SII-SWORD/CoKE huggingface dataset:
TOG domain (TOG)
Type: Domain

XMAP215/Dis1 proteins, such as Alp14 and XMAP215, increase microtubules dynamic polymerization rates by recruiting soluble alpha/beta-tubulin via their conserved TOG domains to polymerizing microtubule plus ends . A TOG domain contains HEAT repeats.

This entry represents a structural domain with an armadillo (ARM)-like fold, consisting of a multi-helical fold comprised of two curved layers of α- helices arranged in a regular right-handed superhelix, where the repeats that make up this structure are arranged about a common axis . These superhelical structures present an extensive solvent-accessible surface that is well suited to binding large substrates such as proteins and nucleic acids. Domains and repeats with an ARM-like fold have been found in a number of proteins, including:

ARM repeat domain, found in beta-catenins, importins, karyopherin and exportins.

HEAT repeat domain, found in protein phosphatase 2a and initiation factor eIF4G.

PHAT domain, found in the RNA-binding protein Smaug.

Leucine-rich repeat variant, which contain an FeS cluster.

Pumilio repeat domain, found in Pumilio protein.

Regulatory subunit H of V-type ATPases.

PBS lyase HEAT-like repeat.

Mo25 protein.

MIF4G domain-like, found in eukaryotic initiation factor eIF4G, translation initiation factor eIF-2b epsilon and nuclear cap-binding protein CBP80.

The N-terminal domain of eukaryotic translation initiation factor 3 subunit 12.

The C-terminal domain of leukotriene A4 hydrolase.

The helical domain of phosphoinositide 3-kinase.

The N-terminal fragment of adaptin alpha-C and beta subunits.

The proximal leg segment and the linker domain of the clathrin heavy chain.

The sequence similarity among these different repeats or domains is low, however they exhibit considerable structural similarity. Furthermore, the number of repeats present in the superhelical structure can vary between orthologues, indicating that rapid loss/gain of repeats has occurred frequently in evolution. A common phylogenetic origin has been proposed for the armadillo and HEAT repeats .
Pectinesterase inhibitor, plant (PMEI_plant)
Type: Family

This entry represents pectinesterase inhibitors (also known as pectin methylesterase inhibitor, PMEI) from plants.
Cell wall/vacuolar inhibitor of fructosidase (C/VIF1)
Type: Family

This entry represents a group of invertase inhibitors, known as cell wall/vacuolar inhibitor of fructosidase (C/VIF1) from plants.

Cell-wall invertases (CWIs) are secreted apoplastic enzymes belonging to the glycoside hydrolase family 32 (

) that catalyze the hydrolytic cleavage of the disaccharide sucrose into glucose and fructose. Their activity is tightly regulated by compartment-specific inhibitor proteins at transcriptional and post-transcriptional levels .
Pla a 1-like (Pla_a_1-like)
Type: Family

This entry includes pollen allergen Pla a 1 protein from Platanus acerifolia (London plane tree) and its homologues, including pectinesterase inhibitor 12 from Arabidopsis .

The major Platanus acerifolia pollen allergen Pla a 1 belongs to a class of allergens related to proteinaceous invertase and pectin methylesterase inhibitors. Platanus acerifolia is an important cause of pollinosis; Pla a 1 has a prevalence of about 80% among plane tree pollen-allergic patients . Recombinant Pla a 1 binds IgE in vitro, similar to its natural counterpart, rendering it suitable for specific diagnosis and structural studies .

Invertase inhibitors are structurally similar to those of pectin methylesterase (PMEIs), an enzyme that is involved in the control of pectin metabolism and is structurally unrelated to invertases . All inhibitors share a size of about 18kDa, two strictly conserved disulfide bridges and only moderate sequence homology (about 20% sequence identity) .
SPOP, C-terminal BACK domain (SPOP_C)
Type: Domain

This entry represents the C-terminal BACK (BTB and C-terminal Kelch) domain of speckle-type POZ protein (SPOP, also known as HIB homologue 1 or Roadkill homologue 1). This domain contains a pair of α-helices which seem to be conserved among Cul3 adaptors .

