SII-SWORD/CoKE huggingface dataset:
Chloramphenicol phosphotransferase-like (CPT)
Type: Family

The members of this family are all similar to chloramphenicol 3-O phosphotransferase (CPT,

) expressed by Streptomyces venezuelae. Chloramphenicol (Cm) is a metabolite produced by this bacterium that can inhibit ribosomal peptidyl transferase activity and therefore protein production. By transferring a phosphate group to the C-3 hydroxyl group of Cm, CPT inactivates this potentially lethal metabolite .
Copper amine oxidase-like, N-terminal (Cu_amine_oxidase-like_N)
Type: Domain

Amine oxidases (AO) are enzymes that catalyse the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. There are two classes of amine oxidases: flavin-containing (

) and copper-containing (

). Copper-containing AO act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor :

RCH
2
NH
2
+ H
2
O + O
2
= RCHO + NH
3
+ H
2
O
2

Copper-containing amine oxidases are found in bacteria, fungi, plants and animals. In prokaryotes, the enzyme enables various amine substrates to be used as sources of carbon and nitrogen . In eukaryotes they have a broader range of functions, including cell differentiation and growth, wound healing, detoxification and cell signalling .

The copper amine oxidases occur as mushroom-shaped homodimers of 70-95kDa, each monomer containing a copper ion and a covalently bound redox cofactor, topaquinone (TPQ). TPQ is formed by post-translational modification of a conserved tyrosine residue. The copper ion is coordinated with three histidine residues and two water molecules in a distorted square pyramidal geometry, and has a dual function in catalysis and TPQ biogenesis. The catalytic domain is the largest of the 3-4 domains found in copper amine oxidases, and consists of a β sandwich of 18 strands in two sheets. The active site is buried and requires a conformational change to allow the substrate access. The two N-terminal domains share a common structural fold, its core consisting of a five-stranded antiparallel β-sheet twisted around an α-helix. The D1 domains from the two subunits comprise the stalk, of the mushroom-shaped dimer, and interact with each other but do not pack tightly against each other .

This entry represents a domain found at the N-terminal of certain copper amine oxidases, as well as in related proteins such as cell wall hydrolase and N-acetylmuramoyl-L-alanine amidase. This domain consists of a five-stranded antiparallel β-sheet twisted around an α helix .
D-aminopeptidase, domain B (DAP_B_dom)
Type: Domain

D-aminopeptidase (

) is a dimeric enzyme with each monomer being composed of three domains. Domain B is organised to form a β barrel made up of eight antiparallel β strands. It is connected to domain A, the catalytic domain, by an eight-residue sequence, and also interacts with both domains A and C via non-covalent bonds. Domain B probably functions in maintaining domain C in a good position to interact with the catalytic domain .
Dendritic cell-specific transmembrane protein-like (DC_STAMP-like)
Type: Domain

This group of sequences is similar to a region of the dendritic cell-specific transmembrane protein (DC-STAMP,

). This is thought to be a novel receptor protein that shares no identity with other multimembrane-spanning proteins . It is thought to have seven putative transmembrane regions , two of which are found in the region featured in this family. DC-STAMP is also described as having potential N-linked glycosylation sites and a potential phosphorylation site for PKC , but these are not conserved.
Archaeal Type IV pilin, N-terminal (Pilin_N_archaeal)
Type: Domain

This entry represents the N-terminal domain of archaeal pilins, which play important roles in surface adhesion. Sequences covered by this domain are not mixed up with sequences having such an extremely high sequence conservation as described in .
Arf3-interacting protein 1, N-terminal domain (Afi1_N)
Type: Domain

This domain occurs at the N terminus of Afi1 (Arf3-interacting protein 1), a protein necessary for vesicle trafficking in yeast. This domain is the interacting region of the protein which binds to Arf3. Afi1 is distributed asymmetrically at the plasma membrane and is required for polarized distribution of Arf3 but not of an Arf3 guanine nucleotide-exchange factor, Yel1p. However, Afi1 is not required for targeting of Arf3 or Yel1p to the plasma membrane. Afi1 functions as an Arf3 polarization-specific adapter and participates in development of polarity . Although Arf3 is the homologue of human Arf6 it does not function in the same way, not being necessary for endocytosis or for mating factor receptor internalisation. In the S phase, however, it is concentrated at the plasma membrane of the emerging bud. Because of its polarized localisation and its critical function in the normal budding pattern of yeast, Arf3 is probably a regulator of vesicle trafficking, which is important for polarized growth.
Protein of unknown function DUF1634 (DUF1634)
Type: Family

