SII-SWORD/CoKE huggingface dataset:
5'-3' DNA helicase ZGRF1-like, N-terminal domain (ZGRF1-like_N)
Type: Domain

This domain can be found at the N-terminal end of human 5'-3' DNA helicase ZGRF1 and similar eukaryotic proteins. ZGRF1 promotes repair of replication-blocking DNA lesions through stimulation of homologous recombination (HR) . This domain can also be found in Mte1 (Mph1-associated telomere maintenance protein 1) from Saccharomyces cerevisiae (also known as YGR042W), which is involved in telomere maintenance and in and fission yeast Dbl2 (C553.01c), involved in in meiotic chromosome segregation .

Mte1 is a D-loop-binding protein that interacts and stimulates the helicase and fork regression activities of Mph1 while inhibiting the ability of Mph1 to dissociate recombination intermediates. Mph1 and Mte1 interdependently colocalise at DNA damage-induced foci and dysfunctional telomeres. Mte1 is indicated to play a role in regulation of crossover recombination, response to replication stress, and telomere maintenance . The fission yeast, Dbl2 is needed for cellular resistance to the topoisomerase I poison camptothecin, forms DNA damage-induced foci, and is needed for the optimal recruitment of Fml1 to DNA damage, while the human ZGRF1 protein has been linked to DNA cross-link repair and mutations of it have been found in a variety of human tumours .

Having said that, there is no evidence to suggest that this domain, which is predicted to adopt an all-β structure, is implicated in DNA damage resistance or nuclear focus formation .
Cryptic loci regulator 2, C-terminal (Tscrpt-silencing_Clr2_C)
Type: Domain

Clr2 (cryptic loci regulator) is a chromatin silencing protein, one of a quartet of proteins forming the core of SHREC, a multienzyme effector complex that mediates hetero-chromatic transcriptional gene silencing in fission yeast . Clr2 does not have any obvious well-conserved domains, but along with the other core proteins binds to the histone deacetylase Clr3. On its own it may also have a role in chromatin organisation at the cnt domain, the site of kinetochore assembly.

This entry represents the C-terminal domain of Clr2.
Protein of unknown function DUF2441 (DUF2441)
Type: Family

This is a family of highly conserved predicted proteins primarily found in Bacillus species. Structurally they form homo-dimers, but their function is unknown.
Protein of unknown function DUF2442 (DUF2442)
Type: Family

Several proteins in this family are annotated as being putative molybdopterin-guanine dinucleotide biosynthesis proteins, but this has not been confirmed. Members of this family also include proteins containing the N-terminal domain of the bacteria NE0471 protein. The function of these proteins is not known.
YkuI, C-terminal (YkuI_C)
Type: Domain

In most cases this highly conserved region of the YkuI protein lies immediately downstream of the EAL (diguanylate cyclase/phosphodiesterase) domain

so that together they form a monomer which dimerises for its enzymatic action. This region contains three α helices and five β strands and forms C-terminal half of the structure .
Utp8, beta-propeller (Utp8_b-prop)
Type: Domain

This entry represents the N-terminal β-propeller of U3 small nucleolar RNA-associated protein 8 from Saccharomyces cerevisiae (Utp8) and similar proteins mainly found in ascomycetes. Utp8 is an essential component of the nuclear tRNA export machinery in S. cerevisiae. It is a tRNA-binding protein that acts at a step between tRNA maturation /aminoacylation, and translocation of the tRNA across the nuclear pore complex . It is also co-purified with the U3 snoRNA containing complex, the small subunit (SSU) processome, which is required for the biogenesis of the 18S rRNA .

This entry also include the C1565.05 protein from Schizosaccharomyces pombe. Its function is not clear.
Nucleolar protein Dnt1-like, N-terminal (Dnt1-like_N)
Type: Domain

Cytokinesis in yeasts involves a family of proteins whose essential function is to bind Cdc14-family phosphatase and prevent this from being sequestered and inhibited in the nucleolus. This is the highly conserved N terminus of a family of proteins which act as cytokinesis checkpoint controls by allowing cells to cope with cytokinesis defects. These proteins are required for rDNA silencing and mini-chromosome maintenance .
Initiator binding domain (Initiator-bd)
Type: Domain

In Trichomonas vaginalis, thought to be the earliest extant eukaryote, the sole initiator element for control of the start of transcription is Inr, and this is recognised by the initiator binding protein IBP39. IBP39 contains an N-terminal Inr binding domain (IBD, represented by this entry) connected via a flexible, proteolytically sensitive, linker (residues 127-145) to a C-terminal domain. The IBD structure reveals a winged-helix-wing conformation with each element binding to DNA, the central helix-turn-helix contributing the majority of the specificity-determining contacts with the Inr core motif TCAPy(T/A). The binding of IBP39 to the Inr directly recruits RNA polymerase II and in this way initiates transcription .
RSE1/DDB1/CPSF1, first beta-propeller domain (Beta-prop_RSE1/DDB1/CPSF1_1st)
Type: Domain

