SII-SWORD/CoKE huggingface dataset:
Alkylmercury lyase (MerB)
Type: Family

Mercury is a highly toxic metal. Toxicity can result from three different mercurial forms: elemental, inorganic ion and organomercurial compounds. The ability of bacteria to detoxify mercurial compounds by reduction and volatilisation is conferred by the Mer genes, which are usually plasmid encoded (although chromosome resistance determinants have also occasionally been identified) . Organomercurial lyase (MerB), also known as alkylmercury lyase, mediates the first of the two steps in the microbial detoxification of organomercurial salts (the other catalysed by mercuric reductase).

Organomercurial lyase catalyses the protonolysis of the C-Hg bond in a wide range of organomercurial salts (primary, secondary, tertiary, alkyl, vinyl, allyl and aryl) to Hg(II) and the respective organic compound :

RHg(+) + H(+) = RH + Hg(2+)

Hg(II) is subsequently detoxified by mercuric reductase.

The enzyme has been purified to homogeneity in Escherichia coli and has been found to be a 22.4kDa monomer with no detectable cofactors or metal ions.
Photosystem I PsaH, reaction centre subunit VI (PSI_PsaH)
Type: Family

Photosystem I, a membrane complex found in the chloroplasts of plants and cyanobacteria uses light energy to transfer electrons from plastocyanin to ferredoxin. The electron transfer components of the photosystem include the primary electron donor chlorophyll P-700 and 5 electron acceptors: chlorophyll (A0), phylloquinone (A1) and three 4Fe-4S iron-sulphur centres, designated Fx, Fa and Fb. The role of this protein, subunit VI or PsaH, may be in docking of the light harvesting complex I antenna to the core complex.
Spanin, inner membrane subunit (I-spanin)
Type: Family

The lysis of Gram-negative hosts by double-strand DNA bacteriophages requires, in addition to the actions of a holin and endolysin, a third step involving the spanin complex. This complex consists of a small outer membrane lipoprotein and an integral cytoplasmic membrane protein, designated as o-spanins and i-spanins, respectively. The spanin complex is involved in the disruption of the outer membrane. Without the spanin function, lysis is blocked and progeny virions are trapped in dead spherical cells .

The first spanins to be characterised were phage lambda Rz and Rz1 . Rz corresponds to the inner membrane or i-spanin, whereas Rz1 represents the outer membrane or o-spanin. Rz and Rz1 (

) represent a unique example of two genes located in different reading frames in the same nucleotide sequence, which encode different proteins that are both required in the same physiological pathway . Rz and Rz1 form a disulfide-linked complex that spans the host inner and outer membranes .
Pneumovirus nucleocapsid protein (Pneumo_ncap)
Type: Family

This family is the Pneumovirus nucleocapsid protein. It is the most abundant protein in the virion and an important element in conferring helical symmetry on the nucleoprotein core as well as interacting with the M protein during virion formation.
Prothymosin/parathymosin (Pro/parathymosin)
Type: Family

Prothymosin alpha and parathymosin are two ubiquitous small acidic nuclear proteins that are thought to be involved in cell cycle progression, proliferation, and cell differentiation .
Retrieval of early ER protein Rer1 (Rer1)
Type: Family

RER1 family proteins are involved in the retrieval of some endoplasmic reticulum membrane proteins from the early golgi compartment. The C terminus of yeast Rer1p interacts with a coatomer complex .
Type specific antigen (TSA)
Type: Family

There are several antigenic variants in Rickettsia tsutsugamushi, and a type-specific antigen (TSA) of 56-kilodaltons located on the rickettsial surface is responsible for the variation . TSA proteins are probably integral membrane proteins.
Tropomodulin (TMOD)
Type: Family

Actin filaments have an intrinsic polarity, each with a fast-growing (barbed) end and a slow-growing (pointed) end. The slow-growing end is regulated by tropomodulins, a family of capping proteins that require tropomyosins for optimal function . Tropomyosins contains two domains: an N-terminal unstructured tropomyosin-binding region which has an actin pointed-end-capping activity, an C-terminal region that contains one compact domain represented by alternating α-helices and β-structures . The tropomyosin-independent actin-capping site is located at the C terminus . The structure of tropomyosin-1 has been solved .

