SII-SWORD/CoKE huggingface dataset:
Calcyphosin-2, PH domain (CAYP2_PH)
Type: Domain

This entry represents the PH domain found in calcyphosin-2 proteins. The domain is found N-terminal to an EF-hand calcium-binding domain (

).

Calcium binding signalling proteins are characterised by their ability to bind calcium, which suggests a role in cellular signalling events. While some members are hypothesised to function as regulatory proteins rather than as calcium buffers or transport proteins, the exact mechanisms by which they influence signalling pathways remain to be fully elucidated. The potential regulatory function implies that these proteins may interact with other cellular components to modulate processes that are sensitive to calcium levels, which is a common second messenger in many signalling cascades. These proteins usually contain EF-hand domains .
CBASS inhibitor Acb3 (Acb3)
Type: Family

This entry represents the Acb3 family of phage proteins that inhibit bacterial CBASS defence systems. Acb3 wraps around the CD-NTase enzyme and makes extensive contact with both the nucleotidyltransferase active site and ligand binding domain. Despite low sequence similarity between different CD-NTases, Acb3 can inhibit diverse CBASS systems and even human cGAS.
CCDC174, alpha/beta GRSR domain (CCDC174_GRSR)
Type: Domain

This entry represents the α/β GRSR domain in Coiled-coil domain-containing protein 174 (CCDC174) and related proteins. This domain is predicted to adopt a minimal structure that is topologically similar to the classical C2H2 zinc fingers but lacks zinc coordinating residues. Proteins with this domain have a highly conserved GRSR sequence motif, after which the domain was named.

CCDC174 is a ubiquitous protein which is restricted to the cell nucleus and co-localises with EIF4A3 . Mutations in this gene have been linked to a syndrome characterised by hypotonia (low muscle tone) and psychomotor developmental delay .
CFAP46, N-terminal TPR repeat (CFAP46_TPR)
Type: Repeat

This region of tetratricopeptide (TPR)-like repeats is found at the N-terminal in human Cilia- and flagella-associated protein 46 (CFAP46) and similar eukaryotic proteins.

CFAP46 is a part of the central apparatus of the cilium axoneme and plays a role in cilium movement and thereby cell motility .

The tetratrico peptide repeat region (TPR) is a structural motif present in a wide range of proteins . It mediates protein-protein interactions and the assembly of multiprotein complexes . The TPR motif consists of 3-16 tandem-repeats of 34 amino acids residues, although individual TPR motifs can be dispersed in the protein sequence. Sequence alignment of the TPR domains reveals a consensus sequence defined by a pattern of small and large amino acids. TPR motifs have been identified in various different organisms, ranging from bacteria to humans. Proteins containing TPRs are involved in a variety of biological processes, such as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neurogenesis and protein folding.

The X-ray structure of a domain containing three TPRs from protein phosphatase 5 revealed that TPR adopts a helix-turn-helix arrangement, with adjacent TPR motifs packing in a parallel fashion, resulting in a spiral of repeating anti-parallel α-helices . The two helices are denoted helix A and helix B. The packing angle between helix A and helix B is ~24 degrees within a single TPR and generates a right-handed superhelical shape. Helix A interacts with helix B and with helix A' of the next TPR. Two protein surfaces are generated: the inner concave surface is contributed to mainly by residue on helices A, and the other surface presents residues from both helices A and B.
CFAP65, eight Ig-like domain (Ig_CFAP65_8th)
Type: Domain

This entry represents the eight Ig-like domain of CFAP65 and related sequences.

Cilia-Flagella-Associated Protein 65 (CFAP65) is involved in the structural and functional integrity of cilia and flagella. This protein is implicated in the process of flagellar formation and is essential for proper sperm motility, suggesting a role in reproductive biology. CFAP65's function in flagellar assembly indicates its importance in the motility and sensory functions of cilia and flagella across different species .
HOIL-1/Sharpin, LUBAC thetering domain (HOIL-1/Sharpin_LTM)
Type: Domain

This entry describes the Linear Ubiquitin Chain Assembly Complex (LUBAC)-tethering domain (LTM) found in the two LUBAC accessory subunits HOIL-1L and SHARPIN in vertebrates. These domains from both proteins heterodimerise and fold into a single globular domain. stabilising the multi-protein E3 ubiquitin ligase LUBAC complex .
MAP kinase-activating death domain protein, C-terminal PH-like domain (PH_MADD)
Type: Domain

This entry represents a C-terminal pleckstrin homology (PH)-like domain found in human MAP kinase-activating death domain (MADD) and similar animal proteins. MADD proteins function as adaptor proteins in cell death and MAP kinase signalling pathways .
CFAP65, seventh Ig-like domain (Ig_CFAP65_7th)
Type: Domain

This entry represents the seventh Ig-like domain of CFAP65 and related sequences.

