SII-SWORD/CoKE huggingface dataset:
Large ribosomal subunit protein uL4, eukaryotic and archaeal type (Ribosomal_uL4_euk/arch)
Type: Family

This family includes ribosomal uL4 from eukaryotes and archaea. uL4 has been structurally characterised as a part of ribosome particle .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
WD repeat Prp46/PLRG1-like (Prp46/PLRG1-like)
Type: Family

This entry represents a group of WD40 repeat containing proteins, including Prp46 from budding yeasts, Prp5 from fission yeasts, PLRG1 from animals and PRL1/2 from plants. Prp46 and Prp5 are involved in pre-mRNA splicing and may be required for both cell cycle progression at G2/M . PLRG1 is a component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing . In Arabidopsis PRL1/2 are pleiotropic regulator of glucose, stress and hormone responses . PRL1 is part of the MAC, a multiprotein complex with a role in plant defense signaling .
Syntaxin (Syntaxin)
Type: Family

Syntaxins are the prototype family of SNARE proteins. They usually consist of three main regions - a C-terminal transmembrane region, a central SNARE domain which is characteristic of and conserved in all syntaxins

, and an N-terminal domain which varies between syntaxin isoforms; in syntaxin 1A (

) it is found as three α-helices with a left-handed twist. It may fold back on the SNARE domain to allow the molecule to adopt a 'closed' configuration that prevents formation of the core fusion complex - it thus has an auto-inhibitory role.

The function of syntaxins is determined by their localisation. They are involved in neuronal exocytosis, ER-Golgi transport and Golgi-endosome transport, for example. They also interact with other proteins as well as those involved in SNARE complexes. These include vesicle coat proteins, Rab GTPases, and tethering factors .
mRNA 3'-end-processing protein Rna14-like (Rna14-like)
Type: Family

This entry includes Rna14 from yeasts, protein suppressor of forked (su(f)) from Drosophila melanogaster, CSTF3 from animals and CstF77 from Arabidopsis. In budding yeasts, Rna14 is part of the cleavage factor I A (CF IA) complex and is required for both the cleavage and polyadenylation activities of CF IA . Protein suppressor of forked may have similar function . CstF77 is involved in floral repressor gene (FLC) silencing .
Phosphoglucomutase (PGM)
Type: Family

This entry represents a group of phosphoglucomutases from bacteria and eukaryotes, including Pgm from bacteria, PGM1/5 from humans, Pgm1/2 from yeasts and chloroplastic/cytoplasmic PGM from plants.

Phosphoglucomutase, alpha-D-glucose phosphate-specific (

) links the anaerobic or aerobic glycolysis of glucose-6-phosphate and glucose-1-phosphate produced by various glycan phosphorylases by catalysing the transfer of a phosphate group between C-1 and C-6 of glucose .
Pre-mRNA 3' end processing protein Pfs2-like (Pfs2-like)
Type: Family

This entry includes a group of pre-mRNA 3' end processing proteins, including Pfs2 from yeasts, WDR33 form animals and FY from Arabidopsis.

In Saccharomyces cerevisiae, Polyadenylation factor subunit 2 (Pfs2) is an integral and essential component of the cleavage and polyadenylation factor (CPF) complex, which plays a key role in polyadenylation-dependent pre-mRNA 3'-end formation and cooperates with cleavage factors including the CFIA complex and NAB4/CFIB .
Argonaute-like, PIWI domain (Piwi_ago-like)
Type: Domain

Argonaute is the central component of the RNA-induced silencing complex (RISC) and related complexes. The PIWI domain is the C-terminal portion of Argonaute and consists of two subdomains, one of which provides the 5' anchoring of the guide RNA and the other, the catalytic site for slicing .
Oxidoreductase Oye-like (Oye-like)
Type: Family

This entry include a group of oxidoreductases, found in the Old yellow enzyme (OYE) family which includes 12-oxophytodienoate reductase, pentaerythritol tetranitrate reductase, morphinone reductase, and related enzymes. It includes Oye2/3 from budding yeasts. Oye2/3 are flavin-dependent NADPH oxidoreductases that have roles in oxidative stress and programmed cell death in yeast .
Putative nuclease HARBI1-like (HARBI1-like)
Type: Family

This entry represents a group of Harbinger transposase-derived proteins, including HARBI1 from animals and ALP1/ALP1L from Arabidopsis. Proteins in this family may have nuclease activity, but do not appear to have transposase activity . ALP1 is a domesticated Harbinger-related nuclease that interacts genetically with several PcG and trxG components and antagonizes PcG silencing .
Co-chaperone protein p23-like (p23-like)
Type: Family

This entry represent s a group of co-chaperone proteins, including p23 (also known as Sba1) from budding yeasts, Wos2 from fission yeasts, prostaglandin E synthase 3 from humans and Atp23-1/2 from Arabidopsis . p23 contains a folded domain and a long unstructured C-terminal tail. p23 and its homologues are co-chaperones of Hsp90 and may be part of the core chaperone cycle required for efficient client activation . It may also has Hsp90-independent functions such as the regulation of gene expression by modulating chromatin remodeling and ribosomal biogenesis .
Lysophosphatidylcholine acyltransferase LPCAT1-like (LPCAT1-like)
Type: Domain

Proteins containing this domain include lysophosphatidylcholine acyltransferase 1 (LPCAT1) and related proteins. LPCAT1 exhibits acyltransferase activity , and is involved in LD (lipid droplet)-associated lipid metabolism . Proteins containing this domain also includes glycerol-3-phosphate acyltransferases, such as GPAT3 and GPAT4, which are involved in de novo triacylglycerol synthesis .
Vacuolar protein sorting-associated protein 4, MIT domain (VPS4_MIT)
Type: Domain

This entry represents the MIT domain found in vacuolar protein sorting-associated protein 4. The molecular function of the MIT domain is unclear .

There are two mammalian VPS4 isoforms, VPS4A and VPS4B. They belong to the AAA ATPase family. VPS4A is a central regulator for early endosome trafficking . VSP4 interacts with the ESCRT complex, which directs multiple cellular membrane remodelling events, ranging from the biogenesis of multivesicular bodies and exosomes to the final membrane abscission stage of cytokinesis . The viral budding via host ESCRT complex can also be regulated by VPS4 .
Nit1/2, carbon-nitrogen hydrolase domain (Nit1/2_C-N_Hydrolase)
Type: Domain

Proteins containing this domain include mammalian Nit1 and Nit2, the Nit1-like domain of the invertebrate NitFhit, yeast Nit3 and various uncharacterised bacterial and archaeal Nit-like proteins. In general, they are amidases involved in various metabolic processes. Nit1 is a deaminated glutathione amidase , while Nit2 is an omega-amidase . They are candidate tumour suppressor proteins . In NitFhit, the Nit1-like domain is encoded as a fusion protein with the non-homologous tumour suppressor, fragile histidine triad (Fhit) . Mammalian Nit1 and Fhit may affect distinct signal pathways, and both may participate in DNA damage-induced apoptosis . Nit1 is a negative regulator in T cells . Overexpression of Nit2 in HeLa cells leads to a suppression of cell growth through cell cycle arrest in G2 .
Ran binding protein RanBP1-like (RanBP1-like)
Type: Family

This entry represents a group of RanGTP-binding proteins that contain a conserved RanGTP-binding motif, also called a Ran-binding domain (RBD). They have been implicated in nucleocytoplasmic transport. NUP358 (RanBP2) is localised to the cytoplasmic filaments protruding from the nuclear pore complex (NPC) into the cytoplasm, while RanBP3/Hba1 are localised to the nucleoplasm and Nup2 is localised to the NPC. In general, RanBP1 and other members of this protein family increase, via their conserved RBDs, the rate of RanGAP1-mediated GTP hydrolysis on Ran .
Ran-specific GTPase-activating protein 1, Ran-binding domain (RanBP1_RanBD)
Type: Domain