This family contains many hypothetical bacterial and archaeal proteins. A few members of this family are annotated as being putative transmembrane proteins, and the region in question in fact contains many hydrophobic residues.
Protein of unknown function DUF1635 (DUF1635)
Type: Family

The members of this family include sequences that are parts of hypothetical proteins expressed by plant species. The region in question is about 170 amino acids long.
Protein of unknown function DUF1636 (DUF1636)
Type: Family

The sequences featured in this family are derived from a number of hypothetical prokaryotic proteins. The region in question is approximately 130 amino acids long.
Cysteine oxygenase/2-aminoethanethiol dioxygenase (PCO/ADO)
Type: Family

This entry includes cysteine oxidases (PCOs) from plants and 2-aminoethanethiol dioxygenases (ADOs) from animals. PCOs oxidize N-terminal cysteine residues, thus preparing the protein for N-end rule pathway-mediated proteasomal degradation . ADO is responsible for endogenous cysteamine dioxygenase activity .
Protein of unknown function DUF1642 (DUF1642)
Type: Family

This entry represents a group of phage and prophage proteins whose function is not known.
Protein of unknown function DUF1644 (DUF1644)
Type: Family

This family consists of sequences found in a number of hypothetical plant proteins of unknown function. The region of interest contains nine highly conserved cysteine residues and is approximately 160 amino acids in length, which probably represent a zinc-binding domain.
Domain of unknown function DUF1648 (DUF1648)
Type: Domain

This domain is found in proteins expressed by bacterial and archaeal species. One such protein is immunity protein SdpI (

) from Bacillus subtilis, which provides protection for the cell against the toxic effects of its own SdpC killing factor, and also functions as a receptor/signal transduction protein .
CopG-like ribbon-helix-helix domain (RHH_5)
Type: Domain

This entry represents a domain found in a group of bacterial proteins that form a ribbon-helix-helix fold. This fold occurs in many examples of bacterial antitoxins .
Protein of unknown function DUF1666 (DUF1666)
Type: Family

These sequences are derived from hypothetical plant proteins of unknown function. The region in question is approximately 250 residues long.
Protein of unknown function DUF1677, Oryza sativa (DUF1668_ORYSA)
Type: Family

The hypothetical proteins found in this family are expressed by Oryza sativa (Rice) and are of unknown function.
Protein of unknown function DUF1670 (DUF1670)
Type: Family

The hypothetical eukaryotic proteins found in this family are of unknown function.
Protein of unknown function DUF1672 (DUF1672)
Type: Family

This family is composed of hypothetical bacterial proteins of unknown function.
Protein of unknown function DUF1673, Methanosarcina species (DUF1673_METspp)
Type: Family

This family contains hypothetical proteins of unknown function found in Methanosarcina acetivorans and Methanosarcina mazei.
Succinate dehydrogenase assembly factor 4 (SDHF4)
Type: Family

This entry includes SDHF4 from animals, Sdh8 from budding yeasts and some uncharacterised proteins from bacteria. Sdh8 is required for assembly of succinate dehydrogenase (SDH). It interacts with the catalytic Sdh1 subunit in the mitochondrial matrix, facilitating its association with Sdh2 and the subsequent assembly of the SDH holocomplex .
Protein of unknown function DUF1677, plant (DUF1677_pln)
Type: Family

The sequences found in this family are all derived from hypothetical plant proteins of unknown function. The region features a number of highly conserved cysteine residues.
Uncharacterised oxidoreductase Dhs-27 (Dhs-27)
Type: Family

This region is found in a number of Caenorhabditis elegans and Caenorhabditis briggsae proteins, in one case (

) as a repeat. In many of the family members, this region is associated with the CHK region described by SMART as being found in zinc finger-C4 and HLH domain-containing kinases.
Non-reducing end beta-L-arabinofuranosidase-like, GH127 catalytic domain (Beta-AFase-like_GH127_cat)
Type: Domain

This entry represents the catalytic domain of Non-reducing end beta-L-arabinofuranosidase from Bifidobacterium longum (Beta-AFase) and similar proteins widespread among all cellular organisms that belong to the glycoside hydrolase family 127 (GH127). This domain folds into an (α/α)6 barrel .

