SII-SWORD/CoKE huggingface dataset:
SMYD3, SET domain (SMYD3_SET)
Type: Domain

This entry represents the SET domain of SET and MYND domain-containing protein 3 (SMYD3). SMYD3 functions as a histone methyltransferase that specifically methylates 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation. It also methylates 'Lys-5' of histone H4 . SMYD3 plays an important role in transcriptional activation as a member of an RNA polymerase complex . It is overexpressed in colorectal, breast, prostate, and hepatocellular tumours, and has been implicated as an oncogene in human malignancies . Methylation of MEKK2 by SMYD3 is important for regulation of the MEK/ERK pathway, suggesting the possibility of selectively targeting SMYD3 in RAS-driven cancers .

The SMYD family consists of five members including SMYD1/2/3/4/5. They contain two highly conserved structural and functional domains, the SET and MYND domains. The SET domain is involved in lysine methylation, while the MYND domain is involved in protein-protein interaction. They are essential in several mammalian developmental pathways .
SMYD4, SET domain (SMYD4_SET)
Type: Domain

This entry represents the SET domain of SET and MYND domain-containing protein 4 (SMYD4). SMYD4 functions as a potential tumour suppressor that plays a critical role in breast carcinogenesis at least partly through inhibiting the expression of PDGFR-alpha . In zebrafish, SMYD4 is ubiquitously expressed in early embryos and becomes enriched in the developing heart; mutants show a strong defect in cardiomyocyte proliferation, which lead to a severe cardiac malformation .

The SMYD family consists of five members including SMYD1/2/3/4/5. They contain two highly conserved structural and functional domains, the SET and MYND domains. The SET domain is involved in lysine methylation, while the MYND domain is involved in protein-protein interaction. They are essential in several mammalian developmental pathways .
SMYD5, SET domain (SMYD5_SET)
Type: Domain

This entry represents the SET domain of SET and MYND domain-containing protein 5 (SMYD5, also termed protein NN8-4AG, or retinoic acid-induced protein 15). SMYD5 functions as a histone lysine methyltransferase that mediates H4K20me3 at heterochromatin regions . It plays an important role in chromosome integrity by regulating heterochromatin and repressing endogenous repetitive DNA elements during differentiation . In zebrafish embryogenesis, it plays pivotal roles in both primitive and definitive hematopoiesis .

The SMYD family consists of five members including SMYD1/2/3/4/5. They contain two highly conserved structural and functional domains, the SET and MYND domains. The SET domain is involved in lysine methylation, while the MYND domain is involved in protein-protein interaction. They are essential in several mammalian developmental pathways .
KMT5B , SET domain (KMT5B_SET)
Type: Domain

Post-translational modification of the core histones H2A, H2B, H3 and H4 play an important part in chromatin biology. Histone H4 lysine 20 methylation (H4K20me) is critical for the biological processes that ensure genome integrity, such as DNA damage repair, DNA replication and chromatin compaction . Suv4-20 family members are a group of histone H4K20 methyltransferases that play an important role in epigenetic regulation. Lower eukaryotes have a single Suv4-20, while mammals have two closely related Suv4-20 paralogs, SUV420H1 and SUV420H2 . In mammals H4K20me2 is generated primarily by SUV420H1/KMT5B (which can also produce H4K20me3), while H4K20me3 is mostly generated by SUV420H2/KMT5C .

This entry represents the SET domain found in KMT5B (also known as SUV420H1). Suv420h1 knockout mice die perinatally and show overall growth retardation . In humans KMT5B may affect neurodevelopment and has been linked to Mental retardation, autosomal dominant 51 .
KMT5C , SET domain (KMT5C_SET)
Type: Domain

Post-translational modification of the core histones H2A, H2B, H3 and H4 play an important part in chromatin biology. Histone H4 lysine 20 methylation (H4K20me) is critical for the biological processes that ensure genome integrity, such as DNA damage repair, DNA replication and chromatin compaction . Suv4-20 family members are a group of histone H4K20 methyltransferases that play an important role in epigenetic regulation. Lower eukaryotes have a single Suv4-20, while mammals have two closely related Suv4-20 paralogs, SUV420H1 and SUV420H2 . In mammals H4K20me2 is generated primarily by SUV420H1/KMT5B (which can also produce H4K20me3), while H4K20me3 is mostly generated by SUV420H2/KMT5C .

