SII-SWORD/CoKE huggingface dataset:
Gasdermin-E (GSDME)
Type: Family

Gasdermin-E, also known as DFNA5, is involved in the p53-regulated cellular response to response to DNA damage probably by cooperating with p53 . It can be cleaved by CASP3 into two parts: GSDME-N and GSDME-C. The GSDME-N fragment can perforate membranes and thereby induce pyroptosis . Purified GSDME-N has been shown to efficiently lyse phosphoinositide/cardiolipin-containing liposomes and form pores on membranes made of artificial or natural phospholipid mixtures .

This entry also includes Pejvakin, a gasdermin family member. It is a peroxisome-associated protein required to protect auditory hair cells against noise-induced damage .
Integral membrane protein DGCR2/IDD (IDD)
Type: Family

DGCR2 is an activity-dependent adhesion protein that has been associated with schizophrenia . It has been shown to regulate critical steps of early corticogenesis possibly through a Reelin-dependent mechanism .
Programmed cell death protein 1 (PDCD1)
Type: Family

Programmed cell death protein 1 (PDCD1), also known as PD1, is an immune-checkpoint receptor mainly expressed by T cells that negatively regulates immune response . It interacts with its ligands PD-L1 and PD-L2 to inhibit T cell effector functions in an antigen-specific manner . The PD1-mediated inhibitory pathway is exploited by some tumours to attenuate anti-tumour immunity and escape destruction by the immune system .
Tumor necrosis factor ligand superfamily member 18 (TNFSF18)
Type: Family

TNFSF18, also known as GITRL (glucocorticoid-induced TNF receptor ligand), binds to its receptor GITR on both effector and regulatory T cells and generates positive costimulatory signals . GITR is also activated by a GITR ligand called SECTM1A . The costimulatory effect of GITR activation in T cells has been shown to increase T cell expansion and cytokine production, exacerbate autoimmune/inflammatory diseases, favour tumour rejection, perform viral and parasite clearance, and potentiate immune/inflammatory responses .
T-cell surface protein tactile (CD96)
Type: Family

T-cell surface protein tactile (CD96) is a membrane bound receptor of the immunoglobulin superfamily. It is expressed by both T and NK cells . CD96 interact with CD155, and the hCD155/hCD96 axis may play a role in target cell elimination by NK cells .
Fibrinogen silencer-binding protein (FSBP)
Type: Family

Fibrinogen silencer-binding protein (FSBP) is a transcription factor that interacts with the neuronal adaptor protein X11alpha. The X11alpha/FSBP complex has been shown to signal to the nucleus to repress glycogen synthase kinase-3beta promoter activity .
Neuromedin-U (NMU)
Type: Family

Neuromedin U (NmU) is a vertebrate peptide which stimulates uterine smooth muscle contraction and causes selective vasoconstriction. Like most other active peptides, it is proteolytically processed from a larger precursor protein. The mature peptides are 8 (NmU-8) to 25 (NmU-25) residues long and C-terminally amidated .
CD160 ANTIGEN (CD160)
Type: Family

CD160 is a GPI-anchored MHC-class I activating receptor mainly expressed on peripheral blood NK cells. It is also expressed on both cytolytic lymphocytes and some unstimulated CD4 T cells . CD160 has different isoforms, including GPI-anchored isoform, a transmembrane isoform, and a secreted isoform. Upon specific engagement of CD160 by its physiological ligand HLA-C, or by mAb cross-linking, CD160 PB-NK cells produce significant levels of IFN-gamma, TNF-alpha, IL-6 as well as IL-8 and MIP-1beta .
Podocalyxin-like protein 2 (PODXL2)
Type: Family

Podocalyxin-like protein 2 (PODXL2), also known as Endoglycan, is a ligand for the vascular selectins . It belongs to the CD34 family, whose members contain an N-terminal acidic region appended to the sialomucin domain .
Bcl-2-like protein 13 (BCL2L13)
Type: Family

