SII-SWORD/CoKE huggingface dataset:
Mitogen-activated protein kinase kinase kinase, N-terminal (MEKK4_N)
Type: Domain

This domain represents the regulatory N-terminal non-catalytic region of Mitogen-activated protein kinase kinase kinase 4 (MEKK4), which contains a putative PH-domain. This N-terminal region acts as an autoinhibitory domain that must be dissociated from the catalytic domain to allow the activation of these kinases .
DnaJ homologue subfamily C, GRV2/DNAJC13, N-terminal domain (GRV2/DNAJC13_N)
Type: Domain

This is the N-terminal domain of DNAJC13/GVR2, which is required for membrane association and interaction with FAM21 tail domain . It contains critical residues mediating phosphatidylinositol 3-phosphate (PI(3)P) binding, required for its association with endosomes .

This entry represents a group of DnaJ homologue subfamily C proteins, including GRV2 from Arabidopsis and DNAJC13 (also known as RME-8) from humans. They are involved in endocytosis. GRV2 functions in vesicle trafficking from the multivesicular body/pre-vacuolar compartment to the lytic vacuole . In Arabidopsis grv2 mutants display enlarged aggregated endosomes, defective vacuole biogenesis and embryogenesis, and reduced gravitropic responses . DNAJC13 plays a role in the endosomal transport machinery, in which it coordinates the activity of the WASH complex with the function of the retromer SNX dimer to control endosomal tubulation .

DNAJC13 has been linked to Parkinson disease . In humans, DNAJC13 localizes to early endosomal compartments via an N-terminal PI(3)P targeting motif and binds the co-chaperone Heat shock cognate-70 (Hsc70) through the central J domain, whereas the remainder interacts with the BAR-domain containing sorting nexin 1 (SNX1) protein and the FAM21 subunit of the WASH complex
.
Domain of unknown function DUF5921 (DUF5921)
Type: Domain

This entry represents a domain of unknown function of the Transcription Factor IIIC 90 kDa subunit (TFIIIC-delta/TFIIIC90, also known as general transcription factor 3C polypeptide 4) found in animals. It is located between the Transcription factor IIIC 90 kDa subunit N-terminal domain and the Putative zinc-finger of the Transcription factor IIIC.

TFIIIC is a multisubunit complex that directly recognises promoter elements and recruits TFIIIB and RNA polymerase III, being absolutely required for RNA polymerase III transcription. TFIIIC90 has an intrinsic histone acetyltransferase activity with a substrate specificity for histone H3 . This domain is likely to be involved in the interaction with other components of the TFIIIC complex.
Domain of unknown function DUF5920 (DUF5920)
Type: Domain

This entry represents a domain of unknown function found in the Telomerase protein component 1 (TEP1) from in animals. It contains an homology region to the Telomerase associated protein from Tetrahymena p80 .

TEP1 is a component of the telomerase ribonucleoprotein complex and is thought to be responsible for catalysing the addition of new telomeres to chromosomes. TEP1 is also a component of the vault particle, a cytoplasmic ribonucleoprotein complex, in which it is required for vault RNA stability and its association with the vault particle . This domain is localised between the TROVE (

) and DUF4062 (

) domains.
Protein NDNF, C-terminal (NDNF_C)
Type: Domain

This is the C-terminal domain of protein NDNF (Neuron-derived Neurotrophic Factor). NDNF is a glycosylated and disulfide-bonded secreted protein expressed in brain and spinal cord that promotes migration and neurite growth of hippocampal neurons. It also promotes endothelial cell survival, vessel formation and plays an important role in the process of revascularization. This domain contains one of the two fibronectin type III domains (FnIII) present in NDNF and one of the two potential consensus sites for N-linked glycosylation .
BMP and activin membrane-bound inhibitor, C-terminal domain (BAMBI_C)
Type: Domain

This entry represents the C-terminal domain of BAMBI proteins. It contains the transmembrane domain and a short intracellular domain that,
unlike all other known TGF-beta type I or type II receptors, does not encode a serine/threonine-kinase domain. However, it shares sequence homology with the E6 and catalytic loops of receptor serine/threonine kinases .

