SII-SWORD/CoKE huggingface dataset:
ABCA1-4-like, C-terminal R2 regulatory domain (R2_ABCA1-4-like)
Type: Domain

This domain is found at the C-terminal of human Phospholipid-transporting ATPases ABCA1-4 and similar sequences predominantly found in animals, which are lipid transporters. ABCA1 catalyses the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP. ABCA2 modulates cholesterol sequestration in the late endosome/lysosome by regulating the intracellular sphingolipid metabolism, in turn participates in cholesterol homeostasis . ABCD3 catalyses the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pulmonary surfactant . ABCD4 is a flippase that catalyses in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates from the lumen to the cytoplasmic leaflet of photoreceptor outer segment disk membranes and prevents the accumulation of excess of 11-cis-retinal and its schiff-base conjugate and the formation of toxic bisretinoid .

This entry represents the regulatory domain R2 which shows a β-sheet and two α-helices on one side .
CD1375-like domain (CD1375-like_dom)
Type: Domain

This entry represents a short uncharacterised domain of about 50 residues. It is found in phage proteins from a variety of phages infecting Bacilli or Clostridia bacteria. Structural predictions suggest it adopts an α-helical fold. Its function is currently unknown.
CDCP1, third and sixth CUB domain (CDCP1_CUB_3rd_6th)
Type: Domain

This domain is found in the human CUB domain-containing protein 1 (CDCP1) and related proteins. This entry represents the third and the sixth of the tandem of CUB domains.

CDCP1 may be involved in cell adhesion and cell matrix association. It also plays a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation . CDCP1 contains a tandem of CUB domains.
Ada2b, tri-helical domain (Ada2b_C)
Type: Domain

This domain is found at the C-terminal of Transcriptional adapter 2B from Drosophila melanogaster (Ada2b) and similar animal proteins. Ada2b is required for the function of some acidic activation domains, which activate transcription from a distant site . This domain is predicted to show a tri-helical structure.
CDCP1, first CUB domain (CUB_CDCP1_1st)
Type: Domain

This domain is found at the N-terminal of human CUB domain-containing protein 1 (CDCP1) and related proteins. This entry represents the first of the tandem of CUB domains.

CDCP1 may be involved in cell adhesion and cell matrix association. It also plays a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation . CDCP1 contains a tandem of CUB domains.
CDCP1, second and fifth CUB domain (CUB_CDCP1_2nd_5th)
Type: Domain

This domain is found in the human CUB domain-containing protein 1 (CDCP1) and related proteins. This entry represents the second and fifth of the tandem of CUB domains.

CDCP1 may be involved in cell adhesion and cell matrix association. It also plays a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation . CDCP1 contains a tandem of CUB domains.
A disintegrin and metalloproteinase with thrombospondin motifs 17/19, C-terminal helical domain (ADAMTS17/19_C)
Type: Domain

This domain is found C-terminal in some members of ADAMTS family (ADAMTS - A Disintegrin And Metalloproteinase domain, with ThromboSpondin type-1 modules) such as human ADAMTS17 and ADAMTS19. Members of the ADAMTS family of zinc-dependent proteases play important roles in a variety of normal and pathological conditions, including arthritis and cancer. This domain contains conserved cysteine residues that may be involved in disulphide bridge formation. It is predicted to adopt a globular structure consisting of four α-helices.
CDGP domain (CDGP_dom)
Type: Domain

This entry represents a domain found in a family of small lipoproteins found in mycobacteriophage and some mycobacteria. These proteins contain a highly conserved motif CDGPXXPDG that is likely to be functionally important. The domain has been named after part of this motif. The structure of the proteins consists of a four stranded β-meander.
ADAMTS-like protein 1 domain (ADAMTSL1_dom)
Type: Domain

This domain is found in human ADAMTS-like protein 1 (ADAMTSL1) and in similar proteins mainly found in vertebrates. This domain is predicted to adopt a mainly α-helical structure.
CDK5 regulatory subunit-associated protein 2/Myomegalin, coiled coil (CDK5RAP2_MYOME_CC)
Type: Domain

This domain is found in human CDK5 regulatory subunit-associated protein 2 (CDK5RAP2), myomegalin (MYOME, also known as PDE4DIP) and related sequences mainly from vertebrates.

