SII-SWORD/CoKE huggingface dataset:
Photosystem II reaction centre protein H (PSII_PsbH)
Type: Family

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .

This family represents the low molecular weight phosphoprotein PsbH found in PSII. The phosphorylation site of PsbH is located in the N terminus, where reversible phosphorylation is light-dependent and redox-controlled. PsbH is necessary for the photoprotection of PSII, being required for: (1) the rapid degradation of photodamaged D1 core protein to prevent further oxidative damage to the PSII core, and (2) the insertion of newly synthesised D1 protein into the thylakoid membrane . PsbH may also regulate the transfer of electrons from D2 (Qa) to D1 (Qb) in the reaction core.
Glutamate/acetylglutamate kinase (Glu/AcGlu_kinase)
Type: Family

Glutamate 5-kinase (

) catalyses the first step in the biosynthesis of proline, the ATP-dependent phosphorylation of glutamate to glutamate 5-phosphate .

This entry also includes N-acetylglutamate kinase (

), which catalyses the phosphorylation of N-acetylglutamate to N-acetylglutamate-5P in the pathway for arginine biosynthesis.
Synuclein (Synuclein)
Type: Family

Synucleins are small, soluble proteins expressed primarily in neural tissue and in certain tumours . The family includes three known proteins: alpha-synuclein, beta-synuclein, and gamma-synuclein. All synucleins have in common a highly conserved α-helical lipid-binding motif with similarity to the class-A2 lipid-binding domains of the exchangeable apolipoproteins .

Synuclein family members are not found outside vertebrates, although they have some conserved structural similarity with plant 'late-embryo-abundant' proteins. The alpha- and beta-synuclein proteins are found primarily in brain tissue, where they are seen mainly in presynaptic terminals . The gamma-synuclein protein is found primarily in the peripheral nervous system and retina, but its expression in breast tumors is a marker for tumor progression . Normal cellular functions have not been determined for any of the synuclein proteins, although some data suggest a role in the regulation of membrane stability and/or turnover. Mutations in alpha-synuclein are associated with rare familial cases of early-onset Parkinson's disease, and the protein accumulates abnormally in Parkinson's disease, Alzheimer's disease, and several other neurodegenerative illnesses .
Translation elongation factor P/YeiP, central (Transl_elong_P/YeiP_cen)
Type: Domain

Elongation factor P (EF-P) is a prokaryotic protein translation factor required for efficient peptide bond synthesis on 70S ribosomes from fMet-tRNAfMet . EF-P enhances the synthesis of certain dipeptides with N-formylmethionyl-tRNA and puromycine in vitro. EF-P binds to both the 30S and 50S ribosomal subunits. EF-P binds near the streptomycine binding site of the 16S rRNA in the 30S subunit. EF-P interacts with domains 2 and 5 of the 23S rRNA. The L16 ribosomal protein of the 50S or its N-terminal fragment are required for EF-P mediated peptide bond synthesis, whereas L11, L15, and L7/L12 are not required in this reaction, suggesting that EF-P may function at a different ribosomal site than most other translation factors. EF-P is essential for cell viability and is required for protein synthesis. EF-P is mainly present in bacteria. The EF-P homologs in archaea and eukaryotes are the initiation factors aIF5A and eIF5A, respectively.
FCH domain (FCH_dom)
Type: Domain

FCH domain is a short conserved region of around 60 amino acids first described as a region of homology between FER and CIP4 proteins . In the CIP4 protein the FCH domain binds to microtubules . The FCH domain is always found N-terminally and is followed by a coiled-coil region. The FCH and coiled-coil domains are structurally similar to Bin/amphiphysin/RVS (BAR) domains . They are α-helical membrane-binding modules that function in endocytosis, regulation of the actin cytoskeleton and signalling .

Proteins containing an FCH domain can be divided in 3 classes :

A subfamily of protein kinases usually associated with an SH2 domain:

Fps/fes (Fujimani poultry sarcoma/feline sarcoma) proto-oncogenes. They are non-receptor protein-tyrosine kinases preferentially expressed in myeloid lineage. The viral oncogene has an unregulated kinase activity which abrogates the need for cytokines and influences differentiation of haematopoietic progenitor cells.

Fes related protein (fer). It is an ubiquitously expressed homologue of Fes.

