SII-SWORD/CoKE huggingface dataset:
Phosphoenolpyruvate carboxylase (PEP_COase)
Type: Family

Phosphoenolpyruvate carboxylase (PEPCase), an enzyme found in all multicellular plants, catalyses the formation of oxaloacetate from phosphoenolpyruvate (PEP) and a hydrocarbonate ion . This reaction is harnessed by C4 plants to capture and concentrate carbon dioxide into the photosynthetic bundle sheath cells. It also plays a key role in the nitrogen fixation pathway in legume root nodules: here it functions in concert with glutamine, glutamate and asparagine synthetases and aspartate amido transferase, to synthesise aspartate and asparagine, the major nitrogen transport compounds in various amine-transporting plant species .
Flagellar hook-length control protein-like, C-terminal (Flagellar_hook_control-like_C)
Type: Domain

This entry represents the C-terminal domain of the flagellar hook-length control protein FliK. This entry also includes YscP of the Yersinia type III secretion system, and equivalent proteins in other pathogenic bacterial type III secretion systems.

FliK controls the length of the flagellar hook. It detects when the flagellar hook substructure has reached its optimal length. Then, it terminates hook export and assembly and transmits a signal to begin filament export, the final stage in flagellar biosynthesis. The exact mechanism of how FliK achieves this is not known . FliK is a two-domain protein with the central portion of the sequence acting as a hinge or connector between the two .
Large ribosomal subunit protein bL35-like (Ribosomal_bL35-like)
Type: Family

This entry represents the large ribosomal subunit protein bL35, previously known as L35, a basic protein of 60 to 70 amino-acid residues . Like many basic polypeptides, it completely inhibits ornithine decarboxylase when present unbound in the cell, but the inhibitory function is abolished upon its incorporation into ribosomes . This family of ribosomal proteins includes proteins from bacteria, plant chloroplast, red algae chloroplasts and cyanelles. In plants it is a nuclear encoded gene product, which suggests a chloroplast-to-nucleus relocation during the evolution of higher plants .

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 .
Large ribosomal subunit protein eL20, eukaryotes (Ribosomal_eL20_eukaryotes)
Type: Family

This entry represent the 60S ribosomal protein eL20 (also known as L20 and previously known as 60S ribosomal protein L18a) from eukaryotes.

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 .
NYN domain (NYN)
Type: Domain

This NYN domain is found in Meiosis regulator and mRNA stability factor 1 (MARF1, also known as limkain-b1) and some bacterial sequences. The NYN domains are found in the eukaryotic proteins typified by the Nedd4-binding protein 1 and the bacterial YacP-like proteins. The NYN (for Nedd4-BP1, YacP-like Nuclease) domain shares a common protein fold with two other previously characterised groups of nucleases, namely the PIN (PilT N-terminal) and FLAP/5' --> 3' exonuclease superfamilies. These proteins share a common set of 4 acidic conserved residues that are predicted to constitute their active site. Based on the conservation of the acidic residues and structural elements it has been suggested that PIN and NYN domains are likely to bind only a single metal ion, unlike the FLAP/5' --> 3' exonuclease superfamily, which binds two metal ions . Based on conserved gene neighbourhoods the bacterial members are likely to be components of the processome/degradosome that process tRNAs or ribosomal RNAs.
Alkaline proteinase inhibitor/ Outer membrane lipoprotein Omp19 (Inh/Omp19)
Type: Domain

This entry represents the metalloprotease inhibitor I38, as well as the outer membrane lipoprotein Omp19.

This family of proteins represent monomeric serralysin inhibitors of about 125 residues, which interact with specific metalloprotease which are synthesised by serralysin secretors and characterised by being plant, insect and animal pathogens. It is probable that the serralysin inhibitors protect the host from proteolysis during export of the protease. The members of this family belong to MEROPS proteinase inhibitor family I38, clan IK.

X-ray crystallography of a complex between the Serratia marcescens protease, SmaPI, and the inhibitor of Erwinia chrysanthemi, Inh, reveals that Inh is folded into an eight-stranded b-barrel with an N-terminal trunk of 10 residues. Residues 1-5 occupy part of the extended active site of the proteinase, thereby preventing access of the substrate. Residues 6-10 form a linker that connects the N-terminal proteinase-binding peptide to the body of the b-barrel. The backbone carbonyl of Ser-1 interacts with the catalytic zinc; the Ser-2 side chain occupies the S1'-binding site and also forms a hydrogen bond to the carboxyl end of the catalytic Glu, whereas Leu-3 occupies the S2' recognition site. Penetration of the trunk region further than 5 residues into the substrate binding cleft appears to be prevented by the b-barrel, which itself interacts with the proteinase near its Met turn (19). Peptide mimetics of the trunk at concentrations up to about 100 mM do not inhibit the protease, demonstrating that the barrel is essential for inhibitory activity .

