SII-SWORD/CoKE huggingface dataset:
DNA-directed RNA polymerase, subunit beta-prime (DNA-dir_RpoC_beta_prime)
Type: Family

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 family also includes the bacterial RNA polymerase (RNAP) subunit beta' and the eukaryotic plastid-encoded subunit RNAP beta". Structure studies suggest that RNAP complexes from different organisms share a crab-claw-shape structure with two pincers defining a central cleft. Beta' and beta, the largest and the second largest subunits of bacterial RNAP, each makes up one pincer and part of the base of the cleft. The C-terminal domain includes a G loop that forms part of the floor of the downstream DNA-binding cavity. The position of the G loop may determine the switch of the bridge helix between flipped-out and normal α-helical conformations .
Zinc finger CCCH domain-containing protein 13/40 (Znf_C3H13/40)
Type: Family

This entry represents a family of plant proteins that contain a C3H1-type zinc finger, including the Zinc finger CCCH domain-containing protein 13 from Oryza sativa subsp. japonica (OsC3H13, also known as the BRI1-kinase domain-interacting protein 105) and the Zinc finger CCCH domain-containing protein 40 from Arabidopsis thaliana (AtC3H40).
Bifunctional polymyxin resistance protein ArnA-like, extended (e) SDRs (Arna-like_SDR_e)
Type: Domain

This entry represents the decarboxylase domain of ArnA. This domain can also be found in plant UDP-D-apiose/UDP-D-xylose synthases, such as AXS1/2 from Arabidopsis thaliana. AXS1 catalyses the conversion of UDP-D-glucuronate to a mixture of UDP-D-apiose and UDP-D-xylose .

ArnA is an enzyme involved in the modification of outer membrane protein lipid A of gram-negative bacteria. It is a bifunctional enzyme that catalyses the NAD-dependent decarboxylation of UDP-glucuronic acid and N-10-formyltetrahydrofolate-dependent formylation of UDP-4-amino-4-deoxy-l-arabinose; its NAD-dependent decaboxylating activity is in the C-terminal 360 residues. This subgroup belongs to the extended SDR family, however the NAD binding motif is not a perfect match and the upstream Asn of the canonical active site tetrad is not conserved. Extended SDRs are distinct from classical SDRs. In addition to the Rossmann fold (α/β folding pattern with a central β-sheet) core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids. Extended SDRs are a diverse collection of proteins, and include isomerases, epimerases, oxidoreductases, and lyases; they typically have a TGXXGXXG cofactor binding motif .
TryX and NRX, thioredoxin domain (TryX_NRX_thioredoxin_dom)
Type: Domain

This entry represents the thioredoxin domain found in tryparedoxin (TryX) from trypanosomes and nucleoredoxin (NRX) from animals and plants. They belong to the Thioredoxin (TRX) family, whose members are evolutionary conserved proteins involved in various biologic processes by regulating the response to oxidative stress . TryX and NRX are disulfide oxidoreductases that alter the redox state of target proteins via the reversible oxidation of an active centre CXXC motif .

TryX is involved in the regulation of oxidative stress in parasitic trypanosomatids by reducing TryX peroxidase, which in turn catalyses the reduction of hydrogen peroxide and organic hydroperoxides. TryX derives reducing equivalents from reduced trypanothione, a polyamine peptide conjugate unique to trypanosomatids, which is regenerated by the NADPH-dependent flavoprotein trypanothione reductase .
Histidine-containing phosphotransfer protein 1-5/Phosphorelay intermediate protein YPD1 (AHP1-5/YPD1)
Type: Family

This protein family includes the Histidine-containing phosphotransfer proteins 1-5 (AHP1-5) from Arabidopsis thaliana and the phosphorelay intermediate protein YPD1 from Saccharomyces cerevisiae and Candida albicans. Members of this entry are predominantly found in plants and fungi.

The phospho-relay system is a variant of the two-component signal transduction system. Here a hybrid sensor histidine kinase (HK) auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate response regulator (RR) protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response . AHP1-5 functions as two-component phosphorelay mediators between cytokinin sensor histidine kinases and response regulators. These proteins play an important role in propagating cytokinin signal transduction through the multistep phosphorelay, thus in the development of female gametophytes. They are localized in the cytoplasm and the nucleus .

