SII-SWORD/CoKE huggingface dataset:
Spt5, KOW domain repeat 3 (KOW_Spt5_3)
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 .
Spt5, KOW domain repeat 4 (KOW_Spt5_4)
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 .
Spt5, KOW domain repeat 5 (KOW_Spt5_5)
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 .
Spt5, KOW domain repeat 6, metazoa (KOW_Spt5_6_metazoa)
Type: Domain

This entry represents the sixth KOW domain of Spt5 from animals .

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 .
ZZZ3, zinc finger, ZZ-type (ZZZ3_ZZ)
Type: Domain

This entry represents the ZZ-type Zinc finger present in ZZZ3 (ZZ finger containing 3) and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding .
Small ribosomal subunit protein eS4, KOW domain (Ribosomal_eS4_KOW)
Type: Domain

Small ribosomal subunit protein eS4 (RPS4) plays a critical role in the core assembly of the small ribosomal subunit with a KOW motif at its C-terminal. RPS4 also acts as a general transcription antiterminator factor and regulates ribosomal RNA expression level. 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 . RPS4 deficiency in human has been associated with Turner syndrome. Archaeal RPS4 (RPS4e) showed substantial identity to the eukaryotic equivalents RPS4, but the archaeal proteins formed a different complex from the eukaryotic proteins .
ADA2-like, zinc finger, ZZ-type (ADA2-like_ZZ)
Type: Domain

This entry represents the ZZ-type Zinc finger found in ADA2-like proteins, including transcriptional adapter 2 (TADA2) from animals and plants, and Ada2 from yeasts. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding .

Ada2 is a component of the SAGA/ADA coactivator complex, which regulates numerous cellular processes by coordinating histone acetylation .

There are two Drosophila Ada2 homologues, dAda2a and dAda2b. dAda2b is a component of Spt-Ada-Gcn5-acetyltransferase (SAGA) complexes, while dAda2a associates with dGcn5 but is not incorporated into dSAGA-type complexes .
Rsc8/Ssr1/Ssr2, zinc finger, ZZ-type (Rsc8/Ssr1/Ssr2_ZZ)
Type: Domain

This entry represents the ZZ-type zinc finger found in budding yeast Rsc8 and related proteins, such as Ssr1/Ssr2 from fission yeasts . Rsc8 is a component of the RSC complex, which is closely related to the SWI/SNF complex and is involved in remodeling chromatin structure . The ZZ motif coordinates a zinc ion and most likely participates in ligand binding or molecular scaffolding .
Large ribosomal subunit protein eL14, KOW motif (Ribosomal_eL14_KOW)
Type: Domain

Large ribosomal subunit protein eL14 (RPL14) is a component of the large ribosomal subunit in both archaea and eukaryotes with KOW motif at its N terminus . 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 . Although RPL14 is well conserved, it is not found in all archaea, and therefore it is presumably not essential .
ZZEF1, zinc finger, ZZ-type (ZZEF1_ZZ)
Type: Domain

This entry represents the ZZ-type zinc finger found in ZZEF1. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding .
HERC2, zinc finger, ZZ-type (ZZ_HERC2)
Type: Domain

This entry represents the ZZ type zinc finger found in HERC2 and related proteins. HERC2 is an E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes . The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding .
Large ribosomal subunit protein uL24, KOW domain (Ribosomal_uL24_KOW)
Type: Domain

Large ribosomal subunit protein uL24 (also known as RPL26) has a KOW motif at the N-terminal. 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 .

RPL26 is one of the proteins from the large ribosomal subunit. In their mature form, these proteins have 103 to 150 amino-acid residues. RPL26 makes a very minor contributions to the biogenesis, structure, and function of 60s ribosomal subunits . However, RPL24 is essential to generate the first intermediate during 50s ribosomal subunits assembly . RPL26 have an extra-ribosomal function to enhances p53 translation after DNA damage .
TOPK, catalytic domain (PKc_TOPK)
Type: Domain

This entry represents the catalytic domain found in TOPK, which belongs to a superfamily that contains other protein kinases, such as RIO kinases, aminoglycoside phosphotransferase, choline kinase and phosphoinositide 3-kinase.

