SII-SWORD/CoKE huggingface dataset:
Streptomyces scabies esterase-like (SEST-like)
Type: Family

This entry represent a family of secreted SGNH-hydrolases similar to Streptomyces scabies esterase (SEST) . The tertiary fold of this enzyme is substantially different from that of the alpha/beta hydrolase family and unique among all known hydrolases; its active site closely resembles two of the three components of typical Ser-His-Asp(Glu) triad from other serine hydrolases, but may lack the carboxylic acid .
CtCE2-like domain (CtCE2-like_dom)
Type: Domain

This entry represents a domain found in a group of bacterial carbohydrate esterases known as CE2 (family CE2 in the CAZy classification), including CjCE2A (

), CjCE2B (

) and CjCE2C (

) from Cellvibrio japonicus . In Clostridium thermocellum, this domain (CtCE2) is linked to the cellulase, CtCel5C; therefore, it is known as CtCel5C-CE2 modular protein. The enzyme also contains a type I dockerin module that, by binding to cohesin modules in the scaffoldin protein, incorporates CtCel5C-CE2 into the multienzyme plant cell-wall-degrading complex known as the cellulosome. CtCE2 displays acetyl esterase activity that is spatially coupled to a noncatalytic cellulose-binding function .
ERp19 (ERp19)
Type: Family

ERp19, also known as ERp18 or thioredoxin domain-containing protein 12, is a endoplasmic reticulum protein that may be involved in disulfide bond formation . In vitro, ERp19 has been shown to possess thiol-disulfide oxidase activity which is dependent on the presence of both active site cysteines .
Thioredoxin-related transmembrane protein 2, thioredoxin domain (TMX2_thioredoxin_dom)
Type: Domain

This entry represents the thioredoxin (TRX) domain found in thioredoxin-related transmembrane protein 2 (TMX2). In TMX2, the TRX domain redox active CXXC motif is replaced with SXXC. In addition to the TRX domain, TMX2 may contain an N-terminal signal peptide, a potential transmembrane domain, an Myb DNA-binding domain repeat signature, an endoplasmic reticulum (ER) membrane retention signal (KKXX-like motif), and a dileucine motif in the tail .
Threonine aspartase 1 (Taspase1)
Type: Family

Threonine aspartase 1 (taspase1) is a threonine aspartase and a member of the type 2 asparaginase family. It catalyzes the cleavage of the mix lineage leukemia (MLL) nuclear protein and transcription factor TFIIA . The Taspase1 proenzyme undergoes autoproteolysis into alpha and beta subunits . The N-terminal residue of the beta subunit is a threonine which is the active catalytic residue. The active enzyme is a heterotetramer .
YlxR (YlxR)
Type: Family

This entry represents YlxR from Bacillus subtilis and its bacterial homologues. YlxR regulate metabolic gene expression . The structure of its homologue SP0554 from Streptococcus pneumoniae (

) revealed an α+β fold with a large positively charged patch on one side of the protein and a putative RNA binding cleft .
ARGOS/ARL/OSR1 (ARGOS/ARL/OSR1)
Type: Family

Overexpression of ARGOS in Arabidopsis increases lateral organ size through prolonged expression of transcription factor ANT, which affects cell proliferation during organ growth . ARGOS-LIKE (ARL) is an ARGOS homologue that appears to regulate organ growth mainly by influencing cell expansion rather than cell proliferation . There is only one orthologue of ARGOS in rice (OsARGOS); its overexpression affects organ growth by promoting both cell proliferation and expansion .

ARGOS and OsARGOS are induced by the phytohormones auxin and cytokinin, whereas ARL is induced by brassinosteroid (BR) .

