SII-SWORD/CoKE huggingface dataset:
D-glutamate N-acetyltransferase-like, N-terminal domain (DgcN-like_N)
Type: Domain

This entry represents a domain found at the N-terminal end of a group of prokaryotic proteins that includes

from Tritonibacter scottomollicae (DgcN), an N-acetyltransferase responsible for N-acetylation of D-Glutamate, an essential component of bacterial peptidoglycans. DgcN consists of two distinct domains. This domain adopts a Rossman-like fold, with four β-strands composing a hydrogen-bonded β-sheet and six α-helices .
Uncharacterized protein YmpT-like (YmpT-like)
Type: Family

This is a family of unknown function mostly found in Bacilli.
Domain of unknown function DUF5405 (DUF5405)
Type: Domain

Proteins containing this domain may have a phage origin being found in bacteriophage P2

. The majority of proteins have a conserved cysteine residue close to their C terminus which may have functional significance.
Gene product 70 (GP70)
Type: Family

This family of unknown function is found in Mycobcterium phage and Actinobacteria.
Protein of unknown function DUF5412 (DUF5412)
Type: Family

This is a family of unknown function found in bacteria. Members of this family have one or two predicted trans-membrane regions.
Protein of unknown function DUF5399 (DUF5399)
Type: Family

This is a family of unknown function mostly found in Chlamydiia.
Phage single-stranded DNA-binding protein (Phi29_Phage_SSB)
Type: Family

DNA replication of phi29 and related phages takes place via a strand displacement mechanism, a process that generates large amounts of single-stranded DNA (ssDNA). Consequently, phage-encoded ssDNA-binding proteins (SSBs) are essential proteins during phage phi29-like DNA replication. Single-stranded DNA-binding proteins (SSBs) destabilize double-stranded DNA (dsDNA) and bind without sequence specificity, but selectively and cooperatively, to single-stranded DNA (ssDNA) conferring a regular structure to it, which is recognized and exploited by a variety of enzymes involved in DNA replication, repair and recombination.

Phage phi29 protein p5 is the SSB protein active during phi29 DNA replication. It protects ssDNA against nuclease degradation and greatly stimulates dNTP incorporation during phi29 DNA replication process. Binding of the SSB to ssDNA prevents non-productive binding of the viral DNA polymerase to ssDNA, and allows the release DNA polymerase molecules that are already titrated by the ssDNA. This effect would be of particular importance in phi29-like DNA replication systems, where large amounts of ssDNA are generated and SSB binding to ssDNA could favor efficient re-usage of templates .

This domain is found in phi29-like SSB proteins, homologues are found in

.
Seminal vesicle secretory protein 4/5/6 (Svs4/5/6)
Type: Family

There are seven major proteins involved in murine seminal vesicle secretion (SVS1-7). Mouse Svs2/Svs6 genes evolved by gene duplication and belong to the same gene family . This entry represents SVS4/5 and 6. SVS4 is a basic, thermostable, secretory protein synthesized by rat seminal vesicle epithelium under strict androgen transcriptional control. This protein has potent nonspecies-specific immunomodulatory, anti-inflammatory, and pro-coagulant activities that have been shown to be located in the N-terminal region of Svs4 (fragment 1-70) . The N-terminal segment has a high amino-acid sequence similarity with the C-terminal segment 34-66 of uteroglobin, a rabbit steroid-inducible, cytokine-like, multifunctional, secreted protein. Furthermore, SVS4 acts as a sperm capacitation inhibitor, by interacting with SVS3 and SVS2 .
Putative DNA-Binding protein G5P (Putative_G5P)
Type: Family

This family consists of Gammaproteobacterial proteins. Members of the family are predicted to be G5P DNA binding proteins. Homologous proteins are found in

.
Phage terminase large subunit, N-terminal (Terminase_L_N)
Type: Domain

This entry represents the N-terminal domain of the large subunit of the terminase protein.

