SII-SWORD/CoKE huggingface dataset:
Protein of unknown function DUF1181 (DUF1181)
Type: Family

This family consists of several hypothetical proteins of around 120 residues in length which are found specifically in Trypanosoma brucei. The function of this family is unknown.
Store-operated calcium entry-associated regulatory factor (SARAF)
Type: Family

SARAF is an endoplasmic reticulum membrane resident protein that serves as a negative regulator of store-operated Ca2+ entry (SOCE) involved in protecting cells from Ca2+ overfilling. It is a single pass ER membrane protein whose systolic-facing domain is responsible for activity and whose luminary-facing domain carries out a regulatory function in conjunction with another membrane protein STIM, an ER single pass membrane protein that detects changes in ER Ca2+ levels through its EF-hand, conserved Ca2+ binding domain. STIM is the major target for SARAF regulation, and thus SARAF negatively regulates the SOCE entry of calcium into cells protecting them from overfilling .
Protein of unknown function DUF1184 (DUF1184)
Type: Family

This family contains a number of hypothetical proteins of unknown function from Arabidopsis thaliana.
Amino acid synthesis, putative (AA_synth_put)
Type: Family

This family of proteins is structurally similar to proteins with the Bacillus chorismate mutase-like (BCM-like) fold. This structure, combined with its genomic context, suggest that it has a role in amino acid synthesis .
Stage III sporulation protein AC (Spore_III_AC)
Type: Family

This family consists of several bacterial stage III sporulation protein AC (SpoIIIAC) sequences. The exact function of this family is unknown.
Membrane protein SUR7/Rim9-like, fungi (SUR7/Rim9-like_fungi)
Type: Family

This entry consists of several fungal-specific membrane proteins, including Sur7 and Rim9.

This entry also includes PalI which is part of a pH signal transduction cascade. Based on the similarity of PalI to the yeast Rim9 meiotic signal transduction component it has been suggested that PalI might be a membrane sensor for ambient pH .
Protein of unknown function DUF1187 (DUF1187)
Type: Family

This family consists of several short, hypothetical bacterial proteins of around 62 residues in length. Members of this family are found in Escherichia coli and Salmonella typhi. The function of this family is unknown.
FeGP cofactor biosynthesis protein, methyltransferase HcgC (HcgC)
Type: Family

The iron guanylylpyridinol (FeGP) cofactor biosynthesis enzymes are encoded in a cluster of at least seven conserved genes (hcgA-G). This family represents the (SAM)-dependent methyltransferase HgcC , which covalently attaches the methyl group at the 3-position of the pyridinol ring. It is predominantly found as a monomer in solution, composed of a Rossmann-like coenzyme-binding-domain consisting of six parallel and one peripheral antiparallel strand flanked by six α-helices and a smaller α/β domain.
Protein of unknown function DUF1189 (DUF1189)
Type: Family

This family is predominantly composed of bacterial proteins. Their function is unknown, although one family member,

, has been suggested to have a role in maltodextrin utilisation .
Melon necrotic spot virus P7B (MNSV_P7B)
Type: Family

This family consists of several Melon necrotic spot virus (MNSV) P7B proteins. The function of this family is unknown.
Biofilm formation YgiB (Biofilm_formation_YgiB)
Type: Family

The proteins in this entry, which include YgiB, are functionally uncharacterised, however, transcription of ygiB is induced upon biofilm formation compared to planktonic growth in both exponential and stationary phase. Induction of expression was found to be dependent on the presence of the F plasmid . Biofilm formation is impaired in mutants of ygiB .
Putative small multi-drug export (Sm_multidrug_ex)
Type: Family

This family contains a small number of putative small multi-drug export proteins.
Cell surface antigen I/II A repeat (Surface_Ag_I_II_A_rpt)
Type: Repeat

This entry represents the A region of alanine-rich repeats found in different species of Streptococcus, which forms a long α-helix that intimately intertwines into a left-handed supercoiled structure with the P repeat polyproline II (PPII) helix to form an unusually long and narrow stalk .

