also amply represented in human gut metagenomic datasets. The function of this family is not clear.
Kiwa protein KwaB-like (KwaB-like)
Type: Family

This family includes Kiwa protein KwaB from E.coli, a component of antiviral defense system Kiwa, composed of KwaA and KwaB. The expression of Kiwa in E.coli (strain MG1655) confers resistance to phages lambda and SECphi18 .

This family includes a phylogenetically broad range of bacteria associated with the human gut microbiome. A member of this family from Lactobacillus casei CRL 705 is part of the gene cluster involved in synthesis of bacteriocin toxin .
Protein of unknown function DUF4869 (DUF4869)
Type: Family

This family consists of uncharacterised proteins around 150 residues in length. Its members are found in human gut Firmicutes and are also abundant in human gut metagenomics datasets. The function of this family is unknown.
von Willebrand factor, VWA N-terminal domain (VWA_N2)
Type: Domain

This domain is found in von Willebrand factor proteins, where it is found N-terminal to the first VWA domain (

).
Ferlin, C-terminal domain (Ferlin_C)
Type: Domain

This domain is found at the C terminus of proteins belonging to the ferlin family, including dysferlin, myoferlin, otoferlin and fer-1-like proteins .
Gram-positive pilin subunit D1, N-terminal (GramPos_pilinD1_N)
Type: Domain

There are three major pilin subunits that form the polymeric backbone of the pilin from S. pneumoniae, constructed of three Ig-like, CnaB, domains along with a crucial N-terminal domain, D1. The three IG-like domains are stabilised by internal Lys-Asn isopeptdie bonds, but this N-terminal domain makes few contact with the rest of the molecule due to the different orientation of its G β-strand. Strand G of D1 also carries the YPKN motif that provides the essential Lys residue for the sortase-mediated intermolecular linkages along the pilus shaft. Gram-positive pili are formed from a single chain of covalently linked subunit proteins (pilins), usually comprising an adhesin at the distal tip, a major pilin that forms the polymer shaft and a minor pilin that mediates cell wall anchoring at the base .
BCL-6 corepressor, PCGF1 binding domain (PUFD)
Type: Domain

This entry represents the minimal domain at the C terminus of BCOR (BCL6 corepressor) that is needed for binding specifically to some of the PCGF proteins (polycomb-group RING finger homologues). Because of the selective binding, this domain has been named PCGF Ub-like fold discriminator (PUFD). PUFD binds to the RAWUL (RING finger- and WD40-associated ubiquitin-like) domain of the particular PCGF, PCGF1. Polycomb group proteins form repressive complexes (PRC) that mediate epigenetic modifications of histones. In humans there are many different PCGF homologues whose functions all vary, but the direct binding partner of PCGF1 is BCOR. BCOR has emerged as an important player in development and health .
Protein of unknown function DUF4871 (DUF4871)
Type: Family

This family consists of uncharacterised proteins around 170 residues in length and is mainly found in various Bacillus species (B. cereus, B. thuringiensis and B. anthracis). The solved structure of B. anthracis homologues (PDB entry 4JG9) has a variant of the Greek-key β barrel fold. The function of this family is not clear.
Protein quaking, putative nuclear localisation signal (Quaking_NLS)
Type: Domain

This entry represents the very C-terminal region of quaking proteins that is purported to be the nuclear localisation signal . Quaking is a RNA-binding protein that plays a central role in myelinisation .
RPN13, DEUBAD domain (RPN13_DEUBAD)
Type: Domain

This entry represents the DEUBiquitinase ADaptor (DEUBAD) domain from RPN13 (ADRM1), located at its C-terminal, that binds to the UCH37-like domain (ULD) of the deubiquitinase UCH37 . This interaction is required for DUB activity activation.
Domain of unknown function DUF4872 (DUF4872)
Type: Domain

This domain can be found in proteins from bacteria and archaea. Its function is not clear.
Flagellar assembly protein T, N-terminal (FlgT_N)
Type: Domain

This entry represents the N-terminal domain of FlgT, a flagellar protein that make up part of the basal body of the flagellum. The flagellum is a large macromolecular assembly composed of three major parts: the basal body, the hook, and the filament. The basal body has two unique ring structures, the T ring and the H ring. FlgT is required to form and stabilise both ring structures. FlgT is composed of three domains, the N-terminal domain (FlgT-N), the middle domain (FlgT-M), and the C-terminal domain (FlgT-C). This N-terminal domain contributes to the construction of the H-ring structure, and adopts a two-layer α-β sandwich architecture composed of a four-stranded anti-parallel β-sheet and two α helices .
Domain of unknown function DUF4873 (DUF4873)
Type: Domain

This entry consists mostly of a standalone domain found in short uncharacterised proteins from various high GC Gram-positive bacteria, primarily Mycobacterium species. However, in some proteins, such as the Rv0943c protein from Mycobacterium tuberculosis H37Rv, this domain is found at the C terminus, following the FAD/NAD(P)-binding domain (

).
Proteasome activator Blm10, N-terminal (Blm10_N)
Type: Domain

The ordered regions of the yeast BLM10 or PA200 (human homologue), full-length protein encode 32 HEAT repeat (HR)-like modules . This entry represents the N-terminal ordered region. Blm10 is a proteasome activator that binds the core proteasome and stimulates proteasome-mediated protein degradation by inducing gate opening. The structure of Blm10 has been revealed .
Centromere kinetochore component CENP-T, N-terminal domain (CENP-T_N)
Type: Domain