Initiation of packaging of double-stranded viral DNA involves the specific interaction of the prohead with viral DNA in a process mediated by a phage-encoded terminase protein. The terminase enzymes are usually hetero-oligomers composed of a small and a large subunit. This region possess an endonuclease and ATPase activity that require Mg2+ and a neutral or slightly basic reaction. This region is also found in bacterial sequences .

Proteins containing this domain include gp2 from Bacillus phage SPP1 .
Phage terminase large subunit, C-terminal (Terminase_L_C)
Type: Domain

Initiation of packaging of double-stranded viral DNA involves the specific interaction of the prohead with viral DNA in a process mediated by a phage-encoded terminase protein. The terminase enzymes are usually hetero-oligomers composed of a small and a large subunit . This entry represents the C-terminal domain of the large subunit.

Proteins containing this domain include gp2 from Bacillus phage SPP1 .
Peptidase M1, alanyl aminopeptidase, Ig-like fold (Peptidase_M1_pepN_Ig-like)
Type: Domain

This entry represents a conserved domain with an Ig-like fold found in alanyl aminopeptidases that belong to MEROPS peptidase family M1 (aminopeptidase N, clan MA).

The M1 family of zinc metallopeptidases contains a number of distinct, well-separated clades of proteins with aminopeptidase activity. Several are designated aminopeptidase N,

, after the Escherichia coli enzyme, suggesting a similar activity profile (see

for a description of catalytic activity).

This group of zinc metallopeptidases belong to MEROPS peptidase family M1 (aminopeptidase N, clan MA); the majority are identified as alanyl aminopeptidases (proteobacteria) that are closely related to E. coli PepN and presumed to have a similar (not identical) function. Nearly all are found in proteobacteria, but members are found also in cyanobacteria, plants, and apicomplexan parasites . This family differs greatly in sequence from the family of aminopeptidases typified by Streptomyces lividans PepN (

) and from the membrane bound aminopeptidase N family in animals.

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .
DUF5382, central domain (DUF5382_central)
Type: Domain

This is a domain of unknown function found in Caenorhabditis, which has an NTF2-like fold.
Protein of unknown function DUF5376 (DUF5376)
Type: Family

This is a family of unknown function found in Bacteria.
FACT complex subunit SSRP1/POB3, N-terminal PH domain (SSRP1/POB3_N)
Type: Domain

This domain is found at the N terminus of yeast POB3 and its metazoan homologue SSRP1 . POB3/SSRP1 is a subunit of the heterodimeric FACT complex involved in transcriptional initiation .
Transcription regulator HTH, AraC- type, ligand binding domain-like (AraC-bd_2)
Type: Domain

This domain is related to the AraC ligand binding domain

.
Spt6, SH2 domain (Spt6_SH2)
Type: Domain

This entry represents the SH2 domain found in Spt6.

Spt6 is an essential transcription elongation factor and histone chaperone that binds the C-terminal repeat domain (CTD) of RNA polymerase II . Spt6 contains a tandem SH2 domain with a novel structure and CTD-binding mode. The tandem SH2 domain binds to a serine 2-phosphorylated CTD peptide in vitro, whereas its N-terminal SH2 subdomain does not. CTD binding requires a positively charged crevice in the C-terminal SH2 subdomain, which lacks the canonical phospho-binding pocket of SH2 domains. The tandem SH2 domain is apparently required for transcription elongation in vivo as its deletion in cells is lethal in the presence of 6-azauracil. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites .
Terminase, large subunit gp17-like, C-terminal (Terminase_6C)
Type: Domain

This entry represents the C-terminal domain found in the terminase large subunits. Terminase is a component of the molecular motor that translocates genomic DNA into empty capsids during DNA packaging . The large subunit heterodimerises with the small terminase protein, which is docked on the capsid portal protein. The latter forms a ring through which genomic DNA is translocated into the capsid. The terminase protein has endonuclease activity to cleave DNA after encapsidation .

