SII-SWORD/CoKE huggingface dataset:
Duc1 FFAT-like motif (Duc1_FFAT-like)
Type: Conserved_site

This entry represents the FFAT-like motif found in proteins such as Duc1 from Schizosaccharomyces pombe , that interact with VAP (VAMP-associated protein) family members like Scs2 and Scs22. The motif is characterised by two adjacent aromatic residues (typically FF, but YF in Duc1) downstream of an acidic tract. It also contains conserved alanine and glutamate residues at the second and fourth positions after the aromatic pair, respectively. This motif mediates interactions with the Major Sperm Protein (MSP) domains of VAP proteins, playing a crucial role in tethering proteins to ER-PM contact sites. In Duc1, the core of this motif is Y374 and F375, which are essential for the protein's interaction with Scs2 and Scs22, and consequently for its proper localization and function in maintaining plasma membrane lipid composition and cytokinetic ring anchoring.
Domain of unknown function DUF7088 (DUF7088)
Type: Domain

This domain is found at the N-terminal of a group of poorly characterised bacterial sequences. It is usually found associated with

. The function of this domain is unknown.
TraK, C-terminal domain (TraK_C)
Type: Domain

This entry represents the C-terminal domain from TraK proteins. The TraK C-terminal domain is observed in constituent proteins of bacterial type IV secretion systems (T4SSs), which are key players in the dissemination of multi-drug resistance. This domain contributes to the formation of the outer-membrane core complex (OMCCF) of T4SS encoded by conjugative F plasmids. The structure of the TraK C-terminal domain shows a compact fold consisting of 4 β-strands and one α-helix. This domain interacts with other components of the OMCCF, including TraV and other TraK C-terminal domains. Within the structural unit of the OMCCF, TraK C-terminal domains assemble as dimers, with each domain flipped 180 degrees relative to the other. The TraK C-terminal dimer sits laterally on top of the TraK N-terminal dimer, contributing to the overall stability of the complex. An electrostatic interaction between specific residues within TraK subunits participates in the stabilisation of the TraK C-terminal dimer .

TraK is known to be essential for pilus assembly but its exact role in this process is unknown .
Bacillithiol biosynthesis BshC, N-terminal Rossmann-like domain (Rossmann-like_BshC)
Type: Domain

This entry represents the N-terminal Rossmann-like domain of the bacillithiol biosynthesis protein BshC from Bacillus subtilis, which has been described as a cysteine-adding enzyme .
Bacillithiol biosynthesis BshC, C-terminal coiled-coil domain (CC_BshC)
Type: Domain

This entry represents the C-terminal coiled-coil domain of the bacillithiol biosynthesis protein BshC from Bacillus subtilis, which has been described as a cysteine-adding enzyme. This domain, found associated with

, shows a four-helix bundle and is responsible for the dimerisation of the protein .
CEMIP, domain X (CEMIP_X)
Type: Domain

This entry represents Domain X of CEMIP, CEMIP2 and closely related sequences . This domain is located after the β-helix domain. Proteins in this entry are involved in the metabolism of hyaluronic acid (HA) and mediate the depolymerization of high-molecular-weight HA into intermediate-sized fragments , a process crucial for various physiological functions, including the regulation of angiogenesis, heart development, and cell migration . This domain has been called domain X in , its function is still unknown.
CEMIP, beta-helix domain (CEMIP_beta-hel_dom)
Type: Domain

This entry represents the β-helix domain of CEMIP, CEMIP2 and related sequences . Proteins in this entry are involved in the metabolism of hyaluronic acid (HA) and mediate the depolymerization of high-molecular-weight HA into intermediate-sized fragments , a process crucial for various physiological functions, including the regulation of angiogenesis, heart development, and cell migration . This domain has the common structural motif of enzymes involved in polysaccharide degradation, encompassing both hydrolases and lyases, however, biochemical experiments failed to detect any hyaluronidase activity in CEMIP2 and the putative active site remains to be elucidated .

