SII-SWORD/CoKE huggingface dataset:
Type I Thoeris inhibitor Tad4-like (Tad4-like)
Type: Family

This entry represents the Tad4 family of phage proteins that inhibit the bacterial Type I Thoeris defence system. Tad4 binds directly to ThsB and blocks its active site via a conserved loop region, preventing production of the immune signalling molecule gcADPR. Interestingly, Tad4 can also bind and inhibit plant and human TIR domain proteins including BdTIR and SARM1. These proteins form a small helical bundle domain structure. This family also includes bacterial prophages.
Type I Thoeris inhibitor Tad6-like (Tad6-like)
Type: Family

This entry represents the Tad6 family of phage proteins that inhibit the bacterial Type I Thoeris defence system. Like Tad3 and Tad4, Tad6 directly blocks the active site pocket of ThsB via a conserved loop region that interacts with the catalytic residues. Mutation of this loop impairs the anti-Thoeris function. This family also includes bacterial prophages.
Type II Thoeris inhibitor Tad8-like (Tad8-like)
Type: Family

This entry represents the Tad8 family of phage proteins that inhibit the bacterial Type II Thoeris defence system. Tad8 forms a homodimer that binds to the Macro domain of the ThsA protein, inserting loops that occupy the His-ADPR binding pocket and prevent recognition of the immune signalling molecule. This family also includes bacterial prophages.
UGP3-like, C-terminal hexapeptide repeats (Hexapep_UGP3_C)
Type: Domain

This region of hexapeptide repeats is found at the C-terminal end of UTP--glucose-1-phosphate uridylyltransferase 3, chloroplastic from Arabidopsis thaliana (UGP3) and similar plant proteins. UGP3 is involved in the biosynthesis of sulfolipids in the chloroplast. It catalyses the first committed step in sulfolipid biosynthesis .
Phage zinc binding (Zn-bd_phage)
Type: Family

This entry represents a family of uncharacterised phage proteins that likely binds to zinc.
Phage zinc binding 6 (Zn-bd_phage_6)
Type: Family

This entry represents a family of short uncharacterised proteins from various bacteriophages, primarily infecting Mycobacterium and Gordonia species. It contains highly conserved histidine and three cysteine residues in a CXH and CXXC motif that may form a zinc binding site. Its function is currently unknown. Structure prediction shows an unusual fold composed of two three stranded β-sheets that although adjacent are not hydrogen bonded together. There is an unusual side chain hydrogen bond between the threonine in the WXT motif in one sheet that bonds to the backbone of the other sheet. Overall the surface of the protein is highly negatively charged.
Phage zinc binding 4 (Zn-bd_phage_4)
Type: Family

This entry represents a small family of uncharacterised phage proteins with a small zinc binding motif at the C-terminal end composed of a CXXC and CXXH motif. The N terminus is composed of an α-helical hairpin. Structure prediction suggests that these two helices might mediate a homodimerisation interaction to form a four helical bundle structure.
Phage zinc binding 5 (Zn-bd_phage_5)
Type: Family

This entry contains a set of uncharacterised phage proteins that are likely to bind to Zn2+ ions using three conserved cysteines and a histidine.
PIC/HAP1/IgA0-like, second beta-solenoid repeat region (PIC_HAP1_IgA0_b-sol2)
Type: Domain

This entry represents the second solenoid-repeat region found in some serine peptidase autotransporters from bacteria, including IgA0 (Immunoglobulin A1 protease autotransporter), HAP1 (Adhesion and penetration protein autotransporter), Pic (Serine protease pic autotransporter), SepA and EspC. These proteins have been associated to virulent strains . Pic and other bacterial autotransporters confer serum resistance but do not degrade immunoglobulin , in contrast to IgA0 which cleaves host immunoglobulin A producing intact Fc and Fab fragments .

