SII-SWORD/CoKE huggingface dataset:
RCHY1, zinc-ribbon (RCHY1_zinc-ribbon)
Type: Domain

This entry represents the zinc-ribbon domain found in RCHY1 and related proteins. RCHY1, also known as Pirh2, is a ubiquitin E3 ligase that mediates E3-dependent ubiquitination and proteasomal degradation of target proteins, including p53/TP53, P73, HDAC1 and CDKN1B .
PL-6 family (PL-6)
Type: Family

Polysaccharide Lyase Family 6 (PL-6) is a family of β-helical polysaccharide lyases. Members include alginate lyase (

) and chondroitinase B (

).
Endo-beta-1,6-galactanase-like (6GAL-like)
Type: Domain

This entry represents a domain found in endo-beta-1,6-galactanase (6GAL) and related proteins. In Trichoderma viride, 6GAL hydrolyzes galactooligomers with a degree of polymerization higher than 3 .
NOT4, modified RING finger, HC subclass (C4C4-type) (NOT4_mRING-HC-C4C4)
Type: Domain

NOT4, also known as CCR4-associated factor 4, E3 ubiquitin-protein ligase CNOT4, or potential transcriptional repressor NOT4, is a component of the multifunctional CCR4-NOT complex, a global regulator of RNA polymerase II transcription. It associates with polysomes and contributes to the negative regulation of protein synthesis . NOT4 functions as an E3 ubiquitin-protein ligase that interacts with a specific E2, Ubc4/5 in yeast, and the orthologue UbcH5B in humans, and ubiquitylates a wide range of substrates, including ribosome-associated factors . Thus, it plays a role in cotranslational quality control (QC) through ribosome-associated ubiquitination and degradation of aberrant peptides. NOT4 contains a C4C4-type RING finger motif, whose overall folding is similar to that of the C3HC4-type RING-HC finger, a central RNA recognition motif (RRM), and a C-terminal domain predicted to be unstructured .
C6orf106, UBA-like domain (C6orf106_UBA-like)
Type: Domain

This entry represents the UBA (ubiquitin-associated)-like domain found in a group of uncharacterised protein, such as C6orf106 and its homologues.
WhiA, LAGLIDADG-like domain (WhiA_LAGLIDADG_dom)
Type: Domain

This domain is found within the sporulation regulator WhiA. It is a LAGLIDADG homing endonuclease-like domain .
YokE-like, PH domain (YokE-like_PH)
Type: Domain

This entry represents the PH domain found in uncharacterised proteins, including Bacillus subtilis YokE.
E3 ubiquitin-protein ligase CBL-B, RING finger, HC subclass (CBL-B_RING-HC)
Type: Domain

CBL-B, also known as RNF56, has been identified as a regulator of antigen-specific, T cell-intrinsic, peripheral immune tolerance, a state also known as clonal anergy. It may inhibit activation of the p85 subunit of phosphoinositide 3-kinase (PI3K), protein kinase C-theta (PKC-theta) and negatively regulates T-cell receptor-induced transcription factor nuclear factor kappaB (NF-kappaB) activation . In addition, CBL-B may target multiple signaling molecules involved in transforming growth factor (TGF)-beta-mediated transactivation pathways .
RING finger family 1, prokaryotic (RING_finger_1_prok)
Type: Family

RING finger family found sporadically in bacteria and archaea, and associated in gene neighbourhoods with other components of the ubiquitin-based signaling and degradation system, including ubiquitin, the E1 and E2 proteins and the JAB-like metallopeptidase. The bacterial versions contain transmembrane helices .
Alpha-L-glutamate ligase-related protein, ATP-grasp domain (RimK-rel_E_lig_ATP-grasp)
Type: Domain

This entry represents the ATP-grasp domain found in alpha-L-glutamate ligase-related proteins . The function of these proteins are not clear.
GPI ethanolamine phosphate transferase 3 (PIGO/GPI13)
Type: Family

PIG-F and PIG-O are required for transferring phosphoethanolamine to the third mannose in glycosylphosphatidylinositol (GPI) synthesis. PIG-O and PIG-F associate with each other, and the stability of PIG-O is dependent upon PIG-F .
E3 ubiquitin-protein ligase RNF126-like, zinc-ribbon (RNF126-like_zinc-ribbon)
Type: Domain

This entry represents the zinc-ribbon domain found in RNF126 and related proteins. RNF126 is a E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins .
GPI ethanolamine phosphate transferase 2 (PIGG/GPI7)
Type: Family

Gpi7 and its human homologue PIGG are involved in glycosylphosphatidylinositol-anchor biosynthesis. They transfer ethanolamine phosphate to the second mannose of the GPI intermediate .
DPM1-like (DPM1-like)
Type: Family

This family belongs to glycosyltransferase 2 superfamily and consists of proteins similar to eukaryotic DPM1, including enzymes from bacteria and archaea.

