SII-SWORD/CoKE huggingface dataset:
Vps72/YL1, C-terminal (Vps72/YL1_C)
Type: Domain

This domain is found at the C terminus in proteins of the Vps72/YL1 family , in which it represents a proline-rich domain . These proteins are involved in chromatin remodelling . This domain is also found in proteins that do not belong to the Vps72/YL1 family.
ADAMTS/ADAMTS-like (ADAMTS/ADAMTS-like)
Type: Family

This entry includes ADAM-TS and ADAM-TS-like proteins, which are closely related to the ADAM family (A Disintegrin and Metalloproteinase) . ADAM-TS proteases are zinc metalloendopeptidases, most of whose substrates are extracellular matrix (ECM) components, whereas ADAM-TS-like proteins lack a metalloprotease domain, reside in the ECM and have regulatory roles . Examples of ADAM-TS-like proteins are papilin and punctin .

Proteolysis of the extracellular matrix plays a critical role in establishing tissue architecture during development and in tissue degradation in diseases such as cancer, arthritis, Alzheimer's disease and a variety of inflammatory conditions . The proteolytic enzymes responsible for this process are members of diverse protease families, including the secreted zinc metalloproteases (MPs) .

ADAM-TS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) is closely related to the ADAM family (A Disintegrin and Metalloproteinase) and is a subfamily of the MP family, consists of at least 20 members sharing a high degree of sequence similarity and conserved domain organisation . The defining domains of the ADAM-TS family are (from N- to C-termini) a pre-pro metalloprotease domain of the reprolysin type, a snake venom disintegrin-like domain, a thrombospondin type-I (TS) module, a cysteine-rich region, and a cysteine-free (spacer) domain . Domain organisation following the spacer domain C terminus shows some variability in certain ADAM-TS members, principally in the number of additional TS domains. These enzymes have a wide-spectrum role in vascular biology and cardiovascular pathophysiology .

Members of the ADAM-TS family have been implicated in a range of diseases . For instance, members of this family have been found to participate directly in processes in the central nervous system (CNS) such as the regulation of brain plasticity . ADAM-TS1 is reported to be involved in inflammation and cancer cachexia , whilst recessively inherited ADAM-TS2 mutations cause Ehlers-Danlos syndrome type VIIC, a disorder characterised clinically by severe skin fragility . ADAM-TS4 is an aggrecanase involved in arthritic destruction of cartilage .
Peptidase M12B, ADAM-TS1 (Pept_M12B_ADAM-TS1)
Type: Family

This entry represents the ADAM-TS1 family of metallopeptidases that belong to MEROPS peptidase family M12, subfamily M12B: adamalysin (clan MA).

Proteolysis of the extracellular matrix plays a critical role in establishing tissue architecture during development and in tissue degradation in diseases such as cancer, arthritis, Alzheimer's disease and a variety of inflammatory conditions . The proteolytic enzymes responsible for this process are members of diverse protease families, including the secreted zinc metalloproteases (MPs) . Recently, a new MP family, ADAM-TS (a disintegrin-like and metalloprotease domain with thrombospondin type I modules) has been identified. The family consists of at least 20 members that share a high degree of sequence similarity and conserved domain organisation . The defining domains of the ADAM-TS family are (from N- to C-termini) a pre-pro metalloprotease domain of the reprolysin type, a snake venom disintegrin-like domain, a thrombospondin type-I (TS) module, a cysteine-rich region, and a cysteine-free (spacer) domain . Domain organisation following the spacer domain C terminus shows some variability in certain ADAM-TS members, principally in the number of additional TS domains. Members of the ADAM-TS family have been implicated in a range of diseases. ADAM-TS1, for example, is reported to be involved in inflammation and cancer cachexia , whilst recessively inherited ADAM-TS2 mutations cause Ehlers-Danlos syndrome type VIIC, a disorder characterised clinically by severe skin fragility . ADAM-TS4 is an aggrecanase involved in arthritic destruction of cartilage . ADAM-TS1 was originally cloned in mice . Human and rat orthologues have also been identified. Expression of ADAMTS-1 is closely associated with acute inflammation .
Peptidase M12B, ADAM-TS2 (Pept_M12B_ADAM-TS2)
Type: Family

This entry contains members of the ADAM-TS2 family of metallopeptidases that belong to MEROPS peptidase family M12, subfamily M12B: adamalysin (clan MA).