Proteins in this entry include Tropomodulin (TMOD)-1/2/3/4 and Leiomodin (LMOD)-1/2/3.
Tymovirus 45/70kDa protein (45/70kDa_tymovirus)
Type: Family

Tymoviruses are single stranded RNA viruses. This family includes a protein of unknown function that has been named based on its molecular weight. Tymoviruses such as the ononis yellow mosaic tymovirus encode only three proteins. Of these two are overlapping this protein overalps a larger ORF that is thought to be the polymerase .
Herpesvirus UL21 (Herpes_UL21)
Type: Family

The UL21 protein appears to be a dispensable component in herpesviruses .
Urea transporter (Urea_transporter)
Type: Family

Proteins in this entry include low-affinity urea transporters found in the erythrocytes and kidneys of higher organisms. The erythrocyte proteins carry the clinically important Kidd (Jk) blood group antigens which help determine blood type. The two commonest forms are Jk(a) and Jk(b), which arise from a single residue variation at position 280; aspartate in Jk(a) and asparagine in Jk(b) . A much rarer phenotype, Jk(null), arises when the protein is not expressed on the erythrocyte surface, and is linked to a urine-concentrating defect . The Kidd blood group is clinically significant as Jk antibodies can cause acute transfusion reactions and haemolytic disease of the newborn (HDN), where the mother's body creates antibodies against the foetal blood cells. HDN associated with Jk antibodies is generally mild, but fatal cases can occur .

The bacterial proteins in this entry also appear to be involved in urea transport, promoting its entry into the cell . This uptake of urea can be advantageous for bacteria as its hydrolysis by urease generates ammonium which is an efficient source of nitrogen and, through its buffering capacity, can also provide resistance to acidic conditions.
Xyloglucan fucosyltransferase (XG_FTase)
Type: Family

Plant cell walls are crucial for development, signal transduction, and disease resistance in plants. Cell walls are made of cellulose, hemicelluloses, and pectins. Xyloglucan (XG), the principal load-bearing hemicellulose of dicotyledonous plants, has a terminal fucosyl residue. This fucosyltransferase adds this residue .
APC10/DOC domain (APC_su10/DOC_dom)
Type: Domain

The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome .

One of the subunits of the APC that is required for ubiquitination activity is APC10, a one-domain protein homologous to a sequence element, termed the DOC domain, found in several hypothetical proteins that may also mediate ubiquitination reactions, because they contain combinations of either RING finger (see

), cullin (see

) or HECT (see

) domains .

The DOC domain consists of a β-sandwich, in which a five-stranded antiparallel β-sheet is packed on top of a three stranded antiparallel β-sheet, exhibiting a 'jellyroll' fold .

Proteins known to contain a DOC domain include:

Eucaryotic Doc1/Apc10.

Mammalian protein associated with the transcription factor Myc (PAM).

Mouse runty-jerky-sterile (RJS) protein.

Human HERC2, the ortholog of RJS.
Adhesin P1, C-terminal domain (Adhesin_P1_C)
Type: Domain

This entry represents a domain found towards the C-terminal of adhesins from Mycoplasmas, such as adhesin P1, first identified as the major determinant for cytoadherence and gliding motility in M. pneumoniae. P1 forms a transmembrane adhesion complex with P40/P90, called 'Nap', which mediates motility and infectivity in these organisms. The C-terminal domain is smaller than the large N-terminal domain, which is highly variable (

). It is followed by a transmembrane domain and acts as a stalk connecting the large N-terminal domain with the outer surface of the cell membranes. The C-terminal domain, mostly conserved, acts as a stalk connecting the large N-terminal domain with the outer surface of the cell membranes .
FP protein, N-terminal domain (FP_N)
Type: Domain

This entry represents the N-terminal domain of the FP protein from Orgyia pseudotsugata multicapsid polyhedrosis virus, which is also found in other uncharacterised sequences from arthropods and baculovirus. The function of the FP protein is not known. The protein is missing in baculovirus FP (Few Polyhedra) mutants .
Roadblock/LAMTOR2 domain (Roadblock/LAMTOR2_dom)
Type: Domain

This domain can be found in the roadblock proteins and LAMTOR2 proteins.
Lepidopteran low molecular weight lipoprotein (Lipoprotein_11)
Type: Family

This family includes Lepidopteran low molecular weight (30kDa) lipoproteins (30KPs), which belong to the Lipoprotein 11 family. They are abundant proteins found in the hemolymph, mainly synthesized in the fat body and then secreted into the hemolymph during the last instar larval stage. They have very similar amino acid and nucleotide sequences which are also similar to those of microvitellogenin in Manduca sexta . Structure resolution of some of its members revealed that they belong to the β-sheet superfamily and share a characteristic fold, with differences in loop conformations thought to confer ligand specificity .

