SII-SWORD/CoKE huggingface dataset:
ASCIZ, forth C2H2 zinc finger domain (Znf_C2H2_ASCIZ_4th)
Type: Domain

This domain is found in the human ATM interactor (also known as ATM/ATR-substrate CHK2-interacting zinc finger protein (ASCIZ)) and related proteins from animals. These proteins are transcription factors that are essential for cell survival and the formation of RAD51 foci, a response to methylating DNA damage . They are also involved in the regulation of ATM (ataxia telangiectasia mutated) kinase activity, particularly in the absence of DNA damage, potentially by stabilising ATM . ASCIZ is predicted to contain four zinc finger domains. This entry represents the forth zinc finger domain.

C2H2-type (classical) zinc fingers (Znf) were the first class to be characterised. They contain a short β-hairpin and an α-helix (β/β/α structure), where a single zinc atom is held in place by Cys(2)His(2) (C2H2) residues in a tetrahedral array. C2H2 Znf's can be divided into three groups based on the number and pattern of fingers: triple-C2H2 (binds single ligand), multiple-adjacent-C2H2 (binds multiple ligands), and separated paired-C2H2 . C2H2 Znf's are the most common DNA-binding motifs found in eukaryotic transcription factors, and have also been identified in prokaryotes . Transcription factors usually contain several Znf's (each with a conserved β/β/α structure) capable of making multiple contacts along the DNA, where the C2H2 Znf motifs recognise DNA sequences by binding to the major groove of DNA via a short α-helix in the Znf, the Znf spanning 3-4 bases of the DNA . C2H2 zinc fingers can also bind to RNA and protein targets .

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.
DHX34-like, C2H2-type zinc finger (DHX34_Znf-C2H2)
Type: Domain

This C2H2-type zinc finger domain is found at the C-terminal end of human Probable ATP-dependent RNA helicase DHX34 and similar animal proteins. DHX34 is required for nonsense-mediated decay degradation of mRNA transcripts containing premature stop codons .
Diacylglycerol kinase iota-like domain (DGKI-like_dom)
Type: Domain

This domain is found in Diacylglycerol kinase iota (DGKI), zeta (DGKZ) and in DGK2. Diacylglycerol kinase converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids . This domain is found C-terminal to the catalytic (

) and accessory (

) domains.
At3g06530-like, ARM-repeats domain (ARM_At3g06530)
Type: Domain

This is a region of armadillo-like repeats found in the uncharacterised protein At3g06530 from Arabidopsis thaliana and similar plant sequences. This region is normally found associated with

.
AVO1/Sin1, ubiquitin-like domain (UBL_AVO1/Sin1)
Type: Domain

This domain is found in the Target of rapamycin complex 2 subunit AVO1, subunit sin1 and related proteins from fungi. AVO1 is a component of TORC2, which regulates cell cycle-dependent polarisation of the actin-cytoskeleton and cell wall integrity . Sin1 is a component of the SAPK pathway and the mechanistic target of rapamycin complex 2 (mTORC2) . Within the mTORC2 complex, sin1 acts as a substrate adapter which recognises and binds AGC protein kinase family members for phosphorylation by tor1 . This domain shares a significant sequence similarity with ubiquitin-like domains and it is predicted to adopt similar structure.
B-cell receptor CD22, first Ig-like domain (Ig_CD22)
Type: Domain

This is the first immunoglobulin-like (Ig-like) domain found in human B-cell receptor CD22 and similar sequences from vertebrates. CD22 plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and trafficking to bone marrow . CD22 binds to alpha 2,6-linked sialic acid residues of surface molecules such as CD22 itself, CD45 and IgM in a cis configuration as well as ligands on other cells as an adhesion molecule in a trans configuration .
Bacterial deaminase MsddA-like domain (MsddA-like)
Type: Domain

This domain is found in bacterial deaminases. Some proteins containing this domain also contain RHS repeats.
YxkI, PH domain (PH_YxkI)
Type: Domain

This entry represents a bacterial PH domain found in a group of proteins containing a Peptidase M48 domain, including the putative membrane metalloprotease YxkI.
Baseplate tube protein p140 (Baseplate_tube_p140)
Type: Family