Antigen I/II (Ag I/II) family proteins are sortase anchored cell surface adhesins that are nearly ubiquitous across streptococci and contribute to many streptococcal diseases, including dental caries, respiratory tract infections, and meningitis. They appear to be multifunctional adhesins with affinities to various host substrates, acting to mediate attachment to host surfaces and stimulate immune responses from the colonized host. Each of the polypeptides possesses seven structural regions, comprising a signal sequence, a highly charged N-terminal region, an alanine-rich repetitive domain (A region), a globular domain termed the V-domain based on the variability observed in this region between strains, a proline-rich repetitive region (P region), a C-terminal domain, and cell wall-anchoring sequences. proteins adopt a cell wall-anchored stalk structure formed by interactions between the intertwined A- and P-domains, which projects the V-domain containing a binding cleft away from the cell surface. This cleft may be used to promote streptococcal colonization of various tissues via both direct cellular adherence or interaction with extracellular matrix components .
Protein of unknown function DUF1192 (DUF1192)
Type: Family

This family consists of several short, hypothetical, bacterial proteins of around 60 residues in length. The function of this family is unknown.
GPI biosynthesis protein Pig-F (GPI_biosynthesis_protein_Pig-F)
Type: Family

Glycosylphosphatidylinositol anchor biosynthesis protein Pig-F is involved in glycosylphosphatidylinositol (GPI) anchor biosynthesis . This family also includes the Pif-F homologue GPI11 (glycosylphosphatidylinositol anchor biosynthesis protein 11) . It is involved in the ethanolamine-phosphate transfer-step of GPI biosynthesis .
FAM20, C-terminal (FAM20_C)
Type: Domain

This entry represents the C-terminal of the eukaryotic secreted Golgi casein kinase protein FAM20C. FAM20C is the Golgi casein kinase that phosphorylates secretory pathway proteins within Ser-x-Glu/pSer motifs. Mutations in the FAM20C gene cause Raine syndrome, an autosomal recessive osteosclerotic bone dysplasia .
Signal peptidase complex subunit 2 (Spc2/SPCS2)
Type: Family

This family represents the Signal peptidase complex subunit 2 (SPCS2) and its homologues, such as Spc2 from budding yeasts. The signal peptidase complex cleaves the signal sequence from proteins targeted to the endoplasmic reticulum (ER). Mammalian signal peptidase is as a complex of five different polypeptide chains , while the budding yeast SPC comprises four proteins . Budding yeast Spc2 has been shown to be a nonessential component of the signal peptidase complex . Spc2 has been shown to enhance the enzymatic activity of the SPC and facilitate the interactions between different components of the translocation site .

Translocation of polypeptide chains across the endoplasmic reticulum (ER) membrane is triggered by signal sequences. Subsequently, signal recognition particle interacts with its membrane receptor and the ribosome-bound nascent chain is targeted to the ER where it is transferred into a protein-conducting channel. At some point, a second signal sequence recognition event takes place in the membrane and translocation of the nascent chain through the membrane occurs. The signal sequence of most secretory and membrane proteins is cleaved off at this stage. Cleavage occurs by the signal peptidase complex (SPC) as soon as the lumenal domain of the translocating polypeptide is large enough to expose its cleavage site to the enzyme. The signal peptidase complex is possibly also involved in proteolytic events in the ER membrane other than the processing of the signal sequence, for example the further digestion of the cleaved signal peptide or the degradation of membrane proteins .
Citrus tristeza virus 6kDa protein (CTV_6kDa)
Type: Family

This family consists of several Citrus tristeza virus (CTV) 6kDa, 51 residue long hydrophobic (P6) proteins. The function of this family is unknown.
Protein of unknown function DUF1198 (DUF1198)
Type: Family

This family consists of several bacterial proteins of around 150 residues in length which are specific to Escherichia coli, Salmonella species and Yersinia pestis. The function of this family is unknown.
Feline immunodeficiency virus, Orf3 (FIV_Orf3)
Type: Family

This family consists of several hypothetical Feline immunodeficiency virus (FIV) proteins. Members of this family are typically around 67 residues long and are often annotated as ORF3 proteins. The function of this family is unknown.
Uncharacterized protein YyaB-like, PH domain (PH_YyaB-like)
Type: Domain

This entry represents the PH domain found in several uncharacterised proteins mainly from bacteroidetes and Bacillus species, whose function is unknown .
Protein Gp5, N-terminal OB-fold domain (Gp5_OB_N)
Type: Domain

This domain is found at the N terminus of the Gp5 baseplate protein of Bacteriophage T4. The baseplate is located at the end of the phage tail. Gp5 is a lysozyme essential for localised hydrolysis of bacterial cell wall, which is necessary for viral DNA injection . This domain binds to the Gp27 protein . It has the common OB fold .
Movement protein p6, Beet yellows virus (Beet_yellows_virus_p6)
Type: Family

Movement proteins (MPs) encoded by many virus genera are specialised proteins essential for plant viral genomes or virions transport within and between cells. There are some models of virus movement, such as Tobacco mosaic virus (TMV) model or the one described in several families of the icosahedral RNA viruses and pararetroviruses. Aditionally, proteins involved in replication or encapsidation are also required in cell-to-cell movement in some viruses .

