SII-SWORD/CoKE huggingface dataset:
PE-PPE, C-terminal (PE-PPE_C)
Type: Domain

The human pathogen Mycobacterium tuberculosis harbours a large number of genes that encode proteins whose N-terminals contain the characteristic motifs Pro-Glu (PE) or Pro-Pro-Glu (PPE). These proteins are exported to the bacterial surface via type VII secretion systems known as ESX . A subgroup of the PE proteins contains polymorphic GC-rich sequences (PGRS), while a subgroup of the PPE proteins contains major polymorphic tandem repeats (MPTR). The function of most of these proteins remains unknown . However, the PE_PGRS proteins from Mycobacterium marinum are secreted by components of the ESX-5 system that belongs to the recently defined type VII secretion systems . It has also been reported that the PE_PGRS family of proteins contains multiple calcium-binding and glycine-rich sequence motifs GGXGXD/NXUX. This sequence repeat constitutes a calcium-binding parallel β-roll or parallel β-helix structure and is found in RTX toxins secreted by many Gram-negative bacteria .

PPE51 member has been described as a small molecule-selective channel required for the uptake of nutrients across the outer mycomembrane . This protein transports glycerol and glucose as well as maltose and lactose disaccharides. It is involved in sensitivity to M.tuberculosis growth inhibitory agrichemical 3,3-bis-di(methylsulfonyl)propionamide (3bMP1) and sensitivity to bactericidal thio-disaccharide T-6 compound .

This domain is found C-terminal to the PE (

) and PPE (

) domains. The secondary structure of this domain is predicted to be a mixture of α-helices and β-strands .
PEGA (PEGA)
Type: Domain

This domain is found in both archaea and bacteria and has similarity to S-layer (surface layer) proteins. It is named after the characteristic PEGA sequence motif found in this domain. The secondary structure of this domain is predicted to be β-strands.
Peptidase M15A, C-terminal (Peptidase_M15A_C)
Type: Domain

This entry represents the C-terminal domain of zinc D-Ala-D-Ala carboxypeptidases from Streptomyces species and non-peptidase homologues that belong to MEROPS peptidase family M15 (subfamily M15A, clan MD) .
Periviscerokinin (Periviscerokinin)
Type: Family

Perviscerokinin neuropeptides are found in the abdominal perisympathetic organs of insects. They mediate visceral muscle contractile activity (myotropic activity). CAPA, which are in the periviscerokinin and pyrokinin peptide families, has potential medical importance. This is due to its myotropic effects on, for example, heart muscles and due to its occurrence in the Ixodoidea (ticks), which are important vectors in the transmission of many animal diseases . These peptides also have a strong diuretic or anti-diuretic effect, suggesting they have significant medical implications .
Bacteriophage T7, Gp1.1 (Phage_T7_Gp1.1)
Type: Family

Gene 1.1 in Bacteriophage T7 encodes a 42 amino acid protein, rich in basic amino acids suggesting its interaction with nucleic acids . Many homologues are present in different T7 and T3-like bacteriophage.
Glycosylphosphatidylinositol-mannosyltransferase I, PIG-X/PBN1 (PIG-X/PBN1)
Type: Family

Mammalian PIG-X and yeast PBN1 are essential components of glycosylphosphatidylinositol-mannosyltransferase I . These enzymes are involved in the transfer of sugar molecules. They probably act by stabilizing the mannosyltransferase PIG-M (GPI14 in yeast) .
PIGA, GPI anchor biosynthesis (PIGA_GPI_anchor_biosynthesis)
Type: Domain

This domain is found on phosphatidylinositol N-acetylglucosaminyltransferase proteins. These proteins are involved in GPI anchor biosynthesis and are associated with the disease paroxysmal nocturnal haemoglobinuria .
PPP domain (PPP_dom)
Type: Domain

This domain is found in some members of the PPP phosphatase family, including serine/threonine-protein phosphatase 5 and serine/threonine-protein phosphatase with EF-hands 1 and 2.
M protein trans-acting positive regulator (MGA), PRD domain (Mga_PRD_dom)
Type: Domain