Lymphokine-activated killer T-cell-originated protein kinase (TOPK), also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis . It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX . It contributes to cancer development and progression by downregulating the function of tumour suppressor p53 and reducing cell-cycle regulatory proteins .
Large ribosomal subunit protein eL27, KOW domain (Ribosomal_eL27_KOW)
Type: Domain

Large ribosomal subunit protein eL27 (RPL27e) has a KOW motif at its N terminus. 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 .
SMCT1, solute-binding domain (SLC5sbd_SMCT1)
Type: Domain

This entry represents the solute-binding domain of SMCT1.

SMCT1 is a high-affinity transporter of various monocarboxylates including lactate and pyruvate, short-chain fatty acids, ketone bodies, nicotinate and its structural analogs, pyroglutamate, benzoate and its derivatives, and iodide . The expression of human SMCT1 is under the control of the C/EBP transcription factor. Its tumour-suppressive role is related to uptake of butyrate, propionate, and pyruvate, these latter are inhibitors of histone deacetylases. SMCT1 may contribute to the intestinal/colonic and oral absorption of monocarboxylate drugs . SMCT1 also mediates iodide transport from thyrocyte into the colloid lumen in thyroid gland and through transporting l-lactate and ketone bodies helps maintain the energy status and the function of neurons . In the kidney its expression is limited to the S3 segment of the proximal convoluted tubule (in contrast to the low-affinity monocarboxylate transporter SMCT2, belonging to a different family, which is expressed along the entire length of the tubule). In the retina, SMCT1 and SMCT2 may play a differential role in monocarboxylate transport in a cell type-specific manner, SMCT1 is expressed predominantly in retinal neurons and in retinal pigmented epithelial (RPE) cells .
G-patch domain and KOW motifs-containing protein, KOW 1 (GPKOW_KOW1)
Type: Domain

GPKOW is also known as T54 protein or MOS2 homologue . It contains one G-patch domain and two KOW motifs. GPKOW is a nuclear protein that is regulated by catalytic (C) subunit of Protein Kinase A (PKA) and binds RNA in vivo . PKA may be involved in regulating multiple steps in post-transcriptional processing of pre-mRNAs. 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 .
G-patch domain and KOW motifs-containing protein, KOW 2 (GPKOW_KOW2)
Type: Domain

GPKOW is also known as T54 protein or MOS2 homologue . It contains one G-patch domain and two KOW motifs. GPKOW is a nuclear protein that is regulated by catalytic (C) subunit of Protein Kinase A (PKA) and binds RNA in vivo . PKA may be involved in regulating multiple steps in post-transcriptional processing of pre-mRNAs. 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 .
Kin17, KOW domain (KOW_KIN17)
Type: Domain

This entry represents the SH3 domain of KIN17, found at the very C-terminal end of these proteins . This domain contains the KOW motif, involved in RNA binding.

The KOW domain of the KIN17 protein contributes to the RNA-binding properties of the whole protein. 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 . KIN17 has functions in DNA replication, DNA repair and cell cycle control .
FAM83H, N-terminal phospholipase D-like domain (PLDc_FAM83H_N)
Type: Domain

This entry represents the N-terminal phospholipase D (PLD)-like domain of FAM83H, which localizes in the intracellular environment and is associated with vesicles, can be regulated by kinases, and plays important roles during ameloblast differentiation and enamel matrix calcification . The gene encoding protein FAM83H is the first gene involved in the etiology of amelogenesis imperfecta (AI), that encodes a non-secreted protein due to the absence of a signal peptide . Defects in gene FAM83H cause autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) . Since the N-terminal PLD-like domain of FAM83H shows only trace similarity to the PLD catalytic domain and lacks the functionally important histidine residue, FAM83H may share a similar three-dimensional fold with PLD enzymes, but is most unlikely to carry PLD activity.
Large ribosomal subunit protein eL6, KOW domain (Ribosomal_eL6_KOW)
Type: Domain

Large ribosomal subunit protein eL6 (RPL6) contains a KOW motif and has an extra ribosomal role regulating the DNA damage response . 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 .
Histamine H3 receptor, 7TM (7tmA_HRH3)
Type: Domain