This entry represents the bacteriophage Baseplate tube protein and related proteins, involved in the assembly of the simplified baseplate structure of bacteriophages. Baseplate tube protein p140, interacts with other proteins including the p132 collar protein ring and components of the cone, namely DTP-pb9 and BHP-pb3, to form a crucial part of the phage's baseplate. This structure is essential for the phage to attach to and penetrate the host bacterial cell wall during infection .
Holin, bacteriophage (Holin_phage)
Type: Family

This entry represents a family of bacteriophage holin proteins. Holins are small membrane proteins that control the timing of host cell lysis during the phage lytic cycle. Holins typically have 2-4 transmembrane helices. The exact mechanism of how holins trigger cell lysis is not fully understood. The holin family is found in phages that infect actinobacteria, primarily mycobacteria and gordonia species.
Baseplate protein gp9-like, C-terminal (Baseplate_gp9_C)
Type: Domain

This entry represents the C-terminal domain of Baseplate protein gp9 from Bacteriophage T4, a component of the viral baseplate . Gp9 connects the long tail fibers of the virus to the baseplate and triggers tail contraction after viral attachment to a host cell. The protein is active as a trimer, with each monomer being composed of three domains. The C-terminal domain is thought to be essential for trimerisation and is organised into an eight-stranded antiparallel β-barrel, which was found to resemble the 'jelly roll' fold found in many viral capsid proteins . Together with gp11, gp10 initiates the assembly of wedges that then go on to associate with a hub to form the viral baseplate .

This domain is also found in the Baseplate wedge protein gp10 which connects the short tail fibres to the baseplate .
Diacylglycerol kinase theta, RNA-binding domain (DGKtheta_RBD)
Type: Domain

This domain is found in human Diacylglycerol kinase theta (DGKtheta) and similar metazoan proteins. This domain is found between

and

and is predicted to adopt an RNA-binding domain (RBD)-like fold.

DGKtheta converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids. DGK-theta has been shown to be the isoform responsive to alpha-thrombin stimulation that leads to the production of two lipid second messengers in the nucleus . DGKtheta has also been shown to activate the transcription of the cAMP-dependent CYP17 gene in the human adrenal cortex .
AprA-like, MT2-like domain (AprA-like_MT2)
Type: Domain

This entry represents a methyltransferase domain (MT2-like) found in AprA Methyltransferase 1 from Moorena bouillonii (

) and similar sequences from bacteria and lower eukaryotes. AprA is an S-adenosylmethionine and Fe3+-dependent dimethyltransferase that acts in the initiation steps of apratoxin A biosynthesis .

This domain is also found in SxtA Methyltransferase from Cylindrospermopsis raciborskii which is involved in the saxitoxin biosynthetic pathway . SxtA MT, and AprA MT1 differ in their metal selectivity (Mn2+ and Fe3+, respectively) and extent of methylation (one and two methyl transfers, respectively) . The structures of these enzymes,

and

, reveal the structural basis for the difference in the control of methylation extent.
AprA-like, N-terminal domain (AprA-like_N)
Type: Domain

This entry represents a domain found N-terminal in AprA Methyltransferase 1 from Moorena bouillonii (

) and similar bacterial sequences. AprA is an S-adenosylmethionine and Fe3+-dependent dimethyltransferase that acts in the initiation steps of apratoxin A biosynthesis . This domain has similarity to winged helix domains.

This domain is also found in SxtA Methyltransferase from Cylindrospermopsis raciborskii which is involved in the saxitoxin biosynthetic pathway . SxtA MT, and AprA MT1 differ in their metal selectivity (Mn2+ and Fe3+, respectively) and extent of methylation (one and two methyl transfers, respectively) . The structures of these enzymes,

and

, reveal the structural basis for the difference in the control of methylation extent.
AprA, winged helix domain (WH_AprA)
Type: Domain

This entry represents a domain found in AprA Methyltransferase 1 from Moorena bouillonii (

) and similar bacterial sequences. AprA is an S-adenosylmethionine and Fe3+-dependent dimethyltransferase that acts in the initiation steps of apratoxin A biosynthesis . This domain is found immediately C-terminal to

, and also has similarity to winged helix domains.

