SII-SWORD/CoKE huggingface dataset:
Autophagy-related protein 5 (Atg5)
Type: Family

This entry represents autophagy protein 5 (Atg5).

Macroautophagy is a bulk degradation process induced by starvation in eukaryotic cells. In yeast, 15 Atg proteins coordinate the formation of autophagosomes. The pre-autophagosomal structure contains at least five Atg proteins: Atg1p, Atg2p, Atg5p, Aut7p/Atg8p and Atg16p, found in the vacuole . The C-terminal glycine of Atg12p is conjugated to a lysine residue of Atg5p via an isopeptide bond. During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. Autophagy protein 16 (Atg16) has been shown to bind to Atg5 and is required for the function of the Atg12p-Atg5p conjugate . Autophagy protein 5 (Atg5) is directly required for the import of aminopeptidase I via the cytoplasm-to-vacuole targeting pathway .
Autophagy-related protein 17 (Atg17)
Type: Family

Macroautophagy is a bulk degradation process induced by starvation in eukaryotic cells. In yeast, 15 Atg proteins coordinate the formation of autophagosomes. The pre-autophagosomal structure contains at least five Atg proteins: Atg1p, Atg2p, Atg5p, Aut7p/Atg8p and Atg16p, found in the vacuole . The C-terminal glycine of Atg12p is conjugated to a lysine residue of Atg5p via an isopeptide bond. During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. Autophagy protein 16 (Atg16) has been shown to bind to Atg5 and is required for the function of the Atg12p-Atg5p conjugate . Autophagy protein 5 (Atg5) is directly required for the import of aminopeptidase I via the cytoplasm-to-vacuole targeting pathway .

Autophagy protein 17 (Atg17) forms complex with Atg29 and Atg31, and this complex is critical for both PAS (preautophagosomal structure) formation and autophagy .
Autophagy-related protein 9 (Autophagy-rel_prot_9)
Type: Family

Macroautophagy is a bulk degradation process induced by starvation in eukaryotic cells. In yeast, 15 Atg proteins coordinate the formation of autophagosomes. The pre-autophagosomal structure contains at least five Atg proteins: Atg1p, Atg2p, Atg5p, Aut7p/Atg8p and Atg16p, found in the vacuole . The C-terminal glycine of Atg12p is conjugated to a lysine residue of Atg5p via an isopeptide bond. During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. Autophagy protein 16 (Atg16) has been shown to bind to Atg5 and is required for the function of the Atg12p-Atg5p conjugate . Autophagy protein 5 (Atg5) is directly required for the import of aminopeptidase I via the cytoplasm-to-vacuole targeting pathway .

Atg9 plays a direct role in the formation of the cytoplasm to vacuole targeting and autophagic vesicles. It colocalizes with Atg2 at the expanding edge of the isolation membrane and acts as a lipid scramblase that translocates phospholipids delivered by Atg2 from the cytoplasmic to the luminal leaflet .
Ubiquitin-like protein Atg12 (Atg12)
Type: Family

Macroautophagy is a bulk degradation process induced by starvation in eukaryotic cells. In yeast, 15 Atg proteins coordinate the formation of autophagosomes. The pre-autophagosomal structure contains at least five Atg proteins: Atg1p, Atg2p, Atg5p, Aut7p/Atg8p and Atg16p, found in the vacuole . The C-terminal glycine of Atg12p is conjugated to a lysine residue of Atg5p via an isopeptide bond. During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. Autophagy protein 16 (Atg16) has been shown to bind to Atg5 and is required for the function of the Atg12p-Atg5p conjugate . Autophagy protein 5 (Atg5) is directly required for the import of aminopeptidase I via the cytoplasm-to-vacuole targeting pathway .

