SII-SWORD/CoKE huggingface dataset:
CIROZ, beta domain (CIROZ_b)
Type: Domain

This entry (ex DUF4556) represents an uncharacterised domain in CIROZ proteins from animals. This domain is predicted to adopt an all-β structure and can be found at the C-terminal in some CIROZ proteins.

CIROZ, formerly known as C1orf127, encodes a secreted protein characterised by an N-terminal signal peptide followed by three zona pellucida N domains (

), consistent with an extracellular localisation. It is specifically expressed in the left-right organiser (LRO) of several vertebrates, including mice, frogs and fish. Bi-allelic inactivation of CIROZ in humans is associated with heterotaxy and congenital heart defects, and knockout studies in mice confirm its essential role in establishing left-right embryonic asymmetry. However, targeted inactivation of the gene in zebrafish and Xenopus does not result in overt laterality defects, suggesting species-specific roles. Evolutionary analysis reveals that CIROZ is either absent or rendered non-functional in certain vertebrate lineages possessing motile cilia at the LRO, such as Carnivora, Atherinomorpha fish and jawless vertebrates. These findings highlight CIROZ as a key regulator of bilateral symmetry in mammals, with its loss or pseudogenisation reflecting divergent mechanisms of left-right axis specification across vertebrate evolution .
ART-PolyVal-like domain (ART-PolyVal_dom)
Type: Domain

This domain is found in a group of ADP-Ribosyltransferases found in polyvalent proteins of phages and conjugative elements. These are in turn related to the Tox-ART-HYD2 group of ADP-Ribosyltransferases that are seen in polymorphic toxin systems and in toxin-antitoxin systems. These are predicted to modify host proteins .
HMG box transcription factor BBX, HMG-box domain (BBX_HMG-box)
Type: Domain

This entry represents a HMG box domain found in human HMG box transcription factor BBX and similar sequences predominantly found in vertebrates. BBX, also called HBP2 or Bobby sox homolog, is a transcription factor that is necessary for cell cycle progression from the G1 to S phase .
ZBTB47, BTB/POZ domain (ZBTB47_BTB_POZ)
Type: Domain

ZBTB47 (Zinc finger and BTB domain-containing protein 47), also called zinc finger protein 651 (ZNF651), is a paralog of ZNF652, a zinc-finger transcriptional repressor. It interacts with CBFA2T3 via its carboxy-terminal proline-rich region . CBFA2T3-ZNF651 functions as a transcriptional co-repressor complex. De novo missense variants in ZBTB47 have been associated with developmental delay . ZBTB47 contains a BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain (this entry), a common protein-protein interaction motif of about 100 amino acids .
Myoregulin (Myoregulin)
Type: Family

Myoregulin (MLN) is encoded by a skeletal muscle-specific RNA Linc-RAM, which is annotated as a putative long noncoding RNA (lncRNA). It is a single-pass transmembrane α-helix that interacts directly with sarcoplasmic reticulum (SR) calcium transporting ATPase (SERCA) and impedes Ca2 uptake into the SR. SERCA is the membrane pump that controls muscle relaxation by regulating Ca2 uptake into the SR. MLN is the dominant regulator of SERCA1 activity in adult skeletal muscle and is a promising drug target for improving muscle performance .
ABC-2 transporter permease NisG-like (ABC_permease_NisG-like)
Type: Family

This family contains homologues of lantibiotic ABC transporter permease subunit NisG, which are highly hydrophobic, integral membrane proteins, and part of the bacitracin ABC transport system that confers resistance to the Gram-positive bacteria in which this system operates, particularly to the lantibiotic nisin. Lantibiotics are small peptides, produced by Gram-positive bacteria, which are ribosomally-synthesized as pre-peptides and act by disrupting membrane integrity. Genes encoding the lantibiotic ABC transporter subunits are highly organized in operons containing all the genes required for maturation, transport, immunity, and synthesis. In Lactococcus lactis and Streptococcus uberis, the lantibiotic nisin is active against other Gram-positive bacteria via various modes of actions; however, its self-protection against the pore-forming nisin is mediated by the ABC transporter composed of NisF, NisE and NisG. In Streptococcus uberis, similar proteins provide self-protection against the pore-forming lantibiotic nisin U. This family contains the NisG and related permease subunits that transport nisin to the surface and expel it from the membrane .
Venom-like beta-defensin domain (DEFBL_dom)
Type: Domain

This entry represents a region of Venom-like beta-defensin from Ornithorhynchus anatinus (platypus) (