This entry also includes Fibrocystin (PKHD), a protein that promotes ciliogenesis within renal epithelial cells, contributing to the formation of kidney tubules and maintaining the lumen architecture . It may participate in the regulation of the cholangiocytes proliferation and the CCN2 production in an CXCL8-dependent manner .
KNTC1, N-terminal (KNTC1_N)
Type: Domain

This entry represents the β-propeller domain found at the N-terminal of KNTC1 (Kinetochore-associated protein 1, also known as ROD) from vertebrates. KNTC1 is the major subunit of the RZZ (ROD-Zwilch-ZW10) complex , which plays a significant role in spindle assembly, kinetochore-microtubule attachment, and spindle pole separation. KNTC1 is required for the assembly of essential complexes onto kinetochores, including dynein-dynactin and MAD1-MAD2 . This domain mediates extensive interactions with the other subunits of the complex, forming a RZZ module that binds Spindly, a DD adaptor that can activate dynein motility .
KNTC1, first ARM-repeats domain (ARM_KNTC1_1st)
Type: Domain

This entry represents the first segment of ARM repeats present in KNTC1 (Kinetochore-associated protein 1, also known as ROD), following the β-propeller domain. KNTC1 is a crucial component of the mitotic checkpoint, ensuring cells do not exit mitosis prematurely . KNTC1 is required for the assembly of essential complexes onto kinetochores, such as dynein-dynactin and MAD1-MAD2. KNTC1 is the major subunit of the RZZ (ROD-Zwilch-ZW10) complex, which plays a significant role in spindle assembly, kinetochore-microtubule attachment, and spindle pole separation .

This domain is also found in MAG2-interacting protein 2 which is required for proper maturation of seed storage proteins. It forms a complex with MAG2, ZW10/MIP1 and MIP3 on the endoplasmic reticulum that may be responsible for efficient transport of seed storage proteins .
KNTC1, second ARM-repeats domain (ARM_KNTC1_2nd)
Type: Domain

This entry represents the second segment of ARM repeats present in KNTC1 (Kinetochore-associated protein 1, also known as ROD), following the β-propeller domain. KNTC1 is a crucial component of the mitotic checkpoint, ensuring cells do not exit mitosis prematurely . KNTC1 is required for the assembly of essential complexes onto kinetochores, such as dynein-dynactin and MAD1-MAD2. KNTC1 is the major subunit of the RZZ (ROD-Zwilch-ZW10) complex, which plays a significant role in spindle assembly, kinetochore-microtubule attachment, and spindle pole separation .
KNTC1, third ARM-repeats domain (ARM_KNTC1_3rd)
Type: Domain

This entry represents the third segment of ARM repeats present in KNTC1 (Kinetochore-associated protein 1, also known as ROD), following the β-propeller domain. KNTC1 is a crucial component of the mitotic checkpoint, ensuring cells do not exit mitosis prematurely . KNTC1 is required for the assembly of essential complexes onto kinetochores, such as dynein-dynactin and MAD1-MAD2. KNTC1 is the major subunit of the RZZ (ROD-Zwilch-ZW10) complex, which plays a significant role in spindle assembly, kinetochore-microtubule attachment, and spindle pole separation .
Maestro/Maestro-like, HEAT-repeats domain (HEAT_Maestro)
Type: Domain

This entry represents a HEAT-repeats domain found in maestro and maestro heat-like repeat-containing proteins, including Maestro heat-like repeat -containing protein family member 2B from mouse (MROH2B, also known as SPIF), which may play a role in the process of sperm capacitation . This region is found at the C-terminal of MROH2B and other members of this entry, while in maestro it represents almost the whole length.
Conjugative transposon TraM, C-terminal (TraM_C)
Type: Domain

This domain is found at the C-terminal end of Conjugative transposon TraM protein and similar proteins found in a proposed transfer region of a class of conjugative transposon from bacteroidetes. This domain is predicted to show a β-barrel structure.
MROH2B-like, HEAT-repeats domain (HEAT_MROH2B-like)
Type: Domain

This entry represents a HEAT-repeats domain from Maestro heat-like repeat-containing protein family member 2B (MROH2B, also known as SPIF and MRO2B) from mouse, Protein SHOOT GRAVITROPISM 6 from Arabidopsis thaliana (SGR6) and similar sequences mainly found in animals and plants. SPIF may play a role in the process of sperm capacitation . SGR6 is involved in inflorescence stems gravitropism, by modulating vacuolar membrane (VMs) dynamics in gravity-sensing cells (e.g. endodermal cells) during the amyloplast sedimentation process .
FAM234A/B, beta-propeller (Beta-prop_FAM234A_B)
Type: Domain

This entry represents the β-propeller domain found in FAM234A/B proteins from mammals and related sequences, whose function is unknown.
CAF1B/HIR1, beta-propeller domain (Beta-prop_CAF1B_HIR1)
Type: Domain

This entry represents the β-propeller domain found in chromatin assembly factor 1 subunit CAF1B (also known as p60 subunit) from animals, and its homologues Cac2 from yeasts and FAS from plants.

These proteins are involved in DNA synthesis-coupled chromatic assembly in S-phase and chromatin assembly following DNA repair alongside other CHAF proteins in what is known as CAF1 complex . In plants, the loss of activity of the CAF1 pathway causes delay and arrest of the cell cycle during pollen development . The CAF1 complex is also required for stable maintenance of telomeres and 45S rDNA in Arabidopsis . This domain is involved in CAF1B interactions with other CAF1 complex subunits .

This entry also includes histone cell cycle regulator HIRA from animals and their yeast orthologues HIR1, which are required in replication-independent chromatic assembly . The β-propeller of HIRA proteins is involved in the protein interactions with Ubinuclein-1 (UBN1) to achieve chromatic-remodelling pathway in senescent cells .
F-box/LRR-repeat protein 15/At3g58940/PEG3-like, LRR domain (LRR_FXL15/At3g58940/PEG3-like)
Type: Domain

This entry represents a domain consisting of leucine-rich repeats (LRRs) mainly found in plant proteins, such as F-box/LRR-repeat protein At3g58940, At1g56610, F-box protein At1g60400 (also known as PEG3) from Arabidopsis thaliana among others. Some of the plant members have been described as components of SCF (ASK-cullin-F-box) E3 ubiquitin ligase complexes, which may mediate the ubiquitination and subsequent proteasomal degradation of target proteins . This entry also includes F-box/LRR-repeat protein 15 from animals, the substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of SMURF1, thereby acting as a positive regulator of the BMP signalling pathway. It is required for dorsal/ventral pattern formation and bone mass maintenance. It also mediates ubiquitination of SMURF2 and WWP2 .
Root UVB sensitive protein, C-terminal (UVB_sens_C)
Type: Domain

This domain is found at the C terminus of a group of root UVB sensitive plant proteins and their eukaryotic RUS homologues. It is predicted to adopt an α/β configuration. This domain is found associated with

.

This entry includes root UVB sensitive proteins and their homologues. In Arabidopsis thaliana, proteins in this family are involved in UVB-sensing and in early seedling morphogenesis and development .

In plants, these proteins play a role in auxin-transport, plant growth and development and appears to be expressed by all cells in the plant as well as in plastids. The family has been shown to play a role in vitamin B6 photo-protection and homoeostasis in plants .

In line with various literature findings describing this family in plants, it was proposed that these proteins may be directly involved in the transport of one or more forms of the vitamin B6.
Matrix protein, C-terminal, Paramyxoviridae (Matrix_Paramyxo_C)
Type: Domain

This entry represents the C-terminal domain found in a variety of paramyxoviruses such as morbillivirus, paramyxovirus, pneumovirus M proteins. The C-terminal domain of the NDV matrix protein, similar to the N-terminal domain, adopts a β-sandwich fold with β-strands in the opposing β-sheets arranged approximately orthogonal to each other. The C-terminal domain is also decorated with several surface-exposed α-helices. It is connected to the N-terminal domain by a ~16 amino acid linker. The C-terminal domain contributes to the formation of the physiologically relevant matrix protein dimer, with the two domains related by an approximate fourfold rotation axis aligned with the dimer twofold axis. Key residues in helix α9 of the C-terminal domain participate in hydrogen bonding and electrostatic interactions across the dimer interface. The C-terminal domain also contains a positively charged surface that faces the viral membrane, facilitating association with the negatively charged membrane .
Disease resistance R13L4/SHOC-2-like, LRR domain (LRR_R13L4/SHOC2-like)
Type: Domain

This entry represents a region containing leucine-rich repeats found mainly in plants, including a variety of plant resistance proteins, such as disease resistance RPP13-like protein 4 (R13L4) from Arabidopsis. R13L4 is a CC-NB-LRR receptor-like protein required for recognition of pathogenic bacteria type III effectors (T3E) such as Pseudomonas syringae HopZ1a and HopF2a and Xanthomonas campestris pv. campestris (Xcc) XopAC/AvrAC. This recognition requires ZED1-related kinases (e.g. PBL2, ZRK3 and ZED1/ZRK5) . Arabidopsis LRR receptor-like serine/threonine-protein kinase GHR1 is also included in this entry, a receptor kinase acting as an early component in abscisic acid (ABA) signalling . GHR1 is required for darkness, ABA, high CO2 and hydrogen peroxide (H2O2) induction of S-type anion currents in guard cells leading to stomatal closure, possibly via the phosphorylation and activation of the anion channel SLAC1 and as a scaffolding component .

