SII-SWORD/CoKE huggingface dataset:
Nitrite reductase [NAD(P)H], large subunit (Nitrite_Rdtase_lsu)
Type: Family

This entry represents the nitrite reductase [NAD(P)H] large subunit.
Uncharacterised conserved protein UCP037158 (UCP037158)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Uncharacterised conserved protein UCP037159 (UCP037159)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
PR-domain zinc finger protein PRDM4 (PRDM4)
Type: Family

PRDM4 may function as a transcription factor that recruits protein arginine methyltransferase 5 (PRMT5) to mediate histone arginine methylation and control neural stem cell proliferation and differentiation .
PR-domain zinc finger protein PRDM5-like (Znf_PRDM5-like)
Type: Family

This entry represents PR-domain zinc finger protein PRDM5, which is a sequence-specific DNA-binding transcription factor that targets hematopoiesis-associated protein-coding and microRNA genes . This entry also includes some related zinc finger proteins from animals.
PR-domain zinc finger protein PRDM12 (Znf_PRDM12)
Type: Family

PRDM12 is involved in the positive regulation of histone H3-K9 dimethylation. It is essential for human pain perception .
Ribosomal protein uL3 glutamine methyltransferase (Ribosome_uL3_MTase)
Type: Family

This entry represents Ribosomal protein uL3 glutamine methyltransferase from Escherichia coli (uL3 MTase) and similar sequences from proteobacteria. uL3 MTase, often annotated as PrmB, specifically methylates ribosomal protein uL3 on 'Gln-150' . It is closely related to HemK, the N(5)-glutamine methyltransferase for a critical residue in peptide release factors RF-1 and RF-2.
Catechol O-methyltransferase, eukaryotic (Catechol_O-MeTrfase_euk)
Type: Family

This entry represents a family of catechol O-methyltransferases found in eukaryotes. Catechol O-methyl transferase (COMT), along with several other enzymes, degrades catecholamines such as dopamine, epinephrine and norepinephrine. It introduces a methyl group, donated by S-adenosyl methionine (SAM) to the catecholamine. It is found in the postsynaptic neurons . COMT inactivates catecholamines as well as catechol drugs such as L-DOPA. It is possible that the COMT gene is involved in neuropsychiatric conditions in which there are abnormalities in catecholamine neurotransmission, including mood disorders, schizophrenia, obsessive compulsive disorder, alcohol and substance abuse and attention deficit hyperactivity disorder . An association between the COMT Val158Met polymorphism and aggressive schizophrenia has been established.
Bifunctional hydroxyisourate hydrolase/2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase (HIU_hydrol/OHCU_decarb)
Type: Family

The proteins in this family are bifunctional having an OHCU decarboxylase domain and a hydroxyisourate hydrolase domain. OHCU decarboxylase are involved in purine catabolism catalysing the conversion of OHCU into S(+)-allantoin . This is the third step of the conversion of uric acid (a purine derivative) to allantoin. Step one is catalysed by urate oxidase (

) and step two is catalysed by hydroxyisourate hydrolase (

).
Cholesteryl ester transfer (Cholesteryl_ester_transfer)
Type: Family

This group represents cholesteryl ester transfer protein, also known as lipid transfer protein 1. This protein shuttles various lipids between lipoproteins, resulting in the net transfer of cholesteryl esters from atheroprotective, high-density lipoproteins (HDL) to atherogenic, lower-density species. Thus, inhibtion of this enzyme raises the concentration of protective HDL and could conceivably be used as a treatment for cardiovascular disease. The protein forms a long tunnel which can accomodate four lipid molecules .
Small ribonucleoprotein associated, SmB/SmN (snRNP-assoc_SmB/SmN)
Type: Family

This entry represents a group of small nuclear ribonucleoprotein associated proteins from animals and plants, including SmB and SmN. Human SmB plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome . It is associated with cerebrocostomandibular syndrome . Human SmN is related to some form of Prader-Willi syndrome .
Sm-like protein Lsm7 (Lsm7)
Type: Family

This entry represents Sm-like protein Lsm7. It could be found in the nuclear Lsm2-8 complex or in the cytoplasmic Lsm1-7 complex.