Cilia-Flagella-Associated Protein 65 (CFAP65) is involved in the structural and functional integrity of cilia and flagella. This protein is implicated in the process of flagellar formation and is essential for proper sperm motility, suggesting a role in reproductive biology. CFAP65's function in flagellar assembly indicates its importance in the motility and sensory functions of cilia and flagella across different species .
CHMP7, winged helix domain (CHMP7_WHD)
Type: Domain

This entry represents the winged helix domain in CHMP7 and similar animal proteins.

Charged multivesicular body protein 7 (CHMP7) is an endosomal sorting complex required for transport (ESCRT)-III-like protein required to recruit the ESCRT-III complex to the nuclear envelope during late anaphase. It plays a role in the endosomal sorting pathway.
CPL3, ARM repeat (ARM_CPL3)
Type: Domain

This entry represents an ARM repeat in RNA polymerase II C-terminal domain phosphatase-like 3 (CPL3). Its precise function is unknown.

CPL3 plays an important role in plant development and defence mechanisms of Arabidopsis thaliana. CPL3 acts as a negative regulator of immune gene expression and immunity to pathogen infections . It directly interacts with DELLA proteins, which are core suppressors in the gibberellic acid signalling pathway and promotes DELLA protein stability by inhibiting its degradation by the 26S proteasome .
Cuticlin, C-terminal domain (CUT_C)
Type: Domain

This entry represents the C-terminal Ig-like domain of Cuticlin proteins from Caenorhabditis elegans. This model doesn't capture the C-terminal strand that, in some of the proteins, is separated by a large irregular insertion.

Cuticlin is a component of the cuticles, which contributes to the formation of extracellular envelopes protecting the organism from the environment . It also plays a role in alae formation in dauer larvae .
Cux, N-terminal domain (Cux_N)
Type: Domain

This domain is found at the N-terminal in Homeobox protein cut-like (Cux) 1 and 2 and similar eukaryotic proteins. This domain is predicted to adopt an α-helical configuration.

Cux1 (also known as Cutl1) and Cux2 are transcription factors involved in the control of neuronal differentiation in the brain. They regulate dendrite development, branching, and synaptogenesis, particularly in cortical layers II-III, and play a role in cell cycle progression . Cux1 and Cux2 proteins carry distinct biochemical functions. Cux2 and Cux1 can perform the CCAAT-displacement activity. However, Cux2 is unlikely to execute transcriptional regulatory functions that require stable interaction with DNA . In fungi, Cux1 is known as CASP (COY1) and may also be involved in intra-Golgi transport .

Cux proteins contain an N-terminal autoinhibitory domain, a coiled-coil region, three CUT domains (C1, C2, C3), a homeodomain, and a C-terminal repression domain . The CUT domains mediate DNA binding with distinct affinities and kinetics depending on their combination, while the homeodomain further contributes to DNA recognition. Cux1 is expressed in several isoforms due to alternative splicing and proteolytic processing. The shorter p110 Cux1 isoform, generated by proteolytic cleavage, lacks the N-terminal region and has different DNA binding and regulatory properties.
DAAF9, domain 2 (DAAF9_2)
Type: Domain

This domain is found in DAAF9 and related proteins. This domain is found C-terminal to

which is also predicted to show an α-β configuration.

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 .
PRP28/DDX23-like, helical domain (PRP28/DDX23-like_helical)
Type: Domain

This short domain is found in DDX23, Pre-mRNA-splicing ATP-dependent RNA helicase (PRP28) and related proteins. This domain adopts an α-helical structure and is usually associated with

and

.

