SII-SWORD/CoKE huggingface dataset:
TIR domain-containing adapter molecule 1/2 (TCAM1/2)
Type: Family

This family includes TIR domain-containing adapter molecule 1 and 2 (TICAM1/2). TICAM1 is involved in innate immunity against invading pathogens. It is an adapter used by TLR3 and TLR4 (through TICAM2) to mediate NF-kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis .

TICAM2 functions as sorting adapter in different signalling pathways to facilitate downstream signaling leading to type I interferon induction . It physically bridges TLR4 and TICAM1 and functionally transmits signal to TICAM1 in early endosomes after endocytosis of TLR4. In TLR2 signalling, physically bridges TLR2 and MYD88 and is required for the TLR2-dependent movement of MYD88 to endosomes following ligand engagement . TICAM2 forms a complex with RAB11FIP2 that is recruited to the phagosomes to promote the activation of the actin-regulatory GTPases RAC1 and CDC42 and subsequent phagocytosis of Gram-negative bacteria .
Transcriptional regulatory protein LytR-like (LytR-like)
Type: Family

This family includes a group of LytTR domain-containing proteins, such as the transcriptional regulatory protein LytR and BtsR, the sensory transduction protein LytT and the Accessory gene regulator protein A. LytTR domain is a DNA-binding, potential winged helix-turn-helix (wHTH) domain , named after Bacillus subtilis LytT and Staphylococcus aureus lytR response regulators, involved in the regulation of cell autolysis .
RING-H2 finger protein ATL20-22-like (ATL20-22-like)
Type: Family

This family represents a group of plant proteins containing a RING-H2 finger, including ATL20, ATL21A-C and ATL22. ATL20 has been predicted as an ubiquitin ligase .
Histone deacetylase 4/5/7/9 (HDAC4/5/7/9)
Type: Family

This family includes animal class II histone deacetylases (

) HDAC4, HDAC5, HDAC7 and HDAC9 . These enzymes are responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Histone acetyltransferases (HATs) cooperate with histone deacetylases to establish and maintain specific patterns of histone acetylation.
DNA-directed RNA polymerase, C-terminal domain, phage-type (DNA-dir_Rpol_C_phage-type)
Type: Domain

DNA-directed RNA polymerases

(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length . The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.

RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.

RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.

This is the C-terminal DNA polymerase domain of phage-type enzymes, a family of single chain polymerases found in bacteriophages and mitochondria . They are distantly related and share conserved mechanisms for substrate binding and nucleotide incorporation. This domain adopts the canonical right hand fold of polymerases of the polA family consisting of thumb, palm, and fingers subdomains flanking the active centre .
N(5)-(carboxyethyl)ornithine synthase (CEOS)
Type: Family

N(5)-(carboxyethyl)ornithine synthase (CEOS) catalyses the NADP-dependent conversion of N5-(L-1-carboxyethyl)-L-ornithine to L-ornithine pyruvate. CEOS is related to the NAD-dependent L-alanine dehydrogenases . Like formate dehydrogenase and related enzymes, CEOS is comprised of 2 domains connected by a long α-helical stretch, each resembling a Rossmann fold NAD-binding domain. The NAD-binding domain is inserted within the linear sequence of the more divergent catalytic domain. These proteins have a partially conserved NAD-binding motif and active site residues that are characteristic of related enzymes such as saccharopine dehydrogenase. .
Glutathione reductase/thioredoxin reductase-like (GSHR/TRXR-like)
Type: Family

There are two major pathways for regulating cellular redox homeostasis, antioxidant defense and to provide reducing equivalents for a variety of chemical transformations in most organisms, which involve glutathione/glutathione disulfide (GSH/GSSG) and the thioredoxin (Trx) dependent systems. They include GSSG reductase (GR) for recycling oxidized glutathione using NADPH , while Trx system includes a NADPH dependent reductase Trx reductase (TrxR). GR and TrxR are closely related oxidoreductases with highly similar structure and reaction mechanism, belonging to the GR superfamily of dimeric flavoenzymes . This family also includes trypanothione reductase, a closely related which also belongs to GR superfamily.
Spore germination GerAC-like, C-terminal (Spore_GerAC-like_C)
Type: Domain

The GerAA, -AB, and -AC proteins of the Bacillus subtilis spore are required for the germination response to L-alanine as the sole germinant. Members of GerAC family are thought to be located in the inner spore membrane. Although the function of this family is unclear, they are likely to encode the components of the germination apparatus that respond directly to this germinant, mediating the spore's response .

