SII-SWORD/CoKE huggingface dataset:
Translation initiation factor 3 complex subunit L (eIF3l)
Type: Family

Eukaryotic translation initiation factor 3 subunit L is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome .
Golgin subfamily A member 7/ERF4 (Golgin_A_7/ERF4)
Type: Domain

Proteins in this entry include Golgin subfamily A member 7 and the Ras modification protein ERF4.
FHF complex subunit HOOK interacting protein (FHIP)
Type: Family

This entry represents FHF complex subunit HOOK interacting proteins (FHIP, also known as FAM160) found in metazoa and fungi, which are components of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell . FHIP2A (FAM160B1) is required for proper functioning of the nervous system . FHIP2B, previously described as retinoic acid-induced protein 16, is able to activate MAPK/ERK and TGFB signalling pathways and may play a role in cell proliferation .
Phosphorylated adapter RNA export protein, RNA-binding domain (PHAX_RNA-binding_domain)
Type: Domain

The phosphorylated adaptor for RNA export (PHAX) protein transports U3 snoRNA from the nucleus after transcription . This entry represents the highly conserved U3 snoRNA-binding domain of PHAX, which is characterised by having two pairs of adjacent glycines with the sequence motif GGx12GG. This domain adopts a novel helical fold and binds non-specific single-stranded RNA and comprises five α-helices linked by short loops containing 1 to 4 residues, apart from helices alpha3 and 4 that are linked by 13 residues. The fold is unique to this kind of RNA binding domains which show no structural homology with other RNA-binding domains .
SAYSvFN domain (SAYSvFN_dom)
Type: Domain

This domain of approximately 75 residues contains a highly conserved SATSv/iFN motif. The function is unknown but the domain is conserved from plants to humans.
Fat storage-inducing transmembrane protein (FIT)
Type: Family

Fat storage-inducing transmembrane protein family (FIT/FITM, also known as Acyl-coenzyme A diphosphatase

) plays an important role in lipid droplet accumulation. They are endoplasmic reticulum (ER) resident membrane proteins that induce lipid droplet accumulation in cell culture and when expressed in mouse liver ; they hydrolyses fatty acyl-CoA to yield acyl-4'-phosphopantetheine and adenosine 3',5'-bisphosphate, with preference of unsaturated long-chain acyl-CoA substrates in the ER . The ability to store fat in the form of cytoplasmic triglyceride droplets is conserved from yeast to humans, important for maintaining ER structure and for lipid droplets (LDs) biogenesis, which are lipid storage organelles involved in maintaining lipid and energy homeostasis . The FIT family of proteins are not involved in triglyceride biosynthesis .

In mammals there are two FIT proteins, FIT1, which is muscle specific and FIT2, which is expressed in most other tissues . Yeast has two FIT2 orthologues, called Scs3p and Yft2p but no FITM1. FIT1 and FIT2 proteins are six-transmembrane-domain containing proteins with both the N and C termini residing in the cytosol. FIT2 is the more ancient conserved homologue of the FIT family; this family of proteins do not share sequence similarity to known proteins or domains.
Selenoprotein T (Selenoprotein_T)
Type: Family

This entry represents selenoprotein T (SelT), which is conserved from plants to humans. SelT is localized to the endoplasmic reticulum through a hydrophobic domain. The protein binds to UDP-glucose:glycoprotein glucosyltransferase (UGTR), the endoplasmic reticulum (ER)-resident protein, which is known to be involved in the quality control of protein folding . Selenium (Se) plays an essential role in cell survival and most of the effects of Se are probably mediated by selenoproteins, including selenoprotein T. SelT may have thioredoxin reductase-like oxidoreductase activity and it may have a role in PACAP signaling during PC12 cell differentiation . SelT protects dopaminergic neurons against oxidative stress and cell death and in fibroblasts, it plays a role in anchorage and redox regulation . In pancreatic islets, it is involved in the control of glucose homeostasis, contributes to prolonged ADCYAP1/PACAP-induced insulin secretion .
Storkhead-box protein, winged-helix domain (Storkhead-box_winged-helix)
Type: Domain

In humans the Storkhead-box protein controls polyploidization of extravillus trophoblast and is implicated in pre-eclampsia . This entry represents the conserved N-terminal winged-helix domain, which is likely to bind DNA.
Mitoguardin (Miga)
Type: Family

Mitoguardin (Miga) was first identified in flies as a mitochondrial outer-membrane protein that promotes mitochondrial fusion. Later, the mammalian Miga homologues, Miga1 and Miga2, were identified. They are found to promote mitochondrial fusion by regulating mitochondrial phospholipid metabolism via MitoPLD .
WASH complex, subunit strumpellin (WASH_strumpellin)
Type: Family

The WASH (WASP and Scar homologue) complex is present at the surface of endosomes and recruits and activates the Arp2/3 complex to induce mediated actin nucleation. The WASH complex plays a key role in the fission of tubules that serve as transport intermediates during endosome sorting .