This entry represents the C-terminal domain of Atg12, which is covalently bound to Atg5 .
Atg6/Beclin (Atg6/Beclin)
Type: Family

In yeasts, vacuolar protein sorting-associated protein 30 (Vps30), also known as autophagy-related protein 6 (Atg6), is a common component of two distinct phosphatidylinositol 3-kinase complexes. In complex I, Atg14 links Vps30 to Vps34 lipid kinase and plays a specific role in autophagy, while in complex II, Vps38 links Vps30 to Vps34 and plays an important role in vacuolar protein sorting . The C-terminal of Vps30 contains a globular fold comprised of three β-sheet-α-helix repeats (also known as β-α repeated, autophagy-specific (BARA) domain) and is required for autophagy through the targeting of complex I to the pre-autophagosomal structure. The N-terminal of Vps30 is required for vacuolar protein sorting .
NAA35-like (Naa35_N)
Type: Family

In budding yeasts, NatC N(alpha)-terminal acetyltransferases contain Mak10, Mak31 and Mak3 subunits. All three subunits are associated with each other to form the active complex . Naa35, also known as MAK10, catalyses acetylation of the N-terminal Met of the L-A virus Gag protein. MAK10 has a role in the propagation of L-A and M viruses, perhaps in the viral assembly. It is apparently directly needed for optimum respiration . The N-terminal acetylation protects proteins from ubiquitination and degradation by the N-end rule pathway . In humans, Naa35 is involved in regulation of apoptosis and proliferation of smooth muscle cells .
GPI transamidase component PIG-T (PIG-T)
Type: Family

Phosphatidylinositol-glycan biosynthesis class T protein (PIG-T, also known as Gpi16 in budding yeasts) is a component of the glycosylphosphatidylinositol (GPI) trans-amidase complex that adds GPIs to newly synthesized proteins . Mammalian GPI transamidase consists of at least five components: Gaa1, Gpi8, PIG-S, PIG-T, and PIG-U, all five of which are required for its function. It is possible that Gaa1, Gpi8, PIG-S, and PIG-T form a tightly associated core that is only weakly associated with PIG-U. The exact function of PIG-S is unclear .
GPI transamidase component Gaa1 (Gaa1)
Type: Family

GPI (glycosyl phosphatidyl inositol) transamidase is a multiprotein complex required for a terminal step of adding the glycosylphosphatidylinositol (GPI) anchor attachment onto proteins. Gpi16, Gpi8 and Gaa1 form a sub-complex of the GPI transamidase.
Ureidoglycolate lyase (Ureidogly_lyase)
Type: Family

Ureidoglycolate lyase (

) is involved in the degradation of ureidoglycolate, an intermediate of purine degradation. It breaks down (S)-ureidoglycolate to produce glyoxylate and urea . This family of ureidoglycolate lyases were initially annotated as ureidoglycolate hydrolases, but this has since been corrected .
Mpv17/PMP22 (Mpv17_PMP22)
Type: Family

The 22kDa peroxisomal membrane protein (PMP22) is a major component of peroxisomal membranes. PMP22 seems to be involved in pore-forming activity and may contribute to the unspecific permeability of the organelle membrane. PMP22 is synthesised on free cytosolic ribosomes and then directed to the peroxisome membrane by specific targeting information . SYM1 in yeast and Mpv17 in higher eukaryotes are closely related peroxisomal proteins required to maintain mitochondrial DNA (mtDNA) integrity and stability . Mpv17 is involved in the development of early-onset glomerulosclerosis .

