SII-SWORD/CoKE huggingface dataset:
CDP-alcohol phosphatidyltransferase, conserved site (CDP_ALCOHOL_P_TRANSF_CS)
Type: Conserved_site

This entry represents a conserved region found in a number of phosphatidyltransferases, which contains three aspartic acid residues.

A number of phosphatidyltransferases, which are all involved in phospholipid biosynthesis and that share the property of catalysing the displacement of CMP from a CDP-alcohol by a second alcohol with formation of a phosphodiester bond and concomitant breaking of a phosphoride anhydride bond share a conserved sequence region . These enzymes are proteins of 200 to 400 amino acid residues, including EPT1 from yeast, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferases from bacteria, CDP-diacylglycerol--serine O-phosphatidyltransferase from animals, among others. Also included in this entry is cardiolipin (CL) synthase (CMP-forming)/mitochondrial hydrolase fusion protein from S.pombe, a tandem fusion protein with a mitochondrial hydrolase. The CL synthase is essential for this organism .
Vacuolar membrane-associated protein Iml1, N-terminal domain (IML1_N)
Type: Domain

This domain is found at the N-terminal of vacuolar membrane-associated protein Iml1 and related proteins. These proteins also contain a DEP domain, which is a globular domain of about 80 residues. This entry includes vacuolar membrane-associated protein Iml1 and DEP domain-containing protein 5/DDB_G0279099. In Saccharomyces cerevisiae, Iml1 is a subunit of both the SEA (Seh1-associated) and Iml1 complexes (Iml1-Npr2-Npr3). SEA complex is associates dynamically with the vacuole and is involved in autophagy . Iml1 complex is required for non-nitrogen-starvation (NNS)-induced autophagy .
Tektin-like (Tektin-like)
Type: Family

Tektins are cytoskeletal proteins. They have been demonstrated in such cellular sites as centrioles, basal bodies, and along ciliary and flagellar doublet microtubules. Tektins form unique protofilaments, organised as longitudinal polymers of tektin heterodimers with axial periodicity matching tubulin. Tektin polypeptides consist of several α-helical regions that are predicted to form coiled coils. Indeed, tektins share considerable structural similarities with intermediate filament proteins. Possible functional roles for tektins are: stabilisation of tubulin protofilaments; attachment of A and B-tubules in ciliary/flagellar microtubule doublets and C-tubules in centrioles; binding of axonemal components .

This entry also includes Tektin-like protein 1 (TEKTL1) that shares many structural features with tektins, including the overall helix-turn-helix fold and head-to-tail association into filaments, but does not seem to assemble into the large oligomeric bundles associated with tektins. Thus, the mechanism by which TEKTL1 and tektins assemble into filaments differs slightly. In both sea urchin and bovine sperm, TEKTL1 binds to the outer inter-protofilament cleft of A11/A12, where it may help stabilise the outer junction .
Domain of unknown function DUF4590 (DUF4590)
Type: Domain

This is an uncharacterised domain found in metazoan proteins, such as glutamate rich 3 (ERICH3) (

) that is involved in neuronal vesicle biogenesis and neurotransmitter vesicular function .

This domain is approximately 120 amino acids in length and it is predicted to fold into a β-sandwich. It contains two conserved sequence motifs: CCE and PCY.
Cyclins, cyclin-box (Cyclins_cyclin-box)
Type: Conserved_site

This entry represents the most conserved region (~32 residues) in the central part of the cyclins' sequences. This region is known as the 'cyclin-box'.

Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles , and regulate cyclin dependent kinases (CDKs). Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). There are two main groups of cyclins, G1/S cyclins, which are essential for the control of the cell cycle at the G1/S (start) transition, and G2/M cyclins, which are essential for the control of the cell cycle at the G2/M (mitosis) transition. G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). In most species, there are multiple forms of G1 and G2 cyclins. For example, in vertebrates, there are two G2 cyclins, A and B, and at least three G1 cyclins, C, D, and E.

