SII-SWORD/CoKE huggingface dataset:
BRPF2, PHD domain (BRPF2_PHD)
Type: Domain

This entry represents the PHD finger of BRPF2 (also known as BRD1) .

BRPF2 is responsible for the bulk of the acetylation of H3K14 and forms a novel monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complex with HBO1 and ING4 . The complex is required for full transcriptional activation of the erythroid-specific regulator genes essential for terminal differentiation and survival of erythroblasts in fetal liver . It contains a cysteine rich region harbouring a plant homeodomain (PHD) finger followed by a non-canonical ePHD finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain.
ATX1/2, PHD domain (ATX1/2_PHD)
Type: Domain

This entry represents the PHD finger of A. thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like proteins ATX1, -2, and similar proteins.

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 .
ATX3/4/5, PHD domain (ATX3/4/5_PHD)
Type: Domain

This entry represents the PHD finger of A. thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like proteins ATX3, ATX4 and ATX5, which belong to the histone-lysine methyltransferase family.

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 .
PHF7/G2E3, PHD domain (PHF7/G2E3_PHD)
Type: Domain

This entry represents the PHD domain found in PHF7 and G2E3.

PHF7 (also known as NYD-SP6) is a testis-specific plant homeodomain (PHD) finger-containing protein that associates with chromatin and binds histone H3 N-terminal tails with a preference for dimethyl lysine 4 (H3K4me2). It may play an important role in stimulating transcription involved in testicular development and/or spermatogenesis. PHF7 contains a canonical Cys4HisCys3 PHD finger and a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, both of which may be involved in activating transcriptional regulation .
PHF7/G2E3, ePHD domain (PHF7/G2E3_ePHD)
Type: Domain

This entry represents the ePHD domain found in PHF7 and G2E3.

PHF7 (also known as NYD-SP6) is a testis-specific plant homeodomain (PHD) finger-containing protein that associates with chromatin and binds histone H3 N-terminal tails with a preference for dimethyl lysine 4 (H3K4me2). It may play an important role in stimulating transcription involved in testicular development and/or spermatogenesis. PHF7 contains a canonical Cys4HisCys3 PHD finger and a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, both of which may be involved in activating transcriptional regulation .
MTF2, PHD domain 1 (MTF2_PHD1)
Type: Domain

This entry represents the first PHD finger found in MTF2.

MTF2 (also known as PCL2), complexes with the polycomb repressive complex-2 (PRC2) in embryonic stem cells and regulates the transcriptional networks during embryonic stem cell self-renewal and differentiation . It recruits the PRC2 complex to the inactive X chromosome and target loci in embryonic stem cells . Moreover, MTF2 is required for PRC2-mediated Hox cluster repression . It activates the Cdkn2a gene and promotes cellular senescence, thus suppressing the catalytic activity of PRC2 locally. MTF2 consists of an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain.
MTF2, PHD domain 2 (MTF2_PHD2)
Type: Domain

This entry represents to the second PHD finger found in MTF2.

MTF2 (also known as PCL2), complexes with the polycomb repressive complex-2 (PRC2) in embryonic stem cells and regulates the transcriptional networks during embryonic stem cell self-renewal and differentiation . It recruits the PRC2 complex to the inactive X chromosome and target loci in embryonic stem cells . Moreover, MTF2 is required for PRC2-mediated Hox cluster repression . It activates the Cdkn2a gene and promotes cellular senescence, thus suppressing the catalytic activity of PRC2 locally. MTF2 consists of an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain.
PHF19, PHD domain 2 (PHF19_PHD2)
Type: Domain

This entry represents the second PHD finger found in PHF19.