This entry represents the 7TM domain found in histamine H3 receptor (HRH3 or H3R), which belongs to the class A of GPCRs. Histamine plays a key role as chemical mediator and neurotransmitter in various physiological and pathophysiological processes in the central and peripheral nervous system. Histamine exerts its functions by binding to four different G protein-coupled receptors (H1-H4). The H3 and H4 receptors couple to the G(i)-proteins, which leading to the inhibition of cAMP formation . The H3R receptor functions as a presynaptic autoreceptors controlling histamine release and synthesis . The H4R plays an important role in histamine-mediated chemotaxis in mast cells and eosinophils .
Sortase D, type 1 (Sortase_D_1)
Type: Family

Class D sortases are cysteine transpeptidases distributed in Gram-positive bacteria (mainly present in Firmicutes). The prototypical subfamily 1 of class D sortase from Bacillus anthracis (named Ba-SrtC) covalently attaches proteins bearing a noncanonical LPNTA sorting signal, such as the BasH and BasI proteins, to the peptidoglycan of the cell wall that facilitate sporulation. BasH is exclusively anchored to the forespore cell wall envelope, while BasI is attached to the diaminopimelic acid moiety of the peptidoglycan of predivisional cells. Ba-SrtC lacks the N-terminal signal peptide and membrane anchor . The family also includes many class D sortase homologues from Gram-negative bacteria, but the functions of these enzymes are unknown.
Sortase D, type 2 (Sortase_D_2)
Type: Family

Class D sortases are cysteine transpeptidases distributed in Gram-positive bacteria (mainly present in Firmicutes). They anchor surface proteins bearing a cell wall sorting signal to peptidoglycans of the bacterial cell wall envelope, which is responsible for spore formation under anaerobic conditions. This involves a transpeptidation reaction in which the surface protein substrate is cleaved at the cell wall sorting signal and covalently linked to peptidoglycan for display on the bacterial surface. The prototypical subfamily 2 of class D sortase from Clostridium perfringens (named Cp-SrtD) recognizes the LPQTGS signal motif for transpeptidation. Its catalytic activity is in a metal cation- and temperature- dependent manner. The presence of magnesium appears to enhance Cp-SrtD catalysis towards the LPQTGS signal motif .
Sortase F (Sortase_F)
Type: Family

Class F sortases are mainly present in Actinobacteria, Chlorobacteria and Firmicutes. Their functions are largely unknown.
Sortase C (Sortase_C)
Type: Family

Class C sortases are membrane-bound cysteine transpeptidases broadly distributed in Gram-positive bacteria (mainly present in Firmicutes and Actinobacteria) . They function as pilin polymerases responsible for the assembly of pili, which are multi-subunit hair-like fibres that extend from the cell surface to promote microbial adhesion and biofilm formation. First, one or more class C sortases form the long thin shaft of the pilus through linking together pilin subunits via isopeptide bonds. The base of the pilus is then anchored to the cell wall by a housekeeping sortase or, in some cases, the class C sortase itself . Depending upon the organism both the number and type of sortase enzymes involved varies, and in some cases, accessory factors appear to be needed.

In three-component spaA pilus from Corynebacterium diphtheriae, the prototypical class C sortase (named Cd-SrtA) catalyzes polymerization of the SpaA-type pilus, consisting of the shaft pilin SpaA, tip pilin SpaC and minor pilin SpaB. The pilus shaft is then attached to the cell wall by a housekeeping class E sortase, Cd-SrtF. In the absence of Cd-SrtF, Cd-SrtA attaches the pilus to the cell wall, albeit at a reduced rate. Cd-SrtA can recognize two distinct sorting signals (LPLTG in SpaA and SpaC, and LAFTG in SpaB) and it can employ lysine residues that originate from different proteins (either Lys190 within the pilin motif of SpaA or Lys139 in SpaB). However, Cd-SrtA cannot be able to polymerize the major pilin subunit SpaH, even though it contains LPLTG motif .

In two-component pili of prototypical Bacillus cereus, the class C sortase (named Bc-SrtD) cleaves related sorting signals within a major pilin protein BcpA (LPVTG) and a minor tip pilin BcpB (IPNTG), and catalyzes a transpeptidation that joins the threonine residues in each signal to the side-chain of Lys162 in BcpA (located within a pilin motif). Unlike the SpaA pilus in C. diphtheriae, in B. cereus Bc-SrtD is unable to covalently attach the pilus to the cell wall without the help of the housekeeping sortase .
Sortase E (Sortase_E)
Type: Family

Class E sortases are membrane-bound cysteine transpeptidases distributed in Gram-positive bacteria (mainly present in Actinobacteria). Genes encoding class A and E sortases are never found in the same organism, and similar to class A sortases, the genes encoding class E sortases are not positioned adjacent to genes encoding potential protein substrates, suggesting a housekeeping sortase function of class E sortases in some high G + C Gram-positive bacteria . Similar to class A sortase, class E sortases are capable of anchoring a large number of functionally distinct surface proteins containing a cell wall sorting signal to an amino group located on the bacterial cell wall. They recognize an LAXTG sorting signal, instead of the canonical LPXTG motif processed by class A sortases .

