SII-SWORD/CoKE huggingface dataset:
Actin cross-linking domain (ACD_dom)
Type: Domain

Actin cross-linking domains (ACDs) are distinct domains found in several bacterial toxins, including the Vibrio cholerae MARTX toxin. ACDs are enzyme ligases that catalyse the formation of an irreversible iso-peptide bond on two actin molecules in an ATP- and Mg/Mn(2+)-dependent manner. Cross-linking depletes the cellular pool of G-actin leading to actin cytoskeleton depolymerisation .

The ACD has an overall V-shape. with the active site composed of five residues in a cleft located within the two arms of the V. The first subdomain, forming the left arm of the V, is mainly composed of β-strands, while the second subdomain, forming the right arm of the V, is helical. The first subdomain is composed of a central anti-parallel β-sheet of 8 β-strands, decorated by two adjacent small β-sheets, one above the central
β-sheet and the second below. A long helix (α1) packs against strands β7-β4-βa5 from the central β-sheet, and strand β8 from the upper β-sheet. Finally, the terminal helix α9 packs against strands β2 and β9. The second subdomain is composed of 7 α-helices (α2-α8) and does not contain any β-strands .
Phosphoinositide phospholipase C, Ca2+-dependent (PI-PLC-C1)
Type: Family

This is a family of calcium-dependent phosphatidylinositol-specific phospholipase C1 enzymes from bacteria and fungi. It includes Streptomyces antibioticus phosphatidylinositol-specific phospholipase C1 (SaPLC1) and similar proteins.

The typical bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13) catalyzes Ca2+-independent hydrolysis of the membrane lipid phosphatidylinositol (PI) to produce phosphorylated myo-inositol and diacylglycerol (DAG). The catalytic mechanism is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. In contrast, SaPLC1 is the first known natural Ca2+-dependent bacterial PI-PLC . It is more closely related to the eukaryotic PI-PLCs rather than the typical bacterial PI-PLCs. It participates in PI metabolism to generate myo-inositol-1-phosphate and myo-inositol-1:2-cyclic phosphate simultaneously . SaPLC1 and other members in this subfamily have two Ca2+-chelating amino acid substitutions which convert them from metal-independent enzymes to metal-dependent bacterial PI-PLC. Additionally, SaPLC1 active site utilizes a mechanism of amino acid juxtaposition, swapping amino acid positions, to adapt a calcium binding pocket and maintain more ideal active site geometry to support efficient catalysis.
Tetratricopeptide repeat protein 5, OB fold domain (TTC5_OB)
Type: Domain

This OB fold domain is located at the C terminus of tetratricopeptide repeat protein 5 (TTC5) and is required for effective p53 response . TTC5 can activate the p53 pathway and inhibit AP-1 transcriptional activity .
Adhesin JlpA, Campylobacter (JLPA)
Type: Family

JlpA is a surface-exposed lipoprotein adhesin that promotes interaction with the host epithelial cells. It is found in the genus Campylobacter, and the structure is an unclosed half β-barrel fold with a wide hydrophobic concave face .
Multiple PDZ domain protein, unstructured region (MPDZ_u10)
Type: Domain

This entry represents a region of natively unstructured but highly conserved sequence found in the multiple-PDZ-containing domain proteins in higher eukaryotes. It lies between two PDZ domains. The function is not known.
Protein of unknown function DUF4809 (DUF4809)
Type: Family

This family of proteins is found in bacteria. Proteins in this family are typically between 120 and 137 amino acids in length. There is a conserved GGCNAC sequence motif.
Protein of unknown function DUF4811 (DUF4811)
Type: Family

This family of proteins is found in bacteria. Proteins in this family are typically between 188 and 241 amino acids in length. There is a single completely conserved residue Y that may be functionally important.
Domain of unknown function DUF4812 (DUF4812)
Type: Domain

This presumed domain is functionally uncharacterised. It is approximately 100 amino acids in length. There are two completely conserved residues (H and I) that may be functionally important.
Protein of unknown function DUF4813 (DUF4813)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is found in eukaryotes. Proteins in this family are typically between 345 and 672 amino acids in length.
Starter unit:ACP transacylase, SAT domain (SAT)
Type: Domain

This entry describes the starter unit:acyl-carrier protein (ACP) transacylase (SAT) domain in nonreducing polyketide synthases (NR-PKSs), polyketide synthases (PKSs), and fatty acid synthases, mostly found in fungi. The SAT domain selects an acyl group as the primer for biosyntehsis . SAT selects the hexanoyl starter unit from a pair of specialised fungal fatty acid synthase subunits (HexA/HexB) and transfers it onto the polyketide synthase A acyl-carrier protein to prime polyketide chain elongation . The SAT domain adopts a globular structure with an α/β-hydrolase core fold. It contains a ferredoxin-like subdomain in addition to the core fold. The active site of the SAT domain is likely to be located in a cleft between the α/β-hydrolase core fold and this ferredoxin-like subdomain .
Peptide chain release factor 3, C-terminal (RF3_C)
Type: Domain

