SII-SWORD/CoKE huggingface dataset:
SprT-like domain-containing protein Spartan (Spartan)
Type: Family

Covalent DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription. Spartan (SPRTN) is a DNA-dependent metalloprotease which cleaves DPCs and plays a key role in maintaining genomic integrity . SPRTN consists of an N-terminal SprT domain (responsible for the proteolytic cleavage of DPCs) followed by a basic region (BR, a DNA-binding element), both contributing to DNA binding. The C-terminal motifs and domains interact with proliferating cell nuclear antigen (PCNA) and ubiquitin, which collectively recruit SPRTN and the associated ATPase p97 or valosin-containing protein (p97 or VCP) to sites of DNA damage. The structure of the human SPRTN revealed a Zn2-binding sub-domain (ZBD) in SprT domain that shields its active site located in the metalloprotease sub-domain (MPD). The ZBD contains an ssDNA-binding site, with a DNA-base-binding pocket formed by aromatic residues and is thought to contribute to the ssDNA specificity of SPRTN, restricts the access of globular substrates, and positions DPCs, which may need to be partially unfolded, for optimal cleavage .

The proteolytic activity of SPRTN is regulated by various mechanisms. To prevent the recruitment of SPRTN to chromatin, SPRTN undergoes monoubiquitylation, which can then be deubiquitylated by an unknown ubiquitin protease triggered by DPC induction. Once SPRTN is recruited to chromatin, DNA binding stimulates its protease activity. It has been shown that SPRTN is uniquely activated by single-stranded DNA (ssDNA). Moreover, SPRTN can degrade itself, which may switch off its proteolytic function when repair is complete .

SPRTN is also an activator of CHK1 (checkpoint kinase 1) during normal DNA replication by mediating proteolytic cleavage of CHK1, thereby promoting CHK1 removal from chromatin and subsequent activation. CHK1 phosphorylate SPRTN at the C-terminal regulatory domain and induces SPRTN recruitment to chromatin promoting DNA replication fork progression and DPC repair .

In humans mutations of SPRTN are linked to human Ruijs-Aalfs syndrome (RJALS), a syndrome characterised by is characterised by genomic instability, premature aging, and hepatocellular carcinoma . In mice, loss of SPRTN is embryonically lethal, and conditional inactivation of SPRTN in murine embryonic fibroblasts (MEFs) blocks cell proliferation .
Zinc finger protein 3-like (ZFP3-like)
Type: Family

C2H2 zinc finger proteins (ZFPs) constitute an abundant family of nucleic acid binding proteins in the genomes of higher and lower eukaryotes. This entry represents a group of plant ZFPs, including ZFP3, KNUCKLES and LATE FLOWERING from Arabidopsis. ZFP3 is a putative transcriptional regulator negatively regulating ABA suppression of seed germination in Arabidopsis. Together with other ZFPs, it regulates light and ABA responses during germination and early seedling development . KNUCKLES plays an important role in the termination of floral meristem activity and LATE FLOWERING controls the transition to flowering .
E3 ubiquitin-protein ligase SPL2-like (SPL2-like)
Type: Family

This entry represents a group of putative E3 ubiquitin-protein ligases, including SPL2 from Arabidopsis. SPL2 shares topological similarity and considerable sequence identity with SP1, and is located in the chloroplast envelope . SP1 is associated with TOC (translocon at the outer envelope of chloroplasts) complexes and mediates ubiquitination of TOC components, promoting their degradation .
Diphthamide biosynthesis protein 3/4-like (DPH3/4-like)
Type: Family

This entry includes DPH3, DPH4 and their homologues.

