SII-SWORD/CoKE huggingface dataset:
PBS lyase HEAT-like repeat (PBS_lyase_HEAT)
Type: Repeat

This short bi-helical repeat is related to HEAT repeats and is present in phycocyanobilin lyases and other proteins.

Cyanobacteria and red algae harvest light energy using macromolecular complexes known as phycobilisomes (PBS), peripherally attached to the photosynthetic membrane. The major components of PBS are the phycobiliproteins. These heterodimeric proteins are covalently attached to phycobilins: open-chain tetrapyrrole chromophores, which function as the photosynthetic light-harvesting pigments. Phycobiliproteins differ in sequence and in the nature and number of attached phycobilins to each of their subunits. These proteins include the lyase enzymes that specifically attach particular phycobilins to apophycobiliprotein subunits. The most comprehensively studied of these is the CpcE/Flyase

,

, which attaches phycocyanobilin (PCB) to the alpha subunit of apophycocyanin . Similarly, MpeU/V attaches phycoerythrobilin to phycoerythrin II, while CpeY/Z is thought to be involved in phycoerythrobilin (PEB) attachment to phycoerythrin (PE) I (PEs I and II differ in sequence and in the number of attached molecules of PEB: PE I has five, PE II has six) .

All the reactions of the above lyases involve an apoprotein cysteine SH addition to a terminal delta 3,3'-double bond. Such a reaction is not possible in the case of phycoviolobilin (PVB), the phycobilin of alpha-phycoerythrocyanin (alpha-PEC). It is thought that in this case, PCB, not PVB, is first added to apo-alpha-PEC, and is then isomerized to PVB. The addition reaction has been shown to occur in the presence of either of the components of alpha-PEC-PVB lyase PecE or PecF (or both). The isomerisation reaction occurs only when both PecE and PecF components are present, i.e. the PecE/F phycobiliprotein lyase is also a phycobilin isomerase . Another member of this family is the NblB protein, whose similarity to the phycobiliprotein lyases was previously noted . This constitutively expressed protein is not known to have any lyase activity. It is thought to be involved in the coordination of PBS degradation with environmental nutrient limitation. It has been suggested that the similarity of NblB to the phycobiliprotein lyases is due to the ability to bind tetrapyrrole phycobilins via the common repeated motif .
Organic anion transporter polypeptide (OATP)
Type: Family

This family consists of several eukaryotic Organic-Anion-Transporting Polypeptides (OATPs). Several have been identified mostly in human and rat. Different OATPs vary in tissue distribution and substrate specificity. Since the numbering of different OATPs in particular species was based originally on the order of discovery, similarly numbered OATPs in humans and rats did not necessarily correspond in function, tissue distribution and substrate specificity (in spite of the name, some OATPs also transport organic cations and neutral molecules) so a scheme of using digits for rat OATPs and letters for human ones was introduced . Prostaglandin transporter (PGT) proteins are also considered to be OATP family members. In addition, the methotrexate transporter OATK is closely related to OATPs. This family also includes several predicted proteins from Caenorhabditis elegans and Drosophila melanogaster. This similarity was not previously noted. All characterised OATPs are predicted to have 12 transmembrane domains and are sodium-independent transport systems .
Protein of unknown function DUF247, plant (DUF247_pln)
Type: Family

The function of the plant proteins constituting this family is unknown.
Putative S-adenosyl-L-methionine-dependent methyltransferase (Put_SAM_MeTrfase)
Type: Family

This is a family of putative S-adenosyl-L-methionine (SAM)-dependent methyltransferases .
Translation elongation factor EFTu/EF1A, C-terminal (Transl_elong_EFTu/EF1A_C)
Type: Domain

Elongation factor EF1A (also known as EF-1alpha or EF-Tu) promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. EF1A consists of three structural domains. Release factor eRF3, which governs translation termination, has a similar overall structure. RF3 has an N-terminal extension and a EF1A-like C-terminal region which comprises a GTP-binding domain (G domain) and two β-barrel domains that are similar to the three respective domains of elongation factor EF-Tu/eEF1A . Archaeal EF1A is both involved in translational elongation and termination, as well as in mRNA surveillance, which explains the lack of an eRF3 orthologue in archaea .

