SII-SWORD/CoKE huggingface dataset:
IFT81, calponin homology domain (IFT81_CH)
Type: Domain

This is the N-terminal domain found in IFT81 proteins. Crystal structure analysis revealed that IFT81-N adopts the fold of a calponin homology (CH) domain with structural similarity to the kinetochore complex component NDC80 with microtubule (MT)-binding properties. Functional analysis show that IFT74 and IFT81 form a tubulin-binding module required for ciliogenesis. It is suggested that IFT81-N binds the globular domain of tubulin to provide specificity, and IFT74-N recognizes the beta-tubulin tail to increase affinity .
Glycosyl hydrolases family 38, C-terminal domain (GH38_C)
Type: Domain

This domain is found at the C-terminal end of various glycosyl hydrolases belonging to family 38. The domain has a β sandwich fold.
Extracellular cadherin domain (EC_dom)
Type: Domain

This entry represents an extracellular cadherin (EC) domain which can be found at the N-terminal region of Pcdh15. Pcdh15 features exceptionally long extracellular domains containing 11 ECs . These repeats are structurally similar, but not identical in sequence, often featuring linkers with conserved calcium-binding sites that confer mechanical strength to them .

Protocadherin-15 (Pcdh15) belongs to the epsilon subfamily of nonclustered protocadherins. It is a component of the tip-links, the extracellular filaments that connect the tips of stereocilia and gate hair cell mechano-electrical transduction channels in the inner ear . Pcdh15 interacts with transmembrane channel-like proteins TMC1 and TMC2, which have been implicated in mechanotransduction in mammalian hair cells . Mutations in genes coding for Pcdh15 cause deafness in both mice and humans . Pcdh15 plays an important role in hair-bundle morphogenesis .
Chromodomain helicase DNA-binding domain (Cdh1_DBD)
Type: Domain

This domain can be found in chromodomain helicase DNA-binding protein 1 (Chd1) present in Saccharomyces cerevisiae. Cdh1 proteins have been associated with the efficient assembly and spacing of nucleosomes . Chd1 consists of a double chromodomain, an Snf2-related ATPase domain and a C-terminal DNA binding domain .

This domain comprises the first four helices of the Chd1 DNA binding domain, which can be divided into regions SANT, HL1 and the β-linker. The HL1 region comprises of some 40 residues specific to budding yeast that are unlikely to form such a prominent feature or perform a conserved function in other species. Basic residues on the α1 helix are thought to be important for DNA interaction .

This domain is also found in the Hrp3 protein, another member of the Cdh1 family in Schizosaccharomyces pombe. Like Cdh1, Hrp3 also comprises two chromo-domains, SNF2-like ATPase/7 helicase domains, and a C-terminal DNA binding domain .
Replication initiator protein A, C-terminal domain (Bac_RepA_C)
Type: Domain

This is the C-terminal domain (CTD) that can be found in the conserved replication initiator, RepA, essential for staphylococcal propagation. RepA CTD shared the strongest structural homology to the Enterococcus faecalis DnaD CTD, yet perform distinct functions. RepA CTD shows strong sequence homology between RepA_N plasmids in genus-specific clusters, suggesting that it may perform host-specific functions necessary for replication. The RepA CTD interacts with the host DnaG primase, which binds the replicative helicase. Structural data indicate that the RepA CTD exists as a monomeric entity, flexibly tethered to the DNA-bound NTD .
Oligosaccharyltransferase, peripheral 2 domain (OST_P2)
Type: Domain

This is a domain found in the C-terminal region of AGLB present in P. furiosus, oligosaccharyltransferase which catalyses the transfer of a heptasaccharide, containing one hexouronate and two pentose residues, onto peptides in an Asn-X-Thr/Ser-motif-dependent manner. This domain, known as the Peripheral 2 (P2) domain, encircles the central core domain .
LST4, longin domain (LST4_longin)
Type: Domain

This is a longin domain which is found in the N-terminal region of Lst4 proteins in yeast. Lst4 is the Fnip1/2 orthologue found in mammals. Lst4 forms a complex with Lst7 and are targeted to the vacuole when the cells are starved of carbon, and to a lesser extent nitrogen. Lst4 and Fnip1/2 belong to the DENN family of proteins which comprise an N-terminal longin domain, commonly found in a variety of trafficking proteins, and a C-terminal DENN domain. This domain is made up of a core five-strand β-sheet, with one short α-helix .
Archaeal glycosylation protein B, peripheral domain (AglB_P1)
Type: Domain