SPOP is an adaptor protein that forms a complex with Cul3, cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex, and is involved in ubiquitination of BMI1, H2AFY, and the death-associated protein 6 (DAXX) . The C-terminal BACK domain of SPOP, may be involved in oligomer formation and in recruiting Cul3 (together with the adjacent BTB domain), whereas the N-terminal MATH domain recruits substrates .
BPM, C-terminal BACK domain (BPM_C)
Type: Domain

This entry represents the C-terminal domain of the plant BTB/POZ and MATH domain-containing (BPM) proteins. Proteins in this entry include Arabidopsis BPM1-6. Arabidopsis BPM proteins may act as a substrate-specific adapter of an E3 ubiquitin-protein ligase complex (CUL3-RBX1-BTB) which mediates the ubiquitination and subsequent proteasomal degradation of target proteins . BPM proteins have also been shown to interact with members of the ethylene response factor/Apetala2 (ERF/AP2) transcription factor family and may play an important role in plant development and stress tolerance .
BTBD9, BACK-like domain (BTBD9_BACK-like_dom)
Type: Domain

BTBD9 contains BTB/POZ, BACK, and two Coagulation factor 5/8 C-terminal (FA58C) domains. Single-nucleotide polymorphisms in the BTBD9 gene have been associated with a higher risk of Restless Legs Syndrome (RLS), a sensory-motor neurological disorder with a circadian component . BTBD9 may be involved in regulating synaptic plasticity and memory .
PHO1, SPX domain (PHO1_SPX)
Type: Domain

This region has been named the SPX domain after (Syg1, Pho81 and XPR1). The domain is found at the amino terminus of a variety of proteins. The PHO1 gene family conserved in plants is involved in a variety of processes, most notably the transport of inorganic phosphate from the root to the shoot of the plant and mediating the response to low levels of inorganic phosphate . PHO1 may play roles in stress response as well as the stomatal response to abscisic acid .
Ketohexokinase (KHK)
Type: Family

Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars . It is found in higher eukaryotes where it is believed to function as a dimer and requires K(+) and ATP to be active . In humans, hepatic KHK deficiency causes fructosuria, a benign inborn error of metabolism .
Mak32 (Mak32)
Type: Family

Mak32 is a protein found primarily in fungi that is necessary for the structural stability of L-A particles. The L-A virus particule is a specialized compartment for the transcription and replication of double-stranded RNA, known to infect yeast and other fungi. Mak32 is part of the host machinery used by the virus to multiply . This entry also includes S. pombe uncharacterised protein SPAC16C9.01c.
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3 (NDUF3)
Type: Family

Human NDUFAF3 (C3ORF60) protein is an essential factor for the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). It interacts with complex I subunits .
Mth938 domain-containing protein (AAMDC)
Type: Family

Mouse LOC66273 isoform 2 (LI2) protein, a novel Mth938 domain-containing protein, may play a role in preadipocyte differentiation and adipogenesis .
Small nuclear ribonucleoprotein G (Sm_G)
Type: Family

This entry represents the small nuclear ribonucleoprotein G.

The eukaryotic Sm proteins (B/B', D1, D2, D3, E, F and G) assemble into a hetero-heptameric ring around the Sm site of the 2,2,7-trimethyl guanosine (m3G) capped U1, U2, U4 and U5 snRNAs (Sm snRNAs) forming the core of the snRNP particle . The snRNP particle, in turn, assembles with other components onto the pre-mRNA to form the spliceosome which is responsible for the excision of introns and the ligation of exons. Members of this family share a highly conserved Sm fold containing an N-terminal helix followed by a strongly bent five-stranded antiparallel β-sheet . Sm subunit G binds subunits E and F to form a trimer which then assembles onto snRNA along with the D1/D2 and D3/B heterodimers forming a seven-membered ring structure .
Small nuclear ribonucleoprotein Sm D3 (SmD3)
Type: Family

This entry represents small nuclear ribonucleoprotein Sm D3.
Small nuclear ribonucleoprotein F (Sm_F)
Type: Family

This entry represents small nuclear ribonucleoprotein F (SmF).
Sm-like protein Lsm4 (Lsm4)
Type: Domain

This entry represents Sm-like protein Lsm4. It could be found in the nuclear Lsm2-8 complex or in the cytoplasmic Lsm1-7 complex.
Small nuclear ribonucleoprotein D1 (Sm_D1)
Type: Domain

The eukaryotic Sm proteins (B/B', D1, D2, D3, E, F and G) assemble into a hetero-heptameric ring around the Sm site of the 2,2,7-trimethyl guanosine (m3G) capped U1, U2, U4 and U5 snRNAs (Sm snRNAs) forming the core of the snRNP particle. The snRNP particle, in turn, assembles with other components onto the pre-mRNA to form the spliceosome which is responsible for the excision of introns and the ligation of exons. Members of this family share a highly conserved Sm fold containing an N-terminal helix followed by a strongly bent five-stranded antiparallel β-sheet .

