SII-SWORD/CoKE huggingface dataset:
Rhino, chromodomain (CD_Rhino)
Type: Domain

This is the chromo domain found at the N-terminal of Drosophila melanogaster Rhino (also known as heterochromatin protein 1-like,

), and similar proteins from Drosophila sp.

Rhino is a female-specific protein that affects chromosome structure and egg polarity that is required for germline PIWI-interacting RNA (piRNA) production . In Drosophila the RDC (rhino, deadlock, and cutoff) complex , composed of rhino, the protein deadlock (Del) and the Rai1-like transcription termination cofactor cutoff (Cuff) binds to chromatin of dual-strand piRNA clusters, special genomic regions, which encode piRNA precursors . The RDC complex is anchored to H3K9me3-marked chromatin in part via the H3K9me3-binding activity of Rhino, and is required for transcription of piRNA precursors .

Chromodomain is a conserved region of about 50 amino acids, found in a variety of chromosomal proteins, and which appears to play a role in the functional organisation of the eukaryotic nucleus. This domain is implicated in the binding, of the proteins in which it is found, to methylated histone tails and maybe RNA. The chromodomain may occur as a single instance, in a tandem arrangement, or followed by a related chromo shadow domain.
Rrp6-like, 3'-5' exonuclease domain (Rrp6p-like_exo)
Type: Domain

This entry represents the DEDDy-type DnaQ-like 3'-5' exonuclease domain possessing three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific YX(3)D pattern at ExoIII . The motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. PM/Scl-100, an autoantigen present in the nucleolar compartment of the cell, reacts with autoantibodies produced by about 50% of patients with polymyositis-scleroderma overlap syndrome .

Rrp6 is a nuclear-specific catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events . In animals is also known as exosome complex component 10 (EXOSC10). In contrast to yeast and humans where Rrp6 is encoded by a single gene, plants such as Arabidopsis thaliana, rice, and polar, have three homologues of Rrp6 .
SAM-dependent methyltransferase RsmB-F/NOP2-type, catalytic core (MeTrfase_RsmB-F_NOP2_cat)
Type: Domain

The catalytic domain of ribosomal RNA cysteine methyltransferases is highly conserved in archaeal, bacterial and eukaryotic proteins . It is located at the C-terminal end in ribosomal RNA methyltransferase B (RsmB, Sun, Fmu) and Nop2 and towards the N-terminal in RsmF. Escherichia coli RsmB methylates cytosine C967 in 16S rRNA . RsmF is a multi-site-specific methyltransferase . Nop2 methylates cytosine C2870 in the 25S rRNA of S. cerevisiae and is critical for 60S biogenesis .
NOL1/NOP2/NSUN 5/7, ferredoxin-like domain (NSUN5_7_fdxn-like)
Type: Domain

This entry represents the ferredoxin-like domain of NOL1/NOP2/Sun domain family members 5 and 7 from eukaryotes. NSUN5 is a SAM-dependent methyltransferase that specifically methylates the C(5) position of cytosine 3782 in 28S rRNA , which promotes protein translation without affecting ribosome biogenesis and fidelity . It is associated with the Williams-Beuren syndrome (WBS) . Its inactivation is a hallmark of glioma . NSUN7 may have S-adenosyl-L-methionine-dependent methyl-transferase activity. It undergoes cancer-specific epigenetic transcriptional silencing in liver tumours . This domain is found N-terminal of the methyltransferase domain (

) .
Solute carrier family 25 member 33/36-like (SLC25A33/36-like)
Type: Family

This family includes a group of mitochondrial carrier proteins from the solute carrier family 25, including the mammalian members SLC25A33/36, its homologues from yeast and Drosphila Rim2 protein . SLC25A33/36 import/export pyrimidine nucleotides into and from mitochondria. They selectively transport uridine, thymidine, guanosine, cytosine and inosine (deoxy)nucleoside di- and triphosphates by an antiport mechanism . They may also participate in mitochondrial genome maintenance, regulation of mitochondrial membrane potential and mitochondrial respiration .
Tricarboxylate transport protein-like (TXTP-like)
Type: Family

This family includes tricarboxylate transport proteins (TXTPs), which belong to the Solute carrier family 25 (SLC25), transport proteins at the inner mitochondrial membrane and functions as carriers for metabolites. Included in this entry is the human TXTP (SLC25A1) and its homologues; it is an electroneutral antiporter that exports citrate from the mitochondria into the cytosol in exchange for malate . It is also able to mediate the exchange of citrate for isocitrate, phosphoenolpyruvate, cis-aconitate and to a lesser extend cis-aconitate, maleate and succinate .

