SII-SWORD/CoKE huggingface dataset:
Mucin-7 (MUC7)
Type: Family

Mucins are high-molecular-weight glycoproteins present on all mucosal surfaces. Mucins are characterised by the presence of tandemly repeated amino acid sequences, the mucin domains that contain high amounts of serine and threonine and thus create an attachment point for O-linked glycosylation .

The mucins and their glycosylation are essential to a variety of saliva properties, including microbial defense and biolubrication. MUC7 has been identified as the major mucin in the low-molecular-weight mucin fraction called mucin glycoprotein 2 (MG2) in saliva . Salivary MG2-MUC7 has been suggested to be important for binding of salivary neutrophils via L-selectin and mediating the interaction between neutrophils and oral bacteria .
Arabinose metabolism transcriptional repressor, ligand-binding domain (AraR_ligand_bind_dom)
Type: Domain

This entry represents the ligand-binding domain of AraR, which is a member of the LacI-GalR family of bacterial transcription regulators. It is involved in L-arabinose-inducible expression of the araABDLMNPQ-abfA metabolic operon and of the araE/araR genes that are organized as a divergent transcriptional unit in Bacillus subtilis .
Proline-rich protein 27 (PRR27)
Type: Family

The function of this proline rich protein is unknown.
Spermatogenesis-associated protein 22 (Spata22)
Type: Family

Spermatogenesis-associated protein 22 (Spata22) is required early in meiotic prophase in both male and female germ cells. It is necessary to achieve normal synapsis and for repair of meiotic DNA double-strand breaks .
Stimulated by retinoic acid gene 8 protein (Stra8)
Type: Family

Stimulated by Retinoic Acid Gene 8 (Stra8) is required for the transition into meiosis in both female and male germ cells. In mammals, Stra8 is expressed in embryonic ovaries just before meiotic initiation, whereas its expression in testes is first detected after birth . Retinoic acid signalling is required for the expression of Stra8 and thereby meiotic initiation in embryonic ovaries .
Retroviral-like aspartic protease 1 (Asprv1)
Type: Family

Retroviral-like aspartic protease 1, also known as aspartic proteinase-like protein (Taps) or Skin ASpartic Protease (SASPase), has been shown to be involved in differentiation and homeostasis of multilayered epithelia and prevention of fine wrinkle formation .
MALT1, immunoglobulin-like domain superfamily (MALT1_IG-like_dom_sf)
Type: Homologous_superfamily

MALT1 (MEROPS identifier C14.026) is a paracaspase that cleaves its substrates on the C-terminal side of an arginine residue . It is a key regulator of antigen-induced NF-kappaB activation in the adaptive immune response . Upon antigen stimulation MALT1 acts as a scaffold for a protein complex formed with CARMA1 (also known as CARD11) and Bcl10, the CBM complex. The CBM complex links AgR (antigen receptor) triggering to NF-kappaB activation .

This entry represents the C-terminal immunoglobulin-like domain of MALT1, which has been suggested to recruit key factors to promote NF-kB activation. It is also proposed to undergo Lys63-linked ubiquitylation via TRAF6 in potentially nine different lysines to recruit the IKK complex .
Dermokine (Dermokine)
Type: Family

Expression of the human dermokine gene (DMKN) leads to the production of four dermokine isoforms. Expression of the secreted alpha, beta and gamma isoforms is restricted to the epidermis . DMKN beta and gamma are specifically expressed by the granular keratinocytes and have a role in cornification . Dermokine levels are increased in inflammatory skin disorders, but decreased in skin cancers .
Transmembrane protein 225 (TM225)
Type: Family

Transmembrane protein 225 (TM225) is specifically expressed in testis . It may be involved in the differentiation and function of spermatozoa through the regulation of PP1gamma2 activity .
Bcl-2-like protein 15 (BCL2L15)
Type: Family

Bcl-2-like protein 15, also known as Bfk, is a member of the bcl2 gene family. It is highly expressed in the epididymis in mouse and in tissues of the gastrointestinal tract, where it may help to protect against the development of gastrointestinal malignancy .
Nuclear receptor subfamily 0 group B member 1/2 (NR0B1/2)
Type: Family

NR0B1 (also known as DAX-1) is an orphan nuclear receptor involved in the development and maintenance of the steroid hormone pathway. It also plays a role in the development of the embryo and maintenance of pluripotent embryonic stem cells . Mutations of the DAX-1 gene cause X-linked adrenal hypoplasia congenita (XL-AHC), a developmental disorder of the adrenal gland that results in profound hormonal deficiencies and is lethal if untreated .

