SII-SWORD/CoKE huggingface dataset:
Centriolar and ciliogenesis-associated protein HYLS1 (HYLS1)
Type: Family

Hydrolethalus syndrome (HLS) is an autosomal recessive lethal malformation syndrome, leading to still-birth, or death shortly after birth. The syndrome is characterised by hydrocephaly, with absent upper midline structures of the brain, micrognathia and polydactyly. A variety of other features (including cleft lip or palate, club feet, anomalies of the ears, eyes and nose, a keyhole-shaped defect in the occipital bone, abnormal genitalia, and congenital heart and respiratory organ defects) have also been observed in affected individuals . Characterisation of the underlying molecular defect is important, as it could both expose new molecular pathway(s) essential for normal human development and provide new insights into foetal malformation syndromes.

The critical HLS region has been defined to a 476 kb interval using cases from 30 Finnish HLS families . Within this region, sequence analysis has revealed a point mutation in a novel gene (termed HYLS1) that results in substitution of a well-conserved Asp by Gly in the Centriolar and ciliogenesis-associated protein HYLS1, which is essential for early development of the human foetus .

HYLS1 is dispensable for centriole assembly and centrosome function in cell division. Instead, HYLS1 plays an essential role in cilia formation that is conserved between C. elegans and vertebrates .
Mas-related G protein-coupled receptor F (MRGPCRF)
Type: Family

Members of the mas-related receptor family (also known as oncogene-like MAS and mas-related G-protein coupled receptor MRG) have been implicated in the development, regulation and function of nociceptive neurons, specifically in the modulation of pain. Most members are orphaned, with no endogeneous ligand identified. Of the human mas-related GPCRs, four (MRGPRD, MRGPRE, MRGPRF and MRGPRG) are also found in rodents, whereas MRGPRX1, MRGPRX2, MRGPRX3 and MRGPRX4 are found exclusively in primates. Certain rodent MRGs have been reported to respond to adenine and to RF-amide peptides, including neuropeptide FF , but the relevance of these findings to man is unclear. MRGs are expressed predominantly in small diameter sensory neurons of the dorsal root ganglia, where there is emerging evidence that they may be mediators of histamine-independent itch .

This entry represents mas-related G protein-coupled receptor F. It is thought to be involved with nociceptor function and development, and directly involved in the modulation of pain. The receptor is currently orphaned; however, it is thought to be activated by a neuropeptide.
Vesicular, overexpressed in cancer, prosurvival protein 1 (VOPP1)
Type: Family

Ectopic expression of vesicular, over-expressed in cancer, pro-survival protein 1, VOPP1 (also known as WW domain binding protein VOPP1) increases NF-kappaB transcriptional activity . This is achieved by promoting nuclear translocation and DNA binding of NF-kappaB. Ecop-induced NF-kappaB activation confers cellular resistance to apoptotic challenge . It is believed that ECop is a key regulator of NF-kappaB signalling, and that high-level, amplification-mediated ECop expression, such as occurs in tumours with amplified EGFR, may contribute to resistance to apoptosis .
Mas-related G protein-coupled receptor E (MRGPCRE)
Type: Family

Members of the mas-related receptor family (also known as oncogene-like MAS and mas-related G-protein coupled receptor MRG) have been implicated in the development, regulation and function of nociceptive neurons, specifically in the modulation of pain. Most members are orphaned, with no endogeneous ligand identified. Of the human mas-related GPCRs, four (MRGPRD, MRGPRE, MRGPRF and MRGPRG) are also found in rodents, whereas MRGPRX1, MRGPRX2, MRGPRX3 and MRGPRX4 are found exclusively in primates. Certain rodent MRGs have been reported to respond to adenine and to RF-amide peptides, including neuropeptide FF , but the relevance of these findings to man is unclear. MRGs are expressed predominantly in small diameter sensory neurons of the dorsal root ganglia, where there is emerging evidence that they may be mediators of histamine-independent itch .

This entry represents mas-related G protein-coupled receptor E, it is thought to be involved with nociceptor function and development, and is directly involved in the modulation of pain. The receptor is currently orphaned, no specific endogenous ligand having been identified.
Protein IBD2 (IBD2)
Type: Family

During mitosis, genomic integrity is maintained by the proper coordination of mitotic events through the spindle checkpoint. The bifurcated spindle checkpoint blocks cell-cycle progression at metaphase by monitoring unattached kinetochores, and inhibits mitotic exit in response to the incorrect orientation of the mitotic spindle. Bfa1p is a budding yeast spindle checkpoint regulator in the Bub2p checkpoint pathway for proper mitotic exit. A Bfa1p interacting protein, termed Ibd2p, has been identified in the budding yeast Saccharomyces cerevisiae .

