SII-SWORD/CoKE huggingface dataset:
Prokaryotic E2 family B domain (Prok-E2_B_dom)
Type: Domain

This entry represents a domain found in the E2/UBC superfamily of proteins found in several bacteria. The active site residues are similar to the eukaryotic E2 proteins but lack the conserved asparagine . Members of this family are usually fused to an E1 domain at the C terminus. The protein is usually in the gene neighbourhood of a gene encoding a member of the pol-beta nucleotidyltransferase superfamily . Many of the operons in this family are in ICE-like mobile elements and plasmids .

Proteins containing this domain include CD-NTase-associated protein 2 (Cap2) from Escherichia coli. Cap2 is associated with CD-NTase protein, which synthesizes cyclic nucleotides in response to infection; these serve as specific second messenger signals .
CppA, N-terminal (CppA_N)
Type: Domain

This is the N-terminal domain of the CppA protein found mainly in species of Streptococcus. CppA is a putative C3-glycoprotein degrading proteinase, involved in pathogenicity .
CppA, C-terminal (CppA_C)
Type: Domain

This is the C-terminal domain of the CppA protein found mainly in species of Streptococcus. CppA is a putative C3-glycoprotein degrading proteinase, involved in pathogenicity .
Protein Cms1 (Cms1)
Type: Family

This family includes fungal and plant Cms1 proteins and Cmss1 (Cms1 ribosomal small subunit homologue) from metazoa. Budding yeast Cms1 may play a role in the regulation of DNA replication and cell cycle control .
Origin recognition complex subunit 4, C-terminal (ORC4_C)
Type: Domain

This entry represents the C terminus of origin recognition complex subunit 4 .

The Origin Recognition Complex (ORC) is a six-subunit ATP-dependent DNA-binding complex encoded by ORC1-6 . ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle . ORC directs DNA replication throughout the genome and is required for its initiation . ORC bound at replication origins serves as the foundation for assembly of the pre-replicative complex (pre-RC), which includes Cdc6, Tah11 (aka Cdt1), and the Mcm2-7 complex . Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase . Cell cycle-regulated phosphorylation of ORC2, ORC6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2/M phase .

In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci Hidden MAT Left (HML) and Hidden MAT Right (HMR) . ORC participates in the assembly of transcriptionally silent chromatin at HML and HMR by recruiting the Sir1 silencing protein to the HML and HMR silencers .
Transcription elongation factor Spt6, helix-hairpin-helix motif (Spt6_HHH)
Type: Domain

This entry represents a helix-hairpin-helix motif found in the transcription elongation factor Spt6 . Spt6 is involved in the regulation of histone modification .
MYCBP-associated protein (MYCBPAP)
Type: Family

This family includes the human MYCBP-associated protein (MYCBPAP) and its homologues from other eukaryotes. Mammalian MYCBPAP proteins may be involved in synaptic processes and may have a role in spermatogenesis .
Microcin J25-processing protein McjB, C-terminal (McjB_C)
Type: Domain

This entry represents a domain found in the C-terminal region of the microcin J25-processing protein McjB from Escherichia coli. This domain is related to the transglutaminase-like domain

.

Microcin J25 (MccJ25) is a lasso peptide secreted by Escherichia coli which exerts a potent antibacterial activity by blocking RNA polymerase . McjB is involved in microcin maturation, which implies cleavage of McjA and head-tail linkage of the 21-residue pro-MccJ25 .
NTF2-like domain superfamily (NTF2-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents a domain covering the whole length of the nuclear transport factor 2 (NTF2). It has a β-α(2)-β insertion after the main helix. NTF2 protein is a nuclear envelope protein facilitating protein transport into the nucleus .

Besides NTF2, proteins containing this domain include:

UPF0225 protein YchJ

3-phenylpropionate/cinnamic acid dioxygenase subunit beta

Large ribosomal subunit protein mL45

NTF1

Type IV secretion system protein virB8

Other related proteins
Ig-like SoxY domain (SoxY)
Type: Domain

This domain is found in the sulfur oxidation protein SoxY. Dissimilatory oxidation of thiosulfate is carried out by the ubiquitous sulfur-oxidizing (Sox) multi-enzyme system. In this system, SoxY plays a key role, functioning as the sulfur substrate-binding protein that offers its sulfur substrate, which is covalently bound to a conserved C-terminal cysteine, to another oxidizing Sox enzyme . The structure of this domain shows an Ig-like fold .

Many times it has been reported that SoxY strictly interacts with SoxZ to form a SoxYZ heterodimer. However, recent studies have shown this stable complex is not an obligate, and that the individual proteins may exist on their own. SoxY exhibits a dimer/tetramer equilibrium that is dependent on the redox state of the cysteines and on the type of sulfur substrate component bound to them. The SoxY tetramer consists of two dimeric β-sandwiches that interact with each other via two small interface patches at the tips of the dimers .
Putative multidrug resistance efflux transporter (EmrE)
Type: Family

This is a membrane protein family whose members are purported to be related to the DMT or Drug/Metabolite Transporter (DMT) Superfamily. Members are all uncharacterised.
Cilium assembly protein DZIP1, N-terminal (DZIP1_N)
Type: Domain

This entry represents the N-terminal region of the cilium assembly protein DZIP1, which acts as a molecular adapter that recruits protein complexes required for cilium assembly and function to the cilium basal body . It also recruits the BBSome, a complex involved in cilium biogenesis, by bridging it to PCM1 at the centriolar satellites of the cilium . DZIP1 is involved in spermatogenesis through its role in organization of the basal body and assembly of the sperm flagellum and it is also indirectly involved in heart development through its function in ciliogenesis . Zebrafish Dzip1 acts as a permissive factor that is required for the proper regulation of Hedgehog (Hh) target genes in response to Hh signals . It is required for establishment of left-right asymmetry during embryogenesis and has a role in primary cilium formation .
Nuclear receptor coactivator 6, TRADD-N domain (NCOA6_TRADD-N)
Type: Domain

This entry represents the TRADD-N domain found in nuclear receptor coactivator 6 (NCOA6) . NCOA6 is involved in the coactivation of different nuclear receptors, such as steroid receptors (GR and ERs), retinoid receptors (RARs and RXRs), thyroid hormone receptors (TRs), vitamin D3 receptor (VDR) and prostanoid receptors (PPARs) .
Biotin-dependent acetyl-/propionyl-coenzyme A carboxylase epsilon subunit (ACC_epsilon)
Type: Family

This family includes the epsilon subunits of propionyl-CoA carboxylase and acetyl-CoA carboxylase. These enzymes are involved in the biosynthesis of long-chain fatty acids. The epsilon subunit is necessary for an efficient interaction between the alpha and beta subunits of these enzymes .

In Mycobacterium tuberculosis, the long-chain acyl-CoA carboxylase complex (LCC) contain the alpha-subunit AccA3, the epsilon-subunit AccE5 and the two beta-subunits AccD4 and AccD5. This entry represents AccE5 that interacts with AccD5 and modulates its carboxylase activity for acetyl-CoA and propionyl-CoA .
Mitochondrial splicing suppressor 51, zinc-finger (Mss51_Znf)
Type: Domain

This entry represents a zinc-finger domain found in mitochondrial splicing suppressor 51 (MSS51). MSS51 is a COX1 mRNA-specific translational activator and Cox1 chaperone .
PiggyBac transposable element-derived protein 4, C-terminal zinc-finger domain (PGBD4_Znf_C)
Type: Domain

This entry represents a zinc-finger domain which is found in piggyBac transposable element-derived protein 4 (PGBD4) protein.

This zinc-finger domain is frequently found at the C terminus of proteins derived from transposable elements. Given the AlphaFold predicted structural model, this domain is probably related to C1 domain observed in Protein kinase C (

).
Glycosyltransferase WbsX (WbsX)
Type: Family

Members of this family are found in within O-antigen biosynthesis clusters in Gram-negative bacteria, where they are predicted to function as glycosyltransferases .
Cysteine-rich CWC (Cys_rich_CWC)
Type: Family

This is a group of uncharacterised proteins mostly from bacteria. Proteins in this family are typically between 74 and 102 amino acids in length. They contain eight conserved cysteines, including a conserved CWC sequence motif.
Deaminases, BURPS668_1122 family (Toxin-deaminase)
Type: Family

This entry represents a member of the nucleic acid/nucleotide deaminase superfamily prototyped by Burkholderia BURPS668_1122 . Members of this family are found as toxins in polymorphic toxin systems in a wide range of bacteria and in the eukaryote Perkinsus. Members of this family typically possess a DxE catalytic motif in Helix-2 of the core fold instead of the more common C[H]xE motif. The Perkinsus versions are predicted to be inactive .
Deaminase, Xanthomonas XOO_2897-like (Deaminase_XOO_2897)
Type: Family

This entry represents a member of the nucleic acid/nucleotide deaminase superfamily prototyped by Xanthomonas XOO_2897 . Members of this family are present in a wide phyletic range of bacteria and are predicted to function as toxins in bacterial polymorphic toxin systems . The Xanthomonas XOO_2897 lack an immunity protein and is predicted to be deployed against its eukaryotic host .
Deaminase, LmjF36.5940-like (Deaminase_LmjF365940)
Type: Family

This entry represents a distinct branch of the CDD/CDA-like deaminases prototyped by Leishmania LmjF36.5940. Members of this family are widely distributed across several microbial eukaryotes such as kinetoplastids, chlorophyte algae, stramenopiles and the alveolate Perkinsus. Domain architectures suggest that these proteins might possess mRNA editing or DNA mutagenizing activity .
Double-stranded DNA deaminase toxin A (DddA-like)
Type: Family

Members of this family are predicted to function as toxins in bacterial polymorphic toxin systems, including DddA from Burkholderia cenocepacia .

DddA is the toxic component of a toxin, immunity protein module that functions within a cellular contact-dependent growth inhibition (CDI) system, enabling bacteria to communicate with and inhibit the growth of closely related neighbouring bacteria through direct contact . It contains a deaminase domain with double-stranded DNA cytidine deaminase activity and has been adapted for CRISPR-free mitochondrial base editing, highlighting its potential in genome engineering applications .
ThiS-like ubiquitin domain (ThiS-like_dom)
Type: Domain

This entry represents a domain found in a members of the ubiquitin superfamily that is often fused to the ThiF-like (E1)- ubiquitin activating enzyme and is present in gene neighbourhoods with components of the thiamine biosynthesis pathway .
Flagellar C1a complex subunit C1a-32 (CLAMP)
Type: Family

This family represents one small subunit, C1a-32, of the C1a projection (the seventh projection of the flagellum in Chlamydomonas) . Numerous studies have indicated that each of the seven projections associated with the central pair of microtubules in the flagellum plays a distinct role in regulating eukaryotic ciliary/flagellar motility. The C1a projection is a complex of proteins including PF6, C1a-86, C1a-34, C1a-32, C1a-18, and calmodulin. C1a projection is involved in modulating flagella beat frequency and this is mediated via the C1a-34, C1a-32, and C1a-18 sub-complex by modulating the activity of both the inner and outer dynein arms .

This entry also includes Cilia- and flagella-associated protein 119, whose function is unknown and ciliary-associated calcium-binding coiled-coil protein 1 (Cabcoco1) from vertebrates, a calcium-binding protein which may have a role in control of sperm flagellar movement .
Bardet-Biedl syndrome 1, N-terminal (BBS1_N)
Type: Domain

This entry represents the N-terminal β-propeller domain of the Bardet-Biedl syndrome 1 protein (BBS1) which interacts with the small GTPase Arl6 and recruits the BBSome to membranes .

Bardet-Biedl syndrome is characterised by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation . Bardet-Biedl syndrome proteins (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10) form the BBSome complex, which functions as a coat complex required for sorting of specific membrane proteins to the primary cilia . The ciliary trafficking function of BBSome is regulated by LZTFL1 (Leucine-zipper transcription factor-like 1) .

Primary cilia are ubiquitous cellular appendages that provide important sensory and signalling functions and their dysfunction underlies numerous human genetic disorders. The proteins disrupted in the human ciliary disorder Bardet-Biedl syndrome (BBS) are required for the localisation of G protein-coupled receptors to primary cilia on central neurons. The alteration of signalling caused by mislocalisation of ciliary signalling proteins underlies the BBS phenotype . Of the 12 known BBS genes, BBS1 is the most commonly mutated .

This entry includes BBS1, is the most important BBSome subunit for cargo recognition as it mediates the interaction of the GTP-bound Arf-like GTPase ARL6 with the BBSome, a critical step in the recruitment of the BBSome to membranes .
tRNA-guanine(15) transglycosylase, C1 domain (TGT_C1)
Type: Domain

This short region is found in tRNA-guanine transglycosylases (TGT) from Thermococcales and acts as the dimerisation domain of the whole protein .
Transglycosylase PBP1b, N-terminal transmembrane domain (PBP1b_TM)
Type: Domain

This is the N-terminal transmembrane domain of penicillin-binding protein (PBP) transglycosylases, the multi-domain membrane proteins essential for cell wall synthesis that are targeted by penicillin antibiotics. The TM domain is a single helix, several of whose residues lie in close proximity to hydrophobic residues in the TGT domain. The TM helix seems to be necessary for stabilising the protein-membrane interaction, and the resulting orientation limits the interaction between PBPb1 and lipid II in the membrane in a 2D lateral diffusion fashion .
Arabinosyltransferase, C-terminal (Arabino_trans_C)
Type: Domain

Arabinosyltransferase is involved in arabinogalactan (AG) biosynthesis pathway in mycobacteria. AG is a component of the macromolecular assembly of the mycolyl-AG-peptidoglycan complex of the cell wall. This enzyme has important clinical applications as it is believed to be the target of the antimycobacterial drug Ethambutol .