This entry consists of several eukaryotic BMP and activin membrane-bound inhibitor (BAMBI) proteins. Members of the transforming growth factor-beta (TGF-beta) superfamily, including TGF-beta, bone morphogenetic proteins (BMPs), activins and nodals, are vital for regulating growth and differentiation. BAMBI is related to TGF-beta-family type I receptors but lacks an intracellular kinase domain .

BAMBI is an essential regulator of cell proliferation and differentiation that represses TGF-beta and enhances Wnt/beta-catenin signalling in various cell types . Thus, it is involved in a high number of physiological and pathological processes . It stably associates with TGF-beta-family receptors and inhibits BMP and activin as well as TGF-beta signalling .
BMP and activin membrane-bound inhibitor, N-terminal domain (BAMBI_N)
Type: Domain

This entry represents the N-terminal domain of the BAMBI proteins. This domain might contain putative extracellular domains .

This entry consists of several eukaryotic BMP and activin membrane-bound inhibitor (BAMBI) proteins. Members of the transforming growth factor-beta (TGF-beta) superfamily, including TGF-beta, bone morphogenetic proteins (BMPs), activins and nodals, are vital for regulating growth and differentiation. BAMBI is related to TGF-beta-family type I receptors but lacks an intracellular kinase domain .

BAMBI is an essential regulator of cell proliferation and differentiation that represses TGF-beta and enhances Wnt/beta-catenin signalling in various cell types . Thus, it is involved in a high number of physiological and pathological processes . It stably associates with TGF-beta-family receptors and inhibits BMP and activin as well as TGF-beta signalling .
FBXL5-like, hemerythrin-like domain (Hr_FBXL5)
Type: Domain

Human FBXL5 (F-box and leucine-rich repeat protein 5) protein plays a role in cellular iron homeostasis . It is part of an E3 ubiquitin ligase complex that targets the iron regulatory protein IRP2 for proteasomal degradation . The FBXL5's stability is regulated by iron concentration, with its iron- and oxygen-binding hemerythrin domain acting as a ligand-dependent regulatory switch .
MobI protein (MobI)
Type: Family

MobI is conserved across conjugative plasmids of incompatibility group C (IncC), integrative conjugative elements of the SXT/R391 family and numerous genomic islands mobilized by IncC plasmids. Alongside a relaxase of the MOBH1 family, this protein is essential to conjugative transfer of these elements and is likely a relaxosome component involved in recognition of the origin of transfer .
eIF3h, C-terminal (eIF3h_C)
Type: Domain

This entry represents a C-terminal helical region present in eukaryotic initiation factor 3 chain H.

Eukaryotic translation initiation factor 3 subunit H (eIF3h) is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome . It is a non-peptidase homologue in peptidase family M67 (MEROPS identifier M67.971).

Results suggest that eIF3h regulates cell growth and viability, and that over-expression of the gene may provide growth advantage to prostate, breast, and liver cancer cells .
MTP large subunit, lipid-binding domain (MTP_lip-bd)
Type: Domain

Microsomal triglyceride transfer protein large subunit (MTTP) catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces, and is required for the secretion of plasma lipoproteins that contain apolipoprotein B. It is a heterodimer consisting of a large MTP alpha-subunit and a protein disulfide isomerase (PDI) beta-subunit. Mutations in microsomal triglyceride transfer protein (MTP) cause abetalipoproteinemia .

