SII-SWORD/CoKE huggingface dataset:
POTRA domain, BamA/TamA-like (BamA/TamA_POTRA)
Type: Domain

In Gram-negative bacteria, β-barrel proteins are integrated into the outer membrane by the β-barrel assembly machinery, with key components of the machinery being the Omp85 family members BamA and TamA . The BamA periplasmic domain is composed of five globular subdomains in tandem called POTRA motifs. They are key to BAM complex formation and interaction with the substrate β-barrel proteins . TamA has three periplasmic POTRA domains . Outer mebrane proteins with a variable number of POTRA motifs are also found in mitochondria and chloroplasts .
Alcohol acetyltransferase/N-acetyltransferase-like (Atf2/Sli1-like)
Type: Family

This entry includes alcohol O-acetyltransferase 2 (Atf2), PSTB2-interacting protein 1 (PBI1) and N-acetyltransferase Sli1 from budding yeasts. Atf2 catalyses the esterification of isoamyl alcohol by acetyl coenzyme A . PBI1 is a phosphatidic acid-binding protein involved in interorganelle phosphatidylserine (PtdSer) transport . Sli1 confers resistance to the sphingolipid biosynthesis inhibitor drug myriocin (ISP-1). It inactivates ISP-1 by converting it into N-acetyl-myriocin . This entry also includes some uncharacterised proteins, such as C18B11.03c.
Cerato-platanin (Cerato-platanin)
Type: Family

This entry represents a group of fungal proteins involved in plant pathogenesis and elicitation of plant defense responses, including Cerato-platanin (CP) from the Ascomycete Ceratocystis fimbriata f. sp. platani, which causes the severe plant disease: canker stain. This protein occurs in the cell wall of the fungus and is involved in the host-plane interaction and induces both cell necrosis and phytoalexin synthesis which is one of the first plant defense-related events. CP, like other fungal surface proteins, is able to self assemble in vitro . CP is a 120 amino acid protein, containing 40% hydrophobic residues and two S-S bridges. It contains four cysteine residues that form two disulphide bonds . The N-terminal region of CP is very similar to cerato-ulmin, a phytotoxic protein produced by the Ophiostoma species belonging to the hydrophobin family, which also self-assembles .
Interleukin-23 alpha (IL-23_alpha)
Type: Family

This entry represents interleukin-23 subunit alpha, IL-23A (also known as Interleukin-23 subunit p19) associates with IL-12B to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity . IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis . Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells .
ProSAAS (ProSAAS)
Type: Family

Prohormone convertases (PCs) 1 and 2 are a family of eukaryotic subtilisins thought to mediate the proteolytic cleavage of many peptide precursors .

This family represents proSAAS, which belongs to MEROPS inhibitor family I49. It is a neuroendocrine secretory protein which is a potent endogenous PC1 inhibitor . ProSAAS consists of an N-terminal domain and a C-terminal domain separated by a furin cleavage site. The inhibitory region of proSAAS is located in the C-terminal domain and includes the LLRVKR hexapeptide sequence .
However, the distribution of ProSAAS and PC1/3 within the brain is different and their expression is also not coregulated and a wider range of neuronal functions has been reported for ProSAAS, including acting as an amyloid anti-aggregant chaperon in Alzheimer's disease , inhibition of the fibrillation of alpha-synuclein in the substantia nigra of patients with Parkinson's disease and exhibits a neuroprotective function .
This protein has also been associated with tau inclusions in Pick's disease . ProSAAS-derived peptides are involved in several physiologically important processes .
Protein of unknown function DUF1439 (DUF1439)
Type: Family

This family consists of several hypothetical bacterial proteins of around 190 residues in length. Several members of this family are annotated as being putative lipoproteins and are often known as YceB. The function of this family is unknown.
SapC (SapC)
Type: Family

This family contains a number of bacterial SapC proteins approximately 250 residues long. In Campylobacter fetus, SapC forms part of a paracrystalline surface layer (S-layer) that confers serum resistance .
Conjugal transfer, TrbH (Conjugal_tfr_TrbH)
Type: Family

This entry represents TrbH, a bacterial conjugal transfer protein approximately 150 residues long. TrbH contains a putative membrane lipoprotein lipid attachment site .
Protein of unknown unction DUF1444 (DUF1444)
Type: Family

This family contains several hypothetical bacterial proteins of unknown function that are approximately 250 residues long.
Acyclic terpene utilisation, N-terminal (AtuA_N)
Type: Domain

