SII-SWORD/CoKE huggingface dataset:
Hydroxyethylthiazole kinase (Hyethyz_kinase)
Type: Family

Most microorganisms and plants can synthesise thiamin de novo . In this de novo pathway, the thiazole and pyrimidine moieties of thiamin are made separately and coupled together to form thiamin phosphate. For the thiazole moiety, 4-methyl-5-(2-hydroxyethyl)thiazole (THZ), the key salvage step is phosphorylation to give 4-methyl-5-(2-phosphonooxyethyl)thiazole (THZ-P). The enzyme hydoxyethylthiazole kinase (

) is responsible for this step. Hydoxyethylthiazole kinase is encoded by thiM in Escherichia coli and other bacteria , and by the C-terminal region of bifunctional proteins in some cases, such as Saccharomyces cerevisiae, in which the N-terminal domain corresponds to the bacterial thiamine-phosphate pyrophosphorylase (

), ThiE . ThiM constitutes a potential target for pro-drug compounds for antibacterial drug development.

The Arabidopsis and maize genomes encode homologues of ThiM .
Ets domain (Ets_dom)
Type: Domain

Transcription factors are protein molecules that bind to specific DNA sequences in the genome, resulting in the induction or inhibition of gene transcription . The ets oncogene is such a factor, possessing a region of 85-90 amino acids known as the ETS (erythroblast transformation specific) domain . This domain is rich in positively-charged and aromatic residues, and binds to purine-rich segments of DNA. The ETS domain has been identified in other transcription factors such as PU.1, human erg, human elf-1, human elk-1, GA binding protein, and a number of others . It is generally localized at the C terminus of the protein, with the exception of ELF-1, ELK-1, ELK-3, ELK-4 and ERF where it is found at the N terminus.

NMR-analysis of the structure of the Ets domains revealed that it contains three α-helices (1-3) and four-stranded β-sheets (1-4) arranged in the order α1-β1-β2-α2-α3-β3-β4 forming a winged helix-turn-helix (wHTH) topology . The third α-helix is responsive to contact to the major groove of the DNA. Different members of the Ets family proteins display distinct DNA binding specificities. The Ets domains and the flanking amino acid sequences of the proteins influence the binding affinity, and the alteration of a single amino acid in the Ets domain can change its DNA binding specificities.
Cell wall mannoprotein PIR repeat (Yeast_PIR_rpt)
Type: Repeat

A number of yeast cell wall glycoproteins are characterised by the presence of tandem repeats of a region of 18 to 19 residues .
Coagulation factor 5/8, C-terminal domain (FA58C)
Type: Domain

Blood coagulation factors V and VIII contain a C-terminal, twice repeated, domain of about 150 amino acids, which is called F5/8 type C, FA58C, or C1/C2- like domain. In the Dictyostelium discoideum (Slime mold) cell adhesion protein discoidin, a related domain, named discoidin I-like domain, DLD, or DS, has been found which shares a common C-terminal region of about 110 amino acids with the FA58C domain, but whose N-terminal 40 amino acids are much less conserved. Similar domains have been detected in other extracellular and membrane proteins In coagulation factors V and VIII the repeated domains compose part of a larger functional domain which promotes binding to anionic phospholipids on the surface of platelets and endothelial cells . The C-terminal domain of the second FA58C repeat (C2) of coagulation factor VIII has been shown to be responsible for phosphatidylserine-binding and essential for activity . It forms an amphipathic α-helix, which binds to the membrane . FA58C contains two conserved cysteines in most proteins, which link the extremities of the domain by a disulphide bond . A further disulphide bond is located near the C-terminal of the second FA58C domain in MFGM

.