This domain is also found in SxtA Methyltransferase from Cylindrospermopsis raciborskii which is involved in the saxitoxin biosynthetic pathway . SxtA MT, and AprA MT1 differ in their metal selectivity (Mn2+ and Fe3+, respectively) and extent of methylation (one and two methyl transfers, respectively) . The structures of these enzymes,

and

, reveal the structural basis for the difference in the control of methylation extent.
Cohesin subunit SCC3/SA, HEAT-repeats domain (HEAT_SCC3-SA)
Type: Domain

This entry includes subunits of the cohesin complex - a protein complex required for sister chromatid cohesion in eukaryotes, including SA-1, SA-2 and SA-3 from vertebrates (STAG1-3), the orthologue from S.pombe Psc3 and the homologue from Arabidopsis, SCC3 . This entry represents a central region of these proteins containing HEAT repeats, which may be involved in binding Scc1 subunit and nucleic acids. In STAG3, mutations in this region cause male infertility due to meiotic arrest .
Fibronectin-III type-like domain, archaea (Fn3_arc)
Type: Domain

This domain is found at the C-terminal end of a group of proteins from halobacteria. It is predicted to show structural similarity to the fibronectin type III domain.
Coilin, tudor domain (Tudor_Coilin)
Type: Domain

This entry represents the C-terminal domain of coilin which is an atypical Tudor domain that contains large unstructured loops .

Coilin is a nuclear phosphoprotein that serves as an assembly centre in Cajal bodies (CBs) and has a role in small nuclear ribonucleoprotein (snRNP) biogenesis, involved in the modification and assembly of nucleoplasmic snRNPs . Coilin also acts to repress polymerase I activity in response to cisplatin-induced DNA damage, which could indicate a link between the DNA damage response and the inhibition of rRNA synthesis .
Microprotein, archaea (Microp_archaea)
Type: Family

This family includes a group of short archaeal proteins encoded by small open reading frames (sORFs) .
Cold shock domain-containing protein E1, CSD domain (CSDE1)
Type: Domain

This entry represents several divergent cold-shock domains found in Cold shock domain-containing protein E1 (CSDE1). These are RNA-binding proteins that play a crucial role in translationally coupled mRNA turnover . Members are involved in the cytoplasmic deadenylation, translation, and decay processes, particularly interacting with the mCRD domain of FOS mRNA. They are essential for the efficient formation of stress granules, cellular structures that form in response to environmental stress, aiding in the storage and management of untranslated mRNAs . Additionally, the human variant is implicated in the internal initiation of translation of human rhinovirus RNA, suggesting a role in microbial infection responses.
Major capsid protein, crassvirus (Crass_capsid)
Type: Family

This entry represents the major capsid protein found in crassviruses. The major capsid protein self-assembles to form an icosahedral capsid. In the bacteriophage crAss001, the capsid has a T=9 symmetry and is about 77 nm in diameter. The major capsid protein displays an HK97-like fold with an insertion domain that protrudes at the capsid surface .
Diels-Alderase, N-terminal domain (DA_N)
Type: Domain

This domain is found at the N-terminal of a number of fungal Diels-Alderases, including cghA, eqx3, poxQ and phmD. In cghA, this domain binds substrate alongside a similarly folded C-terminal domain and achieves catalysis by restricting the movement of the straight-chain substrate into a conformation that facilitates a stereoselective cycloaddition reaction . This domain is also found at the N-terminal of the quinolone epoxide rearrangement proteins PenF from Penicillium thymicola and AsqO from Emericella nidulans .

Diels-Alderases catalyse different pericyclic [4+2] cycloaddition reactions that synthesise potential pharmaceuticals and mycotoxins . These enzymes consist of two similar β-barrel domains with arrangement similar to AttH. Both domains share some similarity to lipocalins.
Ribonuclease II-like, barrel domain (RNase_II_barrel)
Type: Domain

This domain is found at the N-terminal of ribonuclease II (RNR1) from Arabidopsis thaliana and similar sequences from plants and cyanobacteria. This domain may have an RNA-binding activity.