Proteolysis of the extracellular matrix plays a critical role in establishing tissue architecture during development and in tissue degradation in diseases such as cancer, arthritis, Alzheimer's disease and a variety of inflammatory conditions . The proteolytic enzymes responsible for this process are members of diverse protease families, including the secreted zinc metalloproteases (MPs) . Recently, a new MP family, ADAM-TS (a disintegrin-like and metalloprotease domain with thrombospondin type I modules) has been identified. The family consists of at least 20 members that share a high degree of sequence similarity and conserved domain organisation . The defining domains of the ADAM-TS family are (from N- to C-termini) a pre-pro metalloprotease domain of the reprolysin type, a snake venom disintegrin-like domain, a thrombospondin type-I (TS) module, a cysteine-rich region, and a cysteine-free (spacer) domain . Domain organisation following the spacer domain C terminus shows some variability in certain ADAM-TS members, principally in the number of additional TS domains. Members of the ADAM-TS family have been implicated in a range of diseases. ADAM-TS1, for example, is reported to be involved in inflammation and cancer cachexia , whilst recessively inherited ADAM-TS2 mutations cause Ehlers-Danlos syndrome type VIIC, a disorder characterised clinically by severe skin fragility . ADAM-TS4 is an aggrecanase involved in arthritic destruction of cartilage . ADAM-TS2 was initially termed procollagen I/II amino-propeptide processing enzyme (PCINP). It was re-classified as ADAM-TS2 on the basis of cDNA sequence similarity with ADAM-TS1 . In vitro studies have shown that stable expression of ADAM-TS2 cDNA in mammalian cells results in secretion of an active recombinant enzyme that specifically cleaves type I procollagen .
Peptidase M12B, ADAM-TS5 (Pept_M12B_ADAM-TS5)
Type: Family

This entry represents members of the ADAM-TS5 family of metallopeptidases that belong to MEROPS peptidase family M12, subfamily M12B: adamalysin (clan MA), M12.225.

Proteolysis of the extracellular matrix plays a critical role in establishing tissue architecture during development and in tissue degradation in diseases such as cancer, arthritis, Alzheimer's disease and a variety of inflammatory conditions . The proteolytic enzymes responsible for this process are members of diverse protease families, including the secreted zinc metalloproteases (MPs) . Recently, a new MP family, ADAM-TS (a disintegrin-like and metalloprotease domain with thrombospondin type I modules) has been identified. The family consists of at least 20 members that share a high degree of sequence similarity and conserved domain organisation . The defining domains of the ADAM-TS family are (from N- to C-termini) a pre-pro metalloprotease domain of the reprolysin type, a snake venom disintegrin-like domain, a thrombospondin type-I (TS) module, a cysteine-rich region, and a cysteine-free (spacer) domain . Domain organisation following the spacer domain C terminus shows some variability in certain ADAM-TS members, principally in the number of additional TS domains. Members of the ADAM-TS family have been implicated in a range of diseases. ADAM-TS1, for example, is reported to be involved in inflammation and cancer cachexia , whilst recessively inherited ADAM-TS2 mutations cause Ehlers-Danlos syndrome type VIIC, a disorder characterised clinically by severe skin fragility . ADAM-TS4 is an aggrecanase involved in arthritic destruction of cartilage . ADAM-TS5, also termed aggrecanase 2, was identified through expressed sequence tag database searching, pursuing sequences similar to ADAM-TS1-4 . In vitro studies have shown that ADAM-TS5, like ADAM-TS4, is an aggrecanase able to cleave cartilage aggrecan .
Peptidase M12B, ADAM-TS8 (Pept_M12B_ADAM-TS8)
Type: Family

This entry contains members of the ADAM-TS8 family of metallopeptidases that belong to MEROPS peptidase family M12, subfamily M12B: adamalysin (clan MA).