This entry consists of several bacterial and plant proteins of around 400 residues in length. It represents a domain found either as a standalone or at the N terminus of these proteins and combined with distinct domains. One member of this family has been characterised in Pseudomonas citronellolis as AtuA, a member of a gene cluster that is essential for the acyclic terpene utilisation (Atu) pathway .
Inner membrane protein YqiJ, OB-fold domain (YqiJ_OB)
Type: Domain

This entry represents the OB-fold domain found in several bacterial proteins, including the inner membrane protein YqiJ from E. coli (

), whose function is not clear.
Elongation factor G-binding protein, N-terminal (EF-G-binding_N)
Type: Domain

This domain can be found in the N terminus of the FusB (

), FusC (

), and FusD (

) proteins from Staphylococcus aureus. They are elongation factor G (EF-G) binding proteins that are linked to the fusidic acid (FA) resistance in S. aureus .
Uncharacterised protein family AroM (Uncharacterised_AroM)
Type: Family

This family consists of several bacterial and archaeal AroM proteins. In Escherichia coli the aroM gene is cotranscribed with aroL . The function of this family is unknown.
Occludin homology domain (Occludin_ELL)
Type: Domain

This represents a conserved region approximately 100 residues long within eukaryotic occludin proteins and the RNA polymerase II elongation factor ELL. Occludin is an integral membrane protein that localises to tight junctions , while ELL is an elongation factor that can increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by polymerase at multiple sites along the DNA . This shared domain is thought to mediate protein interactions .
Flagellar FlaF (FlaF)
Type: Family

This family consists of several bacterial FlaF flagellar proteins. FlaF and FlaG are trans-acting, regulatory factors that modulate flagellin synthesis during flagellum biogenesis .
N-acetylmuramoyl-L-alanine amidase-like (AmiA-like)
Type: Family

This entry represents a family of bacterial proteins, including N-acetylmuramoyl-L-alanine amidase (AmiA) from Bacteroides uniformis (BACUNI_02947,

). This highly specific enzyme hydrolyses GlcNAc-1,6-anhydro-MurNAc-peptide into disaccharide and stem peptide. It shows an α/β/α three-layered sandwich fold with a catalytic core that consists of a central five-stranded β-sheet and four α-helices. It is structurally related to NlpC/P60 γ-D-Glu-meso-diaminopimelic acid amidases .
Protein of unknown function DUF1465 (DUF1465)
Type: Family

This family consists of several hypothetical bacterial proteins of around 180 residues in length. The function of this family is unknown.
Gonadal family (Gonadal)
Type: Family

This family contains DiGeorge syndrome critical region 6 (DGCR6) proteins (approximately 200 residues long) of a number of vertebrates. DGCR6 is a candidate for involvement in the DiGeorge syndrome pathology by playing a role in neural crest cell migration into the third and fourth pharyngeal pouches, the structures from which derive the organs affected in DiGeorge syndrome . Also found in this family is the Drosophila melanogaster gonadal protein gdl.
Neuroparsin (Neuroparsin)
Type: Family

This family consists of several locust specific neuroparsin proteins. Neuroparsins are produced by the A1 type of protocerebral median neurosecretory cells of the PI-CC system and display pleiotropic activities: inhibition of the effect of juvenile hormone, stimulation of fluid reabsorption of isolated recta, induction of an increase in hemolymph lipid and trehalose levels, and neurotrophic effects .
Defensin-like protein (DEFL)
Type: Family

This family consists of defensin-like proteins from plants. Plant genomes contain several hundred defensin-like (DEFL) genes that encode short cysteine-rich proteins resembling defensins, which are known antimicrobial polypeptides . Arabidopsis thaliana has more than 300 DEFL genes, and they are likely to be involved in both natural immunity and cell-to-cell communication, including pollen-pistil interactions .
Putative stress-induced transcription regulator (ABATE)
Type: Family

The structure of one member of the ABATE domain family consists of a two-domain organisation, with the N-terminal domain presenting a new fold called the ABATE domain that may bind an as yet unknown ligand. The C-terminal domain forms a treble-clef zinc-finger that is likely to be involved in DNA binding. suggests a role as stress-induced transcriptional regulator. Further computational analyses sugeests a role as a stress-induced transcriptional regulator . Members of this family are found in Streptomyces, Rhizobium, Ralstonia, Agrobacterium and Bradyrhizobium species.
DC-EC (CagY_M)
Type: Repeat

