SII-SWORD/CoKE huggingface dataset:
Collagenase NC10/endostatin (Collagenase_NC10/endostatin)
Type: Domain

NC10 stands for Non-helical region 10 and is taken from

. A mutation in this region in

is associated with an increased risk of prostrate cancer. This domain is cleaved from the precursor and forms endostatin. Endostatin is a key tumour suppressor and has been used highly successfully to treat cancer. It is a potent angiogenesis inhibitor .

Endostatin is a C-terminal fragment of collagen XV/XVIII, a proteoglycan/collagen found in vessel walls and basement membranes. This domain has a compact globular fold similar to that of C-type lectins. Endostatin XVIII is monomeric and contains a heparin-binding epitope and zinc binding sites while endostatin XV is trimeric and contains neither of these sites. The generation of endostatin or endostatin-like collagen XV/XVIII fragments is catalyzed by proteolytic enzymes within the protease-sensitive hinge region of the C-terminal domain. Endostatin inhibits endothelial cell migration in vitro and appears to be highly effective in murine in vivo studies .
Sin3 associated polypeptide p18 (SAP18)
Type: Family

This family consists of several eukaryotic Sin3 associated polypeptide p18 (SAP18) sequences. SAP18 is known to be a component of the Sin3-containing complex, which is responsible for the repression of transcription via the modification of histone polypeptides . SAP18 is also present in the ASAP complex which is thought to be involved in the regulation of splicing during the execution of programmed cell death .
Phage tail tube protein, Siphoviridae (L_lac_phage_MSP)
Type: Family

This is a family of Siphoviridae phage tail tube proteins . This family also includes some prophages from Firmicutes.
Flagellar regulatory FleQ (FleQ)
Type: Domain

This domain is found at the N terminus of a subset of sigma54-dependent transcriptional activators that are involved in regulation of flagellar motility e.g. FleQ in Pseudomonas aeruginosa. It is clearly related to

, but lacks the conserved aspartate residue that undergoes phosphorylation in the classic two-component system response regulator (

).
Female-specific protein transformer (Tra)
Type: Family

Tra is a member of the regulatory pathway controlling female somatic sexual differentiation, regulated by Sxl. It activates dsx female-specific splicing by promoting the formation of a splicing enhancer complex which consists of tra, tra2 and sr proteins .
Esterase FrsA-like (FrsA-like)
Type: Family

The FrsA-like family includes FrsA, an esterase found to have the α/β-hydrolase fold . It also includes the hydrolytic polyketide shortening protein Ayg1 from fungi , 2,6-dihydropseudooxynicotine hydrolase from Paenarthrobacter nicotinovorans and Fus2 from Gibberella species .

The enzyme 2,6-dihydroxy-pseudo-oxynicotine hydrolase is involved in the nicotine-degradation pathway of Arthrobacter nicotinovorans .

Fus2 is part of the gene cluster that mediates the biosynthesis of the mycotoxin fusarin C. Fus2 catalyses closure of the 2-pyrrolidone ring of the intermediate 20-hydroxy-prefusarin to form another intermediate, 20-hydroxy-fusarin, which is then oxidized by Fus8 . Hydrolyase poxO from Penicillium oxalicum is part of the gene cluster that mediates the biosynthesis of oxaleimides, cytotoxic compounds containing an unusual disubstituted succinimide moiety .
Fijivirus, VP7-1-like (Fijivirus_VP7-1-like)
Type: Family

This entry contains proteins from Fijiviruses including P7-1 protein from Southern rice black-streaked dwarf virus (SRBSDV) and the probable non-structural 41.0 kDa protein from Maize rough dwarf virus (MRDV). P7-1 induces the formation of virus-containing tubules in infected plant and insect vector cells allowing its efficient transmission especially in high temperatures .
Replication protein C, bacterial (RepC_bac)
Type: Family

This family consists of several bacterial replication protein C (RepC) sequences.
Activator of aromatic catabolism (XylR_N)
Type: Domain

This domain is found at the N terminus of a subset of sigma54-dependent transcriptional activators in several proteobacteria, including activators of phenol degradation such as XylR. It is found adjacent to

.
Signal transduction response regulator, propionate catabolism activator, N-terminal (Sig_transdc_resp-reg_PrpR_N)
Type: Domain

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

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

This entry represents a domain found at the N terminus of several sigma54- dependent transcriptional activators including PrpR, which activates catabolism of propionate. In Salmonella enterica subsp. enterica serovar Typhimurium, PrpR acts as a sensor of 2-methylcitrate (2-MC), an intermediate of the 2-methylcitric acid cycle used by this bacterium to convert propionate to pyruvate .
Auxin response factor domain (ARF_dom)
Type: Domain

This entry represents the C-terminal conserved domain of auxin-responsive transcription factors.

