SII-SWORD/CoKE huggingface dataset:
Protein of unknown function DUF3238 (DUF3238)
Type: Family

Proteins in this family are not characterised.
Protein of unknown function DUF3239 (DUF3239)
Type: Family

This entry contains possible membrane proteins, however this cannot be confirmed. Currently they have no known function.
Antagonist of EGFR signalling, Argos (Argos)
Type: Family

Argos is a natural secreted antagonist of EGFR signalling which functions by binding growth factor ligands that activate EGFR by forming a clamp like structure using three disulphide-bonded β-sheet domains .
Protein of unknown function DUF3240 (DUF3240)
Type: Family

This family of proteins with unknown function appears to be restricted to Proteobacteria.
Proteinaceous host-selective toxin ToxA (Toxin_ToxA)
Type: Family

ToxA is produced by particular Pyrenophora triticirepentis races and is a proteinaceous host-selective toxin. It is necessary and sufficient to cause cell death in sensitive wheat cultivars . ToxA adopts a single-domain, β-sandwich fold which has novel topology. The protein is directly involved in recognition events required for ToxA action, which involves several recognition events, is mediated by an important solvent-exposed Arg-Gly-Asp (RGD) containing loop. This structure is remarkably similar to the classic mammalian RGD-containing domain, the fibronectin type III (FnIII) domain. It is thought to be distantly related to mammalian FnIII proteins, gaining entry to the host via an integrin-like receptor in the plant host .
Protein of unknown function DUF3242 (DUF3242)
Type: Family

This entry includes homologues of the uncharacterised TM1622 protein from Thermotoga maritima, for which the structure has been determined. The protein is composed of seven β strands and three α-helices .
Protein of unknown function DUF3243 (DUF3243)
Type: Family

This family of proteins with unknown function includes uncharacterised proteins ymfJ and yflH. The family appears to be restricted to Firmicutes.
Protein of unknown function DUF3244 (DUF3244)
Type: Family

This family of proteins with unknown function appear to have an immunoglobulin-like β-sandwich fold.
DNA polymerase catalytic subunit Pol, C-terminal (DNAPolymera_Pol_C)
Type: Domain

This family of proteins represents the catalytic subunit, Pol, of the Herpes simplex virus DNA polymerase. Pol binds UL42, making up the DNA polymerase. UL42 is a processivity subunit which binds to the C-terminal of Pol in a similar way that the cell cycle regulator p21 binds to PCNA .
Mediator complex, subunit Med28 (Mediator_Med28)
Type: Family

Mediator is a large complex of up to 33 proteins that is conserved from plants to fungi to humans - the number and representation of individual subunits varying with species . It is arranged into four different sections, a core, a head, a tail and a kinase-activity part, and the number of subunits within each of these is what varies with species. Overall, Mediator regulates the transcriptional activity of RNA polymerase II but it would appear that each of the four different sections has a slightly different function . Subunit Med28 of the Mediator may function as a scaffolding protein within Mediator by maintaining the stability of a submodule within the head module, and components of this submodule act together in a gene-regulatory programme to suppress smooth muscle cell differentiation. Thus, mammalian Mediator subunit Med28 functions as a repressor of smooth muscle-cell differentiation, which could have implications for disorders associated with abnormalities in smooth muscle cell growth and differentiation, including atherosclerosis, asthma, hypertension, and smooth muscle tumours .
Protein of unknown function DUF3245 (DUF3245)
Type: Family

This is a family of proteins conserved in fungi. The function is not known, and there is no S. cerevisiae member.
Protein of unknown function DUF3246 (DUF3246)
Type: Family

This is a small family of fungal proteins one of whose members,

from Pichia stipitis is described as being an extremely serine rich protein-mucin-like protein.
Mediator complex, subunit Med13, N-terminal (Mediator_Med13_N)
Type: Domain

This entry represents the N-terminal domain of Med13.

Mediator is a large complex of up to 33 proteins that is conserved from plants through fungi to humans - the number and representation of individual subunits varying with species . It is arranged into four different sections, a core, a head, a tail and a kinase-activity part, and the number of subunits within each of these is what varies with species. Overall, Mediator regulates the transcriptional activity of RNA polymerase II but it would appear that each of the four different sections has a slightly different function. Med13 is part of the ancillary kinase module, together with Med12, CDK8 and CycC, which in yeast is implicated in transcriptional repression, though most of this activity is likely attributable to the CDK8 kinase. The large Med12 and Med13 proteins are required for specific developmental processes in Drosophila , zebrafish, and Caenorhabditis elegans but their biochemical functions are not understood .
Chromatin assembly factor 1 p150 subunit, acidic region (CAF-1_p150_acidic)
Type: Domain

This entry represents the acidic region of CAF-1 p150 subunit which constitutes part of the histone binding interface .