The prototypical class E sortase from Corynebacterium diphtheria (named Cd-SrtF) is a non-polymerization sortase that is not required for pilus polymerization, and proceeds to complete the assembly process by anchoring the polymer to the cell wall peptidoglycan . Moreover, in Streptomyces coelicolor, one or both of Staphylococcus aureus SrtA homologues may function as class E sortase responsible for the cell wall anchoring of the long chaplin proteins (ChpA-C) containing an LAXTG sorting signal, which presumably mediate aerial hyphae formation . The family also includes some class E sortase homologs from Gram-negative and Archaebacterial species, but the functions of these enzymes are unknown .
BRPF2, ePHD domain (BRPF2_ePHD)
Type: Domain

This entry represents the ePHD finger of bromodomain and PHD finger-containing protein 2 (BRPF2), also known as bromodomain-containing protein 1 (BRD1). The extended plant homeodomain (ePHD) zinc finger is characterised as Cys2HisCys5HisCys2His.

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.
BRPF3, ePHD domain (BRPF3_ePHD)
Type: Domain

This entry represents the ePHD finger of BRPF3. BRF3 is a homologue of BRPF1 and BRPF2.
Sortase A (Sortase_A)
Type: Family

Class A sortases are membrane-bound cysteine transpeptidases distributed in Gram-positive bacteria (mainly present in Firmicutes). They perform a housekeeping role in the cell as members of this group are capable of anchoring a large number of functionally distinct surface proteins containing a cell wall sorting signal to an amino group located on the bacterial cell wall. They do so by catalyzing a transpeptidation reaction in which the surface protein substrate is cleaved at a conserved cell wall-sorting signal (Class A sortases recognize a canonical LPXTG motif, X can be any amino acid), and covalently linked to peptidoglycan for display on the bacterial surface. The prototypical sortase A protein from Staphylococcus aureus (named Sa-SrtA) cleaves the amide bond between threonine and glycine residues of the canonical LPXTG motif in a wide range of protein substrates with diverse functions that can promote bacterial adhesion, nutrient acquisition, host cell invasion, and immune evasion. Next, it catalyzes a transpeptidation reaction by which the proteins are covalently linked to the peptidoglycan precursor lipid II. SrtA is therefore affects the ability of a pathogen to establish successful infection. SrtA contains an N-terminal hydrophobic segment, a linker region and an extra-cellular C-terminal catalytic domain. The hydrophobic segment functions as both a signal peptide for secretion and a stop-transfer signal for membrane anchoring. The catalytic domain contains the catalytic TLXTC signature sequence where X is usually a valine, isoleucine or a threonine. The gene encoding SrtA is generally not located in the same gene cluster as its substrates while the gene encoding SrtB is usually clustered in the same locus as its substrate .
BRPF1, PHD domain (BRPF1_PHD)
Type: Domain

This entry represents the PHD finger of BRPF1.

BRPF1, also termed peregrin, or protein Br140, is a multi-domain protein that binds histones, mediates monocytic leukemic zinc-finger protein (MOZ) -dependent histone acetylation, and is required for Hox gene expression and segmental identity . It is a close partner of the MOZ histone acetyltransferase (HAT) complex and a novel Trithorax group (TrxG) member with a central role during development . BRPF1 is primarily a nuclear protein that has a broad tissue distribution and is abundant in testes and spermatogonia . It contains a plant homeodomain (PHD) zinc finger followed by a non-canonical ePHD finger, a bromodomain and a proline-tryptophan-tryptophan-proline (PWWP) domain. PHD and ePHD fingers both bind to lysine 4 of histone H3 (K4H3), bromodomains interact with acetylated lysines on N-terminal tails of histones and other proteins, and PWWP domains show histone-binding and chromatin association properties. BRPF1 may be involved in chromatin remodeling .