This entry represents the movement protein 6 (p6) from Beet yellows virus and related Closterovirus proteins. P6 is a small protein (6kDa) localised in the endoplasmic reticulum. It has a single-span N-terminal transmembrane domain and a C-terminal hydrophilic domain which faces the cytosol. It is involved, together with Hsp70h, CP, CPm, and P64, in cell to cell movement of the viral genome without any budding, being essential for this process. The mechanism of action of this protein is not clear. It is suggested that it also plays a role in virion formation .
Protein of unknown function DUF1202 (DUF1202)
Type: Family

This family consists of several hypothetical bacterial proteins of around 335 residues in length. Members of this family are found exclusively in Escherichia coli and Salmonella species and are often referred to as YggM proteins. The function of this family is unknown.
Protein of unknown function DUF1203 (DUF1203)
Type: Family

This family consists of several hypothetical bacterial proteins of around 155 residues in length. Family members are present in Rhizobium, Agrobacterium and Streptomyces species.
Transcription regulator HTH, AraC, N-terminal (Tscrpt_reg_HTH_AraC_N)
Type: Domain

This entry represents the N terminus of bacterial ARAC-type transcriptional regulators. In Escherichia coli these regulate the L-arabinose operon through sensing the presence of arabinose, and when the sugar is present, transmitting this information from the arabinose-binding domains to the protein s DNA-binding domains . This family might represent the N-terminal arm of the protein, which binds to the C-terminal DNA binding domains to hold them in a state where the protein prefers to loop and remain non-activating .

This domain is found in HTH-type transcriptional regulator YqhC from Escherichia coli, which positively regulates the expression of the yqhD-dkgA operon .
Bacteriophage DNA replication protein Gp16.7 (Phage_DNA_replic_GP16.7)
Type: Family

The early-expressed gene 16.7 is conserved in bacteriophage phi-29 and related phages. It encodes a membrane protein, GP16.7, consisting of an N-terminal transmembrane domain and a C-terminal DNA-binding and dimerisation domain. GP16.7 plays an important role in organising membrane-associated bacteriophage DNA replication . The C-terminal domain has a similar secondary structure similar to homeodomains, but forms a fundamentally different tertiary structure consisting of a six-helical dimeric fold . Multimerisation of this dimer leads to efficient DNA binding.
Domain of unknown function DUF1204 (DUF1204)
Type: Domain

This family represents the C terminus of a number of Arabidopsis thaliana hypothetical proteins of unknown function. Family members contain a conserved DFD motif.
Domain of unknown function DUF1206 (DUF1206)
Type: Domain

This region consists of two a pair of transmembrane helices and occurs three times in each of the family member proteins.
Apoptosis inducing factor BLCAP (BCALP)
Type: Family

This family consists of a series of short proteins of around 90 residues in length which includes Apoptosis inducing factor BLCAP from human (

), also known as BC10. BCALP acts as a tumor suppressor; it induces growth arrest at G1/S checkpoint and apoptosis via RB1-dependent and p53/TP53- and NF-kappa-B-independent mechanisms . It has been implicated in bladder cancer where the transcription of the gene coding for this protein is nearly completely abolished in highly invasive transitional cell carcinomas (TCCs) .

The protein is a small globular protein containing two transmembrane helices, and it is a multiply edited transcript. All the editing sites are found in either the 5'-UTR or the N-terminal section of the protein, which is predicted to be outside the membrane. The three coding edits are all non-synonymous and predicted to encode exposed residues .
Protein of unknown function DUF1207 (DUF1207)
Type: Family

This family consists of a number of hypothetical bacterial proteins of around 410 residues in length, which seem to be specific to Chlamydia species. The function of this family is unknown.
GPI transamidase subunit PIG-U (PIG-U)
Type: Family

Many eukaryotic proteins are anchored to the cell surface via glycosylphosphatidylinositol (GPI), which is posttranslationally attached to the C terminus by GPI transamidase. The mammalian GPI transamidase is a complex of at least four subunits, GPI8, GAA1, PIG-S, and PIG-T. PIG-U is thought to represent a fifth subunit in this complex and may be involved in the recognition of either the GPI attachment signal or the lipid portion of GPI .
Centromere protein R (CENP-R)
Type: Family

