SII-SWORD/CoKE huggingface dataset:
Non-canonical purine NTP phosphatase/PRRC1 (NTPase/PRRC1)
Type: Domain

This entry represents a domain found in non-canonical purine NTP phosphatases and in PRRC1 (proline-rich and coiled-coil-containing protein 1). These phosphatases hydrolyse non-canonical purine nucleotides such as XTP and ITP to their respective diphosphates derivatives . PRRC1 is a Golgi-associated protein of unknown function .
Protein PRRC1 (PRRC1)
Type: Family

Proline-rich and coiled-coil-containing protein 1 (PRRC1) is a Golgi-associated protein of unknown function .
MRG domain (MRG_dom)
Type: Domain

MORF4 (mortality factor on chromosome 4), MRG15 (MORF4-related gene on chromosome 15) and MRGX (MORF4-related gene on chromosome X) are members of the MRG protein family that were first identified as transcription factors involved in cellular senescence. All expressed members of the MRG family are localized to the nucleus and have predicted motifs that indicate they function as chromatin remodeling complex components. MORF4, MRG15 and MRGX share a common C-terminal part but a different N-terminal part. The C-terminal similarity of all MRG family members (MORF4, MRG15 and MRGX homologues) defines a new conserved protein domain. The ~170 amino acid MRG domain binds a plethora of transcriptional regulators and chromatin-remodeling factors, including the histone deacetylase transcriptional corepressor mSin3A and the nuclear protein PAM14 (protein-associated MRG, 14kDa) .

The MRG domain consists of three conserved blocks. It is predominantly hydrophobic, and consists of mainly α-helices that are arranged in a three layer sandwich topology. The hydrophobic core is stabilised by interactions among a number of conserved hydrophobic residues. The molecular surface is largely hydrophobic, but contains a few hydrophilic patches .
Frizzled-6, 7TM (FZD6_7TM)
Type: Domain

This entry represents the transmembrane domain of Frizzled-6, which is predicted to contain seven transmembrane α-helices. Frizzled-6 deficiency results in a severe midbrain morphogenesis defect in mice . In humans, mutations in Frizzled-6 have been described to cause nail dysplasia .

Frizzleds are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors . They have important regulatory roles during embryonic development .

Frizzleds expose their large N terminus on the extracellular side. The N-terminal, extracellular cysteine-rich domain (CRD) has been implicated as the Wnt binding domain and its structure has been solved . The cysteine-rich domain of Frizzled (Fz) is shared with other receptor tyrosine kinases that have roles in development including the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. The cytoplasmic side of many Fz proteins has been shown to interact with the PDZ domains of PSD-95 family members and is thought to have a role in the assembly of signalling complexes. The conserved cytoplasmic motif of Fz, Lys-Thr-X-X-X-Trp, is required for activation of the beta-catenin pathway, and for membrane localisation and phosphorylation of Dsh.

In Drosophila melanogaster, the frizzled locus is involved in planar cell polarity, which is the coordination of the cytoskeleton of epidermal cells to produce a parallel array of cuticular hairs and bristles . In the wild-type wing, all hairs point towards the distal tip , whereas in Fz mutants, the orientation of individual hairs with respect both to their neighbours and to the organism as a whole is altered. In the developing wing, Fz function is required for cells to respond to the extracellular polarity signal as well as the proximal-distal transmission of an intracellular polarity signal.

In Caenorhabditis elegans, protein mom-5 is the equivalent of frizzled .

Three main signalling pathways are activated by agonist-activated Frizzled proteins: the Fz/beta-catenin pathway, the Fz/Ca2+ pathway and the Fz/PCP (planar cell polarity) pathway . The Wnt/beta-catenin pathway is the best studied signalling pathway involving Fz receptors. In the Wnt/beta-catenin pathway the first downstream cytoplasmic components activated by Fz signalling include Dishevelled (Dsh) and/or its regulatory kinases.
Frizzled-4, 7TM (FZD4_7TM)
Type: Domain

Frizzleds are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors . They have important regulatory roles during embryonic development .