Sm subunit D1 heterodimerizes with subunit D2 and three such heterodimers form a hexameric ring structure with alternating D1 and D2 subunits. The D1 - D2 heterodimer also assembles into a heptameric ring containing DB, D3, E, F, and G subunits .
Sm-like protein Lsm8 (Lsm8)
Type: Domain

This entry represents Sm-like protein Lsm8. It is found in the nuclear Lsm2-8 complex, which associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 snRNP, U4/U6.U5 snRNP, and free U6 snRNP). The Lsm2-8 complex 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 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 .
Sm-like protein Lsm1 (Lsm1)
Type: Domain

This entry represents Sm-like protein Lsm1. It can be found in the cytoplasmic Lsm1-7 complex, which 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 .
Sm-like protein Lsm3 (Lsm3)
Type: Domain

This entry represents Sm-like protein Lsm3. It can 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 .
Peptidyl-Lys endopeptidase-like domain (M35_peptidyl-Lys-like)
Type: Domain

This entry includes a presumed extracellular domain of uncharacterised homologues of peptidase family M35. Some members in this entry are non-peptidase homologues because one or more of the zinc ligands and/or the catalytic glutamic acid in the HExxH motif have been replaced.

Peptidase family M35 contains metalloendopeptidases known as Asp-zincins, in which a single catalytic zinc ion is ligated by two histidines in an HExxH motif and an aspartic acid in a GTXDXXYG or similar motif C-terminal to the HExxH motif. The glutamic acid in the HExxH motif is a catalytic residue .
Lsm16, N-terminal (Lsm16_N)
Type: Domain

This entry represents the N-terminal of the Lsm16 protein.
Peptidase M35-like domain, Proteobacteria (Pept_M35-like_proteobacteria)
Type: Domain

This family contains the peptidase domain of uncharacterised proteins from Proteobacteria similar to the Zn
2+
-metallopeptidases in peptidase family M35 (Asp-zincins), also known as the deuterolysin family.

Peptidase family M35 contains metalloendopeptidases known as Asp-zincins, in which a single catalytic zinc ion is ligated by two histidines in an HExxH motif and an aspartic acid in a GTXDXXYG or similar motif C-terminal to the HExxH motif. The glutamic acid in the HExxH motif is a catalytic residue .
Sm-like protein Lsm11, middle domain (Lsm11_M)
Type: Domain

This entry represents the middle domain of Lsm11.

The eukaryotic Sm and Sm-like (Lsm) proteins associate with RNA to form the core domain of the ribonucleoprotein particles involved in a variety of RNA processing events including pre-mRNA splicing, telomere replication, and mRNA degradation. Members of this family share a highly conserved Sm fold containing an N-terminal helix followed by a strongly bent five-stranded antiparallel β-sheet .
LSM domain containing 1, Sm domain (LSMD1_Sm)
Type: Domain

This entry represents the single Sm-like domain of LSM domain containing 1 (LSMD1) and similar eukaryotic proteins. They form heptameric and hexameric ring structures .

LSMD1, also known as Mak31 or N-alpha-acetyltransferase 38, NatC auxiliary subunit (Naa38), is the auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyses acetylation of N-terminal methionine residues .
Intraflagellar transport protein 27 homologue, eukaryotes (RabL4_euk)
Type: Family

IFT27, also known as RabL4 (Rab-like4), is a small GTPase-like component of the intraflagellar transport (IFT) complex B that promotes the exit of the BBSome complex from cilia via its interaction with ARL6 . It is capable of forming a heterodimer with IFT25 (HSPB11) and is involved in the hedgehog (Hh) signaling pathway .
Golgi-associated plant pathogenesis-related protein 1, SCP domain (SCP_GAPR1-like)
Type: Domain

This SCP-like extracellular protein domain is found in golgi-associated plant pathogenesis-related protein 1 (GAPR-1).The human GAPR-1 protein has been reported to dimerize, and such a dimer may form an active site containing a catalytic triad. GAPR-1 and GLIPR-2 appear to be synonyms .

