SII-SWORD/CoKE huggingface dataset:
Autophagy-related protein 27 (Autophagy-rel_prot_27)
Type: Family

Autophagy is a degradative transport pathway that delivers cytosolic proteins to the lysosome (vacuole) and is induced by starvation . Cytosolic proteins appear inside the vacuole enclosed in autophagic vesicles. Autophagy significantly differs from other transport pathways by using double membrane layered transport intermediates, called autophagosomes . The breakdown of vesicular transport intermediates is a unique feature of autophagy . Autophagy can also function in the elimination of invading bacteria and antigens .

There are more than 25 AuTophaGy-related (ATG) genes that are essential for autophagy, although it is still not known how the autophagosome is made. Atg9 is a potential membrane carrier to deliver lipids that are used to form the vesicle. Atg27 is another transmembrane protein, and is a cycling protein .

It acts as an effector of VPS34 phosphatidylinositol 3-phosphate kinase signalling and regulates the cytoplasm to vacuole transport (Cvt) vesicle formation. It is also required for autophagy-dependent cycling of ATG9.
Elongation factor 1 beta central acidic region, eukaryote (EF-1_beta_acid_region_euk)
Type: Domain

Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome . EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.

Elongation factor EF1B (also known as EF-Ts or EF-1beta/gamma/delta) is a nucleotide exchange factor that is required to regenerate EF1A from its inactive form (EF1A-GDP) to its active form (EF1A-GTP). EF1A is then ready to interact with a new aminoacyl-tRNA to begin the cycle again. EF1B is more complex in eukaryotes than in bacteria, and can consist of three subunits: EF1B-alpha (or EF-1beta), EF1B-gamma (or EF-1gamma) and EF1B-beta (or EF-1delta) .

This region is found in the centre of the beta subunits of Elongation factor-1.
Seminal vesicle protein repeat (Seminal_vesicle_protein_repeat)
Type: Repeat

The rat seminal vesicle contains six major androgen-dependent secretory proteins referred to as SVS I-VI. The SVS I-III proteins appear to be components of the rat copulatory plug, with the SVS II protein being the major component .

This entry represents a repeat that is found in seminal vesical proteins.
Oligosaccaryltransferase (Oligosaccaryltransferase)
Type: Family

Ost4 is a very short, approximately 30 residues, enzyme found from fungi to vertebrates. It is a member of the ER oligosaccaryltansferase complex,

, that catalyses the asparagine-linked glycosylation of proteins. It appears to be an integral membrane protein that mediates the en bloc transfer of a pre-assembled high-mannose oligosaccharide onto asparagine residues of nascent polypeptides as they enter the lumen of the rough endoplasmic reticulum.
DNA polymerase lambda, fingers domain (DNA_pol_lambd_fingers_domain)
Type: Domain

DNA polymerases catalyse the addition of dNMPs onto the 3-prime ends of DNA chains. There is a general polymerase fold consisting of three subdomains that have been likened to the fingers, palm, and thumb of a right hand. This entry represents the central three-helical region of DNA polymerase lambda referred to as the F and G helices of the fingers domain. Contacts with DNA involve this conserved helix-hairpin-helix motif in the fingers region which interacts with the primer strand. This motif is common to several DNA binding proteins and confers a sequence-independent interaction with the DNA backbone .
PhoD-like phosphatase, metallophosphatase domain (PhoD-like_MPP)
Type: Domain

Alkaline phosphatase D (PhoD) catalyses the reaction: phosphate monoester + H(2)O = an alcohol + phosphate. PhoD is similar to Ca(2+)-dependent phospholipase D , which catalyses the hydrolysis of the ester bond between the phosphatidic acid and alcohol moieties of phospholipids .

PhoD (also known as alkaline phosphatase D/APaseD in Bacillus subtilis) is a secreted phosphodiesterase encoded by phoD of the Pho regulon in Bacillus subtilis. PhoD homologs are found in prokaryotes, eukaryotes, and archaea. PhoD contains a twin arginine (RR) motif and is transported by the Tat (Twin-arginine translocation) translocation pathway machinery (TatAyCy) . Proteins containing this domain also includes the Fusarium oxysporum Fso1 protein .
Neuromodulin, N-terminal (Neuromodulin_N)
Type: Domain

This entry represents the neuromodulin N-terminal domain.