The PRP28 and DDX23 proteins are ATP-dependent RNA helicases that play a crucial role in pre-mRNA splicing. These helicases are involved in destabilising the U1/5'-splice site duplex, allowing effective competition for the 5'-splice site by the U6 snRNA, thereby facilitating the switch between U1 and U6 at the 5'-splice site. Additionally, they may act to unwind the U4/U6 base-pairing interaction within the U4/U6/U5 snRNP, aiding the first covalent step of splicing. The phosphorylated form of some of these proteins is required for spliceosomal B complex formation and helps suppress the formation of aberrant R-loops during transcription. They are components of the U5 snRNP and the U4/U6-U5 tri-snRNP complexes, interacting with various other spliceosomal proteins .
Microtubule-associated protein 1A/B/S-like, MBL-like domain (MAP1A/B/S-like_MBL)
Type: Domain

This domain is found in the Microtubule-associated proteins MAP1B, MAP1A, MAP1S and related animal proteins. MAP1B is required for proper microtubule dynamics and plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension . MAP1S mediates aggregation of mitochondria resulting in cell death and genomic destruction . The domain represented by this entry has a weak sequence similarity to members of the metallo-beta-lactamase superfamily and is predicted to adopt a very similar structure.
Decapeptide repeat (Decapeptide)
Type: Repeat

This entry corresponds to a region composed of a 10 residue repeat that forms an α-helical solenoid structure found in uncharacterised eukaryotic proteins and putative IcmE proteins in bacteria.
Dep-1, third Fn3-like domain (Fn3_Dep-1_3rd)
Type: Domain

This entry represents the third Fn3-like domain.

This domain is found in the Receptor-type tyrosine-protein phosphatase Dep-1 from Caenorhabditis elegans and related proteins. Dep-1 is involved in the dephosphorylation of the receptor let-23 and the β-integrin subunit pat-3. It is involved in the regulation of the cell fate during the development of the vulva and the excretory system . It is also involved indirectly in the negative regulation of let-23 signalling and vulval induction . Dep-1 is a multidomain protein which is predicted to contain a number of Fn3-like domains arranged in tandem.
Mechanosensitive channel protein 2/3, transmembrane domain (MSL2/3_TM_dom)
Type: Domain

This domain is found in Mechanosensitive ion channel protein 2 and 3 from Arabidopsis thaliana (MSL2/3) and similar plant sequences. MSL2/3 control plastid size, shape, and perhaps division during normal plant development by altering ion flux in response to changes in membrane tension . This domain is predicted to contain five transmembrane helices and is found N-terminal to

and

.
Diatom pyrenoid component 1, conserved motif (DPC1)
Type: Conserved_site

DPC1 is localised at the pyrenoid matrix/stroma interface in diatoms . This entry represents a conserved motif found in DPC1 and its homologues. The function is currently unknown but could be a short linear motif involved in a protein-protein interaction.
Moderate conductance mechanosensitive channel YbiO-like, transmembrane helix 1 (YbiO-like_TM1)
Type: Domain

This entry represents the first transmembrane helix (TM1) domain of Moderate conductance mechanosensitive channel YbiO from Moderate conductance mechanosensitive channel YbiO and similar small conductance mechanosensitive channels (MscS) found in proteobacteria. YbiO protects cells against hypoosmotic stress when highly overexpressed. Members of this group of proteins assemble to a homo-heptameric complex . Each monomer consists of a N-terminal transmembrane region and a large cytoplasmic segment composed of a five-stranded antiparallel β-sheet (middle/second) domain and a C-terminal α/β-domain . The N-terminal region consists of three membrane spanning helices (TM1, TM2 and TM3). In the heptamer, the permeation pathway is formed by the packing of TM3s, flanked by TM1-TM2 helical hairpins .
Diatom pyrenoid component 2 (DPC2)
Type: Domain

This entry represents a conserved motif within DPC2 and its homologues. DCP2 localises to the pyrenoid matrix in diatoms and interacts with Rubisco. It is relatively abundant, suggesting a potential role in matrix assembly/organisation . The region defined here contains multiple HxxYLDxxH motifs, where H means hydrophobic residues.
Diatom pyrenoid component 3 (DPC3)
Type: Family

DPC3 localises to the pyrenoid periphery and co-localises with Shell4. DPC3 may act as an intermediary between the Rubisco matrix and the shell . It has low abundance compared to Shell proteins and shows no structural similarity to Shell proteins.
Diatom pyrenoid component 4, C-terminal motif (DPC4_C)
Type: Conserved_site

This entry represents a small motif found in two copies at the C-terminal of DPC4.

DPC4 localises throughout the pyrenoid matrix in diatoms. Shows matrix-type localisation and interacts with Shell4 and Rubisco but function currently unknown. May have a role in matrix assembly/organisation.
Menorin, C-terminal domain (Menorin_C)
Type: Domain

This entry represents the C-terminal domain of Menorin from C. elegans and related sequences mainly from nematodes. This domain may adopt a β-sandwich fold comprising 14 antiparallel β-strands.