This region counts with insertions between β-solenoid repeats which have been suggested to be involved in forming a unique structure for recognition and binding of protein substrate .
PIGBOS1-like (PIGBOS1)
Type: Family

This protein family includes human Protein PIGBOS1 and similar sequences from eukaryotes. PIGBOS1 plays a role in the regulation of the unfolded protein response triggered by the endoplasmic reticulum (ER) stress resulting from the presence of unfolded proteins in the ER lumen . It is primarily found in the mitochondrial outer membrane and interacts with CLCC1, an endoplasmic reticulum (ER) protein, at ER-mitochondria contact sites .
5MP1/2-like, HEAT domain (HEAT_5MP1_2)
Type: Domain

This domain is formed by HEAT repeats, and it is found in the two human paralogs eIF5-mimic protein 1 and 2 (5MP1 and 5MP2) and related proteins. It is located at the N-terminal, and it likely contributes to the role of these proteins in translation regulation. It shares some sequence, structural, and functional similarities with the corresponding region of eIF4G.

eIF5-mimic proteins 1 and 2 5MP1 and 5MP2 (also known as basic leucine zipper and W2 domain-containing proteins 1 and 2 (BZW1 and BZW2)) act as competitors of eIF5 and can inhibit general translation by interaction with eIF2 and inhibiting the tertiary complex binding to the ribosome . These translation regulatory proteins exist in nearly all eukaryotes except in nematodes, yeasts, and some protozoans. 5MP1/2 contain MA3- and W2-type (

) C-terminal HEAT domains that resemble the HEAT domain of eIF5 . They enable cadherin binding activity . The orthologue in Drosophila melanogaster, known as protein krasavietz (kra), is involved in several processes, including behavioural response to ethanol, long-term memory, and positive regulation of filopodium assembly. Kra is located in several cellular components, including the axonal growth cone, filopodium, and neuronal cell body .

The elf5-mimic protein family functions as translation initiation regulators. They are known to repress non-AUG-initiated translation and repeat-associated non-AUG (RAN)-initiated translation, acting as competitive inhibitors of eukaryotic translation initiation factor 5 (EIF5). These proteins increase the accuracy of translation initiation by competing with EIF5 for interaction with EIF2S2 within the 43S pre-initiation complex, in a manner dependent on binding to EIF3C. Additionally, some members of this family are involved in enhancing histone H4 gene transcription, although they do not directly bind to DNA .
Receptor-type adenylate cyclase GRESAG 4.1/3, periplasmic binding protein-like domain 2 (GRESAG4.1/3_peripasmic_2)
Type: Domain

This entry represents the second periplasmic binding protein-like domain found in receptor-type adenylate cyclase GRESAG 4.1/3 and its homologues, mainly found in trypanosoma. It is usually found N-terminal to the adenylyl cyclase class-3/4/guanylyl cyclase domain (A/G_cyclase) (

). In Trypanosoma brucei, the A/G_cyclase domain was crystalized and was named the catalytic domain (

) .

Receptor-type adenylate cyclase GRESAG 4.1/3 are class II adenylate cyclases (ACs) (

) that occur as multiple isozymes in Trypanosoma brucei. GRESAG 4.1 likely acts as a receptor for an unknown ligand and is involved in cyclic AMP (cAMP) production. cAMP is a critical signalling molecule in T. brucei, playing a role in processes such as differentiation and adaptation to environmental changes. GRESAG 4.1 is expressed in both bloodstream and procyclic forms of the parasite, suggesting it has a role across multiple life stages. Its localisation on the flagellum indicates it may be involved in sensing extracellular signals and transmitting them via cAMP signalling pathways, which are essential for parasite survival and development .
Receptor-type adenylate cyclase GRESAG 4.1/3, periplasmic binding protein-like domain 1 (GRESAG4.1/3_peripasmic_1)
Type: Domain

This entry represents the first periplasmic binding protein-like domain found in receptor-type adenylate cyclase GRESAG 4.1/3 and its homologues, mainly found in trypanosoma.

