SII-SWORD/CoKE huggingface dataset:
Microtubule-binding protein TANGLED1 (TAN1)
Type: Family

TANGLED1 (TAN1) is a microtubule-binding protein that localizes to the division site and mitotic microtubules and plays a critical role in division plane orientation in plants . It acts as a component of a cortical guidance cue that remains behind when the preprophase band (PPB) is disassembled and directs the expanding phragmoplast to the former PPB site during cytokinesis . It has been shown to mediate microtubule zippering or end-on microtubule interactions, depending on their contact angle .
PLASTID TRANSCRIPTIONALLY ACTIVE protein 6 (PTAC6)
Type: Family

PLASTID TRANSCRIPTIONALLY ACTIVE protein 6 (PTAC6) plays an important part in plastid gene expression . It is an essential subunit of the PEP (plastid-encoded RNA polymerase) complex. MTERF5 interacts with PTAC6, and thereby recruits the PEP complex to the transcriptionally paused region of psbEFLJ (a gene that encodes four key subunits of photosystem II) . PTAC6 also promotes leaf greening .
Egg cell-secreted protein 1.1-1.5 (EC11-15)
Type: Family

Plant small cysteine-rich EC1 (EGG CELL 1) proteins accumulate in storage vesicles of the egg cell. They are involved in the regulation of gamete interactions during the double fertilization and to prevent multiple-pollen tube attraction. They mediate the redistribution of the gamete fusogen HAP2/GCS1 to the cell surface after secretion upon sperm arrival . This family includes Egg cell-secreted protein 1.1/1.2/1.3/1.4/1.5 from Arabidopsis.
NAD/FAD transporter SLC25A32-like (SLC25A32-like)
Type: Family

This entry represents a group of substrate carrier proteins that are related to the nicotinamide adenine dinucleotide transporter found in mitochondria, including human NAD/FAD transporter SLC25A32, yeast Yea6/Flx1/Yia6, and AtNDT1/AtNDT2/PXN/AtFOLT1 from Arabidopsis. Structurally, they consist of three tandem repeats of a domain of approximately one hundred residues. Each of these domains contains two transmembrane regions.

In budding yeasts, Yea6 and Yia6 are mitochondrial inner membrane carrier protein that mediates the import of NAD+ into mitochondria . Flx1 transports FAD from the cytosol to the mitochondrial matrix .

In humans, SLC25A32 transports folate and FAD across the inner membranes of mitochondria . Mutations in the SLC25A32 gene cause neural tube defects (NTD) . SLC25A32 has also been implicated in multiple acyl-CoA dehydrogenase deficiency (MADD) or glutaric aciduria type II (GAII) .
DnaJ homolog subfamily A member 1/2-like (DNJA1/2-like)
Type: Family

The DnaJ proteins, also known as heat shock protein 40 (Hsp40 or Hsc40), are proteins originally identified in Escherichia coli that act as cochaperones to the molecular chaperone DnaK (Hsp70), which is responsible for several cellular processes such as rescuing misfolded proteins, folding polypeptide chains, transport of polypeptides through membranes, assembly and disassembly of protein complexes, and control of regulatory proteins .

Structurally, the DnaJ protein consists of an N-terminal conserved domain (called 'J' domain) of about 70 amino acids, a glycine-rich region ('G' domain') of about 30 residues, a central domain containing four repeats of a CXXCXGXG motif ('CRR' domain) and a C-terminal region of 120 to 170 residues.

This entry represents a group of DnaJ domain containing proteins, including DNJA1/2/4 from humans, Scj1/Mas5/Xdj1/Apj1 from budding yeasts, and DNAJ2/3/19 from Arabidopsis. .

In humans, DNAJA1, DNAJA2 and HSC70 have been shown to play key roles in both the folding and degradation of wild-type and mutant CFTR (cystic fibrosis transmembrane conductance regulator) . They also function as co-chaperone for HSPA1B and negatively regulates the translocation of BAX from the cytosol to mitochondria in response to cellular stress, thereby protecting cells against apoptosis .
BTB/POZ domain-containing protein AtSIBP1-like (AtSIBP1-like)
Type: Family