Menorin is involved in generation of neurons and regulation of dendrite extension .
Diatom pyrenoid component 4, N-terminal motif (DPC4_N)
Type: Conserved_site

This entry represents a short N-terminal motif that is found in two copies in DPC4.

DPC4 localises throughout the pyrenoid matrix in diatoms. Shows matrix-type localisation and interacts with Shell4 and Rubisco but function currently unknown. May have a role in matrix assembly/organisation.
Diatom pyrenoid shell (DiatomPyrShell)
Type: Family

Shell proteins form the shell encapsulating the pyrenoid matrix in diatoms, essential for the CO2-concentrating mechanism (CCM) function. Each member contains two predicted β-sheet domains. Shell1/2 (93% identical) form the main structural component. Shell1 can self-assemble into tubes and sheets in vitro. Shell4 is critical for organising the pyrenoid-penetrating thylakoid and shell-matrix interaction but lacks the C-terminal extension found in Shell1/2. Shells 3, 5, and 6 also localise to the pyrenoid periphery, but their specific functions remain unknown. The family is found in stramenopiles, pelagophytes, and haptophytes, all algae with red plastids from secondary endosymbiosis .
Metal transporter CNNM1/2/4, immunoglobulin-like domain (Ig_CNNM1/2/4_N)
Type: Domain

This domain is found at the N-terminal end of human Metal transporter CNNM1/2/4 and similar proteins mainly found in vertebrates. CNNM4 may play a role in sensory neuron functions and in biomineralisation and retinal function .
PH-like domain, RdRP associated (PH_RdRP-assoc)
Type: Domain

This entry represents a PH-like domain found towards the N terminus of some predicted metazoan RNA-dependent RNA polymerases. This domain appears to have similar domain organisation to

found in fungi.
[F-actin]-monooxygenase MICAL1-3-like, Rossman domain (Rossman_Mical)
Type: Domain

This domain is found towards the N terminus of a group of animal monooxygenases that play a crucial role in the regulation of the actin cytoskeleton, including [F-actin]-monooxygenase MICAL1-3 from humans. These enzymes promote the depolymerisation of F-actin by oxidising specific methionine residues on actin, leading to the formation of methionine-sulfoxide, which results in actin filament disassembly and prevents repolymerisation . This domain adopts a Rossman fold.
Mitochondrial chaperone BCS1-like, ATPase lid domain (AAA_lid_BCS1)
Type: Domain

This ATPase lid domain is found at the C-terminal end of human Mitochondrial chaperone BCS1 and similar eukaryotic proteins. BCS1 is a chaperone necessary for the incorporation of Rieske iron-sulfur protein UQCRFS1 into the mitochondrial respiratory chain complex III. It plays an important role in the maintenance of mitochondrial tubular networks, respiratory chain assembly and formation of the LETM1 complex . This domain is normally found immediately C-terminal to [

] and also associated with

.
FAN-like, N-terminal PH domain (FAN-like_PH)
Type: Domain

This entry represents the pleckstrin homology (PH) domain found at the N-terminal of the Factor Associated with Neutral sphingomyelinase activation (FAN) protein and its orthologue BEACH domain-containing protein lvsF in Dictyostelium discoideum. The PH domain binds specifically to phosphatidylinositol 4,5-bisphosphate (PIP2) and is essential for the plasma membrane localisation of FAN. This domain interacts physically and functionally with the adjacent BEACH domain, and both are required for TNF-induced neutral sphingomyelinase activation .

The FAN proteins are involved in coupling the p55 TNF-receptor (TNF-R55/TNFR1) to neutral sphingomyelinase (N-SMASE). This interaction is crucial for the regulation of ceramide production by N-SMASE. The proteins specifically bind to the N-smase activation domain of TNF-R55, suggesting a role in signal transduction pathways associated with TNF-R55. The presence of a BEACH domain indicates potential involvement in vesicular trafficking or membrane dynamics .
Rtel1 helicase, ARCH domain (Rtel1_ARCH)
Type: Domain

This domain is found in Regulator of telomere elongation helicase 1. The ARCH domain follows the N-terminal Rad3-like domain ([

]). The structure of the ARCH domain is predicted to share similarity with the ARCH domain of XPD despite low sequence similarity and to contain a four-stranded antiparallel β-sheet with four α-helices packed on it. This domain contains two large insertions that are not present in XPD. The ARCH domain probably plays a key role by interacting with the DNA translocating strand. Mutation found within this domain also emphasise the importance of the Rtel1 ARCH domain .

