SII-SWORD/CoKE huggingface dataset:
DNA integrity scanning protein, DisA, N-terminal (DNA_integrity_scan_DisA_N)
Type: Domain

Cyclic di-AMP (c-di-AMP) is a bacterial secondary messenger molecule, which is associated with various physiological functions. It is involved in several important cellular processes, such as cell wall metabolism, maintenance of DNA integrity, ion transport, transcription regulation, and allosteric regulation of enzyme function. The 120-amino acid-long diadenylate cyclase (DAC) domain converts two ATP or ADP molecules into one c-di-AMP molecule. The majority of DAC domain-containing proteins are found in bacterial species, but a small number are also present in archaea of the phylum Euryarchaeota. In bacteria, DAC domain proteins are most frequently found in Gram-positive bacteria belonging to the phyla Firmicutes and Actinobacteria, including pathogenic bacteria such as Listeria monocytogenes or
Staphylococcus aureus
. Compared with the majority of bacterial species which encode only one DAC enzyme, members of the genus
Bacillus
generally encode three DAC domain-containing proteins: DisA, CdaA (previously named YbbP in the genus
Bacillus
or DacA in other genera) and CdaS (previously named YojJ in the genus
Bacillus
or DacB in others) .

The DAC domain exhibits an overall globular α/β fold with the long N-terminally located helix (alpha1) flanking the core. A slightly twisted central β-sheet, made up of seven mixed-parallel and antiparallel β-strands, forms the core globular part. Both sides of the β-sheets are flanked by a total of five α-helices (alpha1-alpha5), resulting in the observed globular shape .

The DisA protein is a bacterial checkpoint protein that dimerises into an octameric complex. The protein consists of three distinct domains. The DAC domain is the first and is a globular, nucleotide-binding region; the next 146-289 residues constitute the DisA-linker family,

that consists of an elongated bundle of three α helices (alpha-6, alpha-10, and alpha-11), one side of which carries an additional three helices (alpha7-9), which thus forms a spine like-linker between domains 1 and 3. The C-terminal residues, of domain 3, are represented by family HHH,

the specific DNA-binding domain. The octameric complex thus has structurally linked nucleotide-binding and DNA-binding HhH domains and the nucleotide-binding domains are bound to a cyclic di-adenosine phosphate such that DisA is a specific di-adenylate cyclase. The di-adenylate cyclase activity is strongly suppressed by binding to branched DNA, but not to duplex or single-stranded DNA, suggesting a role for DisA as a monitor of the presence of stalled replication forks or recombination intermediates via DNA structure-modulated c-di-AMP synthesis.
Adenoviral preterminal protein (Adeno_preterminal)
Type: Family

The adenovirus terminal protein precursor or preterminal protein (pTP) functions as a primer for the initiation of virus DNA replication. It forms a heterodimer with Ad DNA polymerase (pol) . pTP is processed at two sites by the virus-encoded protease to yield mature terminal protein (TP) via an intermediate (iTP) .
Patched domain-containing protein, SSD domain (PTHD_SSD)
Type: Domain

This entry represents the sterol-sensing domain (SSD) of patched domain-containing proteins 1, 3, 4 and 18.

PTCHD3 may play a role in sperm development or sperm function , however, it may not play an essential role in spermatogenesis or male fertility . PTCH1 is required for the development and function of the thalamic reticular nucleus (TRN), a part of the thalamus that is critical for thalamocortical transmission, generation of sleep rhythms, sensorimotor processing and attention . It can bind cholesterol in vitro . PTCHD4 may act as a repressor of canonical hedgehog signalling by antagonising the effects of SMO, as suggested by down-regulation of hedgehog target genes, including GLI1, PTCH1, and PTCH2 in PTCHD4-expressing cells .
Ammonia monooxygenase/particulate methane monooxygenase, subunit A (NH3_CH4_mOase_A)
Type: Family

Ammonia monooxygenase and the particulate methane monooxygenase are both integral membrane proteins, occurring in ammonia oxidisers and methanotrophs respectively, which are thought to be evolutionarily related . These enzymes have a relatively wide substrate specificity and can catalyse the oxidation of a range of substrates including ammonia, methane, halogenated hydrocarbons and aromatic molecules . These enzymes are composed of 3 subunits -A (

), B (

) and C (

) -and contain various metal centres, including copper. Particulate methane monooxygenase from Methylococcus capsulatus str. Bath is an ABC homotrimer, which contains mononuclear and dinuclear copper metal centres, and a third metal centre containing a metal ion whose identity in vivo is not certain.