This entry represents the C-terminal domain (domain III) of peptide chain release factor 3 (RF3), a bacterial class 2 release factor . TRF3 is believed to have a role in dissociating the class 1 release factors from the ribosome following termination.
Maltogenic amylase-like, C-terminal (Malt_amylase-like_C)
Type: Domain

This domain is found at the C terminus of maltogenic amylase and other glycosidases, such as trehalose synthase/amylase TreS. Maltogenic amylases hydrolyse starch material and are central to carbohydrate metabolism . TreS catalyses the reversible interconversion of maltose and trehalose by transglucosylation .
Type IV Pilus-assembly protein W (PilW)
Type: Family

PilW is one of the component proteins of the pilus biogenesis process whereby pilus fibres are assembled in the periplasm, emerge onto the cell surface and are there stabilised, to allow bacterial attachment to host cells. PilW is an outer-membrane protein necessary for both the functionality of fibres and their stabilisation .
Phospholipase D, N-terminal (PhoD_N)
Type: Domain

This domain can be found in the N-terminal of Phospholipase D (PLD). PLD catalyses the hydrolysis of the ester bond between the phosphatidic acid and alcohol moieties of phospholipids .
Meso-diaminopimelate D-dehydrogenase, C-terminal (Meso-DAP_DH_C)
Type: Domain

This entry represents the C-terminal domain of diaminopimelic acid dehydrogenase. Diaminopimelate dehydrogenase is a NADPH-dependent enzyme that catalyses the oxidative deamination of meso-2,6-diaminopimelate, which is the direct precursor of L-lysine in bacterial lysine biosynthesis .
Saccharopine dehydrogenase-like, C-terminal (Sacchrp_dh-like_C)
Type: Domain

This entry represents the C-terminal domain of saccharopine dehydrogenase and related proteins. In some organisms this enzyme is found as a bifunctional polypeptide with lysine ketoglutarate reductase. The saccharopine dehydrogenase can also function as a saccharopine reductase .
Domain of unknown function DUF4815 (DUF4815)
Type: Domain

This domain is found in viral and bacterial proteins. Its function is not known.
Acyltransferase, C-terminal domain (Acyltransf_C)
Type: Domain

This domain is found at the C terminus of several lysophospholipid acyltransferases, including 1-acyl-sn-glycerol-3-phosphate acyltransferase (also known as lysophosphatidic acid acyltransferase), acyl-CoA:lysophosphatidylglycerol acyltransferase 1, and lysocardiolipin acyltransferase 1, which has both lysophosphatidylinositol and lysophosphatidylglycerol acyltransferase activities .
Axin-1/2, tankyrase-binding domain (Axin_TNKS-bd)
Type: Domain

This is the N-terminal tankyrase binding domain described for Axin-1 .

Axin (axis inhibition protein) is a scaffold protein that is involved in many signalling pathways, including the Wnt, transforming growth factor-beta, MAP kinase pathways, as well as p53 activation cascades . It controls many biological processes ranging from sugar intake, cell proliferation, and organ development to cell death .
Sodium/hydrogen exchanger, regulatory region (NHE_CaM-bd)
Type: Domain

This entry represents a coiled-coil domain found as part of the regulatory, C-terminal region of the 12-14 TM sodium/proton exchangers (NHEs) of the solute carrier 9 (SLC9) family in all animal kingdoms. The C- lobe of CaM binds the first α-helix of the NHE, or CaM b binging region, and the N-lobe of CaM binds the second helix of CaM b binging region .
Spaetzle (Spaetzle)
Type: Domain

Spaetzle is a nerve growth factor-like ligands for the Toll receptor and is required in the pathway that establishes the dorsal-ventral pattern of the embryo . It forms a cystine knot structure .
2-oxoglutarate dehydrogenase E1 component, N-terminal domain (2-oxogl_dehyd_N)
Type: Domain

This domain is found at the N terminus of 2-oxoglutarate dehydrogenase component E1 .

