SII-SWORD/CoKE huggingface dataset:
Dexamethasone-induced protein (Dexamethasone-induced)
Type: Family

Dexamethasone is a member of the glucocorticoid group of steroid hormones; it functions as an anti-inflammatory and immunosuppressant. A differentially- expressed transcript of unknown function has been identified in emphysematous lungs - this has been named Dexamethasone-Induced transcript (DEXI). It is suggested that the up-regulation of DEXI in emphysema patient's tissues may be a direct result of their treatment with corticosteroids.

The human DEXI protein is a 95-residue acidic polypeptide, predicted to contain a central transmembrane domain and a C-terminal leucine zipper . It is unclear how dexamethasone influences proteins within this family. However, the leucine zipper contains a predicted casein kinase II phosphorylation site, suggesting that interaction may possibly be regulated by phosphorylation. It is hoped that further studies will eventually help to elucidate the function of this protein and its role in emphysema and inflammatory-airway disease.
Cysteine/serine-rich nuclear protein family (Cys/Ser-rich_nuc_prot)
Type: Family

Members of the cysteine/serine-rich nuclear protein family (CSRNP) contain cysteine- and serine-rich regions and a basic domain. They are nuclear proteins that possess a transcriptional activation domain and bind the sequence AGAGTG . The proteins actively influence transcriptional activity, but it has not been established which of their domains are involved in DNA binding. It is thought that this may potentially be mediated by the conserved cysteine-rich or the basic domain.

It has been shown that CSRNP genes are down-regulated in various different cancers, suggesting that they act as tumour suppressors . This would usually imply a relation to reduced apoptosis, but this has yet to be proven; in some studies, a reduction in apoptosis was not detected as a result of deficiencies of CSRNP genes.
Autophagy-related protein 14 (Autophagy-related_protein_14)
Type: Family

Macroautophagy is a bulk degradation process induced by starvation in eukaryotic cells . In yeast, 15 autophagy (Apg) proteins coordinate the formation of autophagosomes. Apg14p and Vps30p/Apg6p, components of an autophagy-specific phosphatidylinositol 3-kinase complex, together with Apg9p and Apg16p, are required for localisation of Apg5p and Aut7p to a pre-autophagosome structure that functions in autophageosome formation . Mutations in the Saccharomyces cerevisiae APG14 gene have been shown to cause defects in autophagy .
Active regulator of SIRT1 (AROS)
Type: Family

Human SIRT1, an NAD+-dependent deacetylase, plays a role in cell death/ survival, senescence, and endocrine signalling . Its substrates are well characterised, but evidence for the identity of its direct regulators has been wanting. Recently, the nuclear protein AROS (also termed 40S ribosomal protein S19-binding protein 1 ) has been implicated in the direct regulation of SIRT1 function - this protein has been dubbed 'active regulator of SIRT1. The protein has been shown to enhance SIRT1-mediated deacetylation of p53, in vitro and in vivo, and to inhibit p53-mediated transcriptional activity. It is the first direct SIRT1 regulator to have been identified that modulates p53-mediated growth regulation.
Activity-regulated cytoskeleton-associated protein (Arc)
Type: Family

The Activity-Regulated Cytoskeleton-associated protein (Arc), also referred to as Arg3.1 (Activity-Regulated Gene), is an immediate-early gene predominantly found in mammals that has been related to synaptic plasticity, learning and memory processes . It has been shown that Arc/Arg3.1 expression increases with strong synaptic activation . Its mRNA is transported to activated dendritic regions, conferring on the protein-distribution temporal correlation with the inducing stimulus and spatial specificity .

