SII-SWORD/CoKE huggingface dataset:
Peptidase S1A, alpha-lytic prodomain (Pept_S1_alpha_lytic)
Type: Domain

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

The alpha-lytic protease prodomain is associated with serine peptidases, specifically the alpha-lytic endopeptidases and streptogrisin A, B, C, D and E, which are bacterial enzymes and which belong to MEROPS peptidase subfamily S1A (

). The protease precursor in Gram-negative bacterial proteases may be a general property of extracellular bacterial proteases . The proteases are encoded with a large (166 amino acid) N-terminal pro region that is required transiently both
in vivo
and
in vitro
for the correct folding of the protease domain . The pro region also acts as a potent inhibitor of the mature enzyme .
Fibronectin binding repeat (Fibron_repeat-bd)
Type: Repeat

The ability of bacteria to bind fibronectin is thought to enable the colonisation of wound tissue and blood clots. The fibronectin binding repeat is found in bacterial fibronectin binding proteins and serum opacity factor. Each fibronectin binding repeat is an array of short motifs that bind to fibronectin type I domains . Fibronectin binding repeats are natively unfolded in the absence of fibronectin and are thought to adopt a well-defined conformation (tandem β-zipper) upon binding .
Late embryogenesis abundant protein ECP63-like domain (ECP63-like_dom)
Type: Domain

This entry represents a domain found in Late embryogenesis abundant protein ECP63 from Arabidopsis thaliana and similar plant proteins. ECP63, a member of the LEA family, is though to be involved in the BHLH109-mediated regulation of somatic embryogenesis .

LEA (late embryogenesis abundant) proteins were first identified in land plants. Plant LEA proteins have been found to accumulate to high levels during the last stage of seed formation (when a natural desiccation of the seed tissues takes place) and during periods of water deficit in vegetative organs. Later, LEA homologues have also been found in various species . They have been classified into several subgroups in Pfam and according to Bray and Dure .
Protein of unknown function DUF228 (DUF228)
Type: Family

This group comprises proteins of unknown function from Borrelia burgdorferi, the causitive organism of Lyme disease.
Nonaspanin (TM9SF) (EMP70)
Type: Family

The transmembrane 9 superfamily protein (TM9SF) may function as a channel or small molecule transporter. Proteins in this group are endosomal integral membrane proteins.
Autophagy protein Atg8 ubiquitin-like (Atg8-like)
Type: Family

A number of autophagy-related proteins have been identified in yeast, including the key autophagic protein Atg8, which is a ubiquitin-like protein with a structure consisting of two amino-terminal α-helices and a ubiquitin-like core . Many other eukaryotes contain multiple Atg8 orthologues. Atg8 genes of multicellular animals can be divided into three subfamilies: microtubule-associated protein 1 light chain 3 (MAP1LC3 or LC3) , gamma-aminobutyric acid receptor-associated protein (GABARAP) and Golgi-associated ATPase enhancer of 16kDa (GATE-16) . Family members are involved in diverse intracellular trafficking and autophagy processes.
Transposon, En/Spm-like (Transposase_21)
Type: Family

This family includes a En/Spm-like transposable element, Tdc1 from carrot . The function of these proteins is unknown.
Minor capsid protein VI (McpVI)
Type: Family

Protein VI is a structural protein of the adenoviral capsid. It shuttles between the nucleus and the cytoplasm and links hexon to the nuclear import machinery via an importin alpha/beta-dependent mechanism . It also mediates adenovirus endosome penetration during cell entry .
Transposase, L1 (Transposase_22)
Type: Family

Many human L1 elements are capable of retrotransposition. Some of these have been shown to exhibit reverse transcriptase (RT) activity .

