SII-SWORD/CoKE huggingface dataset:
RNA-binding protein Musashi homologue, RNA recognition motif 2 (MSI_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of Musashi-1, which is a highly conserved RNA binding protein that was initially identified in Drosophila by its ability to regulate sensory organ development and asymmetric cell division . Mammalian Musashi-1 has multiple functions in normal and abnormal processes by mediating different post-transcriptional processes. It has been implicated in the maintenance of the stem-cell state, differentiation, and tumorigenesis. It translationally regulates the expression of a mammalian numb gene by binding to the 3'-untranslated region of mRNA of Numb, encoding a membrane-associated inhibitor of Notch signaling, and further influences neural development . Moreover, Musashi-1 represses translation by interacting with the poly(A)-binding protein and competes for binding of the eukaryotic initiation factor-4G (eIF-4G) .

Proteins containing this domain also includes Musashi-2, which has been identified as a regulator of the hematopoietic stem cell (HSC) compartment and of leukemic stem cells after transplantation of cells with loss and gain of function of the gene . It influences proliferation and differentiation of HSCs and myeloid progenitors, and further modulates normal hematopoiesis and promotes aggressive myeloid leukemia . Musashi-1 and Musashi-2 contain two conserved N-terminal tandem RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), along with other domains of unknown functio
CX3C chemokine domain (Chemokine_CX3C)
Type: Domain

Chemokine CX3C is one of four chemokine subgroup designations based on the arrangement of the two N-terminal cysteines. Currently, the only member of this group identified to date is CX3C chemokine ligand 1 (CX3CL1), also known as fractalkine or neurotactin. The primary source of fractalkine is neurons, and it exhibits cell adhesion and chemoattractive properties in the central nervous system . Fractalkine differs structurally from the other subgroups in that it is attached to a membrane-spanning domain via a mucin-like stalk and can be proteolytically cleaved to a freely diffusible form . Fractalkine combines properties of chemoattractant and adhesion molecule . It is chemotatic for T cells, monocytes, and natural killer cells .

This entry represents the N-terminal chemokine domain of fractalkine .
K02A2.6-like peptidase catalytic domain (K02A2.6-like)
Type: Domain

This entry includes a retropepsin-like domain of invertebrate retrotransposons with long terminal repeats . Although none of the proteins have been characterised, the retropepsin-like domain is presumed to be an aspartate endopeptidase. While fungal and mammalian pepsins are bilobal proteins with structurally related N- and C-terminal, retropepsins are half as long as their fungal and mammalian counterparts . The monomers are structurally related to one lobe of the pepsin molecule and retropepsins function as homodimers. The active site aspartate occurs within a motif (Asp-Thr/Ser-Gly), as it does in pepsin. In aspartate endopeptidases, Asp residues are ligands of an activated water molecule in all examples where catalytic residues have been identified. The retrotransposon aspartyl endopeptidase is synthesized as part of a polyprotein that also contains a reverse transcriptase and an integrase. The polyprotein is presumed to undergo specific enzymatic cleavage to yield the mature proteins. This group of aspartate endopeptidases is classified by MEROPS as peptidase family A28 .
Cathepsin D-like catalytic domain (Cathepsin_D-like)
Type: Domain

This entry includes the peptidase domain of uncharacterised aspartic endopeptidases from animals with similarities to cathepsin D.

Cathepsin D (

and MEROPS identifier A01.009) is an aspartic endopeptidase located in the lysosome of animal cells. It is synthesized as an inactive precursor and activated in the lysosome, either autolytically or by other lysosomal peptidases . Its optimum pH is ~3.5 . Quantitative N-terminal proteomics has been used to study the specificity of the enzyme . Although primarily thought to be involved in lysosomal catabolism of proteins, knockout of the mouse CATD gene is neonatally fatal and associated with numerous defects . Cathepsin D has been shown to induce apoptosis . Procathepsin D is also secreted in some cancers, where it can be activated at the acidic pH of the tumour microenvironment and promote the growth of cancer tissue or metastasis by degradation of extracellular matrix , or act as a mitogen .
DAZ-associated protein 1, RNA recognition motif 2 (DAZAP1_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 of DAZAP1.

