SII-SWORD/CoKE huggingface dataset:
Protein of unknown function DUF1652 (DUF1652)
Type: Family

The proteins in this entry have not been characterised.
Bacteriophage F116, Orf28 (Phage_F116_Orf28)
Type: Family

This entry is represented by Bacteriophage F116 (Pseudomonas phage F116), Orf28. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

This family consists of proteins from the Pseudomonadaceae.
Bacteriophage bIL310, Orf15 (Phage_bIL310_Orf15)
Type: Family

This entry is represented by Bacteriophage bIL310, Orf15. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

The proteins in this family have unknown function and are found in some Lactococcus lactis prophages .
Protein of unknown function DUF1656 (DUF1656)
Type: Family

The proteins in this entry have no known function and belong to the AaeX family.
Protein of unknown function DUF1657 (DUF1657)
Type: Family

This domain appears to be restricted to the Bacillales.
Domain of unknown function DUF1659 (DUF1659)
Type: Domain

This entry represents a domain of unknown function in hypothetical uncharacerised bacterial proteins mainly terrabaceria. This domain contains a β-sheet connected to a small α-helix.
Protein of unknown function DUF1660 (DUF1660)
Type: Family

This protein family of unknown function is found in several bacteriophages and suspected prophages.
Protein of unknown function DUF1661 (DUF1661)
Type: Family

The proteins in this entry have not been characterised.
Domain of unknown function DUF1663 (DUF1663)
Type: Domain

The members of this family are hypothetical proteins expressed by Trypanosoma cruzi, a eukaryotic parasite that causes Chagas disease in humans. This region is found as multiple copies per protein.
Domain of unknown function DUF1664 (DUF1664)
Type: Domain

The region featured in this entry is approximately 100 amino acids long. It is found in hypothetical plant proteins of unknown function.
Ribosomal RNA-processing protein 15 (Rrp15)
Type: Family

Rrp15 is a constituent of pre-60S ribosomal particles. It is required for large subunit rRNA maturation, in particular processing of the 27S pre-rRNA at the A3 and B1 sites to yield 5.8S and 25S rRNA .
Protein of unknown function DUF1667 (DUF1667)
Type: Family

Hypothetical archaeal and bacterial proteins make up this family. A few proteins are annotated as being potential metal-binding proteins, and in fact the members of this family have four highly conserved cysteine residues, but no further literature evidence was found in this regard.
Scaffolding anchor of CK1 domain (SACK1)
Type: Domain

This entry represents the scaffolding anchor of CK1 domain (SACK1 domain) found at the N-terminal of FAM83 proteins, which includes FAM83A-H. This domain was formerly known as DUF1669 and it has been identified as a CK1 binding domain, which allows the correct subcellular localisation of both FAM83 proteins and the CK1 binding partners and their function .

These proteins are involved in diverse biological processes, depending on their subcellular localisation and binding partners. FAM83A-H interact with the alpha and alpha-like isoforms of CK1, while FAM83A, B, E, and H also interact with the delta and epsilon isoforms of CK1. FAM83 members have been described as oncogenes that function as intermediaries in EGFR/RAS signalling . They activate both the EGFR itself and downstream RAS/MAPK and PI3K/AKT/TOR signalling cascades . FAM83D has been reported to localize to the mitotic spindle and interact with the chromokinesin kinesin family member 22 (KIF22, also called Kid), the microtubule-binding protein hyaluronan-mediated motility receptor (HMMR), and the light chain of the motor protein dynein (DYNLL1) to correctly orient the metaphase plate in mitosis . FAM83G, also known as PAWS1 [protein associated with suppressor of mothers against decapentaplegic 1 (SMAD1)] interacts with the transcription factor SMAD1 and promotes the transcription of non-canonical bone morphogenetic protein (BMP) target genes . FAM83H mutations have been reported in both familial and spontaneous cases of amelogenesis imperfecta (AI) .
UfSP1/2/DUB, catalytic domain (UfSP1/2_DUB_cat)
Type: Domain

This is the C-terminal catalytic domain of human Ufm1-specific protease 2 (UfSP2), Zinc finger-containing ubiquitin peptidase 1 (DUB) and similar eukaryotic proteins. It shows seven α-helices and seven β-strands, resembling the papain-like structure .

