SII-SWORD/CoKE huggingface dataset:
Cytochrome c oxidase subunit IV (Cyt_c_oxidase_su4)
Type: Family

Cytochrome c oxidase (COX) subunit IV is a mitochondrial inner membrane protein that forms part of the 13-subunit COX complex, the terminal oxidase in the mitochondrial electron transport chain. The enzyme catalyses the reaction:
4 ferrocytochrome c + O(2) = 4 ferricytochrome c + 2 H(2)O
This polypeptide belongs to a wider family of proteins that includes the Dictyostelium discoideum (Slime mold) COX VI and the Saccharomyces cerevisiae (Baker's yeast) protein YGX6. The 3D structure of the whole bovine heart cytochrome c oxidase has been determined to 2.8A resolution by means of X-ray crystallography . The structure reveals 13 different subunits, five phosphatidyl ethanolamines, three phosphatidyl glycerols, two cholates, two haems A, and a number of copper, magnesium and zinc ions . A hydrogen-bonded system, including a propionate of haem A, part of the peptide backbone, and an imidazole ligand of CuA, may provide an electron transfer pathway between CuA and haem A .
CBFA2T family (CBFA2T1/2/3)
Type: Family

This entry represents the CBFA2T family, whose members include CBFA2T1/2/3. They are transcriptional corepressors which facilitate transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes .
Protein CBFA2T1 (CBFA2T1)
Type: Family

Protein CBFA2T1 is a transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes . It can repress the expression of MMP7 in a ZBTB33-dependent manner and can repress transactivation mediated by TCF12 .
Myeloid transforming gene-related protein-1 (MTGR1) (MTGR1)
Type: Family

Transcriptional activation and repression is required for control of cell proliferation and differentiation during embryonic development and homeostasis in the adult organism. Perturbations of these processes can lead to the development of cancer . The Eight-Twenty-One (ETO) gene product is able to form complexes with corepressors and deacetylases, such as nuclear receptor corepressor (N-CoR), which repress transcription when recruited by transcription factors . The ETO gene derives its name from its association with many cases of acute myelogenous leukaemia (AML), in which a reciprocal translocation, t(8;21), brings together a large portion of the ETO gene from chromosome eight and part of the AML1 gene from chromosome 21. The human ETO gene family currently comprises three major subfamilies: ETO/myeloid transforming gene on chromosome 8 (MTG8); myeloid transforming gene related protein-1 (MTGR1) and myeloid transforming gene on chromosome 16 (MTG16). ETO proteins are composed of four evolutionarily conserved domains termed nervy homology regions (NHR) 1-4. NHR1 is thought to stabilise the formation of high molecular weight complexes, but is not directly responsible for repressor activity. NHR2 and its flanking sequence comprise the core repressor domain, which mediates 50% of the wild type repressor activity. Furthermore, there is evidence that the amphipathic helical structure of NHR2 promotes the formation of ETO/AML1 homodimers . NHR3 and NHR4 have been shown to act in concert to bind N-CoR. NHR4 contains two zinc finger motifs, which are thought to play a role in protein interactions rather than DNA binding . Screening of dbEST with the entire ETO cDNA sequence revealed a number of ESTs showing significant similarity to the query sequence. Of those identified, two overlapping clones were sequenced, revealing an ORF coding for a putative 575 amino acid protein. This was subsequently mapped to chromosome 20 and named EHT (ETO Homologous on chromosome Twenty), and later as MTGR1 .
Protein CBFA2T3 (CBFA2T3)
Type: Family

CBFA2T3 is a transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes .
Nervy (Nervy)
Type: Family

Transcriptional activation and repression is required for control of cell proliferation and differentiation during embryonic development and homeostasis in the adult organism. Perturbations of these processes can lead to the development of cancer . The Eight-Twenty-One (ETO) gene product is able to form complexes with corepressors and deacetylases, such as nuclear receptor corepressor (N-CoR), which repress transcription when recruited by transcription factors . The ETO gene derives its name from its association with many cases of acute myelogenous leukaemia (AML), in which a reciprocal translocation, t(8;21), brings together a large portion of the ETO gene from chromosome eight and part of the AML1 gene from chromosome 21. The human ETO gene family currently comprises three major subfamilies: ETO/myeloid transforming gene on chromosome 8 (MTG8); myeloid transforming gene related protein-1 (MTGR1) and myeloid transforming gene on chromosome 16 (MTG16). ETO proteins are composed of four evolutionarily conserved domains termed nervy homology regions (NHR) 1-4. NHR1 is thought to stabilise the formation of high molecular weight complexes, but is not directly responsible for repressor activity. NHR2 and its flanking sequence comprise the core repressor domain, which mediates 50% of the wild type repressor activity. Furthermore, there is evidence that the amphipathic helical structure of NHR2 promotes the formation of ETO/AML1 homodimers . NHR3 and NHR4 have been shown to act in concert to bind N-CoR. NHR4 contains two zinc finger motifs, which are thought to play a role in protein interactions rather than DNA binding . The ultrabithorax (Ubx) gene is a homeotic gene in Drosophila that determines the morphological characteristics of each segment. Ubiquitous expression of Ubx gave rise to increased expression of several mRNAs; one of these transcripts was localised to the nervous system precursor cells of the head, thoracic and abdominal segments, and was termed nervy. Analysis of nervy cDNA revealed that it shared significant sequence similarity with the human ETO gene; it was also found to contain a region of similarity to the TATA binding protein-associated factor TAF110 .
Protein LBH (LBH)
Type: Family

