SII-SWORD/CoKE huggingface dataset:
Protein of unknown function DUF321 (DUF321)
Type: Repeat

This entry represents a group of tandem repeats, found in Arabidopsis species, whose sequence is distantly related to the FARP (FMRFamide) group of neuropeptides (

). The function of these repeats is not known, being mostly found in uncharacterised proetins, but they are also present in the nuclear migration protein NUM1 .
SPW repeat-containing integral membrane domain (SPW)
Type: Domain

This entry represents a small integral membrane domain found in a small family of membrane-bound proteins. It contains a conserved SPW motif in the first of two transmembrane helices .
Alkaline shock protein Asp23 (Asp23)
Type: Family

Asp23 was identified as an alkaline shock protein expressed in a sigmaB-dependent manner in Staphylococcus aureus (

) . Following an alkaline shock, Asp23 accumulates in the soluble protein fraction of the S. aureus cell. Asp23 is one of the most abundant proteins in the cytosolic protein fraction of stationary S. aureus cells, with a copy-number of >25000 per cell. It is linked to the staphylococcal cell membrane and anchored there by AmpA. The overall function for the family is thus a cell envelope-related one in Gram-positive bacteria. .
Sulfatase-modifying factor enzyme-like domain (SUMF_dom)
Type: Domain

This domain is found in sulfatase-modifying factors (SUMFs) and Chlamydia serine/threonine-protein kinase pkn1 . It is also found in iron(II)-dependent oxidoreductase from Mycobacterium .
AMOP domain (AMOP_dom)
Type: Domain

This entry represents the AMOP domain found in ISM1/2, Mucin-4, Susd2 and related proteins. The AMOP domain (for adhesion-associated domain in MUC4 and other proteins) is a ~100-residue-long extracellular domain that contains eight invariant cysteine residues that are predicted to be involved in disulphide bonds. The AMOP domain is found associated with extracellular domains involved in cell adhesion, such as NIDO, sushi, somatomedin B, VWFD, EGF, IPT, or TSP1. The presence of the AMOP domain in cell adhesion molecules could be indicative of a role for this domain in adhesion . This domain contains an initial region rich in α helix followed by four β strands .

Isthmin-1 (ISM1) is a secreted 60 kDa protein first identified in the Xenopus brain isthmus that functions as an endogenous angiogenesis inhibitor. ISM1 binds to cell surface glucose-regulated protein 78 (GRP78) and αvβ5 integrin receptors, inducing endothelial cell apoptosis through both clathrin-dependent endocytosis and direct mitochondrial translocation. It exhibits potent antitumour activity by selectively targeting tumour endothelium and cancer cells overexpressing cell-surface GRP78 .

Sushi domain-containing protein 2 (Susd2) is a possible cytokine receptor for GPR15LG. May be a tumour suppressor; together with GPR15LG has a growth inhibitory effect on colon cancer cells, which includes G1 cell cycle arrest . It is known as Defecation cycle abnormal dec-7 (dec-7) in Caenorhabditis elegans and Protein mesh in Drosophila melanogaster.
Curli production assembly/transport component CsgG (Curli_assmbl/transp-comp_CsgG)
Type: Family

CsgG is an outer membrane-located lipoprotein that is highly resistant to protease digestion. During curli assembly, an adhesive surface fibre, CsgG is required to maintain the stability of CsgA and CsgB . May be involved in the biogenesis of curli organelles.
Cyclotide (Cyclotide)
Type: Family

Cyclotides (cyclo peptides) are plant peptides of ~30 amino acids with a head to-tail cyclic backbone and six cysteine residues involved in three disulphide bonds. The cyclotides are extremely resistant to proteolysis and are remarkably stable. Cyclotides display a diverse range of biological activities, including uterotonic activity, inhibition of neurotensin binding, hemolytic, anti-HIV and anti-microbial activity. This range of biological activities makes cyclotides amenable to potential pharmaceutical and agricultural applications. Although their precise role in plants has not yet been reported, it appears that they are most likely present as defence molecules .

The three-dimensional structure of cyclotides is compact and contains a number of β-turns, three β-strands arranged in a distorted triple-stranded β-sheet, a short helical segment, and a network of disulphide bonds which form a cystine knot. The cystine knot consists of an embedded ring in the structure, formed by two disulphide bonds and their connecting backbone segments is threaded by a third disulphide bond. Although the cystine knot motif is now well known in a wide variety of proteins, the cyclotides remain as the only example in which a cystine knot is embedded within a circular protein backbone, a motif that is referred to as the cyclic cystine knot (CCK) .

Cyclotides can be separated into two sub-families, one of which tends to contain a larger number of positively charged residues and has a bracelet-like circularisation of the backbone. The second subfamily contains a backbone twist due to a cis-Pro peptide bond and may conceptually be regarded as a molecular Moebius strip . Bracelet and Moebius families of cyclotides possess a Knottin scaffold. The cyclotide family of proteins is abundant in plants from the Rubiaceae and Violaceae families and includes:

Kalata B1.

Circulins.

Cyclopsychotride A.

Cycloviolacin O1.

Also included in this entry are cliotides from the leguminous plant Clitoria ternatea. These are cyclotides with known medicinal properties that have antimicrobial activities against Escherichia coli and are cytotoxic to HeLa cells .

This entry also includes chassatides. There are 18 chassatides peptides: 14 new cyclotides and 4 uncyclotides from the Rubiaceae family. Uncyclotides are the most potent chassatides for antimicrobial, cytotoxic, and hemolytic activities. All uncyclotides belong to the bracelet subfamily, all lacking the Asn/Asp residue at their C termini, which is crucial for backbone cyclization. Genetic characterization of novel cyclotides revealed that their precursors are highly shortened. They consist of five bracelet, two Möbius, and two hybrid cyclotides. Two Met-oxidized derivatives of chassatide C2 and C11 have been isolated, while we know that oxydation of methionine to methionine sulfoxide (MetO) causes a complete loss of biological activities .
Peptidase C25, Ig-like domain (Peptidase_C25_Ig-like_domain)
Type: Domain

This domain is found in almost all members of MEROPS peptidase family C25, (clan CD). Peptidase family C25 is a protein family found in the bacteria Porphyromonas gingivalis (Bacteroides gingivalis) a Gram-negative anaerobic bacterial species strongly associated with adult periodontitis. One of its distinguishing characteristics and putative virulence properties is the ability to agglutinate erythrocytes . It is a highly proteolytic organism which metabolises small peptides and amino acids. Indirect evidence suggests that the proteases produced by this microorganism constitute an important virulence factor . Protease-encoding genes have been shown to contain multiple copies of repeated nucleotide sequences. These conserved sequences have also been found in haemagglutinin genes .
CRISPR type III-associated protein (RAMP_III_fam)
Type: Domain

This entry represents a group of CRISPR-associated proteins belonging to the type III RAMP (Repair Associated Mysterious Proteins) family . Members including in this family are Csm3, Csm5, Cmr6, Cmr4 and Cmr1.

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
LrgA/CidA family (LrgA/CidA)
Type: Family

This family consists of CidA and LrgA, which are bacterial holin-/antiholin-like proteins that function to control cell death and lysis during biofilm development . The cidAB operon encodes the holin-like counterpart of the lrgAB operon and acts in a manner opposite from that of lrgAB by increasing extracellular murein hydrolase activity and increasing sensitivity to penicillin-induced killing .

This family also includes uncharacterised UPF0299 membrane proteins.
ELK domain (ELK_dom)
Type: Domain

Homeobox genes, which encode homeodomain (HD) transcription factors, are known to be key regulators of both plant and animal development. In plants homeobox genes are divided into several groups by sequences, one of which is the KNOX (for knotted1-type homeobox) family. Proteins of this family share other conserved domains, the KNOX domain and ELK domain, which is immediately upstream of the HD. The ELK domain spans ~21 amino acids and was dubbed for a highly conserved series of Glu, Leu, and Lys amino acids. It could function as a nuclear localization signal. The ELK domain also is considered to act as a protein-protein interaction domain, but the precise role of this domain has not been determined .

