SII-SWORD/CoKE huggingface dataset:
Signal transducer and activator of transcription 4, DNA-binding domain (STAT4_DBD)
Type: Domain

Signal transducer and activator of transcription 4 (STAT4) transduces interleukin-12, interleukin-23, and type I interferon cytokine signals in T cells and monocytes . It plays an important role in CD4+ Th1 lineage differentiation and IFN-gamma protein expression by CD4+ T cells . It is crucial for both innate and adaptive immune responses to viral infection . Variations of the STAT4 gene affect the susceptibility to autoimmune diseases , such as systemic lupus erythematosus 11 (SLEB11) and rheumatoid arthritis (RA) .

STAT proteins have a dual function: signal transduction and activation of transcription. When cytokines are bound to cell surface receptors, the associated Janus kinases (JAKs) are activated, leading to tyrosine phosphorylation of the given STAT proteins . Phosphorylated STATs form dimers, translocate to the nucleus, and bind specific response elements to activate transcription of target genes . STAT proteins contain an N-terminal domain (NTD), a coiled-coil domain (CCD), a DNA-binding domain (DBD), an α-helical linker domain (LD), an SH2 domain, and a transactivation domain (TAD). The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6 .

This entry represents the DNA-binding domain (DBD) of STAT4. It has an immunoglobulin-like structural fold.
Cyclin-dependent kinase inhibitor 1 (CDKN1A)
Type: Family

This entry represents the cyclin-dependent kinase inhibitor 1 (CDKN1A, also known as p21) from animals. It is a direct transcriptional target of p53 and may repress apoptosis . It mediates several important physiological effects of p53, including DNA-damage-induced cell cycle checkpoints . p21 plays a critical role in regulating cell growth and the cell response to DNA damage .
Kelch-like protein 6, BTB/POZ domain (BTB_POZ_KLHL6)
Type: Domain

Kelch-like protein 6 (KLHL6) is involved in B-lymphocyte antigen receptor signalling and germinal centre formation . Mutations in KLHL6 gene have been linked to chronic lymphocytic leukaemia (CLL) . This entry represents the BTB/POZ domain.

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .
Protein AMBP (AMBP)
Type: Family

Protein AMBP is a precursor that gives rise to two different secreted proteins upon endopeptidase cleavage in hepatocytes . One of the two proteins after cleavage, alpha1-microglobulin is a glycoprotein that belongs to the lipocalin family. It has immunoregulatory properties and is involved in heme-catabolism . The second protein, bikunin, is a Kunitz-type proteinase inhibitor of the inter-alpha-inhibitor family .
V-set and immunoglobulin domain-containing protein 1 (VSIG1)
Type: Family

V-set and immunoglobulin domain-containing protein 1 (VSIG1, also konwn as A34) belongs to the immunoglobulin superfamily (IgSF), whose members have one or more Ig-like domains in the extracellular region that is implicated in cell-cell adhesion, a transmembrane domain, and one cytoplasmic C-terminal region . VSIG1 is required for the proper differentiation of glandular gastric epithelia .
Myelin protein zero-like protein 2, Ig-like domain (MPZL2_Ig-like_dom)
Type: Domain

Myelin protein zero-like protein 2 (MPZL2), also known as epithelial V-like antigen (EVA), is a transmembrane protein that contains an extracellular immunoglobulin (Ig)-like V-type (variable) structural domain, and therefore has a putative role in cell adhesion. In mice Mpzl2 can compensate for the deficiency of Cadm1 (cell adhesion molecule-1) in the earlier spermatogenic cells . It is is expressed in the thymus and in several epithelial structures early in embryogenesis, and therefore it may participate in the earliest phases of thymus organogenesis .

