SII-SWORD/CoKE huggingface dataset:
LDLRAD1-like, C-terminal domain (LDLRAD1_C)
Type: Domain

This domain is found at the C-terminal end of human Low-density lipoprotein receptor class A domain-containing protein 1 (LDLRAD1) and similar sequences from vertebrates. This domain is often found associated with

. Its specific function is unknown.
Light dependent period A-like, Fe-S cluster-binding domain (LdpA_Fe-S-bd)
Type: Domain

This entry represents the Fe-S cluster-binding domain of Light dependent period A (LpdA) from Synechococcus elongatus, which is inserted in the TIM barrel domain (

). LpdA plays a role in controlling the redox state in cyanobacteria to modulate its circadian clock . This entry also includes uncharacterised sequences from plants and archaea.
Lin-15A/B-like domain (Lin-15A/B-like_dom)
Type: Domain

This domain is found in a group of proteins from Caenorhabditis, including Protein lin-15A/B from Caenorhabditis elegans, synthetic multivulva class A/B proteins respectively that are required to repress the induction of vulval development . Protein lin-56, which also belongs to this group of proteins, is required for translation, stability and/or localisation of lin-15S . This domain is predicted to have a mainly α configuration.
Lipase maturation factor 1/2, C-terminal domain (LMF1/2_C)
Type: Domain

This entry represents the C-terminal domain of a family transmembrane proteins that includes the lipase maturation factors 1 and 2 (LMF1/2). Lipoprotein lipase and hepatic lipase require LMF1 to fold into their active states . LMF1 acts as a chaperone required for maturation and transport of active lipoprotein lipase (LPL), through the secretory pathway .
Lipase maturation factor 1/2, N-terminal domain (LMF1/2_N)
Type: Domain

This entry represents the N-terminal domain of a family transmembrane proteins that includes the lipase maturation factors 1 and 2 (LMF1/2). Lipoprotein lipase and hepatic lipase require LMF1 to fold into their active states . LMF1 acts as a chaperone required for maturation and transport of active lipoprotein lipase (LPL), through the secretory pathway .
Lips (Lips)
Type: Family

This entry corresponds to an uncharacterised protein family. A structure prediction of the dimer of this protein gives rise to a large complex with a pair of hydrophobic lips that might interact with a cell membrane. STRING networks suggest that this protein may interact with RNA polymerase.
Lnb-like, transmembrane domain (5TMH_Lnb)
Type: Domain

This domain is found C-terminal in Lipoprotein N-acyltransferase Lnb from Bacteroides and related uncharacterised bacterial proteins. Lnb functions as a lipoprotein N-acyltransferase in its native cell environment . It is composed of two domains, N-terminal periplasmic domain and C-terminal α-helical transmembrane domain (this entry) which is predicted to contain five transmembrane helices. This domain is often found associated with

.
PIF1/LRR1, pleckstrin homology domain (PIF1/LRR1_PH)
Type: Domain

This entry represents the pleckstrin homology (PH) domain found in the N-terminal region of human ATP-dependent DNA helicase PIF1, Leucine-rich repeat protein 1 (LRR1), and similar sequences specific to animals. PIF is a DNA-dependent ATPase and 5'-3' DNA helicase required for the maintenance of both mitochondrial and nuclear genome stability. It resolves G4 structures, preventing replication pausing and double-strand breaks (DSBs) at G4 motifs. This protein is also involved in the maintenance of telomeric DNA . LRR1 is a substrate recognition subunit of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins . The PH domain interacts with the zinc finger domains of MCM2 and MCM6, parental dsDNA and the N-terminal region of the TIMELESS α-solenoid. The domain is connected to a C-terminal LRR domain by a flexible linker.
Angiopoietin-1/2/4 domain (ANG-1/2/4)
Type: Domain

This presumed domain is found in Angiopoietin-1, 2 and 4 (ANG-1/2/4) and similar animal sequences. This domain, which is predicted to adopt an α-helical configuration, is often associated with

.

Angiopoietin-1 (ANG-1) plays an important role in the regulation of angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganisation of the actin cytoskeleton and maintenance of vascular quiescence. It is required for normal angiogenesis and heart development during embryogenesis .
At1g68980-like, TPR repeats (At1g68980-like_TPR)
Type: Domain

This is a region of tetratricopeptide (TPR)-like repeats found at the N-terminal end of At1g68980 from Arabidopsis thaliana and similar plant sequences.