LBH (limb-bud and heart) protein may act as a transcriptional activator in mitogen-activated protein kinase signalling pathway to mediate cellular functions. It has been shown to regulate cardiac gene expression by modulating the combinatorial activities of key cardiac transcription factors, as well as their individual functions in cardiogenesis in mice .
Myelin and lymphocyte (MAL) protein (MAL)
Type: Family

Myelin is a product of myelinating cells: Schawnn cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). The processes of these myelinating cells wrap around axon segments to form a sheath. This sheath possesses insulating properties, allowing rapid propagation of action potentials (the electrical signal propagated by nerve cells) between the myelinating cell intervening nodes. Without myelin insulation, axons would need a 10-30-fold increase in diameter to achieve comparable conduction velocities. At the onset of myelination, during development, large amounts of myelin-specific lipids and proteins are synthesised and transported to the developing myelin sheath. The major protein component of PNS and CNS myelin differs between the 2 nervous systems. However, some of the minor protein components, including the 4 transmembrane (TM)-domain-containing myelin and lymphocyte protein (MAL), are found in both systems. Outside the nervous system, MAL is also found in T-cells and some epithelial cells (e.g., kidney, stomach and thyroid) . Glycosphingolipids are enriched in both epithelial cells and myelin, and are believed to decrease the permeability of lipid membranes to small molecules and increase the ability for membrane curvature. MAL co-purifies with glycosphingolipids in detergent-insoluble domains, suggesting a possible interaction. In Madin Darby Canine Kidney (MDCK) cells, MAL is found mainly in transport vesicles, and recent studies suggest that MAL is required for efficient vesicular transport of proteins across apical cell membranes . In myelinating cells, MAL appears to play a similar role, interacting with glycosphingolipids to decrease membrane permeability; however, here this property most likely manifests itself as an improved insulating ability of the myelin . In lymphocytes, however, MAL appears to act as a TM-linker protein in T-cell signal transduction, linking the cell surface glycosyl phosphatidylinositol anchored protein CD59 to the intracellular tyrosine kinase Lck .
HSPB1-associated protein 1 (HSPB1-associated_protein_1)
Type: Family

The small heat shock proteins of vertebrates are thought to play a major role in the cellular response to stress, and appear to play a role in a range of other physiological activities. Indeed, in response to many forms of stress, including heat, the expression of heat shock proteins is increased, and coincidentally these cells become more stress-resistant. One of these proteins is Heat Shock Protein (hsp) 27, for which 3 hypotheses currently exist to explain its mechanism of action: (i) it has chaperone-like activity, serving as a site where denatured, unfolding proteins can bind until hsp70-dependent refolding can occur; (ii) it stabilises microfilaments, strengthening the cytoskeleton; and (iii) it enhances levels of the cellular antioxidant glutathione . It was hypothesised that hsp27 associates with different protein partners in order to effect its various cellular functions. Thus, a yeast two-hybrid screen was performed on a rat Sertoli cell cDNA library, which identified a novel binding protein, termed HSPB1-associated protein 1 or Protein Associated with Small Stress protein 1.
Neuropeptide B/W precursor family (Neuropept_BW_pre)
Type: Family

Two closely related neuropeptide precursors, which share no significant sequence similarity with other known neuropeptides, have recently been identified and named preproneuropeptide B and preproneuropeptide W . In humans, each precursor contains a signal sequence and two dibasic cleavage sites. Alternative cleavage of these sites results in long (29 or 30 amino acid) and short (23 amino acid) forms of the resultant neuropeptides . Murine, rat and bovine versions of preproneuropeptide B, however, contain only the second cleavage site, resulting in only the long form of neuropeptide B . Neuropeptide B is expressed in both the central nervous system (CNS) and in the periphery. In the CNS, the highest levels of the peptide are found in the substantia nigra and hypothalamus, suggesting a possible role in locomotor control and the release of pituitary hormones . In the periphery, the peptide is most abundant in testis, ovary, uterus, placenta, spleen, lymph nodes and peripheral blood leukocytes, indicating potential roles in the reproductive and immune systems . Unusually, neuropeptide B purified from bovine hypothalamus was found to be brominated at its N terminus . Neuropeptide W has a more limited distribution in the brain than neuropeptide B, and is found at highest levels in the substantia nigra, again suggesting an involvement in locomotor control . In the periphery, neuropeptide W is more widespread than neuropeptide B. In addition to the reproductive and immune tissues in which neuropeptide B is expressed, neuropeptide W has been found at high levels in the liver, stomach and trachea . Intracerebroventricular administration of neuropeptide W in rats has been reported to produce an acute increase in food intake and to stimulate prolactin release .