The WASH complex consists of several subunits: F-actin-capping protein subunit alpha (CAPZA1, CAPZA2 or CAPZA3), F-actin-capping protein subunit beta (CAPZB), WASH (WASH1, WASH2P, WASH3P, WASH4P, WASH5P or WASH6P), FAM21 (FAM21A, FAM21B or FAM21C), KIAA1033, KIAA0196 (strumpellin) and CCDC53.

Strumpellin contains one known domain called a spectrin repeat that consists of three α-helices of a characteristic length wrapped in a left-handed coiled coil. The spectrin proteins have multiple copies of this repeat, which can then form multimers in the cell. Spectrin associates with the cell membrane via spectrin repeats in the ankyrin protein. The spectrin repeat is a structural platform for cytoskeletal protein assemblies. Two closely situated point mutations in human strumpellin lead to the condition of hereditary spastic paraplegia.
Testis-specific protein TEX28/transmembrane and coiled-coil domains protein (TEX28/TMCC)
Type: Family

This entry includes testis-specific TEX28 and transmembrane and coiled-coil domains protein 1/2/3 (TMCC1/2/3). TMCC1 is an ER protein. Overexpression of TMCC1 or its transmembrane domains has been shown to cause defects in ER morphology .

The Drosophila TMCC2 is an an amyloid protein precursor-interacting and apolipoprotein E-binding protein. It is required for normal development of the brain .
Transmembrane protein 161A/B (Transmembrane_161A/B)
Type: Family

This entry represents a family of conserved eukaryotic proteins. Members are putative transmembrane proteins but otherwise the function is not known.
Transmembrane Fragile-X-F-associated protein (TM_Fragile-X-F-assoc)
Type: Family

This entry represents conserved transmembrane proteins that in humans are expressed from a region upstream of the FragileXF site and appear to be intimately linked with Fragile-X syndrome. The absence of the human TMEM185A protein does not necessarily lead to developmental delay, but might, in combination with other, currently unknown, factors. Alternatively, the TMEM185A protein is either redundant, or its function can be complemented by the highly similar chromosome 2 retro-pseudogene product, TMEM185B .
Uncharacterised protein family TMEM39 (Uncharacterised_TMEM39)
Type: Family

This is a family of putative, eukaryote, transmembrane proteins but the function is unknown.
Pre-rRNA-processing protein TSR2 (Pre-rRNA_process_TSR2)
Type: Family

The pre-rRNA-processing protein TSR2 is required for 20S pre-rRNA processing . This family contains a distinctive WGG motif.
Parkin co-regulated protein (Parkin_co-regulated_protein)
Type: Family

This family of proteins is transcribed anti-sense along the DNA to the Parkin gene product and the two appear to be transcribed under the same promoter. The protein has predicted α-helical and β-sheet domains which suggest its function is in the ubiquitin/proteasome system . Mutations in parkin are the genetic cause of early-onset and autosomal recessive juvenile parkinsonism.
Peptidase C65, otubain (Peptidase_C65_otubain)
Type: Family

This family of proteins is a highly specific ubiquitin iso-peptidase that removes ubiquitin from proteins . The modification of cellular proteins by ubiquitin (Ub) is an important event that underlies protein stability and function in eukaryotes, as it is a dynamic and reversible process. Otubain carries several key conserved domains: (i) the OTU (ovarian tumour domain) in which there is an active cysteine protease triad (ii) a nuclear localisation signal, (iii) a Ub interaction motif (UIM)-like motif phi-xx-A-xxxs-xx-Ac (where phi indicates an aromatic amino acid, x indicates any amino acid and Ac indicates an acidic amino acid), (iv) a Ub-associated (UBA)-like domain and (v) the LxxLL motif .
Zinc finger, CHCC-type (Znf_CHCC)
Type: Domain

This entry represents a short conserved zinc-finger domain. It contains the sequence motif Cx8Hx14Cx2C.