UfSP1 and UfSP2 are cysteine peptidases required for the processing and activation of Ubiquitin fold modifier 1 (Ufm1,

) and for its release from conjugated cellular proteins. UfSP1 and UfSP2 are 217 aa and 461 aa respectively . The peptidases belong to MEROPS peptidase family C78, clan CA. The UfSP2 family have an N-terminal extension with one or more zinc finger domains of the C2H2 type, which have been shown to be involved in protein:protein interaction. UfSP2 is present in most, if not all, multi-cellular organisms including plants, nematodes, flies, and mammals, whereas UfSP1 is not present in plants and nematodes .

DUB is a deubiquitinase with endodeubiquitinase activity that specifically interacts with and cleaves 'Lys-63'-linked long polyubiquitin chains . It plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage .
Ethylene-responsive binding factor-associated repression (Ninja_motif)
Type: Domain

The EAR motif is the ethylene-responsive element binding factor-associated amphiphilic repression motif. This motif binds to the Groucho/Tup1-type co-repressor TOPLESS (TPL) and TPL-related proteins. The motif is frequently to be find at the N terminus of NINJA, or Novel INteractor of JAZ, proteins . The EAR motif, defined by the consensus sequence patterns of either LxLxL or DLN xxP, is the most predominant form of transcriptional repression motif so far identified in plants. It is highly conserved in transcriptional regulators that are known to function as negative regulators in a broad range of developmental and physiological processes across evolutionarily diverse plant species . This family is closely related to family AUX_IAA (

) which also has an LxLxL signature.
Protein of unknown function DUF1676 (DUF1676)
Type: Family

This family contains proteins of unknown function expressed by Drosophila melanogaster and Anopheles gambiae.
Protein of unknown function DUF1678 (DUF1678)
Type: Family

This family is composed of uncharacterised proteins expressed by Methanopyrus kandleri, a hyperthermophilic archaeon.
NECAP, PHear domain (NECAP_PHear)
Type: Domain

This PH-like domain can be found in the N-terminal region of NECAPs (also known as adaptin ear-binding coat-associated proteins). NECAPs are alpha-ear-binding proteins that enrich on clathrin-coated vesicles (CCVs). NECAP-1 is expressed in brain and non-neuronal tissues and cells while NECAP-2 is ubiquitously expressed. The PH-like domain of NECAPs is a protein-binding interface that mimics the FxDxF motif binding properties of the alpha-ear and is called PHear (PH fold with ear-like function) domain .

PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes .
Protein of unknown function DUF1684 (DUF1684)
Type: Family

The sequences featured in this family are found in hypothetical archaeal and bacterial proteins of unknown function. The region in question is approximately 200 amino acids long. It adopts a β-barrel fold (

) that has some similarity to Core-binding factor subunit beta (

).
Protein of unknown function DUF1686 (DUF1686)
Type: Family

The members of this family are all hypothetical proteins of unknown function expressed by the eukaryotic parasite Encephalitozoon cuniculi GB-M1. The region in question is approximately 250 amino acids long.
Protein of unknown function DUF1688 (DUF1688)
Type: Family

This family of uncharacterised fungal and bacterial proteins includes URC4 from the yeast Saccharomyces kluyveri. URC4 is a protein involved in uracil catabolism, but its exact function is not known .
PDR1 up-regulated protein 1-like (Pup1-like)
Type: Family

This entry represents a group of fungal proteins, including Pup1 from Candida glabrata. Pup1 is a mitochondrial protein that contributes to the enhanced virulence of C.glabrata strains that acquired azole resistance .
Protein of unknown function DUF1690 (DUF1690)
Type: Family

Family of uncharacterised fungal proteins.
Mitochondrial adapter protein MCP1, transmembrane domain (MCP1_TM)
Type: Domain

This entry represents the transmembrane domains found in Mitochondrial adapter protein MCP1 from yeast, a mitochondrial protein involved in mitochondrial lipid homeostasis . MCP1 recruits the lipid transfer protein Vps13 to mitochondria promoting vacuole-mitochondria contacts .
Fibritin C-terminal (Fibritin_C)
Type: Domain

This domain is found at the C terminus of the Bacteriophage T4 protein fibritin (

