SII-SWORD/CoKE huggingface dataset:
UL116 (HCMV_UL116)
Type: Family

This entry represents the human cytomegalovirus (HCMV) UL116 protein, which forms a complex with glycoprotein H (gH) independently from glycoprotein L (gL). UL116 acts as a chaperone for gH and promotes the expression of gH/gL complexes and is required for efficient production of infectious cell-free virions. UL116 interacts with UL148, a viral endoplasmic reticulum (ER)-resident glycoprotein, and promotes the incorporation of gH/gL complexes into virions. Unlike gL, UL116 does not form a disulfide linkage to gH. UL116 is found in betaherpesviruses, particularly in human and primate cytomegaloviruses.
UL15A (HCMV_UL15A)
Type: Family

This entry represents the Human cytomegalovirus (HCMV) UL15A protein family. UL15A is a small single-pass membrane protein found in betaherpesviruses. The protein contains an extracellular N-terminal domain, a transmembrane helix, and a short cytoplasmic C-terminal domain. The N-terminal region is largely disordered and contains a predicted N-linked glycosylation site. The specific function of UL15A remains unknown.
HFD-like domain (HFD)
Type: Domain

This entry represents the C-terminal domain of the head fibre dimeric protein (HFD) found in crassviruses from the order Crassvirales. This entry also contains a small number of other non-phage proteins that share this domain; in these proteins, this domain is not at the C-terminal. In the crAss001 virus, this protein (gp29) forms dimers that bind to winged hexon pockets at the capsid surface. The N-terminal domain (residues 1-58) interacts with the major capsid protein, while the C-terminal domain (residues 58-118) forms a β-sandwich with structural similarity to the immunoglobulin-like fold. This protein is likely involved in host recognition and binding, with the two different fibre proteins (dimeric and trimeric) providing different binding specificities to external molecules. Homologues of this protein are present primarily in the Steigviridae (beta) and Crevaviridae (gamma) groups of crassviruses.

This entry also contains some other non-phage proteins that share this domain; in these proteins, this domain is not at the C-terminal.
RRP12, N-terminal HEAT domain (HEAT_RRP12_N)
Type: Domain

This entry represents the N-terminal region of human RRP12-like protein, which consists of HEAT repeats. This domain is often found associated with

.

Ribosomal RNA-processing protein 12 (RRP12) proteins are members of pre-ribosome-associated HEAT repeats-containing proteins . They are involved in the maturation and nuclear export of both pre-40S and pre-60S ribosomal subunits. They are required for the processing of RNA components within pre-ribosomes, which is a critical step in the assembly of functional ribosomes. They are associated with the late maturation of the 18S and 5.8S rRNA of the pre-40S ribosomes and for maturation of the 25S and 5.8S rRNA of the pre-60S ribosomes .
BDLF2/ORF27-like (BDLF2/ORF27-like)
Type: Family

This entry represents a family of gamma-herpesvirus glycoproteins involved in intercellular viral spread. Members of this family include the BDLF2 protein from Epstein-Barr virus, ORF27 from Human herpesvirus 8 and VG27 from other herpesviruses. This glycoprotein forms a complex with another viral protein (ORF58/BMRF2) that manipulates the actin cytoskeleton to induce the outgrowth of branched plasma membrane fronds. These membrane structures create an intercellular network for virion traffic, enhancing viral spread between neighbouring cells. The cytoplasmic tail of this glycoprotein is critical for its function and appears to activate RhoA-dependent signalling to induce actin polymerisation and membrane remodelling .
Glycoprotein Q2/Q1/105 (Q2/Q1/105)
Type: Domain

This entry represents the Glycoprotein Q1, Q2 and 105 of human herpesvirus-6 (HHV-6).

Glycoprotein Q2 (gQ2) forms a tetrameric complex with glycoproteins gH, gL, and gQ1 that is essential for viral entry. In HHV-6A, this complex binds to the cellular receptor CD46, while in HHV-6B the complex has different receptor specificity. Both HHV-6A gQ1 and gQ2 are critical for CD46 binding, and their interaction is important for receptor specificity .

