SII-SWORD/CoKE huggingface dataset:
ASCIZ, first and second C2H2 zinc finger domains (C2H2_ASCIZ_1st_2nd)
Type: Domain

This domains are found in the human ATM interactor (also known as ATM/ATR-substrate CHK2-interacting zinc finger protein (ASCIZ)) and related proteins from animals. These proteins are transcription factors that are essential for cell survival and the formation of RAD51 foci, a response to methylating DNA damage . They are also involved in the regulation of ATM (ataxia telangiectasia mutated) kinase activity, particularly in the absence of DNA damage, potentially by stabilising ATM . ASCIZ is predicted to contain four zinc finger domains. This entry represents the first two of them.

C2H2-type (classical) zinc fingers (Znf) were the first class to be characterised. They contain a short β-hairpin and an α-helix (β/β/α structure), where a single zinc atom is held in place by Cys(2)His(2) (C2H2) residues in a tetrahedral array. C2H2 Znf's can be divided into three groups based on the number and pattern of fingers: triple-C2H2 (binds single ligand), multiple-adjacent-C2H2 (binds multiple ligands), and separated paired-C2H2 . C2H2 Znf's are the most common DNA-binding motifs found in eukaryotic transcription factors, and have also been identified in prokaryotes . Transcription factors usually contain several Znf's (each with a conserved β/β/α structure) capable of making multiple contacts along the DNA, where the C2H2 Znf motifs recognise DNA sequences by binding to the major groove of DNA via a short α-helix in the Znf, the Znf spanning 3-4 bases of the DNA . C2H2 zinc fingers can also bind to RNA and protein targets .
MreB/MamK-like (MreB_MamK-like)
Type: Family

This entry consists of bacterial MreB and MreB-like (Mbl) proteins and the related MamK proteins .

MreB forms membrane-associated dynamic filaments that are essential for cell shape determination . Genes coding for MreB/Mbl are only found in elongated bacteria, not in coccoid forms. It has been speculated that constituents of the eukaryotic cytoskeleton (tubulin, actin) may have evolved from prokaryotic precursor proteins closely related to today's bacterial proteins FtsZ and MreB/Mbl .

MamK ia an actin-like protein with ATPase activity which forms dynamic cytoplasmic filaments . It is found in magnetotactic bacteria, being important to organise magnetosome organelles into chains that are used for navigation along geomagnetic fields .
NUP160, helical domain (NUP160_helical)
Type: Domain

This entry represents the central helical domain of NUP160, from animals.

NUP160 is one of up to 60 proteins that constitute the Nuclear Pore Complex (NPC) as a component of the NUP107-160 subcomplex . NUP160, in conjunction with NUP133, interacts with NUP98 and NUP153, mediating mRNA export . NUP160 depletion could restore autophagy and inhibit fibrosis and inflammatory response in high glucose-treated . NUP160 mutations have been associated with Steroid-Resistant Nephrotic Syndrome (SRNS). Silencing Drosophila NUP160 specifically in nephrocytes results in functional abnormalities, reduced cell size and nuclear volume, as well as a disorganised nuclear membrane structure .
Nucleoporin nup120-like, HEAT repeat domain, fungal (HEAT_Nup120)
Type: Domain

These HEAT repeats form an elongated α-helical stack at the C-terminal end of Nucleoporin nup120 from Schizosaccharomyces pombe and similar sequences mainly from fungi. Nup120 functions as a component of the nuclear pore complex (NPC).