DAZAP1, initially identified as a binding partner of Deleted in Azoospermia (DAZ), is a multi-functional ubiquitous RNA-binding protein expressed most abundantly in the testis and is essential for normal cell growth, development, and spermatogenesis . DAZAP1 is a shuttling protein whose acetylated form is predominantly nuclear and the nonacetylated form is in cytoplasm . DAZAP1 also functions as a translational regulator that activates translation in an mRNA-specific manner . It also interacts with numerous hnRNPs, including hnRNP U, hnRNP U like-1, hnRNPA1, hnRNPA/B, and hnRNP D, suggesting DAZAP1 might associate and cooperate with hnRNP particles to regulate adenylate-uridylate-rich elements (AU-rich element or ARE)-containing mRNAs . DAZAP1 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal proline-rich domain .

This entry also includes the orthologue from Drosophila melanogaster Heterogeneous nuclear ribonucleoprotein 27C (Rbp7).
Retropepsin Saci-like domain (RP_Saci-like)
Type: Domain

This entry includes the peptidase domains of retropepsin-like aspartic endopeptidases from retrotransposons with long terminal repeats (LTR) including Saci-1, -2 and -3 of Schistosoma mansoni . Retropepsins are related to fungal and mammalian pepsins. While fungal and mammalian pepsins are bilobal proteins with structurally related N- and C-termini, retropepsins are half as long as their fungal and mammalian counterparts. The monomers are structurally related to one lobe of the pepsin molecule and retropepsins function as homodimers. The active site aspartate occurs within a motif (Asp-Thr/Ser-Gly), as it does in pepsin. Asp residues are ligands of an activated water molecule in all examples where catalytic residues have been identified. Retrotransposon aspartic endopeptidase is synthesized as part of a polyprotein that also contains a reverse transcriptase and an integrase. The polyprotein is presumed to undergo specific enzymatic cleavage to yield the mature proteins. This group of aspartic endopeptidases is classified by MEROPS as the peptidase family A28, subfamily A28B .
Chemokine CC, DCCL motif-cointaining domain (Chemokine_CC_DCCL)
Type: Domain

This domain is found in a subgroup of CC chemokines based on the presence of a DCCL motif involving the two N-terminal cysteine residues. This subgroup includes a number of small inducible cytokines capable of reversibly inhibiting normal hematopoietic progenitor proliferation by blocking progression through the cell cycle; including Exodus-1 (also known as CCL20, MIP-3alpha, LARC, ST38 (mouse)), Exodus-2 (also known as CCL21, SLC, 6-Ckine, TCA4, CKbeta9), and Exodus-3 (also known as CCL-19, ELC, MIP-3beta, CKbeta11) . Exodus-3 was shown to inhibit the growth of human breast cancer cells in vivo in a mouse model . Exodus-1, -2, and -3 were all shown to significantly inhibit chronic myelogenous leukemia progenitor cell proliferation . Exodus-2 and -3 show potent immunotherapeutic activity toward solid tumours . They are found only in vertebrates.
DAZ-associated protein 1, RNA recognition motif 1 (DAZAP1_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 of DAZAP1.

DAZAP1, initially identified as a binding partner of Deleted in Azoospermia (DAZ), is a multi-functional ubiquitous RNA-binding protein expressed most abundantly in the testis and is essential for normal cell growth, development, and spermatogenesis . DAZAP1 is a shuttling protein whose acetylated form is predominantly nuclear and the nonacetylated form is in cytoplasm . DAZAP1 also functions as a translational regulator that activates translation in an mRNA-specific manner . It also interacts with numerous hnRNPs, including hnRNP U, hnRNP U like-1, hnRNPA1, hnRNPA/B, and hnRNP D, suggesting DAZAP1 might associate and cooperate with hnRNP particles to regulate adenylate-uridylate-rich elements (AU-rich element or ARE)-containing mRNAs . DAZAP1 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a C-terminal proline-rich domain .
Renin-like domain (Renin-like_dom)
Type: Domain

This entry represents a domain found in renin, a member of the aspartic peptidase A1 family . Aspartyl proteases (APs), also known as acid proteases, ([ec:3.4.23.-]) are a widely distributed family of proteolytic enzymes known to exist in vertebrates, fungi, plants, retroviruses and some plant viruses. APs use an Asp dyad to hydrolyze peptide bonds .