The SCP domain is also known as CAP domain . The wider family of SCP containing proteins includes plant pathogenesis-related protein 1 (PR-1), CRISPs, mammalian cysteine-rich secretory proteins, which combine SCP with a C-terminal cysteine rich domain, and allergen 5 from vespid venom. It has been proposed that SCP domains may function as endopeptidases.
Ras-related protein Rab-23 (Rab23)
Type: Family

Rab23 is a member of the Rab family of small GTPases. In mouse, Rab23 has been shown to function as a negative regulator in the sonic hedgehog (Shh) signaling pathway. Rab23 mediates the activity of Gli2 and Gli3, transcription factors that regulate Shh signaling in the spinal cord, primarily by preventing Gli2 activation in the absence of Shh ligand . Rab23 also regulates a step in the cytoplasmic signal transduction pathway that mediates the effect of Smoothened (one of two integral membrane proteins that are essential components of the Shh signaling pathway in vertebrates) .

In humans, Rab23 is expressed in the retina . Mice contain an isoform that shares 93% sequence identity with the human Rab23 and an alternative splicing isoform that is specific to the brain. This isoform causes the murine open brain phenotype, indicating it may have a role in the development of the central nervous system .
Peptidyl-Lys metallopeptidase catalytic domain (M35_peptidyl-Lys)
Type: Domain

This entry includes the family M35 Zn
2+
-metallopeptidase extracellular domain from proteins characterised as peptidyl-Lys metalloendopeptidases (MEP; peptidyllysine metalloproteinase; EC 3.4.24.20; MEROPS identifier M35.004), including some well-characterised domains in Armillaria mellea , Aeromonas salmonicida subsp. achromogenes (AsaP1) and Grifola frondosa (GfMEP) . These proteins specifically cleave peptidyl-lysine bonds (-X-Lys- where X may even be Pro) in proteins and peptides. AsaP1 peptidase (MEROPS identifier M35.003) is important in the virulence of A. salmonicida subsp. Achromogenes, having a major role in the fish's innate immune response . AsaP1 is synthesised as an inactive precursor, the structure of which shows that the propeptide inhibits activity by inserting a lysine into the S1' pocket of the active site .

Peptidase family M35 contains metalloendopeptidases known as Asp-zincins, in which a single catalytic zinc ion is ligated by two histidines in an HExxH motif and an aspartic acid in a GTXDXXYG or similar motif C-terminal to the HExxH motif. The glutamic acid in the HExxH motif is a catalytic residue .
AGE domain (AGE_dom)
Type: Domain

N-acyl-D-glucosamine 2-epimerase (also known as AGE) is responsible for intermediate epimerization during biosynthesis of N-acetylneuraminic acid. The catalytic mechanism is believed to be via nucleotide elimination and readdition and is ATP modulated. AGE is structurally and mechanistically distinct from the other four types of epimerases. The AGE domain monomer is composed of an α(6)/α(6)-barrel, the structure of which is also found in glucoamylase and cellulase. The active form is a homodimer. The alignment also contains subtype III mannose 6-phosphate isomerases .
Cysteine-rich secretory protein, SCP domain (SCP_CRISP)
Type: Domain

This SCP-like extracellular protein domain is found in cysteine-rich secretory proteins (CRISPs). Involvement of CRISP in response to pathogens, fertilization, and sperm maturation have been proposed . One member, Tex31 from the venom duct of Conus textile, has been shown to possess proteolytic activity sensitive to serine protease inhibitors . SCP has also been proposed to be a Ca2 chelating serine protease. The Ca2-chelating function would fit with various signaling processes that members of this family, such as the CRISPs, are involved in, and is supported by sequence and structural evidence of a conserved pocket containing two histidines and a glutamate. It also may explain how helothermine, a toxic peptide secreted by the beaded lizard, blocks Ca++ transporting ryanodine receptors . One member, DE or CRISP-1, has been shown to mediate gamete fusion by binding to the egg surface; a sequence motif in the SCP domain plays a role in that binding .

