SII-SWORD/CoKE huggingface dataset:
Protein of unknown function DUF5541 (DUF5541)
Type: Family

This is a family of unknown function found in primates.
Thymine dioxygenase JBP1, DNA-binding domain (DB_JBP1)
Type: Domain

The J-binding protein 1 (JBP1) is essential for biosynthesis and maintenance of DNA base-J (beta-d-glucosyl-hydroxymethyluracil). Base-J and JBP1 are confined to some pathogenic protozoa and are absent from higher eukaryotes, prokaryotes and viruses. JBP1 recognizes J-containing DNA (J-DNA) through the DNA-Binding JBP1 domain (DB-JBP1), which binds to J-DNA with approximately the same affinity and specificity as full-length JBP1. Structure analysis of DB-JBP1 revealed a helix-turn-helix variant fold, a 'helical bouquet' with a 'ribbon' helix encompassing the amino acids responsible for DNA binding. Mutation of a single residue (Asp525) in the ribbon helix abrogates specificity toward J-DNA .
Putative HNHc nuclease (HNHc_6)
Type: Family

This family is found in Gammaproteobacteria. It may be an HNH-like nucleases. The shorter matches are likely to be from phage proteins whereas the longer members are probably from the bacterial genomes.
STI1/HOP, DP domain (STI1/HOP_DP)
Type: Domain

This entry corresponds to the Asp/Pro-rich domains (DP) of STI1/HOP and similar proteins , including TIC40, a co-chaperone during protein import into chloroplasts . STI1/HOP proteins are cochaperones that belong to the foldosome, a system consisting in Hsp70 and Hsp90 chaperones. STI1/HOP acts as an adapter protein capable of transferring client proteins from the first to the second molecular chaperone . This domain is found in two copies in STI1, named DP1 and DP2 , while in others is present in one copy, such as Hsp70-Hsp90 organising protein from P. falciparum. This domain (and specifically DP2 from STI1), is involved in client activation .
Large ribosomal subunit protein bL27m, C-terminal (Ribosomal_bL27m_C)
Type: Domain

This is the C-terminal domain of the large ribosomal subunit protein bL27m (also known as 54S ribosomal protein L2) found in yeast. bL27 C-terminal region interacts with an expansion segment of 21S rRNA to form part of the central protuberance .
CARMIL, pleckstrin homology domain (CARMIL_PH)
Type: Domain

This is a non-canonical pleckstrin homology (PH) domain connected to a 16-leucine-rich repeat domain found in CARMIL (CP Arp2/3 complex myosin-I linker) proteins. The PH domain is interconnected with an N-terminal helix (N-helix), residues 10-20 and a C-terminal linker (Linker), residues 129-147 in

. Structural and functional studies indicate that the PH domain involved in direct binding to the PM (plasma membrane) and a HD (helical domain) responsible for antiparallel dimerization and enhancement of CARMIL's membrane-binding activity. Furthermore, it appears that CARMIL's PH domain mediates non-specific binding to the membrane, in contrast to other PH domains that bind polyphosphorylated phosphatidylinositides, which are thought to function as signalling lipids .
Bacterial alpha-2-macroglobulin MG10 domain (Bact_MG10)
Type: Domain

Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. However, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. Bacterial A2Ms are located in the periplasm where they are believed to provide protection to the cell by trapping external proteases through a covalent interaction with an activated thioester. This domain is found on the C-terminal region in A2Ms in bacteria. Structure analysis of Salmonella enterica ser A2Ms (SA-A2Ms) show that they are composed of 13 domains, all of which fold as variants of β sandwiches with the exception of the TED, which consists of 14 α helices. Most of the β sandwich domains appear to serve a structural role and are referred to as the macroglobulin-like (MG) domains. This is the MG10 domain. MG10 is markedly different from the other MG domains in that it has more β strands and an α helix. The position of MG10 is stabilized by, in addition to other hydrogen bonds, the formation of a β sheet with MG9 .
Rad52 family (Rad52_fam)
Type: Family