The plant hormone auxin (indole-3-acetic acid) can regulate the gene expression of several families, including Aux/IAA, GH3 and SAUR families. Two related families of proteins, Aux/IAA proteins (

) and the auxin response factors (ARF), are key regulators of auxin-modulated gene expression . There are multiple ARF proteins, some of which activate, while others repress transcription. ARF proteins bind to auxin-responsive cis-acting promoter elements (AuxREs) using an N-terminal DNA-binding domain. It is thought that Aux/IAA proteins activate transcription by modifying ARF activity through the C-terminal protein-protein interaction domains found in both Aux/IAA and ARF proteins.
Sodium ion transport-associated domain (Na_trans_assoc_dom)
Type: Domain

This entry represents a domain specific to animal sodium channels or their subunits, many of which are voltage-gated. Members very often also contain between one and four copies of

and, less often, one copy of

. This domain shows a helical structure .
Photosystem II PsbU, oxygen evolving complex (PSII_PsbU)
Type: Family

In PSII, the oxygen-evolving complex (OEC) is responsible for catalysing the splitting of water to O(2) and 4H+. The OEC is composed of a cluster of manganese, calcium and chloride ions bound to extrinsic proteins. In cyanobacteria there are five extrinsic proteins in OEC (PsbO, PsbP-like, PsbQ-like, PsbU and PsbV), while in plants there are only three (PsbO, PsbP and PsbQ), PsbU and PsbV having been lost during the evolution of green plants .

This family represents the PSII extrinsic protein PsbU, which forms part of the OEC in cyanobacteria and red algae. PsbU acts to stabilise the oxygen-evolving machinery of PSII against heat-induced inactivation, which is crucial for cellular thermo-tolerance .

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .
NADH-ubiquinone reductase complex 1 MLRQ subunit (B12D)
Type: Family

The MLRQ subunit of mitochondrial NADH-ubiquinone reductase complex I is nuclear and is found in plants , insects, fungi and higher metazoans . It appears to act within the membrane and, in mammals, is highly expressed in muscle and neural tissue, indicative of a role in ATP generation .
Zinc finger protein NOA36 (NOA36)
Type: Family

This family consists of several NOA36 proteins (also known as zinc finger protein 330) which contain 29 highly conserved cysteine residues. In mitosis it associates with centromeres and concentrates at the midbody in cytokinesis .
Sulfocyanin (SoxE)
Type: Family

Members of this family are blue-copper redox proteins designated sulfocyanin, mainly from the archaeal genera Sulfolobus . Sulfocyanin is a component of the respiratory supercomplex SoxM .
Vertebrate interleukin-3 regulated transcription factor (Vert_IL3-reg_TF)
Type: Domain

This entry includes vertebrate transcription factors, some of which are regulated by IL-3/adenovirus E4 promoter binding protein . Others were found to strongly repress transcription in a DNA-binding-site-dependent manner .
Bacteriophage 933W, GpQ (Phage_933W_GpQ)
Type: Family

This entry is represented by Bacteriophage 933W, GpQ. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

This family consists of several phage antitermination protein Q and related bacterial sequences. Phage 993W gene Q encodes a phage-specific positive regulator of late gene expression, thought, by analogy to the corresponding gene of phage lambda, to be a transcription antiterminator. GpQ positively regulates expression of the phage late gene operons. Bacterial host RNA polymerase modified by antitermination proteins transcribes through termination sites that otherwise prevent expression of the regulated genes .
Protein of unknown function DUF1110 (DUF1110)
Type: Family

This entry contains proteins with no known function at present, found in the Poaceae (true grasses).
Repulsive guidance molecule, N-terminal (RGM_N)
Type: Domain

This entry represents the N-terminal domain of repulsive guidance molecule (RGM), mainly found in animals.

