SII-SWORD/CoKE huggingface dataset:
STARD11, START domain (STARD11_START)
Type: Domain

This entry represents the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain of STARD11. STARD11 is also known as Collagen type IV alpha-3-binding protein, or COL4A3BP. STARD11 acts as a non-vesicular ceramide-carrier protein . STARD11 is synthesized from two major transcripts: a long one encoding Goodpasture-antigen-binding protein (GPBP), also named CERTL; and a shorter one lacking one exon, GPBPdelta26/CERT (also known as CERT). It is likely that these two carry out different functions in specific sub-cellular locations. GPBP/CERTL exists in multiple isoforms originating from alternative translation initiation sites and post-translational modifications. Recombinant STARD11 binds and phosphorylates Goodpasture antigen, the C-terminal region of the alpha3 chain of collagen IV, which is involved in the autoimmune disease Goodpasture disease .
YdeP, molybdopterin-binding oxidoreductase-like domain (YdeP_MopB)
Type: Domain

YdeP is a putative oxidoreductase involved in acid resistance . This entry represents a molybdopterin-binding oxidoreductase-like domain with a putative molybdopterin cofactor binding site found in YdeP and related bacterial proteins. These members belong to the molybdopterin_binding (MopB) superfamily of proteins.
Trimethylamine-N-oxide reductase-like, molybdopterin-binding domain (CT_DMSOR/BSOR/TMAOR)
Type: Domain

This entry is the conserved molybdopterin-binding C-terminal domain found in dimethylsulfoxide reductase (DMSOR), biotin sulfoxide reductase (BSOR), trimethylamine N-oxide reductase (TMAOR) and other related proteins. DMSOR always catalyzes the reduction of DMSO to dimethylsulfide, but its cellular location and oligomerization state are organism-dependent. For example, in Rhodobacter sphaeriodes and Rhodobacter capsulatus, it is an 82kDa monomeric soluble protein found in the periplasmic space; in E. coli, it is membrane-bound and exists as a heterotrimer. BSOR catalyzes the reduction of biotin sulfixode to biotin, and is unique among Mo enzymes because no additional auxiliary proteins or cofactors are required . TMAOR is similar to DMSOR, but its only natural substrate is TMAO .
ATX3/4/5, ePHD domain (ATX3/4/5_ePHD)
Type: Domain

This entry represents the ePHD finger of A. thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like proteins ATX3, ATX4 and ATX5, which belong to the histone-lysine methyltransferase family. The extended plant homeodomain (ePHD) zinc finger is characterised as Cys2HisCys5HisCys2His.

These proteins show distinct phylogenetic origins from the family of ATX1 and ATX2. They are multi-domain proteins that consist of an N-terminal PWWP domain, a canonical PHD finger, a non-canonical extended PHD (ePHD) finger, and a C-terminal SET domain .
ATX1/2, ePHD domain (ATX1/2_ePHD)
Type: Domain

This entry represents the ePHD finger of A. thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like proteins ATX1, -2, and similar proteins. The extended plant homeodomain (ePHD) zinc finger is characterised as Cys2HisCys5HisCys2His.

ATX1 and -2 are sister paralogs originating from a segmental chromosomal duplication; they are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins . ATX1 is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression . ATX1 regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways . ATX2 is involved in dimethylating histone H3 at lysine 4 (H3K4me2) . ATX1 and ATX2 are multi-domain proteins that consist of an N-terminal PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical PHD finger, a non-canonical ePHD finger, and a C-terminal SET domain .
Nitrate reductase NapA-like, molybdopterin-binding domain (CT_Nitrate-R-NapA-like)
Type: Domain

Nitrate reductases catalyze the reduction of nitrate to nitrite. Nitrate reductases are classified into three distinct types: periplasmic nitrate reductase (Nap), membrane-bound respiratory nitrate reductase (Nar) and assimilatory nitrate reductase (Nas) . The soluble nitrate reductases are present in either the periplasm (Nap) or the cytoplasm (Nas). The catalytic subunit (NapA) from periplasmic nitrate reductase can be monomeric or heterodimeric, in a complex with a di-c-haem subunit (NapB) . This entry represents the conserved molybdopterin-binding C-terminal domain found in NapA, NasA, and NarB.
KMT2A, ePHD domain (KMT2A_ePHD)
Type: Domain