Neuromodulin (also known as growth-associated protein 43 or GAP-43) is a component of the motile growth cones. It is membrane protein whose expression is widely correlated with successful axon elongation . It is a crucial component of an effective regeneration response in the nervous system . Although its function is uncertain, the N-terminal region is well conserved and contains both a calmodulin binding domain, and sites for acylation, membrane attachment and protein kinase C phosphorylation. Structure predictions suggest that the C-terminal region may exist as an extended, negatively-charged rod with some similarity to the side arms of neurofilaments, indicating that the biological role of neuromodulin may depend on its ability to form a dynamic membrane-cytoplasm-calmodulin complex .
GTP-binding protein TrmE, N-terminal (GTP-bd_TrmE_N)
Type: Domain

This entry represents the N-terminal domain of tRNA modification GTPase MnmE (also known as TrmE) and similar proteins found in bacteria and eukaryotes. MnmE is a guanine nucleotide-binding protein involved in the modification of the wobble position of certain tRNAs that binds and hydrolyses GTP. TrmE actively participates in the formylation reaction of uridine and regulates the ensuing hydrogenation reaction of a Schiff's base intermediate. This domain consists of five β-strands and three α-helices and is necessary for mediating dimer formation within the protein. It is homologous to the tetrahydrofolate-binding domain of N,N-dimethylglycine oxidase and indeed binds formyl-tetrahydrofolate .
Disulphide bond isomerase, DsbC/G, N-terminal (DiS-bond_isomerase_DsbC/G_N)
Type: Domain

This is the N-terminal domain of the disulphide bond isomerase DsbC and DsbG.

The whole molecule is V-shaped, where each arm is a DsbC monomer of two domains linked by a hinge; and the N-termini of each monomer join to form the dimer interface at the base of the V, so are vital for dimerisation . DsbC is required for disulphide bond formation and functions as a disulphide bond isomerase during oxidative protein-folding in bacterial periplasm. It also has chaperone activity .
Fumarase C, C-terminal (Fumarase_C_C)
Type: Domain

Fumarase C catalyses the stereo-specific interconversion of fumarate to L-malate as part of the Krebs cycle. The full-length protein forms a tetramer with visible globular shape. FumaraseC_C is the C-terminal 65 residues referred to as domain 3. The core of the molecule consists of a bundle of 20 α-helices from the five-helix bundle of domain 2. The projections from the core of the tetramer are generated from domains 1 and 3 of each subunit . This entry does not appear to be part of either the active site or the activation site but is helical in structure forming a little bundle.
2'-5'-oligoadenylate synthetase 1, domain 2/C-terminal (2-5-oligoAdlate_synth_1_dom2/C)
Type: Domain

This is the largely α-helical, C-terminal half of 2'-5'-oligoadenylate synthetase 1, being described as domain 2 of the enzyme and homologous to a tandem ubiquitin repeat. It carries the region of enzymic activity between residues 320 and 344 at the extreme C-terminal end . Oligoadenylate synthetases are antiviral enzymes that counteract viral attack by degrading viral RNA. The enzyme uses ATP in 2'-specific nucleotidyl transfer reactions to synthesise 2'.5'-oligoadenylates, which activate latent ribonuclease, resulting in degradation of viral RNA and inhibition of virus replication . This domain is often associated with

.
AMP nucleoside phosphorylase, N-terminal (AMP_nucleoside_Pase_N)
Type: Domain

This is the N-terminal domain of bacterial AMP nucleoside phosphorylase (AMNp). The N- and C-termini form distinct domains which intertwine with each other to form a stable monomer which associates with five other monomers to yield the active hexamer. The N terminus consists of a long helix and a four-stranded sheet with a novel topology. The C terminus binds the nucleoside whereas the N terminus acts as the enzymatic regulatory domain. AMNp (

) catalyses the hydrolysis of AMP to form adenine and ribose 5-phosphate. thereby regulating intracellular AMP levels .
Beta-galactosidase, domain 2 (Betagal_dom2)
Type: Domain

