SII-SWORD/CoKE huggingface dataset:
Ubiquitin carboxyl-terminal hydrolase 25/28, UIM (USP25/28_UIM)
Type: Conserved_site

This entry represents the N-terminal ubiquitin-interacting motif (UIM) found in ubiquitin carboxyl-terminal hydrolase 25 and 28, which are ubiquitin-specific proteases (USP) . This domain provides a structural basis for the recognition and recruitment of ubiquitin substrates, potentially conferring USP display of catalytic activity .

USP25 functions in various biological processes including inflammation, immune response . It modulates the Wnt/beta-catenin pathway by deubiquitinating and stabilizing tankyrases TNKS1 and TNKS2 . USP25 regulates KEAP1-NRF2 axis in the defense against oxidative assaults by deubiquitinating KEAP1 and protecting it from degradation leading to degradation of the NRF2 transcription factor that is responsible for mounting an anti-oxidation gene expression program .

USP28 is involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN . It is also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. It deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells .
UBA-like domain (UBA_8)
Type: Domain

This entry represents a UBA-like domain.
Endo-beta-N-acetylglucosaminidase D-like, D2 domain (EndoD-like_D2)
Type: Domain

This entry represents the D2 domain of Endo-beta-N-acetylglucosaminidase D (EndoD,

) from Streptococcus pneumoniae and similar sequences, which belong to family 85 of glycoside hydrolases (GH85 endohexosaminidases). These enzymes cleave the glycosidic linkage between the two N-acetylglucosamine units that make up the chitobiose core of N-glycans.This domain adopts a typical fibronectin Ig-like fold .
PG_1098, N-terminal domain (PG_1098_N)
Type: Domain

This small α-helical domain is found at the N-terminal of putative methyltransferase proteins. The structure of a member has been determined

.
Glycosyltransferase 99, N-terminal domain (Glyco_transf_99_N)
Type: Domain

This entry represents the N-terminal domain found in a new family of glycosyltransferases (GTs) assigned as family Glycosyltransferase 99 (GT99) in the CAZy database .

The GT99 family includes a prototype beta-Kdo GT from WbbB ([swissprot Q6U8B0]), a modular protein participating in lipopolysaccharide (LPS) O-antigen synthesis in Raoultella terrigena. Kdo (3-deoxy-D-manno-oct-2-ulosonic acid) is an eight-carbon sugar mostly found in Gram-negative bacteria, where it is involved in attaching surface polysaccharides to their lipid anchors. Alpha-Kdo provides a bridge between lipid A and the core oligosaccharide in all bacterial LPSs, while an oligosaccharide of beta-Kdo residues links group 2 capsular polysaccharides to (lyso)phosphatidylglycerol. beta-Kdo is also found in a small number of other bacterial polysaccharides. The structure and function of the prototypical cytidine monophosphate-Kdo-dependent alpha-Kdo glycosyltransferase from LPS assembly is well characterised. The WbbB2-401 protein structure is built around two α/β domains with recognisable Rossmann-fold topology, broadly meeting the criteria of conforming to a GT-B fold .
ORC6, second cyclin-like domain (ORC6_cyclin-like_2nd)
Type: Domain

The metazoan and plant origin recognition complex subunit 6 (ORC6) contains two homologous domains that are arranged in tandem and both adopting a cyclin-like topology . This entry represents the second cyclin-like domain of ORC6, a protein that directs DNA replication by binding to replication origins and is also involved in transcriptional silencing; interacts with Spp1 and with trimethylated histone H3; phosphorylated by Cdc28 .

The Origin Recognition Complex (ORC) is a six-subunit ATP-dependent DNA-binding complex encoded by ORC1-6 . ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle . ORC directs DNA replication throughout the genome and is required for its initiation . ORC bound at replication origins serves as the foundation for assembly of the pre-replicative complex (pre-RC), which includes Cdc6, Tah11 (aka Cdt1), and the Mcm2-7 complex . Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase . Cell cycle-regulated phosphorylation of ORC2, ORC6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2/M phase .

