SII-SWORD/CoKE huggingface dataset:
Sporulation initiation factor Spo0A, C-terminal (Spo0A_C)
Type: Domain

The response regulator Spo0A is comprised of a phosphoacceptor domain and a transcription activation domain. This domain corresponds to the transcription activation domain and forms an α helical structure comprising of 6 α helices. The structure contains a helix-turn-helix and binds DNA .
Sulphur oxidation protein SoxZ (SoxZ_dom)
Type: Domain

SoxZ forms an anti parallel β structure and forms a complex with SoxY. Sulphur oxidation occurs at the thiol of a conserved cysteine residue of the SoxY subunit .
Nin one binding (NOB1), Zn-ribbon-like domain (NOB1_Zn-bd)
Type: Domain

This entry corresponds to a zinc ribbon and is found on the RNA binding protein NOB1.
Cathepsin C exclusion (CathepsinC_exc)
Type: Domain

Cathepsin C (dipeptidyl peptidase I) is the physiological activator of a group of serine proteases. This protein corresponds to the exclusion domain whose structure excludes the approach of a polypeptide apart from its termini and confers its exopeptidase specificity . It forms an enclosed β barrel structure composed from 8 anti-parallel β strands . Based on a structural comparison and interaction data, it is suggested that the exclusion domain originates from a metallo-protease inhibitor .
VRR-NUC domain (VRR_NUC)
Type: Domain

This entry contains proteins with the VRR-NUC domain, such as FAN1, a structure-selective DNA repair nuclease with 5' flap endonuclease activity, involved in the repair of interstrand DNA crosslinks. FAN1 is the only eukaryotic protein with a VRR-NUC domain . This domain is a member of the PD-(D/E)XK nuclease superfamily, that also includes type III restriction modification enzymes . This domain is found in TseVs antibacterial effectors secreted by the type VI secretion system (T6SS). TseVs are evolutionary related to Holliday junction resolvases and enzymes involved in DNA interstrand crosslink repair .
ParB protein family, C-terminal (ParB_fam_C)
Type: Domain

ParB is a component of the par system which mediates accurate DNA partition during cell division. It recognises A-box and B-box DNA motifs. ParB forms an asymmetric dimer with 2 extended helix-turn-helix (HTH) motifs that bind to A-boxes. The HTH motifs emanate from a β sheet coiled coil DNA binding module . Both DNA binding elements are free to rotate around a flexible linker, this enables them to bind to complex arrays of A- and B-box elements on adjacent DNA arms of the looped partition site .
VASP tetramerisation (VASP_tetra)
Type: Domain

Vasodilator-stimulated phosphoprotein (VASP) is an actin cytoskeletal regulatory protein. This region corresponds to the tetramerisation domain which forms a right handed α helical coiled coil structure .
La protein, xRRM domain (La_xRRM)
Type: Domain

This entry represents the atypical RRM, named xRRM, found in La and La-related proteins (LaRPs). They belong to an ancient superfamily of proteins that are conserved in nearly all eukaryotes, except Plasmodium. These proteins are broadly involved in critical processes of RNA use and metabolism in the nucleus and the cytoplasm. The LaRP superfamily is distinguished by a conserved bipartite RNA-binding unit called the La-module, composed by a Lupus antigen motif (LaM) followed by an RNA-Recognition motif (RRM). Beyond this, each LaRP family is characterised by distinct family specific domains and motifs that contribute to structure and function. Genuine La and La-related proteins group 7 (LARP7) bind to the non-coding RNAs transcribed by RNA polymerase III (RNAPIII), which end in UUU. The La-module of these proteins bind the UUU-3'OH, protecting the RNA from degradation, while other domains may be important for RNA folding or other functions. The La and LaRP7 protein families have a C-terminal domain that contains a novel class of atypical RRM, named xRRM (for atypical RRM with extended alpha3), which uses a unique mode of single- and double-strand RNA binding .
HIF-1 alpha, C-terminal transactivation domain (HIF-1_CTAD)
Type: Domain

This entry corresponds to the C-terminal transactivation domain of HIF1A and similar sequences from vertebrates.

Hypoxia inducible factor-1 alpha (HIF-1 alpha) plays a key role in cellular response to low oxygen tension, as well as in embryonic vascularisation, tumour angiogenesis and pathophysiology of ischaemic disease .
Structural accessory protein ORF7a, SARS-CoV-like (ORF7a_SARS-CoV-like)
Type: Family

This entry represents the structural accessory protein ORF7a from SARS-CoV-like virus, including SARS-CoV, SARS-CoV-2 and bat SARS-like coronavirus.