Beta-AFase, an unusual beta-L-arabinofuranosidase enzyme (

), releases l-arabinose from the l-arabinofuranose (Araf)-beta1,2-Araf disaccharide and also transglycosylates 1-alkanols with retention of the anomeric configuration. Terminal beta-l-arabinofuranosyl residues have been found in arabinogalactan proteins from a number of different plant species. Beta-l-Arabinofuranosyl linkages with 1-4 arabinofuranosides are also found in the sugar chains of extensin and solanaceous lectins, hydroxyproline (Hyp)2-rich glycoproteins that are widely observed in plant cell wall fractions. The critical residue for catalytic activity is Glu-338, in a ET/SCAS sequence context .
PAT complex subunit CCDC47 (CCDC47)
Type: Family

This family represents CCDC47 proteins which are a component of the PAT complex, an endoplasmic reticulum (ER)-resident membrane multiprotein complex that facilitates multi-pass membrane proteins insertion into membranes . The PAT complex, formed by CCDC47 and Asterix proteins, acts as an intramembrane chaperone by directly interacting with nascent transmembrane domains (TMDs), releasing its substrates upon correct folding, and is needed for optimal biogenesis of multi-pass membrane proteins . WDR83OS/Asterix is the substrate-interacting subunit of the PAT complex, whereas CCDC47 (

) is required to maintain the stability of WDR83OS/Asterix . The PAT complex favors the binding to TMDs with exposed hydrophilic amino acids within the lipid bilayer and provides a membrane-embedded partially hydrophilic environment in which TMD1 binds .

CCDC47 is associated with various membrane-associated processes and is a component of a ribosome-associated ER translocon complex involved in multi-pass membrane protein transport into the ER membrane and biogenesis . It is also involved in the regulation of calcium ion homeostasis in the ER , being also required for proper protein degradation via the ERAD (ER-associated degradation) pathway .

This entry also includes the uncharacterised proteins YNR021W from S. cerevisiae, C2G5.01 from S. pombe and At5g49945 from Arabidopsis.
Gryzun, putative trafficking through Golgi (Gryzun)
Type: Domain

The proteins featured in this family are all eukaryotic, and many of them are annotated as being Gryzun. Gryzun is distantly related to, but distinct from, the Trs130 subunit of the TRAPP complex but is absent from S. cerevisiae. RNAi of human Gryzun (

) blocks Golgi exit. Thus the family is likely to be involved with trafficking of proteins through membranes, perhaps as part of the TRAPP complex .
Protein of unknown function DUF1685 (DUF1685)
Type: Family

The members of this family are hypothetical eukaryotic proteins of unknown function. The region in question is approximately 100 amino acid residues long.
Putative redox protein Fmp46 (Fmp46)
Type: Family

This entry includes a group of putative redox proteins from fungi, including Fmp46 from yeasts .
ERp29, N-terminal (ERp29_N)
Type: Domain

ERp29 (

) is a ubiquitously expressed endoplasmic reticulum protein, and is involved in the processes of protein maturation and protein secretion in this organelle . The protein exists as a homodimer, with each monomer being composed of two domains. The N-terminal domain featured in this family is organised into a thioredoxin-like fold that resembles the a domain of human protein disulphide isomerase (PDI) . However, this domain lacks the C-X-X-C motif required for the redox function of PDI; it is therefore thought that the function of ERp29 is similar to the chaperone function of PDI . The N-terminal domain is exclusively responsible for the homodimerisation of the protein, without covalent linkages or additional contacts with other domains .

The Drosophila homologue, Wind, is the product of windbeutel, an essential gene in the development of dorsal-ventral patterning. Wind is required for correct targeting of Pipe, a Golgi-resident type II transmembrane protein with homology to 2-O-sulfotransferase .
Excisionase-like (Excisionase-like)
Type: Domain

The phage-encoded excisionase protein (Xis,

) is involved in excisive recombination by regulating the assembly of the excisive intasome and by inhibiting viral integration. It adopts an unusual winged-helix structure in which two α helices are packed against two extended strands. Also present in the structure is a two-stranded anti-parallel β-sheet, whose strands are connected by a four-residue wing. During interaction with DNA, helix alpha2 is thought to insert into the major groove, while the wing contacts the adjacent minor groove or phosphodiester backbone. The C-terminal region of Xis is involved in interaction with phage-encoded integrase (Int), and a putative C-terminal α helix may fold upon interaction with Int and/or DNA .
Sdz-33, F-box domain (F-box_Sdz-33)
Type: Domain

This entry represents an F-box domain

in Sdz-33, Sdz-15, Hecw-1
and uncharacterised proteins in Caenorhabditis elegans.

