SII-SWORD/CoKE huggingface dataset:
Nuclear receptor-binding SET domain-containing protein 1, second PWWP domain (PWWP_NSD1_rpt2)
Type: Domain

This entry represents the second PWWP domain of NSD1 and similar sequences from vertebrates. The PWWP domain specifically recognises DNA and histone methylated lysines.

Nuclear receptor-binding SET domain-containing protein 1 (NSD1), also called Histone-lysine N-methyltransferase H3 lysine-36 specific, is a lysine methyltransferase that preferentially methylates H3 on Lysine36 (H3-K36) and H4 on Lysine20 (H4-K20), which is primarily associated with active transcription . It plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukaemia, breast cancer, neuroblastoma, and glioblastoma formation . It can alter transcription by interacting with the protein NSD1-interacting zinc finger protein 1 (NIZP1). It also mitigates caspase-1 activation by listeriolysin o (LLO) in macrophages, and requires functional LLO for the regulation of IL-1beta secretion. Moreover, NSD1 regulates RNA polymerase II (RNAP II) recruitment to bone morphogenetic protein 4 (BMP4). NSD1 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD domains are involved in protein-protein interactions . In humans, NSD1 is altered in approximately 10% of head and neck cancer patients with 55% decrease in risk of death in NSD1-mutated versus non-mutated patients; its disruption promotes favourable chemotherapeutic responses linked to hypomethylation.
RNA-binding protein FXR2, second type I K homology domain (KH_I_FXR2_rpt2)
Type: Domain

FXR2 contains three K-homology (KH) RNA-binding domains, the second one is represented in this entry.

FXR2 is an RNA-binding protein that associates with polyribosomes, predominantly with 60S large ribosomal subunits and recognises methylated lysine and bind H4K20me1/2/3. It is one of the autosomal paralogues of FMRP protein, part of a family of RNA-binding proteins that are involved the regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of a subset of mRNAs, playing a crucial role in neuronal development and synaptic plasticity, involved in the development of fragile X syndrome (FXS) . They are highly similar to one another and also retain highly conserved domain architecture comprising two tandem Tudor Agenet-like domains at the N-terminal, three ribonucleoprotein K homology (KH) domains and a cluster of arginine and glycine residues that constitute the RGG box . The KH domains and RGG box constitute a large region that is important for RNA binding and polyribosome association. FRX2 has been shown to specifically regulate hippocampal neurogenesis by reducing the stability of Noggin mRNA .
RNA-binding protein FXR1, first Tudor-like Agenet domain (Tudor_Agenet_FXR1_rpt1)
Type: Domain

This entry represents the first Tudor-like Agenet domain of FXR1 and its homologues.

FXR1 is one of the autosomal paralogues of fragile X messenger ribonucleoprotein 1 (FMRP/FMR1), part of a family of RNA-binding proteins . These proteins associate with polyribosomes, and play a central role in neuronal development and synaptic plasticity. They recognize methylated lysine and bind H4K20me1/2/3 through their Tudor-like Agenet domains and they are involved the regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of a subset of mRNAs, playing a crucial role in neuronal development and synaptic plasticity, involved in the development of fragile X syndrome (FXS) . They are highly similar to one another and also retain highly conserved domain architecture comprising two tandem Tudor Agenet-like domains at the N-terminal, three ribonucleoprotein K homology (KH) domains and a cluster of arginine and glycine residues that constitute the RGG box . The KH domains and RGG box constitute a large region that is important for RNA binding and polyribosome association.

FXR1 interacts with FXR2 and FMR1. FXR1 is highly expressed in muscle cells and is required for proper development of this tissue. It may regulate intracellular transport and local translation of certain mRNAs .
Histone-lysine N-methyltransferase NSD1 / NSD2, first PHD finger (PHD1_NSD1_2)
Type: Domain

This entry represents the first PHD finger found in NSD1 and NSD2, and similar sequences from vertebrates.

Nuclear receptor-binding SET domain-containing protein 1 (NSD1), also called Histone-lysine N-methyltransferase H3 lysine-36 specific, is a lysine methyltransferase that preferentially methylates H3 on Lysine36 (H3-K36) and H4 on Lysine20 (H4-K20), which is primarily associated with active transcription. It plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukaemia, breast cancer, neuroblastoma, and glioblastoma formation. It can alter transcription by interacting with the protein NSD1-interacting zinc finger protein 1 (NIZP1). It also mitigates caspase-1 activation by listeriolysin o (LLO) in macrophages, and requires functional LLO for the regulation of IL-1beta secretion. Moreover, NSD1 regulates RNA polymerase II (RNAP II) recruitment to bone morphogenetic protein 4 (BMP4) .