This entry includes the structural accessory protein ORF7a, also called NS7a, X4 and U122, of Severe Acute Respiratory Syndrome Coronaviruses (SARS-CoV) from betacoronavirus subgenera Sarbecovirus (lineage B), including SARS-CoV-2. ORF7a/NS7a from betacoronavirus in the subgenera Sarbecovirus (B lineage) are not related to NS7a proteins from other coronavirus lineages. The structure of the structural accessory protein ORF7a, shows similarities to the immunoglobulin-like fold with some features resembling those of the Dl domain of ICAM-1 and suggests a binding activity to integrin I domains . In SARS-CoV-infected cells, ORF7a is expressed and retained intracellularly within the Golgi network . ORF7a is thought to play an important role during the SARS-CoV replication cycle . Expression studies of ORF7a have shown that biological functions include induction of apoptosis through a caspase-dependent pathway, activation of the p38 mitogen-activated protein kinase signaling pathway, inhibition of host protein translation, and suppression of cell growth progression. These results collectively suggested that ORF7a protein may be involved in virus-host interactions . Studies in SARS-CoV-2 revealed that ORF7a plays a role as antagonist of host tetherin (BST2), disrupting its antiviral effect. ORF7a binds to BST2 and sequesters it to the perinuclear region, thereby preventing its antiviral function at cell membrane .
Transcription factor DP, C-terminal (Transc_factor_DP_C)
Type: Domain

The transcription factor DP (dimerization partner) forms a heterodimer with E2F and regulates genes involved in cell cycle progression. The transcriptional activity of E2F is inhibited by the retinoblastoma protein which binds to the E2F-DP heterodimer and negatively regulates the G1-S transition.
c-SKI SMAD4-binding domain (c-SKI_SMAD4-bd_dom)
Type: Domain

This entry represents the SMAD4-binding domain of c-SKI, which is an oncogene that inhibits TGF-beta signalling through interaction with SMAD proteins .
DWNN domain (DWNN_domain)
Type: Domain

The ~75-residue DWNN (Domain With No Name) domain is highly conserved through eukaryotic species but is absent in prokaryotes. The DWNN domain is found only at the N terminus of the RBBP6 family of proteins which includes:

Mammalian RBBP6, a splicing-associated protein that plays a role in the induction of apoptosis and regulation of the cell cycle.

Drosophila melanogaster (Fruit fly) SNAMA (something that sticks like glue), a protein that appears to play a role in apoptosis.

All of the identified RBBP6 homologues include the DWNN domain, a CCHC-type zinc finger (see

) and a RING-type zinc finger (see

). The three domain form is found in plants, protozoa, fungi and microsporidia. The RBBP6 homologues in vertebrates, insects and worms are longer and include additional domains. In addition to forming part of the full-length RBBP6 protein, the DWNN domain is also expressed in vertebrates as a small protein containing a DWNN domain and a short C-terminal tail (RBBP6 variant 3). The DWNN domain adopts a fold similar to the ubiquitin one, characterised by two α-helices and four β-sheets ordered as β-β-α-β-α-β along the sequence. The similarity of DWNN domain to ubiquitin and the presence of the RING finger suggest that the DWNN domain may act as an ubiquitin-like modifier, possibly playing a role in the regulation of the splicing machinery .
Replication protein A, C-terminal (RPA_C)
Type: Domain

This protein corresponds to the C-terminal of the single stranded DNA binding protein RPA (replication protein A). RPA is involved in many DNA metabolic pathways including DNA replication, DNA repair, recombination, cell cycle and DNA damage checkpoints.
Ku, C-terminal (Ku_PK_bind)
Type: Domain

The non-homologous end joining (NHEJ) pathway is one method by which double stranded breaks in chromosomal DNA are repaired. Ku is a component of a multi-protein complex that is involved in the NHEJ. Ku has affinity for DNA ends and recruits the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Ku also binds RNA, mediating the assembly of DNA-PKcs which has a role in ribosomal RNA biogenesis . This domain is found at the C-terminal of Ku which binds to DNA-PKcs .
Inner membrane lipoprotein DcrB/EagT6 (DcrB/EagT6)
Type: Family