The A subunit from Methylococcus capsulatus str. Bath resides primarily within the membrane and consists of 7 transmembrane helices and a β-hairpin which interacts with the soluble region of the B subunit. A conserved glutamate residue is thought to contribute to a metal centre .
Porin, opacity type (Porin_opacity)
Type: Domain

Pathogenic Neisseria spp. possess a repertoire of phase-variable opacity proteins that mediate various pathogen/host cell interactions . These proteins are integral membrane proteins related to other porins and the Haemophilus influenzae OpA protein.
RecF/RecN/SMC, N-terminal (RecF/RecN/SMC_N)
Type: Domain

This domain is found at the N terminus of structural maintenance of chromosomes (SMC) proteins, which function together with other proteins in a range of chromosomal transactions, including chromosome condensation, sister-chromatid cohesion, recombination, DNA repair and epigenetic silencing of gene expression . The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics . This domain is also found in RecF and RecN proteins, which are involved in DNA metabolism and recombination.

This domain is also found in urease accessory protein 2 (URE2) which is a central component of cohesin, a complex required for chromosome cohesion during the cell cycle, and Is unrelated to urease function in C.neoformans .
Photosystem II PsbN (PSII_PsbN)
Type: Family

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .

This family represents the low molecular weight bitopic transmembrane protein PsbN found in PSII. It localises in stroma lamellae and contains a highly conserved C-terminal region, exposed to the stroma. Although PsbN is not a constituent subunit of PSII, it is required for repair from photoinhibition and efficient assembly of the PSII reaction centers .
Mce/MlaD (Mce/MlaD)
Type: Domain

This domain is found in all 24 mce genes associated with the four mammalian cell entry (mce) operons of Mycobacterium tuberculosis and MlaD proteins from other Actinomycetales . The archetype (mce1A, Rv0169), was isolated as being necessary for colonisation of, and survival within, the macrophage . The domain is also found in:

Chloroplast Ycf22 and related cyanobacterial homologues, the majority of which have an N-terminal transmembrane domain and are putative ABC transporters.

Proteobacterial homologues, which include MlaD, PqiB, YrbD, YebT, VpsC and Ttg2C. MlaD is part of the ABC transporter complex MlaFEDB that actively prevents phospholipid accumulation at the cell surface . MlaFEDB complex is composed of two ATP-binding proteins (MlaF), two transmembrane proteins (MlaE), two cytoplasmic solute-binding proteins (MlaB) and a probable periplamic solute-binding protein (MlaD). Through the Mla pathway, Gram-negative bacteria maintains lipid asymmetry in the outer membrane by retrograde trafficking of phospholipids from the outer membrane to the inner membrane .
Biopolymer transport protein ExbD/TolR (ExbD)
Type: Family

This group of proteins are membrane bound transport proteins essential for ferric ion uptake in bacteria . The family consists of ExbD, and TolR which are involved in TonB-dependent transport of various receptor bound substrates including colicins .
Herpesvirus immediate early protein (IE68)
Type: Family