This entry includes L1RE1 and L1TD1 from human. L1RE1 is essential for retrotransposition of LINE-1 elements in the genome. It functions as a nucleic acid chaperone binding its own transcript and therefore preferentially mobilizing the transcript from which they are encoded . L1TD1 plays an important role in the regulation of stemness, being required for human embryonic stem cells (hESC) self-renewal and cancer cell proliferation. .
Protein of unknown function DUF229 (DUF229)
Type: Family

Members of this family are uncharacterised with a long conserved region that may contain several domains.
Lentiviral Vpr-like protein (Lentiviral_Vpr-like)
Type: Family

This family consists of Vpr-like accessory proteins from maedi-visna and caprine/ovine lentivirus. This small open reading frame (ORF) in maedi-visna virus (MVV) and caprine arthritis encephalitis virus (CAEV) was initially named "tat" by analogy with a similarly placed ORF in the primate lentiviruses .
Borrelia plasmid, OrfD (Borrelia_plasmid_OrfD)
Type: Family

Borrelia burgdorferi supercoiled plasmids encode multicopy tandem open reading frames called OrfA, OrfB, OrfC and OrfD. This entry represents the protein encoded by OrfD, known as Outer membrane lipoprotein BBA14, which could act as a component of a potential toxin-antitoxin system in this organism and serve as a plasmid stabilization mechanism in a growing bacterial population .
Somatostatin (Somatostatin)
Type: Family

Somatostatin (SST) also known as somatotropin release-inhibiting factor (SRIF), is a hypothalamic hormone, a pancreatic hormone, and a central and peripheral neurotransmitter. Somatostatin, acting through the 5 somatostatin receptors, it has been found to regulate the secretion of various hormones such as pituitary growth hormone (GH) , thyroid-stimulating hormone (TSH) , prolactin , pituitary, insulin and glucagon . It also inhibits secretion in the intestine (including gastric acid in the stomach) , pancreatic acinar cells and pancreatic beta-cells , cell proliferation , stimulates absorption in the intestine and modulates smooth muscle contractility . Somatostatin has a wide distribution throughout the central nervous system as well as in peripheral tissues, for example in the pituitary, pancreas and stomach and is released from the hypothalamus. In the CNS, it is a neurotransmitter and neuromodulator activating a hyperpolarising K+ current and inhibiting Ca2+ influx, and is believed to play important roles in regulating locomotor activity and cognitive function. These various actions are mediated by a family of seven transmembrane domain G protein-coupled receptors that comprise of five distinct subtypes: Somatostatin receptor 1 (SSTR1), Somatostatin receptor 2 (SSTR2), Somatostatin receptor 3 (SSTR3), Somatostatin receptor 4 (SSTR4) and Somatostatin receptor 5 (SSTR5) .

This entry represents the somatostatin family, including somatostatin and cortistatin from humans.
Pox virus entry-fusion-complex G9/A16 (Pox_virus_G9/A16)
Type: Family

This family includes two of the eight entry-fusion complex proteins of pox viruses. The viral fusion proteins are components of the mature virion, MV, membrane. Extracellular enveloped virions (EVs), the infecting particles, are MVs with an additional membrane that is opened or removed prior to the fusion of the MV and cell membrane during virus entry. G9 (also known as Entry-fusion complex protein OPG094) and A16 (Virion membrane protein OPG143) interact closely with each other and each is required for membrane fusion and virus entry as well as for interaction with A56/K2 .
Probable transposase, Ptta/En/Spm, plant (Probable_transposase_24)
Type: Family

Transposase proteins are necessary for efficient DNA transposition. This family includes various probable plant transposases from the Ptta and En/Spm families .
AdipoR/Haemolysin-III-related (AdipoR/HlyIII-related)
Type: Family

Members of this family are integral membrane proteins. This family includes a protein with hemolytic activity from Bacillus cereus . YOL002c (AdipoR-like receptor IZH2) from Saccharomyces cerevisiae encodes a protein that plays a key role in metabolic pathways that regulate lipid and phosphate metabolism . In eukaryotes, members are seven-transmembrane pass molecules found to encode functional receptors with a broad range of apparent ligand specificities, including progestin and adiponectin (AdipoQ) receptors (AdipoR), and hence have been named PAQR proteins . The mammalian members include progesterone binding proteins . Unlike the case with GPCR receptor proteins, the evolutionary ancestry of the members of this family can be traced back to the Archaea.
O-acyltransferase, WSD1-like, N-terminal (O-acyltransferase_WSD1_N)
Type: Domain