). This peptide was found to display potent antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa . Structurally it resembles the beta defensins .
Metallothionein zym1-like (Zym1-like)
Type: Family

This entry represents a small family of eukaryotic metallothioneins, including Metallothionein zym1 from Schizosaccharomyces pombe (

). Zym1 is involved in tolerance to zinc and cadmium .
EC042_2821-like Restriction Endonuclease-like domain (EC042_2821)
Type: Domain

This entry represents an uncharacterised domain that is likely to adopt a restriction endonuclease-like fold. In some proteins this domain is fused to a HEPN-like domain (

) (EC042_2821) .
Antifreeze protein repeat (AFP_rpt)
Type: Repeat

This entry represents a repeat found in a small family of bacterial proteins involved in stopping the formation of ice crystals at low temperatures (Antifreeze proteins, AFPs), including

from Marinomonas primoryensis. The structure folds as a Ca(2+)-bound parallel β-helix with an extensive array of ice-like surface waters that are anchored via hydrogen bonds directly to the polypeptide backbone and adjacent side chains .
GTPase-associated protein 1-like, C-terminal domain (GAP1-like_C)
Type: Domain

This entry represents the C-terminal domain found in the multidomain GTPase-associated protein 1 (GAP1) of the GTPase-centric systems, a class of NTP-dependent biological conflict systems. This domain is predicted to mediate effector deployment in the GTPase-centric systems .
TraN-like (TraN)
Type: Family

This entry represents a family of proteins from proteobacteria, including TraN (

), a subunit of the P-type Type IV secretion system (T4SS) encoded by the conjugative plasmid pKM101 from Escherichia coli that is the homologue of the F-type T4SS protein VirB7 (

). This protein forms spokes radially crossing the entire assembly of the T4SS in the periphery of the outer membrane complex. It forms a complex with TraO (the homologue of VirB9) that surrounds the inner ring formed by TraF (VirB10 homologue) .
Testis-expressed protein 13A/C/D, zinc finger domain (TEX13A/C/D_Znf)
Type: Domain

This entry represents the RANBP2-type zinc finger domain found at the C-terminal of human Testis-expressed protein 13A/C/D (TEX13A/C/D). These proteins have been related to male fertility in mammals .
Glycophorin A/B (GYPA_B)
Type: Family

This entry represents a family of mammal proteins, including human Glycophorin A and B (GYPA/B). GYPA and B are components of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane .
Properdin, thrombospondin type 1 repeat 0 (CFP_TSR-0)
Type: Repeat

This entry represents the N-terminal thrombospondin type I repeat (TSR-0) found in human Properdin (CFP) and similar proteins from vertebrates. Properdin is a glycoprotein constructed from a common pool of structure units or modules, which are homologous to the thrombospondin type 1 repeat, TSR. It is a positive regulator of the complement system that stabilises the alternative pathway C3-convertase C3bBb. Properdin also inhibits the factor H-mediated cleavage of C3b by factor I. In addition, this protein acts as a pattern recognition molecule capable of identifying and interacting with microbial surfaces, apoptotic cells, and necrotic cells . However this role of pattern recognition is controversial . Studies indicate that this domain is a TSR variants. It is suggested that the TSR-0 domain of properdin which possesses only the six Cys residues and no CWR-layered motif (which is usually found in other TSR domains) may constitute a truncated TSR domain .
Antitoxin RelB-like (RelB-like)
Type: Family

This entry represents a family of prokaryotic proteins, including antitoxin RelB from Methanocaldococcus jannaschii. RelE-RelB (RelBE) is a toxin-antitoxin (TA) protein complex. It is suggested that the toxic action of RelE is counteracted by antitoxin RelB, which wraps around RelE, blocks its active site and prevents sterically the binding to the ribosomal A-site. The long α-helix of the tightly bound antitoxin RelB covers the presumed active site of the toxin RelE that is formed by a central β-sheet .
Plectin-like, spectrin-like repeat (PCN-like_spectrin-like_rpt)
Type: Repeat

This entry represents a spectrin repeat found in human Plectin (PCN) and similar animal proteins. PCN interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes .
Spore photoproduct lyase (SPL)
Type: Family