The Lsm2-8 complex associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 snRNP, U4/U6.U5 snRNP, and free U6 snRNP). It binds and stabilizes the 3'-terminal poly(U) tract of U6 snRNA and facilitates the assembly of U4-U6 di-snRNP and U4-U6-U5 tri-snRNP . The Lsm1-7 complex associates with deadenylated mRNA and promotes decapping in the 5'-3' mRNA decay pathway .

The Sm and the Lsm proteins, characterised by the Sm-domain, have RNA-related functions. The Sm heptamer ring associates with four (U1, U2, U4, U5) snRNPs, while Lsm2-8 heptamer is part of the U6 snRNP. Another Lsm heptameric complex, Lsm1-7, which differs from Lsm2-8 by one Lsm protein, functions in mRNA decapping, a crucial step in the mRNA degradation pathway .
L-tyrosine isonitrile synthase (PvcA)
Type: Family

This protein family represents L-tyrosine isonitrile synthase (PvcA), which is involved in the biosynthesis of paerucumarin, a cyclized isocyano derivative of tyrosine .
Ubiquitin-protein ligase E3A (UBE3A)
Type: Family

UBE3A (also known as E6-AP) is an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates. It regulates cell proliferation by promoting proteasomal degradation of p27 . It can also serve as a molecular circadian clock through regulating the BMAL1 transcription factor .
D-glutamate cyclase, mitochondrial (D-Glu_cyclase_mito)
Type: Family

This family includes mitochondrial D-glutamate cyclase (

), which converts D-glutamate to 5-oxo-D-proline .
Uncharacterised conserved protein UCP037205 (UCP037205)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Arginine-tRNA-protein transferase 1, eukaryotic (Arg-tRNA-P_Trfase_1_euk)
Type: Family

Arginine-tRNA-protein transferase catalyses the post-translational conjugation of arginine to the N terminus of a protein. In eukaryotes, this functions as part of the N-end rule pathway of protein degradation by conjugating a destabilising amino acid to the N-terminal aspartate or glutamate of a protein, targeting the protein for ubiquitin-dependent proteolysis . In Saccharomyces cerevisiae, Cys20, 23, 94 and/or 95 are thought to be important for activity . Of these, only Cys 94 appears to be completely conserved in this family.

This entry represents eukaryotic type arginyl-tRNA--protein transferase 1 (

) .
Aspartate/glutamate leucyltransferase (Asp_Glu_LeuTrfase)
Type: Family

This entry represents a family of prokaryotic aminoacyl-transferases, specifically aspartate/glutamate leucyltransferase.

Aspartate/glutamate leucyltransferase (also known as bacterial protein transferase or Bpt) functions in the N-end rule pathway of protein degradation where it conjugates Leu from its aminoacyl-tRNA to the N-termini of proteins containing an N-terminal aspartate or glutamate. This protein shows sequence similarity to the eukaryotic N-end rule pathway component arginyl-transferase Ate1 .
Uncharacterised conserved protein UCP037213 (UCP037213)
Type: Family

There is currently no experimental data for members of this family of archaeal proteins, nor do they exhibit features indicative of any function.
ThermoDBP-related, archaea (ThermoDBP-RPs_arc)
Type: Family

This entry represents a group of proteins related to archaeal non-canonical single-stranded DNA-binding proteins (ThermoDBPs) named ThermoDBP-related proteins. These proteins have been related to genome maintenance in particularly challenging environments, but their specific function is still unknown .
Peptidase M20, carboxypeptidase S (Pept_M20_carboxypep)
Type: Family

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This group represents carboxypeptidase S (also known as Gly-X carboxypeptidase), a member of the MEROPS peptidase family M20 (clan MH) . Carboxypeptidase S has a preference for releasing an amino acid attached to Gly . The peptidases of this clan have two catalytic zinc ions at the active site, bound by His/Asp, Asp, Glu, Asp/Glu and His. The catalysed reaction involves the release of an N-terminal aminoacid, usually neutral or hydrophobic, from a polypeptide .
The peptidases in this entry belong to the M20A sub-family.
Nitric oxide synthase, oxygenase subunit (Nitric_oxide_synthase_Oase-su)
Type: Family