CDK5RAP2 is a potential regulator of CDK5 activity that plays a role in the spindle checkpoint activation and regulates centrosomal maturation . It plays a role in the spindle checkpoint activation by acting as a transcriptional regulator of both BUBR1 and MAD2 promoter. Together with EB1/MAPRE1, it may promote microtubule polymerization, bundle formation, growth and dynamics at the plus . It forms a complex with MYOME isoform 13/MMG8/SMYLE, MAPRE1 and AKAP9, to contribute to microtubules nucleation and extension from the centrosome to the cell periphery . MYOME participates in microtubule dynamics, promoting microtubule assembly. Depending upon the cell context, may act at the level of the Golgi apparatus or that of the centrosome . It forms a complex with AKAP9, and recruits CAMSAP2 to the Golgi apparatus and tethers non-centrosomal minus-end microtubules to the Golgi, an important step for polarised cell movement .

This entry represents a centrally located region that forms an α-helical coiled-coil (CC) in these proteins.
Adhesion G-protein coupled receptor F3, Ig-like domain (Ig_ADGRF3)
Type: Domain

This immunoglobulin-like (Ig-like) domain is found in human Adhesion G-protein coupled receptor F3 (ADGRF3) and similar proteins from vertebrates. ADGRF3 is an orphan receptor.

In homo sapiens, ADGRF3 is a receptor for soluble FNDC4 (sFNDC4), required for proper systemic glucose tolerance, specifically sensitising white adipose tissue to insulin .

The adhesion GPCR (aGPCR) family plays critical physiological functions in the human immune system, central nervous system, cellular communication, reproduction, organ development, homeostasis, and other processes As the second largest group in the GPCR superfamily, aGPCRs are differentiated from other GPCRs by a large extracellular region (ECD) that contains a tandem adhesion domain, followed by the SEA domain

, a conserved GPCR autoproteolysis-inducing (GAIN) domain (GAIN A

and GAIN B

) juxtaposed to a canonical seven-transmembrane domain (7TM) (

). Most aGPCRs are orphan receptors with few known ligand associations identified. The synthesised Stachel peptide is capable of activating aGPCRs, suggesting that the Stachel peptide plays a critical role in aGPCR activation.
Cdr2, UBA domain (UBA_Crd2)
Type: Domain

The protein kinase Cdr2 from S.pombe promotes mitotic entry by organising cortical oligomeric nodes that lead to inhibition of Wee1 which itself inhibits the cyclin-dependent kinase Cdk1 . Cdr2 may act as a dosage-dependent regulator of cell size by sequestering its substrate Wee1 in cytoplasmic clusters, away from Cdk1 in the nucleus . This protein consists of a kinase domain at the N-terminal [

], followed by a ubiquitin-associated domain (UBA) and a KA1 domain at the C-terminal [

]. This entry represents the UBA domain which is thought to be necessary for kinase activity .
AtC3H46-like, PABC-like domain (AtC3H46-like_PABC-like)
Type: Domain

This PABC-like domain is found N-terminal in Zinc finger CCCH domain-containing protein 46 (AtC3H46) from Arabidopsis thaliana and related proteins specific to plants. AtC3H46 is know to possess RNA-binding and ribonuclease activities in vitro .
AIP/AIPL, N-terminal FKBP-type PPIase domain (PPIase_AIP)
Type: Domain

This is the FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) domain of human AH receptor-interacting protein (AIP), AIPL1 and similar animal proteins. AIP may play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signalling. This domain shows a typical FKBP fold with five antiparallel β-strands forming a half β-barrel wrapped around a central α-helix and an additional N-terminal α-helix and a rather long insert that covers the putative active site .
CdrL-like, middle region (CdrL_M)
Type: Domain

This entry represents a region found in the middle of CdrL (cell division regulator long, HVO_0583,

) from Haloferax volcanii and similar sequences from halobacteria . CdrL has

at the N-terminal and

at the C-terminal. According to structure predictions, this region may consist of an α-helix followed by a disordered part.
Aip3p/Bud6, N-terminal domain (Aip3p_Bud6_N)
Type: Domain

This domain is commonly located at the N-terminal end of Aip3p/Bud6 from fungi. This region is essential for its proper localisation on the plasma membrane and to bind to the microtubule (+) end binding protein Bim1 . Its absence results in altered localisation patterns, although the secretory pathway remains functional . The N-terminal region of Bud6 contains the major binding site for Aip5, which is required for the formation of actin cables . This domain may adopt a four-helix bundle fold.
AIPP2-like, SPOC-like domain (AIPP2-like_SPOC)
Type: Domain

