SII-SWORD/CoKE huggingface dataset:
Orn/Lys/Arg decarboxylase, N-terminal (OKR_de-COase_N)
Type: Domain

This domain has a flavodoxin-like fold, and is termed the "wing" domain because of its position in the overall 3D structure. Ornithine decarboxylase from Lactobacillus 30a (L30a OrnDC,

) is representative of the large, pyridoxal-5'-phosphate-dependent decarboxylases that act on lysine, arginine or ornithine. The crystal structure of the L30a OrnDC has been solved to 3.0 A resolution. Six dimers related by C6 symmetry compose the enzymatically active dodecamer (approximately 10
6
Da). Each monomer of L30a OrnDC can be described in terms of five sequential folding domains. The amino-terminal domain, residues 1 to 107, consists of a five-stranded β-sheet termed the "wing" domain. Two wing domains of each dimer project inward towards the centre of the dodecamer and contribute to dodecamer stabilisation .

Proteins containing this domain include the ornithine decarboxylase, the lysine decarboxylase and the biodegradative arginine decarboxylase.
PapG, chaperone-binding (PapG_chaper-bd_C)
Type: Domain

PapG, the adhesin of the P-pili, is situated at the tip and is only a minor component of the whole pilus structure. A two-domain structure has been postulated for PapG; a carbohydrate binding N terminus and chaperone binding C terminus (this domain). The chaperone-binding domain is highly conserved, and is essential for the correct assembly of the pili structure when aided by the chaperone molecule PapD .
PapG, carbohydrate-binding domain (PapG_carb-bd_N)
Type: Domain

PapG, the adhesin of the P-pili, is situated at the tip and is only a minor component of the whole pilus structure. A two-domain structure has been postulated for PapG; a carbohydrate binding N terminus (this domain) and chaperone binding C terminus. The carbohydrate-binding domain interacts with the receptor glycan .

There are 3 PapG alleles, class I-III, which bind to different receptor isotypes, GbO3, GbO4, and GbO5, respectively .
Penicillin-binding protein, dimerisation domain (PBP_dimer)
Type: Domain

This entry represents the N terminus domain of Class B High Molecular Weight Penicillin-Binding Proteins. Its function has not been precisely defined, but is strongly implicated in PBP polymerisation. The domain forms a largely disordered "sugar tongs" structure.
Protein of unknown function DUF1759 (DUF1759)
Type: Family

This is a small family of proteins of unknown function.
Peptidase N2 (Peptidase_N2)
Type: Family

The asparagine endopeptidases are all autocatalytic endopeptidases utilizing Asn at position P1. Cleavage occurs as a consequence of cyclization of the Asn residue .

This group of peptidases belongs to the MEROPS family N2 (clan NA). In the Nudaurelia capensis omega virus capsid protein the residues that form the catalytic dyad in the active site are Glu103 and Asn570. The cleavage mediated by the enzyme is an autolytic one, and the catalytic Asn is also the P1 residue in the cleavage site, Asn570-|-Phe571 releasing a 74-residue fragment from the C terminus of the coat protein. This cleavage occurs during the late stages of virion assembly. Heterologous expression of the coat protein gene of tetravirus in a baculovirus system results in the spontaneous assembly of virus-like particles (VLPs) that remain uncleaved when purified at neutral pH .
Dipeptidyl-peptidase 3 (Dipeptidyl-peptase3)
Type: Family

This entry represents dipeptidyl peptidase 3 (

), the best characterised member of Peptidase family M49. The dipeptidyl peptidase III aminopeptidases are zinc-dependent enzymes that cleave dipeptides from the N-terminal of peptides consisting of four or more amino acids and have a broad specificity. The active site residues occur in the motif HEXXXH which coordinates a single zinc ion via the histidines residues and the glutamic acid acts as a base in peptide hydrolysis . It has been determined a second linear motif in these enzymes, EEXR(K)AE(D), in which the second glutamic acid residue is involved in zinc coordination in the active site .
Outer membrane porin, bacterial (OM_porin_bac)
Type: Family