This entry represents the β-propeller found towards the N-terminal of RSE1/SF3B3/DDB1/CPSF1/CFT1 proteins from eukaryotes, which share a domain architecture consisting of three β-propellers. Members of the family have diverse functions, primarily related to RNA/DNA binding. Pre-mRNA-splicing factor RSE1 plays an important role in the spliceosome, a complex that removes introns from pre-mRNAs . Its orthologue, splicing factor 3B subunit 3 (SF3B3) also forms part of the U2 small nuclear ribonucleoprotein particle (snRNP) and has been identified as part of the SAGA transcriptional coactivator complex in Drosophila melanogaster . Also included in this entry is DNA damage-binding protein 1 (DDB1), which is both involved in the recognition and repair of UV-induced DNA damage, as part of the UV-DDB complex, and in protein ubiquitination, as part of the DCX (DDB1-CUL4-X-box) complex . Additionally, this family includes cleavage and polyadenylation specificity factor subunit 1 (CPSF1) and its orthologue protein CFT1, both involved in the cleavage and polyadenylation of pre-mRNAs .
Monopolin complex, subunit Mam1 (Monopolin_cplx_su_Mam1)
Type: Family

Monopolin is a protein complex, originally identified in Saccharomyces cerevisiae (Baker's yeast), that is required for the segregation of homologous centromeres to opposite poles of a dividing cell during meiosis I . MAM1 is required in S. cerevisiae for monopolar attachment .
WIYLD domain (WIYLD_domain)
Type: Domain

This entry represents the plant-specific WIYLD domain, named based on the pattern of the most conserved residues . This is a ubiquitin-binding domain that adopts a four-helix bundle structure, in contrast to the three-helix bundles of other ubiquitin binding domains. It is found in histone-lysine N-methyltransferase SUVR4 and related proteins SUVR1 and SUVR2. SUVR4 is an active histone methyltransferase with a preference for H3K9me1 and ubiquitin binding mediated by this domain facilitates the addition of two methyl groups to monomethylated lysine 9 of histone H3 . SUVR2 has no histone methyltransferase activity and is involved in transcriptional gene silencing . SUVR2 forms a complex with SUVR1 and associates with the SNF2-related chromatin-remodeling proteins. No histone methyltransferase activity has been detected for SUVR1 neither .
Nucleolar 27S pre-rRNA processing, Urb2/Npa2, C-terminal (Urb2/Npa2_C)
Type: Domain

This entry represents a conserved domain found towards the C terminus of proteins involved in ribosome biogenesis, such as the Urb2 protein from yeast .
Mitochondrial escape protein 2, C-terminal (Mt_escape_2_C)
Type: Domain

Mitochondrial escape protein 2 (also known as RNA12) plays a role in maintaining the mitochondrial genome and in controlling mtDNA escape . It is also involved in the regulation of mtDNA nucleotide structure and number . Additionally, this protein have a dispensable role in the early maturation of pre-rRNA . This domain is C-terminal to the RRM domain and includes a P-loop motif suggesting this domain may bind to NTP.
Borealin, N-terminal (Borealin_N)
Type: Domain

This entry represents the N-terminal domain of borealin, a component of the chromosomal passenger complex (CPC), which acts as a key regulator of mitosis .
Protein of unknown function DUF2456 (DUF2456)
Type: Family

This entry represents a family of uncharacterised proteins.
Protein of unknown function DUF2457 (DUF2457)
Type: Family

This entry represents a family of uncharacterised proteins.
Proteasome chaperone 3/4 (Psome_chaperone_3/4)
Type: Family

This entry represents the fungal 20S proteasome chaperones 3 and 4 (also known as DMP1 and DMP2), which function in early 20S proteasome assembly. The structures of these chaperones have been solved, and they closely resemble that of the mammalian proteasome assembling chaperone PAC3, although there is little sequence similarity between them .
Proteasome chaperone 1, fungi (Psome_chaperone_1_fun)
Type: Family

This entry represents fungal proteosome chaperone 1, a chaperone of the 20S proteasome which functions in early 20S proteasome assembly .
CST complex subunit Stn1, N-terminal (Stn1_N)
Type: Domain

The budding yeast protein Stn1 is a DNA-binding protein which has specificity for telomeric DNA. Structural profiling has predicted an OB-fold . This entry represents the N-terminal part of the molecule, which adopts the OB fold. Protection of telomeres by multiple proteins with OB-fold domains is conserved in eukaryotic evolution .
TORC1 complex, subunit TCO89 (TORC1_cplx_su_TCO89)
Type: Family

TC089 is a component of the TORC1 complex. TORC1 is responsible for a wide range of rapamycin-sensitive cellular activities .
Protein of unknown function DUF2458 (DUF2458)
Type: Family

This entry represents a family of uncharacterised proteins.
BAR domain-containing family (BAR_dom-cont)
Type: Family

Endocytosis and intracellular transport involve several mechanistic steps:

For the internalisation of cargo molecules, the membrane needs to bend to form a vesicular structure, which requires membrane curvature and a rearrangement of the cytoskeleton;

Following its formation, the vesicle has to be pinched off the membrane;

The cargo has to be subsequently transported through the cell and the vesicle must fuse with the correct cellular compartment.

Members of the Amphiphysin protein family are key regulators in the early steps of endocytosis, involved in the formation of clathrin-coated vesicles by promoting the assembly of a protein complex at the plasma membrane and directly assist in the induction of the high curvature of the membrane at the neck of the vesicle. Amphiphysins contain a characteristic domain, known as the BAR (Bin-Amphiphysin-Rvs)-domain, which is required for their
in vivo
function and their ability to tubulate membranes .

The crystal structure of these proteins suggest the domain forms a crescent-shaped dimer of a three-helix coiled coil with a characteristic set of conserved hydrophobic, aromatic and hydrophilic amino acids. Proteins containing this domain have been shown to homodimerise, heterodimerise or, in a few cases, interact with small GTPases.

This entry identifies several fungal BAR domain-containing proteins, such as Gvp36, that are not detected by

.
Anaphase-promoting complex, subunit CDC26 (APC_suCDC26)
Type: Family

This entry represents subunit CDC26, whose exact function is not known .

The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome .
Transmembrane protein 201, C-terminal (TMEM201_C)
Type: Domain

TMEM201, also known as SAMP1, is a RanGTP binding transmembrane protein found in the inner nuclear membrane . It is functionally associated with the LINC complex protein Sun1 and proteins of the A-type lamina network .

This entry represents the C-terminal domain of TMEM201.
Eukaryotic translation initiation factor 4E binding protein (eIF4E-T)
Type: Family

This entry represents a group of eIF4E binding proteins, including eIF4E transporter (eIF4E-T) from mammals, cup protein from D. melanogaster and ifet-1 from C. elegans.

Protein cup functions in Smaug-mediated translational repression .

Ifet-1 is a broad-scale translational repressor in C. elegans .
Nucleoporin Nup188, N-terminal (Nucleoporin_Nup188_N)
Type: Domain

This protein folds into an extended stack of helices where the N-terminal forms a closed ring (subdivided into subdomains I-III in ) and the C-terminal forms a more regular, superhelical structure . This entry represents the N-terminal helical repeats from Nup188.

Nup188 is one of the many peptides that make up the nucleoporin complex (NPC), and is found across eukaryotes . The Nup188 subcomplex (Nic96p-Nup188p-Nup192p-Pom152p) is one of at least six that make up the NPC, and as such is symmetrically localised on both faces of the NPC at the nuclear end, being integrally bound to the C terminus of Pom34p .
Inactive serine/threonine-protein kinase 19-like (STK19-like)
Type: Family

This entry represents a group of eukaryotic proteins, including human Inactive serine/threonine-protein kinase 19 (STK19, also known as Winged helix repair factor 1, WHR1), a transcription-coupled repair factor required for nucleotide excision repair . It is unlikely to show intrinsic kinase activity as reported, but rather more likely to control NRAS activity via an associated kinase . The homologue from Schizosaccharomyces pombe (MUG51) has a role in meiosis .
Zinc-finger domain of monoamine-oxidase A repressor R1 (Znf-4CXXC_R1)
Type: Domain

R1 is a transcription factor repressor that inhibits monoamine oxidase A gene expression. This domain is a four-CXXC zinc finger putative DNA-binding domain found at the C-terminal end of R1. The domain carries 12 cysteines of which four pairs are of the CXXC type .
Cell division protein borealin (Cell_div_borealin)
Type: Family