Organ size related 1 (OSR1) from Arabidopsis is involved in regulation of organ growth and overall organ size. It appears to act redundantly with the proteins ARGOS and ARGOS-like during organ growth .
Putative actin-fragmin kinase (Put_AFK)
Type: Family

This family of proteins from protists includes Dictyostelium's four homologues of actin-fragmin kinase. Only one of these homologues conserves all the putative catalytic residues . To date actin-fragmin kinase has only been described in Physarum , and is not included in this entry.
Protein IVY1 (IVY1)
Type: Family

IVY1 is a phospholipid-binding protein from yeast that interacts with both the GTPase Ypt7 and the Sec1-related Vps33 protein. It seems to be involved in vacuole membrane homeostasis . Its overexpression causes vacuole fragmentation .
Protein TIC56 (TIC56)
Type: Family

Preproteins are imported into chloroplasts through the translocon complexes of the outer (TOC) and inner (TIC) envelope membranes . The TIC translocon consists of Tic56, together with Tic20, Tic100,and Tic214 . Tic56 mutant plants have an albino phenotype, but protein import in Tic56 mutant plants is functional to a considerable degree .
Methyl-CpG-binding domain-containing protein 8 (MBD8)
Type: Family

MBD8 is a protein with a putative Methyl-CpG-Binding Domain (MBD) that is involved in control of flowering time in the C24 ecotype of Arabidopsis thaliana .
Rubber oxygenase Lcp-like (Lcp-like)
Type: Family

Rubber oxygenase Lcp (for latex clearing protein) is involved in the initial step of rubber degradation . It catalyses the extracellular cleavage of poly (cis-1,4-isoprene) in Gram-positive rubber degrading bacteria such as Streptomyces sp. K30 . This family consists of Lcp, but also includes uncharacterised proteins from Gram-negative bacteria and fungi.
Sca1 complex scaffold protein ScaA (ScaA)
Type: Family

ScaA/Sca1 is a component of the Sca1 complex, a regulator of cell motility, chemotaxis and signal relay (cAMP production) in Dictyostelium. The Sca1/RasGEF/PP2A complex controls the RasC-TORC2-PKB/PKBR1 pathway at the leading edge of chemotaxing cells. The Sca1 complex is recruited to the plasma membrane upon chemoattractant stimulation. ScaA acts as a molecular scaffold, bringing together GEFA, GEFH and PHR with PP2A .
Kinetochore protein Sos7 (Sos7)
Type: Family

Attachment of sister chromatids to microtubules in the fission yeast Schizosaccharomyces pombe is mediated by the kinetochore complex NMS (Ndc80-MIND-Spc7). Sos7 is a component of the MIND complex and is required for kinetochore targeting of Spc7 . This fungal kinetochore family represented by Sos7 is not present in yeasts belonging to the Saccharomyces complex. Instead, these organisms have proteins homologous to the S. cerevisiae Spc105 interaction partner Kre28.
PCH1 (PCH1)
Type: Family

This entry represents Protein PHOTOPERIODIC CONTROL OF HYPOCOTYL 1 (also known as PCH1At2g16365) and its homologues including Protein PHOTOPERIODIC CONTROL OF HYPOCOTYL 1-LIKE (PCHL). Both PCH1 and its homologue, PCHL suppress phyB dark reversion, resulting in plants with dramatically enhanced light sensitivity . In plants, a photoreceptor called phytochrome B (phyB) responds to red light and regulates the ability of plants to grow. PCH1 regulates photoperiod-responsive growth by integrating the plant clock with light perception pathways. PCH1 stabilizes the structure of phyB so that it remains active, even in the dark. This prolonged activity acts as a molecular memory of prior exposure to light and helps to prevent plants from growing too much in the winter, when there are fewer hours of daylight. PCH1 is also found in other species of plants .
Protein disulfide-isomerase SCO2 (SCO2)
Type: Family

SCO2 (SNOWY COTYLEDON 2) is a chloroplast protein disulphide isomerase, which is thought to be involved in protein folding . It interacts with LHCB1 (light-harvesting chlorophyll binding 1) and affects chloroplast biogenesis in cotyledons . It has been shown to have a role in leaf variegation in both Lotus japonicus and Arabidopsis thaliana .
YwkD-like domain (YwkD-like_dom)
Type: Domain

Proteins containing this domain include Bacillus subtilis YwkD and related proteins. They belong to an uncharacterised subfamily of the vicinal oxygen chelate (VOC) family. The VOC superfamily is composed of structurally related proteins with paired beta.alpha.beta.beta.beta motifs that provide a metal coordination environment with two or three open or readily accessible coordination sites to promote direct electrophilic participation of the metal ion in catalysis .