This family contains bacterial outer membrane porins with serine protease activity . The serine peptidase domain belongs to MEROPS peptidase family S43 (clan PA(S)).
Peptidase S48, DNA-binding transcriptional activator HetR (Pept_S48_HetR)
Type: Family

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

This group of serine peptidases, which includes HetR, are associated with heterocystous cyanobacteria and belong to MEROPS peptidase family S48 (clan S-). HetR is a DNA-binding serine-type protease required for heterocyst differentiation in heterocystous cyanobacteria under conditions of nitrogen deprivation. Mutation of HetR from of Anabaena sp. (strain PCC 7120) by site-specific mutagenesis of Ser-152 showed that this residue was one of the peptidase active site residues. It was suggested that peptidase activity might be needed for repression of HetR overproduction under conditions of nitrogen deprivation . Modification of Cys-48 prevented disulphide-bond formation and homodimerisation of HetR and DNA-binding. The homodimer of HetR binds the promoter regions of hetR, hepA, and patS, suggesting a direct control of the expression of these genes by HetR. The pentapeptide RGSGR, which is present at the C terminus of PatS, blocks heterocyst formation, inhibits the DNA binding of HetR and prevents hetR up-regulation .
Peptidase S51 (Peptidase_S51)
Type: Family

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

This group of serine peptidases belong to MEROPS peptidase family S51 (clan PC(S)). The type example being dipeptidase E (alpha-aspartyl dipeptidase) from Escherichia coli. The family contains alpha-aspartyl dipeptidases (dipeptidase E) and cyanophycinases.

The three-dimensional structure of Salmonella typhimurium aspartyl dipeptidase, peptidase E has been determine at 1.2-A resolution. The structure of this 25kDa enzyme consists of two mixed β-sheets forming a V, flanked by six α-helices. The active site contains a Ser-His-Glu catalytic triad and is the first example of a serine peptidase/protease with a glutamate in the catalytic triad. The active site Ser is located on a strand-helix motif reminiscent of that found in alpha/beta-hydrolases, but the polypeptide fold and the organisation of the catalytic triad differ from those of the known serine proteases. This enzyme appears to represent a new example of convergent evolution of peptidase activity .

Alpha-aspartyl dipeptidase hydrolyses dipeptides containing N-terminal aspartate residues, asp-|-xaa. It does not act on peptides with N-terminal Glu, Asn or Gln, nor does it cleave isoaspartyl peptides. In the cyanobacteria, cyanophycinase is an exopeptidase that catalyses the hydrolytic cleavage of multi-l-arginyl-poly-l-aspartic acid (cyanophycin; a water- insoluble reserve polymer) into aspartate-arginine dipeptides.
Peptidase S58, DmpA (Peptidase_S58_DmpA)
Type: Family

This group of serine peptidases belong to MEROPS peptidase family S58 (DmpA aminopeptidase family, clan PE). The protein fold of the peptidase unit for members of this family resembles that of archaean proteasome subunit B, the type example of clan PB. The type example is aminopeptidase DmpA from Ochrobactrum anthropi. This family also contains proteins that have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for the catalytic activity of peptidases in the family.

L-aminopeptidase D-Ala-esterase/amidase (DmpA) from O. anthropi releases the N-terminal L and/or D-Ala residues from peptide substrates. This is the only known enzyme to liberate N-terminal amino acids with both D and L stereospecificity. DmpA active form is an alphabeta heterodimer, which results from a putative autocatalytic cleavage of an inactive precursor polypeptide. DmpA shows structural homology to N-terminal nucleophile (Ntn) hydrolase family members, and may work by a similar catalytic mechanism, however their secondary structure elements differ significantly .
Pullulanase, carbohydrate-binding module 41 (CBM41_pullulanase)
Type: Domain

This entry repreesents the family 41 carbohydrate-binding module from pullulanase-like enzymes.