The phosphorelay intermediate protein YPD1 is part of the two-component regulatory system which controls gene expression in response to changes in the osmolarity of the extracellular environment. It catalyses the phosphoryl group transfer from the membrane-bound osmosensing histidine kinase SLN1 to two distinct response regulator proteins, SSK1 in the cytoplasm, and transcription factor SKN7 in the nucleus . In C. albicans, this system is studied as a potential target for antifungal drugs .
ADP-ribosylation factor 1-5 (Arf1-5-like)
Type: Family

Arf GTPases are involved in the formation of coated carrier vesicles by recruiting coat proteins. This entry includes Arf1, Arf2, Arf3, Arf4, Arf5, and related proteins. Each contains an N-terminal myristoylated amphipathic helix that is folded into the protein in the GDP-bound state. GDP/GTP exchange exposes the helix, which anchors to the membrane. Following GTP hydrolysis, the helix dissociates from the membrane and folds back into the protein. A general feature of Arf1-5 signaling may be the cooperation of two Arfs at the same site. Arfs1-5 are generally considered to be interchangeable in function and location, but some specific functions have been assigned .

Arf1 localizes to the early/cis-Golgi, where it is activated by GBF1 and recruits the coat protein COPI. It also localizes to the trans-Golgi network (TGN), where it is activated by BIG1/BIG2 and recruits the AP1, AP3, AP4, and GGA proteins . Humans, but not rodents and other lower eukaryotes, lack Arf2. Human Arf3 shares 96% sequence identity with Arf1 and is believed to generally function interchangeably with Arf1. Human Arf4 in the activated (GTP-bound) state has been shown to interact with the cytoplasmic domain of epidermal growth factor receptor (EGFR) and mediate the EGF-dependent activation of phospholipase D2 (PLD2), leading to activation of the activator protein 1 (AP-1) transcription factor . Arf4 has also been shown to recognise the C-terminal sorting signal of rhodopsin and regulate its incorporation into specialised post-Golgi rhodopsin transport carriers (RTCs) . There is some evidence that Arf5 functions at the early-Golgi and the trans-Golgi to affect Golgi-associated alpha-adaptin homology Arf-binding proteins (GGAs) .
ADP-ribosylation factor-like protein 2 (Arl2)
Type: Family

Arl2 (Arf-like 2) GTPases are members of the Arf family that bind GDP and GTP with very low affinity. Unlike most Arf family proteins, Arl2 is not myristoylated at its N-terminal helix. The protein PDE-delta, first identified in photoreceptor rod cells, binds specifically to Arl2 and is structurally very similar to RhoGDI. Despite the high structural similarity between Arl2 and Rho proteins and between PDE-delta and RhoGDI, the interactions between the GTPases and their effectors are very different. In its GTP bound form, Arl2 interacts with the protein Binder of Arl2 (BART), and the complex is believed to play a role in mitochondrial adenine nucleotide transport . In its GDP bound form, Arl2 interacts with tubulin- folding Cofactor D; this interaction is believed to play a role in regulation of microtubule dynamics that impact the cytoskeleton, cell division, and cytokinesis .

This entry also includes Alp41 from fission yeasts which is essential for the cofactor-dependent biogenesis of microtubules .
Rust resistance kinase Lr10/LRL2.1-2.5-like (LRK10/LRL21-25-like)
Type: Family

This entry includes a group of plant proteins, such as Rust resistance kinase Lr10 (LRK10) from maize and LEAF RUST 10 DISEASE-RESISTANCE LOCUS RECEPTOR-LIKE PROTEIN KINASE-like 2.1-2.5 from Arabidopsis, which contain a protein kinase domain. Their function is not clear
Nuclear transport factor 2 (NTF2)
Type: Family

This entry represents a group of nuclear transport proteins, including NTF2 from eukaryotes.

Nuclear transport factor 2 (NTF2) is a homodimer which stimulates efficient nuclear import of a cargo protein. NTF2 binds to both RanGDP and FxFG repeat-containing nucleoporins. NTF2 folds into a cone with a deep hydrophobic cavity, the opening of which is surrounded by several negatively charged residues. RanGDP binds to NTF2 by inserting a conserved phenylalanine residue into the hydrophobic pocket of NTF2 and making electrostatic interactions with the conserved negatively charged residues that surround the cavity .
Pathogenesis-related homeodomain protein, PHD finger (PRHA-like_PHD-finger)
Type: Domain