The MTP large subunit has and N-terminal β-barrel domain, a central α-helical domain and a C-terminal 2-β-sheet domain. This is the highly conserved MTP C-terminal domain involved in lipid-binding and transfer activity, with preference of neutral 3 chain-containing lipids. The β-sheets are named A and C and form a sandwich comprising the lipid-binding site between them. Half of the A-sheet interacts with the β-barrel. This domain also interacts with a' and b' domains of PDI .
DAHL domain (DAHL)
Type: Domain

The DAHL (Double All-Helical Ligand-binding) domain is a novel periplasmic sensory domain, which is found in major types of bacterial signal transduction proteins: histidine kinases and diguanylate cyclases/phosphodiesterases, and, occasionally in chemoreceptors. The majority of the DAHL domain-containing proteins were found in alpha-, beta-, gamma- and epsilonproteobacteria. It is also present in some cyanobacterial species. Secondary structure prediction suggested that DAHL consists predominantly of α-helical regions. The DAHL domain has been identified in the Tlp10 chemoreceptor from the human pathogen Campylobacter jejuni and in the VirA sensor histidine kinase from a plant pathogen Agrobacterium tumefaciens . This domain recognises Asp, Ile, purine, fumarate, malate, alpha-ketoglutarate, mannose, rhamnose, fucose, sialic acid, Arg, thiamine and galactose .
Cysteine-rich motor neuron 1 protein, C-terminal (CRIM1_C)
Type: Domain

Cysteine-rich motor neuron 1 protein (CRIM1) interacts with growth factors implicated in motor neuron differentiation and survival, playing a role in central nervous system development. It is upregulated in endothelial cells during tube formation. CRIM1 also modulates bone morphogenetic protein activity, which affects its processing and delivery to the cell surface. This is CRIM1 C-terminal domain containing the transmembrane region . Members of this entry are found in chordates.
Integrator complex subunit 14, beta-barrel domain (IntS14_b-barrel)
Type: Domain

This entry represents the central β-barrel domain of Integrator complex subunit 14 (IntS14), a component of the integrator complex which is involved in the transcription of small nuclear RNAs (snRNA) and their 3'-box-dependent processing. This complex is also involved in the 3'-end processing of the U7 snRNA, and the spliceosomal snRNAs U1 and U5 . IntS14 interacts with IntS13, both of them consist of an N-terminal von-Willebrand type A like domain (VWA,

), followed by a central β-barrel domain (this entry) and a C-terminal α-helical domain (

) connected through a linker. The interface involves all domains of both proteins, both β-barrel domains form the centre of the complex and contribute to the major contact between Ints13-IntS14 .
Neutrophin-3, N-terminal (NTF3_N)
Type: Domain

This entry represents the N-terminal domain of Neutrophin-3 (NTF3). It contains two precursor homology regions located upstream of the mature NTF3 sequence. These regions play important and specific roles in the folding, processing and transport of neurotrophic factors .
Protein angel homolog 2, N-terminal (ANGEL2_N)
Type: Domain

This entry represents the N-terminal unstructured domain of protein angel homolog 2 (ANGEL2) . This protein is a member of the CCR4 nocturin family of deadenylases and has 2',3'-cyclic phosphatase activity involved in RNA processing and modification .
Dynamin-like GTPase OPA1, C-terminal (OPA1_C)
Type: Domain

This entry represents the C-terminal domain of Dynamin-like GTPase OPA1. This protein is involved in mitochondrial fusion and inner membrane remodelling, essential for normal mitochondrial morphology by regulating the equilibrium between mitochondrial fusion and mitochondrial fission . Mutations in human OPA1 cause optic atrophy . This domain includes the helix bundle (HB) domains HB1 (at the extreme C-terminal) and HB2 (equivalent to bundle signaling element (BSE) and to the stalk domain of dynamin-1, respectively) that associate with the N-terminal G domain and the lipid-interacting stalk (LIS, equivalent to the PH domain of dynamin-1) .
Gamma-tubulin complex component 6, N-terminal (GCP6_N)
Type: Domain

This entry represents the most N-terminal α-helical domain of the Gamma-tubulin complex component 6 (GCP6). It has been shown that the N-terminal domains define the functional identity of gamma-tubulin complex proteins .

