SII-SWORD/CoKE huggingface dataset:
Glabrous enhancer-binding protein-like, C-terminal domain (GeBP-like_C)
Type: Domain

This entry represents the C-terminal domain present in GLABROUS1 enhancer-binding protein (GeBP) and GeBP-like proteins, such as storekeeper and storekeeper-like (STKL) transcription factors. GeBP and GeBP-like proteins play a redundant role in cytokinin hormone pathway regulation . Storekeeper was identified as a B-box motif binding factor that regulates expression of patatin, a storage protein in potato . Storekeeper-like transcription factors STKL1 and STKL2 function as transcription factors in the glucose signalling pathway .
HTTM domain (HTTM_dom)
Type: Domain

This entry represents the HTTM (for horizontally transferred transmembrane) domain found at the N-terminal in metazoan Vitamin K-dependent gamma-carboxylase and in diverse domain architectures in bacterial proteins. This domain contains four transmembrane regions .

This domain is also found in Sporulation-delaying protein SdpB which is required for the maturation of SdpC to SDP .
Vitamin K-dependent gamma-carboxylase, lumenal domain (VKGC_lumenal_dom)
Type: Domain

Using reduced vitamin K, oxygen, and carbon dioxide, gamma-glutamyl carboxylase (VKGC) post-translationally modifies certain glutamates by adding carbon dioxide to the gamma position of those amino acids. In vertebrates, the modification of glutamate residues of target proteins is facilitated by an interaction between a propeptide present on target proteins and the gamma-glutamyl carboxylase . This entry represents the lumenal domain found in animals and bacteria. This domain is associated with the HTTM domain (

) .
Wntless, GOLD domain (WLS_GOLD)
Type: Domain

This entry represents the GOLD domain from wntless (WLS) proteins.

WLS are membrane trafficking and secretion chaperones for lipidated Wnt signaling proteins. They are homologous to GPR180, TMEM145, and TMEM181, which have been described as GOST proteins (for GOLD domain seven-transmembrane helix proteins) together with TMEM87A/B, GPR107, and GPR108, as they share the same domain architecture consisting of a GOLD domain atop of a membrane-spanning seven-transmembrane helix domain .
GOST, seven transmembrane domain (GOST_TM)
Type: Domain

This entry represents the transmembrane domain of a group of related proteins that share the same domain architecture, termed GOST (GOLD domain seven-transmembrane helix) proteins, including TMEM87A/B, GPR107/GPR108 from human and the homologues from yeast, PTM1 . This entry also includes plant proteins, CAND6/7 . Some members of this entry, such as TMEM87A/B, do not signal as a GPCR.
PTM1-like, N-terminal domain (PTM1-like_N)
Type: Domain

This entry represents the N-terminal domain of fungal proteins, such as PTM1 from S.cerevisiae and its closely homologues from S.pombe. They have been identified as orthologues of TMEM87A/B from human. Structure predictions suggest that these proteins has the same domain architecture as GOST (GOLD seven-transmembrane helix) proteins consisting of a GOLD domain atop of a membrane-spanning seven-transmembrane helix domain this domain .

This domain represents the GOLD domain. Members of this entry localise to the Golgi and early endosomes; the function is unknown .
UTP25, C-terminal domain (UTP25_C)
Type: Domain

UTP25 is a family of eukaryotic proteins. The family displays limited sequence similarity to DEAD-box RNA helicases, having alternative residues at the Walker A and DEAD-box sites, but conservation of structural and other key residues . This entry represents the C-terminal domain that is required and sufficient for the interaction of Utp25 with Utp3. UTP25 interacts with nucleolar protein Nop19 in S. cerevisiae, and Nop19p is essential for the incorporation of Utp25p into pre-ribosomes . Proteins in this entry consist of two domains; the C-terminal one is represented in this model.
UTP25, NTP hydrolase-like domain (UTP25_NTPase-like)
Type: Domain

UTP25 (U3 small nucleolar RNA-associated protein 25) is a DEAD-box RNA helicase-like protein component of the ribosomal small subunit processome for the biogenesis of ribosomes, which functions in pre-ribosomal RNA (pre-rRNA) processing . U3 small nucleolar RNA-associated protein 25 homologue (UTP25, also known as Digestive organ expansion factor (DEF)) from animals is essential for embryonic development in part through the regulation of p53 pathway and controls the expansion growth of digestive organs and liver . UTP25 mediates, with CAPN3, the proteasome-independent degradation of p53/TP53 . These proteins display limited sequence similarity to DEAD-box RNA helicases, having alternative residues at the Walker A and DEAD-box sites, but conservation of structural and other key residues .

Members of this entry consist of two domains; this entry represents the bigger one, towards the N-terminal which is structurally related to NTPases, lacking the conserved motifs typically found in helicases (WalkerA/B motifs and motif Q). The C-terminal domain is represented in

and is required and sufficient for the interaction of UTP25 with Utp3. UTP25 interacts with nucleolar protein Nop19 in S. cerevisiae, and Nop19p is essential for the incorporation of Utp25p into pre-ribosomes .
Csm6, HEPN domain (Csm6_HEPN)
Type: Domain

This entry represents the HEPN domain of CRISPR system endoribonuclease Csm6 from Enterococcus italicus and similar bacterial sequences. Csm6 is a Cas (CRISPR-associated) protein from type III-A CRISPR-Cas system. It consists of a CARF domain at the N-terminal (

), a six-helix domain and a C-terminal HEPN domain at the C-terminal, which has RNase activity .
Ribosomal RNA large subunit methyltransferase K/L-like, conserved site (RlmKL-like_Mtase_CS)
Type: Conserved_site

This entry represents a conserved site found in ribosomal RNA large subunit methyltransferase K/L from Escherichia coli (RmlKL) and related proteins. RmlKL specifically methylates the guanine in positions 2445 and 2069 of 23S rRNA before its assembly into 50S subunits . This conserved site is defined by a D-P-[LIVMF]-C-G-[ST]-G-x(3)-[LI]-E conserved motif located within the methyltransferase domain.
Shieldin complex subunit 2, second OB fold domain (SHLD2_OB2)
Type: Domain

This entry represents the second OB fold domain found in the middle of Shieldin complex subunit 2 (SHLD2, formerly known as FAM35A) and in similar sequences mainly found in vertebrates. SHLD2 is a component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs) . In some homologues, this domain has undergone changes and decay and have lost the barrel-like shape.
Phosphoinositide phospholipase C beta 1-4-like, EF-hand domain (PLCB1-4-like_EFh)
Type: Domain

This entry represents the first EF-hand domain found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-4 (PLCB1-4) from human and related animal proteins. PLC-beta isoforms mediate the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) to propagate signals for several physiological responses .
YscD-like, Bon-like domain 3 (YscD_ppl_3rd)
Type: Domain

This entry represents the third of three periplasmic BON domains.

YscD is a single-pass inner membrane protein required for the export process of the Yop proteins. It is an essential component of the type III secretion system. YscD contains an N-terminal cytoplasmic domain (

), a transmembrane linker and a large periplasmic region formed by the three BON domains (

), (

) and (

). YscD forms part of the inner membrane component of the bacterial type III secretion injectosome apparatus .
YscD-like, Bon-like domain 2 (YscD_ppl__2nd)
Type: Domain

This entry represents the second of three periplasmic BON domains in YscD proteins from proteobacteria.

YscD is a single-pass inner membrane protein required for the export process of the Yop proteins. It is an essential component of the type III secretion system. YscD contains an N-terminal cytoplasmic domain (

), a transmembrane linker and a large periplasmic region formed by the three BON domains (

), (

) and (

). YscD forms part of the inner membrane component of the bacterial type III secretion injectosome apparatus .
SBE2/SBE22, N-terminal domain (SBE2/SBE22_N)
Type: Domain

This entry represents a domain found at the N-terminal of SBE2 and its paralogue, SBE22 from budding yeast. These proteins are involved in bud growth and yeast cell wall formation . They may be also involved in the transport of cell wall components from the Golgi apparatus to the cell surface periphery .
SBE2/SBE22, middle domain (SBE2/SBE22_M)
Type: Domain

This entry represents a domain found central in SBE2, its paralogue, SBE22 from budding yeast, and similar proteins from ascomycetes. These proteins are involved in bud growth and yeast cell wall formation . They may be also involved in the transport of cell wall components from the Golgi apparatus to the cell surface periphery .
CAP, N-terminal domain (CAP_N)
Type: Domain

Cyclase-associated proteins (CAPs) are highly conserved actin-binding proteins present in a wide range of organisms including yeast, fly, plants, and mammals. CAPs are multifunctional proteins that regulate actin remodelling in response to cellular signals . They consist of an N-terminal conserved motif (

) followed by an N-terminal and C-terminal (

) domains which are separated by a Pro-rich region.

