SII-SWORD/CoKE huggingface dataset:
Inactive Sirtuin (iSirtuin)
Type: Domain

This entry represents an inactive sirtuin domain found mainly in proteobacteria .
p53, central conserved site (P53_central_site)
Type: Conserved_site

This entry represents a conserved stretch of 13 residues located in the central region of the p53. This region, known as domain IV in , is involved (along with an adjacent region) in the binding of the large T antigen of SV40. In homo sapiens, this region is the focus of a variety of point mutations in cancerous tumours. This entry also represents the central conserved site in related tumour proteins.

The p53 tumour suppressor is a protein found in increased amounts in a wide variety of transformed cells. It is also detectable in many proliferating non-transformed cells, but it is undetectable or present at low levels in resting cells. It is frequently mutated or inactivated in many types of cancer. p53 seems to act as a tumour suppressor in some, but probably not all, tumour types. p53 has been implicated in cell cycle regulation, particularly in the monitoring of genomic DNA integrity prior to replication; for this reason it has been dubbed 'guardian of the genome'. p53 can be divided into different functional domains: an N-terminal transactivation domain (

), a proline-rich domain, a DNA-binding domain (

) which contains a conserved site (

), a tetramerisation domain (

) and a C-terminal regulatory region.
ILCR1 Ig-like domain (Ig_ILCR1)
Type: Domain

This domain is found in ILCR1 from Caenorhabditis elegans and related proteins. The domain represented by this entry is predicted to adopt a β-sandwich with an Ig-like topology.

Interleukin cytokine receptor-related protein 1 (ILCR1) forms a receptor complex together with receptor ILCR2, which upon activation acts as a modulator of neuronal activity. When IL-17 binds to the ILCR-1/2 receptor complex, a signaling cascade is triggered that activates the downstream signaling components and results in increased neuronal activity in response to input from oxygen-sensing neurons . It is also predicted to enable interleukin-17 receptor activity. Is an ortholog of human IL17RA (interleukin 17 receptor A) and IL17RB (interleukin 17 receptor B) .
Partner of xrn-2 protein 1-like, C-terminal (Paxt-1-like_C)
Type: Domain

This domain is found at the C-terminal end of Partner of xrn-2 protein 1 from Caenorhabditis elegans (Paxt-1) and similar sequences from worms. Paxt-1 plays a role in maintenance of steady-state concentration and turnover of microRNAs (miRNA) by degradation of mature miRNA in complex with the exoribonuclease xrn-2 . This domain is found associated with

and is predicted to be organised into two similar α-β structures.

The Partner of xrn-2 protein 1 family is involved in the regulation of microRNA (miRNA) levels within the cell. Members of this family are characterised by the presence of an XTBD domain, which is essential for their interaction with the exoribonuclease xrn-2. The primary function of the family is to play a role in the maintenance of steady-state concentrations and turnover of miRNAs by facilitating the degradation of mature miRNA in complex with xrn-2. Additionally, the family stabilises and enhances the accumulation and activity of xrn-2, thereby contributing to the miRNA turnover process .
IML1, N-terminal, fungi (IML1_N_fung)
Type: Domain

This entry represents the N-terminal double-psi β-barrel domain found in vacuolar membrane-associated IML1 proteins from fungi. In Saccharomyces cerevisiae, Iml1 is a GAP subunit of both the SEA (Seh1-associated) and Iml1 complexes (Iml1-Npr2-Npr3). SEA complex is associated dynamically with the vacuole and is involved in autophagy . Iml1 complex is required for non-nitrogen starvation (NNS)-induced autophagy .
Immunoglobulin A1 protease autotransporter, domain 2 (IgA0_D2)
Type: Domain

This entry represents what has been called domain 2 of the immunoglobulin A1 protease autotransporter (IgA0) from proteobacteria. These proteases serve as virulence factors by cleaving IgA in humans and great apes . This domain has been suggested to be involved in protein-protein interactions and may contribute to substrate recognition by forming a binding surface for IgA .
Inactive HKD-Rease (HKD_inactive)
Type: Domain

This entry represents an inactive HKD-REase domain typically fused to the ParB-CE domain [

] and predicted to be involved in conflict .
INO2 bHLH domain (bHLH_INO2)
Type: Domain