2-oxoglutarate dehydrogenase is a key enzyme in the TCA cycle, converting 2-oxoglutarate, coenzyme A and NAD(+) to succinyl-CoA, NADH and carbon dioxide . This activity of this enzyme is tightly regulated and it is a major determinant of the metabolic flux through the TCA cycle. This enzyme is composed of multiple copies of three different subunits: 2-oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3) which is often shared with similar enzymes such as pyruvate dehydrogenase . The E2 component forms a large multimeric core which binds the peripheral E1 and E3 subunits. The substrate is transferred between the active sites of the different subunits by a lipoyl moiety, bound to a lysine residue from the E2 polypeptide.
CLIP1, zinc knuckle (CLIP1_ZNF)
Type: Domain

This zinc knuckle domain is found tandemly repeated at the C terminus of the cytoplasmic linker protein CLIP1 (CLIP170). It forms a complex with the CAP-Gly domain of dynactin .
Bacterial Ig-like domain (group 3) (Big_3_5)
Type: Domain

This entry represents a domain with an Ig-like fold.
Clostridium phage holin (Clostridium_phage_holin)
Type: Family

This is a family of small hydrophobic proteins with three transmembrane domains. These proteins are holins produced by double-stranded DNA bacteriophages that use an endolysin-holin strategy to achieve lysis of their hosts. The endolysins are peptidoglycan-degrading enzymes that are usually accumulated in the cytosol until access to the cell wall substrate is provided by the holin membrane lesion .
Caskin, C-terminal (Caskin_C)
Type: Domain

This domain is found at the C terminus of Caskin proteins. Caskins are CASK-binding synaptic scaffolding proteins . Part of this domain is predicted to be in coiled-coil conformation. Its function is not known.
Bacteriophage holin HP1 family (Phage_holin_HP1)
Type: Family

This is a family of small hydrophobic phage proteins called holins with one transmembrane domain. Holins are produced by double-stranded DNA bacteriophages that use an endolysin-holin strategy to achieve lysis of their hosts. The endolysins are peptidoglycan-degrading enzymes that are usually accumulated in the cytosol until access to the cell wall substrate is provided by the holin membrane lesion .
Mycobacterial phage holin (Myco_phage_holin)
Type: Family

This is a family of two transmembrane mycobacteriophage holins, small hydrophobic proteins that participate, together with a mycobacteria-specific lysin lysB, in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles from the host cell . Holins accumulate harmlessly in the cytoplasmic membrane until it reaches a critical concentration that triggers the formation of micron-scale pores (holes) causing host cell membrane disruption and endolysin escape into the periplasmic space . Holin determines the precise timing of host cell lysis.
Bacteriophage F116-like holin (Phage_F116_holin)
Type: Family

This is a family of small hydrophobic phage proteins called holins with one transmembrane domain. Holins are produced by double-stranded DNA bacteriophages that use an endolysin-holin strategy to achieve lysis of their hosts. The endolysins are peptidoglycan-degrading enzymes that are usually accumulated in the cytosol until access to the cell wall substrate is provided by the holin membrane lesion .
LydA-like holin (LydA_holin)
Type: Family

This is a family of small hydrophobic holin proteins with one or more transmembrane domains. Holins are encoded within the genomes of Gram-positive and Gram-negative bacteria as well as those of the bacteriophages of these organisms. Their primary function appears to be transport of murein hydrolases across the cytoplasmic membrane to the cell wall where these enzymes hydrolyse the cell wall polymer as a prelude to cell lysis. When chromosomally encoded, these enzymes are therefore autolysins. Holins may also facilitate leakage of electrolytes and nutrients from the cell cytoplasm, thereby promoting cell death. Some may catalyse export of nucleases. LydA and lydB are encoded on the dar operon. The phenotype of a rapid lysis in the absence of active LydB suggests that this protein might be an antagonist of the holin LydA .
LydA-holin antagonist LydB (LydB)
Type: Family

LydB is a family of proteins that are antagonistic to the lysing action of holin LydA .
Pyocin R2, holin (Pyocin_R2_holin)
Type: Family

This is a family of holins classified as 1.E.20 in the TC database.Holin functions in conjunction with the lytic enzyme, Lys, a glycosyl hydrolase that breaks-up the murein in the bacterial cell-wall, causing lysis of the cell and hence entry of phage particles. Several members of this family are annotated as pyocin R2 when encoded on the chromosome of Pseudomonas aeruginosa .
Protein of unknown function DUF5056 (DUF5056)
Type: Family

This family consists of uncharacterised proteins, around 360 residues in length, and mainly found in various Bacteroides species. The function of this family is unknown.
Protein of unknown function DUF4816 (DUF4816)
Type: Family

This family of proteins is functionally uncharacterised. Proteins in this family are typically between 178 and 456 amino acids in length. There is a conserved WKP sequence motif.
Helix-turn-helix domain (DUF4817) (DUF4817)
Type: Domain