In long proteins, this entry is only found at the C-terminal, while in shorter proteins it covers the full length.
ORF28, N-terminal domain (ORF28_N)
Type: Domain

This entry represents a conserved domain at the N-terminal in the uncharacterised protein ORF28 from Ictalurid herpesvirus 1. This domain contains conserved cysteine residues that may form a zinc-binding motif. The function of this domain remains unknown, but it is primarily found in herpesviruses that infect fish.
ORF30 (ORF30)
Type: Family

This entry represents the Ictalurid herpesvirus (IcHV-1) uncharacterised protein ORF30. This protein contains a conserved CXXC motif (CPI) at positions 74-77, which may indicate a potential zinc-binding function. ORF30 is encoded by channel catfish virus, which is the type species of the Alloherpesviridae family, distinctly different from mammalian and avian herpesviruses.
ORF32/34 (ORF32/34)
Type: Domain

This entry represents the herpesvirus ORF32 phosphoprotein. It includes the phosphoprotein 32 from Varicella-zoster virus (HHV-3) and homologous proteins such as Gene 34 from Equine herpesvirus 1. The ORF32 protein is known to be phosphorylated by the ORF47 protein in Varicella-zoster virus. The function of this protein remains to be fully characterised.
U21 glycoprotein (HHV_U21)
Type: Family

This entry represents the U21 glycoprotein found in human herpesviruses. U21 is a viral membrane protein from betaherpesviruses, including human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7). U21 functions as an immunoevasin that plays a role in viral immune evasion by targeting multiple host proteins. It has been shown to redirect HLA class I molecules to the lysosomal compartment for degradation . Additionally, U21 targets ULBP3, a ligand for the activating NK cell receptor NKG2D, which helps the virus escape immune recognition by NK cells . U21 primarily localises to the endoplasmic reticulum and late endosomes, where it facilitates the lysosomal degradation of its target proteins.
Major capsid protein VP21 (VP21)
Type: Family

This entry represents the major capsid protein (VP21) of His1 virus, a spindle-shaped virus that infects the extremely halophilic euryarchaeon Haloarcula hispanica. The His1 virion is composed of one major structural protein, VP21 and a few minor structural proteins. VP21 exists in two forms, with the higher molecular mass form being lipid-modified. Interestingly, there is no lipid bilayer in the His1 virion, but the lipid modification of VP21 likely enables hydrophobic interactions, leading to the flexible nature of the virion. His1 belongs to the genus Salterprovirus that differs from fuselloviruses by having a linear genome rather than a circular one, although both share a similar spindle-shaped morphology.
Hydroxymethylglutaryl-CoA reductase-like (HMG-CoA)
Type: Domain

This domain is found at the N-terminal end in Hydroxymethylglutaryl-CoA (HMG-CoA) reductase from Candidatus Promineifilum . This domain also covers the whole length of some HMG-CoA. This domain is predicted to adopt a mostly β configuration.
YO34 (HP1_YO34)
Type: Family

This entry represents a family of phage proteins predicted to be involved in the sheath-tube baseplate complex such as uncharacterised protein YO34. Members of this family show structural similarity to the Pvc7 component of contractile injection systems

, suggesting a likely structural role in the phage tail assembly. The C-terminal region of the protein is predicted to be disordered.
TOCA, HR1 domain (HR1_TOCA)
Type: Domain

This entry represents the HR1 (homology region 1) domain found in TOCA proteins including TOCA1, CIP4, FBP1 and FBP17. This domain forms an antiparallel coiled-coil structure that mediates binding to the small GTPase Cdc42. Unlike other HR1 domains that bind to RhoA or Rac1 with high affinity, the TOCA family HR1 domains bind Cdc42 with relatively low (micromolar) affinity. The domain contains two α-helices connected by a loop region. The binding interface with Cdc42 includes both helices and the connecting loop. NMR studies suggest that the TOCA1 HR1 domain can be displaced from Cdc42 by the N-WASP GBD domain, suggesting an effector handover mechanism in which TOCA1 binding to Cdc42 positions N-WASP and Cdc42 for subsequent high-affinity interaction to initiate actin polymerisation . This entry also includes Nostrin proteins, which are members of the F-BAR domain protein family as TOCA proteins.