This entry represents the Ran-binding domain (RBD) found in RanBP1 from humans and Yrb1 from budding yeasts. RanBP1 and Yrb1 are involved in nuclear import and export. RanBP1 and Yrb1 have been shown to shuttle between the nucleus and cytoplasm and the conserved RBD is necessary and sufficient for the essential function and nucleocytoplasmic shuttling . RanBP1/Yrb1 acts as a negative regulator of Regulator of chromosome condensation 1 (RCC1) by inhibiting RCC1-stimulated guanine nucleotide release from Ran .
Dihydrolipoamide acetyltransferase/Pyruvate dehydrogenase protein X component (E2/Pdx1)
Type: Family

In prokaryotes and eukaryotes, pyruvate dehydrogenase complex (PDC) contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3) . PDC catalyses the overall conversion of pyruvate to acetyl-CoA and CO2. In eukaryotes, PDC is located in the mitochondrial matrix .

This entry represents a group of E3-binding proteins, including dihydrolipoamide acetyltransferase (E2) and pyruvate dehydrogenase protein X component (known as Pdx1). Pdx1, found only in eukaryotes, plays a structural role in the complex by binding and positioning dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide acetyltransferase (E2) core . Mutations in the Pdx1 gene has been linked to human disease . Mutations in the E2 gene cause pyruvate dehydrogenase deficiency .
ArfGAP ACAP1/2/3-like (ACAP1/2/3-like)
Type: Family

ADP-ribosylation factors (ARFs) function in diverse physiological and molecular activities . This entry represents a group of GTPase-activating proteins (GAPs) for the ADP ribosylation factors (ARFs). This entry includes ACAP1-3 from animals, Age1 from budding yeasts and AGD1-4 from plants. ACAP1 and ACAP2 are Arf6 GTPase-activating proteins that function coordinately in the cell periphery . AGD1 is necessary for straight root hair growth in Arabidopsis .
Guanine nucleotide-exchange factor Sec12-like (Sec12-like)
Type: Family

This entry represents a group of guanine nucleotide-exchange factors, including Sec12 and its paralogue, Sed4, from budding yeasts. Sec12 is an ER type II membrane protein and a guanine nucleotide-exchange factor for Sar1 (a small GTPase). It is required for the initiation of COPII vesicle formation in ER to Golgi transport . Sed4 has been shown to bind to cargo-free Sar1, stimulates Sar1 GTP hydrolysis and promotes limited coat disassembly .
MICRORCHIDIA ATPase family (MORC_ATPase)
Type: Family

This entry includes MICRORCHIDIA-like ATPases, such as MORC1-7 from Arabidopsis and MORC3/4 from animals. MORC1-7 are required for heterochromatin condensation and gene silencing . MORC3/4 are CW-type zinc finger nuclear proteins. MORC3 has been shown to exist in an autoinhibited state and is activated through binding to methylated histone mark H3K4me3 , while MORC4 has an intrinsic DNA-dependent but histone-independent ATPase activity . MORC3 has been linked to autoimmune disorders, Down syndrome, and cancer . MORC4 has been associated with acute and chronic pancreatitis, inflammatory disorders and cancer .
Sugar transport protein STP/Polyol transporter PLT, plant (STP/PLT_plant)
Type: Family

This entry includes sugar transport protein STP and polyol transporter PLT from plants.

Sugar transport proteins (STPs), also known as hexose transporters, including STP1-STP14 from Arabidopsis and Sugar transport proteins MST1-8 from Oryza sativa subsp. japonica . They mediate the active uptake of hexoses such as glucose, 3-O-methylglucose, fructose, xylose, mannose, galactose, fucose, 2-deoxyglucose and arabinose, by sugar/hydrogen symport. Several STP family transporters are expressed in a tissue-specific manner, or at specific developmental stages. STP1 is the member with the highest expression level of all members and high expression is detected in photosynthetic tissues, such as leaves and stems, while roots, siliques, and flowers show lower expression levels. It plays a major role in the uptake and response of Arabidopsis seeds and seedlings to sugars .

The plant Polyol transporter (PLT) subfamily includes PLT1-6 from Arabidopsis thaliana and similar transporters . The best characterised member of the group is Polyol transporter 5, also called Sugar-proton symporter PLT5, which mediates the H-symport of numerous substrates including linear polyols (such as sorbitol, xylitol, erythritol or glycerol), cyclic polyol myo-inositol, and different hexoses, pentoses (including ribose), tetroses, and sugar alcohols. It functions to transport a wide range of substrates into specific sink tissues in the plant . The PLT subfamily belongs to the Glucose transporter-like (GLUT-like) family of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement .
Glucose transporter GLUT (GLUT)
Type: Family

This entry includes Class I and II glucose transporters.

Facilitative sugar transport is mediated by members of the GLUT transporter family, which form an aqueous pore across the membrane through which sugars can move in a passive (i.e., energy-independent) manner. The GLUT family of glycosylated transmembrane proteins are predicted to span the membrane 12 times with both amino- and carboxyl-termini located in the cytosol. On the basis of sequence homology and structural similarity, three subclasses of sugar transporters have been defined: Class I (GLUTs 1-4) are glucose transporters; Class II (GLUTs 5, 7, 9 and 11) are fructose transporters; and Class III (GLUTs 6, 8, 10, 12 and HMIT1) are structurally atypical members of the GLUT family, which are poorly defined at present, indeed GLUT6 may only be a pseudo-gene .
SPXM, SPX domain (SPXM_SPX_plant)
Type: Domain

This domain has been named the SPX domain after (Syg1, Pho81 and XPR1). The SPX domain is found at the amino terminus of a variety of proteins. Proteins containing this domain, mostly found in plants, contains a C-terminal MFS domain (major facilitator superfamily), suggesting a function as a secondary transporter. The function of this N-terminal region is unclear, although it might be involved in regulating transport .
AIR12, DOMON domain (AIR12_DOMON)
Type: Domain

This entry represents the DOMON domain found in AIR12 and related proteins. Proteins containing this domain are plant proteins that may have a cytochrome b561 domain C-terminal to the DOMON domain. In Arabidopsis, AIR12 is a plasma membrane b-type cytochrome specific to flowering plants . AIR12 functions as either antioxidant in its oxidized state or a pro-oxidant in its reduced state depending on the redox status of the plasma membrane and the apoplast .

DOMON domains were initially thought to confer protein-protein interactions. They were subsequently found as a heme-binding motif in cellobiose dehydrogenase, an extracellular fungal oxidoreductase that degrades both lignin and cellulose, and in ethylbenzene dehydrogenase, an enzyme that aids in the anaerobic degradation of hydrocarbons. The domain interacts with sugars in the type 9 carbohydrate binding modules (CBM9), which are present in a variety of glycosyl hydrolases, and it can also be found at the N terminus of sensor histidine kinases .
Copper-dependent monooxygenases, DOMON domain (DOH_DOMON)
Type: Domain

This DOMON domain can be found in dopamine beta-hydroxylase (DBH), monooxygenase X (MOX), and various other proteins, some of which contain DOMON domains exclusively. DBH is a membrane-bound enzyme that converts dopamine to L-norepinephrine, and plays a central role in the metabolism of catecholamine neurotransmitters .