Bcl-2-like protein 13 (BCL2L13), also known as Bcl-rambo, localizes to mitochondria and induces apoptosis .
Sperm microtubule associated protein 2-like (SPMAP2-like)
Type: Family

This entry represents homologs of Sperm microtubule associated protein 2 (SPMAP2, formerly testicular haploid enriched gene or THEG) and Sperm microtubule associated protein 2-like (SPMAP2L, formerly Testicular haploid expressed gene-like THEGL). These proteins are axonemal wedge-MAPs (microtubule-associated proteins) that were identified in the sperm doublet microtubules (DMTs) . These proteins have an unique tubulin binding mode stretching laterally across several protofilaments of the B tubule. SPMAP2 binds along the α/β tubulin interface and periodically dips into the inter-protofilament clefts .
Epididymal secretory protein E3-alpha/beta (EDDM3A/EDDM3B)
Type: Family

The function of Epididymal secretory protein E3-alpha (EDDM3A) and Epididymal secretory protein E3-beta (EDDM3B) is not clear. EDDM3A may function in sperm maturation .
Spt21/Ams2 (Spt21/Ams2)
Type: Family

This entry includes Spt21 from budding yeasts and Ams2 (CENP-A multicopy suppressor protein 2), also known as GATA transcription factor, from fission yeasts. Spt21 is required for transcriptional silencing in Saccharomyces cerevisiae . Ams2 is required for proper chromosome segregation via regulation of CENP-A localization to the centromere .
KATNB1-like protein 1 (KATNBL1)
Type: Family

Microtubule-severing enzyme Katanin is composed of a catalytic p60 subunit (A subunit, KATNA1) and a regulatory p80 subunit (B subunit, KATNB1). KATNBL1 functions as a regulator of Katanin A subunit microtubule-severing activity during mitosis .
Protrudin (Protrudin)
Type: Family

Protrudin is a membrane protein that regulates polarized vesicular trafficking in neurons. It interacts with KIF5, a motor protein that mediates anterograde vesicular transport in neurons . Protrudin contains a Rab11-binding domain, a FYVE (lipid-binding) domain, and a short sequence motif designated FFAT (two phenylalanines in an acidic tract) between the Rab11 binding domain and the FYVE domain. The FFAT motif mediates the interaction of protrudin with vesicle-associated membrane protein-associated protein (VAP) as well as with Kif5A. Protrudin has been linked to Hereditary spastic paraplegia (HSP), an inherited neurological disorders characterised by progressive lower-limb spasticity and weakness. .
Vitamin K epoxide reductase complex subunit 1 (VKORC1/VKORC1L1)
Type: Family

This entry represents the vitamin K epoxide reductase complex subunit VKORC1 and VKORC1L1 mostly from animals.

VKORC1 is an integral membrane protein that catalyzes the reduction of vitamin K 2,3-epoxide and vitamin K to vitamin K hydroquinone, an essential co-factor subsequently used in the γ-carboxylation of glutamic acid residues in blood coagulation enzymes . All homologues of VKOR contain an active site CXXC motif, which is switched between reduced and disulfide-bonded states during the reaction cycle . Warfarin, a widely used oral anticoagulant used in medicine as well as rodenticides, inhibits the activity of VKOR, resulting in decreased levels of reduced vitamin K, which is required for the function of several clotting factors . However, anticoagulation effect of warfarin is significantly associated with polymorphism of certain genes, including VKORC1. Interestingly, in rodents, an adaptive trait appears to have evolved convergently by selection on new or standing genetic polymorphisms in VKORC1 as well as by adaptive introgressive hybridization between species, likely brought about by human-mediated dispersal .
Protein NCBP2AS2 (NCBP2-AS2)
Type: Family

NCBP2-AS2, also known as HIAR (hypoxia-induced angiogenesis regulator), has been found to promote endothelial sprouting through enhanced VEGF signaling in cancer-associated fibroblasts .
Transducin beta-like protein 2 (WBSCR13)
Type: Family