Receptor-type adenylate cyclase GRESAG 4.1/3 are class II adenylate cyclases (ACs) (

) that occur as multiple isozymes in Trypanosoma brucei. GRESAG 4.1 likely acts as a receptor for an unknown ligand and is involved in cyclic AMP (cAMP) production. cAMP is a critical signalling molecule in T. brucei, playing a role in processes such as differentiation and adaptation to environmental changes. GRESAG 4.1 is expressed in both bloodstream and procyclic forms of the parasite, suggesting it has a role across multiple life stages. Its localisation on the flagellum indicates it may be involved in sensing extracellular signals and transmitting them via cAMP signalling pathways, which are essential for parasite survival and development .
ADGRF3/5-like, N-terminal domain (ADGRF3/5_N)
Type: Domain

This domain is found at the N-terminal end of Homo sapiens adhesion G-protein-coupled receptor F3 and F5 (ADGRF3/F5), orphan receptors. This domain is predicted to have an α-β configuration.

In homo sapiens, ADGRF3 is a receptor for soluble FNDC4 (sFNDC4), required for proper systemic glucose tolerance, specifically sensitising white adipose tissue to insulin .

The adhesion GPCR (aGPCR) family plays critical physiological functions in the human immune system, central nervous system, cellular communication, reproduction, organ development, homeostasis, and other processes As the second largest group in the GPCR superfamily, aGPCRs are differentiated from other GPCRs by a large extracellular region (ECD) that contains a tandem adhesion domain, followed by the SEA domain

, a conserved GPCR autoproteolysis-inducing (GAIN) domain (GAIN A

and GAIN B

) juxtaposed to a canonical seven-transmembrane domain (7TM) (

). Most aGPCRs are orphan receptors with few known ligand associations identified. The synthesised Stachel peptide is capable of activating aGPCRs, suggesting that the Stachel peptide plays a critical role in aGPCR activation.
Adt-1/2-like domain (Adt-1/2-like_dom)
Type: Domain

This domain is found in A disintegrin and metalloproteinase with thrombospondin motifs adt-1/2 from Caenorhabditis elegans and similar proteins. This domain is predicted to mostly acquire a β-structure. This domain is usually found in association with

. It is also found in putative ADAM metallopeptidase and other uncharacterised animal proteins.

Adt-1 plays a role in ray morphogenesis in the male tail, probably by remodelling the extracellular matrix (ECM) in the cuticle . Its orthologue in Rattus norvegicus is known as ADAM metallopeptidase with thrombospondin type 1 motif, 16.
BBC1/AIM3, cysteine proteinase-fold domain (AIM3_BBC1_C)
Type: Domain

This entry represents a C-terminal domain that contains a cysteine peptidase-like fold but appears to lack the conserved catalytic residues. It is mainly found in fungal proteins such as myosin tail region-interacting protein MTI1 (BBC1) in Saccharomyces cerevisiae and its orthologue SH3 domain-containing protein C23A1.17 in Schizosaccharomyces pombe. BBC1 is involved in the regulation of actin patch assembly. It interacts with the actin assembly factor Las17p and with the SH3 domains of Type I myosins Myo3p and Myo5p . This domain is also found in altered inheritance of mitochondrial protein 3 (AIM3) protein in Debaryomyces hansenii, which is involved in mitochondrial inheritance, though the specific role of this domain remains to be determined . This domain also represents uncharacterised proteins found in bacteria.
Aladin, seven-bladed propeller (Beta-prop_Aladin)
Type: Domain

This entry represents the seven-bladed β-propeller of Aladin and related proteins from eukaryotic organisms.