This entry represents the C-terminal domain of both EF1A and eRF3, which adopts a β-barrel structure. In EF1A, this domain is involved in binding to both charged tRNA and to EF1B (or EF-Ts,

) .
Translation elongation factor EFTu-like, domain 2 (EFTu-like_2)
Type: Domain

This entry represents a domain found in a number of translation factors that is homologous to domain 2 of EF2-Tu (also known as EF1A and EF-1alpha).

EF2-Tu (EF1A) consists of three structural domains. This entry represents domain 2, which adopts a β-barrel structure, and is involved in binding to both charged tRNA . This domain is structurally related to the C-terminal domain of EF2-Tu (

), to which it displays weak sequence matches. This domain is also found in other proteins such as translation initiation factor IF-2 and tetracycline-resistance proteins.

EF-Tu (also known as EF-1alpha or EF1A) is a G-protein. It forms a ternary complex of EF-Tu (EF1A)-GTP-aminoacyltRNA. The binding of aminoacyl-tRNA stimulates GTP hydrolysis by EF-Tu (EF1A), causing a conformational change in EF-Tu (EF1A) that causes EF-Tu (EF1A)-GDP to detach from the ribosome, leaving the aminoacyl-tRNA attached at the A-site. Only the cognate aminoacyl-tRNA can induce the required conformational change in EF-Tu (EF1A) through its tight anticodon-codon binding . EF-Tu (EF1A)-GDP is returned to its active state, EF-Tu (EF1A)-GTP, through the action of another elongation factor, EF1B (also known as EF-Ts or EF-1beta/gamma/delta).

Translation elongation factors are responsible for two main processes during protein synthesis on the ribosome . EF1A (or EF-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the A-site (acceptor site) of the ribosome. EF2 (or EF-G) is responsible for the translocation of the peptidyl-tRNA from the A-site to the P-site (peptidyl-tRNA site) of the ribosome, thereby freeing the A-site for the next aminoacyl-tRNA to bind. Elongation factors are responsible for achieving accuracy of translation and both EF1A and EF2 are remarkably conserved throughout evolution.
E3 ubiquitin-protein ligase SINA-like, animal (SINA-like_animal)
Type: Family

Proteins in this entry are E3 ubiquitin-protein ligases that mediate ubiquitination and subsequent proteasomal degradation of target proteins. Proteins in this entry include Sina and Sinah (Sina homologue) from flies and SIAH1/2 from humans.

The seven in absentia (sina) gene was first identified in Drosophila. The Drosophila Sina protein is essential for the determination of the R7 pathway in photoreceptor cell development: the loss of functional Sina results in the transformation of the R7 precursor cell to a non-neuronal cell type. The Sina protein contains an N-terminal RING finger domain C3HC4-type. Through this domain, Sina binds E2 ubiquitin-conjugating enzymes (UbcD1). Sina also interacts with Tramtrack (TTK88) via PHYL. Tramtrack is a transcriptional repressor that blocks photoreceptor determination, while PHYL down-regulates the activity of TTK88. In turn, the activity of PHYL requires the activation of the Sevenless receptor tyrosine kinase, a process essential for R7 determination. It is thought that Sina targets TTK88 for degradation, therefore promoting the R7 pathway. Murine and human homologues of Sina have also been identified. The human homologue SIAH1 also binds E2 enzymes (UbcH5) and through a series of physical interactions, targets beta-catenin for ubiquitin degradation. Siah-1 expression is enhanced by p53, itself promoted by DNA damage. Thus this pathway links DNA damage to beta-catenin degradation .
Coenzyme A transferase binding site (CoA_transf_BS)
Type: Binding_site

Coenzyme A (CoA) transferases belong to an evolutionary conserved family of enzymes catalyzing the reversible transfer of CoA from one carboxylic acid to another. They have been identified in many prokaryotes and in mammalian tissues. The bacterial enzymes are heterodimer of two subunits (A and B) of about 25 Kd each while eukaryotic SCOT consist of a single chain which is colinear with the two bacterial subunits. This entry corresponds to a region in the N-terminal of the A subunit that may be implicated in the binding of CoA to the enzyme.
Coenzyme A transferase active site (CoA_transf_AS)
Type: Active_site

Coenzyme A (CoA) transferases belong to an evolutionary conserved family of enzymes catalyzing the reversible transfer of CoA from one carboxylic acid to another. They have been identified in many prokaryotes and in mammalian tissues. The bacterial enzymes are heterodimers of two subunits (A and B) of about 25 Kd each while eukaryotic SCOT consists of a single chain which is colinear with the two bacterial subunits. This signature corresponds to a region in the N terminus of the B subunit which contains a glutamate that is involved in the catalytic mechanism.
Coenzyme A transferase family I (CoA_trans_fam_I)
Type: Family

This family consists of 3-oxoacid CoA-transferases and related CoA-transferases from family I.