Transducin beta-like protein 2 (TBL2), also known as WBSCR13, has been linked to Williams-Beuren syndrome . It contains an N-terminal transmembrane region and the C-terminal WD40 domain . Under endoplasmic reticulum (ER) stress, TBL2 is involved in ATF4 translation through its association with the mRNA .
WD repeat-containing protein 27 (WDR27)
Type: Family

The function of WD repeat-containing protein 27 (WDR27) is not clear.
Homeobox protein prophet of Pit-1 (PROP1)
Type: Family

Prophet of Pit-1 (Prop1) is a homeodomain transcription factor involved in morphogenesis, apoptosis and proliferation in the developing pituitary, and in pituitary organogenesis including the differentiation of cell lineages .
T-cell surface glycoprotein CD8 beta chain (CD8B)
Type: Family

CD8 on thymocytes and thymus-derived T cells consists of disulfide-linked CD8alpha and CD8 beta chains, which are transmembrane proteins containing N-terminal Ig domains, extended and glycosylated hinge and stalk regions and transmembrane and cytoplasmic portions . CD8alphabeta plays important roles in thymic selection, CD8 T-cell differentiation, and antigen recognition . CD8 also can be expressed as a CD8alphaalpha homodimer. Both CD8alphaalpha and CD8alphabeta bind similarly to MHC class I molecules. However, CD8alphabeta, but not CD8alphaalpha, associates with TCR/CD3, strengthens pMHC binding, and promotes CD8 association with lipid rafts and p56lck (lymphocyte-specific tyrosine kinase, lck) and hence TCR signaling via lck-mediated phosphorylation of CD3 ITAMs .
Protein canopy homolog (CNPY)
Type: Family

This entry includes a group of ER-resident saposin-like proteins, including CNPY1/2 from mammals and protein seele from Drosophila melanogaster. They contain a saposin B-type domain, which is an endoplasmic reticulum (ER) retention domain. Seele is involved in embryonic dorsal-ventral patterning . Zebrafish CNPY1 acts as a positive feedback regulator of FGF that contributes to the development of left-right body asymmetry by controlling stem cell clustering during Kupffer's vesicle organogenesis . CNPY2 interacts with MYLIP, an E3 ubiquitin ligase that marks its targets for lysosomal degradation. CNPY2 protects targets of MYLIP from lysosomal degradation .
Oligosaccharyltransferase complex subunit OSTC (OSTC)
Type: Family

The oligosaccharyltransferase complex catalyzes the transfer of oligosaccharide from a dolichol pyrophosphate donor en bloc onto a free asparagine residue of a newly synthesized nascent chain during the translocation in the endoplasmic reticulum lumen. OSTC, also known as DC2, is a oligosaccharyltransferase (OST) complex subunit. Together with KCP2, DC2 regulates the gamma-secretase-directed processing of amyloid precursor protein (APP) .
Partner and localizer of BRCA2 (PALB2)
Type: Family

PALB2 (partner and Localizer of BRCA2) binds to the N-terminal region of BRCA2, and is vital for its function by facilitating its subnuclear localization . It binds BRCA1 and BRCA2 and serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex, which is required for homologous recombination repair . It has also been shown to bind DNA and physically interacts with RAD51 . Biallelic mutations in PALB2 cause Fanconi anemia (FA) subtype FA-N, whereas monoallelic mutations predispose to breast, and pancreatic familial cancers .
Thioredoxin domain-containing protein 15 (TXNDC15)
Type: Family

The function of Thioredoxin domain-containing protein 15 (TXNDC15) is not clear.
Leucine-rich repeat-containing protein 31 (LRC31)
Type: Family

The function of Leucine-rich repeat-containing protein 31 (LRC31) is not clear.
Ankycorbin/UACA (RAI14/UACA)
Type: Family

This family includes a group of membrane-shaping proteins that can promote local membrane curvatures, termed N-Ank proteins, which use their ankyrin repeat array and an N-terminal amphipathic helix to bind and shape membranes. The N-Ank superfamily can be divided in two subfamilies, the smaller one contains ankycorbin (also known as RAI14), UACA, Ankyrin repeat domain-containing protein 24 and 35 (Ankrd24/35); the larger second subfamily includes the uncharacterised proteins of the Ankrd18, Ankrd30 and Ankrd20 subfamilies, which all are specific to primates, or even to humans, as well as Ankrd7, Ankrd26, Ankrd36 and Ankrd62 .