Frizzleds expose their large N terminus on the extracellular side. The N-terminal, extracellular cysteine-rich domain (CRD) has been implicated as the Wnt binding domain and its structure has been solved . The cysteine-rich domain of Frizzled (Fz) is shared with other receptor tyrosine kinases that have roles in development including the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. The cytoplasmic side of many Fz proteins has been shown to interact with the PDZ domains of PSD-95 family members and is thought to have a role in the assembly of signalling complexes. The conserved cytoplasmic motif of Fz, Lys-Thr-X-X-X-Trp, is required for activation of the beta-catenin pathway, and for membrane localisation and phosphorylation of Dsh.

Three main signaling pathways are activated by agonist-activated Frizzled proteins: the Fz/beta-catenin pathway, the Fz/Ca2 pathway and the Fz/PCP (planar cell polarity) pathway . The Wnt/beta-catenin pathway is the best studied signalling pathway involving Fz receptors. In the Wnt/beta-catenin pathway the first downstream cytoplasmic components activated by Fz signalling include Dishevelled (Dsh) and/or its regulatory kinases.

This entry represents the C-terminal transmembrane domain of Frizzled-4. Together with Frizzled-8, this protein has a major role in controlling ureteric growth in the developing kidney . In humans, mutations in the gene encoding Frizzled-4 are related to familial exudative vitreoretinopathy, a disorder characterised by the incomplete development of the retinal vasculature .
KAT8 regulatory NSL complex subunit 3/Testis-expressed sequence 30 protein (NSL3/Tex30)
Type: Family

This entry includes the animal KAT8 regulatory NSL complex subunit 3 (KANSL3 or NSL3, also known as testis development protein PRTD), the testis-expressed sequence 30 proteins and their homologues, such as C. elegans SUMV-2 protein.

KAT8 regulatory NSL complex subunit 3 is part of the NSL complex that is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription . The function of the testis-expressed sequence 30 protein is not known.

SUMV-2 interacts with SUMV-1, and they may function together with MYS-2 in a nematode KAT8/MOF-like complex to antagonise the activity of the synMuv (synthetic multivulva) genes .
Probable transcriptional regulatory protein YeeN (Transcrip_reg_TACO1_YeeN)
Type: Family

This is entry represents the probable transcriptional regulatory protein YeeN family. In Pseudomonas aeruginosa, a member of this family, PmpR, is involved in regulation of the quinolone signal (PQS) system and of pyocyanine production. It negatively regulates the quorum-sensing response regulator pqsR of the PQS system by binding to its promoter region .
Transcriptional regulator TACO1-like, domain 3 (Transcrip_reg_TACO1-like_dom3)
Type: Homologous_superfamily

Transcriptional regulator TACO1-like proteins consist of three domains. This entry represents domain 3 .
Putative pyruvate, phosphate dikinase regulatory protein (PPDK_reg)
Type: Family

This is a family of proteins which are putative bifunctional serine/threonine kinase/phosphorylases involved in the regulation of the pyruvate, phosphate dikinase (PPDK) by catalysing its phosphorylation/dephosphorylation .
Large ribosomal subunit protein bL28 (Ribosomal_bL28)
Type: Family

This entry consists of large ribosomal subunit protein bL28 from bacteria and eukaryotes, including the mitochondrial bL28m (also known as 39S ribosomal protein L28, MRLP28) from vertebrates, mitochondrial bL28m (also known as 54S ribosomal protein L24, MRLP24) from yeast and bL28c (also known as 50S ribosomal protein L28, RPL28) from plants. They are components of the mitochondrial or non-mitochondrial large ribosomal subunits.

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 .
Coiled-coil domain-containing protein 86 (CCDC86)
Type: Family

Coiled-coil domain-containing protein 86 (also known as Cyclon) is a cytokine-induced protein . It has been shown to interact with hepatitis C virus (HCV) protein NS5A .
Transmembrane protein 186 (Tmem186)
Type: Family

This is a family of uncharacterised proteins known as transmembrane protein 186.
Transmembrane protein 267 (TMEM267)
Type: Family

This family of transmembrane proteins has no known function.
Modulator protein MzrA (Modulator_MzrA)
Type: Family

MzrA modulates the activity of the EnvZ/OmpR two-component regulatory system, probably by directly modulating EnvZ enzymatic activity and increasing stability of phosphorylated OmpR . EnvZ/OmpR mediates regulation of OmpF and OmpC, the two major pore-forming outer membrane proteins (OMPs).
Cyclic nucleotide phosphodiesterase GpdQ/CpdA-like (GpdQ/CpdA-like)
Type: Family

This entry includes a group of cyclic nucleotide phosphodiesterases, including GpdQ and CpdA. They belong to the metallophosphatase (MPP) superfamily.