VOC domain is found in a variety of structurally related metalloproteins, including the bleomycin resistance protein, glyoxalase I, and type I ring-cleaving dioxygenases. A bound metal ion is required for protein activities for the members of this superfamily. A variety of metal ions have been found in the catalytic centres of these proteins including Fe(II), Mn(II), Zn(II), Ni(II) and Mg(II). The protein superfamily contains members with or without domain swapping. The proteins of this family share three conserved metal binding amino acids with the type I extradiol dioxygenases, which shows no domain swapping .
Tautomerase, MSAD family (Tauto_MSAD)
Type: Family

Members of the tautomerase superfamily (TSF) are characterised by a β-α-β building block and a catalytic amino terminal proline . There are five known TSF families, which are named for the first characterised member .

This entry represents the malonate semialdehyde decarboxylase (MSAD) family . MSAD is part of a bacterial pathway for the degradation of the soil fumigant known as 1,3-dichloropropene . There are five homologues identified, including YusQ/YodA/YrdN from Bacillus subtilis, IolK from Lactobacillus casei strain BL23, and Bp4401 from Burkholderia phymatum. IolK was found in a degradative pathway for myo-inositol, but its disruption does not affect growth or myo-inositol utilization . Bp4401 has a modest hydratase activity. YrdN, YodA, and IolK have comparable decarboxylase and hydratase activities, but this activity is missing in YusQ and Bp4401 .
YihR-like (YihR-like)
Type: Family

Proteins similar to Escherichia coli YihR are uncharacterised members of aldose-1-epimerase superfamily. Aldose 1-epimerases or mutarotases are key enzymes of carbohydrate metabolism, catalyzing the interconversion of the alpha- and beta-anomers of hexose sugars such as glucose and galactose. This interconversion is an important step that allows anomer specific metabolic conversion of sugars. Studies of the catalytic mechanism of the best known member of the family, galactose mutarotase, have shown a glutamate and a histidine residue to be critical for catalysis; the glutamate serves as the active site base to initiate the reaction by removing the proton from the C-1 hydroxyl group of the sugar substrate, and the histidine as the active site acid to protonate the C-5 ring oxygen .
Protein LacX (LacX)
Type: Family

This entry includes Lactococcus lactis lacX and related proteins . They are uncharacterised members of aldose-1-epimerase superfamily. Aldose 1-epimerases or mutarotases are key enzymes of carbohydrate metabolism, catalyzing the interconversion of the alpha- and beta-anomers of hexose sugars such as glucose and galactose. This interconversion is an important step that allows anomer specific metabolic conversion of sugars. Studies of the catalytic mechanism of the best known member of the family, galactose mutarotase, have shown a glutamate and a histidine residue to be critical for catalysis; the glutamate serves as the active site base to initiate the reaction by removing the proton from the C-1 hydroxyl group of the sugar substrate, and the histidine as the active site acid to protonate the C-5 ring oxygen .
ST1585, MBL-fold (ST1585_MBL-fold)
Type: Domain