The extended plant homeodomain (ePHD) zinc finger is characterised as Cys2HisCys5HisCys2His. This entry represents the ePHD finger of Histone-lysine N-methyltransferase 2A (KMT2A), which is a histone methyltransferase that belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2). It regulates chromatin-mediated transcription through the catalysis of methylation of histone 3 lysine 4 (H3K4), and is frequently rearranged in acute leukaemia . KMT2A functions as the catalytic subunit in the MLL1 complex, which also contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex . The MLL1 complex is highly active and specific for H3K4 methylation. KMT2A contains a CxxC (x for any residue) zinc finger domain, three PHD fingers, a Bromodomain domain, this extended PHD finger, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain .
KMT2B, ePHD domain (KMT2B_ePHD)
Type: Domain

The extended plant homeodomain (ePHD) zinc finger is characterised as Cys2HisCys5HisCys2His. This entry represents the ePHD finger of Histone-lysine N-methyltransferase 2B (KMT2B), also known as MLL2. KMT2B is a second human homologue of Drosophila trithorax, located on chromosome 19 . It belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2) and is vital for normal mammalian embryonic development . KMT2B functions as the catalytic subunit in the MLL2 complex, which contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL2 complex is highly active and specific for histone 3 lysine 4 (H3K4) methylation, which stimulates chromatin transcription in a SAM- and H3K4-dependent manner . Moreover, KMT2B plays a critical role in memory formation by mediating hippocampal H3K4 di- and trimethylation . It is also required for RNA polymerase II association and protection from DNA methylation at the MagohB CpG island promoter . KMT2B contains a CxxC (x for any residue) zinc finger domain, three PHD fingers, this ePHD finger, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain.
Geranylgeranyl transferase type-1 subunit beta (GGTase_I_beta)
Type: Family

This entry represents the beta subunit (α6 - α6 barrel fold) of geranylgeranyltransferase type I (GGTase-I)-like proteins containing the protein prenyltransferase (PTase) domain. GGTase-I is a subgroup of the protein prenyltransferase family of lipid-modifying enzymes PTases, which catalyze the carboxyl-terminal lipidation of Ras, Rab, and several other cellular signal transduction proteins, facilitating membrane associations and specific protein-protein interactions. Prenyltransferases employ a Zn2+ ion to alkylate a thiol group catalyzing the formation of thioether linkages between cysteine residues at or near the C terminus of protein acceptors and the C1 atom of isoprenoid lipids (geranylgeranyl (20-carbon) in the case of GGTase-I) . GGTase-I prenylates the cysteine in the terminal sequence, 'CAAX' when X is Leu or Phe. Substrates for GTTase-I include the gamma subunit of neural G-proteins and several Ras-related G-proteins . PTases are heterodimeric with both alpha and beta subunits required for catalytic activity.
KMT2D, ePHD1 domain (KMT2D_ePHD1)
Type: Domain

This entry represents the first ePHD finger found at the N-terminal end of KMT2D.

The extended plant homeodomain (ePHD) zinc finger is characterised as Cys2HisCys5HisCys2His. KMT2D (Histone-lysine N-methyltransferase 2D), also known as ALR or MLL4, is a fourth human homologue of Drosophila trithorax, located on chromosome 12 . KMT2D enzymatically generates trimethylated histone H3 at Lys 4 (H3K4me3). It acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription . It is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and KMT2D. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis . KMT2D contains the catalytic domain SET, five PHD fingers, two ePHD fingers, a RING finger, an HMG (high-mobility group)-binding motif, and two FY-rich regions.