PHF19 (also known as PCL3), is a component of the Polycomb repressive complex 2 (PRC2), which is the major H3K27 methyltransferase that regulates pluripotency, differentiation, and tumorigenesis through catalysis of histone H3 lysine 27 trimethylation (H3K27me3) on chromatin . PHF19 consists of an N-terminal Tudor domain followed by two plant homeodomain (PHD) fingers, and a C-terminal MTF2 domain. It binds H3K36me3 through its Tudor domain and recruits the PRC2 complex and the H3K36me3 demethylase NO66 to embryonic stem cell genes during differentiation . Moreover, PHF19 and its upstream regulator, Akt, play roles in the phenotype switch of melanoma cells from proliferative to invasive states .
Glycerol kinase, metazoan-type (GK1-3_metazoan-type)
Type: Family

This entry corresponds to a group of eukaryotic glycerol kinases (GKs), including members coded by X chromosome-linked GK genes, and glycerol kinase (GK)-like proteins, coded by autosomal testis-specific GK-like genes GK2, GK3 and Gykl1 (in mouse). These are thought to have arise by the transposition of Gk located on the X chromosome . Sequence comparison shows that metazoan GKs and GK-like proteins in this family are closely related to the bacterial GKs, which catalyse the Mg-ATP dependent phosphorylation of glycerol to yield glycerol 3-phosphate (G3P). The metazoan GKs do have GK enzymatic activity. However, the GK-like metazoan proteins do not exhibit GK activity and their biological functions are not yet clear . Some of them lack important functional residues involved in the binding of ADP and Mg2+, which may result in the loss of GK catalytic function. Others that have conserved catalytic residues have lost their GK activity as well; the reason remains unclear. It has been suggested the conserved catalytic residues might facilitate them performing a distinct function. GK2 seem to be necessary for the formation of the mitochondrial sheath during spermatogenesis .

GKs belong to the FGGY family of carbohydrate kinases, the monomers of which contain two large domains, which are separated by a deep cleft that forms the active site .
ING2, PHD domain (ING2_PHD)
Type: Domain

This entry represents the PHD domain of ING2.

Members of the ING (inhibitor of growth protein) family of tumour suppressors regulate cell cycle progression, senescence, apoptosis, and DNA repair as important cofactors of p53. Inhibitor of growth protein 2 (ING2) seems to be involved in p53/TP53 activation and p53/TP53-dependent apoptotic pathways, probably by enhancing acetylation of p53/TP53 . It is also a component of a chromatin-modifying complex containing the transcriptional co-repressor SIN3A and HDAC1 (histone deacetylase 1), which is involved in deacetylation of nucleosomal histones . The stability of ING2 is regulated by nuclear phosphatidylinositol-5-phosphate at discrete chromatin targets in response to DNA damage .
ING3, PHD domain (ING3_PHD)
Type: Domain

This entry represents the PHD domain of ING3.

Inhibitor of growth protein 3 (ING3) is a member of the ING family of tumour suppressors that regulate cell cycle progression, apoptosis and DNA repair . ING3 is a component of the NuA4 histone acetyltransferase complex and the SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AFZ from the nucleosome . ING3 contains an N-terminal ING domain and a C-terminal plant homeodomain (PHD) finger.
KMT2A, PHD domain 1 (KMT2A_PHD1)
Type: Domain

This entry represents the first PHD domain of KMT2A.

Histone-lysine N-methyltransferase 2A (KMT2A;

) is the catalytic subunit of the MLL1/MLL complex, mediating methylation of 'Lys-4' of histone H3 (H3K4me), a specific tag for epigenetic transcriptional activation . KMT2A is processed by the threonine endopeptidase taspase, releasing products N320 and C180 . KMT2A contains a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD) fingers, a Bromodomain domain, an extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain.
D-xylulose kinase (D-XK_euk)
Type: Family

This entry is composed of eukaryotic D-xylulose kinases (XK, also known as xylulokinase;

), which catalyse the rate-limiting step in the ATP-dependent phosphorylation of D-xylulose to produce D-xylulose 5-phosphate (X5P) and ADP .
KMT2A, PHD domain 2 (KMT2A_PHD2)
Type: Domain

This entry represents the second PHD domain of KMT2A.