The DNA single-strand annealing proteins (SSAPs), such as RecT, Red-beta, ERF and Rad52, function in RecA-dependent and RecA-independent DNA recombination pathways. This family includes proteins related to Rad52. These proteins contain two helix-hairpin-helix motifs .
YDG domain (YDG)
Type: Domain

This presumed domain is found in a wide variety of bacterial cell surface proteins. This domain has a highly conserved YDG motif near its N terminus. This domain is likely related to the MBG domain (PF17883).
DZIP3-like HEPN domain (HEPN_DZIP3)
Type: Domain

This entry represents the DZIP3-like HEPN nuclease domain. It has been found fused to TPR, Zn-ribbon, RING, Ankyrin, CARD, NACHT ATPase, DEATH and LRR in various animal lineages .

DZIP3 is a RNA-binding ubiquitin-protein ligase that targets H2AK119 (lysine 119 of histone H2A) . It interacts with CARM1 (coactivator-associated arginine methyltransferase 1) through its RING domain and may act as a coactivator of ERalpha target gene expression
.
ParA helix turn helix domain (HTH_54)
Type: Domain

The accurate segregation of DNA is essential for the faithful inheritance of genetic information. Segregation of the prototypical P1 plasmid par system requires two proteins, ParA and ParB, and a centromere. When bound to ATP, ParA mediates segregation by interacting with centromere-bound ParB, but when bound to ADP, ParA fulfills a different function: DNA-binding transcription autoregulation. ParA consists of an elongated N-terminal α-helix which mediates dimerization, a winged-HTH and a Walker-box containing C-domain. This entry describes the N-terminal α helix domain combined with the winged HTH region .
SAGA-associated factor 73, zinc finger domain (Znf_C2H2_13)
Type: Domain

The SAGA (Spt-Ada-Gcn5-acetyltransferase) complex performs multiple functions in transcription activation including deubiquitinating histone H2B, which is mediated by a subcomplex called the deubiquitinating module (DUBm). The yeast DUBm comprises a catalytic subunit, Ubp8, and three additional subunits, Sgf11, Sus1 and Sgf73, all of which are required for DUBm activity. A portion of the non-globular Sgf73 subunit lies between the Ubp8 catalytic domain and the zinc finger (Znf)-UBP domain and has been proposed to contribute to deubiquitinating activity by maintaining the catalytic domain in an active conformation. Sgf73 contributes to maintaining both the organization and ubiquitin-binding conformation of Ubp8, thereby contributing to overall DUBm activity. This domain is a Sgf73 fragment in the DUB module. It is a zinc finger (Znf) domain whose integrity is essential for the incorporation of this subunit into DUBm as well as for the catalytic activity of Ubp8, as either a short deletion or point mutations in Sgf73 zinc-coordinating residues disrupt the association of Sgf73 with the rest of the DUBm .
RL domain (RL)
Type: Domain

The RRM-like (RL) domain is found in the N-terminal region of the polyA polymerase PAPD1. It contributes to PAPD1 dimerization and has a fold similar to RNP-type RBDs .
Carbohydrate binding module 77 (CBM77)
Type: Domain

This domain is the non-catalytic carbohydrate binding module 77 (CBM77) present in Ruminococcus flavefaciens. CBMs fulfil a critical targeting function in plant cell wall depolymerisation. In CBM77, a cluster of conserved basic residues (Lys1092, Lys1107 and Lys1162) confer calcium-independent recognition of homogalacturonan .
Proprotein convertase subtilisin/kexin type 9, C-terminal domain 1 (PCSK9_C1)
Type: Domain