IBD2 (Inhibition of Bud Division 2) is not an essential gene. However, over-expression of Ibd2p has been shown to induce mitotic arrest, with increased levels of Clb2p in wild type and mad2Delta, but not in deletion mutants of BUB2 and BFA1. Overall, it is thought likely that IBD2 encodes a novel component of the BUB2-dependent spindle checkpoint pathway that functions upstream of BUB2 and BFA1 .
Mas-related G protein-coupled receptor D (MRGPCRD)
Type: Family

Members of the mas-related receptor family (also known as oncogene-like MAS and mas-related G-protein coupled receptor MRG) have been implicated in the development, regulation and function of nociceptive neurons, specifically in the modulation of pain. Most members are orphaned, with no endogeneous ligand identified. Of the human mas-related GPCRs, four (MRGPRD, MRGPRE, MRGPRF and MRGPRG) are also found in rodents, whereas MRGPRX1, MRGPRX2, MRGPRX3 and MRGPRX4 are found exclusively in primates. Certain rodent MRGs have been reported to respond to adenine and to RF-amide peptides, including neuropeptide FF , but the relevance of these findings to man is unclear. MRGs are expressed predominantly in small diameter sensory neurons of the dorsal root ganglia, where there is emerging evidence that they may be mediators of histamine-independent itch .

This entry represents mas-related G protein-coupled receptor D (MRGPRD), it is thought to be involved with nociceptor function and development, and is directly involved in the modulation of pain. It has been demonstrated that beta-alanine can act as an agonist at MRGPRD .
Mas-related G protein-coupled receptor A (MRGPCRA)
Type: Family

This entry represents mas-related G protein-coupled receptor A, it is found in rodents and is expressed only in specific subsets of sensory neurons that are known to detect painful stimuli. The receptor is coupled to the Galpha (q/11) signalling pathway, and potently activated by members of the rf-amide(npff/npaf) neuropeptide family. Stimulation by rf-amide agonists results in a dose-dependent release of free cytoplasmic Ca2+ .

Members of the mas-related receptor family (also known as oncogene-like MAS and mas-related G-protein coupled receptor MRG) have been implicated in the development, regulation and function of nociceptive neurons, specifically in the modulation of pain. Most members are orphaned, with no endogeneous ligand identified. Of the human mas-related GPCRs, four (MRGPRD, MRGPRE, MRGPRF and MRGPRG) are also found in rodents, whereas MRGPRX1, MRGPRX2, MRGPRX3 and MRGPRX4 are found exclusively in primates. Certain rodent MRGs have been reported to respond to adenine and to RF-amide peptides, including neuropeptide FF , but the relevance of these findings to man is unclear. MRGs are expressed predominantly in small diameter sensory neurons of the dorsal root ganglia, where there is emerging evidence that they may be mediators of histamine-independent itch .
Mas-related G protein-coupled receptor family (MRGPCRFAMILY)
Type: Family

Members of the mas-related receptor family (also known as oncogene-like MAS and mas-related G-protein coupled receptor MRG) have been implicated in the development, regulation and function of nociceptive neurons, specifically in the modulation of pain. Most members are orphaned, with no endogeneous ligand identified. Of the human mas-related GPCRs, four (MRGPRD, MRGPRE, MRGPRF and MRGPRG) are also found in rodents, whereas MRGPRX1, MRGPRX2, MRGPRX3 and MRGPRX4 are found exclusively in primates. Certain rodent MRGs have been reported to respond to adenine and to RF-amide peptides, including neuropeptide FF , but the relevance of these findings to man is unclear. MRGs are expressed predominantly in small diameter sensory neurons of the dorsal root ganglia, where there is emerging evidence that they may be mediators of histamine-independent itch .

This entry represents the mas-related G protein-coupled receptor family.
Inheritance of peroxisomes protein 2 (INP2)
Type: Family

Faithful inheritance of organelles by daughter cells is essential to retain the benefits afforded to eukaryotic cells by compartmentalisation of biochemical functions. In Saccharomyces cerevisiae, the class V myosin, Myo2p, is involved in transporting different organelles, including the peroxisome, along actin cables to the bud .

