SII-SWORD/CoKE huggingface dataset:
Protein of unknown function DUF1372 (DUF1372)
Type: Family

This family consists of several Streptococcus bacteriophage sequences and related proteins from Streptococcus species. Members of this family are typically around 100 residues in length and their function is unknown.
Protein of unknown function DUF1375 (DUF1375)
Type: Family

This family consists of several hypothetical, putative lipoproteins of around 80 residues in length. Members of this family seem to be specific to the class Gammaproteobacteria. The function of this family is unknown.
Protein of unknown function DUF1376 (DUF1376)
Type: Family

This entry includes Bacteriophage PBC5 (Sinorhizobium phage PBC5), Orf49. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

This family consists of several hypothetical bacterial proteins of around 95 residues in length. The function of this family is unknown.
Merozoite surface protein-type (Merozoite_SPAM)
Type: Family

This entry consists of several Plasmodium falciparum SPAM (secreted polymorphic antigen associated with merozoites) proteins, also know as merozoite surface proteins. Variation among SPAM alleles is the result of deletions and amino acid substitutions in non-repetitive sequences within and flanking the alanine heptad-repeat domain. Heptad repeats in which the a and d position contain hydrophobic residues generate amphipathic α-helices which give rise to helical bundles or coiled-coil structures in proteins. SPAM is an example of a P. falciparum antigen in which a repetitive sequence has features characteristic of a well-defined structural element .
Autographa californica nuclear polyhedrosis virus (AcMNPV), Protein AC18 (AcMNPV_AC18)
Type: Family

This entry represents Protein AC18 from Autographa californica nuclear polyhedrosis virus (AcMNPV) and similar proteins from the viral family Baculoviridae. AC18 may play a role in occlusion-derived virions (ODV) formation and/or regulation of late viral gene expression . It interacts with the protein FP25, which is related to polyhedrin formation .
Protein of unknown function DUF1385 (DUF1385)
Type: Family

This family contains a number of hypothetical bacterial proteins of unknown function approximately 300 residues in length. Some family members are predicted to be metal-dependent.
VDE lipocalin domain (VDE_dom)
Type: Domain

This entry represents the conserved lipocalin domain within plant violaxanthin de-epoxidase (VDE), which is thought to bind xanthophyll molecules in all-trans configuration. In higher plants, violaxanthin de-epoxidase forms part of a conserved system that dissipates excess energy as heat in the light-harvesting complexes of photosystem II (PSII), thus protecting them from photo-inhibitory damage .
Terminase small subunit, Skunalikevirus-type (Terminase_ssu_Skunalikevirus)
Type: Family

This family consists of several putative Lactococcus bacteriophage terminase small subunit proteins . The exact function of this family is unknown.
Repeat of unknown function DUF1388 (DUF1388)
Type: Repeat

This entry consists of several repeats of around 29 residues in length. Members of this family are found in the variable surface lipoproteins in Mycoplasma bovis and in mammalian neurofilament triplet H (NefH or NF-H) proteins. This repeat contains several Lys-Ser-Pro (KSP) motifs and in NefH these are thought to function as the main target for neurofilament directed protein kinases in vivo .
AttH domain (AttH_dom)
Type: Domain

This domain is found in bacterial and fungal proteins that contain the AttH-like fold characterised by two flattened, orthogonally packed, β-barrels of lipocalin-like topology. Proteins containing this domain include

(also known as NE1406), an all-β protein with an AttH-like fold .
Protein of unknown function DUF1389 (DUF1389)
Type: Family

This family consists of several hypothetical bacterial proteins, which seem to be specific to Chlamydiia. Members of this family are typically around 400 residues in length. The function of this family is unknown.
Large ribosomal subunit protein mL37/mL65 (Ribosomal_mL37/mL65)
Type: Family

This entry consists of several eukaryotic mitochondrial 28S ribosomal protein mL65 (previously known as mitochondrial ribosomal protein MRPS30 and programmed cell death protein 9 PDCD9). The exact function is unknown although it is known to be a component of the mitochondrial ribosome and a component in cellular apoptotic signalling pathways . This entry also contains the mitochondrial 39S ribosomal protein mL37.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Maltose operon periplasmic (MalM)
Type: Family

This family consists of several maltose operon periplasmic protein precursor (MalM) sequences. The function of this family is unknown .
Prenylcysteine lyase (Prenylcys_lyase)
Type: Domain

This entry represents a conserved region found in a group of prenylcysteine lyases (

) that are approximately 500 residues long. Prenylcysteine lyase is a FAD-dependent thioether oxidase that degrades a variety of prenylcysteines, producing free cysteine, an isoprenoid aldehyde and hydrogen peroxide as products of the reaction . It has been noted that this enzyme has considerable homology with ClP55, a 55kDa protein that is associated with chloride ion pumps .
B9-type C2 domain (C2_B9-type_dom)
Type: Family

