SII-SWORD/CoKE huggingface dataset:
Ribonucleoprotein PTB-binding 2, RNA recognition motif 2 (RAVER2_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of RAVER2.

Ribonucleoprotein PTB-binding 2 (RAVER2) has a similar domain structure to RAVER1: three N-terminal RRMs and a Pro-rich C terminus. Similar to RAVER1, RAVER2 binds to PTB, an important regulator of alternative splicing .
Negative elongation factor E, RNA recognition motif (NELFE_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of NELFE.

Negative elongation factor E (NELFE) is an essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II . The NELF complex is found in higher eukaryotes, but is absent in some species of nematodes, S. cerevisiae, and plants. It may repress transcription by inducing transcriptional pausing and can be regulated by integrator complex subunits (INTScom) .
Polysaccharide lyase family 11 (RGL11)
Type: Family

The rhamnogalacturonan lyase of the polysaccharide lyase family 11 (RGL11) cleaves glycoside bonds in polygalacturonan as well as RG (rhamnogalacturonan) type-I through a beta-elimination reaction. Functionally characterised members of this family, YesW and YesX from Bacillus subtilis, cleave glycoside bonds between rhamnose and galacturonic acid residues in the RG-I region of plant cell wall pectin. YesW and YesX work synergistically, with YesW cleaving the glycoside bond of the RG chain endolytically, and YesX converting the resultant oligosaccharides through an exotype reaction . There are two types of RG lyases, which both cleave the alpha-1,4 bonds of the RG-I main chain through a beta-elimination reaction, but belong to two structurally unrelated polysaccharide lyase (PL) families, 4 and 11.
Proteasome subunit alpha6 (Proteasome_subunit_alpha6)
Type: Family

The proteasome (or macropain) (

) is a multicatalytic proteinase complex in eukaryotes and archaea, and in some bacteria, that is involved in an ATP/ubiquitin-dependent non-lysosomal proteolytic pathway. In eukaryotes the 20S proteasome is composed of 28 distinct subunits which form a highly ordered ring-shaped structure (20S ring) of about 700kDa. Proteasome subunits can be classified on the basis of sequence similarities into two groups, alpha (A) and beta (B). The proteasome consists of four stacked rings composed of α/β/β/α subunits. There are seven different alpha subunits and seven different beta subunits . Three of the seven beta subunits are peptidases, each with a different specificity. Subunit beta1c (MEROPS identifier T01.010) has a preference for cleaving glutaminyl bonds ("peptidyl-glutamyl-like" or "caspase-like"), subunit beta2c (MEROPS identifier T01.011) has a preference for cleaving arginyl and lysyl bonds ("trypsin-like"), and subunit beta5c (MEROPS identifier T01.012) cleaves after hydrophobic amino acids ("chymotrypsin-like") . The proteasome subunits are related to N-terminal nucleophile hydrolases, and the catalytic subunits have an N-terminal threonine nucleophile.

This entry includes the non-proteolytic alpha6 subunit of the 19S proteasome (MEROPS identifier T01.971). The equivalent subunit in Saccharomyces cerevisiae is known as alpha1. A single nuclear polymorphism is associated with a higher risk of myocardial infarction in a Japanese population, possibly because of an increased risk of atherosclerosis .
Mitochondrial ribosomal protein S7, plants (RPS7_plant)
Type: Family

uS7, also known as ribosomal protein S7 (RPS7) is a key component of the small ribosomal subunit in the mitochondrion. This family includes RPS7 from Viridiplantae.

The ribosome small subunit is one of the two subunits of ribosome organelles that use mRNA as a template for protein synthesis in a process called translation. The small subunits of bacteria and eukaryotes have the same shape of head, body, platform, beak, and shoulder. RPS7 is located at the head of the small subunit. RPS7 is a primary ribosomal RNA (rRNA) binding protein that assists in rRNA folding and the binding of other proteins during small subunit assembly in all species. RPS7 is also involved in the formation of the mRNA exit channel at the interface of the large and small subunits . Some ribosomal proteins have extra ribosomal functions in cell differentiation and apoptosis .
ADCK3-like domain (ADCK3_dom)
Type: Domain

This domain is found in the atypical yeast protein kinase Abc1p (also called Coq8p), its human homologue ADCK3 (also called COQ8A), and similar proteins. Abc1p is required for the biosynthesis of Coenzyme Q (ubiquinone or Q), which is an essential lipid component in respiratory electron and proton transport. It is necessary for the formation of a multi-subunit Q-biosynthetic complex and may also function in the regulation of Q synthesis. Human ADCK3 is able to rescue defects in Q synthesis and the phosphorylation state of Coq proteins in yeast Abc1 (or Coq8) mutants . Mutations in ADCK3 cause progressive cerebellar ataxia and atrophy due to Q10 deficiency .