This entry also includes dicarboxylate transport proteins from plants and fungi, such as Succinate/fumarate mitochondrial transporter SFC1, which transports citrate, isocitrate and aconitate, succinate and fumarate. It catalyses a fast counter-exchange transport as well as a low uniport of substrates, having a higher transport affinity for tricarboxylates than dicarboxylates .
DsbA-like, N-terminal domain (DsbA-like_N)
Type: Domain

This domain is found at the N-terminal end of Putative secreted protein from Corynebacterium diphtheriae (DsbA,

). It is usually found associated with

. Its specific function is unknown. It adopts an α/β structure with a central antiparallel β-sheet and α-helices packed on it (

).
Bd2520-like, N-terminal (Bd2520-like_N)
Type: Domain

This domain is found at the N-terminal end of Putative lactoylglutathione lyase from Bdellovibrio bacteriovorus (Bd2520,

) and similar sequences predominantly found in prokaryotes. It adopts an antiparallel β-sheet and α-helix packed on it (

).
WDR59/RTC1-like, RING zinc finger domain (WDR59_RTC1-like_RING_Znf)
Type: Domain

This entry represents a RIGN zinc finger domain commonly found in the C-terminal region of various animal and fungal proteins, including WDR59 [

], a component of the GATOR complex in vertebrates and the fungal protein RTC1 [

], which is a component of the SEA complex .
GATOR complex protein WDR59-like (WDR59-like)
Type: Family

The WDR59 family is a group of proteins involved in cellular nutrient sensing and regulation. They play a crucial role in the GATOR (GAP Activity Towards Rags) complex, specifically in the GATOR2 subcomplex, which helps modulate the mTORC1 signalling pathway, thereby influencing cell growth and metabolism .

In fungi, the homologue of WDR59 is called MTC5 (Maintenance of telomere capping protein 5) and has been identified as a component of the SEA complex. This complex associates with the vacuolar membrane and plays a role in intracellular trafficking, autophagy, response to nitrogen starvation, and amino acid biogenesis .

This entry also includes similar uncharacterised eukaryotic proteins such as DDB_G0292056 from Dictyostelium discoideum.
Mst2, SARAH domain (Mst2_SARAH)
Type: Domain

This entry represents the C-terminal SARAH (Salvador-RassF-Hippo) domain found in human Mst2 and similar sequences from vertebrates. Mst2, also called serine/threonine-protein kinase 3 (STK3) or STE20-like kinase Mst2, is a STE20 family stress-activated, pro-apoptotic serine/threonine-protein kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation . It is a key component of the Hippo signalling pathway which plays a pivotal role in organ size control and tumour suppression by restricting proliferation and promoting apoptosis . This C-terminal SARAH domain is known to mediate the homodimerisation of MST2. Like MST1, MST2 can also form heterodimers with other proteins containing SARAH domains .
Helicase with zinc finger, DEAD-box 1 (HELZ_DEAD-box_1)
Type: Domain

This entry represents first DEAD-like helicase domain present in the Helicase with zinc finger (HELZ) family. HELZ acts as a helicase that plays a role in RNA metabolism during development . Their helicase core consists of two similar DEAD-like domains that resemble the fold of the recombination protein RecA .
HELZ is a member of the family I class of RNA helicases of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding .
YedF (YedF)
Type: Family

This entry represents the putative sulfur carrier protein YedF from Escherichia coli and similar sequences from proteobacteria. YedF is a bacterial SirA-like protein probably related with pathogenesis . SirA (also known as UvrY, and YhhP) belongs to a family of a two-component response regulators that controls secondary metabolism and virulence. The other member of this two-component system is a sensor kinase called BarA which phosphorylates SirA. A variety of microorganisms have similar proteins, all of which contain a common CPxP sequence motif in the N-terminal region. YhhP is suggested to be important for normal cell division and growth in rich nutrient medium .
Serine/threonine kinase NIM1, catalytic domain (NIM1K_STKc)
Type: Domain

This entry represents the serine/threonine kinase (STK) domain present in the NIM1K family. STKs catalyse the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1K (

) is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1K kinase activity is only observed in the brain and testis. NIM1K is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1K has yet to be elucidated .
YciK (YciK)
Type: Family