Proteins containing this domain include the uncharacterised Sulfolobus tokodaii ST1585 protein . It belongs to the MBL-fold metallo-hydrolase superfamily which is comprised mainly of hydrolytic enzymes which carry out a variety of biological functions. The class B metal beta-lactamases (MBLs) from which this fold was named are only a small fraction of the activities which are included in this superfamily. Activities carried out by superfamily members include class B beta-lactamases, hydroxyacylglutathione hydrolases, AHL (acyl homoserine lactone) lactonases, persulfide dioxygenases, flavodiiron proteins, cleavage and polyadenylation specificity factors such as the Int9 and Int11 subunits of Integrator, Sdsa1-like and AtsA-like arylsulfatases, 5'-exonucleases human SNM1A and yeast Pso2p, ribonuclease J and ribonuclease Z, cyclic nucleotide phosphodiesterases, insecticide hydrolases, and proteins required for natural transformation competence. Classical members of the superfamily are di-, or less commonly mono-, zinc-ion-dependent hydrolases, however the diversity of biological roles is reflected in variations in the active site metallo-chemistry .
YjjU-like (YjjU-like)
Type: Family

This entry includes patatin-like phospholipase similar to the YjjU protein of Escherichia coli.
AmhX-like (AmhX-like)
Type: Family

This entry includes Bacillus subtilis AmhX and related proteins that form a subfamily of the peptidase M20 family . They are predicted amidohydrolases. These are a class of zinc binding homodimeric enzymes involved in hydrolysis of N-acetylated proteins . N-terminal acetylation of proteins is a widespread and highly conserved process that is involved in protection and stability of proteins. Several types of aminoacylases can be distinguished on the basis of substrate specificity. Aminoacylase 1 (ACY1) breaks down cytosolic aliphatic N-acyl-alpha-amino acids (except L-aspartate), especially N-acetyl-methionine and acetyl-glutamate into L-amino acids and an acyl group. However, ACY1 can also catalyze the reverse reaction, the synthesis of acetylated amino acids. ACY1 may also play a role in xenobiotic bioactivation as well as the inter-organ processing of amino acid-conjugated xenobiotic derivatives (S-substituted-N-acetyl-L-cysteine) .
Peroxisome biogenesis protein 22 (PEX22)
Type: Family

Peroxisomal proteins, called peroxins, participate in the process of peroxisome assembly. Specific amino acid sequences (PTS or peroxisomal targeting signal) at the C terminus (PTS1) or N terminus (PTS2) are present in peroxisomal matrix proteins, which signals them to be imported. The protein receptors Pex5 and Pex7 accompany their cargoes (containing a PTS1 or a PTS2 amino acid sequence, respectively) into the peroxisome. Ubiquitination appears to be crucial for the export of Pex5 from the peroxisome to the cytosol. The monoubiquitination of the PTS1-receptor Pex5p is catalyzed by the E2 enzyme Pex4.

Pex22 anchors Pex4 to the peroxisome membrane . Moreover, Pex4 requires the interaction with Pex22 to display full activity . The N-terminal portion of Pex22 has a membrane anchoring function, whereas the C-terminal domain harbours its biological activity. The soluble C-terminal domain of Pex22 is essential for peroxisomal biogenesis and efficient monoubiquitination of the import receptor Pex5 .
G-protein-coupled receptor GPR139 (GPR139)
Type: Family

GPR139, a vertebrate orphan receptor, is very closely related to GPR142, but they have different expression patterns in the brain and in other tissues . These receptors couple to inhibitory G proteins and activate phospholipase C. GPR142 is predominantly expressed in pancreatic beta-cells and plays an important role in mediating insulin secretion and maintaining glucose homeostasis, whereas GPR139 is expressed almost exclusively in the brain and is suggested to play a role in the control of locomotor activity . Tryptophan and phenylalanine have been identified as putative endogenous ligands of GPR139 . These orphan receptors are phylogenetically clustered with invertebrate FMRFamide receptors such as Drosophila melanogaster DrmFMRFa-R .
G-protein coupled receptor 146 (GPR146)
Type: Family

G-protein coupled receptor 146 (GPR146) is an orphan G-protein coupled receptor that belongs to the class A of seven-transmembrane GPCR superfamily. The endogenous ligand for GPR146 is not known. It has been suggested that GPR146 may be a part of the C-peptide signaling complex .