This entry represents the SET domain found in KMT5C (also known as SUV420H2). KMT5C acts as an upstream epigenetic regulator of epithelial/mesenchymal state control .
Suv4-20, SET domain (Suv4-20_SET)
Type: Domain

Post-translational modification of the core histones H2A, H2B, H3 and H4 play an important part in chromatin biology. Histone H4 lysine 20 methylation (H4K20me) is critical for the biological processes that ensure genome integrity, such as DNA damage repair, DNA replication and chromatin compaction . Suv4-20 family members are a group of histone H4K20 methyltransferases that play an important role in epigenetic regulation. Lower eukaryotes have a single Suv4-20, while mammals have two closely related Suv4-20 paralogs, SUV420H1 and SUV420H2 . In mammals H4K20me2 is generated primarily by SUV420H1/KMT5B (which can also produce H4K20me3), while H4K20me3 is mostly generated by SUV420H2/KMT5C .

This entry represents the SET domain found in Suv4-20 from lower eukaryotes .
LegAS4-like, SET domain (LegAS4-like_SET)
Type: Domain

LegAS4 (

) is a type IV secretion system effector of Legionella pneumophila. It contains a SET domain that is involved in the modification of Lys4 of histone H3 (H3K4) in the nucleolus of the host cell, thereby enhancing heterochromatic rDNA transcription. It also contains an ankyrin repeat domain of unknown function at its C-terminal region . This entry represents the SET domain found in LegAS4 and related proteins.
SETD3, SET domain (SETD3_SET)
Type: Domain

This entry represents the SET domain found in SETD3 and related proteins.

SETD3 is a protein-histidine N-methyltransferase that specifically mediates methylation of actin at 'His-73' . It was initially reported to have histone methyltransferase activity and methylate 'Lys-4' and 'Lys-36' of histone H3 (H3K4me and H3K36me). However, this conclusion was based on mass spectrometry data wherein mass shifts were inconsistent with a bona fide methylation event. In vitro, the protein-lysine methyltransferase activity is weak compared to the protein-histidine methyltransferase activity .
SETD4, SET domain (SETD4_SET)
Type: Domain

This entry represents the SET domain found in SETD4, which is a cytosolic and nuclear functional lysine methyltransferase that plays a crucial role in breast carcinogenesis . However, its specific substrates and modification sites remain to be disclosed. Proteins containing this domain also include budding yeast Rkm2, which is a ribosomal protein lysine methyltransferase responsible for trimethylation of the lysine residue at position 3 of Rpl12A and Rpl12B .
SETD6, SET domain (SETD6_SET)
Type: Domain

This entry represents the SET domain found in SETD6 and related proteins.

SET domain methyltransferases can be involved both in translational and transcriptional roles. N-lysine methyltransferase SETD6 is a SET domain protein that specifically monomethylates 'Lys-310' of the RELA subunit of NF-kappa-B complex, leading to down-regulation of NF-kappa-B transcription factor activity . Homologues in yeast monomethylate 60S ribosomal protein L42 (RPL42A and RPL42B) at 'Lys-55' .
RBCMT, SET domain (SET_RBCMT)
Type: Domain

This entry represents the SET domain found in a group of ribulose-bisphosphate carboxylase]-lysine N-methyltransferases (RBCMTs) and related proteins from plants.

In pea (Pisum sativum), the protein-lysine methyltransferase (PsLSMT, also known as RBCMT) catalyses the trimethylation of Lys-14 in the large subunit (LS) of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) . Arabidopsis homologue of RBCMT, LSMT, is a protein-lysine methyltransferase methylating chloroplastic fructose 1,6-bisphosphate aldolases . The sequence conservation pattern and structure analysis of the SET domain provides clues regarding the possible active site residues of the domain. There are three conserved sequence motifs in most of the SET domain. The N-terminal motif (I) has characteristic glycines. The central motif (II) has a distinct pattern of polar and charged residues (Asn, His). The C-terminal conserved motif (III) has a characteristic dyad of polar residues and the hydrophobic residue tyrosine.
Set10/Efm1, SET domain (Set10/Efm1_SET)
Type: Domain

This entry represents the SET domain found in budding yeast Efm1 and fission yeast Set10. They are S-adenosyl-L-methionine-dependent protein-lysine N-methyltransferases. Efm1 monomethylates elongation factor 1-alpha (TEF1/TEF2) at 'Lys-30' , while Set10 methylates ribosomal protein L23 (rpl23a and rpl23b) .
SETD5, SET domain (SETD5_SET)
Type: Domain

This entry represents the SET domain found in SETD5, which is a chromatin regulator required for brain development . SETD5 is essential for regulating histone acetylation during gene transcription . Haploinsufficiency of SETD5 is implicated in syndromic autism spectrum disorder (ASD) .
KMT2E, SET domain (KMT2E_SET)
Type: Domain

This entry represents the SET domain found in KMT2E.

