SII-SWORD/CoKE huggingface dataset:
Cytochrome oxidase c subunit VIb-like (COX6B-like)
Type: Family

This family represents cytochrome c oxidase heme-binding subunit IVb, a component of the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation [

] . Cytochrome c oxidase assembly factor 6 (COA6) from yeast and its homologues are also included in this entry, which are involved in the maturation of the mitochondrial respiratory chain complex IV subunit MT-CO2/COX2, therefore, it may regulate early steps of complex IV assembly .

This entry also includes CHCHD7, a putative substrate of the mitochondrial Mia40-dependent import machinery. This protein folds into three α-helices stabilised by two disulfide bonds

.

Cytochrome c oxidase (

) is an oligomeric enzymatic complex that is a component of the respiratory chain complex and is involved in the transfer of electrons from cytochrome c to oxygen . In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane.

In eukaryotes, in addition to the three large subunits, I, II and III, that form the catalytic centre of the enzyme complex, there are a variable number of small polypeptide subunits. One of these subunits is the potentially haem-binding subunit, VIb, which is encoded in the nucleus . Subunit VIb is one of three mammalian subunits that lacks a transmembrane region. It is located on the cytosolic side of the membrane and helps form the dimer interface with the corresponding subunit on the other monomer complex .
Cytochrome c oxidase assembly factor 6, fungal (COA6_fun)
Type: Family

This entry represents Cytochrome c oxidase assembly factor 6 and related proteins found in fungi.

COA6 is involved in the maturation of the mitochondrial respiratory chain complex IV subunit MT-CO2/COX2 . Mutations in the COA6 gene cause cardioencephalomyopathy due to cytochrome c oxidase deficiency 4 (CEMCOX4), and an infantile disorder with a fatal course in the first weeks of life, characterised by hypertrophic cardiomyopathy, left ventricular non-compaction, lactic acidosis, metabolic hypotonia, and mitochondrial complex IV deficiency .
Cytochrome c oxidase assembly factor 6, plants (COA6_pln)
Type: Family

This entry represents Cytochrome c oxidase assembly factor 6 and related proteins from plants.

COA6 is involved in the maturation of the mitochondrial respiratory chain complex IV subunit MT-CO2/COX2 . Mutations in the COA6 gene cause cardioencephalomyopathy due to cytochrome c oxidase deficiency 4 (CEMCOX4), and an infantile disorder with a fatal course in the first weeks of life, characterised by hypertrophic cardiomyopathy, left ventricular non-compaction, lactic acidosis, metabolic hypotonia, and mitochondrial complex IV deficiency .
S-adenosylmethionine decarboxylase-like (AdoMetDC-like)
Type: Family

This entry includes S-adenosylmethionine decarboxylase (AdoMetDC) and its homologues. It also includes the inactive AdoMetDC prozyme that is essential to activate AdoMetDC but probably has no catalytic activity due to the loss of several residues required for processing and catalysis .

S-adenosylmethionine decarboxylase (AdoMetDC) catalyses the removal of the carboxylate group of S-adenosylmethionine to form S-adenosyl-5'-3-methylpropylamine which then acts as the n-propylamine group donor in the synthesis of the polyamines spermidine and spermine from putrescine.

The catalytic mechanism of AdoMetDC involves a covalently-bound pyruvoyl group. This group is post-translationally generated by a self-catalyzed intramolecular proteolytic cleavage reaction between a glutamate and a serine. This cleavage generates two chains, beta (N-terminal) and alpha (C-terminal). The N-terminal serine residue of the alpha chain is then converted by non hydrolytic serinolysis into a pyruvoyl group.
Erythromycin biosynthesis protein CIII-like, N-terminal domain (EryCIII-like_N)
Type: Domain

This entry represents the conserved N-terminal domain found in Erythromycin biosynthesis protein CIII (EryCIII) from Saccharopolyspora erythraea, also known as 3-alpha-mycarosylerythronolide B desosaminyl transferase (

), and similar bacterial proteins. EryCIII is organised into two domains, both of them with a Rossmann-like α/β fold. This domain contains the acceptor binding site .
Integrin alpha, second immunoglobulin-like domain (Integrin_alpha_Ig-like_2)
Type: Domain

This entry represents the second immunoglobulin-like domain of the three found in integrin alpha and integrin alpha precursors to the C terminus of a number of FG-GAP repeats (

) and to the N terminus of the cytoplasmic region

.
Integrin alpha, third immunoglobulin-like domain (Integrin_alpha_Ig-like_3)
Type: Domain

This entry represents the third immunoglobulin-like domain of the three found in integrin alpha and integrin alpha precursors to the C terminus of a number of FG-GAP repeats (

) and to the N terminus of the cytoplasmic region

.
Thrombospondin-like, N-terminal domain (TSPN-like_N)
Type: Domain

This entry represents the heparin-binding and cell adhesion domain of thrombospondin and related proteins such as protein kinase C-binding protein NELL1 and NELL2, and collagen alpha.

Thrombospondins (TSPs) are secreted, calcium-binding glycoproteins that play an essential role in regulating cell-cell and cell-matrix interactions. They are divided into trimeric subgroup A (TSP-1 and TSP-2) and pentameric subgroup B (TSP-3-5). The actions of TSPs depend on their binding partners in a given environment. The N-terminal domain of TSPs plays an integral role in the interaction of TSPs with other secreted and transmembrane proteins, and proteoglycans. This domain folds into a β-sandwich typical for concanavalin A-like lectins/glucanases superfamily (

) .
Programmed cell death protein 10, dimerisation domain (PDCD10_N)
Type: Domain

This entry represents the N-terminal dimerisation domain of human Programmed cell death protein 10 (PDCD10/CCM3) and similar animal proteins. PDCD10 is part of the CCM complex and is required for neuronal migration . Outside of this complex, it is crucial in vascularization and in angiogenesis as it functions in vessel permeability and stability . This protein plays an essential role in early embryonic angiogenesis and cardiovascular development. PDCD10/CCM3 interacts with a variety of proteins, including paxillin, membrane receptor vascular epidermal growth factor receptor 2, CCM complex component CCM2 and germinal centre kinase III proteins (GCKIII). PDCD10/CCM3 contains an N-terminal dimerisation domain and a C-terminal focal adhesion targeting-homology (FAT-H) domain .

This domain is also found at the C-terminal of GCKIIIs (STK24/MST3, STK25, STK26/MST4), which adopts a closely related fold. GCKIIIs are involved in the regulation of apoptosis, cell proliferation, polarity, migration, and cytoskeleton remodelling. This domain mediates homo and heterodimerisation . PDCD10/CCM3 forms a heterodimer with GCKIIIs analogous to CCM3 homodimer.
NsCP33-like, RNA recognition motif 2 (RRM2_NsCP33-like)
Type: Domain

The entry includes the second RRM motif of NsCP33 (

), Arabidopsis thaliana chloroplastic 31 kDa ribonucleoprotein (CP31A) (

), glycine-rich RNA-binding protein 2 (AtGR-RBP2) (

) and related plant and fungal proteins. This entry also includes uncharacterised bacterial sequences.

NsCP33 may be involved in splicing and/or processing of chloroplast RNA's. AtCP31A, also called RNA-binding protein 1/2/3 (AtRBP33), or RNA-binding protein CP31A, or RNA-binding protein RNP-T, or RNA-binding protein cp31, is required for specific RNA editing events in chloroplasts and stabilizes specific chloroplast mRNAs, as well as for normal chloroplast development under cold stress conditions by stabilizing transcripts of numerous mRNAs under these conditions. CP31A may modulate telomere replication through RNA binding domains. AtGR-RBP2, also called AtRBG2, or glycine-rich protein 2 (AtGRP2), or mitochondrial RNA-binding protein 1a (At-mRBP1a), plays a role in RNA transcription or processing during stress. It binds RNAs and DNAs sequence with a preference to single-stranded nucleic acids. AtGR-RBP2 displays strong affinity to poly(U) sequence. It exerts cold and freezing tolerance, probably by exhibiting an RNA chaperone activity during the cold and freezing adaptation process.
Zona pellucida domain, chordate-type (ZP_chr)
Type: Domain

This entry represents the zona pellucida (ZP) domain that is found mainly in chordates.

The zona pellucida (ZP) domain is a protein polymerisation module of ~260 amino acid module, which is found at the C terminus of many secreted eukaryotic glycoproteins that play fundamental roles in development, hearing, immunity, and cancer . Proteins containing a ZP domain include:

Sperm receptor proteins ZP2 and ZP3. Along with protein ZP1, proteins ZP2 and ZP3 are responsible for sperm-adhesion to the zona pellucida. ZP3 first binds to specific sperm proteins, thus mediating sperm contacts with the oocyte. ZP2 acts as a second sperm receptor reinforcing the interactions. ZP1 cross-links the polymers formed by ZP2 and ZP3.

Zona pellucida sperm-binding protein B (ZP-B) (also known as ZP-X in rabbit and ZP-3 α in pig).

Glycoprotein GP2, the major component of pancreatic secretory granule membranes.

TGF-beta receptor type III (also known as betaglycan). This protein is a proteoglycan that binds to TGF-beta and could be involved in capturing and retaining TGF-beta for presentation to the signalling receptors.

Uromodulin (also known as Tamm-Horsfall urinary glycoprotein). The function of this protein, which is the most abundant in human urine, is not yet clear.

Chicken beta-tectorin, a major glycoprotein of avian tectorial membrane.

Most ZP domain proteins are synthesized as precursors with carboxy-terminal transmembrane domains or glycosyl phosphatidylinositol (GPI) anchors .

The ZP domain contains eight strictly conserved cysteines, which form disulphide bridges. The disulphide bonds within the ZP domains are divided into two groups, suggesting that the ZP domain consists of two subdomains. In addition to the conserved cysteines, only a few aromatic or hydrophobic amino acids are absolutely invariant, probably as a result of structural rather than functional constraints .
Phage tail fibre adhesin Gp38, N-terminal domain (Gp38_N)
Type: Domain

This entry represents the N-terminal domain from several Gp38 proteins from T-even-like phages. Gp38 is a receptor binding protein that is at the tip of the long tail fibers and serves as the phage recognition site for the attachment host receptor. This domain interacts with the Gp37 tail fiber protein .
SDA1, C-terminal domain (SDA1_C)
Type: Domain

This entry includes SDA1 and its homologues. SDA1 is a Saccharomyces cerevisiae protein which is involved in the control of the actin cytoskeleton, essential for cell viability . It is a HEAT repeat-containing protein , required for 60S pre-ribosomal subunits export to the cytoplasm and may also be required for 60S ribosomal subunit maturation and accumulation . This entry represents the C-terminal region of SDA1 proteins.
DNA helicase PIF1/RRM3/pfh1 (PIF1_RRM3_pfh1)
Type: Family

This entry includes a group of DNA helicases, including Pif1 and Rrm3 from budding yeasts and Pfh1 from fission yeast.

Pif1 is a DNA helicase conserved from bacteria to humans . It suppresses both G-quadruplex-associated DNA damage and telomere lengthening. In budding yeast, it exists in two forms, nuclear form and mitochondrial form. Its nuclear form inhibits telomerase, while its mitochondrial form is involved in repair and recombination of mitochondrial DNA .
Reovirus core-spike protein lambda-2-like, C-terminal domain (Reovirus_L2_8th)
Type: Domain

Reovirus core-spike protein VP1/lambda-2 (VP1/L2) forms a pentamer that mediates enzymatic reactions in 5' capping of the viral plus-strand transcripts . It forms a hollow cylinder with projecting turrets. Each VP1/L2 monomer consists of eight domains with the most N-terminal domain at the base of the turret and the most C-terminal domain at the top. This entry represents the C-terminal (eighth) domain which, together with the sixth and seventh domains, forms a three-domain flap at the top of the turret, that may serve as a gate to retard exit of the 5' terminus of the mRNA . This domain has a Ig-like, resembling a truncated V region of an antibody light chain.
DUF4785, C-terminal domain (DUF4785_C)
Type: Domain

This entry represents the C-terminal immunoglobulin-like domain found in a group of proteins from bacteria. Proteins in this family are typically between 392 and 442 amino acids in length.
DUF4785, central domain (DUF4785_central)
Type: Domain

This entry represents the central immunoglobulin-like domain found in a group of proteins mainly from proteobacteria. Proteins in this family also contain the domains

and

and are typically between 392 and 442 amino acids in length.
Domain of unknown function DUF936, plants (DUF936_dom_pln)
Type: Domain

This domain is found at the N-terminal of several hypothetical proteins from plants, whose function is unknown. This domain is predicted to adopt a globular structure that folds into a barrel similar to OB-fold barrels.
Influenza RNA polymerase PB2, CAP binding domain (Flu_PB2_CAP-bd)
Type: Domain

This entry represents the CAP binding domain of RNA-directed RNA polymerase subunit PB2 (also known as Polymerase basic protein 2) from Influenza A virus and similar proteins from influenzavirus (prthomyxoviridae).

Influenza virus encodes a large, multidomain RNA-dependent RNA polymerase that can both transcribe and replicate the viral RNA genome. In influenza virus, the polymerase is composed of three polypeptides: PB1, PB2 and PA/P3. PB1 houses the polymerase active site, whereas PB2 and PA/P3 contain, respectively, cap-binding and endonuclease domains required for transcription initiation by cap-snatching .
Group II intron-interrupted relaxase LtrB, central domain (LtrB_central)
Type: Domain

This entry represents the central domain of Group II intron-interrupted relaxase LtrB from Lactococcus lactis and similar sequences from Lactobacillales. LtrB mediates initiation of the conjugal transfer of the plasmid pRS01 possibly by introducing a single-stranded nick at the potential origin of transfer, to initiate single strand transfer from donor to recipient .
TACO1/YebC-like, second and third domains (TACO1_YebC-like_2nd/3rd_dom)
Type: Domain

This entry represents a domain found in transcriptional regulators. In mammals, it activates the transcription of mitochondrially-encoded COX1 . In bacteria, it negatively regulates the quorum-sensing response regulator by binding to its promoter region . This entry represents the second and third domains in this protein, with one domain nested within the other.
Endonuclease NucS, C-terminal domain (NucS_C)
Type: Domain

This entry represents the C-terminal domain of endonuclease NucS, which adopts an α/β structure with a five-stranded central β-sheet and four flanking α-helices, representing a minimal-endonuclease fold. This domain contains an active site with a sequence motif conserved in the family of RecB-like nucleases.

NucS cleaves both 3' and 5' ssDNA extremities of branched DNA structures and it binds to ssDNA .
Endonuclease NucS, N-terminal PH-like domain (NucS_N)
Type: Domain

This entry represents the N-terminal domain of endonuclease NucS, which adopts a β-barrel structure. This domain is involved in dimerisation achieved via domain swapping. The dimer formation it likely critical for the folding and stabilisation of the NucS structure.

NucS cleaves both 3' and 5' ssDNA extremities of branched DNA structures and it binds to ssDNA .
Type VI lipase adapter protein Tla3, C-terminal domain (Tla3_C)
Type: Domain

This entry represents the C-terminal domain of Type VI lipase adapter protein Tla3, an adapter protein that targets and loads the Tle3 toxin onto the H2 type VI secretion system (H2-T6SS) machinery through an interaction with the TTR domain of VgrG2b and it seems specific for Tle3 . This domain and its N-terminal (

), are both required for the interaction with the toxin .
3-octaprenyl-4-hydroxybenzoate carboxy-lyase-like, Rift-related domain (UbiD_Rift_dom)
Type: Domain

This entry represents the central RIFT-related domain of 3-octaprenyl-4- hydroxybenzoate carboxy-lyase enzymes . This enzyme catalyses the third reaction in ubiquinone biosynthesis. For optimal activity, the carboxylase was shown to require Mn2 .
PAE0736-like, C-terminal domain (PAE0736-like_C)
Type: Domain

This entry represents the C-terminal domain of the highly thermostable protein PAE0736 from Pyrobaculum aerophilum (

) and similar disulphide-rich uncharacterised proteins from thermophilic archaea. PAE0736, which contains three disulphide bonds, may play a role in the formation or maintenance of intracellular protein disulfide bonds in disulfide-rich organisms. This domain harbours one of these disulphide bonds and shows an all-β structure. However, its specific function is still unknown .
Rotavirus non-structural protein 35, C-terminal domain (Rota_NS35_C)
Type: Domain

Rotavirus non-structural protein 35 (NS35, also known as NSP2) is a basic protein which possesses RNA-binding and helix-destabilising activities in addition to nucleoside and 5' RNA triphosphatase (NTPase/RTPase) and nucleoside-diphosphate (NDP) kinase-like activities . NS35 forms a functional octamer which is essential for genome replication and formation of viroplasms . This entry represents the C-terminal domain, which has nucleotide triphosphatase (NTPase) and nucleoside diphosphate kinase (NDP kinase) activities, required for dsRNA synthesis. Additionally, basic residues in a C-terminal helix of this domain contributes to sequence-independent RNA binding of NSP2 .
Oligosaccharyl transferase STT3, N-terminal domain (STT3_N)
Type: Domain

This entry represents the N-terminal domain of the oligosaccharyltransferase STT3 subunit and related proteins. The STT3 subunit is part of the oligosaccharyl transferase (OTase) complex of proteins and is required for its activity . In eukaryotes, OTase transfers a lipid-linked core-oligosaccharide to selected asparagine residues in the ER . In the archaea, STT3 occurs alone, rather than in an OTase complex, and is required for N-glycosylation of asparagines . The N-terminal domain consists of transmembrane helices.
G6b-B extracellular V-set Ig-like domain (G6B_V-set)
Type: Domain

This entry represents the N-terminal extracellular HS binding domain.

G6b-B is a unique platelet ITIM-containing receptor that is highly expressed in mature megakaryocytes and platelets . It inhibits platelet aggregation and activation by agonists such as ADP and collagen-related peptide. It appears to operate in a calcium-independent manner . It is a type I transmembrane protein that consists of a single N-glycosylated immunoglobulin-variable (IgV)-like domain in its extracellular region, a single transmembrane domain and a cytoplasmic tail containing an ITIM and an immunoreceptor tyrosine-based switch motif (ITSM) . The human G6B gene encodes a number of splice forms that are translated into both cell-surface and secreted isoforms. Cell-surface isoforms G6B-A and G6B-B have the same extracellular N-terminal Ig-like domain but differ in their C-terminal cytoplasmic tails. The extracellular matrix heparan sulfate (HS) proteoglycan perlecan was identified as a G6b-B binding partner . Subsequent in vitro biochemical studies and a cell-based genetic screen demonstrated that the interaction is specifically mediated by the HS chains of perlecan .
GxGYxYP putative glycoside hydrolase, third N-terminal domain (GxGYxYP_N_3rd)
Type: Domain

This entry represents a domain that is found repeated in three copies per protein and is likely to be involved in binding the bacterial cell wall. This domain can be found in the N-terminal region of a group of proteins that carry a characteristic sequence motif, GxGYxYP, and are putative glycoside hydrolases. This domain represents the third one, and it is found in association with

.
GxGYxYP putative glycoside hydrolase, second N-terminal domain (GxGYxYP_N_2nd)
Type: Domain

This entry represents a domain that is found repeated in three copies per protein and is likely to be involved in binding the bacterial cell wall. This domain can be found in the N-terminal region of a group of proteins that carry a characteristic sequence motif, GxGYxYP, and are putative glycoside hydrolases. This domain corresponds to the second one and it is found in association with

.
Antiactivator protein ExsD, helical hairpin domain (ExsD_M)
Type: Domain

This entry represents the central helical hairpin domain of ExsD.

The antiactivator protein ExsD represses the transcriptional activator ExsA. ExsA activates expression of type III secretion system genes. ExsD inhibits the DNA-binding and self-association properties of ExsA . Repression of ExsA by ExsD is relieved by the secretion chaperone ExsC .
Antiactivator protein ExsD, C-terminal domain (ExsD_C)
Type: Domain

This entry represents the C-terminal domain of ExsD.

The antiactivator protein ExsD represses the transcriptional activator ExsA. ExsA activates expression of type III secretion system genes. ExsD inhibits the DNA-binding and self-association properties of ExsA . Repression of ExsA by ExsD is relieved by the secretion chaperone ExsC .
DUF5382, N-terminal domain (DUF5382_N)
Type: Domain

This is a domain of unknown function found at the N-terminal of proteins from Caenorhabditis. It has an NTF2-like fold.
DUF5382, C-terminal domain (DUF5382_C)
Type: Domain

This is a domain of unknown function found at the C-terminal of proteins from Caenorhabditis. It has an NTF2-like fold.
ZSWIM9, central RNaseH-like domain (ZSWIM9_RNaseH-like)
Type: Domain

This entry represents the central domain from a chordate proteins that includes ZSWIM9 (also known as C19orf68). These proteins appear to be transposon related. This domain appears to be closely related to the MULE RNaseH domain (

).
DUF5580, N-terminal domain (DUF5580_N)
Type: Domain

This is the N-terminal calmodulin-like domain found in metazoan proteins of unknown function.
DUF5581, Fn3-like domain (DUF5581_C)
Type: Domain

This entry represents the C-terminal fibronectin type III domain found in a group of proteins of unknown function from chordates.
Autophagy protein ATG5, UblB domain (ATG5_UblB)
Type: Domain

ATG5 is directly required for the import of aminopeptidase I via the cytoplasm-to-vacuole targeting pathway . ATG5 is conjugated to ATG12; this conjugate exhibits E3 ligase-like activity which facilitates the lipidation of members of the LC3 family, and therefore autophagosome formation . ATG5 comprises N- and C-terminal ubiquitin-like domains (UblA and UblB) that flank the helical-rich region (HBR). This entry represents the UblB domain, found at the C-terminal .

Macroautophagy is a bulk degradation process induced by starvation in eukaryotic cells. In yeast, 15 Atg proteins coordinate the formation of autophagosomes. The pre-autophagosomal structure contains at least five Atg proteins: Atg1p, Atg2p, Atg5p, Aut7p/Atg8p and Atg16p, found in the vacuole . The C-terminal glycine of Atg12p is conjugated to a lysine residue of Atg5p via an isopeptide bond. During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. Autophagy protein 16 (Atg16) has been shown to bind to Atg5 and is required for the function of the Atg12p-Atg5p conjugate . Autophagy protein 5 (Atg5) is directly required for the import of aminopeptidase I via the cytoplasm-to-vacuole targeting pathway .