Centromere protein R (CENP-R, also known as NRIF3) is a transcription co-regulator that can have both co-activator and co-repressor functions . It is involved in the co-activation of nuclear receptors for retinoid X (RXRs) and thyroid hormone (TRs) in a ligand-dependent fashion . It is a probable component of a centromeric complex involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation .
CBY1-interacting BAR domain-containing protein/FAM92 (CBAR/FAM92)
Type: Family

This entry represents a group of CBY1-interacting BAR domain-containing proteins formerly known as FAM92. Proteins in this family have a role in embryogenesis, being essential for ectoderm and axial mesoderm development . They may regulate cell proliferation and apoptosis . During spermatogenesis, these proteins regulate distal elongation of the basal-body and their anchoring to the plasma membrane and as a consequence, regulates the initiation and proper elongation of axonemal microtubules . They have been shown to interact with Cby1 to promote ciliogenesis via regulation of membrane-remodeling processes .
Microtubule associated protein Futsch (MAP_Futsch)
Type: Repeat

The central domain of Drosophila protein Futsch is highly repetitive and it is represented in this entry .

The Drosophila protein Futsch has homology to MAP1B and controls synaptic growth at the Drosophila neuromuscular junction through the regulation of the synaptic microtubule cytoskeleton. Futsch protein colocalises with microtubules and identifies cytoskeletal loops that traverse the lateral margin of select synaptic boutons. Futsch mutations disrupt synaptic microtubule organisation, reduce bouton number, and increase bouton size. These deficits can be partially rescued by neuronal overexpression of a Futsch MAP1B homology domain . The translation of Futsch is repressed by fragile X messenger ribonucleoprotein 1 (FMR1/FMRP), an RNA binding protein that acts as a negative translational regulator .
LsmAD domain (LsmAD_domain)
Type: Domain

This domain can be found in eukaryotic ataxin-2 . Ataxin-2 is predicted to consist of mostly non-globular domains . This domain has been shown to interact with RNA helicase DDX6 .

Ataxin-2 has many functions, such as endocytic receptor cycling , translational regulation, embryonic development , energy metabolism and weight regulation . Mutations of the Ataxin-2 gene cause spinocerebellar ataxia 2 (SCA2), a neurodegenerative disorder leading to predominant loss of Purkinje cells in the cerebellum and impairment of motor coordination . In SCA2, expansion of a CAG repeat in exon 1 of the Ataxin-2 (ATXN2) gene causes expansion of a polyQ domain in the ATXN2 protein . ATXN2 has been shown to interact with many proteins. It interacts with multiple RNA-binding proteins (RBPs), staufen, IP3R, RGS8 mRNA, endophilins and CIN85 .

Proteins containing this domain also include Pbp1 from budding yeasts, Pbp1 interacts with Pab1 to regulate mRNA polyadenylation . It promotes mating-type switching in mother cells by positively regulating HO mRNA translation and forms a condensate in response to respiratory status to regulate TORC1 signaling . It is also involved in P-body-dependent granule assembly .
Domain of unknown function DUF1216 (DUF1216)
Type: Domain

This entry represents a conserved region within Arabidopsis thaliana proteins of unknown function. Proteins in this entry sometimes contain more than one copy of the domain.
DESIGUAL/Modifying wall lignin-1/2 (DEAL/Modifying_wall_lignin1/2)
Type: Family

This entry represents a group of proteins from Streptophytes, including Protein VASCULATURE COMPLEXITY AND CONNECTIVITY (also known as DEAL1), Protein DESIGUAL 2-4 (DEAL2-4) and Protein MODIFYING WALL LIGNIN-1/2 (MWL-1/2). DEAL1 is required for embryo provasculature development and cotyledon vascular complexity and connectivity . DEAL2 and 3 ensure bilateral symmetry development and early leaf margin patterning, probably via the regulation of auxin and CUC2 distribution . MWL1 and 2 are involved in secondary cell wall biology, specifically lignin biosynthesis . Proteins included in this family contain a number of conserved cysteine residues.
Enhancer of polycomb, C-terminal (Enhancer_polycomb_C)
Type: Domain

This entry represents the C terminus of eukaryotic enhancer of polycomb proteins, which have roles in heterochromatin formation .
Bradykinin (Bradykinin)
Type: Family