This entry represents the oxidoreductase YciK from Escherichia coli (

) and similar proteins mainly found in enterobacterales that are members of the short-chain dehydrogenases/reductases family (SDR). SDRs are a functionally diverse family of oxidoreductases that have a structurally conserved Rossmann fold. Substrates for these enzymes include sugars, steroids, alcohols, and aromatic compounds. The standard reaction mechanism is a proton relay involving a conserved Tyr and Lys, as well as Asn (or Ser) .
Protein tyrosine phosphatase domain-containing protein 1, PTP domain (PTPDC1_PTP)
Type: Domain

This entry represents the protein tyrosine phosphatase (PTP) domain present in protein tyrosine phosphatase domain-containing protein 1 (PTPDC1). PTPDC1 is an uncharacterised non-receptor class protein-tyrosine phosphatase (PTP) that may play roles in cilia formation and/or maintenance . PTPs catalyse the dephosphorylation of phosphotyrosine peptides .
Spheroidene monooxygenase CrtA-like (CrtA-like)
Type: Family

This entry includes spheroidene monooxygenase CrtA from Rhodobacter sphaeroides (

) and similar sequences. CrtA catalyses the asymmetrical introduction of one keto group at the C-2 position of spheroidene and two keto groups at the C-2 and C-2' positions of spirilloxanthin in carotenoid pathways. Spectroscopic analysis suggests CrtA may have a 5-coordinated heme at its active site and that it may be a novel oxygenase and not a P450 enzyme .
Anti-sigma factor RsiG/AmfC-like (RsiG-like)
Type: Family

This entry represents the anti-sigma factor RsiG from actinomycetes. RsiG binds and sequesters the sporulation-specific sigma factor WhiG in a fashion dependent on 3',5'-cyclic diguanylic acid (c-di-GMP). RsiG can bind the cyclic dinucleotide in the absence of sigma factor WhiG, and does so in a specific manner via a unique signature conserved in all Streptomyces. This gene was originally named amfC (aerial mycelium formation protein) but no specific role was established, and was later renamed rsiG (regulator of sigma WhiG) .
Histidine decarboxylase HDC-like (HDC-like)
Type: Family

This entry includes a group of uncharacterised histidine decarboxylases (HDC) from bacteria, including Lactobacillus parabuchneri, one of the major causes of elevated histamine levels in cheese. Histamine positive strain FAM21731 from L. parabuchneri has been shown to contain a histidine decarboxylase gene cluster present on a genomic island, which seems to have undergone transfer within the same species as well as between other lactobacilli .
GDP-mannose pyrophosphorylase, N-terminal domain (GMPP_N)
Type: Domain

This entry represents the N-terminal domain of GDP-mannose-1-phosphate guanylyltransferase, also known as GDP-mannose pyrophosphorylase (GDP-MP). GDP-MP catalyses the formation of GDP-mannose from mannose-1-phosphate and GTP. Mannose is a key monosaccharide for glycosylation of proteins and lipids. GDP-mannose is the activated donor for mannosylation of various biomolecules. This enzyme is known to be bifunctional, as both mannose-6-phosphate isomerase and mannose-1-phosphate guanylyltransferase. The isomerase function of these members is located at the C-terminal half (

) .
CAXIP1-like, GIY-YIG domain (CAXIP1-like_GIY-YIG_dom)
Type: Domain

The entry represents the GIY-YIG domain found in CAX-interacting protein-1 (CXIP1)-like proteins and iron-sulfur cluster assembly proteins found in a group of cyanobacteria and some plant sequences.

Members of this entry are similar to CAXIP1 from Arabidopsis, a novel PICOT (protein kinase C-interacting cousin of thioredoxin) domain-containing protein, that activates H+/Ca2 exchanger CAX1, and its homologue CAX4, but not CAX2 or CAX3. Iron-sulfur cluster assembly proteins in this family also contain a C-terminal NifU-like domain that corresponds to a common region between the NifU protein from nitrogen-fixing bacteria and rhodobacterial species. The biochemical function of NifU is unknown.
G protein-coupled receptors 26/78-like (GPR26/78-like)
Type: Family

This entry represents human G-protein coupled receptors 26 and 78 (GPR26778) and similar proteins from vertebrates. These proteins are constitutively active and coupled to increased cAMP formation. They are closely related based on sequence homology and comprise a conserved subgroup within the class A G-protein coupled receptor (GPCR) superfamily. Both receptors are widely expressed in selected tissues of the brain but their endogenous ligands are unknown . GPR26 knockout mice showed increased levels of anxiety- and depression-like behaviours, whereas GPR78 has been implicated in susceptibility to bipolar affective disorder and schizophrenia .