GpdQ (glycerophosphodiesterase Q, also known as Rv0805 in Mycobacterium tuberculosis) is a binuclear metallophosphoesterase from Enterobacter aerogenes that catalyzes the hydrolysis of mono-, di-, and triester substrates, including some organophosphate pesticides and products of the degradation of nerve agents . The GpdQ homologue, Rv0805, has 2',3'-cyclic nucleotide phosphodiesterase activity .

CpdA hydrolyses cAMP to 5'-AMP. It plays an important regulatory role in modulating the intracellular concentration of cAMP, thereby influencing cAMP-dependent processes . In Pseudomonas is specifically required for regulation of virulence factors and can also hydrolyse cGMP .
Proofreading thioesterase EntH (Thioesterase_EntH)
Type: Family

EntH is required for optimal synthesis of enterobactin, a siderophore synthesised in response to iron limitation. EntH acts as a proofreading enzyme that prevents carrier protein EntB misacylation by hydrolysing the thioester bound existing between EntB and wrongly charged molecules .
Replication modulator SeqA, C-terminal DNA-binding domain (SeqA_DNA-bd_C)
Type: Domain

The binding of the negative modulator of initiation of replication (SeqA) protein to hemimethylated GATC sequences is important in the negative modulation of chromosomal initiation at oriC, and in the formation of SeqA foci necessary for Escherichia coli chromosome segregation . SeqA tetramers are able to aggregate or multimerize in a reversible, concentration-dependent manner . Apart from its function in the control of DNA replication, SeqA may also be a specific transcription factor .

The C-terminal domain binds DNA, binding to hemimethylated GATC sequences at oriC . The structure of the C-terminal domain consists of seven α-helices and three-stranded β-sheet.
L-carnitine dehydrogenase (L-carnitine_dehydrogenase)
Type: Family

L-carnitine dehydrogenase catalyses the NAD+-dependent oxidation of L-carnitine to 3-dehydrocarnitine. Its substrates are L-carnitine and NAD+ but not D,L-3-hydroxybutyrate, L-lactate, ethanol, L-malate, and D,L-isocitrate. This enzyme is involved in a L-carnitine degradation pathway that allows bacteria (such as P.aeruginosa, Xanthomonas translucens and Rhizobium sp. YS-240) to grow on L-carnitine as the sole source of carbon and nitrogen . This entry also includes L-carnitine dehydrogenase/betainyl-CoA thioesterase, a multifuntional enzyme that catalyses the NAD+-dependent oxidation of L-carnitine to 3-dehydrocarnitine and the cleavage of betainyl-CoA (N,N,N-trimethylglycyl-CoA) into glycine betaine and coenzyme A .
Cell division protein FtsQ (FtsQ)
Type: Family

FtsQ is an essential cell division protein. It may link together the upstream cell division proteins, which are predominantly cytoplasmic, with the downstream cell division proteins, which are predominantly periplasmic . FtsQ may control the correct divisome assembly .
Cell division protein DivIB (DivIB)
Type: Family

DivIB is a cell division protein from Gram-positive bacteria, probably homologous to Escherichia coli FtsQ. DivIB interacts with FtsL, DivIC and PBP-2B . DivIB plays an essential role in division at high temperatures, maybe by protecting FtsL from degradation or by promoting formation of the FtsL-DivIC complex . It is also required for efficient sporulation at all temperatures .
TCP10L/CENPJ (TCP10L/CENPJ)
Type: Family

Proteins in this family include T-complex protein 10 homolog 1 (TCP10L) and its paralogue centromere protein J (CENPJ, also known as Centrosomal P4.1-associated protein, CPAP). TCP10L is expressed specifically in the nucleus of spermatogenic cells during spermatogenesis and it interacts with DAPK-3 which implies that TCP10L might play crucially important roles in spermatogenesis through its interaction with DAPK-3 . It may be involved in transcriptional regulation . It acts as a tumour suppressor in hepatocellular carcinoma (HCC) cells .