This entry includes a group of BTB/POZ domain-containing protein, including At1g55760 (AtSIBP1) and At1g21780 from Arabidopsis. AtSIBP1 is induced by salt and other stresses and can positively regulate salt signalling . The function of At1g21780 is not clear. Its BTB domain has been shown to interact with itself and with AtCUL3A. It might form an E3 ubiquitin ligase complex with RBX1 and AtCUL3A .
WD repeat-containing protein 86-like (WDR86-like)
Type: Family

This entry represents a group of WD repeat-containing protein, including WDR86 from humans, C3H17 from Oryza sativa and C3H48/59/62/63 from Arabidopsis. C3H48/62/63 contain an extra zinc finger CCCH domain N-terminal to their WD repeat.
Transcriptional corepressor LEUNIG-like (LEUNIG-like)
Type: Family

This entry includes the transcriptional corepressor LEUNIG homologue (LUH) from Arabidopsis. LEUNIG (LUG) and LUH are similar to the animal and fungal Gro/Tup1-type corepressors . LUH has been shown to activate MYC2-directed transcription of JAZ2 and LOX2 via the Mediator complex coactivator and the histone acetyltransferase HAC1 . LUH contains the N-terminal LUFS domain, which is essential for the direct interaction with its cofactor SEUSS . LUH and LUG exhibit both redundant and divergent functions in embryonic development, floral homeotic gene regulation, and plant biotic and abiotic stress responses .

This entry also includes uncharacterised sequences from fungi.
Nicotinamidase 1 (NIC1)
Type: Family

This entry represents a group of amidohydrolases from plants and bacteria, including AtNIC1 from Arabidopsis. AtNIC1 catalyses the deamidation of nicotinamide, an early step in the NAD+ salvage pathway. It prevents the accumulation of intracellular nicotinamide, a known inhibitor of poly(ADP-ribose) polymerases (PARP enzymes) .
E3 ubiquitin-protein ligase HOS1 (HOS1)
Type: Family

HOS1 is an E3 ubiquitin-protein ligase that acts as a common regulator in the signalling pathways that control flowering time . It mediates ubiquitination and subsequent proteasomal degradation of the transcription factor ICE1 under cold treatment . In Arabidopsis, CONSTANS (CO) activates transcription of the floral integrators, FLOWERING LOCUS T (FT) and TWIN SISTER OF FT (TSF) genes, which in turn govern the flowering time . Together with Nup96, HOS1 regulates CO protein turnover and thereby prevents precocious flowering in long-day conditions .
Protein TIC 62-like (TIC62)
Type: Family

This entry includes a group of NAD(P)-binding domain-containing proteins from plants and Cyanobacteria, including TIC62 from Arabidopsis. TIC62 is part of the Tic complex (a redox regulon) involved in translocation of nuclear-encoded preproteins across the inner envelope of chloroplasts . TIC62 binds to ferredoxin-NADP(H) oxidoreductase (FNR) and acts as a redox sensor of the complex .
Zinc finger protein HVO_2753-like (HVO_2753-like)
Type: Family

This family represents a group of archaeal proteins, including Zinc finger protein HVO_2753 (also known as Small CPxCG-related zinc finger protein) from Haloferax volcanii . NMR 3D structure analysis revealed the content of four C(P)XCG motifs, suggesting the presence of two zinc-binding pockets. However, only C(P)XCG motifs 2 and 4 (comprising Cys-32 to Cys-35 and Cys-50 to Cys-53) form a zinc binding pocket and binds one zinc atom, while C(P)XCG motifs 1 and 3 (comprising Cys-12 to Cys-15 and Cys-39 to Cys-42) form a four-Cys cluster that do not bind zinc. The four C(P)XCG motifs are critical for protein stability, folding and functionality .
Glutamate gated chloride channel, transmembrane domain (GluCl_TM)
Type: Domain

This entry represents the transmembrane (TM) domain of the glutamate-gated chloride channel (GluCl) found only in protostomia but are closely related to mammalian glycine receptors. The transmembrane region consists of four transmembrane-spanning α-helical segments (M1-M4) that are linked by loops. The intracellular loop that links M1 and M2 determines the ion selectivity of the channel. These GluCl channels have several roles in these invertebrates, including controlling locomotion and feeding, and mediating sensory inputs into behaviour .

