SII-SWORD/CoKE huggingface dataset:
NADH-ubiquinone oxidoreductase 1 subunit C1 (NDUFC1)
Type: Family

Subunit C1 is a accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. NADH dehydrogenase complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone .
NADH-ubiquinone oxidoreductase flavoprotein 3 (NDUFV3)
Type: Family

NADH dehydrogenase [ubiquinone] flavoprotein 3 (NDUFV3) is a accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone .
Prolactin-releasing peptide (PrRP)
Type: Family

Prolactin-releasing peptide (PrRP) stimulates prolactin (PRL) release and regulates the expression of prolactin through its receptor GPR10. It may stimulate lactotrophs directly to secrete PRL .
P-selectin glycoprotein ligand 1 (PSGL-1)
Type: Family

P-selectin glycoprotein ligand 1 (PSGL-1) is a SLe(x)-type glycan, which through high affinity, calcium-dependent interactions with E-, P- and L-selectins, mediates rapid rolling of leukocytes over vascular surfaces during the initial steps in inflammation. PSGL-1 is critical for the initial leukocyte capture .
Secretogranin III (SCG3)
Type: Family

Secretogranin-3 is a family of vertebrate proteins that is one of the granin family. Granins are rich in acidic amino acids, exhibit aggregation at low pH, and possess a high capacity for calcium binding. Because granins are restricted in their localisation to secretory granules of neuroendocrine cells, two interesting characteristics of their sorting mechanisms have been observed. These are, first, that they aggregate on low pH/high calcium concentrations and second that two of them carry an N-terminal disulfide loop, mutations in which lead to mis-sorting. Thus, granins are thought to be essential for the sorting of secretory proteins at the trans-Golgi network. Chromogranin A (CgA) binds to SGIII in secretory granules of endocrine cells . SGIII directly binds to cholesterol components of the secretory granule membrane and targets CgA to secretory granules in pituitary and pancreatic endocrine cells . Mutations in the SGIII gene may influence the risk of obesity through possible regulation of hypothalamic neuropeptide secretion .

Secretogranin-3 interacts with cromogranin A; this interaction is optimal in conditions mimicking the lumenal milieu of the trans-Golgi network, i.e. pH 5.5 and 10 mM Ca(+2) .
TYRO protein tyrosine kinase-binding protein (Tyrobp)
Type: Family

TYRO protein tyrosine kinase-binding protein (Tyrobp), also called DNAX-activation protein 12 (DAP12), is expressed by NK cells and myeloid cells and mediates signalling for numerous cell-surface receptors expressed by these cells. It has been shown to both potentiate and attenuate the activation of these cells . More than 20 receptor chains have been shown to associate with DAP12. It is involved for instance in neutrophil activation mediated by integrin .
Centrosomal protein of 290kDa (Cep290)
Type: Family

Centrosomal protein of 290kDa (Cep290) is part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition. It activates ATF4-mediated transcription. It is required for the correct localisation of ciliary and phototransduction proteins in retinal photoreceptor cells and may play a role in ciliary transport processes .
Golgin subfamily B member 1 (GOLGB1)
Type: Family

Golgin subfamily B member 1 (also called Macrogolgin/Giantin) may participate in forming intercisternal cross-bridges of the Golgi complex .
Intracellular hyaluronic acid binding protein (IHABP)
Type: Family

The extracellular matrix component hyaluronan plays important roles in various processes of organogenesis, cell migration and cancer . Recognition of and binding to hyaluronan is mediated by cell surface receptors.

The proteins in this family were initially called receptor for hyaluronan mediated motility (RHAMM), and were thought to be involved in cell motility . However, several lines of evidence suggest that they do not function as a conventional motility receptors for hyaluronan, leading to the suggestion they should be renamed intracellular hyaluronic acid binding protein (IHABP) .

IHABP is overexpressed in many cancers and may be involved in cellular transformation and metastasis formation , and in regulating extracellular-regulated kinase (ERK) activity .
GRIP1-associated protein 1 (GRIPAP1)
Type: Family

GRIP1-associated protein 1 (GRIPAP1, also known as GRASP-1) is expressed in the CNS and interacts with GRIP1, GRIP2 and AMPA receptors . It may regulate neuronal ras signaling and contribute to the regulation of AMPA receptor distribution by NMDA receptor activity .
Progesterone-induced-blocking factor 1 (PIBF1)
Type: Family