This entry represents the immunoglobulin (Ig)-like domain of MPZL2.
Dyslexia-associated protein KIAA0319-like (KIAA0319-like)
Type: Family

Several dyslexia-associated proteins have been identified: ROBO1, KIAA0319, KIAA0319L, S100B, DOCK4, FMR1, DIP2A, GTF2I, DYX1C, DCDC2, SLIT2, HMGB1 and VAPA . This entry includes KIAA0319 and KIAA0319-like (KIAA0319L) proteins. KIAA0319 is required for neuronal migration during the formation of the cerebral neocortex . KIAA0319L has a possible role in axon guidance through interaction with nogo receptor 1 .
Steroidogenic acute regulatory protein (StAR)
Type: Family

Steroidogenic acute regulatory protein (StAR) facilitates the biosynthesis of steroid hormones by regulating the transfer of cholesterol from the outer to the inner mitochondrial membrane . Mitochondrial fusion and ERK phosphorylation can direct StAR to the outer mitochondrial membrane to achieve a large number of steroid molecules per unit of StAR .
StAR-related lipid transfer protein 3, C-terminal (STARD3_MLN64_C)
Type: Domain

StAR-related lipid transfer protein 3 (STARD3, also known as MLN64) is an integral membrane protein localised to the late endosome and plasma membrane. It may function as a mediator of cholesterol transport from endosomal membranes to the plasma membrane and/or mitochondria . It contains an N-terminal membrane-spanning domain that shares homology with the MENTHO protein and a C-terminal steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain that binds lipids, including sterols . Its transport to the late endosome is regulated by binding to 14-3-3 .
Rho-associated protein kinase 2, catalytic domain (ROCK2_cat)
Type: Domain

Rho-associated protein kinases (ROCKs) were originally identified as small GTPase Rho effectors. Later, ROCKs were found actively phosphorylating many actin-binding proteins and intermediate filament proteins to modulate their functions . Two ROCK isoforms have been identified:
ROCK1 (ROKb, p160ROCK) and ROCK2. As major downstream effectors of the small GTPase RhoA, they regulate cellular contraction, motility, morphology, polarity, cell division, and gene expression .

This entry represents the catalytic domain of ROCK2. ROCK2 has a predominant role in vascular smooth muscle cell contractility .
Kinase non-catalytic C-lobe domain-containing protein 1 (KNDC1)
Type: Family

Kinase noncatalytic C-lobe domain containing 1 (KNDC1), also known as very-KIND, is a brain-specific Ras guanine nucleotide exchange factor (RasGEF) that regulates microtubule-associated protein 2 (MAP2) during dendrite morphogenesis . It contains two kinase noncatalytic C-lobe domains (KIND1 and KIND2), a RasGEF N-terminal domain (RasN) and a putative RasGEF domain . The KIND2 domain regulates dendrite complexity via targeting of v-KIND to MAP2 associated with the dendritic microtubule cytoskeleton .
Protein Spire (Spire)
Type: Family

This entry represents the Spire (Spir) family, including vertebrate Spire-1 and Spire-2, Ciona savignyi PEM-5 and Drosophila dSpire. They contain a KIND (kinase noncatalytic C-lobe) domain and four actin-binding WH2 (WASP homology 2) domains . They act as actin nucleation factors and are involved in a novel actin-dependent mechanism for long range vesicle transport . Although Spire proteins are capable of nucleating actin polymerisation in vitro by themselves, they have been found to act in cooperation with members of another family of actin nucleators: the formin subgroup (FMN) of formins . Spire/formin cooperation is considered to have a major regulatory function in mammalian oocyte maturation . The structure of Spire has been revealed .
RmlD-like substrate binding domain (RmlD-like-bd)
Type: Domain

L-rhamnose is a saccharide required for the virulence of some bacteria. Its precursor, dTDP-L-rhamnose, is synthesised by four different enzymes. RmlD catalyses the final step of the dTDP-L-rhamnose synthesis. This entry represents the RmlD substrate binding domain, which is responsible for binding a sugar nucleotide .
Protein Spire homolog 1, FYVE-related domain (Spir-1_FYVE-rel_dom)
Type: Domain

This entry represents the FYVE-related domain of Spire homolog 1 (Spir-1) and similar proteins from chordates. Spir-1 acts as an actin nucleation factor that remain associated with the slow-growing pointed end of the new filament . It is involved in intracellular vesicle transport along actin fibres, providing a novel link between actin cytoskeleton dynamics and intracellular transport . The structure of Spire has been revealed . It contains an N-terminal KIND (kinase noncatalytic C-lobe) domain and four actin-binding WH2 (WASP homology 2) domains, a Rab GTPase-interaction Spir-box, and a C-terminal FYVE zinc-binding domain (this entry) .