The ELK domain contains repeating hydrophobic residues and has been predicted to form an amphipathic helix .
KNOX1 (KNOX1)
Type: Domain

The MEINOX region is comprised of two domains, KNOX1 and KNOX2. KNOX1 plays a role in suppressing target gene expression. KNOX2, essential for function, is thought to be necessary for homo-dimerization .
KNOX2 (KNOX2)
Type: Domain

The MEINOX region is comprised of two domains, KNOX1 and KNOX2. KNOX1 plays a role in suppressing target gene expression. KNOX2, essential for function, is thought to be necessary for homo-dimerization .
PBX, PBC domain (PBX_PBC_dom)
Type: Domain

Pbx proteins are members of the TALE (three-amino-acid loop extension) family of atypical homeodomain proteins, whose members
are characterised by a three-residue insertion between helix 1 and 2 and plays essential roles during embryonic development by participating in interactive TF networks. The heterodimerization of TALE proteins serves as a trigger for precise execution of developmental programs. Examination
of Pbx1 has shown that, in addition to the homeodomain, a short 16-residue C-terminal tail is essential for maximal cooperative interactions with
Hox partners as well as for maximal monomeric binding of Pbx1 to DNA.
PASTA domain (PASTA_dom)
Type: Domain

The PASTA domain (for penicillin-binding protein and serine/threonine kinase associated domain) is an extracellular module of ~70 residues that is found in the C-termini of eukaryotic-like serine/threonine kinases (PSTKs) and high molecular weight penicilin-binding proteins (PBPs). The PASTA domain is distributed mainly in the GRAM-positive bacteria, most notably among species of the genera Bacillus and Clostridia. It is not found in eukaryotes. The PASTA domain occurs both singly and in multiple copies, which suggests that it is a domain rather than a structural repeat. It is found in association with other domains, such as transpeptidase, protein kinase or transglycolase .

The PASTA domain is a small globular fold consisting of three β strands and an α helix, with a loop region of variable length between the first and second β strands .
YCII-related (YCII)
Type: Domain

The majority of proteins in this group contain a single copy of this domain, though it is also found as a repeat. A strongly conserved histidine and a aspartate suggest that the domain has an enzymatic function. This entry also covers what was previously known as the DGPF domain (COG3795), named after the most conserved motif in the alignment. Although its function is unknown it is found fused to a sigma-70 factor family domain in

, suggesting that this domain may plays a role in transcription initiation.
Autotransporter beta-domain (Autotransporte_beta)
Type: Domain

This entry represents a domain found at the C terminus of the bacterial autotransporter proteins it occurs in .

Secretion of protein products occurs by a number of different pathways in bacteria. One of these pathways known as the type V pathway was first described for the IgA1 protease . The protein component that mediates secretion through the outer membrane is contained within the secreted protein itself, hence the proteins secreted in this way are called autotransporters. This family corresponds to the presumed integral membrane β-barrel domain that transports the protein.
Cell division protein FtsQ/DivIB, C-terminal (Cell_div_FtsQ/DivIB_C)
Type: Domain

FtsQ is an essential cell division protein. It may link together the upstream cell division proteins, which are predominantly cytoplasmic, with the downstream cell division proteins, which are predominantly periplasmic . FtsQ may control the correct divisome assembly .

DivIB is a cell division protein from Gram-positive bacteria, probably homologous to Escherichia coli FtsQ. DivIB interacts with FtsL, DivIC and PBP-2B . DivIB plays an essential role in division at high temperatures, maybe by protecting FtsL from degradation or by promoting formation of the FtsL-DivIC complex . It is also required for efficient sporulation at all temperatures .

FtsQ and DivIB have a short N-terminal cytoplasmic domain and a larger C-terminal periplasmic domain . This entry represents the C-terminal region.
Kinetochore protein Nuf2, N-terminal (Kinetochore_Nuf2_N)
Type: Domain

This entry represents the N-terminal domain of kinetochore protein Nuf2, which is part of the Ndc80 complex. This domain fold as a CH domain consisting of a four-helix bundle containing the parallel helices alphaA, alphaC, alphaE, and alphaG, similar to that in Ndc80. These CH domains from Nuf2 and Ndc80 forms the globular rod at one end the complex . The ability of the Ndc80 complex to bind microtubules resides on the tightly packed CH domains from Nuf2 and Ndc80 . This complex binds to the spindle and is required for chromosome segregation and spindle checkpoint activity .
Kinetochore protein Ndc80 (Kinetochore_Ndc80)
Type: Family

Members of this family are components of the mitotic spindle. Ndc80 acts as 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, which is required for chromosome segregation and spindle checkpoint activity . It has been shown that Ndc80 from yeast is part of a complex called the Ndc80p complex . The four Ndc80 complex subunits associate as two rod-like heterodimers (Ndc80:Nuf2 and Spc24:Spc25) . This protein is required for kinetochore integrity and the organisation of stable microtubule binding sites in the outer plate of the kinetochore . Moreover, the NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules .
Apo-citrate lyase phosphoribosyl-dephospho-CoA transferase (CitX)
Type: Family