Renin, also known as angiotensinogenase (MEROPS identifier A01.007), is a circulating enzyme that participates in the renin-angiotensin system that mediates extracellular volume, arterial vasoconstriction, and consequently mean arterial blood pressure. The enzyme is secreted by the kidneys from specialized juxtaglomerular cells in response to decreases in glomerular filtration rate (a consequence of low blood volume), diminished filtered sodium chloride and sympathetic nervous system innervation. The enzyme circulates in the blood stream and hydrolyzes angiotensinogen secreted from the liver into the peptide angiotensin I . Angiotensin I is further cleaved in the lungs by endothelial bound angiotensin converting enzyme (ACE) into angiotensin II, the final active peptide. The enzyme is a member of peptidase family A1 .

Mice have an additional renin secreted by the submandibular salivary gland and known as renin-2 (MEROPS identifier A01.008) .
Topoisomerase 6 subunit A/Spo11, TOPRIM domain (TOPRIM_Topo6A/Spo11)
Type: Domain

This topoisomerase-primase (TOPRIM) nucleotidyl transferase/hydrolase domain is found in the type II topoisomerase VIA and Spo11. This subgroup contains proteins similar to Sulfolobus shibatae topoisomerase VIA (TopoVIA) and Saccharomyces cerevisiae meiotic recombination factor Spo11 . Type II DNA topoisomerases catalyze the ATP-dependent transport of one DNA duplex through another, in the process generating transient double strand breaks via covalent attachments to both DNA strands at the 5' positions. TopoVI enzymes are heterotetramers found in archaea and plants . Spo11 plays a role in generating the double strand breaks that initiate homologous recombination during meiosis . S. shibatae TopoVI relaxes both positive and negative supercoils, and in addition has a strong decatenase activity .

The TOPRIM domain has two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). For topoisomerases, the conserved glutamate is believed to act as a general base in strand joining, and as a general acid in strand cleavage . The DXD motif may co-ordinate Mg2+, a cofactor required for full catalytic function.
RecR, TOPRIM domain (TOPRIM_RecR)
Type: Domain

This topoisomerase-primase (TOPRIM) nucleotidyl transferase/hydrolase domain is found in RecR . RecR participates in the RecFOR pathway of homologous recombinational repair in prokaryotes . This pathway provides a single-stranded DNA molecule coated with RecA to allow invasion of a homologous molecule. The RecFOR system directs the loading of RecA onto gapped DNA coated with single-strand DNA binding-protein .

The TOPRIM domain has two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). In RecR sequences this glutamate in the first turn of the TOPRIM domain is semiconserved, the DXD motif is not conserved .
Nucleolar protein 8, RNA recognition motif (NOP8_RRM)
Type: Domain

This entry represents the RNA recognition motif of NOP8 (also known as NOP132). In humans, NOP132 associates with proteins involved in ribosome biogenesis and RNA metabolism, including the DEAD-box RNA helicase protein, DDX47 . Budding yeast NOP8 is required for 60S ribosomal subunit synthesis .
OLD protein-like, TOPRIM domain (TOPRIM_OLD)
Type: Domain

This topoisomerase-primase (TOPRIM) nucleotidyl transferase/hydrolase domain is found in bacterial and archaeal nucleases of the OLD (overcome lysogenization defect) family. The bacteriophage P2 OLD protein, which has DNase as well as RNase activity , consists of an N-terminal ABC-type ATPase domain and a C-terminal Toprim domain ; the nuclease activity of OLD is stimulated by ATP, though the ATPase activity is not DNA-dependent. OLD hologues are divided in two classes based on sequence length and the presence/absence of a unique UvrD/PcrA/Rep-like helicase gene immediately downstream in the genome. Despite degenerate conservation in the C-terminal domain between classes, they conserve the catalytic mechanism for DNA cleavage . Functional details on OLD are scant and further experimentation is required to define the relationship between the ATPase and Toprim nuclease domains, but in vitro studies on P2 OLD suggest that ATPase and nuclease activities are required for OLD function .