F-box associated domain-containing protein SDZ-33 (Sdz-33) functions as the substrate recognition component of the E3 ubiquitin-protein ligase complex, mediating the ubiquitination and subsequent proteasomal degradation of target proteins such as MDL-1 . It plays a positive role in axon regeneration by targeting MDL-1 for ubiquitin-mediated degradation, likely reducing the levels of MDL-1-MXL-1 heterodimers. This reduction allows free MXL-1 to form complexes with TDPT-1, thereby inhibiting TDPT-1-dependent sumoylation of ETS-4 .

E3 ubiquitin-protein ligase HECW-1 (Hecw-1) is believed to function in the OLL neurones of the anterior ganglion to inhibit avoidance behaviour towards microbial pathogens such as Pseudomonas aeruginosa . While C. elegans still displays avoidance by vacating a P. aeruginosa lawn within 24 hours, HECW-1 likely acts by inhibiting the neuropeptide receptor NPR-1, thereby modulating the behavioural response to pathogenic bacteria .
Formiminotransferase, N-terminal subdomain (Formiminotransferase_N)
Type: Domain

The formiminotransferase (FT) domain of formiminotransferase-cyclodeaminase (FTCD) forms a homodimer, with each protomer being comprised of two subdomains. The formiminotransferase domain has an N-terminal subdomain that is made up of a six-stranded mixed β-pleated sheet and five α-helices, which are arranged on the external surface of the β-sheet. This, in turn, faces the β-sheet of the C-terminal subdomain to form a double β-sheet layer. The two subdomains are separated by a short linker sequence, which is not thought to be any more flexible than the remainder of the molecule. The substrate is predicted to form a number of contacts with residues found in both the N-terminal and C-terminal subdomains .

This entry represents the N-terminal subdomain of the formiminotransferase domain.
GDP-fucose pyrophosphorylase domain (GDP_fucose_pyrophosphorylase)
Type: Domain

This entry represents the fucose pyrophosphorylase domain found at the N-terminal of the bifunctional L-Fucokinase/GDP-Fucose Pyrophosphorylase (FKP) enzymes such as FKGP from Arabidopsis and L-fucose kinase from animals . In fucose-1-phosphate guanylyltransferase from human, this is the main domain of the protein, which catalyses the formation of GDP-L-fucose from GTP and L-fucose-1-phosphate and functions as a salvage pathway to reutilise L-fucose arising from the turnover of glycoproteins and glycolipids . In the salvage pathway, cells use fucose from the extracellular or lysosomal sources to synthesise GDP-fucose. First, the fucokinase catalyses the formation of fucose-1-phosphate from fucose, with ATP consumption and then, the GDP-fucose pyrophosphorylase (GFPP) uses fucose-1-phosphate and GTP to synthesise GDP-fucose. I some members, the two independent catalytic reactions in the salvage pathway can be accomplished by a single enzyme, the fucokinase/GDP-fucose pyrophosphorylase (FKP). The structure of the bifunctional enzyme from Bacteroides fragilis have been determined .
L-fucose isomerase, N-terminal-1 (Fucose_iso_N1)
Type: Domain

Proteins containing this domain are similar to L-fucose isomerase expressed by Escherichia coli (

,

). This enzyme corresponds to glucose-6-phosphate isomerase in glycolysis, and converts an aldo-hexose to a ketose to prepare it for aldol cleavage. The enzyme is a hexamer, with each subunit being wedge-shaped and composed of three domains. Both domains 1 and 2 contain central parallel β-sheets with surrounding α helices. Domain 1 demonstrates the β-α-β-α-β Rossman fold. The active centre is shared between pairs of subunits related along the molecular three-fold axis, with domains 2 and 3 from one subunit providing most of the substrate-contacting residues, and domain 1 from the adjacent subunit contributing some other residues .
L-fucose isomerase, N-terminal-2 (Fucose_isomerase_N2)
Type: Domain

Proteins containing this domain are similar to L-fucose isomerase expressed by Escherichia coli (