Studies from Bombyx mori, showed that these proteins function as storage proteins during growth and development but they are used only during embryonic development, thought to act as storage units of amino acids for use in de novo synthesis of other proteins. They are also involved in energy transport and metabolic processes such as release of diacylglycerol and the transport of steroids and hormones. 30KPs may be involved in defense response mechanisms as they can be conjugated to glucose, dextran, maltose and glycoproteins . These proteins may also inhibit apoptosis, thereby having a role in cell survival .
Cyclin-dependent kinase 5 activator (CDK5_activator)
Type: Family

These proteins are neuron specific activators of cyclin-dependent kinase 5 (CDK5) . They form a heterodimer with the catalytic subunit (CDK5) .
Coronavirus 6B/7B protein (Corona_6B_7B)
Type: Family

The function of the Coronavirus 6B and 7B proteins is not known.
Cucumovirus protein 2B (Cucumo_2B)
Type: Family

This family of cucumovirus proteins may be long-distance movement proteins.
Deoxyribonuclease II (DNase_II)
Type: Family

Deoxyribonuclease II (

) hydrolyses DNA under acidic conditions with a preference for double-stranded DNA. It catalyses the endonucleolytic cleavage of DNA to 3'-phosphomononucleotide and 3'-phosphooligonucleotide end-products. The enzyme may play a role in apoptosis.
This family also includes hypothetical proteins from Caenorhabditis elegans.
Nucleoside-triphosphatase, THEP1 type (Nuc-triphosphatase_THEP1)
Type: Family

This entry represents a family of nucleoside-triphosphatases which have activity towards ATP, GTP, CTP, TTP and UTP and may hydrolyse nucleoside diphosphates with lower efficiency . It includes proteins from bacteria to human, and the function was determined first in a hyperthermophilic bacterium to be an NTPase . The structure of one member-sequence represents a variation of the RecA fold, and implies that the function might be that of a DNA/RNA modifying enzyme . The sequence carries both a Walker A and Walker B motif which together are characteristic of ATPases or GTPases. The protein exhibits an increased expression profile in human liver cholangiocarcinoma when compared to normal tissue .
Protein of unknown function DUF267, Caenorhabditis species (DUF267_CAE_spp)
Type: Family

This family of proteins, from Caenorhabditis species, have not been characterised though a number are annotated as 'serpentine receptor, class r' proteins.
Protein of unknown function DUF268, Caenorhabditis species (DUF268_CAE_spp)
Type: Family

This family consists of proteins of unknown function found in Caenorhabditis species.
NifX-associated nitrogen fixation protein (NifX-assoc_nitrogen_fix)
Type: Family

This family includes several proteins of unknown function, which are strictly limited to nitrogen-fixing species, although not universal among them. The gene typically is found next to the nifX gen .
EB1, C-terminal (EB1_C)
Type: Domain

A group of microtubule-associated proteins called +TIPs (plus end tracking proteins), including EB1 (end-binding protein 1) family proteins, label growing microtubules ends specifically in diverse organisms and are implicated in spindle dynamics, chromosome segregation, and directing microtubules toward cortical sites. EB1 members have a bipartite composition: the N-terminal CH domain (

) mediates microtubule plus end localization and a C-terminal cargo binding domain (EB1-C) that captures cell polarity determinants. The EB1-C domain comprises a unique EB1-like sequence motif that acts as a binding site for other +TIP proteins. It interacts with the carboxy terminus of the adenomatous polyposis coli (APC) tumor suppressor, a well conserved +TIP phosphoprotein with a pivotal function in cell cycle regulation. Another binding partner of the EB1-C domain is the well conserved +TIP protein dynactin, a component of the large cytoplasmic dynein/dynactin complex .

The ~80-residue EB1-C domain starts with a long smoothly curved helix (alpha1), which is followed by a hairpin connection leading to a short second helix (alpha2) running antiparallel to alpha1. The two parallel alpha1 helices of the EB1-C domain dimer wrap around each other in a slightly left-handed supercoil. The two alpha2 helices run antiparallel to helices alpha1 and form a similar fork in the opposite orientation and rotated by 90 degrees. As a result, two helical segments from each monomer form a four-helix bundle. The side chain forming the hydrophobic core of this bundle are highly conserved .

Some protein known to contain an EB1-C domain are listed below:

Yeast protein BIM1.

Fission yeast microtubule integrity protein mal3.

Vertebrate microtubule-associated protein RP/EB family member 1 (EB1).