In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci Hidden MAT Left (HML) and Hidden MAT Right (HMR) . ORC participates in the assembly of transcriptionally silent chromatin at HML and HMR by recruiting the Sir1 silencing protein to the HML and HMR silencers .
Major tropism determinant, second domain (Mtd_2nd)
Type: Domain

This entry represents the second domain of major tropism determinant (Mtd). Mtd, the receptor-binding protein of Bordetella bacteriophage, varies greatly in sequence . It is the tail fibre protein located at the distal ends of the fibres that binds to the adhesion receptors on the host surface, thereby determining the host range. Variation in Mtd depends on a phage-encoded retroelement that belongs to a family of retroelements implicated in generating sequence diversity in various phage and bacterial genomes. The second domain, represented by this entry, forms a β-sandwich structure (

).
Magnesium and cobalt efflux protein CorC, N-terminal domain (CorC_N)
Type: Domain

This entry represents a pair of helices found at the N-terminal of some CBS domain proteins. A pair of these regions dimerise to form a four helical bundle. Proteins in this family have this region followed by two CBS domains and a Transporter-associated domain (

).
Cas12a, REC2 domain (Cas12a_REC2)
Type: Domain

This entry represents the REC2 domain found in Cpf1, also known as CRISPR-associated endonuclease Cas12a. Cpf1 is an RNA-guided endonuclease of a type V CRISPR-Cas system that has been harnessed for genome editing. The REC2 domain is a part of the REC lobe of the bilobed architecture of Cpf1, which consists of both REC1 and REC2 domains. The REC2 domain comprises 10 α-helices and 2 β-strands that form a small antiparallel β-sheet . The crRNA-target DNA heteroduplex is accommodated within the positively charged, central channel formed by the REC1, REC2, and RuvC domains, and is recognised by the protein in a sequence-independent manner.
Thermus phage P23-45 portal protein (P23-45_portal)
Type: Family

This entry represents the Thermus phage P23-45 portal protein. The portal protein is a key component of many double-stranded DNA viruses, governing capsid assembly and genome packaging. Twelve subunits of the portal protein define a tunnel, through which DNA is translocated into the capsid .
Ski7, domain III (Ski7_3rd)
Type: Domain

This entry represents the third domain (domain III) of the Superkiller protein 7 (Ski7), a cofactor of the cytoplasmic exosome that functions in mRNA turnover and non-stop decay (NSD). The C-terminal region of these proteins is organised into three domains, with domain I adopting the α/β fold of GTP-binding domains, and domains II and III each adopting the structure of a closed β-barrel. Domains II and III appear to form a single unit and interact with the G domain, and the three domains interact intra-molecularly not only via their globular folds but also via extended segments. The Ski7 domain II shares overall sequence similarity with the translational GTPase (trGTPase) Hbs1, but unlike other trGTPases, Ski7 might function as a GTP-binding protein rather than a GTP-hydrolyzing enzyme .
Ski7, domain II (Ski7_2nd)
Type: Domain

This entry represents the second domain (domain II) of the Superkiller protein 7 (Ski7), a cofactor of the cytoplasmic exosome that functions in mRNA turnover and non-stop decay (NSD). The C-terminal region of these proteins is organised into three domains, with domain I adopting the α/β fold of GTP-binding domains, and domains II and III each adopting the structure of a closed β-barrel. Domains II and III appear to form a single unit and interact with the G domain, and the three domains interact intra-molecularly not only via their globular folds but also via extended segments. The Ski7 domain II shares overall sequence similarity with the translational GTPase (trGTPase) Hbs1, but unlike other trGTPases, Ski7 might function as a GTP-binding protein rather than a GTP-hydrolyzing enzyme .
Penicillin binding protein A, dimerisation domain (PBPA_dimer)
Type: Domain

This domain is found in peptidoglycan D,D-transpeptidase also known as penicillin-binding protein A (PBPA). This domain consists of a four-stranded mixed β-sheet with three short helices packed on one side . Compared to the N-terminal domains of other class B High Molecular Mass (HMM) PBPs, the NTD of PBPA is relatively small because it contains only the so-called inter-domain linker region .
Peptidoglycan-binding protein ArfA, BON-like domain (ArfA_BON-like)
Type: Domain

This entry represents BON-like domain found in Peptidoglycan-binding protein ArfA from Mycobacterium tuberculosis, which appears to lack the first α-helix of the classical BON domain structure. ArfA is thought to play a role in ammonia secretion, although it does not play a direct role in ammonia transport. This domain precedes the BON domain (

) and shows an α-β configuration .
Gp138-like, beta-helical trimerization domain (Gp138-like_C)
Type: Domain

This domain is found in Gp138 from Escherichia phage phi92 (

) and similar sequences found in tailed bacteriophages and prophages from proteobacteria. Gp138 forms an spike-shaped trimer with three highly intertwined chains. Each polypeptide has an oligonucleotide/oligosaccharide-binding (OB-fold) domain (