Diphthamide is a unique post-translationally modified histidine residue found only in translation elongation factor 2 (eEF-2). It is conserved from archaea to humans and serves as the target for diphteria toxin and Pseudomonas exotoxin A. These two toxins catalyse the transfer of ADP-ribose to diphtamide on eEF-2, thus inactivating eEF-2, halting cellular protein synthesis, and causing cell death . The biosynthesis of diphtamide is dependent on at least five proteins, DPH1 to -5, and a still unidentified amidating enzyme. DPH3 and DPH4 share a conserved region, which encode a putative zinc finger, the DPH-type or CSL-type (after the the final conserved cysteine of the zinc finger and the next two residues) MB domain contains a Cys-X-Cys...Cys-X2-Cys motif which tetrahedrically coordinates both Fe and Zn. The Fe containing DPH-type MBD has an electron transfer activity .
Probable E3 ubiquitin-protein ligase XERICO-like (XERICO-like)
Type: Family

This entry represents a group of RING zinc-finger proteins, including XERICO from Arabidopsis. XERICO has been shown to interact with an E2 ubiquitin-conjugating enzyme (AtUBC8) and ASK1-interacting F-box protein (AtTLP9) . It promotes accumulation of abscisic acid (ABA) that antagonizes GA effects during development .
Isochorismate synthase MenF-like (MenF-like)
Type: Family

This entry represents a group of Isochorismate synthases, including MenF from bacteria and AtIcs1/2 from Arabidopsis. MenF catalyses the conversion of chorismate to isochorismate, the initial step of menaquinone biosynthesis . ICS1 and ICS2 are targeted to the plastids and are involved in the salicylic acid (SA) biosynthesis .
Chromo domain-containing protein LHP1 (LHP1-like)
Type: Family

LIKE HETEROCHROMATIN PROTEIN1 (LHP1) is a polycomb repressive complex1 subunit required for epigenetic silencing of FLOWERING LOCUS C (FLC), which encodes a repressor of flowering . It also interacts with LIF2, which is a heterogeneous nuclear ribonucleoprotein involved in Arabidopsis thaliana cell fate and stress responses .
Large ribosomal subunit protein P3 (RPP3)
Type: Family

This entry represents the large ribosomal subunit protein P3 (also known as 60S acidic ribosomal protein P3) and related proteins from plants .
Thioredoxin-like 3-1/3-2 (WCRKC1/2)
Type: Family

Thioredoxins play key regulatory roles in chloroplasts by linking photosynthetic light reactions to a series of plastid functions. This entry represents a group of thioredoxin-like proteins, including WCRKC-1 and WCRKC-2 from Arabidopsis. They are targeted to the stroma .
BRCT domain-containing protein At4g02110-like (At4g02110-like)
Type: Family

This entry represents a group of plant BRCA1 C terminus (BRCT) domain-containing proteins, including At4g02110 from Arabidopsis. Their function is not clear.
Protein Dr1 homolog (Dr1-like)
Type: Family

This entry includes Dr1 homologues from plants. They are putative transcription factors. Human Dr1 has been shown to interact with TATA-binding protein (TBP) and block its ability to activate transcription . Arabidopsis Dr1 may affect the regulatory pathway for sexual development .
High chlorophyll fluorescence 244-like (HCF244-like)
Type: Family

This entry represents a group of plant and bacterial proteins, including ycf39 from bacteria and HCF244 from Arabidopsis. HCF244/OHP1/OHP2 complex is involved in the photosystem II reaction center assembly and repair . It is required for the recruitment of ribosomes to psbA mRNA, which encodes D1 (PSII reaction center protein) .
Protein TRM32-like (TRM32-like)
Type: Family

This entry represents a group of plant proteins, including TRM32 from Arabidopsis. TRM32 (TON1-RECRUITING MOTIF protein 32) shares the conserved sequence motifs with other TRM proteins. Its function is not clear .
Heavy metal-associated isoprenylated plant protein 9-like (HIPP09-like)
Type: Family

Heavy-metal-associated (HMA) isoprenylated plant proteins (HIPPs) only exist in vascular plants. They contain a metal binding domain (HMA) and a C-terminal isoprenylation motif. They play important roles in responses to biotic/abiotic stresses, heavy-metal homeostasis, and detoxification. This entry includes AtHIP09, which may act as a metallochaperone .
Peptidyl-prolyl cis-trans isomerase CYP37-like (CYP37-like)
Type: Family