Histone-lysine N-methyltransferase NSD2 is overexpressed frequently in the t(4;14) translocation in 15% to 20% of multiple myeloma. It plays important roles in cancer cell proliferation, survival, and tumour growth, by mediating constitutive NF-kappaB signalling via the cytokine autocrine loop. It also enhances androgen receptor (AR)-mediated transcription. The principal chromatin-regulatory activity of NSD2 is dimethylation of histone H3 at lysine 36 (H3K36me2) .

Both NSD1 and NSD2 contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). In addition, NSD2 harbors a high mobility group (HMG) box. The SET domain is responsible for histone methyltransferase activity. The PWWP, HMG, and PHD fingers mediate chromatin interaction and recognition of histone marks .
RNA-binding protein FXR1, second Tudor-like Agenet domain (Tudor_Agenet_FXR1_rpt2)
Type: Domain

FXR1 contains two copies of the Tudor-like Agenet domain which contain an aromatic cage with potential for binding methylated lysine. This entry corresponds to the second one, which been shown to interact with methylated lysine .

FXR1 is one of the autosomal paralogues of fragile X messenger ribonucleoprotein 1 (FMRP/FMR1), part of a family of RNA-binding proteins . These proteins associate with polyribosomes, and play a central role in neuronal development and synaptic plasticity. They recognize methylated lysine and bind H4K20me1/2/3 through their Tudor-like Agenet domains and they are involved the regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of a subset of mRNAs, playing a crucial role in neuronal development and synaptic plasticity, involved in the development of fragile X syndrome (FXS) . They are highly similar to one another and also retain highly conserved domain architecture comprising two tandem Tudor Agenet-like domains at the N-terminal, three ribonucleoprotein K homology (KH) domains and a cluster of arginine and glycine residues that constitute the RGG box . The KH domains and RGG box constitute a large region that is important for RNA binding and polyribosome association.

FXR1 interacts with FXR2 and FMR1. FXR1 is highly expressed in muscle cells and is required for proper development of this tissue. It may regulate intracellular transport and local translation of certain mRNAs .
Nuclear receptor-binding SET domain-containing protein 1, second PHD finger (PHD2_NSD1)
Type: Domain

This entry represents the second PHD finger found in NSD1 and similar sequences from vertebrates.

Nuclear receptor-binding SET domain-containing protein 1 (NSD1), also called Histone-lysine N-methyltransferase H3 lysine-36 specific, is a lysine methyltransferase that preferentially methylates H3 on Lysine36 (H3-K36) and H4 on Lysine20 (H4-K20), which is primarily associated with active transcription . It plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukaemia, breast cancer, neuroblastoma, and glioblastoma formation . It can alter transcription by interacting with the protein NSD1-interacting zinc finger protein 1 (NIZP1). It also mitigates caspase-1 activation by listeriolysin o (LLO) in macrophages, and requires functional LLO for the regulation of IL-1beta secretion. Moreover, NSD1 regulates RNA polymerase II (RNAP II) recruitment to bone morphogenetic protein 4 (BMP4). NSD1 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD domains are involved in protein-protein interactions . In humans, NSD1 is altered in approximately 10% of head and neck cancer patients with 55% decrease in risk of death in NSD1-mutated versus non-mutated patients; its disruption promotes favourable chemotherapeutic responses linked to hypomethylation.
Nuclear receptor-binding SET domain-containing protein 1, third PHD finger (PHD3_NSD1)
Type: Domain

This entry represents the third PHD finger found in NSD1 and similar sequences from vertebrates.

Nuclear receptor-binding SET domain-containing protein 1 (NSD1), also called Histone-lysine N-methyltransferase H3 lysine-36 specific, is a lysine methyltransferase that preferentially methylates H3 on Lysine36 (H3-K36) and H4 on Lysine20 (H4-K20), which is primarily associated with active transcription . It plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukaemia, breast cancer, neuroblastoma, and glioblastoma formation . It can alter transcription by interacting with the protein NSD1-interacting zinc finger protein 1 (NIZP1). It also mitigates caspase-1 activation by listeriolysin o (LLO) in macrophages, and requires functional LLO for the regulation of IL-1beta secretion. Moreover, NSD1 regulates RNA polymerase II (RNAP II) recruitment to bone morphogenetic protein 4 (BMP4). NSD1 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD domains are involved in protein-protein interactions . In humans, NSD1 is altered in approximately 10% of head and neck cancer patients with 55% decrease in risk of death in NSD1-mutated versus non-mutated patients; its disruption promotes favourable chemotherapeutic responses linked to hypomethylation.
Nuclear receptor-binding SET domain-containing protein 1, fourth PHD finger (PHD4_NSD1)
Type: Domain

This entry represents the fourth PHD finger found in NSD1 and similar sequences from vertebrates.