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
Frag1/DRAM/Sfk1 (Frag1/DRAM/Sfk1)
Type: Family

This entry includes Frag1, DRAM and Sfk1 proteins. Frag1 (FGF receptor activating protein 1, also known as post-GPI attachment to proteins factor 2) is a protein that is conserved from fungi to humans. There are four potential iso-prenylation sites throughout the peptide, CILW (x2), CIIW and CIGL. Frag1 is a membrane-spanning protein that is ubiquitously expressed in adult tissues suggesting an important cellular function . DRAM is a family of proteins conserved from nematodes to humans with six hydrophobic transmembrane regions and an endoplasmic reticulum signal peptide. It is a lysosomal protein that induces macro-autophagy as an effector of p53-mediated death, where p53 is the tumour-suppressor gene that is frequently mutated in cancer. Expression of DRAM is stress-induced . DRAM-3 (also known as modulator of macroautophagy TMEM150B) has been shown to be a modulator of both macroautophagy and cell survival under starvation conditions . This region is also part of a family of small plasma membrane proteins, referred to as Sfk1, that may act together with or upstream of Stt4p to generate normal levels of the essential phospholipid PI4P, thus allowing proper localisation of Stt4p to the actin cytoskeleton .
Mediator complex, subunit Med19, metazoa (Mediator_Med19_met)
Type: Family

The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.

The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11.

Med19 represents a family of conserved proteins which are members of the multi-protein co-activator Mediator complex .
Mediator complex, subunit Med11 (Mediator_Med11)
Type: Family

This entry represents subunit Med11 of the Mediator complex .

The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.

The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11.
Lactonase, 7-bladed beta-propeller (Lactonase_7-beta_prop)
Type: Family

This entry contains bacterial 6-phosphogluconolactonases (6PGL) YbhE-type

. This entry also contains the fungal muconate lactonizing enzyme carboxy-cis,cis-muconate cyclase

and muconate cycloisomerase

, which convert cis,cis-muconates to muconolactones and vice versa as part of the microbial beta-ketoadipate pathway. Structures have been reported for the E. coli 6-phosphogluconolactonase and Neurospora crassa muconate cycloisomerase. Structures of proteins in this family have revealed a 7-bladed β-propeller fold .

The surface antigen Lp49 from Leptospira interrogans, the causative agent of leptospirosis, contains a C-terminal β propeller domain that is also included in this entry. The structure of the Lp49 protein has been solved, and because it is an antigen is a potential drug target .

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

(

) .
Aprataxin and PNK-like factor, PBZ domain (APLF_PBZ)
Type: Domain

The PBZ (PAR-binding zinc-finger) domain is a zinc-finger motif that can be found in humans APLF (aprataxin- and PNK-like forkhead association domain-containing protein) . The Znf is highly conserved both in primary sequence and in the spacing between the putative zinc coordinating residues and is configured CX5CX6HX5H. Many of the proteins containing the APLF-like Znf are involved in DNA strand break repair and/or contain domains implicated in DNA metabolism .
Cytoplasmic tRNA 2-thiolation protein 2 (CTU2)
Type: Family

Cytoplasmic tRNA 2-thiolation protein 2 (also known as Ncs2/Tuc2 in budding yeasts) is responsible for 2-thiolation of mcm5S2U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln) . Its fission yeast homologue, Ctu2 forms a complex with Ctu1 (Ncs6/Tuc1 homologue) and serves as a putative enzyme for the formation of 2-thiouridine .
7TM GPCR, serpentine receptor class ab (Srab) (7TM_GPCR_serpentine_rcpt_Srab)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The nematode Caenorhabditis elegans has only 14 types of chemosensory neuron, yet is able to sense and respond to several hundred different chemicals because each neuron detects several stimuli . Chemoperception is one of the central senses of soil nematodes like C. elegans which are otherwise 'blind' and 'deaf' . Chemoreception in C. elegans is mediated by members of the seven-transmembrane G-protein-coupled receptor class (7TM GPCRs). More than 1300 potential chemoreceptor genes have been identified in C. elegans, which are generally prefixed sr for serpentine receptor. The receptor superfamilies include Sra (Sra, Srb, Srab, Sre), Str (Srh, Str, Sri, Srd, Srj, Srm, Srn) and Srg (Srx, Srt, Srg, Sru, Srv, Srxa), as well as the families Srw, Srz, Srbc, Srsx and Srr . Many of these proteins have homologues in Caenorhabditis briggsae.

