SII-SWORD/CoKE huggingface dataset:
Carboxypeptidase E, carboxypeptidase domain (M14_CPE_CPD)
Type: Domain

This entry represents the carboxypeptidase domain found in carboxypeptidase (CP) E (CPE, also known as carboxypeptidase H, and enkephalin convertase;(

); MEROPS identifier M14.005). CPE belongs to subfamily M14B (N/E subfamily) of the M14 family of metallocarboxypeptidases (MCPs) . It is an important enzyme responsible for the proteolytic processing of prohormone intermediates (such as pro-insulin, pro-opiomelanocortin, or pro-gonadotropin-releasing hormone) by specifically removing C-terminal basic residues . In addition, it has been proposed that the regulated secretory pathway (RSP) of the nervous and endocrine systems utilizes membrane-bound CPE as a sorting receptor. A naturally occurring point mutation in CPE reduces the stability of the enzyme and causes its degradation, leading to an accumulation of numerous neuroendocrine peptides that result in obesity and hyperglycemia . Reduced CPE enzyme and receptor activity could underlie abnormal placental phenotypes from the observation that CPE is down-regulated in enlarged placentas of interspecific hybrid (interspecies hybrid placental dysplasia, IHPD) and cloned mice .

The carboxypeptidase A family can be divided into four subfamilies: M14A (carboxypeptidase A or digestive), M14B (carboxypeptidase H or regulatory), M14C (gamma-D-glutamyl-L-diamino acid peptidase I) and M14D (AGTPBP-1/Nna1-like proteins) . Members of subfamily M14B have longer C-termini than those of subfamily M14A , and carboxypeptidase M (a member of the H family) is bound to the membrane by a glycosylphosphatidylinositol anchor, unlike the majority of the M14 family, which are soluble . The zinc ligands have been determined as two histidines and a glutamate, and the catalytic residue has been identified as a C-terminal glutamate, but these do not form the characteristic metalloprotease HEXXH motif . Members of the carboxypeptidase A family are synthesised as inactive molecules with propeptides that must be cleaved to activate the enzyme. Structural studies of carboxypeptidases A and B reveal the propeptide to exist as a globular domain, followed by an extended α-helix; this shields the catalytic site, without specifically binding to it, while the substrate-binding site is blocked by making specific contacts .
Nucleolin, RNA recognition motif 2 (Nucleolin_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of ubiquitously expressed protein nucleolin.

Nucleolin is a multifunctional major nucleolar phosphoprotein that has been implicated in various metabolic processes, such as ribosome biogenesis, cytokinesis, nucleogenesis, cell proliferation and growth, cytoplasmic-nucleolar transport of ribosomal components, transcriptional repression, replication, signal transduction, inducing chromatin decondensation, etc . Nucleolin exhibits intrinsic self-cleaving, DNA helicase, RNA helicase and DNA-dependent ATPase activities . It can be phosphorylated by many protein kinases, such as the major mitotic kinase Cdc2, casein kinase 2 (CK2), and protein kinase C-zeta .
Nucleolin, RNA recognition motif 3 (Nucleolin_RRM3)
Type: Domain

This entry represents the RNA recognition motif 3 (RRM3) of ubiquitously expressed protein nucleolin.

Nucleolin is a multifunctional major nucleolar phosphoprotein that has been implicated in various metabolic processes, such as ribosome biogenesis, cytokinesis, nucleogenesis, cell proliferation and growth, cytoplasmic-nucleolar transport of ribosomal components, transcriptional repression, replication, signal transduction, inducing chromatin decondensation, etc . Nucleolin exhibits intrinsic self-cleaving, DNA helicase, RNA helicase and DNA-dependent ATPase activities . It can be phosphorylated by many protein kinases, such as the major mitotic kinase Cdc2, casein kinase 2 (CK2), and protein kinase C-zeta .
Nucleolin, RNA recognition motif 4 (Nucleolin_RRM4)
Type: Domain

This entry represents the RNA recognition motif 4 (RRM4) of ubiquitously expressed protein nucleolin.