The founding member of this family is the bHLH domain of yeast protein INO2. It is mainly found in saccharomycetales and pichiales yeast. This protein is a positive regulatory factor involved in the transcriptional regulation of phospholipid biosynthetic genes. INO2 forms a heterodimer with INO4 and this complex specifically recognises the inositol/choline-responsive element, followed by the transcription activation of the phospholipid biosynthetic gene. Ternary INO2(bHLH)/INO4(bHLH)/DNA complex showed that the recognition and binding of promoter DNA is mediated by the presence of both protein domains . There's no known homologue of INO2 protein in Schizosaccharomyces pombe.
INO4, bHLH domain (bHLH_INO4)
Type: Domain

The founding member of this family is the bHLH domain of yeast protein INO4. This protein is a positive regulatory factor involved in the transcriptional regulation of phospholipid biosynthetic genes. INO4 forms a heterodimer with INO2 and this complex specifically recognises the inositol/choline-responsive element, followed by the transcription activation of the phospholipid biosynthetic gene. Ternary INO2(bHLH)/INO4(bHLH)/DNA complex showed that the recognition and binding of promoter DNA is mediated by the presence of both protein domains . There is no known homologue of INO2 protein in Schizosaccharomyces pombe
Integrin beta, epidermal growth factor-like domain 2 (EGF_integrin_2)
Type: Domain

This entry represents the second EGF-like domain that is found in several integrin beta proteins, including integrin beta-1/2/3/5/6/8. This domain has two characteristically long loops.

EGF-like domains in beta subunits contain three disulphide groups with the same connectivity as in other EGF domains. The disulphide bonds function as critical "locks" for integrin inactivity, with bond disruption enabling activation . Each EGF-like domain contains three β strands, with the first two antiparallel strands (A and B) forming a major β sheet found in classical EGF domains. Strand C is hydrogen bonded to strand D, which is contributed in part by the consecutive domain, with strands C and D forming a minor β sheet-like conformation .

Integrin beta subunits consist of an extracellular domain with a head region, a stalk/leg section, a transmembrane domain, and a cytoplasmic tail. The head region contains a β-I-like domain inserted into a hybrid domain, connected to a plexin-semaphorin-integrin (PSI) [

]. C-terminal to the PSI domain is an A-domain, which has been predicted to adopt a Rossmann fold similar to that of the alpha subunit, but with additional loops between the second and third β strands. This domain is referred to as VWA [

]. Many VWA domains bind metal ions via a noncontiguous sequence motif called metal ion-dependent adhesion site (MIDAS) . This is followed by a β-subunit stalk/leg section that contains four cysteine-rich integrin epidermal growth factor-like (I-EGF) modules [

], [

],

]. Finally, this is followed by the β-ankle TM domain [

] and a cytoplasmic tail [

] .

Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton, and activate many intracellular signalling pathways . An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a VWA domain inserted within the integrin domain at the N-terminal.

Most integrins recognise relatively short peptide motifs and, in general, require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits . There are at least 18 types of alpha and 8 types of beta subunits recognised in humans . Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule . Each association of alpha and beta subunits has its binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activates or inhibits another.
Ionotropic receptor 75a, N-terminal (IR75A_N)
Type: Domain

This entry represents the N-terminal domain of the Ionotropic receptor 75a (IR75A) from Drosophila melanogaster and related sequences from arthropods. IR75A is an odorant receptor for acetic and propionic acid. It functions as part of an olfactory receptor complex including the ionotropic receptor coreceptor Ir8a . This domain is predicted to adopt a periplasmic-binding protein domain fold.
Iron-related transcription factor 3, bHLH domain (bHLH_IRO3)
Type: Domain

This entry represents the bHLH domain of iron-related transcription factor 3 from Oryza sativa. This transcription factor acts as a negative regulator of the iron deficiency response and plays an important role for iron homeostasis in rice . This domain is also found in a number of plant transcription factors, such as bHLH11, bHLH47, BHLH062 and bHLH121 .
HTH-like domain, caenorhabditis (HTH_71)
Type: Domain

This presumed domain is found towards the N-terminal end of a group of uncharacterised proteins from Caenorhabditis. It shares significant sequence similarity to the HTH 3-helical bundle domains and it is predicted to adopt a similar structure.
HTH-like domain 2, caenorhabditis (HTH_72)
Type: Domain

This domain is found C-terminal to

in uncharacterised proteins from Caenorhabditis. It shares sequence similarity to the HTH 3-helical bundle domains and it is predicted to adopt a similar structure.
HYR-like domain (HYR-4C)
Type: Domain