DOMON domains were initially thought to confer protein-protein interactions. They were subsequently found as a heme-binding motif in cellobiose dehydrogenase, an extracellular fungal oxidoreductase that degrades both lignin and cellulose, and in ethylbenzene dehydrogenase, an enzyme that aids in the anaerobic degradation of hydrocarbons. The domain interacts with sugars in the type 9 carbohydrate binding modules (CBM9), which are present in a variety of glycosyl hydrolases, and it can also be found at the N terminus of sensor histidine kinases .
Cyclin-dependent kinase 11/PITSLRE, catalytic domain (CDK11/PITSLRE_STKc)
Type: Domain

This entry represents the catalytic domain found in a group of cyclin-dependent kinases, including CDK11A/B from humans, CDKG1 from Arabidopsis, Ppk23 from fission yeasts and PITSLRE from Drosophila melanogaster. CDK11 has three isoforms that show peculiar expression patterns: the largest, mid-sized, and smallest isoforms of CDK11 are designated as CDK11/p110, CDK11/p58, and CDK11/p46, respectively. CDK11/p58, included in this entry, is translated from the same mRNA as CDK11/p110 and is expressed only during G2 and M phases. CDK11/p58 facilitates M phase progression by promoting centrosome maturation and bipolar spindle formation . CDKG1 regulates pre-mRNA splicing of CALLOSE SYNTHASE5 (CalS5) and, therefore, pollen wall formation . It is also part of the CDKG1/CYCLINL complex is essential for synapsis and recombination during male meiosis .
Serine/threonine-protein kinase Atg1-like (Atg1-like)
Type: Family

This entry represents a group of Serine/threonine-protein kinases, including Atg1 from yeasts, Unc-51 from C. elegans, Ulk1-3 from humans and ATG1a/b/c/t from Arabidopsis.

Atg1 is required for vesicle formation in autophagy and the cytoplasm-to-vacuole targeting (Cvt) pathway .

Ulk1-3 are involved in autophagy in response to starvation . Ulk1 and Ulk2 regulate filopodia extension and branching of sensory axons. They are important for axon growth, playing an essential role in neurite extension of cerebellar granule cells .

Unc-51 is important for axonal elongation and axonal guidance . It is required for either the maintenance of axons (membrane turnover) or for an unknown neuronal function. C elegans worms lacking Unc-51 exhibit various abnormalities in axonal elongation and axonal structures. Unc-51 could also help control cell size along with Bec-1, as mutations in their corresponding genes results in a reduction in small body size without affecting cell number . Unc-51 is also a component of the Unc-51/Atg-13 complex that is probably recruited by lgg-1 to preautophagosomes and is required for autophagosome formation .

In plants, the ATG1/13 complex is both a regulator and a target of autophagy .
Serine/Threonine Kinase AGC, catalytic domain (STKc_AGC)
Type: Domain

This entry represents the catalytic domain of AGC family of Serine/Threonine Kinases.

AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Proteins containing this domain include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others .

AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension .
Receptor-like protein kinase ANXUR1/2-like (ANXUR1/2-like)
Type: Family

This entry represents a group of receptor-like protein kinase mostly from plants, including ANXUR1/2 (ANX1/2), FERONIA (FERON), HERCULES1(HERK1) and THESEUS 1 (THE1) from Arabidopsis.

ANX1 and ANX2 are male factors that control pollen tube behaviour by directing rupture at proper timing .

FERONIA/SIRENE mediates the female control of male gamete delivery during fertilisation , FERON is a positive regulator of auxin-promoted growth that represses the abscisic acid (ABA) signalling via the activation of ABI2 phosphatase . It is required for RALF1-mediated extracellular alkalinisation in a signalling pathway preventing cell expansion .

FERON, HERK1 and THE1 are required for cell elongation during vegetative growth, mostly in a brassinosteroid-(BR-) independent manner .
Receptor-like kinase WAK-like (WAK-like)
Type: Family

This entry represents a group of plant receptor-like kinases, including Wall-associated receptor kinases (WAKs) and ZRKs. ZRKs may be pseudokinases . ZRK3 is required for RPP13L4/ZAR1 recognition of the Pseudomonas syringae type III effector (T3E) HopF2a . ZED1 works with RPP13L4/ZAR1 and is involved in the ambient temperature-sensitive aerial organ development and in the plant immune system . The WAKs are wall-associated kinases that bind to pectin and regulate cell expansion or stress responses . Some WAKs may mediate resistance to diseases caused by biotrophic/hemibiotrophic pathogens in several plant species .