Nup120 is conserved from fungi to plants to humans, and is homologous with the Nup160 of vertebrates. The nuclear core complex, or NPC, mediates macromolecular transport across the nuclear envelope. Deletion of the NUP120 gene causes clustering of NPCs at one side of the nuclear envelope, moderate nucleolar fragmentation and slower cell growth . The vertebrate NPC is estimated to contain between 30 and 60 different proteins. most of which are not known. Two important ones in creating the nucleoporin basket are Nup98 and Nup153, and Nup120, in conjunction with Nup 133, interacts with these two and itself plays a role in mRNA export . Nup160, Nup133, Nup96, and Nup107 are all targets of phosphorylation. The phosphorylation sites are clustered mainly at the N-terminal regions of these proteins, which are predicted to be natively disordered. The entire Nup107-160 subcomplex is stable throughout the cell cycle, thus it seems unlikely that phosphorylation affects interactions within the Nup107-160 subcomplex, but rather that it regulates the association of the subcomplex with the NPC and other proteins .
Nucleolar protein 4, helical domain (HTH_NOL4)
Type: Domain

This domain is found in human Nucleolar protein 4 (NOL4), Nucleolar protein 4-like (NOL4L) and similar animal sequences. This domain is predicted to form an α-helical bundle.

NOL4 has been identified as a methylation target for cervical and head and neck cancer . NOL4L was first identified in acute myeloid leukaemia and was shown to be involved in cell progression in neuroblastoma . NOL4L effects gene expression in the PI3K/AKT pathway and is critical for tumor progression and metastasis in ovarian cancer cells .
Nucleolar protein 10-like, second domain (NOL10_2nd)
Type: Domain

This domain is found in human Nucleolar protein 10 (NOL10) and similar eukaryotic sequences including the orthologue from yeast, Ribosome biogenesis protein (ENP2). This domain is normally found N-terminal to

. It is predicted to adopt an α-β configuration.

NOL10 (also known as Polyglutamine binding protein 5 (PQBP5)) binds to polyglutamine tract sequences and is expressed in the nucleolus. It makes up the skeletal structure of the nucleolus, constituting the granule meshwork in the granular component area, and functions as an anchor for reassembly of other nucleolar proteins .

ENP2 was identified in a set of proteins involved in rRNA-processing and ribosome biosynthesis .
Nucleolar protein 10-like, N-terminal domain (Beta-prop_NOL10_N)
Type: Domain

This domain is found at the N-terminal of human Nucleolar protein 10 (NOL10) and similar eukaryotic sequences including the orthologue from yeast Ribosome biogenesis protein (ENP2). This domain is normally found N-terminal to

. This entry includes a entire β-propeller structure and two α-helices.

NOL10 (also known as Polyglutamine binding protein 5 (PQBP5)) binds to polyglutamine tract sequences and is expressed in the nucleolus. It makes up the skeletal structure of the nucleolus, constituting the granule meshwork in the granular component area, and functions as an anchor for reassembly of other nucleolar proteins .

ENP2 was identified in a set of proteins involved in rRNA-processing and ribosome biosynthesis .
Ribonuclease kappa-like (Ribonucl_Kappa)
Type: Family

This protein family represents a group of short protein sequences from eukaryotes, including the small open reading reading frame (smORF) encoded V-type proton ATPase subunit f from Saccharomyces cerevisiae (V-ATPase subunit f/RNK) and human Ribonuclease kappa (RNK) . These proteins play a role in the activity of vacuolar (H+)-ATPase (V-ATPase), which is responsible for acidifying and maintaining the pH of intracellular compartments .

Ribonuclease kappa is an endoribonuclease which preferentially cleaves ApU and ApG phosphodiester bonds . It was shown to regulate the activity of vacuolar (H+)-ATPase (V-ATPase) .