Pullulanases are a group of starch-debranching enzymes, catalyzing the hydrolysis of the alpha-1,6-glucosidic linkages of alpha-glucans, preferentially pullulan. Pullulan is a polysaccharide in which alpha-1,4 linked maltotriosyl units are combined via an alpha-1,6 linkage. These enzymes are of importance in the starch industry, where they are used to hydrolyze amylopectin starch .

Pullulanases consist of multiple distinct domains, including a catalytic domain belonging to the glycoside hydrolase (GH) family 13 and carbohydrate-binding modules (CBM), including CBM41 . CBM41 domains themselves are known to have glycogen/starch binding functions .
Small ribosomal subunit protein uS5, C-terminal (Ribosomal_uS5_C)
Type: Domain

This entry represents the C-terminal of the ribosomal protein uS5, which is related to the 30S ribosomal protein S5P from Sulfolobus acidocaldarius (

). Ribosomal protein uS5 is one of the proteins from the small ribosomal subunit. In Escherichia coli, uS5 is known to be important in the assembly and function of the 30S ribosomal subunit. Mutations in uS5 have been shown to increase translational error frequencies.
Protein of unknown function DUF308, membrane (DUF308_memb)
Type: Repeat

This represents a group of short repeats that occurs in a limited number of membrane proteins. It may divide further in short repeats of around 7-10 residues of the pattern G-#-X(2)-#(2)-X (#=hydrophobic) .
Plectin/eS10, N-terminal (Plectin_eS10_N)
Type: Domain

This domain is found at the N terminus of some isoforms of the cytoskeletal muscle protein plectin as well as the eukaryotic small ribosomal subunit protein eS10. This domain may be involved in RNA binding.
Small hydrophobic protein (SHP)
Type: Family

The small hydrophobic integral membrane protein, SH (previously designated 1A) is found to have a variety of glycosylated forms . This protein is a component of the mature respiratory syncytial virion where it may form complexes and appears to play a structural role.
Sic protein repeat (Sic)
Type: Repeat

Serotype M1 group A Streptococcus strains cause epidemic waves of human infections. This 30 aa repeat occurs in the sic protein, an extracellular protein (streptococcal inhibitor of complement) that inhibits human complement .
Sorting nexin, N-terminal (Sorting_nexin_N)
Type: Domain

Sorting nexins (SNXs) are hydrophilic molecules that are localised in the cytoplasm and have the potential for membrane association either through their lipid-binding PX domains (

) or through protein-protein interactions with membrane-associated protein complexes . Indeed, several of the SNXs require several targeting motifs for their appropriate cellular localisation. In almost every case studied, mammalian SNXs can be shown to have a role in protein sorting, with the most commonly used experimental model being plasma-membrane receptor endocytosis and sorting through the endosomal pathway. However, it is equally probable that SNXs sort vesicles that are not derived from the plasma membrane, and have a function in the accurate targeting of these vesicles and their cargo.

The N-terminal domain appears to be specific to sorting nexins 1 and 2. SNX1 and SNX2 are members of the retromer complex involved in protein sorting within the endocytic pathway . SNX1 is both membrane-associated and cytosolic, where it probably exists as a tetramer in large protein complexes and may hetero-oligomerize with SNX2.
MHYT domain (MHYT_dom)
Type: Domain

The MHYT domain is an about 190-residue domain, which was named after its conserved amino acid pattern. The MHYT domain consists of six predicted transmembrane (TM) segments, connected by short arginine-rich cytoplasmic loops and periplasmic loops that are also rich in charged amino acid residues. Three of its TM segments have a very similar amino acid sequence motif with highly conserved methionine, histidine and tyrosine residues located near the outer face of the cytoplasmic membrane.