The TOPRIM domain has two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). The conserved glutamate may act as a general acid in strand cleavage by nucleases. The DXD motif may co-ordinate Mg2+, a cofactor required for full catalytic function .
Ecto-NOX disulfide-thiol exchanger, RNA recognition motif (ENOX_RRM)
Type: Domain

This entry represents the conserved RNA recognition motif (RRM) in ECTO-NOX proteins (ENOX).
Ribonuclease M5-like, TOPRIM domain (TOPRIM_RNase_M5-like)
Type: Domain

This topoisomerase-primase (TOPRIM) nucleotidyl transferase/hydrolase domain is found in Ribonuclease M5 (RNase M5) and other small primase-like proteins from bacteria and archaea. RNase M5 catalyzes the maturation of 5S rRNA in low G+C Gram-positive bacteria .

The TOPRIM domain has two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). The conserved glutamate may act as a general base in nucleotide polymerization by primases. The DXD motif may co-ordinate Mg2+, a cofactor required for full catalytic function .
Reverse gyrase, TOPRIM domain (TOPRIM_RevGyr)
Type: Domain

This topoisomerase-primase (TOPRIM) domain found in members of the type IA family of DNA topoisomerases (Topo IA) is similar to the ATP-dependent reverse gyrase found in archaea and thermophilic bacteria. Type IA DNA topoisomerases remove (relax) negative supercoils in the DNA by: cleaving one strand of the DNA duplex, covalently linking to the 5' phosphoryl end of the DNA break and, allowing the other strand of the duplex to pass through the gap . Reverse gyrase is also able to insert positive supercoils in the presence of ATP and negative supercoils in the presence of AMPPNP .

The TOPRIM domain has two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). For topoisomerases the conserved glutamate is believed to act as a general base in strand joining and, as a general acid in strand cleavage. The DXD motif may co-ordinate Mg
2+
, a cofactor required for full catalytic function .
snRNP70, RNA recognition motif (snRNP70_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of snRNP70 (also known as U1-70K), a key component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome .

U1-70K plays an essential role in targeting the U1 snRNP to the 5' splice site through protein-protein interactions with regulatory RNA-binding splicing factors, such as the RS protein ASF/SF2. It can also specifically bind to stem-loop I of the U1 small nuclear RNA (U1 snRNA) contained in the U1 snRNP complex. It also mediates the binding of U1C, another U1-specific protein, to the U1 snRNP complex .

U1-70K contains a conserved RNA recognition motif (RRM), followed by an adjacent glycine-rich region at the N-terminal half, and two serine/arginine-rich (SR) domains at the C-terminal half. The RRM is responsible for the binding of stem-loop I of U1 snRNA molecule. Additionally, the most prominent immunodominant region that can be recognized by auto-antibodies from autoimmune patients may be located within the RRM. The SR domains are involved in protein-protein interaction with SR proteins that mediate 5' splice site recognition . For instance, the first SR domain is necessary and sufficient for ASF/SF2 binding .

Proteins containing this domain also includes Drosophila U1-70K that is an essential splicing factor required for viability in flies, but its SR domain is dispensable .
DNA topoisomerase 3-like, TOPRIM domain (TOPRIM_TopoIII)
Type: Domain

This topoisomerase-primase (TOPRIM) domain is found in members of the type IA family of DNA topoisomerases (Topo IA) similar to topoisomerase III. Type IA DNA topoisomerases remove (relax) negative supercoils in the DNA by cleaving one strand of the DNA duplex, covalently linking to the 5' phosphoryl end of the DNA break, and allowing the other strand of the duplex to pass through the gap . Esherichia coli harbours two type IA enzymes: topoisomerase I and III. Topoisomerase III functions as the principal cellular decatenase and participates in efficient chromosome segregation .

The TOPRIM domain has two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). For topoisomerases the conserved glutamate is believed to act as a general base in strand joining and, as a general acid in strand cleavage. The DXD motif may co-ordinate Mg2+, a cofactor required for full catalytic function .
snRNP35, RNA recognition motif (snRNP35_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of snRNP35 (also known as U11/U12-35K), which is one of the components of the U11/U12 snRNP, a spliceosome required for splicing U12-type nuclear pre-mRNA introns .