All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) α-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes .
Uncharacterized protein At2g33490-like (At2g33490-like)
Type: Family

This is a family of uncharacterised proteins from plants, including At2g33490 from Arabidopsis.
DNA repair RAD52-like protein (RAD52-like)
Type: Family

Homologues of the DNA-repair protein RAD52 are present in all plants. There are two identified RAD52 genes in Arabidopsis thaliana (RAD52-1 and RAD52-2), which encode four open reading frames (ORFs) through differential splicing, each of which specifically localized to the nucleus, mitochondria, or chloroplast, which suggests a role in maintaining nuclear and organellar genomes. The diverse plant RAD52 proteins affect DNA repair and fertility .
WPP domain-associated protein (WAP)
Type: Family

This family of plant proteins consists of WPP domain-associated proteins (WAPs). WAP interacts through its coiled-coil domain with several WPP-domain containing proteins and it is localized at the Golgi. It is required for complex formation of WPP-domain proteins .
Low-temperature-induced 78kDa/65kDa (LTI78/LTI65)
Type: Family

This family of plant low-temperature-induced (LTI) proteins is involved in responses to abiotic stresses. The homologous genes RD29A (LTI78) and RD29B (LTI65) from Arabidopsis are induced by cold, drought, and salt , and by abscisic acid (ABA) . Subsequent dehydration stresses change the rate of transcription of RD29B, but not RD29A, indicative of a form of transcriptional memory for RD29B .
Exodeoxyribonuclease III-like (ExoIII-like)
Type: Family

This entry includes Escherichia coli ExoIII and related proteins. They are AP endonucleases that belong to the large EEP (exonuclease/endonuclease/phosphatase) superfamily. ExoIII removes the damaged DNA at cytosines and guanines by cleaving on the 3'-side of the AP site by a beta-elimination reaction. It exhibits 3'-5'-exonuclease, 3'-phosphomonoesterase, 3'-repair diesterase and ribonuclease H activities .

Cellular DNA is spontaneously and continuously damaged by environmental and internal factors such as X-rays, UV light and agents such as the antitumor drugs bleomycin and neocarzinostatin or those that generate oxygen radicals. Apurinic/apyrimidinic (AP) sites form both spontaneously and as highly cytotoxic intermediates in the removal of the damaged base by the base excision repair (BER) pathway. DNA repair at the AP sites is initiated by specific endonuclease cleavage of the phosphodiester backbone. Such endonucleases are also generally capable of removing blocking groups from the 3'terminus of DNA strand breaks. AP endonucleases can be classified into two families on the basis of sequence similarity and structure. ExoIII belongs to family 1 .
Rubisco accumulation factor 1 (RAF1)
Type: Family

Ribulose-1,5-bis-phosphate carboxylase/oxygenase (Rubisco) is the rate-limiting carbon fixing enzyme of photosynthesis. Rubisco is a complex of eight large (RbcL) and eight small (RbcS) subunits that requires assembly chaperones. Rubisco accumulation factor 1 (Raf1) is a mayor chaperone involved in Rubisco assembly . It acts downstream of chaperonin-assisted RbcL folding by stabilizing RbcL antiparallel dimers for assembly into RbcL8 complexes with four Raf1 dimers bound. Raf1 displacement by RbcS results in holoenzyme formation . It might regulate RuBisCO condensation and decondensation .
CLAVATA3/ESR (CLE)-related protein 41/42/44 (CLE41/42/44)
Type: Family

This entry includes CLAVATA3/ESR (CLE)-related protein 41/42/44 (CLE41/42/44) from Arabidopsis and TDIF from Zinnia violacea. TDIF functions as a phloem-derived, non-cell-autonomous signal that controls stem cell fate in the procambium .

Tracheary element differentiation inhibition factor (TDIF and CLE41/CLE44 peptides act as inhibitors of tracheary element differentiation. TDIF/CLE41/CLE44 promote the proliferation of vascular cells and prevent them from differentiating into xylem by regulating WOX4 expression through the TDR/PXY receptor . CLE42 binds PXL2 (PXY-like 2) . TDIF-related peptides also have activity to enhance axillary bud formation .

The CLE proteins share a C-terminal CLE domain with CLV3, a small secreted polypeptide that is active as a ligand and has a function in shoot apical meristem maintenance . In general, the CLE-related proteins are C-terminally processed to generate an active CLE peptide . These small secreted peptide hormones then function in a variety of developmental and physiological processes . CLV3 and other A-type CLE peptides are involved in the suppression of stem cell development in root and shoot development, in contrast to the B-type CLE peptides, CLE41 and CLE44, in the case of Arabidopsis, which are not .
BEN domain-containing protein 6-like (BEND6-like)
Type: Family

The Notch signaling pathway regulates genes involved in cell fate decision throughout development. Its activity relies notably on the CSL transcription factors. BEND6 is a BEN-solo (bears a single BEN domain) factor that binds CSL via its BEN domain and acts as a CSL co-repressor. BEND6 associates with and represses Notch target genes, antagonizing Notch signaling in neural stem cells, thereby opposing their self-renewal and promoting neurogenesis .

This entry also includes BEN-solo factors from Drosophila, namely protein insensitive, Elba 1 and Elba2, which share functional attributes with BEND6. They recognise CCAATTGG palindromes to mediate transcriptional repression .
Protein PROTON GRADIENT REGULATION 5 (PGR5)
Type: Family

PGR5 is involved in the regulation of the cyclic electron flow around Photosystem I . Two types of electron transfer contribute to the proton concentration gradient across the thylakoid membrane: linear electron flow (LEF) and cyclic electron flow (CEF), which is divided into NDH- and PGR5-dependent pathways. The PGR5-PGRL1 complex mediates the second CET circuit, accepting electrons from ferrodoxin and reducing the plastoquinone pool. PGR5 is important to regulate and facilitate CET, and is essential for photoprotection in Arabidopsis .
Protein MULTIPOLAR SPINDLE 1 (Msp1)
Type: Family

The spindle assembly checkpoint (SAC) ensures the fidelity of chromosome segregation. In plants, Msp1 (also known as AtPRD2) has been identified as one of the SAC components . Msp1 is required for meiotic spindle organization and DNA double-strand break formation .

In flowering plants, gametophyte formation relies on meiosis. In meiosis I, the homologous chromosomes are separated into two daughter cells. In meiosis II, the sister chromosomes are then separated into newly formed daughter cells. During prophase I, several events occurs: sister chromatid cohesion, homologous chromosome synapsis, recombination, crossover formation and chromosome segregation. Homologous recombination is initiated from the formation of DNA double-strand breaks (DSBs). The formation of DSBs is catalyzed by Spo11 and its homologues. So far, six Arabidopsis proteins, AtSPO11-1, AtSPO11-2, AtPRD1, AtPRD2, AtPRD3 and AtDFO, have been shown to be involved in DSB formation .
Protein TPLATE (TPLATE)
Type: Family

Cytokinesis in plants, in contrast to animals and yeasts, starts with targeted secretion and fusion of vesicles between the separated chromosomes at the centre of the cell. TPLATE is a plant-specific protein with similarity to the Adaptin/Coatomer proteins that is recruited during plant somatic cytokinesis . TPLATE is part of a unique multisubunit protein complex (the TPLATE complex, TPC) that acts in concert with the AP2 complex, dynamin-related proteins and clathrin, and that it is essential for clathrin-mediated endocytosis in plants .

Besides TPLATE, this entry also includes TSET complex member tstA from Dictyostelium discoideum (Slime mold). TSET is a membrane trafficking complex .