This entry represents the N-terminal domain which contains the adenylyl cyclase binding site and has an all-α structure consisting of six helices in a bundle with a left-handed twist and up-and-down topology .
K+ potassium transporter, integral membrane domain (K_trans_N)
Type: Domain

This is a family of K+ potassium transporters that are conserved across phyla, including bacterial (KUP) , yeast (HAK) , and plant (AtKT) . This entry represents the N-terminal integral membrane domain.
K+ potassium transporter, C-terminal domain (K_trans_C)
Type: Domain

This is a family of K+ potassium transporters that are conserved across phyla, including bacterial (KUP)

, yeast (HAK)

, and plant (AtKT)

. This entry represents the C-terminal non-membrane domain.
Siroheme decarboxylase NirL-like, HTH domain (NirdL-like_HTH)
Type: Domain

This entry represents the helix-turn-helix (HTH) domain found in siroheme decarboxylase NirdL from Hydrogenobacter thermophilus and related sequences, from bacteria and archaea . NirdL is involved in heme d1 biosynthesis. It catalyses the decarboxylation of siroheme into didecarboxysiroheme.
Domain of unknown function DUF7023 (DUF7023)
Type: Domain

This domain is found in human Protein dispatched homolog 3 (DISP3) and related proteins mainly from vertebrates. DISP3 (PTCHD2), a sterol-sensing domain- containing protein, is highly expressed in neural tissue, promotes cell proliferation and alters expression of genes that are involved in tumorigenesis. The function of this domain is unknown.
Csm6, CARF domain (Csm6_CARF)
Type: Domain

This entry represents the CARF domain of CRISPR system endoribonuclease Csm6 from Enterococcus italicus and similar bacterial sequences. Csm6 is a Cas (CRISPR-associated) protein from type III-A CRISPR-Cas system. It consists of a CARF domain at the N-terminal, a six-helix domain and a C-terminal HEPN domain at the C-terminal (

). This domain is a ring nuclease .
NPC1, middle luminal domain (NPC1_MLD)
Type: Domain

NPC intracellular cholesterol transporter 1 (NPC1) is a endosomal/lysosomal membrane protein that facilitates the trafficking of cholesterol and other cargo from lysosomes and is involved in cholesterol homeostasis . Mutations in the NPC1 gene cause the rare neurodegenerative disease Niemann-Pick Type C (NPC). This entry represents the middle luminal domain (MLD) of NPC1, which contains the Ebola glycoprotein interacting site .
DUF2089, zinc ribbon (DUF2089_Zn_ribbon)
Type: Domain

This entry represents the zinc ribbon found at the N-terminal of a group of hypothetical prokaryotic proteins that often contain (

). In some members, it occurs as a fusion of ZnR+HTH+SHOCT-like.
HMGCR/SNAP/NPC1-like, sterol-sensing domain (HMGCR/SNAP/NPC1-like_SSD)
Type: Domain

This entry represents the sterol-sensing domain found in a group of proteins related to cholesterol metabolism and transport, such as HMG-CoA reductase (HMGCR), Sterol regulatory element-binding protein cleavage-activating protein (SCAP), NPC1, patched and related proteins, which are membrane-bound transcription factors that promote lipid synthesis in animal cells . They are embedded in the membranes of the endoplasmic reticulum (ER) in a helical hairpin orientation and are released from the ER by a two-step proteolytic process . SCAP is a key player in the sterol regulatory element-binding protein (SREBP) pathway that controls the cellular homeostasis of sterol, HMGCR catalyses the rate-limiting step of cholesterol synthesis, and NPC1 is essential for cholesterol egress from the lysosomes and late endosomes to other cellular compartments .

The sterol-sensing domain plays a regulatory role and belongs to a larger transmembrane region that traverses the membrane eight times .
YvlB, N-terminal domain (YvlB_N)
Type: Domain

This entry represents a small domain found at the N-terminal of the uncharacterised protein YvlB from Bacillus subtilis, the putative adhesin domain-containing protein LiaX from Enterococcus faecalis and similar prokaryotic sequences. In some members, this domain occurs as a fusion of ZnR+DUF2089-HTH+SHOCT-like, where it is found at the C-terminal of DUF2089 (

). LiaX from is involved in cell membrane remodeling, perhaps acting by negative modulation of the liaFSR and liaXYZ gene clusters, thereby regulating content and localization of anionic phospholipids . It binds to the antibiotic daptomycin (DAP) and to cationic antimicrobial peptides, such as human LL-37, likely functioning as a sensor that activates the cell envelope stress response .
XRCC4, N-terminal domain (XRCC4_N)
Type: Domain

This represents the N-terminal β-sandwich domain of a family consisting of several eukaryotic DNA double-strand break repair and V(D)J recombination protein XRCC4 sequences. In the non-homologous end joining pathway of DNA double-strand break repair, the ligation step is catalysed by a complex of XRCC4 and DNA ligase IV. It is thought that XRCC4 and ligase IV are essential for alignment-based gap filling, as well as for final ligation of the breaks .