Inp2p has been identified as the peroxisome-specific receptor for Myo2p. Cells lacking Inp2p fail to partition peroxisomes to the bud, although they are unaffected in the inheritance of other organelles. Inp2p is a peroxisomal membrane protein, interacting directly with the globular tail of Myo2p. Cells that over-produce Inp2p often transfer their entire populations of peroxisomes to buds. Levels of Inp2p oscillate with the cell cycle. Organelle-specific receptors like Inp2p illustrate how a single motor can move different organelles in distinct and specific patterns. Inp2p is the first peroxisomal protein implicated in the vectorial movement of peroxisomes .
Integrator complex subunit 2, metazoa (Int2_metazoa)
Type: Family

The C-terminal domain (CTD) of RNA polymerase II (RNAPII) is an essential component of transcriptional regulation and RNA processing of protein-coding genes. CTD is implicated in the transcription and processing of RNAPII-mediated small nuclear RNAs (snRNAs), but the identity of the complex (or complexes) that associates with the CTD and mediates the processing of snRNAs has been elusive .

An RNA polymerase II complex termed the Integrator, which contains at least 12 novel subunits and core RNAPII subunits has been identified. Two of the Integrator subunits share similarity with subunits of the cleavage and polyadenylation specificity factor (CPSF) complex. Integrator has been shown to be recruited to the U1 and U2 snRNA genes, and to mediate the snRNAs' 3' end processing. The Integrator complex is evolutionarily conserved in metazoans, and directly interacts with the C-terminal domain of the RNA polymerase II largest subunit .
Probable serine/threonine-protein kinase GDT family (STKINASEGDT)
Type: Family

The life-cycle of Dictyostelium consists of two distinct phases: growth and development . The control of the growth-differentiation transition (GDT) is not fully understood, and only a handful of genes involved in the process have been elucidated. Amongst these is a family containing at least 9 closely related genes, of which gdt1 and gdt2 were the first members to be identified . It is thought that the different family members may control similar cellular processes, but respond to different environmental cues .

The gdt1 and gdt2 gene products, GDT1 and GDT2, are similar in many ways, but there are important differences. GDT1 is a 175kDa protein with 4 putative transmembrane (TM) domains . The C-terminal amino acid sequence shares some similarity with the catalytic domain of protein kinases; while this domain is well conserved in GDT2, it is thought to be non-functional in GDT1 . Similar observations have been made for other family members: hence, for example, GDT3 and GDT4 encode complete well conserved kinase domains, and are therefore probably functional ; conversely, GDT6 and GDT8 appear to encode proteins with degenerate protein kinase domains; and the C-terminal sequence of GDT5 seems unrelated to protein kinases, while GDT7 appears to be truncated, and stops before the protein kinase domain.
Protein INCA1 (INCA1)
Type: Family

The CDK2-associated cyclin A1 is essential for spermatogenesis, and contributes to leukemogenesis, but its detailed molecular functions are unclear. Several novel cyclin A1/CDK2 interaction partners have been identified by means of a yeast triple-hybrid approach, including INCA1, KARCA1 and PROCA1. These proteins link the cyclin A1-CDK2 complex to diverse cellular processes, such as DNA repair, signalling and splicing .

One of the new genes has been cloned and characterised, and named INCA1 (inhibitor of CDK interacting with cyclin A1). The nuclear INCA1 protein is evolutionarily conserved but shares no similarity with any known gene. This novel protein and two other interacting partners serve as substrates for the cyclin A1-CDK2 kinase complex .
Immunogenic miracidial antigen 8I' (Miracidia_Ag_8I')
Type: Family

Antigens of schistosome eggs are released from live and dead eggs that are trapped in host tissue. Many such egg antigens, a large portion of which are presumed to originate from the enclosed miracidia, elicit a host-immune response during infections .

Several immunopositive clones have been isolated; three of these were studied in detail and found to contain members of a large, closely related gene family encoding an immunogenic miracidial antigen. At least two members of this family are tightly linked to the Schistosoma japonicum (blood fluke) genome. The fact that there are so many gene copies encoding this antigen, which is reactive with both chronically infected human and mouse sera, make this a potentially important antigen .
GLC7-interacting protein 4 (GIP4)
Type: Family

Faithful chromosome segregation depends on the opposing activities of the budding yeast Glc7/PP1 protein phosphatase and Ipl1/Aurora protein kinase. It is believed that Glc7 ensures accurate chromosome segregation by dephosphorylating Ipl1 targets (rather than regulating the Ipl1 kinase) .