Gamma-tubulin complex component 6 (GCP6) is indispensable for assembly of the gamma-tubulin complex and for microtubule nucleation. It is located at the centrioles and the pericentriolar material, being required for centriole formation and reduplication. GCP6 carries a large internal insertion phosphorylated by Plk4 and contains a domain of interaction with keratins .
Tetratricopeptide repeat protein 7, N-terminal (TTC7_N)
Type: Domain

This is the N-terminal domain of TTC7, a protein that forms the regulatory subunit of the PI4KIIIalpha complex (also known as PI4KA). This complex is composed of PI4KIIIalpha, TTC7 and FAM126A and catalyses the first step in plasma membrane phosphoinositide synthesis. This TTC7 N-terminal domain contains basic residues suitable for interaction with the acidic inner leaflet of the plasma membrane and is required for localising the active site near its substrate. TTC7 acts as a bridge between PI4KA and EFR3B-FAM126A, via direct interactions. ERF3B is not part of the complex but contributes to its recruitment to the membrane .
CLEC16A/TT9, C-terminal (CLEC16A/TT9_C)
Type: Domain

This entry represents a domain found at the C terminus of CLEC16A and TT9.

CLEC16A (C-Type Lectin Domain Containing 16A) an evolutionarily conserved endosomal membrane protein required for trafficking of fluid-phase and receptor-mediated endocytic cargos. It is required for mitophagy, autophagy and endosome maturation . This protein has been identified as a susceptibility gene for autoimmune diseases like type 1 diabetes, multiple sclerosis and adrenal dysfunction . It has an inhibitory role in autophagy, probably by activating the mTOR pathway .

GFS9/TT9 (TRANSPARENT TESTA 9) is a protein from Arabidopsis required for vacuolar development through membrane fusion at vacuoles. It contributes to intracellular membrane trafficking and flavonoid accumulation .
Beta-1,3-galactosyltransferase 2, N-terminal (B3GT2_N)
Type: Domain

This entry represents the N-terminal domain of beta-1,3- galactosyltransferase 2 (B3GT2) from vertebrates. This enzyme (

) contains a short cytosolic region and a transmembrane domain, which indicates that this protein has a type II transmembrane topology, typical for all mammalian glycosyltransferases and a stem region with two putative N-glycosylation sites. It catalyses the synthesis of type 1 carbohydrate chains, which contain the beta-N-acetylglucosamine (beta-GlcNAc) linkage . As a glycosyltransferase, B3GT2 plays an essential role in the nervous system .

Glycosyltransferase family 31 (

) comprises enzymes with a number of known activities; N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase (

); beta-1,3-galactosyltransferase (

); fucose-specific beta-1,3-N-acetylglucosaminyltransferase (

); globotriosylceramide beta-1,3-GalNAc transferase (

) .
CO dehydrogenase/acetyl-CoA synthase complex beta subunit , C-terminal (ACS_CODH_B_C)
Type: Domain

Acetyl-CoA synthase/CO dehydrogenase (ACS/CODH) is a bifunctional enzyme that catalyses the reversible reduction of CO2 to CO (CODH activity, the beta subunit) and the synthesis or degradation of acetyl-CoA (catalysed by ACS, the alpha subunit). This domain represents the middle and C-terminal regions of CODH which have an α/β Rossmann-like fold .
Type II secretion system protein TadB-like, N-terminal domain (T2SS_TadB-like_N)
Type: Domain

This presumed domain, mainly found in Alphaproteobacteria, is functionally uncharacterised. It is found at the N-terminal of predicted type II secretion proteins, such as TadB. It is found in association with