This entry represents the C-terminal domain of spore germination proteins predominantly found in firmicutes, including GerAC (also known as spore germination protein A3, -KC, and -AC from Bacillus subtilis .
Myb family transcription factor PHR1-like (PHR1-like)
Type: Family

This family of plant proteins includes Myb family transcription factor protein PHOSPHATE STARVATION RESPONSE 1 from Arabidopsis thaliana (PHR1) and similar proteins from plants, including PHLs from A.thaliana and MPH1/MOF1 from rice. They belong to a family of MYB-CC transcription factors and are regarded as the key components of the central regulatory system controlling plant transcriptional responses to phosphate (Pi) starvation .

PHR1 is a transcription factor and a master regulator of phosphate starvation responses (PSRs) .

PHL1 (PHR1-LIKE 1), PHL2, and perhaps also PHL3, act redundantly with PHR1 to regulate plant Pi starvation responses . However, PHL4 has only a minor role in the regulation of plant responses to Pi starvation . PHL10 (also known as MYR1) acts redundantly with PHL9 (also known as MYR2) as a repressor of flowering and organ elongation under decreased light intensity .

MPH1 is likely a transcription factor involved in the regulation of plant height by elongating internode cell length . It is involved in the positive regulation of grain yield . MPH may play a role in the regulation of genes related to cell elongation and cell wall synthesis, which are associated with plant height and yield phenotypes . It also plays a role in tolerance to cadmium stress .

MOF1 is a transcriptional repressor that plays a role in the regulation of organ identity and spikelet meristem determinacy . It interacts with the TPR corepressors to possibly repress the expression of downstream target genes .
Receptor-like protein 23-like (RLP23-like)
Type: Family

This family represents a group of Leucine rich-repeat (LRR) receptor-like proteins (RLP) from plants, including RLP23 from Arabidopsis, which is a component of the RLP23-SOBIR1-BAK1 complex that mediates NLP-triggered immunity . Many members confer resistance to fungal pathogens. In Arabidopsis, at least 57 members have been described, some of them are known to be involved in basal developmental processes, whereas others are involved in defence responses . RLP42 recognises fungal endopolygalacturonases (PGs) and acts as a novel microbe-associated molecular pattern receptor . Receptor-like protein 9DC3/9DC2 and Cf-9 homologue from Solanum pimpinellifolium are also included in this family. 9DC3 is involved in plant defence; it confers resistance to the fungal pathogen C.fulvum through recognition of the AVR9 elicitor protein . Receptor-like protein EIX1 from Solanum lycopersicum confers resistance to the fungal pathogen T.viride through recognition of the EIX elicitor protein .
Receptor-like cytosolic serine/threonine-protein kinase RBK1/2/STUNTED (RBK1/2/STUNTED)
Type: Family

This family includes a group of receptor-like cytosolic serine/threonine-protein kinases including RBK1/2 and the protein kinase STUNTED. RBK1 is involved in regulating Casparian strip formation and it also plays a roles in trichome branching and in the control of basal resistance to powdery mildew . STUNTED promotes cell proliferation in the gibberellic acid (GA) signaling pathway, acting downstream of RGA, and possibly through a negative regulation of two cyclin-dependent kinase inhibitors SIM and SMR1 .
Pollen receptor-like kinase 1-6/SFR4-like (PRK1-6/SRF4-like)
Type: Family

This family includes a group of plant LRR receptor-like serine/threonine-protein kinases including pollen receptor-like kinases 1-6 (PRKs 1-6) and some members of STRUBBELIG-RECEPTOR FAMILY (SRF1/4/7). This family also include inactive kinase At1g60630. PRK1 and PRK2 are involved in the control of pollen germination and pollen tube polar growth . SRF4 is required for the control of leaf size .
Pentatricopeptide repeat-containing protein At4g14850-like, plant (PPR_At4g14850-like_plant)
Type: Family

This entry represents a group of plant pentatricopeptide repeat-containing proteins (PPRs) part of the plant combinatorial and modular protein (PCMP) family, including At4g14850, At3g57430, At3g11460 and CRR2. The PPR proteins have been proposed to contact the RNA sequence with selected repeats at specific nucleotides . At4g14850, also known as Lovastatin insensitive 1, plays regulatory roles in cytosolic and plastidial isoprenoid biosynthesis through RNA editing . At3g57430 also acts as a RNA editing factor in chloroplasts . At3g11460, also known as MEF10, is required for RNA editing in mitochondria . CRR2 is required for the intergenic processing between chloroplast rsp7 and ndhB transcripts and it is necessary for chloroplast NADH dehydrogenase-like (NDH) complex-dependent cyclic electron transport around photosystem I .