Structurally and functionally these inhibitors are closely related to the lipocalins, fatty acid-binding proteins, avidins and the enigmatic triabin. Together these five protein families constitute the calycin superfamily . The proteins are characterised by their high specificity for small hydrophobic molecules and by their ability to form complexes with soluble macromolecules either through intramolecular disulphides or protein-protein interactions .
Pyrimidine dimer DNA glycosylase, endonuclease V type (Pyr-dimer_DNAGlyclase_EndonucV)
Type: Family

Pyrimidine dimer DNA glycosylases are enzymes responsible for initiating the base excision repair pathway, excising pyrimidine dimers by hydrolysis of the glycosylic bond of the 5' pyrimidine, followed by the intra-pyrimidine phosphodiester bond . One such enzyme is T4 endonuclease V, an enzyme responsible for the first step of a pyrimidine-dimer-specific excision-repair pathway . Bacteriophage T4 that are deficient in these enzymes are extremely sensitive to UV.
Uncharacterised protein family UPF0597 (UPF0597)
Type: Family

This family consists of several hypothetical proteins of unknown function from bacteria and L-cysteine desulfidases from the archaea Methanocaldococcus .
Portal protein SPP1 Gp6-like (Portal_protein_SPP1_Gp6-like)
Type: Family

The bacteriophage portal protein forms a gateway, or portal, enabling DNA passage during packaging and ejection of the phage genome. It also forms the junction between the phage head (capsid) and the tail proteins . During SPP1 morphogenesis, Gp6 participates in the procapsid assembly reaction .

In the mature SPP1 virion, the portal protein, GP6, exists as a dodecamer, whereas recombinant SPP1 Gp6 has been shown to form 13-subunit assemblies .

This entry includes Bacillus phage SPP1-type portal proteins, Mycobacterium phage portal proteins and putative portal proteins of the Listeria phage A118-type.
Phage gp6-like head-tail connector protein (Phage_gp6-like_head-tail)
Type: Family

This family of proteins contain head-tail connector proteins related to gp6 from bacteriophage HK97 . The gp15 protein of Bacillus phage SPP1, for which the tertiary structure is known, is included in this entry .

This family contain head-tail connector proteins related to gp6 from bacteriophage HK97 . These proteins show similarities to the gp6 protein of phage HK97, and, probably, it is part of the head-tail connector by binding to the portal protein and to the tail completion protein . The bacteriophage HK97 gp6 protein is critical in the assembly of the connector, a specialized structure that serves as an interface for head and tail attachment, as well as a point at which DNA exits the head during infection by the bacteriophage . The gp15 protein of Bacillus phage SPP1, for which the tertiary structure is known, is included in this entry .
Protein of unknown function DUF697 (DUF697)
Type: Family

Proteins in this entry have no known function.
Polysaccharide biosynthesis domain (Polysacc_synth_dom)
Type: Domain

This entry includes PBDC1 protein from mammals and its homologues from fungi.

Protein PBDC1 homolog from S. cerevisiae also known as Ypl225w (Chp1, Chaperone 1 for eEF1A) functions as a co-translational chaperone by forming dual interactions with the eEF1A G domain nascent chain and the UBA domain of ribosome-bound nascent polypeptide-associated complex . This protein primes the eEF1A nascent chains for binding to GTP as part of a folding mechanism which is tightly coupled to chaperone recycling .
Oligosaccharyl transferase complex, subunit OST3/OST6 (OligosaccharylTrfase_OST3/OST6)
Type: Family

During N-linked glycosylation of proteins, oligosaccharide chains are assembled on the carrier molecule dolichyl pyrophosphate in the following order: 2 molecules of N-acetylglucosamine (GlcNAc), 9 molecules of mannose, and 3 molecules of glucose. These 14-residue oligosaccharide cores are then transferred to asparagine residues on nascent polypeptide chains in the endoplasmic reticulum (ER). As proteins progress through the Golgi apparatus, the oligosaccharide cores are modified by trimming and extension to generate a diverse array of glycosylated proteins .

The oligosaccharyl transferase complex (OST complex)

transfers 14-sugar branched oligosaccharides from dolichyl pyrophosphate to asparagine residues . The complex contains nine protein subunits: Ost1p, Ost2p, Ost3p, Ost4p, Ost5p, Ost6p, Stt3p, Swp1p, and Wbp1p, all of which are integral membrane proteins of the ER. The OST complex interacts with the Sec61p pore complex involved in protein import into the ER.

This entry represents subunits OST3 and OST6. OST3 is homologous to OST6 , and several lines of evidence indicate that they are alternative members of the OST complex. Disruption of both OST3 and OST6 causes severe underglycosylation of soluble and membrane-bound glycoproteins and a defect in the assembly of the complex. Hence, the function of these genes seems to be essential for recruiting a fully active complex necessary for efficient N-glycosylation . This entry also includes the magnesium transporter protein 1, also known as OST3 homologue B, which might be involved in N-glycosylation through its association with the oligosaccharyl transferase (OST) complex.
Ubiquinol-cytochrome c chaperone (Ubiq_cyt_c_chap)
Type: Domain

Saccharomyces cerevisiae ubiquinol-cytochrome C chaperone (CBP3) is required for assembly of coenzyme QF-2-cytochrome C reductase. This protein is organised into two domains: a variable N-terminal domain of unknown function present in mitochondrial Cbp3 homologues and a conserved C-terminal ubiquinol-cytochrome c chaperone domain (this entry). The crystal structure of this domain has been resolved in the homologue from the bacteria Brucella abortus, showing an all-helical fold . This domain is also found other proteins mainly from eukaryotes and Proteobacteria.

In vertebrates, CBP3 homologs are known as Ubiquinol-cytochrome c reductase complex assembly factors 1 (Uqcc1)

Some members of this group are annotated as part of the UPF0174 family.
GINS subunit, domain A (GINS_A)
Type: Domain

This entry represents an α-helical domain found in the DNA replication complex GINS proteins.

The GINS complex is essential for initiation of DNA replication in Xenopus egg extracts . In eukaryotes, GINS consists of four different subunits (Sld5, Psf1, Psf2, and Psf3), while in archaea it forms as a tetramer of two subunits (Gins15 and Gins23) . Only Gins23 is included in this entry. GINS associates with MCM (Minichromosome Maintenance) and Cdc45 to form the CMG (Cdc45-MCM-GINS) complex, which functions as the replicative helicase essential for DNA unwinding during replication. The archaeal GINS complex has a more symmetrical structure compared to its eukaryotic counterpart, and this is reflected in the archaeal CMG containing two copies of Cdc45. In Sulfolobus, the Gins15 subunit interacts with Cdc45 through its C-terminal B domain , while Gins23 interacts with the N-terminal domains of MCM .

Electron microscopy of GINS shows that it forms a ring-like structure , reminiscent of the structure of PCNA , the DNA polymerase delta replication clamp. The eukaryotic GINS subunits are homologous. The four subunits of the complex consist of two domains each, termed the α-helical (A) and β-strand (B) domains. The A and B domains of Sld5/Psf1 are permuted with respect to Psf1/Psf3 .

DNA replication in eukaryotes results from a highly coordinated interaction between proteins, often as part of protein complexes, and the DNA template. One of the key early steps leading to DNA replication is formation of the pre-replication complex, or pre-RC. The pre-RC is formed by the sequential binding of the origin recognition complex (ORC), Cdc6 and Cdt1 proteins, and the MCM complex. Activation of the pre-RC into the initiation complex (IC) is achieved via the action of S-phase kinases, eventually leading to the loading of the replication machinery.

A novel replication complex, GINS (for Go, Ichi, Nii, and San; meaning 5-1-2-3 in Japanese, after the four related subunits of the complex Sld5, Psf1, Psf2 and Psf3), has been identified . The GINS complex is conserved in eukaryotic cells and is essential for DNA replication. When the DNA replication fork is opened, GINS is required to maintain the association between the MCM and Cdc45 in the large replicator complex . The GINS complex acts as a replicative helicase that unlocks the double-stranded DNA prior to the moving replication fork .

Psf2's expression is up regulated in many diseases, especially tumors, and adversely affects prognosis .
Herpesvirus UL31 (Herpes_UL31)
Type: Family

During primary envelopment Human herpesvirus 1 (HHV-1, HSV-1) nucleocapsids translocate from the nucleus to the cytoplasm. Lining the inside of the INM is the nuclear lamina, which is composed of a meshwork of proteins with spaces too small for the capsid to move through without some disruption of the lamina. The lamina is mainly made up of lamin A/C and lamin B proteins, with smaller amounts of other proteins also present; this lamina must be disrupted before the nucleocapsids can egress.

This entry includes Herpesvirus UL31 protein, also known as nuclear egress protein 1 (NEC1). Within the host nucleus, NEC1 interacts with the newly formed capsid and directs it to the inner nuclear membrane by associating with nuclear egress protein 2 (UL34 or NEC2) . The NEC1/NEC2 complex, known as the nuclear egress complex (NEC), induces the budding of the capsid at the inner nuclear membrane and its envelopment into the perinuclear space, where the complex promotes the fusion of the enveloped capsid with the outer nuclear membrane and the subsequent release of the viral capsid into the cytoplasm .
Heat-inducible transcription repressor HrcA, C-terminal (HrcA_C)
Type: Domain

Prokaryotic cells have a defence mechanism against a sudden heat-shock stress. Commonly, they induce a set of proteins that protect cellular proteins from being denatured by heat. Among such proteins are the GroE and DnaK chaperones whose transcription is regulated by a heat-shock repressor protein HrcA. HrcA is a winged helix-turn-helix repressor that negatively regulates the transcription of dnaK and groE operons by binding the upstream CIRCE (controlling inverted repeat of chaperone expression) element. In Bacillus subtilis this element is a perfect 9 base pair inverted repeat separated by a 9 base pair spacer.

This entry represents the C terminus of HrcA, consisting of the GAF-like domain with the inserted dimerising domain.
Poxvirus E2/O1 (Poxvirus_E2/O1)
Type: Family

The function of the E2 and O1 viral proteins is not known.
Transcription elongation factor A-like/Brain expressed X-linked (TF_A-like/BEX)
Type: Family

This is a family of transcription elongation factors which includes those referred to as Bex (brain-expressed X-linked) proteins as well as those named TCEAL (transcription elongation factor A protein-like). Bex proteins are expressed in a wide range of tissues and are known to play a role in neuronal development. They seem to have have distinct roles in cancers . Bex1 was shown to be a novel link between neurotrophin signalling, the cell cycle, and neuronal differentiation, suggesting it might function by coordinating internal cellular states with the ability of cells to respond to external signals . TCEAL7 has been shown negatively to regulate the NF-kappaB pathway, hence being important in ovarian cancer as it one of the genes frequently downregulated in this cancer . Apart from TCEAL7, there are other five members of the TCEAL family, i.e. TCEAL1, TCEAL3, TCEAL4, TCEAL5 and TCEAL8. TCEAL1 was shown involved in the apoptosis of human cancer cells .
Cytochrome c1, transmembrane anchor, C-terminal (Cyt_c1_TM_anchor_C)
Type: Homologous_superfamily

This entry represents the transmembrane anchor of the cytochrome c1 subunit from the cytochrome bc1 complex. This region contains a single transmembrane helix.

Cytochrome bc1 complex (ubiquinol:ferricytochrome c oxidoreductase) is found in mitochondria, photosynthetic bacteria and other prokaryotes. It is minimally composed of three subunits: cytochrome b, carrying a low- and a high-potential haem group; cytochrome c1 (cyt c1); and a high-potential Rieske iron-sulphur protein. The general function of the complex is electron transfer between two mobile redox carriers, ubiquinol and cytochrome c; the electron transfer is coupled with proton translocation across the membrane, thus generating proton-motive force in the form of an electrochemical potential that can drive ATP synthesis. In its structure and functions, the cytochrome bc1 complex bears extensive analogy to the cytochrome b6f complex of chloroplasts and cyanobacteria; cyt c1 plays an analogous role to cytochrome f, in spite of their different structures .
Peptidase M10A, cysteine switch, zinc binding site (Pept_M10A_Zn_BS)
Type: Binding_site

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This group of metallopeptidases belong to the MEROPS peptidase family M10 (clan MA(M)), subfamily M10A.

The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA.

Sequences having this domain are extracellular metalloproteases, such as collagenase and stromelysin, which degrade the extracellular matrix, are known as matrixins. They are zinc-dependent, calcium-activated proteases synthesised as inactive precursors (zymogens), which are proteolytically cleaved to yield the active enzyme . All matrixins and related proteins possess 2 domains: an N-terminal domain, and a zinc-binding active site domain. The N-terminal domain peptide, cleaved during the activation step, includes a conserved PRCGVPDV octapeptide, known as the cysteine switch, whose Cys residue chelates the active site zinc atom, rendering the enzyme inactive . The active enzyme degrades components of the extracellular matrix, playing a role in the initial steps of tissue remodelling during morphogenesis, wound healing, angiogenesis and tumour invasion .