The chromosomal passenger complex of Aurora B kinase, INCENP, and Survivin has essential regulatory roles at centromeres and the central spindle in mitosis. Cell division cycle-associated protein 8, also known as Borealin, is also a member of the complex. Approximately half of Aurora B in mitotic cells is complexed with INCENP, Borealin, and Survivin . Depletion of Borealin by RNA interference delays mitotic progression and results in kinetochore-spindle mis-attachments and an increase in bipolar spindles associated with ectopic asters .
Bcl2-associated agonist of cell death (BAD)
Type: Family

BAD is a Bcl-2 homology domain 3 (BH3)-only pro-apoptotic member of the Bcl-2 protein family that is regulated by phosphorylation in response to survival factors . Binding of BAD to mitochondria is thought to be exclusively mediated by its BH3 domain. Membrane localisation of BAD mediates membrane translocation of Bcl-XL. The C-terminal part of BAD is sufficient for membrane binding. There are two segments with differing lipid-binding preferences, LBD1 and LBD2, that are responsible for this binding: (i) LBD1 located in the proximity of the BH3 domain (amino acids 122-131) and (ii) LBD2, the putative C-terminal α-helix-5 . Phosphorylation-regulated 14-3-3 protein binding may expose the cholesterol-preferring LBD1 and bury the LBD2, thereby mediating translocation of BAD to raft-like micro-domains .
Tti2 family (Tti2)
Type: Family

This family includes budding yeast Tel2-interacting protein 2 (Tti2) and similar proteins from animals and fungi. Tti2 is a component of the tel2-tti1-tti2 (TTT) complex, which is involved in the cellular resistance to DNA damage stresses, like ionizing radiation (IR), ultraviolet (UV) and mitomycin C (MMC). Its homologue from humans, together with the TTT complex and HSP90, may participate in the proper folding of newly synthesised phosphatidylinositol 3-kinase-related protein kinase (PIKK) proteins . In fission yeast, it was shown that the TTT complex stabilizes protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins .
GLEYA adhesin domain (GLEYA_adhesin_domain)
Type: Domain

The GLEYA domain is related to lectin-like binding domains found in the Saccharomyces cerevisiae Flo proteins and the Candida glabrata Epa proteins . It is a carbohydrate-binding domain that is found in fungal adhesins (also referred to as agglutinins or flocculins) . Adhesins with a GLEYA domain possess a typical N-terminal signal peptide and a domain of conserved sequence repeats, but lack glycosylphosphatidylinositol (GPI) anchor attachment signals . They contain a conserved motif G(M/L)(E/A/N/Q)YA, hence the name GLEYA. Based on sequence homology, it is suggested that the GLEYA domain would predominantly contain β sheets . The GLEYA domain is also found in Schizosaccharomyces pombe protein

, thought to be a kinetochore protein (Sim4 complex subunit), however no direct evidence for kinetochore association has been found . Furthermore, a global protein localisation study in S. pombe identified it as a secreted protein localized to the Golgi complex .
Zn-cluster domain (Zn-cluster-dom)
Type: Domain

This zinc binding domain is found associated with the WRKY domain

.
KilA-N, DNA-binding domain (KilA-N_DNA-bd_domain)
Type: Domain

This entry represents an N-terminal DNA-binding domain found in a wide range of proteins from bacterial and eukaryotic DNA viruses and their bacterial homologues, they include the poxvirus D6R/N1R and baculoviral Bro protein families. The KilA-N domain is considered to be homologous to the fungal DNA-binding APSES domain. Both the KilA-N and APSES domains share a common fold with the nucleic acid-binding modules of the LAGLIDADG nucleases and the amino-terminal domains of the tRNA endonuclease .

This entry represents the amino-terminal domain of the Enterobacteria phage P22 antirepressor (

) . It is found associated with

.
Bacteriophage Mx8, p63, C-terminal (Phage_Mx8_p63_C)
Type: Domain

This entry represents the C-terminal domain from p63 (

), one of the proteins of Myxococcus phage Mx8. The function of these proteins are unknown .
Antirepressor protein ant, N-terminal (Antirepressor_Ant_N)
Type: Domain

The Antirepressor protein ant from Salmonella phage P22 prevents the prophage p22 c2 repressor protein from binding to its operators. It also inhibits the action of other prophage repressor proteins, including those of phages lambda and 434. The synthesis of antirepressor is negatively regulated by the protein products of the two other immi genes, mnt and arc .
Bacteriophage P22, antirepressor protein, C-terminal (Phage_P22_antirepressor_C)
Type: Domain

This entry represents the carboxy-terminal domain of the Enterobacteria phage P22 antirepressor ((

) . It is found associated with

.
Bacteriophage P22, Orf201, C-terminal (Phage_P22_Orf201_C)
Type: Domain

This entry represents the carboxy-terminal domain from ORF11 (

), one of the proteins of Pseudomonas phage D3 (Bacteriophage D3). The function of these proteins are unknown .
ORF6C domain (ORF6C_dom)
Type: Domain