This entry represents the first subdomain found in the C-terminal cysteine/histidine-rich domain (CRD) of PCSK9 (also known as neural apoptosis-regulated convertase, NARC-1) . PCSK9 has been shown to regulate circulating LDL-R levels by controlling LDL-R degradation. Furthermore, numerous mutations in the PCSK9 gene have been identified and associated with hypercholesterolemia (gain of function) or hypocholesterolemia (loss of function) . The fully folded CRD, shows structural similarity to the resistin homotrimer, a small cytokine associated with obesity and diabetes. The C-terminal domain from PCSK9 consists of three, three-stranded β-subdomains arranged in a pseudo threefold, and each of the subdomains in the CRD of PCSK9 consists of three structurally conserved disulfide bonds .
LpxI N-terminal domain (LpxI_N)
Type: Domain

This entry represents the N-terminal domain of the LpxI enzyme that is involved in biosynthesis of lipid A. Specifically it carries out the hydrolysis of UDP-2,3-diacyl- glucosamine. This step is either carried out by LpxI or LpxH . This domain has a Rossmann fold.
CDI immunity protein (CdiI_4)
Type: Domain

Contact-dependent growth inhibition (CDI) is a mechanism of inter-cellular competition in which Gram-negative bacteria exchange polymorphic toxins using type V secretion systems. Structure analysis of the CDI toxin from Escherichia coli NC101 reveals that it has moderate structural homology to Whirly-like proteins found in plastids, but appears to lack the characteristic Whirly RNA-binding site .
Adenomatous polyposis coli (APC) repeat (APC_rep)
Type: Repeat

Adenomatous polyposis coli contains an armadillo repeat and uses its highly conserved surface groove to recognize the APC-binding region (ABR) of Asef . This entry represents a single repeat unit of the Armadillo region.
Large polyvalent protein-associated domain 18 (LPD18)
Type: Domain

This is a mostly all beta domain which contains conserved acidic residues. It is mainly found in polyvalent proteins of conjugative elements .
Sld7 C-terminal domain (Sld7_C)
Type: Domain

This is an α helical domain found at the C-terminal region of Sld7 proteins. Yeast Sld3 and its metazoan counterpart treslin are the hub proteins mediating protein associations critical for formation of the replicative helicase at the replication origins of chromosomes. Sld7 forms a complex with Sld3 throughout the cell cycle, and associates with and dissociates from origins in an Sld3-dependent manner and is thought to regulate the function of Sld3. Structural analysis of S. cerevisiae Sld7 indicates that two Sld7 molecules form a homodimer using their C-terminal domains .
ATP-grasp domain, R2K clade family 2 (R2K_2)
Type: Domain

This domain can be found in a subfamily of ATP-grasp enzymes belonging to the R2K clade, wherein one of the absolutely-conserved lysine residues has migrated to the RAGYNA domain which is a part of the core ATP-grasp module. Proteins containing this domain are predicted to catalyze peptide ligation reactions on protein substrates in biological conflict contexts, probably between bacteriophages and their hosts .
Spore germination GerD, central core domain (GerD_central)
Type: Domain

This is the central core domain found in GerD, which plays a critical role in nutrient receptor-mediated spore germination in Bacillus species. The crystal structure of GerD reveals this domain as a trimeric superhelical rope fold. Alterations in GerD structure have profound effects on spores' nutrient germination .
Gasdermin, PUB domain (Gasdermin_PUB)
Type: Domain

This entry represents the PUB domain found in Gasdermin and GSDMB .

GSDMB (GSDM) may play a role in achieving and maintaining the final differentiation state of epithelial cells . A deletion/insertion mutation in GSDMB (DFNA5) is associated with an autosomal dominant non-syndromic hearing impairment form .

Certain gasdermins are cleaved by inflammatory and apoptotic caspases . Gasmedin E is cleaved by caspase-3 and the N-terminal fragment released forms pores in the cell membrane, switching from cell death by apoptosis to pyroptosis .
SidC, N-terminal (SidC_N)
Type: Domain

This is the N-terminal domain of SidC.

