SII-SWORD/CoKE huggingface dataset:
Ubiquitin-binding protein CUE2, CUE domain 1 (CUE2_CUE1)
Type: Domain

CUE2 contains two tandem CUE domains at the N terminus that may be involved in the intramolecular monoubiquitination . This entry represents the first CUE domain.

CUE2 is a mRNA endonuclease involved in the No-Go Decay (NGD) pathway, which catalyses mRNA cleavage and degradation in response to ribosome collisions . It acts downstream of the ribosome collision sensor HEL2 . This protein specifically recognises and binds RPS7/eS7 polyubiquitinated by MOT2/NOT4 and HEL2, promoting CUE2 recruitment to stalled ribosomes, where it mediates mRNA cleavage upstream of the colliding ribosome . It also mediates mRNA cleavage within colliding ribosomes; once recruited to colliding ribosomes downstream of the RQT (ribosome quality control trigger) complex, following disassembly of stalled ribosomes and cleaves mRNAs partially released from the colliding ribosome .
Ubiquitin-binding protein CUE2, CUE domain 2 (CUE2_CUE2)
Type: Domain

CUE2 contains two tandem CUE domains at the N terminus that may be involved in intramolecular monoubiquitination . This entry represents the second CUE domain.

CUE2 is a mRNA endonuclease involved in the No-Go Decay (NGD) pathway, which catalyses mRNA cleavage and degradation in response to ribosome collisions . It acts downstream of the ribosome collision sensor HEL2 . This protein specifically recognises and binds RPS7/eS7 polyubiquitinated by MOT2/NOT4 and HEL2, promoting CUE2 recruitment to stalled ribosomes, where it mediates mRNA cleavage upstream of the colliding ribosome . It also mediates mRNA cleavage within colliding ribosomes; once recruited to colliding ribosomes downstream of the RQT (ribosome quality control trigger) complex, following disassembly of stalled ribosomes and cleaves mRNAs partially released from the colliding ribosome .
RAD23A/RAD23B, UBA1 domain (RAD23A/B_UBA1)
Type: Domain

Proteins containing this domain include mammalian orthologues of yeast nucleotide excision repair (NER) proteins Rad23 (in Saccharomyces cerevisiae) and Rhp23 (in Schizosaccharomyces pombe). Rad23 proteins play dual roles in DNA repair as well as in proteosomal degradation. They have affinity for both the proteasome and ubiquitinylated proteins and participate in translocating polyubiquitinated proteins to the proteasome. Rad23 proteins carry a ubiquitin-like (UBL) and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. The UBL domain is responsible for binding to proteasome. Both the UBL domain and the XPC-binding domain are necessary for efficient NER function of Rad23 proteins .
Ubiquitin carboxyl-terminal hydrolase 5, UBA1 domain (UBP5_UBA1)
Type: Domain

UBP5, also known as isopeptidase T or USP5, is a deubiquitinating enzyme largely responsible for the disassembly of the majority of unanchored polyubiquitin in the cell . Zinc is required for its catalytic activity. UBP5 contains four ubiquitin (Ub)-binding sites including an N-terminal zinc finger (Znf) domain, a catalytic ubiquitin-specific processing protease (UBP) domain (catalytic C-box and H-box), and two ubiquitin-associated (UBA) domains. Znf domain binds the proximal ubiquitin. UBP domain forms the active site. UBA domains are involved in binding linear or K48-linked polyubiquitin . This entry represents the UBA1 domain.
Alpha-2-macroglobulin, TED domain (A2M_TED)
Type: Domain

This entry represents the TED (thiol ester-containing domain) domain found in alpha2-macroglobulin (alpha(2)-M) and related proteins . This domain has a short highly conserved region of proteinase-binding alpha-macro-globulins containing the cysteine and a glutamine of a thiol-ester bond that is cleaved at the moment of proteinase binding, and mediates the covalent binding of the alpha-macro-globulin to the proteinase. The GCGEQ motif is highly conserved .