This entry also includes several proteins from animals, such as Leucine-rich repeat protein SHOC-2 from human and its orthologue from Drosophila melanogaster. It is a core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates activation of the MAPK pathway, acting as a scaffolding protein .
SV2A/B/C, luminal domain (LD_SV2)
Type: Domain

This entry represents the luminal domain found in synaptic vesicle protein 2 A, B and C (SV2A, SV2B and SV2C) from animals. SV2s are specific to vesicles that undergo calcium-regulated secretion and are essential for normal nervous system function, particularly for neurotransmission . SV2s have also been identified as targets for botulinum neurotoxins (BoNTs) serotypes A, D, E and F . In the case of VS2C, this domain interacts directly and allows BoNT/A transport into host cells .
Leucine--tRNA ligase, RagD-binding domain (RBD_LARS1)
Type: Domain

This is the RagD-binding domain (RBD) of human Leucine--tRNA ligase, a synthetase that catalyses the specific attachment of leucine to its cognate tRNA. This domain shows three α-helices .
Ubiquitin fusion degradation protein UFD1, N-terminal subdomain 1 (UFD1_N1)
Type: Domain

This entry corresponds to the first subdomain of UFD1 UT3 which forms a double-psi β-barrel fold.

Post-translational ubiquitin-protein conjugates are recognised for degradation by the ubiquitin fusion degradation (UFD) pathway. Several proteins involved in this pathway have been identified . UFD1 is a 40kD protein that is essential for vegetative cell viability . The human UFD1 gene is expressed at high levels during embryogenesis, especially in the eyes and in the inner ear primordia and is thought to be important in the determination of ectoderm-derived structures, including neural crest cells. In addition, this gene is deleted in the CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate and hypocalcaemia with deletions on chromosome 22) syndrome. This clinical syndrome is associated with a variety of developmental defects, all characterised by microdeletions on 22q11.2. Two such developmental defects are the DiGeorge syndrome (), and the velo-cardio- facial syndrome (). Several of the abnormalities associated with these conditions are thought to be due to defective neural crest cell differentiation . UFD1 is composed of an N-terminal conserved region (UT3) and a C-terminal disordered region (UT6) which contains the binding sites for both Npl4 and Cdc48 . UFD1 N-terminal domain contains the binding site for ubiquitin and has a similar structure to p97. It is made of two subdomains .
Ubiquitin fusion degradation protein UFD1, N-terminal subdomain 2 (UFD1_N2)
Type: Domain

This entry corresponds to the second subdomain of UFD1 UT3 which has a mixed α/β roll structure .

Post-translational ubiquitin-protein conjugates are recognised for degradation by the ubiquitin fusion degradation (UFD) pathway. Several proteins involved in this pathway have been identified . UFD1 is a 40kD protein that is essential for vegetative cell viability . The human UFD1 gene is expressed at high levels during embryogenesis, especially in the eyes and in the inner ear primordia and is thought to be important in the determination of ectoderm-derived structures, including neural crest cells. In addition, this gene is deleted in the CATCH-22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate and hypocalcaemia with deletions on chromosome 22) syndrome. This clinical syndrome is associated with a variety of developmental defects, all characterised by microdeletions on 22q11.2. Two such developmental defects are the DiGeorge syndrome (), and the velo-cardio- facial syndrome (). Several of the abnormalities associated with these conditions are thought to be due to defective neural crest cell differentiation . UFD1 is composed of an N-terminal conserved region (UT3) and a C-terminal disordered region (UT6) which contains the binding sites for both Npl4 and Cdc48 . UFD1 N-terminal domain contains the binding site for ubiquitin and has a similar structure to p97. It is made of two subdomains .
Periplakin/Envoplakin, N-terminal (Spectrin_PEPL/EVPL)
Type: Domain

This domain consists of spectrin-like repeats found at the N-terminal in human Periplakin and related vertebrate proteins including Envoplakin and Envoplakin-like proteins. Periplakin is a component of the cornified envelope of keratinocytes. It coimmunoprecipitates with Envoplakin and both proteins form a network radiating from desmosomes. These two proteins probably provide a scaffolding onto which the cornified envelope is assembled . Envoplakin and periplakin are the two proteins that are most commonly targeted by pathogenic autoantibodies.
Trafficking protein particle complex II-specific subunit 65, IgD3 (IgD3_Trs65)
Type: Domain

This entry represents the IgD3 domain of Trs65 and similar fungal proteins.

This entry includes Trafficking protein particle complex II-specific subunit 65 from Saccharomyces cerevisiae (Trp65), an essential subunit of the TRAPP Golgi trafficking complex . TRAPP subunits are found in three forms-core TRAPP/TRAPPI, TRAPPII, and TRAPPIII and they function in various vesicle trafficking pathways. TRAPPI mediates transport from endoplasmic reticulum to cis-Golgi by tethering COPII-coated vesicles; TRAPPII interacts with COPI-coated vesicles in mammalian cells and aids in endosome-to-Golgi transport, and TRAPPIII plays a unique role in autophagy. TRAPP complexes act as GEFs and play an essential role in catalysing nucleotide exchange for Ypt/Rab GTPase. The three complexes share a core of six different proteins (Bet3, Bet5, Trs20, Trs23, Trs31, and Trs33) that make up core TRAPPI. TRAPPII contains four additional proteins (Trs120, Trs130, Trs65, and Tca17), and TRAPPIII has one additional Trs85 in yeast . While Trp65 has been implicated in cell wall biogenesis and stress response, the role of Trs65 in TRAPPII is supported by the findings that the protein co-localises with Trs130p, and deletion of Trs65 in yeast leads to a conditional lethal phenotype if either one of the other TRAPPII-specific subunits is modified . Trs65 is essential to the formation of TRAPPII dimer and consists of three Ig-like domains (IgD1, IgD2 and IgD3) .
Transmembrane protein TMEM132, cohesin-like domain (TMEM132_3rd)
Type: Domain

This is the third domain of TMEM132 family, which includes TMEM132A-E. This is a β-sandwich domain closely related to cohesin, which may be involved in cellular adhesion .

The transmembrane protein 132 family (TMEM132) consists of TMEM132A, TMEM132B, TMEM132C, TMEM132D, TMEM132E. These are transmembrane proteins that regulate neuronal structure and function. In mammalian cells, they may regulate NAP1 in the WAVE regulatory complex (WRC) to finely modulate actin nucleation, cellular cytoskeletal and morphological changes . TMEM132 members have been associated with panic disorders, anxiety and major depressive disorders .

TMEM132A may play a role in embryonic and postnatal development of the brain. It increased resistance to cell death induced by serum starvation in cultured cells. It regulates cAMP-induced GFAP gene expression via STAT3 phosphorylation .

These proteins consist of six globular domains: N-terminal

, 2nd

, 3rd

, 4th

, 5th

and 6th

. The latter three are a tandem of Ig-like domains .

represents the C-terminal region which includes a single transmembrane helix.
Transmembrane protein TMEM132, second Ig-like domain (Ig_TMEM132_2nd)
Type: Domain

This entry represents the second Ig-like domain found in TMEM132 family of proteins.

The transmembrane protein 132 family (TMEM132) consists of TMEM132A, TMEM132B, TMEM132C, TMEM132D, TMEM132E. These are transmembrane proteins that regulate neuronal structure and function. In mammalian cells, they may regulate NAP1 in the WAVE regulatory complex (WRC) to finely modulate actin nucleation, cellular cytoskeletal and morphological changes . TMEM132 members have been associated with panic disorders, anxiety and major depressive disorders .

TMEM132A may play a role in embryonic and postnatal development of the brain. It increased resistance to cell death induced by serum starvation in cultured cells. It regulates cAMP-induced GFAP gene expression via STAT3 phosphorylation .

These proteins consist of six globular domains: N-terminal

, 2nd

, 3rd

, 4th

, 5th

and 6th

. The latter three are a tandem of Ig-like domains .

represents the C-terminal region which includes a single transmembrane helix.
Transmembrane protein TMEM132, fifth domain (Ig_TMEM132_5th)
Type: Domain

This is the fifth domain of TMEM132 family of proteins.

The transmembrane protein 132 family (TMEM132) consists of TMEM132A, TMEM132B, TMEM132C, TMEM132D, TMEM132E. These are transmembrane proteins that regulate neuronal structure and function. In mammalian cells, they may regulate NAP1 in the WAVE regulatory complex (WRC) to finely modulate actin nucleation, cellular cytoskeletal and morphological changes . TMEM132 members have been associated with panic disorders, anxiety and major depressive disorders .

TMEM132A may play a role in embryonic and postnatal development of the brain. It increased resistance to cell death induced by serum starvation in cultured cells. It regulates cAMP-induced GFAP gene expression via STAT3 phosphorylation .

These proteins consist of six globular domains: N-terminal

, 2nd

, 3rd

, 4th

, 5th

and 6th

. The latter three are a tandem of Ig-like domains .

represents the C-terminal region which includes a single transmembrane helix.