DcrB is a bacterial protein required for phages C1 and C6 adsorption . It may be involved in the opening or formation of diffusion channels in the outer membrane . It plays a role in cell envelope biogenesis, maintenance of cell envelope integrity and membrane homeostasis . DcbrB is essential for lipoprotein maturation under conditions where membrane fluidity may be altered . Structurally, it consist of an antiparallel β sheet with some α helical regions.
Alginate lyase 2 (Alginate_lyase_2)
Type: Domain

Alginate lyases are enzymes that degrade the linear polysaccharide alignate. They cleave the glycosidic linkage of alignate through a beta-elimination reaction. This region forms an all β fold, which is different to the all α fold of

.
NHR2-like (NHR2)
Type: Domain

Transcriptional activation and repression are required for control of cell proliferation and differentiation during embryonic development and homeostasis in the adult organism. Perturbations of these processes can lead to the development of cancer . The Eight-Twenty-One (ETO) gene product is able to form complexes with corepressors and deacetylases, such as nuclear receptor corepressor (N-CoR), which repress transcription when recruited by transcription factors . The ETO gene derives its name from its association with many cases of acute myelogenous leukaemia (AML), in which a reciprocal translocation, t(8;21), brings together a large portion of the ETO gene from chromosome eight and part of the AML1 gene from chromosome 21. The human ETO gene family currently comprises three major subfamilies: ETO/myeloid transforming gene on chromosome 8 (MTG8); myeloid transforming gene related protein-1 (MTGR1) and myeloid transforming gene on chromosome 16 (MTG16). ETO proteins are composed of four evolutionarily conserved domains termed nervy homology regions (NHR) 1-4. NHR1 is thought to stabilise the formation of high molecular weight complexes, but is not directly responsible for repressor activity. NHR2 and its flanking sequence comprise the core repressor domain, which mediates 50% of the wild type repressor activity. Furthermore, there is evidence that the amphipathic helical structure of NHR2 promotes the formation of ETO/AML1 homodimers . NHR3 and NHR4 have been shown to act in concert to bind N-CoR. NHR4 contains two zinc finger motifs, which are thought to play a role in protein interactions rather than DNA binding .

This entry represents the NHR2 (Nervy homology 2) domain found in ETO proteins. It mediates oligomerisation and protein-protein interactions, forming an α-helical tetramer .
PBCV-specific basic adaptor domain (PBCV_basic_adap)
Type: Domain

The small PBCV-specific basic adaptor protein is found fused to S/T protein kinases and the 2-Cysteine domain .
Zinc finger, C2H2, LYAR-type (Znf_C2H2_LYAR)
Type: Domain

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This C2HC zinc finger domain is found in LYAR proteins such as

, which are involved in cell growth regulation.
Viral late gene transcription factor 3 , zinc ribbon (VLTF-3_Zn_ribbon)
Type: Domain

This zinc ribbon domain is found in the viral late gene transcription factor 3, which acts with RNA polymerase to initiate transcription from late gene promoters .
2-cysteine adaptor (2-cysteine_adaptor)
Type: Domain

The virus-specific 2-cysteine adaptor is found fused to OTU/A20-like peptidases and S/T protein kinases. The associations to these proteins indicate that they might function as viral adaptors connecting the kinases and OTU/A20 peptidases to specific targets .
Factor H binding protein-like, C-terminal (FHBP-like_C)
Type: Domain

Factor H binding protein (also known as GNA1870) is a surface exposed lipoprotein in Neisseria meningitidis that is a potent antigen and a potential candidate for a vaccine against meningococcal disease . The structure of the C-terminal domain consists of an anti-parallel β-barrel overlaid by a short α-helical region . This entry includes sequences mainly found in beta and gammaproteobacteria.
Protein of unknown function DUF1796 (DUF1796)
Type: Family

The proteins in this entry are uncharacterised; but are related to papain-like cysteine peptidases.
YkuJ-like (YkuJ-like)
Type: Family

YkuJ is a mixed α/β fold protein consisting of an antiparallel β-sheet with C- and N-terminal helices packed against one side (PDBe: 2ffg) . The function of YkuJ is not clear.
HIRAN domain (HIRAN)
Type: Domain