The mammalian genome encodes two Spir proteins, Spir-1 and Spir-2. In adult tissues, the spir-2 gene shows a rather broad expression pattern, whereas spir-1 is mainly expressed in neuronal cells of the nervous system. Spir-1 may have a role in neural function .
Trichome birefringence-like family (TBL)
Type: Family

Trichome birefringence-like (TBL) is a plant protein family. In Arabidopsis this family includes 46 members (TBR, TBL1-45) . The TBL family is proposed to encode wall polysaccharide specific O-acetyltransferases . They contain a TBL domain with a conserved glycine-aspartate-serine (GDS) signature, similar to the conserved motif (GDSL) found in some esterases/lipases . Members of the TBL protein family had been shown to impact pathogen resistance, freezing tolerance, and cellulose biosynthesis .
LIM domain only protein 7 (LMO-7)
Type: Family

LIM domain only protein 7 (LMO-7) contains a LIM zinc-binding domain and a PDZ domain. LMO7 is involved in the regulation of cell adhesion and signaling . In humans it has several isoforms; isoform 2 and isoform 4 are predominantly expressed in brain . It may have roles in embryonic development and cancer progression .
Kaptin (Kptn)
Type: Family

Kaptin (Kptn) is an actin-associated protein that may be involved in the actin organisation in platelets and neurons . Mutations in the kaptin gene cause mental retardation, autosomal recessive 41 (MRT41) . Kaptin is a component of the KICSTOR complex which is found in the lysosome and interacts with the GATOR1 complex, binding it to the lysosomal membrane surface. KICSTOR is a negative regulator of mTORC1 signalling during amino acid or glucose starvation .
Plant galacturonosyltransferase GAUT (GAUT)
Type: Family

Galacturonosyltransferase 1 (GAUT1) is an alpha1,4-D-galacturonosyltransferase that transfers galacturonic acid from uridine 5'-diphosphogalacturonic acid onto the pectic polysaccharide homogalacturonan . The GAUT1-related gene family from Arabidopsis thaliana encodes 15 GAUT and 10 GAUT-like (GATL) proteins . This entry represent the GAUT proteins.
Scaffold protein salvador (Sav)
Type: Family

Salvador (sav, also known as Shar-pei) is a scaffold protein that plays an important role in the Hippo/SWH (Sav/Wts/Hpo) signalling pathway, which is involved in organ size control and tumour suppression by restricting proliferation and promoting apoptosis . In Drosophila it mediates cell proliferation arrest during imaginal disc growth . It also promotes both cell cycle exit and apoptosis .
PDZ domain-containing protein MAGIX (MAGIX)
Type: Family

MAGIX is a PDZ domain-containing protein. Its function is not clear.
Alpha-catulin 1 (CTNNAL1)
Type: Family

Alpha-catulin 1 (also known as catenin alpha-like protein 1, CTNNAL1) belongs to the alpha catenin family, whose members are involved in cell adhesion. CTNNAL1 may modulate Rho pathway signalling by providing a scaffold for the Lbc Rho guanine nucleotide exchange factor . It is downregulated in asthma patients and animal models .
Survival protein SurE (SurE)
Type: Family

SurE is one of the several proteins that is expressed when bacterial cells are subjected to environmental stresses and in the stationary growth phase of bacteria . In E. coli, surE is next to pcm, an L-isoaspartyl protein repair methyltransferase that is also required for stationary phase survival. It was originally predicted to be an acid phosphatase, however, subsequent work showed this is not the case . SurE has been shown to possess phosphatase activity and appears to be specific to nucleoside monophosphates . In E. coli, Thermotoga maritima, and Pyrobaculum aerophilum SurE acts strictly on nucleoside 5'- and 3'-monophosphates.
Taste receptor type 2 member 38 (TAS2R38)
Type: Family

Taste receptor type 2 member 38 (TAS2R38), a member of the G-protein-coupled bitter receptor family, is the bitter taste receptor responsible for the ability to taste phenylthiocarbamide (PTC) . This protein also has a crucial role in neutrophil-mediated host immunity against Pseudomonas aeruginosa infection in mice .
Taste receptor type 2 member 4 (TAS2R4)
Type: Family

The taste receptors type 2 (T2R) are implicated in the perception of bitter compounds .

