SII-SWORD/CoKE huggingface dataset:
Dedicator of cytokinesis protein 2, DHR2 domain (DHR2_DOCK2)
Type: Domain

DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . DOCK proteins are required during several cellular processes, such as cell motility and phagocytosis. The N-terminal SH3 domain of the DOCK proteins functions as an inhibitor of GEF, which can be relieved upon its binding to the ELMO1-3 adaptor proteins, after their binding to active RhoG at the plasma membrane . DOCK family proteins are categorised into four subfamilies based on their sequence homology: DOCK-A subfamily (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11) . All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker).

DOCK2 is a hematopoietic cell-specific, class A DOCK and is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. It plays an important role in lymphocyte migration and activation, T-cell differentiation, neutrophil chemotaxis, and type I interferon induction .

This entry represents the DHR-2 domain of DOCK2, which contains the catalytic GEF activity for Rac. Class A DOCKs, like DOCK2, are specific GEFs for Rac. DOCK2 then activates RAC1 and RAC2, but not CDC42. It may also participate in IL2 transcriptional activation via the activation of RAC2 .
Dedicator of cytokinesis protein 3, DHR2 domain (DHR2_DOCK3)
Type: Domain

DOCK3, also called modifier of cell adhesion (MOCA), is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. DOCK3 is a specific GEF for Rac. It regulates N-cadherin dependent cell-cell adhesion, cell polarity, and neuronal morphology. It promotes axonal growth by stimulating actin polymerization and microtubule assembly . DOCK3 is linked to Alzheimer disease due to its interaction with presenilin proteins and ability to stimulate Tau/MAPT phosphorylation .

This entry represents the DHR-2 domain of DOCK3, which contains the catalytic GEF activity for Rac .

DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . DOCK proteins are required during several cellular processes, such as cell motility and phagocytosis. The N-terminal SH3 domain of the DOCK proteins functions as an inhibitor of GEF, which can be relieved upon its binding to the ELMO1-3 adaptor proteins, after their binding to active RhoG at the plasma membrane . DOCK family proteins are categorised into four subfamilies based on their sequence homology: DOCK-A subfamily (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11) . All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker).
Transmembrane protein 160 (TMEM160)
Type: Family

This entry represents a family of uncharacterised transmembrane proteins.
Odontogenic ameloblast-associated protein (Odam)
Type: Family

Odontogenic ameloblast-associated protein, also known as apin, is a tooth-associated epithelia protein that probably plays a role in odontogenesis, the complex process that results in the initiation and generation of the tooth. It may be incorporated in the enamel matrix at the end of mineralisation process .
GW182, middle domain (GW182_M_dom)
Type: Domain

This entry represents the M (middle region) domain of GW182 . GW182 (also known as Gawky) plays a role in RNA-mediated gene silencing by micro-RNAs (miRNAs) .
Protein CDV3 (CDV3)
Type: Family

Protein CDV3 (carnitine deficiency-associated protein 3) is up-regulated in ventricles of juvenile visceral steatosis mice . Another study showed that CDV3 is phosphorylated by Abl, a tyrosine kinase involved in normal B cell development .
Cip1-interacting zinc finger protein (CIZ1)
Type: Family

Cip1-interacting zinc finger protein may regulate the subcellular localization of p21(CIP/WAF1) . p21(CIP/WAF1) has a critical role in the negative control of cell growth. The Drosophila melanogaster orthologue, protein zinc finger protein on ecdysone puffs, may have a role in the activation of early and late genes .
Flavodoxin domain (Flavodoxin_dom)
Type: Domain

This entry represents the flavodoxin domain. Proteins with this domain include protoporphyrinogen IX dehydrogenase (HemG). HemG catalyses the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX using menaquinone as electron acceptor .
Guanine nucleotide exchange factor Ect2 (Ect2)
Type: Family

Epithelial Cell Transforming Sequence 2 (Ect2) is a guanine nucleotide exchange factor (GEF) that catalyses the exchange of GDP for GTP. Like other GEFs, Ect2 serves as molecular switches in diverse signaling pathways, including cell polarity, mitotic spindle assembly, cytokinesis, etc . Ect2 interacts with several members of the Rho GTPase family including, RhoA, RhoB, RhoC, RhoG, Rac1 and Cdc42 . Ect2 regulates the formation of the actomyosin contractile ring at mitotic exit through activation of RhoA and functions in metaphase for the process of spindle assembly through activation of Cdc42 . Ect2 is regulated through a number of mechanisms including phosphorylation, intracellular localization and intra- and inter-molecular interactions .
Adenomatous polyposis coli (APC) family (Apc_fam)
Type: Family