Proteolysis of the extracellular matrix plays a critical role in establishing tissue architecture during development and in tissue degradation in diseases such as cancer, arthritis, Alzheimer's disease and a variety of inflammatory conditions . The proteolytic enzymes responsible for this process are members of diverse protease families, including the secreted zinc metalloproteases (MPs) . Recently, a new MP family, ADAM-TS (a disintegrin-like and metalloprotease domain with thrombospondin type I modules) has been identified. The family consists of at least 20 members that share a high degree of sequence similarity and conserved domain organisation . The defining domains of the ADAM-TS family are (from N- to C-termini) a pre-pro metalloprotease domain of the reprolysin type, a snake venom disintegrin-like domain, a thrombospondin type-I (TS) module, a cysteine-rich region, and a cysteine-free (spacer) domain . Domain organisation following the spacer domain C terminus shows some variability in certain ADAM-TS members, principally in the number of additional TS domains. Members of the ADAM-TS family have been implicated in a range of diseases. ADAM-TS1, for example, is reported to be involved in inflammation and cancer cachexia , whilst recessively inherited ADAM-TS2 mutations cause Ehlers-Danlos syndrome type VIIC, a disorder characterised clinically by severe skin fragility . ADAM-TS4 is an aggrecanase involved in arthritic destruction of cartilage . ADAM-TS8, also termed METH2, was identified by searching expressed sequence tag databases for sequences that contained TS modules . In vitro studies have shown recombinant ADAM-TS8 to be effective in blocking angiogenesis, and to inhibit endothelial cell growth .
Apoptosis regulator, Bcl-2 (Apop_reg_Bcl2)
Type: Family

Apoptosis, or programmed cell death (PCD), is a common and evolutionarily conserved property of all metazoans . In many biological processes, apoptosis is required to eliminate supernumerary or dangerous (such as pre-cancerous) cells and to promote normal development. Dysregulation of apoptosis can, therefore, contribute to the development of many major diseases including cancer, autoimmunity and neurodegenerative disorders. In most cases, proteins of the caspase family execute the genetic programme that leads to cell death.

Bcl-2 proteins are central regulators of caspase activation, and play a key role in cell death by regulating the integrity of the mitochondrial and endoplasmic reticulum (ER) membranes . At least 20 Bcl-2 proteins have been reported in mammals, and several others have been identified in viruses. Bcl-2 family proteins fall roughly into three subtypes, which either promote cell survival (anti-apoptotic) or trigger cell death (pro-apoptotic). All members contain at least one of four conserved motifs, termed Bcl-2 Homology (BH) domains. Bcl-2 subfamily proteins, which contain at least BH1 and BH2, promote cell survival by inhibiting the adapters needed for the activation of caspases.

Pro-apoptotic members potentially exert their effects by displacing the adapters from the pro-survival proteins; these proteins belong either to the Bax subfamily, which contain BH1-BH3, or to the BH3 subfamily, which mostly only feature BH3 . Thus, the balance between antagonistic family members is believed to play a role in determining cell fate. Members of the wider Bcl-2 family, which also includes Bcl-x, Bcl-w and Mcl-1, are described by their similarity to Bcl-2 protein, a member of the pro-survival Bcl-2 subfamily . Full-length Bcl-2 proteins feature all four BH domains, seven α-helices, and a C-terminal hydrophobic motif that targets the protein to the outer mitochondrial membrane, ER and nuclear envelope.
Apoptosis regulator, Bcl-X (Apop_reg_BclX)
Type: Family

Apoptosis, or programmed cell death (PCD), is a common and evolutionarily conserved property of all metazoans . In many biological processes, apoptosis is required to eliminate supernumerary or dangerous (such as pre-cancerous) cells and to promote normal development. Dysregulation of apoptosis can, therefore, contribute to the development of many major diseases including cancer, autoimmunity and neurodegenerative disorders. In most cases, proteins of the caspase family execute the genetic programme that leads to cell death.

Bcl-2 proteins are central regulators of caspase activation, and play a key role in cell death by regulating the integrity of the mitochondrial and endoplasmic reticulum (ER) membranes . At least 20 Bcl-2 proteins have been reported in mammals, and several others have been identified in viruses. Bcl-2 family proteins fall roughly into three subtypes, which either promote cell survival (anti-apoptotic) or trigger cell death (pro-apoptotic). All members contain at least one of four conserved motifs, termed Bcl-2 Homology (BH) domains. Bcl-2 subfamily proteins, which contain at least BH1 and BH2, promote cell survival by inhibiting the adapters needed for the activation of caspases.

Pro-apoptotic members potentially exert their effects by displacing the adapters from the pro-survival proteins; these proteins belong either to the Bax subfamily, which contain BH1-BH3, or to the BH3 subfamily, which mostly only feature BH3 . Thus, the balance between antagonistic family members is believed to play a role in determining cell fate. Members of the wider Bcl-2 family, which also includes Bcl-x, Bcl-w and Mcl-1, are described by their similarity to Bcl-2 protein, a member of the pro-survival Bcl-2 subfamily . Full-length Bcl-2 proteins feature all four BH domains, seven α-helices, and a C-terminal hydrophobic motif that targets the protein to the outer mitochondrial membrane, ER and nuclear envelope.