The SCP domain is also known as CAP domain . The wider family of SCP containing proteins includes plant pathogenesis-related protein 1 (PR-1), CRISPs, mammalian cysteine-rich secretory proteins, which combine SCP with a C-terminal cysteine rich domain, and allergen 5 from vespid venom. It has been proposed that SCP domains may function as endopeptidases.
Protein S100-A6 (S-100A6)
Type: Family

S100A6 is a member of the S100 domain family within the EF-hand Ca
2+
-binding proteins superfamily. Note that the S-100 hierarchy, to which this S-100A6 group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately . S100 proteins exhibit unique patterns of tissue- and cell type-specific expression and have been implicated in the Ca
2+
-dependent regulation of diverse physiological processes, including cell cycle regulation, differentiation, growth, and metabolic control .
PQQ-dependent type I alcohol dehydrogenase (ADHI)
Type: Family

This entry includes a bacterial family of homodimeric ethanol dehydrogenases that utilize pyrroloquinoline quinone (PQQ) as a cofactor . It represents proteins whose expression may be induced by ethanol, and which are similar to quinoprotein methanol dehydrogenases, but have higher specificities for ethanol and other primary and secondary alcohols. Dehydrogenases with PQQ cofactors, such as ethanol, methanol, and membrane-bound glucose dehydrogenases, form an 8-bladed β-propeller .

Characterised proteins in this entry includes QedH from Pseudomonas putida and Boh from Thauera butanivorans . Other characterised members are exaF that catalyses the oxidation of ethanol to acetaldehyde or acetate, but only in the presence of lanthanides ; PedE and PedH that catalyses the oxidation of a range of substrates, including linear and aromatic primary and secondary alcohols, as well as aldehydes, but only in the presence of lanthanides, allowing bacterial growth with a variety of volatile organic compounds as carbon and energy sources .
Glioma pathogenesis-related protein 1-like, SCP domain (SCP_GLIPR-1-like)
Type: Domain

This SCP-like extracellular protein domain is found in the glioma pathogenesis-related protein (GLIPR) subfamily, which consists of GLIPR1, GLIPR1-like 1 (GLIPR1L1), and GLIPR1-like 2 (GLIPR1L2). GLIPR1 and GLIPR1L2 are expressed in several tissues, whereas GLIPR1L1 is expressed predominantly in the testis and is involved in the binding of sperm to the oocyte complex .

The SCP domain is also known as CAP domain . The wider family of SCP containing proteins includes plant pathogenesis-related protein 1 (PR-1), CRISPs, mammalian cysteine-rich secretory proteins, which combine SCP with a C-terminal cysteine rich domain, and allergen 5 from vespid venom. It has been proposed that SCP domains may function as endopeptidases.
Retropepsin-like domain, bacterial (Retropepsin-like_bacterial)
Type: Domain

This entry includes bacterial aspartate proteases that are retropepsin-like, i.e. like the enzymes from retrovirus and retrotransposons. While fungal and mammalian pepsin-like aspartate proteases are bilobal proteins with structurally related N- and C-termini, this family of bacterial aspartate proteases is half as long as their fungal and mammalian counterparts. The monomers are structurally related to one lobe of the pepsin molecule and function as homodimers. The active site aspartate occurs within a motif (Asp-Thr/Ser-Gly), as it does in pepsin. In aspartate peptidases, Asp residues are ligands of an activated water molecule in all examples where catalytic residues have been identified. This group of aspartate proteases is classified by MEROPS as the peptidase family A32. The RC1339/APRc protein from Rickettsia conorii has been characterised and its tertiary structure determined .
RBM6, RNA recognition motif 1 (RBM6_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of RBM6 (also known as lung cancer antigen NY-LU-12, or protein G16, or RNA-binding protein DEF-3), which has been predicted to be a nuclear factor based on its nuclear localization signal .
RBM6, RNA recognition motif 2 (RBM6_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of RBM6 (also known as lung cancer antigen NY-LU-12, or protein G16, or RNA-binding protein DEF-3), which has been predicted to be a nuclear factor based on its nuclear localization signal .