In algae and higher plants, ABC1 kinases have proliferated to more than 15 subfamilies, most of which are located in plastids or mitochondria . Subfamily 13 (ABC1K13) of plant ABC1 kinases belongs in this group with yeast Abc1p and human ADCK3. ABC1 kinases are not related to the ATP-binding cassette (ABC) membrane transporter family.
CELF-3/4/5/6, RNA recognition motif 1 (CELF3/4/5/6_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of CELF-3, CELF-4, CELF-5, CELF-6, all of which belong to the CUGBP1 and ETR-3-like factors (CELF) or BRUNOL (Bruno-like) family of RNA-binding proteins . The CELF family members have three RRMs . It has been shown that either RRM1 or RRM2 of CELF-4 are necessary and sufficient for muscle-specific splicing enhancer (MSE) RNA binding .

The human CELF family has six members, which can be divided into two subfamilies based on their phylogeny: CELF1-2 and CELF3-6. They all possess alternative splicing activity in the nucleus and all have cytoplasmic roles, including regulating mRNA adenylation status, stability, and translation in various cell types .
Hsp70-interacting protein, N-terminal (Hip_N)
Type: Domain

The Hsc70/Hsp70-interacting protein (Hip, also p48 or suppressor of tumorigenicity ST13) functions as a regulator of the cyclic action of Hsp70. Hip forms homodimers, and this entry represents the N-terminal dimerization domain, which may not be directly involved in its regulatory function. A central domain of Hip that contains TPR repeats binds the ATPase domain of Hsp70 and slows the release of ADP .
YuaB-like (YuaB-like)
Type: Family

BslA (YuaB) is a protein from Bacillus subtilis acting as a hydrophobin, which forms surface layers around biofilms and participates in biofilm assembly . BslA contains an unusually hydrophobic "cap structure", which is essential for its activity and for the ability of bacteria to form hydrophobic, non-wetting biofilms . This family also includes BslA paralogue YweA (also known as bslB). YweA appears to have only a minor role in biofilm formation .
SRSF7, RNA recognition motif (SRSF7_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of SRSF7 (also termed splicing factor 9G8), which is a splicing regulatory serine/arginine (SR) protein that plays a crucial role in both constitutive splicing and alternative splicing of many pre-mRNAs . Its localization and functions are tightly regulated by phosphorylation. SRSF7 is predominantly present in the nucleus and can shuttle between nucleus and cytoplasm. It cooperates with the export protein, Tap/NXF1, helps mRNA export to the cytoplasm, and enhances the expression of unspliced mRNA . SRSF7 inhibits tau E10 inclusion through directly interacting with the proximal downstream intron of E10, a clustering region for frontotemporal dementia with Parkinsonism (FTDP) mutations .
Signal recognition particle subunit SRP68, RNA-binding domain (SRP68-RBD)
Type: Domain

Signal recognition particles (SRPs) are ribonucleoprotein complexes that target particular nascent pre-secretory proteins to the endoplasmic reticulum. The SRP complex targets the ribosome-nascent chain complex to the SRP receptor (SR), which is anchored in the ER, where SR compaction and GTPase rearrangement drive cotranslational protein translocation into the ER . SRP68 is one of the two largest proteins found in SRPs (the other being SRP72), and it forms a heterodimer with SRP72. Heterodimer formation is essential for SRP function . SRP68 binds to SRP RNA directly, while SRP72 binds the SRP RNA largely via nonspecific electrostatic interaction. The binding of SRP72 with SRP RNA enhances the affinity of SRP68 for the RNA. This entry describes the N-terminal RNA-binding domain (RBD) of SRP68, a tetratricopeptide-like module. Interactions between SRP68-RBD and SRP RNA (7SL RNA) are thought to facilitate a conformation of SRP RNA that is required for interactions with ribosomal RNA .
SPF45, RNA recognition motif (SPF45_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of SPF45. This domain is also found in DNA-damage-repair/toleration protein 111.