Adaptor proteins usually associated with a C-terminal SH3 domain:

Schizosaccharomyces pombe CDC15 protein. It mediates cytoskeletal rearrangements required for cytokinesis. It is essential for viability.

CD2 cytoplasmic domain binding protein.

Mammalian Cdc42-interacting protein 4 (CIP4). It may act as a link between Cdc42 signaling and regulation of the actin cytoskeleton.

Mammalian PACSIN proteins. A family of cytoplasmic phosphoproteins playing a role in vesicle formation and transport.

A subfamily of Rho-GAP proteins:

Mammalian RhoGAP4 proteins. They may down-regulate Rho-like GTPases in hematopoietic cells.

Yeast RHO GTPase-activating protein RGD1 (also known as YBR260C).

Caenorhabditis elegans hypothetical protein ZK669.1.
Transcription antitermination protein, NusG (Transcrpt_antiterm_NusG)
Type: Family

Bacterial transcription antitermination protein, NusG, is a component of the transcription complex and interacts with the termination factor Rho and RNA polymerase . NusG is a bacterial transcriptional elongation factor involved in transcription termination and antitermination .
Large ribosomal subunit protein uL22 (Ribosomal_uL22)
Type: Family

Large ribosomal subunit protein uL22 (also known as L22 in bacteria and previously known as L17 in eukaryotes) is a core protein of the large ribosomal subunit . It is the only ribosomal protein that interacts with all six domains of 23S rRNA, and is one of the proteins important for directing the proper folding and stabilizing the conformation of 23S rRNA. uL22 is the largest protein contributor to the surface of the polypeptide exit channel, the tunnel through which the polypeptide product passes. uL22 is also one of six proteins located at the putative translocon binding site on the exterior surface of the ribosome .

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 .
Beta/gamma crystallin (Beta/gamma_crystallin)
Type: Domain

The crystallins are water-soluble structural proteins that occur in high concentration in the cytoplasm of eye lens fibre cells. Four major groups of crystallin have been distinguished on the basis of size, charge and immunological properties: alpha-, beta- and gamma-crystallins occur in all vertebrate classes (though gamma-crystallins are low or absent in avian lenses); and delta-crystallin is found exclusively in reptiles and birds .

This entry represents beta and gamma-crystallin which form a family of related proteins . Structurally, beta- and gamma-crystallins are composed of two similar domains which, in turn, are each composed of two similar motifs with the two domains connected by a short connecting peptide. Each motif, which is about forty amino acid residues long, is folded in a distinctive 'Greek key' pattern.
Muscarinic acetylcholine receptor M2 (Musac_Ach_M2_rcpt)
Type: Family

Muscarinic acetylcholine receptors are members of rhodopsin-like G-protein coupled receptor family. They play several important roles; they mediate many of the effects of acetylcholine in the central and peripheral nervous system and modulate a variety of physiological functions, such as airway, eye and intestinal smooth muscle contraction, heart rate and glandular secretions. The receptors have a widespread tissue distribution and are a major drug target in human disease. They may be effective therapeutic targets in Alzheimer's disease, schizophrenia, Parkinson's disease and chronic obstructive pulmonary disease .

Muscarinic acetylcholine receptor M2 is highly expressed in the heart and has a profound role in the control of myocyte contraction . The release of acetylcholine from vagal parasympathetic neurones reduces the heart beating frequency by acting almost exclusively at M2 muscarinic receptors . The M2 receptor is found at much lower levels in the CNS, where it has limited distribution . It is co-expressed with the M3 muscarinic receptors in smooth muscle and it appears to play a much smaller role in the smooth muscle contractile response . M2 receptors are also expressed in the thermo-regulatory centres of the hypothalamus and are likely to be involved in the regulation of body temperature .
5-Hydroxytryptamine 7 receptor (5HT_7_rcpt)
Type: Family