SidC is one of the effectors delivered by Legionella pneumophila into the host cell. Like its paralogue SdcA, SidC anchors on the Legionella-containing vacuole (LCV) to facilitate the recruitment of endoplasmic reticulum (ER) proteins. This protein is organised into four domains that are packed into an arch-like shape: the N- terminal SNL domain (

), the INS domain (which is inserted within the SNL domain), the P4C domain, and a C-terminal domain .
Propionyl-coenzyme A carboxylase, BT domain (PCC_BT)
Type: Domain

This domain is found in Propionyl-coenzyme A carboxylase (PCC), present in Roseobacter denitrificans. PCC is a mitochondrial biotin-dependent enzyme that is essential for the catabolism of certain amino acids, cholesterol, and fatty acids with an odd number of carbon atoms. Since this domain mediates biotin carboxylase-carboxyltransferase interactions it is referred to as the BT domain. The BT domain is located between biotin carboxylase and the biotin carboxyl carrier protein domains. The BT domain shares some structural similarity with the pyruvate carboxylase tetramerization domain of pyruvate carboxylase .
EDS1, EP domain (EDS1_EP)
Type: Domain

This entry represents the C-terminal domain found in a group of sequences from plants, including Protein EDS1 (also known as Enhanced disease susceptibility 1), Lipase-like PAD4 (also termed Protein PHYTOALEXIN DEFICIENT 4) and Senescence-associated carboxylesterase 101 (SAG101) from Arabidopsis thaliana. Members of this group of proteins are involved in signalling by cell surface and intracellular immune receptors .
NACHT, LRR and PYD domains-containing protein, helical domain HD2 (NLRP_HD2)
Type: Domain

This entry represents the second of two helical domains (HD2) found in the NLRC proteins , the NOD2 protein and NACHT, LRR and PYD domains-containing proteins .
CCDC81-like prokaryotic HU domain 2 (HU-CCDC81_bac_2)
Type: Domain

This entry represents the second of two HU domains found in bacterial proteins typically fused to a C-terminal transmembrane helix and an extracellular peptidoglycan-binding domain. The HU domains in many of these proteins are predicted to function in tethering the nucleoid to the cell envelope .
Sulfhydryl oxidase, Trx-like domain (QSOX_Trx1)
Type: Domain

This domain is found in Quiescin sulfhydryl oxidase (QSOX), an oxidoreductase present in Homo sapiens capable of both generating and transferring disulfide modules within a single polypeptide. The domain is thioredoxin-like, hence referred to as Trx1 domain. Trx1 domain has a di-cysteine motif (Cys-X-X-Cys) which is related to the redox-active domains of protein disulfide isomerase. The Trx1 domain is responsible for intramolecular disulfide transfer through the di-cysteine motif .
Phage ABA sandwich domain (Phage_ABA_S)
Type: Domain

This domain is found in a prophage protein BC1872 from B. cereus. The domain forms a three-layer β/α/β sandwich. Three α-helices, alpha1, alpha2, and alpha3, are sandwiched on one side by three-stranded antiparallel β-sheet (beta3, beta4, and beta5) and on the other by a β-hairpin (beta1 and beta2) .
Alpha-glutamyl/putrescinyl thymine pyrophosphorylase clade 3 (AGPT-Pplase3)
Type: Domain

This entry represents an α helical domain related to the α-helical DNA glycosylases, predicted to catalyze the in situ synthesis of hypermodified bases such as alpha-glutamyl, putrescinyl thymine, 5-(2-aminoethoxy)methyluridine or 5-(2-aminoethyl)uridine. The enzyme is predicted to utilize a high-energy pyrophosphate DNA base intermediate which is subject to a nucleophilic attack by the modifying moiety. It is mainly found in bacterial mobile operons .
N-acetyl-beta-D-glucosaminidase, N-terminal (GcnA_N)
Type: Domain