CENPJ is involved in centriole-length regulation. It allows persistent slow growth of the centriolar microtubule plus end and its overexpression leads to abnormally long microtubules . CENPJ not only inhibits microtubule nucleation from the centrosome, but acts as a microtubule plus-end tracking protein that stabilises centriolar microtubules and inhibits microtubule polymerisation and extension from the distal ends of centrioles .
Glucose 1-dehydrogenase, archaea (Glc_1-DH_arc)
Type: Family

Glucose 1 dehydrogenase (

) belongs to the medium-chain alcohol dehydrogenase superfamily and requires zinc for catalysis . It catalyses the NAD(P)(+)-dependent oxidation of D-glucose to D-gluconate via gluconolactone. It is involved in the degradation of glucose through a modified version of the Entner-Doudoroff pathway in Halobacteria and a non-phosphorylative variant of the Entner-Doudoroff pathway in other organisms.

This entry includes a group of glucose 1 dehydrogenases from archaea.
Rad9 (Rad9)
Type: Family

This entry includes DNA damage checkpoint proteins Rad9. Rad9 is required for transient cell-cycle arrests and transcriptional induction of DNA repair in response to DNA damage . This entry includes the mamalian Rad9, which is homologous to the fission yeast Rad9 and the budding yeast Ddc1. Members of this family do not share the sequence homology with the budding yeast Rad9.

Rad9 forms a complex with Hus1 and Rad1, called 9-1-1 complex. In human, 9-1-1 binds to TopBP1 and activates the ATR-Chk1 checkpoint pathway . Rad9 also shows 3'-5' exonuclease activity . Besides its function in the 9-1-1 complex, Rad9 can act as a transcriptional factor, participate in immunoglobulin class switch recombination . Aberrant Rad9 expression has been associated with prostate, breast, lung, skin, thyroid, and gastric cancers .
Alpha-1,4-glucan:maltose-1-phosphate maltosyltransferase (GlgE)
Type: Family

Alpha-1,4-glucan:maltose-1-phosphate maltosyltransferase (GlgE) uses maltose 1-phosphate (M1P) as the sugar donor to elongate linear or branched alpha-(1->4)-glucans. It is involved in a branched alpha-glucan biosynthetic pathway from trehalose, together with TreS, Pep2 and GlgB .
Type 2 tetrahydrodipicolinate N-succinyltransferase family (Type2_DapD)
Type: Family

This entry represents 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferases that belong to the type 2 tetrahydrodipicolinate N-succinyltransferase family. This enzyme catalyses the conversion of the cyclic tetrahydrodipicolinate (THDP) into the acyclic N-succinyl-L-2-amino-6-oxopimelate using succinyl-CoA .
Sirtuin, class II (Sirtuin_class_II)
Type: Family

The sirtuin (also known as Sir2) family is broadly conserved from bacteria to human. Yeast Sir2 (silent mating-type information regulation 2),
the founding member, was first isolated as part of the SIR complex required for maintaining a modified chromatin structure at telomeres. Sir2 functions
in transcriptional silencing, cell cycle progression, and chromosome stability . Although most sirtuins in eukaryotic cells are located in the nucleus, others are cytoplasmic or mitochondrial.

This family is divided into five classes (I-IV and U) on the basis of a phylogenetic analysis of 60 sirtuins from a wide array of organisms . Class I and class IV are further divided into three and two subgroups, respectively. The U-class sirtuins are found only in Gram-positive bacteria . The S. cerevisiae genome encodes five sirtuins, Sir2 and four additional proteins termed 'homologues of sir two' (Hst1p-Hst4p) . The human genome encodes seven sirtuins, with representatives from classes I-IV .

Sirtuins are responsible for a newly classified chemical reaction, NAD-dependent protein deacetylation. The final products of the reaction are the
deacetylated peptide and an acetyl ADP-ribose . In nuclear sirtuins this deacetylation reaction is mainly directed against histones acetylated lysines .