This entry represents the N-terminal catalytic domain of a number of wax ester synthase/diacylglycerol acyltransferases (WS/DGATs), predominantly from bacteria and plants. They catalyse the condensation of a fatty alcohol and a fatty acyl-Coenzyme A (acyl-CoA) and they can also catalyse the transesterification of acyl-CoAs with diacylglycerols. These are bifunctional enzymes that share low overall sequence similarity but all WS/DGATs share a conserved HHXXXDG motif, which is also found in other acyltransferases . This domain contains the conserved HHXXXDG motif and consists of a mixed β-sheet flanked by four α-helices and a small antiparallel β-sheet .
Domain of unknown function DUF234 (DUF234)
Type: Domain

This entry represents a domain of unknown function found in bacterial and archaeal sequences. In some instances it is fused to a prokaryotic putative DEXX-box ATPase domain, found at its C-terminal (

) .
Equine arteritis virus (EAV), glycoprotein 4 (Equine_arteritis_virus_Gp4)
Type: Family

This family contains a predicted structural envelope protein Gp4 from Equine arteritis virus (EAV).
Duffy-binding-like domain (DBL)
Type: Domain

Plasmodium Duffy Binding-Like (DBL) domains mediate diverse receptor-ligand interactions critical for invasion, cytoadherence, sequestration and the pathogenesis of malaria . Members of the erythrocyte binding-like (EBL) superfamily contain one or two extracellular cysteine-rich DBL domains.
Phosphoprotein M1-like (PP_M1-like)
Type: Family

This family includes the M1 phosphoprotein non-structural RNA polymerase alpha subunit (

) from various strains of Rabies virus . The M1 phosphoprotein is thought to be a component of the active polymerase, and may be involved in template binding.
Pyrimidine dimer DNA glycosylase (Pyr-dimer_DNA_glycosylase)
Type: Family

Pyrimidine dimer DNA glycosylases are enzymes responsible for initiating the base excision repair pathway, excising pyrimidine dimers by hydrolysis of the glycosylic bond of the 5' pyrimidine, followed by the intra-pyrimidine phosphodiester bond . One such enzyme is T4 endonuclease V, an enzyme responsible for the first step of a pyrimidine-dimer-specific excision-repair pathway . Bacteriophage T4 that are deficient in these enzymes are extremely sensitive to UV.
Hepatitis E virus structural protein 2, N-terminal domain (SP2_N)
Type: Domain

This entry represents the N-terminal domain of structural protein 2 of the hepatitis E virus. The high basic amino acid content of this protein has lead to the suggestion of a role in viral genomic RNA encapsidation.

The Hepatitis E virus (HEV) structural protein 2 (also known as ORF2) is a major viral capsid protein that encapsidates the viral genome. It has been shown to bind to the 5' end of the genomic RNA .

Interestingly, ORF2 has an secreted isoform that inhibits antibody-mediated neutralization from the host .
Exostosin-like (Exostosin)
Type: Family

There are five identified human EXT family proteins (EXT1, EXT2, EXTL1, EXTL2 and EXTL3), which are members of the hereditary multiple exostoses family of tumor suppressors . They are glycosyltransferases required for the biosynthesis of heparan sulfate. Hereditary multiple exostoses (EXT) is an autosomal dominant disorder that is characterised by the appearance of multiple outgrowths of the long bones (exostoses) at their epiphyses . Mutations in two homologous genes, EXT1 and EXT2, are responsible for the EXT syndrome. The human and mouse EXT genes have at least two homologues in the invertebrate Caenorhabditis elegans, indicating that they do not function exclusively as regulators of bone growth. EXT1 and EXT2 have both been shown to encode glycosyltransferases involved in the chain elongation step of heparan sulphate biosynthesis .