The C2 domain is one of the most prevalent eukaryotic lipid-binding domains deployed in diverse functional contexts. Distinct versions of the C2 domain have been recognized, the classical C2, the PI3K-type, the tensin-type, the B9-type, the DOCK-type, the NT-type and the Aida-type. Despite their limited sequence similarity, all C2 domains contain at their core a compact β-sandwich composed of two four-stranded β-sheets with highly variable inter-strand regions that might contain one or more α-helices. One feature that is highly conserved in the C2 domains is the pair of hydrophobic residues on the upper part of the β-sheet, which are involved in imparting a curvature of the sheet that allows formation of a concave ligand-binding area .

This entry represents a family of B9-type C2 domain containing proteins, found in ciliary basal body associated proteins. Although its specific function is unknown, a cilia-specific role has been suggested for the poorly characterised B9-type C2 domain .

Some proteins known to contain a B9-type C2 domain are listed below:

Mammalian Tectonic-like complex member MKS1 (also known as Meckel syndrome 1 , MKS1). The tectonic-like complex is localised at the transition zone of primary cilia and acts as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. It is involved in centrosome migration to the apical cell surface during early ciliogenesis . The homologue in Drosophila melanogaster is required for ciliary structure and function .

Mammalian proteins B9D1 and B9D2. B9D1 is required for ciliogenesis and sonic hedgehog/SHH signaling .
Peroxisome assembly protein 26 (Pex26)
Type: Family

Pex26 is a type II peroxisomal membrane protein that recruits Pex6-Pex1 complexes to peroxisomes . Mutations in the Pex26 gene cause peroxisome biogenesis disorder complementation group 8 (PBD-CG8) and peroxisome biogenesis disorder 7A/B (PBD7A/B) .
Triadin (Triadin)
Type: Family

Triadin was first identified from rabbit skeletal muscle sarcoplasmic reticulum as an abundant single transmembrane protein . It binds to ryanodine receptor and calsequestrin in a Ca2+-dependent manner . Later, several triadin isoforms produced by the alternative splicing of a single TRDN gene were identified . These isoforms have different localisations and binding partners .
Microcystin LR degradation protein MlrC, C-terminal (MlrC_C)
Type: Domain

Proteins in this entry are involved in degradation of the cyanobacterial heptapeptide hepatotoxin microcystin LR, and are encoded in the mlr gene cluster . MlrC from Sphingomonas wittichii (strain RW1 / DSM 6014 / JCM 10273) is believed to mediate the last step of peptidolytic degradation of the tetrapeptide. It is suspected to be a metallopeptidase based on homology to known peptidases and its inhibition by metal chelators. The proteins encoded by the mlr cluster may be involved in cell wall peptidoglycan cycling and subsequently act fortuitously in hydrolysis of microcystin LR.

This entry represents the C-terminal region of these proteins.
Glycine rich protein (GRP)
Type: Family

This family consists of glycine rich proteins, including Arabidopsis AtGRP3 (At2g05520). AtGRP3 interacts with the receptor-like kinase AtWAK1 and functions in root size determination during development and in Aluminum stress .
Fibronectin-attachment (FAP)
Type: Domain

This family contains bacterial fibronectin-attachment proteins (FAP) which are rich in alanine and proline and seem to be restricted to mycobacteria. These proteins contain a fibronectin-binding motif that allows mycobacteria to bind to fibronectin in the extracellular matrix .
Domain of unknown function DUF1400 (DUF1400)
Type: Domain

This domain is specific to cyanobacterial proteins, its function and the function of the proteins it is associated with, are uncharacterised.
Citrus tristeza virus P33 (CTV_P33)
Type: Family

This family consists of several Citrus tristeza virus (CTV) P33 proteins. The function of P33 is unclear although it is known that the protein is not needed for virion formation .
Kaposi s sarcoma-associated herpesvirus K8 (KSHV_K8)
Type: Family

This family consists of Human herpesvirus 8 (HHV-8, Kaposi's sarcoma-associated herpesvirus) K8 proteins. HHV-8 is a human Gammaherpesvirus related to Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4) and Saimiriine herpesvirus 2 (Herpesvirus saimiri). HHV-8 open reading frame K8 encodes a basic region-leucine zipper protein of 237 aa that homodimerises. K8 interacts and co-localises with human SNF5 (