Histone-lysine N-methyltransferase 2A (KMT2A;

) is the catalytic subunit of the MLL1/MLL complex, mediating methylation of 'Lys-4' of histone H3 (H3K4me), a specific tag for epigenetic transcriptional activation . KMT2A is processed by the threonine endopeptidase taspase, releasing products N320 and C180 . KMT2A contains a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD) fingers, a Bromodomain domain, an extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain.
Peripherin, extracellular domain (Peripherin_LEL)
Type: Domain

This entry represents the extracellular domain or large extracellular loop (LEL) of the tetraspanin peripherin and related proteins. This extracellular domain lies between the 3rd and 4th trans-membrane segment. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane . Tetraspanins are involved in diverse processes and their various functions may relate to their ability to act as molecular facilitators . Tetraspanins associate laterally with one another and cluster dynamically with numerous parnter domains in membrane microdomains, forming a network of multimolecular complexes, the 'tetraspanin web' . Peripherin, or RDS (retinal degradation slow) is a glycoprotein expressed in vertebrate photoreceptors, located at the rim of the disc membranes of the photoreceptor outer segments . RDS is thought to play a major role in folding and stacking of the discs. Mutations in RDS have been linked to hereditary retinal dystrophies, which typically exhibit a wide phenotypic spectrum .
CD63, extracellular domain (CD63_LEL)
Type: Domain

This entry represents the extracellular domain or large extracellular loop (LEL) of CD63. This extracellular domain lies between the 3rd and 4th trans-membrane segment. CD63 is present in platelets, neutrophils, and endothelial cells, amongst others. In platelets it associates with the integrin alphaIIBbeta3 and may modulate alphaIIBbeta3-dependent cytoskeletal reorganization .
Chaperone protein HscC, nucleotide-binding domain (HscC_NBD)
Type: Domain

This entry includes Escherichia coli HscC (also called heat shock cognate protein C, Hsc62, or YbeW) and the the putative DnaK-like protein Escherichia coli ECs0689. It belongs to the heat shock protein 70 (Hsp70) family of chaperones that assist in protein folding and assembly and can direct incompetent 'client' proteins towards degradation. Typically, Hsp70s have a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). The nucleotide sits in a deep cleft formed between the two lobes of the NBD. The two subdomains of each lobe change conformation between ATP-bound, ADP-bound, and nucleotide-free states. ATP binding opens up the substrate-binding site; substrate-binding increases the rate of ATP hydrolysis .

Hsp70 chaperone activity is regulated by various co-chaperones: J-domain proteins and nucleotide exchange factors (NEFs). Two genes in the vicinity of the HscC gene code for potential cochaperones: J-domain containing proteins, DjlB/YbeS and DjlC/YbeV. HscC and its co-chaperone partners may play a role in the SOS DNA damage response .
SKA1 microtubule binding domain superfamily (SKA1_MBD_sf)
Type: Homologous_superfamily

This superfamily corresponds to the microtubule binding domain (MBD) in SKA1, spindle and kinetochore associated protein 1. Its structure is a variation of the winged helix domain which, in addition of the three helix-bundle and anti-parallel β-sheets found in canonical winged-helix domains, it contains an extended helix (αB) as part of three helix bundle and an additional helix (αC) inserted between αB and βA .

Spindle and kinetochore-associated protein 1 (SKA1, also known as SKA complex subunit 1) is a component of the SKA1 complex (consists of Ska1, Ska2, and Ska3/Rama1), a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation . It is required for timely anaphase onset during mitosis, when chromosomes undergo bipolar attachment on spindle microtubules leading to silencing of the spindle checkpoint . The SKA1 complex is a direct component of the kinetochore-microtubule interface and directly associates with microtubules as oligomeric assemblies. The complex facilitates the processive movement of microspheres along a microtubule in a depolymerisation-coupled manner. SKA1 contains a microtubule-binding domain that interacts with tubulins using multiple contact sites that allow the Ska complex to bind microtubules in multiple modes .
Viral RNA-directed RNA polymerase, 4-helical domain (RNA-dir_pol_4-hel_dom)
Type: Homologous_superfamily

RNA-directed RNA polymerase (RdRp) (

) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage . It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear.
The postulated RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product .