Members of this protein family are annotated as CitX, containing the CitX domain, the domain is also found in the CitXG bifunctional protein, of the citrate lyase system. CitX transfers the prosthetic group 2'-(5''-triphosphoribosyl)-3'-dephospho-CoA to the citrate lyase gamma chain, an acyl carrier protein. This enzyme may be designated holo-ACP synthase, holo-citrate lyase synthase, or apo-citrate lyase phosphoribosyl-dephospho-CoA transferase. In a few genera, including Haemophilus, this protein occurs as a fusion protein with CitG (

), an enzyme involved in prosthetic group biosynthesis. This CitX family is easily separated from the holo-ACP synthases of other enzyme systems.
Scramblase (Scramblase)
Type: Family

This entry represents phospholipid scramblases. These are plasma membrane proteins, which are conserved from worms to humans. They have been originally identified based on their ability to accelerate the transbilayer movement of phospholipids in a calcium-dependent manner .

Scramblase is palmitoylated and contains a potential protein kinase C phosphorylation site. Scramblase exhibits Ca
2+
-activated phospholipid scrambling activity in vitro. There are also possible SH3 and WW binding motifs. Scramblase is involved in the redistribution of phospholipids after cell activation or injury .
Cytoadherence-linked asexual protein (CLAG)
Type: Family

Clag (cytoadherence linked asexual gene) is a malaria surface protein which has been shown to be involved in the binding of Plasmodium falciparum infected erythrocytes to host endothelial cells, a process termed cytoadherence. The cytoadherence phenomenon is associated with the sequestration of infected erythrocytes in the blood vessels of the brain, cerebral malaria. Clag is a multi-gene family in P. falciparum with at least 9 members identified to date. Orthologous proteins in the rodent malaria species Plasmodium chabaudi suggest that the gene family is found in other malaria species and may play a more generic role in cytoadherence.
NOL6/Upt22 (NOL6/Upt22)
Type: Family

This entry includes NOL6 (or Nrap) from animals and Upt22 from yeasts. Upt22 is a component of the small-subunit processome . It plays a role in channelling aminoacyl-tRNA to the nuclear tRNA export receptor exportin-t .
M-factor (M-factor)
Type: Family

The M-factor is a pheromone produced upon nitrogen starvation in fission yeasts. The production of M-factor is increased by the pheromone signal. The protein undergoes post-translational modification to remove the C-terminal signal peptide, the carboxy-terminal cysteine residue is carboxy-methylated and S-alkylated with a farnesyl residue .
SUN family (SUN)
Type: Family

This entry represents the Sun family from fungi. In budding yeasts there are four identified members: Nca3, Sim1, Sun4 and Uth. They hey share a common C-terminal domain of 258 amino acids bearing 75-85% identity. These C-terminal regions comprise a putative Fe-binding domain consisting in Cys residues organised in a Cys-X5-Cys-X3-Cys-X24-Cys motif . Despite this remarkable homology, the SUN family members have been linked to various, often unrelated cellular processes such as those connected to mitochondrial and cell wall functions. Interestingly, they seem to be involved in the remodelling of the yeast cell wall during the various phases of yeast culture development and under various environmental conditions .
Colicin immunity protein (Colicin_im)
Type: Family

Colicin immunity proteins are plasmid encoded proteins necessary for protecting the cell against colicins. Colicins are toxins released by bacteria during times of stress .
Crustacean neurohormone H (Crust_neurhormone_H)
Type: Domain

Arthropod express a family of neuropeptides which so far consist of the following types of neurohormones:

Crustacean hyperglycemic hormone (CHH). CHH is primarily involved in blood sugar regulation, but also plays a role in the control of molting and reproduction.

Molt-inhibiting hormone (MIH). MIH inhibits Y-organs where molting hormone (ecdysteroid) is secreted. A molting cycle is initiated when MIH secretion diminishes or stops.

Gonad-inhibiting hormone (GIH), also known as vitellogenesis-inhibiting hormone (VIH) because of its role in inhibiting vitellogenesis in female animals.

Mandibular organ-inhibiting hormone (MOIH). MOIH represses the synthesis of methyl farnesoate, the precursor of insect juvenile hormone III in the mandibular organ.