This entry also includes At1g15510, At3g16610 and At2g39620. The PPR proteins have been proposed to contact the RNA sequence with selected repeats at specific nucleotides . At1g15510 also known as Protein EARLY CHLOROPLAST BIOGENESIS 2, regulates the RNA editing of the chloroplast transcript accD, and is essential for the early stages of chloroplast biogenesis . It is required for the RNA editing of the chloroplast transcript ndhF .
VIP/GHRH-like (VIP/GHRH-like)
Type: Family

A number of peptidic hormones, expressed in the intestine, the pancreas or hypothalamus, belong to a group of structurally related peptides of the glucagon family . This family includes vasoactive intestinal peptide (VIP), growth hormone releasing factor (GHRH) and Pituitary adenylate cyclase-activating polypeptide (PACA).
Reticulon 1-4 (RTN1-4)
Type: Family

Eukaryotic proteins of the reticulon (RTN) family all share an association with the endoplasmic reticulum (ER). Whereas amino-terminal regions are not related to one another, all reticulon proteins share a 200 amino acid residue region of sequence similarity at the C-terminal. This region contains two large hydrophobic regions separated by a 66 residue hydrophilic segment. The conserved hydrophobic C-terminal portion has been shown to play an essential role in the association of reticulons with the ER membrane. The hydrophobic portions are supposed to be membrane-embedded and the hydrophilic 66 residue localized to the lumenal/extracellular face of the membrane. Most reticulons have a di-lysine ER retention motif at the C-terminal. Because of their likely association with the rough as well as the smooth ER, the reticulons might play some role in transport processes or in regulation of intracellular calcium levels. It has been suggested that the reticulons may be serving as ER-associated channel-like complexes .

This family includes reticulon member from metazoans, including reticulon 1-4 (RTN1-4) from human . They inhibit amyloid precursor protein processing, probably by blocking BACE1 activity . RTN3 is also involved in membrane trafficking in the early secretory pathway .
Cyclin A/B-like (Cyclin_A/B-like)
Type: Family

This entry includes cyclin A, cyclin B and related sequences. Cyclin A/B are essential (and the most active) for the control of the cell cycle at the G2/M (mitosis) transition. They confer different substrate recognition properties on CDK2 . DENR, an oncogene identified in several tumours, is phosphorylated by Cyclin A/CDK2 and Cyclin B/CDK1 at the onset of mitosis which promotes mitotic protein translation and faithful cell division .

Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles , and regulate cyclin dependent kinases (CDKs). Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). There are two main groups of cyclins, G1/S cyclins, which are essential for the control of the cell cycle at the G1/S (start) transition, and G2/M cyclins, which are essential for the control of the cell cycle at the G2/M (mitosis) transition. G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). In most species, there are multiple forms of G1 and G2 cyclins. For example, in vertebrates, there are two G2 cyclins, A and B, and at least three G1 cyclins, C, D, and E.

Cyclin homologues have been found in various viruses, including Saimiriine herpesvirus 2 (Herpesvirus saimiri) and Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus). These viral homologues differ from their cellular counterparts in that the viral proteins have gained new functions and eliminated others to harness the cell and benefit the virus .
Glucoamylase, active site (Glucoamylase_active_site)
Type: Conserved_site

Glucoamylase (GA) (

) is an enzyme that catalyses the release of D-glucose from the non-reducing ends of starch and other oligo- or polysaccharides. Extensive studies of fungal GA have shown that three closely clustered acidic residues play a role in the catalytic mechanism of GA. The region that includes these residues is also conserved in a bacterial GA . This entry represents the GA active site.
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2, EF-hand domain (PLCbeta2_EF)
Type: Domain

Phosphoinositide-specific phospholipase C (PI-PLC), also known as 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, plays a role in the inositol phospholipid signaling by hydrolysing phosphatidylinositol-4,5-bisphosphate to produce the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). These cause the increase of intracellular calcium concentration and the activation of protein kinase C (PKC), respectively.

The PLC family in murine or human species is comprised of multiple subtypes. On the basis of their structure, they have been divided into five classes, beta (beta-1, 2, 3 and 4), gamma (gamma-1 and 2), delta (delta-1, 3 and 4), epsilon, zeta, and eta types .

PLC-beta-2 may be involved in the transduction of bitter taste stimuli .

This entry represents the region of this enzyme that contains several EF hands, which appears C-terminal to the PH domain

.
TSP/COMP, coiled-coil domain superfamily (TSP/COMP_CC_sf)
Type: Homologous_superfamily

Thrombospondins (TSP) are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. Cartilage oligomeric matrix protein (TSP5/COMP) may play a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as collagen and fibronectin .