This superfamily represents a subdomain of the viral RNA-directed RNA polymerase. Its structure consists of 4 α-helices.
Big defensin, N-terminal domain (Defensin_big_N)
Type: Homologous_superfamily

Big defensins are antimicrobial peptides. They consist of a hydrophobic N-terminal half, which is active against Gram-positive bacteria, and a cationic C-terminal half, which is active against Gram-negative bacteria. The C-terminal half adopts a beta-defensin-like structure .

This superfamily represents the N-terminal domain found in big defensins.
Host-nuclease inhibitor Gam superfamily (Gam_sf)
Type: Homologous_superfamily

This superfamily represents the host-nuclease inhibitor protein Gam. Structurally, it consists of 4 α helices, 2 long and 2 short.
Within bacteriophage lambda protein Gam, one of the long helices (H4) acts as a dimerisation interface to form an antiparallel helix. The two short helices (H2 and H3) from each dimer form a 'cross-brace', while the other long helix (H1) protrudes out of the protein . Within bacteriophage lambda, Gam is involved in inhibiting host nucleases.
DEAH helicase, winged-helix domain (DEAH_win-hel_dom)
Type: Homologous_superfamily

The DEAH/RNA helicase A (RHA) helicase family comprises proteins involved in splicing, ribosome biogenesis and transcription regulation . Structurally, the domain represented by this superfamily contains a winged-helix with a weakly defined β-sheet .
Ribosomal RNA-processing protein 8, N-terminal domain (RRP8_N)
Type: Homologous_superfamily

Ribosomal RNA processing protein 8 (Rrp8) is a nucleolar Rossman-fold like methyltransferase. In yeast, it is involved in pre-rRNA cleavage at site A2 and is responsible for a base methylation of the 25S rRNA . In humans it is also known as nucleomethylin (NML), and it is important for mediating the assembly of the energy-dependent nucleolar silencing complex (eNoSC), which regulates rRNA transcription in response to glucose deprivation . NML represses rDNA transcription by promoting H3K9 methylation and establishing heterochromatin across the rDNA .

This superfamily represents the N-terminal domain of the ribosomal RNA-processing protein 8 (RRP8).
MukE, C-terminal domain (MukE_C)
Type: Homologous_superfamily

MukE is involved in the segregation and condensation of prokaryotic chromosomes. MukE along with MukF (

) interact with MukB (

) in vivo forming a complex, which is required for chromosome condensation and segregation in Escherichia coli . The Muk complex appears to be similar to the SMC-ScpA-ScpB complex in other prokaryotes where MukB is the homologue of SMC . ScpA (

) and ScpB (

) have little sequence similarity to MukE or MukF, though they are predicted to be structurally similar, being predominantly α-helical with coiled coil regions.

This superfamily represents the MukE C-terminal domain. Structurally, it consists of 4 helices and 3 small β strands.
MukE, N-terminal domain (MukE_N)
Type: Homologous_superfamily

MukE is involved in the segregation and condensation of prokaryotic chromosomes. MukE along with MukF (

) interact with MukB (

) in vivo forming a complex, which is required for chromosome condensation and segregation in Escherichia coli . The Muk complex appears to be similar to the SMC-ScpA-ScpB complex in other prokaryotes where MukB is the homologue of SMC . ScpA (

) and ScpB (

) have little sequence similarity to MukE or MukF, though they are predicted to be structurally similar, being predominantly α-helical with coiled coil regions.

This superfamily represents the MukE N-terminal domain. Structurally, it consists of 3 helices and 2 small β strands.
HscA chaperone, nucleotide-binding domain (HscA_NBD)
Type: Domain

Escherichia coli HscA (heat shock cognate protein A, also called Hsc66), belongs to the heat shock protein 70 (HSP70) family of chaperones that assist in protein folding and assembly and can direct incompetent 'client' proteins towards degradation. Typically, HSP70s have a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). The nucleotide sits in a deep cleft formed between the two lobes of the NBD. The two subdomains of each lobe change conformation between ATP-bound, ADP-bound, and nucleotide-free states. ATP binding opens up the substrate-binding site; substrate-binding increases the rate of ATP hydrolysis. HSP70 chaperone activity is regulated by various co-chaperones: J-domain proteins and nucleotide exchange factors (NEFs). HscA's partner J-domain protein is HscB; it does not appear to require a NEF, and has been shown to be induced by cold-shock . The HscA-HscB chaperone/co-chaperone pair is involved in [Fe-S] cluster assembly or tranfer .
Protein transport protein Tip20, domain E (Tip20p_domE)
Type: Homologous_superfamily