Comparison of the GluCl gene families between organisms shows that insect gene family is relatively simple, while that found in nematodes tends to be larger and more diverse. Glutamate is an inhibitory neurotransmitter that shapes the responses of projection neurons to olfactory stimuli in the Drosophila . GluCls are targeted by the macrocyclic lactone family of anthelmintics and pesticides in arthropods and nematodes, thus making the GluCls of considerable medical and economic importance. In Drosophila melanogaster, GluCl mediates sensitivity to the antiparasitic agents ivermectin and nodulisporic acid, suggesting that their drug target is the same throughout the Ecdysozoa .
SecA, C-terminal helicase domain (SecA_SF2_C)
Type: Domain

SecA is a DEAD-like helicase belonging to superfamily SF2, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. SecA helicase core consists of two similar protein domains that resemble the fold of the recombination protein RecA. This entry represents the C-terminal domain, also called HelicC .

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component . From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.

The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral membrane complex (SecCY, SecE and SecG), and two additional membrane proteins that promote the release of the mature peptide into the periplasm (SecD and SecF) . The chaperone protein SecB is a highly acidic homotetrameric protein that exists as a "dimer of dimers" in the bacterial cytoplasm. SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane protein ATPase SecA for secretion .

SecA is a cytoplasmic protein of 800 to 960 amino acid residues. Homologues of secA are also encoded in the chloroplast genome of some algae as well as in the nuclear genome of plants . It could be involved in the intraorganellar protein transport into thylakoids.
UBL4A-like, ubiquitin-like domain (Ubl_UBL4A-like)
Type: Domain

UBL4A (also known as GdX) is a ubiquitously expressed ubiquitin-like (Ubl) protein that forms a complex with partner proteins and participates in the protein processing through endoplasmic reticulum (ER), acting as a chaperone. As a key component of the BCL2-associated athanogene 6 (BAG6) chaperone complex, UBL4A plays a role in mediating DNA damage signaling and cell death . UBL4A also regulates insulin-induced Akt plasma membrane translocation through promotion of Arp2/3-dependent actin branching . Moreover, UBL4A specifically stabilises the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis .

This is the ubiquitin-like domain of UBL4A and related proteins.
CBS domain-containing protein CBSX3, CBS domain (CBSX3_CBS_dom)
Type: Domain

CBS domains are evolutionarily conserved structural domains found in a variety of non functionally-related proteins from all kingdoms of life. These domains pair together to form a intramolecular dimeric structure (CBS pair), termed Bateman domain . CBS domains have been shown to bind mainly ligands with an adenosyl group such as AMP, ATP and S-AdoMet, but may also bind metal ions, or nucleic acids . Hence, they play an essential role in the regulation of the activities of numerous proteins, and mutations in them are associated with several hereditary diseases . CBS domains are found attached to a wide range of other protein domains suggesting that CBS domains may play a regulatory role making proteins sensitive to adenosyl-carrying ligands. The region containing the CBS domains in cystathionine-beta synthase is involved in regulation by S-AdoMet . CBS domain pairs from AMPK bind AMP or ATP . The CBS domains from IMPDH, which bind ATP, have shown to have a role in the regulation of adenylate nucleotide synthesis .

This entry represents the CBS domain found in bacteria and plants proteins, including mitochondrial CBSX3 from Arabidopsis. CBSX3 interacts with and activates o-type thioredoxin (Trx-o2) Trx-o2, increasing its activity, which is known to play regulatory roles in the electron transport chain (ETC) complex II. This interaction regulates ROS generation in mitochondria and plays a key role in the modulation of plant development and growth .
ABC transporter C family, six-transmembrane helical domain 2 (ABCC_6TM_D2)
Type: Domain

This entry represents the six-transmembrane domain 2 (TMD2) of the ABC transporters that belong to the ABCC subfamily . This TM subunit exhibits the type 3 ATP-binding cassette (ABC) exporter fold, which is characterised by 6 TM helices per subunit (domain), or a total of 12 TM helices for the complete transporter. The type 3 ABC exporters are found in both prokaryotes and eukaryotes, where they mediate the cellular secretion of toxic compounds, a various type of lipids and polypeptides .

ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily, which uses the hydrolysis of ATP to energise diverse biological systems. ABC transporters minimally consist of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These can be found on the same protein or on two different ones. Most ABC transporters function as a dimer and therefore are constituted of four domains, two ABC modules and two TMDs.