Mutations in the KMT2D gene have been linked to Kabuki syndrome .
BsuBI/PstI restriction endonuclease, N-terminal domain superfamily (BsuBI/PstI_N_sf)
Type: Homologous_superfamily

Type II restriction endonucleases (

) are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. These site-specific deoxyribonucleases catalyse the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. Of the 3000 restriction endonucleases that have been characterised, most are homodimeric or tetrameric enzymes that cleave target DNA at sequence-specific sites close to the recognition site. For homodimeric enzymes, the recognition site is usually a palindromic sequence 4-8 bp in length. Most enzymes require magnesium ions as a cofactor for catalysis. Although they can vary in their mode of recognition, many restriction endonucleases share a similar structural core comprising four β-strands and one α-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin . However, there is still considerable diversity amongst restriction endonucleases . The target site recognition process triggers large conformational changes of the enzyme and the target DNA, leading to the activation of the catalytic centres. Like other DNA binding proteins, restriction enzymes are capable of non-specific DNA binding as well, which is the prerequisite for efficient target site location by facilitated diffusion. Non-specific binding usually does not involve interactions with the bases but only with the DNA backbone .

This superfamily represents the N terminus of bacterial enzymes similar to type II restriction endonucleases BsuBI and PstI (

). The structure contains a winged-helix-turn-helix DNA binding structure. The enzymes of the BsuBI restriction/modification (R/M) system recognise the target sequence 5'CTGCAG and are functionally identical with those of the PstI R/M system .
BsuBI/PstI restriction endonuclease, C-terminal domain superfamily (BsuBI/PstI_C_sf)
Type: Homologous_superfamily

Type II restriction endonucleases (

) are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. These site-specific deoxyribonucleases catalyse the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. Of the 3000 restriction endonucleases that have been characterised, most are homodimeric or tetrameric enzymes that cleave target DNA at sequence-specific sites close to the recognition site. For homodimeric enzymes, the recognition site is usually a palindromic sequence 4-8 bp in length. Most enzymes require magnesium ions as a cofactor for catalysis. Although they can vary in their mode of recognition, many restriction endonucleases share a similar structural core comprising four β-strands and one α-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin . However, there is still considerable diversity amongst restriction endonucleases . The target site recognition process triggers large conformational changes of the enzyme and the target DNA, leading to the activation of the catalytic centres. Like other DNA binding proteins, restriction enzymes are capable of non-specific DNA binding as well, which is the prerequisite for efficient target site location by facilitated diffusion. Non-specific binding usually does not involve interactions with the bases but only with the DNA backbone .

This superfamily represents the C terminus of bacterial enzymes similar to type II restriction endonucleases BsuBI and PstI (

). The enzymes of the BsuBI restriction/modification (R/M) system recognise the target sequence 5'CTGCAG and are functionally identical with those of the PstI R/M system .
KMT2D, ePHD2 domain (KMT2D_ePHD2)
Type: Domain

The extended plant homeodomain (ePHD) zinc finger is characterised as Cys2HisCys5HisCys2His. KMT2D (Histone-lysine N-methyltransferase 2D), also known as ALR or MLL4, is a fourth human homologue of Drosophila trithorax, located on chromosome 12 . KMT2D enzymatically generates trimethylated histone H3 at Lys 4 (H3K4me3). It acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription . It is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and KMT2D. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis . KMT2D contains the catalytic domain SET, five PHD fingers, two ePHD fingers, a RING finger, an HMG (high-mobility group)-binding motif, and two FY-rich regions.

Mutations in the KMT2D gene have been linked to Kabuki syndrome .

This entry represents the second ePHD finger of KMT2D.
Putative transposon-transfer assisting superfamily (TTRAP_sf)
Type: Homologous_superfamily

This entry represents the transposon-transfer assisting protein (TTRAP). TTRAP are small bacterial proteins largely from Clostrium difficile. From comparative and other structural studies of the PDB:

(

), it has been suggested that this family is required for interacting with other proteins in order to facilitate the transfer of the transposon CTn4 between different bacterial species. The

structure comprises an α-helical fold of four α-helices leading to the production of two clefts, the larger of which displays two highly conserved residues in close proximity, Glu-8 and Lys-48. The gene concerned is part of an operon within transposon CTn4, and is expressed alongside a putative DNA primase, a DNA topoisomerase and conjugal transfer proteins .
LOTUS-like domain (LOTUS-like)
Type: Homologous_superfamily

This superfamily represents a RNA-binding domain identified when studying Tudor domain containing proteins and was designed LOTUS after Limkain, Oskar and TUdor-containing proteins 5 and 7.