DPM1 is the catalytic subunit of eukaryotic dolichol-phosphate mannose (DPM) synthase. DPM synthase is required for synthesis of the glycosylphosphatidylinositol (GPI) anchor, N-glycan precursor, protein O-mannose, and C-mannose. In higher eukaryotes,the enzyme has three subunits, DPM1, DPM2 and DPM3. DPM is synthesized from dolichol phosphate and GDP-Man on the cytosolic surface of the ER membrane by DPM synthase and then is flipped onto the luminal side and used as a donor substrate . In Saccharomyces cerevisiae and Trypanosoma brucei, DPM synthase consists of a single component (Dpm1p and TbDpm1, respectively) that possesses one predicted transmembrane region near the C terminus for anchoring to the ER membrane. In contrast, the Dpm1 homologues of fission yeast, fungi, and animals, have no transmembrane region, suggesting the existence of adapter molecules for membrane anchoring .

Polyprenol monophosphomannose synthase (Ppm1) also belongs to this family. Ppm1 is a bifunctional protein that transfers mannose from GDP-mannose to lipid acceptors to form polyprenol monophosphomannose (PPM), which acts as a sugar donor for lipoglycan synthesis in mycobacteria .
GPI inositol-deacylase (PGAP1/BST1)
Type: Family

PGAP1 (Bst1 in yeast) functions as a GPI inositol-deacylase; this deacylation is important for the efficient transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi body . Mutations of the PGAP1 gene cause mental retardation, autosomal recessive 42 (MRT42) .
RNA-directed RNA polymerase L methyltransferase domain, rhabdovirus (L_methyltransferase_rhabdo)
Type: Domain

This entry represents the methyltransferase region of the Mononegavirales single-stranded RNA viral RNA polymerase enzymes, mainly from Mononegavirales single-stranded RNA viral RNA polymerase enzymes (L proteins). This region is involved in the mRNA-capping of the virion particles .
Transcriptional regulator TetR, C-terminal, Firmicutes type (TetR_C_Firmicutes)
Type: Domain

This domain can be found in the C terminus of a group of putative tetracycline repressors mostly from Firmicutes .
Arylsulfotransferase-like (ASST-like)
Type: Family

This entry represents a group of arylsulfotransferase-like proteins from eukaryotes, archaea and bacteria.
Transcriptional regulator TetR, C-terminal, Proteobacteria type (TetR_C_Proteobacteria)
Type: Domain

This domain can be found in the C terminus of a group of putative tetracycline repressors mostly from Proteobacteria. This domain can also be found in AefR transcriptional regulator from P. syringae .
Retrotransposon Ty1/copia-like (Retrotran_Ty1/copia-like)
Type: Family

This entry represents the Ty1/copia-like retrotransposons mostly from eukaryotes, including Copia from Drosophila melanogaster , Tnt1 from Nicotiana tabacum and Ty1 from Saccharomyces cerevisiae . Copia-like elements share the same general structure including a long terminal repeat (LTR), and encode a polyprotein that includes major domains with highly conserved amino acid sequences such as gag and pol, and the integrase domain located at the 5' end of the reverse transcriptase domain .
BetI-type transcriptional repressor, C-terminal (BetI_C)
Type: Domain

This entry represents the C-terminal portion of proteins that belong to the TetR family of transcriptional regulators. The C terminus represents the regulatory region, and does not include the DNA binding helix-turn-helix domain. The target proteins that are repressed are involved in the transcriptional control of multi-drug efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic stress and toxic chemicals, control of catabolic pathways, differentiation processes, and pathogenicity . One of the target proteins is BetI, an osmoprotectant which controls the choline-glycine betaine pathway in E.coli .
Ras GTPase-activating protein-binding protein (Ras_GTPase_bind_prot)
Type: Family