This entry represents the SPOC-like domain found at the C-terminal of PHD-containing proteins present in plants, including ASI1-immunoprecipitated protein 2 (AIPP2 or PHD3) and PHD finger-containing protein 1/6 from Arabidopsis thaliana. Together with AIPP3/BDT1, these proteins cooperate to form a BAH-PHD bivalent histone reader complex able to read histone H3 lysine 27 trimethylation (H3K27me3) and low-methylated H3K4 histone marks in order to regulate transcription, especially to prevent early flowering . This domain might be involved in protein interactions .
ATG1a/b/c, MIT domain (MIT_ATG1a/b/c)
Type: Domain

This is the MIT domain found at the C-terminal of ATG1a/b/c proteins from Arabidopsis thaliana and related plant sequences. These proteins are serine/threonine protein kinases involved in autophagy. They form the ATG1-ATG13 protein kinase complex which initiates autophagosome formation and regulates downstream events required for autophagosome enclosure and/or vacuolar delivery .
MROH2B-like, N-terminal HEAT-repeats domain (MROH2B-like_N_HEAT)
Type: Domain

This entry represents a region of HEAT repeats found at the N-terminal end of maestro heat-like repeat-containing proteins, including Maestro heat-like repeat -containing protein family member 2B from mouse (MROH2B, also known as SPIF), which may play a role in the process of sperm capacitation .
CdsD, C-terminal (CdsD_C)
Type: Domain

This domain is found at the C-terminal of CdsD from Chlamydia trachomatis (

) and similar sequences. CdsD is a structural contact-dependent secretion (Cds) protein that form part of the basal body of the type III secretion system (T3SS) injectisome of the bacteria. The periplasmic part of this protein contains at least 3 domains: PD1, PD2 (

) and PD3 (

), all of them sharing the same α-β-β-α-β topology, known as the BON fold . This domain may consist of seven antiparallel β-strands.
AIR9-like, A9 domain (AIR9-like_A9)
Type: Domain

This entry represents an Ig-like domain known as the A9 domain that is repeated 10/11 times in AIR9 (187-kDa microtubule-associated protein AIR9) from Arabidopsis thaliana . This domain is also found only once, often associated with

in a group of plant and bacterial uncharacterised proteins. AIR9 and TAN1 function redundantly to maintain POK1 at the division site to ensure correct cell wall placement and interactions between POK1 and AIR9 are important for division plane orientation and plant growth .
CdsD, PD1 domain (CdsD_PD1)
Type: Domain

This domain is found in CdsD from Chlamydia trachomatis (

) and similar sequences. CdsD is a structural contact-dependent secretion (Cds) protein that forms part of the basal body of the type III secretion system (T3SS) injectisome of the bacteria. The periplasmic part of this protein contains 3 domains: PD1 (represented in this entry), PD2 (

) and PD3 (

), all of them sharing the same α-β-β-α-β topology, known as the BON fold .
CELSR1-3-like, ninth cadherin domain (Cadherin_CELSR1-3_9th)
Type: Domain

This entry represents the last of 9 tandem cadherin domains occurring in human Cadherin EGF LAG seven-pass G-type receptor 1-3 (CELSR1-3), its orthologue form Drosophila stan/Flamingo and similar proteins predominantly found in animals. CELSR2 is a receptor that may have an important role in cell/cell signalling during nervous system formation, involved in planar cell polarity . Stan is involved in the fz signalling pathway that controls wing tissue polarity. It also mediates homophilic cell adhesion and it may play a role in initiating prehair morphogenesis. Stan may play a critical role in tissue polarity and in formation of normal dendrite fields . During planar cell polarity, stabilises asymmetric PCP domains together with ATP6AP2 . The orthologue from C. elegans, fmi-1, promotes motorneuron development by positively regulating the extension of the anterior neurite of ventral D-type GABAergic motorneurons along the anterior-posterior axis of the ventral nerve cord . It plays a role in synaptogenesis by regulating synaptic vesicle accumulation at GABAergic and cholinergic neuromuscular junctions . The N-terminal cadherin domains are represented by

.
AIR9, PH-like domain (PH_AIR9)
Type: Domain

This is a PH-like domain found at the C-terminal of AIR9 from Arabidopsis thaliana and similar proteins from plants that often have 9/11 repetitions of