Bcl-X is a dominant regulator of programmed cell death in mammalian cells. The long form (Bcl-X(L)) displays cell death repressor activity, but the short isoform (Bcl-X(S)) and the b-isoform (Bcl-Xb) promote cell death. Bcl-X(L), Bcl-X(S) and Bcl-Xb are three isoforms derived by alternative RNA splicing. Bcl-X(S) forms heterodimers with Bcl-2. Homologues of Bcl-X include the rat Bax and mouse Bak proteins which also influence apoptosis.

In healthy cells, Bcl-x resides in the cytoplasm and becomes membrane-associated in response to cytotoxic insults. Its 3D structure comprises a bundle of five amphipathic α-helices surrounding two central hydrophobic helical regions. A hydro- phobic groove, formed by residues from BH1-BH3, is capable of binding the BH3 α-helix from a pro-apoptotic BH3-only family member .
Apoptosis regulator, Bcl-W (Apop_reg_BclW)
Type: Family

Apoptosis, or programmed cell death (PCD), is a common and evolutionarily conserved property of all metazoans . In many biological processes, apoptosis is required to eliminate supernumerary or dangerous (such as pre-cancerous) cells and to promote normal development. Dysregulation of apoptosis can, therefore, contribute to the development of many major diseases including cancer, autoimmunity and neurodegenerative disorders. In most cases, proteins of the caspase family execute the genetic programme that leads to cell death.

Bcl-2 proteins are central regulators of caspase activation, and play a key role in cell death by regulating the integrity of the mitochondrial and endoplasmic reticulum (ER) membranes . At least 20 Bcl-2 proteins have been reported in mammals, and several others have been identified in viruses. Bcl-2 family proteins fall roughly into three subtypes, which either promote cell survival (anti-apoptotic) or trigger cell death (pro-apoptotic). All members contain at least one of four conserved motifs, termed Bcl-2 Homology (BH) domains. Bcl-2 subfamily proteins, which contain at least BH1 and BH2, promote cell survival by inhibiting the adapters needed for the activation of caspases.

Pro-apoptotic members potentially exert their effects by displacing the adapters from the pro-survival proteins; these proteins belong either to the Bax subfamily, which contain BH1-BH3, or to the BH3 subfamily, which mostly only feature BH3 . Thus, the balance between antagonistic family members is believed to play a role in determining cell fate. Members of the wider Bcl-2 family, which also includes Bcl-x, Bcl-w and Mcl-1, are described by their similarity to Bcl-2 protein, a member of the pro-survival Bcl-2 subfamily . Full-length Bcl-2 proteins feature all four BH domains, seven α-helices, and a C-terminal hydrophobic motif that targets the protein to the outer mitochondrial membrane, ER and nuclear envelope.

In healthy cells, Bcl-w resides in the cytoplasm, and becomes membrane-associated in response to cytotoxic insults. Its 3D structure comprises a bundle of five amphipathic α-helices surrounding two central hydrophobic helical regions. A hydrophobic groove, formed by residues from BH1-BH3, is capable of binding the BH3 α-helix from a pro-apoptotic BH3-only family member .
Apoptosis regulator, Mcl-1 (Apop_reg_Mc1)
Type: Family

Apoptosis, or programmed cell death (PCD), is a common and evolutionarily conserved property of all metazoans . In many biological processes, apoptosis is required to eliminate supernumerary or dangerous (such as pre-cancerous) cells and to promote normal development. Dysregulation of apoptosis can, therefore, contribute to the development of many major diseases including cancer, autoimmunity and neurodegenerative disorders. In most cases, proteins of the caspase family execute the genetic programme that leads to cell death.

Bcl-2 proteins are central regulators of caspase activation, and play a key role in cell death by regulating the integrity of the mitochondrial and endoplasmic reticulum (ER) membranes . At least 20 Bcl-2 proteins have been reported in mammals, and several others have been identified in viruses. Bcl-2 family proteins fall roughly into three subtypes, which either promote cell survival (anti-apoptotic) or trigger cell death (pro-apoptotic). All members contain at least one of four conserved motifs, termed Bcl-2 Homology (BH) domains. Bcl-2 subfamily proteins, which contain at least BH1 and BH2, promote cell survival by inhibiting the adapters needed for the activation of caspases.