NR0B2 lacks a conventional DNA binding domain (DBD) and represses the transcriptional activity of various nuclear receptors
.

Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands . The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner . In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.

NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.
Centrosomal protein of 89kDa (CEP89)
Type: Family

CEP89 is a component of the distal appendages of centrioles, and is required for ciliogenesis . CEP89 has also been shown to be required for mitochondrial metabolism and neuronal and cognitive function .
NFAT activation molecule 1 (NFAM1)
Type: Family

NFAT activation molecule 1 (NFAM1) is a cell surface molecule of the immunoglobulin superfamily that plays a role in immune signalling. It contains an N-terminal signal peptide, an extracellular immunoglobulin domain, a transmembrane region, and a cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM), all characteristic of this protein family . NFAM1 activates the calcineurin/NFAT signalling pathway, promoting downstream transcription of cytokine genes and modulating immune responses . It has also been shown to regulate B cell development through ITAM-mediated signalling, suggesting a functional role in lymphocyte maturation .
Dynein regulatory complex subunit 7 (DRC7/lobo)
Type: Family

DRC7 or coiled-coil domain-containing protein 135 (CCD135), known as lobo in Drosophila, is a protein involved in flagelar motility . It is a component of the nexin-dynein regulatory complex, which is an important regulatory node of dynein activity . Lobo is involved in Drosophila sperm motility .
TCF3 fusion partner (TFPT)
Type: Family

TFPT, also known as INO80F or amida, plays an important role in p53-independent cellular apoptosis . There is also evidence that it plays a role in cell cycle arrest and spermatogenesis . It is a putative regulatory component of the chromatin remodeling INO80 complex .
Phospholipase A1-II (PLA)
Type: Family

This entry includes Arabidopsis phospholipases A1-II alpha/beta/gamma/delta. They are acylhydrolases that catalyze the hydrolysis of phospholipids at the sn-1 position .
Ciliary microtubule-associated protein 2 (CIMAP2)
Type: Family

This entry represents the homologues of Ciliary microtubule-associated protein 2 (CIMAP2 formerly lymphocyte expansion molecule - LEM1). CIMAP2 is an axoneme microtubule associated protein (MAP). In the sperm EM structure, it occupies the inter-protofilament cleft between protofilaments A03/A04. It repeats alternately CIMAP3 with along the DMT, resulting in an overall periodicity of 96 nm . CIMAP2 belongs to axonemal wedge-MAPs that bind deeper into the inter-protofilament cleft and make extensive contacts with flanking protofilaments. Expression of these wedge-MAPs is not restricted to the testis suggesting that they may have general functions in cilia .
Intraflagellar transport protein 25 (IFT25)
Type: Family

Intraflagellar transport (IFT) is the bidirectional movement of multimeric protein particles, termed IFT particles, between the cell body and the distal tip of a flagellum. IFT particle proteins are thought to serve as scaffolds to facilitate the attachment of cargo proteins to IFT motors, mediating the transport of flagellar precursors . The main constituents of IFT particles are organized into two protein complexes, A and B.

IFT25 is a component of the intraflagellar transport (IFT) complex B. It directly interacts with IFT27, forming a subcomplex that may be involved in the regulation of IFT . IFT25 is required for Hedgehog signalling in cilia .
Fas-binding factor 1 (FBF1)
Type: Family

Intraflagellar transport (IFT) machinery is required for the assembly and maintenance of cilia. Fas-binding factor 1 (FBF1) is a transition fibre protein required for the ciliary import of assembled IFT particles at the ciliary base . FBF1, also known as albatross, has also being shown to be involved in regulating polarization in epithelial cells .
Patatin-like phospholipase domain-containing protein (PLPL)
Type: Family

This entry includes patatin-like phospholipase domain-containing proteins 1-5 (PNPLA1-5) from humans and Atgl-1 from Caenorhabditis elegans. They are a group of lipid hydrolases.

