SII-SWORD/CoKE huggingface dataset:
Secretoglobin (Secretoglobin)
Type: Family

Secretoglobins are relatively small, secreted, disulphide-bridged dimeric proteins with encoding genes sharing substantial sequence similarity . Members of this family include:

Uteroglobin, a mammalian, steroid-inducible, secreted anti-inflammatory/immunomodulatory protein .

Mammaglobin, expressed in ovarian cancer cells .

Lipophilin B, which exists as a complex with mammary-specific mammaglobin A .

Clara cell 17kDa protein, which inhibits phospholipase A2 and papain, and also binds to progesterone .

Allergen Fel d 1 (Felis silvestris catus (Cat) allergen 1) chains 1 and 2, a tetrameric glycoprotein formed by two heterodimers that elicit IgE responses in people with allergy to cats .

Secretoglobin proteins have a four-helical structure, and in the case of uteroglobin, form homodimers, whereas allergen Fel d 1 forms a tetramer of two heterodimers (chains 1 and 2). The conservation of this primary and quaternary structure indicates that the genome of the eutherian common ancestor of cats, rodents, and primates contained a similar gene pair.

Uteroglobin (blastokinin or Clara cell protein CC10) is a mammalian steroid-inducible secreted protein originally isolated from the uterus of rabbits during early pregnancy . The mucosal epithelia of several organs that communicate with the external environment express uteroglobin. Its tissue-specific expression is regulated by steroid hormones, and is augmented in the uterus by non-steroidal prolactin. Uteroglobin may be a multi-functional protein with anti-inflammatory/immunomodulatory properties, acting to inhibit phospholipase A2 activity , and binding to (and possibly sequestering) several hydrophobic ligands such as progesterone, retinols, polychlorinated biphenyls, phospholipids and prostaglandins . In addition, uteroglobin has anti-chemotactic, anti-allergic, anti-tumourigenic and embryo growth-stimulatory properties. Uteroglobin may have a homeostatic role against oxidative damage, inflammation, autoimmunity and cancer . However, the true biological function of uteroglobin is poorly understood. Uteroglobin consists of a disulphide-linked homodimer with a large hydrophobic pocket located between the two dimers . Each monomer being composed of four helices that do not form a canonical four helix-bundle motif but rather a boomerang-shaped structure in which helices H1, H3, and H4 are able to bind a homodimeric partner . The hydrophobic pocket binds steroids, particularly progesterone, with high specificity. It is a member of the secretoglobin superfamily.
Pyosin/cloacin translocation domain (Pyosin/cloacin_T_dom)
Type: Domain

This entry represents a structural domain with a complex fold made of several coiled β-sheets. This domain is found at the N-terminal of both colicin E3 and colicin B, and acts as a translocation domain. It also occurs in S-type pyocin. Both pyocin and cloacin are bacteriocins, protein antibiotics that kill bacteria closely related to the producing species. Colicins are a subgroup of bacteriocins that are produced by and target Escherichia coli. The lethal action of most colicins is exerted either by formation of a pore in the cytoplasmic membrane of the target cell, or by an enzymatic nuclease digestion mechanism .
Peptidase family C14A, His active site (Caspase_his_AS)
Type: Active_site

Interleukin-1 beta converting enzyme (

) (ICE) is responsible for the cleavage of the IL-1 beta precursor at an Asp-Ala bond to generate the mature biologically active cytokine. ICE a thiol protease composed of two subunits of 10 (p10) and 20 Kd (p20), both derived by the autocleavage of a 45 Kd precursor (p45). Two residues are implicated in the catalytic mechanism: a cysteine and an histidine. They are located in the P20 subunit after cleavage of the precursor. ICE belongs to a family of peptidases which is implicated in programmed cell death (apoptosis) and which has been termed 'caspase' for cysteine aspase. ICE is known as Caspase-1 and the other members of this family include:

Caspase-2 (ICH-1, NEDD-2).

Caspase-3 (also known as apopain, CPP32, Yama), a protease which, at the onset of apoptosis, proteolytically cleaves poly(ADP-ribose) polymerase at an Asp-Gly bond.

Caspase-4 (ICH-2, TX, ICErel-II).

Caspase-5 (ICH-3, TY, ICErel-III).

Caspase-6 (MCH-2).

Caspase-7 (MCH-3, ICE-LAP3, CMH-1, SCA-2, LICE2).