The protein known as histone-lysine N-methyltransferase 2E (KMT2E, mixed-lineage leukemia 5 or MLL5) has been shown to lack key residues and an essential loop in the the SET-I subdomain required for binding substrate and cofactors . MLL5 had been thought to be specific for mono- and dimethylation of 'Lys-4' of histone H3 (H3K4me1 and H3K4me2; which are specific tags for epigenetic transcriptional activation), and a component of an MLL5 complex, but the paper describing this alleged complex has been retracted by the authors . MLL5 mediates hematopoietic cell homeostasis, spermatogenesis, cell cycle progression, and survival . It is recruited to gene-rich euchromatic regions via the interaction of its plant homeodomain finger with the histone mark H3K4me3 . Overexpression of the MLL5 gene induced cell cycle arrest in G(1) phase .
Set3/4, SET domain (Set3/4_SET)
Type: Domain

This entry represents the SET domain found in Set3 and Set4 from fungi. They contain both SET and PHD domains. In budding yeasts, Set3 forms a single complex, Set3C, with Snt1, YIL112w, Sif2, Cpr1, and two putative histone deacetylases, Hos2 and NAD-dependent Hst1. Set3C is the yeast analog of the mammalian HDAC3/SMRT complex .
SETD7, SET domain (SETD7_SET)
Type: Domain

This entry represents the SET domain found in SETD7, an enzyme that specifically monomethylate Lys-4 of histone H3, thereby creating a specific tag for epigenetic transcriptional activation. Methylation of lysine residues in the N-terminal tails of histones is thought to represent an important component of the mechanism that regulates chromatin structure. SETD7 plays a central role in the transcriptional activation of genes such as collagenase and insulin. It is recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription. SETD7 also has methyltransferase activity toward non-histone proteins, including TAF10 and p53/TP53. SETD7 monomethylates Lys-189 of TAF10, which increases the affinity of TAF10 for RNA polymerase II. SETD7 monomethylates Lys-372 of p53/TP53, which stabilises p53/TP53 and increases p53/TP53-mediated transcriptional activation .
SETD2/Set2, SET domain (SETD2/Set2_SET)
Type: Domain

This entry represents the SET domain found in SETD2 from animals, ASHH2 from plants and Set2 from fungi. Proteins containing this domain are a group of histone methyltransferases that methylates histone H3 to form H3K36me .

Yeast Set2 is involved in transcription elongation as well as in transcription repression . The methyltransferase activity of budding yeast Set2 requires the recruitment to the RNA polymerase II, which is CTK1 dependent . Plant ASHH2 is required for the correct expression of genes essential to reproductive development .

SETD2 acts as histone-lysine N-methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using demethylated 'Lys-36' (H3K36me2) as substrate . SETD2 is also required for DNA double-strand break repair and activation of the p53-mediated checkpoint . SETD2-inactivation has been linked to tumour development . SETD2 also methylates alpha-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy . Moreover, SETD2 is also involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription .

SETD2 has been linked to several human diseases, including Renal cell carcinoma (RCC) , Luscan-Lumish syndrome (LLS) , Leukemia, acute lymphoblastic (ALL) and Leukemia, acute myelogenous (AML) .
EZH1, SET domain (EZH1_SET)
Type: Domain

This entry represents the SET domain found in EZH1.

The Polycomb Repressive Complex 2 (PRC2) is a chromatin modifying complex that consists of three core components: EED, SUZ12 and one of the two histone H3K27 methyltransferases, EZH1 or EZH2 . The PRC2 complex catalyses di- and trimethylation of histone H3 lysine 27 (H3K37me2/3), which has a repressive role. Even though EZH1 and EZH2 form similar PRC2 complexes, they exhibit contrasting repressive roles. In terms of their expression in mice, EZH1 is more abundant in nonproliferative adult organs, while EZH2 expression is tightly associated with proliferation .
EZH2, SET domain (EZH2_SET)
Type: Domain

This entry represents the SET domain found in EZH2.

