SII-SWORD/CoKE huggingface dataset:
Carbamoyl-phosphate synthase small subunit, GATase1 domain (CPSase_GATase1)
Type: Domain

Glutamine amidotransferase (GATase) enzymes catalyse the removal of the ammonia group from glutamine and then transfer this group to a substrate to form a new carbon-nitrogen group . The GATase domain exists either as a separate polypeptidic subunit or as part of a larger polypeptide fused in different ways to a synthase domain. Two classes of GATase domains have been identified : class-I (also known as trpG-type or triad) and class-II (also known as purF-type or Ntn). In class I glutamine amidotransferases, a triad of conserved Cys-His-Glu forms the active site, wherein the catalytic cysteine is essential for the amidotransferase activity . Different structures show that the active site Cys of type 1 GATase is located at the tip of a nucleophile elbow.

The E.coli carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III). CPSase catalyses the synthesis of carbamoyl phosphate from biocarbonate, ATP and glutamine or ammonia, and represents the first committed step in pyrimidine and arginine biosynthesis in prokaryotes and eukaryotes, and in the urea cycle in most terrestrial vertebrates . The small subunit catalyses the hydrolysis of glutamine to ammonia, which in turn used by the large chain to synthesize carbamoyl phosphate. The C-terminal domain of the small subunit of CPSase has glutamine amidotransferase activity.
TRIM17, PRY/SPRY domain (TRIM17_PRY/SPRY)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (terf). TRIM17 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein, expressed almost exclusively in the testis. It exhibits E3 ligase activity, causing protein degradation of ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates proliferation of breast cancer cells . TRIM17 undergoes ubiquitination in COS7 fibroblast-like cells but is inhibited and stabilized by TRIM44 .
Sodium/iodide cotransporter (SLC5A5)
Type: Family

NIS (product of the SLC5A5 gene) transports iodide (I-), and other anions including ClO4-, SCN-, and Br-. NIS is expressed in the thyroid, colon, ovary, and in human breast cancers. It mediates the active transport and the concentration of iodide from the blood into thyroid follicular cells, a fundamental step in thyroid hormone biosynthesis, and is the basis of radioiodine therapy for thyroid cancer . Mutation in the SLC5A5 gene can result in a form of thyroid hormone dysgenesis . Human NIS exists mainly as a dimer stabilized by a disulfide bridge . This subgroup belongs to the solute carrier 5 (SLC5) transporter family.
ORC ubiquitin ligase 1, RING finger (OBI1_RING-HC)
Type: Domain

ORC ubiquitin ligase 1 (OBI1, also known as RNF219) is essential for DNA replication origin activation during S phase. It acts as a replication origin selector which selects the origins to be fired and catalyses the multi-mono-ubiquitination of a subset of chromatin-bound ORC3 and ORC5 during S-phase . Common genetic variants at the OBI1 locus had been associated with alterations in lipid metabolism and cognitive performance . This entry represents the C3HC4-type RING-HC finger.
Integrin-linked protein kinase, pseudokinase domain (PK_ILK)
Type: Domain

The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Human Integrin linked kinase (ILK), also known as Scaffold protein ILK, contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration . ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase . In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation . The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin .
Tyrosine-protein kinase Fgr, SH2 domain (Fgr_SH2)
Type: Domain

Tyrosine-protein kinase Fgr belongs to the SRC family of the Tyr protein kinases. It is a non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration . It contains a protein kinase domain, an SH2 domain and an SH3 domain. Fgr interacts with tyrosine phosphorylated SYK, FLT3 and HCLS1 via its SH2 domain .

This entry represents the SH2 domain of Fgr.
Endophilin-B1, BAR domain (SH3GLB1_BAR)
Type: Domain

This entry represents the BAR domain of endophilin-B1.
DNA-directed RNA polymerase III subunit RPC1, N-terminal (RNAP_III_RPC1_N)
Type: Domain

RPC1 (C160) subunit forms part of the active site region of RNA polymerase III (RNAP III). The N-terminal domain of Rpb1, the largest subunit of RNAP II in yeast, forms part of the active site, making up the head and core of the one clamp, as well as the pore and funnel structures of RNAP II. The strong homology between RPC1 and Rpb1 suggests a similar functional and structural role .

DNA-directed RNA polymerases

(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length . The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.

RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.

RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.
DNA-directed RNA polymerase III subunit RPC1, C-terminal (RNAP_III_Rpc1_C)
Type: Domain

DNA-directed RNA polymerases

(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length . The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.

RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.

RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.

RPC1 (C160) subunit forms part of the active site region of RNA polymerase III (RNAP III). The C-terminal domain of Rpb1, the largest subunit of RNAP II, makes up part of the foot and jaw structures of RNAP II. The similarity between this domain and the C-terminal domain of Rpb1, its counterpart in RNAP II, suggests a similar functional and structural role .
Dynein heavy chain, hydrolytic ATP-binding dynein motor region (AAA_6)
Type: Domain

Dyneins are multiprotein complexes that move cargo along microtubules in the minus end direction. The largest component of the dynein complex is the heavy chain. Its C terminus forms the motor unit .

The 380kDa motor unit of dynein belongs to the AAA class of chaperone-like ATPases. The core of the 380kDa motor unit contains a concatenated chain of six AAA modules, of which four correspond to the ATP binding sites with P-loop signatures described previously, and two are modules in which the P loop has been lost in evolution. This domain is the D1 unit of the motor and contains the hydrolytic ATP binding site .

This is the AAA1 large (AAA1L) subdomain with the accompanying small subdomain (AAA1S). AAA1L, AAA1S and AAA2L enclose ADP.vanadate (ADP.Vi, ATP-hydrolysis transition state analogue). The AAA1L sensor-I loop, which varies in position depending on dynein's nucleotide state, swings in to contact AAA2L forming the important AAA1 nucleotide-binding site .
Rsc1/Rsc2, bromodomain (Rsc1/Rsc2_Bromo)
Type: Domain

This entry represents the bromodomain of Rsc1 and Rsc2 from budding yeasts. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine.

The chromatin structure remodeling (RSC) complex consists at least of fifteen subunits, one of them being either RSC1 or RSC2. Neither RSC1 nor RSC2 is essential for viability, suggesting that they have some redundant function .

RSC is involved in transcription regulation and nucleosome positioning . It is responsible for the transfer of a histone octamer from a nucleosome core particle to naked DNA . The reaction requires ATP and involves an activated RSC-nucleosome intermediate. The remodeling reaction also involves DNA translocation, DNA twist and conformational change. As a reconfigurer of centromeric and flanking nucleosomes, RSC complex is required both for proper kinetochore function in chromosome segregation and, via a PKC1-dependent signaling pathway, for organisation of the cellular cytoskeleton .
In addition to being essential for mitotic growth, the RSC complex is also required for sporulation .
Caspase-10, death effector domain (CASP10_DED2)
Type: Domain

Caspase-10 (CASP10) is the initiator of the extrinsic activation pathway. This protein activates Caspase-3, -4, -6, -7, -8, and -9 . Activation of executor caspases 3, 6 and 7 leads to apoptosis.

Isoform C of human caspase-10 is proteolytically inactive .

This entry represents the second repeat of the Death effector domain (DED2) found in CASP10. This domain plays a unique structural role.
Caspase-2, CARD domain (CASP2_CARD)
Type: Domain

Caspase-2 (CASP2) is involved in the activation cascade of caspases responsible for apoptosis execution . Many cytoplasmic proteins have been identified as substrates for caspase-2 . One of these proteins is Bid, which is inactivated by caspase-2 and the serine endopeptidase granzyme B, and which ultimately leads to the release of cytochrome C from the mitochondrion and activation of the executor caspases by caspase-9 .

This entry represents the Caspase activation and recruitment domain (CARD) of CASP2. It is predicted to consist of six antiparallel α-helices, showing a death domain fold .
SNX18, PX domain (SNX18_PX)
Type: Domain

Sorting nexin-18 (SNX18) is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1 . It binds FIP5 and is required for apical lumen formation . It may also play a role in axonal elongation . SNXs are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system . SNX18 also contains BAR and SH3 domains.

The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes .
SNX8/Mvp1, PX domain (SNX8/Mvp1_PX)
Type: Domain

Sorting nexin-8 (SNX8) belongs to the sorting nexin family, which contains a conserved PX (phox homology) domain that is responsible for binding to specific phosphoinositides . It may play a role in intracellular protein transport from early endosomes to the trans-Golgi network . SNX8 yeast counterpart, Mvp1, is required for sorting proteins to the vacuole .

The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions . Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system . The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway .
Dynein heavy chain, ATP-binding dynein motor region (AAA_9)
Type: Domain

Dyneins are multiprotein complexes that move cargo along microtubules in the minus end direction. The largest component of the dynein complex is the heavy chain. Its C terminus forms the motor unit .

The 380kDa motor unit of dynein belongs to the AAA class of chaperone-like ATPases. The core of the 380kDa motor unit contains a concatenated chain of six AAA modules, of which four correspond to the ATP binding sites with P-loop signatures described previously, and two are modules in which the P loop has been lost in evolution .

This is the fifth AAA+ domain subdomain AAA5S. Structural analysis reveal that it is the coiled-coil buttress interface. The relative movement of AAA5S together with the stalk (AAA4S), is coupled to rearrangements in the AAA+ ring. Closure of the AAA1 site and the rigid body movement of AAA2-AAA4 force the AAA4/AAA5 interface to close and the AAA6L subdomain to rotate towards the ring centre. The AAA5S subdomain rotates as a unit together with AAA6L, and this movement pulls the buttress relative to the stalk .
RutC family, YoaB-like (YoaB-like)
Type: Family

This group of proteins belong to a large family of YjgF/YER057c/UK114-like proteins present in bacteria, archaea, and eukaryotes with no definitive function. The conserved domain is similar in structure to chorismate mutase but there is no sequence similarity and no functional connection. Members of this family have been implicated in isoleucine (Yeo7, Ibm1, aldR) and purine (YjgF) biosynthesis, as well as threonine anaerobic degradation (tdcF) and mitochondrial DNA maintenance (Ibm1) . This protein homotrimerizes forming a distinct intersubunit cavity that may serve as a small molecule binding site .
Archaeal gltB (Archaeal_gltB)
Type: Family

This entry represents the archaeal-type gltB proteins. Proteins in this entry share sequence similarity with a region of unknown function found in the large subunit of glutamate synthase, which is encoded by gltB and found in most bacteria and eukaryotes. It is predicted to be homologous to the C-terminal domain of glutamate synthase based upon sequence similarity coupled with genome organization data, showing that this protein is found in a gene cluster with other proteins of Glts, which are annotated. Proteins in this entry are found in archaea, but are also present in a few bacteria, likely as a result of lateral gene transfer .
TRADD (TRADD)
Type: Family

This entry represents TRADD (or tumour necrosis factor receptor type 1-associated DEATH domain protein). TRADD interacts with the cytoplasmic domain of activated TNFRSF1A/TNFR1, which in turn enables it to interact with FADD. Overexpression of TRADD results in apoptosis and activation of NF-kappa-B . TRADD shuttles from the cytoplasm into the nucleus. The nuclear form of TRADD is a tumour suppressor, which by interacting with TRIP12 disrupts its complex with isoform p19ARF/ARF of CDKN2A, preventing ubiquitination and degradation .
RAG1 importin-binding (RAG1_imp-bd)
Type: Domain

This region of RAG1 is responsible for binding to importin alpha .
Metallothionein-like protein Crs5 (Crs5)
Type: Family

This entry includes metallothionein-like protein Crs5 from budding yeasts .
Cortactin, SH3 domain (Cortactin_SH3)
Type: Domain

Cortactin was originally identified as a substrate of Src kinase . It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments . It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion .
Drebrin-like protein, SH3 domain (Drebrin-like_SH3)
Type: Domain

Drebrin-like protein (also known as HIP-55 or ABP1) is a F-actin binding protein that is involved in receptor-mediated endocytosis, vesicle recycling and dorsal ruffle formation . It plays important roles in immune function and in cytoskeletal processes during neuronal network formation .

ABP1 contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins . This entry represents the SH3 domain of ABP1.
Fungal actin-binding protein 1, second SH3 domain (Abp1_fungi_SH3_C2)
Type: Domain

Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking . It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins, such as that from Schizosaccharomyces pombe, contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization . The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization . It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis .

This entry represents the second SH3 domain of Abp1 from fungi such as Schizosaccharomyces pombe.
Fungal actin-binding protein 1, first SH3 domain (Abp1_fungi_SH3_C1)
Type: Domain

Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking . It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins, such as that from Schizosaccharomyces pombe, contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization . The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization . It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis .

This entry represents the SH3 domain of fungal Abp1 and the first SH3 domain of app1 from Schizosacchormyces pombe.
SAM and SH3 domain-containing protein 1, SH3 domain (SASH1_SH3)
Type: Domain

SASH1 is a potential tumour suppressor in breast and colon cancer. Its decreased expression is associated with aggressive tumour growth, metastasis, and poor prognosis . It is widely expressed in normal tissues (except lymphocytes and dendritic cells) and is localized in the nucleus and the cytoplasm . SASH1 interacts with the oncoprotein cortactin and is important in cell migration and adhesion. It is a member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) and SH3 domains .

This entry represents the SH3 domain of SASH1.
SAM and SH3 domain-containing protein 3, SH3 domain (SASH3_SH3)
Type: Domain

SASH3, also called SLY/SLY1 (SH3-domain containing protein expressed in lymphocytes), is expressed exclusively in lymhocytes and is essential in the full activation of adaptive immunity . It is involved in the signaling of T cell receptors . It was the first described member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) and SH3 domains .

This entry represents the SH3 domain of SASH3.