Via interactions with dynamin and endophilin isoforms, the Arc/Arg3.1 protein enhances receptor endocytosis . Specifically, it modulates trafficking of neuronal AMPA-type glutamate receptors (AMPARs) by accelerating endocytosis and reducing surface expression . In particular, Arc/Arg3.1 has been shown to reduce the number of GluR2/3 receptors, leading to a decrease in AMPAR-mediated synaptic currents . These observations are consistent with a role in homeostatic regulation of synaptic strength .
ABC transporter, acetoin utilisation, predicted permease Ytrc/YtrD (ABC_transptr_acetoin_YtrC/YtrD)
Type: Family

The genome of Bacillus subtilis, a well-characterised Gram-positive bacterium, encodes 4,100 protein-coding genes .Within the genome, six ytr genes form a single operon, ytrABCDEF, which may play a role in acetoin utilisation during stationary phase and sporulation, and is believed to encode a putative ATP-binding cassette (ABC) transport system .It has been suggested that YtrC and YtrD, which are highly hydrophobic proteins, may form a channel through the cell membrane: YtrC is predicted to contain nine TM segments and YtrD only eight .
Aquaporin 12 (Aquaporin_12)
Type: Family

Aquaporin-11 and aquaporin-12 (AQP12) belong to a new aquaporin subfamily termed superaquaporins . AQP12 is exclusively found in pancreatic acinar cells , and is not localised in the plasma membrane. No specific localisation has yet been established for this subfamily, but its presence in the pancreas implies some role in the secretion of digestive enzymes and fluids in the pancreatic cells . A structural characteristic of AQP12 is the lack of a cytoplasmic N-terminal region, by contrast with all other known aquaporins.

The aquaporins (AQPs) are a family of integral membrane proteins composed of two subfamilies: the orthodox aquaporins, which transport only water, and the aquaglyceroporins, which transport glycerol, urea, or other small solutes . AQP1 in pleural mesothelial cells participate in the formation of pleural fluid , renal AQP2 is involved in levels of solutes and changes in AQP9 in the hippocampus are related to delayed neuronal death . Aquaporins contain two tandem repeats, each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).
Aquaporin 11 (Aquaporin_11)
Type: Family

The aquaporins (AQPs) are a family of integral membrane proteins composed of two subfamilies: the orthodox aquaporins, which transport only water, and the aquaglyceroporins, which transport glycerol, urea, or other small solutes . AQP1 in pleural mesothelial cells participate in the formation of pleural fluid , renal AQP2 is involved in levels of solutes and changes in AQP9 in the hippocampus are related to delayed neuronal death . Aquaporins contain two tandem repeats, each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).

Aquaporin-11 (AQP11) and aquaporin-12 belong to a new aquaporin subfamily termed superaquaporins . AQP11 is found in the endoplasmic reticulum and has been connected to policystic kidney disease through knock-out experiments . It has also been shown that although the characteristic NPA motif may not be fully conserved in both tandem repeats, the molecule nevertheless preserves its water-transport function .
RNA (C5-cytosine) methyltransferase (RCMT)
Type: Family

RNA (C5-cytosine) methyltransferases (RCMTs) catalyse the transfer of a methyl group to the 5th carbon of a cytosine base in RNA sequences to produce C5-methylcytosine. RCMTs use the cofactor S-adenosyl-L-methionine (SAM) as a methyl donor . The catalytic mechanism of RCMTs involves an attack by the thiolate of a Cys residue on position 6 of the target cytosine base to form a covalent link, thereby activating C5 for methyl-group transfer. Following the addition of the methyl group, a second Cys residue acts as a general base in the beta-elimination of the proton from the methylated cytosine ring. The free enzyme is restored and the methylated product is released .

Numerous putative RCMTs have been identified in archaea, bacteria and eukaryota ; most are predicted to be nuclear or nucleolar proteins . The Escherichia coli Ribosomal RNA Small-subunit Methyltransferase Beta (RSMB) FMU (FirMicUtes) represents the first protein identified and characterised as a cytosine-specific RNA methyltransferase. RSMB was reported to catalyse the formation of C5-methylcytosine at position 967 of 16S rRNA .