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

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

The 5-HT7 receptor has been shown to positively modulate cAMP formation and activate the mitogen-activated protein kinase, ERK, in primary neuronal cultures . The receptor is expressed in a variety of human tissues, particularly in the brain, the gastrointestinal tract, and in various blood vessels . It has an extensive vascular distribution and is responsible for the prominent, persistent vasodilator response to 5-HT7 in anaesthetised animals . 5-HT7 receptors are involved in thermoregulation circadian rhythm , learning and memory, and sleep . This receptor has been a drug development target for the treatment of several clinical disorders . Atypical antipsychotics, e.g. clozapine, risperidone and antidepressants, have high affinity for the 5-HT7 receptor and it has been speculated that the 5-HT7 receptor may be involved in mood regulation, suggesting that it may be a useful target in the treatment of depression .
Polyomavirus coat protein VP2 (Polyoma_coat_VP2)
Type: Family

This family includes the VP2 and VP3 internal coat proteins from Polyomaviruses, which are small dsDNA tumour viruses. Their capsids contain 360 copies of the VP1 proteins

arranged in 72 pentamers. This capsid encloses the internal proteins VP2 and VP3, as well as the viral DNA. A single copy of VP2 or VP3 associates with each VP1 pentamer. A crystal structure shows that the C-terminal region of the VP2/VP3 protein interacts with the VP1 pentamer .
RNA ligase, Pab1020 family (RNA_ligase_Pab1020)
Type: Family

Members of this family are found, so far, in a single copy per genome and largely in thermophiles, of which only Aquifex aeolicus is bacterial rather than archaeal. PSI-BLAST converges after a single iteration to the whole of this family and reveals no convincing similarity to any other protein. The member protein Pab1020 has been characterised as an RNA ligase with circularization activity .
C1q domain (C1q_dom)
Type: Domain

This entry represents the C-terminal domain of C1q. C1q is a subunit of the C1 enzyme complex that activates the serum complement system. C1q comprises 6 A, 6 B and 6 C chains. These share the same topology, each possessing a small, globular N-terminal domain, a collagen-like Gly/Pro-rich central region, and a conserved C-terminal region, the C1q domain . The C1q protein is produced in collagen-producing cells and shows sequence and structural similarity to collagens VIII and X . This domain is also found in multimerin and EMILIN proteins.

The C-terminal globular domain of the C1q subcomponents and collagen types VIII and X is important both for the correct folding and alignment of the triple helix and for protein-protein recognition events . For collagen type X it has been suggested that the domain is important for initiation and maintenance of the correct assembly of the protein . The globular head is a trimer of C1q domains. Each individual C1q adopts a 10-strand Jelly-roll fold arranged in two antiparallel 5-stranded β-sheets . There are two well conserved regions within the C1q domain: an aromatic motif is located within the first half of the domain, the other conserved region is located near the C-terminal extremity.
O-methyltransferase, C-terminal domain (COMT_C)
Type: Domain

This domain includes a range of O-methyltransferases (COMT) some of which utilise S-adenosyl methionine as substrate . In prokaryotes, the major role of DNA methylation is to protect host DNA against degradation by restriction enzymes. In eukaryotes, DNA methylation has been implicated in the control of several cellular processes, including differentiation, gene regulation, and embryonic development. O-methyltransferases have a common catalytic domain structure, which might be universal among S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases .

Methyltransferases (EC [ec:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
2-oxoacid dehydrogenase acyltransferase, catalytic domain (2-oxoacid_DH_actylTfrase)
Type: Domain

This domain is found in the lipoamide acyltransferase component of the branched-chain alpha-keto acid dehydrogenase complex

, which catalyses the overall conversion of alpha-keto acids to acyl-CoA and carbon dioxide . It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3). The domain is also found in the dihydrolipoamide succinyltransferase component of the 2-oxoglutarate dehydrogenase complex

. These proteins contain one to three copies of a lipoyl binding domain followed by the catalytic domain.
Galectin, carbohydrate recognition domain (Galectin_CRD)
Type: Domain

Galectins (also known as galaptins or S-lectin) are a family of proteins defined by having at least one characteristic carbohydrate recognition domain (CRD) with an affinity for beta-galactosides and sharing certain sequence elements. Members of the galectins family are found in mammals, birds, amphibians, fish, nematodes, sponges, and some fungi. Galectins are known to carry out intra- and extracellular functions through glycoconjugate-mediated recogntion. From the cytosol they may be secreted by non-classical pathways, but they may also be targeted to the nucleus or specific sub-cytosolic sites. Within the same peptide chain some galectins have a CRD with only a few additional amino acids, whereas others have two CRDs joined by a link peptide, and one (galectin-3) has one CRD joined to a different type of domain .