Adenomatous polyposis coli (APC) is a tumor suppressor protein that induces the degradation of oncogenic beta-catenin and negatively regulates Wnt signalling . It has roles in regulating cell migration, DNA replication/repair, mitosis and apoptosis . APC regulates cell-cell adhesion and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (GEF; Asef) . It acts as a mediator of ERBB2-dependent stabilisation of microtubules at the cell cortex . It is required for the localisation of MACF1/ACF7 to the cell membrane and this localisation of MACF1/ACF7 is critical for its function in microtubule stabilisation . APC mutations are particularly prevalent in colorectal cancer .

The adenomatous polyposis coli protein family also includes APC2 and APC-related protein 1 .
Iminophenyl-pyruvate dimer synthase (VioB/RebD_dom)
Type: Domain

Following the action of a flavin-dependent L-amino acid oxidase that converts L-tryptophan to indole-3-pyruvate imine, the enzymes VioB, RebD, and StaD can ligate two molecules, forming a coupled iminophenyl-pyruvate dimer. In the violacein biosynthesis pathway, this compound is acted on by VioE before it cyclizes spontaneously to chromopyrrolic acid . In the pathways of homologue StaD (staurosporine), chromopyrrolate is formed, and the enzyme is referred to as chromopyrrolate synthase. RebD is very similar to StaD, but acts on chlorinated Trp-derived molecules .
Spp2/MOS2, G-patch domain (Spp2/MOS2_G-patch)
Type: Domain

Spp2 is a yeast G-patch protein and spliceosome component that interacts with the ATP-dependent DExH-box splicing factor Prp2 . This interaction involves the G-patch sequence in Spp2 and is required for the recruitment of Prp2 to the spliceosome before the first catalytic step of splicing. It has been proposed that Spp2 might be an accessory factor that confers spliceosome specificity on Prp2 .

Proteins containing this G-patch domain also include the plant MOS2 protein, which is required for innate and induced resistance to pathogens, and MOS2 homologues from Metazoa .
Complement Clr-like EGF domain (cEGF)
Type: Domain

Complement Clr-like EGF (cEGF) domains have six conserved cysteine residues disulfide-bonded into the characteristic pattern 'ababcc'. They are found in blood coagulation proteins such as fibrillin, Clr and Cls, thrombomodulin, and the LDL receptor. The core fold of the EGF domain consists of two small β-hairpins packed against each other. Two major structural variants have been identified based on the structural context of the C-terminal cysteine residue of disulfide 'c' in the C-terminal hairpin: hEGFs and cEGFs . In cEGFs the C-terminal thiol resides on the C-terminal β-sheet, resulting in long loop-lengths between the cysteine residues of disulfide 'c', typically C[10+]XC. These longer loop-lengths may have arisen by selective cysteine loss from a four-disulfide EGF template such as laminin or integrin. Tandem cEGF domains have five linking residues between terminal cysteines of adjacent domains. cEGF domains may or may not bind calcium in the linker region. cEGF domains with the consensus motif CXN4X[F,Y]XCXC are hydroxylated exclusively on the asparagine residue.
Vacuole morphology and inheritance protein 14 (Vac14)
Type: Family

Vac14 is a component of the PI(3,5)P2 regulatory complex, which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) . This complex is composed of Atg18, Fig4, Fab1, Vac14 and Vac7 in yeast. In mammals it consists of PIKfyve, FIG4 and VAC14. Fab1/PIKfyve (Fab1 in yeast and PIKfyve in mammals) is a kinase that converts PI(3)P into PI(3,5)P2 by phosphorylation at the 5-position; conversely Fig4 dephosphorylates PI(3,5)P2 back to PI(3)P. Vac14 is a scaffolding adaptor protein whose multimerisation is a prerequisite step for PI(3,5)P2 complex assembly and function .
Suppressor APC domain-containing protein 1/2 (SAPC2_1/2)
Type: Family

This entry consists of the suppressor APC domain-containing protein 1 and 2 (SAPC1 and SAPC2).