This entry represents proteins with an N-terminal NTF2 (nuclear transport factor 2) domain and a C-terminal RRM (RNA recognition motif) domain. It includes mammalian ATP- and magnesium-dependent helicase Ras GTPase-activating protein-binding proteins 1 and 2 and UBP3-associated protein Bre5 from yeast, which is a co-factor required for de-ubiquitination . This entry also includes AtMBD6 from Arabidopsis. AtMBD6 maintains gene silencing in Arabidopsis by interacting with RNA binding proteins .
UBL3-like, ubiquitin domain (UBL3-like_ubiquitin_dom)
Type: Domain

This entry represents the ubiquitin domain found in ubiquitin-like protein 3 (UBL3) and related proteins, such as MUB1-6 from Arabidopsis . The AtMUB proteins localize a specific subset of ubiquitin-conjugating (E2) enzymes to the plasma membrane .
Metallophosphoesterase 1, metallophosphatase domain (MPP_MPPE1)
Type: Domain

Metallophosphoesterase 1 (MPPE1), also known as PGAP5, acts as a phosphodiesterase removing an ethanolamine phosphate (EtN-P) from mannose 2 of the glycosylphosphatidylinositol (GPI) anchor, thus permitting efficient endoplasmic reticulum (ER) to Golgi transport of GPI proteins . Before GPI-anchored proteins exist the ER, two remodeling reaction, inositol deacylation by PGAP1 and removal of the second EtNP by PGAP5, occur in mammalian cells. The MPPE1 gene has been identified as a candidate susceptibility gene for Bipolar disorder .

MPPE1 belongs to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain consisting of a double β-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.
Endoplasmic reticulum vesicle transporter, N-terminal (Erv_N)
Type: Domain

This entry represents the N-terminal domain of the endoplasmic reticulum vesicle transporter proteins (Ervs), also known as endoplasmic reticulum-Golgi intermediate compartment (ERGIC) proteins.

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

Proteins containing this domain also include disulfide isomerase (PDI)-C subfamily members from Arabidopsis. They are chimeric proteins containing the thioredoxin (Trx) domain of PDIs, and the conserved N- and C-terminal domains of Erv cargo receptors .
Tim44-like (Tim44-like)
Type: Family

This entry includes mitochondrial import inner membrane translocase subunit Tim44 and its bacterial homologues. All possess a Tim44-like domain.

Tim44 is an essential component of the PAM complex, which is required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. It recruits mitochondrial HSP70 to drive protein translocation into the matrix using ATP as an energy source .
Post-GPI attachment to proteins factor 2 (PGAP2)
Type: Family

PGAP2, also known as FRAG1, is involved in the lipid remodeling steps of glycosylphosphatidylinositol (GPI)-anchor maturation . Immediately after attachment of GPI to newly synthesized proteins, inositol-linked palmitate is removed by deacylase PGAP1 in the ER. The inositol-deacylation is essential for subsequent steps in fatty acid remodeling in the Golgi. PGAP3 removes an unsaturated fatty chain at sn-2 and PGAP2 reacylation of sn-2 with stearic acid follows .
Jade-1, PHD finger (Jade-1_PHD)
Type: Domain

Jade-1 is a novel binding partner of von Hippel-Lindau (VHL) tumour suppressor Pvhl, a key regulator of the cellular oxygen sensing pathway . It is highly expressed in renal proximal tubules. Jade-1 functions as an essential regulator of multiple cell signaling pathways. It may be involved in the serine/threonine kinase AKT/AKT1 pathway during renal cancer pathogenesis and normally prevents renal epithelial cell proliferation and transformation . It also acts as a pro-apoptotic and growth suppressive ubiquitin ligase to inhibit canonical Wnt downstream effector beta-catenin for proteasomal degradation , and as a transcription factor associated with histone acetyltransferase activity and with increased abundance of cyclin-dependent kinase inhibitor p21 . Moreover, Jade-1 is required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and Eaf6 to form a HBO1 complex, and plays a role in epithelial cell regeneration . It has also been identified as a novel component of the nephrocystin protein (NPHP) complex and interacts with the ciliary protein nephrocystin-4 (NPHP4) .
Large ribosomal subunit protein eL19 (Ribosomal_eL19)
Type: Family

This entry represents the large ribosomal subunit protein eL19, found in archaea and eukaryotes .
JADE2, PHD domain (JADE2_PHD)
Type: Domain

Jade-2, also termed PHD finger protein 15 (PHF15), is a PHD ("plant homeodomain") zinc finger protein that is closely related to Jade-1, which functions as an essential regulator of multiple cell signaling pathways. Like Jade-1, Jade-2 is required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and Eaf6 to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. Jade-2 contains a canonical Cys4HisCys3 PHD finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, both of which are zinc-binding motifs. This entry represents the canonical Cys4HisCys3 PHD finger .
JADE2, ePHD domain (JADE2_ePHD)
Type: Domain