This entry also includes Arabidopsis Xyloglucan galactosyltransferase KATAMARI1 (

) and Drosophila melanogaster EXT homologues .
Transposase, Tnp1/En/Spm-like (Transposase_23)
Type: Domain

Proteins in this group are TNP1/EN/SPM-like transposon proteins with no known function from plants .
Dirigent protein (Dirigent)
Type: Family

Dirigent proteins impart stereoselectivity on the phenoxy radical-coupling reaction, yielding optically active lignans from two molecules of coniferyl alcohol in the biosynthesis of lignans, flavonolignans, and alkaloids and thus plays a central role in plant secondary metabolism . This family also includes homologue DRR206 (disease resistance response protein 206). DRR206 is induced by the metabolite pinoresinol monoglucoside and is involved in phytoalexin (lignan) biosynthesis as a defense response .
Influenza C virus M2 protein (CM2)
Type: Family

This family represents the matrix protein, M2, of Influenza C virus. The M1 protein is the product of a spliced mRNA (see

). Small quantities of the unspliced mRNA are found in the cell additionally encoding the M2 protein.
Peptidoglycan biosynthesis protein MurJ (MurJ)
Type: Family

Peptidoglycan synthesis (PG) biosynthesis involves the formation of peptidoglycan precursor lipid II (undecaprenyl-pyrophosphate-linked N-acetyl glucosamine-N-acetyl muramic acid-pentapeptide) on the cytosolic face of the cell membrane. Lipid II is then translocated across the membrane and its glycopeptide moiety becomes incorporated into the growing cell wall mesh.

MviN, renamed as MurJ, is a lipid II flippase essential for cell wall peptidoglycan synthesis . Unlike most MviN proteins, the mycobacterial MviN orthologue possess an extended C-terminal region that contains an intracellular pseudo-kinase domain and an extracellular domain resembling carbohydrate-binding proteins .
Folate receptor (Folate_rcpt)
Type: Family

Folic acid and its reduced derivatives are transported via two widely expressed transporters, the reduced folate carrier (RFC) and the proton-coupled folate transporter (PCFT), and via a family of glycosyl-phosphatidylinositol (GPI)-anchored receptors with limited expression profiles known as folate receptors (FRs) .

Folate receptors (FR) are high affinity receptors that transport folate via endocytosis. Human FR exists in three isoforms, alpha and beta equipped with GPI anchors, and gamma not possessing a GPI anchor .
Papillomavirus E5, alphapapillomavirus (Papilloma_E5_alpha)
Type: Family

The E5 protein from papillomaviruses is about 80 amino acids long and contain three regions that have been predicted to be transmembrane α helices. The function of this protein is unknown.
Influenza C virus M1 protein (CM1)
Type: Family

This family represents the matrix protein, M1, of Influenza C virus. The M1 protein is the product of a spliced mRNA. Small quantities of the unspliced mRNA are found in the cell additionally encoding the M2 protein (see

).
Dynein heavy chain region D6 P-loop domain (Dynein_heavy_D6_P-loop)
Type: Domain

This entry represents the C-terminal region of dynein heavy chain. The chain also contains ATPase activity and microtubule binding ability and acts as a motor for the movement of organelles and vesicles along microtubules. Dynein is also involved in cilia and flagella movement. The dynein subunit consists of at least two heavy chains and a number of intermediate and light chains . The 380kDa motor unit of dynein belongs to the AAA class of chaperone-like ATPases. The core of the 380kDa motor unit contains a concatenated chain of six AAA modules, of which four correspond to the ATP binding sites with P-loop signatures described previously, and two are modules in which the P loop has been lost in evolution. This C-terminal domain carries the D6 region of the dynein motor where the P-loop has been lost in evolution but the general structure of a potential ATP binding site appears to be retained .
FCP1 homology domain (FCP1_dom)
Type: Domain

Yeast FCP1 is an essential protein serine phosphatase (

) that dephosphorylates the C-terminal domain (CTD) of RNA polymerase II. FCP1 orthologs are present in all known eukaryote proteomes. The N-terminal domain of FCP1 corresponds to the catalytic unit of the phosphatase and has been refered to as the FCP1 homology domain. The FCP1 homology domain, which is a ~180-residue module, is also found in many other proteins of unknown function. It contains a DxDx(T/V) motif preceded by four hydrophobic residues characteristic of a large family of metal-dependent phosphohydrolases and phosphotransferases. The first aspartate residue is likely to participate in catalysis, whereas the second could have a role in substrate recognition .
Frog antimicrobial peptide, propeptide (Frog_antimicrobial_propeptide)
Type: Domain

In addition to the highly specific cell-mediated immune system, vertebrates possess an efficient host-defence mechanism against invading microorganisms which involves the synthesis of highly potent antimicrobial peptides with a large spectrum of activity.