Gip3 and Gip4 have been identified amongst several genes as ipl1 dosage suppressors, and encode proteins that physically interact with Glc7 . Over-expression of the GIP3 and GIP4 suppressors was shown to alter Glc7 localisation, indicating they are previously unidentified Glc7 regulatory subunits, and that Gip3 and Gip4 over-expression may impair Glc7's mitotic functions. It has been proposed, therefore, that over- expression of Glc7 regulatory subunits can titrate Glc7 away from relevant Ipl1 targets, thereby suppressing ipl1-321 cells by restoring the balance of phosphatase/kinase activity .
HAUS augmin-like complex subunit 2, metazoa (HAUS2_metazoa)
Type: Family

Assembly of a robust microtubule-based mitotic spindle is essential for accurate segregation of chromosomes to progeny. Spindle assembly relies on the concerted action of centrosomes, spindle microtubules, molecular motors and non-motor spindle proteins . A number of novel regulators of spindle assembly have been identified: one of these is HAUS, an 8-subunit protein complex that shares similarity with Drosophila Augmin .

HAUS augmin-like complex subunit 2 is a component of the HAUS augmin-like complex, which localises to the centrosomes and interacts with the gamma-tubulin ring complex (gamma-TuRC) . The interaction between augmin and gamm-TuRC is important for spindle microtubule generation and affects the mitotic progression and cytokinesis . HAUS2 may also increase the tension between spindle and kinetochore allowing for chromosome segregation during mitosis .
HAUS augmin-like complex subunit 1 (HAUS1)
Type: Family

Assembly of a robust microtubule-based mitotic spindle is essential for accurate segregation of chromosomes to progeny . Spindle assembly relies on the concerted action of centrosomes, spindle microtubules, molecular motors and non-motor spindle proteins . A number of novel regulators of spindle assembly have been identified: one of these is HAUS, an 8-subunit protein complex that shares similarity with Drosophila Augmin . Plants also have a augmin complex consisting of eight subunits. Subunits AUG1 to AUG6 can be aligned with the human HAUS1 to HAUS6 proteins .

HAUS localises to interphase centrosomes and to mitotic spindle micro- tubules; its disruption induces microtubule-dependent fragmentation of centrosomes, and an increase in centrosome size. HAUS disruption results in the destabilisation of kinetochore microtubules and eventual formation of multipolar spindles. Such severe mitotic defects are alleviated by co-depletion of NuMA, indicating that both factors regulate opposing activities. HAUS disruption alters NuMA localisation, suggesting that mis-localised NuMA activity contributes to the observed spindle and centrosome defects. The Augmin complex (HAUS) is thus a critical, evolutionarily conserved multi-subunit protein complex that regulates centrosome and spindle integrity .

The HAUS (Homologous to AUgmin Subunits) individual subunits have been designated HAUS1 to HAUS8 . HAUS1 contains multiple coiled-coil domains that are essential for its interactions within the complex. The N-terminal forms a dumbbell-shaped structure with HAUS4 connected by a coiled-coil, while the C-terminal region contains three coiled-coils that interact with HAUS4 to form the heterodimer . HAUS1 forms a stable heterodimer with HAUS4

, with the two proteins forming part of the filamentous tail of the augmin complex.
Protein FRG2 (FRG2)
Type: Family

FRG2, a member of a chromosomally dispersed gene family, has been identified and characterised . Low levels of FRG2 expression were detectable in differentiating myoblasts of autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) patients, partly from chromosome 4, but originating largely from its homologue on chromosome 10 . In non-FSHD myopathy patients, only distantly-related FRG2 homologues are transcribed, while differentiating myoblasts from healthy controls do not express any member of this gene family . The localisation of FRG2 genes close to the D4Z4 repeats on chromosomes 4 and 10, their transcriptional up-regulation in FSHD myoblast cultures, potential involvement in myogenesis, and promoter properties, render FRG2 an attractive candidate for FSHD pathogenesis. Nevertheless, sequence- and motif-based searches have shed no light on the function of the predicted protein .
Fibrous sheath-interacting protein 1 (Fsip1)
Type: Family

Found in the main part of the sperm flagellum, the fibrous sheath is a cytoskeletal structure comprising two longitudinal columns connected by closely spaced circumferential ribs . A-kinase anchoring proteins (AKAPs) secure cyclic AMP-dependent protein kinases within specific cytoplasmic domains; most abundant in the fibrous sheath is AKAP4 . AKAP4 has been shown to bind AKAP3 and two spermatogenic cell-specific proteins, Fibrous Sheath Interacting Proteins 1 and 2 (FSIP1, FSIP2) .

