SII-SWORD/CoKE huggingface dataset:
Haemolymph juvenile hormone binding (Haemolymph_juvenile_hormone-bd)
Type: Family

This family consists of several insect specific haemolymph juvenile hormone binding proteins (JHBP). Juvenile hormone (JH) has a profound effect on insects. It regulates embryogenesis, maintains the status quo of larva development and stimulates reproductive maturation in the adult forms. JH is transported from the sites of its synthesis to target tissues by a haemolymph carrier called juvenile hormone-binding protein (JHBP). JHBP protects the JH molecules from hydrolysis by non-specific esterases present in the insect haemolymph . The crystal structure of the JHBP from Galleria mellonella (Wax moth) shows an unusual fold consisting of a long α-helix wrapped in a much curved antiparallel β-sheet, the so-called TULIP domain . The folding pattern for this structure closely resembles that found in some tandem-repeat mammalian lipid-binding and bactericidal permeability-increasing proteins, with a similar organisation of the major cavity and a disulphide bond linking the long helix and the β-sheet. It would appear that JHBP forms two cavities, only one of which, the one near the N- and C-termini, binds the hormone; binding induces a conformational change, of unknown significance .

Proteins in this entry includes protein Daywake (dyw) and Takeout (to) from fruit flies . Dyw functions in neurons as a day-specific anti-siesta gene, with little effect on sleep levels during the nighttime or in the absence of light . Protein Takeout is implicated in circadian control of feeding behaviour and affects male courtship behaviour .
TraK, N-terminal (TraK_N)
Type: Domain

This entry represents the N-terminal domain observed in several TraK proteins from Escherichia coli and related proteins.

TraK is known to be essential for pilus assembly but its exact role in this process is unknown .
Protein of unknown function DUF1137 (DUF1137)
Type: Family

This family consists of several hypothetical proteins specific to Chlamydia species. The function of this family is unknown.
Muskelin, N-terminal (Muskelin_N)
Type: Domain

This entry represents the N-terminal region of muskelin and is found in conjunction with several

repeats. Muskelin is an intracellular, kelch repeat protein that is needed in cell-spreading responses to the matrix adhesion molecule, thrombospondin-1 .
Haemolysin-type calcium binding-related (Haemolys_ca-bd)
Type: Domain

This family consists of a number of bacteria specific domains, which are found in haemolysin-type calcium binding proteins. This family is found in conjunction with

and is often found in multiple copies.
Clostridium P47 protein (Clostridium_P47)
Type: Family

This family consists of several proteins (P47 and OrfX cluster) from various Clostridium species as well as related sequences from other bacteria. P47 and OrfX cluster proteins adopt a complex fold which has an internal structural duplication. They share structural similarity to lipopolysaccharide binding protein (LBP) and have been shown to bind to several types of phosphatidylinositol-phosphate (PIP) lipids .
Chlorovirus glycoprotein repeat (Chlorovirusi_glycop_rpt)
Type: Repeat

This entry contains a number of repeats found in Chlorovirus glycoproteins. The function of these proteins is unknown.
Myotubularin-like, phosphatase domain (Myotubularin-like_Pase_dom)
Type: Domain

This entry represents the phosphatase domain within eukaryotic myotubularin-related proteins. Myotubularin is a dual-specific lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bi-phosphate . Mutations in gene encoding myotubularin-related proteins have been associated with disease . The protein exists as a dimer with twofold symmetry, in which the dimerization is mediated by the phosphatase domain .

Myotubularin phosphatases are members of the protein tyrosine phosphatase (PTP) superfamily. The PTP domain is found in a diverse group of enzymes that catalyse phosphoester hydrolysis using a cysteine nucleophile and an arginine residue that binds to oxygen atoms of the phosphate. These two catalytically essential residues are found in a Cys-x(5)-Arg motif, which is a hallmark of PTP domains. The PTP superfamily of enzymes includes tyrosine-specific, dual specificity, low molecular weight, and Cdc25 phosphatases. All of these enzymes utilise phosphoproteins as substrates. Unlike these members of PTPs, enzymes that contain the tensin and myotubularin PTP domain utilise the phosphoinositide as its physiologic substrate. Myotubularins are 3-phosphatases specific for membrane-embedded PtdIns3P and PtdIns(3,5)P2, two PIs that function within the endosomal-lysosomal pathway .