This entry represents the oxygenase subunit of nitric oxide synthase (

), which is the enzyme's catalytic centre responsible for the production of nitric oxide . This enzyme uses haem as a cofactor, as well as either tetrahydrobiopterin (H4B). It can also use tetrahydrofolate (THF) in place of H4B but binds THF with much lower affinity than H4B. This protein is similar to the oxygenase domain of eukaryotic nitric oxide synthases but lacks the reductase domain which, in eukaryotes, is responsible for transfer of electrons to the ferric haem during nitric oxide synthesis.
Uncharacterised conserved protein UCP037225 (UCP037225)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Xaa-Arg dipeptidase (Xaa-Arg_dipeptidase)
Type: Family

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This family includes Xaa-Arg dipeptidases (

also known as beta-Ala-Lys dipeptidases), metallopeptidases that belong to the M20A peptidase family, subfamily D (MEROPS M20.021). These proteins catalyse the peptide bond hydrolysis in dipeptides having basic amino acids lysine, ornithine or arginine at C-terminal. They may function in a metabolite repair mechanism by eliminating alternate dipeptide by-products formed during carnosine synthesis .
Aminobenzoyl-glutamate utilization protein B (Aminobenzoyl-glu_utiliz_pB)
Type: Family

This entry contains proteins that are related to glutamate carboxypeptidase and classed as non-peptidase homologues belonging to MEROPS peptidase family M20 (glutamate carboxypeptidase, clan MH) .

The bacterial amidohydrolase abgB catalyses the cleavage of p-aminobenzoyl-glutamate, a folate catabolite in Escherichia coli, to p-aminobenzoate and glutamate. p-Aminobenzoyl-glutamate is a natural end product of folate catabolism, and its utilization is initiated by the abg region gene product, AbgT, by enabling uptake of its into the cell in a concentration-dependent, saturable manner. It is subsequently cleaved by AbgA and AbgB (sometimes referred to as AbgAB) .
Type 2 lantibiotic biosynthesis protein LanM (Lanti_2_LanM)
Type: Family

Lantibiotics are peptide antimicrobials characterised by the unique amino acids lanthionine and methyllanthionine, which are introduced by dehydration of Ser/Thr residues and linkage of the resulting dehydrated amino acids with Cys residues. Members of this family are known generally as LanM, a multifunctional enzyme of lantibiotic biosynthesis . This catalysis by LanM distinguishes the type 2 lantibiotics, such as lacticin 481, mersacidin, cinnamycin, and lichenicidin, from LanBC-produced type 1 lantibiotics such as nisin and subtilin.

The N-terminal domain of LanM enzymes contains regions associated with Ser and Thr dehydration . The C-terminal region is a LanC-type domain (

) that catalyses the formation of the lanthionine bridge .
Tricalbin (Tricalbin)
Type: Family

Tricalbins constitute a synaptotagmin-like yeast protein family. Tricalbins contain several copies of C2 domains and are thought to be involved in membrane traffic . As extended synaptotagmins, tricalbins also possess a synaptotagmin-like mitochondrial lipid-binding protein (SMP) domain that is found in proteins localized to ER-organelle contact sites . The ER-plasma membrane tethering function of tricalbins mediates the formation of ER-PM contacts sites which are thought to mediate transport glycerolipids between the two bilayers . The family consists of three members: tricalbin 1-3. The C2 domains of tricalbins 1 and 3 are calcium-dependent lipid-binding units comparable to mammalian synaptotagmin C2 domains, while tricalbin 2 does not seem to bind lipids in response to calcium signaling .
Vacuolar protein sorting-associated protein 13, fungi (VPS13_fungi)
Type: Family

This group represents a vacuolar protein sorting-associated protein Vps13, fungal type. It is involved in the delivery of proteins to the vacuole in vegetatively growing yeast and also regulates membrane morphogenesis during sporulation . Mediates the transfer of lipids between membranes at organelle contact sites . Vps13 from S. cerevisiae is involved in mitochondrial lipid homeostasis, in a MCP1-dependent manner .
Glutathione degradosome, Dug2 (GSH_degradosome_Dug2)
Type: Family

