SII-SWORD/CoKE huggingface dataset:
NUP50, Ran-binding domain (RanBD_NUP50_plant)
Type: Domain

This entry represents the Ran-binding domain found in plant NUP50 protein. NUP50 is a nuclear pore complex component involved in nucleocytoplasmic transport via its interactions with importins and Ran .
rRNA biogenesis protein Rrp5 (Rrp5)
Type: Family

Rrp5 is involved in the biogenesis of rRNA. It is required for formation of both 18S and 5.8S rRNA in budding yeasts . In humans, it is also known as NFBP, which is essential for the generation of 18S rRNA . In Arabidopsis, it is essential for normal development of female gametophytes .
PUB protein, U-box domain, plant (RING-Ubox_PUB)
Type: Domain

The plant PUB proteins, also known as U-box domain-containing proteins, are much more numerous in Arabidopsis which has 62 in comparison with the typical 6 in most animals. The majority of AtPUB of this family are known as ARM domain-containing PUB proteins which contain a C-terminal located, tandem ARM (armadillo) repeat protein-interaction region in addition to the U-box domain. They have been implicated in the regulation of cell death and defense. They also play important roles in other plant-specific pathways, such as controlling both self-incompatibility and pseudo-self-incompatibility, as well as acting in abiotic stress. A subgroup of ARM domain-containing PUB proteins harbors a plant-specific U-box N-terminal domain .
TFP11/STIP/Ntr1 (TFP11/STIP/Ntr1)
Type: Family

This entry includes tuftelin-interacting protein 11 (TFP11) from humans, septin/tuftelin-interacting protein 1 (STIP1) from Drosophila melanogaster and Ntr1 (also known as Spp382) from budding yeasts.

Ntr1 forms the NTR complex (NineTeen Complex) with Ntr2 and Prp43 (a DExD/H-box RNA helicase) that catalyses disassembly of ntron-lariat spliceosomes (ILS) and defective earlier spliceosomes. Ntr1 has been shown to interact with Prp43 through the N-terminal G-patch domain, with Ntr2 through a middle region, and with itself through the carboxyl half of the protein . The G-patch domain of Ntr1 activates Prp43 for spliceosome disassembly, while its C-terminal domain may have a safeguarding role preventing Prp43-mediated disassembly of wild-type spliceosomes other than the IL spliceosome .

Septin and tuftelin interacting proteins (STIPs) are G-patch domain proteins involved in spliceosome disassembly . The mouse protein, known as TFT11 was originally identified as a protein interacting with tuftelin, one of the presumed enamel matrix proteins . The Drosophila protein STP1 was originally identified as a septin-interacting protein . In both cases these interactions were identified by a yeast two-hybrid system and their function and direct physical association were not characterised. Subsequent studies show that these proteins are widely expressed and function as splicing factors . STIP is essential for embryogenesis in Caenorhabditis elegans .
Malic enzyme, NAD-binding domain, bacterial type (Malic_NAD-bd_bact_type)
Type: Domain

This entry represents the NAD-binding domain found in malic enzymes from bacteria and archaea.

Malic enzymes (malate oxidoreductases) catalyse the oxidative decarboxylation of malate to form pyruvate, a reaction important in a number of metabolic pathways - e.g. carbon dioxide released from the reaction may be used in sugar production during the Calvin cycle of photosynthesis . There are 3 forms of the enzyme : an NAD-dependent form that decarboxylates oxaloacetate; an NAD-dependent form that does not decarboxylate oxalo-acetate; and an NADPH-dependent form . Other proteins known to be similar to malic enzymes are the Escherichia coli scfA protein; an enzyme from Zea mays (Maize), formerly thought to be cinnamyl-alcohol dehydrogenase ; and the hypothetical Saccharomyces cerevisiae protein YKL029c.

Studies on the duck liver malic enzyme reveals that it can be alkylated by bromopyruvate, resulting in the loss of oxidative decarboxylation and the subsequent enhancement of pyruvate reductase activity . The alkylated form is able to bind NADPH but not L-malate, indicating impaired substrate or divalent metal ion-binding in the active site . Sequence analysis has highlighted a cysteine residue as the point of alkylation, suggesting that it may play an important role in the activity of the enzyme , although it is absent in the sequences from some species.

Malic enzyme is a tetramer comprised of subunits with four domains each .
Surfeit locus 1/4 (Surf1/Surf4)
Type: Family

This entry includes SURF1 and Shy1 proteins. The surfeit locus 1 gene (SURF1 or surf-1) encodes a conserved protein of about 300 amino-acid residues that seems to be involved in the biogenesis of cytochrome c oxidase . Vertebrate SURF1 is evolutionary related to yeast protein Shy1, which is a mitochondrial inner membrane protein required for assembly of cytochrome c oxidase . There seems to be two transmembrane regions in these proteins, one in the N-terminal, the other in the C-terminal.

Defects in SURF1 are a cause of Leigh syndrome (LS). LS is a severe neurological disorder characterised by bilaterally symmetrical necrotic lesions in subcortical brain regions that is commonly associated with systemic cytochrome c oxidase (COX) deficiency .

The surfeit locus gene SURF4 (or surf-4) encodes a conserved integral eukaryotic membrane protein of about 270 to 300 amino-acid residues that seems to be located in the endoplasmic reticulum .
Casein Kinase 2, subunit alpha (CK2_alpha)
Type: Family

Ser/Thr protein kinase CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits . It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection . CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumour cells .
Patatin-like phospholipase domain containing protein 8-like (PNPLA8-like)
Type: Domain

Patatin-like phospholipase domain containing protein 8 (PNPLA8, also known as iPLA2-gamma) is a Ca-independent myocardial phospholipase which maintains mitochondrial integrity. In humans, it is predominantly expressed in heart tissue. iPLA2-gamma can catalyse both phospholipase A1 and A2 reactions (PLA1 and PLA2 respectively). This family includes PNPLA8 (iPLA2-gamma) from mammals and AtPLAI from Arabidopsis .
Protein DA1-like (DA1-like)
Type: Family

This entry includes DA1 and DAR1-7 from Arabidopsis and LIM domain-containing protein HDR3 from rice . This entry also includes uncharacterised proteins from bacteria.

In Arabidopsis thaliana, DA1 is a ubiquitin-activated endopeptidase that limits final seed and organ size by restricting the period of cell proliferation . DA1 is activated by the RING E3 ligases Big Brother and DA2, both of which are then inactivated by cleavage by the active peptidase. DA1 also cleaves and inactivates deubiquitinase UBP15 and transcription factors TCP15 and TCP22, all of which promote cell proliferation. Presence of an HEXXH motif, which when mutated leads to inactivity, suggests that DA1 is a metalloendopeptidase .
PKD- and KLD-Associated Transmembrane (PKAT)
Type: Family

This family includes Melanocyte protein PMEL (also known as PMEL-17), Transmembrane glycoprotein NMB (GPNMB) and Transmembrane protein 130, previously described as melanocyte protein PMEL-17-related family. Regarding the highly conserved domain architecture of these family members, including the PKD, KLD and transmembrane (TM) domains, the name was updated and now referred to as PKD- and KLD-Associated Transmembrane (PKAT) protein family . TMEM130 has been identified as the most ancient paralogue of PMEL and GPNMB.

PMEL and GPNMB share overlapping phenotypes and disease associations, such as melanin-based pigmentation, cancer, neurodegenerative disease and glaucoma.
Oxidoreductase FRHB/FDHB/HCAR-like (FRHB/FDHB/HCAR-like)
Type: Family

This entry includes a group of oxidoreductases, including F420 hydrogenase and dehydrogenase beta subunits (FRHB) , Methanobacterium formicicum formate dehydrogenase beta chain (FDHB) (

,

) and chloroplastic 7-hydroxymethyl chlorophyll a reductase (HCAR) (

) . Coenzyme F420 hydrogenase (

) reduces the low-potential two-electron acceptor coenzyme. It also includes F(420)H(2) dehydrogenase subunit F (FpoF), which is part of the energy-conserving F(420)H2:heterodisulfide oxidoreductase system .
Sphingomyelin synthase-like (Sphingomyelin_synth-like)
Type: Family