Coenzyme A (CoA) transferases belong to an evolutionary conserved family of enzymes catalyzing the reversible transfer of CoA from one carboxylic acid to another. They have been identified in many prokaryotes and in mammalian tissues. The bacterial enzymes are heterodimer of two subunits (A and B) of about 25 Kd each while eukaryotic SCOT consist of a single chain which is colinear with the two bacterial subunits.

CoA-transferases are found in organisms from all kingdoms of life. They catalyse reversible transfer reactions of coenzyme A groups from CoA-thioesters to free acids. There are at least three families of CoA-transferases, which differ in sequence and reaction mechanism:

Family I consists of CoA-transferases for 3-oxoacids (

,

), short-chain fatty acids (

,

) and glutaconate (

). Most use succinyl-CoA or acetyl-CoA as CoA donors.

Family II consists of the homodimeric alpha-subunits of citrate lyase and citramalate lyase (

,

). These enzymes catalyse the transfer of acyl carrier protein (ACP) with a covalently bound CoA derivative, but can accept free CoA thioesters as well.

Family III consists of formyl-CoA:oxalate CoA-transferase , succinyl-CoA:(R)-benzylsuccinate CoA-transferase , (E)-cinnamoyl-CoA:(R)-phenyllactate CoA-transferase , succinyl-CoA:mesaconate CoA-transferase and butyrobetainyl-CoA:(R)-carnitine CoA-transferase . These CoA-transferases occur in prokaryotes and eukaryotes, and catalyse CoA-transfer reactions in a highly substrate-and stereo-specific manner .
Alpha-type protein kinase, alpha-kinase domain (a-kinase_dom)
Type: Domain

This entry represents a protein kinase catalytic domain with no detectable similarity to conventional kinases that is found in eukaryotic alpha-kinases . This domain is shared by EF-2 kinase and the myosin heavy chain kinase A (MHCK A) .

As in classical kinase, this domain consists of two lobes that bind nucleotide at the interface between them. The N-terminal lobe is very similar in structure to that of classical protein kinases, whereas its C-terminal lobe resembles that of ATP-grasp proteins more closely. A conserved C-terminal glycine rich motif which locates in the region that corresponds to the activation loop of classical kinases is essential for the enzymatic activity .
Peripheral subunit-binding domain (PSBD)
Type: Domain

The ubiquitous 2-oxoacid dehydrogenases are a family of very large multienzyme complexes consisting of multiple copies of at least three enzymes which catalyze the oxidative decarboxylation of several different 2-oxoacids, resulting in acyl-CoA products. Members of this family include pyruvate dehydrogenase (PDH), 2-oxoglutarate dehydrogenase (OGDH) and branched-chain 2- oxoacid dehydrogenase (BCDH). The three enzymes assembling to form these complexes are the decarboxylase E1 (called E1p, E1o and E1b in PDH, OGDH and BCDH, respectively), dihydrolipoamide acetyl, succinyl and branched-chain transferase E2 (E2p, E2o and E2b, respectively) and dihydrolipoamide dehydrogenase E3. The E3 component is identical in all three complexes (PDH, OGDH and BCDH) and catalyzes the same reaction. The structural core of all 2- oxoacid dehydrogenase complexes (ODHc) is formed of multiple copies of E2 subunits, with the E1 and E3 subunits bound on the periphery. The E2 component of the ODHc's of both bacteria and eukaryotes serves as the structural core of these multienzyme complexes and is comprised of three types of domains. Starting with the N terminus, there are 1-3 tandem repeated lipoyl domains (LD), followed by a peripheral subunit-binding domain (PSBD) responsible for binding E1/E3 chains. The third domain is the C-terminal catalytic domain (CD). The individual domains are separated by long, flexible linker regions allowing large movements of the lipoyl domain(s) to enable active site coupling. The PSBD domain binds E1 or E3, but not both simultaneously. The flexible linker allows the PSBD domain (associated with either E1 or E3) to move quite freely with respect to the core formed E2 catalytic domains .