+------------------------------------------------------------------------+
| +-+ |
| | | |
CxPLGxxQITASxxxxxRLxxxWxxxxWxxxxxxQGxxxxxxxxxxxxGNxxxxxxxxxxRxPxcxcLRxExGC

'C': conserved cysteine involved in a disulphide bond.
'c': cysteine involved in a disulphide bond in MFGM

.
'x': any amino acid.
upper case letters: conserved residues.
3,4-dihydroxy-2-butanone 4-phosphate synthase, RibB (DHBP_synthase_RibB)
Type: Family

3,4-dihydroxy-2-butanone 4-phosphate synthase (

) (DHBP synthase) (RibB) catalyses the conversion of D-ribulose 5-phosphate to formate and 3,4-dihydroxy-2-butanone 4-phosphate, the latter serving as the biosynthetic precursor for the xylene ring of riboflavin . In Photobacterium leiognathi, the riboflavin synthesis genes ribB (DHBP synthase), ribE (riboflavin synthase), ribH (lumazone synthase) and ribA (GTP cyclohydrolase II) all reside in the lux operon . RibB is sometimes found as a bifunctional enzyme with GTP cyclohydrolase II that catalyses the first committed step in the biosynthesis of riboflavin (

). No sequences with significant homology to DHBP synthase are found in the metazoa.
Primosome PriB/single-strand DNA-binding (Primosome_PriB/ssb)
Type: Family

The Escherichia coli single-strand binding protein (gene ssb), also known as the helix-destabilising protein, is a protein of 177 amino acids. It binds tightly, as a homotetramer, to single-stranded DNA (ss-DNA) and plays an important role in DNA replication, recombination and repair. Closely related variants of SSB are encoded in the genome of a variety of large self-transmissible plasmids. SSB has also been characterised in bacteria such as Proteus mirabilis or Serratia marcescens. Eukaryotic mitochondrial proteins that bind ss-DNA and are probably involved in mitochondrial DNA replication are structurally and evolutionary related to prokaryotic SSB.

Primosomal replication protein N (PriB) is a specialist protein from bacteria that binds single-stranded DNA at the primosome assembly site (PAS). The primosome is a mobile multiprotein replication priming complex which is believed to operate on the lagging-strand template at the E. coli DNA replication fork . The primosome consists of one monomer of PriC and DnaT, two monomers of PriA, two dimers of PriB and one hexamer of DnaB .
Major intrinsic protein (MIP)
Type: Family

The major intrinsic protein (MIP) family is large and diverse, possessing over 100 members that form transmembrane channels. These channel proteins function in water, small carbohydrate (e.g., glycerol), urea, NH3, CO2 and possibly ion transport, by an energy independent mechanism. They are found ubiquitously in bacteria, archaea and eukaryotes.

The MIP family contains two major groups of channels: aquaporins and glycerol facilitators. The known aquaporins cluster loosely together as do the known glycerol facilitators. MIP family proteins are believed to form aqueous pores that selectively allow passive transport of their solute(s) across the membrane with minimal apparent recognition. Aquaporins selectively transport water (but not glycerol) while glycerol facilitators selectively transport glycerol but not water. Some aquaporins can transport NH3 and CO2. Glycerol facilitators function as solute nonspecific channels, and may transport glycerol, dihydroxyacetone, propanediol, urea and other small neutral molecules in physiologically important processes. Some members of the family, including the yeast FPS protein and tobacco NtTIPA may transport both water and small solutes.
Proteasome alpha-subunit, N-terminal domain (Proteasome_asu_N)
Type: Domain

The proteasome (or macropain) (

) is a multicatalytic proteinase complex in eukaryotes and archaea, and in some bacteria, that is involved in an ATP/ubiquitin-dependent non-lysosomal proteolytic pathway. In eukaryotes the 20S proteasome is composed of 28 distinct subunits which form a highly ordered ring-shaped structure (20S ring) of about 700kDa. Proteasome subunits can be classified on the basis of sequence similarities into two groups, alpha (A) and beta (B). The proteasome consists of four stacked rings composed of α/β/β/α subunits. There are seven different alpha subunits and seven different beta subunits . Three of the seven beta subunits are peptidases, each with a different specificity. Subunit beta1c (MEROPS identifier T01.010) has a preference for cleaving glutaminyl bonds ("peptidyl-glutamyl-like" or "caspase-like"), subunit beta2c (MEROPS identifier T01.011) has a preference for cleaving arginyl and lysyl bonds ("trypsin-like"), and subunit beta5c (MEROPS identifier T01.012) cleaves after hydrophobic amino acids ("chymotrypsin-like") . The proteasome subunits are related to N-terminal nucleophile hydrolases, and the catalytic subunits have an N-terminal threonine nucleophile.