Chromatin assembly factor 1 (CAF-1) consists of three evolutionary conserved subunits, p150, p60, and p48 (yeast homologues Cac1, cac2 and cac3 respectively), and mediates the assembly of nucleosomes onto newly replicated DNA. The p150 subunit (CAF-1_p150, also known as subunit A) is the core component of the CAF-1 histone chaperone complex, which functions in depositing newly synthesised and acetylated histones H3/H4 into chromatin during DNA replication and repair , being essential for cell viability and efficient DNA replication . The p150 subunit contains the interaction regions with proliferating cell nuclear antigen (PCNA), heterochromatin protein 1 (HP1), the CAF-1 p60 subunit among others proteins . It is thought that the DNA association with two histone-bound CAF-1 complexes may promote the formation of the (H3-H4)2 tetramer on DNA .
Shal-type voltage-gated potassium channels, N-terminal (Shal-type_N)
Type: Domain

This entry represents the N-terminal helical region of the Shal-type voltage-gated potassium channels. This domain interact with Kv channel-interacting proteins to modulate cell surface expression and function of Kv4 channels. The interaction of the Shal-type protein Kv4.2 and the Kv interacting protein KChiP1 forms a structure which is like the structure between calmodulin and its target peptides when they interact. Interactions of an N-terminal α helix in Kv4.2 and a C-terminal α helix in KChIP1 are essential for the modulation of Kv4.2 by KChIPs .
Sir1, ORC-binding domain (Sir1_ORC-binding)
Type: Domain

This entry represents the ORC-binding domain of Sir1. Sir1 interacts with the BAH domain of the Orc1 subunit of the origin recognition complex (ORC) resulting in the establishment of silent chromatin at HMR and HML in S.cerevisiae . The amino acids from the ORC interaction region of Sir1 are presented on a conserved, convex surface that forms a complementary interface with the Orc1 BAH domain, critical for transcriptional silencing .
Copper binding periplasmic protein CusF (CusF_Ec)
Type: Family

CusF is a periplasmic protein involved in copper and silver resistance in Escherichia coil. CusF forms a five-stranded β-barrel OB fold. Cu(I) binds to H36, M47 and M49 which are conserved residues in the protein .
Vacuolar protein sorting protein 36, GLUE domain (GLUE_dom)
Type: Domain

Vps36 is a subunit of ESCRT-II, a protein complex involved in driving protein sorting from endosomes to lysosomes. The GLUE domain of Vps36 allows for a tight interaction to occur between the protein and Vps28, a subunit of ESCRT-I. This interaction is critical for ubiquitinated cargo progression from early to late endosomes .

The multivesicular body (MVB) protein-sorting pathway targets transmembrane proteins either for degradation or for function in the vacuole/lysosomes. The signal for entry into this pathway is monoubiquitination of protein cargo, which results in incorporation of cargo into luminal vesicles at late endosomes. Another crucial player is phosphatidylinositol 3-phosphate (PtdINS(3)P), which is enriched on early endosomes and on the luminal vesicles of MVBs. The ESCRT complexes are critical for MVB budding and sorting of monoubiquitinated cargo into the luminal vesicles. Various Ub-binding domains (UBDs), such as UIM, UEV and NZF are found in such machineries. The Vps 36 subunit of the ESCRT-II trafficking complex binds both phosphoinositides and ubiquitin. All members of the Vps36 family contain a divergent GRAM/PH-like domain and yeast and some other fungi have one or two NZF domains inserted in the GRAM/PH-like domain.

The N-terminal region of Vps36 (EAP45) has been named the GLUE (GRAM-like ubiquitin-binding in EAP45) domain. The GLUE domain acts as a central cog driving the endosomal ESCRT machinery, through simultaneous interactions with PtdIns3P-containing membranes, ubiquitin, and ESCRT-I. Like other known ubiquitin-binding domains, the GLUE domain interacts with the hydrophobic surface patch of ubiquitin. The GLUE domain is the first ubiquitin-binding domain shown to bind phosphoinositides, and the ability of the same domain to bind both ubiquitin and a phosphoinositide opens interesting possibilities for coordination of membrane interactions and cargo recognition .