This repeat is found in the CagY proteins - part of the CAG pathogenicity island - and involved in delivery of the protein CagA into host cells . It forms part of a surface needle structure, and this repeat may form an α-helical rod structure . The repeat contains a conserved -DC- and -EC-, which are regularly spaced in the alignment.
YdgH/BhsA/McbA-like domain (YdgH/BhsA/McbA-like_dom)
Type: Domain

This domain is found in several Enterobacterial proteins of around 90 residues in length, including E. coli YdgH, YhcN, BhsA and McbA, which play a role in stress response, biofilm formation, and pathogenesis . BhsA (also known as ComC) reduces the permeability of the outer membrane to copper and may decrease biofilm formation by repressing cell-cell interaction and cell surface interaction . Members of this entry have one copy of this domain with the exception of YdgH, which has three. The function of this domain is unknown, however, it is suggested to be directly involved in host-pathogen interaction .
Cytomegalovirus IE1/IE2 (Cytomega_IE1/IE2)
Type: Family

Expression from a human cytomegalovirus early promoter (E1.7) has been shown to be activated in trans by the IE2 gene product. Although the IE1 gene product alone had no effect on this early viral promoter, maximal early promoter activity was detected when both IE1 and IE2 gene products were present . The IE1 protein from cytomegalovirus is also known as UL123.
Gig2-like (Gig2-like)
Type: Family

This entry represents a family of proteins predominantly found in fungi and bacteria, including Gig2 from Candida albicans (

) and Uncharacterized protein YbiU from Escherichia coli. Gig2 is a putative oxidoreductase thought to play a role in the undefined GlcNAc metabolic network. It folds into a single large domain with a cupin like double stranded β-helix core made of eight β-sheets grouped into four major and four minor sheets, which form the distorted β-barrel open at one end, surrounded by 20 α-helices. This protein shows similarity with 2- oxoglutarate dependent Fe containing oxygenases .
Zona-pellucida-binding (Sp38-bd)
Type: Family

This family contains a number of zona-pellucida-binding proteins that seem to be restricted to mammals. These are sperm proteins that bind to the 90kDa family of zona pellucida glycoproteins in a calcium-dependent manner . These represent some of the specific molecules that mediate the first steps of gamete interaction, allowing fertilisation to occur .
Protein of unknown function DUF1481 (DUF1481)
Type: Family

This family consists of several hypothetical bacterial proteins of around 230 residues in length. Members of this family are often referred to as YjaH and are found in the Orders Vibrionales and Enterobacteriales. The function of this family is unknown.
CAMP factor (CAMP_factor)
Type: Family

This family consists of several bacterial CAMP factor (Cfa) proteins, which seem to be specific to Streptococcus species. The CAMP reaction is a synergistic lysis of erythrocytes by the interaction of an extracellular protein (CAMP factor) produced by some streptococcal species with the Staphylococcus aureus sphingomyelinase C (beta-toxin) .
Protein of unknown function DUF1492 (DUF1492)
Type: Family

This entry includes Streptococcus phage 7201, Orf19. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

This entry consists of several hypothetical, highly conserved Streptococcal and related phage proteins. The function of this family is unknown.
Protein of unknown function DUF1493 (DUF1493)
Type: Family

This family consists of several bacterial proteins of around 115 residues in length. Members of this family are largely found in Salmonella and Yersinia species and several have been described as being putative cytoplasmic proteins. The function of this family is unknown.
Regulator EarA-like (EarA-like)
Type: Family

This entry represents EarA from Methanococcus maripaludis (MMP1718,

) and similar sequences widely distributed archaea except for extreme halophiles . EarA is a transcriptional activator that directly regulates the fla operon, which contains genes involved in archaella formation . However, this protein might not always be required for transcription , This protein family was previously known as DUF1495.
D-lyxose isomerase (D-lyxose_isomer)
Type: Family

Members of this family of sugar isomerases belong to the cupin superfamily . The enzyme from Cohnella laevoribosii has been shown to be specific for D-lyxose, L-ribose, and D-mannose . E. coli sugar isomerase (EcSI) has been structurally and functionally characterised and shows a preference for D-lyxose and D-mannose .
Protein of unknown function DUF1499 (DUF1499)
Type: Family

This family consists of several hypothetical bacterial and plant proteins of around 125 residues in length. The function of this family is unknown.
Alpha-2,8-polysialyltransferase (A-2_8-polyST)
Type: Family