Ion transport peptide (ITP) from locust. ITP stimulates salt and water reabsorption and inhibits acid secretion in the ileum of the locust.

These neurohormones are peptides of 70 to 80 residues which are processed from larger size precursors. They contain six conserved cysteines that are involved in disulphide bonds, as shown in the following schematic representation.

Crustacean neurohormone H proteins are referred to as precursor-related peptides as they are typically co-transcribed and translated with the CHH neurohormone (

). However, in some species this neuropeptide is synthesized as a separate protein. Furthermore, neurohormone H can undergo proteolysis to give rise to 5 different neuropeptides .
CG-1 DNA-binding domain (CG-1_dom)
Type: Domain

CG-1 domains are highly conserved domains of about 130 amino-acid residues containing a predicted bipartite nuclear localisation signal. They are named after a partial cDNA clone isolated from parsley encoding a sequence-specific DNA-binding protein . CG-1 domains are found in CAMTA proteins (for CAlModulin -binding Transcription Activator), which are transcription factors containing a calmodulin-binding domain and ankyrin repeats .
Protein of unknown function DUF326 (DUF326)
Type: Repeat

This entry is a small cysteine-rich repeat. The cysteines mostly follow a C-X(2)-C-X(3)-C-X(2)-C-X(3) pattern, though they often appear at other positions in the repeat as well .
ANTAR domain (ANTAR)
Type: Domain

ANTAR (AmiR and NasR transcription antitermination regulators) is an RNA-binding domain found in bacterial transcription antitermination regulatory proteins . This domain has been detected in various response regulators of two-component systems, which are structured around two proteins, a histidine kinase and a response regulator. This domain is also found in one-component sensory regulators from a variety of bacteria. Most response regulators interact with DNA, however ANTAR-containing regulators interact with RNA. The majority of the domain consists of a coiled-coil.
SpoVA (SpoVA)
Type: Family

Members of this family are all transcribed from the spoVA operon .

Bacillus and Clostridium are two well studied endospore forming bacteria. Spore formation provides a resistance mechanism in response to extreme or unfavourable environmental conditions such as heat, radiation, and chemical agents or nutrient deprivation. The reverse process termed germination takes place where spores develop into growing cells in response to nutrient availability or stress reduction. Nutrient germinant receptors (GRs) and the SpoVA proteins are important players in the germination process. In B. subtilis SpoVAC and SpoVAEB, belonging to this family, are predicted to be membrane proteins, with two to five membrane spanning. Biophysical and biochemical studies suggest that SpoVAC acts as a mechano-sensitive channel with properties that would allow the release of Ca-DPA (dipicolinic acid) and amino acids during germination of the spore. The release of Ca-DPA is a crucial event during spore germination. When expressed in E. coli SpoVAC provides protection against osmotic downshift. Furthermore, SpoVAC acts as channel that facilitates the efflux down the concentration gradient of osmolytes up to a mass of at least 600 Da . Another conserved SpoVA protein in all spore-forming bacteria is SpoVAEb, which appears to be an integral membrane protein with no known function .
Assembly protein (A_protein)
Type: Family

This entry represents assembly/maturation protein (A-protein, MP) from Enterobacteria phages, including bacteriophage MS2. The single-stranded RNA genome of bacteriophage MS2 is 3,569 nt long and encodes four gene products: maturation protein, coat protein, and lysis and replicase proteins . The maturation protein is a necessary constituent in the assembly process of the virus . It is located on the surface of the phage particle and influences the global arrangement of the virus coat . It binds to sequences located toward each end of the genome, hence circularizing it . The single-copy viral maturation protein breaks the symmetry of the capsid, suggesting an exit route for the genome during infection, and it is involved in receptor and genome binding .
Major capsid protein GpE (Major_capsid_GpE)
Type: Family

This entry represents the major capsid protein found in bacteriophages. Major capsid protein assembles to form an icosahedral capsid with a T=7 symmetry . It plays a role in the stabilisation of the condensed form of the DNA molecule in phage heads .

This protein is also found in bacteria, suggesting prophage matches also occur.
Haemolysin activator HlyB, C-terminal (Hemolysn_activator_HlyB_C)
Type: Domain

Haemolysin (HlyA) and related toxins are secreted across both the cytoplasmic and outer membranes of Gram-negative bacteria in a process which proceeds without a periplasmic intermediate. HlyA is directed by an uncleaved C-terminal targeting signal and the HlyD and HlyB translocator proteins .