Members of this family are predicted to contain two transmembrane helices.
Mug60/KHD4, KH type I domain (KH_Mug60-KHD4)
Type: Domain

This is a type I KH domain found in Meiotically up-regulated gene 60 protein (Mug60) from Schizosaccharomyces pombe and KHD4 from Ustilago maydis. KHD4 is a RNA-binding protein that recognises the sequence AUACCC . It plays an essential role in filamentous growth and virulence . Mug60 plays a role in meiosis .
NFD4, C-terminal domain (NFD4_C)
Type: Domain

This domain is found at the C-terminal of Protein NUCLEAR FUSION DEFECTIVE 4 from Arabidopsis thaliana (NFD4) and similar sequences predominantly found in plants. NFD4 is required for karyogamy during female gametophyte development, when the two polar nuclei fuse to form the diploid central cell nucleus . This protein is predicted to organise into two α-helical domains, represented by

and this entry.
Lysophospholipase NTE1-like, P-loop domain (NTE1_P-loop_dom)
Type: Domain

This domain is found in a variety of phospholipases such as Lysophospholipase NTE1, Neuropathy target esterase sws and related proteins. This domain appears to be structurally related to P-loop ATPases, but it appears to not contain the typical APT-binding motifs. Sws is an intracellular phospholipase B that catalyses the double deacylation of phosphatidylcholine (PC) to glycerophosphocholine (GroPCho). This enzyme plays a crucial role in membrane lipid homeostasis and are responsible for the rapid turnover of PC in response to various stimuli such as inositol, elevated temperatures, or choline presence. NTE1 is involved in the signaling mechanisms between neurons and glia, regulating glia wrapping during brain development and ensuring cell survival.
NELF-A, N-terminal domain (NELF-A_N)
Type: Domain

This entry represents the N-terminal domain of Negative elongation factor A (NELF-A) and related eukaryotic proteins. This domain adopts a novel helical fold, comprising five α-helices, with significant structural similarity to the HIV integrase-binding domain present in the human PSIP1 protein. The NELF-A N-terminal domain is involved in interaction with the NELF-C subunit, forming a stable heterodimer interface. Two invariant tryptophan residues in this domain insert into hydrophobic pockets on NELF-C, mediating this interaction. NELF-A is a subunit of the Negative Elongation Factor (NELF) complex, which plays a key role in regulating transcription elongation by RNA Polymerase II. The NELF complex induces promoter-proximal pausing of Pol II, a rate-limiting step in transcription regulation that allows integration of additional signals before productive elongation .
LAMB1/2/3/4, helical domain (LAMB1-4_helical)
Type: Domain

This domain is found in human Laminin subunit beta-1/2/3/4 (LAMB1-4) and related proteins from animals. LAMB1 is thought to mediate the attachment, migration and organisation of cells into tissues during embryonic development by interacting with other extracellular matrix components . This domain, which is located C-terminal to multiple Laminin EGF domains (

), is predicted to adopt a mainly α-helical fold.
Nodulin homeobox, C-terminal domain (NDX_C)
Type: Domain

This domain is found at the C-terminal of NDX, and it has a detectable partial sequence similarity to PUA domains but it is predicted to adopt a β-barrel with SH3 topology.

This entry represents a group of plant proteins, including nodulin homeobox protein (NDX) from Arabidopsis. AtNDX associates with single-stranded DNA and inhibits COOLAIR transcription, which in turn modifies FLC (FLOWERING LOCUS C) expression . It is a key heterochromatin regulator that functions in pericentromeric regions to control siRNA production and non-CG methylation .
Nodulin homeobox, homeobox-like domain (HTH_NDX)
Type: Domain

This domain is found towards the C-terminal of NDX. It has a detectable sequence similarity to known homeobox domains, and it is predicted to adopt similar structure.

This entry represents a group of plant proteins, including nodulin homeobox protein (NDX) from Arabidopsis. AtNDX associates with single-stranded DNA and inhibits COOLAIR transcription, which in turn modifies FLC (FLOWERING LOCUS C) expression . It is a key heterochromatin regulator that functions in pericentromeric regions to control siRNA production and non-CG methylation .
NFP/LYK4/5, first LysM domain (LysM1_NFP_LYK)
Type: Domain

This entry represents the first LysM domain found in proteins from plants, including the NFP from Medicago truncatula and LYK4/5 from Arabidopsis thaliana. The LysM domain adopt a β-α-α-β fold .