RNR1 is a 3'-5' exoribonuclease that catalyses 3' maturation of chloroplast and mitochondrion ribosomal RNAs. It degrades short nucleotidic extensions to generate the mature 3'-ends . It is involved in the maturation of 23S, 16S and 5S rRNAs.
Ribonuclease II-like, double HTH domain (HTH_RNase_II)
Type: Domain

This entry represents a double HTH domain found in a set of ribonuclease II proteins mainly found in bacteria and plants .

RNR1 is a 3'-5' exoribonuclease that catalyses 3' maturation of chloroplast and mitochondrion ribosomal RNAs. It degrades short nucleotidic extensions to generate the mature 3'-ends . It is involved in the maturation of 23S, 16S and 5S rRNAs.
CUL7/CUL9, ARM-repeats domain (ARM_CUL7_CUL9)
Type: Domain

This domain is found in human Cillin-7 (CUL7), Cullin-9 (CUL9) and related proteins. CUL7 is a core component of the 3M and Cul7-RING(FBXW8) complexes, which mediates the ubiquitination of target proteins . CUL9, a core component of the Cul9-RING ubiquitin-protein ligase complex, acts downstream of the 3M complex, which inhibits the CUL9 activity, leading to prevent ubiquitination of BIRC5 . This domain is composed of ARM repeats.
CWZF3/5/7, THD domain (THD_CWZF3/5/7)
Type: Domain

This domain is found at the C-terminal end of Cysteine-tryptophan domain-containing zinc finger proteins 3, 5 and 7 from Oryza sativa and related plant proteins. This domain has a significant similarity to the THD domain (TPRL with Handle Region Dimerisation Domain) of AFF4, which is a scaffold protein that recruits other components of Super elongation complex. The THD domain is composed of α-helices and is involved in dimerisation. The domain represented by this entry is predicted to adopt similar structure and similarly could be involved in dimer formation.

Members of this entry contain a CW-type zinc finger domain (

), which is implicated in the recognition of methylated histones, particularly histone H3 lysine 4 (H3K4me). These proteins are involved in chromatin modification and gene expression regulation. They can bind to specific methylated forms of histone H3, facilitating the recruitment of various effectors to mediate gene expression . Some members act as transcriptional activators, directly binding to DNA sequences to regulate target gene transcription, thereby influencing cellular processes such as the regulation of grain size in plants . They are also capable of promoting active chromatin states by increasing levels of specific histone modifications at target loci.
CSLinker motif (CSLinker)
Type: Conserved_site

The CSLinker motif is found in the pyrenoid linker protein from Chlorella sorokiniana . It binds to the large subunit of Rubisco (RbcL) and is involved in phase separation of Rubisco in the pyrenoid, a sub-compartment of the chloroplast that is part of the CO2-concentrating mechanism in algae. The motif consists of an α-helical region of approximately 10 residues that interacts with the N-terminal region of RbcL via two salt bridges and hydrophobic interactions. The key residues involved in binding are highly conserved. CSLinker is able to phase separate Rubisco from various species across the green lineage, including some plants, demonstrating its potential for engineering pyrenoids in crop plants to enhance CO2 fixation.
CT021-like (CT021-like)
Type: Family

This entry represents the hypothetical protein CT021 from Chlamydia trachomatis (

) and related proteins. The structure of this protein (

) consists of β-meander that folds into an open β-barrel packed on a side with two α-helices. It structurally resembles the N-terminal domain of Sigma-E factor regulatory protein rseB (

).
CYK3, C-terminal Ig-like domain (Ig_CYK3_C)
Type: Domain

This domain is found at the C terminus of yeast Cytokinesis protein 3 (CYK3) and related fungal proteins. CYK3 is involved in cytokinesis by recruiting INN1 to the bud neck. It is found in association with the actin ring and the mother-bud neck . This domain is predicted to fold into a β-sandwich with an Ig-like topology.
Cyanophage outer membrane protein-like, beta-barrel domain (Phage_OMP)
Type: Domain

This entry includes a family of small uncharacterised membrane bound β-barrel-like proteins found in cyanophage. The putative membrane β-barrel is incomplete, composed of only 6 β-strands. However, the proteins form a confident homodimer composed of a flattened 12 stranded β-barrel. The proteins likely contain an N-terminal signal peptide that is cleaved during membrane insertion.
Cysteinyl-tRNA ligase, anticodon binding domain (CysS_C)
Type: Domain

This entry represents the C-terminal anticodon binding domain from Cysteinyl-tRNA ligase mainly from bacteria and archaea, but also from plants. The entry also includes the C-terminal domain of YqeB from B. subtilis (

).