This domain is found in Archaeal Glycosylation B protein (AglB-Long) in A. fulgidus. When the domain, known as peripheral l (Pl), is combined with the central core (CC) and insertion (IS) sub-units, they form the C-terminal domain. It is thought that the C-terminal domain may contribute toward the increased thermal stability of the AglB proteins in the hyper-thermophilic .
FERM F1 lobe ubiquitin-like domain (FERM_F1)
Type: Domain

This is an F1 lobe domain consisting of a ubiquitin like fold found in FERM region of Jak-family tyrosine kinases . Multidomain JAK molecules interact with receptors through their FERM and SH2-like domains, triggering a series of phosphorylation events, resulting in the activation of their kinase domains . Overall, the FERM region maintains the typical three-lobed architecture, with an F1 lobe consisting of a ubiquitin-like fold, an F2 lobe consisting of an acyl-CoA binding protein fold, and an F3 lobe consisting of a pleckstrin-homology (PH) fold .
Transmembrane protein 250 (TM250)
Type: Family

Transmembrane protein 250 is implicated in cellular processes related to cell proliferation, specifically by aiding the transition into the S phase of the cell cycle. Additionally, it has a role in viral pathogenesis, as it is known to enhance the proliferation of human herpes simplex virus 1 (HHV-1) .
Up-regulated in Daf-2 (PUD1/2)
Type: Domain

This entry includes C. elegans PUD-1 and PUD-2, two proteins up-regulated in daf-2 (loss-of-function) (PUD), which are homologous 17kDa proteins with similar β-sandwich folds that further associate with each other into a V-shaped heterodimer .
Cue1, Ubc7p-binding domain (Cue1_U7BR)
Type: Domain

Cue1p (coupling of ubiquitin conjugation to ER degradation protein 1) is an integral component of yeast endoplasmic reticulum (ER)-associated degradation (ERAD) ubiquitin ligase (E3) complexes. It tethers the ERAD ubiquitin-conjugating enzyme (E2), Ubc7p, to the ER and prevents its degradation, and also activates Ubc7p. This domain represents the Ubc7p-binding region (U7BR) of Cue1p with Ubc7p. The U7BR is as E2-binding domain that includes three α-helices that interact extensively with the 'backside' of Ubc7p. U7BR stimulates both RING-independent and RING-dependent ubiquitin transfer from Ubc7p. Moreover, the U7BR enhances ubiquitin-activating enzyme (E1)-mediated charging of Ubc7p with ubiquitin .
SLOG cluster2 (LD_cluster2)
Type: Family

This is a subfamily of the SLOG superfamily, observed associating with distinct effector domains including the patatin lipase or a protein containing one enzymatically active and one inactive copy of the TIR domain .
Tenascin, EGF-like domain (EGF_Tenascin)
Type: Domain

This entry represents the EGF-like domains found in Tenascin proteins (TN, TN-R, TN-X, TN-N). A common feature of all EGF-like domains is that they are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin G/H synthase). The EGF-like domain includes six cysteine residues which have been shown to be involved in disulfide bonds. The structure of several EGF-like domains has been solved. The fold consists of two-stranded β-sheet followed by a loop to a C-terminal short two-stranded sheet .

Tenascins are extracellular matrix glycoproteins that act both as integrin ligands and as modifiers of fibronectin-integrin interactions to regulate cell adhesion, migration, proliferation and differentiation. Tenascins are usually composed of repeated epidermal growth factor (EGF)-like domains, fibronectin-type III (FNIII) domains and a C-terminal fibrinogen related domain (FReD) .
Bacterial HORMA domain 1 (Bact_HORMA_1)
Type: Domain

This entry represents a set of bacterial HORMA domains found in proteins from the CBASS (cyclic oligonucleotide-based antiphage signaling system), a system that provides immunity against bacteriophage. This domain is found in CD-NTase-associated protein 7 (Cap7) from E.coli, that acts as a sensor protein of CBSS and binds to a closure peptide allowing it to activate the CD-NTase CdnC for second messenger synthesis and, therefore, it activates a diverse range of effectors .
Ret, cadherin like domain 1 (Ret_CLD1)
Type: Domain

Ret is a single transmembrane-spanning receptor tyrosine kinase (RTK) that plays critical roles in the development of vertebrates. It contains four consecutive cadherin-like domains (CLD). This entry represents the first CLD at the N-terminal. Several regions within RET-CLD1 have been shown to be important for ligand-coreceptor binding. CLD1 and CLD2 have a distinctive clamshell shape and CLD1 is essential for CLD2 folding. CLD1 contains 2 sites for GDNF receptor alpha 1 binding .
SLOG cluster4 (LDcluster4)
Type: Family