A classification of RCMTs has been proposed on the basis of sequence similarity . According to this classification, RCMTs are divided into 8 distinct subfamilies . Recently, a new RCMT subfamily, termed RCMT9, was identified . Members of the RCMT contain a core domain, responsible for the cytosine-specific RNA methyltransferase activity. This 'catalytic' domain adopts the Rossman fold for the accommodation of the cofactor SAM . The RCMT subfamilies are also distinguished by N-terminal and C-terminal extensions, variable both in size and sequence .
RNA (C5-cytosine) methyltransferase, putative Rsm-related, plant (RCMT_RsmB-rel_pln)
Type: Family

RNA (C5-cytosine) methyltransferases (RCMTs) catalyse the transfer of a methyl group to the 5th carbon of a cytosine base in RNA sequences to produce C5-methylcytosine. RCMTs use the cofactor S-adenosyl-L-methionine (SAM) as a methyl donor . The catalytic mechanism of RCMTs involves an attack by the thiolate of a Cys residue on position 6 of the target cytosine base to form a covalent link, thereby activating C5 for methyl-group transfer. Following the addition of the methyl group, a second Cys residue acts as a general base in the beta-elimination of the proton from the methylated cytosine ring. The free enzyme is restored and the methylated product is released .

Numerous putative RCMTs have been identified in archaea, bacteria and eukaryota ; most are predicted to be nuclear or nucleolar proteins . The Escherichia coli Ribosomal RNA Small-subunit Methyltransferase Beta (RSMB) FMU (FirMicUtes) represents the first protein identified and characterised as a cytosine-specific RNA methyltransferase. RSMB was reported to catalyse the formation of C5-methylcytosine at position 967 of 16S rRNA .

A classification of RCMTs has been proposed on the basis of sequence similarity . According to this classification, RCMTs are divided into 8 distinct subfamilies . Recently, a new RCMT subfamily, termed RCMT9, was identified . Members of the RCMT contain a core domain, responsible for the cytosine-specific RNA methyltransferase activity. This 'catalytic' domain adopts the Rossman fold for the accommodation of the cofactor SAM . The RCMT subfamilies are also distinguished by N-terminal and C-terminal extensions, variable both in size and sequence .

Proteins related to the RsmB subfamily of RCMTs have been detected in the genomes of Viridiplantae . They were provisionally assigned to the RsmB subfamily , which hitherto was considered to be restricted to Eubacteria, based solely on similarity to the prototypic member of this subfamily, the E.coli protein .
RNA (C5-cytosine) methyltransferase, subfamily 9 (RCMT_subfamily_9)
Type: Family

RNA (C5-cytosine) methyltransferases (RCMTs) catalyse the transfer of a methyl group to the 5th carbon of a cytosine base in RNA sequences to produce C5-methylcytosine. RCMTs use the cofactor S-adenosyl-L-methionine (SAM) as a methyl donor . The catalytic mechanism of RCMTs involves an attack by the thiolate of a Cys residue on position 6 of the target cytosine base to form a covalent link, thereby activating C5 for methyl-group transfer. Following the addition of the methyl group, a second Cys residue acts as a general base in the beta-elimination of the proton from the methylated cytosine ring. The free enzyme is restored and the methylated product is released .

Numerous putative RCMTs have been identified in archaea, bacteria and eukaryota ; most are predicted to be nuclear or nucleolar proteins . The Escherichia coli Ribosomal RNA Small-subunit Methyltransferase Beta (RSMB) FMU (FirMicUtes) represents the first protein identified and characterised as a cytosine-specific RNA methyltransferase. RSMB was reported to catalyse the formation of C5-methylcytosine at position 967 of 16S rRNA .

A classification of RCMTs has been proposed on the basis of sequence similarity . According to this classification, RCMTs are divided into 8 distinct subfamilies . Recently, a new RCMT subfamily, termed RCMT9, was identified . Members of the RCMT contain a core domain, responsible for the cytosine-specific RNA methyltransferase activity. This 'catalytic' domain adopts the Rossman fold for the accommodation of the cofactor SAM . The RCMT subfamilies are also distinguished by N-terminal and C-terminal extensions, variable both in size and sequence .