SPF45, also termed RNA-binding motif protein 17 (RBM17), is an RNA-binding protein consisting of an unstructured N-terminal region, followed by a G-patch motif and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbours a RNA recognition motif (RRM) and an Arg-Xaa-Phe sequence motif. SPF45 is a bifunctional protein that functions in splicing and DNA repair. It is involved in regulating alternative splicing of the apoptosis regulatory gene FAS (also called CD95). Its UHM binds UHM-ligand motifs (ULMs) present in the 3' splice site-recognizing factors U2AF65, SF1 and SF3b155 . It binds to the Holliday junction, which is a key DNA intermediate in the homologous-recombination pathway .

DNA-damage-repair/toleration protein 111 is a component of the SWAP1-SFPS-RRC1 splicing factor complex which modulates photomorphogenesis by regulating the gene expression and pre-messenger RNA (mRNA) alternative splicing of a large number of genes .
Alginate biosynthesis protein AlgX, N-terminal (AlgX_N)
Type: Domain

The alginate biosynthesis protein AlgX appears to be directly involved in the O-acetylation of alginate, an exopolysaccharide that is associated with the formation of persistent biofilms, such as those by mucoid strains of Pseudomonas aeruginosa that affect patients suffering from cystic fibrosis . This N-terminal catalytic domain resembles SGNH hydrolases, though with a permuted topology. The active site matches that of the SGNH hydrolases, is well conserved, and has been verified experimentally . AlgX also contains a C-terminal carbohydrate binding domain.
Alginate O-acetyltranferase AlgJ (AlgJ)
Type: Domain

The alginate biosynthesis protein AlgX appears to be directly involved in the O-acetylation of alginate, an exopolysaccharide that is associated with the formation of persistent biofilms . Its N-terminal catalytic domain resembles SGNH hydrolases, though with a permuted topology . The active site matches that of the SGNH hydrolases, is well conserved, and has been verified experimentally. AlgJ closely resembles AlgX in sequence and function, although it lacks the C-terminal carbohydrate binding domain of AlgX. AlgJ is part of an alginate biosynthetic gene cluster which is required for alginate O acetylation . AlgJ exhibits acetylesterase activity that is mediated through the Ser-His-Asp catalytic triad similar to that of the SGNH hydrolase-like enzyme AlgX .
Atypical protein kinase C, catalytic domain (Atypical_PKC)
Type: Domain

PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their N-terminal regulatory domain . Atypical protein kinases C (aPKCs) have a PB1 and an atypical C1 domain, which only accepts phosphatidylserine .

In mammals there are two aPKC isoforms, zeta and iota/lambda (iota is the human orthologue and lambda the mouse orthologue) . aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation . They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes .

This entry consists mainly of invertebrate aPKCs. In Drosophila, aPKC is also involved in polarity maintenance, cytoskeletal regulation and cell cycle progression, and proliferation .
DinB/YfiT-like putative metalloenzymes (DinB/YfiT-like)
Type: Homologous_superfamily

DinB from Bacillus subtilis and related Gram-positive bacteria is a DNA-damage-induced gene and the corresponding protein contains a four helix bundle. This fold is shared by diverse proteins, including MDMPI (mycothiol-dependent maleylpyruvate isomerase) and YfiT, a putative metal-dependent hydrolase .
Atypical protein kinase C iota type, catalytic domain (aPKC_iota)
Type: Domain

PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their N-terminal regulatory domain . Atypical protein kinases C (aPKCs) have a PB1 and an atypical C1 domain, which only accepts phosphatidylserine .

In mammals there are two aPKC isoforms, zeta and iota/lambda (iota is the human orthologue and lambda the mouse orthologue) . aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation . They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes .

PKC-iota is directly implicated in carcinogenesis . It is critical to oncogenic signalling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumour-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumour cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers . PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions .
Atypical Protein Kinase C zeta, catalytic domain (aPKC_zeta)
Type: Domain

PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their N-terminal regulatory domain . Atypical protein kinases C (aPKCs) have a PB1 and an atypical C1 domain, which only accepts phosphatidylserine .

In mammals there are two aPKC isoforms, zeta and iota/lambda (iota is the human orthologue and lambda the mouse orthologue) . aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation . They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes .

PKC-zeta plays a critical role in activating the glucose transport response . PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells . In addition, it affects actin remodeling in muscle cells .
Classical Protein Kinase C alpha, catalytic domain (cPKC_alpha)
Type: Domain

Protein kinases C (PKCs) constitute a family of Ser/Thr kinases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain . Conventional PKCs (cPKCs) have functional C1A and C1B domains, and a C2 domain. PKCs undergo three phosphorylations in order to take mature forms . In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine for activation. There are three conventional PKC isoenzymes (alpha, beta, and gamma).

PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility . It plays a role in the signalling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumours . In addition, PKC-alpha is required for HER2 dependent breast cancer invasion .
Classical protein kinase C beta, catalytic domain (cPKC-beta)
Type: Domain

Protein kinases C (PKCs) constitute a family of Ser/Thr kinases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain . Conventional PKCs (cPKCs) have functional C1A and C1B domains, and a C2 domain. PKCs undergo three phosphorylations in order to take mature forms . In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine for activation. There are three conventional PKC isoenzymes (alpha, beta, and gamma).

The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function . PKC-beta is also being explored as a therapeutic target in cancer . It contributes to tumour formation and is involved in the tumour host mechanisms of inflammation and angiogenesis .
Novel protein kinase C eta, catalytic domain (nPKC_eta)
Type: Domain

Protein kinases C (PKCs) constitute a family of Ser/Thr kinases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain . Novel PKCs (nPKCs) comprise delta, epsilon, eta, and theta isoforms, which have tandem C1 domains and a C2 domain that does not bind calcium . nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity.

PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation . It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development . PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM .
Arp2/3 complex subunit 2/4 (ARPC2/4)
Type: Homologous_superfamily

Arp2/3 binds to pre-existing actin filaments and nucleates new daughter filaments, and thus becomes incorporated into the dynamic actin network at the leading edge of motile cells and other actin-based protrusive structures . In order to nucleate filaments, Arp2/3 must bind to a member of the N-WASp/SCAR family protein . Arp2 and Arp3 are thought to be brought together after activation, forming an actin-like nucleus for actin monomers to bind and create a new actin filament. In the absence of an activating protein, Arp2/3 shows very little nucleation activity. Recent research has focused on the binding and hydrolysis of ATP by Arp2 and Arp3 , and crystal structures of the Arp2/3 complex have been solved .

The human complex consists of Arp2/3 complex composed of ARP2, ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC. This superfamily represents the ARPC2/4 subunits.
Novel protein kinase C delta, catalytic domain (nPKC_delta)
Type: Domain

Protein kinases C (PKCs) constitute a family of Ser/Thr kinases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain . Novel PKCs (nPKCs) comprise delta, epsilon, eta, and theta isoforms, which have tandem C1 domains and a C2 domain that does not bind calcium . nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity.

PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types . It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses . It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis .
Novel protein kinase C theta, catalytic domain (nPKC_theta)
Type: Domain

Protein kinases C (PKCs) constitute a family of Ser/Thr kinases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain . Novel PKCs (nPKCs) comprise delta, epsilon, eta, and theta isoforms, which have tandem C1 domains and a C2 domain that does not bind calcium . nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity.

PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology . Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation . It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases .
Novel protein kinase C epsilon, catalytic domain (nPKC_epsilon)
Type: Domain

Protein kinases C (PKCs) constitute a family of Ser/Thr kinases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain . Novel PKCs (nPKCs) comprise delta, epsilon, eta, and theta isoforms, which have tandem C1 domains and a C2 domain that does not bind calcium . nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity.

PKC-epsilon has been shown to behave as an oncoprotein . Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumour invasion and metastasis . PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage . Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility .

This entry also includes PKCs from invertebrates, such as Pkc98E from Drosophila, which exhibits sequence identity to PKC-epsilon .
Checkpoint kinase 1, catalytic domain (Chk1_catalytic_dom)
Type: Domain

Checkpoint kinase 1 (Chk1) is a serine/threonine kinase implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability . Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress . Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1 .
Hormonally up-regulated neu tumour-associated kinase, catalytic domain (Hunk)
Type: Domain

Serine/threonine kinase HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumours, but is not necessary for c-myc-induced primary tumour formation or normal development. It is required for HER2/neu-induced tumour formation and maintenance of the cells' tumourigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas . HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity .