SII-SWORD/CoKE huggingface dataset:
Ripply family (Ripply_fam)
Type: Family

The precise function of this family is not clear, but it is thought to play a role in somitogenesis, development and transcriptional repression . This family contains two conserved sequence motifs: WRPW and FPVQATI. The WRPW motif is thought to be required for binding to tle/groucho proteins . Ripply2.2 is also known as Bowline and is an associate protein of the transcriptional co-repressor XGrg-4 . Ripply3 is also known as Down Syndrome Critical Region Protein 6 homologue .
Vasculin family (Vasculin_fam)
Type: Family

Vasculin (also known as GC-rich promoter-binding protein, GPBP) functions as a GC-rich promoter-specific transcription factor . This protein also binds RNA, which may mediate different RNA-dependent cellular processes .
Consortin, C-terminal domain (Consortin_C)
Type: Domain

Consortin is a trans-Golgi network cargo receptor involved in targeting connexins to the plasma membrane . This entry represents the C-terminal domain of Consortin and similar proteins from vertebrates.
Dermcidin (Dermcidin)
Type: Family

Dermcidin is an antibiotic peptide secreted by sweat glands. It is proteolytically processed to generate a 47-amino acid peptide with antimicrobial activity in response to a variety of pathogenic microorganisms .
Tubulinyl-Tyr carboxypeptidase (VASH1)
Type: Family

This entry represents a family of tubulinyl-Tyr carboxypeptidases. These regulate microtubule function by removing a C-terminal tyrosine residue from alpha-tubulin . Tubulinyl-Tyr carboxypeptidase 1 is also known as vasohibin-1 (VASH1), and it act as an angiogenesis inhibitor . VASH1 is predominantly expressed in endothelial cells and it is induced by vascular endothelial growth factor (VEGF) or fibroblast growth factor 2 (FGF-2). Tubulinyl-Tyr carboxypeptidase 2 (VASH2) is thought to be expressed in cells other than endothelial cells .

Angiogenesis, the formation of new vessels from existing ones, is a key event both under physiological and pathologic conditions. It is determined by the local balance between angiogenesis stimulators and inhibitors.
Dynamitin (Dynamitin)
Type: Family

Dynactin is a multiprotein complex necessary for the function of microtubule motor protein dynein. The dynein-dynactin complex is involved in a variety of cellular events, including membrane vesicle transport, mitotic spindle assembly and centrosome separation .

Dynamitin (dynactin subunit 2, DCTN2) is a subunit of the dynactin complex. In Saccharomyces cerevisiae it is also known as Jnm1. Dynactin contains two distinct structural domains: a projecting sidearm that interacts with dynein and an actin-like minifilament backbone that is thought to bind cargo. Dynamitin holds together both structural domains . Dynamitin is implicated in cell adhesion by binding to macrophage-enriched myristoylated alanine-rice C kinase substrate (MacMARCKS) . In mice, DCTN2 is involved in anchoring microtubules to centrosomes and may play a role in synapse formation during brain development .
Ubiquitin-like domain, USP-type (Ub_USP-typ)
Type: Domain

This ubiquitin-like (UBL) domain is found in several ubiquitin carboxyl-terminal hydrolases, also known as ubiquitin specific proteases (USP) , and in gametogenetin-binding protein.
Syncollin (Syncollin)
Type: Family

Syncollin is a protein associated with the luminal surface of the zymogen granule membrane in the pancreatic acinar cell . It functions in exocytosis regulating the maturation and concentration of zymogens in zymogen granules . Syncollin is also present in neutrophilic granulocytes and promyelocytic HL-60 cells .
Neuropeptide S (Neuropeptide_S)
Type: Family

Neuropeptide S (NPS) is a bioactive peptide that may be involved in several biological processes, including food intake, locomotion, wakefulness, arousal, and anxiety. NPS activates its cognate G protein-coupled receptor (NPSR1) at low nanomolar agonist concentrations and induces elevation of intracellular Ca2+ and cAMP .
Humanin family (Humanin)
Type: Family

Humanin (HN) and humanin-like proteins are found exclusively in humans. Humanin is a short anti-apoptotic peptide that inhibits the activation of Bax (Bcl-2-associated X protein), which is involved in apoptosis . Humanin suppresses neuronal cell death caused by Alzheimer's disease (AD)-specific insults . Humanin also interacts with the insulin-like growth factor-binding protein-3 (IGFBP-3), which is essential in the regulation of cell survival . This entry represents the humanin family, and also matches some uncharacterised non-human proteins, mainly from chimpanzee.
Protein TraM (TraM)
Type: Family