U11/U12-35K is highly conserved among bilateria and plants, but is lacking in some organisms, such as Saccharomyces cerevisiae and Caenorhabditis elegans. Moreover, U11/U12-35K shows significant sequence similarity to U1 snRNP-specific 70kDa protein (U1-70K or snRNP70) .
RBM40, RNA recognition motif 1 (RBM40_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of RBM40 (also known as U11/U12-65K). RBM40 serves as a bridging factor between the U11 and U12 snRNPs . It contains two repeats of an RNA recognition motif (RRM), connected by a linker that includes a proline-rich region. It binds to the U11-associated 59K protein via its RRM1 and employs the RRM2 to bind hairpin III of the U12 small nuclear RNA (snRNA). The proline-rich region might be involved in protein-protein interactions .
NCBP2, RNA recognition motif (NCBP2_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of CBP20 (also known as NCBP2). CBP20 is the small subunit of the nuclear cap binding complex (CBC), which is a conserved eukaryotic heterodimeric protein complex binding to 5'-capped polymerase II transcripts and plays a central role in the maturation of pre-mRNA and uracil-rich small nuclear RNA (U snRNA). CBP20 is most likely responsible for the binding of capped RNA . It contains an RNA recognition motif (RRM) and interacts with the second and third domains of CBP80, the large subunit of CBC .
DNA topoisomerase 1, TOPRIM domain (TOPRIM_TopoI)
Type: Domain

This topoisomerase-primase (TOPRIM) domain is found in members of the type IA family of DNA topoisomerases (Topo IA) similar to Escherichia coli DNA topoisomerase I. Type IA DNA topoisomerases remove (relax) negative supercoils in the DNA by cleaving one strand of the DNA duplex, covalently linking to the 5' phosphoryl end of the DNA break, and allowing the other strand of the duplex to pass through the gap . E. coli DNA topoisomerase I is primarily involved in the relaxation of negatively supercoiled DNA by the stand passage mechanism .

The TOPRIM domain has two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). For topoisomerases the conserved glutamate is believed to act as a general base in strand joining and, as a general acid in strand cleavage. The DXD motif may co-ordinate Mg
2+
, a cofactor required for full catalytic function .
SF3B6, RNA recognition motif (SF3B6_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of SF3B14 (p14), also known as splicing factor 3B subunit 6 (SF3B6), which is part of the SF3B complex that is an integral part of the U2 small nuclear ribonucleoprotein (snRNP) and the U11/U12 di-snRNP . SF3B14 associates directly with another SF3B subunit called SF3B155 . SF3B14 can be cross-linked to the branch-point adenosine of pre-mRNA introns within the spliceosome .
Bacterial DnaG primase, TOPRIM domain (TOPRIM_DnaG_bac)
Type: Domain

This topoisomerase-primase (TORPIM) nucleotidyl transferase/hydrolase domain is found in proteins similar to Escherichia coli DnaG. The active site of the primase is located within the TOPRIM domain . Primases synthesize RNA primers for the initiation of DNA replication. DnaG type primases are often closely associated with DNA helicases in primosome assemblies .

The TOPRIM domain has two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). This glutamate and two aspartates, cluster together to form a highly acid surface patch. The conserved glutamate may act as a general base in nucleotide polymerization by primases. The DXD motif may co-ordinate Mg2+, a cofactor required for full catalytic function. E. coli DnaG is a single subunit enzyme .
SLIRP, RNA recognition motif (SLIRP_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of SLIRP, a widely expressed small steroid receptor RNA activator (SRA) binding protein, which binds to STR7, a functional substructure of SRA. SLIRP is localized predominantly to the mitochondria and plays a key role in modulating several nuclear receptor (NR) pathways. It functions as a co-repressor to repress SRA-mediated nuclear receptor co-activation. It modulates SHARP- and SKIP-mediated co-regulation of NR activity. The RNA recognition motif of SLIRP is required for SLIRP's corepression activities .
Archaeal primase DnaG/twinkle-like, TOPRIM domain (TOPRIM_DnaG/twinkle)
Type: Domain

This topoisomerase-primase (TOPRIM) nucleotidyl transferase/hydrolase domain is found in archaeal DnaG-type primases and in mitochondrial twinkle helicase. In archaea, DnaG is tightly associated with the RNA-degrading exosome . DnaG of Sulfolobus solfataricus has been shown to exhibit primase activity in vitro . Twinkle is needed for mitochondrial DNA replication and may be involved in recombinational repair of mitochondrial DNA .

The TOPRIM domain has two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). This glutamate and two aspartates, cluster together to form a highly acid surface patch. The conserved glutamate may act as a general base in nucleotide polymerization by primases. The DXD motif may co-ordinate Mg
2+
, a cofactor required for full catalytic function .