Vertebrate microtubule-associated protein RP/EB family member 2 (EB2 or RP1).

Vertebrate microtubule-associated protein RP/EB family member 3 (EBF3).
Putative mucin/carbohydrate-binding domain (Mucin-bd)
Type: Domain

This entry represents a putative binding domain for the substrates of enhancin, and other similar metallopeptidases . This is not the enzymatically active (peptidase) part of the proteins.

The baculovirus enhancin protein, or enhancing factor, is involved in disruption of the peritrophic membrane and fusion of nucleocapsids with mid-gut cells . This metallopeptidase belongs to the MEROPS peptidase family M60 (enhancin family, clan MA(E)).
Baculovirus Gp64, envelope glycoprotein (Baculovirus_Gp64)
Type: Family

Gp64 is the major envelope fusion glycoprotein in some, though not all, baculoviruses . It is found on the surface of both infected cells and budded virions as a homotrimer, and by determining the viral receptor preferences it defines the host range and infection efficiency. Baculovirus enters its host cells by endocytosis followed by a low-pH-induced fusion of the viral envelope with the endosomal membrane, allowing viral entrance into the cell cytoplasm. This membrane fusion, and also the efficient budding of virions from the infected cell, is dependent on Gp64. Gp75 is a homologous envelope glycoprotein from Thogotoviruses that, like Gp64, forms homotrimers and is involved in both binding and entering the host cell .
Foamy virus BEL 1/2 protein (Foamy_BEL)
Type: Family

Foamy virus (FV) gene expression is strictly dependent on their transactivator proteins called Bel1/Tas. The presence of a functionally active, internal promoter, besides the conventional LTR promoters, is unique to FVs. The nuclear Bel1/Tas protein of primate prototype FV binds DNA target sites directly and consists of at least two functional domains, an N-terminal/central DNA binding and a C-terminal activation domain .
Gag polyprotein, N-terminal domain (Gag_N)
Type: Domain

This is the conserved N-terminal domain of the Gag polyprotein from Foamyviruses (FVs) or Spuma-retroviruses. Gag is the major structural protein required for genome packaging virion assembly, trafficking and egress. This region corresponds to the Env-binding domain containing the cytoplasmic targeting and retention sequence (CTRS) .

The Gag polyprotein is a core viral polyprotein that undergoes specific enzymatic cleavages in vivo to yield the mature protein. It is involved in capsid formation and genome binding. Shortly after infection, interaction between incoming particle-associated Gag proteins and host dynein allows centrosomal targeting of the viral genome (associated to Gag), prior to nucleus translocation and integration into host genome .
Herpesvirus UL4 (Herpes_UL4)
Type: Family

This is a family of Herpes virus UL4 proteins, which are related to Human herpesvirus 1 (HHV-1), Human herpesvirus 2 (HHV-2), Equid herpesvirus 1 (Equine herpesvirus 1, EHV-1) 58, and Human herpesvirus 3 VZV-32 56 proteins.
Bacterial effector protein IpgB-like (Bac_effector_IpgB-like)
Type: Family

This family consists of IpgB1 and IpgB2 from Shigella as well as related proteins TrcA, Map, EspM from Escherichia coli. Members of this family seem to be involved in pathogenicity and have been identified as small GTPases mimicking or activating proteins .
Bacterial lipid A biosynthesis acyltransferase (LipA_acyltrans)
Type: Family

Bacterial lipopolysachharides (LPS) are glycolipids that make up the outer monolayer of the outer membranes of most Gram-negative bacteria. Though LPS molecules are variable, they all show the same general features: an outer polysaccharide which is attached to the lipid component, termed lipid A . The polysaccharide component consists of a variable repeat-structure polysaccharide known as the O-antigen, and a highly conserved short core oligosaccharide which connects the O-antigen to lipid A. Lipid A is a glucosamine-based phospholipid that makes up the membrane anchor region of LPS . The structure of lipid A is relatively invariant between species, presumably reflecting its fundamental role in membrane integrity. Recognition of lipid A by the innate immune system can lead to a response even at picomolar levels. In some genera, such as Neisseria and Haemophilus, lipooligosaccharides (LOS) are the predominant glycolipids . These are analogous to LPS except that they lack O-antigens, with the LOS oligosaccharide structures limited to 10 saccharide units.