This predicted RNA-binding domain found in insect Oskar and vertebrate TDRD5/TDRD7 proteins that nucleate or organise structurally related ribonucleoprotein (RNP) complexes, the polar granule and nuage, is poorly understood . The domain adopts the winged helix-turn-helix fold and binds RNA with a potential specificity for dsRNA . In eukaryotes, this domain is often combined in the same polypeptide with protein-protein- or lipid- interaction domains that might play a role in anchoring these proteins to specific cytoskeletal structures. Thus, proteins with this domain might have a key role in the recognition and localisation of dsRNA, including miRNAs, rasiRNAs and piRNAs hybridized to their targets. In other cases, this domain is fused to ubiquitin-binding, E3 ligase and ubiquitin-like domains, indicating a previously under-appreciated role for ubiquitination in regulating the assembly and stability of nuage-like RNP complexes. Both bacteria and eukaryotes encode a conserved family of proteins that combines this predicted RNA-binding domain with a previously uncharacterised RNAse domain belonging to the superfamily that includes the 5'->3' nucleases, PIN and NYN domains .
KMT2C, ePHD1 (KMT2C_ePHD1)
Type: Domain

This entry represents the first ePHD finger of Histone-lysine N-methyltransferase 2C (KMT2C).

The extended plant homeodomain (ePHD) zinc finger is characterised as Cys2HisCys5HisCys2His. KMT2C, also known as MLL3, is a histone H3 lysine 4 (H3K4) lysine methyltransferase that functions as a circadian factor contributing to genome-scale circadian transcription . It is a component of a large complex that acts as a coactivator of multiple transcription factors, including the bile acid (BA)-activated nuclear receptor, farnesoid X receptor (FXR), a critical player in BA homeostasis. The MLL3 complex is essential for p53 transactivation of small heterodimer partner (SHP) . KMT2C is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and its paralog MLL4 . The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis . KMT2C contains several PHD fingers, two ePHD fingers, an ATPase alpha beta signature, a high mobility group (HMG)-1 box, a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain and two FY (phenylalanine tyrosine)-rich domains.
KMT2C, ePHD2 (KMT2C_ePHD2)
Type: Domain

This entry represents the second ePHD finger of Histone-lysine N-methyltransferase 2C (KMT2C).

The extended plant homeodomain (ePHD) zinc finger is characterised as Cys2HisCys5HisCys2His. KMT2C, also known as MLL3, is a histone H3 lysine 4 (H3K4) lysine methyltransferase that functions as a circadian factor contributing to genome-scale circadian transcription . It is a component of a large complex that acts as a coactivator of multiple transcription factors, including the bile acid (BA)-activated nuclear receptor, farnesoid X receptor (FXR), a critical player in BA homeostasis. The MLL3 complex is essential for p53 transactivation of small heterodimer partner (SHP) . KMT2C is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and its paralog MLL4 . The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis . KMT2C contains several PHD fingers, two ePHD fingers, an ATPase alpha beta signature, a high mobility group (HMG)-1 box, a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain and two FY (phenylalanine tyrosine)-rich domains.
Intermembrane lipid transfer protein VPS13D, UBA domain (VP13D_UBA)
Type: Domain

This entry represents the UBA domain of the intermembrane lipid transfer protein VP13D (also known as vacuolar protein sorting-associated protein 13D), which is a ubiquitin-binding protein that contains two putative domains, ubiquitin-associated (UBA) domain and lectin domain of ricin B chain profile (ricin-B-lectin) . The UBA domain of Vps13D has been shown to bind K63 ubiquitin chains. Vps13D plays important roles in mitochondrial health and development. It is also necessary for autophagy, mitochondrial size, and mitochondrial clearance in Drosophila .
Rup1, UBA domain (Rup1_UBA)
Type: Domain

Rup1 mediates the association of Rsp5 and Ubp2. The N-terminal UBA domain is responsible for antagonizing Rsp5 function, as well as bridging the Rsp5-Ubp2 interaction .
Gawky, UBA domain (Gawky_UBA)
Type: Domain

This entry represents the UBA domain of Gawky.