Woronin sorting complex protein from Neurospora crassa is also included in this family. It is involved in both Woronin bodies (WB) formation and inherence .
DOP1, N-terminal (DOP1_N)
Type: Domain

Dop1 is the founding member of the Dopey family and is required for correct cell morphology and spatiotemporal organisation of multicellular structures in the filamentous fungus Emericella nidulans (Aspergillus nidulans) . Dop1 homologues are found in mammals, where they may play a role in regulating membrane trafficking of cargo proteins. Together with ATP9A and MON2, it regulates SNX3 retromer-mediated endosomal sorting of WLS away from lysosomal degradation . In Saccharomyces cerevisiae, Dop1 is essential for viability and, affects cellular morphogenesis . Loss of Dop1 activity affects endosome to Golgi transport and causes a severe perturbation of the organization of the endoplasmic reticulum; Mon2, a relative of large Arf exchange factors, recruits Dop1 to the Golgi apparatus .
Heat shock protein 9/12 (HSP9_HSP12)
Type: Family

These heat shock proteins (Hsp9 and Hsp12) are strongly expressed and undergo an increase of 100 fold, upon entry into stationary phase in yeast .
Low affinity iron permease, Fet4 (Iron_permease_Fet4)
Type: Family

Although originally identified as a low-affinity iron(II) permease , Fet4 has since been shown to import several other transition metal ions, including copper and zinc . Copper, cobalt, and cadmium inhibit Fet4 . Fet4 is an integral protein of the plasma membrane . FET4 is not essential, not even in fet3 fet4 double mutants . Over expression of FET4 improves growth under alkaline conditions .
Nuclear pore protein 84/107 (Nup84/Nup107)
Type: Family

Nup84 forms a complex with five proteins, including Nup120, Nup85, Sec13, and a Sec13 homologue. This Nup84 complex in conjunction with Sec13-type proteins is required for correct nuclear pore biogenesis . Nup107 is the vertebrate homologue of Nup84. The Nup107-160 complex (Nup84 complex in yeast) forms the cytoplasmic and nucleoplasmic rings of the nuclear pore complex (NPC) scaffold, which consists of three stacked rings .
Cell wall binding repeat 2 (Cell_wall-bd_2)
Type: Repeat

This repeat, also known as CWB2, is found in multiple tandem copies in proteins including amidase enhancers , N-acetylmuramoyl-L-alanine amidase LytC and adhesins .

CWB2 is found in Cwp8 protein from C. difficile whose structure was determined . Cwp8 contains 3 CWB2 arranged in triangular trimer. Each CWB2 is composed of a central four-stranded parallel β-sheet surrounded by two pairs of α-helices positioned on alternate sides of the β-sheet. In the middle, the three domains come together to form the central three-helical bundle. The trimer binding arrangement contains highly conserved residues and is shared between CWB2 and the SLH S-layer/cell wall-anchoring modules, suggesting a common or convergent evolutionary origin . The Cwp8 structure closely resembles the SlpA structure .
Protein of unknown function DUF373 (DUF373)
Type: Family

This family consists of functionally uncharacterised proteins with six transmembrane regions.
Conserved oligomeric Golgi complex subunit 8 (COG8)
Type: Family

Conserved oligomeric Golgi complex subunit 8 acts as component of the peripheral membrane COG complex that is involved in intra-Golgi protein trafficking .
TM1367-like (TM1367-like)
Type: Family

This entry represents a group of proteins from bacteria and archaea, including TM1367 from Thermotoga maritima (

) and AF2241 from Archaeoglobus fulgidus (

). These proteins show cyclophilin-like assemblies but lack the conserved residues related to the peptidylprolyl isomerase (PPIase) activity typical of the enzyme Cyclophilin A . Its specific function remains unknown.
DNA replication complex GINS protein Psf2 (GINS_Psf2)
Type: Family

DNA replication in eukaryotes results from a highly coordinated interaction between proteins, often as part of protein complexes, and the DNA template. One of the key early steps leading to DNA replication is formation of the prereplication complex, or pre-RC. The pre-RC is formed by the sequential binding of the origin recognition complex (ORC), Cdc6 and Cdt1 proteins, and the MCM complex. Activation of the pre-RC into the initiation complex (IC) is achieved via the action of S-phase kinases, eventually leading to the loading of the replication machinery.

Recently, a novel replication complex, GINS (for Go, Ichi, Nii, and San; five, one, two, and three in Japanese), has been identified .