This entry represents the neuropeptide B/W precursor family.
Neuropeptide B precursor (Neuropept_B_pre)
Type: Family

Two closely related neuropeptide precursors, which share no significant sequence similarity with other known neuropeptides, have recently been identified and named preproneuropeptide B and preproneuropeptide W . In humans, each precursor contains a signal sequence and two dibasic cleavage sites. Alternative cleavage of these sites results in long (29 or 30 amino acid) and short (23 amino acid) forms of the resultant neuropeptides . Murine, rat and bovine versions of preproneuropeptide B, however, contain only the second cleavage site, resulting in only the long form of neuropeptide B . Neuropeptide B is expressed in both the central nervous system (CNS) and in the periphery. In the CNS, highest levels of the peptide are found in the substantia nigra and hypothalamus, suggesting a possible role in locomotor control and the release of pituitary hormones . In the periphery, the peptide is most abundant in testis, ovary, uterus, placenta, spleen, lymph nodes and peripheral blood leukocytes, indicating potential roles in the reproductive and immune systems . Unusually, neuropeptide B purified from bovine hypothalamus was found to be brominated at its N terminus .

This entry represents the neuropeptide B precursor.
Neuropeptide W precursor (Neuropept_W_pre)
Type: Family

Two closely related neuropeptide precursors, which share no significant sequence similarity with other known neuropeptides, have recently been identified and named preproneuropeptide B and preproneuropeptide W . In humans, each precursor contains a signal sequence and two dibasic cleavage sites. Alternative cleavage of these sites results in long (29 or 30 amino acid) and short (23 amino acid) forms of the resultant neuropeptides . Murine, rat and bovine versions of preproneuropeptide B, however, contain only the second cleavage site, resulting in only the long form of neuropeptide B . Neuropeptide W has a more limited distribution in the brain than neuropeptide B and is found at highest levels in the substantia nigra, suggesting an involvement in locomotor control . In the periphery, neuropeptide W is more widespread than neuropeptide B. Like neuropeptide B, it is expressed at high levels in testis, ovary, uterus, placenta, spleen, lymph nodes and peripheral blood leukocytes, indicating potential roles in the reproductive and immune systems . In addition, however, neuropeptide W has been found at high levels in the liver, stomach and trachea . Intracerebroventricular administration of neuropeptide W in rats has been reported to produce an acute increase in food intake and to stimulate prolactin release .

This entry represents the neuropeptide W precursor.
Wnt-7 protein (Wnt7)
Type: Family

Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) . It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals . Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease .

Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in development . Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other .

Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.

Wnt-7 cDNA was isolated from mouse using a PCR-based strategy, where it was found to be expressed in adult tissues, particularly in brain and lung . Two subtypes are known to exist, designated Wnt-7A and B. Wnt-7A has been implicated in development of the uterus, cerebellum and limbs; Wnt-7B is believed to play a role in lung and placental development.
Wnt-8 protein (Wnt8)
Type: Family

Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) . It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals . Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease .

Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in development . Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other .

Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.

This entry represents Wnt-8. It was first isolated from Xenopus, with orthologues later being identified in several other species including human, mouse and zebrafish. Alternative exon splicing gives rise to several Wnt-8 isoforms .
Wnt-10 protein (Wnt10)
Type: Family

Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) . It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals . Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease .

Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in development . Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other .

Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.

Two subtypes of the Wnt-10 protein exist, designated Wnt-10a and Wnt-10b. In mouse, these proteins share 62% sequence identity, compared to 59% in human . Their expression pattern indicates that they function in tissues responsible for the formation and maturation of red blood cells.
Wnt-9a protein (Wnt9a)
Type: Family

Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) . It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals . Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease .

Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in development . Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other .

Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.

Human Wnt-9a (previously Wnt-14) maps to chromosome 1 and originates, together with Wnt-9b (previously Wnt-15), from an ancestral branch of the Wnt gene family, which includes the Wnt-9 sequences found in jawless and cartilaginous fishes . Wnt-9a (Wnt14) mRNA is expressed in various types of human cancer, such as gastric and pancreatic cancer .