This entry represents a subfamily of the SLOG superfamily, observed as a standalone domain with little informative genome context, although related families in the SLOG superfamily are predicted to function in diverse conflict contexts .
Cas6, N-terminal domain, archaea (Cas6_N_arch)
Type: Domain

This entry represents the N-terminal domain of Cas 6, which is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability . Structural analysis of Sulfolobus sulfotaricus P2 Cas6 (SsCas6) proteins indicate that SsCas6 is able to bind and cleave the nonstructured RNA by stabilizing an otherwise unstable duplex of two base pairs near the cleavage site, leading to an inline conformation around the scissile phosphate necessary for its breakage .
LapB, rubredoxin metal binding domain (Rubredoxin_2)
Type: Domain

LapB (lipopolysaccharide assembly protein B) contains three major structural motifs: the N-terminal transmembrane helix, several tetratricopeptide repeats (TPR), and a C-terminal rubredoxin metal binding domain. This entry represents the rubredoxin-like metal binding domain. Rubredoxin proteins form small non-heme iron binding sites that use four cysteine residues to coordinate a single metal ion in a tetrahedral environment. Rubredoxins are most commonly found in bacterial systems, but have also been found in eukaryotes. The key features of these rubredoxin-like domains are the extended loops or 'knuckles' and the tetracysteine mode of iron binding. Structural analysis of LapB from Escherichia coli show that the rubredoxin metal binding domain is intimately bound to the TPR motifs and that this association to the TPR motifs is essential to LPS regulation and growth in vivo .
SAVED-fused 2TM effector domain (Saf_2TM)
Type: Domain

This is a predicted pore-forming effector domain directly fused to predicted SAVED sensor domain. Binding of a ligand via the SAVED sensor is predicted to activate the Saf-2TM and initiate a cell suicide response. It is a component of a class of conflict systems reliant on the production of second messenger nucleotide or nucleotide derivative .
L-Lysine epsilon oxidase, N-terminal (LodA_N)
Type: Domain

This is the N-terminal domain found in antimicrobial protein (LodA) with lysine-epsilon oxidase activity (

) which is produced by Gram-negative marine bacteria such as Marinomonas mediterranea . The enzyme, previously named marinocine, catalyzes the oxidative deamination of l-lysine into 6-semialdehyde 2-aminoadipic acid, ammonia, and hydrogen peroxide (H2O2). Orthologous proteins have been detected in other bacterial genera, where they participate in biofilm development and dispersal . It has been shown that M. mediterranea LodA and its homologues induce cell death in the microcolonies formed in the process of biofilm development due to the hydrogen peroxide generated by their enzymatic activity. Moreover, cells dispersed from the biofilm by means of this mechanism show a phenotypic variation in growth and biofilm formation. The active form of LodA containing the quinonic cofactor is generated intracellularly only in the presence of LodB, suggesting that the latter protein is involved in this process .
Alpha helical domain (Alpha_helical)
Type: Domain

This is the N-terminal domain found in putative tRNA-binding proteins found in archaea. Structural analysis from Pyrococcus horikoshii indicate that it is a helical domain where many conserved residues are found in the first three helices and are mainly located on the inverse side of the putative tRNA-binding site. A structural homology search suggested that this fold prefers to bind proteins/peptides .
RING/Ubox-like zinc-binding domain (Znf-RING_14)
Type: Domain

This is a RING zinc finger domain found in parkin proteins. Parkin consists of a ubiquitin-like (Ubl) domain and a 60-amino acid linker followed by RING0 and three additional zinc finger domains characteristic of the RBR family. This entry relates to RING1 zinc binding domain. The RING1 domain displays the C3HC4 cross-brace motif characteristic of RING domains. The N-terminal Ubl domain binds to RING1 .
SDR-like Ig domain (SDR_Ig)
Type: Domain

This entry represents a bacterial Ig-fold domain that is found in members of the serine-aspartate repeat-containing protein (SDR) family .
Esterase, Ig-like N-terminal (EstA_Ig-like_N)
Type: Domain

This is an N-terminal immunoglobulin (Ig)-like domain found in esterases such as EstA. Analysis of the EstA structure confirms that it is a member of the alpha/beta hydrolase family, with a conserved Ser-Asp-His catalytic triad. The Ig-like domain presumably plays a role in the multimerization of EstA into an unusual hexameric structure. Additionally, it may also participate in the catalysis of EstA by guiding the substrate to the active site .
L-lysine epsilon oxidase, C-terminal (LodA_C)
Type: Domain

This is the C-terminal domain found in antimicrobial protein (LodA) with lysine-epsilon oxidase activity (

