SII-SWORD/CoKE huggingface dataset:
T-cell antigen CD7 (CD7)
Type: Family

CD7 is a member of the immunoglobulin superfamily. Normal expression of CD7 is largely confined to T cells and natural killer (NK) cells. However, it is highly expressed in acute T-cell leukemia (T-ALL) and in a subset of peripheral T-cell lymphomas .
Aryl hydrocarbon receptor/Aryl hydrocarbon receptor repressor (AHR/AHRR)
Type: Family

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the biological and toxic effects of dioxin-like compounds . Upon ligand binding, the receptor translocates into the nucleus where it heterodimerises with ARNT (AHR nuclear translocator) . The aryl hydrocarbon receptor repressor (AHRR) competes with AHR for the binding of ARNT, and thereby repressing AHR's transcription activity .
Aryl hydrocarbon receptor repressor, basic helix-loop-helix domain (AHRR_bHLH)
Type: Domain

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the biological and toxic effects of dioxin-like compounds . Upon ligand binding, the receptor translocates into the nucleus where it heterodimerises with ARNT (AHR nuclear translocator) . The aryl hydrocarbon receptor repressor (AHRR) competes with AHR for the binding of ARNT, and thereby repressing AHR's transcription activity .

This entry represents the basic helix-loop-helix (bHLH) domain of AHRR.
Protein XRP2 (XRP2)
Type: Family

XRP2, also known as RP2, acts as a GTPase-activating protein (GAP). It has been shown to bind the GTP form of the small G protein Arf-like 3 (Arl3) ; this interaction regulates the trafficking of ciliary tip kinesins . Mutations in the retinitis pigmentosa 2 (RP2) gene cause a severe form of X-linked retinal degeneration .
Transcription factor 19, PHD finger (TCF19_PHD)
Type: Domain

TCF-19, also termed transcription factor SC1, was identified as a putative trans-activating factor with expression beginning at the late G1-S boundary in dividing cells . It also functions as a novel islet factor necessary for proliferation and survival in the INS-1 beta cell line. It plays an important role in susceptibility to both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM); it has been suggested that it may positively impact beta cell mass under conditions of beta cell stress and increased insulin demand .

TCF-19 contains an N-terminal fork head association domain (FHA), a proline rich region, and a C-terminal plant homeodomain (PHD) finger. The FHA domain may serve as a nuclear signaling domain or as a phosphoprotein binding domain. The proline rich region is a common characteristic of trans-activating factors. The PHD finger may allow TCF-19 to interact with chromatin via methylated histone H3 .
TERF1-interacting nuclear factor 2 (TINF2)
Type: Family

TERF1-interacting nuclear factor 2, also known as TIN2, is a component of the shelterin complex (telosome), which is involved in the protection and maintenance of telomeres . TINF2 plays a role in shelterin complex assembly . In humans, one of its isoforms may have an additional role in tethering telomeres to the nuclear matrix .
Pannexin (Pannexin)
Type: Family

Pannexins, including pannexins 1, 2 and 3, are a family of proteins exhibiting channel activity. Pannexin channels have many biological functions such as propagation of calcium waves, release of IL-1beta, and responses to ischemic conditions . Pannexin shares sequence homology with the invertebrate gap junction proteins, innexins. However, pannexins are functional in single membranes, but not as intercellular channels in appositional membranes seen in the gap junction hemichannels .
Ribosome maturation protein Sdo1/SBDS-like (Sdo1/SBDS-like)
Type: Family

Shwachman-Bodian-Diamond syndrome (SDS) is an autosomal disorder with pancreatic, skeletal and bone marrow deficiencies and a predisposition to hematological dysfunction. The syndrome is associated with mutations in the SBDS gene, which encodes a protein that is required for biogenesis of the 60S ribosomal subunit and activation of the ribosome . Maturation of the ribosomal 60S subunit requires SBDS and the GTPase EFL1, which release the anti-association factor eIF6 from the surface of the ribosomal subunit 60S . In yeast, SBDS is known as Sdo1, which with the EF-2-like GTPase Ria1, may trigger the GTP-dependent release of Tif6 from 60S pre-ribosomes in the cytoplasm, thereby activating them .
Thioredoxin-related transmembrane protein 2 (TMX2)
Type: Family