TSP3/4 and TSP5/COMP contain a five-stranded coiled-coil domain represented by this entry. This domain has a binding site between two internal rings formed by Leu37 and Thr40 .
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, EF-hand motif (PLC-eta2_EFh)
Type: Domain

Phosphoinositide-specific phospholipase C (PI-PLC), also known as 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, plays a role in the inositol phospholipid signaling by hydrolysing phosphatidylinositol-4,5-bisphosphate to produce the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). These cause the increase of intracellular calcium concentration and the activation of protein kinase C (PKC), respectively.

The PLC family in murine or human species is comprised of multiple subtypes. On the basis of their structure, they have been divided into five classes, beta (beta-1, 2, 3 and 4), gamma (gamma-1 and 2), delta (delta-1, 3 and 4), epsilon, zeta, and eta types .

PLC-eta-2 may function downstream of G-protein-coupled receptors and may be important for formation and maintenance of the neuronal network in the postnatal brain .

This entry represents the EF-hand domain of PLC-eta2. This domain is composed of two EF-loops; a canonical loop involved in Ca+2-sensing (EF-loop 1) and a non-canonical loop (EF-loop 2) .
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1, EF-hand motif (PLCeta1_EF)
Type: Domain

Phosphoinositide-specific phospholipase C (PI-PLC), also known as 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, plays a role in the inositol phospholipid signaling by hydrolysing phosphatidylinositol-4,5-bisphosphate to produce the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). These cause the increase of intracellular calcium concentration and the activation of protein kinase C (PKC), respectively.

The PLC family in murine or human species is comprised of multiple subtypes. On the basis of their structure, they have been divided into five classes, beta (beta-1, 2, 3 and 4), gamma (gamma-1 and 2), delta (delta-1, 3 and 4), epsilon, zeta, and eta types .

The PLC-eta gene is transcribed to several splicing variants. This entry represents PLC-eta-1, which may have an important role in the brain .

PLC-eta-1 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs (represented by this entry), a PLC catalytic core, and a single C2 domain.
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, catalytic domain (PLC-epsilon1_cat)
Type: Domain

Phosphoinositide-specific phospholipase C (PI-PLC), also known as 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, plays a role in the inositol phospholipid signaling by hydrolysing phosphatidylinositol-4,5-bisphosphate to produce the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). These cause the increase of intracellular calcium concentration and the activation of protein kinase C (PKC), respectively.

The PLC family in murine or human species is comprised of multiple subtypes. On the basis of their structure, they have been divided into five classes, beta (beta-1, 2, 3 and 4), gamma (gamma-1 and 2), delta (delta-1, 3 and 4), epsilon, zeta, and eta types .

PLC-epsilon-1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organisation and T-cell activation .

This entry represents the catalytic domain of PLC-epsilon-1, a TIM barrel with two highly conserved regions (X,

, and Y,

) split by a highly degenerate linker sequence .
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, EF-hand domain (PLC_epsilon1_EF)
Type: Domain

Phosphoinositide-specific phospholipase C (PI-PLC), also known as 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, plays a role in the inositol phospholipid signaling by hydrolysing phosphatidylinositol-4,5-bisphosphate to produce the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). These cause the increase of intracellular calcium concentration and the activation of protein kinase C (PKC), respectively.

The PLC family in murine or human species is comprised of multiple subtypes. On the basis of their structure, they have been divided into five classes, beta (beta-1, 2, 3 and 4), gamma (gamma-1 and 2), delta (delta-1, 3 and 4), epsilon, zeta, and eta types .

PLC-epsilon-1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organisation and T-cell activation .

PLC-epsilon1 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs domain (represented by this entry), a PLC catalytic core, and a single C2 domain.
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1, EF-hand domain (PLC-delta1_EF)
Type: Domain

Phosphoinositide-specific phospholipase C (PI-PLC), also known as 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, plays a role in the inositol phospholipid signaling by hydrolysing phosphatidylinositol-4,5-bisphosphate to produce the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). These cause the increase of intracellular calcium concentration and the activation of protein kinase C (PKC), respectively.

The PLC family in murine or human species is comprised of multiple subtypes. On the basis of their structure, they have been divided into five classes, beta (beta-1, 2, 3 and 4), gamma (gamma-1 and 2), delta (delta-1, 3 and 4), epsilon, zeta, and eta types .

PLC-delta-1 is required for the maintenance of skin homeostasis. It functions as a calcium amplifier within the cell and is essential in trophoblasts for placental development. It is involved in Alzheimer's disease and hypertension. Furthermore, it regulates cell proliferation and cell-cycle progression . Both PLC-delta-1 and PLC-delta-3 are essential in trophoblasts for placental development .

PLC-delta1 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs domain (represented by this entry), a PLC catalytic core, and a single C2 domain.