This domain represents the C-terminal extracellular domain that is likely to bind to carbohydrate .
Spermatogenesis-associated protein 6, N-terminal (SPATA6_N)
Type: Domain

This domain is found in the spermatogenesis associated protein 6 (Spata6) from eukaryotes, and is approximately 140 amino acids in length. Spata6 has similarity with the motor domain of kinesin related proteins and the Caenorhabditis elegans neural calcium sensor protein (NCS-2) .
HAUS augmin-like complex subunit 3, N-terminal (HAUS3_N)
Type: Domain

This domain is found in the HAUS augmin-like complex subunit 3 (HAUS3) . The HAUS-augmin complex (made up of eight subunits) interacts with gamma-TuRC, and attenuation of this interaction severely impairs spindle MT generation. The HAUS complex is required for mitotic spindle assembly and for maintenance of centrosome integrity .
DDB1- and CUL4-associated factor 15, WD40 repeat-containing domain (DCAF15_WD40)
Type: Domain

DCAFs, Ddb1- and Cul4-associated factors, are substrate receptors for the Cul4-Ddb1 Ubiquitin Ligase. There are 18 different factors, the majority of which are WD40-repeat-proteins . DDB1- and CUL4-associated factor 15 (DCAF15) is the substrate-recognition component of the DCX(DCAF15) complex, a cullin-4-RING E3 ubiquitin-protein ligase complex that mediates ubiquitination and degradation of target proteins , and acts as a regulator of the natural killer (NK) cells effector functions . Aryl sulfonamide anticancer agents appear to promote binding of DCAF15 to the RNA-recognition motif (RRM) of RBM39, which suggests that derivatives of the aryl-sulfonamides may be used to target other RRM-containing proteins .

This entry represents the WD40 repeat-containing N-terminal domain found in DCAF15 and similar animal proteins.
BROMI, middle region (BROMI_M)
Type: Domain

This entry represents the middle domain of BROMI, which may consist of an α-solenoid.

The Broad-minded family of proteins is essential for the proper response to Sonic hedgehog (Shh) signalling during neural tube development. Members of the Broad-minded family collaborate with cyclin-dependent kinase 20 (CDK20) to regulate the structure of the primary cilium. They are involved in the coordination of the ciliary membrane and axoneme assembly, which is crucial for the activation of the GLI2 transcription factor in response to Shh signalling . It interacts with CCRK/CDK20, which phosphorylates and activates the intestinal cell kinase (ICK)/CILK1 kinase, to regulate the change in direction of the IFT machinery at the ciliary tip. Mutations in this protein in humans cause ciliopathies .
Protein hinderin (Hinderin)
Type: Family

Protein hinderin shares structural similarity to the SMC family members. It interacts with SMC3 and may affect the availability of SMC3 to engage in the formation of multimeric protein complexes .
Plasminogen-binding protein PgbA, C-terminal (PGBA_C)
Type: Domain

This entry represents the C-terminal domain of bacterial proteins that bind plasminogen (PgbA and PgbB). This activity was identified in Helicobacter pylori where it is thought to contribute to the virulence of this bacterium. Both PgbA and PgbB are surface-exposed proteins that mediate binding to plasminogen such that it can be converted into plasmin in the presence of a plasminogen activator .
TBC1 domain family member 30, C-terminal (Tbc1d30_C)
Type: Domain

This entry represents the C-terminal domain of the TBC1 domain family member 30 (Tbc1d30). Tbc1d30 is a GTPase-activating protein (GAP) with broad specificity .
MRN complex-interacting protein (MRNIP)
Type: Family

This family of proteins is found in eukaryotes and includes MRN complex-interacting protein (MRNIP), which plays a role in preventing the accumulation of damaged DNA in cells. It associates with the MRE11-RAD50-NBS1 (MRN) damage-sensing complex and is rapidly recruited to sites of DNA damage. Phosphorylation of a serine promotes nuclear localization of MRNIP .
SGNH hydrolase-type esterase, N-terminal (GxDLY)
Type: Domain

This domain lies upstream of SGNH hydrolase domain (

), but its function is not known. There is a highly conserved GxDLY sequence-motif.
SLS1, first KH domain (Sls1_KH-1)
Type: Domain

This entry represents the first of two KH domains found in the SLS1 protein.