This entry represents the signal peptide and propeptide regions found in a number of these defence peptides secreted from the skin of amphibians, including caerins, dermaseptins, brevinin, dermorphin, tryptophillin, pleurain and phylloseptin . This domain does not include the active peptides.
Glycosyltransferase family 28, N-terminal domain (GlycoTrans_28_N)
Type: Domain

Glycosyltransferase family 28

comprises enzymes with a number of known activities; 1,2-diacylglycerol 3-beta-galactosyltransferase (

); 1,2-diacylglycerol 3-beta-glucosyltransferase (

); beta-N-acetylglucosamine transferase (

).

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

Phosphatidyl serine synthase is also known as serine exchange enzyme (

). This family represents eukaryotic PSS I and II, membrane bound proteins that catalyse the replacement of the head group of a phospholipid (phosphotidylcholine or phosphotidylethanolamine) by L-serine .

Proteins in this entry include Pss from Drosophila melanogaster. Pss has been shown to regulate cell growth, lipid storage and mitochondrial function .
Minor capsid protein VP2 (VP2)
Type: Family

This entry represents Minor capsid protein VP2 from Caliciviruses. VP2 is a minor structural protein that forms a portal-like structure at a unique three-fold axis of symmetry, following binding to the host receptor . This structure contains twelve copies of VP2, arranged with their hydrophobic N termini pointing away from the virion surface. VP2 is known to be essential for productive replication that results in the synthesis and maturation of infectious virions and thus critical for the production of infectious virus .

Caliciviruses are a small round-structured virus group defined by RNA-dependent RNA polymerase and capsid diversity.
Perilipin (Perilipin)
Type: Family

The perilipin family includes lipid droplet-associated protein (perilipin) and adipose differentiation-related protein (adipophilin). Perilipin is a modulator of adipocyte lipid metabolism and adipophilinis are involved in the development and maintenance of adipose tissue. The relative expression of these proteins and protective nature of lipid droplets from lipase activity depends on the balance of lipid storage and utilisation in specific cells . TIP47, also known as perilipin-3, is a cargo selection device for mannose 6-phosphate receptor trafficking that is also included in this group .
Herpesvirus UL95 (Herpes_UL95)
Type: Family

Members of this family are functionally uncharacterised proteins from herpesviruses.
Interleukin-12 alpha (IL-12_alpha)
Type: Family

Interleukin 12 (IL-12) is a disulphide-bonded heterodimer consisting of a 35kDa alpha subunit and a 40kDa beta subunit. It is involved in the stimulation and maintenance of Th1 cellular immune responses, including the normal host defence against various intracellular pathogens, such as Leishmania, Toxoplasma, Measles virus and Human immunodeficiency virus 1 (HIV). IL-12 also has an important role in pathological Th1 responses, such as in inflammatory bowel disease and multiple sclerosis. Suppression of IL-12 activity in such diseases may have therapeutic benefit. On the other hand, administration of recombinant IL-12 may have therapeutic benefit in conditions associated with pathological Th2 responses .

This entry represents interleukin-12 alpha.
Chloroplast envelope membrane protein, CemA (CemA)
Type: Family

Members of this family are probable integral membrane proteins. Their molecular function is unknown. CemA proteins are found in the inner envelope membrane of chloroplasts but not in the thylakoid membrane . A cyanobacterial member of this family (proton extrusion protein PcxA) is involved in light-induced Na(+)-dependent proton extrusion and has been implicated in CO2 transport, but is probably not a CO2 transporter itself .
Late expression factor 2 (Lef-2)
Type: Family

The late expression factor 2 (lef-2) protein from Orgyia pseudotsugata multicapsid polyhedrosis virus (OpMNPV) is required for expression of late genes. The lef-2 protein has been shown to be specifically required for expression from the vp39 and polh promoters .
Birnavirus VP5 protein (Birna_VP5)
Type: Family

Birnaviruses are ds RNA viruses. Non structural protein VP5 is found in RNA segment A. The function of this small viral protein is unknown.