Proteins containing this domain also include pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha(2)-M is a major carrier protein in serum. The structural thioester of alpha(2)-M, is involved in the immobilization and entrapment of proteases. PZP is a trace protein in the plasma of non-pregnant females and males which is elevated in pregnancy. Alpha(2)-M and PZP bind to placental protein-14 and may modulate its activity in T-cell growth and cytokine production contributing to fetal survival. It has been suggested that thioester bond cleavage promotes the binding of PZP and alpha(2)-M to the CD91 receptor clearing them from circulation .
Type III secretion system virulence factor YopR, core domain (YopR_core)
Type: Homologous_superfamily

This superfamily entry represents a type III secretion system regulator, the secreted virulence factors YopR (Yersinia outer protein R), characterised in Yersinia pestis. Yersinia employs a type III secretion system (T3SS) to secrete and translocate virulence factors into to the cytoplasm of mammalian host cells. YopR, encoded by the YscH (Yersinia secretion H) gene. This Yop protein is unusual in that it is released to the extracellular environment rather than injected directly into the target cell as are most Yop proteins .

The YopR core domain, predominantly found in the Gammaproteobacteria virulence factor YopR, is composed of five α-helices, four of which are arranged in an antiparallel bundle. Little is known about this domain, though it may contribute to the virulence of the protein YopR . YopR controls the selective access of early (YscF, YscI and YscP) substrates to the type III secretion machines of yersiniae and other Gammaproteobacteriae. YopR is a mobile regulatory component thought to function as a checkpoints probing the completion of discrete intermediary stages in the assembly of the type III injection pathway. The location of secreted YopR (into the medium) is directly controlling the secretion of YscF, the polymerised needle protein (

) thereby impacting the assembly of type III machines .
Rab35 (Rab35)
Type: Family

Ras-related protein Rab35 is a member of the large Rab GTPase family. Rab35 is involved in many cellular functions, including endocytic recycling, cytokinesisis and endosomal trafficking . It is one of several Rab proteins to be found to participate in the regulation of osteoclast cells in rats . In addition, Rab35 has been identified as a protein that interacts with nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) in human cells. Overexpression of NPM-ALK is a key oncogenic event in some anaplastic large-cell lymphomas; since Rab35 interacts with NPM-ALK, it may provide a target for cancer treatments .

Rabs are regulated by GTPase activating proteins (GAPs), which interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins .
Lariat debranching enzyme, N-terminal metallophosphatase domain (Dbr1_N)
Type: Domain

Dbr1 is an RNA lariat debranching enzyme that hydrolyzes 2'-5' phosphodiester bonds at the branch points of excised intron lariats . This entry represents the N-terminal metallophosphatase domain of Dbr1. This domain belongs to the metallophosphatase (MPP) superfamily.
Rab39 (Rab39)
Type: Family

This entry includes Ras-related proteins Rab39a/b and its homologues. Rab39a is involved in phagosome maturation, inflammatory activation and neuritogenesis . It also interacts with PI3K and negatively regulates the LPS-induced autophagy in macrophages . Rab39b has also been found to be involved in autophagy and neuritogenesis . Rab39a is widely expressed, while Rab39b is enriched in the brain .

Rabs are regulated by GTPase activating proteins (GAPs), which interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins .
Rab4 (Rab4)
Type: Family

Rab4 is a member of the large Rab GTPase family. It has been implicated in numerous functions within the cell. It helps regulate endocytosis through the sorting, recycling, and degradation of early endosomes. Mammalian Rab4 is involved in the regulation of many surface proteins including G-protein-coupled receptors, transferrin receptor, integrins, and surfactant protein A. Experimental data implicate Rab4 in regulation of the recycling of internalized receptors back to the plasma membrane. It is also believed to influence receptor-mediated antigen processing in B-lymphocytes, in calcium-dependent exocytosis in platelets, in alpha-amylase secretion in pancreatic cells, and in insulin-induced translocation of Glut4 from internal vesicles to the cell surface . Rab4 is known to share effector proteins with Rab5 and Rab11 .

Rabs are regulated by GTPase activating proteins (GAPs), which interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins .
Rab30 (Rab30)
Type: Family

Ras-related protein Rab30 is a member of the large Rab GTPase family. Rab30 appears to be associated with the Golgi stack and is required for the structural integrity of the Golgi apparatus . It is expressed in a wide variety of tissue types and in humans maps to chromosome 11 . Rab30 mediates autophagy against pathogenic microorganisms .