The ~35-residue PSBD domain has a compact structure consisting of two short, parallel α-helices (H1 and H2) separated by a loop (L1), a single helical turn, and a further, less well-ordered loop (L2) (see PDB:1BAL). The compact structure of the PSBD domain is stabilized mainly by hydrophobic interactions. The interactions between the PSBD domain and E3 are all mediated by charged side chains, forming an 'electrostatic zipper'. The residues of the PSBD domain involved in the interactions are all provided by helix H1 of this domain. Helix H2 of PSBD does not interact with E3, but may be involved in binding E1 .
PPAK motif (PPAK_motif)
Type: Repeat

PPAK is a repeated protein motif found in the PEVK (Pro-Glu-Val-Lys) domain of the titin protein and in a number of other proteins. Titin (

) is a giant elastic protein found in striated muscle that is a key component in the assembly and functioning of sarcomeres . PPAK motifs (PPAK refers to the four amino acids found at the beginning of the motif) occur 60 times in human soleus titin . PPAK motifs occur in groups of 2-12 that are separated by regions rich in glutamic acid (approximately 45%) and termed polyE segments. The charge fluctuation between the PPAK and polyE regions suggests ionic interactions between these segments and their involvement in the elastic function of titin.
Spider toxin (Spidertoxin)
Type: Family

This family contains spider toxins that include the omega-Aga-IVB, a P-type calcium channel antagonist from venom of the funnel web spider, Agelenopsis aperta , as well as purotoxin-1 (PT1), a spider peptide venom of the Central Asian spider Geolycosa sp., which specifically exerts inhibitory action on P2X3 purinoreceptors at nanomolar concentrations . These spider toxins, which are ion channel blockers, share a common structural motif composed of a triple-stranded antiparallel β-sheet, stabilized by internal disulfide bonds known as cystine knots .
WWE domain (WWE_dom)
Type: Domain

The WWE domain is named after three of its conserved residues and is predicted to mediate specific protein-protein interactions in ubiquitin and ADP ribose conjugation systems. This domain is found as a tandem repeat at the N-terminal of Deltex, a cytosolic effector of Notch signalling thought to bind the N-terminal of the Notch receptor . It is also found as an interaction module in protein ubiquination and ADP ribosylation proteins .
cAMP-dependent protein kinase inhibitor (cAMP_dep_PKI)
Type: Family

Members of this family are extremely potent competitive inhibitors of cAMP-dependent protein kinase activity. These proteins interact with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains.
L27 domain (L27_dom)
Type: Domain

The L27 domain is a ~50-amino acid module, initially identified in the Lin-2 and Lin-7 proteins, that exists in a large family of animal scaffold proteins . The L27 domain is a specific protein-protein interaction module capable of forming heteromeric complexes that can integrate multiple scaffold proteins into supramolecular assemblies required for establishment and maintenance of cell polarity. The L27 domain can be found as a single occurrence or as a duplication in association with other domains such as PDZ, SH3, the guanylate kinase domain or the serine/threonine protein kinase domain.

The main features of the L27 domain are conserved negatively charged residues and a conserved aromatic amino acid . Study of individual L27 domains revealed largely unfolded domains that require the formation of obligate heterodimers to achieve well-folded structures. Each L27 domain is composed of three helices. The two L27 domains heterodimerize by building a compact structure consisting of a four-helix bundle formed by the first two helices of each L27 domain and one coiled-coil formed by the third helix of each domain .
3H domain (3H_domain)
Type: Domain

The 3H domain is named after its three highly conserved histidine residues. The 3H domain appears to be a small molecule-binding domain, based on its occurrence with other domains . Several proteins carrying this domain are transcriptional regulators from the biotin repressor family. The transcription regulator TM1602 from Thermotoga maritima is a DNA-binding protein thought to belong to a family of de novo NAD synthesis pathway regulators. TM1602 has an N-terminal DNA-binding domain and a C-terminal 3H regulatory domain. The N-terminal domain appears to bind to the NAD promoter region and repress the de novo NAD biosynthesis operon, while the C-terminal 3H domain may bind to nicotinamide, nicotinic acid, or other substrate/products . The 3H domain has a 2-layer α/β sandwich fold.
Head-to-tail joining protein W (GpW)
Type: Family