This entry represents the second domain of the five-domain beta-galactosidase enzyme that altogether catalyses the hydrolysis of beta(1-3) and beta(1-4) galactosyl bonds in oligosaccharides as well as the inverse reaction of enzymatic condensation and trans-glycosylation. This domain is made up of 16 antiparallel β-strands and an α-helix at its C terminus. The fold of this domain appears to be unique. In addition, the last seven strands of the domain form a subdomain with an immunoglobulin-like (I-type Ig) fold in which the first strand is divided between the two β-sheets. In penicillin spp this strand is interrupted by a 12-residue insertion which forms an additional edge-strand to the second β-sheet of the sub-domain. The remainder of the second domain forms a series of β-hairpins at its N terminus, four strands of which are contiguous with part of the Ig-like sub-domain, forming in total a seven-stranded antiparallel β-sheet.
Branched-chain alpha-ketoacid dehydrogenase kinase/Pyruvate dehydrogenase kinase, N-terminal (BCDHK/PDK_N)
Type: Domain

Catabolism and synthesis of leucine, isoleucine and valine are finely balanced, allowing the body to make the most of dietary input but removing excesses to prevent toxic build-up of their corresponding keto-acids. Regulating the activity of the branched-chain alpha-ketoacid dehydrogenase (BCDH) complex is the primary means by which these processes are coordinated. BCDH kinase regulates BCDH by phosphorylation, thereby inactivating it when synthesis is required.
Zinc finger, C3HC4 RING-type (Znf_C3HC4_RING-type)
Type: Domain

The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid . Many proteins containing a RING finger play a key role in the ubiquitination pathway .

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
Knr4/Smi1-like domain (Knr4/Smi1-like_dom)
Type: Domain

This domain is found in the yeast cell wall assembly regulator Smi1 (also known as Knr4) .
Domain of unknown function DUF1989 (DUF1989)
Type: Domain

This domain can be found in TMAO demethylase (Tdm) from M. silvestris and R. pomeroyi. Tdm catalyzes the first step in TMAO degradation . Proteins containing this domain are mostly uncharacterised.
Domain of unknown function DUF1990 (DUF1990)
Type: Domain

This entry represents proteins that are functionally uncharacterised.
DnaJ homologue, subfamily C, member 28, conserved domain (DnaJ_homolog_subfam-C_membr-28)
Type: Domain

This entry represents a domain found in a group of sequences that may have a role in protein folding or as a chaperone. DnaJ is a member of the J-protein family, which are defined by the presence of a J domain that can regulate the activity of 70kDa heat-shock proteins . Some of the proteins in this entry contain a J domain.
Domain of unknown function DUF1995 (DUF1995)
Type: Domain

This entry includes proteins from bacteria and plants. This domain can be found in a chloroplastic protein, LOW PSII ACCUMULATION 3 (LPA3, At1g73060), from Arabidopsis. LPA3 is involved in assisting chlorophyll a binding protein psbC assembly within photosystem II (PSII) . This domain can also be found in some putative adenylate kinases, such as At5g35170 from Arabidopsis and Os08g0288200 from rice.
Mycobacteriophage D29, Gp19 (Mycophage_D29_Gp19)
Type: Family

This entry is represented by Mycobacteriophage D29, Gp19 . The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
Bacteriophage phiJL001, Gp84, C-terminal (Phage_phiJL001_Gp84_C)
Type: Domain

This entry describes the C-terminal region of a family of proteins found almost exclusively in phage or in prophage regions of bacterial genomes, including the phage-like Rhodobacter capsulatus (Rhodopseudomonas capsulata) gene transfer agent, which packages DNA. An apparent exception is Wolbachia pipientis wMel, a bacterial endosymbiont of the fruit fly, which has several candidate phage-related genes physically separate from obvious prophage regions.
Ubiquitin-activating enzyme E1, C-terminal (Ub-activating_enz_E1_C)
Type: Domain

This domain is found at the C terminus of Ubiquitin-activating enzyme E1 proteins. It binds to E2 enzymes .
VTC domain (VTC_domain)
Type: Domain

This domain is found in the yeast vacuolar transport chaperone proteins VTC2, VTC3 and VTC4 . This domain is also found in a variety of bacterial proteins.
Iron-binding zinc finger, CDGSH type (FeS-contain_CDGSH-typ)
Type: Domain

This entry represents iron-sulphur domain containing proteins that have a CDGSH sequence motif (although the Ser residue can also be an Ala or Thr), and is found in proteins from a wide range of organisms with the exception of fungi. The CDGSH-type domain binds a redox-active pH-labile 2Fe-2S cluster. The conserved sequence C-X-C-X2-(S/T)-X3-P-X-C-D-G-(S/A/T)-H is a defining feature of this family .