Rabs are regulated by GTPase activating proteins (GAPs), which interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins .
CG11883-like, N-terminal metallophosphatase domain (CG11883_N)
Type: Domain

This entry represents the metallophosphatase domain of Drosophila melanogaster CG11883 and related proteins . CG11883 is an uncharacterised Drosophila melanogaster UshA-like protein with two domains, an N-terminal metallophosphatase domain and a C-terminal nucleotidase domain. The N-terminal metallophosphatase domain belongs to a large superfamily of distantly related metallophosphatases (MPPs) that includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases) .
Rab33A/B (Rab33A/B)
Type: Family

Ras-related protein Rab33 is a member of the large Rab GTPase family. Rab33B is ubiquitously expressed in mouse tissues and cells, where it is localized to the medial Golgi cisternae. It colocalizes with alpha-mannose II. Together with the other cisternal Rabs, Rab6A and Rab6A', it is believed to regulate the Golgi response to stress and is likely a molecular target in stress-activated signaling pathways . Rab33A (previously known as S10) is expressed primarily in the brain and immune system cells. In humans, it is located on the X chromosome at Xq26 and its expression is down-regulated in tuberculosis patients. Experimental evidence suggests that Rab33A is a novel CD8+ T cell factor that likely plays a role in tuberculosis disease processes .

Rabs are regulated by GTPase activating proteins (GAPs), which interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins .
YHR202W-like, N-terminal metallophosphatase domain (YHR202W_N)
Type: Domain

YHR202W is an uncharacterised Saccharomyces cerevisiae UshA-like protein with two domains, an N-terminal metallophosphatase domain and a C-terminal nucleotidase domain. The N-terminal metallophosphatase domain belongs to a large superfamily of distantly related metallophosphatases (MPPs) that includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases) .
Rab9 (Rab9)
Type: Family

Ras-related protein Rab9 is a member of the large Rab GTPase family. It is found in late endosomes, together with mannose 6-phosphate receptors (MPRs) and the tail-interacting protein of 47kDa (TIP47). Rab9 is a key mediator of vesicular transport from late endosomes to the trans-Golgi network (TGN) by redirecting the MPRs . Rab9 has been identified as a key component for the replication of several viruses, including HIV1, Ebola, Marburg, and measles, making it a potential target for inhibiting a variety of viruses .

Rabs are regulated by GTPase activating proteins (GAPs), which interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins .
SA0022-like, N-terminal metallophosphatase domain (SA0022_N)
Type: Domain

SA0022 is an uncharacterised Staphylococcus aureus UshA-like protein with two putative domains, an N-terminal metallophosphatase domain and a C-terminal nucleotidase domain. SA0022 also contains a putative C-terminal cell wall anchor domain. The N-terminal metallophosphatase domain belongs to a large superfamily of distantly related metallophosphatases (MPPs) that includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases) .
Rab15 (Rab15)
Type: Family

Rab15 colocalizes with the transferrin receptor in early endosome compartments, but not with late endosomal markers. It codistributes with Rab4 and Rab5 on early/sorting endosomes, and with Rab11 on pericentriolar recycling endosomes. It is believed to function as an inhibitory GTPase that regulates distinct steps in early endocytic trafficking .

Rabs are regulated by GTPase activating proteins (GAPs), which interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins .
CpdB, N-terminal metallophosphatase domain (CpdB_N)
Type: Domain

CpdB is a bacterial periplasmic protein with an N-terminal metallophosphatase domain and a C-terminal 3'-nucleotidase domain. This entry represents the N-terminal metallophosphatase domain, which has 2',3'-cyclic phosphodiesterase activity, hydrolyzing the 2',3'-cyclic phosphates of adenosine, guanosine, cytosine and uridine to yield nucleoside and phosphate. CpdB also hydrolyzes the chromogenic substrates p-nitrophenyl phosphate (PNPP), bis(PNPP) and p-nitrophenyl phosphorylcholine (NPPC). CpdB is thought to play a scavenging role during RNA hydrolysis by converting the non-transportable nucleotides produced by RNaseI to nucleosides which can easily enter a cell for use as a carbon source . This family also includes YfkN, a Bacillus subtilis nucleotide phosphoesterase with two copies of each of the metallophosphatase and 3'-nucleotidase domains . The N-terminal metallophosphatase domain belongs to a large superfamily of distantly related metallophosphatases (MPPs) that includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases).
Rab24 (Rab24)
Type: Family

Rab24 is distinct from other Rabs in several ways. It exists primarily in the GTP-bound state, having a low intrinsic GTPase activity; it is not efficiently geranyl-geranylated at the C terminus; it does not form a detectable complex with Rab GDP-dissociation inhibitors (GDIs); and it has recently been shown to undergo tyrosine phosphorylation when overexpressed in vitro . The specific function of Rab24 still remains unknown. It is found in a transport route between ER-cis-Golgi and late endocytic compartments. It is putatively involved in an autophagic pathway, possibly directing misfolded proteins in the ER to degradative pathways .