Cyclin homologues have been found in various viruses, including Saimiriine herpesvirus 2 (Herpesvirus saimiri) and Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus). These viral homologues differ from their cellular counterparts in that the viral proteins have gained new functions and eliminated others to harness the cell and benefit the virus .
Cytochrome b/b6, N-terminal domain, eukaryotic/bacterial (Cytochrome_b_N_euk/bac)
Type: Domain

This entry represents the N-terminal domain of Cytochrome b/b6 found mainly in eukaryotes and bacteria. Cytochrome b is a subunit of cytochrome bc1, an 11-subunit mitochondrial respiratory enzyme. Cytochrome b spans the mitochondrial membrane with 8 transmembrane helices (A-H) in eukaryotes. In plants and cyanobacteria, cytochrome b6 is analogous to eukaryotic cytochrome b, containing two chains: helices A-D are encoded by the petB gene and helices E-H are encoded by the petD gene in these organisms. Cytochrome b/b6 contains two bound hemes and two ubiquinol/ubiquinone binding sites .
Cytochrome b/b6, C-terminal domain, eukaryotic/bacterial (Cytochrome_b_C_euk/bac)
Type: Domain

This entry represents the C-terminal domain of Cytochrome b/b6 found mainly in eukaryotes and bacteria.

In the mitochondrion of eukaryotes and in aerobic prokaryotes, cytochrome b is a component of respiratory chain complex III (

) - also known as the bc1 complex or ubiquinol-cytochrome c reductase. In plant chloroplasts and cyanobacteria, there is a analogous protein, cytochrome b6, a component of the plastoquinone-plastocyanin reductase (

), also known as the b6f complex.

Cytochrome b/b6 is an integral membrane protein of approximately 400 amino acid residues that probably has 8 transmembrane segments. In plants and cyanobacteria, cytochrome b6 consists of two subunits encoded by the petB and petD genes. The sequence of petB is colinear with the N-terminal part of mitochondrial cytochrome b, while petD corresponds to the C-terminal part. Cytochrome b/b6 non-covalently binds two haem groups, known as b562 and b566. Four conserved histidine residues are postulated to be the ligands of the iron atoms of these two haem groups.

Apart from regions around some of the histidine haem ligands, there are a few conserved regions in the sequence of b/b6. The best conserved of these regions includes an invariant P-E-W triplet which lies in the loop that separates the fifth and sixth transmembrane segments. It seems to be important for electron transfer at the ubiquinone redox site - called Qz or Qo (where o stands for outside) - located on the outer side of the membrane. This entry is the C terminus of these proteins.
PPIase chaperone SlpA/SlyD-like, insertion domain superfamily (SlpA/SlyD-like_ins_sf)
Type: Homologous_superfamily

This entry represents the insertion (described as insert-in-flap) domain of a group of FKBP-type peptidyl-prolyl cis-trans isomerases, including the metallochaperone SlpA (also known as FKBP-type 16 kDa peptidyl-prolyl cis-trans isomerase), SlyD from E.coli and related sequences. Members of this entry consist of two domains, the FKBP-type peptidyl-prolyl cis-trans isomerase (PPIase) domain (

) which provides the PPIase activity, and the autonomously folded insert-in-flap (IF) domain, which gives the chaperone activity .
BRCA2, OB2 domain (BRCA2_OB_2_dom)
Type: Domain

This entry corresponds to the second OB fold domain (OB2) of BRCA2 (breast cancer susceptibility gene 2) protein.

BRCA2 participates in homologous recombination-mediated repair of double-strand DNA breaks. It stimulates the displacement of Replication protein A (RPA), the most abundant eukaryotic ssDNA binding protein. It also facilitates filament formation. Mutations that map throughout the BRCA2 protein are associated with breast cancer susceptibility. BRCA2 is a large nuclear protein and its most conserved region is the C-terminal. This region binds to ssDNA in vitro, and is composed of five structural domains, three of which are OB folds (OB1, OB2, and OB3) . OB2 contains a large insertion, named tower domain that is represented separately by

but included in this entry.
Arb2 (Arb2)
Type: Family

Members of this entry contain the Arb2 domain that gets its name from S. pombe Argonaute-binding protein 2 (Arb2), which is the orthologue of the vertebrate cotranscriptional regulator ARB2A (also known as FAM172 family) . Human FAM172A protein is associated with CHARGE syndrome, a severe multi-organ developmental disorder mainly affecting derivatives of cranial and cardiac neural crest cells (NCCs). CHARGE syndrome has been suggested to be a spliceosomopathy, due to perturbation of chromatin-mediated alternative splicing . FAM172A and its homologues contain a large Arb2 domain split into two halves by a classical bipartite NLS that helps to stabilise the chromatin-spliceosome interface as part of a complex that includes CHD7 and AGO2 . It has been suggested that FAM172A can connect the alternative splicing machinery to specific transcribed regions . S. pombe Arb2 is a member of the argonaute siRNA chaperone (ARC) complex which is required for histone H3K9 methylation, heterochromatin assembly and siRNA generation. The Arb2 domain has clear homology to α/β-hydrolases but it lacks the catalytic triad of these enzymes.
Chlorophyllase (Chlorophyllase)
Type: Family