At1g68980 is implicated in mitochondrial stress responses, as mutations in mitochondrial proteins, alter hormone concentrations (e.g., gibberellic acid and ethylene) and touch-induced transcriptomic changes . However, its function is not fully understood.

The tetratrico peptide repeat region (TPR) is a structural motif present in a wide range of proteins . It mediates protein-protein interactions and the assembly of multiprotein complexes . The TPR motif consists of 3-16 tandem-repeats of 34 amino acids residues, although individual TPR motifs can be dispersed in the protein sequence. Sequence alignment of the TPR domains reveals a consensus sequence defined by a pattern of small and large amino acids. TPR motifs have been identified in various different organisms, ranging from bacteria to humans. Proteins containing TPRs are involved in a variety of biological processes, such as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neurogenesis and protein folding.

The X-ray structure of a domain containing three TPRs from protein phosphatase 5 revealed that TPR adopts a helix-turn-helix arrangement, with adjacent TPR motifs packing in a parallel fashion, resulting in a spiral of repeating anti-parallel α-helices . The two helices are denoted helix A and helix B. The packing angle between helix A and helix B is ~24 degrees within a single TPR and generates a right-handed superhelical shape. Helix A interacts with helix B and with helix A' of the next TPR. Two protein surfaces are generated: the inner concave surface is contributed to mainly by residue on helices A, and the other surface presents residues from both helices A and B.
At2g24240-like, C-terminal beta-propeller (Beta_prop_At2g24240)
Type: Domain

This is the β-propeller found at the C-terminal end of BTB/POZ domain-containing protein At2g24240 from Arabidopsis thaliana and similar plant proteins.

The function of At2g24240 remains uncharacterised. However, given the presence of a BTB/POZ domain (

) and a C-terminal β-propeller, it is likely to be involved in ubiquitin-mediated protein degradation or chromatin remodelling. Specifically, it may function as a substrate-specific adaptor within an E3 ubiquitin-protein ligase complex (CUL3-RBX1-BTB), facilitating the ubiquitination and subsequent proteasomal degradation of target proteins.
At4g14310, 8-bladed propeller (Beta-prop_At4g14310)
Type: Domain

This domain is found in the KIN14B-interacting protein At4g14310 from Arabidopsis thaliana and related proteins. This domain is predicted to fold into an eight-bladed β-propeller.

At4g14310 may be implicated in division plane orientation during plant cell division, a process critical for proper embryonic development and tissue patterning in Arabidopsis . It may function similarly to known division regulators like TANGLED1 (TAN1) and AUXIN-INDUCED-IN-ROOT-CULTURES9 (AIR9), which stabilise cortical microtubule arrays to guide division plane positioning .
At5g54830-like domain (At5g54830-like)
Type: Domain

This domain is found in At5g54830 from Arabidopsis thaliana and similar plant proteins such as Cytochrome b561, DM13 and DOMON domain-containing proteins. It is predicted to adopt an all-β configuration. The function of this domain has not been characterised yet. This domain is also found in Protein Skeletor isoforms B/C from Drosophila melanogaster.

At5g54830 may act as a catecholamine-responsive trans-membrane electron transporter. It is formed by DM13 domain at the N-terminal (

), followed by DOMON domain (

), an uncharacterised domain (

) and Cytochrome B561 (

) at the C-terminal.
AtC3H23-like, CCCH zinc finger domain (Znf-CCCH_AtC3H23-like)
Type: Domain

This CCCH-type zinc finger is found in Zinc finger CCCH domain-containing protein 23 (AtC3H23,

) and similar plant proteins.
ATM-like, TPR repeat (ATM_TPR)
Type: Repeat

This region of tetratricopeptide (TPR)-like repeats is found in Serine/threonine-protein kinase ATM from Arabidopsis thaliana and similar plant proteins.

ATM acts as a DNA damage sensor upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA) . It regulate DNA damage response mechanism through recognising the substrate consensus sequence [ST]-Q and phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at double strand breaks (DSBs) . On DNA damage, autophosphorylation dissociates ATM into monomers rendering them catalytically active . It can phosphorylate DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9 and DCLRE1C . ATM is also required for telomere elongation . ATM also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes . It is also involved in signal transduction and cell cycle control and may function as a tumour suppressor .