Pathogenesis-related homeodomain protein (PRHA) is a homeodomain protein encoded by a single-copy Arabidopsis thaliana homeobox gene, prha. It shows the capacity to bind to TAATTG core sequence elements but requires additional adjacent bases for high-affinity binding. PRHA contains a plant homeodomain (PHD) finger, a homeodomain, peptide repeats and a putative leucine zipper dimerization domain . This entry represents the PHD finger.
RNA-binding protein ZFP36-like (ZFP36-like)
Type: Family

This entry represents a group of CCCH-type zinc finger proteins, including ZFP36/ZFP36L1/ZFP36L2 from animals, Zfs1 from fission yeasts and CTH1/2 from budding yeasts. ZFP36/ZFP36L1/ZFP36L2, Zfs1 and CTH1/2 are mRNA decay activator proteins that bind to specific AU-rich elements (ARE) in the 3'-untranslated region of target mRNAs and promotes their degradation .

This entry includes RNA-binding protein pos-1 that coordinates cell fate specification and differentiation during early embryogenesis in C.elegans .
Guanine nucleotide-binding protein subunit gamma 1/2 (GG1/2)
Type: Family

This protein family represents Guanine nucleotide-binding protein subunit gamma 1 from Arabidopsis thaliana (GG1) and Guanine nucleotide-binding protein subunit gamma 2 (GG2) from Oryza sativa. These G proteins are involved as modulators or transducers in various transmembrane signaling systems . Members of this family are only found in streptophytes.

In Arabidopsis thaliana GG1 and GG2 are functionally interchangeable in specific pathways .
Cytochrome b561, DM13 and DOMON domain-containing protein At5g54830 (B561A)
Type: Family

This entry represents the Cytochrome b561, DM13 and DOMON domain-containing protein At5g54830 from Arabidopsis thaliana (b561A). This protein is thought to act as a catecholamine-responsive trans-membrane electron transporter . Most members of this family are found in streptophytes.
ZCF37 (ZCF37)
Type: Family

Proteins in this group of proteins have been annotated as ZCF37. Their function is not clear.
METABOLIC NETWORK MODULATOR 1-like (MNM1-like)
Type: Family

This entry represents a group of plant proteins, including METABOLIC NETWORK MODULATOR 1 (MNM1, AT5G54930), also known as AT hook motif-containing protein, from Arabidopsis. MNM1 is involved in primary metabolism .
GROWING PLUS-END TRACKING 1/2 (GPT1/2)
Type: Family

This entry represents a group of plant proteins, including GROWING PLUS-END TRACKING 1 (GPT1, At2g37070) and GROWING PLUS-END TRACKING 2 (GPT2, At3g53320) from Arabidopsis. GPT1/2 are microtubule-associated proteins that contain the basic MT-binding regions at their central and C-terminal regions, and bind directly to MTs in vitro. They track the plus ends of growing MTs independently of EB1 and SPR1 .
Transmembrane protein At4g13530-like (At4g13530-like)
Type: Family

This entry represents a group of plant transmembrane proteins, including At4g13530 from Arabidopsis.
Transmembrane protein At5g59350-like (At5g59350-like)
Type: Family

This entry represents a group of plant transmembrane proteins, including At5g59350 from Arabidopsis.
N-acetylgalactosaminyltransferase (GalNAc-T)
Type: Domain

This entry represents a domain found in N-acetylgalactosaminyltransferases (also known as pp-GalNAc-T). They initiate the formation of mucin-type, O-linked glycans by catalysing the transfer of alpha-N-acetylgalactosamine (GalNAc) from UDP-GalNAc to hydroxyl groups of Ser or Thr residues of core proteins to form the Tn antigen (GalNAc-a-1-O-Ser/Thr). These enzymes are type II membrane proteins with a GT-A type catalytic domain and a lectin domain located on the lumen side of the Golgi apparatus . In human, there are 15 isozymes of pp-GalNAc-Ts, representing the largest of all glycosyltransferase families. Each isozyme has unique but partially redundant substrate specificity for glycosylation sites on acceptor proteins .

Interestingly, some members, such as human GALNTL5, lack the C-terminal ricin B-type lectin domain, which contributes to the glycopeptide specificity. No glycosyltransferase activity has been detected for human GALNTL5 in an in vitro assay .