This domain is functionally uncharacterised. Proteins containing this domain can be found primarily in insects, but also some other eukaryotes. They are typically between 109 and 322 amino acids in length. This domain may be involved in DNA-binding.
Neutrophil cytosol factor 1, PBR/AIR (NCF1_PBR/AIR)
Type: Domain

This entry represents the polybasic or autoinhibitory region (PBR/AIR, an arginine/lysine rich region) found after the second SH3 domain in neutrophil cytosol factor 1 (NCF1/p47phox) . NCF1 is one of the cytosolic regulatory components of NADPH oxidase and consists of a PX domain at the N-terminal, two tandem SH3 domains, a PBR/AIR and a proline-rich region at the C-terminal. In the resting state, the SH3 domains of NCF1 are masked by an intramolecular interaction with the PBR/AIR, which maintains the enzyme in an inactive form .
Intersectin-1, AP2 binding region (INTAP)
Type: Domain

This entry represents an unstructured region found in the intersectin 1 proteins, lying between the first pair of SH3 domains, that binds to the clathrin adaptor AP2. This binding forms an intersectin-AP2 complex that functions as an important regulator of clathrin-mediated SV recycling in synapses .
BLOC-1-related complex subunit 7 (BORCS7)
Type: Family

BORC is a multisubunit complex that regulates the positioning of lysosomes at the cell periphery, and consequently affects cell migration. BORC associates with the lysosomal membrane, where it functions to recruit the small GTPase Arl8. This initiates a series of interactions that promote the microtubule-guided transport of lysosomes toward the cell periphery .

The BORC complex consists of 8 subunits. This family represents subunit 7.
Protein of unknown function DUF4818 (DUF4818)
Type: Family

This family of proteins is functionally uncharacterised. Proteins in this family are typically between 176 and 214 amino acids in length. There is a single completely conserved residue W that may be functionally important.
Domain of unknown function DUF4819 (DUF4819)
Type: Domain

This presumed domain is functionally uncharacterised. It is found in a subset of transcriptional repressor capicua proteins .
Domain of unknown function DUF4988 (DUF4988)
Type: Domain

This domain of around 200 residues locates at the N terminus of some uncharacterised proteins, mainly in various Bacteroides and Alistipes species. Its function is unknown.
Protein of unknown function DUF4820 (DUF4820)
Type: Family

This family of proteins is functionally uncharacterised. Proteins in this family are typically between 320 and 483 amino acids in length. There are two conserved sequence motifs: WSLP and RPLPW.
Cilia- and flagella-associated protein 61, N-terminal domain (CFAP61_N)
Type: Domain

This entry represents the N-terminal domain of proteins described as cilia- and flagella-associated protein. Proteins containing this domain includes FAP61 from Chlamydomonas reinhardtii. FAP61 is part of the calmodulin and spoke-associated complex (CSC) required for wild-type motility and for the stable assembly of a subset of radial spokes in motile cilia .
Domain of unknown function DUF4989 (DUF4989)
Type: Domain

This domain of around 300 residues locates at the N terminus of some uncharacterised proteins in various Bacteroides and Alistipes species. Its function is unknown.
BT_4170-like, C-terminal (BT_4170-like_C)
Type: Domain

This domain, previously known as DUF4990, is found at the C terminus of a group of proteins mainly from Bacteroides species, including the rhamnogalacturonan lyase BT_4170 from Bacteroides thetaiotaomicron (

) .
Coatomer subunit gamma, C-terminal (Coatomer_g_Cpla)
Type: Domain

This entry represents the very C-terminal domain of the eukaryotic Coatomer subunit gamma proteins. It acts as a platform domain to the C-terminal appendage. It carries one single protein/protein interaction site, which is the binding site for ARFGAP2 or ADP-ribosylation factor GTPase-activating protein. COPI-coated vesicles mediate retrograde transport from the Golgi back to the ER and intra-Golgi transport. The gamma subunit is part of one of two subcomplexes that make up the heptameric coatomer complex along with the beta, delta and zeta subunits .
Domain of unknown function DUF4992 (DUF4992)
Type: Domain

This domain is around 150 residues and is located at the N terminus of some uncharacterised proteins in various Bacteroides and Prevotella species. The function of this domain is unknown.
Proteasome assembly chaperone 4 (PAC4)
Type: Family

The 26S proteasome plays a critical role in a number of cellular processes including cell-cycle control, transcription, signal transduction and DNA repair . This complex is composed of a catalytic 20S proteasome and two axially positioned 19S regulatory complexes. The overall structure is highly conserved among eukaryotes and is essential for cell viability. Assembly of the catalytic 20S proteasome CP (core particle) initiates with the formation of rings composed of seven alpha subunits and involves proteasome-assembly chaperones PAC1-PAC2, PAC3-PAC4 and UMP1 . Two heterodimeric proteasome-assembly chaperones, PAC1-PAC2 and PAC3-PAC4, interact with alpha subunits and promote the correct assembly of alpha rings. PAC3-PAC4 leaves the complex during subsequent assembly of beta subunits, while PAC1-PAC2 remains bound until the assembly of the CP is completed .

This family consists of proteasome assembly chaperone 4 (PAC4, PSMG4). At the very C terminus there is a crucial HbYX or hydrophobic-tyrosine-X sequence motif that, in proteasome activators, opens the 20S proteasome entry pore .
Domain of unknown function DUF4995 (DUF4995)
Type: Domain

This domain is around 100 residues and is found at the N terminus of some uncharacterised proteins and glucuronyl hydrolases in various Bacteroides species. The function of this domain remains unknown.
Domain of unknown function DUF4996 (DUF4996)
Type: Domain

This domain of around 100 residues is found at the C terminus of some glycerophosphoryl diester phosphodiesterases and uncharacterised proteins. The function of this domain remains unknown.
Domain of unknown function DUF4999 (DUF4999)
Type: Domain

This domain of around 75 residues is found in the N terminus of F5/8 type C domain proteins and some uncharacterised proteins in various Bacteroides species. The function of this domain remains unknown.
Domain of unknown function DUF5000 (DUF5000)
Type: Domain

This domain of around 200 residues is found at the C terminus of some uncharacterised proteins from Bacteroidetes. The function of this domain remains unknown.
Ig-like domain (DUF5001)
Type: Domain

This domain of around 100 residues is found at the C terminus of some uncharacterised proteins in various Bacteroides and Parabacteroides species. The function of this domain remains unknown. It has an Ig like fold.
Protein of unknown function DUF5003 (DUF5003)
Type: Family

This small family of proteins is functionally uncharacterised. This family is found in bacteroidales. Proteins in this family are typically between 500 and 650 amino acids in length.
Protein of unknown function DUF5004 (DUF5004)
Type: Family

This small family of proteins is functionally uncharacterised. This family is found in mainly in Bacteroides and Prevotella spp. Proteins in this family are typically around 150 amino acids in length.
Protein of unknown function DUF5005 (DUF5005)
Type: Family

This small family of proteins is functionally uncharacterised. It is found mainly in bacteroides. Proteins in this family are typically around 440 amino acids in length.
Domain of unknown function DUF5006 (DUF5006)
Type: Domain

Proteins containing this domain are functionally uncharacterised. The function of this domain is not clear.
C-terminal of Roc, COR-A domain (COR-A)
Type: Domain

This entry corresponds to COR-A, located at the N-terminal of COR. It interacts with the Roc domain stabilising the GTPase activity of LRRK2 . COR-A consists of multiple α-helices and a short three-stranded antiparallel sheet .

The C-terminal of Roc domain, COR, along with Roc functions as the putative regulator of kinase activity. It functions as a proper GTP-binding protein with a low GTPase activity somehow stimulating the kinase activity . COR is divided in two subdomains: COR-A and COR-B. The Roc-COR tandem is found in Roco-containing proteins from bacterias and eukaryotes. Its most prominent member is the leucine-rich repeat kinase 2 LRRK2 . It also contains Leucine-rich repeat kinase 1 LRKK1, Death-associated protein kinase 1 DAPK1 and Malignant fibrous histiocytoma amplified sequence 1 MFHAS1 .
Fragile X-related protein 1, C-terminal region 1 (FXR1_C1)
Type: Domain

This is a small highly conserved region of the C terminus of Fragile X-related proteins 1 and 2, FRX1, FRX2. The domain is immediately C-terminal to the core C- terminal region,

, and contains at least one block of RGG repeats that bind to G-quartet sequences in a wide variety of mRNAs .
Protein of unknown function DUF5007 (DUF5007)
Type: Family

This small family of proteins is functionally uncharacterised. This family is found mainly in Bacteroides and Sphingobacterium. The members in this family are around 350 residues in length.
RNA helicase aquarius, N-terminal domain (Aquarius_N)
Type: Domain

This entry represents the ARM repeats domain found at the N-terminal of RNA helicase aquarius (also known as intron-binding protein aquarius) and its orthologue from S.pombe cwf11. Aquarius is a splicing factor which links excision of introns from pre-mRNA with snoRP assembly .
Domain of unknown function DUF5008 (DUF5008)
Type: Domain

Proteins containing this domain are functionally uncharacterised.