Aladin (adracalin) is a nuclear envelope WD-repeat protein. It is encoded by the AAAS gene in humans. Aladin is a component of the nuclear pore complex, where it forms a heterodimer with nucleoporin NDC1 . It regulates Aurora A localisation to ensure robust mitotic spindle formation . There are two ALADIN-NDC1 dimers in each inner ring subunit, one on the cytoplasmic side and the other on the nuclear side . The ALADIN β-propellers are located in close proximity to the nuclear envelope. One side of the ALADIN β-propeller is targeted by 15 achalasia-addisonianism-alacrima syndrome (AAAS)-derived mutations. These mutations either alter the structure or damage the interaction of ALADIN with other proteins.
Protein root UVB sensitive 6, N-terminal (RUS6_N)
Type: Domain

This domain is found at the N-terminal of Protein root UVB sensitive 6 from Arabidopsis thaliana (RUS6) and similar sequences from plants. RUS6 is required for normal embryo development . This domain is normally found associated with

and

.
PRS2-like, N-terminal domain (PRS2-like_N)
Type: Domain

This entry represents the N-terminal domain of archaeal Putative 26S proteasome regulatory subunit homologues (PRS2). The function of this domain is unknown and it may be found in association with an AAA-ATPase domain (

).

The 26S proteasome is a large multiprotein complex involved in the regulated degradation of ubiquitinated proteins. This complex can be divided in two sub-complexes, the core particle (CP, 20S) and the regulatory particle (RP, 19S). The RP consists of 19 subunits organised in two sub-structures, the base and lid complexes. The base consists of a ring of six AAA-ATPases. The C-terminal end of these ATPases dock into pockets present between the α-subunits of the CP .
Pua-like domain (Pua-like_dom)
Type: Domain

Members of the PUA family play a crucial role in binding and recognising RNA and DNA with modified bases. They are often linked with Calcineurin-CE domains, indicating their function as sensors in prokaryotic antiviral immunity by recognising modified DNA in invasive DNA elements . This entry represents a domain often found at the N-terminal of PUA bacterial proteins.
TANGO6, HEAT repeat (HEAT_TANGO6)
Type: Domain

This region is found in the human Transport and Golgi organization protein 6 homolog (TANGO6) and similar proteins predominantly from animals and fungi. It is predicted to form HEAT repeats and is often found N-terminal to

and

.

TANGO6 associates with COPI vesicles. Cytoplasmic TANGO6 tethers to COPI vesicle via a signal anchor and two transmembrane domains. Its N- and C-terminal cytoplasmic domains capture RNA polymerase II subunit B (RPB) 2 in the cis-Golgi during the G1 phase . TANGO6 is also observed in the nucleus where it enters via the COPI-SNARE-ER pathway . The nuclear entry of TANGO6 is assisted by KPNB1.
PRS2-like, AAA+ lid C-terminal domain (PRS2_C_AAA_lid)
Type: Domain

This entry represents the C-terminal AAA+ lid domain of archaeal Putative 26S proteasome regulatory subunit homologues (PRS2). This α-helical bundle is found in association with a core AAA-ATPase domain (

).

The 26S proteasome is a large multiprotein complex involved in the regulated degradation of ubiquitinated proteins. This complex can be divided in two sub-complexes, the core particle (CP, 20S) and the regulatory particle (RP, 19S). The RP consists of 19 subunits organised in two sub-structures, the base and lid complexes. The base consists of a ring of six AAA-ATPases. The C-terminal end of these ATPases dock into pockets present between the α-subunits of the CP .
HVO_B0008-like, N-terminal domain (HVO_B0008-like_N)
Type: Domain

This entry represents a domain found at the N-terminal of uncharacterised proteins from halobacteria, including HVO_B0008 from Haloferax volcanii (

). This domain is predicted to fold into three β-strands and an α-helix.
HVO_B0008-like, C-terminal domain (HVO_B0008-like_C)
Type: Domain

This entry represents a domain found at the C-terminal of uncharacterised proteins from halobacteria, including HVO_B0008 from Haloferax volcanii (

). This domain is predicted to show a helix-turn-helix (HTH) fold.
Intraflagellar transport protein 122 homolog, TPR domain (TPR_IFT122)
Type: Domain

This entry represents the TPR repeat domain that follows the two β-propeller domains in human Intraflagellar transport protein 122 homolog and similar proteins mainly found in animals.