TOCA proteins (TOCA-1, CIP4, and FBP17) comprise a subfamily of the F-BAR domain-containing proteins that function as critical molecular links between membrane deformation and actin cytoskeleton dynamics. These proteins possess an N-terminal F-BAR domain (

) that binds phosphoinositides and induces membrane curvature, and a C-terminal SH3 domain (

) that interacts with actin nucleation-promoting factors, particularly N-WASP and WAVE complex components . TOCA proteins are activated downstream of Cdc42 signalling and promote actin polymerisation by relieving the autoinhibition of N-WASP/WIP complexes . They participate in clathrin-mediated endocytosis, cell migration, and tissue morphogenesis by coordinating membrane invagination with localised actin assembly.
FNBP1L/CIP4, HR1 domain (HR1_CIP4_FNBP1L)
Type: Domain

This entry represents the HR1 domain in FBP1L and CIP4 proteins which are a subset of TOCA proteins. CIP4 and FNBP1L are Cdc42 effectors that bind Wiskott-Aldrich syndrome protein (WASP) and function in endocytosis.

Formin-binding protein 1-like (FNBP1L, also known as Toca-1) is part of the Toca-1-N-WASP complex that induces the formation of filopodia and endocytic vesicles . CIP4 and FNBP1L contain an F-BAR domain (

), a HR1 domain (

) and an SH3 domain (

) . FNBP1L belongs to the CIP4 (Cdc42 interacting protein-4) subfamily of the F-BAR (F for FCH, Fer-CIP4 homology domain) protein family. The F-BAR proteins have been implicated in cell membrane processes such as membrane invagination, tubulation and endocytosis . FNBP1L is required for Cdc42-induced actin assembly and is essential for autophagy of intracellular pathogens.

CIP4 may also play a role in phagocytosis. It functions downstream of Cdc42 in PDGF-dependent actin reorganization and cell migration, and also regulates the activity of PDGFRbeta . It uses Src as a substrate in regulating the invasiveness of breast tumor cells .
Derepression protein (Derepression)
Type: Family

The Derepression protein family is involved in the induction of the P2 prophage helper by P4. This process is essential for the derepression mechanism, which allows the prophage to become active under certain conditions.
CTHRC1, C-terminal domain (CTHRC1_C)
Type: Domain

This domain is found at the C-terminal end of human Collagen triple helix repeat-containing protein 1 (CTHRC1) and similar animal sequences. CTHRC1 may act as a negative regulator of collagen matrix deposition. This domain is predicted to adopt an all-β configuration.
Cryptosporidium parvum virus small dsRNA capsid protein (Crypto_dsRNA_S)
Type: Family

This entry represents the capsid protein encoded by the smaller dsRNA segment (S-dsRNA) of Cryptosporidium parvum virus. This protein is found in the cytoplasm of C. parvum sporozoites and is not detected in other species of the genus. The S-dsRNA is approximately 1374 nucleotides in length and encodes a single large open reading frame of 963 nucleotides that translates to a 319 amino acid protein with limited similarity to mitogen-activated c-Jun NH2 terminal protein kinases (JNK). Unlike most protozoan viruses, the dsRNAs of C. parvum appear to be unencapsidated as attempts to identify virus-like particles were unsuccessful. These dsRNAs are present in various North American isolates of C. parvum and may play a role in the regulation of gene expression or virulence.
Tail hub protein B (crAss_THB)
Type: Family

This entry represents the tail hub protein B (THB) found in bacteriophages. The protein forms a heterotrimer with tail hub protein A (THA), and these heterotrimers further assemble as 12 docking hubs that form a continuous collar around the tail barrel. The C-terminal segment of THB (residues 67-107) extends into the neighbouring hub, resulting in interlocking connections between adjacent hub assemblies. Each docking hub anchors the trimeric tail fibres. The tail hub proteins play an important structural role in phage assembly, serving as the attachment point for the tail fibre appendages. THB has been structurally characterised in the Bacteroides phage crAss001, revealing its role in the architecture of the phage tail .
Tail hub protein A (crAss_THA)
Type: Family