The precise function of GINS is not known. However, genetic and two-hybrid interactions indicate that it mediates the loading of the enzymatic replication machinery at a step after the action of the S-phase kinases . Furthermore, GINS may be a part of the replication machinery itself, since it is found associated with replicating DNA . Electron microscopy of GINS shows that it forms a ring-like structure , reminiscent of the structure of PCNA , the DNA polymerase delta replication clamp.This observation, coupled with the observed interactions for GINS, indicates that the complex may represent the replication clamp for DNA polymerase epsilon .

The GINS complex is essential for initiation of DNA replication in Xenopus egg extracts . This 100kDa stable complex includes Sld5, Psf1, Psf2, and Psf3. Homologues of these components are found also in other eukaryotes. This family of proteins represents the Psf2 component.
Vps52 (Vps52)
Type: Family

Vps52 complexes with Vps53 and Vps54 to form the Golgi-associated retrograde protein (GARP) complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network, regulating membrane trafficking events . It is also part of the EARP (Endosome-Associated Recycling Protein) complex, involved in endocytic recycling .
Gamma-tubulin complex component protein (GCP)
Type: Family

The microtubule organizing centres (MTOCs) of eukaryotic cells are the sites of nucleation of microtubules, and are known as the centrosome in animal cells and the spindle pole body in yeast. Gamma-tubulin, which is 30% identical to alpha and beta tubulins that form microtubules, appears to be a key protein involved in nucleation of microtubules.

Gamma tubulin can assemble into complexes of various sizes with members of the GCP family. In budding yeast, the gamma tubulin-containing small complex (gammaTuSC) contains gamma tubulin, GCP2 and GCP3 (also known as Spc97 and Spc98). In Drosophila and vertebrates, gamma tubulin forms much larger assemblies, termed gamma-tubulin ring complexes (gammaTuRCs), with gamma tubulin, GCP2, GCP3, GCP4, GCP5 and GCP6. The purified gammaTuSC and gammaTuRC complexes exhibit a 'lock washer' shape . However, the purified gammaTuSC has been shown to have a much lower microtubule-nucleating activity than intact gammaTuRC . Several models have been proposed to explain their assembly and nucleation mechanism .
Putative N-acetylmannosamine-6-phosphate epimerase (NanE)
Type: Family

This family represents a putative epimerase that converts N-acetylmannosamine-6-phosphate (ManNAc-6-P) to N-acetylglucosamine-6-phosphate (GlcNAc-6P) in the N-acetylmannosamine utilization pathway, found mainly in pathogenic bacteria. It is encoded by the yhcJ/nanE gene . This reaction is part of the pathway that allows the usage of sialic acid as a carbohydrate source .
Vps55/LEPROT (Vps55/LEPROT)
Type: Family

This entry includes Vps55 from budding yeasts and obesity receptor gene-related protein (OB-RGRP or LEPROT) from animals. Both Vps55 and OB-RGRP are important for functioning membrane trafficking to the vacuole/lysosome of eukaryotic cells .

Vps55 is involved in the secretion of the Golgi form of the soluble vacuolar carboxypeptidase Y, but not the trafficking of the membrane-bound vacuolar alkaline phosphatase .
DCC1-like thiol-disulfide oxidoreductase family (DCC1-like)
Type: Family

Members of this family have two highly conserved cysteine residues within the DxxCxxC motif at the N-terminal. This motif is conserved in the thiol-disulfide oxidoreductase family . This family includes At5g50100 (also known as DCC1) from Arabidopsis thaliana, a thioredoxin that modulates ROS homeostasis resulting in de novo shoot initiation and may be involved in the improvement of the capacity of plant regeneration . Uncharacterised proteins from bacteria are also included in this family.
H/ACA ribonucleoprotein complex, subunit Nop10 (H/ACA_rnp_Nop10)
Type: Family