Intraflagellar transport protein 122 homolog IFT122 is one of the core components (together with WDR19/IFT144 and IFT140) of the IFT-A complex which is required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), being involved in cilia function and/or assembly . IFT-A polymerises interacts with IFT-B, and uses an array of β-propeller and TPR domains to create 'carriages' of the IFT train that engage TULP adaptor proteins .
Integrator complex subunit 4/Protein SIEL, C-terminal Ig-like domain (INTS4_C)
Type: Domain

This entry represents the C-terminal domain of animal Integrator complex subunit 4 (INTS4) and plant Protein SIEL. The domain has been structurally identified near the INTS9 beta-CASP domain but is poorly resolved in current structures, suggesting flexibility. Its specific function remains to be determined.

INTS4 is a component of the Integrator complex which plays essential roles in snRNA 3' end processing and transcription termination . INTS4 along with INTS9 and INTS11 constitute the Integrator cleavage module, which contains endonuclease activity and resembles the cleavage module of the cleavage and polyadenylation specific factor required for 3' processing of mRNA transcripts.

SIEL (for SHR INTERACTING EMBRYONIC LETHAL) is an intracellular shuttle that promotes movement of the SHORT-ROOT (SHR) protein from the stele into the endodermis . It is required for SHR association to endosomes and localisation, and for intercellular movement of SHR .
Integrator complex subunit 6-like, beta-barrel domain (Beta-barrel_INTS6)
Type: Domain

This entry represents a domain found in the human Integrator complex subunit 6 (INTS6) and related proteins, including its paralogue Integrator complex subunit 6-like (INTS6L). The domain represented by this entry folds into a β-barrel structure with topological similarity to SPOC domains.

INTS6 is a component of the Integrator (INT) complex, a complex that is involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. INTS6 and other subunits bind to and position PP2A phosphatase to dephosphorylate the C-terminal domain of Pol II subunit RPB1 . In the inactive closed conformation of the INT-PP2A complex, INTS6 blocks the PP2A phosphatase active site.
Interferon regulatory factor 2-binding protein 1/2-like, C3HC4 zinc finger domain (Zf-C3HC4_IRF-2BP1_2)
Type: Domain

This entry represents the C3HC4-type zinc finger domain found toward the C-terminal end of Interferon regulatory factor 2-binding protein 1 and 2 (IRF-2BP1/2) and their homologue IRF-2BP-like (also known as IRF-2BPL or C14orf4). These proteins are nuclear transcriptional repressors that bind to the C-terminal repression domain of IRF-2 and can inhibit both enhancer-activated and basal transcription. They contain N-terminal zinc finger and C-terminal RING finger domains . Mutations in IRF-2BP2 are responsible for a familial form of Common Variable Immunodeficiency Disorder (CVID), one of the most frequently diagnosed forms of primary immunodeficiency characterised by low quantity of IgG and IgA and poor specific antibody production . IRF-2BPL may play a role in the development of the central nervous system and in neuronal maintenance .
Cytochrome b6-f complex iron-sulfur subunit-like, transmembrane anchor (TM_PetC)
Type: Domain

This transmembrane domain, consisting of a single transmembrane helix, is found in Cytochrome b6-f complex iron-sulfur subunit (PetC) and related proteins. PetC, is a crucial component of the cytochrome b6f complex, which plays a central role in oxygenic photosynthesis . PetC contains a [2Fe-2S] cluster, which is is essential for the electron transfer process within the complex. PetC interacts with other subunits to form the functional cytochrome b6f complex. The complex functions as a dimer, with each monomer composed of eight subunits in total .
ISE2-like, SH3 domain (SH3_ISE2)
Type: Domain

This predicted SH3 domain is found in DExH-box ATP-dependent RNA helicase DExH15 chloroplastic from Arabidopsis thaliana (ISE2) and similar plant proteins. ISE2 is involved in group II intron splicing. It is required during embryogenesis and is involved in post-transcriptional gene silencing .
PH-like domain 2, trypanosoma (PH-like_trypanosoma)
Type: Domain

This entry represents a domain found at the N-terminal of a small group of uncharacterised proteins from trypanosoma species. This domain adopts a PH-like fold.
PH-like domain, kinetoplastida (PH-like_kinetoplastida)
Type: Domain

This entry represents a domain found at the C-terminal end of a small group of uncharacterised kinetoplastid proteins. This domain adopts a PH-like fold.
PH-like domain 2, kinetoplastida (PH-like_2_kinetoplastida)
Type: Domain

This entry represents a domain found centrally in a small group of uncharacterised kinetoplastid proteins. This domain adopts a PH-like fold. It is found in proteins that have an α-helical solenoid N-terminal domain, a central PH domain (this entry) and a long α helix at the C terminus that presumably forms a coiled-coil.
Lambda-carrageenase, beta-propeller domain (Beta-prop_CGLA)
Type: Domain

This entry represents the β-propeller domain found at the N-terminal end of Pseudoalteromonas Lambda-carrageenases (CGLA), a protein that hydrolyses lambda-carrageenan with inversion of anomeric configuration .
Lambda-carrageenase, middle domain (CGLA_M)
Type: Domain

This entry represents a domain found in the middle of Pseudoalteromonas Lambda-carrageenase (CGLA), a protein that hydrolyses lambda-carrageenan with inversion of anomeric configuration .
Lambda-carrageenase, C-terminal domain (CGLA_C)
Type: Domain

This entry represents the C-terminal domain of Pseudoalteromonas Lambda-carrageenase (CGLA), a protein that hydrolyses lambda-carrageenan with inversion of anomeric configuration . This domain is predicted to adopt a β-sandwich fold.
Doublecortin domain-containing protein 1-like, ubiquitin domain (Ubiquitin_DCDC1)
Type: Domain

This is the ubiquitin domain found in DCDC1 and similar proteins from animals.

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 .
DUF2921, lipocalin-like domain (DUF2921_N)
Type: Domain

This entry represents an eight-stranded flattened β barrel domain which shows structural similarity to the lipocalin fold. The domain shows is found in three copies towards the N terminus of DUF2921 family proteins.
E3 ubiquitin-protein ligase RNF31, third UBA domain (RNF31_UBA_3)
Type: Domain

This domain is found in human E3 ubiquitin-protein ligase RNF31 and similar animal proteins. RNF31 is a component of the LUBAC complex which conjugates linear polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. This domain is often found C-terminal of

.
E3 ubiquitin-protein ligase WAV3-like, C-terminal domain (WAV3_C)
Type: Domain

This domain is found towards the C-terminal end of E3 ubiquitin -protein ligase WAV3, WAVH1, WAVH2 and EDA40 from Arabidopsis thaliana and similar plant proteins. WAV3 is involved in the regulation of root growth and acts as a positive regulator of root gravitropism . This domain is predicted to show an all-α configuration and is often found associated with

and

.
EFHB, C-terminal EF-hand domain (EFHB_EF-hand_C)
Type: Domain

This entry represents the C-terminal EF-hand domain found in EFHB (EF-hand domain-containing family member B) proteins. EF-hand domains are helix-loop-helix structural motifs that typically bind calcium ions.
eIF2D, winged helix domain (WH_eIF2D)
Type: Domain

This entry represents a winged helix domain found in eukaryotic translation reinitiation factor 2D (elF2D). The domain interacts with ribosomal RNA helix h44 and is located between the MCT-1-like and DENR-like halves of eIF2D. The domain plays a role in translation reinitiation by helping position the initiator tRNA on the small ribosomal subunit .