SII-SWORD/CoKE huggingface dataset:
2-haloacid dehalogenase, DehI (2-haloacid_dehalogenase_DehI)
Type: Family

Haloacid dehalogenases catalyse the removal of halides from organic haloacids. The 2-haloacid dehalogenase DehI can process both L- and D-substrates. A crucial aspartate residue is predicted to activate a water molecule for nucleophilic attack of the substrate chiral centre resulting in an inversion of the configuration of either L- or D-substrates in contrast to D-only enzymes .
Haemolysin XhlA (Haemolysin_XhlA)
Type: Family

Haemolysin XhlA from Bacillus subtilis is a cell-surface associated haemolysin that lyses the two most prevalent types of insect immune cells (granulocytes and plasmatocytes) as well as rabbit and horse erythrocytes . This entry also includes Holin-like protein 24.1 from Bacillus phage SPP1. Protein 24.1 may act like holin that it triggers the formation of micron-scale pores (holes) after reaching a critical concentration in the membrane .
Large ribosomal subunit protein mL53 (Ribosomal_mL53)
Type: Family

This entry represents the large ribosomal subunit protein mL53, previously known as L53 (also known as L44), which is part of the 39S ribosome .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Dextransucrase DSRB (Dextransucrase_DSRB)
Type: Family

DSRB is a novel dextransucrase which produces a dextran different from the typical dextran, as it contains (1-6) and (1-2) linkages, when this strain is grown in the presence of sucrose .
Protein of unknown function DUF2602 (DUF2602)
Type: Family

This entry represents a family of proteins predominantly found in Firmicutes, including Uncharacterized protein YpeQ from Bacillus subtilis. Members of this group adopt the structure of a zinc-finger domain of the C2HC type with an additional cysteine. They have no known function.
Protein of unknown function DUF2599 (DUF2599)
Type: Family

The function of the bacterial proteins in this entry is not known.
Plasmid stability protein, StbB (Plasmid_stability_protein_StbB)
Type: Family

This family is conserved in the Enterobacteriales. It is a putative plasmid stability protein in that it is expressed from the operon involved in stability, but its actual function has not yet been characterised but it may be involved in the control of plasmid partition.
NADH-ubiquinone oxidoreductase, 21kDa subunit, N-terminal (NADH-UbQ_OxRdtase_su21_N)
Type: Domain

This domain is found in the N-terminal region of NADH-ubiquinone oxidoreductase 21kDa subunits from plants and fungi .
HI_0552 protein family (HI_0552_fam)
Type: Family

This entry represents proteins conserved in Firmicutes and Proteobacteria. Some members are annotated as being glucose-6-phosphate 1-dehydrogenase but there is no evidence supporting this.
Uncharacterised protein, YfmQ (Uncharacterised_YfmQ)
Type: Family

This family of proteins is uncharacterised.
Uncharacterised protein family UPF0763 (UPF0763)
Type: Family

This entry represents a conserved protein in epsilonproteobacteria. The function is not known.
Bacteriophage T4, P15K, RNA polymerase binding (Phage_T4_P15K_Rpol-bd)
Type: Family

Upon infection, the RpbA encoded phage protein binds to the ADP-ribosylated core RNA polymerase and modulates function to preferentially bind T4 promoters. This is a non-essential protein to the phage life cycle.
Protein of unknown function DUF2604 (DUF2604)
Type: Family

This entry represents bacterial proteins with undetermined function.
ATP synthase, F0 complex, subunit F, mitochondria, fungi (ATP_synth_F0_fsu_mt_fun)
Type: Family

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (

) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the α(3)β(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis . These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.

This entry represents subunit F found in the F0 complex of F-ATPases from fungal mitochondria . The membrane bound F1-FO-type H+ ATP synthase of mitochondria catalyses the terminal step in oxidative respiration converting the generation of the electrochemical gradient into ATP for cellular biosynthesis. The general structure and the core subunits of the enzyme are highly conserved in both prokaryotic and eukaryotic organisms.
Protein of unknown function DUF2605 (DUF2605)
Type: Family

This entry represents a protein conserved in Cyanobacteria. The function is not known.
Gloverin-like protein (Gloverin-like_protein)
Type: Family