This family contains the bacterial enzyme alpha-2,8-polysialyltransferase (approximately 500 residues long). This catalyses the polycondensation of alpha-2,8-linked sialic acid required for the synthesis of polysialic acid (PSA) .
NPR nonapeptide (NPR_nonapeptide)
Type: Repeat

This is a nine residue repeat, which was called NPR after NonaPeptide Repeat. It is found in two malarial proteins and has the consensus EEhhEEhhP where h stands for a hydrophobic amino acid.
Tumor suppressor ARF (Tumor_suppres_ARF)
Type: Family

ARF (also known as p14ARF in the human and p19ARF in the mouse) is an alternative transcript of the INK4a/ARF tumour-suppressor locus that encodes p16INK4a, an inhibitor of cyclin dependent kinases. ARFs are tumour suppressors participating in p53-dependent or independent pathways that restrain abnormal cell growth and maintain genomic stability . ARF interacts with MDM2 and neutralizes MDM2's inhibition of p53 . Mdm2 may also regulate ARF turnover by mediating its degradation through the proteasome . p14ARF has also been shown to interact with E2F factors to form p14ARF-E2F/partner-DNA complexes repressing E2F-dependent transcription .
Protein of unknown function DUF1501 (DUF1501)
Type: Family

This family contains a number of hypothetical bacterial proteins of unknown function approximately 400 residues long.
Phosphate-selective porin O/P (Porin_O/P)
Type: Family

This entry represents the bacterial phosphate-selective porins O and P. These are anion-specific porins, the binding sites of which has a higher affinity for phosphate than chloride ions. Porin O has a higher affinity for polyphosphates, while porin P has a higher affinity for orthophosphate . In Pseudomonas aeruginosa, porin O was found to be expressed only under phosphate-starvation conditions during the stationary growth phase .
Protein of unknown function DUF1502 (DUF1502)
Type: Repeat

This family consists of a number of repeats of around 34 residues in length. Members of this family seem to be found in Talaromyces stipitatus and in Murid herpesvirus 4 (MuHV-4) proteins. The function of these repeats and the proetins in which they are found is unknown.
MDMPI C-terminal (MDMPI_C-term_domain)
Type: Domain

This domain is found at the C terminus of the mycothiol maleylpyruvate isomerase enzyme (MDMPI). The structure of this protein has been solved . This domain appears weakly similar to

.
Telomere-binding protein subunit beta (TEBB)
Type: Family

Telomeres are specialised protein-DNA complexes that compose the ends of eukaryotic chromosomes. Telomeres protect chromosome termini from degradation and recombination and act together with telomerase to ensure complete genome replication. TEBP beta forms a complex with TEBP alpha and this complex is able to recognise and bind ssDNA to form a sequence-specific, telomeric nucleoprotein complex that caps the very 3' ends of chromosomes .

This entry represents Telomere-binding protein subunit beta (TEBB, also known as TEBP beta), mainly found in the eukaryotic taxon Oxytrichidae.
Protein of unknown function DUF1506 (DUF1506)
Type: Family

This entry represents proteins found primarily in Borrelia species. Their function is unknown.
C1orf43 (C1orf43)
Type: Family

This family consists of several eukaryotic C1orf43 and related proteins. C1orf43 is also known as NICE-3. The gene encoding C1orf43 is part of the epidermal differentiation complex (EDC), which comprises a large number of genes that are of crucial importance for the maturation of the human epidermis . The function of C1orf43 is unknown.
Bacteriophage Mu, Baseplate protein gp46 (Phage_Mu_Gp46)
Type: Family

This entry represents Baseplate protein gp46 from Bacteriophage Mu (also known as Gene product V or GpV), a probable connector between the central and peripheral parts of the baseplate that may be involved in tail assembly .