All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) α-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signalling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes .
Slit-Robo GTPase Activating Protein 3, F-BAR domain (SrGAP3_F-BAR)
Type: Domain

This entry represents a F-BAR domain present in SLIT-ROBO Rho GTPase-activating protein 3 (SrGAP3). Slit-Robo GTPase Activating Proteins (SrGAPs) are Rho GAPs that interact with Robo1, the transmembrane receptor of Slit proteins. Slit proteins are secreted proteins that control axon guidance and the migration of neurons and leukocytes. Vertebrates contain three isoforms of SrGAPs. SrGAP3, also called MEGAP (MEntal disorder associated GTPase-Activating Protein), is a Rho GAP with activity towards Rac1 and Cdc42 . The association between SrGAP3 haploinsufficiency and mental retardation is under debate . SrGAP3 contains an N-terminal F-BAR domain, a Rho GAP domain, and a C-terminal SH3 domain. F-BAR domains form banana-shaped dimers with a positively-charged concave surface that binds to negatively-charged lipid membranes . They are dimerisation modules that bind and bend membranes and are found in proteins involved in membrane dynamics and actin reorganisation .
Tripartite motif-containing protein 9, B-box-type 1 zinc finger (TRIM9_Bbox1)
Type: Domain

This entry represents a Bbox1 zinc finger domain found in TRIM9 proteins in vertebrates. TRIM9 (the human orthologue of rat Spring), also termed RING finger protein 91 (RNF91), is a brain-specific E3 ubiquitin-protein ligase collaborating with an E2 ubiquitin conjugating enzyme UBCH5b . TRIM9 plays an important role in the regulation of neuronal functions and participates in neurodegenerative disorders through its ligase activity. It interacts with the WD repeat region of beta-transducer repeat-containing protein (beta-TCP) through its N-terminal degron motif depending on the phosphorylation status, and thus negatively regulate nuclear factor-kappaB (NF-kappaB) activation in the NF-kappaB pro-inflammatory signalling pathway . Moreover, TRIM9 acts as a critical catalytic link between Netrin-1 and exocytosis soluble NSF attachment receptor protein (SNARE) machinery in murine cortical neurons . It promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner.

TRIM9 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, the fibronectin type III domain and the SPRY/B30.2 domain positioned C-terminal to the RBCC domain. The type 1 B-box (Bbox1) zinc finger is characterised by a C6H2 zinc-binding consensus motif .
Peregrin, PWWP domain (BRPF1_PWWP)
Type: Domain

This entry represents a PWWP domain found in human Peregrin (BRPF1) and similar proteins from vertebrates. BRPF1, also called protein Br140, is a multi-domain protein that binds histones, mediates monocytic leukemic zinc-finger protein (MOZ)-dependent histone acetylation, and is required for Hox gene expression and segmental identity . It is a close partner of the MOZ histone acetyltransferase (HAT) complex and a novel Trithorax group (TrxG) member with a central role during development . It contains a plant homeodomain (PHD) zinc finger followed by a non-canonical extended PHD (ePHD) finger, C2HC5HC2H, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. The PHD finger binds to methylated lysine 4 of histone H3 (K4H3), the bromodomain interacts with acetylated lysines on N-terminal tails of histones and other proteins, and the PWWP domain shows histone-binding and chromatin association properties .
CdiI immunity protein EcoliA0-like (CdiI_EcoliA0-like)
Type: Family

CDI toxins are expressed by Gram-negative bacteria as part of a mechanism to inhibit the growth of neighboring cells. This entry represents the inhibitor (CdiI, also called CdiI immunity protein) of the CdiA effector protein from Escherichia coli A0 34/86, and similar proteins.