RGM is a GPI-linked axon guidance molecule of the retinotectal system, and controls cell motility, adhesion, immune cell regulation and systemic iron metabolism . RGM is repulsive for a subset of axons, those from the temporal half of the retina. Temporal retinal axons invade the anterior optic tectum in a superficial layer, and encounter RGM expressed in a gradient with increasing concentration along the anterior-posterior axis. Temporal axons can receive posterior-dependent information by sensing gradients or concentrations of guidance cues. Thus, RGM will likely provide positional information for temporal axons invading the optic tectum in the stratum opticum .
Avian adenovirus fibre, N-terminal (Avian_adenovirus_fibre_N)
Type: Domain

This entry represents the N-terminal domain of the avian adenovirus fibre proteins, which have been linked to variations in virulence . Avian adenoviruses possess penton capsomers that consist of a pentameric base associated with two fibres .
Di-haem oxidoreductase, putative peroxidase (DHOR)
Type: Family

DHOR is a family of di-haem oxidoredictases. It carries the two characteristic Cys-X-Y-Cys-His haem-binding motifs. The C-terminal high-potential site functions as an electron transfer centre, and the N-terminal low-potential site corresponds to the peroxidatic centre. Its probable function is as a peroxidase .
Bax inhibitor 1 like (BaxI_1-like)
Type: Family

This entry represents a group of Bax-inhibitor-1 sequences that is conserved from bacteria to humans .
Putative ABC-transporter type IV CmpB/TMEM229 (CmpB_TMEM229)
Type: Family

This entry includes a group of transmembrane proteins, including CmpB from bacteria and TMEM229 from animals.
Small nuclear ribonucleoprotein Prp3, C-terminal domain (Prp3_C)
Type: Domain

This domain is found at the C-terminal end of U4/U6 and U4/U5/U6-small nuclear ribonucleoprotein Prp3, part of the tri-RNA complex that form the spliceosome. Prp3 plays a key role in the recognition of the snRNA duplex. Defects in PRPF3 are the cause of retinitis pigmentosa type 18 (RP18). RP leads to degeneration of retinal photoreceptor cells . In
Arabidposis thaliana
, protein RDM16 acts as a pre-mRNA splicing factor and functions in RNA-directed DNA methylation by influencing Pol V transcript levels .

This binding domain, highly conserved among eukaryotes, interacts with the 3' end of U6 snRNA. It adopts a ferredoxin-like fold, showing a five-stranded mixed β-sheet with three α-helices, two of them running parallel to the β-strands on one side of the sheet and one on the other. This fold is extended with a long β-hairpin, an extra β-strand, an helix and a final loop at the C terminus .
Vertebrate heat shock transcription factor, C-terminal domain (Vert_HSTF_C)
Type: Domain

This domain represents the C-terminal region of vertebrate heat shock transcription factors. Heat shock transcription factors regulate the expression of heat shock proteins - a set of proteins that protect the cell from damage caused by stress and aid the cell's recovery after the removal of stress . This C-terminal region is found with the N-terminal

, and may contain a three-stranded coiled-coil trimerisation domain and a CE2 regulatory region, the latter of which is involved in sustained heat shock response .
Domain of unknown function DUF1117 (DUF1117)
Type: Domain

This entry represents the C terminus of a number of hypothetical plant proteins.
Signal-peptide peptidase, presenilin aspartyl protease (SPP)
Type: Family

SPP is a family of signal-peptide aspartyl proteases. The family carries the characteristic catalytic aspartate GXGD motif, and members are integral membrane peptidases of the presenilin-type with nine transmembrane regions. UniProtKB:Q18K19 (

) is part of the TCDB family 1.A.54.3.4, the presenilin er Ca(2+) leak channel (presenilin) .
Protein of unknown function DUF1120 (DUF1120)
Type: Family

This family consists of several bacterial proteins, at least one of which is involved in enzyme induction following nitrogen deprivation. The exact function of this family is unknow
Plant specific mitochondrial import receptor subunit TOM20 (TOM20_imprt_rcpt)
Type: Family

This family consists of several plant specific mitochondrial import receptor subunit TOM20 (translocase of outer membrane 20kDa subunit) proteins. Most mitochondrial proteins are encoded by the nuclear genome, and are synthesised in the cytosol. TOM20 is a general import receptor that binds to mitochondrial pre-sequences in the early step of protein import into the mitochondria .
BNIP3 (BNIP3)
Type: Family

This family consists of several mammalian specific BCL2/adenovirus E1B 19kDa protein-interacting protein 3 or BNIP3 sequences. BNIP3 belongs to the Bcl-2 homology 3 (BH3)-only family, a Bcl-2-related family possessing an atypical Bcl-2 homology 3 (BH3) domain, which regulates PCD from mitochondrial sites by selective Bcl-2/Bcl-XL interactions. BNIP3 family members contain a C-terminal transmembrane domain that is required for their mitochondrial localisation, homodimerisation, as well as regulation of their pro-apoptotic activities. BNIP3-mediated apoptosis has been reported to be independent of caspase activation and cytochrome c release and is characterised by early plasma membrane and mitochondrial damage, prior to the appearance of chromatin condensation or DNA fragmentation .
African swine fever virus, IAP-like p27, C-terminal (ASFV_p27_C)
Type: Domain