.
Lanthionine-containing peptide SapB precursor RamS (RamS)
Type: Family

This entry represents a member of a bacterial biosynthetic gene cluster (BGC). The BGC (BGC0000551) is described by MIBiG as an example of the following biosynthetic class, RiPP (ribosomally synthesised and post- translationally modified peptide). This family includes RamS, the precursor of lanthionine-containing peptide SapB (also known as ProSapB). SapB, which does not appear to exhibit antibiotic activity, is formed from RamS through proteolytic cleavage and subsequent creation of lanthionine bridges .
SpaA-like, prealbumin fold domain subgroup 2 (SpaA_PFL_dom_2)
Type: Domain

This entry represents a domain related to SpaA found as tandem repeats in bacterial surface proteins, associated with VWA and PA14 adhesins
Deubiquitinating protein VCPIP1, N-terminal (VCPIP1_N)
Type: Domain

Deubiquitinating protein VCPIP1, also known as VCIP135, is required for the p97/p47 and p97/p37 pathways and is involved in Golgi and ER membrane fusion. It reverses ubiquitination events that occurs during mitotic disassembly, regulating Golgi membrane dynamics during mitosis. This entry represents the N-terminal domain that interacts with WAC (the WW domain-containing adaptor with coiled coil). This interaction increases the deubiquitinating activity of VCPIP1 and is necessary for p97/p47-mediated Golgi membrane fusion .
PKD-like domain, Bacteroidetes (PKD_Bacteroidetes)
Type: Domain

This entry represents the presumed PKD-like domain found as tandem repeats in bacterial cell surface proteins, commonly associated with Bact_lectin adhesive domain.
PKD-like domain (PKD_6)
Type: Domain

This entry represents the presumed PKD-like domain found as tandem repeats in bacterial cell surface proteins. In some proteins this domain is associated with PA14 or DUF11 domains. Members of this family are predominantly found in Bacteroidetes.
AraR-like, winged helix DNA-binding domain (AraR_wHTH_dom)
Type: Domain

This entry represents the C-terminal DNA-binding winged-helix-turn-helix (wHTH) domain of bacterial Nudix hydrolase domain-containing proteins related to AraR.

Winged helix DNA-binding proteins share a related winged helix-turn-helix DNA-binding motif, where the "wings", or loops, are small β-sheets. The winged helix motif consists of two wings (W1, W2), three α-helices (H1, H2, H3) and three β-sheets (S1, S2, S3) arranged in the order H1-S1-H2-H3-S2-W1-S3-W2 . The DNA-recognition helix makes sequence-specific DNA contacts with the major groove of DNA, while the wings make different DNA contacts, often with the minor groove or the backbone of DNA. Several winged-helix proteins display an exposed patch of hydrophobic residues thought to mediate protein-protein interactions.
LIN-9, C-terminal (LIN9_C)
Type: Domain

MuvB transcriptional regulatory complex interacts with B-Myb to form the MMB complex during S-phase of the cell cycle to activate genes required for the G2 and M phases. This is a domain found at the C terminus of LIN9, one of the core members of the MuvB complex that functions as a scaffold protein and forms a subcomplex with the C terminus of LIN152. This subcomplex forms a binding interface that recruits B-Myb to the MuvB complex which is arranged as a three-stranded antiparallel coiled-coil as the core of the structure. LIN9 contributes two helices (α1 and α2) that run antiparallel and are connected through a short linker .
Cell cycle link protein Clink (Clink)
Type: Family

This entry represents the cell cycle link protein Clink from Banana bunchy top virus (BBTV) , which was identified as a suppressor of RNA silencing. It interacts with retinoblastoma-related proteins (pRB) and S-phase kinase-associated protein 1 (SKP1). Clink contains LxCxE and F-box motifs that mediate the interactions with the respective proteins and the capacity of Clink to bind pRB correlates with its ability to stimulate viral replication. pRB is a key cell cycle regulator, which represses onset and progression into S-phase by interacting with a wide range of cell cycle-related proteins.
Astrovirus p19 protein (Astro_p19)
Type: Family