Progesterone-induced-blocking factor 1 (PIBF1) is an immunomodulatory molecule secreted by pregnancy lymphocytes . It exerts immunosuppressive effects by inhibiting NK cell activity, polarising immune responses towards TH2 dominance and down-regulating effector cytokine response . It is thought to play a vital role in preventing rejection of the embryo by the maternal immune response. PIBF1 may also have a role in cancer. It is produced by malignant tumours and may facilitate tumour growth by suppressing local antitumour immune responses .
HAUS augmin-like complex subunit 3 (HAUS3)
Type: Family

HAUS augmin-like complex subunit 3 (HAUS3) contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex . AUGMIN subunit3 (AUG3) is a plant homologue of HAUS3 .
Interleukin-27 alpha (IL-27_alpha)
Type: Family

This entry represents IL27-A proteins (known as IL-30/IL27-p28). Interleukin-27 is a heterodimeric cytokine composed of two subunits; IL27-A (IL27-p28) and Epstein-Barr virus-induced gene 3 (EBI3, also known as IL-27B) .
Wolframin (Wolframin)
Type: Family

Wolframin, a multi-pass membrane protein found in the endoplasmic reticulum, is expressed by the Wolfram syndrome 1 gene (WFS1) . The detailed molecular function of the protein is not known, but it is believed to participate, at least in part, in the regulation of cellular calcium homeostasis by modulating the filling state of the endoplasmic reticulum calcium store.

Defects in WFS1 cause Wolfram Syndrome (WFS), also referred to as DIDMOAD - this syndrome is characterised by diabetes insipidus, childhood-onset diabetes mellitus, gradual loss of vision owing to optic atrophy, and deafness . It is a rare autosomal recessive disorder, and may give rise to other complications affecting the bladder and nervous system.
Wolframin family (Wolframin_fam)
Type: Family

Wolframin, a multi-pass membrane protein found in the endoplasmic reticulum, is expressed by the Wolfram syndrome 1 gene (WFS1) . The detailed molecular function of the protein is not known, but it is believed to participate, at least in part, in the regulation of cellular calcium homeostasis by modulating the filling state of the endoplasmic reticulum calcium store.

Defects in WFS1 cause Wolfram Syndrome (WFS), also referred to as DIDMOAD - this syndrome is characterised by diabetes insipidus, childhood-onset diabetes mellitus, gradual loss of vision owing to optic atrophy, and deafness . It is a rare autosomal recessive disorder, and may give rise to other complications affecting the bladder and nervous system.

Wolframin homologues have been identified in a range of species, from mammals and amphibia to insects. Notwithstanding regions of high similarity, vertebrate and invertebrate wolframins exhibit characteristic lineage- specific differences. This entry represents the Wolframin family, and includes homologues from invertebrates.
Toxin Pg family (Toxin_Pg)
Type: Family

Proteins in this family are disulphide-rich peptides expressed in Gemmula venom ducts in the gem turrids (venomous snails in the family Turridae) .

There are more than 10,000 species of predatory marine snail that use venom as their primary weapon for prey capture. Based on shell morphology, they are traditionally divided into 3 groups: cone snails, augers and turrids. Most molluscan taxonomies assign cone snails to a single large genus, Conus, while augers are assigned to several different genera; by contrast, the turrids represent a group that is much more diverse, and is now thought to comprise the vast majority of conoidean biodiversity .

The venom peptides from several species in the genus Gemmula, the gem turrids, have been characterised. Their translated open reading frames show characteristics typical of the venom peptides from Conus: an N-terminal signal sequence; a C-terminal cysteine-rich mature peptide; and an intervening pro-region. Two of these sequences, Gsp9.1 and Gsp9.2, have highly similar signal and propeptide regions, while their predicted mature peptides are more divergent (although the cysteine residues are completely conserved) . This pattern of highly conserved and more variable regions is characteristic of gene superfamilies encoding the toxin peptides found in Conus venoms.
GIGANTEA (GIGANTEA)
Type: Family

GIGANTEA is involved in regulation of circadian rhythm, and in the control of the photoperiodic flowering.

Photoperiodic control of flowering is a vital developmental process in plants because it directly relates to successful reproduction .

In Arabidopsis, a long-day (LD) plant, flowering is promoted by long days and is delayed by short days. Mutations in the GIGANTEA (GI) gene delay flowering under long days but the effects are minimal under short days. It is believed that GI plays an important role in regulating the expression of flowering-time genes during the promotion of flowering by photo-period , and that it participates in a feedback loop of the plant circadian system . In rice, a short day (SD) plant, GI acts as suppressor of flowering under short-day and long-day conditions .