This regulatory protein is expressed from an immediate early gene in the cell cycle of Herpesviridae. The protein is known by various names including IE-68, US1, ICP22 and IR4. It acts as a general transcriptional regulator of cellular and viral mRNAs, through modifications on the host RNA polymerase II which inhibit host genome transcription, leading to cell cycle deregulation and loss of efficient antiviral response. IE68 also recruits cellular transcription elongation factors to viral genomes for efficient transcription elongation of viral genes . In Herpesvirus type-2, this protein functions as a E3 ubiquitin ligase which interacts with STAT1, STAT2, IFN regulatory factor 9 (IRF9), and other ubiquitinated proteins, promoting its degradation and resulting in the blockade of ISG factor 3 (ISGF3) nuclear translocation. Through this mechanism, the production of ISG54 is inhibited and, thus, it inhibits innate immunity response during viral infection .
Envelope glycoprotein E, Fc-binding domain (Herpes_glycopE_Fc)
Type: Domain

This entry represents the Ig-like domain of Glycoprotein E (gE) from herpesvirus. This protein forms a complex with glycoprotein I (gI), functioning as an immunoglobulin G (IgG) Fc binding protein. gE is involved in virus spread but is not essential for propagation. This domain is identified as the Fc-binding domain .
Glycosyl transferase, family 14 (Glyco_trans_14)
Type: Family

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([ec:2.4.1.-]) and related proteins into distinct sequence based families has been described . This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.

This is the glycosyltransferase family 14

, a family of two different beta-1,6-N-acetylglucosaminyltransferase enzymes, I-branching enzyme (

) and core-2 branching enzyme (

). I-branching enzyme, an integral membrane protein, converts linear into branched poly-N-acetyllactosaminoglycans in the glycosylation pathway, and is responsible for the production of the blood group I-antigen during embryonic development . Core-2 branching enzyme, also an integral membrane protein, forms crucial side-chain branches in O-glycans in the glycosylation pathway .
Merozoite antigen (Merozoite_Agen)
Type: Family

This family represents the immunodominant surface antigen of Theileria parasites including equi merozoite antigen-1 (EMA-1) and equi merozoite antigen-2 (EMA-2) . The protein shows variation at a putative glycosylation site, a potential mechanism for host immune response evasion .
MORN repeat (MORN)
Type: Repeat

This entry represents MORN (Membrane Occupation and Recognition Nexus) repeat. This repeat was identified in multiple copies in several proteins including junctophilins . More recently it was found that MORN repeat proteins are quite ubiquitous and are present in both eukaryotes and prokaryotes. The number of MORN repeats in any given protein can vary greatly, from 2 to over 20, and they are found in combination with a wide range of other domains. MORN repeats are generally assumed to be lipid-binding modules. Structurally, MORN repeat is composed of a β-hairpin followed by a short loop that connects to the next MORN repeat .
HYR domain (HYR_dom)
Type: Domain

The HYR (HYalin Repeat) domain is an extracellular domain of about 80-100 amino acids. It has been named after the hyalin protein, which is composed exclusively of repeats of this domain. The HYR domain is found in several eukaryotic proteins, either in multiple copies as in hyalin or in association with other domains like the CCP (sushi) domain, the Von Willebrand factor type A (VWA) domain, the EGF-like domain, the calcium-binding EGF-like domain, the pentraxin domain, the CUB domain, the LDL-receptor class A domain, the C-type lectin domain or the discoidin domain. As the HYR domains of hyalin have been shown to contain the ligand for the hyalin cell surface receptor, the HYR domain can also be expected to play a direct role in cellular adhesion in other proteins in which it is present .

Secondary structure predictions of the HYR domain indicate an all-β fold including seven β-strands. The HYR domain shares clear sequence similarities limited to the C-terminal region with the Fn3 and PKD domains and is believed to belong to the immunoglobulin-like fold .
Triple gene block 3 (TGBp3)
Type: Family

Members of this family include TGBp3 proteins found in many plant viruses. Triple gene block 3 proteins (TGBp3) are involved in virus momvement. TGBp3 is an integral ER membrane protein with a single transmembrane domain, and a C-terminal region exposed to the cytosol. TGBp3 is able to target TGBp2 to the cortical ER tubules of the cell periphery through the sorting signal in the C-terminal region of TGBp3. Moreover, it plays a key role in virus cell-to-cell movement by enhancing the TGBp2- and TGBp3-dependent plasmodesmata (PD) localization of TGBp1; however, the enhancement is abolished when one of the two conserved Cys residues in the C-terminal region of TGBp3 is replaced with Ala .
Arterivirus GP4 envelope glycoprotein (Arteri_GP4)
Type: Family