The galectin carbohydrate recognition domain (CRD) is a β-sandwich of about 135 amino acid. The two sheets are slightly bent with 6 strands forming the concave side and 5 strands forming the convex side. The concave side forms a groove in which carbohydrate is bound, and which is long enough to hold about a linear tetrasaccharide .
3Fe-4S ferredoxin (3Fe4S_ferredoxin)
Type: Family

In a few bacterial P450-containing systems, the transfer of electrons from flavoprotein reductase to P450 is mediated by 3Fe-4S ferredoxins . Despite functional similarity of such ferredoxins to the adrenodoxin family, they do not share sequence similarity but seem to be similar to some mono-[4Fe-4S] cluster ferredoxins but lack the fourth cysteine residue conserved in 4Fe-4S sequences . It has been shown experimentally that the 4Fe-4S cluster of related ferredoxins from archaebacteria easily converts to a 3Fe-4S cluster .
Fimbrial protein pilin (Pilin)
Type: Family

Pilin is a component of type IV pilus (T4P), a polar flexible filament, which consists of a single polypeptide chain arranged in a helical configuration of five subunits per turn, which is involved cell adhesion, microcolony formation, twitching motility and transformation . Gram-negative bacteria produce pilin which is characterised by the presence of a very short leader peptide of 6 to 7 residues, followed by a methylated N-terminal phenylalanine residue and by a highly conserved sequence of about 24 hydrophobic residues, of the NMePhe type pilin .
Copper fist DNA-binding domain (Cu_fist_DNA-bd_dom)
Type: Domain

Some fungal transcription factors contain an N-terminal domain, the copper fist, which seems to be involved in copper-dependent DNA-binding . These proteins activate the transcription of the metallothionein gene in response to copper. Metallothionein maintains copper levels in yeast . The copper fist domain, which is similar in structure to metallothionein itself, undergoes a large conformational change on copper-binding that allows DNA-binding. The domain contains a conserved array of zinc-binding residues (Cys-X2-Cys-X8-Cys-X-His) and forms a three-stranded antiparallel β-sheet with two short helical segments that project from one end of the β-sheet . Conserved residues form a basic patch that may be important for DNA binding.
Microtubule associated protein, tubulin-binding repeat (MAP_tubulin-bd_rpt)
Type: Repeat

Microtubules consist of tubulins as well as a group of additional proteins collectively known as the Microtubule Associated Proteins (MAP). MAP's have been classified into two classes: high molecular weight MAP's and Tau protein. The Tau proteins promote microtubule assembly and stabilise microtubules.

The C-terminal region of these proteins contains three or four tandem repeats of about thirty amino acid residues which is implicated in tubulin binding and which seem to have a stiffening effect on microtubules.
Serine hydroxymethyltransferase (Ser_HO-MeTrfase)
Type: Family

This entry includes serine hydroxymethyltransferases and related uncharacterised proteins. Serine hydroxymethyltransferase catalyses the reversible interconversion of serine and glycine with tetrahydrofolate serving as the one-carbon carrier. This reaction serves as the major source of one-carbon groups required for the biosynthesis of purines, thymidylate, methionine, and other important biomolecules.
Prephenate dehydratase (Preph_deHydtase)
Type: Domain

Prephenate dehydratase (

, PDT) catalyses the decarboxylation of prephenate to phenylpyruvate. In microorganisms it is part of the terminal pathway of phenylalanine biosynthesis. In some bacteria such as Escherichia coli PDT is part of a bifunctional enzyme (P-protein) that also catalyses the transformation of chorismate into prephenate (chorismate mutase,

,

) while in other bacteria it is a monofunctional enzyme. In the archaea Archaeoglobus fulgidus is part of a trifunctional enzyme . The sequence of monofunctional PDT aligns well with the C-terminal part of P-proteins .

The prephenate dehydratase domain is also found in the six PDT-like homologues of Arabidopsis. They use arogenate more efficiently than prephenate, and consequently they have been classified as arogenate dehydratases .

This domain is also found in bifunctional N-acyl-homoserine lactone acylase/prephenate dehydratase (GqqA1) which is a multifunctional enzyme that acts on N-acyl-homoserine lactones (AHLs), beta-lactam antibiotics and shows prephenate dehydratase activity .