How the fibrous sheath assembles is not yet fully understood. AKAP4 is synthesised and incorporated into the nascent fibrous sheath late in spermatid development; its precursor is processed in the flagellum, and only the mature form of AKAP4 appears to bind AKAP3 . It is likely, therefore, that AKAP3 is involved in organising the basic structure of the fibrous sheath, while AKAP4 helps to complete fibrous sheath assembly.

The FSIP1 protein is 435 amino acids in length, and is rich in glutamine and asparagine . Minimum domains for its binding to AKAP4 have been localised to amino acids 351-359 and 692-721 of AKAP4 constructs .
Endothelial cell-specific chemotaxis regulator (ECSCR)
Type: Family

Endothelial cell-specific chemotaxis regulator, ECSCR (also known as endothelial cell-specific molecule 2, ECMS2), is a novel cell surface protein that regulates endothelial chemotaxis and tube formation; it also interacts with filamin A, implicating a role in angiogenesis via modulation of the actin cytoskeleton .

ECSCR is a 205-amino acid protein containing a putative transmembrane (TM) domain, a conserved intracellular domain and a variable extracellular domain, but no other known functional sites, and no similarity to any other known proteins. It has been shown that the protein is a marker of primary hemangioblasts and endothelial progenitors, and not other hematopoietic progenitor cells , but little else is known about the protein.
Protein Fyv8 (Fyv8)
Type: Family

Little is known about protein Fyv8 (also known as function required for yeast viability protein 8); however, it seems that the Fyv8 gene is needed for survival upon exposure to K1 killer toxin . It also may be involved in the resistance to unfolded protein response (UPR)-inducing agents .
CASTOR family (CASTOR_fam)
Type: Family

CASTOR family members are well-conserved in eukaryotes (including human, chimpanzee, dog, cow, mouse, rat, chicken, zebrafish) . Three subtypes, designated CASTOR1, CASTOR2 and CASTOR3, have been identified in humans.

CASTOR1 can form homodimers and bind arginine. It can also form heterodimers with CASTOR2 . The arginine binding of CASTOR1 disrupts the CASTOR1-GATOR2 interaction, and this triggers downstream activation of mTORC1 . Therefore, CASTOR1 functions as an intracellular arginine sensor for the mTORC1 Pathway . Interestingly, CASTOR1 shares substantial structural homology with the lysine-binding regulatory domain of prokaryotic aspartate kinases .
Inositol 1,4,5-trisphosphate receptor-interacting protein-like (ITPRIP-like)
Type: Family

The inositol 1,4,5-trisphosphate receptor (IP(3)R) is a large, endoplasmic reticulum (ER)-resident protein that is a key regulator of intracellular Ca(2+) signalling . Inositol 1,4,5-trisphosphate is formed in response to the activation of G protein-coupled receptors or tyrosine kinase receptors located in the plasma membrane, which elicit IP(3)R-mediated Ca(2+) release from ER stores .

The IP(3)R contains an N-terminal IP(3) recognition site and a C-terminal Ca(2+)-channel domain; between them is a large interaction domain for regulatory proteins, including calmodulin, chromgranins, glyceraldehyde-3- phosphate dehydrogenase, RACK1 and caldendrin . These proteins regulate IP(3)R in diverse ways, but only two regulators have been shown to influence Ca(2+) sensitivity .

A protein termed DANGER has been identified as a novel IP(3)R-interacting protein . DANGER is membrane-associated and predicted to contain a partial MAB-21 domain. It is expressed in a wide variety of neuronal cell lineages, where it localises with IP(3)R to membranes in the cell periphery. DANGER interacts with IP(3)R in vitro and co-immuno- precipitates with IP(3)R from cellular preparations; it robustly enhances Ca(2+)-mediated inhibition of IP(3)R Ca(2+) release without affecting IP(3) binding in microsomal assays, and inhibits gating in single-channel recordings of IP(3)R. The protein appears to allosterically modulate the sensitivity of IP(3)R to Ca(2+) inhibition, which probably alters IP(3)R-mediated Ca(2+) dynamics in cells where DANGER and IP(3)R are co-expressed .