This domain is found sometimes in tandem arrays in bacterial cell surface proteins. It contains four cysteines that appear to be likely to form two disulphide bridges between adjacent pairs of domains. It seems likely that these domains form rigid stalks. These domains show sequence similarity to HYR domains.
Type 4 adapter protein IcmW-like (IcmW-like)
Type: Family

This entry represent the type 4 adapter protein IcmW from Legionella pneumophila and related proteins found mainly in Gammaproteobacteria. IcmW is a component of Type 4B secretion (T4BS) system that translocates over 300 effectors into the host cell during infection. This protein is part of a subcomplex which recruits effector proteins and delivers them to the core transmembrane subcomplex . In the membrane-embedded T4 coupling complex (T4CC), the DotLMNYZ components form a hetero-pentameric core of the T4CC complex from which the flexible IcmSW module protrudes . These hetero-pentameric complexes assemble and form an inner membrane channel for effectors to pass through. The IcmS/IcmW complex plays an important role in protein translocation by interacting with multiple Dot/Icm effector proteins to facilitate their translocation into host cells . The binding of the IcmSW complex to effectors enhances the effector protein delivery by mediating a conformational change that facilitates T4SS recognition of a translocation domain located in the carboxyl region of the effector protein .
SMP domain-containing protein, PH domain (PH_SMPa)
Type: Domain

This entry represents a PH-like domain found at the N-terminal end of a group of uncharacterised plant proteins that contain an SMP domain

.
PH domain, N-terminal, fungi (PH_N)
Type: Domain

This PH domain is found at the N-terminal one of a pair of PH domains that is found in a group of uncharacterised fungal proteins.
PH domain, C-terminal, fungi (PH_C)
Type: Domain

This PH domain is found as the C-terminal one of a pair of PH domains that is found in a group of uncharacterised fungal proteins.
Phage baseplate wedge subunit (Baseplate_wedge)
Type: Family

This family represents a conserved phage baseplate wedge subunit found in phages infecting Enterobacteria. The baseplate is a complex phage structure that facilitates host cell attachment and injection of the phage DNA into the host cell. The wedge subunits form part of the baseplate structure. The family is part of the ViI-like phage group.
Phage integrase, N-terminal domain (Int_N)
Type: Domain

This domain is found at the N-terminal end of phage integrases, including the member from Escherichia phage P2. This protein is necessary for integration of the phage into the host genome by site-specific recombination .
Irg-7-like, Ig-like domain (Ig_Irg-7)
Type: Domain

This domain is found in Irg-7 from Caenorhabditis elegans and similar animal sequences. This domain is predicted to adopt an immunoglobulin-like fold.

Irg-7 is known as mediator of longevity in germlineless animals. It plays a role in the innate immunity, probably via the atf-7 pathway, and confer resistance to pathogenic bacteria .
Irg-7, N-terminal galactose binding domain (GBD_Irg-7_N)
Type: Domain

This domain is found N-terminal in the nematode Irg-7 protein and related proteins. The domain is predicted to fold into a β-sandwich with topology similar to galactose-binding domains.

Irg-7 is known as mediator of longevity in germlineless animals. It plays a role in the innate immunity, probably via the atf-7 pathway, and confer resistance to pathogenic bacteria .
Phage neck terminator protein gp12-like (Gp12-like)
Type: Domain

This entry represents the neck terminator protein gp12 from cyanophage Pam3 . Six gp12 subunits form a hexameric ring that terminates neck assembly and links to the tail tube/sheath. Each subunit has an N-terminal loop, a conserved globular domain, and a protruding β-sheet domain.
GLRG_09195, thioredoxin-like (GLRG_09195_Thiored)
Type: Domain

This domain is found in a group of uncharacterised fungal proteins, including uncharacterised protein GLRG_09195 from Colletotrichum graminicola. It is predicted to adopt a thioredoxin-like fold. It can be found in association with

. It is also found in fungal uncharacterised 2OG-Fe(II) oxygenase and isochorismatase domain proteins.
T-cell immunomodulatory protein TIP, C2 domain (C2_TIP)
Type: Domain

This entry represents the N-terminal C2 domain present in T-cell immunomodulatory protein TIP proteins (enconded by gene ITFG1). In mammals, TIP promotes the adhesion between neighbouring cells through its extracellular domain and regulates microtubule dynamics through its intracellular domain . In parasites, it may protect the parasite against attack by the host immune system . Its ortologue in Caenorhabditis elegans (named linkin) is involved in gonadal cell migration .
Kinesin-like protein KIF26A/B, helical domain (HTH_KIF26A_B_1st)
Type: Domain

This domain is found in the kinesin-like protein KIF26A/B from Mus musculus and similar sequences mainly found in vertebrates. KIF26A plays a key role in enteric neurone development, while KIF26B is essential for embryonic kidney development . This domain is predicted to form an α-helical bundle.