) which is produced by Gram-negative marine bacteria such as Marinomonas mediterranea . The enzyme, previously named marinocine, catalyzes the oxidative deamination of l-lysine into 6-semialdehyde 2-aminoadipic acid, ammonia, and hydrogen peroxide (H2O2). Orthologous proteins have been detected in other bacterial genera, where they participate in biofilm development and dispersal . It has been shown that M. mediterranea LodA and its homologues induce cell death in the microcolonies formed in the process of biofilm development due to the hydrogen peroxide generated by their enzymatic activity. Moreover, cells dispersed from the biofilm by means of this mechanism show a phenotypic variation in growth and biofilm formation. The active form of LodA containing the quinonic cofactor is generated intracellularly only in the presence of LodB, suggesting that the latter protein is involved in this process .
KRR1 small subunit processome component, first KH domain (KRR1-like_KH1)
Type: Domain

This entry represents the first K homology domain (KH1) in the KRR1 and Dim2 (Pno1) proteins.

Krr1 and Dim2 are structurally related ribosomal assembly factors, present on the 90S pre-ribosome . They both belong to the family of RNA binding domains that contain K homology (KH) domains. Dim2 and Krr1 each contain two sequential KH domains (KH1 and KH2), but the N and C-terminal extensions differ between the two proteins . The two KH domains are evident in the structure of KKr1 from Saccharomyces Cerevisiae .

The KH1 domains in Krr1 and Dim2 lack the typical GXXG RNA binding motif and are involved, instead, in protein-protein interactions. The KH1 domain in Krr1 interacts with the nucleolar assembly factor Kri1 and the KH1 domain of Dim2 interacts with the endonuclease Nob1 .
VLRF1/Vms1 (VLRF1/Vms1)
Type: Domain

This entry represents a domain found in proteins belonging to the VLRF1 clade of the archaeo-eukaryotic RF1 (aeRF1) superfamily. The yeast Vms1 is the founding member the VLRF1 (Vms1-Like Release Factor-1) clade. In addition to the eukaryotic orthologs of Vms1 the VLRF1 clade also contains members from certain bacteria, predominantly bacteroidetes and more divergent versions in certain Archaea .

Proteins containing this domain have a conserved glutamine residue in the release factor catalytic loop, suggesting they function as active peptidyl-tRNA hydrolases at the ribosome .

This domain is also found in Ankyrin repeat and zinc finger domain-containing protein 1 from humans (ANKZF1), which plays a role in the cellular response to hydrogen peroxide and in the maintenance of mitochondrial integrity under conditions of cellular stress . It is an endonuclease that cleaves polypeptidyl-tRNAs downstream of the ribosome-associated quality control (RQC) pathway to release incompletely synthesized polypeptides for degradation .
von Willebrand factor type A, C-terminal domain (VWA_3_C)
Type: Domain

This is the C-terminal domain of uncharacterised bacterial proteins containing a von Willebrand factor type A domain.
Holliday junction resolvase Gen1, C-terminal domain (GEN1_C)
Type: Domain

This is the C-terminal domain found in GEN1 resolvase. It is composed of three-strand antiparallel β sheets and four α helices . GEN1 protein, a member of the XPG/Rad2 family of structure-selective endonucleases, is specialized for the cleavage of Holliday junction recombination intermediates . Structural comparison indicates that the C-terminal domain is similar to a series of chromobox homology proteins . Functional analysis indicates that the chromodomain provides an additional DNA binding site necessary for efficient HJ cleavage, and its truncation severely hampers GEN1's catalytic activity .
RPA43, OB domain (RPA43_OB)
Type: Domain

This entry represents the OB domain found in Rpa43 (also known as A43), which is a component of RNA polymerase I (Pol I) that synthesizes ribosomal RNA precursors. RNA polymerase I subunits A14 and A43 form the heterodimer A14/43, which is distantly related to Rpb4/7 in Pol II and C17/25 in Pol III . A43-A14 heterodimer forms the stalk that provides a platform for initiation factors and interacts with newly synthesized RNA .
Centrosomal protein C10orf90, N-terminal (C10orf90_N)
Type: Domain

This is the N-terminal region found on proteins encoded by C10orf90, also known as FATS. Most of the family members carry ALMS motif on their C-terminal (

). SiRNA mediated functional analysis suggest that the C10orf90 encoded proteins have a role in centrosomal functions .
Nucleotide modification associated domain 2 (Nmad2)
Type: Domain

This entry represents a β-strand rich domain containing a conserved cysteine and charged residues predicted to play a role in modified DNA base biosynthesis .
DR2241 stabilising domain (DR2241_middle)
Type: Domain