The HIRAN domain (HIP116 Rad5p N-terminal) is found in the N-terminal regions of the SWI2/SNF2 proteins typified by HIP116 and Rad5p. HIRAN is found as a standalone protein in several bacteria and prophages, or fused to other catalytic domains, such as a nuclease of the restriction endonuclease fold and TDP1-like DNA phosphoesterases, in the eukaryotes . It has been predicted that this protein functions as a DNA-binding domain that probably recognises features associated with damaged DNA or stalled replication forks .
Pre-mRNA processing factor 4 (PRP4)-like (PRP4-like)
Type: Domain

This small domain is found on PRP4 ribonuleoproteins. PRP4 is a U4/U6 small nuclear ribonucleoprotein that is involved in pre-mRNA processing . It is also found in pre-mRNA-splicing factor 18 .
BT4734-like, N-terminal (BT4734-like_N)
Type: Domain

This domain is found mainly in bacteroidetes. In some instances, it is at the N-terminal of

, such as in the product of BT4734

, which is incorrectly named Virulence protein E. The function of the domain is unknown.
Nucleoporin, Nup133/Nup155-like, N-terminal (Nucleoporin_Nup133/Nup155_N)
Type: Domain

Nucleoporins are the main components of the nuclear pore complex (NPC) in eukaryotic cells, and mediate bidirectional nucleocytoplasmic transport, especially of mRNA and proteins. RNA undergoing nuclear export first encounters the basket of the nuclear pore and many nucleoporins are accessible on the basket side of the pore .

The S. Cerevisiae Nup-170, equivalent to the human Nup-155, contains two structural domains: an N-terminal β-propeller and a C-terminal α-helical domain .

This entry represents the N-terminal domain of nucleoporin 133 (Nup133) and other nucleoporins, including Nup155, Nup15 and Nup170. It forms a seven-bladed β propeller structure .
Putative monooxygenase YdhR (YdhR)
Type: Family

YdhR is a homodimeric protein that comprises of a central four-stranded β sheet and four surrounding α helices . It shows structural homology to the ActVA-Orf6 and YgiN proteins which indicates it could be a mono-oxygenase.
Type 4 secretion system, PilS, N-terminal (PilS_N)
Type: Domain

Type IV pili are bacterial virulence-associated adhesins that promote bacterial attachment to host cells. In Salmonella typhi, the structural pilin protein PilS interacts with the cystic fibrosis transmembrane conductance regulator . Mutagenesis studies suggest that residues on an α-β loop and the C-terminal disulphide-bonded region of PilS might be involved in binding specificity of the pilus .
Selenoprotein F/M domain (Sep15_SelM_dom)
Type: Domain

SelM and Sep15 consists of one catalytic a-domain that assumes a thioredoxin-like fold composed of a mixed four-stranded β-sheet and three interspersed α-helices. The active-site redox motifs of SelM and Sep15 are located between the C terminus of strand beta1 and the N terminus of helix alpha1. SelM and Sep15 may function as thiol-disulphide isomerases involved in disulphide bond formation in the endoplasmic reticulum .
YppE-like (YppE-like)
Type: Family

This family includes the uncharacterised protein YppE, which consists of a four α-helical up-and-down bundle .
RES domain (RES_dom)
Type: Domain

This presumed protein contains 3 highly conserved polar groups that could form an active site. These are an arginine, glutamate and serine, hence the RES domain. RES is found widely distributed in bacteria, it has about 150 residues in length.
Bacteriophage TLS, TfmB (Phage_TLS_TfmB)
Type: Family

This entry is represented by the Bacteriophage TLS, TfmB. The characteristics of the protein distribution suggest prophage matches.
Kinase associated protein B (KapB)
Type: Family

Kinase associated protein B (KapB) is one of the major histidine kinases that provide phosphate input in the phosphorelay to produce SpoOA approximately P, the key transcription factor controlling the initiation of sporulation in Bacillus subtilis . It forms an anti-parallel β sheet with an extending α helical region.
Protein of unknown function DUF1800 (DUF1800)
Type: Family

This is an entry of large bacterial proteins of unknown function.
Phage tail tube protein 3 (Phage_tail_3)
Type: Family

Proteins of this entry include phage tail proteins. They probably include bacterial Ig-like domains related to

. Which also includes a number of phage tail invasin proteins.
XisH protein (XisH)
Type: Family

This family contains XisI proteins, also known as FdxN element excision controlling factors, and similar proteins. FdxN element is excised from the chromosome during heterocyst differentiation in cyanobacteria. This is accomplished by the large serine recombinase XisF (fdxN element site-specific recombinase). The xisH as well as the xisF and xisI genes are required. XisI may function as recombination directionality factor (RDF), and needs XisH which may function as an endonuclease .
Nuclear receptor coactivator, Ncoa-type, interlocking (Nuc_rcpt_coact_Ncoa-typ)
Type: Domain

This entry represents the interlocking domain of the eukaryotic nuclear receptor coactivators Ncoa1, Ncoa2 and Ncoa3. The interlocking domain forms a 3-helical non-globular array that forms interlocked heterodimers with its target.