The myotubularin phosphatase domain consists of a central seven stranded β sheet flanked by thirteen α helices . Although its core structure is similar to that of other PTP superfamily members, the myotubularin phosphatase domain is much larger. It contains an extra C-terminal region, which could be implicated in protein-protein interactions. The active site motif forms a P-loop at the base of a substrate binding pocket that is characteristic of PTP domains. This pocket is significantly deeper than that of other PTP pockets, which could explain the difference in substrate specificity.

The myotubularin family includes catalytically inactive members, or pseudophosphatases, which contain inactivating substitutions in the phosphatase domain .
UpxZ family (UpxZ_fam)
Type: Family

The UpxZ family of proteins acts to inhibit transcription of heterologous capsular polysaccharide loci in Bacteroides species by interfering with the action of the UpxY family of transcription anti-terminators. As antagonists of polysaccharide locus-specific UpxY transcription anti-terminators, the UpxZ proteins exert a hierarchical level of regulation, insuring that only one of the multiple phase-variable capsular polysaccharide loci per cell characteristic of this genus is transcribed at a time .
Outer membrane lipoprotein, Omp19, bacterial (OM_lipoprot_Omp19_bac)
Type: Family

This entry represents the bacterial outer membrane lipoprotein omp19 . Its function is not clear.
Tail spike domain (Tail_dom)
Type: Domain

This is a domain found in a family of prophage tail proteins, including Tail spike protein from Bacillus phage SPP1, which binds to the host entry receptor YueB and triggers viral DNA ejection . Many members of this group are predicted to be endopeptidases.
Major facilitator transporter Str1/Tri12-like (MFS_Str1/Tri12-like)
Type: Family

This entry represents a group of major facilitator transporters mostly from fungi, including Str1 from Schizosaccharomyces pombe and Tri12 from Fusarium sporotrichioides. Str1 is involved in the transport of siderophore iron and has a role in iron homeostasis . Tri12 is a trichothecene efflux pump that may play a role in F. sporotrichioides self-protection against trichothecenes .
L-alanine exporter AlaE (Ala_export_AlaE)
Type: Family

AlaE is an inducible L-alanine exporter .
KorB, C-terminal (KorB_C)
Type: Domain

This domain is found in several KorB transcriptional repressor proteins. The korB gene is a major regulatory element in the replication and maintenance of broad host-range plasmid RK2. It negatively controls the replication gene trfA, the host-lethal determinants kilA and kilB, and the korA-korB operon . This family is found in conjunction with

.
Single-minded, C-terminal (SIM_C)
Type: Domain

In Drosophila, single-minded (sim) is a transcription factor that acts as the master regulator of neurogenesis. Two mammalian homologues of Sim which have been identified, Sim1 and Sim2, are novel heterodimerisation partners for ARNT in vitro, and may function both as positive and negative transcriptional regulators in vivo, during embryogenesis and in the adult organism . SIM2 is thought to contribute to some specific Down syndrome phenotypes . There is a high level of homology among mammalian and Drosophila sim proteins in their amino-terminal half where the conserved bHLH, PAS (

) and PAC motifs are present (

). The PAC region occurs C-terminal to the PAS domains and are proposed to contribute to the PAS domain fold . In contrast, the carboxy-terminal parts are only conserved in vertebrates . The Sim1 C terminus contains a Ser-rich region, whereas the Sim2 C terminus both contain Ser/Thr-rich regions, Pro/Ser-rich regions, Pro/Ala-rich regions, and positively charged regions. Sim2s, a splice variant of Sim2, still contains the Ser/Thr- and Pro/Ser-rich regions shown to harbor repressive activities, but is missing the Pro/Ala-rich repressor region .
MHC class I, alpha chain, C-terminal (MHC_I_a_C)
Type: Domain

This entry represents the C-terminal cytoplasmic tail domain found in MHC class I, alpha chain sequences from mammals.