CdiA secretion is dependent on the outer membrane protein CdiB. Upon binding to a receptor on the surface of target bacteria, the CDI toxin is delivered via its C-terminal domain (CdiA-CT). The CdiI immunity proteins are intracellular proteins that inactivate the toxin/effector protein to prevent auto-inhibition. They are specific for their cognate CdiA-CT and do not protect cells from the toxins of other CDI bacteria. Thus, CDI systems encode a complex network of toxin-immunity protein pairs that are deployed for intercellular competition. This E. coli CdiI binds its cognate toxin CdiA-CT domain with high affinity . E.coli A0 CdiI adopts an α/β structure consisting of a central antiparallel β-sheet and helices packed on it (

).
YciY (YciY)
Type: Family

This entry represents a family of the uncharacterised proteins form proteobacteria, including YciY from E. coli K-12. It is predicted to adopt a single α-helix fold.
TNK(ACK)-like non-receptor tyrosine-protein kinases, SAM domain (TNK-like_SAM)
Type: Domain

This entry represents the SAM (sterile alpha motif) domain of TNK-like subfamily of non-receptor tyrosine-protein kinases. This is a putative protein-protein interaction domain.

This entry includes TNK1 and TNK2 (also known as ACK1) non-receptor tyrosine-protein kinases. The SAM domain is at the N-terminal, followed by a catalytic domain and a few other domains. Members of this group are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Deletion of the SAM domain results in reduction of Ack1 ability to undergo autophosphorylation and dramatically reduces ubiquitination of Ack1 catalysed by HECT E3 ubiquitin ligase (Nedd4-1) during EGF-induced Ack1 degradation. It has been suggested that the lysine-rich region in SAM domain might be a major ubiquitination site. Members of this group are also associated with some cancers. Amplification of the Ack1 gene correlates with prostate and lung cancer progression, and Ack1 overexpression increases invasiveness. Oncogenicity of Tnk1 gene apparently depends on cell context; it may play a role in tumor suppression since Tnk1 knockout mice can develop spontaneous tumors .
DHX8, GH2-like domain (DHX8_GH2-like)
Type: Domain

DHX8 (the human homologue of yeast Prp22), also called RNA helicase HRH1, is an ATP-dependent RNA helicase involved in pre-mRNA splicing as a component of the spliceosome. It facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome.

This entry corresponds to the GH2-like (GIPC-homology 2) domain that has high sequence similarity with the GH2 domain found in GIPC (GAIP C-terminal-interacting protein) family of proteins, which mediate endocytosis by tethering cargo proteins to the motor myosin VI .
NXP-1, middle HEAT-repeat binding domain (NXP1_M-like)
Type: Domain

This entry corresponds to the HEAT-repeat binding domain of NXP-1 located in the middle/central region, which consists of four short helices and two long extended segments. It is responsible for the binding of cohesin HEAT-repeat subunit SA2. The SA2:NXP-1 heterodimer mediates the binding between cohesin and its regulators, including Scc2-Scc4, Pds5, Wapl, and Sgo1.

NXP-1, also called double-strand-break repair protein Rad21 homolog (HR21), or Scc1 homolog, is related to Rad21/Scc1/Mcd1. As a component of the cohesin complex, it is involved in sister chromatid cohesion from the time of DNA replication in S phase to their segregation in mitosis, a function that is essential for proper chromosome segregation, post-replicative DNA repair, and the prevention of inappropriate recombination between repetitive regions. The cohesin complex may also play a role in spindle pole assembly during mitosis. This entry also includes double-strand-break repair protein rad21-like protein 1 (RAD21L), which is a meiosis-specific component of some cohesin complex required during the initial steps of prophase I in male meiosis .
PSMD4, RAZUL domain (PSMD4_RAZUL-like)
Type: Domain

This entry represents the C-terminal Rpn10 AZUL-binding domain (RAZUL) of PSMD4, which is responsible for binding the AZUL domain of E6AP/UBE3A. AZUL stands for amino-terminal zinc-binding domain of ubiquitin E3a ligase.

PSMD4 is also called 26S proteasome regulatory subunit RPN10, 26S proteasome regulatory subunit S5A, antisecretory factor 1, AF, ASF, or multiubiquitin chain-binding protein (MCB1). It acts as a ubiquitin receptor subunit through ubiquitin-interacting motifs and selects ubiquitin-conjugates for destruction. It displays a preferred selectivity for longer polyubiquitin chains. PSMD4 is a component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. The proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair .
CE4 catalytic domain-like (CE4_u4-like)
Type: Domain

This entry includes a group of uncharacterised bacterial proteins with high sequence similarity to the catalytic domain of the six-stranded barrel rhizobial NodB-like proteins, which remove N-linked or O-linked acetyl groups from cell wall polysaccharides and belong to the larger carbohydrate esterase 4 (CE4) superfamily .