Proteins containing this domain include gp17 from bacteriophage T4 (

).
Alginate O-acetyl transferase AlgF (AlgF)
Type: Family

AlgF is essential for the addition of O-acetyl groups to alginate, an extracellular polysaccharide. The presence of O-acetyl groups plays an important role in the ability of the polymer to act as a virulence factor .
M60-like domain, N-terminal (M60-like_N)
Type: Domain

This accessory domain has a jelly roll topology. It is found N-terminal to the M60-like domain (

) .
Antitoxin of toxin-antitoxin, RelE/RelB, TA system (Antitoxin_RelB)
Type: Family

This family represents the RelB antitoxin of toxin-antitoxin stability system or prevent-host death system. Together RelE toxin and the RelB antitoxin form a non-toxic complex. Although toxin-antitoxin gene cassettes were first found in plasmids, it is clear that these loci are abundant in free-living prokaryotes, including many pathogenic bacteria, and these toxin-antitoxin loci provide a control mechanism that helps free-living prokaryotes cope with nutritional stress .
CENP-T/Histone H4, histone fold (CENP-T/H4_C)
Type: Domain

This domain is the C-terminal histone fold domain of CENP-T, which associates with chromatin . Proteins containing this domain also include Histone H4.

Histone H4 is one of the five histones, along with H1/H5, H2A, H2B and H3. Two copies of each of the H2A, H2B, H3, and H4 histones ensemble to form the core of the nucleosome . The nucleosome forms octameric structure that wraps DNA in a left-handed manner. H3 is a highly conserved protein of 135 amino acid residues . Histones can undergo several different types of post-translational modifications that affect transcription, DNA repair, DNA replication and chromosomal stability. The sequence of histone H4 has remained almost invariant in more then 2 billion years of evolution .
Gemin2/Brr1 (Gemin2/Brr1)
Type: Family

This entry includes Gem2 (also known as SIP1) from animals, Brr1 from budding yeasts and Yip11/Yip12 from fission yeasts. Gem2 is part of the survival of motor neurons (SMN) complex that is involved in UsnRNP assembly in the cytoplasm and mediates nuclear import of the assembled UsnRNP . Yip11 is also part of the yeast SMN complex that facilitates the formation of Sm-class ribonucleoproteins involved in mRNA processing (UsnRNPs) .

Brr1 is a nuclear protein and a snRNP protein component of spliceosomal snRNPs involved in mRNA splicing and required for snRNA accumulation and snRNP biogenesis .
Tim10-like domain superfamily (Tim10-like_dom_sf)
Type: Homologous_superfamily

This domain superfamily is found in mitochondrial import inner membrane translocase subunits Tim8, Tim9, Tim10 and Tim13, which are located in the mitochondrial intermembrane space.

The Tim8-Tim13 complex has a complex architecture, similar to the Tim9-Tim10 complex, composed of a hexametric architecture with long helices which look like tentacles extend from a central loop . In each subunit of the Tim9-Tim10 complex, a signature "twin CX3C" motif forms two intramolecular disulfides .

Tim9 plays an important functional role that includes facilitating the initial steps in translocating precursor substrates into the intermembrane space .
Fanconi anemia group F protein (FANCF)
Type: Family

Fanconi anemia (FA) is a human disorder characterised by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages. The FA complex repairs the interstrand cross-linking (ICL) lesions and coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination. It is required for the monoubiquitylation of FANCD2 and FANCI heterodimer. The FA core complex consists of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, FANCT (UBET2), FAAP100 and FAAP24 .

Fanconi anemia group F protein (FANCF) is a component of the FA core complex . FANCF regulates its own expression by methylation at both mRNA and protein levels. Methylation-induced inactivation of FANCF has an important role on the occurrence of ovarian cancers by disrupting the FA-BRCA pathway .