GpW is a 68 residue protein known to be present in phage particles. Extracts of phage-infected cells lacking GpW contain DNA-filled heads, and active tails, but no infectious virions. GpW is required for the addition of GpFII to the head, which is, in turn, required for the attachment of tails. Since GpFII and tails are known to be attached at the connector, GpW is also likely to assemble at this site. The addition of GpW to filled heads increases the DNase resistance of the packaged DNA, suggesting that GpW either forms a plug at the connector to prevent ejection of the DNA, or binds directly to the DNA. The large number of positively charged residues in GpW (its calculated pI is 10.8) is consistent with a role in DNA interaction .
RNA 2',3'-cyclic phosphodiesterase (RNA_CPDase)
Type: Family

Members of this entry are bacterial and archaeal RNA cyclic phosphodiesterases (CPDases). They hydrolyse RNA 2',3'-cyclic phosphodiester to an RNA 2'-phosphomonoester . In vitro, they are able to ligate half-tRNA molecules , though the RNA ligase activity appears to be weak in archaea .
Clp, repeat (R) domain (Clp_R_dom)
Type: Domain

Molecular chaperones recognise unfolded or misfolded proteins by binding to hydrophobic surface patches not normally exposed in the native proteins. Members of the Clp/Hsp100 family of chaperones are present in eubacteria and within organelles of all eukaryotes, promoting disaggregation and disassembly of protein complexes and participating in energy-dependent protein degradation. The ClpA, ClpB, and ClpC subfamilies of the Clp/Hsp100 ATPases contain a conserved N-terminal domain of ~150 amino acids, which in turn consists of two repeats of ~75 residues. Although the Clp repeat (R) domain, also known as the N domain, contains two approximate sequence repeats, it behaves as a single cooperatively folded unit. The Clp R domain is thought to provide a means for regulating the specificity of and to enlarge the substrate pool available to Clp/Hsp100 chaperone or protease complexes. These roles can be assisted through the binding of an adaptor protein. Adaptor proteins bind to the Clp R domain, modulate the target specificity of the Clp/Hsp100 complex to a particular substrate of interest, and may also regulate the activity of the complex . The Clp R domain structure consists of two four-helix bundles connected by a flexible loop . The ClpV R-domain exhibits weak sequence homology to the R-domains of ClpA, ClpB and ClpC. In ClpV, the R-domain interacts with the VipA/VipB complex .
DDHD domain (DDHD_dom)
Type: Domain

The Nir/rdgB (N-terminal domain-interacting receptor/Drosophila retinal degeneration B proteins) family has been identified in a variety of eukaryotic organisms, ranging from worms to mammals. Members of this family are implicated in regulation of lipid trafficking, metabolism, and signaling. The Nir/rdgB proteins contain a 180 amino-acids-long conserved region in the central part of the protein. This domain contains four conserved residues, DDHD, which may form a metal-binding site. This domain is named DDHD after these four residues. This pattern of conservation of metal-binding residues is often seen in phosphoesterase domains .

The DDHD domain is found in the central part of Nir/rdgB proteins, as well as the C-terminal part of the phosphatidic acid-preferring phospholipase A1. The DDHD domain function is not currently known but it may be implicated in phospholipid metabolism, membrane turnover, or intracellular trafficking .
Calmodulin-binding domain (CaM-bd_dom)
Type: Domain

Small-conductance Ca2+-activated K+ channels (SK channels) are independent of voltage and gated solely by intracellular Ca2+. These membrane channels are heteromeric complexes that comprise pore-forming alpha-subunits and the Ca2+-binding protein calmodulin (CaM) . CaM binds to the SK channel through this the CaM-binding domain (CaMBD), which is located in an intracellular region of the alpha-subunit immediately carboxy-terminal to the pore. Channel opening is triggered when Ca2+ binds the EF hands in the N-lobe of
CaM. The structure of this domain complexed with CaM is known . This domain forms an elongated dimer with a CaM molecule bound at each end; each CaM wraps around three α-helices, two from one CaMBD subunit and one from the other.
Sec63 domain (Sec63-dom)
Type: Domain

This domain was named after the yeast Sec63 (or NPL1) (also known as the Brl domain) protein in which it was found. This protein is required for assembly of functional endoplasmic reticulum translocons . Other yeast proteins containing this domain include pre-mRNA splicing helicase BRR2, HFM1 protein and putative helicases.
Protein of unknown function DUF226, Borrelia species (DUF226_BOR_spp)
Type: Family

This family of proteins are found in Borrelia burgdorferi and Borrelia garinii. The proteins are about 190 amino acids long and have no known function.