The GI gene encodes a putative membrane protein containing 6 putative transmembrane (TM) domains . The protein interacts with SPINDLY, a negative regulator of gibberellin signalling in Arabidopsis, via the latter's N-terminal array of 10 tetratricopeptide repeats .
Centrosomal protein of 78kDa (Cep78)
Type: Family

The 78kDa centrosomal proteins are thought to aid the centrosome structure by helping to form microtubules, although this has yet to be been fully confirmed . Their sequences are believed to contain 3 leucine-rich (LRR) repeats, and a potential coiled-coil region towards the C terminus, but the functionality conferred on the proteins by the possession of these domains is currently unknown .
DNA-directed RNA polymerase II subunit GRINL1 (GRINL1)
Type: Family

GRINL1, also known as Gdown1, is a component of the Pol II (G) complex form of RNA polymerase II (Pol II). Pol II synthesizes mRNA precursors and many functional non-coding RNAs and is the central component of the basal RNA polymerase II transcription machinery. Gdown1 associates with Pol II, in competition with TFIIF, during the early stage of transcript elongation, where it facilitates the pausing for promoter-dependent pol II complexes . Pausing during the earliest stage of transcript elongation by Pil II is an universal control point in metazoan gene expression. Gdown1 is a negative regulator of transcriptional activation; this repression is relieved by the Mediator complex, which restores Pol II(G) activator-dependent transcription to a level equivalent to that of Pol II .
HAUS augmin-like complex subunit 4, metazoa (HAUS4_met)
Type: Family

HAUS4 contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex .

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 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 . The HAUS augmin-like complex subunit 4 was previously known as C14orf94.
HAUS complex subunit 5, metazoa (HAUS5_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 . The HAUS (Homologous to AUgmin Subunits) individual subunits have been designated HAUS1 to HAUS8.

HAUS5 contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex . This entry represents HAUS5 from animals.
HDA1 complex subunit 3 (HDA3)
Type: Family

HDA3 is required for activity of HDA1 histone deacetylase complex. It can form heterodimer with HDA2. At least one HDA1 homodimer and one HDA2/HDA3 heterodimer are needed to form the HDA1 histone deacetylase complex. The HDA1 histone deacetylase complex is responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events .
Ddc1 (Ddc1)
Type: Family

This entry represents the budding yeast Ddc1, which is homologous to the fission yeast and human Rad9.

DNA-damage checkpoint protein 1 (Ddc1) forms a checkpoint clamp complex with Mec3 and Rad17 . This complex plays a role in the surveillance system that permits DNA-repair pathways to restore the integrity of DNA in advance of DNA synthesis or separation of replicated chromosomes, thereby ensuring that new phases are not entered if DNA is damaged . Ddc1 can activate Mec1 (the principal checkpoint protein kinase, human ATR homologue) in G1 phase. In G2 phase, Ddc1 can either activate Mec1 directly or recruit Dpb11 (ortholog of human TopBP1) and subsequently activate Mec1 . Ddc1 does not have the DNA exonuclease function .
Heme transporter HRG (HRG)
Type: Family

Haems are metalloporphyrins that serve as prosthetic groups for a variety of biological processes, including respiration, gas sensing, xenobiotic detoxification, cell differentiation, circadian clock control, metabolic reprogramming and microRNA processing. Haem is usually synthesised by a multistep biosynthetic pathway. The cellular pathways and molecules that mediate intracellular haem trafficking are still largely unknown .

Caenorhabditis elegans and related helminths are natural haem auxotrophs that acquire environmental haem for incorporation into haemoproteins. In C.elegans, it has been shown that HRG-1 proteins are essential for haem homeostasis. In worms, depletion of hrg-1, or its paralogue hrg-4, results in the disruption of organismal haem sensing, and an abnormal response to haem analogues .

HRG-1 and HRG-4 are transmembrane (TM) proteins that reside in distinct intracellular compartments. Transient knockdown of hrg-1 in zebrafish leads to hydrocephalus, yolk tube malformations and profound defects in erythropoiesis-phenotypes that are fully rescued by worm HRG-1. Human and worm proteins have been shown to co-localise, and bind and transport haem, thus establishing an evolutionarily conserved function for HRG-1 .

Sequence analysis of HRG-1 has identified 4 predicted TM domains, and a conserved tyrosine and acidic-di-leucine-based sorting signal in the cytoplasmic C terminus. In addition, residues that could potentially either directly bind haem (H90 in TM2) or interact with the haem side chains (FARKY) are situated in the C-terminal tail .
Jagged/Serrate protein (Jagged/Serrate)
Type: Family

The Notch signalling pathway is a conserved intercellular signalling mechanism that is essential for proper embryonic development in numerous metazoan organisms . Members of the Notch gene family encode transmembrane (TM) receptors that are critical for various cell-fate decisions. Multiple ligands that activate Notch and related receptors have been identified, including the Delta and Serrate proteins in Drosophila, and Jagged, the vertebrate orthologue of Serrate .