). Fibritin is responsible for attachment of long tail fibres to virus particle, and forms the "whiskers" or fibres on the neck of the virion. This domain contains an N-terminal coiled-coil portion and the C-terminal globular "foldon" region (residues 457-486), which is essential for fibritin trimerisation and folding . The foldon region consists of a β-hairpin; three such hairpins come together in a β-propeller-like arrangement in the trimer, which is stabilised by hydrogen bonds, salt bridges and hydrophobic interactions .
Frigida-like (Frigida)
Type: Family

This family is composed of plant proteins that are similar to FRIGIDA protein expressed by Arabidopsis thaliana (Mouse-ear cress) (

). This protein is probably nuclear and is required for the regulation of flowering time in the late-flowering phenotype. It is known to increase RNA levels of flowering locus C. Allelic variation at the FRIGIDA locus is a major determinant of natural variation in flowering time .
Fucose-specific lectin (Fungal_lectin)
Type: Family

Lectins are involved in many recognition events at the molecular or cellular level. These fungal lectins, such as Aleuria aurantialectin (AAL,

), specifically recognise fucosylated glycans. AAL is a dimeric protein, with each monomer being organised into a six-bladed β-propeller fold and a small antiparallel two-stranded β-sheet. The β-propeller fold is important in fucose recognition; five binding pockets are found between the propeller blades. The small β-sheet, on the other hand, is involved in the dimerisation process .
mRNA export factor GLE1-like (GLE1)
Type: Family

This family includes human protein GLE1 (

) and its homologues. This protein is localised at the nuclear pore complexes and functions in poly(A)+ RNA export to the cytoplasm . In Arabidopsis, it is required for seed viability .
Glycosyltransferase family 52 (Glyco_transf_52)
Type: Family

This family features glycosyltransferases belonging to glycosyltransferase family 52 , which have alpha-2,3- sialyltransferase (

) and alpha-glucosyltransferase (

) activity. For example, beta-galactoside alpha-2,3- sialyltransferase expressed by Neisseria meningitidis (

) is a member of this family and is involved in a step of lipooligosaccharide biosynthesis requiring sialic acid transfer; these lipooligosaccharides are thought to be important in the process of pathogenesis . This family includes several bacterial lipooligosaccharide sialyltransferases similar to the Haemophilus ducreyi LST protein. Haemophilus ducreyi is the cause of the sexually transmitted disease chancroid and produces a lipooligosaccharide (LOS) containing a terminal sialyl N-acetyllactosamine trisaccharide .
GSG1-like (GSG-1)
Type: Family

This entry represents GSG1 (germ cell-specific gene 1 protein), a protein specifically expressed in testicular germ cells . It has been shown to target testis-specific poly(A) polymerase to the endoplasmic reticulum through protein-protein interactions . Overexpression of the human homologue may be involved in tumourigenesis of human testicular germ cell tumours .
SAP30-binding protein (SAP30BP)
Type: Family

This entry represents the SAP30-binding protein that may act as a transcriptional co-repressor of a gene related to cell survival and induce cell death . Proteins in this entry also include the meiotically up-regulated gene 151 protein from fission yeast .
Heparinase II/III-like, C-terminal (Hepar_II_III_C)
Type: Domain

This is the C-terminal domain of heparin and heparin-sulfate lyase (HepB, also known as heparinase II), heparin-sulfate lyase (HepC, also known as heparinase III) and distantly related sequences. The structures of heparinase II and III have been solved .

HepB cleaves both heparin and heparan sulfate glycosaminoglycans through a beta-elimination mechanism. It cleaves heparin at alpha-D-GlcNp2S6S(1->4) alpha-L-IdoAp2S and heparan sulfate at alpha-D-GlcNp2Ac(or 2S)6OH(1->4)beta-D-GlcAp . HepC specifically cleaves heparan sulfate-rich regions of acidic polysaccharides, it does not act on N,O-desulfated glucosamine or N-acetyl-O-sulfated glucosamine linkages. HepC functions in cleaving metazoan heparan sulfate and providing carbon, nitrogen and sulfate sources for microorganisms .