The GLUE domain has a split PH-domain fold with two curved β sheets and one long α helix. The two sheets (β1/β4 and β5/β7) form a β barrel-like structure, the C-terminal α helix is wedged between the two β sheets, covering a hydrophobic core. The Vps36 GLUE domain binds PtdIns3P via a positively charged lipid binding pocket, delineated by the variable loops β1/β2, β5/β6 and β7/α1, in contrast to the vast majority of characterised PH domains, which use a different lipid binding pocket .
Protein of unknown function DUF3247 (DUF3247)
Type: Family

This family of proteins is the protein product of the gene XC5848 from Xanthomonas campestris. The protein has no known function however its structure has been determined. The protein adopts a Lsm fold however differences with the fold were observed at the N-terminal and internal regions .
Protein of unknown function DUF3248 (DUF3248)
Type: Family

This family of proteins is thought to be the product of the gene TT1592 from Thermus thermophilus however this cannot be confirmed. Currently there is no known function.
Scaffold protein Ste5, Fus3-binding domain (Ste5_Fus-binding)
Type: Domain

This entry represents the Fus3 binding domain of Ste5. Ste5 functions in the yeast mating pathway and is required for signalling through the mating response MAPK pathway. Ste5 has separate binding sites for each member of the MAPK cascade. This region of Ste5 allosterically activates autophosphroylation of Fus3, a mitogen-activated protein kinase. Auto-activated Fus3 has a negative regulatory role, and promotes Ste5 phosphorylation which leads to a decrease in pathway transcriptional output .
CCR4-associated factor 4 (Caf4)
Type: Family

Caf4 is a WD40 repeats containing protein involved in mitochondrial fission. It displays physical interactions with CCR4-NOT complex . It has a paralogue, Mdv1. Both Caf4 and Mdv1 act as adapter proteins, binding to Fis1 on the mitochondrial outer membrane and recruiting the dynamin-like GTPase Dnm1 to form mitochondrial fission complexes . However, Fis1 and Caf4, but not Mdv1, determine the polar localization of Dnm1 clusters on the mitochondrial surface .
Histone-lysine N-methyltransferase EZH1/EZH2 (EZH1/EZH2)
Type: Family

The Polycomb Repressive Complex 2 (PRC2) is a chromatin modifying complex that consists of three core components: EED, SUZ12 and one of the two histone H3K27 methyltransferases, EZH1 or EZH2 . The PRC2 complex catalyses di- and trimethylation of histone H3 lysine 27 (H3K37me2/3), which has a repressive role. Even though EZH1 and EZH2 form similar PRC2 complexes, they exhibit contrasting repressive roles. In terms of their expression in mice, EZH1 is more abundant in nonproliferative adult organs, while EZH2 expression is tightly associated with proliferation .
Putative metal-binding motif (Put_metal-bd)
Type: Repeat

The presence of conserved cysteine residues and the lack of hydrophobic residues suggests that this repeat might be a metal-binding site, perhaps for zinc or calcium ions.
RPGR-interacting protein 1, first C2 domain (C2-C2_1)
Type: Domain

This domain is the first, more N-terminal, C2 domain on X-linked retinitis pigmentosa GTPase regulator-interacting proteins, or RPGR-interacting proteins .
Immunoglobulin-binding protein Sbi, domain IV (IgG-binding_Sbi_dom_IV)
Type: Domain

This entry represents domain IV of the immunoglobulin-binding protein Sbi from Staphylococcus aureus, which binds the central complement protein C3. Sbi-IV interacts with Sbi-III to induce a consumption of complement via alternative pathway activation . When not interacting with Sbi-III, Sbi-IV inhibits the alternative pathway without complement consumption. The structure of Sbi-IV consists of a three-helix bundle fold .
Domain of unknown function DUF3251 (DUF3251)
Type: Domain

This entry represents a domain found in a group of bacterial lipoproteins, such as SadB from Salmonella typhimurium. SadB is required for proper surface expression of the autotransporter adhesin SadA .
NADH dehydrogenase-like complex, subunit S (NdhS)
Type: Family

NdhS/CRR31 (chlororespiratory reduction 31) is a subunit of the chloroplast NADH dehydrogenase-like (NDH) complex . It is also a subunit of the cyanobacterial NDH-1 complex . NAD(P)H-oxidizing subunits have not been found in chloroplasts or cyanobacteria, where ferredoxin is probably the electron donor. NdhS contributes to the formation of a ferredoxin binding site of NDH and is necessary for high affinity binding of ferredoxin .

The cyanobacterial NDH-1 complex, also known as NADPH:plastoquinone oxidoreductase or type I NAD(P)H dehydrogenase, is involved in plastoquinone reduction and cyclic electron transfer (CET) around photosystem I. The chloroplast NDH is more similar to cyanobacterial NDH-1, which is believed to be the origin of chloroplast NDH, than to mitochondrial NADH dehydrogenase present in the same species . The NDH complexes of chloroplasts, however, contain many subunits that are absent from cyanobacterial NDH-1 complexes.
Protein of unknown function DUF3253 (DUF3253)
Type: Family

This bacterial family of proteins has no known function.
TRF2-interacting telomeric protein/Rap1, C-terminal (Rap1_C)
Type: Domain

This family of proteins represents the C-terminal domain of the protein Rap-1, which plays a distinct role in silencing at the silent mating-type loci and telomeres . The Rap-1 C terminus adopts an all-helical fold. Rap1 carries out its function by recruiting the Sir3 and Sir4 proteins to chromatin via its C-terminal domain . Rap1 is otherwise known as TRF2-interacting protein, as it is one of the six subunit components of the Shelterin complex. Shelterin protects telomere ends from attack by DNA-repair mechanisms .
Heterogeneous nuclear ribonucleoprotein A1/A2, C-terminal (HnRNPA1/A2_C)
Type: Domain

This entry includes the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), a nuclear factor that binds to Pol II transcripts. The family of hnRNP proteins is involved in numerous RNA-related activities . hnRNPA1 is involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and modulation of splice site selection . hnRNPA1 plays a role in the splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform . This protein binds to the IRES and inhibits the translation of the apoptosis protease activating factor APAF1. During Enterovirus 71 (EV71) infection, APAF1 expression is essential for virus-induced apoptosis and viral particle release .

hnRNPA1 consists of two RNA recognition motifs (RRM1 and RRM2) followed by an unstructured low complexity (LC) C-terminal domain, represented in this entry . This domain, shared by hnRNPA1 and hnRNPA2/B1, can mediate protein-protein and protein-RNA interactions and it is involved in amyloid aggregation, leading to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and multisystem proteinopathy (MSP) .
T-cell surface glycoprotein CD3 zeta subunit/High affinity IgE receptor gamma subunit (CD3_zeta/IgE_Fc_rcpt_gamma)
Type: Family

The TCR complex of T-lymphocytes consists of either a TCR alpha/beta or TCR gamma/delta heterodimer co-expressed at the cell surface with the invariant subunits of CD3 labelled gamma, delta, epsilon, zeta, and eta . The zeta subunit forms either homodimers or heterodimers with eta , but eta homodimers have not been observed. The structure of the zetazeta transmembrane dimer consists of a left-handed coiled coil with polar contacts. Two aspartic acids are critical for zetazeta dimerisation and assembly with TCR .

The high affinity immunoglobulin epsilon receptor (IgE Fc receptor) subunit gamma associates with a variety of FcR alpha chains to form a functional signaling complex. The gamma subunit has a critical role in allowing the IgE Fc receptor to reach the cell surface and regulates several aspects of the immune response . It has significant structural homology to CD3 zeta and the related CD3 eta subunit and can facilitate T cell receptor expression and signaling in the absence of CD3 zeta and CD3 eta .

This family includes both CD3 zeta subunits and IgE Fc receptor gamma subunits.
Protein of unknown function DUF3255 (DUF3255)
Type: Family

Members in this family of proteins are annotated as YxeF however no function is currently known. The family appears to be restricted to Bacillus.
Mediator complex, subunit Med16, N-terminal (Mediator_Med16_N)
Type: Domain

This entry represents the N-terminal β-propeller domain of human Mediator of RNA polymerase II transcription subunit 16 (MED16) and similar proteins from fungi and animals .

Mediator is a large complex of up to 33 proteins that is conserved from plants through fungi to humans - the number and representation of individual subunits varying with species . It is arranged into four different sections, a core, a head, a tail and a kinase-activity part, and the number of subunits within each of these is what varies with species. Overall, Mediator regulates the transcriptional activity of RNA polymerase II but it would appear that each of the four different sections has a slightly different function. Med16 is one of the subunits of the Tail portion of the Mediator complex and is required for lipopolysaccharide gene-expression . Several members including the human protein,

, have one or more WD40 domains on them.
Troponin I residues 1-32 (Troponin-I_N)
Type: Family

This family of proteins represents the cardiac N-extension of troponin I. This region of the protein (1-32) interacts with the N-lobe of cTnC and modulates myofilament calcium(2) sensitivity .
REDY-like protein HapK (HapK)
Type: Family