This entry includes chlorophyllase (Chlase

), an enzyme involved in chlorophyll degradation and catalyses the hydrolysis of the ester bond to yield chlorophyllide and phytol . It is found in higher plants, green algae and diatoms . It is important for de-greening processes such as fruit ripening and flowering, as well as in the turnover and homeostasis of chlorophyll . It does not seem to be required for chlorophyll degradation during senescence . Chlase may modulate the balance between different plant defense pathways .
Rax2-like, third domain (Rax2-like_third)
Type: Domain

Diploid yeast cells repeatedly polarise and bud from their poles, due probably to the presence of highly stable membrane markers, and Rax2 is one such marker. It is inherited immutably at the cell cortex for multiple generations, and has a half-life exceeding several generations. The persistent inheritance of cortical protein markers would provide a means of coupling a cell's history with the future development of a precise morphogenetic form . Both Rax1 and Rax2 localise to the distal pole as well as to the division site and they interact both with each other and with Bud8p and Bud9p in the establishment and/or maintenance of the cortical markers for bipolar budding . Thus Rax2 is likely to control cell polarity during vegetative growth, and in fission yeast this is done by regulating the localisation of for3p . Rax2 is not involved in responses that require a reorientation of the direction of already established hyphal growth (tropisms) .

This entry represents the third domain in Rax 2 and Polarized growth protein L1 which are structurally similar. This domain is found inserted within the first β-propeller domain.
Rax2-like, second domain (Rax2-like_second)
Type: Domain

Diploid yeast cells repeatedly polarise and bud from their poles, due probably to the presence of highly stable membrane markers, and Rax2 is one such marker. It is inherited immutably at the cell cortex for multiple generations, and has a half-life exceeding several generations. The persistent inheritance of cortical protein markers would provide a means of coupling a cell's history with the future development of a precise morphogenetic form . Both Rax1 and Rax2 localise to the distal pole as well as to the division site and they interact both with each other and with Bud8p and Bud9p in the establishment and/or maintenance of the cortical markers for bipolar budding . Thus Rax2 is likely to control cell polarity during vegetative growth, and in fission yeast this is done by regulating the localisation of for3p . Rax2 is not involved in responses that require a reorientation of the direction of already established hyphal growth (tropisms) .

This entry represents the second domain of Rax2 and Polarized growth protein L1 which are structurally similar. This domain is inserted within a β-propeller domain.
Arginosuccinate synthase-like, N-terminal domain (Arginosuc_syn_N)
Type: Domain

This entry represents the N-terminal domain of the argininosuccinate synthase enzymes. This domain is part of the HUP superfamily.

Argininosuccinate synthase (

) (AS) is a urea cycle enzyme that catalyses the penultimate step in arginine biosynthesis: the ATP-dependent ligation of citrulline to aspartate to form argininosuccinate, AMP and pyrophosphate .

In humans, a defect in the AS gene causes citrullinemia, a genetic disease characterised by severe vomiting spells and mental retardation.

AS is a homotetrameric enzyme of chains of about 400 amino-acid residues. An arginine seems to be important for the enzyme's catalytic mechanism. The sequences of AS from various prokaryotes, archaebacteria and eukaryotes show significant similarity.
Arginosuccinate synthase C-terminal domain (Arginosuc_syn_C)
Type: Domain

This entry represents the C-terminal domain of the Arginosuccinate synthase enzyme.

Argininosuccinate synthase (

) (AS) is a urea cycle enzyme that catalyses the penultimate step in arginine biosynthesis: the ATP-dependent ligation of citrulline to aspartate to form argininosuccinate, AMP and pyrophosphate .