This entry also includes Putative inactive polypeptide N-acetylgalactosaminyltransferase 11/12 from Drosophila, which, although they are strongly related to polypeptide N-acetylgalactosaminyltransferase proteins, they lack the conserved His at position 211 which is part of the Asp-X-His motif that binds the cofactor Mn2, suggesting that they may have lost its activity.
ThiF/MoeB/HesA family (ThiF/MoeB/HesA)
Type: Family

This is a family of E1-like enzymes that contain the NAD/FAD-binding fold . Proteins in this entry include ThiF/MoeB/HesA from bacteria and E1-like enzymes from eukaryotes.

ThiF/MoeB/HesA are involved in molybdopterin and thiamine biosynthesis. The common reaction mechanism catalysed by MoeB and ThiF, like other E1 enzymes, begins with a nucleophilic attack of the C-terminal carboxylate of MoaD and ThiS, respectively, on the alpha-phosphate of an ATP molecule bound at the active site of the activating enzymes, leading to the formation of a high-energy acyladenylate intermediate and subsequently to the formation of a thiocarboxylate at the C termini of MoaD and ThiS. MoeB, as the MPT synthase (MoaE/MoaD complex) sulfurase, is involved in the biosynthesis of the molybdenum cofactor, a derivative of the tricyclic pterin, molybdopterin (MPT) . ThiF catalyses the adenylation of ThiS, as part of the biosynthesis pathway of thiamin pyrophosphate (vitamin B1) .
Endoplasmic reticulum vesicle transporter (Erv)
Type: Family

Proteins included in this entry are conserved from plants and fungi to humans. Erv46 (ERGIC3) works in close conjunction with Erv41 (ERGIC2) and together they form a complex which cycles between the endoplasmic reticulum and Golgi complex. Erv46-41 interacts strongly with the endoplasmic reticulum glucosidase II. Mammalian glucosidase II comprises a catalytic alpha-subunit and a 58kDa beta subunit, which is required for ER localisation. All proteins identified biochemically as Erv41p-Erv46p interactors are localised to the early secretory pathway and are involved in protein maturation and processing in the ER and/or sorting into COPII vesicles for transport to the Golgi .

This entry also includes disulfide isomerase (PDI)-C subfamily members from Arabidopsis. They are chimeric proteins containing the thioredoxin (Trx) domain of PDIs, and the conserved N- and C-terminal domains of Erv cargo receptors .
Methylesterase/Alpha-hydroxynitrile lyase (MES/HNL)
Type: Family

This entry represents a group of α/β-hydrolase fold-containing proteins mostly from plants and bacteria, including methylesterase (MES) and hydroxynitrile lyase (HNL) from Arabidopsis.

There are at least 20 Arabidopsis MES members (AtMES1-AtMES20). The catalytic triad Ser-His-Asp is conserved in 15 of these proteins. However, AtMES19 and AtMES20 lack part of the N-terminal or C-terminal region, respectively, and are therefore likely to be inactive enzymes. Some members have been shown to hydrolyse MeIAA .

AtHNL catalyses the cleavage of cyanohydrins to yield hydrocyanic acid (HCN) and the respective carbonyl compound and are key enzymes in the process of cyanogenesis in plants . Interestingly, HNL homologue from Hevea brasiliensis, known as HbHNL, has opposite enantioselectivities and different reaction mechanisms compared to AtHNL .

Proteins in this entry also include pyrethroid hydrolase PytH from Sphingobium wenxiniae, which catalyses the hydrolysis of pyrethroids pesticides , and Norfluorocurarine synthase 1/2 from Strychnos nux-vomica, hydrolases involved in the biosynthesis of curare monoterpene indole alkaloids (MIAs), natural products such as strychnine, a neurotoxic compound used as a pesticide to control rodents, and its pharmacologically active derivatives, including brucine, used to regulate blood pressure .
BTB/POZ domain-containing protein POB1-like (POB1-like)
Type: Family

This entry represents a subset of proteins from the Bric-a-Brac/Tramtrack/Broad Complex (BTB) family predominantly found in the plant class Magnoliopsida, including POB1 from Arabidopsis. BTB proteins direct the selective ubiquitylation of proteins following their assembly into Cullin3-based ubiquitin ligases. Proteins in this family contain a BTB (broad complex/tramtrack/bric-a-brac, also known as poxvirus and zinc finger (POZ) domain and a BACK (BTB-and-C-terminal-Kelch) domain .