Bacterial spores are remarkable in their resistance to chemical and physical stresses, including exposure to UV radiation. The unusual UV resistance of bacterial spores is a result of the unique photochemistry of spore DNA coupled with the efficient repair of accumulated damage. Exposure of bacterial spores to UV radiation results in the formation of a methylene-bridged thymine dimer, 5-thyminyl-5,6-dihydrothymine, a spore photoproduct, or SP, as the primary photoproduct. SP accumulates in UV-irradiated spores, however it is rapidly repaired upon germination, thus giving rise to the extraordinary UV resistance of bacterial spores. The repair of SP is catalyzed by the enzyme spore photoproduct lyase (SPL), and involves the direct reversal of SP to two thymines without base excision .
Spt6-like, S1/OB domain (Spt6-like_S1)
Type: Domain

This entry represents the S1/OB-fold domain of yeast Spt6 (

) and other plant and fungal proteins. This domain has structural similarity to S1 domain but lacks the typical S1 binding cleft residues involved in nucleic acid binding , therefore, it may be involved in interactions with other partners.
Transcription regulator P7-like (P7-like)
Type: Family

Transcription regulator P7 from Xanthomonas phage Xp10 (

) interacts with the RNA polymerase (RNAP) from bacteria: it prevents transcription termination and inhibits transcription initiation. This protein adopts a compact globular form comprising an α-helix packed against a β-sheet .
TopBP1-like, BRCT0 domain (TopBP1-like_BRCT0)
Type: Domain

Human TopBP1 consists of multiple copies of BRCT domains, with a triple tandem BRCT domains at the N-terminal (designated BRCT0, BRCT1 and BRCT2), also observed in ECT2 that may represent a new type of consecutive BRCT domains . This entry represents the first BRCT domain (BRCT0) of TopBP1 . BRCT1/2 are included in

. Although ECT2 and TopBP1 share a similar cylinder-like crystal structure and distribution of secondary structure, some α-helices exhibit different orientations, especially in the BRCT0 domain.

TopBP1, also known as DNA topoisomerase II-beta-binding protein 1, or DNA topoisomerase II-binding protein 1, functions in DNA replication and damage response, acting as a scaffold protein . It binds double-stranded DNA breaks and nicks as well as single-stranded DNA . It has been shown to activate the ATR-ATRIP complex . TopBP1 contains eight copies of BRCT domain which specifically recognise and bind phosphorylated proteins, bringing proteins together into functional combinations .
Transcription factor tau 138 kDa subunit, extended winged helix (TFC3_eWH)
Type: Domain

This domain is found in a group of proteins from ascomycetes, including Transcription factor tau 138 kDa subunit from Saccharomyces cerevisiae (TFC3) (

). TFC3 may play a role in linking tauA, tauB, and TFIIIB to regulate the formation of the RNA polymerase III pre-initiation complex. This entry represents its extended winged helix (eWH) domain, which is centrally located .
Sulfocyanin-like, C-terminal (SoxE-like_C)
Type: Domain

This family includes Sulfocyanin from Sulfolobus acidocaldarius (SoxE) and similar archaeal and bacterial proteins probably involved in electron transfer.

Sulfocyanin is a blue copper protein with a putative membrane anchoring hydrophobic motif at the N terminus. It may substitute for cytochrome C in electron transfer reactions in archaea .
Glutamyl-tRNA amidotransferase complex subunit Gta3 domain (Gta3_dom)
Type: Domain

This domain is found in a group of fungal proteins, including glutamyl-tRNA amidotransferase complex subunit Gta3 from Schizosaccharomyces pombe (

), an orthologue of yeast GTF1 and human Glutamyl-tRNA(Gln) amidotransferase subunit C (GATC).
WD repeat-containing protein 54, beta-propeller (WDR54_beta_prop)
Type: Domain

This entry represents the β-propeller domain WD repeat-containing protein 54 (WDR54) from human and similar eukaryotic sequences.

WDR54 has a regulatory effect on ERK signaling pathway activity in response to EGF stimulation, when is cross-linked to form dimers and trimers. It colocalizes with the EGF receptor in a WDR54-specific vesicle where it sustains the internalisation and controls the degradation of the EGF receptor after EGF stimulation .
WD repeat-containing protein 93 beta-propeller (WDR93_beta-prop)
Type: Repeat

This entry represents the β-propeller of human WD repeat-containing protein 93 (WDR93,

) and related metazoan proteins. Its function is unknown.
E3 ubiquitin-protein ligase Sina-like, RING finger (Sina-like_RING)
Type: Domain

This is the RING finger domain of Sina and its homologues from animals, such as Siah-1/2 and plants, such as SINAT3 from Arabidopsis . Sina (seven in absentia) was first identified in Drosophila and is essential for the determination of the R7 pathway in photoreceptor cell development. It consists of a RING zinc finger at the N-terminal, followed by two zinc finger (C2H2 type) domains and a C-terminal TRAF-like domain (