Major Histocompatibility Complex (MHC) glycoproteins are heterodimeric cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune responses. MHC molecules can be subdivided into two groups on the basis of structure and function: class I molecules present intracellular antigen peptide fragments (~10 amino acids) on the surface of the host cells to cytotoxic T cells; class II molecules present exogenously derived antigenic peptides (~15 amino acids) to helper T cells. MHC class I and II molecules are assembled and loaded with their peptide ligands via different mechanisms. However, both present peptide fragments rather than entire proteins to T cells, and are required to mount an immune response.

Class I MHC glycoproteins are expressed on the surface of all somatic nucleated cells, with the exception of neurons. MHC class I receptors present peptide antigens that are synthesised in the cytoplasm, which includes self-peptides (presented for self-tolerance) as well as foreign peptides (such as viral proteins). These antigens are generated from degraded protein fragments that are transported to the endoplasmic reticulum by TAP proteins (transporter of antigenic peptides), where they can bind MHC I molecules, before being transported to the cell surface via the Golgi apparatus . MHC class I receptors display antigens for recognition by cytotoxic T cells, which have the ability to destroy viral-infected or malignant (surfeit of self-peptides) cells.

MHC class I molecules are comprised of two chains: a MHC alpha chain (heavy chain), and a beta2-microglobulin chain (light chain), where only the alpha chain spans the membrane. The alpha chain has three extracellular domains (alpha 1-3, with alpha1 being at the N terminus), a transmembrane region and a C-terminal cytoplasmic tail. The soluble extracellular beta-2 microglobulin chain associates primarily with the alpha-3 domain and is necessary for MHC stability. The alpha1 and alpha2 domains of the alpha chain are referred to as the recognition region, because the peptide antigen binds in a deep groove between these two domains.
Stress-associated endoplasmic reticulum protein (ER_stress-assoc)
Type: Family

This entry contains Serp1/Serp2 and yeast Ysy6 stress-associated endoplasmic reticulum proteins. In humans, Serp1 (also known as RAMP4) interacts with target proteins during their translocation into the lumen of the endoplasmic reticulum. It has also been shown to protect unfolded target proteins against degradation during ER stress. It may facilitate glycosylation of target proteins after termination of ER stress and may modulate the use of N-glycosylation sites on target proteins .
Protein of unknown function DUF1152 (DUF1152)
Type: Family

This family consists of proteins of unknown function.
Catalase immune-responsive domain (Catalase_immune_responsive)
Type: Domain

Catalases (

) are antioxidant enzymes that catalyse the conversion of hydrogen peroxide to water and molecular oxygen, serving to protect cells from its toxic effects . Hydrogen peroxide is produced as a consequence of oxidative cellular metabolism and can be converted to the highly reactive hydroxyl radical via transition metals, this radical being able to damage a wide variety of molecules within a cell, leading to oxidative stress and cell death. Catalases act to neutralise hydrogen peroxide toxicity, and are produced by all aerobic organisms ranging from bacteria to man. Most catalases are mono-functional, haem-containing enzymes, although there are also bifunctional haem-containing peroxidase/catalases (

) that are closely related to plant peroxidases, and non-haem, manganese-containing catalases (

) that are found in bacteria .

This entry represents a small conserved region within catalase enzymes that carries the immune-responsive amphipathic octa-peptide that is recognised by T cells .
MltA-interacting MipA (MipA)
Type: Family

This family consists of several bacterial MltA-interacting protein (MipA) like sequences. As well as interacting with the membrane-bound lytic transglycosylase MltA, MipA is known to bind to PBP1B, a bifunctional murein transglycosylase/transpeptidase. MipA is considered to be a structural protein mediating the assembly of MltA to PBP1B into a complex .
Exodeoxyribonuclease 8 (ExoDNase_VIII)
Type: Family

This represents the exodeoxyribonuclease 8 (EXO VIII) proteins from Enterobacteriaceae. Exonuclease VIII from Escherichia coli is involved in the RecE pathway of recombination and has been shown to preferentially degrade linear duplex DNA .
DNA repair protein XRCC4 (DNA_repair_prot_XRCC4)
Type: Family

This entry represents the DNA double-strand break repair and V(D)J recombination protein XRCC4, which is found in certain Metazoans, fungi and plants. XRCC4 binds to DNA, and to DNA ligase IV (LIG4) to form the LIG4-XRCC4 complex . The LIG4-XRCC4 complex is responsible for the ligation step in the non-homologous end joining (NHEJ) pathway of DNA double-strand break repair. XRCC4 enhances the joining activity of LIG4. It is thought that XRCC4 and LIG4 are essential for alignment-based gap filling, as well as for final ligation of the breaks . Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.
Type 3 secretion system stator protein (T3SS_stator_protein)
Type: Family