This family of proteins represents HapK, a protein of unknown function, with two homologues PigK and RedY. The monomer structure of the protein contains a four-stranded anti parallel β-sheet, three α-helices and a short C-terminal tail which it uses for dimer formation . The surface of HapK has a deep cavity with consists of a kinked helix and a β-four strand. HapK could be involved in prodigiosin biosynthesis, specifically the binding of a bipyrrole intermediate such as HBM or MBM .
Telomere-length maintenance and DNA damage repair (TAN)
Type: Domain

ATM is a large protein kinase, in humans, critical for responding to DNA double-strand breaks (DSBs). Tel1, the orthologue from budding yeast, also regulates responses to DSBs. Tel1 is important for maintaining viability and for phosphorylation of the DNA damage signal transducer kinase Rad53 (an orthologue of mammalian CHK2). In addition to functioning in the response to DSBs, numerous findings indicate that Tel1/ATM regulates telomeres. The overall domain structure of Tel1/ATM is shared by proteins of the phosphatidylinositol 3-kinase (PI3K)-related kinase (PIKK) family, but this family carries a unique and functionally important TAN sequence motif, near its N-terminal, LxxxKxxE/DRxxxL. which is conserved specifically in the Tel1/ATM subclass of the PIKKs. The TAN motif is essential for both telomere length maintenance and Tel1 action in response to DNA damage . It is classified as an

.
Bd37, core domain (Bd37_core)
Type: Domain

This entry represents the core domain of Bd37 (also known as Glycosylphosphatidylinositol-anchored merozoite surface protein), a surface antigen of B.divergens which is GPI-anchored at the surface of the merozoite. The structure of the protein consists of mainly α folds and has three sub domains .
Protein of unknown function DUF3256 (DUF3256)
Type: Family

This family of proteins with unknown function appears to be restricted to Bacteroidales.
PD(D/E)XK endonuclease (PD(D/E)XK_Endonuc)
Type: Domain

Proteins containing this domain are endonucleases, including group I intron-encoded endonuclease . They belong to the PD-(D/E)XK superfamily .
Protein of unknown function DUF3258 (DUF3258)
Type: Family

This protein family is found in virus and prophages from proteobacteria, including Uncharacterized protein ORF157 from Acidianus filamentous virus 1. This protein shows two antiparallel β-sheets formed by three and five strands in its N-terminal part and three helices towards the C-terminal, one of them roughly perpendicular to the other two, displaying similarity to the nucleotidyltransferase topology. It has nuclease activity in vitro, but its exact role remains unknown .
RIG-I-like receptor, C-terminal regulatory domain (RLR_CTR)
Type: Domain

Intracellular RIG-I-like receptors (RLRs: retinoic acid-inducible gene I, RIG-I; melanoma differenciation-associated gene 5, MDA-5; and laboratory of genetics and physiology 2, LGP2) recognise viral RNAs as pathogen-associated molecular patterns (PAMPs) and initiate an antiviral immune response. RLRs belong to the superfamily 2 (SF2) helicases or ATPases. Among SF2 ATPases, RIG-I, MDA5, and LGP2 possess a unique domain structure. RIG-I and MDA5 consist of two N-terminal caspase activation and recruitment domains (CARDs), a central SF2 type DECH box ATPase domain (consisting of
two RecA-like helicase domains, Hel1 and Hel2, and an insert domain, Hel2i), and a C-terminal regulatory (CTR) domain. LGP2 lacks the two N-terminal CARDs but contains the DECH box domain, as well as the CTR domain. The CTR domain helps recognise non-self RNAs within the cellular environment. To facilitate the detection of a broad range of non-self RNA
targets, each RLR contains a similar but divergent CTR domain that mediates RLR-specific interactions between bound nucleic acids or neighbouring patterns .

The RLR CTR domain is a globular, slightly flattened domain with a concave and a convex side. It is structurally organised in three leaves consisting of two four-stranded (β1, β2, β9, β10 and β5, β6, β7, β8) and one two-stranded (β3, β4) antiparallel β-sheets. Small helical turns connect the three β-sheets. The two four stranded β-sheets are laterally connected by two protruding loops, each containing two highly conserved cysteine residues. Together, the four thiol groups of these cysteines coordinate a zinc ion .
Bacteriophage T4, Gp14, neck protein (Phage_T4_Gp14_neck-protein)
Type: Family

This family of protein is represented by bacteriophage T4 Gp14, a major component of the neck along with Gp13. When added to completed heads, Gp13 and Gp14 structural proteins activate the heads for tail joining in vitro complementation mixtures. Gp14 is rich is β-sheets. The formation of the neck to the head of the bacteriophage is crucial for the tail attachment .
Protein of unknown function DUF3261 (DUF3261)
Type: Family

This family of proteins with unknown function appears to be restricted in general to Proteobacteria.