NFP/NFR5 class of receptors are crucial for initial lipochitooligosaccharide (LCO) perception and essential for LCO-mediated root nodule symbiosis .

LYK4 is a chitin-binding protein and contributes to chitin-triggered immunity . LYK5 has been identified as a receptor with a very high affinity to chitooligosaccharides . Receptors recognising Nod factors and chitin have a very similar structure but contain two diverging motifs in the LysM1 domain that are necessary for discriminating between immunity and symbiotic functions .
LYK3/4/5, second LysM domain (LysM2_CERK1_LYK3_4_5)
Type: Domain

This entry represents the second LysM domain found in proteins from plants, including LYK3 from Medicago truncatula, CERK1 and LYK4/5 from Arabidopsis thaliana. The LysM domain adopt a β-α-α-β fold. Arabidopsis thaliana has retained the root developmental response to chitin-derived signals, utilising a widely conserved pathway involving CERK1 . Medicago truncatula LYK3 has an active intracellular kinase domain .

LYK4 is a chitin-binding protein and contributes to chitin-triggered immunity . LYK5 has been identified as a receptor with a very high affinity to chitooligosaccharides . Receptors recognising Nod factors and chitin have a very similar structure but contain two diverging motifs in the LysM1 domain that are necessary for discriminating between immunity and symbiotic functions .
LYK4/5, third LysM domain (LysM3_LYK4_5)
Type: Domain

This entry represents the third LysM domain found in proteins from plants, including LYK4/5 from Arabidopsis thaliana. The LysM domain adopt a β-α-α-β fold. LYK4 is a chitin-binding protein and contributes to chitin-triggered immunity . LYK5 has been identified as a receptor with a very high affinity to chitooligosaccharides .
KY-like, immunoglobulin-like domain (Ig-like_KY)
Type: Domain

This domain is found in tandem in human Kyphoscoliosis peptidase (KY), a probable cytoskeleton-associated protease required for normal muscle growth . This domain is predicted to adopt an immunoglobulin-like structure. Proteins containing this domain are mainly found in animals.

This domain is also found in tandem in the Lim and transglutaminase domain protein ltd-1 from C.elegans and Hillarin from D.melanogaster, both distant orthologs of KY.
Activating transcription factor 7-interacting protein, Fn3 domain (Fn3_ATF7IP)
Type: Domain

This entry represents the Fibronectin type III (Fn3) domain found in Activating transcription factor 7-interacting protein (MCAF) family of proteins.

Activating transcription factor 7-interacting protein (MCAF) family consists of MCAF1 and MCAF2 .

MCAF1 (also known as MBD1-containing chromatin-associated factor 1) is a recruiter that couples transcriptional factors to general transcription apparatus and thereby modulates transcription regulation and chromatin formation. It can both act as an activator or a repressor depending on the context .
CPBP family lipoprotein N-acylation protein LnsB-like (Acyl_LnsB_CPBP-like)
Type: Family

This family includes LnsB and related bacterial proteins from the CPBP family. LnsB is involved in a two-protein system for the N-acylation of lipoproteins. It belongs to the CPBP family of Rce1-like glutamic-type intramembrane proteases, which includes the type II CAAX prenyl proteases in eukaryotes and the myxosortases in prokaryotes. However, the typical active site-containing motif, EExxxR, is disrupted in most members of this family, suggesting a loss of endopeptidase activity. The partner protein in this system, LnsA, has some similarities with members of the NlpC/P60 superfamily .
Lipoprotein N-acylation protein LnsA-like (Acyl_LnsA-like)
Type: Family

This family includes LnsA and related bacterial proteins. Together with LnsB, LnsA is involved in a two-protein system for the N-acylation of lipoproteins. LnsA shows some similarity with the NlpC/P60 superfamily .
Flagellar accessory protein ArlH (ArlH)
Type: Family