TMX2 contain the TRX domain, an N-terminal signal peptide, a potential transmembrane domain, an Myb DNA-binding domain repeat signature, an endoplasmic reticulum (ER) membrane retention signal (KKXX-like motif), and a dileucine motif in the tail. In TMX2, the TRX domain redox active CXXC motif is replaced with SXXC . Homologues are found only in metazoa. It is an ER and mitochondria-associated protein that may function as a regulator of cellular redox state and thereby regulates protein post-translational modification, protein folding and mitochondrial activity. It indirectly regulates neuronal proliferation, migration, and organization in the developing brain .
Protein FAM13 (FAM13)
Type: Family

The function of FAM13 family members is not clear. They contain a bipartite nuclear-localization signal and two coil-coiled domains . FAM13A and FAM13B (but not FAM13C) each contains a Rho-GAP (Rho GTPase-activating protein) domain. Homologues are found only in eukaryotes.
Centrosomal protein Spd-2/CEP192 (Spd-2/CEP192)
Type: Family

This entry includes Spd2 (spindle-defective protein 2) from Caenorhabditis elegans, CEP192 (centrosomal protein of 192kDa) from humans, and homologues from metazoa and fungi. Spd2 is required both for centrosome duplication and maturation . CEP19 is required for mitotic centrosome and spindle assembly . They are required for pericentriolar material (PCM) recruitment .
6-phosphogluconolactonase (6PGL)
Type: Family

This entry represents 6PGL proteins found in prokaryotic and eukaryotic organisms.

6-phosphogluconolactonases (6PGL)

are cytosolic enzymes found in all organisms that catalyse the hydrolysis of 6-phosphogluconolactone to 6-phosphogluconic acid in the oxidative phase of the pentose phosphate pathway. Trypanosoma brucei and other characterised 6PGL proteins [

] share an α/β hydrolase fold, with both parallel and anti-parallel β-sheets surrounded by eight α-helices . In Escherichia coli (strain K12), 6PGL (YbhE) is characterised by a 7-bladed β-propeller fold

(

) .
Large ribosomal subunit protein eL30-like (Ribosomal_eL30-like)
Type: Family

This entry includes proteins with a structural fold similar to ribosomal protein eL30 , and includes eL30 from archaean 50S ribosomes, eL30 from eukaryotic 60S ribosomes and some uncharacterised bacterial sequences.
KNL2-like (KNL2-like)
Type: Family

This entry includes Caenorhabditis elegans Knl2 (kinetochore null protein 2) and related proteins. Knl2 is a Myb DNA-binding domain-containing protein required for CENP-A loading and kinetochore assembly .
Signal-transducing adaptor protein STAP1/STAP2 (STAP1/STAP2)
Type: Family

STAP1 and STAP2 are signal-transducing adaptor proteins. They contain Pleckstrin Homology (PH) and SH2 domains along with several tyrosine phosphorylation sites.

STAP1 functions as a docking protein acting downstream of Tec tyrosine kinase in B cell antigen receptor signaling. It is phosphorylated by Tec and participates in a positive feedback loop, increasing Tec activity . STAP-1 has been shown to interact with STAT5 .