Rabs are regulated by GTPase activating proteins (GAPs), which interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins .
SoxB, N-terminal metallophosphatase domain (SoxB_N)
Type: Domain

SoxB (sulfur oxidation protein B) is a periplasmic thiosulfohydrolase and an essential component of the sulfur oxidation pathway in archaea and bacteria. SoxB has a dinuclear manganese cluster and is thought to catalyze the release of sulfate from a protein-bound cysteine S-thiosulfonate. SoxB is expressed from the sox (sulfur oxidation) gene cluster, which encodes 15 other sox genes, and has two domains, an N-terminal metallophosphatase domain and a C-terminal 5'-nucleotidase domain. SoxB binds the SoxYZ complex and is thought to function as a sulfate-thiohydrolase . SoxB is closely related to the UshA, YchR, and CpdB proteins, all of which have the same two-domain architecture. The N-terminal metallophosphatase domain belongs to a large superfamily of distantly related metallophosphatases (MPPs) that includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases).
Rab12 (Rab12)
Type: Family

Ras-related protein Rab12 belongs to the Rab family of small GTPases. Rab12 regulates constitutive degradation of transferrin receptor and is involved in autophagy .

Rabs are regulated by GTPase activating proteins (GAPs), which interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins .
Endonuclease YhcR, metallophosphatase domain (YhcR_MPP)
Type: Domain

This entry represents the metallophosphatase domain of Bacillus subtilis YhcR endonuclease and related proteins. YhcR is a Bacillus subtilis sugar-nonspecific endonuclease. It cleaves endonucleolytically to yield nucleotide 3'-monophosphate products, similar to Staphylococcus aureus micrococcal nuclease. YhcR appears to be located in the cell wall, and is thought to be a substrate for a Bacillus subtilis sortase. YhcR is the major calcium-activated nuclease of B. subtilis . The N-terminal metallophosphatase domain belongs to a large superfamily of distantly related metallophosphatases (MPPs) that includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases).
Synechococcus PhoA, N-terminal metallophosphatase domain (PhoA_N)
Type: Domain

Synechococcus sp. strain PCC 7942 PhoA is a large atypical alkaline phosphatase. It is known to be transported across the inner cytoplasmic membrane and into the periplasmic space. In vivo inactivation of the gene encoding PhoA leads to a loss of extracellular, phosphate-regulated phosphatase activity, but does not appear to affect the cells capacity for phosphate uptake. PhoA may play a role in scavenging phosphate during growth of Synechococcus sp. strain PCC 7942 in its natural environment . PhoA belongs to a domain family which includes the bacterial enzyme UshA and several other related enzymes including SoxB, CpdB, YhcR, and CD73. All members have a similar domain architecture which includes an N-terminal metallophosphatase domain and a C-terminal nucleotidase domain. The N-terminal metallophosphatase domain belongs to a large superfamily of distantly related metallophosphatases (MPPs) that includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases).
Rab21 (Rab21)
Type: Family

Rab21 is a Rab GTPase that has been shown to colocalize with and affect the morphology of early endosomes . In Dictyostelium, GTP-bound Rab21, together with two novel LIM domain proteins, LimF and ChLim, has been shown to regulate phagocytosis .

Rabs are regulated by GTPase activating proteins (GAPs), which interact with GTP-bound Rab and accelerate the hydrolysis of GTP to GDP. Guanine nucleotide exchange factors (GEFs) interact with GDP-bound Rabs to promote the formation of the GTP-bound state. Rabs are further regulated by guanine nucleotide dissociation inhibitors (GDIs), which facilitate Rab recycling by masking C-terminal lipid binding and promoting cytosolic localization. Most Rab GTPases contain a lipid modification site at the C terminus, with sequence motifs CC, CXC, or CCX. Lipid binding is essential for membrane attachment, a key feature of most Rab proteins .