ABC transporters are involved in the export or import of a wide variety of substrates ranging from small ions to macromolecules. The major function of ABC import systems is to provide essential nutrients to bacteria. They are found only in prokaryotes and their four constitutive domains are usually encoded by independent polypeptides (two ABC proteins and two TMD proteins). Prokaryotic importers require additional extracytoplasmic binding proteins (one or more per systems) for function. In contrast, export systems are involved in the extrusion of noxious substances, the export of extracellular toxins and the targeting of membrane components. They are found in all living organisms and in general the TMD is fused to the ABC module in a variety of combinations. Some eukaryotic exporters encode the four domains on the same polypeptide chain .

The ATP-Binding Cassette (ABC) superfamily forms one of the largest of all protein families with a diversity of physiological functions . Several studies have shown that there is a correlation between the functional characterisation and the phylogenetic classification of the ABC cassette . More than 50 subfamilies have been described based on a phylogenetic and functional classification ; (for further information see
Transporter Classification Database
).
Kelch-like protein 42, BTB and C-terminal Kelch domain (KLHL42_BACK)
Type: Domain

This entry represents the BTB and C-terminal Kelch domain found in KLHL42, which is a substrate-specific adaptor of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis. The BCR(KLHL42) E3 ubiquitin ligase complex mediates the ubiquitination and subsequent degradation of KATNA1. KLHL42 is involved in microtubule dynamics throughout mitosis .
ATP-dependent RNA helicase eIF4A, DEAD-box helicase domain (EIF4A_DEADc)
Type: Domain

This entry represents the DEAD-box helicase domain found in eIF4A and related proteins. They are DEAD-box helicases, a diverse family of proteins involved in ATP-dependent RNA unwinding, needed in a variety of cellular processes including splicing, ribosome biogenesis and RNA degradation . Eukaryotic initiation factor 4A-I (DDX2A) is involved in cap recognition and is required for mRNA binding to ribosome . This domain contains the ATP-binding region .
CBS domain-containing protein, bacteria (CBS_bac)
Type: Domain

This entry represents a group of uncharacterised bacterial proteins containing a pair of CBS domains.

CBS domains are evolutionarily conserved structural domains found in a variety of non functionally-related proteins from all kingdoms of life. These domains pair together to form a intramolecular dimeric structure (CBS pair), termed Bateman domain . CBS domains have been shown to bind mainly ligands with an adenosyl group such as AMP, ATP and S-AdoMet, but may also bind metal ions, or nucleic acids . Hence, they play an essential role in the regulation of the activities of numerous proteins, and mutations in them are associated with several hereditary diseases . CBS domains are found attached to a wide range of other protein domains suggesting that CBS domains may play a regulatory role making proteins sensitive to adenosyl-carrying ligands. The region containing the CBS domains in cystathionine-beta synthase is involved in regulation by S-AdoMet . CBS domain pairs from AMPK bind AMP or ATP . The CBS domains from IMPDH, which bind ATP, have shown to have a role in the regulation of adenylate nucleotide synthesis .
Ribonuclease H-like domain, plant type (RNase_H-like_dom_plant)
Type: Domain

Ribonuclease H (RNase H) (

) is a member of the ribonuclease family, which recognises and cleaves the RNA strand of RNA-DNA heteroduplexes. The enzyme is widely present in all three kingdoms of living organisms, including bacteria, archaea, and eukaryotes, and their counterpart domains are also found in reverse transcriptases (RTs) from retroviruses and retroelements . RNases H are classified into two evolutionarily unrelated families, type-I and type-II RNase H, with common structural features of the catalytic domain but different range of substrates for enzymatic cleavage. There appears to be three evolutionarily distinct lineages of cellular Rnase H enzymes . Type-I or RNase HI domains have been found in all Eukarya, one Archaea, many Eubacteria, a few non-LTR retroposons and all LTR retrotransposons. Type II enzymes consist of RNase HII (rnhB) and HIII (rnhC), which are homologous enzymes. RNase HII can be found in Archaea, Eubacteria and all Eukarya, while RNase HIII appears only in some Eubacteria. In eukaryotes and all Archaea, RNase HII enzymes may constitute the bulk of all Rnase H activity, while the reverse is true in Eubacteria like E. coli where RNase HI is the major source of RNH activity . All LTR retrotransposons acquired an enzymatically weak RNase H domain that is missing an important catalytic residue found in all other RNase H enzymes. Vertebrate retroviruses appear to have reacquired their RNase H domains, which are catalytically more active, but their ancestral RNase H domains (found in other LTR retrotransposons) have degenerated to give rise to the tether domain unique to vertebrate retrovirus . Reverse transcriptase (RT) is a modular enzyme carrying polymerase and ribonuclease H (RNase H) activities in separable domains. Retroviral RNase H is synthesised as part of the POL polyprotein that contains an aspartyl protease, a reverse transcriptase, RNase H and integrase. POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins.