STAP2 is a substrate of breast tumour kinase, an Src-type non-receptor tyrosine kinase that mediates the interactions linking proteins involved in signal transduction pathways .
Phosphotyrosine interaction domain containing 1 (PID1)
Type: Family

PID1 (PTB-containing, cubilin and LRP1-interacting protein; also known as NYGGF4) is a phosphotyrosine-binding (PTB) domain-containing protein. It is an inhibitor of insulin-mediated signaling in adipocytes and muscle cells. It binds through its PTB domain to the second NPXY motif in the cytoplasmic tail of the low density lipoprotein receptor-related protein 1 (LRP1). Besides being involved in obesity-associated insulin resistance , PID1 has been shown to inhibit growth of medulloblastoma, glioblastoma and atypical teratoid rhabdoid tumour cell lines .
Autophagy-related protein 29 (ATG29)
Type: Family

Autophagy-related (Atg) proteins play a role in autophagy. Atg29 forms a complex with Atg17 and Atg31. When autophagy is initiated, the Atg17-Atg31-Atg29 complex is first targeted to the phagophore assembly site (PAS) and then recruits other Atg proteins . The complex is recruited to the PAS by Atg11. Atg29 contains an N-terminal functional domain, whereas the C terminus plays a regulatory role. Phosphorylation of the C-terminal domain of Atg29 is required for its interaction with Atg11 and proper PAS localization .
PID1, PTB domain (PID1_PTB)
Type: Domain

PID1 (PTB-containing, cubilin and LRP1-interacting protein; also known as NYGGF4) is a phosphotyrosine-binding (PTB) domain-containing protein. It is an inhibitor of insulin-mediated signaling in adipocytes and muscle cells. It binds through its PTB domain to the second NPXY motif in the cytoplasmic tail of the low density lipoprotein receptor-related protein 1 (LRP1). Besides being involved in obesity-associated insulin resistance , PID1 has been shown to inhibit growth of medulloblastoma, glioblastoma and atypical teratoid rhabdoid tumour cell lines .

This entry represents the PTB domain of PID1.

Proteins encoding phosphotyrosine binding (PTB) domains function as adaptors or scaffolds to organise the signaling complexes involved in wide-ranging physiological processes including neural development, immunity, tissue homeostasis and cell growth. Due to structural differences, PTB domains are divided into three groups represented by phosphotyrosine-dependent IRS-like, phosphotyrosine-dependent Shc-like, and phosphotyrosine-independent Dab-like PTBs. The last two PTBs have been named as phosphotyrosine interaction domain (PID or PI domain). PID domain has an average length of about 160 amino acids .
Coiled-coil domain-containing protein 93 (CCDC93)
Type: Family

Human CCDC93 is part of the COMMD/CCDC22/CCDC93 (CCC) complex that interacts with the multisubunit WASH complex, which is required for endosomal deposition of F-actin and cargo trafficking in conjunction with the retromer . The CCC complex controls Notch activation by modulating its intracellular trafficking .
ABT1/Esf2 (ABT1/Esf2)
Type: Family

This entry represents the nuclear protein ABT1 and its homologous counterpart, pre-rRNA-processing protein Esf2 (eighteen S factor 2), from yeast.

ABT1 associates with the TATA-binding protein (TBP) and enhances basal transcription activity of class II promoters. Meanwhile, ABT1 could be a transcription cofactor that can bind to DNA in a sequence-independent manner .
Ubiquitin domain-containing protein UBFD1 (UBFD1)
Type: Family

UBFD1 has been shown to be involved in NF-kappaB signaling . Homologues are found only in eukaryotes.
Acyl-coenzyme A diphosphatase NUDT19 (NUDT19)
Type: Family

Nucleoside diphosphate-linked moiety X motif 19 (NUDT19 or RP2p) is a coenzyme A diphosphatase. It hydrolases CoA esters, including choloyl-CoA and branched-chain fatty-acyl-CoA esters. Medium and long-chain fatty-acyl-CoA esters are the primary substrates. The protein contains a nudix hydrolase domain, a CoA-binding domain and a peroxisomal targeting signal at the C terminus, and activity in the mouse kidney is restricted to peroxisomes. The enzyme is active at pH 9 or above and requires Mn
2+
or Mg
2+
ions .