This entry represents the smaller N-Ank subfamily. Ankycorbin is an actin binding protein that regulates F-actin dynamics . It plays an important role in early morphogenesis of neurons which depends on ankyrin repeat and N-terminal amphipathic helix. UACA (also known as Nucling) mediates apoptosis, regulates NF-κB and STAT3, sequesters par-4 and acts as an autoantigen in patients with panuveitis . Ankrd24 is a componement of the stereocilia rootlet in hair cells of inner ear. It bridges the apical plasma membrane with the lower rootlet and maintains normal distribution of TRIOBP, thereby reinforcing stereocilia insertion points and organising rootlets for hearing with long-term resilience . ANKRD35 is associated with chronic myeloid leukaemia . ANKRD35 interacts with E3 ligase RBCK1 and is part of the RBCK1-ANKRD35-MITD1-ANXA1 axis in clear cell renal cell carcinoma (ccRCC) that regulates the phosphorylation of AKT and ERK and contributes to the dysregulation of sunitinib in ccRCC cells which constitutes a novel mechanism by which RBCK1 regulates sunitinib sensitivity in ccRCC .
Protein C3orf33-like (C3orf33-like)
Type: Family

This entry includes human C3orf33 and related proteins. C3orf33, also known as AC3-33, is a secretory protein that inhibits Elk1 transcriptional activity via ERK pathway .
Coiled-coil domain-containing protein 103 (CC103)
Type: Family

Coiled-coil domain-containing protein 103 (CC103), also known as dynein axonemal assembly factor 19, functions as a dynein arm attachment factor. Mutations of CC103 cause primary ciliary dyskinesia .
PiggyBac transposable element-derived protein 5 (PGBD5)
Type: Family

PiggyBac transposable element-derived protein 5 (PGBD5) is a DNA transposase that mediates PGBD5-induced DNA rearrangements in rhabdoid tumour cells . It can induce genomic rearrangements that inactivate the HPRT1 gene .
Protein APCDD1 (APCDD1)
Type: Family

APCDD1 (Adenomatosis polyposis coli down-regulated 1) is directly regulated by the beta-catenin/Tcf complex, and its elevated expression promotes proliferation of colonic epithelial cells in vitro and in vivo . APCDD1 has an N-terminal signal-peptide and a C-terminal transmembrane region. APCDD1 is expressed in a broad repertoire of cell types, indicating that it may regulate a diverse range of biological processes controlled by Wnt signalling .
Cysteine-rich DPF motif domain-containing protein 1 (CDPF1)
Type: Family

The function of Cysteine-rich DPF motif domain-containing protein 1 (CDPF1) is not clear.
Zinc finger FYVE domain-containing protein 1 (ZFYV1)
Type: Family

ZFYVE1, also termed double FYVE-containing protein 1 (DFCP1) is a novel tandem FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. The subcellular distribution of exogenously-expressed ZFYVE1 to Golgi, endoplasmic reticulum (ER) and vesicular is governed in part by its FYVE domains but unaffected by Wortmannin, a PI3-kinase inhibitor. It plays a role in the formation of lipid droplets (LDs), regulating their morphology, size and distribution which are storage organelles, central to lipid and energy homeostasis .