) . This domain carries the E3 ubiquitin ligase activity of these proteins.
26S proteasome regulatory subunit RPN7/PSMD6, C-terminal helix (RPN7_PSMD6_C)
Type: Domain

RPN7/PSDM6 are regulatory subunits from the 26S proteasome. This entry represents the C-terminal helix . The 26 proteasome is a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.
RecBCD enzyme subunit RecD, N-terminal domain (RecD_N)
Type: Domain

This domain is found in RecBCD enzyme subunit RecD from Escherichia coli and in similar proteins mostly found in gammaproteobacteria. RecD is a 5'-3' helicase that comprises three domains. This entry represents the N-terminal domain of RecD, which forms the principal interface between RecD and domain 2B of RecC and leads to the conformational change in RecD that has significant effects on the conformation of the RecC subunit .
Polyketide synthase, dehydratase domain, C-terminal (PKS_DH_C)
Type: Domain

This domain is found in the C-terminal of a dehydratase domain (

) found in diverse PKS enzymes. This domain adopts a HotDog fold.

Structural analysis shows these DH domains are double hotdogs in which the active site contains a histidine from the N-terminal hotdog and an aspartate from the C-terminal hotdog. Studies have uncovered that a substrate tunnel formed between the DH domains may be essential for loading substrates and unloading products .

Polyketide synthases (PKSs) are large, multifunctional enzyme complexes that catalyse the biosynthesis of diverse secondary metabolites known as polyketides . These enzymes operate in an assembly line-like manner, utilising multiple domains such as acyltransferase (AT)

, and acyl carrier protein (ACP)

to perform stepwise condensation of simple carboxylic acid units . PKSs can be classified into three main types: type I (modular), type II (iterative), and type III, each with distinct structural and functional characteristics . The modular type I PKSs, in particular, contain additional domains like ketoreductase (KR)

, dehydratase (DH)

, and enoylreductase (ER)

that modify the growing polyketide chain .
Polyketide synthase, dehydratase domain, N-terminal (PKS_DH_N)
Type: Domain

This domain is found in the C-terminal of a dehydratase domain (

) found in diverse PKS enzymes. This domain adopts a HotDog fold.

Structural analysis shows these DH domains are double hotdogs in which the active site contains a histidine from the N-terminal hotdog and an aspartate from the C-terminal hotdog. Studies have uncovered that a substrate tunnel formed between the DH domains may be essential for loading substrates and unloading products .

Polyketide synthases (PKSs) are large, multifunctional enzyme complexes that catalyse the biosynthesis of diverse secondary metabolites known as polyketides . These enzymes operate in an assembly line-like manner, utilising multiple domains such as acyltransferase (AT)

, and acyl carrier protein (ACP)

to perform stepwise condensation of simple carboxylic acid units . PKSs can be classified into three main types: type I (modular), type II (iterative), and type III, each with distinct structural and functional characteristics . The modular type I PKSs, in particular, contain additional domains like ketoreductase (KR)

, dehydratase (DH)

, and enoylreductase (ER)

that modify the growing polyketide chain .
Cyclic-di-AMP phosphodiesterase GdpP-like, PAS domain (GdpP-like_PAS)
Type: Domain

This domain is found at the N-terminal region of Cyclic-di-AMP phosphodiesterase GdpP from Geobacillus thermodenitrificans, following two potential transmembrane regions. GdpP is a stress signaling protein with phosphodiesterase activity against cyclic-di-AMP (c-di-AMP). This protein contains three domains in addition to the two N-terminal transmembrane helices: a Per-ARNT-Sim (PAS) domain, a GGDEF domain, and the DHH/DHHA1 domains (

and

).

This entry represents the PAS domain, which adopts the typical α/β-PAS domain fold formed by several short and distorted α-helices and one five-stranded antiparallel β-sheet. Noticeably, three of the strands and one of the helices are shorter than those found in other typical PAS domains .

This domain is also found at the N-terminal of the membrane protein-large ribosomal subunit bL9 fusion protein from Aster yellows witches'-broom phytoplasma and Onion yellows phytoplasma, which have a large N-terminal domain structurally similar to this group of sequences, although not functionally related.
DNMT3, ADD domain, PHD zinc finger (DNMT3_ADD_PHD)
Type: Domain

This entry represents the C4-type PHD zinc finger of a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, AD-DATRX) found in animal DNMT3 proteins.