In humans, a defect in the AS gene causes citrullinemia, a genetic disease characterised by severe vomiting spells and mental retardation.

AS is a homotetrameric enzyme of chains of about 400 amino-acid residues. An arginine seems to be important for the enzyme's catalytic mechanism. The sequences of AS from various prokaryotes, archaebacteria and eukaryotes show significant similarity.
Ribonuclease ribotoxin, alpha-sarcin type (RNase_U2)
Type: Family

This group represents a ribonuclease ribotoxin, alpha-sarcin type, found in fungi. It includes ribonuclease alpha-sarcin, mitogillin and clavin that have similar substrate specificity.

Alpha-sarcin is specific for purines in both single- and double-stranded RNA. Its toxic action on eukaryotic cells is the result of cleavage of a single phosphodiester bond in the 60S subunit of ribosomes. It inhibits both the Elongation factor 1 (EFl)-dependent binding of aminoacyl-tRNA and the GTP-dependent binding of Elongation factor 2 (EF2) to ribosomes .
Paraneoplastic antigen Ma-like, C-terminal domain (PNMA_C)
Type: Domain

This entry represents a domain found towards the C-terminal of paraneoplastic Ma antigens (PNMAs) and similar proteins. This domain is found at the N-terminal of Zinc finger CCHC domain-containing protein 12.

The paraneoplastic Ma antigens (PNMA) have been identified using sera from patients with paraneoplastic neurological syndromes . This entry includes paraneoplastic antigen PNMA1 , PNMA2 , PNMA3 , PNMA4 (also known as modulator of apoptosis 1 or MOAP-1) and some paraneoplastic antigen-like proteins (PNMA5 and PNMA6). PNMA4/MOAP-1 has a role in death receptor-dependent apoptosis , and it also plays a role in autophagy as it promotes phagophore closure via association with ATG8 proteins .

Zinc finger CCHC domain-containing protein 12 (ZCCHC12, also known as Sizn1 in mouse), also a member of this entry, is a transcriptional coactivator in the bone morphogenetic protein (BMP)-signaling pathway. It positively modulates BMP signaling by interacting with SMAD1 and associating with CBP in the transcription complex. It contributes to the BMP-induced enhancement of cholinergic-neuron-specific gene expression . This protein may be a potential molecular marker of papillary thyroid carcinoma .
Paraneoplastic antigen Ma-like, N-terminal domain (PNMA_N)
Type: Domain

This domain resembles an RNA-binding RRM domain in AlphaFold structure predictions. This domain is found at the N-terminal of various of paraneoplastic Ma antigens (PNMA) and similar proteins.

The paraneoplastic Ma antigens (PNMA) have been identified using sera from patients with paraneoplastic neurological syndromes . This entry includes paraneoplastic antigen PNMA1 , PNMA2 , PNMA3 , PNMA4 (also known as modulator of apoptosis 1 or MOAP-1) and some paraneoplastic antigen-like proteins (PNMA5 and PNMA6). PNMA4/MOAP-1 has a role in death receptor-dependent apoptosis , and it also plays a role in autophagy as it promotes phagophore closure via association with ATG8 proteins .

Zinc finger CCHC domain-containing protein 12 (ZCCHC12, also known as Sizn1 in mouse), also a member of this entry, is a transcriptional coactivator in the bone morphogenetic protein (BMP)-signaling pathway. It positively modulates BMP signaling by interacting with SMAD1 and associating with CBP in the transcription complex. It contributes to the BMP-induced enhancement of cholinergic-neuron-specific gene expression . This protein may be a potential molecular marker of papillary thyroid carcinoma .
Distal tail protein, C-terminal domain (Dit_C)
Type: Domain

This domain is found at the C-terminal end of Distal tail protein from Lactococcus phage p2 (Dit or Gp15) and similar proteins predominantly found in virus. Dit self-associates as two rings organised back to back, with a central channel allowing DNA ejection through the viral tail. This domain is located at the ring periphery and display a galectin fold .