Atgl-1 may play a role in the response of the organism to starvation, enhancing hydrolysis of triglycerides and providing free fatty acids to other tissues to be oxidized in situations of energy depletion .

In humans PNPLA1 has a role in the formation of the epidermal lipid barrier; mutations in this gene are associated with the skin disorder known as ichthyosis . PNPLA1 acts as an omega-hydroxyceramide transacylase involved in the synthesis of omega-O-acylceramides (esterified omega-hydroxyacyl-sphingosine; EOS), which are extremely hydrophobic lipids involved in skin barrier formation . It catalyzes the last step of the synthesis of omega-O-acylceramides by transferring linoleic acid from triglycerides to an omega-hydroxyceramid .

Human PNPLA2 catalyses the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets . PNPLA3 has both triacylglycerol lipase and acylglycerol O-acyltransferase activities . PNPLA4 additionally possesses acylglycerol transacylase and phospholipase A2 activities .
Sodium channel modifier 1 (SCNM1)
Type: Family

SCNM1 (sodium channel modifier 1) is an accessory component of the U1 splicesome protein complex. It interacts with the spliceosomal Sm and U1-70K proteins and has a direct role in splicing . It was originally identified as a disease modifier gene required for efficient splicing of a mutant splice donor site in the sodium channel Scn8a .
NEDD4-binding protein 3 (N4BP3)
Type: Family

N4BP3 was identified as a protein expressed during development that interacts with Nedd4 ubiquitin ligase. N4BP3 is not a ubiquitylation substrate of Nedd4, but it can alter Nedd4 subcellular location, indicating a functional interaction . N4BP3 has been shown to be essential in neurite branching and circuit formation .
DET1- and DDB1-associated protein 1-like (DDA1-like)
Type: Family

DDA1 is a core subunit of multiple Cul4-based E3 ligases (CRL4s), involved in ubiquitination and subsequent proteasomal degradation of target proteins, which regulate key developmental and stress responses in eukaryotes . In mammals, DDA1 binds to DET1 and DDB1 to form DDD complexes, which recruit specific ubiquitin-conjugating UBE2E enzymes to form DDD-E2 complexes . The DDD-E2 complex provides a platform for interaction with Cul4A and beta-transducing (also called WD40) repeat proteins. DDA1 is conserved in higher eukaryotes, including Arabidopsis . This entry also includes protein LOWER TEMPERATURE 1 (LOT1) from Arabidopsis which contains the conserved DDA1 domain. LOT1 supports abscisic acid (ABA) responses and drought tolerance by regulating the dynamic localization and stability (preventing degradation by the proteasome) of CAR proteins (C2-domain ABA-related, e.g. CAR9) .
Aminopeptidase O (AOPep)
Type: Family

Aminopeptidase O (MEROPS identifier M01.028) is an intracellular aminopeptidase. There is a nucleolar location signal located between the peptidase and ARM-repeat domains. Aminopeptidase O has been localized to the nucleolus, and in the mouse a shorter isoform, generated by alternative initiation, is found in adult and embryonic blood vessels, mainly in the endothelial and smooth muscle cells . The AOPEP gene also includes a cluster of microRNAs, one of which modulates expression of the Mef2c gene which encodes myocyte-specific enhancer factor 2C . It is possible that aminopeptidase O is involved in development of vasculature in the embryo and control of blood pressure.
Transmembrane protein 128 (TMEM128)
Type: Family

This entry represents the uncharacterised TMEM128 protein which contains four transmembrane helices. This protein is resident in the endoplasmic reticulum.
Nurim-like (Nurim-like)
Type: Family

Nurim is an inner nuclear membrane protein which may play an important role in the suppression of apoptosis .