Nuclear receptor-binding SET domain-containing protein 1 (NSD1), also called Histone-lysine N-methyltransferase H3 lysine-36 specific, is a lysine methyltransferase that preferentially methylates H3 on Lysine36 (H3-K36) and H4 on Lysine20 (H4-K20), which is primarily associated with active transcription . It plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukaemia, breast cancer, neuroblastoma, and glioblastoma formation . It can alter transcription by interacting with the protein NSD1-interacting zinc finger protein 1 (NIZP1). It also mitigates caspase-1 activation by listeriolysin o (LLO) in macrophages, and requires functional LLO for the regulation of IL-1beta secretion. Moreover, NSD1 regulates RNA polymerase II (RNAP II) recruitment to bone morphogenetic protein 4 (BMP4). NSD1 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD domains are involved in protein-protein interactions . In humans, NSD1 is altered in approximately 10% of head and neck cancer patients with 55% decrease in risk of death in NSD1-mutated versus non-mutated patients; its disruption promotes favourable chemotherapeutic responses linked to hypomethylation.
Fragile X messenger ribonucleoprotein 1, first Tudor-like Agenet domain (Tudor_Agenet_FMR1_rpt1)
Type: Domain

This entry represents the first Tudor-like Agenet domain of FMR1 and similar proteins from vertebrates.

Fragile X messenger ribonucleoprotein 1 (FMRP/FMR1), and its paralogues, FXR1 and FXR2 (RNA-binding protein FXR1 and 2, respectively), comprise a family of RNA-binding proteins . These are multifunctional polyribosome-associated proteins that play a central role in neuronal development and synaptic plasticity. They are involved in regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of a subset of mRNAs . They are highly similar to one another and also retain highly conserved domain architecture comprising two tandem Tudor Agenet-like domains at the N-terminal, three ribonucleoprotein K homology (KH) domains and a cluster of arginine and glycine residues that constitute the RGG box .

FMR1 performs nucleocytoplasmic shuttling of mRNA by a non-canonical nuclear localization signal (NLS) and a nuclear export signal . This protein plays a central role in neuronal development and synaptic plasticity and is able to modulate the DNA damage response. It is also required for ovary development and function . FMR1 has also been shown to interact with components of the miRNA pathway . A large expansion of the CGG trinucleotide repeat in the 5'-untranslated region of the FMR1 gene causes Fragile X syndrome (FXS), an inherited developmental disorder that causes a broad range of intellectual and physical challenges .
Nuclear receptor-binding SET domain-containing protein 1, fifth PHD finger (PHD5_NSD1)
Type: Domain

This entry represents the fifth PHD finger found in NSD1 and similar sequences from vertebrates.

Nuclear receptor-binding SET domain-containing protein 1 (NSD1), also called Histone-lysine N-methyltransferase H3 lysine-36 specific, is a lysine methyltransferase that preferentially methylates H3 on Lysine36 (H3-K36) and H4 on Lysine20 (H4-K20), which is primarily associated with active transcription . It plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukaemia, breast cancer, neuroblastoma, and glioblastoma formation . It can alter transcription by interacting with the protein NSD1-interacting zinc finger protein 1 (NIZP1). It also mitigates caspase-1 activation by listeriolysin o (LLO) in macrophages, and requires functional LLO for the regulation of IL-1beta secretion. Moreover, NSD1 regulates RNA polymerase II (RNAP II) recruitment to bone morphogenetic protein 4 (BMP4). NSD1 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD domains are involved in protein-protein interactions . In humans, NSD1 is altered in approximately 10% of head and neck cancer patients with 55% decrease in risk of death in NSD1-mutated versus non-mutated patients; its disruption promotes favourable chemotherapeutic responses linked to hypomethylation.
Nuclear receptor-binding SET domain-containing protein 1, SET domain (SET_NSD1)
Type: Domain

This entry represents the SET domain (including post-SET domain) of NSD1 and similar sequences from vertebrates .