Protein Gawky (also known as GW182) plays a role in RNA-mediated gene silencing by micro-RNAs (miRNAs) . It is a component of cytoplasmic mRNA processing bodies required for early Drosophila development . GW182 interacts with AGO1, and this interaction is essential for silencing by miRNAs . It recruits the CCR4-NOT deadenylase complex through the interaction with PABPC1 .
Transcription factor 20, ePHD domain (TCF-20_ePHD)
Type: Domain

This entry represents the C-terminal ePHD/ADD (ATRX-DNMT3-DNMT3L) domain of transcription factor 20 (TCF-20).

The extended plant homeodomain (ePHD) zinc finger is characterised as Cys2HisCys5HisCys2His. TCF-20 (also known as SPBP) is involved in transcriptional activation of the MMP3 (matrix metalloprotease 3) promoter. It is strongly enriched on chromatin in interphase HeLa cells, and displays low nuclear mobility, and has been implicated in Smith-Magenis syndrome and Potocki-Lupski syndrome . As a chromatin-binding protein, TCF-20 plays a role in the regulation of gene expression. It also functions as a transcriptional co-regulator that enhances or represses the transcriptional activity of certain transcription factors/cofactors, such as specificity protein 1 (Sp1), E twenty-six 1 (Ets1) , paired box protein 6 (Pax6) , small nuclear RING-finger (SNURF)/RNF4, c-Jun, androgen receptor (AR) and estrogen receptor alpha (ERalpha) . TCF-20 contains an N-terminal transactivation domain, a novel DNA-binding domain with an AT-hook motif, three nuclear localization signals (NLSs) and a C-terminal ePHD/ADD domain.
Spt5, KOW domain repeat 1 (KOW_Spt5_1)
Type: Domain

Spt5, an eukaryotic ortholog of NusG, contains multiple KOW motifs at its C-terminal. Spt5 is involved in transcription elongation and termination. The KOW domain is known as an RNA-binding motif that is shared so far among some families of ribosomal proteins, the essential bacterial transcriptional elongation factor NusG, the eukaryotic chromatin elongation factor Spt5, the higher eukaryotic KIN17 proteins and Mtr4 . Unlike bacterial NusG with its single KOW motif, eukaryotic Spt5 has multiple KOW domains. There are five KOW motifs in yeast Spt5, whereas animals and plants Spt5 have seven . Spt5 KOW domains play critical roles in recruitment of multiple other eukaryotic transcription elongation and RNA biogenesis factors and additionally are involved in the binding of the eukaryotic Spt5 proteins to RNA polymerases .
Ubiquitin carrier protein 27, UBA domain (UBC27_UBA)
Type: Domain

Ubiquitin carrier protein 27 (UBC27), functions as a class II ubiquitin-conjugating (UBC) enzyme (E2). E2, together with E1 (ubiquitin-activating enzyme UBA) and E3 (ubiquitin ligase), is required in the multi-step reaction of ubiquitin conjugation. Unlike other Arabidopsis UBCs, in addition to an N-terminal ubiquitin-conjugating enzyme E2 catalytic domain (UBCc), UBC27 has an additional C-terminal ubiquitin-associated domain (UBA) . This entry represents the UBA domain.
Spt5, KOW domain repeat 2 (KOW_Spt5_2)
Type: Domain

Spt5, an eukaryotic ortholog of NusG, contains multiple KOW motifs at its C-terminal. Spt5 is involved in transcription elongation and termination. The KOW domain is known as an RNA-binding motif that is shared so far among some families of ribosomal proteins, the essential bacterial transcriptional elongation factor NusG, the eukaryotic chromatin elongation factor Spt5, the higher eukaryotic KIN17 proteins and Mtr4 . Unlike bacterial NusG with its single KOW motif, eukaryotic Spt5 has multiple KOW domains. There are five KOW motifs in yeast Spt5, whereas animals and plants Spt5 have seven . Spt5 KOW domains play critical roles in recruitment of multiple other eukaryotic transcription elongation and RNA biogenesis factors and additionally are involved in the binding of the eukaryotic Spt5 proteins to RNA polymerases .