) and a long β-helical C-terminal domain (this entry), which initiates the contact with the host cell membrane. The trimeric β-helix is composed of three antiparallel β-sheets, which swap three C-terminal β-strands with each other around the threefold axis .
CT0912-like, N-terminal domain (CT0912-like_N)
Type: Domain

This domain is found in

from Chlorobaculum tepidum and similar bacterial proteins. It adopts an α-β configuration.
MIC2-associated protein, beta-domain (M2AP_beta_dom)
Type: Domain

This domain is found in MIC2-associated protein from Toxoplasma gondii (M2AP), which is necessary for the proper trafficking and secretion of MIC2 and thus involved in parasite invasion. M2AP is a soluble protein with an N-terminal propeptide, a central β-domain (this entry), and a predicted C-terminal coil domain. This domain folds into a a compact β-sandwich comprising 13 antiparallel β-strands .
MCM5, C-terminal domain (MCM5_C)
Type: Domain

This entry represents the C-terminal domain of MCM5 from humans and its homologues . MCM5 is part of the MCM2-7 complex. This is a HTH domain.
CprB tetracyclin repressor-like, C-terminal domain (CprB_TetR_C)
Type: Domain

This domain is found at the C-terminal of CprB from Streptomyces coelicolor (

) and similar bacterial transcriptional regulators . This region is the ligand-binding domain (LBD) . It is often found associated with

.
Pcf11, C-terminal domain (Pcf11_C)
Type: Domain

This entry represents the C-terminal domain of Pcf11, a CCHC zinc-finger domain which contains a conserved interface for potential binding partners. Mutational studies revealed that mutations in key residues in this conserved region disrupt 3'-end processing . Pfc11 is a highly conserved multidomain protein that links transcriptional elongation, 3'-end processing, and transcription termination.
Pfc11, Rna14/15 interacting domain (Pfc11_Rna14/15-ID)
Type: Domain

This entry represents the Rna14/15 interacting domain (Rna14/15-ID) of Pfc11 from yeast . Pfc11 is a multidomain protein that links transcriptional elongation, 3'-end processing, and transcription termination.
DesT tetracyclin repressor-like, C-terminal domain (DesT_TetR_C)
Type: Domain

This domain is found at the C-terminal end of DesT from Pseudomonas aeruginosa (

) and similar bacterial transcriptional regulators such as the HTH-type transcriptional repressor FabR. DesT is involved in the control of the unsaturated:saturated fatty acid ratio available for membrane lipid synthesis. This region folds into six helices that create the ligand-binding domain . It is normally found associated with

.
Mitochondrial-derived peptide MOTS-c (MT-RNR1)
Type: Family

This protein family represents human Mitochondrial-derived peptide MOTS-c (MT-RNR1), a 16-residue peptide that regulates insulin sensitivity and metabolic homeostasis .
Snake toxin cobra-type (Toxin_cobra-type)
Type: Family

This family represents snake toxins, including short and long neurotoxins, cytotoxins and short toxins mainly from Naja genus of snakes (cobras).

Cytotoxins (CTs, also known as cardiotoxins) are small (~60 amino acids) proteins that mediate their toxic effect through interaction with the cell membrane . Neurotoxins interfere with cholinergic transmission at postsynaptic sites in the peripheral and central nervous systems. Cobrotoxin binds to muscle nicotinic acetylcholine receptor (nAChR) and inhibit acetylcholine from binding to the receptor, thereby impairing neuromuscular transmission . In vivo rat model of arthritis, it showed anti-inflammation and immunosuppression effects . These toxins have three β-stranded loops resembling three fingers.
Consortin, N-terminal domain (Consortin_N)
Type: Domain

Consortin is a trans-Golgi network cargo receptor involved in targeting connexins to the plasma membrane . This entry represents a domain found towards its N-terminal that is predicted to show a helical configuration. Members of this group are mainly found in vertebrates.
T-cell receptor gamma alternate reading frame protein (TARP)
Type: Family

This protein family includes human T-cell receptor gamma alternate reading frame protein (TARP) and similar sequences from vertebrates. TARP is a 7kDa protein with five leucine residues in heptad repeats followed by a basic region. It is expressed at higher levels in several types of cancerous cells .
Protein PAXX, N-terminal domain (PAXX_N)
Type: Domain