Members of the Jagged/Serrate group are single-pass TM proteins. They possess a large extracellular region that contains a highly conserved disulphide-rich Delta/Serrate/LAG-2 (DSL) domain, and a variable number of EGF repeats. The cytoplasmic tail region is relatively short (100-150 amino acids) and, following proteolytic cleavage, may translocate to the nucleus to mediate nuclear signalling events .

Defects in Jagged have been shown to result in Alagille syndrome, an autosomal dominant disorder that results in a paucity of intrahepatic bile ducts .

This entry represents the Jagged/Serrate protein family.
HTLV-1 basic zipper factor (HTLV1ZIPPER)
Type: Family

HTLV-1 encodes two proteins that have been reported to drive oncogenesis: Tax and HTLV-1 basic leucine zipper (bZIP) factor (HBZ). HBZ has been shown to enhance viral infectivity and persistence, and facilitates proliferation of HTLV-1-infected lymphocytes . It has also been shown to attenuates DSB (double-stranded DNA breaks) repair by nonhomologous end joining (NHEJ), in a manner dependent upon the bZIP domain .

HBZ has been shown to negatively regulate basal and Tax-dependent HTLV-1 transcription through its ability to interact with specific basic-leucine zipper (bZIP) proteins. HBZ has been shown to reduce HTLV-1 transcription and virion production. The protein interacts with CREB in vivo and directly in vitro via the bZIP domain of each protein; CREM-Ia and ATF-1 also interact with HBZ-bZIP. The interaction between CREB and HBZ prevents CREB binding to the viral CRE elements in vitro and in vivo, suggesting that the reduction in HTLV-1 transcription by HBZ partly results from the the loss of CREB at the promoter. It has also been shown that HBZ displaces CREB from a cellular CRE, suggesting that HBZ may de-regulate CREB-dependent cellular gene expression .
Mas-related G protein-coupled receptor H (MRGPCRH)
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 H. It is thought to be involved with nociceptor function and development, and directly involved in the modulation of pain. The receptor is currently orphaned, no specific endogenous ligand having been identified.
Apolipoprotein D, vertebrates (ApoD_vertbrte)
Type: Family

Apolipoprotein D is a member of the lipocalin family with a high degree of sequence conservation from insects to mammals. It is a small, soluble carrier protein of lipophilic molecules mostly expressed in neurons and glial cells within the central and peripheral nervous system . It may have a role in anti-aging mechanism .
Hydroxyacyl-thioester dehydratase type 2 (Htd2)
Type: Family

Htd2 is a mitochondrial 3-hydroxyacyl-thioester dehydratase involved in fatty acid biosynthesis. It is required for respiratory growth and for normal mitochondrial morphology .
Protein DPCD (DPCD)
Type: Family

Primary ciliary dyskinesia (PCD) is an autosomal recessive disease that results from mutations affecting the normal function of cilia. Expression of the DPCD product of the uncharacterised gene dpcd has been shown to increase during ciliated cell differentiation . Nevertheless, an analysis of DPCD mutations in cases of human PCD was not able to confirm any specific disease-causing mutations, although one variant could not be ruled out. DPCD therefore remains a novel candidate gene for PCD .
Daughter-specific expression protein 2 (DSE2)
Type: Family

In Saccharomyces cerevisiae, daughter-specific genetic programs induce distinct fates for mother and daughter cells. Some daughter-specific gene products have been shown to contribute to cell separation by degrading the cell wall . A group of these genes (including ENG1, SCW11, DSE1 and DSE2) are regulated by the transcription factor Ace2p .

More specifically, the DSE2 gene has been shown to encode a secreted protein with sequence similarity to glucanases. It is believed that this protein contributes to the degradation of the cell wall from the daughter side, causing daughter cells to separate from mother cells .
Chromatin modification-related protein EAF5 (EAF5)
Type: Family

The only essential histone acetyltransferase complex in Saccharomyces cerevisiae, NuA4, acetylates the N-terminal tails of histones H4 and H2A. Experimental analyses have revealed at least two functionally distinct polypeptide groups in NuA4: Vid21/Yng2 and Eaf5/Eaf7. While the former are required for bulk histone H4 acetylation and are functionally linked to the histone H2A variant Htz1 and the Swr1 ATPase complex (SWR-C) that assembles Htz1 into chromatin, Eaf5 and Eaf7 have an, as yet, undefined role. It is thought that a NuA4/SWR-C/Htz1 pathway may regulate both transcription and centromere function in S.cerevisiae .