Kinesin is a microtubule-associated force-producing protein that play a role in organelle transport. The kinesin motor activity is directed toward the microtubule's plus end. Kinesin is an oligomeric complex composed of two heavy chains and two light chains. The maintenance of the quaternary structure does not require interchain disulphide bonds.
Kinetochore protein NDC80 loop region (NDC80_loop)
Type: Domain

This entry represents the so-called NDC80 'loop' structure found at the coiled coil C-terminal of kinetochore protein NDC80. NDC80 is a conserved coiled-coil protein that forms the mitotic spindle, which is required for kinetochore integrity and the organisation of stable microtubule binding sites in the outer plate of the kinetochore . The Ndc80 'loop' is a stiff, α-helical 'switchback' structure .
Kinase D-interacting substrate of 220 kDa-like, SAM domain (SAM_KIDINS220)
Type: Domain

This is the predicted Sterile alpha motif (SAM) domain of human Kinase D-interacting substrate of 220 kDa (KIDINS220) and similar animal and insect proteins. KIDINS220 promotes a prolonged MAP -kinase signalling by neurotrophins and is involved in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. This protein is rich in ankyrin repeats, has a KAP family P-loop domain ([

]) and a SAM domain (this entry) with a predicted all α-helical structure.
KCTD8/12/16, H1 domain (H1_KCTD8_12_16)
Type: Domain

This entry represents the H1 domain found in the potassium channel tetramerization domain-containing protein 8/12/16 (KCTD8/12/16), which consists of a five-stranded antiparallel β-sheet interrupted by two α-helices, according to the structure described in . The H1 domain found at the C-terminal of these proteins, engages in interactions with G-protein beta-gamma subunits and has been described to be responsible for desensitisation in KCTD12 .
K1 capsule-specific polysaccharide lyase, N-terminal domain (K1-lyase_N)
Type: Domain

This entry represents the N-terminal domain of K1 capsule-specific polysaccharide lyase and related proteins. The N-terminal domain is known as a particle-binding domain. It folds into an open β-barrel structure the curvature of which is completed by an α-helix. Structurally, this domain is very similar to collagen XVIII trimerization domain (

) [

].

K1-lyase functions as a receptor binding protein (RBP) and mediates the attachment to the host capsular exopolysaccharides . This enzyme possesses a lyase activity that specifically degrades the K1-type polysaccharides of Klebsiella pneumoniae capsule .
K1 capsule-specific polysaccharide lyase, Rider domain (K1-lyase_Rider)
Type: Domain

This entry represents the so-called Rider domain of K1 capsule-specific polysaccharide lyase and related proteins. The Rider domain folds into a β-barrel, participates in polysaccharide binding to both carbohydrate-binding sites of the enzyme and makes an important contribution to the structural stability of the trimeric K1-lyase (

) .

K1-lyase functions as a receptor binding protein (RBP) and mediates the attachment to the host capsular exopolysaccharides . This enzyme possesses a lyase activity that specifically degrades the K1-type polysaccharides of Klebsiella pneumoniae capsule .
KRIT1/FRMD8, FERM domain C-lobe (KRIT1_FRMD8_FERM_C)
Type: Domain