This family consists of type III secretion system (T3SS) stator protein, previously known as nodulation protein NolV, from different Rhizobium species . The function of this family is unclear, however, it has been suggested that T3SS stator protein is a component of the T3SS, which is used to inject bacterial effector proteins into eukaryotic host cells.
Melanoplus sanguinipes entomopoxvirus (MsEPV), Orf214 (MsEPV_Orf214)
Type: Family

This entry is represented by a family of Orfs from Melanoplus sanguinipes entomopoxvirus (MsEPV), these include:Orf214, Orf215, Orf216, Orf217 and Orf62; they are a family of uncharacterised viral proteins.
Myb-related protein P/transcription factor Y1, C-terminal (Myb-rel_proteinP/Y1_C)
Type: Domain

This entry represents the C terminus of plant P/Y1 proteins. Members of this entry are transcriptional regulators of genes encoding enzymes for flavonoid biosynthesis . P protein plays a role in the pathway leading to the production of a red phlobaphene pigment , and P proteins are homologous to the DNA-binding domain of myb-like transcription factors . This domain is associated with

domain.
Protein of unknown function DUF1158 (DUF1158)
Type: Family

This family consists of several enterobacterial YbdJ proteins. The function of this family is unknow
ATP11 (ATP11)
Type: Family

This family consists of several eukaryotic ATP11 proteins. The expression of functional F1-ATPase requires two proteins which are encoded by the ATP11 and ATP12 genes . Atp11p is a molecular chaperone of the mitochondrial matrix that participates in the biogenesis pathway to form F1, which is the catalytic unit of ATP synthase. It binds to the free beta subunits of F1, which prevents the beta subunit from associating with itself in non-productive complex. It also allows for the formation of a (alpha beta)3 hexamer .
Extracytoplasmic thiamine-binding lipoprotein (CypI)
Type: Family

Thiamine-binding lipoprotein (Cypl) and related proteins are specific to Mycoplasma species. Cypl, also known as p37, whose gene is part of an operon encoding two additional proteins, which are highly similar to components of the periplasmic binding-protein-dependent transport systems of Gram-negative bacteria. It has been suggested that p37 is part of a homologous, high-affinity transport system in Mycoplasma hyorhinis, a Gram-positive bacterium . Its structure indicates that it is a thiamine pyrophosphate-binding protein . The monomer is a mixed α/β fold split into two globular domains (domains I and II) connected by two linker regions and the C-terminal helix.
Protein of unknown function DUF1159 (DUF1159)
Type: Family

This entry consists of several hypothetical bacterial proteins of unknown function.
Autographa californica nuclear polyhedrosis virus (AcMNPV), Ac75 (AcMNPV_Ac75)
Type: Family

This entry is represented by Autographa californica nuclear polyhedrosis virus (AcMNPV) protein Ac75, which is required for the egress of nucleocapsids from the nucleus, formation of intranuclear microvesicles and subsequent budded virion formation, in addition to protein Ac93. Ac75 is not an integral membrane protein, but it interacts with integral membrane protein Ac76 and is associated with the nuclear membrane .
Protein of unknown function DUF1161 (DUF1161)
Type: Family

This family consists of several short, hypothetical bacterial proteins of unknown function.
Methuselah, N-terminal domain (Methuselah_N_dom)
Type: Domain

Drosophila Methuselah (Mth) mutants have a 35% increase in average lifespan and increased resistance to several forms of stress, including heat, starvation, and oxidative damage. The protein affected by this mutation is related to G protein-coupled receptors of the secretin receptor family. Mth, like secretin receptor family members, has a large N-terminal ectodomain, which may constitute the ligand binding site .