Distal tail protein (Dit) has a structural role and forms the distal part of the tail. It is organised into two domains, a ring domain that shows a split barrel-like fold and a C-terminal galectin domain. Consecutive Dit N-terminal domains form a tight ring with two layers of β-strands. This ring frames a channel sufficiently large for dsDNA passage . This protein is involved in the process of viral genome ejection through the host cell envelope using a long flexible tail mechanism. The distal tail protein forms the distal part of the tail structure and plays a role in DNA ejection. It self-associates as two rings that are arranged back to back, creating a central channel through which the DNA is ejected into the host cell. Additionally, it interacts with the receptor binding protein, facilitating the attachment of the phage to the host cell. At the structural level, the distal tail protein is composed of homohexameric subunits.
Luciferase (Luciferase)
Type: Family

This family includes fungal luciferase which is part of the gene cluster that mediates the fungal bioluminescence cycle . It may use the fungal luciferin 3-hydroxyhispidin as a substrate to produce an endoperoxide as a high-energy intermediate with decomposition that yields oxyluciferin (also known as caffeoylpyruvate) and light emission. The fungal bioluminescence cycle begins with the hispidin synthetase that catalyses the formation of hispidin which is further hydroxylated by the hispidin-3-hydroxylase, yielding the fungal luciferin 3-hydroxyhispidin. The luciferase then produces an endoperoxide as a high-energy intermediate with decomposition that yields oxyluciferin and light emission. Oxyluciferin can be recycled to caffeic acid by caffeoylpyruvate hydrolase . This entry also includes some uncharacterised bacterial sequences.
Mesaconyl-CoA hydratase (MC_hydratase)
Type: Family

This entry includes Mesaconyl-CoA hydratase from bacteria and archaea, which is involved in the methylaspartate cycle. It catalyses the reversible hydration of mesaconyl-CoA to yield beta-methylmalyl-CoA . This enzyme belongs to the HotDog superfamily and contains two HotDog domains and it is is closely related to MaoC dehydratase .
Lantibiotic cinnamycin (Cinnamycin_RiPP)
Type: Family

Members of this family are RiPP precursor peptides from which the lantibiotic cinnamycin is the most heavily studied. Mature cinnamycin is 19 amino acids long with nine post-translational modifications, including lanthionine, methyllanthionine, and lysinoalanine bridge modifications .
Phage tail-like, C-terminal domain (Phage_tail-like_C)
Type: Domain

This entry represents a domain found at the C-terminal of mostly uncharacterised proteins from Firmicutes and phages (also referred to as DUF6558_C) of which some members are phage tail-related proteins. Included in this entry is the prophage-derived protein YomH from Bacillus subtilis (

).
Profilin (PFN)
Type: Family

This entry represents the profilin family, which are small eukaryotic proteins that have different functions. In plants, they are major allergens present in pollens .

The majority of the Profilin family members binds to monomeric actin (G-actin) in a 1:1 ratio thus preventing the polymerisation of actin into filaments (F-actin). They can also, in certain circumstances, promote actin polymerisation . However, some profilin family members, such as Profilin 4 from mammals, does not bind to actin and may have functions distinct from regulating actin dynamics . It plays a role in the assembly of branched actin filament networks, by activating WASP via binding to WASP's proline rich domain . Profilin may link the cytoskeleton with major signalling pathways by interacting with components of the phosphatidylinositol cycle and Ras pathway .

This entry also includes Asgard archaeal profilins (Thor profilin, Loki profilin-1 and Loki profilin-2), which bind to actin and regulate the structure of the cytoskeleton. This indicates that Asgard archaea have a functional eukaryotic-like actin machinery .

Some profilins can also bind to polyphosphoinositides such as PIP2 . Overall sequence similarity among profilin from organisms which belong to different phyla (ranging from fungi to mammals) is low, but the N-terminal region is relatively well conserved. The N-terminal region is thought to be involved in actin binding.
Multidrug resistance protein MdtK-like (MdtK-like)
Type: Family

This entry represents the multidrug resistance protein MdtK and closely related proteins such as NorM, MepA, PmpM and others, that are all members of the larger MATE family.

In general, proteins from the MATE family are involved in exporting metabolites across the cell membrane and are often responsible for multidrug resistance (MDR) . These proteins mediate resistance to a wide range of cationic dyes, fluroquinolones, aminoglycosides and other structurally diverse antibodies and drugs. MATE proteins are found in bacteria, archaea and eukaryotes. These proteins are predicted to have 12 α-helical transmembrane regions, some of the animal proteins may have an additional C-terminal helix .