. It may adopt a partly opened β-barrel topology that is capped by an α-helix. Interaction between AIR9 and POK1 is important for division plane orientation and plant growth in Arabidopsis thaliana .
Centrosomal protein of 76 kDa, C-terminal (CEP76_C)
Type: Domain

This entry represents a domain found at the C-terminal of centrosomal protein of 76 kDa, a protein involved in regulation of centriole duplication to limit centriole duplication to once per cell cycle by preventing centriole reduplication . This domain may adopt a fold similar to the CAP domain. This entry also includes CC2D2A/B from human. CC2D2A is a component of the tectonic-like complex, a complex localised at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. It is required for ciliogenesis and sonic hedgehog/SHH signalling .

This domain is also found in C2 domain-containing proteins TgDOC22 and PfDOC21 from T. gondii and P. falciparum, respectively, which regulate the microneme secretion .
CEP76, N-terminal (CEP76_N)
Type: Domain

This entry represents a domain found at the N-terminal of centrosomal protein of 76 kDa, a protein involved in regulation of centriole duplication to limit centriole duplication to once per cell cycle by preventing centriole reduplication .
CEP76/DRC7, peptidase-like domain (CEPT76/DRC7_peptidase-like_dom)
Type: Domain

This entry represents a domain found in the middle of centrosomal protein of 76 kDa, a protein involved in regulation of centriole duplication to limit centriole duplication to once per cell cycle by preventing centriole reduplication . This domain is also found towards the C-terminal of C2D2A/B, and in dynein regulatory complex subunit 7 (DRC7). C2D2A is a component of the tectonic-like complex, a complex localised at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. It is required for ciliogenesis and sonic hedgehog/SHH signalling . DRC7 is a component of the nexin-dynein regulatory complex (N-DRC) a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes . In DRC7, this model covers the C-terminal part of the domain as it has an insertion not present in the other members of the entry. This domain is may adopt a fold related to peptidases.
Dynein regulatory complex subunit 7, MORN domain (MORN_DRC7)
Type: Domain

Dynein regulatory complex subunit 7 (DRC7) is a component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes . In humans, defective ciliary motility can lead to male infertility and a congenital disorder called primary ciliary dyskinesia (PCD), in which impaired clearance of mucus by the cilia causes chronic respiratory infections . This entry represents the MORN-repeats domain.
Dynein regulatory complex subunit 7, C-terminal (DRC7_C)
Type: Domain

Dynein regulatory complex subunit 7 (DRC7) is a component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes . In humans, defective ciliary motility can lead to male infertility and a congenital disorder called primary ciliary dyskinesia (PCD), in which impaired clearance of mucus by the cilia causes chronic respiratory infections . This entry represents the C-terminal domain, which consists of two α-helices.
CERLI1-like, PH domain (PH_CERLI1)
Type: Domain

This entry represents a PH domain that is found in the Rhoptry Surface Protein CERLI1 family. The Rhoptry Surface Protein CERLI1 family is essential for merozoite invasion of host cells, a critical step in the life cycle of the parasite Plasmodium falciparum. Members of the family control rhoptry secretion, which is pivotal for the successful invasion of host erythrocytes . The family proteins bind to specific lipids, including phosphatidic acid (PA) and phosphatidylinositol 4,5-bisphosphate (PIP2), suggesting a role in assembling the machinery that docks or primes the rhoptry to the parasite cell membrane prior to fusion with the host cell membrane . The cooperation between the C2 domain, which does not bind calcium, and the PH domain within these proteins is crucial for lipid binding and function.
CFAP184, CAP-like domain (CAP-like_CFAP184)
Type: Domain

This entry represents a domain whose function is unknown found in Cilia- and flagella-associated protein 184 (also known as CCDC96,

) from Tetrahymena thermophila and similar sequences. CFAP184 forms a complex with CFAP263, and acts as a regulator of ciliary beating that connects radial spoke 3 (RS3) to the inner dynein arm (IDA) and the nexin-dynein regulatory complex (N-DRC) . This domain may have a CAP-like (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins) fold according to structure predictions and comparison.
CFAP184, CBM-like domain (CBM-like_CFAP184)
Type: Domain

This entry represents a domain of unknown function found in Cilia- and flagella-associated protein 184 (also known as CCDC96,

) from Tetrahymena thermophila and similar sequences. CFAP184 forms a complex with CFAP263, and acts as a regulator of ciliary beating that connects radial spoke 3 (RS3) to the inner dynein arm (IDA) and the nexin-dynein regulatory complex (N-DRC) . This domain may have a CBM-like (carbohydrate-binding module) fold according to structure predictions and comparison.
Cfap43, N-terminal domain (Cfap43_N)
Type: Domain

This entry represents the first β-propeller domain found at the N-terminal of Cfap43 from Trypanosoma sp, and similar sequences from lower eukaryotes, according to structural prediction. These proteins are essential for flagellar function and, consequently, cell proliferation in T. brucei .