The Polycomb Repressive Complex 2 (PRC2) is a chromatin modifying complex that consists of three core components: EED, SUZ12 and one of the two histone H3K27 methyltransferases, EZH1 or EZH2 . The PRC2 complex catalyses di- and trimethylation of histone H3 lysine 27 (H3K37me2/3), which has a repressive role. Even though EZH1 and EZH2 form similar PRC2 complexes, they exhibit contrasting repressive roles. In terms of their expression in mice, EZH1 is more abundant in nonproliferative adult organs, while EZH2 expression is tightly associated with proliferation .
Plant glutamate receptor, periplasmic ligand-binding domain (GABAb_receptor_plant_PBP1)
Type: Domain

This entry represents the periplasmic ligand-binding domain of plant glutamate receptors, which have sequence similarity with animal ionotropic glutamate receptor . Interestingly, despite sharing a common structure, GLRs and iGluRs display major sequence divergences, especially in key domains such as the receptor, the pore, and the 'gate'. Electrophysiological characterisation of PpGLR1, AtGLR3.2, and AtGLR3.3 showed their ligand-independent activity, providing evidence for functional differences between iGluRs and at least these specific GLRs . Animal ionotropic glutamate receptors (iGluRs) function in the nervous system, while plant glutamate receptor-like (GLR) homologues are involved in many plant-specific physiological functions, such as sperm signaling in moss, pollen tube growth, root meristem proliferation, innate immune and wound responses .
Dicer, double-stranded RNA-binding domain (DICER_DSRM)
Type: Domain

This entry represents the DRSM domain found in Dicer and related proteins. Dicer has been linked to human cancers .

Dicer endoribonuclease plays a central role in short dsRNA-mediated post-transcriptional gene silencing. It cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs . Dicer shows two N-terminal helicase domains (

), a dimerisation domain (

), a platform domain (

), a PAZ domain (

), two RNase III a/b domains (

) and a dsRNA-binding domain in its C-terminal region (

).
RNase III, double-stranded RNA binding domain, animal (RNAse_III_DSRM__animal)
Type: Domain

RNase III is a double-stranded RNA (dsRNA)-specific endoribonuclease involved in the initial step of microRNA (miRNA) biogenesis. It is a component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, RNase III cleaves the 3' and 5' strands of a stem-loop in pri-miRNAs (processing centre 11 bp from the dsRNA-ssRNA junction) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs . It is also involved in pre-rRNA processing .

Metazoan RNase III (also known as Drosha) is a larger protein than bacterial RNase III. It contains two RNase III domains in the C-terminal half of the protein followed by a double-stranded RNA binding motif (DSRM) . DSRM is not sequence specific, but highly specific for dsRNAs of various origin and structure. This entry represents the DRSM of Metazoan RNase III.
Large ribosomal subunit protein mL44, dsRNA binding domain, fungi (Ribosomal_mL44_DSRM_fung)
Type: Domain

Large ribosomal subunit protein mL44 (also known as MRPL3 for 54S ribosomal protein L3) is a component of the mitochondrial ribosome (mitoribosome), a dedicated translation machinery responsible for the synthesis of mitochondrial genome-encoded proteins, including at least some of the essential transmembrane subunits of the mitochondrial respiratory chain. mL44 contains a RNase III-like domain and a double-stranded RNA binding motif (DSRM) . DSRM is not sequence specific, but highly specific for dsRNAs of various origin and structure.

This entry represents the DSRM of mL44 from fungi.
Large ribosomal subunit protein mL44, dsRNA binding domain, metazoa (Ribosomal_mL44_DSRM_metazoa)
Type: Domain

Large ribosomal subunit protein mL44 (MRPL44) is a component of the 39S subunit of mitochondrial ribosome. It may play a role in the assembly/stability of nascent mitochondrial polypeptides exiting the ribosome. MRPL44 contains a RNase III-like domain and a double-stranded RNA binding motif (DSRM) . DSRM is not sequence specific, but highly specific for dsRNAs of various origin and structure.

This entry represents the DSRM of MRPL44 from animals. MRPL44 has been linked to human cardiomyopathy
.
DHX9, first double-stranded RNA binding domain (DHX9_DSRM_1)
Type: Domain

DHX9 (also known as RNA helicase A) is a multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction and plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation, and RNA-mediated gene silencing . It contains two double-stranded RNA binding motifs (DSRMs) at the N-terminal region and a DEXH-box helicase domain . Dosage compensation regulator mle from Drosophila is the DHX9 orthologue, it is the RNA helicase component of the male-specific lethal (MSL) histone acetyltransferase complex, a multiprotein complex essential for elevating transcription of the single X chromosome in the male (X chromosome dosage compensation) . Within the MSL complex, the helicase activity of mle remodels roX non-coding RNA (roX1 and roX2)s to promote assembly of the MSL complex .