This entry represents the C-terminal region of the African swine fever virus (ASFV) IAP-like protein p27. This domain is found in conjunction with

. It has been suggested that the domain may be incoded by the gene involved in aspects of infection in the arthropod host, ticks of the genus Ornithodoros .
2'-deoxycytidine 5'-triphosphate deaminase, N-terminal domain (DCD_N)
Type: Domain

This entry includes several bacterial 2'-deoxycytidine 5'-triphosphate deaminase proteins (

) (DCD) from a set of mainly alphaproteobacteria, which consist of two dUTPase-like domains (

). This entry represents the N-terminal catalytic domain, which contains the active site residues Arg115 and Glu138, important for its activity .
Glucose-6-phosphate isomerase, prokaryote (G6P_isomerase_prok)
Type: Domain

This entry consists of several bacterial and archaeal glucose-6-phosphate isomerase (GPI) proteins (

), which are involved in glycolysis and in gluconeogenesis and catalyse the conversion of D-glucose 6-phosphate to D-fructose 6-phosphate. The deduced amino acid sequence of the first archaeal PGI isolated from Pyrococcus furiosus revealed that it is not related to its eukaryotic and many of its bacterial counterparts. In contrast, this archaeal PGI shares similarity with the cupin superfamily that consists of a variety of proteins that are generally involved in sugar metabolism in both prokaryotes and eukaryotes .
CSPG5, sulphate attachment domain (CSPG5_S_attach_dom)
Type: Domain

This entry represents the chondroitin sulphate attachment domain of Chondroitin sulfate proteoglycan 5 (CSPG5, also known as CALEB), which mediates dendritic tree and spine complexity . This domain contains several potential sites of chondroitin sulphate attachment, as well as potential sites of N-linked glycosylation .
Protein of unknown function DUF1133 (DUF1133)
Type: Family

This family consists of a number of hypothetical proteins from Escherichia coli O157:H7 and Salmonella typhi. The function of this family is unknown.
Caenorhabditis elegans ly-6-related (Ly-6-related)
Type: Family

This family consists of several Caenorhabditis elegans specific ly-6-related HOT and ODR proteins. These proteins are involved in the olfactory system. Odr-2 mutants are known to be defective in the ability to chemotax to odorants that are recognised by the two AWC olfactory neurons. Odr-2 encodes a membrane-associated protein related to the Ly-6 superfamily of GPI-linked signalling proteins .
Signal transduction histidine kinase, internal region (Sig_transdc_His_kin_internal)
Type: Domain

This entry represents a region within bacterial histidine kinase enzymes. Two-component signal transduction systems such as those mediated by histidine kinase are integral parts of bacterial cellular regulatory processes, and are used to regulate the expression of genes involved in virulence. Members of this family often contain

and/or

.

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

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

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

This entry represents the C terminus of eukaryotic neogenin precursor proteins, which contains several potential phosphorylation sites . Neogenin is a member of the N-CAM family of cell adhesion molecules (and therefore contains multiple copies of

and

) and is closely related to the DCC tumour suppressor gene product - these proteins may play an integral role in regulating differentiation programmes and/or cell migration events within many adult and embryonic tissues .
Protein LIN-9/Protein ALWAYS EARLY (LIN-9/ALY1)
Type: Family

This entry represents protein LIN-9/ALWAYS EARLY (LIN-9/ALY). LIN-9 from Caenorhabditis elegans is a homologue of the Drosophila always early (ALY) protein, which functions as a repressor of cell cycle regulated genes .

LIN-9 is a component of the evolutionary conserved DREAM (MuvB/DRM) complex, which represses transcription . DREAM complex undergoes a cell cycle dependent switch of subunits. DREAM core binds to the E2F4 transcription factor and to the RBL2 (p130) in quiescent cells, while associates with the transcription factor B-MYB in the S-phase . In humans, LIN-9 acts as a tumor suppressor and plays a role in the expression of genes required for the G1/S transition . In pluripotent embryonic stem cells (ESC), LIN-9 plays an important role for proliferation and genome stability by activating genes with important functions in mitosis and cytokinesis .

In Arabidopsis thaliana, ALY is expressed ubiquitously in vegetative and reproductive tissues .