This entry also includes FtsZ-localized protein C (FzlC), which binds and recruits FtsZ polymers to membranes early in the cell cycle. It may also improve the efficiency of cytokinesis through the regulation of cell wall hydrolysis. This protein has been reported to have sequence similarity to heparinase II/III family proteins .
Kanamycin nucleotidyltransferase, C-terminal (KNTase_C)
Type: Domain

Kanamycin nucleotidyltransferase (KNTase) is involved in conferring resistance to aminoglycoside antibiotics and catalyses the transfer of a nucleoside monophosphate group from a nucleotide to kanamycin. This enzyme is dimeric with each subunit being composed of two domains. The C-terminal domain contains five α helices, four of which are organised into an up-and-down α helical bundle. Residues found in this domain may contribute to this enzyme's active site .
Inner membrane mitoribosome receptor Mba1, Saccharomycetales (Mba1_Saccharomycetales)
Type: Family

This entry represents budding yeast Mba1 proteins.

Mba1 is an inner membrane protein that is part of the mitochondrial protein export machinery . It binds to the large subunit of mitochondrial ribosomes and cooperates with the C-terminal ribosome-binding domain of Oxa1, which is a central component of the insertion machinery of the inner membrane. In the absence of both Mba1 and the C terminus of Oxa1, mitochondrial translation products fail to be properly inserted into the inner membrane and serve as substrates of the matrix chaperone Hsp70 . It is proposed that Mba1 functions as a ribosome receptor that cooperates with Oxa1 in the positioning of the ribosome exit site to the insertion machinery of the inner membrane .
Metallothionein family 7 (Metalthion_7)
Type: Family

The sequence making up family 7 of the metallothionein superfamily are found repeated in metallothionein proteins expressed by two Tetrahymena species. Metallothioneins are low molecular mass, cysteine-rich metal-binding proteins that are thought to be involved in the regulation of levels of trace metals, and detoxification of these metals when present in excess . Some of the metallothioneins found in this family (for example,

) are known to be induced by cadmium and are thought to be involved in the cellular sequestration of toxic metal ions. The high proportion of cysteine residues allows the metal ions to be bound by the formation of clusters of metal-thiolate complexes . Tetrahymena spp. metallothioneins differ from other eukaryotic metallothioneins mainly in the length of their sequences and in the cysteine-containing motifs they exhibit.
Centromere protein I (CENP-I)
Type: Family

Centromere protein I (CENP-I) is a component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation . It may be involved in incorporation of newly synthesized CENP-A into centromeres via its interaction with the CENPA-NAC complex . In humans, CENP-I is required for the localisation of CENPF, MAD1L1 and MAD2 (MAD2L1 or MAD2L2) to kinetochores and is involved in the response of gonadal tissues to follicle-stimulating hormone .
Far11/STRP, N-terminal (Far11/STRP_N)
Type: Domain

This domain can be found in the N terminus of the yeast Far11 protein and the human STRP1/2 proteins.

Budding yeast Far11 interacts with the phosphatases Pph21, Pph22, and Pph3 and may be involved in the regulation of autophagy and the DNA damage signaling . STRP1/2 (also known as FAM40A/B) are regulators of cytoskeletal organization, cell morphology and migration .
Nairovirus M polyprotein-like (Nairovirus_M)
Type: Family

The sequences in this family are similar to the Dugbe virus (Dugbe nairovirus) M polyprotein precursor (

), which includes glycoproteins G1 and G2. Both are thought to be inserted in the membrane of the Golgi complex of the infected host cell, and G1 is known to have a role in infection of vertebrate hosts .
Nodule-specific GRP-repeat (Nod_GRP)
Type: Repeat

The region featured in this family is found repeated in a number of plant proteins, some of which are expressed specifically in nodules formed during symbiotic interactions with certain bacterial species]. Some of these proteins are also termed glycine-rich proteins (GRPs), due to the presence of a glycine-rich C-terminal region in their structures . Bacterial infection is required for the induction of nodule-specific GRP genes, and it is thought that nodule-specific GRPs may play non-redundant roles required at specific stages of nodule development . Members of this group of proteins may be cytosolic, whereas others are thought to be membrane-associated .
Nuclease A inhibitor-like (NucleaseA_inhib-like)
Type: Family

This family represents the nuclease A inhibitor NuiA expressed by Anabaena sp (NuiA,