This entry represents the carboxy-terminal domain from ORF6 (

), an antirepressor protein from Lactococcus phage bIL285 .
MSV199 domain (MSV199_dom)
Type: Domain

This entry represents the MSV199 domain found in proteins from virus .
Bacteriophage P4, Ash protein (Phage_P4_Ash)
Type: Family

This entry is represented by Bacteriophage P4, Ash protein . The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
Mitochondrial protein C2orf69 (C2orf69_mit)
Type: Family

This family includes mitochondrial protein C2orf69 from human, previously known as UPF0565, which is an important regulator of human mitochondrial function and may play a role in the respiratory chain and other metabolic pathways .
Calmodulin-binding domain C0, NMDA receptor, NR1 subunit (CaM-bd_C0_NMDA_rcpt_NR1)
Type: Domain

This is a very short highly conserved domain that is C-terminal to the cytosolic transmembrane region IV of the NMDA-receptor 1. It has been shown to bind Calmodulin-Calcium with high affinity. The ionotropic N-methyl-D-aspartate receptor (NMDAR) is a major source of calcium flux into neurons in the brain and plays a critical role in learning, memory, neural development, and synaptic plasticity. Calmodulin (CaM) regulates NMDARs by binding tightly to the C0 and C1 regions of their NR1 subunit. The conserved tryptophan is considered to be the anchor residue .
Delta carbonic anhydrase (Delta_CA)
Type: Family

Delta carbonic anhydrases are one of the at least five independently evolved families of carbonic anhydrases. Their activities, low CO2-induction, and localizations have been well studied in diatoms . The catalytic mechanism of delta CAs is currently unknown. Proteins of this family are also common in bacteria, but due to more distant relationship (identities less than 30% to the diatom delta CAs) and to the lack of experimental data the carbonic anhydrase activity is only putative in prokaryotic delta CAs.
Glutamate [NMDA] receptor, epsilon subunit, C-terminal (NMDAR2_C)
Type: Domain

This domain is found at the C terminus of many NMDA-receptor proteins, many of which are also associated with

and

. This region is predicted to be a large extra-cellular domain of the NMDA receptor proteins, being highly hydrophilic, and is thought to be integrally involved in the function of the receptor. The region also carries a number of potential N-glycosylation sites .
mRNA-binding domain (mRNA-bd_dom)
Type: Domain

This conserved domain is found in fungal proteins and appears to be involved in RNA-processing. It binds to poly-adenylated RNA, interacts genetically with mRNA 3'-end processing factors, co-purifies with the nuclear cap-binding protein Cbp20p, and is found in complexes containing other translation factors, such as EIF4G as in

and

.
Uncharacterised domain UPF0547 (UPF0547)
Type: Domain

This domain may well be a type of zinc-finger as it carries two pairs of highly conserved cysteine residues though with no accompanying histidines. Several members are annotated as putative helicases.
Myeloid-derived growth factor (MYDGF)
Type: Family

The function of myeloid-derived growth factor is to protect and repair the heart after myocardial infarction .
Uncharacterised protein family UPF0561 (UPF0561)
Type: Family

This family of proteins has no known function.
Arpin (Arpin)
Type: Family

Arpin regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex . It induces cell turning by pausing cell migration .
FAM171 (FAM171)
Type: Family

This family includes FAM171A1, FAM171A2 and FAM171B. FAM171A1 is a type 1 transmembrane glycoprotein also known as astroprincin (APCN) due to its abundant expression in astrocytes. APCN is also expressed in placental trophoblasts, skeletal and heart muscle, kidney and pancreas . APCN is involved in the regulation of the cytoskeletal dynamics, playing a role in actin stress fibre formation. The APCN gene is located on chromosome 10p13, a region that is deleted in DiGeorge type 2 and velocardiofacial syndromes.
Abortive phage infection protein, C-terminal (AIPR_C)
Type: Domain

This entry represents the C-terminal domain of abortive infection phage resistance protein often found in restriction modification system operons .
Retro-transposon transporting motif (Retro-transposon_transp_CS)
Type: Conserved_site

This is the highly conserved motif GRKIxxxxxRRKx of nucleoporins that plays a critical and unique role in the nuclear import of retro-transposons in both yeasts and higher organisms. It would appear that the arginine residues at positions 2 and 9-10 constitute a bipartite nuclear localisation signal, with two basic peptide motifs separated by an interchangeable spacer sequence, that is crucial for the retro-transposon activity .