CDGSH-type domains are found in mitoNEET, an iron-containing integral protein of the outer mitochondrian membrane (OMM). MitoNEET forms a dimeric structure with a NEET fold, and contains two domains: a β-cap region and a cluster-binding domain that coordinated two acid-labile 2Fe-2S clusters (one bound to each protomer) . The CDGSH iron-sulphur domain is oriented towards the cytoplasm and is tethered to the mitochondrial membrane by a more N-terminal domain found in higher vertebrates, (

) . The whole protein regulates oxidative capacity and may function in electron transfer, for instance in redox reactions with metabolic intermediates, cofactors and/or proteins localized at the OMM.
Phasin (Phasin)
Type: Domain

Phasins (or granule-associate proteins) are surface proteins found covering Polyhydroxyalkanoate (PHA) storage granules in bacteria. Polyhydroxyalkanoates are linear polyesters produced by bacterial fermentation of sugar or lipids for the purpose of storing carbon and energy, and are accumulated as intracellular granules by many bacteria under unfavorable conditions, enhancing their fitness and stress resistance . The layer of phasins stabilises the granules and prevents coalescence of separated granules in the cytoplasm and nonspecific binding of other proteins to the hydrophobic surfaces of the granules. For example, in Ralstonia eutropha (strain ATCC 17699/H16/DSM 428/Stanier 337) (Cupriavidus necator (strain ATCC 17699 / H16 / DSM 428 / Stanier 337)), the major surface protein of polyhydroxybutyrate (PHB) granules is phasin PhaP1(Reu), which occurs along with three homologues (PhaP2, PhaP3, and PhaP4) that have the capacity to bind to PHB granules but are present at minor levels . These four phasins lack a highly conserved domain but share homologous hydrophobic regions.

This entry describes a group of phasins that associate with polyhydroxyalkanoate (PHA) inclusions, the most common of which consist of polyhydroxybutyrate (PHB).
Xylulose 5-phosphate/Fructose 6-phosphate phosphoketolase, C-terminal (Xul5P/Fru6P_PKetolase_C)
Type: Domain

Phosphoketolases (PK) are key enzymes of the pentose phosphate pathway of heterofermentative and facultative homofermentative lactic acid bacteria and of the D-fructose 6-phosphate shunt of bifidobacteria. PK activity has been sporadically reported in other microorganisms including eukaryotic yeasts. Xylulose-5-phosphate/fructose-6-phosphate phosphoketolase is a thiamine diphosphate (ThdP)-dependent enzyme found in bacteria such as Bifidobacterium sp . This enzyme has dual-specificity with the following catalytic activities:

: xylose 5-P + Pi = acetyl-P + glyeraldehyde-3-P

: fructose-6-P + Pi = acetyl-P + erythrose-4-P

Phosphoketolases are distantly related to transketolases, e.g.

.
Xylulose 5-phosphate/Fructose 6-phosphate phosphoketolase, N-terminal (Xul5P/Fru6P_PKetolase_N)
Type: Domain

Phosphoketolases (PK) are key enzymes of the pentose phosphate pathway of heterofermentative and facultative homofermentative lactic acid bacteria and of the D-fructose 6-phosphate shunt of bifidobacteria. PK activity has been sporadically reported in other microorganisms including eukaryotic yeasts. Xylulose-5-phosphate/fructose-6-phosphate phosphoketolase is a thiamine diphosphate (ThdP)-dependent enzyme found in bacteria such as Bifidobacterium sp . This enzyme has dual-specificity with the following catalytic activities:

: xylose 5-P + Pi = acetyl-P + glyeraldehyde-3-P

: fructose-6-P + Pi = acetyl-P + erythrose-4-P

Phosphoketolases are distantly related to transketolases, e.g.