DNA repair protein XRCC4 is a DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination . It acts as a scaffold protein that regulates recruitment of other proteins to DNA double-strand breaks . XRCC4 plays a key role in the NHEJ ligation step of the broken DNA during DSB repair via direct interaction with DNA ligase IV (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap filling is completed .
XRCC4, coiled-coil domain (XRCC4_CC)
Type: Domain

This entry represents the dimeric coiled-coil region from the XRCC4 protein. The complex of two proteins, XRCC4 and DNA ligase IV, plays a fundamental role in DNA non-homologous end joining (NHEJ), a cellular function required for double-strand break repair and V(D)J recombination . The BRCT domains of DNA ligase IV bind to this region.

DNA repair protein XRCC4 is a DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination . It acts as a scaffold protein that regulates recruitment of other proteins to DNA double-strand breaks . XRCC4 plays a key role in the NHEJ ligation step of the broken DNA during DSB repair via direct interaction with DNA ligase IV (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap filling is completed .
XRCC4, C-terminal domain (XRCC4_C)
Type: Domain

This entry represents the C-terminal disordered region from the XRCC4 protein. This domain acts as an activator of the phospholipid scramblase activity of XKR4 . Upon apoptotic stimuli, XRCC4 is cleaved by caspases, and its C-terminal fragment with an intrinsically disordered region is released into the cytoplasm. This fragment interacts directly with the Xkr4 dimer to activate it .

DNA repair protein XRCC4 is a DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination . It acts as a scaffold protein that regulates recruitment of other proteins to DNA double-strand breaks . XRCC4 plays a key role in the NHEJ ligation step of the broken DNA during DSB repair via direct interaction with DNA ligase IV (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap filling is completed .
Integrator complex subunit 1, R3 domain (INT1_R3)
Type: Domain

Integrator (INT) complex is involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. It binds the C-terminal domain (CTD) of RNA polymerase II (Pol II) and functions as an RNA endonuclease to cleave different classes of RNAs, regulating the transcription of both protein-coding genes and noncoding elements . Integrator also associates with protein phosphatase 2A (PP2A) core enzyme to form the INTAC complex which regulates transcription through dephosphorylation of Pol II CTD.

This entry includes the Integrator complex subunit 1 (INTS1), which forms the backbone module of the complex (it consists of four modules: backbone, shoulder, phosphatase and endonuclease) through the association with INTS2 and INTS7 to form a rigid scaffold. The backbone and shoulder modules form a central cruciform scaffold. INTS1 contains four repetitive helix hairpin domains towards the C-terminal (R1-R4); this entry represents the R3 domain .
Integrator complex subunit 1, R4 domain (INTS1_R4)
Type: Domain

Integrator (INT) complex is involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. It binds the C-terminal domain (CTD) of RNA polymerase II (Pol II) and functions as an RNA endonuclease to cleave different classes of RNAs, regulating the transcription of both protein-coding genes and noncoding elements . Integrator also associates with protein phosphatase 2A (PP2A) core enzyme to form the INTAC complex which regulates transcription through dephosphorylation of Pol II CTD.

This entry includes the Integrator complex subunit 1 (INTS1) which forms the backbone module of the complex (it consists of four modules: backbone, shoulder, phosphatase and endonuclease) through the association with INTS2 and INTS7 to form a rigid scaffold. The backbone and shoulder modules form a central cruciform scaffold. INTS1 contains four repetitive helix hairpin domains towards the C-terminal (R1-R4); this entry represents R4 domain .
Integrator complex subunit 1, INTS2-binding domain (INTS1_INTS2-bd)
Type: Domain

Integrator (INT) complex is involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. It binds the C-terminal domain (CTD) of RNA polymerase II (Pol II) and functions as an RNA endonuclease to cleave different classes of RNAs, regulating the transcription of both protein-coding genes and noncoding elements . Integrator also associates with protein phosphatase 2A (PP2A) core enzyme to form the INTAC complex which regulates transcription through dephosphorylation of Pol II CTD.