This is the N-terminal domain found in N-acetyl-beta-D-glucosaminidase (GcnA) present in Streptococcus gordonii. GcnA is a family 20 glycosidase that cleaves N-acetyl-beta-D-glucosamine and N-acetyl-beta-D-galactosamine from 4-methylumbelliferylated substrates. Similar N-terminal domains have been observed in all family 20 glycosidases although the number of β-sheet strands may vary from five .
N-acyltransferase, N-terminal domain (NAT_N)
Type: Domain

This entry represents the N-terminal domain found in bacterial N-acyltransferases (NATs), the gene products orf11 and dbv8, which show a a dumbbell-like structure with two domains. The N-terminal domain folds into an all-α configuration, composed of eight helices with two helix-turn-helix motifs in tandem. It is structurally similar to the AAA+ protein family (ATPases associated with various cellular activities) .
Isopullulanase beta-solenoid repeat (IPU_b_solenoid)
Type: Repeat

This isopullulanase (IPU) and dextranase repeat unit includes three (or one long and one short) parallel β-strands . The repeat region as a whole folds into a β-helix, known as β-solenoid .
ESX-1 secretion-associated protein EspB, PE domain (EspB_PE)
Type: Domain

The ESX-1 secretion system is an important for virulence and immunogenicity in Mycobacterium tuberculosis . ESX-1 secreted protein B (EspB) is a member of the PE/PPE family, being the only one described to date to form higher-order oligomers. It contains PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains, and a C-terminal domain, which is processed by MycP1 protease during secretion. Once secreted across the inner mycobacterial membrane, EspB oligomerizes into a cylinder-like heptamer through its N-terminal domain that form channel-like structures, enabling other ESX-1 secreted substrates to pass through and beyond the inner mycobacterial envelope .

This domain represents the PE domain located at the N-terminal region of EspB which carries the conserved YxxxD/E secretion motif .
Vacuolar ATPase subunit I, N-terminal proximal lobe (V_ATPase_prox)
Type: Domain

This domain is found in the cytoplasmic N-terminal domain of vacuolar ATP synthase subunit I present in Meiothermus ruber. Subunit I is a homologue of subunit A which associates with the membrane-bound complex of eukaryotic vacuolar H+-ATPase (V-ATPase) acidification machinery. The domain forms the proximal lobe that caps one end of the α helix bundle, with the distal lobe capping the other end. Although the two lobes exhibit a similar motif, the molecular nature of the coupling with the identical stalks is thought to be dissimilar .
MBG domain, Lactobacillales (MBG_Lactobacillales)
Type: Domain

This domain is found in a variety of bacterial extracellular proteins. Although initially described as having a divergent Ig fold this domain has a novel topology that is like a mirror image of the β-grasp fold. Hence the name of Mirror Bη Grasp (MBG) domain .
Chitinase W immunoglobulin-like domain (ChiW_Ig-like)
Type: Domain

This is an immunoglobulin like domain found in ChiW, a chitinase with high activity towards various chitins. ChiW has a multi-modular architecture composed of six domains to function efficiently on the cell surface: a right-handed β-helix domain (carbohydrate-binding module family 54, CBM-54), a Gly-Ser-rich loop, 1st immunoglobulin-like (Ig-like) fold domain, 1st β/α-barrel catalytic domain (glycoside hydrolase family 18, GH-18), 2nd Ig-like fold domain and 2nd β/α-barrel catalytic domain (GH-18) .
Giardia dicer, N-terminal (Dicer_N)
Type: Domain

This is the N-terminal domain found in dicer proteins from Giardia intestinalis. The N-terminal region (i.e. the platform domain) forms a flat surface composed of antiparallel β sheet and three α helices. This surface contains a large positively charged region that could interact directly with the negatively charged phosphodiester backbone of the modeled dsRNA helix .
Bacterial Ig domain, transpeptidase-associated (Big_10)
Type: Domain

This entry represents a bacterial Ig-like domain found associated with transpeptidase domains .
CD180, leucine-rich repeat (LRR_11)
Type: Repeat

This entry represents one repeat unit found in CD180 from mammals. CD180 may cooperate with MD-1 and TLR4 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) in B-cells .
FYVE-type zinc finger (FYVE_2)
Type: Domain