,

). This enzyme corresponds to glucose-6-phosphate isomerase in glycolysis, and converts an aldo-hexose to a ketose to prepare it for aldol cleavage. The enzyme is a hexamer, with each subunit being wedge-shaped and composed of three domains. Both domains 1 and 2 contain central parallel β-sheets with surrounding α-helices. The active centre is shared between pairs of subunits related along the molecular three-fold axis, with domains 2 and 3 from one subunit providing most of the substrate-contacting residues .
Intron Large complex component GCFC2-like (GCFC2-like)
Type: Family

This entry includes GCFC2 and PAXBP1 from humans, and ILP1 from Arabidopsis thaliana. GCFC2 is involved in pre-mRNA splicing through regulating spliceosome C complex formation . ILP1 and its orthologue in mouse have been shown to be repressors of cyclin genes. In Arabidopsis, all members of the CYCLINA2 family are repressed, and in mouse cyclin A2. The CYCLINA2 cyclins control endoreduplication, in which DNA is replicated but the cell cyle continues without cell division leading to polyploidy. ILP1 therefore regulates endoreduplication through control of CYCA2 expression in Arabidopsis . ILP1 has been shown to be required for efficient splicing .

It's worth noting that GCFC2 was originally thought to be a DNA-binding transcriptional repressor. However, later work showed that the original sequence was a chimera and that the DNA-binding activity was derived from the incorrect N-terminal sequence .
GCK domain (GCK_dom)
Type: Domain

This domain is found in proteins carrying other domains known to be involved in intracellular signalling pathways indicating that it might also be involved in these pathways. It has 4 highly conserved cysteine residues, suggesting that it can bind zinc ions. Moreover, it is found repeated in some members of this entry (such as

), which may indicate that these domains are able to interact with one another, raising the possibility that it mediates heterodimerisation.
Gp58-like (Gp58)
Type: Domain

Sequences found in this entry are derived from a number of bacteriophage and prophage proteins. They are similar to gp58 (

), a minor structural protein of Lactococcus delbrueckii bacteriophage LL-H .
HipA-like, C-terminal (HipA-like_C)
Type: Domain

The members of this entry are similar to a region close to the C terminus of the HipA protein expressed by various bacterial species (for example

). This protein is known to be involved in high-frequency persistence to the lethal effects of inhibition of either DNA or peptidoglycan synthesis . When expressed alone, it is toxic to bacterial cells , but it is usually tightly associated with HipB , and the HipA-HipB complex may be involved in autoregulation of the hip operon. The hip proteins may be involved in cell division control and may interact with cell division genes or their products . The domain is also found in the serine/threonine-protein kinase CtkA from
Helicobacter pylori
which is important in induction of host inflammation by inducing release of cytokines such as TNF-alpha and IL-8 by phosphorylation of NF-kappa-B .
Integrin beta subunit, tail (Integrin_bsu_tail)
Type: Domain

This entry represents the tail domain of the integrin beta subunit. It forms a four-stranded β-sheet that contains parallel and antiparallel strands and faces an α helix found at the N terminus of this domain . Interactions between the α-helix and the β-sheet are mostly hydrophobic and involve a disulphide bond. The rear of the β sheet is covered with a long A-B loop.

Integrin beta subunits consist of an extracellular domain with a head region, a stalk/leg section, a transmembrane domain, and a cytoplasmic tail. The head region contains a β-I-like domain inserted into a hybrid domain, connected to a plexin-semaphorin-integrin (PSI) [

]. C-terminal to the PSI domain is an A-domain, which has been predicted to adopt a Rossmann fold similar to that of the alpha subunit, but with additional loops between the second and third β strands. This domain is referred to as VWA [

]. Many VWA domains bind metal ions via a noncontiguous sequence motif called metal ion-dependent adhesion site (MIDAS) . This is followed by a β-subunit stalk/leg section that contains four cysteine-rich integrin epidermal growth factor-like (I-EGF) modules [

], [

],

]. Finally, this is followed by the β-ankle TM domain [

] and a cytoplasmic tail [

] .

Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton, and activate many intracellular signalling pathways . An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a VWA domain inserted within the integrin domain at the N-terminal.

Most integrins recognise relatively short peptide motifs and, in general, require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits . There are at least 18 types of alpha and 8 types of beta subunits recognised in humans . Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule . Each association of alpha and beta subunits has its binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activates or inhibits another.