KRIT1, also known as CCM1, a Rap1-binding protein, is expressed in endothelial cells where it is present in cell-cell junctions and associated with junctional proteins . Together with CCM2/MGC4607 and CCM3/PDCD10, KRIT1 constitutes a set of proteins whose mutations are found in cerebral cavernous malformations, characterised by cerebral hemorrhages and vascular malformations in the central nervous system. KRIT1 localization is mediated by its FERM domain . This entry represents the FERM domain C-lobe (or F3 subdomain) . This entry also includes the paralogue of KRIT1, FRMD8, a protein that promotes the cell surface stability of iRhom1/RHBDF1 and iRhom2/RHBDF2 and prevents their degradation via the endolysosomal pathway. By acting on iRhoms, FRMD8 is involved in ADAM17-mediated shedding of TNF, amphiregulin/AREG, HBEGF, and TGFA from the cell surface . This entry also includes some fungal putative FERM-containing proteins. Although there is not yet a characterised FERM-containing protein in fungi, the FERM domain first appeared in the ancestors of todays myosin and talin proteins during the separation of plants and Amorphea (amoebae, fungi, and animals) .
LYK3/RLK10-like, LysM domain (LysM_RLK3/10)
Type: Domain

This entry represents a set of LysM domains found in LysM domain receptor-like kinase family LYRK3, RLK10 (

) and similar receptors.

Plant receptor-like kinases and receptor-like proteins (RLKs or LYRK) (

) are involved in innate immunity and symbiotic interactions in plants. Members of this family function as cell surface receptors that recognise specific molecular patterns associated with microbial activity, such as chitin oligosaccharides and peptidoglycans. These receptors play crucial roles in plant defence by detecting pathogen-associated molecular patterns (PAMPs) and microbe-associated molecular patterns (MAMPs), leading to the activation of defence genes. They are also involved in symbiotic relationships, such as the nitrogen-fixing root nodule symbiosis with rhizobia, by recognising Nod factor signals such as LYK3/4 which contains two LysM domains in the extracellular region . The family includes kinases such as CERK1 (Chitin elicitor receptor kinase 1) (

) that phosphorylate downstream partners in response to elicitation, mediating signal transduction from the extracellular to intracellular spaces and contributing to resistance against pathogenic fungi and bacteria .
Macrodomain effector MavL (MavL)
Type: Domain

This entry represents the Legionella macrodomain effector MavL, an ADP-ribosyl hydrolase that reverses the arginine ADP-ribosylation, to minimise potential detrimental effects caused by the modified ubiquitin. Legionella pneumophila mediates atypical ubiquitination of host targets using the SidE effector family . This entry also includes other macrodomain-containing proteins found in small arthropods and diatoms.
MAX effector (MAX_effector)
Type: Family

This entry represents a family of MAX effectors (for Magnaporthe Avrs and ToxB like) from Magnaporthe oryzae (rice blast fungus). MAX effectors share a conserved β-sandwich structure (

), despite sharing low sequence similarity between them They also contain two highly conserved cysteines.

Effectors are small and very diverse proteins secreted by fungi and translocated in plant cells during infection. They are usually secreted during plant infection. The effectors are small proteins (under 200 amino acids) whose specific targets remain only partially known. Effectors show very divergent sequences, sharing a signal peptide on the N-terminal end. This signal peptide is essential for their secretion and then their translocation inside the plant cell .
Mitochondrial microtubule binder MBB1 (MBB1)
Type: Family

This protein family includes the uncharacterised protein mitochondrial microtubule binder MBB1 from Saccharomyces cerevisiae and similar fungal sequences. MBB1 is a small protein that may be involved in metabolic processes .
Non-contractile tail sheath, N-terminal domain (NCTSP_N)
Type: Domain

This entry represents the N-terminal domain found in the non-contractile tail sheath protein (NCTSP) from Bacteriophage N4 (BPN4). This protein is essential for BPN4 infectivity and it is hypothesized that it mediates binding with target cell receptors . The function of this domain is unknown. This entry also includes sequences from bacteria, predominantly from Sphingobium spp.
NTCP5/P3, N-terminal domain (NTCP5_P3_N)
Type: Domain

This entry represents the N-terminal domain of Sodium/bile acid cotransporter 5 (NTCP5) and protein P3 from animals, which may have bile acid:sodium symporter activity. This domain is predicted to adopt a β-sandwich fold.
Phage putative PDDEXK endonuclease (PDDEXK_14)
Type: Family

This entry represents a small family of phage proteins that are structurally related to the PD-(D/E)XK nuclease superfamily. The highest structural similarity is to Holliday junction resolvase Hjc proteins and tRNA-splicing endonucleases from archaebacteria. The exact function of this protein family, which also includes bacterial prophages, is unknown.
Phage ACT-like containing protein (ACT-containing_phage)
Type: Family

This entry represents an uncharacterised phage protein family. It contains an N-terminal domain that looks like an ACT domain.