Protein PAXX (also known as Paralog of XRCC4 and XLF) is a paralog of X-ray repair cross-complementing protein 4 (XRCC4) and XRCC4-like factor (XLF) that is involved in non-homologous end joining (NHEJ), a major pathway to repair double-strand breaks (DSBs) in DNA. It may act as a scaffold required to stabilise the DSB-repair protein Ku heterodimer, composed of XRCC5/Ku80 and XRCC6/Ku70, at double-strand break sites in cells. It functions with XRCC4 and XLF to bring about DSB repair and cell survival in response to DSB-inducing agents . Similar to XRCC4 and XLF, PAXX monomers are comprised of an N-terminal globular head domain, a centrally located coiled-coil, and a C-terminal region. These monomers homodimerize through two homodimerization domains, the N-terminal globular head domain and long extended α-helical coiled-coil regions. This entry represents the N-terminal head domain of PAXX, which is structurally related to other XRCC4-superfamily members .
Dermonecrotic toxin, barrel-like domain (ToxA_barrel)
Type: Domain

Dermonecrotic toxin (ToxA), also known as Pasteurella multocida toxin (PMT), inhibits osteoblastic differentiation in mammals and birds. It consists of an N-terminal domain that binds to target cells, and a large C-terminal domain. This entry represents a presumed barrel-like domain found between the N- and C-terminal domains.
Gp49, pectin lyase-like domain (Gp49_pectate_lyase-like)
Type: Domain

This entry represents the β-helix repeats from the catalytic domain of tailspike Gp49 from phage LKA1 (

) . Gp49 binds and cleaves B-band LPS of Pseudomonas aeruginosa, reducing its virulence .
PRKCH upstream open reading frame 2 (PRKCH_uORF2)
Type: Family

This entry represents human PRKCH upstream open reading frame 2 (PRKCH_uORF2), also known as Protein uPEP2, the product of an upstream open reading frame (uORF). PRKCH_uORF2 exhibits kinase inhibitory functions. It possesses the typical PKC pseudosubstrate motif present in all PKCs that autoinhibits their kinase activity .
TUNAR (TUNAR)
Type: Family

This protein family includes the human protein TUNAR and similar sequences from vertebrates. TUNAR is a 48-amino-acid micropeptide with a single-pass transmembrane domain involved in the regulation of intracellular calcium levels in neurons and in the endoplasmic reticulum of pancreatic beta cells, where it also enhances glucose-stimulated insulin secretion .
Carbapenem resistance protein CarG-like (CarG-like)
Type: Family

This entry represents the carbapenem resistance protein CarG from Serratia sp. and similar sequences mainly found in proteobacteria. CarG shows a unique β-sandwich fold with short terminal α-helices, displaying close structural homology with bacterial inhibitors of invertebrate lysozyme (

) .
AppA, four helical bundle (AppA_4HB)
Type: Domain

This domain is found in AppA protein from Rhodobacter sphaeroides and similar sequences from alphaproteobacteria. AppA is a light-sensing antirepressor involved in oxygen and light control of photosynthesis-gene expression. This protein senses blue-light via its N-terminal sensor of blue-light using FAD (BLUF) domain (

) and oxygen via its sensor containing heme instead of cobalamin (SCHIC) domain. This entry represents the domain that is located in between them, which folds as a four helical bundle (4HB) and acts as a binding platform for the adjacent domains .
TcdA1, receptor binding domain 2 (TcdA1_RBD_2)
Type: Domain

This domain is found in TcdA1 from Photorhabdus luminescens and similar sequences mainly from gammaproteobacteria. TcdA1 is one of the three subunits of the Tc toxins. TcdA1 acts as an injecting device responsible for translocating the actual toxic component into host cells. TcA has four receptor-binding domains. This domain is one of 4 receptor binding domains found in TcA. All four domains have an immunoglobulin (Ig)-like β-sandwich fold of two sheets with antiparallel β-strands .
AppA, SCHIC domain (AppA_SCHIC)
Type: Domain

This domain is found at the C-terminal end of AppA protein from Rhodobacter sphaeroides and similar sequences from alphaproteobacteria. AppA is a light-sensing antirepressor involved in oxygen and light control of photosynthesis-gene expression. This protein senses blue-light via its N-terminal blue-light using FAD (BLUF) domain (

) and oxygen via its sensor containing heme instead of cobalamin (SCHIC) domain (this entry). This domain has a flavodoxin-like fold .
Mannosylglycerate synthase, C-terminal domain (MGS_C)
Type: Domain

Mannosylglycerate synthase catalyses the formation of the stress protectant 2-O-alpha-D-mannosyl glycerate . It consists of an N-terminal GT-like domain and a C-terminal helical domain, which is represented in this entry, that is apparently involved in protein oligomerization .
TcdA1, receptor binding domain 1 (TcdA1_RBD_1)
Type: Domain

