SII-SWORD/CoKE huggingface dataset:
Anti-sigma factor, zinc-finger domain superfamily (Anti_sigma_zinc_sf)
Type: Homologous_superfamily

This superfamily includes a putative zinc-finger domain found at the N terminus of several anti-sigma factor proteins.
Trinucleotide repeat-containing gene 6C protein, UBA domain (TNR6C_UBA)
Type: Domain

Trinucleotide repeat-containing gene 6C protein (TNRC6C) is one of three GW182 paralogs in mammalian genomes. It is enriched in P-bodies and important for efficient miRNA-mediated repression. TNRC6C is composed of an N-terminal glycine/tryptophan (G/W)-rich region containing an Ago hook responsible for Ago protein-binding; a ubiquitin-associated (UBA) domain and a glutamine (Q)-rich region in the middle region; a middle G/W-rich region, a RNA recognition motif (RRM), also called RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal G/W-rich region, at the C terminus. A bipartite C-terminal region including the middle and C-terminal G/W-rich regions is referred to as silencing domain, that triggers silencing of bound transcripts by inhibiting protein expression and promoting mRNA decay via deadenylation. The C-terminal half containing the RRM domain functions as a key effector domain mediating protein synthesis repression by TNRC6C .
HUWE1, UBA domain (UBA_HUWE1)
Type: Domain

HUWE1 (also known as HECT, UBA and WWE domain-containing protein 1, or Mcl-1 ubiquitin ligase E3, amongst other names) may function as a ubiquitin-protein ligase involved in the ubiquitination cascade that targets specific substrate proteins in proteolysis. It can ubiquitylate DNA polymerase beta (Pol beta), the major BER DNA polymerase, and modulates base excision repair (BER) . HUWE1 also acts as a critical mediator of both the p53-independent and p53-dependent tumor suppressor functions of ARF tumor suppressor in p53 regulation . Moreover, HUWE1 is both required and sufficient for the polyubiquitination of Mcl-1, an anti-apoptotic Bcl-2 family member involved in DNA damage-induced apoptosis . Furthermore, HUWE1 plays an important role in the regulation of Cdc6 stability after DNA damage. In addition, HUWE1 works as a partner of N-Myc oncoprotein in neural cells. It ubiquitinates N-Myc and primes it for proteasomal-mediated degradation .

HUWE1 contains a ubiquitin-associated (UBA) domain, a WWE domain, and a Bcl-2 homology region 3 (BH3) domain at the N terminus and a HECT domain at the C terminus. WWE domain plays a role in the regulation of specific protein-protein interactions in a ubiquitin conjugation system. BH3 domain is responsible for the specific binding to Mcl-1. HECT domain is involved in the inhibition of the transcriptional activity of p53 via a ubiquitin-dependent degradation pathway .
Plasmid replication protein, C-terminal domain superfamily (Plasmid_rep_C_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of the plasmid replication (Rep) protein. Rep is a rolling-circle replication (RCR) initiation protein and provides endonuclease activity. It is generally found as hexamer, in contrast to other RCR proteins that are purified as monomers or dimers. Its monomer unit can be viewed as the cartoon representation of the domain in chain. The C-terminal all-helical oligomerization domains form a rigid cylindrical scaffold to which the N-terminal DNA-binding/catalytic domains are attached as highly flexible appendages .
ROS/MUCR transcriptional regulator superfamily (ROS/MUCR_sf)
Type: Homologous_superfamily

This superfamily consists of several ROS/MUCR transcriptional regulator proteins. The ros chromosomal gene is present in octopine and nopaline strains of Agrobacterium tumefaciens as well as in Rhizobium meliloti (Sinorhizobium meliloti). This gene encodes a 15.5kDa protein that specifically represses the virC and virD operons in the virulence region of the Ti plasmid and is necessary for succinoglycan production . S. meliloti can produce two types of acidic exopolysaccharides, succinoglycan and galactoglucan, that are interchangeable for infection of Medicago sativa (Alfalfa) nodules. MucR from S. meliloti acts as a transcriptional repressor that blocks the expression of the exp genes responsible for galactoglucan production therefore allowing the exclusive production of succinoglycan .
NADH-quinone oxidoreductase subunit E, N-terminal (NuoE_N)
Type: Homologous_superfamily

Respiratory-chain NADH dehydrogenase (

) (also known as complex I or NADH-ubiquinone oxidoreductase) is an oligomeric enzymatic complex located in the inner mitochondrial membrane which also seems to exist in the chloroplast and in cyanobacteria (as a NADH-plastoquinone oxidoreductase).