The bacterial lipid A biosynthesis protein, or lipid A biosynthesis (KDO)2-(lauroyl)-lipid IVA acyltransferase

, transfers myristate or laurate, activated on ACP, to the lipid IVA moiety of (KDO)2-(lauroyl)-lipid IVA during lipopolysaccharide core biosynthesis .
Lipase chaperone (Lipase_chaperone)
Type: Family

The proteobacterial lipase chaperone is a lipase helper protein which may be involved in the folding of extracellular lipase during its passage through the periplasm .
Pectinacetylesterase/NOTUM (PAE/NOTUM)
Type: Family

This family includes protein Notum from animals and pectinacetylesterase (PAE) from plants. Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins. Notum constitutes the first known extracellular protein deacylase . PAEs catalyse the deacetylation of pectin, a major compound of primary cell walls .
Phenazine biosynthesis protein A/B (PhzA_PhzB)
Type: Family

The phenazine biosynthesis proteins A and B are involved in the biosynthesis of this antibiotic. Phenazine is a nitrogen-containing heterocyclic molecule with important implications in virulence, competition and biological control .
Paralemmin (Paralemmin)
Type: Family

Paralemmin was identified in the chicken lens as a protein with a molecular weight of 65kDa (isoform 1) and a splice variant of 60kDa (isoform 2). Isoform 2 is predominant during infancy and levels of isoform 1 increase with age. Paralemmin is localised to the plasma membrane of fibre cells, and was not detected in the annular pad cells. Its localisation to the short side of the fibre cell and the sites of fibre cell interlocking suggests that paralemmin may play a role in the development of such interdigitating processes . Palmitoylation is important for localising these proteins to the filopodia of dendritic cells where they have been implicated in the regulation of membrane dynamics and process outgrowth . Paralemmin-3 is an ATP-binding protein that was shown to interacts with single immunoglobulin IL-1 receptor-related molecule (SIGIRR) and may act as a adapter in the Toll-like receptor (TLR) signalling .
Pox virus Ag35 surface protein (Pox_Ag35)
Type: Family

The Pox virus Ag35 surface protein is an evelope protein known as protein H5 or Late transcription elongation factor OPG110. It is involved in the co-transcriptional or post-transcriptional endoribonucleolytic cleavage that generates sequence-homogeneous 3' ends during late transcription and in postreplicative transcription elongation on intermediate and late genes. It plays a role in DNA replication and in multiple steps of virion morphogenesis and is required both for inclusion of virosoplasm into crescents as well as for maturation of immature virions (IV) into mature virions (MV) .
Poxvirus C7/F8A (Poxvirus_C7/F8A)
Type: Family

This family includes Poxvirus C7 and F8A proteins. The C7 protein, also known as Interferon antagonist OPG027, inhibits the antiviral activity induced by type I interferons .
DNA primase/nucleoside triphosphatase, C-terminal (DNA_primase/NTPase_C)
Type: Domain

This domain is found at the C terminus of phage P4 alpha protein and related proteins. Phage P4 DNA replication depends on the product of the alpha gene, which has origin recognition ability, DNA helicase activity, and DNA primase activity. The structure of the protein can be summarised as follows: The N terminus provides the primase activity, the central region is the helicase/nucleoside triphosphatase domain and the ori DNA recognition resides in the C-terminal 1/3 of the protein .

The domain is also found at the C terminus of a number of proteins from orthopox viruses including vaccinia virus D5. D5 encodes a 90kDa protein that is transiently expressed at early times after infection. It has an nucleoside triphosphatase activity which is independent of common nucleic acid cofactors and it can hydrolyse all the common ribo- and deoxyribonucleoside triphosphates to diphosphates in the presence of a divalent cation .
Poxvirus I1 (Poxvirus_I1)
Type: Family

This entry represents a family of proteins from poxvirus, including the vaccinia virus I1L (Late) encoded protein, which is also called Telomere-binding protein OPG077. It is a DNA-binding protein which binds to the hairpin form of the viral telomeric sequence. Required for the production of mature virions (MV) .
mRNA (guanine-N(7))-methyltransferase domain (mRNA_G-N7_MeTrfase_dom)
Type: Domain

This entry represents mRNA (guanine-N(7))-methyltransferase, which can either be found as a single domain protein, or as a domain within the mRNA-capping enzyme catalytic subunit.

mRNA (guanine-N(7))-methyltransferase methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs. It binds RNA containing 5'-terminal GpppC . Viral mRNA capping enzymes, meanwhile, are multidomain proteins that catalyse the first two reactions in the mRNA cap formation pathway . They are heterodimers consisting of a large (catalytic) and small subunit.