Sphingomyelin synthase (also known as phosphatidylcholine:ceramide cholinephosphotransferase) is a bidirectional lipid cholinephosphotransferase capable of converting phosphatidylcholine (PC) and ceramide to sphingomyelin (SM) and diacylglycerol (DAG) and vice versa . This entry also includes sphingomyelin synthase-related proteins, including SAMD8 from humans , SMSr from Drosophila melanogaster and Protein PHLOEM UNLOADING MODULATOR from Arabidopsis .
DNA-directed RNA polymerase II subunit Rpb4-like (Rpb4-like)
Type: Family

Rpb4 is a subunit of , the RNA polymerase II core enzyme (RNAP II). It forms a heterodimeric complex with Rpb7 that is essential for promoter-directed transcription initiation. The Rpb4-Rpb7 subcomplex is necessary for promoter-directed transcription initiation but is not required for recruitment of Pol II to active preinitiation complexes and seems to be dispensable for transcription elongation and termination .
Small ribosomal subunit protein RACK1-like (RACK1-like)
Type: Family

This entry includes the small ribosomal subunit protein RACK1 from eukaryotes, previously known as guanine nucleotide-binding protein subunit beta-like (also known as Asc1 in yeast) . They are core 40S ribosomal proteins that repress gene expression and involved in induction of the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation . The seven-bladed β-propeller structure of RACK1 is located near the mRNA exit tunnel where it makes contacts with the ribosomal RNA through lysine and arginine residues and neighbouring ribosomal proteins . Asc1/RACK1 are key factors in phosphosignaling and functions as a control point at the head of the ribosomal 40S subunit itself regulated through posttranslational modification . RACK1 also serves as a scaffold protein that can recruit other proteins to the ribosome and also for a wide range of kinases and membrane bound receptors . It has been shown to regulates axonal growth and is essential for development in mice, Drosophila melanogaster and Arabidopsis thaliana . This entry also includes MIP11, a RACK1 orthologue .
Homeobox-leucine zipper protein, class I, plant (HDZip_class_I_plant)
Type: Family

Four homeodomain leucine zipper (HD-Zip) families can be distinguished, termed class I, II, III and IV . This entry represents plant class I homeobox-leucine zipper proteins. They are transcription factors involved in developmental processes . AtHB13 conferred to Arabidopsis transgenic plants tolerance to freezing temperatures . AtHB7 and AtHB12 has been shown to regulate protein phosphatases type 2C (PP2C) and repress PYL5 and PYL8, two ABA receptors, in response to ABA stimulus . Moreover, AtHB5, AtHB6 and AtHB20 have been shown to function in ABA responses .
Uracil/uridine/allantoin permease (Uracil/uridine/allantoin_perm)
Type: Family

This entry includes uracil/uridine/allantoin permease homologues from fungi, plants, bacteria and archaea .
DSC E3 ubiquitin ligase complex subunit 3 (Dsc3)
Type: Family

This entry represents DSC E3 ubiquitin ligase complex subunit 3 (Dsc3), a component of the DSC E3 ubiquitin ligase complex (a Golgi-specific protein ubquitination system) that functions in protein homeostasis under non-stress conditions, playing a role in protein quality control through endosome and Golgi-associated degradation pathway (EGAD) which targets membrane proteins at Golgi and endosomes for degradation by cytosolic proteasomes . Dsc3 is also involved in endocytic protein trafficking . Dsc3 has an ubiquitin-like domain and two C-terminal transmembrane regions.

Yeast DSC E3 ubiquitin ligase complex is the homologue of Hrd1 E3 ligase complex from mammals, in which Dsc1, Dsc2 and Dsc3 corresponds to Hrd1, Der1, and Usa1, respectively. Dsc3 is a Herp-like protein that acts as a bridge between Dsc1 and Dsc2 for their interaction .
WD repeat-containing protein WDR18/Ipi3/RID3 (WDR18/Ipi3/RID3)
Type: Family