This superfamily represents the NADH-quinone oxidoreductase subunit E N-terminal domain.
UBXN1, UBA domain (UBA_UBXN1)
Type: Domain

UBXN1 is a widely expressed protein containing an N-terminal ubiquitin-associated (UBA) domain, a coiled-coil region, and a C-terminal ubiquitin-like (UBX) domain. It binds polyubiquitin and valosin-containing protein (VCP), and has been identified as a substrate for stress-activated protein kinases (SAPKs) . UBXN1 specifically binds to Homer2b . It may also interact with ubiquitin (Ub) and may be involved in the Ub-proteasome proteolytic pathways. UBXN1 can associate with autoubiquitinated BRCA1 tumour suppressor and inhibit its enzymatic function through its UBA domain .
Formate dehydrogenase H, N-terminal (Formate_Dh-H_N)
Type: Domain

This entry represents the N-terminal domain of formate dehydrogenase H (Formate-Dh-H), which catalyzes the reversible oxidation of formate to CO2 with the release of a proton and two electrons. Formate-Dh-H is a component of the anaerobic formate hydrogen lyase complex. The E. coli formate dehydrogenase H (Fdh-H) is a monomer composed of a single polypeptide chain with a Mo active site region and a [4Fe-4S] centre .

This domain is also found at the N-terminal of F420-dependent formate dehydrogenase subunit alpha from Methanobacterium formicicum, which catalyses the oxidation of formate to carbon dioxide, with coenzyme F420 as the electron acceptor .

Proteins containing this domain belong to the molybdopterin_binding (MopB) superfamily of proteins.
Formate dehydrogenase H, molybdopterin-binding domain (CT_Formate-Dh_H)
Type: Domain

Formate dehydrogenase H (Formate-Dh-H) catalyzes the reversible oxidation of formate to CO2 with the release of a proton and two electrons. It is a component of the anaerobic formate hydrogen lyase complex. The E. coli formate dehydrogenase H (Fdh-H) is a monomer composed of a single polypeptide chain with a Mo active site region and a [4Fe-4S] centre . This entry represents the conserved molybdopterin-binding C-terminal domain.

This domain is also found at the C-terminal of F420-dependent formate dehydrogenase subunit alpha from Methanobacterium formicicum, which catalyses the oxidation of formate to carbon dioxide, with coenzyme F420 as the electron acceptor .
UBAC1, UBA domain 1 (UBA1_UBAC1)
Type: Domain

UBAC1 (also known as KPC2, or glialblastoma cell differentiation-related protein 1) is one of two subunits of Kip1 ubiquitination-promoting complex (KPC), a novel E3 ubiquitin-protein ligase that also contains KPC1 subunit and regulates the ubiquitin-dependent degradation of the cyclin-dependent kinase (CDK) inhibitor p27 at G1 phase. KPC2 contains a ubiquitin-like (UBL) domain and two ubiquitin-associated (UBA) domains .

This entry represents the first UBA domain.
UBAC1, UBA domain 2 (UBA2_UBAC1)
Type: Domain

UBAC1 (also known as KPC2, or glialblastoma cell differentiation-related protein 1) is one of two subunits of Kip1 ubiquitination-promoting complex (KPC), a novel E3 ubiquitin-protein ligase that also contains KPC1 subunit and regulates the ubiquitin-dependent degradation of the cyclin-dependent kinase (CDK) inhibitor p27 at G1 phase. KPC2 contains a ubiquitin-like (UBL) domain and two ubiquitin-associated (UBA) domains .

This entry represents the second UBA domain.
UBAC2, UBA domain (UBA_UBAC2)
Type: Domain

UBAC2 is a ubiquitin-associated domain (UBA)-domain containing protein encoded by gene UBAC2 (or PHGDHL1), a risk gene for Behcet's disease (BD). It may play an important role in the development of BD through its transcriptional modulation. UBAC2 contains an N-terminal rhomboid-like domain and a C-terminal UBA domain. This entry represents the UBA domain .
Tetrathionate reductase subunit A, N-terminal (Tetrathionate-R_A_N)
Type: Domain