Multiple proteins are assembled on centromeric DNA to form the kinetochore structure. CENP-T is a component of the constitutive centromere associated network (CCAN) of proteins that creates a platform for kinetochore formation. CENP-T associates directly with CENP-W. The N terminus of CENP-T proteins interacts directly with the Ndc80 complex in the outer kinetochore. Importantly, the CENP-T-W complex does not directly associate with CENP-A, but with histone H3 in the centromere region. CENP-T and -W form a hetero-tetramer with CENP-S and -X and bind to a ~100 bp region of nucleosome-free DNA forming a nucleosome-like structure. The DNA-CENP-T-W-S-X complex is likely to be associated with histone H3-containing nucleosomes rather than with CENP-nucleosomes . This entry represents the N terminus of CENP-T.
SGTA, homodimerisation domain (SGTA_dimer)
Type: Domain

This entry represents a short N-terminal domain at the start of small glutamine-rich tetratricopeptide repeat-containing protein (SGTA), a heat-shock protein (HSP) co-chaperone involved in the targeting of tail-anchor membrane proteins to the endoplasmic reticulum. This is the homodimerisation domain that mediates the association with a single copy of Get4 or Get5 proteins, providing a link to the rest of the GET pathway .
Cerebral cavernous malformations 2, harmonin-homology domain (CCM2_C)
Type: Domain

This entry represents the C-terminal folded helical region of cerebral cavernous malformations protein 2 (CCM2, also known as malcavernin), a component of the CCM signalling pathway which is a crucial regulator of heart and vessel formation and integrity . This domain is structurally homologous to the N-terminal domain of harmonin, so it is named the harmonin-homology domain (HHD). The structure of this domain has been revealed .
Dedicator of cytokinesis, N-terminal domain (DOCK_N)
Type: Domain

This domain is found near to the N terminus of some dedicator of cytokinesis (DOCK) proteins, between the variant SH3 domain and the C2 domain . This is an α-helical region that mediates interactions with ELMO subunits and provides a major site for interactions between the SH3 and ARM domains of these proteins .

Dedicator of cytokinesis (DOCK) proteins function as guanine nucleotide exchange factors (GEFs) that activate small GTPases by exchanging bound GDP for free GTP, thus converting them into their active GTP-bound form. These proteins are involved in various cellular processes, including cytoskeletal rearrangements, cell migration, phagocytosis of apoptotic cells, and regulation of adherens junctions between cells. Some family members may also play a role in disease processes such as Alzheimer's disease by interacting with presenilin proteins and affecting Tau phosphorylation. DOCK proteins are characterised by the presence of a conserved DOCKER domain, which is necessary for their GEF activity and interaction with small GTPases like RAC1 and RAC2.
STAR protein, homodimerisation region (STAR_dimer)
Type: Domain

This entry represents the homodimerisation domain of the STAR (signal transducer and activator of RNA) proteins. Quaking is a prototypical member of the STAR family, which plays key roles in post-transcriptional gene regulation by controlling mRNA translation, stability and splicing . Quaking-dimer is a helix-turn-helix dimer with an additional helix in the turn region. The dimerisation of quaking is required for adequate RNA-binding .
ZC3H15/TMA46 family, C-terminal (ZC3H15/TMA46_C)
Type: Domain

This entry represents the C-terminal domain of the translation machinery-associated protein 46 (Tma46), a binding partner for the highly conserved developmentally regulated GTP-binding (DRG) GTPases. The interaction between Tma46 and Rbg1 GTPase (a DRG protein) modulates the function of the GTPase . This domain is also found in ZC3H15 (zinc finger CCCH domain-containing protein 15), also known as DFRP1 (DRG family regulatory protein 1) .
Domain of unknown function DUF4874 (DUF4874)
Type: Domain

This presumed domain is functionally uncharacterised. It is found in bacteria and eukaryotes, and is typically between 161 and 175 amino acids in length. There is a conserved WGE sequence motif.
Polynucleotide kinase-phosphatase, ligase domain (PNKP_ligase_dom)
Type: Domain

This entry represents the ligase domain found in the PNKP (polynucleotide kinase-phosphatase) protein, which is a classical ligase nucleotidyltransferase module of bacteria. PNKP is the end-healing and end-sealing component of an RNA-repair system present in diverse bacteria from ten different phyla. RNA breakage by site-specific 'ribotoxins' is an ancient mechanism by which microbes respond to cellular stress and distinguish self from non-self. Ribotoxins are trans-esterifying endonucleases that generate 5'-OH and 2',3' cyclic phosphate termini. Repair of this type of RNA damage is feasible via sequential enzymatic end-healing and end-sealing steps .
Intracellular hyaluronan-binding protein 4, N-terminal domain (IHABP4_N)
Type: Domain

This is the N-terminal region of intracellular hyaluronan-binding protein 4 and SERPINE1 mRNA-binding protein 1-like proteins. This region carries nuclear localisation sites, and may also be involved in the binding to some of the partners in the translational machinery .
Alternaria alternata allergen 1 (AltA1)
Type: Domain

Alt a 1 family proteins (AA1s) have only been observed in the Dothideomycetes and Sordariomycetes classes of fungi. AA1-like proteins are fungal toxins that can induce plant defense responses and cell death. They may contribute to virulence by protecting the cell wall, thus allowing fungal growth to be maintained and preventing the recognition of degraded beta-1,3-glucan by the plant .
Domain of unknown function DUF4875 (DUF4875)
Type: Domain

This domain is found in a small protein family with members present in few gammaproteobacteria, desulfovibrionia and myxococcia. Its function is unknown.