Pro-apoptotic members potentially exert their effects by displacing the adapters from the pro-survival proteins; these proteins belong either to the Bax subfamily, which contain BH1-BH3, or to the BH3 subfamily, which mostly only feature BH3 . Thus, the balance between antagonistic family members is believed to play a role in determining cell fate. Members of the wider Bcl-2 family, which also includes Bcl-x, Bcl-w and Mcl-1, are described by their similarity to Bcl-2 protein, a member of the pro-survival Bcl-2 subfamily . Full-length Bcl-2 proteins feature all four BH domains, seven α-helices, and a C-terminal hydrophobic motif that targets the protein to the outer mitochondrial membrane, ER and nuclear envelope.
Bcl-2-related protein A1 (Bcl2A1)
Type: Family

Bcl-2-related protein A1 is a proapoptotic member of the Bcl-2 family. It retards apoptosis induced by IL-3 deprivation . It may function in the response of hemopoietic cells to external signals and in maintaining endothelial survival during infectio
RLI1 (RLI1)
Type: Family

This entry represents the ABCE family of ATP-binding cassette (ABC) transporters and solely comprises of the ABCE1 gene product (also known as RNase L inhibitor, RLI1) . RLI1 contains 2 nucleotide-binding domains (NBDs) typical of the ABC transporter protein superfamily ; however, it lacks the transmembrane domains required for membrane transport functions . RLI1 was first identified as an endoribonuclease inhibitor that interacts directly with RNase L to prevent it from binding 2-5A (5'-phosphorylated 2',5'-linked oligo-adenylates) . RNase L plays a major role in the anti-viral and anti-proliferative activities of interferons, and its inhibition by RLI1 occurs in a concentration-dependent manner . Recently, RLI1 has been shown to be essential for the assembly of immature HIV-1 capsids in insect cells and higher eukaryotic cell types . RLI1 expression is induced during HIV type I infection, and is understood to bind HIV-1 Gag (p55) polypeptides following their translation, and to promote their assembly into immature HIV-1 capsids .
Beta-catenin (Beta-catenin)
Type: Family

Three different forms of catenin (designated alpha, beta and gamma) comprise the cytoplasmic domain of the cadherin cell-cell adhesion complex . Beta-catenin forms a cadherin/beta-catenin/alphaE-catenin complex that can tether the tripartite adhesion complex and regulate actin dynamics .

This entry represents the beta catenins and homologues, plakoglobin and the Drosophila Armadillo protein , which are implicated in cell adhesion and Wnt signalling . Originally identified as downstream elements (armadillo phenotype) of the Wnt signalling pathway (wingless phenotype) . The beta-catenin structure has been determined . Beta catenin family proteins contain several ARM repeats, sequences of approximately 50 amino acids involved in protein-protein interactions. Each repeat consists of three helices , with helix 1 and 3 antiparallel to each other and perpendicular to helix 2 . A conserved glycine residue allows the sharp turn between helices 1 and 2 .
Claudin-12 (Claudin12)
Type: Family

Zona occludens (ZO), or tight junctions (TJ), are specialised membrane domains found at the most apical region of polarised epithelial and endothelial cells. They create a primary barrier, preventing paracellular transport of solutes, and restricting the lateral diffusion of membrane lipids and proteins, thus maintaining cellular polarity . They also act as diffusion barriers within plasma membranes, creating and maintaining apical and basolateral membrane domains. Under freeze-fracture electron microscopy, TJs appear as a network of continuous anastomosing intramembranous strands. These strands consist mainly of claudins and occludin (

), which are transmembrane proteins that polymerise within plasma membranes to form fibrils .

Recently, the molecular architecture of tight junctions has begun to be elucidated. One group of proteins thought to be major components of TJs is the claudin family . Immunofluorescence studies have shown that claudins are targeted to and incorporated into tight junctions . Furthermore, when claudins are introduced into cells that lack tight junctions, networks of strands and grooves form at cell-cell contact sites that closely resemble native TJs .

The claudin protein family is encoded by at least 17 human genes, with many homologues cloned from other species. Tissue distribution patterns for the claudin family members are distinct. Claudin-1 and -2, for example, are expressed at high levels in the liver and kidney, whereas claudin-3 mRNA is detected mainly in the lung and liver . This suggests that multiple claudin family members may be involved in tight junction strand formation in a tissue-dependent manner.

Orthologues of the claudin 12 subtype have been identifed in humans and zebrafish. Whilst these proteins clearly belong to the tetraspanin superfamily, they represent the most divergent claudin subtype in terms of primary structure . Claudin 12 mRNA has been detected in the brain, prostate, colon and uterus .