As mentioned above, RCMT9 is a novel subtype of RCMT-related proteins. Putative orthologues of this subfamily have been detected only in Viridiplantae, Alveolata, Euglenozoa and Mycetozoa taxa. Members of this group are distantly related to the Nuclear protein 1 (NCL1) subfamily .
tRNA (C5-cytosine) methyltransferase, NCL1 (RCMT_NCL1)
Type: Family

RNA (C5-cytosine) methyltransferases (RCMTs) catalyse the transfer of a methyl group to the 5th carbon of a cytosine base in RNA sequences to produce C5-methylcytosine. RCMTs use the cofactor S-adenosyl-L-methionine (SAM) as a methyl donor . The catalytic mechanism of RCMTs involves an attack by the thiolate of a Cys residue on position 6 of the target cytosine base to form a covalent link, thereby activating C5 for methyl-group transfer. Following the addition of the methyl group, a second Cys residue acts as a general base in the beta-elimination of the proton from the methylated cytosine ring. The free enzyme is restored and the methylated product is released .

Numerous putative RCMTs have been identified in archaea, bacteria and eukaryota ; most are predicted to be nuclear or nucleolar proteins . The Escherichia coli Ribosomal RNA Small-subunit Methyltransferase Beta (RSMB) FMU (FirMicUtes) represents the first protein identified and characterised as a cytosine-specific RNA methyltransferase. RSMB was reported to catalyse the formation of C5-methylcytosine at position 967 of 16S rRNA .

A classification of RCMTs has been proposed on the basis of sequence similarity . According to this classification, RCMTs are divided into 8 distinct subfamilies . Recently, a new RCMT subfamily, termed RCMT9, was identified . Members of the RCMT contain a core domain, responsible for the cytosine-specific RNA methyltransferase activity. This 'catalytic' domain adopts the Rossman fold for the accommodation of the cofactor SAM . The RCMT subfamilies are also distinguished by N-terminal and C-terminal extensions, variable both in size and sequence .

The prototypical member of the Nuclear protein 1 RCMT subfamily, the S. cerevisiae NCL1 (also known as Trm4), has been demonstrated to methylate cytosine to C5-methylcytosine at positions 34, 40, 48 and 49 in different intron- containing tRNAs and tRNA precursors . Its human homologue, MISU/NSUN2, was found to catalyse the formation of C5-methylcytosine at position 34 of intron-containing pre-tRNAs ; it was not able to modify tRNAs at positions 48 or 49. It was also shown to be involved in Myc-mediated proliferation of cancer cells .
Aquaporin-like (Aquaporin-like)
Type: Homologous_superfamily

This superfamily represents the aquaporin-like structural domain.

The major intrinsic protein (MIP) family is large and diverse, possessing over 100 members that form transmembrane channels. These channel proteins function in water, small carbohydrate (e.g., glycerol), urea, NH3, CO2 and possibly ion transport, by an energy independent mechanism. They are found ubiquitously in bacteria, archaea and eukaryotes.

The MIP family contains two major groups of channels: aquaporins and glycerol facilitators. The known aquaporins cluster loosely together as do the known glycerol facilitators. MIP family proteins are believed to form aqueous pores that selectively allow passive transport of their solute(s) across the membrane with minimal apparent recognition. Aquaporins selectively transport water (but not glycerol) while glycerol facilitators selectively transport glycerol but not water. Some aquaporins can transport NH3 and CO2. Glycerol facilitators function as solute nonspecific channels, and may transport glycerol, dihydroxyacetone, propanediol, urea and other small neutral molecules in physiologically important processes. Some members of the family, including the yeast FPS protein and tobacco NtTIPA may transport both water and small solutes.
Cytochrome C oxidase, subunit VIIB domain superfamily (Cyt_c_oxidase_suVIIB_dom_sf)
Type: Homologous_superfamily

Cytochrome oxidase subunit VIIB is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport . The X-ray structure of azide-bound fully oxidized cytochrome c oxidase from bovine heart at 2.9 A resolution has been determined .