There are related enzymes in bacteria, including methanethiol S-methyltransferase (

), which catalyses the methylation of methanethiol to yield dimethylsulphide (a volatile compound important in climate regulation) , suggesting a potential ancient origin .
BEN domain-containing protein 3 (BEND3)
Type: Family

BEND3 is a transcriptional repressor that associates with the nucleolar-remodeling complex (NoRC) and is involved in ribosomal DNA (rDNA) silencing . SUMOylated BEND3 stabilizes the NoRC component Tip5 via USP21 deubiquitinase . NorC serves as a molecular platform that recruits chromatin modifiers, such as histone deacetylases and histone methyltransferases, leading to deacetylation of histone H4 and trimethylation of H3K9 and H4K20 . NoRC also targets histone deacetylases and histone methyltransferases to rDNA to establish a heterochromatic state that inhibits transcription activation. Hence, BEND3 and NoRC seem to play a concerted role in the maintenance of heterochromatin architecture .

BEND3 has also been shown to mediate Polycomb recruitment in the absence of H3K9Me3 or DNA methylation at the pericentromeric regions . BEND3 interacts with PICH (ERCC6L), a DNA translocase required for the maintenance of chromosome stability, and stimulates its translocase and ATPase activities. This interaction occurs via an interface between a TPR domain in PICH and a BEN domain in BEND3 .
Dynein regulatory complex protein 12-like (DRC12-like)
Type: Family

This entry represents Dynein regulatory complex protein 12 from Tetrahymena thermophila (DRC12, also known as Coiled-coil domain-containing protein 153) and similar eukaryotic sequences. DRC12 is a component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes .
Meiosis 1 arrest protein (M1AP)
Type: Family

Meiosis 1 arrest protein (M1AP), also known as spermatogenesis-associated protein 37 (Spata37), is required for meiosis I progression during spermatogenesis .
Protein phosphatase 1 regulatory subunit 35 (PPP1R35)
Type: Family

Protein phosphatase 1 regulatory subunit 35 has been identified as a PP1 interacting protein and shown to inhibit PP1-alpha phosphatase activity .
N-terminal RASSF family (N-RASSF)
Type: Family

The Ras association domain (RASSF) proteins are named due to the presence of a Ras association (RA) domain in their N or C terminus that can potentially interact with the Ras GTPase family of proteins. These GTPases control a variety of cellular processes, such as membrane trafficking, apoptosis, and proliferation. RASSF proteins contain several other functional domains that modulate associations with other proteins. RASSF proteins with the RA domain at the C terminus (which are termed C-terminal or classical RASSF) usually also include a Salvador-RASSF-Hippo (SARAH) domain involved in several protein-protein interactions and for homo- and heterodimerisation of RASSF isoforms. N-terminal RASSF proteins (with the RA domain in the N terminus) do not usually contain a SARAH domain .

At least 10 RASSF family members have been characterised (with multiple splice variants), many of which have been shown to play a role in tumour suppression. RASSF proteins also act as scaffolding agents in microtubule stability, regulate mitotic cell division, control cell migration and cell adhesion, and modulate NF-KB activity and the duration of inflammation. Loss of RASSF expression through promoter methylation has been shown in numerous types of cancer, including leukemia, melanoma, breast and prostate cancer .

This entry refers to the N-terminal RASSF family of proteins.
RNA polymerase I transcription initiation factor TAF1B/Rrn7 (TAF1B/Rrn7)
Type: Family

Rrn7 is a subunit of the yeast Pol I core factor. It associates strongly with both Rrn6 and Rrn11 to form a complex which itself binds the TATA-binding protein, and is required for transcription by the core domain of the RNA Pol I promoter .