The MHYT domain has been found in several phylogenetically distant bacteria, either as a separate, single domain protein, or fused to a LytTR-type DNA-binding helix-turn-helix, or fused to signaling domains, such as histidine kinase, GGDEF, EAL, and PAS. It has been proposed that the MHYT domain serves as a sensor domain in some bacterial two-component signal transduction systems as well as in a variety of other bacterial proteins. A model of the membrane topology of the MHYT domain indicates that its conserved residues could coordinate one or two copper ions, suggesting a role in sensing oxygen, CO or NO .
Sulfotransferase (Sulfotransferase)
Type: Family

This entry consists of a number of carbohydrate sulphotransferases that transfer sulphate to carbohydrate groups in glycoproteins and glycolipids. These include:

Carbohydrate sulphotransferases 8 and 9, which transfer sulphate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans . They function in the biosynthesis of glycoprotein hormones lutropin and thyrotropin, by mediating sulphation of their carbohydrate structures.

Carbohydrate sulphotransferase 10, which transfers sulphate to position 3 of the terminal glucuronic acid in both protein- and lipid-linked oligosaccharides . It directs the biosynthesis of the HNK-1 carbohydrate structure, a sulphated glucuronyl-lactosaminyl residue carried by many neural recognition molecules, which is involved in cell interactions during ontogenetic development and in synaptic plasticity in the adult.

Carbohydrate sulphotransferases 11 - 13, which catalyze the transfer of sulphate to position 4 of the GalNAc residue of chondroitin . The orthologue in
Caenorhabditis elegans
is known as carbohydrate sulfotransferase chst-1 . Chondroitin sulphate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. Some, thought not all, of these enzymes also transfer sulphate to dermatan.

Carbohydrate sulphotransferase D4ST1, which transfers sulphate to position 4 of the GalNAc residue of dermatan sulphate .

Heparan sulphate 2-O-sulphotransferase (HS2ST). Heparan sulphate (HS) is a co-receptor for a number of growth factors, morphogens, and adhesion proteins. HS biosynthetic modifications may determine the strength and outcome of HS-ligand interactions. Mice that lack HS2ST undergo developmental failure only after midgestation,the most dramatic effect being the complete failure of kidney development .

Heparan-sulphate 6-O-sulphotransferase (HS6ST), which catalyses the transfer of sulphate from adenosine 3'-phosphate, 5'-phosphosulphate to the 6th position of the N -sulphoglucosamine residue in heparan sulphate .

Chondroitin 6-sulphotransferase catalyses the transfer of sulphate to position 6 of the N-acetylgalactosamine residue of chondroitin .
Tomato bushy stunt virus (TBSV), p22, movement protein (TBSV_p22)
Type: Family

Two small nested genes (p19 and p22) are located near the 3' end of the genome of tomato bushy stunt virus (TBSV) -the p19 gene encodes a soluble protein, whereas the p22 gene specifies a membrane-associated protein. p22 is required for cell-to-cell movement in all plants tested .
Transcription factor, TCP (Transcription_factor_TCP)
Type: Family

The TCP transcription factor family was named after: teosinte branched 1 (tb1, Zea mays (Maize)) , cycloidea (cyc) (Antirrhinum majus) (Garden snapdragon) and PCF in rice (Oryza sativa) . The TCP proteins code for structurally related proteins implicated in the evolution of key morphological traits . However, the biochemical function of CYC and TB1 proteins remains to be demonstrated. One of the conserved regions is predicted to form a non-canonical basic-Helix-Loop-Helix (bHLP) structure. This domain is also found in two rice DNA-binding proteins, PCF1 and PCF2, where it has been shown to be involved in DNA-binding and dimerization.

