SII-SWORD/CoKE huggingface dataset:
EGF-like, conserved site (EGF-like_CS)
Type: Conserved_site

This entry represents a conserved site in the EGF-like domain.

A sequence of about thirty to forty amino-acid residues long found in the sequence of epidermal growth factor (EGF) has been shown to be present, in a more or less conserved form, in a large number of other, mostly animal proteins. The list of proteins currently known to contain one or more copies of an EGF-like pattern is large and varied. The functional significance of EGF domains in what appear to be unrelated proteins is not yet clear. However, a common feature is that these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandin G/H synthase). The EGF domain includes six cysteine residues which have been shown (in EGF) to be involved in disulphide bonds. The main structure is a two-stranded β-sheet followed by a loop to a C-terminal short two-stranded sheet. Subdomains between the conserved cysteines vary in length.
Septum formation inhibitor MinC (MinC)
Type: Family

In Escherichia coli FtsZ (

) assembles into a Z ring at midcell. Its assembly at polar sites is prevented by the min system. MinC

, a component of this system, is an inhibitor of FtsZ assembly that is positioned within the cell by interaction with the MinDE proteins. MinC is an oligomer, probably a dimer . The C-terminal half of MinC is the most conserved and interacts with MinD. The N-terminal half is thought to interact with FtsZ. MinC rapidly oscillates between the poles of the cell to destabilise FtsZ filaments that have formed before they mature into polar Z rings.
DNA topoisomerase I, DNA binding, N-terminal domain 1 (DNA_topo_DNA_db_N_dom1)
Type: Homologous_superfamily

DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single-or double-strand breaks, crossing the strands through one another, then resealing the breaks . These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis . DNA topoisomerases are divided into two classes: type I enzymes (

; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (

; topoisomerases II, IV and VI) break double-strand DNA .

Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB . They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases . The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases .

This entry represents a structural motif, consisting of an orthogonal α-helical topology that forms the N-terminal DNA-binding domain of certain eukaryotic topoisomerase I (type IB) enzymes. To cleave the DNA backbone, these enzymes must make a transient phosphotyrosine bond. The N-terminal domain of human topoisomerase I is thought to coordinate the restriction of free strand rotation during the topoisomerisation step of catalysis. A conserved tryptophan residue may be important for the DNA-interaction ability of the N-terminal domain . Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant alkaloid with antitumour activity. A binding mode for the anticancer drug camptothecin has been proposed on the basis of chemical and biochemical information combined with the three-dimensional structures of topoisomerase I-DNA complexes .
Phosphoenolpyruvate carboxykinase, C-terminal (PEP_carboxykinase_C)
Type: Homologous_superfamily

Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the first committed (rate-limiting) step in hepatic gluconeogenesis, namely the reversible decarboxylation of oxaloacetate to phosphoenolpyruvate (PEP) and carbon dioxide, using either ATP or GTP as a source of phosphate. The ATP-utilising (

) and GTP-utilising (

) enzymes form two divergent subfamilies, which have little sequence similarity but which retain conserved active site residues. ATP-utilising PEPCKs are monomers or oligomers of identical subunits found in certain bacteria, yeast, trypanosomatids, and plants, while GTP-utilising PEPCKs are mainly monomers found in animals and some bacteria . Both require divalent cations for activity, such as magnesium or manganese. One cation interacts with the enzyme at metal binding site 1 to elicit activation, while the second cation interacts at metal binding site 2 to serve as a metal-nucleotide substrate. In bacteria, fungi and plants, PEPCK is involved in the glyoxylate bypass, an alternative to the tricarboxylic acid cycle.

PEPCK helps to regulate blood glucose levels. The rate of gluconeogenesis can be controlled through transcriptional regulation of the PEPCK gene by cAMP (the mediator of glucagon and catecholamines), glucocorticoids and insulin. In general, PEPCK expression is induced by glucagon, catecholamines and glucocorticoids during periods of fasting and in response to stress, but is inhibited by (glucose-induced) insulin upon feeding . With type II diabetes, this regulation system can fail, resulting in increased gluconeogenesis that in turn raises glucose levels .

PEPCK consists of an N-terminal and a catalytic C-terminal domain, with the active site and metal ions located in a cleft between them. Both domains have an α/β topology that is partly similar to one another . Substrate binding causes PEPCK to undergo a conformational change, which accelerates catalysis by forcing bulk solvent molecules out of the active site . PCK uses an α/β/α motif for nucleotide binding, this motif differing from other kinase domains. GTP-utilising PEPCK has a PEP-binding domain and two kinase motifs to bind GTP and magnesium.

This superfamily represents the C-terminal domain found in both GTP-utilising and ATP-utilising phosphoenolpyruvate carboxykinase enzymes.
Domain of unknown function DUF1587 (DUF1587)
Type: Domain

A region of similarity shared by several Rhodopirellula baltica cytochrome-like proteins that are predicted to be secreted. These proteins also contain domains

,

,

and

.
Domain of unknown function DUF1588 (DUF1588)
Type: Domain

A region of similarity shared by several Rhodopirellula baltica cytochrome-like proteins that are predicted to be secreted. These proteins also contain domains

,

,

and

.
Coatomer, gamma subunit, appendage, Ig-like subdomain (Coatomer_gsu_app_Ig-like_dom)
Type: Domain

Proteins synthesised on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. This traffic is bidirectional, to ensure that proteins required to form vesicles are recycled. Vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transfer . While clathrin mediates endocytic protein transport, and transport from ER to Golgi, coatomers primarily mediate intra-Golgi transport, as well as the reverse Golgi to ER transport of dilysine-tagged proteins . For example, the coatomer COP1 (coat protein complex 1) is responsible for reverse transport of recycled proteins from Golgi and pre-Golgi compartments back to the ER, while COPII buds vesicles from the ER to the Golgi . Coatomers reversibly associate with Golgi (non-clathrin-coated) vesicles to mediate protein transport and for budding from Golgi membranes . COPI coated vesicle assembly is initiated by recruitment of the small GTPase Arf1 which recruits the coatomer protein complex from the cytoplasm and anchors it at the membrane. Then, Arf1 is activated by a guanine exchange factor and hydrolyses GTP to mediate uncoating of the vesicle which subsequently fuses with its target membrane . As coat proteins polymerise, vesicles are formed and budded from membrane-bound organelles. Coatomer complexes also influence Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. In mammals, coatomer complexes can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins. Coatomer complexes are hetero-oligomers composed of at least an alpha, beta, beta', gamma, delta, epsilon and zeta subunits, and can be subdivided into an outer-coat and an adaptor subcomplex .

This entry represents a β-sandwich structural motif found in the appendage domain of the gamma subunit of coatomer complexes. This subdomain has an immunoglobulin-like β-sandwich fold containing 7 strands in 2 β-sheets in a Greek key topology . The appendage domain of the gamma coatomer subunit has a similar overall fold to the appendage domain of clathrin adaptors, and can also share the same motif-based cargo recognition and accessory factor recruitment mechanisms.
Clathrin adaptor, appendage, Ig-like subdomain superfamily (Clathrin_app_Ig-like_sf)
Type: Homologous_superfamily

Proteins synthesized on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. This traffic is bidirectional, to ensure that proteins required to form vesicles are recycled. Vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transfer .

This superfamily represents a β-sandwich structural motif found in the appendage (ear) domain of alpha-, beta-and gamma-adaptin from AP clathrin adaptor complexes, the GAE (gamma-adaptin ear) domain of GGA adaptor proteins, and the appendage domain of the gamma subunit of coatomer complexes. These domains have an immunoglobulin-like β-sandwich fold containing 7 or 8 strands in 2 β-sheets in a Greek key topology . Although the appendage domains from AP / GGA adaptins and coatomers share a similar fold, there is little sequence identity between them. However, they also share similar motif-based cargo recognition and accessory factor recruitment mechanisms.
Domain of unknown function DUF1592 (DUF1592)
Type: Domain

A region of similarity shared by several Rhodopirellula baltica cytochrome-like proteins that are predicted to be secreted. These proteins also contain

,

,

and

.
Domain of unknown function DUF1595 (DUF1595)
Type: Domain

A region of similarity shared by several Rhodopirellula baltica cytochrome-like proteins that are predicted to be secreted. These proteins also contain

,

,

and

.
Domain of unknown function DUF1548 (DUF1548)
Type: Domain

This domain is found in a small number of Chlamydia proteins of unknown function. It occurs together with

.
Phage baseplate assembly protein V/Gp45 (GpV/Gp45)
Type: Family

This entry represents a family of phage (and bacteriocin) proteins related to the phage P2 V gene product (GpV), which forms the small spikes on the baseplate that bind to the host cell and penetrate through the host membrane . This entry also includes Gp45, which is a component of the baseplate that forms a central needlelike spike used to puncture the host cell membrane for tube insertion during virus entry . At least one member is encoded within a region of Pectobacterium carotovorum (Erwinia carotovora) described as a bacteriocin, a phage tail-derived module able to kill bacteria closely related to the host strain.

The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
Meiotic recombination, Spo11 (Meiotic_Spo11)
Type: Family

Spo11 is a meiosis-specific protein that is responsible for the initiation of recombination during the early stages of meiosis through the formation of DNA double-strand breaks (DSBs) by a type II DNA topoisomerase-like activity . These DSBs initiate homologous recombination, which is required for chromosomal segregation and generation of genetic diversity during meiosis. Spo11 acts in conjunction with several other proteins, including Rec102 in yeast, to bring about meiotic recombination . Mouse and human homologues of Spo11 have been cloned and characterised. The proteins are 82% identical and share ~25% identity with other family members. Mouse Spo11 has been localised to chromosome 2H4, and human SPO11 to chromosome 20q13.2-q13.3, a region amplified in some breast and ovarian tumours .

Similarity between SPO11 and archaebacterial TOP6A proteins points to evolutionary specialisation of a DNA-cleavage function for meiotic recombination . Note that the yeast SPO11 protein shares far less similarity to other SPO11 proteins than the human and mouse homologues do to each other.
Spo11/DNA topoisomerase VI, subunit A, N-terminal (Spo11/TopoVI_A_N)
Type: Domain

This entry represents the N-terminal domain found in Spo11, a meiotic recombination protein found in eukaryotes, and in subunit A of topoisomerase VI, a type IIB topoisomerase found predominantly in archaea . These two types of proteins share structural homology.
Tachykinin/Neurokinin-like, conserved site (Tachy_Neuro_lke_CS)
Type: Conserved_site

Tachykinins are a group of biologically active peptides which excite neurons, evoke behavioral responses, are potent vasodilatators and contract (directly or indirectly) many smooth muscles. This family includes many other peptides. Tachykinins, like most other active peptides, are synthesized as larger protein precursors that are enzymatically converted to their mature forms. Tachykinins are from ten to twelve residues long.
Bacteriophage lambda, CIII, regulatory protein (Phage_lambda_CIII)
Type: Family

Bacteriophage lambda regulatory protein CIII is a small protein that plays a role in stabilising the CII transcriptional activator, via a mechanism that is not yet fully understood . Stabilised CII activates CI, the gene for the repressor protein that prevents transcription of proteins required for lytic development. The central portion of the protein is well conserved and is both necessary and sufficient for the activity of the protein . Comparative analysis of the CIII sequence in lambda, Bacteriophage HK022 and the lambdoid Enterobacteria phage P22 has led to the suggestion that this central region assumes an amphipathic α-helical structure .

The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
Amino acid transporter, transmembrane domain (AA_transpt_TM)
Type: Domain

This transmembrane domain is found in many amino acid transporters including

(UNC-47) and

(MTR). UNC-47 encodes a vesicular amino butyric acid (GABA) transporter, (VGAT) and is is predicted to have 10 transmembrane domains UNC47_CAEEL . MTR is an N system amino acid transporter system protein involved in methyltryptophan resistance MTR_NEUCR. Other proteins with this domain include proline transporters and amino acid transporters whose specificity has not yet been identified.
Tryptophan/tyrosine transporter (Trp_tyr_transpt)
Type: Family

Amino acid permeases are integral membrane proteins involved in the transport of amino acids into the cell. A number of such proteins have been found to be evolutionary related .

Aromatic amino acids are concentrated in the cytoplasm of Escherichia coli by 4 distinct transport systems: a general aromatic amino acid permease, and a specific permease for each of the 3 types (Phe, Tyr and Trp) . It has been shown that some permeases in E. coli and related bacteria are evolutionary related. These permeases are proteins of about 400 to 420 amino acids and are located in the cytoplasmic membrane and, like bacterial sugar/cation transporters, are thought to contain 12 transmembrane (TM) regions - hydropathy analysis, however, is inconclusive, suggesting the possibility of 10 to 12 membrane-spanning domains . The best conserved domain is a stretch of 20 residues which seems to be located in a cytoplasmic loop between the first and second transmembrane region.

This family is specific for aromatic amino acid transporters and includes the tyrosine permease, TyrP, and the tryptophan transporters TnaB and Mtr of E. coli.
Tryptophan/tryrosine permease, conserved site (Trp/try_permease_CS)
Type: Conserved_site

Amino acid permeases are integral membrane proteins involved in the transport of amino acids into the cell. A number of such proteins have been found to be evolutionary related .

Aromatic amino acids are concentrated in the cytoplasm of Escherichia coli by 4 distinct transport systems: a general aromatic amino acid permease, and a specific permease for each of the 3 types (Phe, Tyr and Trp) . It has been shown that some permeases in E. coli and related bacteria are evolutionary related. These permeases are proteins of about 400 to 420 amino acids and are located in the cytoplasmic membrane and, like bacterial sugar/cation transporters, are thought to contain 12 transmembrane (TM) regions - hydropathy analysis, however, is inconclusive, suggesting the possibility of 10 to 12 membrane-spanning domains . The best conserved domain is a stretch of 20 residues which seems to be located in a cytoplasmic loop between the first and second transmembrane region.

This entry represents a conserved site specific for tyryptophan and tyrosine permeases.
Galanin message associated peptide (GMAP) (GMAP)
Type: Domain

Galanin is a peptide hormone that controls various biological activities . Galanin-like immuno-reactivity has been found in the central and peripheral nervous systems of mammals, with high concentrations demonstrated in discrete regions of the central nervous system, including the median eminence, hypothalamus, arcuate nucleus, septum, neuro-intermediate lobe of the pituitary, and the spinal cord. Its localisation within neurosecretory granules suggests that galanin may function as a neurotransmitter, and it has been shown to coexist with a variety of other peptide and amine neurotransmitters within individual neurons .

Although the precise physiological role of galanin is uncertain, it has a number of pharmacological properties: it stimulates food intake, when injected into the third ventricle of rats; it increases levels of plasma growth hormone and prolactin, and decreases dopamine levels in the median eminence ; and infusion into humans results in hyperglycemia and glucose intolerance, and inhibits pancreatic release of insulin, somatostatin and pancreatic peptide. Galanin also modulates smooth muscle contractility within the gastro-intestinal and genito-urinary tracts, all such activities suggesting that the hormone may play an important role in the nervous modulation of endocrine and smooth muscle function .

This domain represents the galanin message-associated peptide (GMAP) domain which is found C-terminal to the galanin domain in the preprogalanin precursor protein. GMAP sequences in different species show a high degree of homology, but the biological function of the GMAP peptide is not known .
Histidine phosphatase superfamily, clade-1 (His_Pase_superF_clade-1)
Type: Family

The histidine phosphatase superfamily is so named because catalysis centres on a conserved His residue that is transiently phosphorylated during the catalytic cycle. Other conserved residues contribute to a 'phosphate pocket' and interact with the phospho group of substrate before, during and after its transfer to the His residue. Structure and sequence analyses show that different families contribute different additional residues to the 'phosphate pocket' and, more surprisingly, differ in the position, in sequence and in three dimensions, of a catalytically essential acidic residue. The superfamily may be divided into two main branches. The relationship between the two branches is not evident by (PSI-)BLAST but is clear from more sensitive sequence searches and structural comparisons .

The larger clade-1 contains a wide variety of catalytic functions, the best known being fructose 2,6-bisphosphatase (found in a bifunctional protein with 2-phosphofructokinase) and cofactor-dependent phosphoglycerate mutase. The latter is an unusual example of a mutase activity in the superfamily: the vast majority of members appear to be phosphatases. The bacterial regulatory protein phosphatase SixA is also in clade-1 and has a minimal, and possible ancestral-like structure, lacking the large domain insertions that contribute to binding of small molecules in clade-1 members.
6-phosphofructo-2-kinase (6Phosfructo_kin)
Type: Domain

6-Phosphofructo-2-kinase (

,

) is a bifunctional enzyme that catalyses both the synthesis and the degradation of fructose-2, 6-bisphosphate. The fructose-2,6-bisphosphatase reaction involves a phosphohistidine intermediate. The catalytic pathway is:

ATP + D-fructose 6-phosphate = ADP + D-fructose 2,6-bisphosphate

D-fructose 2,6-bisphosphate + H
2
O = 6-fructose 6-phosphate + P
i

The enzyme is important in the regulation of hepatic carbohydrate metabolism and is found in greatest quantities in the liver, kidney and heart. In mammals, several genes often encode different isoforms, each of which differs in its tissue distribution and enzymatic activity . The family described here bears a resemblance to the ATP-driven phospho-fructokinases, however, they share little sequence similarity, although a few residues seem key to their interaction with fructose 6-phosphate .

This domain forms the N-terminal region of this enzyme, while

forms the C-terminal domain.