SII-SWORD/CoKE huggingface dataset:
Protein disulfide-isomerase A5, TRX (a) domain (PDI_a_PDIR)
Type: Domain

This entry represents the three redox active TRX (a) domains found in protein disulfide-isomerase A5 (PDIA5, also known as PDIR). PDIR is composed of three redox active TRX (a) domains and an N-terminal redox inactive TRX-like (b) domain. Similar to PDI, it is involved in oxidative protein folding in the endoplasmic reticulum (ER) through its isomerase and chaperone activities. These activities are lower compared to PDI, probably due to PDIR acting only on a subset of proteins. PDIR is preferentially expressed in cells actively secreting proteins and its expression is induced by stress . Similar to PDI, the isomerase and chaperone activities of PDIR are independent; CXXC mutants lacking isomerase activity retain chaperone activity. The TRX-like b domain of PDIR is critical for its chaperone activity .
IKBKB, scaffold dimerization domain superfamily (IKBKB_SDD_sf)
Type: Homologous_superfamily

This superfamily represents 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).
RhoGEF 6/7, PH domain (PH_Cool_Pix)
Type: Domain

There are two forms of Pix proteins: alpha Pix (also called Rho guanine nucleotide exchange factor (GEF) 6, 90Cool-2 or ARHGEF6) and beta Pix (GEF7, p85Cool-1 or ARHGEF7), which activate small GTPases by exchanging bound GDP for free GTP. betaPix contains an N-terminal SH3 domain, a RhoGEF/DH domain, a PH domain, a GIT1 binding domain (GBD), and a C-terminal coiled-coil (CC) domain . It acts as a GEF for both Cdc42 and Rac1 , and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion . alphaPix differs in that it contains a calponin homology (CH) domain, which interacts with beta-parvin, N-terminal to the SH3 domain. alphaPix is an exchange factor for Rac1 and Cdc42 and mediates Pak activation on cell adhesion to fibronectin. Mutations in alphaPix can cause X-linked mental retardation. alphaPix also interacts with Huntington's disease protein (htt), and enhances the aggregation of mutant htt (muthtt) by facilitating SDS-soluble muthtt-muthtt interactions. The DH-PH domain of a Pix was required for its binding to htt. In the majority of Rho GEF proteins, the DH-PH domain is responsible for the exchange activity .

This entry represents the PH domain of ARHGEF6 and ARHGEF7.
DWD HYPERSENSITIVE TO UV-B 1 (DHU1)
Type: Family

This is a plant family of proteins which includes DWD HYPERSENSITIVE TO UV-B 1 protein (DHU1) from Arabidopsis. DHU1 may act as a substrate receptor of a CUL4-RING E3 ubiquitin-protein ligase (CRL4) complex involved in the negative regulation of cellular responses to ultraviolet-B (UV-B) illumination, likely in coordination with RUP1 . It interacts with COP1 and probably prevents the formation of active UVR8-COP1 complex, thus avoiding UVR8-COP1-mediated positive regulation of UV-B responses .
Daxx, histone-binding domain (DAXX_histone-bd)
Type: Domain

Daxx (also known as death domain-associated protein 6) is a nuclear protein that modulates transcription of various genes and is involved in cell death and/or the suppression of growth. Daxx is also a histone chaperone conserved in metazoa that acts specifically on histone H3.3. This entry represents the histone-binding domain of Daxx that interacts with the histone H3.3-H4 dimer, and in doing so competes with DNA binding and interactions between the histone chaperone ASF1/CIA and the H3-H4 dimer .
3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA (cAMP_phosphodiest_CpdA)
Type: Family

This family includes 3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA, which hydrolyses cAMP to 5'-AMP. It plays an important regulatory role in modulating the intracellular concentration of cAMP, thereby influencing cAMP-dependent processes . In Pseudomonas is specifically required for regulation of virulence factors and can also hydrolyse cGMP .
Carboxysome shell protein CcmK (CcmK)
Type: Family

Bacterial microcompartments (BMCs) are large proteinaceous structures comprised of a roughly icosahedral shell and a series of encapsulated enzymes. They are found across bacteria where they play functionally diverse roles including CO(2) fixation and the catabolism of a range of organic compounds. They function as organelles by sequestering particular metabolic processes within the cell. A shell or capsid, which is composed of a few thousand protein subunits, surrounds a series of sequentially acting enzymes and controls the diffusion of substrates and products (including toxic or volatile intermediates) into and out of the lumen. Although functionally distinct BMCs vary in their encapsulated enzymes, all are defined by homologous shell proteins. The shells of BMCs are made primarily of a family of proteins whose structural core is the BMC domain, and variations upon this core provide functional diversity .

This entry represents Carboxysome shell protein CcmK and similar proteins from cyanobacteria. CcmK is one of the shell proteins of the carboxysome, a polyhedral BMC where RuBisCO (ribulose bisphosphate carboxylase) is sequestered for primary carbon production. It assembles into hexamers which make sheets that form the facets of the polyhedral carboxysome . The formation of hexamers might play a role in environmental adaptability .
RuBisCO chaperone RbcX (RbcX)
Type: Family

This entry represents RuBisCO chaperone RbcX and similar proteins from cyanobacteria. RbcX is an RbcL-specific chaperone. All known RbcX proteins exist as homodimers (RbcX2). The central cleft of this homodimer binds the C-terminal of a RbcL monomer, stabilizing it, and the peripheral region of RbcX2 binds a second RbcL monomer, which allows the RbcL homodimers to be in the correct orientation . It is also required for assembly of the RbcL8 core, acting downstream of the major chaperonin (GroEL-GroES), has a transient dynamic interaction with RbcL and is eventually displaced by RbcS .
Rubisco accumulation factor 1, cyanobacterial (Raf1_cyn)
Type: Family

Ribulose-1,5-bis-phosphate carboxylase/oxygenase (Rubisco) is the rate-limiting carbon fixing enzyme of photosynthesis. Rubisco is a complex of eight large (RbcL) and eight small (RbcS) subunits that requires assembly chaperones. Rubisco accumulation factor 1 (Raf1) is a mayor chaperone involved in Rubisco assembly . It acts downstream of chaperonin-assisted RbcL folding by stabilizing RbcL antiparallel dimers for assembly into RbcL8 complexes with four Raf1 dimers bound. Raf1 displacement by RbcS results in holoenzyme formation . It might regulate RuBisCO condensation and decondensation .

This protein family includes Raf1 proteins from cyanobacteria.
N6-succino-2-amino-2'-deoxyadenylate synthase (Phage_PurZ)
Type: Family

This family includes N6-succino-2-amino-2'-deoxyadenylate synthase PurZ from phages. It is involved in the synthesis of the atypical nucleotide dZTP (2-amino-2'-deoxyadenosine-5'-triphosphate) and in the synthesis of N6-succino-2-amino-2'-deoxyadenylate, which undergoes defumarylation and phosphorylation respectively by host PurB and guanylate/nucleoside diphosphate kinases to give dZTP (2-amino-2'-deoxyadenosine-5'-triphosphate). dZTP is integrated into the viral genome instead of adenine by the viral polymerase. This Z-base probably completely replaces adenosine and forms a triple bond to the opposite T-base. The resulting non-standard viral DNA is called Z-genome. The chemically modified DNA is probably harder for the host bacteria to digest with nucleases or restriction enzymes .
Late transcription coactivator, myovirus (LTACT_myovirus)
Type: Family

This family of proteins is found in myovirus and includes the late transcription coactivator (also known as gp33) from Bacteriophage T4. It is a late-transcription coactivator which interacts with the host RNA polymerase forming a part of the initiation complex . It activates transcription at late promoters when the sliding clamp is present . It is able to bind to both the host RNA polymerase (RNAP) and the upstream dsDNA .
Cell division protein DrpB (DrpB)
Type: Family

This entry represents a group of proteins from enterobacteria, including Cell division protein DrpB from Escherichia coli. DrpB is a non-essential division protein that localizes to the septal ring in low ionic strength medium .
RNA polymerase sigma-like factor (T4_sigma-like_factor)
Type: Family

This family represents the Bacteriophage T4 RNA polymerase sigma-like factor (also known as gp55) which plays a role in the transcription of the viral late genes. It recognises late promoters and confers the ability to form a catalytically competent RNA polymerase (RNAP)-promoter open complex . It associates with host RNAP core and, thus, replaces the host sigma-70/rpoD subunit in the complex . Gp55 may also play a role in DNA packaging by interacting with the terminase subunit gp17 .
Carboxysome shell vertex protein CcmL (CcmL)
Type: Family

Bacterial microcompartments (BMCs) are large proteinaceous structures comprised of a roughly icosahedral shell and a series of encapsulated enzymes. They are found across bacteria where they play functionally diverse roles including CO(2) fixation and the catabolism of a range of organic compounds. They function as organelles by sequestering particular metabolic processes within the cell. A shell or capsid, which is composed of a few thousand protein subunits, surrounds a series of sequentially acting enzymes and controls the diffusion of substrates and products (including toxic or volatile intermediates) into and out of the lumen. Although functionally distinct BMCs vary in their encapsulated enzymes, all are defined by homologous shell proteins. The shells of BMCs are made primarily of a family of proteins whose structural core is the BMC domain, and variations upon this core provide functional diversity .

This entry represents carboxysome shell protein CcmL and similar proteins from cyanobacteria. CcmL, which adopts a pentameric assembly, forms vertices in the carboxysome, a polyhedral BMC where RuBisCO (ribulose bisphosphate carboxylase) is sequestered. It induces curvature upon insertion into an otherwise flat hexagonal molecular layer of CcmK subunits (

) .
Sliding-clamp-loader large subunit (T4_Clamp_Loader_L)
Type: Family

This family includes the sliding-clamp-loader large subunit (also known as gp44) from Bacteriophage T4. It forms the sliding-clamp-loader together with the small subunit and functions as an ATPase enzyme . The clamp loader holds the clamp in an open conformation and places it onto the DNA . ATP hydrolysis triggers the detachment of the sliding clamp from the sliding-clamp-loader, freeing the sliding clamp to track along DNA .
Sliding clamp (Sliding_clamp_T4)
Type: Family

This family includes sliding clamp protein from Bacteriophage T4 (also known as gp45), which encircles the genomic DNA and links the DNA polymerase to the template to control the processivity of DNA synthesis. It is responsible for tethering the catalytic subunit of DNA polymerase to DNA during high-speed replication . The interaction with the sliding-clamp-loader opens the sliding clamp so that it can be loaded around the DNA template . During transcription, encircles the DNA and tethers host RNA polymerase (RNAP) to it .
Head completion nuclease (NUCL_HEAD_T4)
Type: Family

This entry represents the head completion endonuclease (also known as gp4 and gp50), which plays an essential role in the head-tail joining step of T4-like phages during phage morphogenesis . It has both exo- and endonuclease activity .
Protein spackle (SPACKLE_T4)
Type: Family

This family represents protein spackle from Bacteriophage T4, which inhibits viral DNA ejection into the host cytoplasm, thereby conferring the infected host bacteria with immunity against secondary phage infection . It localizes to the periplasm and inhibits the activity of tail-associated lysozyme, thereby preventing penetration by the tail tube of incoming phages . It interacts with the baseplate central spike protein gp5, therefore, spackle selectively inhibits the lysozyme activity of gp5, but not that of T4 lysozyme.
DNA primase, bacteriophage T4 (PRIMASE_T4)
Type: Family

This family includes the DNA primase form bacteriophage T4, which synthesizes short RNA primers on the lagging strand that the polymerase elongates using dNTPs. It recognises two trinucleotide sequences 5'-GTT-3' and 5'-GCT-3' in vitro, but uses only the first as the priming site in vivo .
Bacteriophage T4 DnaB-like replicative helicase (Helic_T4)
Type: Family

This entry represents DnaB-like replicative helicase (also known as gp41) from Bacteriophage T4, an ATP-dependent DNA helicase essential for viral DNA replication and recombination . This protein moves 5'->3' on the lagging strand template, unwinding the DNA duplex ahead of the leading strand polymerase at the replication fork and generating ssDNA for both leading and lagging strand synthesis . It interacts with the primase, which allows the primase to initiate lagging strand synthesis and fully activates the helicase . This helicase is loaded by the helicase assembly factor on replication forks that begin at discrete replication origin sequences, as well as on forks that are created during recombination .
Bacteriophage T7 DNA helicase/primase (Helic_Prim_T7)
Type: Family

This entry is represented by bacteriophage T7 DNA helicase/primase (also known as Gp4), an ATP-dependent DNA helicase and primase that is essential for viral DNA replication and recombination . Primase activity synthesizes short RNA primers at the sequence 5'-GTC-3' on the lagging strand that the polymerase elongates using dNTPs and providing the primase is still present .

The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
Bacteriophage T4, Gp32, single-stranded DNA-binding (SSB_T4)
Type: Family

Single-stranded DNA-binding protein (also known as Gp32 or SSB) is essential for bacteriophage T4 DNA replication, recombination and repair, acting to stimulate replisome processing and accuracy through its binding to ssDNA as the replication fork advances . The crystal structure of Gp32 shows an ssDNA binding cleft comprised of regions from three structural subdomains, through which ssDNA can slide freely . The structure of Gp32 is similar to other phage ssDNA-binding proteins such as Gp2.5 from bacteriophage T4, and gene V protein, both of which have a nucleic acid-binding OB-type fold. However, Gp32 contains a zinc-finger subdomain at residues 63-111 that is not found in the other two phage proteins.

This protein stimulates the activities of viral DNA polymerase and DnaB-like SF4 replicative helicase, probably via its interaction with the helicase assembly factor , and together with DnaB-like SF4 replicative helicase and the helicase assembly factor, promotes pairing of two homologous DNA molecules containing complementary single-stranded regions and mediates homologous DNA strand exchange .
Probable inorganic carbon transporter subunit DabB (Transporter_DabB)
Type: Family

This entry represents the probable inorganic carbon transporter subunit DabB from Bacillus anthracis, part of an energy-coupled inorganic carbon pump. This group of bacterial proteins form a small clade among the members of

that are distinct from complex I subunits, which suggests cation transport but does not imply redox activity .
Pre-baseplate central spike protein Gp5 (NEEDLE_T4)
Type: Family

This entry includes the pre-baseplate central spike protein Gp5 from bacteriophage T4 which is a baseplate central spike complex-associated lysozyme, essential for the localized hydrolysis of bacterial cell wall. This allows the tail tube to penetrate to the host inner membrane, through which the phage DNA is ejected .
Acyl-coenzyme A diphosphatase YFT2 (YFT2)
Type: Family

This family represents a group of fungal proteins which belongs to the Fat storage-inducing transmembrane protein family (FITM), including acyl-coenzyme A diphosphatase YFT2 from Saccharomyces cerevisiae, the yeast orthologue of human FIT2 . This protein is required for ER membrane biosynthesis in response to ER stress, for maintaining ER structure and for lipid droplets (LDs) biogenesis . YFT2 may support directional budding of nascent LDs from the ER into the cytosol by reducing DAG levels at sites of LD formation .
DNA-directed RNA polymerase subunit Rpo7 (RNApol_Rpo7)
Type: Family

This family represents archaeal DNA-directed RNA polymerase subunit Rpo7 (previously known as RNA polymerase subunits RpoE). These RNA polymerases catalyse the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Rpo7 shows a two-domain structure with two potential RNA binding motifs . Rpo7 forms a stalk with Rpo4 that extends from the main structure, as seen in the resolved structure of

from Thermococcus kodakarensis .
Acyl-coenzyme A diphosphatase SCS3 (SCS3)
Type: Family

This entry represents Acyl-coenzyme A diphosphatase SCS3 from fungi, a member of the fat storage-inducing transmembrane protein family (FITM) and an orthologue of human FIT2. This protein is required for maintaining ER structure and for lipid droplets (LDs) biogenesis . SCS3 may support directional budding of nascent LDs from the ER into the cytosol by reducing DAG levels at sites of LD formation and it is involved in phospholipid biosynthesis .
Fat storage-inducing transmembrane protein 1/2 (FITM1/2)
Type: Family

This family includes FIT1 and FIT2 proteins.

Fat storage-inducing transmembrane protein family (FIT/FITM, also known as Acyl-coenzyme A diphosphatase

) plays an important role in lipid droplet accumulation. They are endoplasmic reticulum (ER) resident membrane proteins that induce lipid droplet accumulation in cell culture and when expressed in mouse liver ; they hydrolyses fatty acyl-CoA to yield acyl-4'-phosphopantetheine and adenosine 3',5'-bisphosphate, with preference of unsaturated long-chain acyl-CoA substrates in the ER . The ability to store fat in the form of cytoplasmic triglyceride droplets is conserved from yeast to humans, important for maintaining ER structure and for lipid droplets (LDs) biogenesis, which are lipid storage organelles involved in maintaining lipid and energy homeostasis . The FIT family of proteins are not involved in triglyceride biosynthesis .

In mammals there are two FIT proteins, FIT1, which is muscle specific and FIT2, which is expressed in most other tissues . Yeast has two FIT2 orthologues, called Scs3p and Yft2p but no FITM1. FIT1 and FIT2 proteins are six-transmembrane-domain containing proteins with both the N and C termini residing in the cytosol. FIT2 is the more ancient conserved homologue of the FIT family; this family of proteins do not share sequence similarity to known proteins or domains.
Fat storage-inducing transmembrane protein 1 (FIT1)
Type: Family

This family includes FIT1.

Fat storage-inducing transmembrane protein family (FIT/FITM, also known as Acyl-coenzyme A diphosphatase

) plays an important role in lipid droplet accumulation. They are endoplasmic reticulum (ER) resident membrane proteins that induce lipid droplet accumulation in cell culture and when expressed in mouse liver ; they hydrolyses fatty acyl-CoA to yield acyl-4'-phosphopantetheine and adenosine 3',5'-bisphosphate, with preference of unsaturated long-chain acyl-CoA substrates in the ER . The ability to store fat in the form of cytoplasmic triglyceride droplets is conserved from yeast to humans, important for maintaining ER structure and for lipid droplets (LDs) biogenesis, which are lipid storage organelles involved in maintaining lipid and energy homeostasis . The FIT family of proteins are not involved in triglyceride biosynthesis .

In mammals there are two FIT proteins, FIT1, which is muscle specific and FIT2, which is expressed in most other tissues . Yeast has two FIT2 orthologues, called Scs3p and Yft2p but no FITM1. FIT1 and FIT2 proteins are six-transmembrane-domain containing proteins with both the N and C termini residing in the cytosol. FIT2 is the more ancient conserved homologue of the FIT family; this family of proteins do not share sequence similarity to known proteins or domains.
3-oxopimeloyl-[acyl-carrier-protein] synthase (BioZ)
Type: Family

This family includes 3-oxopimeloyl-[acyl-carrier-protein] synthase from bacteria, which is involved in the formation of the biotin precursor pimeloyl-ACP . This protein catalyses the condensation of glutaryl-CoA, an intermediate in lysine degradation, with malonyl-ACP to produce 3-oxopimeloyl-ACP .
ClpXP adapter protein SpxH (Adapter_SpxH)
Type: Family

This entry represents a group of proteins from Firmicutes, including ClpXP adapter protein SpxH, also known as YjbH in Bacillus subtilis. This protein is required for efficient degradation of the RNA polymerase-binding transcription factor Spx by the protease ClpXP under non-stress conditions. It is organised into a DsbA-like thioredoxin domain, a linker and a C-terminal domain reminiscent of the winged helix-turn-helix fold .
Guanosine-inosine kinase (IngK)
Type: Family

This entry represents guanosine-inosine kinase (IngK or Gsk) from Escherichia coli and similar proteins mostly found in gammaproteobacteria. IngK catalyses the phosphorylation of guanosine and inosine to GMP and IMP, respectively. However, it shows a strong preference for guanosine . This protein adopts a dimeric assembly, essential for its activity .
Inner membrane lipoprotein DcrB (DcrB)
Type: Family

DcrB is a bacterial protein required for phages C1 and C6 adsorption . It may be involved in the opening or formation of diffusion channels in the outer membrane . It plays a role in cell envelope biogenesis, maintenance of cell envelope integrity and membrane homeostasis . DcbrB is essential for lipoprotein maturation under conditions where membrane fluidity may be altered . Structurally, it consist of an antiparallel β-sheet with two α-helical regions.
Carboxylic acid reductase (CAR)
Type: Family

This entry represents Carboxylic acid reductase (CAR) from Mycobacterium marinum and similar proteins from Actinobacteria. This enzyme catalyses the ATP- and NADPH-dependent reduction of carboxylic acids to the corresponding aldehydes . It shows an adenylation domain linked via a peptidyl carrier protein (PCP) to a reductase termination domain .
Anamorsin, C-terminal (CIAPIN1)
Type: Domain

This entry represents the C-terminal domain of anamorsin and its homologues which contains two highly conserved cysteine rich motifs that bind Fe-S clusters .

Anamorsin (also named CIAPIN1 for cytokine-induced anti-apoptosis inhibitor 1), is the human homologue of yeast Dre2, a conserved soluble eukaryotic Fe-S cluster protein, that functions in cytosolic Fe-S protein biogenesis . It is found in both the cytoplasm and in the mitochondrial intermembrane space (IMS) . Anamorsin is found to be up-regulated in hepatocellular cancer, is considered to be a downstream effector of the receptor tyrosine kinase-Ras signalling pathway, and is essential in mouse definitive haematopoiesis . In addition, it mediates the anti-apoptotic effects of various cytokines .