In humans, SAPC2 plays a role in planar mitotic spindle orientation. It is also involved in positive regulation of cell proliferation and tumour cell growth . The EF-hand fold is a helix-loop-helix motif that binds calcium . SAPC2 is expressed in many primary gastric carcinoma. It is expressed preferentially in M and G1 phases, compared to S and G2 phases .
Adenomatous polyposis coli protein (APC_dom)
Type: Homologous_superfamily

The tumour suppressor protein adenomatous polyposis coli (APC) has a nuclear export activity as well as many different intracellular functions. The region close to the N terminus, termed APC-(129-250), consists of three α-helices forming two separate antiparallel coiled coils . This entry represents a domain towards the N terminus that covers part of this region.
Asteroid (Asteroid)
Type: Family

This entry represents the protein Asteroid and its homologues, including Single-strand DNA endonuclease ASTE1 (also known as Protein asteroid homolog 1). D. melanogaster protein Asteroid plays a possible role in EGF receptor signalling . Human ASTE1 was shown to promote shieldin-complex-mediated DNA repair by attenuating end resection . ASTE1 localises to DNA damage sites in a shieldin-dependent manner and acts as a structure-specific DNA endonuclease that specifically cleaves single-stranded DNA and 3' overhang DNA .
LHH (LHH)
Type: Domain

This entry represents the LHH domain in the nuclease of the HNH/ENDO VII superfamily, found in toxin YobL from B. subtilis . LHH is a conserved motif that is found in bacterial polymorphic toxin systems and functions as a toxin module . This domain exhibits RNase activity when expressed in E. coli and inhibits growth. These effects are neutralized by the cognate immunity protein YobK .
Toxin YqcG, C-terminal (YqcG_C)
Type: Domain

Toxin YqcG is a toxic component of LXG toxin-immunity modules, which promote kin selection, mediate competition in biofilms, and drive spatial segregation of different strains, indicating that LXG toxins may help avoid warfare between strains in biofilms. It mediates intercellular competition during biofilm formation; disruption of the operon disadvantages the bacteria, but overexpression of the cognate immunity protein restores growth in competition with wild-type. Overexpression alone in situ causes growth arrest but not cell lysis, a large decrease in chromosomal DNA content and the production of anucleate cells. The toxic effect is dependent on the epsA and tapA operons which are required for biofilm formation . This entry represents the C-terminal nuclease domain.
Endospore coat-associated protein YheC/D (YheC/D)
Type: Family

Proteins in this family are involved in sporulation .
Inositolphosphotransferase Aur1/Ipt1 (Aur1/Ipt1)
Type: Domain

This entry includes a group of inositolphosphotransferases, including inositol phosphorylceramide synthase catalytic subunit Aur1 and inositolphosphotransferase 1 (Ipt1) from S. cerevisiae. Aur1 is a catalytic component of the inositol phosphorylceramide synthase which catalyses the addition of a phosphorylinositol group onto ceramide to form inositol phosphorylceramide, an essential step in sphingolipid biosynthesis . Ipt1 is involved in synthesis of mannose-(inositol-P)2-ceramide (M(IP)2C), the most abundant and complex sphingolipid in S. cerevisiae . This entry also includes some uncharacterised archaeal and bacterial proteins.
Nuclease SbcCD subunit D, C-terminal domain (SbcD_C)
Type: Domain

SbcD works in complex with SbcC. SbcCD is a nuclease that cleaves DNA hairpin structures stopping the progress of the replication fork and allowing homologous recombination . It plays an important role in DNA repair and in the maintenance of genome stability . In Staphylococcus aureus, it is involved in the repression of type 5 capsule production as part of the SOS response by down-regulating cap5 genes via arl-mgr pathway .

This entry represents the C-terminal domain of SbcD. This domain is found in bacteria and archaea.
Neurexophilin/NXPE (NXPH/NXPE)
Type: Family

This entry includes neurexophilin and NXPE proteins.
E3 SUMO-protein ligase Nse2 (Mms21) (Nse2(Mms21))
Type: Family

This entry consists of the E3 SUMO-protein ligase Nse2 (also known as Mms21).
Vacuolar protein sorting-associated protein 13 (VPS13)
Type: Family

Vacuolar protein sorting-associated protein 13 (VPS13) is involved in the delivery of proteins to the vacuole in vegetatively growing yeast and also regulates membrane morphogenesis during sporulation . It mediates the transfer of lipids between membranes at organelle contact sites and it is involved in mitochondrial lipid homeostasis . In humans, the hereditary disorders chorea acanthocytosis and Cohen syndrome are caused by mutations in members of this family that are orthologues of yeast VPS13 (VPS13A and VPS13B respectively). Human VPS13A binds phospholipids and is required for the formation or stabilization of ER-mitochondria contact sites which enable transfer of lipids between the ER and mitochondria . It is also required for efficient lysosomal protein degradation .
These proteins belong to the RNG superfamily (repeating β-grooves).
E3 ubiquitin-protein ligase FANCL (Fancl)
Type: Family

Fanconi anemia (FA) is a human disorder characterised by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages. The FA complex repairs the interstrand cross-linking (ICL) lesions and coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination. It is required for the monoubiquitylation of FANCD2 and FANCI heterodimer. The FA core complex consists of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, FANCT (UBET2), FAAP100 and FAAP24 .

FANCL is an ubiquitin ligase that mediates monoubiquitination of FANCD2, a key step in the repair of interstrand DNA crosslinks (ICLs) in the Fanconi anemia (FA) pathway . In humans, defects in FANCL are the cause of Fanconi anemia complementation group L (FANCL). FANCL is a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair .
Autophagy-related protein 2 (ATG2)
Type: Family

Pexophagy is an autophagic process consisting of the rapid and selective degradation of peroxisomes. Autophagy-related protein 2 (ATG2) is required for glucose-induced micropexophagy and ethanol-induced macropexophagy in yeast . Homologues of this protein have also been described in mammals and plants. Mammalian ATG2 proteins are thought to function both in autophagosome (a structure that enclose the cytoplasmic materials) formation and regulation of lipid droplet morphology and dispersion . In plants they have a role in programmed cell death, senescence and disease resistance .

The Atg2 protein, an integral membrane protein, is required for a range of functions including the regulation of autophagy in conjunction with the Atg1-Atg13 complex . It is a lipid transfer protein required for autophagosome completion and peroxisome degradation. It is a member of the RBG (repeating β-grooves) superfamily, together with VPS13, SHIP164, Csf1, and the Hob proteins, which all share the same structure consisting of long hydrophobic grooves made of multiple repeating modules of five β-sheets followed by a loop .
FANCL C-terminal domain (FANCL_C)
Type: Domain

This entry represents the C-terminal domain of the FANCL, which is the E3 ubiquitin ligase subunit of the FA (Fanconi anaemia) complex . This entry represents the RING domain which recruits the UBE2T ubiquitin conjugating E2 enzyme as other RING E3s .
DNA replication ATP-dependent helicase/nuclease Dna2/JHS1, DEXXQ-box helicase domain (Dna2/JHS1_DEXXQ-box)
Type: Domain

Dna2 and its plant homologue JHS1 are DNA replication factors with single-stranded DNA-dependent ATPase, ATP-dependent nuclease, (5'-flap endonuclease) and helicase activities. It is required for Okazaki fragment processing and is involved in DNA repair pathways . The helicase activity is weak and its function remains unclear .

This entry represents DEXXQ-box helicase domain of DNA2 and homologues. It contains the ATP-binding region .
Vacuolar protein sorting-associated protein 13, N-terminal domain (VPS13_N)
Type: Domain

This is the N-terminal chorein domain of VPS13 proteins, which is highly coserved. This domain has a scoop or taco shape whose concave surface is lined by hydrophobic residues which bind glycerophospholipids.

VPS13 proteins have been implicated in processes including vesicle fusion, autophagy, and actin regulation. They bind phospholipids and act as channels that mediate the transfer of lipids between membranes at organelle contact sites . It has been proposed that members of this entry have the capacity to bind and likely transfer tens of glycerolipids at once. Yeast VPS13 acts at multiple cellular sites, namely the interface between mitochondria and the vacuole, on endosomes, on the nuclear-vacuole junction and the vacuole, depending on the carbon source and metabolic state. Most evidence showed that mammalian VPS13A, VPS13C and VPS13D localize at contacts between the ER and other organelles, i.e. VPS13A and VPS13D bridge the ER to mitochondria, VPS13C bridges the ER to late endosomes and lysosomes and VPS13B may localize to endosome-endosome contacts . Mutations in human VPS13 proteins (VPS13A-D) cause different diseases such as Chorea-acanthocytosis, Cohen syndrome, Parkinson's disease, and spastic ataxia, respectively which suggests they have different functions . Members of this entry belong to the repeating β-groove (RBG) superfamily. These proteins share a structure made of multiple repeating modules consisting of five β-sheets followed by a loop .
Sialidase family (Sialidase_fam)
Type: Family

This entry includes sialidase and sialidase 1/2/3/4/A, which are members of the glycoside hydrolase family 33 that also includes trans-sialidase and 2-keto-3-deoxynononic acid sialidase.

Sialidases catalyse hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates. In some bacteria, sialidase have been suggested to be pathogenic factors in microbial infections . This entry includes Sialidase 85-1.1, which is also known as Major 85kDa surface antigen.
Vezatin (Vezatin)
Type: Family

Vezatin is a peroxisome transmembrane receptor that is involved in membrane-membrane and cell-cell adhesions. In the movement of peroxisomes, it binds to class V and class VIIa myosins to guide the organelle through the microtubules and allow pathogens to internalise themselves into host cells . In mouse cells, vezatin is crucial for spermatozoan production . It interacts with the cadherin-catenin complex bridging it to the C-terminal FERM domain of myosin VIIA .
Myosin-binding domain (Myosin-bd)
Type: Domain

This entry represents a myosin-binding domain found in vezatin and inheritance of peroxisomes protein 2 (Inp2).

Vezatin is a peroxisome transmembrane receptor that is involved in membrane-membrane and cell-cell adhesions. In the movement of peroxisomes, it binds to class V and class VIIa myosins to guide the organelle through the microtubules and allow pathogens to internalise themselves into host cells . In mouse cells, vezatin is crucial for spermatozoan production . It interacts with the cadherin-catenin complex bridging it to the C-terminal FERM domain of myosin VIIA .

Inp2 has been identified as the peroxisome-specific receptor for class V myosin, Myo2p .
SH3b2-type SH3 domain (SH3b2-type_SH3)
Type: Domain

This domain appears to be an SH3 domain of the SH3b2-type, and is the second SH3 domain to be found downstream of an N-terminal domain that is probably the stabilising domain for the structure from protein

(PDB:3m1u), which is a four-domain protein. The last domain in this protein, the C-terminal region, is the catalytic domain of the cysteine-peptidase type, ie family NLPC_P60 (

).
Protein CR006, P-loop domain (CR006_AAA)
Type: Domain

This domain contains a P-loop motif that is characteristic of the AAA superfamily. It is found in P-loop containing proteins such as chromosomal cassette SCCmec type IVc uncharacterised protein CR006 and arcadin-4, an actin-like component of the cytoskeleton of the archaeon
Pyrobaculum calidifontis
.
Gamma-glutamyl-hercynylcysteine sulfoxide hydrolase EgtC-like (EgtC-like)
Type: Family

This entry represents a group of glutamine amidotransferase domain containing proteins, including EgtC and DUG3. DUG3, is a component of the GSH degradosomal complex involved in the degradation of glutathione (GSH) and other peptides containing a gamma-glu-X bond . In Mycolicibacterium, EgtC catalyzes the hydrolysis of the gamma-glutamyl amide bond of hercynyl-gamma-L-glutamyl-L-cysteine sulfoxide to produce hercynylcysteine sulfoxide, a step in the biosynthesis pathway of ergothioneine .
Zinc-ribbon domain (Zinc_ribbon_dom)
Type: Domain

This entry consists of a single zinc ribbon domain.
Protein farnesyltransferase subunit beta (FTB)
Type: Family

Protein farnesyltransferase (FTase) is an enzyme responsible for the posttranslational modification (farnesylation) of proteins carrying a carboxy-terminal CaaX motif, including Ras, Ras homologues, and other small G proteins. FTase catalyses the transfer of a farnesyl moiety from farnesyl pyrophosphate to the cysteine at the CaaX motif, where a is a small aliphatic amino acid and X is the carboxy-terminal residue . Prenyltransferase employ a Zn2+ ion to alkylate a thiol group catalyzing the formation of thioether linkages between cysteine residues at or near the C terminus of protein acceptors and the C1 atom of isoprenoid lipids. FTase attaches a 15-carbon farnesyl group to the cysteine within the C-terminal CaaX motif of substrate proteins when X is Ala, Met, Ser, Cys or Gln .