The tetratrico peptide repeat region (TPR) is a structural motif present in a wide range of proteins . It mediates protein-protein interactions and the assembly of multiprotein complexes . The TPR motif consists of 3-16 tandem-repeats of 34 amino acids residues, although individual TPR motifs can be dispersed in the protein sequence. Sequence alignment of the TPR domains reveals a consensus sequence defined by a pattern of small and large amino acids. TPR motifs have been identified in various different organisms, ranging from bacteria to humans. Proteins containing TPRs are involved in a variety of biological processes, such as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neurogenesis and protein folding.

The X-ray structure of a domain containing three TPRs from protein phosphatase 5 revealed that TPR adopts a helix-turn-helix arrangement, with adjacent TPR motifs packing in a parallel fashion, resulting in a spiral of repeating anti-parallel α-helices . The two helices are denoted helix A and helix B. The packing angle between helix A and helix B is ~24 degrees within a single TPR and generates a right-handed superhelical shape. Helix A interacts with helix B and with helix A' of the next TPR. Two protein surfaces are generated: the inner concave surface is contributed to mainly by residue on helices A, and the other surface presents residues from both helices A and B.
Bbp19-like phage (Bbp19-like_phage)
Type: Domain

This entry represents a domain found in uncharacterised phage protein, it is composed of three α helices. There is some evidence from structure predictions that this protein may homodimerise. These dimers are predicted to form a ring of eight dimers. This entry includes the Bbp19 protein (also known as Endopeptidase,

) from Bordetella BPP-1 phage.
BCL-11A-like, CCHC zinc finger (BCL-11A_Znf_CCHC)
Type: Domain

This CCHC zinc finger domain is found N-terminal in the human B-cell lymphoma/leukemia 11A (BCL-11A) and related proteins including its paralogue, which shares significant similarities in structure and function, B-cell lymphoma/leukemia 11B (BCL-11B) and the Zinc finger protein 296 (ZNF296). The zinc finger represented by this entry is a variant of the classical C2H2 zinc fingers.

BCL11B is a key regulator of both the differentiation and survival of T-lymphocytes during thymocyte development in mammals. It is essential for modulating the responsiveness of haematopoietic stem cells to chemotactic signals by controlling the expression of CCR7 and CCR9 receptors, which guide progenitor cell migration from the bone marrow to the thymus. In activated CD4+ T-lymphocytes, BCL11B enhances the expression interleukin-2 by regulating the IL2 promoter. It also functions as a tumour suppressor in T-cell lymphomas, potentially acting within the P53-signalling pathway, and represses transcription through direct binding to a GC-rich response element independently of TFCOUP2. BCL11A is involved in the regulation of the developmental switch from gamma- to beta-globin . This protein is associated with the BAF SWI/SNF chromatin remodelling complex . BCL11A specifically binds to 5'-GGCCGG-3' sequences and functions mainly as a transcriptional repressor .
BPTI-like, C-terminal domain (BPTI_C_nem)
Type: Domain

This entry represents a BPTI-like domain found exclusively in nematodes, primarily within the class Chromadorea. The domain is well-represented across multiple nematode clades including Rhabditina, Tylenchina, and Spirurina. It is found in proteins such as LON-8 in C. elegans, which contains a single copy of this domain.
BRINP, EGF domain (BRINP_EGF)
Type: Domain

This predicted EGF domain is found in BMP/retinoic acid-inducible neural-specific proteins (BRINP) 1, 2 and 3. This domain is often found between

and

.

BRINP proteins are involved in neurogenesis and brain development. These proteins play a role in inhibiting neuronal cell proliferation by negatively regulating cell cycle progression, particularly by suppressing the G1/S transition in postmitotic neurons. This regulation is essential for proper brain development and the functioning of GABAergic neurons. Additionally, certain BRINP proteins have been implicated in promoting the proliferation, migration, and invasion of pituitary gonadotrope cells when overexpressed, suggesting a potential role in pituitary tumour development. BRINP proteins are also characterised by their responsiveness to BMP and retinoic acid, which are key signalling molecules in neural-specific pathways .
BRWD/PHIP, ancillary-like domain (BRWD/PHIP_AD)
Type: Domain

This entry represents a conserved domain found in bromodomain and WD repeat-containing proteins (BRWD) and PH-interacting protein (PHIP). This domain shows structural similarity to the ancillary domain of Auxin Response Factors (

). It is found in BRWD1, BRWD3 and PHIP proteins, which are involved in transcriptional regulation. BRWD1 and BRWD3 proteins contain multiple bromodomains and WD40 repeats, while PHIP contains WD40 repeats and a PH domain.