This protein family also includes proteins from bacterial prophages, such as Mu-like prophage FluMu protein gp46 from Haemophilus influenzae.
Protein of unknown function Gp111 (Gp111)
Type: Family

This family consists of several proteins whose function is not known. It is named after the Streptococcus bacteriophage Gp111 protein.
Domain of unknown function DUF1508 (DUF1508)
Type: Domain

This entry represents a domain that is often found as tandem repeats in proteins such as YegP from Escherichia coli. This domain covers the whole length of the protein in HVO_2922 from Haloferax volcanii ({swissprot:D4GXU1]), a small protein whose expression seem to be stress-regulated. It shows four β-strands and one α-helix . Its specific function remains unknown.
Herpesvirus UL37, HHV-5-related (Herpes_UL37_HHV-5-rel)
Type: Family

This family consists of several Betaherpesvirus immediate-early glycoprotein UL37 sequences. The human cytomegalovirus (HCMV) UL37 immediate-early regulatory protein is a type I integral membrane N-glycoprotein which traffics through the ER and the Golgi network .
Gammaherpesvirus latent membrane protein 2 (Herpes_LMP2)
Type: Family

This family consists of several Gammaherpesvirus latent membrane protein (LMP2) proteins. Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4) is a human gammaherpesvirus that infects and establishes latency in B lymphocytes in vivo. The latent membrane protein 2 (LMP2) gene is expressed in latently infected B cells and encodes two protein isoforms, LMP2A and LMP2B, that are identical except for an additional N-terminal 119 aa cytoplasmic domain which is present in the LMP2A isoform. LMP2A is thought to play a key role in either the establishment or the maintenance of latency and/or the reactivation of productive infection from the latent state. It modulates B-cell receptor signal transduction through its association with the cellular tyrosine kinases Lyn and Syk via specific motifs at the N-terminal tail domain. LMP2A also modulates the immune system reducing infected B cells recognition by EBV-specific CD8+ T cells . The significance of LMP2B and its role in pathogenesis remain unclear. It is suggested that it may be a negative regulator of LMP2A .
Acidic phosphoprotein PCEMA1 (PCEMA1)
Type: Family

This family consists of several acidic phosphoprotein precursor PCEMA1 sequences which appear to be found exclusively in Plasmodium chabaudi. PCEMA1 is an antigen that is associated with the membrane of the infected erythrocyte throughout the entire intraerythrocytic cycle . The exact function of this family is unclear.
Marek disease virus, LORF3 (Marek_disease_virus_LORF3)
Type: Family

This family consists of several uncharacterised viral proteins, which include LORF2 from the Marek's disease-like viruses (Meleagrid herpesvirus 1 (MeHV-1) and LORF3 from Gallid herpesvirus 2. Members of this family are typically around 400 residues in length. The function of this family is unknown.
6-Cysteine (6-Cys) domain (6_CYS_dom)
Type: Domain

This entry represents the 6-Cys domain.

The 6-Cysteine (6-Cys) domain is found in Plasmodium proteins that are expressed in all stages of the parasite life cycle in both the vertebrate and mosquito hosts. The domain is of roughly 120 amino acids and contains six positionally conserved cysteines. It might occur in 1-14 copies per protein, either as the sole globular domain or in combination wih β-helix-forming hexapeptide repeats as is the case of sequestrin. It is generally found in tandem pairs of A-type and B-type domains. Previously believed to be exclusive to Plasmodium, the 6-Cys domain also exists in proteins found in all members of the aconoidasidan (hematozoan) clade of Apicomplexa, which unites the haemosporidians (Plasmodium) and piroplasms) .

The 6-cys domain is a β-sandwich formed by two sheets with a mixture of parallel and antiparallel strands. Three disulfide bonds are present in the 6_Cys domain with C1-C2, C3-C6, and C4-C5 connectivity. C1-C2 and C3-C6 pin together the two sheets of the β-sandwich, whereas C4-C5 links an ancyllary loop to the core domain .

Some Plasmodium proteins known to contain a 6-Cys domain are listed below:

Pfs48/45, involved in male/female gamete fusion in the mosquito midgut. It is predicted to be glycosylphosphatidylinositol (GPI)-anchored to the gamete surface.

Pfs230, involved in male/female gamete fusion in the mosquito midgut. It is a soluble protein that associates with the gamete membrane by binding to Pfs48/45.

Pfs47, involved in male/female gamete fusion in the mosquito midgut. It is found on female gametes.

P52, expressed in the sporozoite. May be required for invasion of hepatocytes and to promote normal development in the liver.

P36, expressed in the sporozoite. May be required for invasion of hepatocytes and to promote normal development in the liver.

Pf41, located on the surface of merozoites and has a signal sequence.

Pf38, located on the surface of merozoites. It has a signal sequence and is GPI-anchored to the merozoite surface.

Pf12, located on the surface of merozoites. It has a signal sequence and is GPI-anchored to the merozoite surface.

Pf92, located on the surface of merozoites. It has a signal sequence and is GPI-anchored to the merozoite surface.