POB1 (also known as light-response BTB2, Lrb2) is predicted to be involved in ubiquitination and to negatively regulate the ABA-mediated inhibition of germination .
Zinc transporter ZIP9 (ZIP9)
Type: Family

This entry represents the zinc transporter ZIP9 from eukaryotes. It also includes metal homeostasis factor ATX2 from yeast, which is involved in homeostasis of manganese ions. Some bacterial and archaeal zinc transporters are also included in this entry.

In humans, ZIP9 is one of the 14 members of the ZIP (ZRT-and Irt-like Protein, SLC39A) family that regulates zinc homeostasis by transporting zinc across cell and organelle membranes into the cytoplasm. ZIP9 plays an important role in the activation of Akt and Erk in response to B cell-receptor activation . It has been shown to mediate rapid testosterone-dependent signaling, zinc influx, and apoptosis in breast and prostate cancer cell lines .
Prolycopene isomerase-like (CrtISO-like)
Type: Family

This entry represents a family of proteins involved in the metabolism of carotenoids (such as propycopene and myxoxanthophyll), including the Prolycopene isomerase from Arabidopsis (CrtISO). Members of this family are predominantly found in plants and cyanobacteria.

CrtISO is a carotene cis-trans-isomerase (

) that converts 7,9,9'-tri-cis-neurosporene to 9'-cis-neurosporene and 7,9,9',7'-tetra-cis-lycopene (also known as prolycopene) into all-trans-lycopene .

Members of this family include the Slr1293 protein, a carotenoid biosynthesis protein which was shown to be the C-3',4' desaturase (CrtD) of myxoxanthophyll biosynthesis in Synechocystis sp. (strain PCC 6803), and close homologues (presumed to be functionally equivalent) from other cyanobacteria, where myxoxanthophyll biosynthesis is either known or expected. This enzyme can act on neurosporene and so presumably catalyses the first step that is committed to myxoxanthophyll
.
FREE1 (FREE1)
Type: Family

FYVE domain protein required for endosomal sorting 1 (FREE1), also known as FYVE domain-containing protein 1 (FYVE1) is a component of the endosomal sorting complex required for transport (ESCRT), involved in multivesicular body (MVB) protein sorting and plant growth . It negatively regulates salt stress tolerance via a negative feedback loop involving abscisic acid (ABA) signaling pathway .
At5g08430-like (At5g08430-like)
Type: Family

This entry represents At5g08430 from Arabidopsis thaliana and related proteins from plants. Proteins in this family contain a SWIB/MDM2, a Plus3 and a GYF domain.
Transcription factor bHLH91-like (bHLH91-like)
Type: Family

This entry represents a group of plant transcription factors containing a Myc-type, basic helix-loop-helix (bHLH) domain, including the transcription factors bHLH010, bHLH089, bHLH91 and bHLH138 from Arabidopsis thaliana and the transcription factors TIP2 and EAT1 from Oryza sativa.

bHLH010, bHLH089 and bHLH91 are involved in pollen development. They are important for the development of the Arabidopsis anther, possibly by forming a feed-forward loop with DYT1 .

TDR INTERACTING PROTEIN2 (TIP2) is necessary in the meristemoid transition and differentiation during early anther development. TDR and EAT1 are paralogs of TIP2. TIP2 acts upstream of TDR and EAT1 and regulates their expression .

EAT1 participates in the regulation of tapetum programmed cell death (PCD) and degradation during male reproductive development in rice .
Transcription factor MYC1-like, bHLH domain (MYC1-like_bHLH)
Type: Domain

This entry represents the basic helix-loop-helix (bHLH) domain found in a group of plant transcription factors. This entry includes MYC1 and bHLH91 from Arabidopsis thaliana and EAT1 from Oryza sativa.

MYC1 (also known as BHLH12) is an important regulator of trichome and root hair initiation .

bHLH91 is involved in pollen development. This protein is important for the normal transcriptome of the developing Arabidopsis anther, possibly by forming a feed-forward loop with DYT1 .

EAT1 participates in the regulation of tapetum programmed cell death (PCD) and degradation during male reproductive development in rice .
Lipid binding protein BPI/LBP, plants (BPI/LBP_pln)
Type: Family

This entry represents a group of uncharacterised plant proteins similar to the putative BPI/LBP family protein At3g20270 from Arabidopsis thaliana. Proteins in this family show protein sequence similarity with the bactericidal permeability-increasing protein (BPI) and the lipopolysaccharide-binding protein (LBP), which may represent a common gene family of lipid-binding proteins .