Mga is a DNA-binding protein that activates the expression of several important virulence genes in group A streptococcus in response to changing environmental conditions . This region corresponds to the PRD like region.
DNA primase/helicase Gp4, N-terminal, Bacteriophage T7-like (Phage_T7_Gp4_N)
Type: Domain

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

The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

This entry represents a zinc binding domain found in the N-terminal region of the bacteriophage T7 Gp4 and P4 alpha protein. P4 is a multifunctional protein with origin recognition, helicase and primase activities .
RNA polymerase III, subunit Rpc25 (RNA_pol_III_Rbc25)
Type: Domain

Rpc25 is a strongly conserved subunit of RNA polymerase III and has homology to Rpa43 in RNA polymerase I, Rpb7 in RNA polymerase II and the archaeal RpoE subunit. Rpc25 is required for transcription initiation and is not essential for the elongating properties of RNA polymerase III .
RNA polymerase I, subunit Rpa14, fungi (RNA_polI_Rpa14)
Type: Family

Saccharomyces cerevisiae RNA polymerase I (Pol I) is a complex consisting of 14 subunits. Subunit Rpa14 forms part of a Pol I subcomplex consisting of Rpa14 and and Rpa43. The Rpa14 and Rpa43 heterodimer is proposed to play a role in the recruitment of Pol I to the promoter . This protein contains a HRDC domain homologous to that found in archaeal RNAP subunit F and RPB4 from eukaryotes .
DNA-directed RNA polymerase I, subunit RPA34 (DNA-dir_RNA_pol1_su_RPA34)
Type: Family

This is a family of proteins conserved from yeasts to human. Subunit A34 of RNA polymerase I is a non-essential subunit which is thought to help Pol I overcome topological constraints imposed on ribosomal DNA during the process of transcription . It forms a heterodimer with RPA49 which stimulates transcript elongation by Pol I .
RNase P, subunit Pop3 (RNase_P_Pop3)
Type: Family

This family of fungal proteins form a subunit of RNase P, the ribonucleoprotein enzyme that cleaves the leader sequence of precursor tRNAs to generate mature tRNAs. The structure of Pop3 has been assigned the L7Ae/L30e fold . This RNA-binding fold is also present in human RNase P subunit Rpp38, raising the possibility that Pop3p and Rpp38 are functional homologues.
SCA7 domain (SCA7_dom)
Type: Domain

SAGA (Spt-Ada-Gcn5 acetyltransferase), a coactivator complex involved in chromatin remodelling, harbours both histone acetylation and deubiquitination activities. SAGA-associated factor 73 (Sgf734/ATXN7) and Ataxin-7-like protein 3 (ATXN7L3), two subunits of the SAGA deubiquitination module, contain an ~50-residue SCA7 domain characterised by an atypical zinc- finger (Znf) with a Cys-X(9,10)-Cys-X(5)-Cys-X(2)-His motif and a long sequence insertion between the first two zinc coordinating residues.

The SCA7 domain is found exclusively in members of the ATXN7 gene family, which includes two distinct subunits of SAGA complexes: ATXN7 and ATXN7L3 orthologues. The analysis of multiple alignments highlights the consensus signature for the SCA7 domain, encompassing the putative zinc- coordinating residues, but also reveals the distinct features of the two proteins. Marked differences are found mostly in the carboxy-terminal of the domain, suggesting that divergent evolution of the SCA7 Znf domain occurred in order to achieve specific functions in the SAGA complex. Both SCA7 domains contain disordered regions, albeit not in the same region. Whereas the first and last 10 residues of ATXN7-SCA7 are not folded, the N- terminal region of ATXN7L3-SCA7 is well structured and the last 30 residues of this domain are not folded. In both ATXN7-SCA7 and ATXN7L3-SCA7, the large sequence insertion between the first and second zinc- coordinating cysteines corresponds to a protruding extended hairpin structure. The core of the zinc-binding sites shows a conserved structure formed by two short adjacent loops located at the bottom of the hairpin. Although the SCA7 domains of both ATXN7 and ATXN7L3 contain two α-helices, these are not located at similar positions in the sequences. In ATXN7-SCA7, the two α-helices are located downstream from the zinc-binding site and are separated by a loop containing a large number of positively charged residues. In ATXN7L3- SCA7, the two helices lie to either side of the zinc-binding site, leading to a different packing of the two helices. In ATXN7-SCA7, the two helices have an almost perpendicular orientation, the α2 helix being anchored to the zinc- binding site. In ATXN7L3-SCA7, the helices α1 and α2 adopt an antiparallel orientation defined by hydrophobic interactions. The ATXN7-SCA7 domain binds to the core or the C-terminal ends of the histone H2A and H2B dimer, a region located on the lateral face of the nucleosome that contains the ubiquitinated Lys 120 of H2B. This property is lost in the ATXN7-SCA7 domain .