This entry also includes homologues from plants.
Nitrile-specifier protein 1/2/3 (NSP1/2/3)
Type: Family

This entry includes nitrile-specifier protein 1/2/3 from Arabidopsis. Nitrile-specifier protein convert allylglucosinolate and benzylglucosinolate to their corresponding simple nitriles in the presence of myrosinase. They contain lectin-like jacalin domains, which share a common ancestry with the jacalin domains of the putative Arabidopsis myrosinase-binding proteins MBP1 and MBP2 .
Phosphoprotein P region PNT disordered (Paramyxo_PNT)
Type: Domain

The is the N-terminal half of the phosphoprotein P of the Paramyxovirinae viruses. The very first 60 residues have been built as the family Soyouz-module,

. The remaining part of the region, here, is disordered, and is liable to induced folding under the right physiological conditions. The region undergoes an unstructured-to-structured transition upon binding to Measles virus tail, C, unstructured region .
BLOC-2 complex member HPS5 (HPS5)
Type: Family

Lysosome-related organelles comprise a group of specialised intracellular compartments that include melanosomes and platelet dense granules in mammals and eye pigment granules in insects. Hermansky-Pudlak syndrome (HPS) is a disorder of lysosome-related organelle biogenesis. Genes associated with HPS encode subunits of three complexes that are known as biogenesis of lysosome-related organelles complex (BLOC)-1, -2 and -3 . There are eight known HPS proteins of the BLOCs ]. Organelles affected in HPS include the melanosome, resulting in hypopigmentation, and the platelet delta (dense) granule, resulting in prolonged bleeding times.

HPS in humans or mice is caused by mutations in any of 15 genes, five of which encode subunits BLOC-1. BLOC-1 and BLOC-2 act sequentially in the same pathway. Melanosome maturation requires at least two cargo transport pathways directly from early endosomes to melanosomes. One pathway mediated by AP-3, and one pathway mediated by BLOC-1 and BLOC-2 . The adaptor protein AP-3 complex is a component of the cellular machinery that controls protein sorting from endosomes to lysosomes and melanosomes. BLOC-1 interacts physically and functionally with AP-3 to facilitate the trafficking of a known AP-3 cargo, CD63, and of tyrosinase-related protein 1 (Tyrp1). BLOC-1 also interacts with BLOC-2 to facilitate Tyrp1 trafficking by a mechanism apparently independent of AP-3 function. Both BLOC-1 and -2 predominantly localise to early endosome-associated tubules .

Complex-2 (BLOC-2) contains the HPS3, HPS5 and HPS6 proteins as subunits. Fibroblasts deficient in the BLOC-2 subunits HPS3 or HPS6 have normal basal secretion function of the lysosomal enzyme beta-hexosaminidase .

This entry also includes HPS5 homologues from insects. Fruit fly HPS5 (also known as p) has a role in the biogenesis of eye pigment granules .
NFU1-like (NFU1-like)
Type: Family

This entry includes NFU1-like proteins from eukaryotes and some uncharacterised proteins from prokaryotes.

Nfu functions as a scaffold protein for assembly and delivery of rudimentary Fe-S clusters to target proteins . A human Nfu homologue, HIRA-interacting protein 5 (HIRIP5), was first identified in a two-hybrid screen for proteins that interact with the transcription regulator HIRA . It seems that two human Nfu isoforms are generated by alternative explicing, which are subsequently targeted to different subcellular compartments .
Glutamate--cysteine ligase, bacteria and plant (GCL_bact_plant)
Type: Family

This entry represents glutamate--cysteine ligase (GCL) from bacteria and plants, including EgtA from Actinobacteria and chloroplastic GCL from Arabidopsis.

EgtA resembles the glutamate--cysteine ligase of the two-step pathway for glutathione (GSH) biosynthesis, but instead are involved in the biosynthesis of the histidine-derived thiol, ergothioneine (EGT). Successful in vitro reconstitution of EGT biosynthesis using EgtBCDE and gamma-L-glutamyl-L-cysteine suggests that this enzyme is a bone fide glutamate--cysteine ligase .
Diphthamide synthesis DHP1/DPH2, eukaryotes and archaea (DPH1/DPH2_euk_archaea)
Type: Family

This entry includes diphthamide synthesis DPH1 from eukaryotes and archaea and DPH2 from archaea.