.
Protein of unknown function DUF1997 (DUF1997)
Type: Family

This family of proteins are functionally uncharacterised.
Sas10 C-terminal domain (Sas10_C_dom)
Type: Domain

Sas10 is an Essential subunit of U3-containing Small Subunit (SSU) processome complex involved in the production of the 18S rRNA and assembly of the small ribosomal subunit .
MrfA-like Zn-binding domain (MZB)
Type: Domain

This is the C-terminal MrfA (Mitomycin repair factor A, also known as YprA in Bacillus subtilis) Zn+2-binding domain (MZB, also referred to as DUF1998) which contains a conserved four-cysteine signature motif. These four Cys reside in a short coil between two α-helices and form a metal ion-binding site . This domain is frequently found at the C-terminal of ndNTPases, however, it is also found encoded in a standalone gene, downstream of putative helicase domain-encoding genes associated with bacterial anti-phage defense system DISARM. MrfA is a DNA helicase that supports repair of mitomycin C-induced DNA damage. MrfA homologues are widely distributed in bacteria and are also present in archaea, fungi and plants. The MrfA-homologue in yeast, Hrq1, also reduces mitomycin C sensitivity. Hrq1 has high similarity to human RecQ4 and was therefore assigned to the RecQ-like helicase family . MrfA homologues appear to be missing in Enterobacteria, however, certain pathogenic Escherichia coli and Salmonella strains harbour Z5898-like helicases with this domain .
Tex-like protein, N-terminal (Tex-like_N)
Type: Domain

This presumed domain is found at the N terminus of

. This protein defines a novel family of prokaryotic transcriptional accessory factors .
Pseudomurein-binding repeat (Pseudomurein-binding_repeat)
Type: Repeat

Methanothermobacter thermautotrophicus (Methanobacterium thermoformicicum) is a methanogenic Gram-positive microorganism with a cell wall consisting of pseudomurein. This repeat specifically binds to pseudomurein. This repeat is found at the N terminus of PeiW and PeiP which are pseudomurein binding phage proteins.
Imelysin-like domain (Imelysin-like)
Type: Domain

EfeO is an essential component of the EfeUOB operon which is highly conserved in bacteria. However, its biochemical function is unknown. EfeO contains an N-terminal cupredoxin (CUP)-like domain and C-terminal imelysin-like domain that may bind iron . Algp7, a member of the EfeO family of proteins from Sphingomonas sp. A1, is found to bind alginate at neutral pH, but does not contain the CUP domain, thus having a role that does not seem to be related to iron uptake . The imelysin-like domain of these proteins contains the GxHxxE sequence motif, suggesting a similar role, whereas in other imelysin-like proteins, such as IPPA from Psychrobacter arcticus, the histidine in the GxHxxE motif region is no longer conserved (GxxxxE), indicating a possible loss of enzymatic function or a change in substrate preference .
NurA domain (NurA_domain)
Type: Domain

This domain is found in several uncharacterised proteins and in NurA, a nuclease exhibiting both single-stranded endonuclease activity and 5'-3' exonuclease activity on single-stranded and double-stranded DNA from the hyperthermophilic archaeon Sulfolobus acidocaldarius .
Ribosome maturation protein SDO1/SBDS, central domain (SDO1/SBDS_central)
Type: Domain

This entry represents the central domain of proteins that are highly conserved in species ranging from archaea to vertebrates and plants . This entry contains several Shwachman-Bodian-Diamond syndrome (SBDS) proteins from both mouse and humans. Shwachman-Diamond syndrome (OMIM 260400) is an autosomal recessive disorder with clinical features that include pancreatic exocrine insufficiency, haematological dysfunction and skeletal abnormalities. It is characterised by bone marrow failure and leukemia predisposition.

Members of this entry play a role in RNA metabolism . In yeast, SBDS orthologue SDO1 is involved in the biogenesis of the 60S ribosomal subunit and translational activation of ribosomes. Together with the EF-2-like GTPase RIA1 (EfI1), it triggers the GTP-dependent release of TIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating TIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. This data links defective late 60S subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition .

The SBDS protein is composed of three domains. The N-terminal (FYSH,

) domain is the most frequent target for disease mutations and contains a novel mixed α/β-fold, the central domain (represented in this entry) consists of a three-helical bundle and the C-terminal domain (

) has a ferredoxin-like fold .