This family of transcription factors are exclusive to higher plants. They can be divided into two groups, TCP-C and TCP-P, that appear to have separated following an early gene duplication event . This duplication event may have led to functional divergence and it has been proposed that that the TCP-P subfamily are transcriptional repressors, while the TPC-C subfamily are transcription activators .
Dynein light chain Tctex-1 like (Tctex-1-like)
Type: Family

Tctex-1 is a dynein light chain. Dynein translocates rhodopsin-bearing vesicles along microtubules and it has been shown that Tctex-1 can bind to the cytoplasmic tail of rhodopsin for retrograde or apical transport . An efficient vectorial transport system must be required to deliver large numbers of newly synthesised rhodopsin molecules (~10
7
molecules per day per photoreceptor) to the base of the outer segment of the photoreceptor, Tctex-1 may well play a role in this process. C-terminal rhodopsin mutations responsible for retinitis pigmentosa inhibit the interaction between Tctex-1 and rhodopsin, which may be the molecular basis of retinitis pigmentosa .

In the mouse, the chromosomal location and pattern of expression of Tctex-1 make it a candidate for involvement in male sterility .

This entry also includes Topoisomerase I damage affected protein 2 (TDA2) whose crystal structure revealed that it belongs to the dynein light chain family. It is part of the endocytic machinery and required for normal internalisation of native cargo in yeast .
Terminase small subunit (Terminase_ssu)
Type: Family

Packaging of double-stranded viral DNA concatemers requires interaction of the prohead with virus DNA. This process is mediated by a phage-encoded DNA recognition and terminase protein. The terminase enzymes described so far, which are hetero-oligomers composed of a small and a large subunit, do not have a significant level of sequence homology. The small terminase subunit is thought to form a nucleoprotein structure that helps to position the terminase large subunit at the packaging initiation site . The small terminase protein is essential for the initial recognition of viral DNA and regulates the motor's ATPase and nuclease activities during DNA translocation and for switching between viral DNA replication and packaging. DNA packaging in tailed bacteriophages and in evolutionarily related herpesviruses is controlled by a viral-encoded terminase. The terminase complex characterised in Bacillus subtilis bacteriophages SF6 and SPP1 consists of two proteins: G1P and G2P .
Mitochondrial pyruvate carrier (MPC)
Type: Family

This entry represents the mitochondrial pyruvate carrier proteins, including Mpc 1/2 and their homologues. They mediate the uptake of pyruvate into mitochondria . In humans, Mpc1 and Mpc2 associate to form an ~150-kilodalton complex in the inner mitochondrial membrane .
RapZ-like family (RapZ-like)
Type: Family

This entry represents RapZ family. RapZ plays a central role in RNA-mediated regulation of amino-sugar metabolism. It is a RNA-binding protein that recruits the major endoribonuclease RNase E to sRNAs GlmZ . Bacterial small RNAs (sRNAs) regulate diverse cellular processes; GlmY and GlmZ are sRNAs that act hierarchically to activate mRNA glmS, which encodes glucosamine-6-phosphate (GlcN6P) synthase.

RapZ is composed of two domains . The N-terminal domain is similar to P-loop nucleotide/nucleoside kinases whereas the C-terminal domain share similarity with a domain found at C terminus of phosphofructokinases. The C-terminal domain of RapZ is sufficient to bind RNA but on its own is incapable in mediating GlmZ processing.
Anhydro-N-acetylmuramic acid kinase (Anhydro_N_Ac-Mur_kinase)
Type: Family

This entry represents the enzyme Anhydro-N-acetylmuramic acid kinase, predominantly found in bacteria. This protein catalyses the specific phosphorylation of 1,6-anhydro-N-acetylmuramic acid (anhMurNAc) with the simultaneous cleavage of the 1,6-anhydro ring, generating MurNAc-6-P. It is also required for the utilisation of anhMurNAc, either imported from the medium, or derived from its own cell wall murein, and in so doing plays a role in cell wall recycling .

This family also includes Levoglucosan kinase from the oleaginous yeast Lipomyces starkeyi, which catalyses the transfer of a phosphate group from ATP to levoglucosan (1,6-anhydro-beta-D-glucopyranose, LG) to yield glucose 6-phosphate in the presence of magnesium ion and ATP .