This family consists of several Bradykinin sequences. The skins of anuran amphibians, in addition to mucus glands, contain highly specialised poison glands, which, in reaction to stress or attack, exude a complex noxious cocktail of biologically active molecules. These secretions often contain a plethora of peptides among which Bradykinin or structural variants have been identified . Bradykinin, widespread among frogs, is able to pass through epithelial barriers independently and interfere in multiple physiological processes without the need of other substances to enhance the uptake . The diversity of bioactive peptides found in the skin secretions of amphibian species great potential for drug discovery and biotechnological applications .
Phosphonate metabolism PhnG (Phosphonate_metab_PhnG)
Type: Family

This family consists of several bacterial phosphonate metabolism protein PhnG sequences. In Escherichia coli, the phn operon encodes proteins responsible for the uptake and breakdown of phosphonates. The exact function of PhnG is unknown, however it is thought likely that along with six other proteins PhnG makes up the the C-P (carbon-phosphorus) lyase .
CbtA toxin of type IV toxin-antitoxin system (CbtA_toxin)
Type: Family

CbtA is a family of bacterial and archaeal toxins of type IV toxin-antitoxin system. Toxins from such systems in free-living bacteria inhibit cell growth by targeting essential functions of cellular metabolism . In this case the toxin inhibits cell-division leading to changes in morphology and finally lysis, by interacting with two essential cytoskeletal proteins, FtsZ and MreB. For FtsZ it inhibits its GTPase activity and GTP-dependent polymerisation, and for MreB it inhibits its ATP-dependent polymerisation. These actions of CbtA appear to occur simultaneously . he cognate antitoxin family is represented by

.
IcmF-related (IcmF-rel)
Type: Domain

This entry represents a conserved region within several bacterial proteins that resemble IcmF, which has been proposed to be involved in Vibrio cholerae cell surface reorganisation, resulting in increased adherence to epithelial cells and increased conjugation frequency. Note that many entry members are hypothetical proteins.

Type VI secretion component TssM1 from Pseudomonas aeruginosa is also a member of this entry. TssM1 plays a role in the release of toxins targeting both eukaryotic and prokaryotic species, plays an essential role in stabilization of assembled TssK1 structure at a fixed perimembrane site and forms part of the tip complex .
Lipase maturation factor (LMF)
Type: Family

This family of transmembrane proteins includes the lipase maturation factors LMF1 and LMF2. Lipoprotein lipase and hepatic lipase require LMF1 to fold into their active states . LMF1 acts as a specific chaperone for dimeric lipases, required both for maturation and transport of active lipoprotein lipase (LPL) through the secretory pathway .
Toxin YoeB (YoeB_toxin)
Type: Family

This is a family of bacterial toxins that forms one component of the type II toxin-antitoxin system in E. coli whose antitoxin is represented by YefM, found in

. The plasmid encoded Axe-Txe proteins in Enterococcus faecium act as an antitoxin-toxin pair. When the plasmid is lost, the antitoxin is degraded relatively quickly by host enzymes. This allows the toxin to interact with its intracellular target, thus killing the cell or impeding cell growth . These toxins are highly potent protein synthesis inhibitors, specifically blocking the initiation of translation. In the case of YoeB, it binds to the 50 S ribosomal subunit in 70 S ribosomes and interacts with the A site leading to mRNA cleavage at this site. As a result, the 3'-end portion of the mRNA is released from ribosomes, and translation initiation is effectively inhibited .
Viral desmoplakin, N-terminal (Desmo_N)
Type: Domain

This entry represents the N terminus of viral desmoplakin. Desmoplakin is a component of mature desmosomes, which are the main adhesive junctions in epithelia and cardiac muscle. Desmoplakin is also essential for the maturation of adherens junctions . Note that many family members are hypothetical.
Seipin family (Seipin)
Type: Family

Seipin is a cell-autonomous regulator of lipolysis essential for adipocyte differentiation . Seipin is predicted to contain two transmembrane domains at residues 28-49 and 237-258, in humans, and a third transmembrane domain might be present at residues 155-173. Mutations in the Seipin gene underlie human congenital generalized lipodystrophy . Seipin may also be implicated in Silver spastic paraplegia syndrome and distal hereditary motor neuropathy type V .

This entry also includes Seipin homologues from fission yeasts and plants. There are three SEIPIN homologues in Arabidopsis thaliana, designated SEIPIN1, SEIPIN2, and SEIPIN3. Similar to their animal homologus, plant and yeast Seipins also play roles in lipid droplet (LD) biogenesis .
Erp protein (Erp)
Type: Family

This entry represents bacterial Erp proteins that seem to be specific to Borrelia burgdorferi (a causative agent of Lyme disease). Borrelia Erp proteins are particularly heterogeneous, which might enable them to interact with a wide variety of host components .