Sirtuins typically consist of two optional and highly variable N- and C-terminal domain (50-300 aa) and a conserved catalytic core domain (~250 aa). Mutagenesis experiments suggest that the N- and C-terminal regions help direct catalytic core domain to different targets .

The 3D-structure of an archaeal sirtuin in complex with NAD reveals that the protein consists of a large domain having a Rossmann fold and a small domain containing a three-stranded zinc ribbon motif. NAD is bound in a pocket between the two domains .
Choice-of-anchor A domain (Choice_anch_A)
Type: Domain

This domain may occur as essentially the full length of a protein, except for an N-terminal sequence and a C-terminal protein-sorting signal such as PEP-CTERM or LPXTG. Most often, the putative surface protein is longer, in which this domain is found N-terminal to repeating stalk domains in bacterial surface proteins. This is one of very few domains for which both anchoring domains occur, and designated choice-of-anchor A domain. The structure model of this domain is highly similar to the Ice_binding adhesive proteins (

). However, some of the bacterial species in which this domain can be found, are less likely to be water-based and thus the function seems unlikely to be ice-binding. This domain is found in a Bacillus anthracis protein with the gene name BA_0871 or BASH2_04951, which was described to be collagen binding and to be involved in the bacterial pathogenicity . BA0871, has five CNA-family protein B-type repeats toward the C terminus and an LPXTG cell wall attachment motif .
Cell division protein FtsP (FtsP)
Type: Family

This family represents the cell division protein FtsP that is required for growth during stress conditions. FtsP may be involved in protecting or stabilising the divisomal assembly under conditions of stress .
Sirtuin family, catalytic core domain (Ssirtuin_cat_dom)
Type: Domain

This entry represents the complete catalytic core domain of sirtuin proteins.

The sirtuin (also known as Sir2) family is broadly conserved from bacteria to human. Yeast Sir2 (silent mating-type information regulation 2),
the founding member, was first isolated as part of the SIR complex required for maintaining a modified chromatin structure at telomeres. Sir2 functions
in transcriptional silencing, cell cycle progression, and chromosome stability . Although most sirtuins in eukaryotic cells are located in the nucleus, others are cytoplasmic or mitochondrial.

This family is divided into five classes (I-IV and U) on the basis of a phylogenetic analysis of 60 sirtuins from a wide array of organisms . Class I and class IV are further divided into three and two subgroups, respectively. The U-class sirtuins are found only in Gram-positive bacteria . The S. cerevisiae genome encodes five sirtuins, Sir2 and four additional proteins termed 'homologues of sir two' (Hst1p-Hst4p) . The human genome encodes seven sirtuins, with representatives from classes I-IV .

Sirtuins are responsible for a newly classified chemical reaction, NAD-dependent protein deacetylation. The final products of the reaction are the
deacetylated peptide and an acetyl ADP-ribose . In nuclear sirtuins this deacetylation reaction is mainly directed against histones acetylated lysines .

Sirtuins typically consist of two optional and highly variable N- and C-terminal domain (50-300 aa) and a conserved catalytic core domain (~250 aa). Mutagenesis experiments suggest that the N- and C-terminal regions help direct catalytic core domain to different targets .

The 3D-structure of an archaeal sirtuin in complex with NAD reveals that the protein consists of a large domain having a Rossmann fold and a small domain containing a three-stranded zinc ribbon motif. NAD is bound in a pocket between the two domains .
Sirtuin, catalytic core small domain superfamily (Sirtuin_cat_small_dom_sf)
Type: Homologous_superfamily

The catalytic core of sirtuin proteins consists of a large and a small domains. The large domain has a Rossmann fold and binds NAD+. The small domain is composed of residues from two insertions in the Rossmann fold that form a helical and a zinc binding modules . This superfamily represents the catalytic core small domain.
Outer membrane protein assembly factor BamE (BamE)
Type: Family

BamE is part of the outer membrane protein (OMP) assembly Bam complex (composed of the outer membrane protein BamA, and four lipoproteins BamB, BamC, BamD and BamE), which is involved in assembly and insertion of β-barrel proteins into the outer membrane . E. coli BamE is a nonessential member of the complex that stabilizes the interaction between the essential proteins BamA and BamD. It may modulate the conformation of BamA, likely through interactions with BamD .