H/ACA ribonucleoprotein particles (RNPs) are a family of RNA pseudouridine synthases that specify modification sites through guide RNAs. The function of these H/ACA RNPs is essential for biogenesis of the ribosome, splicing of precursor mRNAs (pre-mRNAs), maintenance of telomeres and probably for additional cellular processes . All H/ACA RNPs contain a specific RNA component (snoRNA or scaRNA) and at least four proteins common to all such particles: Cbf5, Gar1, Nhp2 and Nop10. These proteins are highly conserved from yeast to mammals and homologues are also present in archaea . The H/ACA protein complex contains a stable core composed of Cbf5 and Nop10, to which Gar1 and Nhp2 subsequently bind .

In eukaryotes Nop10 is a nucleolar protein that is specifically associated with H/ACA snoRNAs. It is essential for normal 18S rRNA production and rRNA pseudouridylation by the ribonucleoprotein particles containing H/ACA snoRNAs (H/ACA snoRNPs). Nop10 is probably necessary for the stability of these RNPs .
Conserved oligomeric Golgi complex, subunit 3 (COG_su3)
Type: Family

This entry includes Conserved oligomeric Golgi complex subunit 3 (COG3, also known as Sec34), a component of the peripheral membrane COG complex that is involved in intra-Golgi protein trafficking . COG is a member of the complexes associated with tethering containing helical rods (CATCHR) family which also includes the exocyst, GARP and DSL1 complexes, which are evolutionarily related and share structural features consisting of α-helical bundles towards the C-terminal and an N-terminal coiled-coil region .
Endoplasmic reticulum oxidoreductin 1 (Ero1)
Type: Family

Ero1 and PDI form the disulfide relay system of the ER that supports correct disulfide bond formation of secretory proteins. This entry represents Ero1 (endoplasmic oxidoreductin-1) from yeasts and its homologues from mammals, Ero1-alpha and Ero1-beta. Ero1 is an flavoprotein that directly transfers disulfide bonds to disulfide isomerase PDI . Ero1 acts as an thiol oxidoreductase responsible for catalyzing disulfide bond formation in nascent polypeptide substrates via electron transfer through protein disulfide isomerase (PDI) with oxygen acting as the final electron acceptor . Newly generated disulfides are transferred from a FAD (flavin adenine dinucleotide)-associated active site via a "shuttle disulfide" cysteine pair in Ero1 to PDI and from there on to substrate proteins . The activity of Ero1 is regulated by PDI (also known as Pdi1). This regulation of Ero1 through reduction and oxidation of regulatory bonds within Ero1 is essential for maintaining the proper redox balance in the ER .
GtrA/DPMS, transmembrane domain (GtrA_DPMS_TM)
Type: Domain

This entry represents a domain found in prokaryotic members of the GtrA family, which are predicted to be integral membrane proteins with three or four transmembrane spans. They are involved in the synthesis of cell surface polysaccharides. GtrA is involved in O antigen modification by Shigella flexneri bacteriophage X (SfX), but does not determine the specificity of glucosylation. Its function remains unknown, but it may play a role in translocation of undecaprenyl phosphate linked glucose (UndP-Glc) across the cytoplasmic membrane . Another member of this family is a DTDP-glucose-4-keto-6-deoxy-D-glucose reductase, which catalyses the conversion of dTDP-4-keto-6-deoxy-D-glucose to dTDP-D-fucose, which is involved in the biosynthesis of the serotype-specific polysaccharide antigen of Actinobacillus actinomycetemcomitans Y4 (serotype b) . This family also includes the teichoic acid glycosylation protein, GtcA, which is a serotype-specific protein in some Listeria innocua and Listeria monocytogenes strains. Its exact function is not known, but it is essential for decoration of cell wall teichoic acids with glucose and galactose .

This domain usually covers most of the length of these sequences.