Rrn7 human orthologue, TATA box-binding protein-associated factor RNA polymerase I subunit B (TAF1B), is also a component of RNA polymerase I core factor complex. It acts as a GTF2B/TFIIB-like factor and plays a key role in multiple steps during transcription initiation . Both Rrn7 and TAF1B are TFIIB-like factors. Although distantly related, they share many activities associated with TFIIB-like factors .
Ras association domain-containing protein 1, RA domain (RASSF1_RA)
Type: Domain

The Ras association domain (RASSF) proteins are named due to the presence of a Ras association (RA) domain in their N or C terminus that can potentially interact with the Ras GTPase family of proteins. These GTPases control a variety of cellular processes, such as membrane trafficking, apoptosis, and proliferation. RASSF proteins contain several other functional domains that modulate associations with other proteins. RASSF proteins with the RA domain at the C terminus (which are termed C-terminal or classical RASSF) usually also include a Salvador-RASSF-Hippo (SARAH) domain involved in several protein-protein interactions and for homo- and heterodimerisation of RASSF isoforms. N-terminal RASSF proteins (with the RA domain in the N terminus) do not usually contain a SARAH domain .

At least 10 RASSF family members have been characterised (with multiple splice variants), many of which have been shown to play a role in tumour suppression. RASSF proteins also act as scaffolding agents in microtubule stability, regulate mitotic cell division, control cell migration and cell adhesion, and modulate NF-KB activity and the duration of inflammation. Loss of RASSF expression through promoter methylation has been shown in numerous types of cancer, including leukemia, melanoma, breast and prostate cancer .

RASSF1 is one of the C-terminal (also known as classical) RASSF proteins, characterised by an RA domain and a SARAH domain (

) in the C terminus . Human RASSF1 has multiple transcripts as a result of alternative splicing and differential promoter usage. RASSF1A and 1C are the most widely studied and characterised of these. While they are both involved in regulation of growth and migration via microtubule localization, they have very different biological properties .

RASSF1A is a tumour suppressor primarily important in microtubule stability, but implicated in a number of different functions, including cell-cycle regulation, spindle assembly, chromosome attachment, apoptosis and inflammation control, amongst others .

In contrast, RASSF1C has not been shown to be a tumour suppressor, and has even been implicated as an oncogene by a number of mechanisms . It has been reported to activate cell proliferation through interaction with IGFBP-5, and may also interact with TFPI-2, which is involved in angiogenesis and tumour growth/metastasis . RASSF1C has also been reported to interact with and stabilise microtubules .

This entry represents the Ras-associating (RA) domain of RASSF1, which has a β-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases.
Ciliary microtubule-associated protein 3 (CIMAP3)
Type: Family

This entry represents homologues of Ciliary microtubule-associated protein 3 (CIMAP3, also known as Protein Pitchfork). CIMAP3 is an axonemal microtubule-associated (MAP). It belongs to the group of wedge-MAPs that occupy the inter-protofilament cleft between protofilaments A03/A04. It alternates with CIMAP2 along the DMT, resulting in an overall periodicity of 96 nm .

The primary cilium (PC) is a microtubule (MT)-based organelle that emanates from the cell surface of most mammalian cell types during growth arrest. It is anchored by the mother centriole of the centrosome, known as basal body (BB). Pitchfork associates with ciliary targeting complexes and regulates primary cilia (PC) disassembly. It interacts and co-localizes with alpha, beta, gamma-Tubulin, MT-dependent motor proteins, small GTPases involved in vesicular trafficking and is dynamically transported along ciliary axonemal MTs. It has been shown to activate Aurora A, a protooncogenic kinase that induces cilia retraction . In vertebrates, the PC acts as the key-signalling hub for the Hedgehog pathway, which regulates diverse aspects of embryonic development and tissue homeostasis. Pitchfork is involved, together with Gprasp2, in targeting Smoothened to the primary cilium for the activation of the Hedgehog pathway .
Centrosomal protein of 44kDa (CEP44)
Type: Family

CEP44 is a centrosomal protein that localises to the centriole .
E3 ubiquitin-protein ligase RNF152, RING finger domain (RING_RNF152)
Type: Domain

RING finger protein 152 (RNF152) has E3 ligase activity involved in lysosome-related apoptosis . It is a negative regulator of the mTORC1 pathway by targeting RagA for K63-linked ubiquitination .

RNF152 contains an N-terminal C3HC4-type RING-HC finger and a C-terminal transmembrane domain, both of which are responsible for its E3 ligase activity. This entry represents the RING-type zinc finger.