Caspase-8 (MCH-5, MACH, FLICE).

Caspase-9 (MCH-6, ICE-LAP6).

Caspase-10 (MCH-4, FLICE2).

Caspase-11.

Caspase-12.

Caspase-13 (ERICE).

Caspase-14.

Caenorhabditis elegans ced-3 involved in the initiation of apoptosis.

Drosophila Ice.

This entry represents a conserved region containing the histidine active site.
Protein-tyrosine phosphatase, active site (Tyr_Pase_AS)
Type: Active_site

This entry includes proteins of two subfamilies: Ser/Thr (

) and Tyr dual specificity protein phosphatase and tyrosine specific protein phosphatase (

). Both of these subfamilies may also have inactive phosphatase domains, and dependent on the domain composition this loss of catalytic activity has different effects on protein function. Inactive single domain phosphatases can still specifically bind substrates, and protect against dephosphorylation, while the inactive domains of tandem phosphatases can be further subdivided into two classes. Those which bind phosphorylated tyrosine residues may recruit multi-phosphorylated substrates for the adjacent active domains and are more conserved, while the other class have accumulated several variable amino acid substitutions and have a complete loss of tyrosine binding capability. The second class shows a release of evolutionary constraint for the sites around the catalytic centre, which emphasises a difference in function from the first group. There is a region of higher conservation common to both classes, suggesting a regulatory centre .

Ser/Thr and Tyr dual specificity phosphatases are a group of enzymes with both Ser/Thr (

) and tyrosine specific protein phosphatase (

) activity able to remove both the serine/threonine or tyrosine-bound phosphate group from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. Dual specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle. Tyrosine specific protein phosphatases catalyze the removal of a phosphate group attached to a tyrosine residue. They are also very important in the control of cell growth, proliferation, differentiation and transformation.
Haemerythrin, iron-binding site (Haemerythrin_Fe_BS)
Type: Binding_site

The hemerythrin family is composed of hemerythrin proteins found in invertebrates, and a broader collection of bacterial and archaeal homologues. Hemerythrin is an oxygen-binding protein found in the vascular system and coelomic fluid, or in muscles (myohemerythrin) in invertebrates . Many of the homologous proteins found in prokaryotes are multi-domain proteins with signal-transducing domains such as the GGDEF diguanylate cyclase domain (

) and methyl-accepting chemotaxis protein (MCP) signalling domain (

). Most hemerythrins are oxygen-carriers with a bound non-haem iron, but at least one example is a cadmium-binding protein, apparently with a role in sequestering toxic metals rather than in binding oxygen. The prokaryote with the most instances of this domain is Magnetococcus sp. MC-1, a magnetotactic bacterium.

Hemerythrins and myohemerythrins are small proteins of about 110 to 129 amino acid residues that bind two iron atoms. They are left-twisted 4-α-helical bundles, which provide a hydrophobic pocket where dioxygen binds as a peroxo species, interacting with adjacent aliphatic side chains via van der Waals forces . In both hemerythrins and myohemerythrins, the active centre is a binuclear iron complex, bound directly to the protein via 7 amino acid side chains , 5 His, 1 Glu and 1 Asp . Ovohemerythrin , a yolk protein from the leech Theromyzon tessulatum seems to belong to this family of proteins, it may play a role in the detoxification of free iron after a blood meal .

This entry represents the iron-binding site found in haemerythrin and in related proteins. This site is located in the central region of these proteins and contains four of the iron-ligands: three histidines and a glutamate or glutamine.
Phytochrome chromophore attachment domain (Phyto_chromo_attachment)
Type: Domain

Phytochrome is a plant protein that acts as a regulatory photoreceptor and which mediates red-light effects on a wide variety of physiological and molecular responses. Phytochrome can undergo a reversible photochemical conversion between a biologically inactive red light-absorbing form and the active far-red light-absorbing form. Phytochrome is a dimer of identical 124 Kd subunits, each of which contains a covalently attached linear tetrapyrrole chromophore.

The chromophore is attached to a cysteine which is located in a highly conserved region that can be used as a signature pattern.

Synechocystis strain PCC 6803 hypothetical protein slr0473 contains a domain similar to that of plants phytochrome and seems to also bind a chromophore.
Insect cysteine-rich antifreeze protein (Insect_cyst_antifreeze_prot)
Type: Homologous_superfamily

Antifreeze proteins (AFPs) are a class of proteins that are able to bind to and inhibit the growth of macromolecular ice, thereby permitting an organism to survive subzero temperatures by decreasing the probability of ice nucleation in their bodies . These proteins have been characterised from a variety of organisms, including fish, plants, bacteria, fungi and arthropods. This entry represents insect AFPs of the type found in Tenebrio molitor iridescent virus and in Dendroides canadensis (Pyrochroid beetle).

The structure of these AFPs consists of a right-handed β-helix with 12 residues per coil. The β-helices of insect AFPs present a highly rigid array of threonine residues and bound water molecules that can effectively mimic the ice lattice. As such, β-helical AFPs provide a more effective coverage of the ice surface compared to the α-helical fish AFPs .

A second insect antifreeze from Choristoneura fumiferana (Spruce budworm) (

) also consists of β-helices, however in these proteins the helices form a left-handed twist; these proteins show no sequence homology to the current entry, but may act by a similar mechanism. The β-helix motif may be used as an AFP structural motif in non-homologous proteins from other (non-fish) organisms as well.
Dockerin domain (Dockerin_dom)
Type: Domain

Plant cell wall polysaccharides comprise the most abundant reservoir of organic carbon in the biosphere. The cellulosome is a large multienzyme
complex used by many anaerobic bacteria for the efficient degradation of plant-cell wall polysaccharides. The principal component of the cellulosome is a scaffolding subunit, a large enzyme-integrating protein, that contains cohesin modules (usually in multiple copies) for incorporation of the
different enzymes and other cellulosomal components. The enzymes contain a complementary type of module, the dockerin domain, that binds tenaciously to the cohesin modules of the scaffoldin subunit .

The dockerin domains consist of about 70 amino acid residues and contain two duplicated segments, each of about 22 amino acid residues. The first 12 residues of these duplicated sequences bear remarkable resemblance to the calcium-binding loop of the EF-hand motif, in which all the
calcium-binding residues (i.e., aspartic acids and asparagines) are highly conserved. The second halves of the duplicated sequences appear to form α helices. These helices would be analogous to the F helix of the EF-hand motif .

The dockerin domain comprises three α-helices. Helices H1 and H3, which are antiparallel to one another, and the two calcium-binding loops (Ca1 and Ca2) correspond to the tandem duplicated sequences that form the two F-hand motifs. A short loop region and helix H2 connect the F-hand motifs. The 12-residue Ca(2+)-binding loop of each motif coordinates one Ca2 ion in the typical pentagonal bipyramid configuration of EF-hand
Ca2-binding proteins .
Ubiquitin-conjugating enzyme/RWD-like (UBQ-conjugating_enzyme/RWD)
Type: Homologous_superfamily

This superfamily represents a structural domain with an α-β(4)-α(3) core fold. Domains of this structure are found in:

Ubiquitin conjugating enzyme E2, as well as related proteins such as ubiquitin carrier protein 4 and ubiquitin-protein ligase W .

The UEV domain in tumour susceptibility gene 101 and vacuolar protein sorting-associated protein .

RWD domain, found in RING finger and WD repeat-containing proteins, such as EIF-2 kinase 4 (GCN2-like protein) .

UFC1-like domain found in Ufm1-conjugating enzyme 1 .
DNA helicase DnaB, N-terminal/DNA primase DnaG, C-terminal (DNA_helicase_N/primase_C)
Type: Homologous_superfamily

This superfamily represents a structural domain with a multi-helical structure that forms an orthogonal bundle; a segment-swapped dimer. This domain is found at the N-terminal of the DNA helicase DnaB and replicative DNA helicase DnaC, as well as at the C-terminal of the DNA primase DnaG .

The hexameric helicase DnaB unwinds the DNA duplex at the Escherichia coli chromosome replication fork. Although the mechanism by which DnaB both couples ATP hydrolysis to translocation along DNA and denatures the duplex is unknown, a change in the quaternary structure of the protein involving dimerization of the N-terminal domain has been observed and may occur during the enzymatic cycle. This N-terminal domain is required both for interaction with other proteins in the primosome and for DnaB helicase activity.
RGS domain (RGS)
Type: Domain

This entry represents a structural domain with a multi-helical fold consisting of a 4-helical bundle with a left-handed twist and an up-and-down topology. This domain can be divided into two all-α subdomains. This domain is found in regulation of G-protein signalling (RGS) proteins, as well as other related proteins, including:

RGS4 .

RGS9 .

G-alpha interacting protein GaIP .

Axin .

p115RhoGEF .

Pdz-RhoGEF .

G-protein coupled receptor kinase 2 N-terminal domain .

RGS (Regulator of G Protein Signalling) proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways. Upon activation by GPCRs, heterotrimeric G proteins exchange GDP for GTP, are released from the receptor, and dissociate into free, active GTP-bound alpha subunit and beta-gamma dimer, both of which activate downstream effectors. The response is terminated upon GTP hydrolysis by the alpha subunit (

), which can then bind the beta-gamma dimer (

,

) and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound alpha subunits by stabilising the G protein transition state.

All RGS proteins contain an 'RGS-box' (or RGS domain), which is required for activity. Some small RGS proteins such as RGS1 and RGS4 are comprised of little more than an RGS domain, while others also contain additional domains that confer further functionality. RGS domains can be found in conjunction with a variety of domains, including: DEP for membrane targeting (

), PDZ for binding to GPCRs (

), PTB for phosphotyrosine-binding (

), RBD for Ras-binding (

), GoLoco for guanine nucleotide inhibitor activity (

), PX for phosphatidylinositol-binding (

), PXA that is associated with PX (

), PH for stimulating guanine nucleotide exchange (

), and GGL (G protein gamma subunit-like) for binding G protein beta subunits (

). Those RGS proteins that contain GGL domains can interact with G protein beta subunits to form novel dimers that prevent G protein gamma subunit binding and G protein alpha subunit association, thereby preventing heterotrimer formation.
Ribosome-inactivating protein, subdomain 1 (Ribosome_inactivat_prot_sub1)
Type: Homologous_superfamily

A number of bacterial and plant toxins act by inhibiting protein synthesis in eukaryotic cells. The toxins of the shiga and ricin family inactivate 60S ribosomal subunits by an N-glycosidic cleavage which releases a specific adenine base from the sugar-phosphate backbone of 28S rRNA . Members of the family include shiga and shiga-like toxins, and type I (e.g. trichosanthin and luffin) and type II (e.g. ricin, agglutinin and abrin) ribosome inactivating proteins (RIPs). All these toxins are structurally related. RIPs have been of considerable interest because of their potential use, conjugated with monoclonal antibodies, as immunotoxins to treat cancers. Further, trichosanthin has been shown to have potent activity against HIV-1-infected T cells and macrophages . Elucidation of the structure-function relationships of RIPs has therefore become a major research effort. It is now known that RIPs are structurally related. A conserved glutamic residue has been implicated in the catalytic mechanism ; this lies near a conserved arginine, which also plays a role in catalysis .

This entry contains proteins that have a subdomain with a 3-layer α/β/α-sandwich topology.
Ribosome-inactivating protein, subdomain 2 (Ribosome_inactivat_prot_sub2)
Type: Homologous_superfamily

A number of bacterial and plant toxins act by inhibiting protein synthesis in eukaryotic cells. The toxins of the shiga and ricin family inactivate 60S ribosomal subunits by an N-glycosidic cleavage which releases a specific adenine base from the sugar-phosphate backbone of 28S rRNA . Members of the family include shiga and shiga-like toxins, and type I (e.g. trichosanthin and luffin) and type II (e.g. ricin, agglutinin and abrin) ribosome inactivating proteins (RIPs). All these toxins are structurally related. RIPs have been of considerable interest because of their potential use, conjugated with monoclonal antibodies, as immunotoxins to treat cancers. Further, trichosanthin has been shown to have potent activity against HIV-1-infected T cells and macrophages . Elucidation of the structure-function relationships of RIPs has therefore become a major research effort. It is now known that RIPs are structurally related. A conserved glutamic residue has been implicated in the catalytic mechanism ; this lies near a conserved arginine, which also plays a role in catalysis .

This entry contains proteins with a subdomain with an irregular topology.
Bifunctional inhibitor/plant lipid transfer protein/seed storage helical domain (Bifunc_inhib/LTP/seed_store)
Type: Domain

This entry represents a structural domain consisting of 4-helices with a folded leaf topology, and forming a right-handed superhelix. This domain occurs in several proteins, including:

Plant lipid-transfer proteins, such as the non-specific lipid-transfer proteins ns-LTP1 and ns-LTP2 .