This is the middle domain found in DR2241, a multi-domain protein with an N-terminal cobalamin (vitamin B12) chelatase domain. DR2241 is found in D. radiodurans. The middle domain has four α-helices (α7-α10) in contact with the N-terminal domains and C-terminal domain and five anti-parallel β-strands with strand order 12354 at the outer side of one monomer. The middle domain, as well as the C-terminal domain, are heavily involved in the tetramer stabilisation .
Leptin receptor, immunoglobulin-like domain (LEP-R_IGD)
Type: Domain

This is the immunoglobulin-like domain (IGD) found in leptin receptors (LEP-R), also known as obesity receptors (ObR). ObR is a single membrane-spanning receptor belonging to the class I cytokine receptor family. All isoforms have an identical extracellular part consisting of six domains: an N-terminal domain (NTD), two CRH domains (CRH1 and CRH2), an immunoglobulin-like domain (IGD), and two additional membrane-proximal fibronectin type III (FN III) domains. ObR activation depends on the CRH2, IGD, and FN III domains, however the CRH2 domain is the major leptin-binding determinant in the receptor. The IGD and membrane-proximal domains have no detectable affinity for the ligand, but are nonetheless indispensable for receptor activation. Deletion of the IGD results in a receptor with wild-type affinity for leptin, but completely devoid of biological activity .
Cyclophilin-like (Cyclophilin-like)
Type: Domain

This entry represents a domain found in cyclophilin-like proteins from a range of bacterial species.
T6 antigen, Ig-like domain (T6_Ig-like)
Type: Domain

This is an N-terminal immunoglobulin-like domain. Family members carrying this domain include trypsin-resistant surface T6 protein found in Streptococcus pyogenes .
IKBKB, scaffold dimerization domain (IKBKB_SDD)
Type: Domain

This is the C-terminal scaffold dimerization domain (SDD) found in inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) . IKBKB is one of the core component of IKB kinases (IKK), which is an enzyme that quickly becomes active in response to diverse stresses. The SDD consists primarily of two long α-helices . This domain can also be found in inhibitor of nuclear factor kappa-B kinase subunit alpha (IKKA).
Domain of unknown function DUF3823_C (DUF3823_C)
Type: Domain

This domain is found in uncharacterised proteins from Bacteroidetes. It has an Ig-like fold.
ARS-binding protein 1, N-terminal (HTH_ABP1_N)
Type: Domain

This domain can be found in CENP-B homologue protein 1/2 (CBHP-1/2)and ARS-binding protein 1 (Abp1) from Shizosaccharomyces pombe. The domain, referred to as domain 1, is DNA-binding and makes up half of the N-terminal region .
Transcription factor IIB, C-terminal module 1 (TFIIB_C_1)
Type: Domain

In the pathogenic trypanosome, Trypanosoma brucei, transcription factor IIB (tTFIIB) is essential for spliced leader (SL) RNA gene transcription and cell viability, but has a highly divergent primary sequence in comparison to TFIIB in other eukaryotes. Structure analysis of the C-terminal region of trypanosome TFIIB, reveals 2, closely packed helical modules followed by a C-terminal extension of 32 aa. The trypanosome-specific region comprises the second helical module and the C-terminal extension. Both helical modules contain the canonical 5-helix cyclin fold characteristic of TFIIB proteins . This domain is mostly found in Trypanosomatidae.
Midasin AAA lid domain 5 (Midasin_AAA_lid_5)
Type: Domain

This entry represents the α helical AAA+ lid domain that is found to the C terminus of AAA domains . This lid domain is found in midasin, which is a nuclear chaperone required for maturation and nuclear export of pre-60S ribosome subunits .
pPIWI_RE three-gene island domain Y (pPIWI_RE_Y)
Type: Domain

This is a poorly-understood domain observed N-terminal to restriction endonuclease (REase) domain, which is part of a conserved three-gene island also containing a DinG-type helicase and the pPIWI_RE module. This three gene island is predicted to form a conflict system which targets R-loop formation of invasive plasmids during plasmid replication .
ZNF451, PIN-like domain (PIN_11)
Type: Domain

This is a eukaryotic/eumetazoan PIN like domain found in the C-terminal region of bilateral ZNF451 proteins such as isoform 1 of human ZNF451. ZNF451 was shown to interact with p300 by the PIN-like domain and to negatively regulate TGF-beta signalling in a p300-dependent and sumoylation-independent manner. This domain is suggested to posses a potential active nuclease due to the presence of at least four conserved Asp residues in the predicted active site. Furthermore, it contains several conserved Cys and His residues, which may suggest stabilization of the domain structure with an embedded short zinc-binding loop .