This FYVE-type zinc finger is found at the N terminus of effector proteins including rabphilin-3A and regulating synaptic membrane exocytosis protein 2 .
Leucine-rich repeat unit (LRR_12)
Type: Repeat

This Pfam entry includes some leucine-rich repeats (LRRs) that fail to be detected with

. This entry represents one repeat unit.
Fungal defensin Copsin (Copsin)
Type: Domain

This domain is present in Copsin from Coprinopsis cinerea. Copsin is a defensin that interferes with peptidoglycan synthesis and has a CS-α-β fold. Copsin is stabilized by a unique connectivity of six cysteine bonds in contrast to most other CS-α-β defensins which are linked by three or four disulfide bonds .
MID domain of medPIWI (MID_MedPIWI)
Type: Domain

MID domain of the medPIWI PIWI/Argonaute module. medPIWI is the core globular domain of the Med13 protein. Med13 is one member of the CDK8 subcomplex of the Mediator transcriptional coactivator complex. The medPIWI module in Med13 is predicted to bind double-stranded nucleic acids, triggering the experimentally-observed conformational switch in the CDK8 subcomplex which regulates the Mediator complex .
MBG domain, YGX type (MBG_2)
Type: Domain

This domain is found in a variety of bacterial extracellular proteins. This domain is related to the MBG domain (

), but it replaces the characteristic YDG motif close the N terminus with a YGX motif.
Protein of unknown function DUF5548 (DUF5548)
Type: Family

This is a family of unknown function found in primates.
Bacterial archaeo-eukaryotic release factor family 3 (Bact_RF_family3)
Type: Family

Bacterial family of the archaeo-eukaryotic release factor superfamily. Likely to play roles in biological conflicts or regulation under stress conditions at the ribosome .
Tle cognate immunity protein 4, C-terminal domain (Tli4_C)
Type: Domain

T6SS bacteria employ toxic effectors to inhibit rival cells and concurrently use effector cognate immunity proteins to protect their sibling cells. The effector and immunity pairs (E-I pairs) endow the bacteria with a great advantage in niche competition. This is the C-terminal domain of Tli4. The Tle cognate immunity proteins (Tlis) can directly disable the transported Tle protein and thereby mediate the self-protection process. The Tle-Tli effector-immunity (E-I) pairs confer substantial advantage to the donor cell during interbacterial competition. Tli4 displays a two-domain structure, in which a large lobe and a small lobe form a crab claw-like conformation. Tli4 uses this crab claw to grasp the cap domain of Tle4, especially the lid2 region, which prevents the interfacial activation of Tle4 and thus causes enzymatic dysfunction of Tle4. Structural comparison indicates similarity between this C-terminal domain of Tli4 and Tsi3, which is the cognate immunity protein of the effector protein Tse3 in P. aeruginosa PDB:4n7s .
Histone methyltransferase, Tudor domain 1 (TUDOR_5)
Type: Domain

This is the first TUDOR domain found in SETDB1 enzymes (

) from animals, also known as Eggless in Drosophila . In Drosophila, SetdB1 (Egg) is important for oogenesis and the silencing of chromosome 4 . SET domain, bifurcated 1 (SETDB1) is a histone methyltransferase (HMT) that methylates lysine 9 on histone H3 (H3K9). The enzymatic activity of SETDB1, in association with MBD1-containing chromatin-associated factor 1 (MCAF1), converts H3K9me2 to H3K9me3 and represses subsequent transcription. SETDB1 is amplified in cancers such as melanoma and lung cancer, and increased expression of SETDB1 promotes tumorigenesis in a zebrafish melanoma model. In addition, SETDB1 is required for endogenous retrovirus silencing during early embryogenesis, inhibition of adipocyte differentiation, and differentiation of mesenchymal cells into osteoblasts . The tandem Tudor domains in the N-terminal region are involved in protein-protein interactions .