), a cellular chromatin-remodelling factor, both
in vivo
and
in vitro
. K8 is thought to function as a transcriptional activator under specific conditions and its transactivation activity requires its interaction with the cellular chromatin remodelling factor hSNF5 .
Poxvirus, TNF receptor-II, C-terminal (Poxvirus_TNF-rcpt-II_C)
Type: Domain

This domain is found at the C-terminal end of Soluble TNF receptor II from Cowpox virus (CRMB1) and Cytokine response-modifying protein B from Variola virus (CrmB), and differently located in other sequences from poxvirus, including Protein OPG192 and Protein C8 from Vaccinia virus. CRMB1 and CrmB inhibit host immune defence by binding to host TNF and various chemokines in the extracellular space . They bind host CC chemokines (beta chemokines) and CXC chemokines (alpha chemokines) . The function of OPG192 and C8 proteins is unknown.
YfgJ-like (YfgJ-like)
Type: Family

This family, previously known as DUF1407, consists of several short bacterial proteins, including Uncharacterised protein YfgJ from E. coli (

) and other related proteins mainly from proteobacteria. Members of this entry have 8 highly conserved cysteine residues, which form two zinc ribbon domains.
Chemotaxis protein CheA, P2 response regulator-binding (CheA_P2-bd)
Type: Domain

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions . Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk . These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more . Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) . The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.

A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response .

Signal transducing histidine kinases are the key elements in two-component signal transduction systems, which control complex processes such as the initiation of development in microorganisms . Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation , and CheA, which plays a central role in the chemotaxis system . Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and (with bifunctional enzymes) the phosphotransfer from aspartyl phosphate back to ADP or to water . The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily.

The response regulators for CheA bind to the P2 domain, which is found between

and

as either one or two copies. Highly flexible linkers connect P2 to the rest of CheA and impart remarkable mobility to the P2 domain. This feature is thought to enhance the inter CheA dimer phosphotransfer reactions within the signalling complex, thereby amplifying the phosphorylation signal .
Flagellar hook-associated protein 2, C-terminal (FliD_C)
Type: Domain

The flagellar hook-associated protein 2 (HAP2 or FliD) forms the distal end of the flagella, and plays a role in mucin specific adhesion of the bacteria . This alignment covers the C-terminal region of the flagellar hook-associated protein 2.
Flagellin hook, IN motif (Flagellin_hook_IN_motif)
Type: Conserved_site

The function of this region is not clear, but it is found in many flagellar hook proteins, including FliD homologues . This motif is found in single copy or repeated in various flagellar proteins. Conserved Ile-Asn (IN) residues are seen at the centre of the motif. The diversity of these motifs makes it likely that some members of the family are not identified.
Domain of unknown function DUF1409 (DUF1409)
Type: Domain

This represents a short conserved region (approximately 50 residues long), sometimes repeated, within a number of hypothetical Oryza sativa proteins of unknown function.
Hypersensitivity response secretion-like, HrpJ (HrpJ-like)
Type: Domain

This entry represents a conserved region approximately 200 residues long within a number of bacterial hypersensitivity response secretion protein HrpJ and similar proteins. HrpJ forms part of a type III secretion system through which, in phytopathogenic bacterial species, virulence factors are thought to be delivered to plant cells . This entry also includes the InvE invasion protein from Salmonella. This protein is involved in host parasite interactions and mutations in the InvE gene render Salmonella typhimurium non-invasive . InvE S. typhimurium mutants fail to elicit a rapid Ca2+ increase in cultured cells, an important event in the infection procedure and internalisation of S. typhimurium into epithelial cells . This family includes bacterial SepL and SsaL proteins. SepL plays an essential role in the infection process of enterohemorrhagic Escherichia coli and is thought to be responsible for the secretion of EspA, EspD, and EspB . SsaL of Salmonella typhimurium is thought to be a component of the type III secretion system .
Protein of unknown function DUF1413 (DUF1413)
Type: Family

This family consists of several hypothetical bacterial proteins, which seem to occur in predominantly firmicute species. Members of this family are typically around 100 residues in length. The function of this family is unknown.
Protein of unknown function DUF1416 (DUF1416)
Type: Family

This family consists of several hypothetical bacterial proteins of around 100 residues in length. Members of this family appear to be Actinomycete specific. The function of this family is unknown.
Protein of unknown function DUF1418 (DUF1418)
Type: Family

This family consists of several hypothetical Enterobacterial proteins of around 100 residues in length. Members of this family are often described as YbjC. In Escherichia coli the ybjC gene is located downstream of nfsA (which encodes the major oxygen-insensitive nitroreductase). It is thought that nfsA and ybjC form an operon an its promoter is a class I SoxS-dependent promoter . The function of this family is unknown.
Heterokaryon incompatibility Het-C (Het-C)
Type: Family