Taste receptor type 2 member 4 (TASR4 or T2R4) is expressed in subsets of taste receptor cells of the tongue, palate epithelium and on airway ciliated epithelium. It is a receptor for denatonium (a very bitter compound) and N(6)-propyl-2-thiouracil (a thiouracil-derived drug used to treat hyperthyroidism). In airway epithelial cells, binding of denatonium increases the intracellular calcium ion concentration and stimulates ciliary beat frequency. .
Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1, I-BAR domain (Baiap2l1_I-BAR_dom)
Type: Domain

Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (Baiap2l1, also known as IRTKS or insulin receptor tyrosine kinase substrate) is an I-BAR (Bin/amphipysin/Rvs) domain containing protein. I-BAR domain is a type of the BAR domain, which forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. The BAR domain containing proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature .

Baiap2l1 binds small GTPase Rac rather than Cdc42 . It serves as an adaptor of the insulin receptor (IR), modulates IR-IRS1-PI3K-AKT signalling via regulating the phosphorylation of IR . It has been linked to the formation of actin-rich membrane protrusions, called pedestals, during the infection process of enterohemorrhagic Escherichia coli in vertebrates .

This entry represents the N-terminal I-BAR domain, also known as IRSp53/MIM homology Domain (IMD), of Baiap2l1. This domain binds and bundles actin filaments, binds membranes, and interacts with the small GTPase Rac.
Xin actin-binding repeat-containing protein 1/2 (XIRP1/XIRP2)
Type: Family

Proteins in this family contains Xin repeats, which define an actin-binding motif. In humans two Xin-repeat proteins have been identified, XIRP1 and XIRP2. They are expressed during early developmental stages of cardiac and skeletal muscles and have an important role in cardiac development and function . They bind to and stabilise F-actin .

The homologues in mouse and chicken localise in the adherens junction complex of the intercalated disc in cardiac muscle and in the myotendon junction of skeletal muscle. Mouse Xin may co-localise with Vinculin which is known to attach the actin to the cytoplasmic membrane . Human XIRP1 binds the EVH1 domains of Ena/VASP proteins and filamin C . It also binds the SH3 domain of nebulin and nebulette . The multiplicity of binding partners suggests that Xin acts as a multi-adaptor protein during myofibril development and repair .
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D 2, SWIB domain (SMARCD2_SWIB_dom)
Type: Domain

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member (SMARCD1, also known as Brg/Brm-associated factor 60B, BAF60B) is part of the SWI/SNF complex, which is an ATP-dependent chromatin remodelling complex that regulates gene expression through regulating nucleosome remodelling. BAF60B interacts with multiple transcription factors and may bridge transcription factors with SWI/SNF complexes . It can be regulated by ubiquitination controlled by Rac GTPase and the RING finger protein Unkempt . This protein plays a role in the ATM-p53 pathway in sensing chromatin opening by facilitating ATM recruitment to the SWI/SNF complex, as well as ATM activation. It also regulates transcriptional networks controlling differentiation of neutrophil granulocytes. Thus, it acts as a key factor controlling myelopoiesis and is a potential tumour suppressor in leukaemia .

This entry represents the SWIB domain of SMARCD2.
AT-rich interactive domain-containing protein 1A, ARID/BRIGHT DNA binding domain (ARID1A_ARID_BRIGHT_DNA-bd)
Type: Domain

AT-rich interactive domain-containing protein 1A (ARID1A or BAF250a) is part of the SWI/SNF-like ATP-dependent chromatin remodelling complex that regulates gene expression through regulating nucleosome remodelling . In humans there are two BAF250 isoforms, BAF250a/ARID1A and BAF250b/ARID1B . Both BAF250a and BAF250b bind DNA non-specifically . They are thought to be E3 ubiquitin ligases that target histone H2B . BAF250a plays key roles in maintaining embryonic stem cell pluripotency and in cardiac development and function . The BAF250a gene is a tumour suppressor gene that is frequently mutated in ovarian clear cell carcinoma .