This entry represents the p19 protein found in human astrovirus. This protein is part of the non-structural 1a polyprotein .
Csd3-like, second N-terminal domain (Csd3_N2)
Type: Domain

This entry represents the second N-terminal domain from the Csd3 peptidase (also known as HdpA), a bi-functional enzyme with delta, delta-endopeptidase activity and delta, delta-carboxypeptidase activity . This domain has a similar structure to

despite low sequence similarity .
Astrovirus transmembrane protein 1A (Astro_1A)
Type: Family

This entry represents the transmembrane protein 1A from human astrovirus. This protein is part of the non-structural 1a polyprotein .
Astrovirus VPg protein (Astro_VPg)
Type: Family

This entry represents the presumed VPg protein from human astrovirus. Viral genome-linked proteins (VPgs) are virus-encoded small proteins that are covalently linked to the 5' terminus of many RNA viral genomes through a phosphodiester bond. Viral genome-linked proteins (VPgs) have been identified in several single-stranded positive-sense RNA virus families. The protein resulting from this putative VPg coding region is a highly disordered protein . A common feature of VPgs is that they are rich in basic amino acids [mostly Lys (K), Gly (G), Thr (T), and Arg (R)], which favors the interaction with the negatively charged RNA. Tyr-693 at the conserved TEEEY-like motif has been postulated to be the residue responsible for the covalent linkage to viral RNA. Mutagenesis of Tyr-693 in the VPg protein is lethal for HAstV replication .
Bacterial toxin, RNase RnlA/LsoA, N-terminal (RnlA_toxin_N)
Type: Domain

Toxin/antitoxin (TA) systems are highly conserved among bacteria and archaea. They play a role in plasmid maintenance, biofilm formation, persister cell formation, general stress response, and phage defense and consist of a stable toxin and an unstable antitoxin. Toxins RnlA (RNase LS) and LsoA are type II TA systems that play a role in phage defence . RnlA and LsoA have endoribonuclease activity, activated after bacteriophage T4 infection. RnlA is the stable toxin that causes inhibition of cell growth and rapidly degrades T4 late mRNAs to prevent their expression, and this is neutralised by the activity of the unstable antitoxin RnlB .

The crystal structure of RnlA revealed that it consist of an N-terminal domain (NTD), an N-Repeated Domain (NRD) and a Dmd-Binding Domain (DBD), being this structure unique and different from all known toxin structures .

This entry represents the N-terminal domain composed of four-stranded twisted antiparallel β-sheet and two α-helices .
DEPDC5, C-terminal (DEPDC5_CTD)
Type: Domain

This entry represents the C-terminal domain (CTD) (residues 1,291-1,603) of the DEPDC5 protein . It contains two structurally similar lobes and has a pseudo-2-fold rotational symmetry. Each half consists of a five-stranded β-sheet, with an α-helix covering one side. The CTD is located in the core of DEPDC5 and contacts all the other domains of DEPDC5 except the NTD, making it the central organizer of this multi-domain protein .
Mgp-operon protein 3, C-terminal domain (MGP3_C)
Type: Domain

This entry represents the C-terminal domain of the Mycoplasma genitalium p110 adhesin protein (also known as Mgp-operon protein 3). This domain has a compact Ig fold and is adjacent to the membrane. It contains a bound potassium ion .
Ariadne domain (Ariadne)
Type: Domain

This entry represents the Ariadne domain found in the Ariadne subfamily E3 ubiquitin ligase proteins . The C-terminal Ariadne domain adopts an elongated four-helix bundle consisting of an antiparallel arrangement of seven-to-ten-turn long helices. The Ariadne domain is straddled on one side by the IBR domain, and on the other by the RING2 domain. Notably, the Ariadne domain embraces the surface of RING2 containing the catalytic Cys357 . The Ariadne domain masks the HHARI catalytic Cys357 and inhibits intrinsic E3 Activity .