This entry includes the Integrator complex subunit 1 (INTS1) which forms the backbone module of the complex (it consists of four modules: backbone, shoulder, phosphatase and endonuclease) through the association with INTS2 and INTS7 to form a rigid scaffold. The backbone and shoulder modules form a central cruciform scaffold. INTS1 is an all-α helical protein with four repetitive helix hairpin domains towards the C-terminal (R1-R4) . This entry represents a domain found in the middle region of INTS1, after

, which interacts with the INTS2 subunit .
Flagellar hook protein FlgE/F/G-like, D1 domain (LlgE_F_G-like_D1)
Type: Domain

This entry represents the D1 domain found in three closely related flagellar proteins, usually denoted FlgE, FlgF and FlgG and related proteins. In FlgE, there is an additional domain D2 (

) outside D1 . The flagellar hook is a short, highly curved tubular structure that connects the flagellar motor to the long filament acting as a helical propeller.
BF9343_1606-like, C-terminal (BF9343_1606-like_C)
Type: Domain

This domain is found at the C-terminal of BF9343_1606 from Bacteroides fragilis (

). This domain, whose structure has been solved (

), is associated with

.
Gag1-like, lock domain (Lock_Gag1-like)
Type: Domain

This domain found in Gag1 from Saccharomyces cerevisiae and similar fungal sequences. Gag1 interacts with Cka2, the fourth subunit of the eukaryotic kinase CK2. This protein is organised into three domains: lock (this entry), Gag and Clamp (

) . This short domain is predicted to adopt a predominantly α-helical configuration.
RavZ, PI3P-binding domain (RavZ_C)
Type: Domain

The intracellular pathogen Legionella pneumophila interferes with autophagy by delivering an effector protein, cysteine protease RavZ, into the host cytosol. This effector protein cleaves membrane-conjugated Atg8/LC3 proteins from pre-autophagosomal structures . RavZ is a two domain protein consisting of an N-terminal catalytic domain and a C-terminal phosphatidylinositol 3-phosphate (PI3P)-binding domain, the latter is represented in this entry . RavZ targets the autophagosome via the PI3P-binding domain.
CofB-like, beta-repeat domain (CofB-like_b-rpt_dom)
Type: Domain

CofB is a minor pilin involved in type IV pili assembly. It consists of a pilin domain at the N-terminal (

), followed by a β-repeat hinge-like domain and a C-terminal β-sheet-rich lectin domain . This entry represents the central β-repeat domain which has two three-stranded anti-parallel β-sheets .
CofB, C-terminal domain (CofB_C)
Type: Domain

CofB is a minor pilin involved in type IV pili assembly. It consists of a pilin domain at the N-terminal (

), followed by a β-repeat hinge-like domain (

) and a C-terminal β-sheet-rich domain, similar to H-type lectins . This entry represents the C-terminal domain which is required for CofB to initiate pilus assembly .
Endoplasmic reticulum metallopeptidase 1-like, C-terminal domain (ERMP1-like_C)
Type: Domain

Endoplasmic reticulum metallopeptidase 1 (ERMP1, also known as Felix-ina, FXNA or Fxna peptidase) is a multi-pass membrane protein located in the endoplasmic reticulum membrane. In humans, it may play a crucial role in processing proteins required for the organisation of somatic cells and oocytes into discrete follicular structures, although which proteins are hydrolysed has not yet been determined .

According to AlphaFold structure predictions, these proteins consist of a M28 peptidase domain (

), a TM domain and a C-terminal elongated banana-shaped all β-sheet domain (represented in this entry), structurally similar to the Mu homology domain (

), a protein-protein interaction module found in endocytic proteins involved in clathrin-mediated endocytosis .
Endoplasmic reticulum metallopeptidase 1/1-A, TM domain (ERMP1_1-A_TM)
Type: Domain

Endoplasmic reticulum metallopeptidase 1 (ERMP1, also known as Felix-ina, FXNA or Fxna peptidase) is a multi-pass membrane protein located in the endoplasmic reticulum membrane. In humans, it may play a crucial role in processing proteins required for the organisation of somatic cells and oocytes into discrete follicular structures, although which proteins are hydrolysed has not yet been determined .

According to AlphaFold structure predictions, these proteins consists of a M28 peptidase domain (

), a transmembrane (TM) domain and a C-terminal elongated banana-shaped, all β-sheet domain (

) structurally similar to the Mu homology domain (

, based on structure comparisons). This entry represents the TM domain.