This superfamily represents a structural domain of cytochrome C oxidase, subunit VIIB.
RNA (C5-cytosine) methyltransferase, NOP2 (RCMT_NOP2)
Type: Family

The prototypical member of the Nucleolar Protein 2 RCMT subfamily, the S.cerevisiae NOP2, is an essential nucleolar protein required for pre-rRNA processing and 60S ribosomal subunit assembly that acts as a ribosomal RNA methyltransferase . Its human homologue, the proliferation-associated nucleolar antigen P120, is a promising tumour marker . P120 has been demonstrated to be implicated in rRNA biogenesis , and is also proposed to act as an rRNA methyltransferase .

RNA (C5-cytosine) methyltransferases (RCMTs) catalyse the transfer of a methyl group to the 5th carbon of a cytosine base in RNA sequences to produce C5-methylcytosine. RCMTs use the cofactor S-adenosyl-L-methionine (SAM) as a methyl donor . The catalytic mechanism of RCMTs involves an attack by the thiolate of a Cys residue on position 6 of the target cytosine base to form a covalent link, thereby activating C5 for methyl-group transfer. Following the addition of the methyl group, a second Cys residue acts as a general base in the beta-elimination of the proton from the methylated cytosine ring. The free enzyme is restored and the methylated product is released .

Numerous putative RCMTs have been identified in archaea, bacteria and eukaryota ; most are predicted to be nuclear or nucleolar proteins . The Escherichia coli Ribosomal RNA Small-subunit Methyltransferase Beta (RSMB) FMU (FirMicUtes) represents the first protein identified and characterised as a cytosine-specific RNA methyltransferase. RSMB was reported to catalyse the formation of C5-methylcytosine at position 967 of 16S rRNA .

A classification of RCMTs has been proposed on the basis of sequence similarity . According to this classification, RCMTs are divided into 8 distinct subfamilies . Recently, a new RCMT subfamily, termed RCMT9, was identified . Members of the RCMT contain a core domain, responsible for the cytosine-specific RNA methyltransferase activity. This 'catalytic' domain adopts the Rossman fold for the accommodation of the cofactor SAM . The RCMT subfamilies are also distinguished by N-terminal and C-terminal extensions, variable both in size and sequence .
Aquaporin 1 (Aquaporin_1)
Type: Family

Aquaporins are water channels, present in both higher and lower organisms, that belong to the major intrinsic protein family. Most aquaporins are highly selective for water, though some also facilitate the movement of small uncharged molecules such as glycerol . In higher eukaryotes these proteins play diverse roles in the maintenance of water homeostasis, indicating that membrane water permeability can be regulated independently of solute permeability. In microorganisms however, many of which do not contain aquaporins, they do not appear to play such a broad role. Instead, they assist specific microbial lifestyles within the environment, e.g. they confer protection against freeze-thaw stress and may help maintain water permeability at low temperatures . The regulation of aquaporins is complex, including transcriptional, post-translational, protein-trafficking and channel-gating mechanisms that are frequently distinct for each family member.

Structural studies show that aquaporins are present in the membrane as tetramers, though each monomer contains its own channel . The monomer has an overall "hourglass" structure made up of three structural elements: an external vestibule, an internal vestibule, and an extended pore which connects the two vestibules. Substrate selectivity is conferred by two mechanisms. Firstly, the diameter of the pore physically limits the size of molecules that can pass through the channel. Secondly, specific amino acids within the molecule regulate the preference for hydrophobic or hydrophilic substrates.

Aquaporins are classified into two subgroups: the aquaporins (also known as orthodox aquaporins), which transport only water, and the aquaglyceroporins, which transport glycerol, urea, and other small solutes in addition to water .

Aquaporin-1 is the major water channel present in the kidney proximal renal tubule. Members of the family contain approximately 275 amino acids. Aquaporin-1 is under complex regulation, including hormones and homeostatic factors like hypertonicity . It is also expressed in red blood cells, the gastrointestinal tract, lungs and in the brain, where it may have a role in cerebral oedema after surgery or trauma . Apart from controlling the water balance of the organism , aquaporin-1 is thought to have an impact on various cellular processes, such as angiogenesis, and cell migration and metastasis observed in some human malignancies. Its expression has also been proposed as a characteristic feature of an aggressive sub-group of breast carcinomas.