Archaeal and eukaryotic translation elongation factor 2 (EF-2) contain a unique posttranslationally modified histidine residue called diphthamide, which become the target for ADP-ribosylation by diphtheria toxin . DPH1 catalyzes the first step of diphthamide biosynthesis and is required for the modification of EF-2 . The human DPH1 is also known as OVCA1 (for ovarian cancer gene 1), a tumour suppressor gene that plays a crucial role in the regulation of cell proliferation, embryonic development, and tumorigenesis .
Dystrophin/utrophin (Dystrophin/utrophin)
Type: Family

Dystrophin anchors the extracellular matrix to the cytoskeleton via F-actin and is a ligand for dystroglycan. It is a component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems and has a structural function in stabilising the sarcolemma .

Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD), which is the most common form of muscular dystrophy and a sex-linked recessive disorder .

Utrophin (dystrophin-related protein 1) is normally expressed on the sarcolemma of developing and regenerating muscle fibres . It is ultimately replaced by dystrophin in the sarcolemma of normal maturing fibres and in normal conditions it is confined to the neuromuscular and myotendinous junctions. However, in the absence of dystrophin, utrophin is expressed on the sarcolemma of dystrophic fibres acting to mitigate necrosis .
SNase-like, OB-fold superfamily (SNase_OB-fold_sf)
Type: Homologous_superfamily

This superfamily is composed of the Staphylococcal nuclease (SNase-like), OB-fold domain.

Staphylococcus aureus nuclease (SNase) homologues, previously thought to be restricted to bacteria and archaea, are also in eukaryotes. Staphylococcal nuclease has a multi-domain organisation . The human cellular coactivator p100 contains four repeats, each of which is a SNase homologue. These repeats are unlikely to possess SNase-like activities as each lacks equivalent SNase catalytic residues, yet they may mediate p100's single-stranded DNA-binding function . A variety of proteins including many that are still uncharacterised belong to this group.

SNase domains have an OB-fold consisting of a closed or partly open β-barrel with Greek key topology .
Zinc finger FYVE domain containing protein, SARA/endofin (SARA/endofin)
Type: Family

This group represents zinc finger FYVE domain-containing proteins SARA and endofin.

SARA (also known as zinc finger FYVE domain-containing protein 9) is a component of the TGFbeta pathway that functions to recruit Smad2 to the TGFbeta receptor . Endofin (zinc finger FYVE domain-containing protein 16) facilitates TGF-beta signaling by bringing Smad4 to the proximity of the receptor complex . Both are involved in regulating membrane trafficking in the endosomal pathway .
UPF0145 domain superfamily (UPF0145_dom_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in the uncharacterised protein family UPF0145.
Methyl-accepting chemotaxis protein, four helix bundle domain superfamily (4HB_MCP_dom_sf)
Type: Homologous_superfamily

This entry represents a four-helix bundle that operates as a ubiquitous sensory module in prokaryotic signal-transduction, which is known as four-helix bundles methyl-accepting chemotaxis protein (4HB_MCP) domain. The 4HB_MCP is always found between two predicted transmembrane helices indicating that it detects only extracellular signals. In many cases the domain is associated with a cytoplasmic HAMP domain suggesting that most proteins carrying the bundle might share the mechanism of transmembrane signalling which is well-characterised in E coli chemoreceptors .

Methyl-accepting chemotaxis proteins (MCPs) are a family of bacterial receptors that mediate chemotaxis to diverse signals, responding to changes in the concentration of attractants and repellents in the environment by altering swimming behaviour . Environmental diversity gives rise to diversity in bacterial signalling receptors, and consequently there are many genes encoding MCPs . For example, there are four well-characterised MCPs found in Escherichia coli: Tar (taxis towards aspartate and maltose, away from nickel and cobalt), Tsr (taxis towards serine, away from leucine, indole and weak acids), Trg (taxis towards galactose and ribose) and Tap (taxis towards dipeptides).