Nuclear receptor-binding SET domain-containing protein 1 (NSD1), also called Histone-lysine N-methyltransferase H3 lysine-36 specific, is a lysine methyltransferase that preferentially methylates H3 on Lysine36 (H3-K36) and H4 on Lysine20 (H4-K20), which is primarily associated with active transcription . It plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukaemia, breast cancer, neuroblastoma, and glioblastoma formation . It can alter transcription by interacting with the protein NSD1-interacting zinc finger protein 1 (NIZP1). It also mitigates caspase-1 activation by listeriolysin o (LLO) in macrophages, and requires functional LLO for the regulation of IL-1beta secretion. Moreover, NSD1 regulates RNA polymerase II (RNAP II) recruitment to bone morphogenetic protein 4 (BMP4). NSD1 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD domains are involved in protein-protein interactions . In humans, NSD1 is altered in approximately 10% of head and neck cancer patients with 55% decrease in risk of death in NSD1-mutated versus non-mutated patients; its disruption promotes favourable chemotherapeutic responses linked to hypomethylation.
Nuclear SET domain-containing protein 2, first PWWP domain (PWWP_NSD2_rpt1)
Type: Domain

This entry represents the first PWWP domain of NSD2 and similar sequences from vertebrates. The PWWP domain specifically recognises DNA and histone methylated lysines.

Histone-lysine N-methyltransferase NSD2, also known as Nuclear SET domain-containing protein 2 or wolf-Hirschhorn syndrome candidate 1 protein (WHSC1), is overexpressed frequently in the t(4;14) translocation in 15% to 20% of multiple myeloma . It plays important roles in cancer cell proliferation, survival, and tumour growth, through mediating constitutive NF-kappaB signalling via the cytokine autocrine loop . It also enhances androgen receptor (AR)-mediated transcription . The principal chromatin-regulatory activity of NSD2 is dimethylation of histone H3 at lysine 36 (H3K36me2). NSD2 is highly overexpressed in several types of human cancers, including small-cell lung cancers, neuroblastoma, carcinomas of stomach and colon, and bladder cancers, and its overexpression tends to be associated with tumour aggressiveness . It is frequently deleted in Wolf-Hirschhorn syndrome. NSD2 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, a high mobility group (HMG) box, five PHD (plant-homeodomain) zinc finger motifs, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP, HMG, and PHD domains mediate chromatin interaction and recognition of histone marks.
Nuclear SET domain-containing protein 2, second PWWP domain (PWWP_NSD2_rpt2)
Type: Domain

This entry represents the second PWWP domain of NSD2 and similar sequences from vertebrates. The PWWP domain specifically recognises DNA and histone methylated lysines.

Histone-lysine N-methyltransferase NSD2, also known as Nuclear SET domain-containing protein 2 or wolf-Hirschhorn syndrome candidate 1 protein (WHSC1), is overexpressed frequently in the t(4;14) translocation in 15% to 20% of multiple myeloma . It plays important roles in cancer cell proliferation, survival, and tumour growth, through mediating constitutive NF-kappaB signalling via the cytokine autocrine loop . It also enhances androgen receptor (AR)-mediated transcription . The principal chromatin-regulatory activity of NSD2 is dimethylation of histone H3 at lysine 36 (H3K36me2). NSD2 is highly overexpressed in several types of human cancers, including small-cell lung cancers, neuroblastoma, carcinomas of stomach and colon, and bladder cancers, and its overexpression tends to be associated with tumour aggressiveness . It is frequently deleted in Wolf-Hirschhorn syndrome. NSD2 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, a high mobility group (HMG) box, five PHD (plant-homeodomain) zinc finger motifs, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP, HMG, and PHD domains mediate chromatin interaction and recognition of histone marks.
Fragile X messenger ribonucleoprotein 1, second Tudor-like Agenet domain (Tudor_Agenet_FMR1_rpt2)
Type: Domain

This entry represents the second Tudor-like Agenet domain of FMR1, which been shown to interact with methylated lysine .

Fragile X messenger ribonucleoprotein 1 (FMRP/FMR1), and its paralogues, FXR1 and FXR2 (RNA-binding protein FXR1 and 2, respectively), comprise a family of RNA-binding proteins . These are multifunctional polyribosome-associated proteins that play a central role in neuronal development and synaptic plasticity. They are involved in regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of a subset of mRNAs . They are highly similar to one another and also retain highly conserved domain architecture comprising two tandem Tudor Agenet-like domains at the N-terminal, three ribonucleoprotein K homology (KH) domains and a cluster of arginine and glycine residues that constitute the RGG box .

FMR1 performs nucleocytoplasmic shuttling of mRNA by a non-canonical nuclear localization signal (NLS) and a nuclear export signal . This protein plays a central role in neuronal development and synaptic plasticity and is able to modulate the DNA damage response. It is also required for ovary development and function . FMR1 has also been shown to interact with components of the miRNA pathway . A large expansion of the CGG trinucleotide repeat in the 5'-untranslated region of the FMR1 gene causes Fragile X syndrome (FXS), an inherited developmental disorder that causes a broad range of intellectual and physical challenges .