Cfap43 is an evolutionarily conserved protein which contains two β-propellers at its N-terminal and 6 low/high probability coiled-coils at its C-terminal. Cfap43 is involved in sperm flagellum axoneme organisation and function and in the regulation of the beating frequency of motile cilia on the epithelial cells of the respiratory tract .
Cfap43, second beta-propeller domain (Beta-prop_Cfap43_2nd)
Type: Domain

This entry represents the second β-propeller domain found in Cfap43 protein from Trypanosoma brucei brucei and related sequences mainly from Kinetoplastids. This protein is located between the doublet microtubules 5 and 6 and associated with the axoneme along the paraflagellar rod .

Cfap43 is an evolutionarily conserved protein which contains two β-propellers at its N-terminal and 6 low/high probability coiled-coils at its C-terminal. Cfap43 is involved in sperm flagellum axoneme organisation and function and in the regulation of the beating frequency of motile cilia on the epithelial cells of the respiratory tract .
AlkZ related (AlkZ-rel)
Type: Family

This entry represents uncharacterised bacterial proteins that have similarity to AlkZ-like proteins

. AlkZ adopts a unique fold in which three tandem winged helix-turn-helix (HTH) motifs scaffold a positively charged concave surface shaped for binding to duplex DNA . In contrast, the members of this family contain two instead of three tandem HTH motifs. They still probably retain the basic interface to bind DNA, however it is unclear whether these proteins possess enzymatic activity.
CFAP61, dimerisation domain (CFAP61_dimer)
Type: Domain

This entry represents a domain found at the C-terminal of the FAD reductase domain of cilia and flagella associated protein 61 (CFAP61), which may be involved in dimerisation. CFAP61 is located at the midpiece of the sperm, where it apparently functions in flagellum formation .
Alpha-amylase SusG-like, C-terminal domain (SusG-like_C)
Type: Domain

This entry represents the C-terminal domain found in the starch utilization system protein G (SusG) from bacteria. SusG forms part of the SusDEFG lipoprotein complex tethered to the outer surface of the cell and is involved in starch hydrolysis and subsequent utilization of the resulting sugars as an energy source . SusG has been shown to have enzymatic starch-hydrolysing activity . This entry also represents the C-terminal domain of other oligo-1,6-glucosidases, such as the trehalose-6-phosphate hydrolase TreA, Palatinase (PalQ) and Oligo-1,6-glucosidase 1 (MalL) from bacteria. The function of this domain is unknown.
Alpha-glucan water dikinase-like, N-terminal Ig-like domain (GWD-like_N_Ig)
Type: Domain

This domain is found twice in the N-terminal region of alpha-glucan water dikinases (GWD) from plants including alpha-glucan water dikinase 1 (GWD1) from Arabidopsis thaliana and related plant proteins such as alpha-amylase 3 (AMY3).

GWD1 is involved in the incorporation of phosphate into starch-like alpha-glucan, with preferred C-6 position of glucose units. It acts as an overall regulator of starch mobilization and it is required for starch degradation . AMY3 is involved in the determination of the final structure of glucans by shortening long linear phospho-oligosaccharides in the chloroplast stroma. This enzyme can function on both soluble and insoluble glucan substrates to release small linear and branched malto-oligosaccharides .

The domain represented by this entry is predicted to adopt a globular structure with an Ig-like topology. This domain is distantly related to CBM98 carbohydrate-binding family and is found associated with

in many members of this group.
ATP-dependent helicase CHD1-2/hrp3, HTH domain (CHD1-2/Hrp3_HTH)
Type: Domain

This domain is found in ATP-dependent helicase hrp3 (Hrp3) from Schizosaccharomyces pombe and Chromodomain-helicase-DNA-binding protein 1 and 2 (CHD1-2) from eukaryotes. Hrp3 is involved in heterochromatin silencing. It is predicted to adopt an HTH structure and is often found C-terminal to

.