Arteriviruses are small, enveloped, animal viruses with an icosahedral core containing a positive-sense RNA genome. The arteriviruses are highly species specific, but share many biological and molecular properties, including virion morphology, a unique set of structural proteins, genome organisation and replication strategy. This is a family of minor envelope glycoproteins from Arteriviridae that corresponds to open reading frame 4 (ORF4) of the virus .
Type II secretion system protein GspI, C-terminal (T2SS_GspI_C)
Type: Domain

This entry represent the C-terminal domain of GspI, which is a pseudopilin component of the type II secretion system (T2SS). It contains the prepilin signal sequences . In Pseudomonas aeruginosa GspI homologue, known as XcpV, has been suggested to be the central component and initiator of pseudopilus formation .

The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space . T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK . GspD has been shown to interact with the inner membrane component GspC .
Polyphosphate kinase (PP_kinase)
Type: Family

Polyphosphate kinase (Ppk) (

) catalyzes the formation of polyphosphate from ATP, with chain lengths of up to a thousand or more orthophosphate molecules. It is a membrane protein and goes through an intermediate stage during the reaction where it is autophosphorylated with a phosphate group covalently linked to a basic amino acid residue through an N-P bond.
Telomere-binding protein, alpha subunit, Spirotrichea (Telomere-bd_alpha)
Type: Family

This entry represents the alpha subunit of the telomere-binding protein in ciliates. The telomer-binding protein forms a heterodimer in consisting of an alpha and a beta subunit. This complex may function as a protective cap for the single-stranded telomeric overhang, and may also participate in telomere length regulation during DNA replication. It binds specifically to the T4G4-containing extension on the 3' strand and protects this region of the telomere from nuclease digestion and chemical modification .
MgtC/SapB/SrpB/YhiD family (MgtC/SapB/SrpB/YhiD_fam)
Type: Family

This entry includes a group of transmembrane proteins, including MgtC, SapB, SrpB and YhiD from bacteria.
Core-binding factor, beta subunit (CBF_beta)
Type: Family

Core binding factor (CBF) is a heterodimeric transcription factor essential for genetic regulation of hematopoiesis and osteogenesis. The beta subunit binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including Murine leukemia virus, Polyomavirus enhancer, T-cell receptor enhancers etc. The beta subunit enhances DNA-binding ability of the alpha subunit
in vitro
, and has been show to have a structure related to the OB fold . Also included in this family are the Drosophila melanogaster brother and big brother proteins, which regulate the DNA-binding properties of Runt.
Fumarate reductase, subunit D (Fumarate_red_D)
Type: Family

Fumarate reductase is a membrane-bound flavoenzyme consisting of four subunits . Subunits A and B comprise the membrane-extrinsic catalytic domain and C and D link the catalytic centres to the electron-transport chain. This family consists of the 13kDa hydrophobic subunit D. This component may be required to anchor the catalytic components of the fumarate reductase complex to the cytoplasmic membrane.
Methanol dehydrogenase, beta subunit (Meth_DH_bsu)
Type: Family

Methanol dehydrogenase (MDH) (

), found in Gram-negative bacteria, is a pyrroloquinoline quinone (PQQ)-containing enzyme which oxidises methanol to formaldehyde. It is located in the periplasmic space and passes electrons derived from the oxidation of methanol to the soluble cytochrome cL . The enzyme is a tetramer composed of two large alpha subunits and two smaller beta subunits. The alpha subunit binds the PQQ cofactor and contains the active site, while the function of the beta subunit is currently unknown . The alpha subunit forms an eight-bladed propeller structure, with several novel tryptophan-docking motifs linking the individual blades together.