ZFYVE1 harbors two B-box domains, both of which show high sequence similarity with B-Box-type 1 zinc finger found in tripartite motif-containing proteins (TRIMs). The type 1 B-box (Bbox1) zinc finger is characterised by a C6H2 zinc-binding consensus motif .
Swi5-dependent recombination DNA repair protein 1 homolog (SFR1)
Type: Family

SFR is a component of the SWI5-SFR1 complex, a complex required for double-strand break repair via homologous recombination . It interacts with estrogen receptor alpha and may be a transcriptional modulator for estrogen receptor alpha .
DENN domain-containing protein 10 (FAM45)
Type: Family

This family includes DENN (differentially expressed in normal cells and neoplasia) domain-containing protein 10 (also known as FAM45A) and DENN domain-containing protein 10B (also known as FAM45B). DENN domain-containing protein 10 is a guanine nucleotide exchange factor (GEF) for Rab small GTPases. It has been shown to define a novel regulatory step in the homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion .
Cytochrome c oxidase assembly factor 1, fungi (Coa1_fungi)
Type: Family

This entry includes Cytochrome c oxidase assembly factor 1 (Coa1) from fungi. Coa1 is an assembly factor for cytochrome c oxidase found in the mitochondrial inner membrane .
Allograft inflammatory factor 1 (AIF1/AIF1L)
Type: Family

This entry includes AIF1 (also know as Iba1, ionized calcium-binding adapter molecule 1) and AIF1L (Iba2) from humans. They are actin-binding proteins . AIF1 has been shown to promote vascular smooth muscle cell migration . AIF1L is involved in the stabilization of podocyte morphology by titrating actomyosin contractility and membrane dynamics .

This entry also includes calcium-binding protein B from Dictyostelium discoideum.
Anosmin-1 (Anosmin-1)
Type: Family

Anosmin-1 (ANOS1) is an extracellular matrix protein that functions in the development of craniofacial structures . It has been linked to hereditary Kallmann's syndrome (KS), a human disorder of olfactory and gonadotropin-releasing hormone (GnRH) neuronal ontogeny .
E3 ubiquitin-protein ligase CCNB1IP1 (CCNB1IP1)
Type: Family

CCNB1IP1, also knwon as HEI10, is a RING finger protein and a E3 ubiquitin ligase that functions in mitotic progression through regulation of cyclin B levels. It is found to both interact with an ubiquitin conjugating enzyme, and to induce its own auto-ubiquitination in vitro . HEI10 interacts with Merlin tumor suppressor protein and regulates cancerous cell migration and invasion .
Ubiquitin-activating enzyme E1, inactive adenylation domain, subdomain 1 (Ub-E1_IAD_1)
Type: Homologous_superfamily

The post-translational attachment of ubiquitin (

) to proteins (ubiquitinylation) alters the function, location or trafficking of a protein, or targets it to the 26S proteasome for degradation . Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2,

), and a ubiquitin ligase (E3,

,

), which work sequentially in a cascade . The E1 enzyme is responsible for activating ubiquitin, the first step in ubiquitinylation. The E1 enzyme hydrolyses ATP and adenylates the C-terminal glycine residue of ubiquitin, and then links this residue to the active site cysteine of E1, yielding a ubiquitin-thioester and free AMP. To be fully active, E1 must non-covalently bind to and adenylate a second ubiquitin molecule. The E1 enzyme can then transfer the thioester-linked ubiquitin molecule to a cysteine residue on the ubiquitin-conjugating enzyme, E2, in an ATP-dependent reaction.

The Ubiquitin-activating enzyme E1 (Ub-E1) consists of four building blocks: First, the adenylation domains composed of two MoeB/ThiF-homology motifs (IAD and AAD, for "inactive" and "active" adenylation domain, respectively), AAD binds ATP and Ub; second, the catalytic cysteine half-domains, which contain the E1 active site cysteine (FCCH and SCCH, for "first" and "second" catalytic cysteine half-domain, respectively) inserted into each of the adenylation domains; third, a four-helix bundle that represents a second insertion in the IAD and immediately follows the FCCH; and fourth, the C-terminal ubiquitin-fold domain (UFD), which recruits specific E2 .