This domain is found predominantly in plants, including the putative ribonuclease H protein At1g65750 from Arabidopsis.
Butanol dehydrogenase-like (BDH-like)
Type: Family

Butanol dehydrogenase (BDH) is involved in the final step of the butanol formation pathway, in which it catalyses the conversion of butyraldehyde to butanol with the cofactor NAD(P)H being oxidised in the process. The NADH-BDH has higher activity with longer chained aldehydes and is inhibited by metabolites containing an adenine moiety. This protein family belongs to the so-called iron-containing alcohol dehydrogenase superfamily. Members in this family use divalent ions, preferentially iron or zinc . This family also includes E. coli YqhD enzyme, an NADP-dependent dehydrogenase whose activity measurements with several alcohols demonstrate preference for alcohols longer than C3 . The active site of YqhD contains a zinc atom, and a modified NADPH cofactor bearing OH groups on the saturated C5 and C6 atoms, possibly due to oxygen stress on the enzyme, which would functionally work under anaerobic conditions.

This entry also includes Long-chain-alcohol dehydrogenase 2 from Geobacillus thermodenitrificans which is able to oxidise a broad range of alkyl alcohols from methanol to 1-triacontanol (C1 to C30), whose best substrate is 1-octanol. In contrast to other members of the family, it apparently does not use iron or other metals as cofactor . Aldehyde-alcohol dehydrogenase has both aldehyde and alcohol dehydrogenase activities. It can use acetaldehyde, butyraldehyde, butanol and ethanol.
SMAP1-like, ArfGAP domain (ArfGAP_SMAP1-like)
Type: Domain

This entry represents the ArfGAP domain found in stromal membrane-associated protein 1 (SMAP1) and related proteins. SMAP1 binds to clathrin heavy chain molecules and is involved in the trafficking of clathrin-coated vesicles and preferentially exhibits GAP toward Arf6. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin . This entry also includes the uncharacterised protein C824.09c from Schizosaccharomyces pombe, a predicted GTPase activating protein.

Proteins containing this domain include ARF1-directed GTPase-activating protein, the cycle control GTPase activating protein (GAP) GCS1 which is important for the regulation of the ADP ribosylation factor ARF, a member of the Ras superfamily of GTP-binding proteins . The GTP-bound form of ARF is essential for the maintenance of normal Golgi morphology, it participates in recruitment of coat proteins which are required for budding and fission of membranes. Before the fusion with an acceptor compartment the membrane must be uncoated. This step required the hydrolysis of GTP associated to ARF. These proteins contain a characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) which displays some similarity to the C4-type GATA zinc finger. The ARFGAP domain display no obvious similarity to other GAP proteins.

The 3D structure of the ARFGAP domain of the PYK2-associated protein beta has been solved . It consists of a three-stranded β-sheet surrounded by 5 α helices. The domain is organised around a central zinc atom which is coordinated by 4 cysteines. The ARFGAP domain is clearly unrelated to the other GAP proteins structures which are exclusively helical. Classical GAP proteins accelerate GTPase activity by supplying an arginine finger to the active site. The crystal structure of ARFGAP bound to ARF revealed that the ARFGAP domain does not supply an arginine to the active site which suggests a more indirect role of the ARFGAP domain in the GTPase hydrolysis .
AP-1 complex subunit sigma (AP1_sigma)
Type: Family

The heterotetrameric adaptor protein (AP)-1 complex consists of one large gamma-, one beta-, one mu-, and one sigma-subunit. AP complexes link the cytosolic domains of the cargo proteins to the protein coat that induces vesicle budding in the donor compartment during vesicle transport . In the case of AP-1 the coat protein is clathrin. AP-1 binds the phospholipid PI(4)P which plays a role in its localisation to the trans-Golgi network (TGN)/endosome . This entry represents the sigma subunit, which comprises a single longin domain and plays a role in binding dileucine-based sorting signals.