This domain is also found at the C terminus of the glycosyltransferase 2 (GH2) family member Dolichol-phosphate mannosyltransferase from Pyrococcus furiosus (DPMS) and similar prokaryotic proteins. This protein transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylinositol membrane anchoring, and O-mannosylation of proteins. This entry represents the transmembrane (TM) domain that shows four TM helices (TMHs) arranged as two TMH dimers .
Rad9/Ddc1 (Rad9/Ddc1)
Type: Family

This entry represents the DNA damage checkpoint protein Rad9 and its homologue in budding yeast, Ddc1. Rad9 forms a complex with Hus1 and Rad1 (called 9-1-1 complex). Ddc1 forms a similar complex with Mec1 and Rad17. Structurally, the 9-1-1 / Ddc1-Mec3-Rad17 complex is similar to the PCNA complex, which forms trimeric ring-shaped clamps. The 9-1-1 / Ddc1-Mec3-Rad17 complex plays a role in checkpoint activation that permits DNA-repair pathways to prevent cell cycle progression in response to DNA damage and replication stress .

In humans, 9-1-1 binds to TopBP1 and activates the ATR-Chk1 checkpoint pathway . Besides its function in the 9-1-1 complex, Rad9 can also act as a transcriptional factor and participate in immunoglobulin class switch recombination . It also shows 3'-5' exonuclease activity . Aberrant Rad9 expression has been associated with prostate, breast, lung, skin, thyroid, and gastric cancers .

In budding yeast, 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 (the orthologue of human TopBP1) and subsequently activate Mec1 . Ddc1 does not have DNA exonuclease function .

It is worth noting that the Rad9 proteins referred to in this entry are the mammalian and fission yeast homologues of budding yeast Ddc1. Members of this family do not share the sequence homology another DNA damage-dependent checkpoint protein from budding yeast, confusingly also called Rad9.
Isoprenylcysteine carboxyl methyltransferase (ICMT_MeTrfase)
Type: Family

The isoprenylcysteine o-methyltransferase (

) carries out carboyxl methylation of cleaved eukaryotic proteins that terminate in a CaaX motif. In Saccharomyces cerevisiae, this methylation is carried out by Ste14p, an integral endoplasmic reticulum membrane protein. Ste14p is the founding member of the isoprenylcysteine carboxyl methyltransferase (ICMT) family, whose members share significant sequence homology .

This entry also includes ICMT from Methanosarcina acetivorans (

). It comprises a core of five transmembrane α-helices and a cofactor-binding pocket enclosed within a highly conserved C-terminal catalytic subdomain .
Nucleotide-sugar transporter (Nuc_sug_transpt)
Type: Family

This family of membrane proteins transport nucleotide sugars from the cytoplasm into golgi vesicles. SLC35A1 (

) transports CMP-sialic acid, SLC35A2 (

) transports UDP-galactose and SLC35A3 (

) transports UDP-GlcNAc .
Sulphur transport TsuA/YedE (Sulf_transp_TsuA/YedE)
Type: Family

This family represents transporter proteins that are primarily involved in the uptake of thiosulfate, a sulfur-containing oxyanion. Members of this family are characterised by their ability to mediate the transport of thiosulfate across the cellular membrane, which is essential for sulfur metabolism in various organisms . The proteins have an hourglass-shaped architecture, which facilitates the binding and translocation of thiosulfate . The positively charged outer concave side of these transporters is likely involved in the initial interaction with thiosulfate ions . Proteins in this family contains several conserved glycines and an invariant cysteine that is probably an important functional residue.
SCAMP (SCAMP)
Type: Family

In vertebrates, secretory carrier membrane proteins (SCAMPs) 1-3 constitute a family of putative membrane-trafficking proteins composed of cytoplasmic N-terminal sequences with NPF repeats, four central transmembrane regions (TMRs), and a cytoplasmic tail. SCAMPs probably function in endocytosis by recruiting EH-domain proteins to the N-terminal NPF repeats but may have additional functions mediated by their other sequences .