The ADD domain is composed of three clearly distinguishable modules that pack
together through extensive hydrophobic interactions to form a single globular
domain. Packed against the N-terminal GATA1-like finger there is a second subdomain,
which binds two zinc ions and closely resembles the structure reported for
several PHD fingers. Finally, there is a long C-terminal α-helix that runs
out from the PHD finger and makes extensive hydrophobic contacts with the N-
terminal GATA1-like finger, bringing the N- and C-termini of the ADD domain close
together. This combination of fused GATA1-like and PHD fingers within a single
domain is thus far unique .

The ADD domains of the DNMT3 family have a decisive role in blocking DNMT activity in the areas of the genome with chromatin containing methylated H3K4. Furthermore, the ADD domain of DNMMT3A (ADD-3A) competes with the chromodomain (CD) of heterochromatin protein 1 alpha (HP1alpha, CDHP1alpha) for binding to the H3 tail. The DNA methyltransferase (DNMT) 3 family members DNMT3A and DNMT3B and the DNMT3-like non-enzymatic regulatory factor DNMT3L, are involved in de-novo establishment of DNA methylation patterns in early mammalian development .
GDT1-like, conserved site (GDT1-like_CS)
Type: Conserved_site

This entry represents a conserved region which seems, in the eukaryotic proteins of this entry, to directly follow the second transmembrane domain.

Budding yeast GDT1 is a Golgi-localized calcium transporter required for stress-induced calcium signalling and protein glycosylation . Its human homologue, TMEM165, also a Golgi protein, transports Ca2+ and Mn2+, which are both required for proper protein glycosylation in cells . Defects in the human protein TMEM165 cause a subtype of Congenital Disorders of Glycosylation . In Arabidopsis , this protein is variously known as CCHA1 (a chloroplast-localized potential Ca(2+)/H(+) antiporter), chloroplastic PAM71 (photosynthesis affected mutant 71), and GDT1-like protein 1, chloroplastic. It has been reported to be a putative chloroplast-localized Ca(2+)/H(+) antiporter with critical functions in the regulation of PSII and in chloroplast Ca(2+) and pH homeostasis . It has also been suggested that it may function in Mn(2+) uptake into thylakoids, ensuring optimal PSII performance .
Phomoidride biosynthesis cluster protein B (PhiB)
Type: Family

This entry includes fungal PhosphatidylEthanolamine-Binding Proteins (PEBP), including phomoidride biosynthesis cluster protein B (PhiB), which is part of the gene cluster that mediates the biosynthesis of the antihypercholesterolemic agents phomoidrides which are dimeric anhydrides .
Transketolase conserved site (Transketolase_CS)
Type: Conserved_site

This entry represents a short region of conserved residues that are located in the N-terminal section of a group of transketolase proteins widespread among all cellular organisms. This region contains a histidine residue that appears to function in proton transfer during catalysis .

Transketolase

(TK) catalyses the reversible transfer of a two-carbon ketol unit from xylulose 5-phosphate to an aldose receptor, such as ribose 5-phosphate, to form sedoheptulose 7-phosphate and glyceraldehyde 3- phosphate. This enzyme, together with transaldolase, provides a link between the glycolytic and pentose-phosphate pathways. TK requires thiamine pyrophosphate as a cofactor. In most sources where TK has been purified, it is a homodimer of approximately 70 Kd subunits. TK sequences from a variety of eukaryotic and prokaryotic sources show that the enzyme has been evolutionarily conserved. In the peroxisomes of methylotrophic yeast Pichia angusta (Yeast) (Hansenula polymorpha), there is a highly related enzyme, dihydroxy-acetone synthase (DHAS)

(also known as formaldehyde transketolase), which exhibits a very unusual specificity by including formaldehyde amongst its substrates.

1-deoxyxylulose-5-phosphate synthase (DXP synthase) is an enzyme so far found in bacteria (gene dxs) and plants (gene CLA1) which catalyses the thiamine pyrophosphoate-dependent acyloin condensation reaction between carbon atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (dxp), a precursor in the biosynthetic pathway to isoprenoids, thiamine (vitamin B1), and pyridoxol (vitamin B6). DXP synthase is evolutionary related to TK. The N-terminal section, contains a histidine residue which appears to function in proton transfer during catalysis . This entry represents the central section there are conserved acidic residues that are part of the active cleft and may participate in substrate-binding . This group of proteins includes transketolase enzymes

and 2-oxoisovalerate dehydrogenase beta subunit

. Both these enzymes utilise thiamine pyrophosphate as a cofactor, suggesting there may be common aspects in their mechanism of catalysis.