This entry represents proteins that are Gloverin-like. Gloverin is a 13.8kDa inducible antibacterial insect protein which inhibits the synthesis of vital outer membrane proteins leading to a permeable outer membrane. Gloverin contains a large number of glycine residues .
Protein of unknown function DUF2606 (DUF2606)
Type: Family

This entry represents bacterial proteins with unknown function.
Protein of unknown function DUF2607 (DUF2607)
Type: Family

This entry represents conserved protein found in in Gammaproteobacteria. The function is not known.
Sigma-S stabilisation anti-adaptor protein (SigmaS_Anti-adapt_IraP)
Type: Family

This entry is conserved in Enterobacteriaceae. It is one of a series of proteins, expressed by these bacteria in response to stress, that help to regulate Sigma-S, the stationary phase sigma factor of Escherichia coli and Salmonella. IraP is essential for Sigma-S stabilisation in some but not all starvation conditions .
Uncharacterised protein family YhfT (Uncharacterised_YhfT)
Type: Family

This entry represents a group of proteins from Firmicutes, Proteobacteria and Actinobacteria, including Uncharacterized protein YhfT from Escherichia coli, which is predicted to be a membrane protein. Its function is unknown.
Tetratricopeptide repeat (TPR_rpt)
Type: Repeat

The tetratrico peptide repeat region (TPR) is a structural motif present in a wide range of proteins . It mediates protein-protein interactions and the assembly of multiprotein complexes . The TPR motif consists of 3-16 tandem-repeats of 34 amino acids residues, although individual TPR motifs can be dispersed in the protein sequence. Sequence alignment of the TPR domains reveals a consensus sequence defined by a pattern of small and large amino acids. TPR motifs have been identified in various different organisms, ranging from bacteria to humans. Proteins containing TPRs are involved in a variety of biological processes, such as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neurogenesis and protein folding.

The X-ray structure of a domain containing three TPRs from protein phosphatase 5 revealed that TPR adopts a helix-turn-helix arrangement, with adjacent TPR motifs packing in a parallel fashion, resulting in a spiral of repeating anti-parallel α-helices . The two helices are denoted helix A and helix B. The packing angle between helix A and helix B is ~24 degrees within a single TPR and generates a right-handed superhelical shape. Helix A interacts with helix B and with helix A' of the next TPR. Two protein surfaces are generated: the inner concave surface is contributed to mainly by residue on helices A, and the other surface presents residues from both helices A and B.
Synapsin, conserved site (Synapsin_CS)
Type: Conserved_site

The synapsins are a family of neuron-specific phosphoproteins that coat synaptic vesicles and are involved in the binding between these vesicles and the cytoskeleton (including actin filaments). The family comprises 5 homologous proteins Ia, Ib, IIa, IIb and III. Synapsins I, II, and III are encoded by 3 different genes. The a and b isoforms of synapsin I and II are splice variants of the primary transcripts .

Synapsin I is mainly associated with regulation of neurotransmitter release from presynaptic neuron terminals . Synapsin II, as well as being involved in neurotransmitter release, has a role in the synaptogenesis and synaptic plasticity responsible for long term potentiation . Recent studies implicate synapsin III with a developmental role in neurite elongation and synapse formation that is distinct from the functions of synapsins I and II .

Structurally, synapsins are multidomain proteins, of which 3 domains are common to all the mammalian forms. The N-terminal `A' domain is ~30 residues long and contains a serine residue that serves as an acceptor site for protein kinase-mediated phosphorylation. This is followed by the `B' linker domain, which is ~80 residues long and is relatively poorly conserved. Domain `C' is the longest, spanning approximately 300 residues. This domain is highly conserved across all the synapsins (including those from Drosophila) and is possessed by all splice variants. The remaining six domains, D-I, are not shared by all the synapsins and differ both between the primary transcripts and the splice variants.

This entry represents a highly conserved stretch of 11 residues located in the centre of the 'C' domain.
Synapsin, phosphorylation site (Synapsin_P_site)
Type: PTM

This entry represents a conserved octapeptide in the immediate N-terminal domain, which contains the phosphorylated serine residue.

The synapsins are a family of neuron-specific phosphoproteins that coat synaptic vesicles and are involved in the binding between these vesicles and the cytoskeleton (including actin filaments). The family comprises 5 homologous proteins Ia, Ib, IIa, IIb and III. Synapsins I, II, and III are encoded by 3 different genes. The a and b isoforms of synapsin I and II are splice variants of the primary transcripts .

Synapsin I is mainly associated with regulation of neurotransmitter release from presynaptic neuron terminals . Synapsin II, as well as being involved in neurotransmitter release, has a role in the synaptogenesis and synaptic plasticity responsible for long term potentiation . Recent studies implicate synapsin III with a developmental role in neurite elongation and synapse formation that is distinct from the functions of synapsins I and II .

Structurally, synapsins are multidomain proteins, of which 3 domains are common to all the mammalian forms. The N-terminal `A' domain is ~30 residues long and contains a serine residue that serves as an acceptor site for protein kinase-mediated phosphorylation. This is followed by the `B' linker domain, which is ~80 residues long and is relatively poorly conserved. Domain `C' is the longest, spanning approximately 300 residues. This domain is highly conserved across all the synapsins (including those from Drosophila) and is possessed by all splice variants. The remaining six domains, D-I, are not shared by all the synapsins and differ both between the primary transcripts and the splice variants.
Homeobox engrailed-type, conserved site (Homeobox-engrailed_CS)
Type: Conserved_site

This entry identifies a conserved region of some 20 amino-acid residues, specific to engrailed proteins, located at the C-terminal of the 'homeobox' domain; the specific function of these residues is unclear.

Homeodomain proteins are transcription factors that share a related DNA-binding homeodomain . The homeodomain was initially identified in Drosophila melanogaster (Fruit fly) homeotic and segmentation proteins, but is well conserved throughout metazoans . The homeodomain binds DNA through a helix-turn-helix (HTH) structure, consisting of approximately 20 residues . The HTH motif is comprised of two α-helices that make intimate contacts with the DNA; the second helix binds to DNA via a number of hydrogen bonds and hydrophobic interactions. These interactions occur between specific side chains and the exposed bases and thymine methyl groups within the major groove of the DNA. The first helix helps to stabilise the structure and is joined to the second through a short turn.

Most proteins which contain a homeobox domain can be classified , on the basis of their sequence characteristics, into three subfamilies, engrailed, antennapedia and paired. A number of different proteins contain homeodomains, including Drosophila engrailed, yeast mating type proteins, hepatocyte nuclear factor 1a and Hox proteins. Hox genes encode homeodomain-containing transcriptional regulators that operate differential genetic programs along the anterior-posterior axis of animal bodies . The homeodomain motif is very similar in sequence identity and structure to domains in other DNA-binding proteins, including recombinases, GARP response regulators, human telomeric protein, AraC type transcriptional activator and tetracycline repressor .
Myelin P0 protein, conserved site (Myelin_P0_CS)
Type: Conserved_site

The P0 protein is a major structural glycoprotein of the peripheral nervous system (PNS) myelin, which probably plays an important role for the formation and the maintenance of myelin structure; it is well conserved across species . P0 is a protein of about 28 Kd that consists of three domains: a N-terminal extracellular domain of about 125 residues which seems to form a V-type immunoglobulin domain; a transmembrane region, and a cytoplasmic C-terminal domain of about 70 residues which contains many positively charged residues and which is a substrate of some serine protein kinases.
CTF transcription factor/nuclear factor 1, conserved site (CTF/NFI_DNA-bd_CS)
Type: Conserved_site

Nuclear factor I (NF-I) or CCAAT box-binding transcription factor (CTF) (also known as TGGCA-binding proteins) are a family of vertebrate nuclear proteins which recognise and bind, as dimers, the palindromic DNA sequence 5'-TGGCANNNTGCCA-3'. This family was first described for its role in stimulating the initiation of adenovirus DNA replication . In vertebrates there are four members NFIA, NFIB, NFIC, and NFIX and an orthologue from Caenorhabditis elegans has been described, called Nuclear factor I family protein (NFI-I) . The CTF/NF-I proteins are individually capable of activating transcription and DNA replication, thus they function by regulating cell proliferation and differentiation. They are involved in normal development and have been associated with developmental abnormalities and cancer in humans . In a given species, there are a large number of different CTF/NF-I proteins, generated both by alternative splicing and by the occurrence of four different genes. CTF/NF-1 proteins contain 400 to 600 amino acids. The N-terminal 200 amino-acid sequence, almost perfectly conserved in all species and genes sequenced, mediates site-specific DNA recognition, protein dimerisation and Adenovirus DNA replication. The C-terminal 100 amino acids contain the transcriptional activation domain. This activation domain is the target of gene expression regulatory pathways elicited by growth factors and it interacts with basal transcription factors and with histone H3 .