Regulator of telomere elongation helicase 1 (Rtel1) is the animal functional analogue of yeast Srs2, which is a DNA helicase and DNA-dependent ATPase involved in DNA repair and checkpoint recovery . Rtel1 is an essential DNA helicase that disassembles a variety of DNA secondary structures to facilitate DNA replication, repair, and recombination processes, and to maintain both telomeric and genomic stability . It is recruited by Trf2 to telomeres in S phase to promote T-Loop unwinding . It is also required for the export and the correct cytoplasmic trafficking of the small nuclear (sn) RNA pre-U2, a component of the major spliceosome complex . Human Rtel1 is implicated in the etiology of Dyskeratosis congenital (DC, is an inherited bone marrow failure and cancer predisposition syndrome) . Point mutations in its helicase domains, and truncations which result in loss of its C terminus have been discovered in DC families. It acts as anti-recombinase and antagonises homologous recombination by promoting the disassembly of D loop recombination intermediates in a reaction dependent upon ATP hydrolysis . Rtel1 is also a candidate gene influencing glioma susceptibility .
FKB95-like, N-terminal Kelch domain (Kelch_FKB95)
Type: Domain

This entry represents the N-terminal Kelch domain found in plant proteins that are also associated with a F-box domain (

), such as FKB95 from Arabidopsis thaliana, also known as At1g61540.

FKB95 is a component of SCF (ASK-cullin-F-box) E3 ubiquitin ligase complexes, which mediate the ubiquitination and subsequent proteasomal degradation of target proteins .

The F-box/kelch-repeat proteins are involved in various cellular processes through the formation of SCF (SKP1-cullin-F-box) E3 ubiquitin ligase complexes. These complexes play a crucial role in the ubiquitination and subsequent proteasomal degradation of target proteins, thereby regulating protein turnover. Some proteins are also known to be involved in seed germination. The F-box domain is essential for the interaction with SKP1 (ASK in Arabidopsis), while the kelch repeats may be involved in substrate recognition .
DCK1-like, fourth C2 domain (C2_DCK1_4th)
Type: Domain

This entry represents the C2 domain found in the dock-like protein 1 (DCK1) from Saccharomyces cerevisiae and similar fungal proteins. C2 domains typically function as calcium-dependent membrane-targeting modules. The domain is found in proteins related to membrane trafficking.

DCK1 forms a transient heterodimeric complex with LMO1, functioning as a guanine nucleotide exchange factor (GEF) for the small GTPase RHO5. Under oxidative stress, DCK1, LMO1, and RHO5 translocate to the mitochondria, where they promote cell death. This signalling module also regulates mitochondrial turnover through mitophagy during nitrogen starvation and contributes to cell wall integrity signalling .
Deubiquitinating enzyme, PH domain (DeUb_enz_PH)
Type: Domain

This entry represents the PH domain of a group of uncharacterised fungal proteins that contain a peptidase C48 domain (

). This suggests that these proteins may overall function as deubiquitinating enzymes.
PH-like domain, fungal (PH_25)
Type: Domain

This entry represents a PH domain found in uncharacterised actinomycete proteins.
RdRP-like, PH domain (PH_RdRP)
Type: Domain

This entry represents a PH-like domain found at the N-terminal in a group of predicted RNA-dependent RNA polymerases from actinomycetes that also contain

.
SH3b, T C-terminal domain (SH3b_T_C)
Type: Domain

This domain is found twice towards the C-terminal end of the staphylococcal phage protein

(IPLA5_0029) and in similar peptidoglycan-degrading enzymes mainly from bacteriophages. This domain, found associated with

and

in some members of this group, is involved in the binding of ligands at the bacterial surface.
GPCPD1-like, C2 domain (C2_GPCPD1)
Type: Domain

This entry represents the C2 domain in GPCPD1 and related proteins such as GDE1 its orthologue in fungi. C2 domains are protein structural domains involved in targeting proteins to cell membranes, often in a calcium-dependent manner. This domain likely helps localise the phosphodiesterase activity to cellular membranes where their glycerophosphocholine substrates are found.

The Glycerophosphocholine phosphodiesterase (GPCPG1) proteins are involved in the hydrolysis of intracellular glycerophosphocholine into glycerol-phosphate and choline. This process is crucial for the synthesis of phosphatidylcholine and the utilisation of glycerophosphocholine as a phosphate source. Some of these proteins may also play a role in the negative regulation of skeletal muscle differentiation, independent of their enzymatic activity. Additionally, certain proteins can utilise glycerophosphoinositol as a substrate .