This entry represents a group of predicted peptidyl-prolyl cis-trans isomerases, including CYP37 from Arabidopsis. CYP37 is a thylakoid membrane protein .
F-box protein SKIP8-like (SKIP8-like)
Type: Family

This entry represents a group of plant F-box proteins, including SKIP8 and At4g23960 from Arabidopsis. Their function is not clear.
Pyruvate dehydrogenase [ubiquinone] (Pyruvate_dehydrogenase)
Type: Family

This entry represents a group of pyruvate dehydrogenases, including PoxB from Escherichia coli. PoxB is a peripheral membrane protein catalysing the oxidative decarboxylation of the central metabolite pyruvate to CO(2) and acetate .
(S)-8-amino-7-oxononanoate synthase BioU-like (BioU-like)
Type: Family

This entry represents a group of proteins from cyanobacteria and archaea, including BioU from Synechocystis sp. BioU is involved in biotin biosynthesis. It is a suicide enzyme that loses the Lys124 amino group after a single round of reaction. It catalyses the formation of (S)-8-amino-7-oxononanoate (DAN-carbamic acid) from (7R,8S)-8-amino-7-(carboxyamino)nonanoate (DAN), a function equivalent to the canonical BioA reaction and the first half-reaction of BioD .
RNA ligase 2, viral (Rnl2_vir)
Type: Family

This entry represents the RNA ligase 2 (Rnl2) mainly from phages such as bacteriophage T4. It repairs 3'-OH/5'-PO4 nicks in duplex RNA or RNA:DNA hybrid in which the broken 3'-OH strand is RNA . This process comprises three steps: in the first one, the RNA ligase reacts with ATP in the absence of nucleic acid to form a covalent ligase-AMP intermediate releasing pyrophosphate; in the second the ligase-AMP binds to the nicked duplex nucleic acid and transfers the adenylate to the 5'-PO4 terminus to form an adenylylated nicked intermediate and in the third step the RNA ligase directs the attack of the nick 3'-OH on the 5'-phosphoanhydride linkage, resulting in a repaired 3' - 5' phosphodiester and release of AMP .
Protoporphyrinogen IX dehydrogenase [quinone] HemG (HemG)
Type: Family

Protoporphyrinogen oxidase (PPO) catalyses the six-electron oxidation of protoporphyrinogen IX to the fully conjugated protoporphyrin IX. HemG is a membrane-localized protein and a menadione-dependent flavodoxin with protoporphyrinogen oxidase activity . In E. coli HemG abstracts six electrons from its substrate and transfers them via ubiquinone, cytochrome bo(3) (Cyo) and cytochrome bd (Cyd) oxidase to oxygen. Under anaerobic conditions electrons are transferred via menaquinone, fumarate (Frd) and nitrate reductase (Nar). Cyo, Cyd and Nar contribute to the proton motive force that drives ATP formation .
Terminase, large subunit BPP22-like (Terminase_large_su_BPP22)
Type: Family

Many DNA viruses package their genomes in a reaction catalysed by a powerful DNA-packaging motor, a complex that consists of a dodecameric portal protein and a terminase that converts ATP hydrolysis into linear translation of DNA. The terminase is formed by a small subunit, which binds to packaging initiation sites to prepare for genome packaging, and a large subunit which has ATPase activity and binds directly to the portal protein. The small subunit is essential for binding to DNA and also activates the large subunit ATPase activity .

This family includes the terminase large subunit from Salmonella phage P22 , an ATPase required for viral DNA translocation into empty capsids and it also acts as an endonuclease that cuts the viral genome to initiate and to end a packaging reaction .
Phosphoserine phosphatase YsaA (PSP_YsaA)
Type: Family

This entry represents a group of bacterial phosphatases, including YsaA from Bacillus subtilis. YsaA is a functional equivalent of E. coli SerB, which catalyses the last step of the phosphorylated serine biosynthetic pathway .
Terminase, large subunit, gp17-like (Terminase_large_su_gp17-like)
Type: Family

Many DNA viruses package their genomes in a reaction catalysed by a powerful DNA-packaging motor, a complex that consists of a dodecameric portal protein and a terminase that converts ATP hydrolysis into linear translation of DNA. The terminase is formed by a small subunit, which binds to packaging initiation sites to prepare for genome packaging, and a large subunit which has ATPase activity and binds directly to the portal protein. The small subunit is essential for binding to DNA and also activates the large subunit ATPase activity .