Glutathione (GSH), the major low-molecular-weight thiol compound in most eukaryotic cells, is normally degraded through the gamma-glutamyl cycle initiated by the action of gamma-glutamyl transpeptidase. A novel pathway for the degradation of GSH that requires the participation of three previously uncharacterised genes has been identified in Saccharomyces cerevisiae. These genes are Dug1 (YFR044c), Dug2 (YBR281c), and Dug3 (YNL191w), which is defective in utilization of glutathione. Although dipeptides and tripeptides with a normal peptide bond, such as cys-gly or glu-cys-gly, can be hydrolysed by the Dug1 protein (a metallopeptidase), the presence of an unusual peptide bond, such as in GSH, requires the participation of the Dug2 and Dug3 gene products as well. The Dug3 gene encodes a protein with a glutamine amidotransferase domain. These three proteins form a GSH degradosomal complex .
Peptidase M20, glutamate carboxypeptidase (Pept_M20_glutamate_carboxypep)
Type: Family

Glutamate carboxypeptidase (also known as carboxypeptidase G2, CPDG2, CPG2 or folate hydrolase G2) belongs to the peptidase M20 family. It is a periplasmic enzyme that is synthesized with a signal peptide. CPDG2 is a dimeric zinc-dependent exopeptidase, with two domains, a catalytic domain, which provides the ligands for the two zinc ions in the active site, and a dimerization domain . CPDG2 cleaves the C-terminal glutamate moiety from a wide range of N-acyl groups, including peptidyl, aminoacyl, benzoyl, benzyloxycarbonyl, folyl, and pteroyl groups to release benzoic acid, phenol, and aniline mustards. It is used clinically to treat methotrexate toxicity by hydrolyzing it to inactive and non-toxic metabolites. It is also proposed for use in antibody-directed enzyme prodrug therapy; for example, glutamate can be cleaved from glutamated benzoyl nitrogen mustards, producing nitrogen mustards with effective cytotoxicity against tumor cells .
5'-3' exoribonuclease type 2 (Xrn2/3/4)
Type: Family

5'-3'-exoribonucleases are enzymes that degrade RNA by removing terminal nucleotides from the 5' end. Hydrolytic exoribonucleases, to which this entry belongs, produce nucleotide monosphosphates. An exosome and a 5'-3'-exoribonuclease are important in the degradation of very unstable transcripts .

This entry includes 5'-3'exoribonuclease type 2 (Xrn2, also known as Rat1), which occurs in animal, plant and fungal lineages. They act as post-transcriptional gene silencing (PTGS) suppressors . In Saccharomyces cerevisiae, Rat1 serves to terminate RNA polymerase II (RNAPII) molecules engaged in the production of uncapped RNA . This entry also includes plant Xrn3 and Xrn4.
Cytosolic nonspecific dipeptidase/DUG1 (CNDP/DUG1)
Type: Family

This peptidase M20 subfamily includes CNDP1 (beta-Ala-His dipeptidase), CNDP2 (cytosolic nonspecific dipeptidase) and DUG1 from yeast, which are metallopeptidases .

Two genes, CN1 and CN2, that degrade carnosine (beta-alanyl-L-histidine) and homocarnosine (gamma-aminobutyric acid-L-histidine), two naturally occurring dipeptides with potential neuroprotective and neurotransmitter functions, have been identified. CN1 encodes for serum carnosinase and has narrow substrate specificity for Xaa-His dipeptides, where Xaa can be beta-alanine (carnosine), N-methyl beta-alanine, alanine, glycine and gamma-aminobutyric acid (homocarnosine). CN2 corresponds to the cytosolic nonspecific dipeptidase (CNDP2) and is not limited to Xaa-His dipeptides. CNDP2 requires Mn(2+) for full activity and does not hydrolyze homocarnosine .