This entry represents the N-terminal domain of the Methuselah protein.
D-glucuronyl C5-epimerase, C-terminal (C5-epim_C)
Type: Domain

This entry represents the C terminus conserved region of known or predicted D-glucuronyl C5-epimerases. D-glucuronyl C5-epimerase converts D-glucuronic acid residues adjacent to N-sulfate sugar residues to L-iduronic acid residues, both in maturing heparan sulfate (HS) and heparin chains .
Connector enhancer of kinase suppressor of ras 2/3 domain (CNK2/3_dom)
Type: Domain

This region is found in Connector enhancer of kinase suppressor of ras 2 (CNK2), Connector enhancer of kinase suppressor of ras 3 (CNK3) and CNK3/IPCEF1 fusion protein. This domain of unknown function is situated between the PDZ

and PH

domains in CNK2 and CNK3/IPCEF1 proteins and after the PDZ domain in CNK3 (which does not have a PH domain). CNK2 is predominantly expressed in neural tissues, being critical for postsynaptic density morphology, implicated in X-linked intellectual disability (ID). CNK2 was first described as a regulator of Ras/MAPK signalling by binding to the Ras effector RAF that lead to further studies concluding that it act as a scaffold for multiple signal cascades. It is able to direct the localisation of regulatory proteins within the cell and influences the behaviour of important regulatory molecules . CNK3 regulates aldosterone-induced and epithelial sodium channel (ENaC)-mediated sodium transport through regulation of ENaC cell surface expression, acting as a scaffold protein that coordinates the assembly of an ENaC-regulatory complex (ERC) . CNK3/IPCEF1 is required for hepatocyte growth factor (HGF)-dependent activation of Arf6 and HGF-stimulated cell migration .
Inter-alpha-trypsin inhibitor heavy chain, C-terminal (ITI_HC_C)
Type: Domain

This entry represents the C-terminal region of inter-alpha-trypsin inhibitor heavy chains. Inter-alpha-trypsin inhibitors are glycoproteins with a high inhibitory activity against trypsin, built up from different combinations of four polypeptides: bikunin and the three heavy chains that belong to this family (HC1, HC2, HC3). The heavy chains do not have any protease inhibitory properties but have the capacity to interact
in vitro
and
in vivo
with hyaluronic acid, which promotes the stability of the extra-cellular matrix. This domain is associated with the VWA domain

.
Protein of unknown function DUF1182 (DUF1182)
Type: Family

This family consists of several hypothetical proteins of around 360 residues in length and seems to be specific to Caenorhabditis elegans. The function of this family is unknown.
Protein of unknown function DUF1186 (DUF1186)
Type: Family

This family consists of several hypothetical bacterial proteins of around 250 residues in length and is found in several Chlamydia and Anabaena species. The function of this family is unknown.
Zinc finger, ClpX C4-type (Znf_CppX_C4)
Type: Domain

The ClpX heat shock protein of Escherichia coli is a member of the universally conserved Hsp100 family of proteins, and possesses a putative zinc finger motif of the C4 type . This presumed zinc binding domain (ZBD) is found at the N terminus of the ClpX protein. ClpX is an ATPase which functions both as a substrate specificity component of the ClpXP protease and as a molecular chaperone. ZBD is a member of the treble clef zinc finger family, a motif known to facilitate protein-ligand, protein-DNA, and protein-protein interactions and forms a constitutive dimer that is essential for the degradation of some, but not all, ClpX substrates .

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
Plant AUGMIN subunit 7 (Plant_AUG7)
Type: Family

Augmin is a protein complex required for centrosome-independent microtubule generation within the spindle . In plants, which lack a centrosome structure, an augmin complex also exists. The plant augmin complex contains eight subunits . This family consist of AUGMIN subunit 7.
Protein of unknown function DUF1191 (DUF1191)
Type: Family

This family contains hypothetical plant proteins of unknown function.
Mib-herc2 (Mib_Herc2)
Type: Domain

Mib is a RING ubiquitin ligase in the Notch pathway. Mib interacts with the intracellular domain of Delta to promote its ubiquitylation and internalisation. Cell transplantation studies suggest that mib function is essential in the signalling cell for efficient activation of Notch in neighbouring cells. This domain has been named 'mib/herc2 domain' in and usually the protein also contains an E3 ligase domain (either Ring or Hect).
Protein of unknown function DUF1194 (DUF1194)
Type: Family

This family consists of several hypothetical Rhizobiales specific proteins of around 270 residues in length. The function of this family is unknown.