) and similar bacterial proteins. This protein adopts an α+β fold described as an 'open jaw', which shares some similarity to the PR-1-like fold . NuiA regulates the activity of Nuclease A (NucA). The NucA inhibition by NuiA involves an unusual divalent metal ion bridge that connects the nuclease with its inhibitor. A highly conserved glutamate extends into the active site, mimicking the charge of a phosphate. In addition, a second interaction site located on one of the two 'jaws' of the NuiA structure, contribute to the specificity and strength of the NuiA-NucA interaction .
PaRep2a (PaRep2a)
Type: Family

This is a family of proteins expressed by the crenarchaeon Pyrobaculum aerophilum. The members are highly variable in length and level of conservation. The presence of numerous frameshifts and internal stop codons in multiple alignments are thought to indicate that most family members are no longer functional .
Protein Red1/Rec10 (Red1/Rec10)
Type: Family

Budding yeast Red1 is involved in meiotic recombination and chromosome segregation during homologous chromosome formation. Red1 is a component of the axial element protein cores in synaptonemal complexes (SC). Synaptonemal complexes are found at synapses between homologous chromosomes during meiosis, and form when sister chromatids condense upon axial elements . Besides its structural role in SC, Red1 also couples checkpoint signalling to SC formation .
Protein RED, C-terminal (RED_C)
Type: Domain

This domain is found at the C terminus of Red protein (

). This and related proteins are thought to be localised to the nucleus, and contain a RED repeat which consists of a number of RE and RD sequence elements . The function of Red protein is unknown, but efficient sequestration to nuclear bodies suggests that its expression may be tightly regulated or that the protein self-aggregates extremely efficiently .
Renin receptor-like (Renin_rcpt)
Type: Family

The sequences featured in this family are similar to the human renin receptor (

) which contains a putative transmembrane spanning segment . The renin receptor is involved in intracellular signal transduction by the activation of the ERK1/ERK2 pathway, and it also serves to increase the efficiency of angiotensinogen cleavage by receptor-bound renin, therefore facilitating angiotensin II generation and action on a cell surface . Members of this family include the Drosophila homologue known as dPRR .

Renin receptor is a multifunctional protein which functions as a renin, prorenin cellular receptor and is involved in the assembly of the lysosomal proton-transporting V-type ATPase (V-ATPase) and the acidification of the endo-lysosomal system . Through its function in V-type ATPase (v-ATPase) assembly and acidification of the lysosome it regulates protein degradation and may control different signalling pathways important for proper brain development, synapse morphology and synaptic transmission .
Reovirus minor core protein, Mu-2 (Reovirus_Mu2)
Type: Family

This family represents the Reovirus core protein Mu-2. Mu-2 is a microtubule associated protein and is thought to play a key role in the formation and structural organisation of reovirus inclusion bodies .
TadE-like domain (TadE-like_dom)
Type: Domain

This entry represents a domain that is similar to a region of the protein product of the bacterial tadE locus (

). In various bacterial species, the tad locus is closely linked to flp-like genes, which encode proteins required for the production of pili involved in adherence to surfaces . It is thought that the tad loci encode proteins that act to assemble or export an Flp pilus in various bacteria . All tad loci but TadA have putative transmembrane regions , and in fact the region in question is this family has a high proportion of hydrophobic amino acid residues.
TMC domain (TMC_dom)
Type: Domain

These sequences are similar to a region conserved amongst various protein products of the transmembrane channel-like (TMC) gene family, such as Transmembrane channel-like protein 3 (

) and EVIN2 (

) - this region is termed the TMC domain . Mutations in these genes are implicated in a number of human conditions, such as deafness and epidermodysplasia verruciformis . TMC proteins are thought to have important cellular roles, and may be modifiers of ion channels or transporters .
Neurotoxin B-IV-like (Neurotoxin_B-IV)
Type: Family

The members of this family resemble neurotoxin B-IV (

), which is a crustacean-selective neurotoxin produced by the marine worm Cerebratulus lacteus. This highly cationic peptide is approximately 55 residues and is arranged to form two antiparallel helices connected by a well-defined loop in a hairpin structure. The branches of the hairpin are linked by four disulphide bonds. Three residues identified as being important for activity, namely Arg-17, -25 and -34, are found on the same face of the molecule, while another residue important for activity, Trp30, is on the opposite side. The protein's mode of action is not entirely understood, but it may act on voltage-gated sodium channels, possibly by binding to an as yet uncharacterised site on these proteins. Its site of interaction may also be less specific, for example it may interact with negatively charged membrane lipids .