There are numerous uncharacterised bacterial and archaeal homologues.
Protein phosphatase PTC7 homolog (PPTC7)
Type: Family

This entry includes Protein phosphatase PTC7 homologue fig from Drosophila, Protein phosphatase PTC7 homologue from human and related proteins. Human PTC7 is a protein phosphatase which positively regulates biosynthesis of the ubiquinone, coenzyme Q . It dephosphorylates the ubiquinone biosynthesis protein COQ7 which is likely to lead to its activation . The homologue from the fission yeast Schizosaccharomyces pombe is known as 5-azacytidine resistance protein azr1, because it suppresses sensitivity to the C5 DNA methyltransferase inhibitor 5-azacytidine .
Fungal antigen PRA1-like (PRA1-like)
Type: Family

This is a family of fungal antigens. PRA1 from Candida albicans is a cell surface protein involved in the host-parasite interaction during infection . Asp f 2 from Aspergillus fumigatus is a major allergen associated with allergic bronchopulmonary aspergillosis . Similarly, ASPND1 from Aspergillus nidulans is specifically recognized by sera from patients with aspergilloma . Members of this family have a domain containing a His-Arg-Xaa-Xaa-His motif, reminiscent of the His-Glu-Xaa-Xaa-His zinc-binding motif found in some metallopeptidases.
GPCR family 2, glucagon-like peptide 2 receptor, 7TM (7tmB1_GLP2R)
Type: Domain

Glucagon-like peptide 2 (GLP2) acts through G protein-coupled receptor GLP2R and plays a physiological role in the control of food intake and glucose homeostasis. It promotes intestinal epithelial homeostasis and function, enhances intestinal nutrient absorption and blood flow and assists gut immune defense . GLP2R belongs to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino acid residues such as secretin, calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor . It is not only expressed in nutrient-sensing endocrine cells (such as enteroendocrine cells and pancreatic alpha-cells), but also in neurons . GLP2R in hypothalamic POMC neurons is required for promoting hepatic insulin sensitivity and glycemic control. Through GLP2R-p85alpha interaction, GLP2 activates PI3K-Akt-FoxO1 signaling in POMC neurons .

This entry represents the transmembrane region of GLP2R .
Gamma-glutamylaminecyclotransferase (GGACT)
Type: Family

Gamma-glutamyl cyclotransferase (

) (GGACT) is a ubiquitous enzyme found in bacteria, plants, and metazoans from Dictyostelium through to humans. It converts gamma-glutamylamines to free amines and 5-oxoproline . It also degrades the cross-link between a lysine and a glutamic acid residue generated by transglutaminases. GGACT is structurally related to glutamylcyclotransferase (GGCT) .
Multifunctional methyltransferase subunit Trm112 (Trm112)
Type: Family

Trm112 is a component of several multifunctional methyltransferases. When associated with methyltransferase Mtq2, the enzyme methylates 'Gln-182' of eRF1. Mtq2 is the catalytic subunit, and Trm112 is required for its solubility and activity . When associated with methyltransferase Trm11, the enzyme forms 2-methylguanosine at position 10 (m2G10) in tRNA . When associated with methyltransferase Bud23, the enzyme forms 7-methylguanine at position 1575 (m7G1575) in 18S rRNA .
Activating signal cointegrator 1-like (TRIP4-like)
Type: Family

Activating signal cointegrator 1 (TRIP4) is a transcription coactivator that interacts with nuclear receptors, including thyroid hormone receptor , the androgen receptor and ESR1 , provided ligand is bound to the receptor. This interaction facilitates nuclear receptor-mediated transcription. TRIP4 contains a C4-type zinc finger. It is polyufmylated by the UFM1-conjugating system and deufmylated by the protease UFSP2; ufmylation promotes the recruitment of additional transcriptional coactivators . TRIP4 also functions as part of the RQC trigger (RQT) complex that activates the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation .

This entry also includes TRIP4 orthologues from yeast, RQT4, which is part of the RQC trigger (RQT) complex that activates the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation .
Complex I intermediate-associated protein 30, mitochondrial (NDUFAF1)
Type: Family

Mitochondrial complex I intermediate-associated protein 30 (CIA30) is present in human and mouse, and also in Schizosaccharomyces pombe (Fission yeast) which does not contain the NADH dehydrogenase component of complex I, or many of the other essential subunits. This means it is not directly involved in oxidative phosphorylation . In Drosophila it has been shown to be a chaperone required for assembly complex I .
E3 ubiquitin-protein ligase RNF25 (RNF25)
Type: Family

E3 ubiquitin-protein ligase RNF25 (also known as AO7) ubiquitinates NKD2, leading to its degradation by the proteasome . It interacts with other Ub ligases .
Single-strand selective monofunctional uracil DNA glycosylase (SMUG1)
Type: Family

Single-strand selective monofunctional uracil DNA glycosylase (SMUG1) recognizes breaks in the genome and initiates repair. SMUG1 is a DNA glycosylase specific for uracil (U) residues in DNA, and with a preference for single-stranded DNA substrates. SMUG1 excises uracil and its derivatives . Its activity is greater towards mismatched U:G than for mismatch U:A .
N-acetyltransferase 9-like (NAT9-like)
Type: Family

This entry includes acetyltransferases such as N-acetyltransferase 9 (NAT9). The NAT9 gene is an important reproduction related gene and is associated with psoriatic arthritis and possibly with Crohn's disease . NAT9 contains a GNAT domain and mediates the acetylation of the N-terminal residues of alpha- and beta-tubulin. It is required for microtubule stability and regulation of JNK signalling to promote cell survival during developmental stages .
NUFIP1-like (NUFIP1-like)
Type: Family

FMR1-interacting protein 1 (Nufip1) has been implicated in the assembly of the large subunit of the ribosome and in telomere maintenance . It is known to bind RNA and is phosphorylated upon DNA damage .
5'-AMP-activated protein kinase alpha 1 catalytic subunit, C-terminal (AMPKA1_C)
Type: Domain

AMPK, a serine/threonine protein kinase (STK), catalyzes the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. It acts as a sensor for the energy status of the cell and is activated by cellular stresses that lead to ATP depletion such as hypoxia, heat shock, and glucose deprivation, among others. AMPK is a heterotrimer of three subunits: alpha, beta, and gamma . The alpha subunit is the catalytic subunit and it contains an N-terminal kinase domain, a putative autoinhibitory domain (AID) and a C-terminal region required for beta subunit binding. The beta scaffolding subunit mediates AMPK assembly by bridging alpha and gamma subunits. The C-terminal domain of the AMPK alpha 1 subunit interacts with the C-terminal region of the beta subunit to form a tight alpha-beta complex that is associated with the gamma subunit. The AMPK alpha subunit auto-inhibitory region interacts with the kinase domain; this inhibition is negated by the interaction with the AMPK gamma subunit .

AMPK has been implicated in a number of diseases related to energy metabolism including type 2 diabetes, obesity and cancer . AMPK is activated by rising AMP concentrations coupled with falling ATP concentrations. Activation of AMPK is also dependent on the phosphorylation of alpha subunit by upstream kinases such as LKB1 .

Vertebrates contain two isoforms of the alpha subunit, alpha1 and alpha2, which are encoded by different genes, PRKAA1 and PRKAA2, respectively, and show varying expression patterns. AMPKalpha1 is the predominant isoform expressed in bone; it plays a role in bone remodeling in response to hormonal regulation . AMPK alpha1 impacts the regulation of fat metabolism . It also mediates the vasoprotective effects of estrogen through phosphorylation of another in vivo substrate, RhoA .
Coiled-coil domain-containing protein 170-like (CCDC170-like)
Type: Family

The function of CCDC170 is not clear. It may play a role in Golgi-associated microtubule organization and stabilization . It has been linked to breast cancer . Homologues are found only in metazoa.
NRF1/Ewg family (NRF1/Ewg)
Type: Family

Nuclear respiratory factor-1 is a transcriptional activator that has been implicated in the nuclear control of respiratory chain expression in vertebrates. The first 26 amino acids of nuclear respiratory factor-1 are required for the binding of dynein light chain. The interaction with dynein light chain is observed for both ewg and Nrf-1, transcription factors that are structurally and functionally similar between humans and Drosophila .