Bacteria can regulate their gene expression in response to their population density in a process called quorum sensing . In some Proteobacteria, quorum sensing can be regulated by the TraR transcription factor that activates genes controlling Ti plasmid replication and conjugal transfer . TraM inhibits TraR activity through binding to TraR and forming a large, stable antiactivation TraM-TraR complex . TraM has been shown to form a homodimer in which the monomer primarily consists of two long coiled a -helices, and one of the helices from each monomer also bundles to form the dimeric interface .
GET complex subunit Get2/sif1 (Get2/sif1)
Type: Family

This entry represents the GET complex subunit Get2 and its homologue, sif1 from Schizosaccharomyces pombe. The Golgi to ER traffic (GET) complex is composed of Get1, Get2 and Get3. The complex is involved in the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum . Get1 and Get2 form a transmembrane complex and interact with Get3, an ATPase which recognises and selectively binds the transmembrane domain of TA proteins in the cytosol . In Schizosaccharomyces pombe, sif1 interacts with Kms1 and Sad1, which are constitutive membrane-bound components of the SPB (spindle pole body) that interact with each other .
Cysteine-rich transmembrane domain (CYSTM_dom)
Type: Domain

Proteins containing CYSTM domain are short cysteine-rich membrane proteins that most probably dimerise together to form a transmembrane sulfhydryl-lined pore. The CYSTM domain is always present at the extreme -terminus of the protein in which it is present. Furthermore, like the yeast prototypes, the majority of the proteins also possess a proline/glutamine-rich segment upstream of the CYSTM domain that is likely to form a polar, disordered head in the cytoplasm. The presence of an atypical well-conserved acidic residue at the C-terminal end of the TM helix suggests that this might interact with a positively charged moiety in the lipid head group. Consistently across the eukaryotes, the different versions of the CYSTM domain appear to have roles in stress-response or stress-tolerance, and, more specifically, in resistance to deleterious substances, implying that these might be general functions of the whole family . This entry also includes Protein CADMIUM TOLERANCE 1-5 from rice, which confers resistance to heavy metal ions such as cadmium and copper .
Synaptonemal complex central element protein 3 (Synaptonemal_3)
Type: Family

Synaptonemal complex central element protein 3 (SYCE3), also known as testis-specific expressed gene 2, is a major component of the transverse central element (CE) of meiosis-specific synaptonemal complexes. SYCE3 enables chromosome loading of the other CE-specific proteins, which in turn promotes synapsis between homologous chromosomes . SYCE3 may participate in the apoptosis of spermatogenic cells and the pathogenesis of cryptorchidism .
Glucosidase II beta subunit, N-terminal (PRKCSH_N)
Type: Domain

This entry represents the N-terminal domain of the glucosidase 2 subunit beta, which is also known as protein kinase C substrate 80K-H (PRKCSH). The enzyme catalyses the sequential removal of two alpha-1,3-linked glucose residues in the second step of N-linked oligosaccharide processing . The beta subunit is required for the solubility and stability of the heterodimeric enzyme, and is involved in retaining the enzyme within the endoplasmic reticulum .
NELL2-interacting cofactor for lumicrine signalling (NICOL)
Type: Family

Nicol protein (also known as C4ORF48 in humans) is a small secreted protein crucial for lumicrine signalling. It forms a complex with NELL2, facilitating sperm maturation in the epididymis. Males lacking NICOL are sterile, but fertility can be restored by NICOL expression in testicular germ cells, highlighting its importance in male reproduction .
Immunity protein 74 (Imm74)
Type: Family

This family consists of predicted immunity proteins with an α+β fold. They are encoded by genes present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Tox-ARC family. They are also found in heterogeneous polyimmunity loci .
Tantalus-like (Tantalus-like)
Type: Domain

This entry consist of an α+β fold domain found in metazoan proteins such as tantalus from Drosophila . Tantalus is a potential cofactor involved in sensory organ development. It binds the chromatin protein additional sex combs (Asx) and also binds DNA in vitro . Proteins containing this domain also include proline-rich protein 14 (PRR14) and related proteins from mammals.
Lustrin, cysteine-rich repeated (Lustrin_cystein)
Type: Repeat

This repeated is found in proteins from lower eukaryotes in lustrin, perlucin, pearl nacre, and other similar protein-types. Each repeat lies between Kunitz-BPTI repeats, in certain species, which are also cysteine-rich .
Transmembrane protein C12orf23, UPF0444 (UPF0444)
Type: Family

Proteins in this family are multi-pass membrane proteins from eukaryotes.
Proteins in this family are typically between 94 and 119 amino acids in length.
AMP-dependent ligase, C-terminal (AMP-dep_Lig_C)
Type: Domain

This is a small domain that is found C-terminal to

. It has a central β sheet core that is flanked by α helices. Proteins containing this domain include phenylacetate-coenzyme A ligase, which catalyses the activation of phenylacetic acid (PA) to phenylacetyl-CoA (PA-CoA) .
RPA-interacting protein, central domain (RPA_interact_central)
Type: Domain

This entry represents the middle domain of replication protein A (RPA) interacting protein. RPA interacting protein is involved in the import of RPA into the nucleus. This domain is responsible for interaction with RPA .
RPA-interacting protein (RIP)
Type: Family

This entry represents the replication protein A (RPA) interacting protein. RPA is a single stranded DNA-binding protein involved in DNA replication, repair, and recombination . After synthesis in the cytoplasm, RPA is transported into the nucleus mediated by RPA interacting protein . In humans, RPA interacting protein has several splice isoforms, including hRIPalpha, hRIPbeta, hRIPgamma, hRIPdelta1, hRIPdelta2, and hRIPdelta3. hRIPbeta transports RPA into the PML nuclear body and releases RPA upon UV irradiation . It seems that the number of splice isoforms of RIPalpha is species-specific and has a tendency to increase in higher eukaryotes .
PELOTA RNA-binding domain (PELOTA_dom)
Type: Domain

This RNA-binding PELOTA domain is at the C terminus of a phosphoribosyltransferase (PRTase) family . These PRTase+Pelota genes are found in the biosynthetic operon associated with the Ter stress response operon, and are predicted to be involved in the biosynthesis of a ribo-nucleoside involved in stress response . However, at least one protein predicted to possess this domain (

) has been shown to posses cysteine protease activity .
RPA-interacting protein, N-terminal domain (RPA_interact_N_dom)
Type: Domain

This entry represents the N-terminal domain of replication protein A (RPA) interacting protein. RPA is a single stranded DNA-binding protein involved in DNA replication, repair, and recombination . RPA interacting protein is involved in the import of RPA into the nucleus . The N-terminal domain is is rich in basic residues and responsible for interaction with importin beta .
RPA-interacting protein, C-terminal domain (RPA_interact_C_dom)
Type: Domain

This entry represents the C-terminal domain of replication protein A (RPA) interacting protein (RIP). RPA is a single stranded DNA-binding protein involved in DNA replication, repair, and recombination . RPA interacting protein is involved in the import of RPA into the nucleus . The C-terminal domain contains a putative zinc finger .
Ribosome biogenesis protein Slx9-like (Slx9-like)
Type: Family

Slx9 is required for pre-rRNA processing. In Saccharomyces cerevisiae, Slx9 is associated with the 90S pre-ribosome and 43S small ribosomal subunit precursor .

The early stages of ribosomes biogenesis includes processing of the 35S pre-ribosomal RNA transcript into the mature 18S, 5.8S, and 25S rRNA molecules. The 35S precursor contains external transcribed spacer elements (5' and 3'-ETS) at either end as well as internal transcribed spacers (ITS1 and ITS2) that separate the mature sequences . Slx9 is implicated in the processing events that remove the ITS1 spacer sequences .
Siroheme biosynthesis protein Met8-like (Met8-like)
Type: Family

This entry represents a family of proteins from fungi and prokaryotes, including Siroheme biosynthesis protein met8 from budding and fission yeast, Precorrin-2 dehydrogenase from the archaea Methanosarcina barkeri (Mba_PC2_DH) and Precorrin-2 dehydrogenase from Bacillus subtilis (SirC).

In Saccharomyces cerevisiae, Met8 is a bifunctional dehydrogenase (

) and ferrochelatase (

) . It catalyses the final two steps in the biosynthesis of sirohaem, involving a NAD(+)-dependent dehydrogenation of precorrin-2 to generate sirohydrochlorin followed by ferrochelation to yield sirohaem . Siroheme is a heme-like prosthetic group used by sulfite and nitrite reductases . The structure of Met8 has been resolved. A single active site, Asp141, has been shown to play an essential role in both dehydrogenase and chelatase processes .

Mba_PC2_DH is involved in the archaeal biosynthesis of heme. It catalyses the oxidation of precorrin-2 into sirohydroclorin .

SirC catalyses the dehydrogenation of precorrin-2 to form sirohydrochlorin which is used as a precursor in both siroheme biosynthesis and in the anaerobic branch of adenosylcobalamin biosynthesis .
Siroheme biosynthesis protein Met8, C-terminal (Met8_C)
Type: Domain

This entry represents the C-terminal domain of the siroheme biosynthesis protein Met8. In Saccharomyces cerevisiae, Met8 is a bifunctional dehydrogenase (

) and ferrochelatase (

) . It catalyses the final two steps in the biosynthesis of sirohaem, involving a NAD(+)-dependent dehydrogenation of precorrin-2 to generate sirohydrochlorin followed by ferrochelation to yield sirohaem .
HAUS augmin-like complex subunit 6, N-terminal (HAUS_6_N)
Type: Domain

This entry represents the N-terminal domain of the subunit 6 of the HAUS augmin-like complex, involved in mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis . Subunit 6 interacts with the NEDD1-gamma-tubulin complex and recruits this complex to the spindle, which in turn promotes microtubule polymerisation .
TMEM61 protein family (TMEM61)
Type: Family

This s a group of uncharacterised multi-pass membrane proteins found in eukaryotes. Proteins in this family are typically between 150 and 211 amino acids in length.
TMEM125 protein family (TMEM125)
Type: Family

This is a family of uncharacterised transmembrane proteins found in eukaryotes.
Bifunctional transglycosylase second domain (UB2H)
Type: Domain

UB2H is the second domain of the transglycosylases, or penicillin-binding proteins (PBP1bs), the multi-domain membrane proteins essential for cell wall synthesis that are targeted by penicillin antibiotics. The exact function of the UB2H domain is uncertain, but it may act as the binding component of PBP1b with different binding partners, or it may participate in the regulation between DNA repair and/or synthesis and cell wall formation during the bacterial cell cycle .
KASH5-like coiled-coil domain (KASH5_CC)
Type: Domain

This is the central coiled-coil region of the protein KASH5 (also known as CCDC155). KASH5 may be involved in meiotic chromosome dynamics and homologue pairing . The domain also appears to be present in a number of other proteins.
Raftlin family (Raftlin)
Type: Family

Raftlin plays an important role in the formation and/or maintenance of lipid rafts . In B-cells, Raftlin is localised exclusively in lipid rafts by fatty acylation of N-terminal Gly2 and Cys3, and is co-localised with B-cell antigen receptor (BCR) .
Protein KASH5 (KASH5)
Type: Family

KASH5 (also known as CCDC155) is a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton . KASH5 interacts (via the last 22 AA) with SUN1; this interaction mediates telomere localisation .
Codanin-1, C-terminal domain (Codanin-1_C)
Type: Domain

This domain is found near to the C terminus of codanin-1 .

Codanin-1 may act as a negative regulator of histone chaperone anti-silencing function 1 (ASF1) in chromatin assembly . Proteins containing this domain also include the protein disks lost (dlt, also known as protein vanaso) from Drosophila. dlt regulates cell proliferation and cell survival of differentiated cells independent of cell division .

Mutations in the codanin-1 gene cause congenital dyserythropoietic anemia 1 (CDA1), which is an autosomal recessive blood disorder characterised by morphological abnormalities of erythroblasts, ineffective erythropoiesis, macrocytic anemia and secondary hemochromatosis .
Intraflagellar transport protein 20 (FT20)
Type: Family

Intraflagellar transport (IFT) particle, which consists of complex A and B, is involved in assembling and maintaining eukaryotic cilia and flagella. Intraflagellar transport protein 20 (IFT20) is a subunit of the intraflagellar transport complex B (consists of IFT172, 88, 81, 80, 74/72, 57/55, 52, 46, 27, 20) . IFT20 is associated with the Golgi complex and may play a role in the trafficking of ciliary membrane proteins from the Golgi complex to the cilium . Besides its function in cilia, IFT20 also regulates immune synapse assembly in T cells . In an yeast two hybrid experiment, IFT20 exhibited a strong interaction with IFT57/Hippi and the kinesin II subunit, KIF3B .
Augurin (Augurin)
Type: Family

Augurin is alternatively named oesophageal cancer-related gene 4 protein. The function of this family of transmembrane proteins is to induce the senescence of oligodendrocyte and neural precursor cells, characterised by G1 arrest, RB1 dephosphorylation and accelerated CCND1 and CCND3 proteasomal degradation . Augurin is a posible hormone that has been found to stimulate the release of adrenocorticotropic hormone (ACTH) via the release of hypothalamic corticotrophin-releasing factor (CRF) .
Fibroblast growth factor receptor 1, catalytic domain (FGF_rcpt_1)
Type: Domain

Fibroblast growth factors (FGFs) are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types . FGFs are mitogens, which stimulate growth or differentiation of cells of mesodermal or neuroectodermal origin. The function of FGFs in developmental processes include mesoderm induction, anterior-posterior patterning, limb development, and neural induction and development. In mature tissues, they are involved in diverse processes including keratinocyte organisation and wound healing . FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects . Fibroblast growth factors are heparin-binding proteins and interactions with cell-surface-associated heparan sulfate proteoglycans have been shown to be essential for FGF signal transduction. FGFs have internal pseudo-threefold symmetry (β-trefoil topology) . There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules . They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 , which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active .

The FGFRs consist of an extracellular ligand-binding domain composed of three immunoglobulin-like domains (D1-D3), a single transmembrane helix domain, and an intracellular domain with tyrosine kinase activity . The three immunoglobin(Ig)-like domains, D1, D2, and D3, present a stretch of acidic amino acids (known as the acid box) between D1 and D2. This acid box can participate in the regulation of FGF binding to the FGFR. Immunoglobulin-like domains D2 and D3 are sufficient for FGF binding. FGFR family members differ from one another in their ligand affinities and tissue distribution . Most FGFs can bind to several different FGFR subtypes. Indeed, FGF1 is sometimes referred to as the universal ligand, as it is capable of activating all of the different FGFRs . However, there are some exceptions. For example, FGF7 only interacts with FGFR2 and FGF18 was recently shown to only activate FGFR3 .

Fibroblast growth factor receptor 1 (FGFR1) binds both acidic and basic fibroblast growth factors and is involved in limb induction . FGFR1 has been shown to be associated with Pfeiffer syndrome , and cleft lip and/or palate . Fibroblast growth factor receptor 1 has been shown to interact with growth factor receptor-bound protein 14 (GRB14) , Src homology 2 domain containing adaptor protein B (SHB) , fibroblast growth factor receptor substrate 2 (FRS2) and fibroblast growth factor 1 (FGF1) .

This entry represents the catalytic domain of FGFR1.
SLP adapter and CSK-interacting membrane protein (SCIMP)
Type: Family

SLP adapter and CSK-interacting membrane protein (SCIMP) is a lipid tetraspanin-associated transmembrane adapter/mediator involved in major histocompatibility complex class II (MHC-II) signaling transduction . SCIMP is expressed in B cells and other professional antigen-presenting cells (APCs) and is localised in the immunological synapse. Upon MHC-II stimulation, phosphorylated SCIMP binds to the SLP65 and to the inhibitory kinase Csk. SLP65 binding initiates the downstream signaling cascades, while Csk binding functions as a negative regulatory loop .
BMP-2-inducible protein kinase, C-terminal (BMP2K_C)
Type: Domain

This domain is found at the C terminus of BMP-2-inducible protein kinase (BMP2K) and related proteins. BMP2K may be involved in osteoblast differentiation .
Ubiquinol-cytochrome-c reductase complex assembly factor 5 (UQCC5)
Type: Family

This entry represents a family of proteins from animals, including Ubiquinol-cytochrome-c reductase complex assembly factor 5 (UQCC5), also known as small integral membrane protein 4 (SMIM4) from humans . These proteins mediates early mitochondrial ubiquinol-cytochrome c reductase complex (complex III) biogenesis and are required for its assembly and stability . They participate in regulating the levels of electron transport chain proteins, and therefore energy supply, in response to changes in energy demand . SMIM4/UQCC5 is also involved in the first steps of cytochrome c oxidase complex (complex IV) assembly .
Transcription cofactor vestigial-like protein 4 (VGLL4)
Type: Family

Transcription cofactor vestigial-like protein 4 (Vgl-4) is a member of the Vgl family of TEF-1 (transcriptional enhancer factor-1) cofactors. Vgl-4 has two TDU motifs and is the only Vgl member expressed in the heart . Vgl-4 modulates the activity of TEF-1 factors and counteracts alpha1-adrenergic activation of gene expression in cardiac myocytes .
Immunity protein 70 (Imm70)
Type: Family

This entry represents a predicted immunity protein with an α+β fold and conserved tyrosine and tryptophan residues. Proteins in this entry are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the Tox-REase-10 family .