This entry represents the beta subunit of methanol dehydrogenase.
Opine dehydrogenase (Opine_DH)
Type: Domain

This group of enzymes act on the CH-NH substrate bond using NAD(+) or NADP(+) as an acceptor. This domain is found primarily in octopine dehydrogenase (

), nopaline dehydrogenase (

), and lysopine dehydrogenase (

). NADPH is the preferred cofactor, but NADH is also used. Octopine dehydrogenase is involved in the reductive condensation of arginine and pyruvic acid to D-octopine .

Opine dehydrogenases can be found in both bacteria and marine cephalopods. In bacteria, some of these opine dehydrogenases are involved in crown gall tumours that are produced by Agrobacterium spp., and which encode for the opine dehydrogenases on a Ti-plasmid. These bacteria can transfer a portion of this plasmid (T-DNA) to a susceptible plant cell; the T-DNA then integrates into the plant nuclear genome, where its genes can be expressed. Some of these genes direct the synthesis and secretion of unusual amino acid and sugar derivatives called opines - these opines are used as a carbon and sometimes a nitrogen source by the infecting bacteria.

Opine dehydrogenases are also found in the marine invertebrate cephalopods (octopuses, squid, and cuttlefish). For example in marine cephalopods, octopine dehydrogenase activity in mantle muscle is significantly correlated with a species' ability to buffer the acidic end products of anaerobic metabolism, with activity declining strongly with a species' habitat depth .
Cytochrome b-c1 complex, subunit 6 (Cyt_b-c1_6)
Type: Family

The ubiquinol-cytochrome C reductase complex (cytochrome bc1 complex) is a respiratory multienzyme complex . The bc1 complex contains 11 subunits; 3 respiratory subunits (cytochrome B, cytochrome C1, Rieske protein), 2 core proteins and 6 low molecular weight proteins. This family represents the 'hinge' protein of the complex, subunit 6, which is thought to mediate formation of the cytochrome c1 and cytochrome c complex. Proteins in this entry from an α-helical hairpin.
Outer membrane efflux protein (OMP_efflux)
Type: Family

The OEP family (Outer membrane efflux protein) form trimeric channels that allow export of a variety of substrates in Gram-negative bacteria. Each member of this family is composed of two repeats. The trimeric channel is composed of a 12
stranded all β sheet barrel that spans the outer membrane, and a long all helical barrel that spans the periplasm. Examples include the Escherichia coli TolC outer membrane protein, which is required for proper expression of outer membrane protein genes; the Rhizobium nodulation protein; and the Pseudomonas FusA protein, which is involved in resistance to fusaric acid.
Egg-laying hormone/atrial gland peptide (ELH)
Type: Family

This family consists of egg-laying hormone (ELH) precursor and atrial gland peptides from the little (Aplysia parvula) and california (Aplysia californica) sea hares. The family also includes ovulation prohormone precursor from the great pond snail (Lymnaea stagnalis). This family thus represents a conserved gastropoda ovulation and egg production prohormone. Note that many of the proteins present are further cleaved to give individual peptides . Neuropeptidergic bag cells of the marine mollusc A. californica synthesize an egg-laying hormone (ELH) precursor protein which is cleaved to generate several bioacitve peptides including ELH, bag cell peptides (BCP) and acidic peptide (AP) .
CCB3/YggT (CCB3/YggT)
Type: Family

This family includes YlmG from bacteria, CCB3 and YlmG homologue proteins (YLMG1-1, YLMG1-2, YLMG2) from Arabidopsis . This family also includes uncharacterised protein YggT, associated with bacteria outside of the cyanobacteria. YlmG might be involved in chloroplast and cyanobacterial division processes .

Cofactor maturation pathways such as the CCB system (system IV) for cytochrome c-heme attachment are conserved in all organisms performing oxygenic photosynthesis . The CCB system consists of four proteins: CCB1-4. CCB2 and CCB4 are paralogues derived from a unique cyanobacterial ancestor . Orthologues are conserved in higher plants .