This entry represents the tail hub protein A (THA) found in bacteriophages. The protein forms a heterotrimer with tail hub protein B (THB), with each assembly consisting of two copies of THA and one copy of THB (

). These heterotrimers further assemble as 12 docking hubs that form a continuous collar around the tail barrel. The docking hubs interact with the trimeric tail fibre protein, accommodating its N-terminal region. THA forms disulfide bonds with THB and with the ring proteins of the tail barrel, contributing to the stability of the tail assembly. The tail hub proteins play an important structural role in phage architecture, serving as the attachment point for the tail fibre appendages that are involved in host recognition. THA has been structurally characterised in the Bacteroides phage crAss001, revealing its role in the architecture of the phage tail .
Phage tail ring protein 3/4 (CrAss_Ring_3_4)
Type: Family

This entry represents the Ring 3 and 4/5 proteins, which are part of the tail assembly in crassviruses. These proteins forms two of five stacked dodecameric rings that make up the tail barrel. These proteins share a conserved fold consisting of two domains: an α-helical domain and a β-sandwich domain. The extended tail barrel formed by these ring proteins is a distinctive feature of crassviruses. It may assist the tail muzzle in reaching the outer cell membrane through the compact capsular polysaccharide layer of the host bacteria.
Phage tail ring protein 2 (CrAss_Ring_2)
Type: Family

This entry represents the Ring 1 (R2) protein, also known as gp40, which is part of the tail assembly in crassviruses. The R2 protein forms one of five stacked dodecameric rings that make up the tail barrel. These proteins share a conserved fold consisting of two domains: an α-helical domain and a β-sandwich domain. The extended tail barrel formed by these ring proteins is a distinctive feature of crassviruses. It may assist the tail muzzle in reaching the outer cell membrane through the compact capsular polysaccharide layer of the host bacteria.
Portal vertex auxiliary protein (crAss_PVA)
Type: Family

This entry represents the portal vertex auxiliary protein found in bacteriophages. This protein forms a homodimer stabilised by disulfide bonds between residues 25-88 and 47-47 of the two subunits. It is localised at the portal vertex of the viral capsid, with two copies per virion. The protein interacts with the major capsid protein and substitutes for the capsid auxiliary protein at the portal vertex. The portal vertex auxiliary protein has been structurally characterised in the Bacteroides phage crAss001, where it plays an important role in the assembly and stability of the portal-containing vertex of the viral capsid.
Inhibitor of histone-like protein HU (HU_inhibitor)
Type: Family

This entry represents a bacteriophage protein that acts as an inhibitor of bacterial histone-like protein HU. The protein binds to HU, occupying its DNA binding motif and preventing HU-DNA complex formation. This inhibition leads to defects in chromosome segregation and causes filamentous cell morphology in bacteria. The protein forms a 1:2 complex with HU dimers, utilising electrostatic interactions and key hydrophobic contacts. Key residues F22 and D63 are important for the interaction with HU. The protein can bind HU proteins from a wide range of bacteria and Apicomplexan parasites due to the conservation of key interaction residues .
Little elongation complex subunit 1, C-terminal domain (ICE1_C)
Type: Domain

This domain is found at the C-terminal end of ICE1 mainly in animals. This domain is predicted to adopt an all-α configuration.

Little elongation complex subunit 1 (ICE1) acts as a scaffold protein that promotes the LEC complex formation and recruitment and RNA polymerase II occupancy at small nuclear RNA (snRNA) genes in subnuclear bodies.
Cytosolic endo-beta-N-acetylglucosaminidase, C-terminal domain (ENGase_C)
Type: Domain

This domain is found at the C-terminal in ENGase found in plants and vertebrates. This domain is predicted to adopt an immunoglobulin (Ig)-like fold.

Endo-β-N-acetylglucosaminidase (ENGase) is a glycosyl hydrolase that cleaves the β-1,4-glycosidic bond within the di-N-acetylchitobiose core of N-glycosylated proteins, leaving one N-acetylglucosamine residue attached to the protein and releasing the remainder of the glycan. It plays a key role in the cytosolic degradation of free oligosaccharides derived from the endoplasmic reticulum, aiding in the recycling of sugars. ENGases possess an eight-stranded α/β barrel structure and belong to glycosyl hydrolase family 85 (GH85), sharing sequence similarity with

chitinases .