The ePHD ("extended plant homeodomain") zinc finger is characterised as Cys2HisCys5HisCys2His. This entry represents the ePHD finger of Jade-2. Jade-2 is a homeodomain (PHD) zinc finger protein that is closely related to Jade-1, which functions as an essential regulator of multiple cell signaling pathways. Like Jade-1, Jade-2 is required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and Eaf6 to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. Jade-2 contains a canonical PHD finger followed by this non-canonical ePHD finger, both of which are zinc-binding motifs .
JADE3, PHD domain (JADE3_PHD)
Type: Domain

Jade-3, also termed PHD finger protein 16 (PHF16), is a PHD ("plant homeodomain") zinc finger protein that is closely related to Jade-1, which functions as an essential regulator of multiple cell signaling pathways. Like Jade-1, Jade-3 is required for ING4 and ING5 to associate with histone acetyl transferase (HAT) HBO1 and Eaf6 to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. Jade-3 contains a canonical Cys4HisCys3 PHD domain followed by a non-canonical extended PHD (ePHD) domain, Cys2HisCys5HisCys2His, both of which are zinc-binding motifs. This model corresponds to the canonical Cys4HisCys3 PHD finger .
Choline/carnitine acyltransferase domain (Cho/carn_acyl_trans)
Type: Domain

The choline/carnitine acyltransferase domain is found in a number of eukaryotic acetyltransferases. These enzymes include:

Choline o-acetyltransferase

, an enzyme that catalyses the biosynthesis of the neurotransmitter acetylcholine .

Carnitine o-acetyltransferase

.

Peroxisomal carnitine octanoyltransferase

, a fatty acid beta-oxidation pathway enzyme which is involved in the transport of medium-chain acyl-coenzyme A's from peroxisome to mitochondria .

Mitochondrial carnitine palmitoyltransferases I and II

(CPT), enzymes involved in fatty acid metabolism and transport .

Mycoplasma pneumoniae putative acetyltransferase C09_orf600.

This domain is also found at the C terminus of highly reducing polyketide synthase SdnO. SdnO is part of the gene cluster that mediates the biosynthesis of glycoside antibiotics sordarin and hypoxysordarin .
Transposase IS66, C-terminal (IS66_C)
Type: Domain

This entry represents the C-terminal region of the insertion element IS66 transposase .
Prefoldin-like (Prefoldin-like)
Type: Family

This family includes prefoldin subunits that are not detected by

.
HigA2-like, helix-turn-helix domain (HigA2-like_HTH)
Type: Domain

This entry represents the helix-turn-helix domain found in a group of HigA2-like proteins. HigA2 is a putative antitoxin component of a type II toxin-antitoxin (TA) system .
F plasmid transfer operon protein (TraF/TrbB)
Type: Family

TraF protein undergoes proteolytic processing associated with export. The 19 amino acids at the amino terminus of the polypeptides appear to constitute a typical membrane leader peptide - not included in this family, while the remainder of the molecule is predicted to be primarily hydrophilic in character . F plasmid TraF and TraH are required for F pilus assembly and F plasmid transfer, and they are both localised to the outer membrane in the presence of the complete F transfer region, especially TraV, the putative anchor .

TrbB is closely related to TraF which is somewhat longer, lacks the cysteine motif and is apparently not functional as a disulfide bond isomerase. TrbB may be involved in pilin assembly .
ICL/PEPM domain (ICL/PEPM)
Type: Domain

Proteins containing this domain are members of the ICL/PEPM enzyme family and catalyze either P-C or C-C bond formation/cleavage. Known members are phosphoenolpyruvate mutase (PEPM), phosphonopyruvate hydrolase (PPH), carboxyPEP mutase (CPEP mutase), oxaloacetate hydrolase (OAH), isocitrate lyase (ICL), and 2-methylisocitrate lyase (MICL) .