Flagellar accessory protein ArlH (also known as FlaH) is part of the motor of the archaellum membrane-anchored archaeal motility structure, together with ArlX and ArlI. ArlH forms a hexameric ring, and binds ATP, which is essential for its interaction with ArlI and for archaellum assembly . The C-terminal region of ArlX, which is crucial for both forming the ArlX ring structure and binding to ArlI, also serves as an interaction site for ArlH .
Flagella accessory protein ArlJ-like (ArlJ-like)
Type: Family

This family includes ArlJ from Halobacterium salinarum (

), FlaJ from Methanocaldococcus jannaschii and related prokaryotic proteins that are involved in the formation and function of flagella, which are whip-like structures that enable motility in various types of cells. They are accessory components that may interact with other flagellar proteins to facilitate the assembly or stability of the flagellar apparatus.
PilB3-like, N-terminal (PilB3-like_N)
Type: Domain

This domain is found at the N-terminal of PilB3 from Haloferax volcanii and similar archaeal proteins. This domain is found associated with

and

.

PilB3 is involved in the biosynthesis and assembly of type IV pili, which are filamentous protein structures on the cell surface that play various roles in cellular processes. PilB3 works in conjunction with PilC3 as part of the PilB3-C3 system in Haloferax volcanii .
PilB3-like, C-terminal (PilB3-like_C)
Type: Domain

This domain is found at the C-terminal of PilB3 from Haloferax volcanii and similar archaeal proteins. This domain, normally found C-terminal to

, is predicted to show an α-β structure.

PilB3 is involved in the biosynthesis and assembly of type IV pili, which are filamentous protein structures on the cell surface that play various roles in cellular processes. PilB3 works in conjunction with PilC3 as part of the PilB3-C3 system in Haloferax volcanii .
PaaD, zinc beta ribbon domain (Zn_ribbon_PaaD)
Type: Domain

This domain is found in PaaD from Escherichia coli and similar sequences from bacteria and some archaeal proteins. This domain is predicted to adopt a zinc β-ribbon fold and contains two invariant CxxC sequence motifs. In addition, towards the C-terminal it has a semi-conserved [EQ]PF[DEQ] sequence motif .

PaaD from Escherichia coli is thought to be a component of 1,2-phenylacetyl-CoA epoxidase multicomponent enzyme system which catalyses the reduction of phenylacetyl-CoA to form 1,2-epoxyphenylacetyl-CoA .
Legume lectins, beta-barrel domain (Lectin_L-type_dom)
Type: Domain

The L-type (legume-type) lectins are a highly diverse family of carbohydrate binding proteins that generally display no enzymatic activity toward the sugars they bind . This family includes arcelin, concanavalinA, the lectin-like receptor kinases, the ERGIC-53/VIP36/EMP46 type1 transmembrane proteins, and an alpha-amylase inhibitor . L-type lectins have a dome-shaped β-barrel carbohydrate recognition domain with a curved seven-stranded β-sheet referred to as the "front face" and a flat six-stranded β-sheet referred to as the "back face" . This domain homodimerises so that adjacent back sheets form a contiguous 12-stranded sheet and homotetramers occur by a back-to-back association of these homodimers. Though L-type lectins exhibit both sequence and structural similarity to one another, their carbohydrate binding specificities differ widely .
MAP kinase-activating death domain protein, death domain (Death_MADD)
Type: Domain

This entry represents the death domain found in MAP kinase-activating death domain (MADD) proteins. MADD proteins function as guanyl-nucleotide exchange factors that regulate small GTPases of the Rab family, facilitating the conversion of GDP-bound inactive forms to GTP-bound active forms. Their targets include RAB27A, RAB27B, RAB3A, RAB3C, and RAB3D, which are crucial for synaptic vesicle exocytosis and secretion . MADD proteins are involved in synaptic vesicle formation, vesicle trafficking at neuromuscular junctions, and up-regulating synaptic exocytosis in central synapses . They may interact with motor proteins like KIF1B and KIF1A for vesicle transport to presynaptic terminals . Additionally, they play roles in TNFA-mediated MAPK pathway activation, potentially linking TNFRSF1A with MAP kinase activation, and may regulate TNFA-induced apoptosis . In Caenorhabditis elegans, they are implicated in presynaptic activity regulation, dense-core vesicle trafficking, body muscle contractions, and fatty acid uptake by intestinal cells during the defecation motor program .
MCM3-like, winged helix domain (WH_MCM3_C)
Type: Domain