Srab is part of the Sra superfamily of chemoreceptors. The expression pattern of the srab genes is biologically intriguing. Of the six promoters successfully expressed in transgenic organisms, one was exclusively expressed in the tail phasmid neurons, two were exclusively expressed in a head amphid neuron, and two were expressed both in the head and tail neurons as well as a limited number of other cells .
Lysine methyltransferase (Methyltransf_16)
Type: Family

This entry represents a group of lysine methyltransferases. Characterised members of this family are protein methyltransferases targetting Lys residues in specific proteins, including calmodulin, VCP, Kin17 and Hsp70 proteins .
MMM1 domain (MMM1_dom)
Type: Domain

This is entry represents a domain found in mitochondrial distribution and morphology proteins Mdm12 and Mdm34, and in maintenance of mitochondrial morphology protein Mmm1. These proteins are components of the ERMES/MDM complex, which serves as a molecular tether to connect the endoplasmic reticulum and mitochondria .
IML2-like/Tetratricopeptide repeat protein 39-like (IML2/TPR_39)
Type: Family

This entry represents a family of proteins conserved from fungi to humans, including fungal Iml2 protein, animal tetratricopeptide repeat protein 39A/B/C (TT39A/B/C) and some related proteins. Members of this family carry a tetratricopeptide repeat (

) at their C-terminal.

IML2 is an inclusion body (IB) resident protein that interacts strongly with lipid droplet (LD) proteins. Involved in LD-mediated IB clearing after protein folding stress, probably by enabling access to the IBs of an LD-stored soluble sterol derivative that acts as a chaperone in inclusion clearing .
DSC E3 ubiquitin ligase complex subunit 3, ubiquitin-like domain (Dsc3_ub-like_dom)
Type: Domain

This is the N-terminal ubiquitin-like domain of DSC E3 ubiquitin ligase complex subunit 3 (Dsc3). Dsc3 is a component of the DSC E3 ubiquitin ligase complex (a Golgi-specific protein ubiquitination system) that functions in protein homeostasis under non-stress conditions, playing a role in protein quality control through endosome and Golgi-associated degradation pathway (EGAD) which targets membrane proteins at Golgi and endosomes for degradation by cytosolic proteasomes . Dsc3 is also involved in endocytic protein trafficking .

Yeast DSC E3 ubiquitin ligase complex is the homologue of Hrd1 E3 ligase complex from mammals, in which Dsc1, Dsc2 and Dsc3 corresponds to Hrd1, Der1, and Usa1, respectively. Dsc3 is a Herp-like protein that acts as a bridge between Dsc1 and Dsc2 for their interaction .
RNA polymerase II assembly factor Rtp1, C-terminal domain 2 (Rtp1_C2)
Type: Domain

This domain is found towards the C terminus of required for the nuclear transport of RNA pol II protein (Rtp1). Rtp1 is required for the nuclear localisation of RNA polymerase II . This domain is found in association with

.

This domain is also found in transport and Golgi organisation protein 6 (Tango6) .
FMP27, SW motif-containing RBG unit (FMP27_SW_RBG)
Type: Domain

This entry represents a conserved region within a RBG unit of FMP27 that contains the SW and GKG sequence motifs.

Fungal proteins FMP27 (also known as Hob1) and Hob2 (YPR117W) are tube-forming lipid transport proteins which bind to phosphatidylinositols and affects phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) distribution . They belong to the repeating β-groove (RBG) superfamily together with VPS13, ATG2, SHIP164, Csf1/BLTP1 proteins, which are all conserved lipid transfer proteins containing long hydrophobic grooves . They all share the same structure consisting of multiple repeating modules comprising five β-sheets followed by a loop.
Nuclear cap-binding protein subunit 3 (NCBP3)
Type: Family

The cap-binding complex (CBC) consisting of NCBP2 and its adaptor NCBP1 is believed to bind all capped RNA and to be necessary for its processing and intracellular localisation. Nuclear cap-binding protein subunit 3 (NCBP3), together with NCBP1, forms an alternative CBC in higher eukaryotes. NCBP3 binds mRNA, associates with components of the mRNA processing machinery and contributes to poly(A) RNA export .
Domain of unknown function DUF2415 (DUF2415)
Type: Domain

This entry represents a short (30 residues) domain of unknown function found in a family of fungal proteins. It contains a characteristic DLL sequence motif.
Altered inheritance of mitochondria protein 19 (AIM19)
Type: Family

This entry represents conserved proteins with unknown function and is restricted to fungi.