Nuclear receptors are ligand-activated transcription factors involved in the regulation of many processes, including development, reproduction and homeostasis. Nuclear receptor coactivators act to modulate the function of nuclear receptors. Coactivators associate with promoters and enhancers primarily through protein-protein contacts to facilitate the interaction between DNA-bound transcription factors and the transcription machinery. In addition to their role as coactivators of various nuclear receptors, Ncoa1 and Ncoa3 both have histone acetyltransferase activity (

), but Ncoa2 does not .
EsaB (EsaB)
Type: Family

This group represents an EsaB protein. EsaB seems to regulate secreted factors that contribute to the establishment of persistent infections in the host. It is a negative regulator of EsaC, which is a secretion substrate of the Ess pathway in some Staphylococcus aureus strains . This entry also includes the uncharacterised ubiquitin-like protein YukD from Bacillus subtilis.
YdhG-like domain (YdhG-like)
Type: Domain

This α/β domain is found in the Intracellular iron chaperone frataxin from Bacillus subtilis (formerly known as YdhG) and the uncharacterised protein YdeI from Bacillus subtilis. Frataxin plays an essential role in iron intracellular trafficking to iron cofactor biogenesis systems including iron-sulfur cluster (Fe-S) or heme assembly . It promotes the biosynthesis of Fe-S clusters by delivering Fe to the complex composed of the cysteine desulfurase SufS and the zinc-dependent sulfurtransferase SufU . Frataxin also plays a critical role in coproporphyrin-dependent heme b biogenesis and thus provides an essential function for the bacterial global metabolism.

YdeI is important for resistance to polymyxin B in broth and for bacterial survival in mice upon oral, but not intraperitoneal, inoculation, suggesting a role for YdeI in the gastrointestinal tract of mice .
Protein of unknown function DUF1802 (DUF1802)
Type: Family

The function of this family is unknown. This region is found associated with a

suggesting they could be part of a restriction modification system.
Protein of unknown function DUF1803 (DUF1803)
Type: Family

This small domain is found in one or two copies in bacteria. The function of this domain is unknown.
CGGC domain (CGGC_dom)
Type: Domain

This putative domain contains a quite highly conserved sequence of CGGC in its central region. The domain has many conserved cysteines and histidines, suggesting it may have a zinc binding function.
Bacteriophage D3112, Orf24 (Phage_D3112_Orf24)
Type: Family

This entry is represented by Bacteriophage D3112, Orf24. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
Putative peptidoglycan binding (PG-bd_2)
Type: Domain

This entry may be a peptidoglycan binding domain.
Serine rich protein interaction domain (Serine_rich_dom)
Type: Domain

This is a serine rich protein that is found in the docking protein p130(cas) (Crk-associated substrate). The protein folds into a four helix bundle which is associated with protein-protein interactions .
E2 binding (E2-binding)
Type: Domain

E1 and E2 enzymes play a central role in ubiquitin and ubiquitin-like protein transfer cascades. This is an E2 binding domain that is found on NEDD8 activating E1 enzyme. The protein resembles ubiquitin, and recruits the catalytic core of the E2 enzyme Ubc12 in a similar manner to that in which ubiquitin interacts with ubiquitin binding domains .
Myotonic dystrophy protein kinase, coiled coil (Myotonic_dystrophy_kinase_coil)
Type: Domain

This domain is found in the myotonic dystrophy protein kinase (DMPK) and adopts a coiled coil structure. It plays a role in dimerisation .
Protein of unknown function DUF1805 (DUF1805)
Type: Family

This protein is found in bacteria and archaea and has an N-terminal tetramerisation region that is composed of β sheets.
Doublesex dimerisation (DSX_dimer)
Type: Domain

Doublesex (DSX) is a transcription factor that regulates somatic sexual differences in Drosophila. The structure has revealed a novel dimeric arrangement of ubiquitin-associated folds that has not previously been identified in a transcription factor .