Bromodomain and WD repeat-containing proteins are involved in the regulation of cell morphology and cytoskeletal organisation, playing a key role in maintaining and controlling cell shape. These proteins may also act as transcriptional activators and participate in chromatin remodelling. Additionally, some members are believed to regulate insulin and insulin-like growth factor signalling pathways, promoting cell proliferation and exhibiting anti-apoptotic activity through AKT1 phosphorylation and activation. They include proteins that bind to acetylated lysine residues on histones, as well as others that interact with key signalling proteins such as SMARCA4, IRS1, and IRS2, indicating a broader involvement in complex protein interactions and regulatory pathways .
BRWD/PHIP, N-terminal domain (BRWD/PHIP_N)
Type: Domain

This domain is found at the N-terminal of Bromodomain and WD repeat-containing protein (BRWD) and WD repeat-containing proteins (BRWD) and PH-interacting protein (PHIP). It is found in BRWD1, BRWD3 and PHIP proteins, which are involved in transcriptional regulation. BRWD1 and BRWD3 proteins contain multiple bromodomains and WD40 repeats, while PHIP contains WD40 repeats and a PH domain.

Bromodomain and WD repeat-containing proteins are involved in the regulation of cell morphology and cytoskeletal organisation, playing a key role in maintaining and controlling cell shape. These proteins may also act as transcriptional activators and participate in chromatin remodelling. Additionally, some members are believed to regulate insulin and insulin-like growth factor signalling pathways, promoting cell proliferation and exhibiting anti-apoptotic activity through AKT1 phosphorylation and activation. They include proteins that bind to acetylated lysine residues on histones, as well as others that interact with key signalling proteins such as SMARCA4, IRS1, and IRS2, indicating a broader involvement in complex protein interactions and regulatory pathways .
BSD2, cysteine rich domain (BSD2_CRD)
Type: Domain

This domain is found in the chloroplastic Protein BUNDLE SHEATH DEFECTIVE 2 (BSD2) from Arabidopsis thaliana and related proteins. This domain has a hairpin architecture arranged around two Zn atoms, each coordinated by four cysteines . Proteins with this domain contain a highly conserved CxxCxGxG sequence motif.

Chloroplastic chaperone proteins play a critical role in the biogenesis, assembly, and maintenance of major photosynthetic complexes, including RuBisCo and photosystem I (PSI). These proteins stabilise intermediate assembly states of such complexes, ensuring proper formation and functionality once all required subunits are available. A key example is BSD2, a chloroplast chaperone essential for RuBisCo biogenesis and the translational regulation of its large subunit . BSD2 stabilises an end-state assembly intermediate composed of eight large subunits until the small subunits can be incorporated. Beyond their role in complex assembly, these chaperones are also involved in chloroplast development and differentiation, such as chromoplast formation for carotenoid accumulation and the preservation of photosystem II activity under stress conditions. Furthermore, they contribute to the regulation of carbon distribution, influencing plant development and enhancing stress responses by maintaining transcriptional activity within the chloroplast.
C17orf113, probable zinc finger (Znf_C17orf113)
Type: Domain

This domain is found in the human uncharacterised protein C17orf113 and related proteins. It contains two pairs of invariant cysteine and histidine residues that may be involved in metal coordination. This domain contains a zinc finger like fold.
CAPS, C2 domain (CAPS_C2)
Type: Domain

This entry represents the C2 domain found in CAPS proteins, which are essential regulators of dense-core vesicle exocytosis. This domain has a typical C2 superfamily fold consisting of an eight-stranded β-sandwich but lacks calcium-binding capacity. Instead, it works together with the adjacent PH domain through a conserved hydrophobic interface to bind PI(4,5)P2. A polybasic patch (K457, K459, R477) in the C2 domain cooperates with the PH domain's PI(4,5)P2 binding site to enhance membrane binding. The tight association between the C2 and PH domains is essential for CAPS function in neurotransmitter release.