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.
NFAM1, Ig-like domain (Ig_NFAM1)
Type: Domain

This entry describes the immunoglobin domain found in NFAM1 and similar proteins mostly found in animals.

NFAT activation molecule 1 (NFAM1) is a cell surface molecule of the immunoglobulin superfamily that plays a role in immune signalling. It contains an N-terminal signal peptide, an extracellular immunoglobulin domain, a transmembrane region, and a cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM), all characteristic of this protein family . NFAM1 activates the calcineurin/NFAT signalling pathway, promoting downstream transcription of cytokine genes and modulating immune responses . It has also been shown to regulate B cell development through ITAM-mediated signalling, suggesting a functional role in lymphocyte maturation .
RIMS-binding protein 1/2/3, Fn3 domain (FN3_RIM-BP1/2/3)
Type: Domain

This immunoglobulin (Ig)-like domain is found in RIMS-binding protein 1, 2, 3 and similar proteins, mainly found in animals. It has a similar fold to Fibronectin type III (Fn3) (

).

RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2 . RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3 . RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery . RIM-BPs contain three SH3 domains (

) and two to three fibronectin III repeats (

). Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3 . RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis . The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits .
VWDE-like, Ig-like domain (Ig_VWDE)
Type: Domain

This predicted immunoglobulin (Ig) domain is found in VWDE and similar sequences. This domain is often found associated with

and

.

von Willebrand factor D and EGF domain-containing protein (WWDE) is predicted to enable signalling receptor binding activity and to be active in the cell surface and extracellular region.
Inovirus capsid (Inovirus_capsid)
Type: Family

This entry represents the Inovirus capsid protein family, which is involved in the formation of helical capsids that encapsulate viral genomic DNA. This family includes Capsid protein G8P (VIII) and Phi-Lf prophage-derived major coat protein (gVIII-1). These proteins self-assemble to create a filamentous structure with dimensions ranging from 760 to 1950 nm in length and 6 to 8 nm in width. The assembly and budding of the virion occur at the host's inner membrane, facilitating the viral life cycle. This structural role is crucial for the protection and delivery of viral genetic material during infection.
IQ motif and ubiquitin-like domain-containing protein, helical domain (IQUB_helical)
Type: Domain

This domain is found in IQUB and similar proteins mainly found in vertebrates. This domain is predicted to adopt a predominantly α-structure.

IQ motif and ubiquitin-like domain-containing protein (IQUB) is an adapter protein that anchors the radial spoke 1 (RS1) complex to the A microtubule of outer doublet microtubules in axonemes . The triple radial spokes (RS1, RS2 and RS3) are required to modulate the beating of the sperm flagellum . IQUB may also play a role in inhibiting signalling via MAPK1/ERK2 and MAPK3/ERK1 . It may play roles in cilia formation and/or maintenance . Defects in this protein may lead to spermatogenic failure with radial spoke defects. The ubiquitin domain in IQUB is represented by

.
Crassvirus muzzle protein, C-terminal domain (crAss_MUZ_C)
Type: Domain

This entry represents the C-terminal β-sandwich domain from the muzzle protein found at the distal end of the tail in bacteriophages of the Crassviridae family.

This large protein forms a hexameric assembly at the tip of the tail barrel and exhibits a novel fold designated as the 'crass fold'. The muzzle protein is composed of five domains: a ring-joining domain, a seven-bladed β-propeller domain, two immunoglobulin-like domains (IG1 and IG2), and the crass domain. The muzzle protein forms a gate-like structure that likely serves as a gatekeeper controlling the ejection of cargo proteins and viral DNA during infection. The gate is formed by a loop within blade 4 of the propeller domain. The crass domain, with its exposed surface loops, likely plays a role in contacting the host cell surface, initiating conformational changes that open the gate. The muzzle protein is highly conserved among crassviruses, though with length variations resulting from insertions in the crass and IG2 domains that affect surface properties. This protein has been structurally characterised in Bacteroides phage crAss001 .