Proteinase/alpha-amylase inhibitors, such as trypsin/alpha-amylase inhibitor RBI from Eleusine coracana (Indian finger millet) and Hageman factor/amylase inhibitor from Zea mays (Maize) .

Seed storage proteins, such as napin from Brassica napus (Rape) and 2S albumin from Ricinus communis (Castor bean) .
Citrate synthase-like, large alpha subdomain (Citrate_synth-like_lrg_a-sub)
Type: Homologous_superfamily

This entry represents the large α-helical domain from type I and II citrate synthase enzymes, as well as a homologous domain found in the related enzyme 2-methylcitrate synthase. 2-Methylcitrate (

) synthase catalyses the conversion of oxaloacetate and propanoyl-CoA into (2R,3S)-2-hydroxybutane-1,2,3-tricarboxylate and coenzyme A. This enzyme is induced during bacterial growth on propionate, while type II hexameric citrate synthase is constitutive .

Citrate synthase

is a member of a small family of enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors. It catalyses the first reaction in the Krebs' cycle, namely the conversion of oxaloacetate and acetyl-coenzyme A into citrate and coenzyme A. This reaction is important for energy generation and for carbon assimilation. The reaction proceeds via a non-covalently bound citryl-coenzyme A intermediate in a 2-step process (aldol-Claisen condensation followed by the hydrolysis of citryl-CoA).
Citrate synthase-like, small alpha subdomain (Citrate_synth-like_sm_a-sub)
Type: Homologous_superfamily

This entry represents the small α-helical domain from type I and II citrate synthase enzymes, as well as a homolgous domain found in the related enzyme ATP citrate synthase. ATP citrate synthase (

) (also known as ATP citrate lyase) catalyses the MgATP-dependent, CoA-dependent cleavage of citrate into oxaloacetate and acetyl-CoA, a key step in the reductive tricarboxylic acid pathway of CO2 assimilation used by a variety of autotrophic bacteria and archaea to fix carbon dioxide . ATP citrate synthase is composed of two distinct subunits. In eukaryotes, ATP citrate synthase is a homotetramer of a single large polypeptide, and is used to produce cytosolic acetyl-CoA from mitochondrial-produced citrate .

Citrate synthase

is a member of a small family of enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors. It catalyses the first reaction in the Krebs' cycle, namely the conversion of oxaloacetate and acetyl-coenzyme A into citrate and coenzyme A. This reaction is important for energy generation and for carbon assimilation. The reaction proceeds via a non-covalently bound citryl-coenzyme A intermediate in a 2-step process (aldol-Claisen condensation followed by the hydrolysis of citryl-CoA).
Pili assembly chaperone, N-terminal (Pili_assmbl_chaperone_N)
Type: Domain

Most Gram-negative bacteria possess a supramolecular structure - the pili - on their surface, which mediates attachment to specific receptors. Many interactive subunits are required to assemble pili, but their assembly only takes place after translocation across the cytoplasmic membrane. Periplasmic chaperones assist pili assembly by binding to the subunits, thereby preventing premature aggregation . Pili chaperones are structurally, and possibly evolutionarily, related to the immunoglobulin superfamily : they contain two globular domains, with a topology identical to an immunoglobulin fold .

This entry represents the N-terminal domain which consists of seven β-strands (A1-G1) arranged in two sheets of four and three strands each. There is a cleft between the N- and C-terminal domains containing conserved hydrophobic residues that are critical to subunit binding .
Pili assembly chaperone, C-terminal (Pili_assmbl_chaperone_C)
Type: Domain

Most Gram-negative bacteria possess a supramolecular structure - the pili - on their surface, which mediates attachment to specific receptors. Many interactive subunits are required to assemble pili, but their assembly only takes place after translocation across the cytoplasmic membrane. Periplasmic chaperones assist pili assembly by binding to the subunits, thereby preventing premature aggregation . Pili chaperones are structurally, and possibly evolutionarily, related to the immunoglobulin superfamily : they contain two globular domains, with a topology identical to an immunoglobulin fold.

This entry represents the C-terminal domain of pili assembly chaperone PapD consisting of an Ig-like fold containing seven β-strands arranged in two sheets with a Greek key topology.