This entry represents the N-terminal domain found in tetrathionate reductase subunit A (TtrA) and other related proteins. The Salmonella enterica tetrathionate reductase catalyses the reduction of trithionate but not sulfur or thiosulfate . TtrA belongs to the molybdopterin-binding superfamily of proteins.
Acetylene hydratase (Acetylene_hydratase)
Type: Domain

This entry represents a domain found in acetylene hydratase (Ahy) and other related proteins. The acetylene hydratase of Pelobacter acetylenicus is a tungsten iron-sulfur protein involved in the fermentation of acetylene to ethanol and acetate . Proteins containing this domain belong to the molybdopterin-binding superfamily of proteins.
Bacterial DNA polymerase III alpha subunit, thumb domain (DNA_pol3_alpha_thumb_dom)
Type: Homologous_superfamily

DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. This DNA polymerase also exhibits 3' to 5' exonuclease activity. The alpha chain is the DNA polymerase .

This superfamily represents the thumb domain found in DNA polymerase III alpha subunit. The thumb domain is involved in positioning the duplex DNA and in translocation and in processivity of the polymerase - holding the template strand in place so that binding doesn't need to occur with each dNTP added to the strand . It is composed of 4 compact α helices between two small β strands.
Phenylacetyl-CoA:acceptor oxidoreductase, N-terminal (Phenylacetyl-CoA-OR_N)
Type: Domain

This entry represents the N-terminal domain found in the phenylacetyl-CoA:acceptor oxidoreductase, large subunit (PadB), and other related proteins. The phenylacetyl-CoA:acceptor oxidoreductase has been characterised as a membrane-bound molybdenum-iron-sulfur enzyme involved in anaerobic metabolism of phenylalanine in the denitrifying bacterium Thauera aromatica . Proteins containing this domain belong to the molybdopterin_binding superfamily of proteins.
BIRC2/BIRC3, UBA domain (BIRC2/BIRC3_UBA)
Type: Domain

The entry represents the UBA domain found in c-IAPs, including BIRC2 (also known as C-IAP1) and BIRC3 (also known as C-IAP2). c-IAPs function as ubiquitin E3 ligases that mediate the ubiquitination of the substrates involved in apoptosis, nuclear factor-kappaB (NF-kappaB) signaling, and oncogenesis . Unlike other apoptosis proteins such as XIAP, c-IAPs exhibit minimal binding to caspases and may not play an important role in the inhibition of these proteases. c-IAP1 is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-kappaB signaling pathways in the cytoplasm. It can also regulate E2F1 transcription factor-mediated control of cyclin transcription in the nucleus . c-IAP2 also influences ubiquitin-dependent pathways that modulate innate immune signalling by activation of NF-kappaB . c-IAPs contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of polyubiquitin (polyUb), a caspase activation and recruitment domain (CARD) that serves as a protein interaction surface, and a RING domain at the carboxyl terminus that is required for ubiquitin ligase activity .
NAD glycohydrolase, helical linker domain (NAD_glyco_helical_dom)
Type: Homologous_superfamily

This superfamily represents a helical linker domain found in several bacterial nicotine adenine dinucleotide glycohydrolase (NGA) proteins which appear to be specific to Streptococcus pyogenes. NAD glycohydrolase (NADase) is a potential virulence factor. Streptococcal NADase may contribute to virulence by its ability to cleave beta-NAD at the ribose-nicotinamide bond, depleting intracellular NAD pools and producing the potent vasoactive compound nicotinamide . The helical linker domain is composed of 4 helices.
HetR, flap domain (HetR_flap)
Type: Homologous_superfamily

HetR is a DNA-binding serine-type protease required for heterocyst differentiation in the nitrogen-fixing cyanobacteria under conditions of nitrogen deprivation. The protein binds to a DNA palindrome upstream of hetP and other genes. The HetR monomer is composed of three distinct domains: the N-terminal domain which is involved in DNA binding, the middle domain designated the "flap", and a slightly smaller C-terminal domain designated the "hood" . HetR forms a dimer upon DNA binding. That structure contains four distinct domains: an extended DNA-binding unit containing helix-turn-helix (HTH) motifs comprised of two canonical α-helices in the DNA-binding domain and an auxiliary α-helix from the flap domain of the neighboring subunit; two histidine-rich flaps protruding on either side of the extended structure; and finally a hood comprised of the two C-terminal sequences . The whole HetR dimer becomes more symmetric in the presence of DNA. Overall, the flap orientations are adjusted to provide a more extended interaction with the twofold symmetric DNA duplex.