This entry represents a specific signature for this family of proteins, which includes the four vertebrate members NFIA, NFIB, NFIC and NFIX. The signature is a perfectly conserved, highly charged 12-residue peptide located in the DNA-binding domain of CTF/NF-I. It does not contain the four conserved Cys residues, which are required for its DNA-binding activity .
Pyridoxamine 5'-phosphate oxidase, conserved site (Pyridox_Oxase_CS)
Type: Conserved_site

Pyridoxamine 5'-phosphate oxidase (

) is a FMN flavoprotein involved in the de novo synthesis of pyridoxine (vitamin B6) and pyridoxal phosphate. It oxidizes pyridoxamine-5-P (PMP) and pyridoxine-5-P (PNP) to pyridoxal-5-P. The sequences of the enzyme from bacterial (genes pdxH or fprA) and fungal (gene PDX3) sources show that this protein has been highly conserved throughout evolution. PdxH is evolutionary related to one of the enzymes in the phenazine biosynthesis protein pathway, phzD (also known as phzG) .

This entry represents a highly conserved region located in the C-terminal part of these enzymes.
Galactokinase, conserved site (Galactokinase_CS)
Type: Conserved_site

This entry represents a conserved signature pattern located in the N-terminal domain of galactokinases.

Galactokinase catalyses the first reaction in the galactose metabolism pathway, the ATP-dependent phosphorylation of galactose, yielding galactose-1-phosphate . Deficiency in this enzyme results in the disease galactosemia, which is responsible for the formation of cataracts in newborn babies, and is possibly responsible for presenile cataracts in adults . In yeast, the GAL3 gene product is required for the GAL4-mediated induction of other enzymes involved in galactose metabolism. The induction of GAL1 production then reinforces this process, increasing the expression of other galactose-inducible genes. GAL3 has been shown to be similar to the GAL1 protein .
Alpha-2-macroglobulin, conserved site (MacrogloblnA2_CS)
Type: Conserved_site

This entry represents a conserved region, located towards the C terminus, which contains the two residues involved in the thiol ester bond.

This entry contains serum complement C3 and C4 precursors and alpha-macrogrobulins.

The alpha-macroglobulin (aM) family of proteins includes protease inhibitors , typified by the human tetrameric a2-macroglobulin (a2M); they belong to the MEROPS proteinase inhibitor family I39, clan IL. These protease inhibitors share several defining properties, which include (i) the ability to inhibit proteases from all catalytic classes, (ii) the presence of a 'bait region' and a thiol ester, (iii) a similar protease inhibitory mechanism and (iv) the inactivation of the inhibitory capacity by reaction of the thiol ester with small primary amines. aM protease inhibitors inhibit by steric hindrance . The mechanism involves protease cleavage of the bait region, a segment of the aM that is particularly susceptible to proteolytic cleavage, which initiates a conformational change such that the aM collapses about the protease. In the resulting aM-protease complex, the active site of the protease is sterically shielded, thus substantially decreasing access to protein substrates. Two additional events occur as a consequence of bait region cleavage, namely (i) the h-cysteinyl-g-glutamyl thiol ester becomes highly reactive and (ii) a major conformational change exposes a conserved COOH-terminal receptor binding domain (RBD). RBD exposure allows the aM protease complex to bind to clearance receptors and be removed from circulation . Tetrameric, dimeric, and, more recently, monomeric aM protease inhibitors have been identified .
Involucrin, conserved site (Involucrin_CS)
Type: Conserved_site

Involucrin is a highly reactive, soluble, transglutaminase substrate protein present in keratinocytes of epidermis and other stratified squamous epithelia. Involucrin first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase thus helping in the formation of an insoluble envelope beneath the plasma membrane functioning as a glutamyl donor during assembly of the cornified envelope.

This entry represents the signature pattern for involucrin, which is located at the N-terminal extremity of these proteins.