This entry represents the ARID/BRIGHT DNA binding domain of ARI1A. It binds DNA in a non-sequence-specific manner similar to ARID1B .
SWI/SNF complex subunit BRG1, ATP-binding (BRG1_ATP-bd)
Type: Domain

BRG1 (also know as SMARCA4 or BAF190A) is a core enzymatic subunit of the SWI/SNF complex, an ATP-dependent chromatin remodelling complex that regulates gene expression through regulating nucleosome remodelling . In humans BRG1 shares 73% sequence identity with hBRM (human Brahma) and has similar ATPase function in the SWI/SNF complex . BRG1 contains a conserved ATPase domain and a C-terminal bromodomain that may anchor the entire SWI/SNF complex to promoter nucleosomes . BRG1 may function as tumour suppressor .

This entry represents the ATP-binding region of BRG1.
Actin-binding protein IPP, BTB/POZ domain (BTB_POZ_IPP)
Type: Domain

The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding , while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins . In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins . Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases .

IPP (also known as Kelch-like protein 27) belongs to the KLHL family. It binds to actin through its kelch repeat domain . It may play a role in organizing the actin cytoskeleton, however, its exact function is not clear. This entry represents the BTB/POZ domain.
Actin-filament associated protein (AFAP)
Type: Family

The actin-filament associated protein (AFAP) family of adaptor proteins include AFAP1, AFAP1L1, and AFAP1L2/XB130 . They contain the pleckstrin homology (PH) domain that plays a role in recruiting proteins to different membranes.
F-BAR domain only protein 2, F-BAR domain (FCHo2_F-BAR)
Type: Domain

F-BAR domain only protein 2 (FCHo2) belongs to the F-BAR family, whose members have been implicated in cell membrane processes such as membrane invagination, tubulation and endocytosis . FCHo2 organises clathrin-coated structures and interacts with adaptor Disabled-2 for low-density lipoprotein receptor endocytosis . The structure of the FCHo2 F-BAR domain has been solved .

This entry represents the N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of FCHo2. This domain form banana-shaped dimers with a positively-charged concave surface that binds to negatively-charged lipid membranes. These dimers can induce membrane deformation in the form of long tubules .
SPIN90/Ldb17 (SPIN90/Ldb17)
Type: Family

This entry includes SPIN90 from animals, Ldb17 from budding yeasts and Dip1 from fission yeasts.

Protein Ldb17 is recruited to cortical actin patches before actin polymerisation and regulates normal coat dynamics and actin assembly . It is a component of the endocytic machinery .

SPIN90, also known as NCK interacting protein with SH3 domain (NCKIPSD), is an F-actin binding protein that regulates actin polymerization and endocytosis . It associates with the Arp2/3 complex near actin filaments and determines filament localization at the leading edge of lamellipodia . SPIN90 is expressed in the early stages of neuronal differentiation and plays a role in regulating growth cone dynamics and neurite outgrowth . It also interacts with IRSp53 and regulates cell motility by playing a role in the formation of membrane protrusions . SPIN90 contains an N-terminal SH3 domain, a proline-rich domain, and a C-terminal VCA (verprolin-homology and cofilin-like acidic) domain .
Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 2, I-BAR domain (Baiap2l2_I-BAR_dom)
Type: Domain

Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 2 (Baiap2l2), also known as BAR/IMD domain-containing adapter protein 2-like 2 and planar intestinal and kidney specific BAR domain protein (Pinkbar), is an I-BAR (Bin/amphipysin/Rvs) domain containing protein. BAR domain forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. BAR domain proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature .

In humans Baiap2l2 is specifically expressed in intestinal epithelial cells, where it localises to Rab13-positive vesicles and to the plasma membrane at intercellular junctions . The BAR domain of Baiap2l2 does not induce membrane protrusions or invaginations; instead, it promotes the formation of planar membrane sheets .

This entry represents the N-terminal I-BAR domain, also known as IRSp53/MIM homology Domain (IMD), of Baiap2l2.
I-BAR domain containing protein MTSS1/MTSS2 (MTSS1/MTSS2)
Type: Family

This entry represents a subgroup of I-BAR (Bin/amphipysin/Rvs) domain-containing proteins, including MIM (MTSS1) and MTSS2 (also known as ABBA or MTSS1-like). BAR domain forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. BAR domain proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature . Most I-BAR proteins, including MIM and MTSS2, have an additional C-terminal WH2 domain, which binds G-actin .