ICL catalyzes the conversion of isocitrate to succinate and glyoxylate, the first committed step in the glyoxylate pathway. This carbon-conserving pathway is present in most prokaryotes, lower eukaryotes and plants, but has not been observed in vertebrates .
AHAS, ACT domain (AHAS_ACT)
Type: Domain

This entry represents the N-terminal ACT domain of the Escherichia coli IlvH-like regulatory subunit of acetolactate synthase (acetohydroxyacid synthase; AHAS). AHAS catalyses the first common step in the biosynthesis of the three branched-chain amino acids (leucine, isoleucine, and valine). The first step involves the condensation of either pyruvate or 2-ketobutyrate with the two-carbon hydroxyethyl fragment derived from another pyruvate molecule, covalently bound to the coenzyme thiamine diphosphate. Bacterial AHASs generally consist of regulatory and catalytic subunits. The effector (valine) binding sites are proposed to be located in two symmetrically related positions in the interface between a pair of N-terminal ACT domains with the C-terminal domain of IlvH contacting the catalytic dimer. Plants Arabidopsis and Oryza have tandem IlvH subunits; both the first and second ACT domain sequences are present in this entry .
Prolyl 3,4-dihydroxylase TPA1/OFD1, N-terminal domain (TPA1/OFD1_N)
Type: Domain

This entry represents the N-terminal domain of prolyl 3,4-dihydroxylase Ofd1 from Schizosaccharomyces pombe and homologues in S. cerevisiae (TPA1) and mammals (OGFOD1) .

Ofd1 is a prolyl 4-hydroxylase-like 2-oxoglutarate-Fe(II) dioxygenase that accelerates the degradation of Sre1N (the N-terminal transcription factor domain of Sre1) in the presence of oxygen . Yeast Sre1 is the orthologue of mammalian sterol regulatory element binding protein (SREBP), and it responds to changes in oxygen-dependent sterol synthesis as an indirect measure of oxygen availability. However, unlike the prolyl 4-hydroxylases that regulate mammalian hypoxia-inducible factor, Ofd1 uses multiple domains to regulate Sre1N degradation by oxygen; the Ofd1 N-terminal dioxygenase domain is required for oxygen sensing and this Ofd1 C-terminal domain accelerates Sre1N degradation in yeasts .
Altered inheritance of mitochondria protein 6, PI-PLC-like catalytic domain (AIM6_PI-PLC-like_dom)
Type: Domain

This entry represents the PI-PLC (phosphoinositide-specific phospholipase C) -like catalytic domain found in baker's yeast Aim6 (altered inheritance of mitochondria protein 6) and related proteins. The function of Aim6 is not clear.
Potyviral polyprotein protein 3 (Potyvirid-P3)
Type: Domain

This is the P3 protein section of the Potyviridae polyproteins. The function is not known except that the protein is essential to viral survival .
Peptidase M15C (Peptidase_M15C)
Type: Domain

This entry includes members of the peptidase M15C family, including CwlK from Bacillus subtilis and L-alanyl-D-glutamate peptidase Lys from Escherichia phage T5. CwlK is a peptidoglycan L-alanyl-D-glutamate endopeptidase . Lys is a metal ion-dependent L-alanoyl-D-glutamate peptidase .
Membrane fusion protein, biotin-lipoyl like domain (MFP_biotin_lipoyl_2)
Type: Domain

This entry represents the biotin-lipoyl like domain found in some bacterial membrane fusion proteins MdtA. MdtA is part of the MdtABC tripartite complex that confers resistance against novobiocin and deoxycholate .

MFPs are a component of the RND family of transporters (RND refers to resistance, nodulation, and cell division). MFPs are proposed to span the periplasm in some way linking the inner and outer membranes . However, some members of this family are found in Gram-positive bacteria, where there is no outer membrane. MFPs are involved in the export of a variety of compounds, from drug molecules to large polypeptides, and are united by their similar overall structural organisation, combined with some conserved regions .
Peptidase C39 single domain protein (Peptidase_C39_single_dom)
Type: Domain

This entry represents a subgroup of peptidase family C39. Peptidase family C39 mostly contains bacteriocin-processing endopeptidases from bacteria. The cysteine peptidases in family C39 cleave the 'double-glycine' leader peptides from the precursors of various bacteriocins (mostly non-lantibiotic). The cleavage is mediated by the transporter as part of the secretion process. Bacteriocins are antibiotic proteins secreted by some species of bacteria that inhibit the growth of other bacterial species. The bacteriocin is synthesized as a precursor with an N-terminal leader peptide, and processing involves removal of the leader peptide by cleavage at a Gly-Gly bond, followed by translocation of the mature bacteriocin across the cytoplasmic membrane. Most endopeptidases of family C39 are N-terminal domains in larger proteins (ABC transporters) that serve both functions. The proposed protease active site is conserved in this subgroup of proteins with a single peptidase domain, which are lacking the nucleotide-binding transporter signature or have different domain architectures .