This entry represents the flap domain, or the middle domain, which interacts with the phosphate backbone of the DNA. It is composed of four α-helices, one helix, and a β-hairpin . The β-hairpin in the flap domain runs along the minor groove of DNA. In the dimer, the two flap domains protrude away from the central N-terminal-C-terminal core structure. These domains are also in position to contact DNA, perhaps at the exterior phosphates, which could enhance the interaction with DNA throughout the length of HetR.
HetR, N-terminal DNA-binding domain (HetR_DNA-bd_N)
Type: Homologous_superfamily

HetR is a DNA-binding serine-type protease required for heterocyst differentiation in the nitrogen-fixing cyanobacteria under conditions of nitrogen deprivation. The protein binds to a DNA palindrome upstream of hetP and other genes. The HetR monomer is composed of three distinct domains: the N-terminal domain which is involved in DNA binding, the middle domain designated the "flap", and a slightly smaller C-terminal domain designated the "hood" . HetR forms a dimer upon DNA binding. That structure contains four distinct domains: an extended DNA-binding unit containing helix-turn-helix (HTH) motifs comprised of two canonical α-helices in the DNA-binding domain and an auxiliary α-helix from the flap domain of the neighboring subunit; two histidine-rich flaps protruding on either side of the extended structure; and finally a hood comprised of the two C-terminal sequences . The whole HetR dimer becomes more symmetric in the presence of DNA. Overall, the flap orientations are adjusted to provide a more extended interaction with the twofold symmetric DNA duplex.

This superfamily represents the DNA-binding domain, located at the N terminus, containing HTH motifs that penetrate the major groove of the DNA. This part of the HetR surface is positively charged. The DNA-binding unit should obey twofold symmetry, consistent with the palindromic nature of the HetR recognition sequence identified experimentally. The size of the DNA-binding unit suggests that the DNA target is approximately 16-17 bp long. A cavity between the two HTH motifs is clearly large enough to accommodate the minor groove and phosphate units of DNA. The positively charged patch extends beyond the HTH motifs into the flap domains, so the DNA target interacting with HetR may be longer. The HetR DNA-binding surface shows some curvature, suggesting that the bound DNA target might be bent. Additionally, three nests were found in the DNA-binding domain (S31G32H33, H68H69L70, and L11G12P13). These nests are in close proximity to each other and two of them are on the interface between the DNA-binding unit and the flap domain .
SPRE, EVH1 domain (SPRE_EVH1)
Type: Domain

The SPRE (also known as SPRED) proteins have the following domains: an N-terminal EVH1 domain, a unique KBD (c-Kit kinase binding) domain which is phosphorylated by the stem cell factor receptor c-Kit, and a C-terminal cysteine-rich SPR (Sprouty-related) domain which is involved in membrane localization. This entry represents the EVH1 domain of SPRE. Proteins containing this domain include Spred1 which interacts with both Ras and Raf through its SPR domain; Spred2 which is the most abundant isoform; and Spred3 which has a non-functional KBD and maintains the inhibitory action on Raf. Legius syndrome is caused by heterozygous mutations in Spred1. Both EVH1 and SPR domains are involved in the inhibition of the MAP kinase pathway by SPRE proteins. The specific function of the EVH1 domain is unknown and there are no known interacting proteins to date. EVH1 has a PH-like fold, despite having minimal sequence similarity to PH or PTB domains .
Histone-lysine N-methyltransferase, N-terminal domain (Hist-Lys_N-MTase_N)
Type: Homologous_superfamily

Methyltransferases (EC [ec:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.

This superfamily represents the helical N-terminal domain found in histone-lysine N-methyltransferase.
Putative dimethyl sulfoxide reductase catalytic subunit A, C-terminal (DmsA_C)
Type: Domain

DmsA is encoded in operon, dmsREABCD. dmsA is required for anaerobic respiration on DMSO and TMAO in the archaeon Halobacterium. This haloarchael DmsA has been classified as a type II molybdopterin oxidoreductase . This entry represents the C-terminal domain of DmsA.
GPR156, 7TM domain (GPR156_7TM)
Type: Domain