Subunits that belong to the A group are proteins of from 210 to 290 amino acids. They are classified as non-peptidase homologues in MEROPS peptidase family T1 (clan PB(T)).
Papillomavirus E2, C-terminal (Papillomavirus_E2_C)
Type: Domain

E2 is an early regulatory protein found in the dsDNA papillomaviruses. The viral genome is a 7.9-kb circular DNA that codes for at least eight early and two late (capsid) proteins. The products of the early genes E6 and E7 are oncoproteins that destabilise the cellular tumour suppressors p53 and pRB. The product of the E1 gene is a helicase necessary for viral DNA replication. The products of the E2 gene play key roles in the regulation of viral gene transcription and DNA replication. During early stages of viral infection, the E2 protein represses the transcription of the oncogenes E6 and E7, reintroduction of E2 into cervical cancer cell-lines leads to repression of E6/E7 transcription, stabilisation of the tumour suppressor p53, and cell-cycle arrest at the G1 phase of the cell cycle. E2 can also induce apoptosis by a p53-independent mechanism.
Copper ion binding protein (Cu-bd)
Type: Family

Proteins in this family are copper ion-binding proteins, including copper chaperone CopZ and COP-associated protein (COPP). They contain a conserved 30-residue HMA domain, which has been found in a number of other heavy metal transport or detoxification proteins . CopZ is a chaperone that serves for the intracellular sequestration and transport of Cu+, and delivers copper ions to the copper-transporting ATPase CopA . COPP is part of a cation-transporting system which is associated with copper export out of the cells .
Proteinase inhibitor I14, hirudin (Prot_inh_hirudin)
Type: Family

The hirudin family are proteinase inhibitors that belong to MEROPS inhibitor family I14, clan IM. Hirudin is a potent thrombin inhibitor secreted by the salivary glands of the Hirudinaria manillensis (Buffalo leech) and Hirudo medicinalis (Medicinal leech) . It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen.
5-Hydroxytryptamine 5B receptor (5HT5B_rcpt)
Type: Family

5-hydroxytryptamine (5-HT) or serotonin, is a neurotransmitter that it is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS). It is implicated in a vast array of physiological and pathophysiological pathways. Receptors for 5-HT mediate both excitatory and inhibitory neurotransmission, and modulate the release of many neurotransmitters including glutamate, GABA, dopamine, epinephrine/norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin and cortisol. In the CNS, 5-HT receptors can influence various neurological processes, such as aggression, anxiety and appetite and, as a, result are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics and anorectics .

The 5-HT receptors are grouped into a number of distinct subtypes, classified according to their antagonist susceptibilities and their affinities for 5-HT. With the exception of the 5-HT3 receptor, which is a ligand-gated ion channel , all 5-HT receptors are members of the rhodopsin-like G protein-coupled receptor family , and they activate an intracellular second messenger cascade to produce their responses.

This entry represents the 5-HT5B receptor. As yet it has only been experimentally characterised in rodents, but not in humans . The 5HT5B protein has a structure consistent with GPCRs, however, the human 5-HT5B gene does not encode a functional protein, because its coding sequence is interrupted by stop codons . It is believed that the function of the 5HT5B receptor has been replaced in humans by some other subclass of 5-HT receptor . In the CNS, it is found in the habenula, hippocampus and inferior olivary of rat brains . Known agonists for 5-HT5B include ergotamine and LSD, and known antagonists include methiothepin. 5-HT5B receptors may play a role in sleep and serve as an presynaptic serotonin autoreceptor .
DNA mismatch repair protein MutS, C-terminal (DNA_mismatch_repair_MutS_C)
Type: Domain

This entry represents the C-terminal domain found in proteins in the MutS family of DNA mismatch repair proteins. The C-terminal region of MutS is comprised of the ATPase domain and the HTH (helix-turn-helix) domain, the latter being involved in dimer contacts. Yeast MSH3 , bacterial proteins involved in DNA mismatch repair, and the predicted protein product of the Rep-3 gene of mouse share extensive sequence similarity. Human MSH has been implicated in non-polyposis colorectal carcinoma (HNPCC) and is a mismatch binding protein.

Mismatch repair contributes to the overall fidelity of DNA replication and is essential for combating the adverse effects of damage to the genome. It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex. The post-replicative Mismatch Repair System (MMRS) of Escherichia coli involves MutS (Mutator S), MutL and MutH proteins, and acts to correct point mutations or small insertion/deletion loops produced during DNA replication . MutS and MutL are involved in preventing recombination between partially homologous DNA sequences. The assembly of MMRS is initiated by MutS, which recognises and binds to mispaired nucleotides and allows further action of MutL and MutH to eliminate a portion of newly synthesized DNA strand containing the mispaired base . MutS can also collaborate with methyltransferases in the repair of O(6)-methylguanine damage, which would otherwise pair with thymine during replication to create an O(6)mG:T mismatch . MutS exists as a dimer, where the two monomers have different conformations and form a heterodimer at the structural level . Only one monomer recognises the mismatch specifically and has ADP bound. Non-specific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. Mismatch binding induces ATP uptake and a conformational change in the MutS protein, resulting in a clamp that translocates on DNA.
Polycystic kidney disease type 1 protein (PC1)
Type: Family

Polycystin-1 (PC1) plays a critical role in renal tubule diameter control. Mutations in the polycystin-1 gene cause cyst formation in human autosomal dominant polycystic kidney disease . It may serve as a cell surface signaling receptor at cell-cell/cell-matrix junctions and as a mechano-sensor in renal primary cilia that activates signalling pathways involved in renal tubular differentiation .

Polycystin-1 contains an REJ (receptor for egg jelly) domain and a GPS (G protein-coupled receptor proteolytic site) domain in its N-terminal extracellular region (ectodomain). It can be cleaved into N-terminal fragment (NTF) and C-terminal fragment (CTF) at the GPS domain . The GPS cleavage may play an important role for the biological function of PC1 .
Tektins (Tektins)
Type: Family

This entry represents the tektins family. Its members include tektin 1-5, tektin-B1.
Sushi/SCR/CCP domain (Sushi_SCR_CCP_dom)
Type: Domain

The extracellular sushi domain is characterised by a consensus sequence spanning ~60 residues containing four invariant cysteine residues forming two disulfide-bridges (I-III and II-IV), a highly conserved tryptophan, and conserved glycine, proline, and hydrophobic residues . Sushi domains are known to be involved in many recognition processes, including the binding of several complement factors to fragments C3b and C4b . The sushi domain is also known as the complement control protein (CCP) module or the short consensus repeat (SCR).
Acetyl-CoA carboxylase carboxyl transferase, beta subunit (Acetyl_CoA_COase_Trfase_b_su)
Type: Family

Fatty acid synthesis involves a set of reactions, starting with carboxylation of acetyl-CoA to malonyl-CoA. This is an irreversible reaction, catalysed by the acetyl-CoA carboxylase complex (

); a heterohexamer of biotin carboxyl carrier protein, biotin carboxylase and two non-identical carboxyl transferase subunits (alpha and beta) in a 2:2 association .
The reaction involves two steps:

Biotin carrier protein + ATP + HCO
3
-
= Carboxybiotin carrier protein + ADP + P
i

Carboxybiotin carrier protein + Acetyl-CoA = Malonyl-CoA + Biotin carrier protein

In the first step, biotin carboxylase catalyses the carboxylation of the carrier protein to form an intermediate. Next, the transcarboxylase complex transfers the carboxyl group from the intermediate to acetyl-CoA forming malonyl-CoA.
Large ribosomal subunit protein eL15 (Ribosomal_eL15)
Type: Family

A number of eukaryotic and archaebacterial ribosomal proteins can be grouped on the basis of sequence similarities . One of these families consists of:

Mammalian eL15.

Insect eL15.

Plant eL15.

Yeast YL10 (L13) (Rp15r).

Archaebacterial eL15 (known as L15e).

These proteins have about 200 amino acid residues.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
NADH:ubiquinone/plastoquinone oxidoreductase, chain 3 (NADH_UbQ/plastoQ_OxRdtase_su3)
Type: Family

This family contains chain 3 of the NADH-ubiquinone / plastoquinone oxidoreductase.
Islet amyloid polypeptide (IAPP)
Type: Family

Islet amyloid polypeptide (IAPP) (also known as diabetes-associated peptide or amylin) is a pancreatic islet hormone that is stored with insulin in beta cell granules . IAPP has a propensity to form islet cell-disrupting amyloid deposits, and opposes the action of insulin in peripheral tissues; the peptide may therefore have a significant role in the development of Type 2 diabetes mellitus . It is thought that an intrinsic structural motif of IAPP, which only occurs in species that develop age-associated or Type 2 diabetes (e.g., Homo sapiens (Human) and Felis silvestris catus (Cat)), is linked to its amyloidogenicity . IAPP is a short, 37-residue peptide. The hormone selectively inhibits insulin-stimulated glucose utilisation and glycogen deposition in muscle, but does not affect adipocyte glucose metabolism. The sequences of amylin and the calcitonin gene-related peptides (CGRPs) show strong similarity: both peptides have a conserved N-terminal intramolecular disulphide bridge, and both have a C-terminal glycine, which suggests that the C-terminal residue of amylin, like that of CGRP, is amidated . Near- and far-UV CD spectra of human alpha CGRP, analogues and fragments of CGRP, and amylin have been recorded in aqueous solution and in trifluoro- ethanol/water mixtures . The peptides were shown to contain significant amounts of α-helix in aqueous solution, this amount increasing upon addition of TFE. Amylin appears to contain less helix than CGRP .
Helix-hairpin-helix motif (HhH_motif)
Type: Conserved_site

The HhH motif is a stretch of approximately 20 amino acids that is present in prokaryotic and eukaryotic non-sequence-specific DNA binding proteins . The HhH motif is similar to, but distinct from, the HtH motif. Both of these motifs have two helices connected by a short turn. In the HtH motif the second helix binds to DNA with the helix in the major groove. This allows the contact between specific base and residues throughout the protein. In the HhH motif the second helix does not protrude from the surface of the protein and therefore cannot lie in the major groove of the DNA. Crystallographic studies suggest that the interaction of the HhH domain with DNA is mediated by amino acids located in the strongly conserved loop (L-P-G-V) and at the N-terminal end of the second helix . This interaction could involve the formation of hydrogen bonds between protein backbone nitrogens and DNA phosphate groups . The structural difference between the HtH and HhH domains is reflected at the functional level: whereas the HtH domain, found primarily in gene regulatory proteins and binds DNA in a sequence specific manner, the HhH domain is rather found in proteins involved in enzymatic activities and binds DNA with no sequence specificity .
FAD-dependent glycerol-3-phosphate dehydrogenase (G3P_DH_FAD-dep)
Type: Family

FAD-dependent glycerol-3-phosphate dehydrogenase (G3PDH;

) catalyses the conversion of glycerol-3-phosphate into dihydroxyacetone phosphate:

sn-glycerol-3-phosphate + a quinone = glycerone phosphate + a quinol

Insulin exposure often stimulates G3PDH activity , and thus is key to reducing the effects of the disease diabetes. In obese people, where insulin resistance has been demonstrated, the amount of G3PDH has been shown to be correspondingly lower than that in normal weight people . In bacteria it is associated with the utilisation of glycerol coupled to respiration. In Escherichia coli and Haemophilus influenzae, two isozymes are known: one expressed under anaerobic conditions (gene glpA) and one in aerobic conditions (gene glpD). In eukaryotes, a mitochondrial form of GPD participates in the glycerol phosphate shuttle in conjunction with an NAD-dependent cytoplasmic GPD (

) . This mechanism is responsible for the preservation of a redox balance . In this environment, the enzyme has been recorded to increase activity in the presence of calcium . These enzymes are proteins of about 60 to 70 Kd which contain a probable FAD-binding domain in their N-terminal extremity. The mammalian enzyme differs from the bacterial or yeast proteins by having an EF-hand calcium-binding region (see

) in its C-terminal extremity.
Rhabdovirus nucleocapsid (Rhabdo_ncapsid)
Type: Domain

The Nucleocapsid (N) Protein is said to have a 'tight' structure. The carboxyl end of the N-terminal domain possesses an RNA binding domain. Sequence alignments show 2 regions of reasonable conservation, approx. 64-103 and 201-329 . A whole functional protein is required for encapsidation to take place .