SLS1 is a fungal protein found bound to the mitochondrial inner-membrane . It reacts physically with fungal Kar2p to promote translocation across the endoplasmic-reticulum membrane. This action seems to be mediated via the promotion of the Sec63p-mediated activation of Kar2p's ATPase activity. This indicates that the Sls1p protein is a GrpE-like protein in the endoplasmic reticulum. In S.cerevisiae, the SLS1 gene (ScSLS1) is not essential but is also involved in ERAD and folding .
INO80 complex subunit 3, N-terminal (Iec3_N)
Type: Domain

This entry includes fungal chromatin re-modelling proteins found in one of the chromatin-central complexes, Ino80. The function was identified in Schizosaccharomyces pombe but there is no orthologue in S. cerevisiae . INO80 complex remodels chromatin by shifting nucleosomes and is involved in DNA repair . This entry represents the helical section found at the N-terminal of this group of proteins.
FAM47 family (FAM47)
Type: Family

The function of this family of proteins from metazoa is not known. Human FAM47E localizes the arginine methyltransferase PRMT5 to chromatin and, thus, promotes histone methylation .
Insulin growth factor-like family (IGFL)
Type: Family

This family includes the insulin growth factor-like proteins. These proteins are potential ligands for the IGFLR1 cell membrane receptor .
G protein-regulated inducer of neurite outgrowth, C-terminal (GRIN_C)
Type: Domain

This entry represents the C terminus of the G protein-regulated inducer of neurite outgrowth proteins .
Treslin, M domain (Treslin_M)
Type: Domain

This entry represents the M domain of Treslin, a checkpoint regulator which plays a role in DNA replication preinitiation complex formation . This domain adopts a Ku70-like β-barrel fold which engage in homotypic interactions with MTBP, which is also essential for replication in human cells .

Treslin is the metazoan counterpart of Sld3 from yeast, which are the hub proteins mediating protein associations critical for the helicase formation . Treslin, as Sld3, interacts with TopBP1 in a Cdk2-dependent manner, which then collaborate in the Cdk2-mediated loading of Cdc45 onto replication origins. Treslin and Sld3 differ in their molecular sizes and amino acid sequences, however, they share a conserved Sld3/Treslin domain (STD) . According to their similarities, it has been suggested that helicase activation in mammals has diverged in complexity during evolution from that in yeasts and may involve additional partners that interact with TopBP1 .
FMR1-interacting protein 2 (NUFIP2)
Type: Family

FMR1-interacting protein 2 (NUFIP2, also known as 82-FIP) is an RNA binding protein that shows a cell cycle-dependent intracellular localisation .
Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG)
Type: Family

PAG, or Cbp/PAG (Csk binding protein/phospho-protein associated with glycosphingolipid-enriched microdomains) is a transmembrane protein that has a negative regulatory role in T-cell activation through being an adapter for C-terminal Src kinase, Csk. This family of proteins is found in eukaryotes .
Frog antimicrobial peptide Nigrocin (Nigrocin)
Type: Family

This family includes the antimicrobial peptide Nigrocin which is secreted from frog skin .
Transposon Tn7 transposition protein TnsD, C-terminal (TnsD_C)
Type: Domain

This entry represents the C-terminal domain of TnsD, which is a putative Tn7-like transposition protein type D .
Protein fuseless (Fuseless)
Type: Family

This family includes Drosophila fuseless protein and contains four WXGXW motifs. Fuseless is a transmembrane protein which regulates pre-synaptic calcium channels .
DC-UbP/UBTD2, N-terminal domain (DC-UbP/UBTD2_N)
Type: Domain

This domain can be found in the N terminus of DC-UbP/UBTD2. It has a novel structural fold and acts as a Ub-binding domain (UBD) but with low affinity .
Leucine-rich repeat-containing protein 37, N-terminal (LRRC37_N)
Type: Domain

This domain is found in vertebrates, and is approximately 70 amino acids in length. The function of this domain is unknown.
Translin-associated factor X-interacting protein 1, N-terminal (TSNAXIP1_N)
Type: Domain

This domain is found at the N terminus of translin-associated factor X-interacting protein, a protein which may play a role in spermatogenesis .
Domain of unknown function DUF4685 (DUF4685)
Type: Domain

This domain is found in vertebrates, and is typically between 106 and 131 amino acids in length. There are two conserved sequence motifs: SGE and VRF.
Domain of unknown function DUF4683 (DUF4683)
Type: Domain

This domain is found in Neurite extension and migration factor, Transcription factor Gibbin and DNA polymerase zeta catalytic subunit from eukaryotes. It is typically between 384 and 400 amino acids in length.