This entry represents the first DSRM motif of DHX9 .
DHX9, second double-stranded RNA binding domain (DHX9_DSRM_2)
Type: Domain

DHX9 (also known as RNA helicase A) is a multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction and plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation, and RNA-mediated gene silencing . It contains two double-stranded RNA binding motifs (DSRMs) at the N-terminal region and a DEXH-box helicase domain . Dosage compensation regulator mle from Drosophila is the DHX9 orthologue, it is the RNA helicase component of the male-specific lethal (MSL) histone acetyltransferase complex, a multiprotein complex essential for elevating transcription of the single X chromosome in the male (X chromosome dosage compensation) . Within the MSL complex, the helicase activity of mle remodels roX non-coding RNA (roX1 and roX2)s to promote assembly of the MSL complex .

This entry represents the second DSRM motif of DHX9 .
DHX9, DEXH-box helicase domain (DHX9_DEXHc)
Type: Domain

DHX9 (also known as RNA helicase A) is a multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction and plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation, and RNA-mediated gene silencing . It contains two double-stranded RNA binding motifs (DSRMs) at the N-terminal region and a DEXH-box helicase domain . Dosage compensation regulator mle from Drosophila is the DHX9 orthologue, it is the RNA helicase component of the male-specific lethal (MSL) histone acetyltransferase complex, a multiprotein complex essential for elevating transcription of the single X chromosome in the male (X chromosome dosage compensation) . Within the MSL complex, the helicase activity of mle remodels roX non-coding RNA (roX1 and roX2)s to promote assembly of the MSL complex .

This entry represents the DEXH-box helicase domain of DHX9. This domain contains the ATP-binding region .
DND1, double-stranded RNA binding domain (DND1_DSRM)
Type: Domain

Dead end protein 1 (DND1) is an RNA-binding protein that is required for the survival of primordial germ cells (PGCs) and suppresses the formation of germ-cell tumors . DND1 binds a UU(A/U) trinucleotide motif predominantly in the 3' untranslated regions of mRNA, and destabilizes target mRNAs . It also counteracts the function of several microRNAs (miRNAs), which are inhibitors of gene expression, by binding mRNAs and prohibiting miRNAs from associating with their target sites . DND1 contains two RNA recognition motifs (RRMs) and a C-terminal double-stranded RNA binding motif (DSRM) that is not sequence specific, but highly specific for dsRNAs of various origin and structure.

This entry represents the DSRM of DND1.
Rnt1/Pac1, double-stranded RNA binding domain, fungi (Rnt1/Pac1_DSRM_fungi)
Type: Domain

This entry represents the double-stranded RNA binding domain found in Rnt1 from budding yeasts and Pac1 from fission yeasts. They are RNase III homologues . Rnt1 is a dsRNA-specific nuclease that cleaves eukaryotic pre-ribosomal RNA at the U3 snoRNP-dependent A0 site in the 5'-external transcribed spacer (ETS) and in the 3'-ETS. Rnt1 contains a double-stranded RNA binding motif (DSRM) at the C terminus. DSRM is not sequence specific, but highly specific for dsRNAs of various origin and structure . Pac1 converts long double-stranded RNAs into short oligonucleotides and also cleaves a small hairpin RNA substrate .
AtDRB-like, first double-stranded RNA binding domain, plant (AtDRB-like_DSRM_1)
Type: Domain

This entry represents the first double-stranded RNA binding domain of Arabidopsis thaliana double-stranded RNA-binding proteins (AtDRB1-5). They bind double-stranded RNA (dsRNA) and may be involved in RNA-mediated silencing. Members of this family contain two to three double-stranded RNA binding motifs (DSRMs) .
AtDRB-like, second double-stranded RNA binding domain, plant (AtDRB-like_DSRM_2)
Type: Domain

This entry represents the second double-stranded RNA binding domain of Arabidopsis thaliana double-stranded RNA-binding proteins (AtDRB1-5). They bind double-stranded RNA (dsRNA) and may be involved in RNA-mediated silencing. Members of this family contain two to three double-stranded RNA binding motifs (DSRMs) .