In filamentous fungi, het loci (for heterokaryon incompatibility) are believed to regulate self/nonself-recognition during vegetative growth. As filamentous fungi grow, hyphal fusion occurs within an individual colony to form a network. Hyphal fusion can occur also between different individuals to form a heterokaryon, in which genetically distinct nuclei occupy a common cytoplasm. However, heterokaryotic cells are viable only if the individuals involved have identical alleles at all het loci .
HemY, N-terminal (HemY_N)
Type: Domain

This entry represents the N terminus (approximately 150 residues) of bacterial HemY porphyrin biosynthesis proteins. These are membrane protein involved in a late step of protoheme IX synthesis .
Protein of unknown function DUF1420 (DUF1420)
Type: Family

This family consists of several hypothetical putative lipoproteins which seem to be found specifically in the bacterium Leptospira. Members of this family are typically around 670 resides in length and their function is unknown.
N-acylglucosamine 2-epimerase/Cellobiose 2-epimerase (AGE/CE)
Type: Family

This protein family includes cellobiose 2-epimerase, N-acylglucosamine 2-epimerase (GlcNAc 2-epimerase), sulfoquinovose isomerase enzymes and similar sequences from cellular organisms . N-acylglucosamine 2-epimerase converts N-acyl-D-glucosamine to N-acyl-D-mannosamine. Cellobiose 2-epimerase enzymes catalyse the reversible epimerization of cellobiose to 4-O-beta-D-glucopyranosyl-D-mannose (Glc-Man). Sulfoquinovose isomerase catalyses the isomerization of sulfoquinovose (SQ) to 6-deoxy-6-sulfo-D-fructose (SF).
UBA-like domain DUF1421 (DUF1421)
Type: Domain

This domain represents a conserved region that has a UBA-like fold. It is found in a number of plant proteins of unknown function.
Portal protein Gp20 (Portal_Gp20)
Type: Family

This family consists of several bacteriophage T4-like capsid assembly (or portal) proteins. The exact mechanism by which the double-stranded (ds) DNA bacteriophages incorporate the portal protein at a unique vertex of the icosahedral capsid is unknown. In phage T4, there is evidence that this vertex, constituted by 12 subunits of gp20, acts as an initiator for the assembly of the major capsid protein and the scaffolding proteins into a prolate icosahedron of precise dimensions. The regulation of portal protein gene expression is an important regulator of prohead assembly in bacteriophage T4 . This family represents the protease responsible for the proteolysis of head proteins, a critical step in the morphogenesis of many tailed phages, Cleavage facilitates the conversion of the prohead to the mature capsid. All these cleavages are carried out by action at consensus S/A/G-X-E recognition sequences at 39 cleavage sites. Evidence of multiple processing sites in nine phiKZ proteins appears to represent a built-in mechanism by which the phage ensures that the majority of the propeptide regions are removed, and emphasizes the essential nature of processing in phiKZ-head morphogenesis . The family is classified by MEROPS as a serine peptidase.
Protein of unknown function DUF1425 (DUF1425)
Type: Family

This family consists of uncharacterised bacterial proteins predominantly found in Proteobacteria, including YcfL from Escherichia coli and Putative lipoprotein from Campylobacter jejuni. The protein adopts a single domain configuration with two β-sheets formed respectively by three and four β-strands (β-sandwich) and contains a Greek key motif, representing a singular variant of the Ig-like fold. Many proteins of this group have a lipid attachment site at the N-terminal of this domain, which together with the structure solved, suggests a role in bacterial lipoproteins .
Stress-inducible humoral factor Turandot (Turandot)
Type: Family

This family consists of several Drosophila species specific Turandot proteins. The Turandot A (TotA) gene encodes a humoral factor, which is secreted from the fat body and accumulates in the body fluids. TotA is strongly induced upon bacterial challenge, as well as by other types of stress such as high temperature, mechanical pressure, dehydration, UV irradiation, and oxidative agents. It is also upregulated during metamorphosis and at high age. Flies that overexpress TotA show prolonged survival and retain normal activity at otherwise lethal temperatures. Although TotA is only induced by severe stress, it responds to a much wider range of stimuli than heat shock genes such as hsp70 or immune genes such as Cecropin A1 . This proteins are regulated by the JAK/STAT and Imd pathways and Mekk1 .
Phlebovirus glycoprotein G1 (Phlebovirus_G1)
Type: Domain

This domain is found in several Phlebovirus glycoprotein G1 sequences. Members of the Bunyaviridae family acquire an envelope by budding through the lipid bilayer of the Golgi complex. The budding compartment is thought to be determined by the accumulation of the two heterodimeric membrane glycoproteins G1 and G2 in the Golgi .