This family represents the terminase large subunit found in phages. It is an ATPase necessary for viral DNA translocation into empty capsids and it also acts as an endonuclease that cuts the viral genome to initiate and to end a packaging reaction. Included in this family is the terminase large subunit from Bacteriophage T4 and from Thermus thermophilus phage P23-45 .
Phosphatidylinositol phosphate synthase PgsA1 (PIP_synthase_PgsA1)
Type: Family

This group of phosphotransferases are mainly from Actinobacteria, including PgsA1 from Mycobacterium. PgsA1 catalyses the conjugation of the 1'-hydroxyl group of D-myo-inositol-3-phosphate (also named L-myo-inositol-1-phosphate) with a lipid tail of cytidine diphosphate diacylglycerol (CDP-DAG), forming phosphatidylinositol phosphate (PIP) and CMP .
Terminase, large subunit SPP1-like (Terminase_large_su_SPP1-like)
Type: Family

Many DNA viruses package their genomes in a reaction catalysed by a powerful DNA-packaging motor, a complex that consists of a dodecameric portal protein and a terminase that converts ATP hydrolysis into linear translation of DNA. The terminase is formed by a small subunit, which binds to packaging initiation sites to prepare for genome packaging, and a large subunit which has ATPase activity and binds directly to the portal protein. The small subunit is essential for binding to DNA and also activates the large subunit ATPase activity .

This entry represents the terminase large subunit, an ATPase necessary for viral DNA translocation into empty capsids and it also acts as an endonuclease that cuts the viral genome to initiate and to end a packaging reaction. Included in this family is the terminase large subunit from Bacillus phage SPP1 and related sequences.
Archaetidylinositol phosphate synthase (AIP_synthase)
Type: Family

This entry represents a group of archaetidylinositol phosphate synthases (AIP synthases), including MTH1691 from Methanothermobacter thermautotrophicus. AIP synthase catalyses the formation of archaetidylinositol phosphate (AIP) from CDP-archaeol (CDP-ArOH or CDP-2,3-bis-(O-phytanyl)-sn-glycerol) and 1L-myo-inositol 1-phosphate (IP or 1D-myo-inositol 3-phosphate) .
Terminase, large subunit gp19 (Terminase_large_su_gp19)
Type: Family

This entry represents the terminase large subunit from Enterobacteria phage T3 and T7 (also known as Gp19). This is an ATPase required for viral DNA translocation into empty capsids and it also acts as an endonuclease that cuts the viral genome at a unique and precise dsDNA sequence to initiate and to end a packaging reaction .

Many DNA viruses package their genomes in a reaction catalysed by a powerful DNA-packaging motor, a complex that consists of a dodecameric portal protein and a terminase that converts ATP hydrolysis into linear translation of DNA. The terminase is formed by a small subunit, which binds to packaging initiation sites to prepare for genome packaging, and a large subunit which has ATPase activity and binds directly to the portal protein. The small subunit is essential for binding to DNA and also activates the large subunit ATPase activity .
Transcription factor PIF3-like (PIF3-like)
Type: Family

This entry represents a group of plant transcription factors that belongs to the basic helix-loop-helix (bHLH) family, including PIF3/PIF3-like from Arabidopsis, and APG/PIL15 from rice.

Phytochrome interacting factors (PIFs) are transcription factors that regulate various light responses . PIF3 (PHYTOCHROME INTERACTING FACTOR 3) is a phytochrome-interacting bHLH factor that targets G-box motifs through its bHLH domain . PIF3 binds to phytochrome B, and the PAS domain of PIF3 is a major contributor to this interaction . PIF3, together with PIF4/5, plays a key role promoting dark-induced senescence.

In rice PIL15 plays important roles in red light-mediated (phyA and/or phyB-dependent) signal transduction pathways . APG interacts with POSITIVE REGULATOR OF GRAIN LENGTH 1 (PGL1), and this interaction represents a grain length and weight-controlling pathway in which APG is a negative regulator whose function is inhibited by PGL1 .
E3 ubiquitin-protein ligase RFI2 (RFI2)
Type: Family

This entry includes RFI2, IPI1 and related proteins. In Arabidopsis RFI2 is an E3 ubiquitin-protein ligase that mediates phytochrome (phyA and phyB)-controlled seedling deetiolation responses such as hypocotyl elongation in response to red and far-red light . In rice IPI1 affects plant architecture through precisely tuning IPA1 protein levels in different tissues .
Cyclin-dependent kinase inhibitor, plant (KRP)
Type: Family

This entry represents a group of plant cyclin-dependent kinase inhibitors (CKIs), including KRP1-7 (Kip-related proteins 1-7) from Arabidopsis .

Plant CKIs fall into 2 distinct families, KIP-RELATED PROTEINS (KRPs) and SIAMESE-RELATED proteins (SMRs). KRPs share very little sequence similarity with mammalian KIP proteins outside the C-terminal conserved region. Compare to mammalian CKIs, plant KRP1-KRP7 bind to active cyclin D2 (CYCD2)/CDKA and CYCD2/CDKB complexes to a similar extent, however, they inhibit kinase activity to a different extent . KRPs function as a dose-dependent cell cycle inhibitors and have an important function in cell proliferation as well as in cell cycle exit and in turning from a mitotic to an endoreplicating cell cycle mode .
Coiled-coil SMC6 And NSE5 INteracting (CANIN) domain (CANIN_dom)
Type: Domain

This domain is found at the C terminus of the SMC5-SMC6 complex localization factor 2 (SFL2, also known as NSE6 and FAM178A) which bridges the interaction between SMC6 and SFL1 (NSE5), being responsible for targeting the SMC5/6 complex to double-strand DNA breaks (DSBs) repair sites. It is suggested to be a regulatory element in SMC5/6 complex dynamics by locking its coiled-coiled arms together, thus being named as Coiled-coil And Nse INteracting (CANIN) domain . This domain is essential for the interaction with SFL1. It forms a U-shaped structure that seems to be structurally conserved in eukaryotes . This domain is also found in FAM178B protein.
GBF-interacting protein 1 (GIP1)
Type: Family

This entry includes GIP1 and GIP1L from plants. GIP1 may act as a coactivator that regulates transcription factors involved in lateral organ development of plants, such as bZIP transcription factors and LBD18 . The function of GIP1L is not clear.
Transcription factor BHLH95-like (BHLH95-like)
Type: Family

This entry represents a group of plant transcription factors, including AtbHLH95 (also known as ZHOUPI) from Arabidopsis . It is an endosperm-specific transcription factor necessary for endosperm degradation, embryo growth, embryo-endosperm separation, and normal embryo cuticle formation .
Sorting nexin 2A/B (SNX2A/B)
Type: Family

This entry represents a group of plant sorting nexins and related proteins, including AtSNX2A/B from Arabidopsis. The AtSNX2B PX domain has been shown to bind to phosphatidylinositol 3-phosphate. AtSNX2B may be involved in vesicular trafficking from endosomes to the vacuole .
Transcriptional activator Hac1/HY5 (Hac1/HY5)
Type: Family

This entry represents a group of basic leucine zipper (bZIP) transcription factors, including Hac1 from yeasts and HY5/HY5-like from Arabidopsis. Hac1 regulates the unfolded protein response (UPR) induced by abnormal accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) in Saccharomyces cerevisiae . HY5 promotes photomorphogenesis in light . HY5-like protein, also known as HYH, is involved in blue-light regulation of development and gene expression. HYH and HY5 can, respectively, act as heterodimers and homodimers, thus mediating light-regulated expression of overlapping as well as distinct target genes . It recruits the histone deacetylase HDA15 to the promoters of a subset of cell wall organization and auxin signaling-related genes .
U3 snoRNP protein/Ribosome production factor 1 (IMP4/RPF1)
Type: Family

This family represents the U3 small nucleolar ribonucleoprotein protein IMP4 and Ribosome production factor 1 RPF1 that belong to the IMP4 superfamily. This superfamily contains a Brix (biogenesis of ribosomes in Xenopus) domain, a region of 150-180 residues length, and it is characterised by the sigma70-like motif, a sequence motif first identified in the sigma70 family of prokaryotic transcription factors, which is sufficient to confer RNA binding activity . IMP4 is a component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP) and it is required for the early cleavages during pre-18S ribosomal RNA processing . RPF1 is a essential protein involved in ribosome biogenesis .
Armadillo repeat protein ABAP1/ARIA (ABAP1/ARIA)
Type: Family

This entry represents a group of plant Armadillo (Arm) repeat proteins, including ABAP1/ARIA from Arabidopsis. ARIA interacts with a transcriptional regulator of abscisic acid-responsive gene expression . ABAP1 is involved in a negative feedback loop regulating mitotic DNA replication during leaf development .
Transcription factor FAMA/SPEECHLESS/MUTE-like (FAMA/SPEECHLESS/MUTE-like)
Type: Family

This entry represents a group of plant bHLH transcription factors, including FAMA, SPEECHLESS and MUTE from Arabidopsis. These proteins have been shown to play important parts in stomatal lineage development. SPEECHLESS (SPCH) generates stem cells and promotes their asymmetric division while MUTE regulates the meristemoid to Guard Mother Cell (GMC) transition. FAMA confers guard cell (GC) fate and is expressed at the equal division producing the two young GCs, but not in mature stomata .

SPCH can be regulated through phosphorylation by MAPK-mediated and BIN2 (BR INSENSITIVE2). It has been suggested that SPCH integrates brassinosteroid and stomata signalling pathways .
Regulatory protein NPR5/6 (NPR5/6)
Type: Family

This entry represents a group of plant BTB/POZ domain and ankyrin repeat-containing proteins, including NPR5/6 from Arabidopsis and NOOT1 from Medicago truncatula .

NPR5 and NPR6, also known as BLADE ON PETIOLE 2 and 1 (BOP2/1), regulates Arabidopsis thaliana lateral organ cell fate and polarity through regulation of LOB domain and adaxial-abaxial polarity genes . They function as transcriptional activators during Arabidopsis thaliana leaf formation . They are also required for maintaining floral fate .

In Gossypium hirsutum BLADE-ON-PETIOLE1 homologue, GhBOP1, is involved in in plant defence against a fungal pathogen .
Periodic tryptophan protein 1 (PWP1)
Type: Family

This family represents the periodic tryptophan protein 1 (PWP1), a chromatin-associated factor that regulates transcription during developmental growth as part of the TORC1 and Myc signaling pathway in response to nutrients. It regulates Pol I-mediated rRNA biogenesis and the epigenetic status of rDNA . Drosophila melanogaster PWP1, also known as Protein no child left behind (nclb), is required in males for both germline stem cell (GSC) maintenance and early stages of germ cell differentiation of germ cell cysts . In females it is necessary to regulate germ cell differentiation and egg chamber development .
E3 ubiquitin-protein ligase SINA-like, plant (SINL_plant)
Type: Family

This entry represents the E3 ubiquitin-protein ligase SINA-like proteins from plants, including SINL1-11 from Arabidopsis. Seven in absentia (SINA) proteins are E3 ligases containing an N-terminally located RING finger domain, followed by the conserved SINA domain that is involved in substrate binding and dimerization. Plant SINA-like proteins are putative E3 ubiquitin ligases .