The calcium-dependent secretion activator proteins (CAPS) facilitate the exocytosis of neurotransmitter- and neuropeptide-filled vesicles. These proteins likely act upstream of membrane fusion, contributing to the biogenesis or maintenance of mature secretory vesicles. They specifically mediate calcium-dependent exocytosis of large dense-core vesicles and other dense-core vesicles. Some members also regulate neurotrophin release and catecholamine loading and may participate in the exocytosis of small clear synaptic vesicles. These proteins are characterised by a PH domain (

), which is essential for regulated exocytosis and phospholipid binding. Additionally, they interact with dopamine receptors and are involved in multiple signalling pathways .
GRDP, C2 domain (GRDP_C2)
Type: Domain

This entry represents a C2 domain found in GRDP1 and GRDP2 proteins.

Glycine-rich domain-containing proteins (GRDPs) plays a regulatory role in abscisic acid (ABA) signalling and tolerance to abiotic stress during germination. It may be involved in the regulation of the ABI transcriptional factors and in the development of stress responses .

The C2 domain is a Ca
2+
-dependent membrane-targeting module found in many cellular proteins involved in signal transduction or membrane trafficking. C2 domains are unique among membrane targeting domains in that they show wide range of lipid selectivity for the major components of cell membranes, including phosphatidylserine and phosphatidylcholine. This C2 domain is about 116 amino-acid residues and is located between the two copies of the C1 domain in Protein Kinase C and the protein kinase catalytic domain . Regions with significant homology to the C2-domain have been found in many proteins. The C2 domain is thought to be involved in calcium-dependent phospholipid binding and in membrane targetting processes such as subcellular localisation.

The 3D structure of the C2 domain of synaptotagmin has been reported , the domain forms an eight-stranded β-sandwich constructed around a conserved 4-stranded motif, designated a C2 key . Calcium binds in a cup-shaped depression formed by the N- and C-terminal loops of the C2-key motif. Structural analyses of several C2 domains have shown them to consist of similar ternary structures in which three Ca
2+
-binding loops are located at the end of an 8 stranded antiparallel β-sandwich.
SYDE1/2, C2 domain (SYDE1/2_C2)
Type: Domain

This entry represents the C2 domain found in synapse-defective Rho GTPase-activating proteins (SYDE). This domain appears to be specific to vertebrates and is notably conserved between SYDE1 and SYDE2, though SYDE2 shows higher sequence conservation across species.

The Rho GTPase-activating proteins function as activators for Rho-type GTPases, converting them to an inactive GDP-bound state. These proteins play a crucial role in cytoskeletal remodelling by regulating the activity of GTPases such as RHOA, CDC42, and RAC1. They are involved in various biological processes, including placental development, trophoblast cell migration, presynaptic development, and axon identity specification. Additionally, they influence synaptic functions by promoting the anchoring of synaptic components and recruiting proteins to active zones. Rho GTPase-activating proteins are also implicated in controlling movement, egg-laying, and the localisation of specific proteins within cells .

The C2 domain is a Ca
2+
-dependent membrane-targeting module found in many cellular proteins involved in signal transduction or membrane trafficking. C2 domains are unique among membrane targeting domains in that they show wide range of lipid selectivity for the major components of cell membranes, including phosphatidylserine and phosphatidylcholine. This C2 domain is about 116 amino-acid residues and is located between the two copies of the C1 domain in Protein Kinase C and the protein kinase catalytic domain . Regions with significant homology to the C2-domain have been found in many proteins. The C2 domain is thought to be involved in calcium-dependent phospholipid binding and in membrane targetting processes such as subcellular localisation.

The 3D structure of the C2 domain of synaptotagmin has been reported , the domain forms an eight-stranded β-sandwich constructed around a conserved 4-stranded motif, designated a C2 key . Calcium binds in a cup-shaped depression formed by the N- and C-terminal loops of the C2-key motif. Structural analyses of several C2 domains have shown them to consist of similar ternary structures in which three Ca
2+
-binding loops are located at the end of an 8 stranded antiparallel β-sandwich.