This entry represents the SCA7 domain.
Sec39 domain (Sec39_domain)
Type: Domain

This entry represents a Sec39 domain, which can be found in yeast Sec39, human NBAS (neuroblastoma-amplified sequence) and Arabidopsis MIP2 (MAG2-INTERACTING PROTEIN 2) . They may be involved in Golgi-to-ER transport.

Sec39 was originally identified as a protein involved in ER-Golgi transport in a large scale promoter shut down analysis of essential yeast genes . A subsequent study found that Sec39p (Dsl3p) is required for Golgi-ER retrograde transport and is part of a very stable protein complex that also includes Dsl1p (in mammals ZW10), Tip20p (Rint-1) and the ER localized Q-SNARE proteins Ufe1p (syntaxin-18), Sec20p and Use1p . This was confirmed in a genome-wide analysis of protein complexes .
SAGA complex, Sgf11 subunit (SAGA_su_Sgf11)
Type: Family

The Sgf11 (SAGA-associated factor 11) family is a SAGA complex subunit in Saccharomyces cerevisiae (Baker's yeast). The SAGA complex is a multisubunit protein complex involved in transcriptional regulation. SAGA combines proteins involved in interactions with DNA-bound activators and TATA-binding protein (TBP), as well as enzymes for histone acetylation and deubiquitylation .
Secretory component protein Psh3/Shr3 (Psh3/Shr3)
Type: Family

This family of proteins are membrane localised chaperones that are required for correct plasma membrane localisation of amino acid permeases (AAPs) . Shr3 prevents AAPs proteins from aggregating and assists in their correct folding. In the absence of Shr3, AAPs are retained in the ER.
RNA polymerase sigma factor 70, region 4 type 2 (RNA_pol_sigma70_r4_t2)
Type: Domain

This entry represents region 4 of sigma-70 like sigma-factors involved in binding to the -35 promoter element via a helix-turn-helix motif .

The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.

With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors .

The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors .
DASH complex subunit Spc19 (DASH_Spc19)
Type: Family

Spc19 is a component of the DASH complex, which is a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. The DASH complex mediates the formation and maintenance of bipolar kinetochore-microtubule attachments by forming closed rings around spindle microtubules and establishing interactions with proteins from the central kinetochore .
Kinetochore-Ndc80 subunit Spc24 (Ndc80_Spc24)
Type: Family

Spc24 is a component of the evolutionarily conserved kinetochore-associated Ndc80 complex, which is implicated in several essential outer kinetochore functions, including microtubule binding and control the spindle assembly checkpoint .
Spc7 kinetochore protein domain (Spc7_domain)
Type: Domain

This domain is found in cell division proteins which are required for kinetochore-spindle association . Proteins containing this domain include budding yeast Spc105 and fission yeast Spc7.

Spc7 is a component of the NMS (Ndc80-MIND-Spc7) super complex, which has a role in kinetochore function during late meiotic prophase and throughout the mitotic cell cycle . Spc105 and Kre28 forms a kinetochore complex, which is required for kinetochore binding by a discrete subset of kMAPs (BIM1, BIK1 and SLK19) and motors (CIN8, KAR3) .
Sperm-activating peptide (Sperm_act_pept)
Type: Family

The sperm-activating peptides (SAPs) are isolated in egg-conditioned media (egg jelly) of sea urchins. SAPs have several effects on sea urchin spermatozoa: stimulate sperm respiration and motility through intracellular alkalinization, transient elevation of cAMP, cGMP and Ca
2+
levels in sperm cells .
Chromosome segregation protein Spc25, C-terminal (Spc25_C)
Type: Domain

The Ndc80 complex is a conserved outer kinetochore protein complex consisting of Ndc80 (Hec1), Nuf2, Spc24 and Spc25. The Ndc80 complex is required for chromosome segregation and spindle checkpoint activity .

This entry represents the C-terminal domain of Spc25 .
Chromatin SPT2 (Chromatin_SPT2)
Type: Family

This entry includes the Saccharomyces cerevisiae (Baker's yeast) protein SPT2 which is a chromatin protein involved in transcriptional regulation .

These proteins shows conservation of several domains across numerous species, including having a cluster of positively charged amino acids. This cluster probably functions in the binding properties of the proteins . Sin1p/Spt2p probably modulates the local chromatin structure by binding two strands of double-stranded DNA at their crossover point.

Sin1p/Spt2p has sequence similarity to HMG1 and serves as a negative transcriptional regulator of a small family of genes that are activated by the SWI/SNF chromatin-remodelling complex. It is also involved in maintaining the integrity of chromatin during transcription elongation. Sin1p/Spt2 is required for, and is directly involved in, the efficient recruitment of the mRNA cleavage/polyadenylation complex . Spt2 is also involved in regulating levels of histone H3 over transcribed regions .
Set2 Rpb1 interacting domain (SRI)
Type: Domain

The SRI (Set2 Rpb1 interacting) domain mediates RNA polymerase II interaction and couples histone H3K36 methylation with transcript elongation . This domain is conserved from yeast to humans. Members of this family form a compact, closed three-helix bundle, with an up-down-up topology. The first and second helices are antiparallel to each other and are of similar length; the third helix, which is packed across helices α1 and α2 is slightly shorter, consisting of only 15 amino acids. Most conserved hydrophobic residues are largely buried in the interior of the structure and form an extensive and contiguous hydrophobic core that stabilises the packing of the three-helix bundle. This domain mediates RNA polymerase II interaction and couples histone H3K36 methylation with transcript elongation .

This domain is also found in ATP-dependent DNA helicase Q5 (RECQ5), which enables REQ5 tointeract with Pol II .
Striatin, N-terminal (Striatin_N)
Type: Domain

This domain is associated with the N terminus of striatin. Striatin is an intracellular protein which has a caveolin-binding motif, a coiled-coil structure, a calmodulin-binding site, and a WD (

) repeat domain . It acts as a scaffold protein and is involved in signalling pathways .
Sulfakinin (Sulfakinin)
Type: Family

The sulfakinin (SK) family of neuropeptides have only been identified in crustaceans and insects. For most species there is the potential for producing two sulfakinin peptides, one has a short sulfakinin sequence. The function of the sulfakinins is difficult to assess. For the Periplaneta americana (American cockroach), various forms of the endogenous sulfakinins have been shown to be active on the hindgut, and also on the heart. In Calliphora vomitoria (Blue blowfly) the peptides act as neurotransmitters or neuromodulators, linking the brain with all thoracic and abdominal ganglia. In adults of Penaeus monodon (Penoeid shrimp) they appear to be restricted to a few neurones in the brain with a neural pathway extending along to the ventral thoracic and abdominal ganglia . Drosulfakinins (sulfakinins expressed in drosopholis) have been shown to regulate gut muscle contraction in adults but not in larvae .
mRNA splicing factor SYF2 (mRNA_splic_SYF2)
Type: Family

Proteins in this entry are involved in cell cycle progression and pre-mRNA splicing .
Mitochondrial import inner membrane translocase subunit Tim21 (Tim21)
Type: Family

Tim21 is an essential component of the TIM23 complex, which mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. Tim21 is required to keep the TOM and the TIM23 complexes in close contact. At some point, it is released from the TOM23 complex to allow protein translocation into the mitochondrial matrix .
Outer membrane protein, MIM1/TOM13, mitochondrial (OMP_MIM1/TOM13_mt)
Type: Family

The TOM13 family of proteins are mitochondrial outer membrane proteins that mediate the assembly of β-barrel proteins .
DNA topoisomerase I, zinc ribbon-like, bacterial-type (TopoI_Znr_bac)
Type: Domain

DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single-or double-strand breaks, crossing the strands through one another, then resealing the breaks . These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis . DNA topoisomerases are divided into two classes: type I enzymes (

; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (

; topoisomerases II, IV and VI) break double-strand DNA .

Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB . They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases . The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases .

This entry represents the C-terminal zinc-ribbon-like domain found in bacterial topoisomerase I (type IA) enzymes. Escherichia coli topoisomerase I proteins contain five copies of a zinc-ribbon-like domain at their C terminus, two of which have lost their cysteine residues and are therefore probably not able to bind zinc . This domain is still considered to be a member of the zinc-ribbon superfamily despite not being able to bind zinc.
DNA primase DNAG, catalytic core, N-terminal (DNAG_N)
Type: Domain

DNA primase (DNAG) is a a nucleotidyltransferase which synthesises the oligoribonucleotide primers required for DNA replication on the lagging strand of the replication fork. It can also prime the leading strand and has been implicated in cell division . Primases comprise three domains: a zinc-binding domain at the N-terminal

, a polymerase domain (catalytic core), and a domain that interacts with the replicative helicase

. The catalytic core consists of an alpha+beta domain at the N-terminal (this entry) and a TOPRIM domain at the C-terminal

.
TRI9, Fusarium species (TRI9_FUSspp)
Type: Family

This entry contains putative genes, of 129 bp, from the Trichothecene gene cluster of Fusarium sporotrichioides and Gibberella zeae (Fusarium graminearum) that encode a predicted protein of 43 amino acids whose function is unknown .
Tryptophyllin skin active peptide (Tryptophillin)
Type: Family

PdT-3 or Tryptophyllin-3 peptide is a subfamily of the family Tryptophyllin and of the superfamily FSAP (Frog Skin Active Peptide). Originally identified in skin extracts of Neotropical leaf frogs, Phyllomedusa sp. This subfamily has an average length of 13 amino acids. The pharmacological activity of the tryptophyllins remains to be established but it seems that these peptides possess an action on liver protein synthesis and body weight . It is thought to possesses insulin-releasing activity .
Hepatitis TT virus, Orf2a (Hepatitis_TTV_Orf2a)
Type: Family

Most isolated ORF2 of TT virus (TTV) encode a 49 amino acid protein (pORF2a) because of an in-frame stop codon. ORF2s isolated from G1 TTV encode a 202 amino acid protein (pORF2ab) .
U3 small nucleolar RNA-associated protein 16 (UTP16)
Type: Family

This family of proteins is associated with U3 snoRNA . U3 snoRNA is required for nucleolar processing of pre-18S ribosomal RNA. Proteins in this family include U3 small nucleolar RNA-associated protein 16 (UTP16, also known as Bud21) from S. cerevisiae. Bud21 is a component of small ribosomal subunit (SSU) processosome and has a role in bud site selection maybe via the regulation of expression of bipolar budding components . This protein functions as a connector between Utp4 and Noc4 .
Herpesvirus UL2 (Herpes_UL2)
Type: Family

This entry contains Orf UL2 of Human cytomegalovirus (HHV-5) (Human herpesvirus 5), which is a short protein of unknown function .
CD47 immunoglobulin-like (CD47_Vset)
Type: Domain

This entry represents the V-set like Ig domain found at the N-terminal end of Leukocyte surface antigen CD47 proteins from chordates and CD47-like proteins A38, also known as Protein OPG166, from Poxvirus.

Human CD47 is an adhesive protein that mediates cell-to-cell interactions . It is involved in signal transduction, cardiovascular homeostasis, inflammation, apoptosis, angiogenesis, cellular self-renewal, and immunoregulation .

OPG166 from Vaccinia virus promotes, when overexpressed, the influx of extracellular Ca2 , leading to membrane permeability and host cell necrosis .