This domain is found in TcdA1 from Photorhabdus luminescens and similar sequences from proteobacteria. TcdA1 is one of the three subunits of the Tc toxins. TcdA1 acts as an injecting device responsible for translocating the actual toxic component into host cells. TcA has four receptor-binding domains. This domain is one of 4 receptor binding domains found in TcA. All four domains have an immunoglobulin (Ig)-like β-sandwich fold of two sheets with antiparallel β-strands .
Mannosylglycerate synthase, GT domain (MGS_GT)
Type: Domain

Mannosylglycerate synthase catalyses the formation of the stress protectant 2-O-alpha-D-mannosyl glycerate . It consists of a N-terminal GT-like domain and a C-terminal helical domain . This entry represents the N-terminal glycosyltransferase domain (GT) which, at the sequence level, is most similar to family-GT2 inverting GTs, however, MGS is a retaining GT .
HOXB-AS3 peptide (HOXB-AS3)
Type: Family

This family represents human HOXB-AS3 peptide, a 53-residues peptide that suppresses colon cancer (CRC) growth but is associated with a poor prognosis in oral squamous cell carcinoma (OSCC) .
Transcriptional regulator PINT87aa (LINC-PINT)
Type: Family

This protein family represents human Transcriptional regulator PINT87aa (LINC-PINT), an 87-residues peptide encoded by a circular RNA (circRNA) that suppresses glioblastoma cell proliferation in vitro and in vivo. It has been established as a biomarker and a key regulator of cellular senescence in hepatocellular carcinoma (HCC) .
ASNSD1 upstream open reading frame protein (ASNSD1-SEP)
Type: Family

This family includes human ASNSD1 upstream open reading frame protein (ASNSD1-SEP, for small/short open reading frame -encoded polypeptide) and similar sequences predominantly found in vertebrates. ASNSD1-SEP is a subunit of the prefoldin-like (PFDL) module of the PAQosome, an 11-subunit chaperone involved in the biogenesis of several human protein complexes. It shows great structural homology to β-prefoldin .
Small integral membrane protein 43 (SMIM43)
Type: Family

This protein family includes human Small integral membrane protein 43 (SMIM43, also known as NEMEP) and similar sequences from vertebrates. This protein has been associated with HIV and hepatitis C infection as well as with brain tumours and probably with essential tremor, cerebellar atrophy and other disorders . It is required for mesendoderm differentiation . It interacts with glucose transporters and promotes glucose uptake .
Transcriptional regulator SEHBP (SEHBP)
Type: Family

This protein family represents human Transcriptional regulator SEHBP (short ORF-encoded histone binding protein), a conserved microprotein that interacts with chromatin-associated proteins and acts as a transcription factor .
TR61B, FKBP-like domain (TR61B_FKBP-like)
Type: Domain

This is the FKBP-like domain found towards the N-terminal of TR61B (tRNA (adenine(58)-N(1))-methyltransferase) from human and similar proteins. This mitochondrion-specific protein catalyses the formation of N1-methyladenine at position 58 (m1A58) in various tRNAs and the formation of 1-methyladenosine at position 947 of mitochondrial 16S ribosomal RNA which is most likely important for mitoribosomal structure and function . TR61B is most similar to bacterial TrmI than to eukaryotic Trmt61A, according to phylogenetic tree analysis . The function of this domain is not clear but it may be necessary for overall folding and full enzymatic activity.
YajR, YAM domain (YajR_YAM)
Type: Domain

This entry represents the C-terminal YAM domain of YajR, an Escherichia coli transporter that belongs to the major facilitator superfamily and similar bacterial proteins. The YAM domain precise regulatory role is not yet known, it may sense environmental changes, such as pH and halogen ion variation .
Tailspike protein, galactose-binding domain-like (G7C_GBD)
Type: Domain

This entry represents the Tailspike galactose-binding domain-like domain, also known as domain 5 (d5) of the tailspike receptor-binding protein (RBP) gp63.1 of bacteriophage G7C. This domain is structurally similar to carbohydrate-binding modules (CBMs) and is involved in substrate binding. Specifically, gp63.1 deacetylates surface polysaccharides of E. coli 4s using the esterase domain located within d5, while other domains mediate the interaction between gp63.1 and gp66 to form a stable complex. CBMs, including d5, are non-catalytic domains found in multidomain polysaccharide depolymerases where they play a role in substrate binding and determine the substrate specificity of the entire enzyme .