Cysteine-tRNA ligase (also known as Cysteinyl-tRNA synthetase) (

) is an alpha monomer and belongs to class Ia . It is highly specific despite not possessing the amino acid editing activity characteristic of many other tRNA ligases .
Cytochrome c-type biogenesis protein H, Ig-like domain (Ig_CycH)
Type: Domain

This entry represents the immunoglobulin-like domain found in cytochrome c-type biogenesis protein CycH from bacteria. CycH is involved in the attachment of heme to cytochrome c apoproteins . This entry also represents the Ig-like domain of the uncharacterised protein AQ_1241 from Aquifex aeolicus. The function of this domain is unknown.
Cytochrome c-type biogenesis protein H, TPR domain (TPR_CcmH_CycH)
Type: Domain

This entry represents the TPR domain found in cytochrome c-type biogenesis proteins CcmH and CycH from bacteria. These proteins are membrane-anchored thiol-oxidoreductases that are essential in the maturation of c-type cytochromes . In the case of CycH, it has been hypothesised that this TPR domain interacts with other proteins in order to mediate the assembly of c-type cytochromes . This entry also represents a TPR domain found in other proteins such as NrfG, NrfF.
DAAF9, CobW C-like domain (DAAF9_CobW_C)
Type: Domain

This domain is found in the human DAAF9 and related proteins. It binds newly synthesised outer dynein arm complexes . It shares a significant sequence similarity with the C-terminal domain of CobW and it is predicted to adopt a similar structure consisting of a flat antiparallel β-sheet and two α-helices packed on it.

Dynein axonemal assembly factor 9 DNAAF9 (Shulin) is a dynein axonemal assembly factor that regulates the transport and activation of outer dynein arms (ODAs) in cilia. It binds and inhibits ODAs in the cytoplasm, maintaining them in a closed conformation until they are delivered to cilia. It may interact with ARL-3. This GTP-dependent interaction might ensure spatiotemporal control of dynein function, critical for proper ciliary beating in multiciliated cells such as airway epithelia. Dysregulation of DNAAF9 is linked to primary ciliary dyskinesia (PCD), characterised by impaired mucociliary clearance and respiratory defects .
DCDC1, second doublecortin-like domain (DCX2_DCDC1)
Type: Domain

This is the second doublecortin-like domain (DCX2) of DCDC1. This domain shows an ubiquitin-like fold.

Doublecortin domain-containing protein 1 (DCDC1), also known as DCDC5, is a member of doublecortin (DCX) family. It is a microtubule-associated protein (MAP) with stable double tandem DCX repeats of ubiquitin-like tertiary fold. DCDC1 is expressed during mitosis and is involved in coordinating late cytokinesis. DCDC1 interacts with cytoplasmic dynein and Rab8, as well as with the Rab8 nucleotide exchange factor Rabin8 .
DBL homology domain, fungi (DH_2_fung)
Type: Domain

This domain is found in uncharacterised fungal proteins. It shares significant sequence similarity to known DBL homology domains (DH-domains) and it is predicted to adopt similar structure. Proteins containing this domain also contain a PH-domain located upstream the DH-domain and are likely members of the Dbl family of guanine nucleotide exchange factors.
Tail tube terminator protein p142 (Phage_tail_terminator_p142)
Type: Family

The Tail Tube Terminator Protein family is involved in the assembly of bacteriophage tail structures. Members of this family, such as the Tail Tube Terminator Protein p142, are responsible for capping the tail tube during its polymerisation, ensuring that it reaches the correct length . This capping function is crucial for the proper formation of the phage tail, which is essential for the phage's ability to infect host bacteria by facilitating the injection of genetic material.