The Dsl1p vesicle tethering complex is composed of three subunits, essential for trafficking from the Golgi apparatus to the ER. Two of the three subunits, Tip20p and Dsl1p, resemble known subunits of the exocyst complex, establishing a structural connection among several multi-subunit tethering complexes and implying that many of their subunits are derived from a common progenitor. The structure of Tip20p consists entirely of α-helices and intervening loops of variable length, organised into a series of helix bundle domains .

This superfamily represents the Tip20p subunit domain E.
Protein transport protein Tip20, domain A (Tip20p_domA)
Type: Homologous_superfamily

The Dsl1p vesicle tethering complex is composed of three subunits, essential for trafficking from the Golgi apparatus to the ER. Two of the three subunits, Tip20p and Dsl1p, resemble known subunits of the exocyst complex, establishing a structural connection among several multi-subunit tethering complexes and implying that many of their subunits are derived from a common progenitor. The structure of Tip20p consists entirely of α-helices and intervening loops of variable length, organised into a series of helix bundle domains .

This superfamily represents the Tip20p subunit domain A.
Protein transport protein Tip20, domain B (Tip20p_domB)
Type: Homologous_superfamily

The Dsl1p vesicle tethering complex is composed of three subunits, essential for trafficking from the Golgi apparatus to the ER. Two of the three subunits, Tip20p and Dsl1p, resemble known subunits of the exocyst complex, establishing a structural connection among several multi-subunit tethering complexes and implying that many of their subunits are derived from a common progenitor. The structure of Tip20p consists entirely of α-helices and intervening loops of variable length, organised into a series of helix bundle domains .

This superfamily represents the Tip20p subunit domain B.
Protein transport protein Tip20, domain C (Tip20p_domC)
Type: Homologous_superfamily

The Dsl1p vesicle tethering complex is composed of three subunits, essential for trafficking from the Golgi apparatus to the ER. Two of the three subunits, Tip20p and Dsl1p, resemble known subunits of the exocyst complex, establishing a structural connection among several multi-subunit tethering complexes and implying that many of their subunits are derived from a common progenitor. The structure of Tip20p consists entirely of α-helices and intervening loops of variable length, organised into a series of helix bundle domains .

This superfamily represents the Tip20p subunit domain C.
EXOC6/PINT-1/Sec15/Tip20, C-terminal, domain 2 (EXOC6PINT-1/Sec15/Tip20_C_dom2)
Type: Homologous_superfamily

This superfamily represents a subdomain known as domain D found at the C terminus of Tip20, which is part of the Dsl1p vesicle tethering complex essential for trafficking from the Golgi apparatus to the ER. The structure of Tip20p consists entirely of α-helices and intervening loops of variable length, organised into a series of helix bundle domains .

Subunits of the vesicle tethering complex (such as Tip20 and Dsl1) share protein sequence similarity with known subunits of the exocyst complex, establishing a structural connection among several multi-subunit tethering complexes and implying that many of their subunits are derived from a common progenitor.

Proteins containing this domain includes EXOC6/PINT-1 from animals, Tip20 from budding yeast, Sec15 from fission yeasts and MAIGO2 (Mag2) from plants. Sec15 (EXOC6 homologue) is an exocyst complex component that links Sec4 and downstream fusion effectors at discrete cellular locations. Its C-terminal domain mediates Rab GTPases binding which occurs in a GTP-dependent manner . PINT-1/Tip20/MAIGO2 play a role in anterograde transport from the endoplasmic reticulum (ER) to the Golgi and/or retrograde transport from the Golgi to the ER. They share a similar domain organisation with an N-terminal leucine heptad repeat rich coiled coil and an ~500-residue C-terminal RINT1/TIP20 domain, which might be a protein-protein interaction module necessary for the formation of functional complexes.