In Drosophila, the erect wing (ewg) protein is required for proper development of the central nervous system and the indirect flight muscles. The fly ewg gene encodes a novel DNA-binding domain that is also found in four genes previously identified in sea urchin, chicken, zebrafish, and human .

The highest level of expression of both ewg and Nrf-1 was found in the central nervous system, somites, first branchial arch, optic vesicle, and otic vesicle. In the mouse Nrf-1 protein,

, there is also an NLS domain at 88-116, and a DNA binding and dimerisation domain at 127-282. Ewg is a site-specific transcriptional activator, and evolutionarily conserved regions of ewg contribute both positively and negatively to transcriptional activity .
Glucosamine 6-phosphate N-acetyltransferase-like (GNPNAT1-like)
Type: Family

This family groups acetyltransferases with broad specificity from bacteria, archaea and eukaryotes, including glucosamine 6-phosphate N-acetyltransferase (GNPNAT1;

) from mammals and plants, and GCN5-related N-acetyltransferase 3 (GNAT3) from plants.

GNPNAT1 is a component in the pathway for UDP-N-acetyl-alpha-D-glucosamine biosynthesis. GNPNAT1 transfers the acetyl group from acetyl-CoA to D-glucosamine 6-phosphate to generate N-acetyl-D-glucosamine 6-phosphate . The enzyme contains a GNAT domain and is naturally a homodimer . The enzyme from
Aspergillus fumigatus
, the causative agent of aspergillosis, is a potential drug target .

GNAT3 is an acetyltransferase with dual specificity triggering both N-alpha-acetylation (NTA) and epsilon-lysine acetylation (KA), possibly with a low efficiency or toward specific plastid substrates .
Aveugle-like, SAM domain (Aveugle-like_SAM_dom)
Type: Domain

The SAM (sterile alpha motif) domain of aveugle-like proteins is a protein-protein interaction domain . In Drosophila, the aveugle (AVE) protein (also known as HYP (Hyphen)) is involved in normal photoreceptor differentiation, and required for epidermal growth factor receptor (EGFR) signaling between ras and raf genes during eye development and wing vein formation. SAM domain of the HYP(AVE) protein interacts with SAM domain of CNK, the multidomain scaffold protein connector enhancer of kinase suppressor of Ras. CNK/HYP(AVE) complex interacts with KSR (kinase suppressor of Ras) protein. This interaction leads to stimulation of Ras-dependent Raf activation . Proteins containing this domain also includes vertebrate AVE homologues - Samd10 and Samd12. Their function is unknown.
Large ribosomal subunit protein mL40, metazoa/plants (Ribosomal_mL40_metazoa/plant)
Type: Family

This entry represents the large ribosomal subunit protein mL40 from animals and plants, previously known as L40. mL40 is a component of the mitochondrial large ribosomal subunit (39S), it binds to the major groove of the anticodon stem of mt-tRNA(Val) in the central protuberance .
G patch domain and ankyrin repeat-containing protein 1 (GPANK1)
Type: Family

The function of GPANK1 is not clear. Homologues contain ankyrin repeats and a G-patch domain, and are mostly found in eukaryotes.
Ankyrin repeat and SOCS box protein 17 (ASB17)
Type: Family

ASB17 (ankyrin repeat and SOCS box protein 17) is expressed in testis and may play essential roles in testis development and spermatogenesis . Homologues contain an ankyrin repeat and a SOCS box domain, and are found only in metazoa.