The adenylation domain, which is composed of two MoeB/ThiF-homology motifs (hereafter, IAD and AAD, for 'inactive' and 'active' adenylation domain, respectively), the latter of which binds ATP and Ub .
Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1)
Type: Family

Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1), also known as elongation factor p18, is a nonenzyme factor associated with a macromolecular tRNA synthetase complex. It shares sequence homology to elongation factor subunits (EF-1). It interacts with ATM/ATR for the activation of p53 and works as a potent tumour suppressor .
ZPR1, A/B domain (ZPR1_A/B_dom)
Type: Homologous_superfamily

The zinc finger protein ZPR1 is a eukaryotic protein that comprises tandem ZPR1 domains and which, in response to growth stimuli, binds to eukaryotic translation elongation factor 1A (eEF1A) , assembles into multiprotein complexes with the survival motor neurons (SMN) protein, and accumulates in subnuclear structures, such as gems and Cajal bodies. ZPR1 has a conserved tandem architecture consisting of a duplicated module, the ZPR1 domain, comprised of two apparently modular domains: an elongation initiation factor 2-like zinc finger (Znf) and a double-stranded β helix with a helical hairpin insertion (A/B domain). In consequence, the N- and C-terminal ZPR1 domains are referred to as the Znf1-A domain and Znf2-B domain modules, respectively. The Znf2-B domain module is required for viability, whilst the Znf1-A domain module is required for normal cell growth and proliferation .

This superfamily represents the A/B domain found in ZPR1.
ZPR1, zinc finger domain (ZPR1_Znf1/2)
Type: Homologous_superfamily

The zinc finger protein ZPR1 is a eukaryotic protein that comprises tandem ZPR1 domains and which, in response to growth stimuli, binds to eukaryotic translation elongation factor 1A (eEF1A) , assembles into multiprotein complexes with the survival motor neurons (SMN) protein, and accumulates in subnuclear structures, such as gems and Cajal bodies. ZPR1 has a conserved tandem architecture consisting of a duplicated module, the ZPR1 domain, comprised of two apparently modular domains: an elongation initiation factor 2-like zinc finger (Znf) and a double-stranded β helix with a helical hairpin insertion (A/B domain). In consequence, the N- and C-terminal ZPR1 domains are referred to as the Znf1-A domain and Znf2-B domain modules, respectively. The Znf2-B domain module is required for viability, whilst the Znf1-A domain module is required for normal cell growth and proliferation .

This superfamily represents the zinc finger domain (Znf1/2) found in ZPR1.
WD repeat-containing protein 53 (WDR53)
Type: Family

The function of WD repeat-containing protein 53 (WDR53) is not clear.
CXADR-like membrane protein (CLMP)
Type: Family

CXADR-like membrane protein (CLMP), also known as ACAM, belongs to the CTX family, whose members are type I transmembrane proteins within the immunoglobulin superfamily (IgSF). It is a component of epithelial tight junctions . It has been implicated in adipocyte maturation and development of obesity . Mutations of the CLMP gene cause Congenital Short Bowel Syndrome (CSBS) .
Dedicator of cytokinesis, N-terminal, subdomain 1 (DOCK_N_sub1)
Type: Homologous_superfamily

This superfamily represents the subdomain 1 found in the N-terminal domain of the protein dedicator of cytokinesis DOCK. Its function is unknown. The N-terminal domain is found between the variant SH3 domain and the C2 domain .
Junctional adhesion molecule A (F11R)
Type: Family

F11R, also known as Junctional adhesion molecule A (JAM-1), belongs to the immunoglobulin superfamily. It is a cell adhesion molecule involved in platelet aggregation and in transendothelial migration of leukocytes . It binds PAR-3, and may recruit PAR-3 to tight junctions . JAM-1 has also been shown to act as a receptor for Mammalian reovirus sigma-1 and Human Rotavirus strain Wa .
Thiosulfate:glutathione sulfurtransferase, mammalian (TSTD1_mml)
Type: Family

This entry represents the human Thiosulfate:glutathione sulfurtransferase (TSTD1,

) and related proteins. TSTD1 catalyzes a predicted thiosulfate-dependent conversion of glutathione to GSS(-), a central intermediate in hydrogen sulfide metabolism .