Nucleolin is a multifunctional major nucleolar phosphoprotein that has been implicated in various metabolic processes, such as ribosome biogenesis, cytokinesis, nucleogenesis, cell proliferation and growth, cytoplasmic-nucleolar transport of ribosomal components, transcriptional repression, replication, signal transduction, inducing chromatin decondensation, etc . Nucleolin exhibits intrinsic self-cleaving, DNA helicase, RNA helicase and DNA-dependent ATPase activities . It can be phosphorylated by many protein kinases, such as the major mitotic kinase Cdc2, casein kinase 2 (CK2), and protein kinase C-zeta .
Caa3-type Cytochrome c oxidase subunit II, cupredoxin domain (CuRO_CcO_Caa3_II)
Type: Domain

Cytochrome c oxidase (CcO), the terminal oxidase in the respiratory chains of most bacteria, is a multi-chain transmembrane protein located in the inner membrane of the cell membrane of prokaryotes. It catalyzes the reduction of O
2
and simultaneously pumps protons across the membrane.

The four-subunit Caa3-type CcO is unusual in that the subunits are encoded as fused polypeptides: the subunit I with III (I/III) and the subunit II with the soluble electron donor, cytochrome c (II/c) . Subunit II/c consists of a two N-terminal transmembrane (TM) helices anchoring a cupredoxin domain that contains the electron accepting homo-binuclear copper (CuA)-centre, and a C-terminal fusion to a cytochrome c domain . This entry represents the cupredoxin domain.
FOX1, RNA recognition motif (FOX1_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of the C. elegans RNA binding protein Fox (feminizing locus on X)-1 and its homologues. The Fox-1 family proteins are evolutionarily conserved regulators of tissue-specific alternative splicing in metazoans . They bind specifically to an RNA element, UGCAUG .

In mammals, there are three Fox-1 homologues, RBFOX1-3 (RNA binding protein Fox-1 homologue 1-3). RBFOX1 is predominantly expressed in neurons, skeletal muscle and heart . RBFOX1 binds to the C terminus of ataxin-2 and forms an ataxin-2/A2BP1 complex involved in RNA processing . RBFOX2 is expressed in ovary, whole embryo, and human embryonic cell lines in addition to neurons and muscle . RBFOX2 activates splicing of neuron-specific exons . RBFOX3 is a nuclear RNA-binding protein that regulates alternative splicing of the RBFOX2 pre-mRNA, producing a message encoding a dominant negative form of the RBFOX2 protein. Its message is detected exclusively in post-mitotic regions of embryonic brain . RBFOX3 modulates brain and muscle-specific splicing of exon EIIIB of fibronectin, exon N1 of c-src, and calcitonin/CGRP . Members in this family harbour one RNA recognition motif (RRM).
Ephrin type-B receptor 2, ligand binding domain (EphB2_rcpt_lig-bd)
Type: Domain

This entry represents the ligand-binding domain found in ephrin type-B receptor 2 (EphB2). EphB2 plays a role in cell positioning in the gastrointestinal tract by being expressed in proliferating progenitor cells . It also has been implicated in colorectal cancer . A loss of EphB2, as well as EphA4, also precedes memory decline in a murine model of Alzheimers disease .

Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands .

Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling) .
Metallocarboxypeptidase Z, carboxypeptidase domain (M14_CPZ_CPD)
Type: Domain

This entry represents the carboxypeptidase domain (CPD) found in carboxypeptidase Z. Carboxypeptidase Z (CPZ; MEROPS identifier M14.012) belongs to subfamily M14B (N/E subfamily) of the M14 family of metallocarboxypeptidases (MCPs) . CPZ is a secreted Zn-dependent enzyme whose biological function is largely unknown. Unlike other members of the N/E subfamily, CPZ has a bipartite structure, which consists of an N-terminal cysteine-rich domain (CRD) whose sequence is similar to Wnt-binding proteins, and a C-terminal CP catalytic domain that removes C-terminal Arg residues from substrates. CPZ is enriched in the extracellular matrix and is widely distributed during early embryogenesis . That the CRD of CPZ can bind to Wnt4 suggests that CPZ plays a role in Wnt signaling .

The carboxypeptidase A family can be divided into four subfamilies: M14A (carboxypeptidase A or digestive), M14B (carboxypeptidase H or regulatory), M14C (gamma-D-glutamyl-L-diamino acid peptidase I) and M14D (AGTPBP-1/Nna1-like proteins) . Members of subfamily M14B have longer C-termini than those of subfamily M14A , and carboxypeptidase M (a member of the H family) is bound to the membrane by a glycosylphosphatidylinositol anchor, unlike the majority of the M14 family, which are soluble . The zinc ligands have been determined as two histidines and a glutamate, and the catalytic residue has been identified as a C-terminal glutamate, but these do not form the characteristic metalloprotease HEXXH motif . Members of the carboxypeptidase A family are synthesised as inactive molecules with propeptides that must be cleaved to activate the enzyme. Structural studies of carboxypeptidases A and B reveal the propeptide to exist as a globular domain, followed by an extended α-helix; this shields the catalytic site, without specifically binding to it, while the substrate-binding site is blocked by making specific contacts .
eIF3G, RNA recognition motif (eIF3G_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of eIF-3G (Eukaryotic translation initiation factor 3 subunit G) and similar proteins. eIF-3G is the RNA-binding subunit of eIF3, a large multisubunit complex that plays a central role in the initiation of translation by binding to the 40 S ribosomal subunit and promoting the binding of methionyl-tRNAi and mRNA . eIF-3G binds 18 S rRNA and beta-globin mRNA, and therefore appears to be a nonspecific RNA-binding protein . eIF-3G is one of the cytosolic targets and interacts with mature apoptosis-inducing factor (AIF) . eIF-3G contains one RNA recognition motif (RRM). Proteins containing this motif include yeast eIF3-p33 (also known as Tif35) . eIF3-p33 is a homologue of vertebrate eIF-3G, and plays an important role in the initiation phase of protein synthesis. It binds both mRNA and rRNA fragments due to an RRM near its C terminus .
Methylamine utilization protein MauL (MauL)
Type: Domain

MauL is one of the products from the methylamine utilization gene cluster in Methylobacterium extorquens AM1 . Mutants generated by insertions in mauL were not able to grow on methylamine or any other primary amine as carbon sources. MauL belongs to the blue or type I copper protein family, which are involved in electron transfer reactions, with the Cu centre transitioning between the oxidized Cu(II) form and the reduced Cu(I) form .
Rrt5, RNA recognition motif 1 (Rrt5_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of yeast Rrt5 (regulator of rDNA transcription protein 5). Rrt5 may play roles in the modulation of rDNA transcription . Rrt5 contains two RNA recognition motifs (RRMs).
Ephrin type-B receptor 3, ligand binding domain (EphB3_rcpt_lig-bd)
Type: Domain

This entry represents the ligand-binding domain found in ephrin type-B receptor 3 (EphB3). EphB3 plays a role in cell positioning in the gastrointestinal tract by being preferentially expressed in Paneth cells . It also has been implicated in early colorectal cancer and early stage squamous cell lung cancer .

Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands .

Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling) .
Sulfocyanin, C-terminal (Sulfocyanin_C)
Type: Domain

Sulfocyanin is a blue copper protein with a putative membrane anchoring hydrophobic motif at the N terminus. It may substitute for cytochrome C in electron transfer reactions in archaea .
Rrt5, RNA recognition motif 2 (Rrt5_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of yeast Rrt5 (regulator of rDNA transcription protein 5). Rrt5 may play roles in the modulation of rDNA transcription . Rrt5 contains two RNA recognition motifs (RRMs).
Carboxypeptidase A, carboxypeptidase domain (CPA_M14_CPD)
Type: Domain

This entry represents the carboxypeptidase domain (CPD) found in carboxypeptidase (CP) A (CPA; MEROPS identifier M14.001). CPA belongs to subfamily M14B (A/B subfamily) of the M14 family of metallocarboxypeptidases (MCPs) . CPA enzymes generally favour hydrophobic residues. A/B subfamily enzymes are normally synthesized as inactive precursors containing preceding signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases. The procarboxypeptidase A (PCPA) is produced by the exocrine pancreas and stored as a stable zymogen in the pancreatic granules until secretion into the digestive tract occurs. Proteins containing this domain includes carboxypeptidases A1, A2 (M14.002), A4 (M14.017) and A5. There are slightly different specificities, with A1 and A5 preferring aliphatic and small aromatic residues, and A2 and A4 preferring the bulkier aromatic side chains . CPA4, detected in hormone-regulated tissues, is thought to play a role in prostate cancer .