This small C-terminal winged helix (WH) domain is found in the human DNA replication licensing factor MCM3 and similar eukaryotic sequences. MCM3 is a minichromosome maintenance (MCM) protein, a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighbouring subunits .
MGAT4 A/B/C, C-terminal domain (MGAT4_A/B/C_C)
Type: Domain

This domain is found C-terminal in Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A/B/C (MGAT4A/B/C) and related proteins. MGAT4A catalyses the transfer of GlcNAc from UDP-GlcNAc to the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans. This domain selectively interacts with the product N-glycans having a beta1-4 GlcNAc branch. Mutation of the residue critical for the sugar recognition impairs the enzymatic activity, suggesting that the lectin domain is a regulatory subunit for efficient catalytic reaction . This domain adopts a β-sandwich fold typical for galactose binding domains.
Gp84-like (Phage_Gp84)
Type: Domain

This entry represents a domain found in phage proteins, including the Gp84 protein from Mycobacteriophage L5 (

). An AlphaFold model of a member (

) has a compact fold of one α-helix followed by a three stranded β-sheet. The function of these proteins is unknown.
N4BP1, C-terminal UBA domain (UBA_N4BP1_C)
Type: Domain

This domain is found in the N4BP1 family which includes NEDD4-binding protein 1, KHNYN and other related proteins. This domain has a significant sequence and structural similarity to known UBA domains. It was shown that in KHNYN, this domain is responsible for binding ubiquitin-like protein NEDD8 (

). In N4BP1, this domain is required for binding to linear polyubiquitin (

) .

N4BP1 is a potent suppressor of cytokine production that acts as a regulator of innate immune signalling and inflammation . It acts as a restriction factor against some viruses, such as HIV-1. N4BP1 restricts HIV-1 replication by binding to HIV-1 mRNAs and mediating their degradation via its ribonuclease activity .
E3 UFM1-protein ligase 1-like, N-terminal (Ufl1_N)
Type: Domain

This entry represents the N-terminal region of E3 UFM1-protein ligase 1 (Ufl1) and similar sequences mainly found in animals and plants.

The ubiquitin fold modifier 1 (Ufm1) is the most recently discovered ubiquitin-like modifier whose conjugation (ufmylation) system is conserved in multicellular organisms. Ufm1 is known to covalently attach with cellular protein(s) via a specific E1-activating enzyme (Uba5), an E2-conjugating enzyme (Ufc1), and a E3-ligating enzyme (Ufl1) . Ufl1 mediates the covalent attachment of the ubiquitin-like modifier Ufm1 to lysine residues on target proteins and plays a key role in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress .
E3 UFM1-protein ligase 1-like domain (Ufl1_dom)
Type: Domain

This domain is found in human E3 UFM1-protein ligase 1 (Ufl1) and similar eukaryotic sequences. This domain, which is predicted to show an all-α configuration, is often found associated to the Ufl1 N-terminal domain

.

The ubiquitin fold modifier 1 (Ufm1) is the most recently discovered ubiquitin-like modifier whose conjugation (ufmylation) system is conserved in multicellular organisms. Ufm1 is known to covalently attach with cellular protein(s) via a specific E1-activating enzyme (Uba5), an E2-conjugating enzyme (Ufc1), and a E3-ligating enzyme (Ufl1) . Ufl1 mediates the covalent attachment of the ubiquitin-like modifier Ufm1 to lysine residues on target proteins and plays a key role in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress .