SII-SWORD/CoKE huggingface dataset:
Hematopoietic SH2 domain-containing protein, Src homology 2 domain (HSH2D_SH2)
Type: Domain

HSH2D (hematopoietic SH2 domain-containing protein, also known as ALX) is an adapter protein involved in tyrosine kinase and CD28 signaling . It is expressed exclusively in hematopoietic cells. It contains an Src homology 2 (SH2) domain, four PXXP polyproline sequences, and two likely sites of tyrosine phosphorylation. The SH2 domain plays a critical role in ALX function downstream of CD28 .

This entry represents the Src homology 2 (SH2) domain of HSH2.
EAT-2, SH2 domain (EAT2_SH2)
Type: Domain

This entry represents the SH2 domain of EAT-2 (EWS-Fli1-activated transcript-2) and ERT (EAT-2-related transducer).

The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5-residue N-terminal, a single SH2 domain, and a short 25-residue C-terminal tail . XLP is characterised by an extreme sensitivity to the Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84 .
SLAP, SH2 domain (SLAP_SH2)
Type: Domain

This entry represents the SH2 domain found in SLAP/SLAP2.

Src-like adapter proteins (SLAP and SLAP2) are involved in the regulation of immune cell surface expression and signaling. They negatively regulate T cell receptor signaling and act as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke . They contain adjacent Src homology 3 (SH3) and Src homology 2 (SH2) domains. SLAP has been shown to regulate receptor tyrosine kinase (RTK) signaling . It also binds to the receptor tyrosine kinase Flt3 and plays a role in signal transduction downstream of Flt3 . SLAP2 acts as a negative regulator of FLT3 signaling .
RPK118-like, kinase domain (STK_RPK118-like)
Type: Domain

This entry represents the catalytic domain of the serine/threonine kinase RPK118 (also known as ribosomal protein S6 kinase delta-1) and similar proteins. RPK118 contains an N-terminal Phox homology (PX) domain, a microtubule-interacting and Trafficking (MIT) domain, and a kinase domain containing a long uncharacterised insert. This domain is also present in human RPK60 (or ribosomal protein S6 kinase-like 1), which also contains a MIT domain, but lacks a PX domain.

RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signalling . RPK118 also binds the antioxidant peroxiredoxin-3 (PRDX3). RPK118 may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria .
MST4, kinase domain (STK_MST4)
Type: Domain

This entry represents the catalytic domain of serine/threonine-protein kinase 26, also known as MST4 or MASK (MST3 and SOK1-related kinase). MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis . It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway . MST4 may also play a role in tumor formation and progression . It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration .
SH2B1, SH2 domain (SH2B1_SH2)
Type: Domain

This entry represents the SH2 domain of SH2B adapter protein 1.

SH2B adapter protein 1 (SH2B1) belongs to the SH2B family of adapter proteins . It promotes insulin expression and glucose metabolism in beta-cells in mice . It is also involved in brain-derived neurotrophic factor-induced neurite outgrowth .

SH2B family contains three members of adaptor proteins: SH2B1, 2 and 3 . Typical SH2B proteins contain a SH2 (Src homology 2) and a PH (pleckstrin homology) domain. They serve as adaptors involved in signalling by the receptors for growth factors, such as insulin-like growth factor 1, platelet-derived growth factor and nerve growth factor .
SH2B2, SH2 domain (SH2B2_SH2)
Type: Domain

This entry represents the SH2 domain of SH2B2.

SH2B adapter protein 2 (SH2B2, also known as APS) belongs to the SH2B family of adapter proteins . SH2B2 is involved in multiple signalling pathways, including cytokine signalling and insulin receptor signalling . It also binds to Vav3, a member of the vav proto-oncogene family, and increases its activity .

SH2B family contains three members of adaptor proteins: SH2B1, 2 and 3 . Typical SH2B proteins contain a SH2 (Src homology 2) and a PH (pleckstrin homology) domain. They serve as adaptors involved in signalling by the receptors for growth factors, such as insulin-like growth factor 1, platelet-derived growth factor and nerve growth factor .
SH2B3, SH2 domain (SH2B3_SH2)
Type: Domain

This entry represents the SH2 domain of SH2B3.

SH2B adapter protein 3 (SH2B3) belongs to the SH2B family of adapter proteins . It is involved in the homeostasis of hematopoietic stem cells and lymphoid progenitors, and plays a tumour suppressor role in the acute lymphoblastic leukemia . SH2B3 (Lnk) may also influence inflammatory immune responses in peripheral lymphoid tissues . A link has been established between polymorphism in this adaptor protein and autoimmune diseases, including type 1 diabetes and celiac disease .

SH2B family contains three members of adaptor proteins: SH2B1, 2 and 3 . Typical SH2B proteins contain a SH2 (Src homology 2) and a PH (pleckstrin homology) domain. They serve as adaptors involved in signalling by the receptors for growth factors, such as insulin-like growth factor 1, platelet-derived growth factor and nerve growth factor .
Serine/threonine kinase 25, catalytic domain (STK_STK25)
Type: Domain

STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130 . It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis . Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype .
Shark-like, N-terminal SH2 domain (Shark-like_SH2_N)
Type: Domain

This entry represents the SH2 domain found in Drosophila shark protein and hydra protein HTK16.

Shark and HTK16 are non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling .

Drosophila Shark transduces intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal . It is essential for Draper-mediated signalling .
Kic1p-like serine/threonine kinase, catalytic domain (STK_Kic1p-like)
Type: Domain

This catalytic domain is found in Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner .
p21-activated kinase 3, catalytic domain (STK_PAK3)
Type: Domain

This entry represents the catalytic domain of serine/threonine kinase p21-activated kinase (PAK) 3.

PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis . Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation . PAK3 belongs to the group I PAKs.

Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac .
p21-activated kinase 2, catalytic domain (STK_PAK2)
Type: Domain

PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis . PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response . PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1 . PAK2 belongs to the group I PAKs.

Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac .

This entry corresponds to the PAK2 C-terminal catalytic domain.
Serine/threonine-protein kinase PAK 6, catalytic domain (STKc_PAK6)
Type: Domain

PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway . PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory . Increased expression of PAK6 is found in primary and metastatic prostate cancer .

PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites . PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac .

This entry represents the C-terminal catalytic domain of PAK6.
V-type ATPase subunit C/D (V-type_ATPase_csu/dsu)
Type: Homologous_superfamily

This superfamily represents the first and second domains of V-type ATP synthase subunits C and d. Structurally, these subunits are divided into three similar domains, each of which has essentially the same topology consisting of two central and four peripheral helices .

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

The V-ATPases (or V1V0-ATPase) and A-ATPases (or A1A0-ATPase) are each composed of two linked complexes: the V1 or A1 complex contains the catalytic core that hydrolyses/synthesizes ATP, and the V0 or A0 complex that forms the membrane-spanning pore. The V-ATPase folding, localisation, and stability is made possible through the formation of a luminal glycan coat by the glycolipids and the glycosylated V0 subunits . The V- and A-ATPases both contain rotary motors, one that drives proton translocation across the membrane and one that drives ATP synthesis/hydrolysis . The V- and A-ATPases more closely resemble one another in subunit structure than they do the F-ATPases, although the function of A-ATPases is closer to that of F-ATPases.
Metalloprotease TldD/PmbA, N-terminal (TldD/PmbA_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain found in a group metalloproteases, including TldD and PmbA . TldD and PmbA (TldE) were originally identified as regulators of DNA gyrase. Later, they are shown to be metalloproteases involved in CcdA degradation .
TTHA1013/TTHA0281-like (TTHA1013/TTHA0281-like)
Type: Homologous_superfamily

TTHA0281 is a hypothetical protein from Thermus thermophilus HB8 that belongs to an uncharacterised protein family UPF0150. The TTHA0281 monomer adopts an α-β-β-β-α fold and forms a homotetramer. Based on the properties and functions of structural homologues of the TTHA0281 monomer, such as the HicB protein from the HicAB cassette toxin antitoxin system , the TTHA0281 protein is speculated to be involved in RNA metabolism, including RNA binding and cleavage .

TTHA1013 is annotated as a hypothetical protein from Thermus thermophilus HB8. The overall fold of this protein consists of one α-helix and four β-strands .
Streptogrisin prodomain (Streptogrisin_prodomain)
Type: Homologous_superfamily

Streptogrisins and alpha-lytic endopeptidase are extracellular bacterial proteins composed of two α-β layers. This entry represents the precursor Pro-domain.
At2g17340, three-helix bundle domain (At2g17340_3_helix_bundle)
Type: Homologous_superfamily

This superfamily represents a three-helix bundle domain found at the N-terminal end of the damage-control phosphatase At2g17340 from Arabidopsis thaliana . It is a metal-dependent phosphatase with probable damage-control functions . The C-terminal portion of several eukaryotic pantothenate kinases also contains this domain.
EspA/CesA-like (EspA/CesA-like)
Type: Homologous_superfamily

EspA, together with EspB, EspD and Tir are exported by a type III secretion system. These proteins are essential for attaching and effacing lesion formation. EspA is a structural protein and a major component of a large, transiently expressed, filamentous surface organelle which forms a direct link between the bacterium and the host cell .

CesA acts as a chaperone of secreted protein EspA, trapping EspA in a monomeric state and inhibiting its polymerization. Both adopt similar substructures in the heterodimer. CesA adopts an extended all-helical topology with an overall hairpin shape. EspA contains two long α-helices, which are involved in extensive coiled-coil interactions with CesA .
PRMT5 arginine-N-methyltransferase (PRMT5)
Type: Domain

This entry represents a domain found in arginine-N-methyltransferase PRMT5. Proteins containing this domain include Skb1 from S. pombe , Hsl7 from S. cerevisiae and their homologues PRMT5 from animals and plants .

Skb1 is a mediator of hyperosmotic stress response in Schizosaccharomyces pombe . Plant PMRT15 is involved in the post-transcriptional regulation of the circadian clock . Human PRMT5 is a component of multiple protein complexes and contributes to essential cellular processes, such as RNA transport and splicing, cell cycle regulation, tumour growth, and chromatin remodelling, leading to either gene silencing or activation .
Snake toxin/toxin-like (Toxin/TOLIP)
Type: Domain

This domain is predominantly found in venomous neurotoxins and cytotoxins from snakes, but also structurally similar (non-snake) toxin-like proteins (TOLIPs) such as Lymphocyte antigen 6D and Ly6/PLAUR domain-containing protein. Snake toxins are short proteins with a compact, disulphide-rich structure. TOLIPs have similar structural features (abundance of spaced cysteine residues, a high frequency of charge residues, a signal peptide for secretion and a compact structure) but, are not associated with a venom gland or poisonous function. They are endogenous animal proteins that are not restricted to poisonous animals .
Phosphoenolpyruvate carboxykinase, C-terminal P-loop domain (PEP_carboxykinase_GTP_C)
Type: Domain

Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the first committed (rate-limiting) step in hepatic gluconeogenesis, namely the reversible decarboxylation of oxaloacetate to phosphoenolpyruvate (PEP) and carbon dioxide, using either ATP or GTP as a source of phosphate. The ATP-utilising (

) and GTP-utilising (

) enzymes form two divergent subfamilies, which have little sequence similarity but which retain conserved active site residues. ATP-utilising PEPCKs are monomers or oligomers of identical subunits found in certain bacteria, yeast, trypanosomatids, and plants, while GTP-utilising PEPCKs are mainly monomers found in animals and some bacteria . Both require divalent cations for activity, such as magnesium or manganese. One cation interacts with the enzyme at metal binding site 1 to elicit activation, while the second cation interacts at metal binding site 2 to serve as a metal-nucleotide substrate. In bacteria, fungi and plants, PEPCK is involved in the glyoxylate bypass, an alternative to the tricarboxylic acid cycle.

PEPCK helps to regulate blood glucose levels. The rate of gluconeogenesis can be controlled through transcriptional regulation of the PEPCK gene by cAMP (the mediator of glucagon and catecholamines), glucocorticoids and insulin. In general, PEPCK expression is induced by glucagon, catecholamines and glucocorticoids during periods of fasting and in response to stress, but is inhibited by (glucose-induced) insulin upon feeding . With type II diabetes, this regulation system can fail, resulting in increased gluconeogenesis that in turn raises glucose levels .

PEPCK consists of an N-terminal and a catalytic C-terminal domain, with the active site and metal ions located in a cleft between them. Both domains have an α/β topology that is partly similar to one another . Substrate binding causes PEPCK to undergo a conformational change, which accelerates catalysis by forcing bulk solvent molecules out of the active site . PCK uses an α/β/α motif for nucleotide binding, this motif differing from other kinase domains. GTP-utilising PEPCK has a PEP-binding domain and two kinase motifs to bind GTP and magnesium.

This entry represents the C-terminal P-loop domain found in GTP-utilising phosphoenolpyruvate carboxykinase enzymes.
Phosphoenolpyruvate carboxykinase, GTP-utilising, N-terminal (PEP_carboxykinase_GTP_N)
Type: Domain

Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the first committed (rate-limiting) step in hepatic gluconeogenesis, namely the reversible decarboxylation of oxaloacetate to phosphoenolpyruvate (PEP) and carbon dioxide, using either ATP or GTP as a source of phosphate. The ATP-utilising (

) and GTP-utilising (

) enzymes form two divergent subfamilies, which have little sequence similarity but which retain conserved active site residues. ATP-utilising PEPCKs are monomers or oligomers of identical subunits found in certain bacteria, yeast, trypanosomatids, and plants, while GTP-utilising PEPCKs are mainly monomers found in animals and some bacteria . Both require divalent cations for activity, such as magnesium or manganese. One cation interacts with the enzyme at metal binding site 1 to elicit activation, while the second cation interacts at metal binding site 2 to serve as a metal-nucleotide substrate. In bacteria, fungi and plants, PEPCK is involved in the glyoxylate bypass, an alternative to the tricarboxylic acid cycle.

PEPCK helps to regulate blood glucose levels. The rate of gluconeogenesis can be controlled through transcriptional regulation of the PEPCK gene by cAMP (the mediator of glucagon and catecholamines), glucocorticoids and insulin. In general, PEPCK expression is induced by glucagon, catecholamines and glucocorticoids during periods of fasting and in response to stress, but is inhibited by (glucose-induced) insulin upon feeding . With type II diabetes, this regulation system can fail, resulting in increased gluconeogenesis that in turn raises glucose levels .

PEPCK consists of an N-terminal and a catalytic C-terminal domain, with the active site and metal ions located in a cleft between them. Both domains have an α/β topology that is partly similar to one another . Substrate binding causes PEPCK to undergo a conformational change, which accelerates catalysis by forcing bulk solvent molecules out of the active site . PCK uses an α/β/α motif for nucleotide binding, this motif differing from other kinase domains. GTP-utilising PEPCK has a PEP-binding domain and two kinase motifs to bind GTP and magnesium.

This entry represents the N-terminal domain found in GTP-utilising phosphoenolpyruvate carboxykinase enzymes.
Floricaula/Leafy protein, SAM domain (LFY_SAM)
Type: Domain

FLO and LFY proteins are floral meristem identity proteins . Mutations in the sequences of these proteins affect flower and leaf development. LFY has been shown to bind semi-palindromic 19-bp DNA elements through its highly conserved C-terminal DNA-binding domain (DBD). In addition to its well-characterised DBD, LFY possesses a second conserved domain at its amino terminus (LFY-N). Crystallographic structure determination shows that LFY-N is a sterile alpha motif (SAM) domain that mediates LFY oligomerisation. It allows LFY to bind to regions lacking high-affinity LFY-binding sites and to access closed chromatin regions. Experiments revealed that altering the capacity of LFY to oligomerize compromised floral function. It has been suggested that the biochemical properties of the SAM domain are evolutionarily conserved in all plant species .

This entry represents a SAM domain found in various plant proteins which are homologues of floricaula (FLO) and Leafy (LFY).
Lacto-N-biose phosphorylase-like, N-terminal TIM barrel domain (Lact_bio_phlase-like_N)
Type: Domain

This entry represents the N-terminal TIM barrel domain found in lacto-N-biose phosphorylase (lnpA) from Bifidobacterium . Proteins containing this domain also include D-galactosyl-beta-1->4-L-rhamnose phosphorylase (Cphy_1920) from Lachnoclostridium phytofermentans .

LnpA can reversibly phosphorolyzes lacto-N-biose to Gal1-P and N-acetylglucosamine (GlcNAc) and galacto-N-biose to Gal1-P and N-acetylgalactosamine (GalNAc). It is involved in the lacto-N-biose I/galacto-N-biose (LNB/GNB) degradation pathway, which is important for host intestinal colonization by bifidobacteria .

Cphy_1920 can reversibly phosphorolyzes beta-D-galactosyl-(1->4)-L-rhamnose to form alpha-D-galactose 1-phosphate and L-rhamnose. But it does not phosphorolyze galacto-N-biose or lacto-N-biose .
(5-formylfuran-3-yl)methyl phosphate synthase, archaea (4HFCP_synth_arc)
Type: Family

This entry represents the (5-formylfuran-3-yl)methyl phosphate synthase (also known as 4-HFC-P synthase or MfnB), which has a classical TIM-barrel structure whose biological unit is a homohexamer. It is involved in the production of methanofuran. MfnB from Methanocaldococcus jannaschii catalyzed at least 10 separate chemical reactions in converting two molecules of glyceraldehyde-3-P (GA-3-P) to 4-(hydroxymethyl)-2-furancarboxaldehyde-P (4-HFC-P), the first discrete intermediate in the biosynthetic pathway to the furan moiety of the coenzyme methanofuran .
Nrap protein domain 1 (Nrap_D1)
Type: Domain

Members of this family are nucleolar RNA-associated proteins (Nrap) which are highly conserved from yeast (Saccharomyces cerevisiae) to human. In the mouse, Nrap is ubiquitously expressed and is specifically localised in the nucleolus . Nrap is a large nucleolar protein (of more than 1000 amino acids). Nrap appears to be associated with ribosome biogenesis by interacting with pre-rRNA primary transcript .

This domain has a nucleotidyltransferase structure.