This entry represents a group of WD repeat-containing proteins, including Ipi3 from yeasts, WDR18 from animals and RID3 from Arabidopsis. Ipi3 is part of the Rix1 complex required for the processing of 35S pre-rRNA in pre-60S ribosomal particles and for the initiation of DNA replication . It interacts with pre-RC proteins, binds chromatin predominantly at ARS sequences in a cell cycle-regulated and ORC- and Noc3-dependent manner . WDR18, the human Ipi3 homologue, is a component of the Five Friends of Methylated CHTOP (5FMC) complex, which is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes . It is also involved in human DNA replication licensing . RID3 acts as negative regulator of the CUC-STM pathway in shoot apical meristem (SAM) neo-formation .
Phosphatase Gpp1/Gpp2-like (Gpp1/Gpp2-like)
Type: Family

This entry includes Arabidopsis thaliana AtGpp1 and AtGpp2, human pseudouridine-5'-phosphatase PUDP, the orthologue in Drosophila GS1-like protein (Dmel\Gs1l) . AtGpp1 and AtGpp2 are constitutively expressed in all the Arabidopsis tissues and unaffected under abiotic stress. Overexpression of AtGpp2 in transgenic Arabidopsis plants increases the specific DL-glycerol-3-phosphatase activity and improves the plants tolerance to salt, osmotic and oxidative stress . PUDP dephosphorylates pseudouridine 5'-phosphate, a potential intermediate in rRNA degradation .
Thiamine pyrophosphate enzyme (TPP_enz)
Type: Family

A number of enzymes require thiamine pyrophosphate (TPP) (vitamin B1) as a cofactor. It has been shown that some of these enzymes are structurally related .
Zinc finger protein MBS1/2-like (MBS1/2-like)
Type: Family

This entry represents a group of zinc finger proteins, including MBS1/2 from Arabidopsis and ZNF706 from animals. MBS1/2 are required for induction of singlet oxygen-dependent gene expression and is involved in ROS signalling . ZNF706 may act as a transcription repressor involved in the exit of embryonic stem cells (ESCs) from self-renewal . MBS1 is involved in the singlet oxygen signalling downstream of beta-cyclocitral .
Protein Yip1/4-like (Yip1/4-like)
Type: Family

This entry includes Yip1 from yeasts and YIPF4-7 from animals. They are multi-span, transmembrane proteins mainly localised in the Golgi apparatus Budding yeast Yip1 functions in ER to Golgi and intra-Golgi transport at the vesicle docking/fusion step . YIPF4-7 form complexes 1 (YIPF5/7) , 2 (YIPF4), and 3 (YIPF6), and are mainly localised at the early, middle, and late compartments of the Golgi apparatus, respectively .
Protein FAM234 (FAM234)
Type: Family

This entry includes FAM234A/B from animals and Protein DEFECTIVE IN EXINE FORMATION 1 (DEX1) from Arabidopsis. The function of FAM234A/B is not clear. DEX1 is required for exine pattern formation during pollen development . Rice DEX1 is a Ca2+ binding protein involved in regulating rice tapetal cell degradation and pollen formation .
Mannose-1-phosphate guanyltransferase, N-terminal domain (GMPPB_N)
Type: Domain

This entry represents the N-terminal domain of mannose-1-phosphate guanyltransferase.

Mannose-1-phosphate guanyltransferase (Mpg1 or GMPPB) catalyses the formation of GDP-mannose, an essential precursor of glycan moieties of glycoproteins and glycolipids. It contains an N-terminal catalytic domain and a C-terminal Lefthanded-β-Helix fold domain. In fission yeasts Mpg1 is required for proper septum structure and is involved cell cycle progression through cell-size checkpoint . In budding yeasts Psa1 plays an important part in maintenance of cell-wall integrity .
RING finger protein Unkempt-like (Unkempt-like)
Type: Family

This entry represents a group of RING finger proteins from animals and plants, including Unkempt and related proteins.

Unkempt is an evolutionary conserved RNA-binding protein that regulates translation of its target genes and is required for the establishment of the early bipolar neuronal morphology. It carries six CCCH zinc fingers (Znfs) forming two compact clusters, Znf1-3 and Znf4-6, that recognise distinct trinucleotide RNA substrates. These clusters, recognise an unexpectedly short stretch of RNA sequence-only three consecutive ribonucleotides-with a varying degree of specificity. Znf1-3 binds to the UUA motif of RNA substrates .

Proteins in this entry also include Zinc finger CCCH domain-containing proteins from Arabidopsis. They are involved in regulating stress responses , light-dependent seed germination and embryogenesis .
PuuE/HpPgdA-like (PuuE_HpPgdA-like)
Type: Family

This family contains many uncharacterised prokaryotic polysaccharide deacetylases (DCAs) that show high sequence similarity to the catalytic domain of bacterial PuuE allantoinases and Helicobacter pylori peptidoglycan deacetylase (HpPgdA) . PuuE allantoinase appears to be metal-independent and specifically catalyses the hydrolysis of (S)-allantoin into allantoic acid. Different from PuuE allantoinase, HpPgdA has the ability to bind a metal ion at the active site and is responsible for a peptidoglycan modification that counteracts the host immune response. Both PuuE allantoinase and HpPgdA function as homotetramers. The monomer is composed of a 7-stranded barrel with detectable sequence similarity to the 6-stranded barrel NodB homology domain of DCA-like proteins in the CE4 superfamily, which removes N-linked or O-linked acetyl groups from cell wall polysaccharides. In contrast to typical NodB-like DCAs, PuuE allantoinase and HpPgdA do not exhibit a solvent-accessible polysaccharide binding groove and might only bind a small molecule at the active site .
Reverse rubrerythrin, di-iron-binding domain (RevRr_diiron-bd_dom)
Type: Domain

Rubrerythrin (Rr) is a fusion protein containing an N-terminal diiron-binding domain and a C-terminal domain homologous to rubredoxin . This protein has been related to the response to oxidative stress .

This entry represents the rubrerythrin-like domain, which is a nonheme iron binding domain found in many air-sensitive bacteria and archaea. It is a singular domain (no C terminus rubredoxin domain) and is phylogenetically distinct from rubrerythrin domains of rubrerythrin-rubredoxin proteins . This domain can be found in Rbr3A/B from Clostridium acetobutylicum. They function as the terminal component of an NADH peroxidase and NADH oxidase .
Eukaryotic translation initiation factor 3 subunit M eIF3m/COP9 signalosome complex subunit 7 COPS7 (COPS7/eIF3m)
Type: Family

This entry includes eIF3m and COPS7A/B.

Eukaryotic translation initiation factor 3 subunit M (eIF3m) is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome .

The COP9 signalosome (CSN) is a conserved protein complex that regulates the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes , which leads to a decrease in Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2 . Protein kinases CK2 and D, which phosphorylate proteins such as cJun and p53 resulting in their degradation by the ubiquitin-26S proteasome system, also binds to CSN . The mammalian CSN typically consistis of eight subunits designated CSN1-CSN8. The fission yeast possesses a smaller version of the CSN, consisting only of six subunits, whereas a more distant CSN-like complex has been described in Saccharomyces cerevisiae .
Tim23-like (Tim23-like)
Type: Family

This entry includes mitochondrial import inner membrane translocase subunit Tim23 and chloroplastic outer envelope pore protein 16-1/2 (OEP161/162). In plants OEP161/162 are distantly related to the translocase of the inner mitochondrial membrane Tim17 . OEP161/162 are amino acid-selective channel proteins and translocation pores for NADPH:protochlorophyllide oxidoreductase A (PORA) .

The TIM23 complex forms a dynamic multisubunit machinery that recognises preproteins and can transport them into the inner membrane or into the matrix. It is composed of three subunits, Tim50, Tim23, and Tim17, that expose the domains to the intermembrane space. This entry includes the mitochondrial import inner membrane translocase subunit Tim23, consisting of an N-terminal intermembrane space domain that interacts with Tim50, and a C-terminal membrane-embedded domain that, together with Tim17, forms a protein-conducting channel across the inner membrane. Tim50 helps keeping the Tim23 channel in a closed state in the absence of presequence proteins, regulating the gating through the TIM channel .
Transcription factor bHLH95-like, basic helix-loop-helix domain (bHLH95_bHLH)
Type: Domain

bHLH proteins are the second largest class of plant transcription factors that regulate transcription of genes that are involved in many essential physiological and developmental process. bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. This entry represents the basic helix-loop-helix domain found in a group of plant bHLH proteins, including BHLH95 from Arabidopsis. BHLH95 is an endosperm-specific transcription factor necessary for endosperm degradation, embryo growth, embryo-endosperm separation, and normal embryo cuticle formation .