SII-SWORD/CoKE huggingface dataset:
Histone H3/CENP-A (Histone_H3/CENP-A)
Type: Family

This entry includes histone H3 and its variant, CENP-A (Cse4 in budding yeast, Cnp1 in fission yeast, and CID/CenH3 in fruit flies). Two primate-specific forms of H3, known as H3.X and H3.Y, are found in the brain .

Histone H3 is one of the five histones, along with H1/H5, H2A, H2B and H4. Two copies of each of the H2A, H2B, H3, and H4 histones ensemble to form the core of the nucleosome . The nucleosome forms octameric structure that wraps DNA in a left-handed manner. H3 is a highly conserved protein of 135 amino acid residues . Histones can undergo several different types of post-translational modifications that affect transcription, DNA repair, DNA replication and chromosomal stability.

Eukaryotic centromeres consists of an unique nucleosome in which CENP-A can be found . Human CENP-A nucleosome forms a histone octamer containing two each of histones H2A, H2B, H4 and CENP-A. Similar to the H3-containing nucleosome, the CENP-A nucleosome wraps DNA in a left-handed orientation . CENP-A nucleosomes function as a scaffold on which other kinetochore proteins assemble. CENP-A may serves as an epigenetic marker for kinetochore assembly . Deposition of CENP-A to the centromere requires histone chaperone HJURP (Holliday junction recognition protein) .
Glucoamylase (Glucoamylase)
Type: Family

This entry represents glucoamylase (GA), also known as glucan 1,4-alpha-glucosidase, which belongs to family 15 (

) in the classification of glycosyl hydrolases.

GA catalyses the release of D-glucose from the non-reducing ends of starch and other oligo- or polysaccharides. Studies of fungal GA have indicated 3 closely-clustered acidic residues that play a role in the catalytic mechanism . This region is also conserved in a recently sequenced bacterial GA .

The 3D structure of the pseudo-tetrasaccharide acarbose complexed with glucoamylase II(471) from Aspergillus awamori var. X100 has been determined to 2.4A resolution . The protein belongs to the mainly-α class, and contains 19 helices and 9 strands.
Dehydrin (Dehydrin)
Type: Family

LEA (late embryogenesis abundant) proteins were first identified in land plants. Plant LEA proteins have been found to accumulate to high levels during the last stage of seed formation (when a natural desiccation of the seed tissues takes place) and during periods of water deficit in vegetative organs. Later, LEA homologues have also been found in various species . They have been classified into several subgroups in Pfam and according to Bray and Dure .

Dehydrin has been classified as part of the LEA family (D-11 from Dure, or group 2 from Bray) . Dehydrins contribute to freezing stress tolerance in plants and it was suggested that this could be partly due to their protective effect on membranes .

Dehydrins share a number of structural features. One of the most notable features is the presence, in their central region, of a continuous run of five to nine serines followed by a cluster of charged residues. Such a region has been found in all known dehydrins so far with the exception of pea dehydrins. A second conserved feature is the presence of two copies of a lysine-rich octapeptide; the first copy is located just after the cluster of charged residues that follows the poly-serine region and the second copy is found at the C-terminal extremity.
High potential iron-sulphur protein (High_potential_FeS_prot)
Type: Domain

High potential iron-sulphur proteins (HiPIP) are a specific class of high-redox potential 4Fe-4S ferredoxins that functions in anaerobic electron transport and which occurs commonly in purple photosynthetic bacteria and in other bacteria, such as Paracoccus denitrificans and Thiobacillus ferrooxidans .

HiPIPs seem to react by oxidation of [4Fe-4S]2+ to [4Fe-4S]3+

The HiPIPs are small proteins which show significant variation in their sequences, their sizes (from 63 to 85 amino acids), and in their oxidation- reduction potentials. As shown in the following schematic representation the iron-sulphur cluster is bound by four conserved cysteine residues.

[4Fe-4S cluster]
| | | |
xxxxxxxxxxxxxxxxxxxCxCxxxxxxxCxxxxxCxxxx

'C': conserved cysteine involved in the binding of the iron-sulphur cluster.
Glucose-methanol-choline oxidoreductase, N-terminal (GMC_OxRdtase_N)
Type: Domain

The glucose-methanol-choline (GMC) oxidoreductases are FAD flavoproteins oxidoreductases .
These enzymes include a variety of proteins, including choline dehydrogenase (CHD), methanol oxidase (MOX) and cellobiose dehydrogenase (

) which share a number of regions of sequence similarities. One of these regions, located in the N-terminal section, corresponds to the FAD ADP-binding domain. The function of the other conserved domains is not yet known.
CXC chemokine receptor 1/2 (Chemokine_CXCR_1/2)
Type: Family

Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role . They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system , and endothelial cells, where they may act as either angiogenic or angiostatic factors .

The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).

Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors . Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells . Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).

The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.

CXCR1 and CXCR2, also known as interleukin 8 receptor alpha and beta, respectively , are closely-related receptors. They act as specific receptors for the CXCL8 and CXCL6 chemokines, which have a glutamate-leucine-arginine (ELR) motif in their N-terminal domains . CXCR2 also binds additional ELR motif-containing CXC chemokines (such as
CXCL1, CXCL2, CXCL3, CXCL5 and CXCL7) with high affinity .

CXCR1 and CXCR2 are expressed on all granulocytes, monocytes, and mast cells and on some CD8+ T-cells and CD56+ natural killer (NK) cells . Equal amounts of CXCR1 and CXCR2 are present on neutrophils , but it appears that monocytes and positive lymphocytes express more CXCR2 than CXCR1 .

This entry represents both CXCR1 and CXCR2.
Sodium:neurotransmitter symporter (Na/ntran_symport)
Type: Family

Neurotransmitter transport systems are integral to the release, re-uptake and recycling of neurotransmitters at synapses. High affinity transport proteins found in the plasma membrane of presynaptic nerve terminals and glial cells are responsible for the removal from the extracellular space of released-transmitters, thereby terminating their actions . Plasma membrane neurotransmitter transporters fall into two structurally and mechanistically distinct families. The majority of the transporters constitute an extensive family of homologous proteins that derive energy from the co-transport of Na
+
and Cl
-
, in order to transport neurotransmitter molecules into the cell against their concentration gradient. The family has a common structure of 12 presumed transmembrane helices and includes carriers for gamma-aminobutyric acid (GABA), noradrenaline/adrenaline, dopamine, serotonin, proline, glycine, choline, betaine and taurine. They are structurally distinct from the second more-restricted family of plasma membrane transporters, which are responsible for excitatory amino acid transport. The latter couple glutamate and aspartate uptake to the cotransport of Na
+
and the counter-transport of K
+
, with no apparent dependence on Cl
-
. In addition, both of these transporter families are distinct from the vesicular neurotransmitter transporters .
mRNA methyltransferase-like (mRNA_MeTrfase-like)
Type: Family

This family contains viral proteins that are bifunctional, acting as both an mRNA (nucleoside-2'-O-)-methyltransferase and a poly(A) polymerase processivity factor . The family also includes a number of uncharacterised eukaryotic sequences.
Apple domain (Apple)
Type: Domain

Plasma kallikrein (

) and coagulation factor XI (

) are two related plasma serine proteases activated by factor XIIA and which share the same domain topology: an N-terminal region that contains four tandem repeats of about 90 amino acids and a C-terminal catalytic domain. The 90 amino-acid repeated domain contains 6 conserved cysteines. It has been shown that three disulphide bonds link the first and sixth, second and fifth, and third and fourth cysteines. The domain can be drawn in the shape of an apple (see below) and has been accordingly called the 'apple domain'.

x x x x x x
x C---C x
x x x x
x Cx x x x
x | x x x Schematic representation of an
x Cx x x x apple domain.
x x x x
x x x x
x x x x x
x x
x x x x
C---C
.....x x.....

Apart from the cysteines, there are a number of other conserved positions in the apple domain. The apple domains of plasma prekallikrein are known to mediate its binding to high molecular weight kininogen , the apple domains of factor XI bind to factor XIIa, platelets, kininogen, factor IX and heparin .
Translation initiation factor IF-2, bacterial-like (TF_IF2_bacterial-like)
Type: Family

Initiation factor 2 (IF-2) (gene infB) is one of the three factors required for the initiation of protein biosynthesis in bacteria. IF-2 promotes the GTP-dependent binding of the initiator tRNA to the small subunit of the ribosome. IF-2 is a protein of about 70 to 95 Kd which contains a central GTP-binding domain flanked by a highly variable N-terminal domain and a more conserved C-terminal domain. Bacterial IF-2 is structurally and functionally related to eukaryotic mitochondrial IF-2 (IF-2(mt)) as well as to algal and plants chloroplast IF-2 (IF-2(chl)). Both IF-2(mt) and IF-2(chl) are encoded by nuclear genes and are produced as precursor proteins with a transit peptide. An exception are red algae where IF-2(chl) is encoded by the plastid genome .

This model discriminates eubacterial (and mitochondrial) translation initiation factor 2 (IF-2), encoded by the infB gene in bacteria, from similar proteins in the Archaea and Eukaryotes. In the bacteria and in organelles, the initiator tRNA is charged with N-formyl-Met instead of Met. This translation factor acts in delivering the initator tRNA to the ribosome. It is one of a number of GTP-binding translation factors recognised by the pfam HMM GTP_EFTU.
Membrane dipeptidase, active site (Dipep_AS)
Type: Active_site

This signature defines the active site of peptidases belong to the MEROPS peptidase family M19 (membrane dipeptidase family, clan MJ). The protein fold of the peptidase domain for members of this family resembles that of Klebsiella urease, the type example for clan MJ .

Renal dipeptidase (rDP) (

), also known as microsomal dipeptidase, is a zinc-dependent membrane dipeptidase that hydrolyses a wide range of dipeptides. It is involved in renal metabolism of glutathione and its conjugates. It is a homodimeric disulphide-linked glycoprotein attached to the renal brush border microvilli membrane by a GPI-anchor.

This active site signature contains the glutamate residue that has been shown to be important for the catalytic activity of rDP. rDP seems to be evolutionary related to hypothetical proteins in the PQQ biosynthesis operons of Acinetobacter calcoaceticus and Klebsiella pneumoniae.
GNAT domain (GNAT_dom)
Type: Domain

This entry represents the entire GNAT domain.

The N-acetyltransferases (NAT) ([ec:2.3.1.-]) are enzymes that use acetyl coenzyme A (CoA) to transfer an acetyl group to a substrate, a reaction implicated in various functions from bacterial antibiotic resistance to mammalian circadian rhythm and chromatin remodelling. The Gcn5-related N-acetyltransferases (GNAT) catalyse the transfer of the acetyl from the CoA donor to a primary amine of the acceptor. The GNAT proteins share a domain composed of four conserved sequence motifs A-D . This GNAT domain is named after yeast GCN5 (from General Control Nonrepressed) and related histone acetyltransferases (HATs) like Hat1 and PCAF. HATs acetylate lysine residues of N-terminal histone tails, resulting in transcription activation. Another category of GNAT, the aminoglycoside N-acetyltransferases, confer antibiotic resistance by catalysing the acetylation of amino groups in aminoglycoside antibiotics . GNAT proteins can also have anabolic and catabolic functions in both prokaryotes and eukaryotes .

The acetyltransferase/GNAT domain forms a structurally conserved fold of 6 to 7 β-strands (B) and 4 helices (H) in the topology B1-H1-H2-B2-B3-B4-H3-B5-H4-B6, followed by a C-terminal strand which may be from the same monomer or contributed by another . Motifs D (B2-B3), A (B4-H3) and B (B5-H4) are collectively called the HAT core , while the N-terminal motif C (B1-H1) is less conserved.

Some proteins known to contain a GNAT domain:

Actinobacterial mycothiol acetyltransferase (MshD), which catalyses the transfer of acetyl from acetyl-CoA to desacetylmycothiol to form mycothiol.

Yeast GCN5 and Hat1, which are histone acetyltransferases (EC 2.3.1.48).

Human PCAF, a histone acetyltransferase.

Mammalian serotonin N-acetyltransferase (SNAT) or arylalkylamine NAT (AANAT), which acetylates serotonin into a circadian neurohormone that may participate in light-dark rhythms, and human mood and behaviour.

Mammalian glucosamine 6-phosphate N-acetyltransferase (GNA1) (EC 2.3.1.4).

Escherichia coli RimI and RimJ, which acetylate the N-terminal alanine of ribosomal proteins S18 and S5, respectively (EC 2.3.1.128).

Mycobacterium tuberculosis aminoglycoside 2'-N-acetyltransferase (Aac), which acetylates the 2' hydroxyl or amino group of a broad spectrum of aminoglycoside antibiotics.

Bacillus subtilis BltD and PaiA, which acetylate spermine and spermidine.
Ornithine/DAP/Arg decarboxylase (Orn/DAP/Arg_de-COase)
Type: Family

Pyridoxal-dependent decarboxylases acting on ornithine, lysine, arginine and related substrates can be classified into two different families on the basis of sequence similarities . Members of this family while most probably evolutionary related, do not share extensive regions of sequence similarities. PLP-dependent decarboxylases exhibit two different structural folds, Fold I and Fold III. This family belong to the Fold III group which proceed with retention of configuration at the site of decarboxylation, with the exception of diaminopimelate decarboxylase (DAPDC) and D-ornithine/D-lysine decarboxylase (DOKDC) from Salmonella enterica serovar typhimurium, that are known as stereoinverting decarboxylases . The proteins contain a conserved lysine residue which is known, in mouse ODC , to be the site of attachment of the pyridoxal-phosphate group and it is thought to be responsible for protonation of the product, thus resulting in the retention of configuration for decarboxylation of l-amino acids and inversion for decarboxylation of d-amino acids . The proteins also contain a stretch of three consecutive glycine residues and has been proposed to be part of a substrate-binding region .

These enzymes are collectively known as group IV decarboxylases, and include ornithine and arginine decarboxylases, and diaminopimelate decarboxylase (DAP) .
Bacterial surface antigen (D15) (Bac_surfAg_D15)
Type: Domain

The protein sequences of d15 from various strains of Haemophilus influenzae are highly conserved, with only a small variable region identified near the carboxyl terminus of the protein . D15 is a highly conserved antigen that is protective in animal models and it may be a useful component of a universal subunit vaccine against Haemophilus infection and disease . Membrane proteins from other bacteria have been shown to elicit protective immunity. Oma87 is a protective outer membrane antigen of Pasteurella multocida .
Protein translocase subunit SecA (SecA)
Type: Family

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component . From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.

The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral membrane complex (SecCY, SecE and SecG), and two additional membrane proteins that promote the release of the mature peptide into the periplasm (SecD and SecF) . The chaperone protein SecB is a highly acidic homotetrameric protein that exists as a "dimer of dimers" in the bacterial cytoplasm. SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane protein ATPase SecA for secretion .

SecA is a cytoplasmic protein of 800 to 960 amino acid residues. Homologues of secA are also encoded in the chloroplast genome of some algae as well as in the nuclear genome of plants . It could be involved in the intraorganellar protein transport into thylakoids.
Interleukin-5 (IL-5)
Type: Family

This entry represents interleukin-5 (IL5), also known as eosinophil differentiation factor (EDF), is a lineage-specific cytokine for eosinophilpoiesis . It regulates eosinophil growth and activation , and thus plays an important role in diseases associated with increased levels of eosinophils, including asthma . IL5 has a similar overall fold to other cytokines (e.g., IL2, IL4 and GCSF) , but while these exist as monomeric structures, IL5 is a homodimer. The fold contains an anti-parallel 4-α-helix bundle with a left handed twist, connected by a 2-stranded anti-parallel β-sheet . The monomers are held together by 2 interchain disulphide bonds .
Corticotropin-releasing factor (CRF)
Type: Domain

This entry represents a domain found in the corticotropin-releasing factor family members.

Corticotropin-releasing factor (CRF), urotensin-I, urocortin and sauvagine form a family of related neuropeptides in vertebrates. The family can be grouped into 2 separate paralogous lineages, with urotensin-I, urocortin and sauvagine in one group and CRF forming the other group. Urocortin and sauvagine appear to represent orthologues of fish urotensin-I in mammals and amphibians, respectively. The peptides have a variety of physiological effects on stress and anxiety, vasoregulation, thermoregulation, growth and metabolism, metamorphosis and reproduction in various species, and are all released as preprohormones .

CRF is a hormone found mainly in the paraventricular nucleus of the mammalian hypothalamus that regulates the release of corticotropin (ACTH) from the pituitary gland. From here, CRF is transported to the anterior pituitary, stimulating adrenocorticotropic hormone (ACTH) release via CRF type 1 receptors, thereby activating the hypothalamo-pituitary-adrenocortical axis (HPA) and thus glucocorticoid release.

CRF is evolutionary related to a number of other active peptides. Urocortin acts in vitro to stimulate the secretion of adrenocorticotropic hormone. Urotensin is found in the teleost caudal neurosecretory system and may play a role in osmoregulation and as a corticotropin-releasing factor. Urotensin-I is released from the urophysis of fish, and produces ACTH and subsequent cortisol release in vivo. The nonhormonal portion of the prohormone is thought to be the urotensin binding protein (urophysin). Sauvagine (

), isolated from frog skin, has a potent hypotensive and diuretic effect.
Prokaryotic transglycosylase, active site (Transglyc_AS)
Type: Active_site

Bacterial lytic transglycosylases degrade murein via cleavage of the beta-1,4- glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine, with the concomitant formation of a 1,6-anhydrobond in the muramic acid residue. Escherichia coli has at least three different lytic transglycosylases: two soluble isozymes of 65 Kd and 35 Kd and a membrane-bound enzyme of 38 Kd. The sequence of the 65 Kd enzyme (gene slt) has been determined . A domain of about 90 residues located near the C-terminal section of slt was recently shown to be present in a number of other prokaryotic and phage proteins . This SLT domain shared by these proteins is involved in catalytic activity. The most conserved part of this domain contains the contains two conserved serines and a glutamate which form part of this active site signature .
Angiotensin II receptor type 1 (ATII_AT1_rcpt)
Type: Family

Angiotensin II is a blood-borne hormone produced in the circulation, it is also formed in many tissues such as the brain, kidney, heart, and blood vessels, where angiotensin II functions as a paracrine and autocrine hormone. The known actions of angiotensin II are mediated through two angiotensin receptor subtypes, Angiotensin II receptor 1 and angiotensin II receptor 2, which are members of the seven transmembrane rhodopsin-like G-protein coupled receptor family. These subtypes are important in the renin-angiotensin system, as they are responsible for the signal transduction of the vasoconstricting stimulus of the main effector hormone, angiotensin II . They also stimulate increased fluid intake and regulate the neuroendocrine system .

This entry represents the angiotensin II receptor type 1 (AT1) receptor, it is the major subtype of the angiotensin family and are found in blood vessels, other smooth muscles e.g., the uterus and bladder, and endocrine glands. It is also present in the kidney, liver and on presynaptic nerve terminals, where they potentiate release of noradrenaline. The AT1 receptor mediates the major cardiovascular effects of angiotensin II, which include vasoconstriction and aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. Angiotensin II receptor antagonists are drugs indicated for hypertension, diabetic nephropathy and congestive heart failure . The signal transduction mechanisms of AT1 receptor depends on at least five different effectors: phospholipase C, voltage-dependent Ca2+ channels, phospholipase D, phospholipase A2 and adenylate cyclase. It has also been demonstrated that AT1 stimulates the phosphorylation of several tyrosine-containing proteins such as mitogen-activated protein (MAP) kinase and activates the JAK-STAT pathway .
Aminotransferase class V domain (Aminotrans_V_dom)
Type: Domain

Aminotransferases share certain mechanistic features with other pyridoxal-phosphate dependent enzymes, such as the covalent binding of the pyridoxal-phosphate group to a lysine residue. On the basis of sequence similarity, these various enzymes can be grouped into subfamilies. This entry represents an aminotransferase class-V domain, which is found in amino transferases and other related, though functionally distinct enzymes, including cysteine desulfurase.