Metallodipeptidase DUG1 is a subunit of the GSH degradosomal complex, involved in the degradation of glutathione (GSH) and other peptides containing a gamma-glu-X bond. Although dipeptides and tripeptides with a normal peptide bond, such as cys-gly or glu-cys-gly, can be hydrolysed by the DUG1 protein, the presence of an unusual peptide bond, such as in GSH, requires the participation of the DUG2 and DUG3 gene products as well. These three proteins form a GSH degradosomal complex .
PC4-like (PC4-like)
Type: Family

This family includes PC4-like proteins predominantly found in bacteria, such as SP_0782 from Streptococcus pneumoniae (

). The crystal structure of this protein has similarity with PC4 and YdbC (

), but it binds shorter ssDNA lengths. This protein adopts a dimeric assembly in which each monomer folds into an anti-parallel β-sheet made of four β-strands in the N-terminal and one α-helix in the C-terminal .
Histone-lysine N-methyltransferase SETD7 (Hist-Lys_N-MeTrfase_SETD7)
Type: Family

This entry represents histone-lysine N-methyltransferase SETD7 (also known as SET7/9) (

), which contains a SET domain . This enzyme specifically monomethylate Lys-4 of histone H3, thereby creating a specific tag for epigenetic transcriptional activation. Methylation of lysine residues in the N-terminal tails of histones is thought to represent an important component of the mechanism that regulates chromatin structure. As such SETD7 plays a central role in the transcriptional activation of genes such as collagenase and insulin. It is recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription . SETD7 also has methyltransferase activity toward non-histone proteins, including TAF10 and p53/TP53. SETD7 monomethylates Lys-189 of TAF10, which increases the affinity of TAF10 for RNA polymerase II. SETD7 monomethylates Lys-372 of p53/TP53, which stabilises p53/TP53 and increases p53/TP53-mediated transcriptional activation .
Carboxysome assembly protein CcmM (CcmM)
Type: Family

This entry represents CcmM, which functions as a scaffold protein for the assembly of β-carboxysomes, initiates carboxysome assembly via its N-terminal domain binding to CcaA, CcmK and CcmL. Binds HCO3-, suggesting it may play a role in the activity or regulation of bicarbonate dehydration .

Aquatic photosynthetic organisms, like cyanobacteria, respond to low-CO(2) conditions by inducing a CO(2) concentrating mechanism (CCM) in the carboxysome. The CCM allows photosynthesis to proceed in CO2-limited aquatic environments . Carbonic anhydrases (CAs) and zinc metalloenzymes are important parts of the CCM. They catalyse the interconversion of CO(2) and HCO(3)(-) .

The CCM components include at least four modes of active inorganic carbon uptake, including two bicarbonate transporters and two CO(2) uptake systems associated with the operation of specialised NDH-1 complexes. This results in the accumulation of HCO(3)(-) in the cytosol of the cell, which is subsequently used by the ribulose 1.5-bisphosphate carboxylase/oxygenase (RubisCO)-containing carboxysome protein micro-compartment within the cell to elevate CO(2) around RubisCO . Carboxysomal carbonic anhydrase is thought to dehydrate abundant cytosolic bicarbonate and provide RubisCO, sequestered within the carboxysome, with sufficiently high concentrations of CO(2) to permit its efficient fixation onto ribulose 1,5-bisphosphate .
Arylacetamide deacetylase (Arylacetamide_deacetylase)
Type: Family

The lipase arylacetamide deacetylase is involved in the utilisation of triacylglycerol (TAG) for the assembly of very-low-density lipoprotein (VLDL) in the secretory apparatus of the hepatocyte, as the process is mobilized by lipolysis of the cytosolic TAG pool, followed by re-esterification . The enzyme competes with cytosolic arylamine N-acetyltransferase, which catalyses one of the initial biotransformation pathways for arylamine and heterocyclic amine carcinogens in many tissues in many species .
Transcription regulator, CBS domain-containing, predicted (Tscrpt-reg_CBS-contain_prd)
Type: Family

This entry represents a family of predicted transcriptional regulators, which contain CBS domains.
Gremlin-1/2 (Gremlin-1/2)
Type: Family

This entry includes Gremlin-1 and -2. Gremlin 1 (grem 1) is known for its antagonistic reaction with bone morphogenetic proteins (BMPs) in the TGF beta signalling pathway. Grem 1 acts as a cytokine that regulates embryonic morphogenesis via BMP family members .
Uncharacterised conserved protein UCP037256 (UCP037256)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Uncharacterised conserved protein UCP037266 (UCP037266)
Type: Family

Members in this family are found in various hypothetical prokaryotic proteins. Their function is not clear. They contain a probable winged helix DNA-binding domain.