This entry represents the seven-transmembrane (7TM) domain found in orphan GPR156 that is closely related to the type B receptor for gamma-aminobutyric acid (GABA-B), which is activated by its endogenous ligand GABA, the principal inhibitory neurotransmitter. The functional GABA-B receptor is an obligatory heterodimer composed of two related subunits, GABA-B1, which is primarily involved in GABA ligand binding, and GABA-B2, which is responsible for both G-protein coupling and trafficking of the heterodimer to the plasma membrane. Activation of GABA-B couples to G(i/o)-type G proteins, which in turn modulate three major downstream effectors: adenylate cyclase, voltage-sensitive Ca2+ channels, and inwardly-rectifying K+ channels. Consequently, GABA-B receptor produces slow and sustained inhibitory responses by decreased neurotransmitter release via inhibition of Ca2+ channels and by postsynaptic hyperpolarization via the activation of K+ channels through the G-protein beta-gamma dimer. The GABA-B is expressed in both pre- and postsynaptic sites of glutamatergic and GABAergic neurons in the brain where it regulates synaptic activity. Thus, the GABA-B receptor agonist, baclofen, is used to treat muscle tightness and cramping caused by spasticity in multiple sclerosis patients. Moreover, GABA-B antagonists improve cognitive performance in mammals, while GABA-B agonists suppress cognitive behavior. In most of the class C family members, the extracellular Venus-flytrap domain in the N terminus is connected to the seven-transmembrane (7TM) via a cysteine-rich domain (CRD). However, in the GABA-B receptor, the CRD is absent in both subunits and the Venus-flytrap ligand-binding domain is directly connected to the 7TM via a 10-15 amino acids linker, suggesting that GABA-B receptor may utilize a different activation mechanism .
PHF13, PHD finger (PHD_PHF13)
Type: Domain

PHF13, also termed survival time-associated PHD finger protein in ovarian cancer 1 (SPOC1), is a novel plant homeodomain (PHD) finger-containing protein that shows strong expression in spermatogonia and ovarian cancer cells, modulates chromatin structure and mitotic chromosome condensation, and is important for proper cell division. It is also required for spermatogonial stem cell differentiation and sustained spermatogenesis. The overexpression of PHF13 associates with unresectable carcinomas and shorter survival in ovarian cancer .

This entry represents the PHD finger found in PHF13.
RNA ligase 1/2, C-terminal domain superfamily (Rnl1/2_C_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of RNA ligase 1 and 2 (Rnl1/2). The C-terminal domain consists of a four-helix bundle. It is thought to be critical for binding the Rnl2 to adenylylated nicked duplex. This is known as step 2 of the ligation pathway .
STARD7, START domain (START_STARD7)
Type: Domain

This entry represents the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain of STARD7 (also known as gestational trophoblastic tumor 1/GTT1). The gene encoding STARD7 is overexpressed in choriocarcinoma . STARD7 appears to be involved in the intracellular trafficking of phosphatidycholine (PtdCho) to mitochondria . STARD7 was shown to be surface active and to interact differentially with phospholipid monolayers, it showed a preference for phosphatidylserine, cholesterol, and phosphatidylglycerol .
STARD2, START domain (STARD2_START)
Type: Domain

This entry represents the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain of STARD2 (also known as phosphatidylcholine transfer protein/PC-TP) and related proteins . STARD2 is a cytosolic phosphatidycholine (PtdCho) transfer protein, which traffics PtdCho, the most common class of phospholipids in eukaryotes, between membranes. It represents a minimal START domain structure. STARD2 plays roles in hepatic cholesterol metabolism, in the development of atherosclerosis, and may have a mitochondrial function .
STARD10, START domain (STARD10_START)
Type: Domain

This entry represents the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain of STARD10 (also known as CGI-52, PTCP-like, and SDCCAG28). STARD10 binds phophatidylcholine and phosphatidylethanolamine. It may function in the liver in the export of phospholipids into bile . It is concentrated in the sperm flagellum, and may play a role in energy metabolism. In the mammary gland it may participate in the enrichment of lipids in milk, and be a potential marker of differentiation. Its expression is induced in this gland during gestation and lactation . It is overexpressed in mammary tumours from Neu/ErbB2 transgenic mice, in several breast carcinoma cell lines, and in 35% of primary human breast cancers, and may cooperate with c-erbB receptor signaling in breast oncogenesis . It is a potential marker of disease outcome in breast cancer; loss of STARD10 expression in breast cancer strongly predicts an aggressive disease course . The lipid transfer activity of STRAD10 is downregulated by phosphorylation of its Ser284 by CK2 (casein kinase 2) .