The carboxypeptidase A family can be divided into four subfamilies: M14A (carboxypeptidase A or digestive), M14B (carboxypeptidase H or regulatory), M14C (gamma-D-glutamyl-L-diamino acid peptidase I) and M14D (AGTPBP-1/Nna1-like proteins) . Members of subfamily M14B have longer C-termini than those of subfamily M14A , and carboxypeptidase M (a member of the H family) is bound to the membrane by a glycosylphosphatidylinositol anchor, unlike the majority of the M14 family, which are soluble . The zinc ligands have been determined as two histidines and a glutamate, and the catalytic residue has been identified as a C-terminal glutamate, but these do not form the characteristic metalloprotease HEXXH motif . Members of the carboxypeptidase A family are synthesised as inactive molecules with propeptides that must be cleaved to activate the enzyme. Structural studies of carboxypeptidases A and B reveal the propeptide to exist as a globular domain, followed by an extended α-helix; this shields the catalytic site, without specifically binding to it, while the substrate-binding site is blocked by making specific contacts .
MyD88, death domain (MyD88_Death)
Type: Domain

This entry represents the Death Domain (DD) of Myeloid Differentiation primary response protein 88 (MyD88). MyD88 is an adaptor protein involved in interleukin-1 receptor (IL-1R)- and Toll-like receptor (TLR)-induced activation of nuclear factor-kappaB (NF-kB) and mitogen activated protein kinase pathways that lead to the induction of proinflammatory cytokines . It is a key component in the signaling pathway of pathogen recognition in the innate immune system. MyD88 contains an N-terminal DD and a C-terminal Toll/IL-1 Receptor (TIR) homology domain that mediates interaction with TLRs and IL-1R .

In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN . They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
Ephrin type-A receptor 1, ligand binding domain (EphA1_rcpt_lig-bd)
Type: Domain

This entry represents the ligand-binding domain found in ephrin type-A receptor 1 (EphA1). Alteration in EphA1 expression levels have been reported in colorectal and gastric cancers, as well as melanomas .

Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands .

Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling) .
Ephrin-A ectodomain (Ephrin-A_Ecto)
Type: Domain

Ephrins and their receptors EphR play an important role in cell communication in normal physiology, as well as in disease pathogenesis . Binding of the ephrin (Eph) ligand to EphR requires cell-cell contact, since both molecules are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling, depending on Eph kinase activity) and ephrin-expressing cells (reverse signaling) . Eph signaling controls cell morphology, adhesion, migration and invasion.

Ephrins can be subdivided into two groups, A and B, depending on their respective receptors EphA or EphB. The nine human EphA receptors bind to five GPI-linked ephrin-A ligands . Interactions are promiscuous within each class, and some Eph receptors can also bind to ephrins of the other class. All ephrin As contain a highly conserved receptor binding ectodomain described by this entry. Although ephrin As do not have a cytoplasmic tail (in contrast to ephrin Bs), they are still capable of downstream activation of Src family kinases and phosphoinositide-3-kinases, most likely involving co-receptors such as neurotrophin receptors .
Carboxypeptidase B, carboxypeptidase domain (CPB_M14_CPD)
Type: Domain

This entry represents the carboxypeptidase domain found in carboxypeptidase B-like peptidases. Carboxypeptidase B (CPB; MEROPS identifier M14.003) belongs to subfamily M14A (A/B subfamily) of the M14 family of metallocarboxypeptidases (MCPs) . Carboxypeptidase B (CPB) releases the basic residues lysine or arginine . A/B subfamily enzymes are normally synthesized as inactive precursors containing a signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases . Procarboxypeptidase B (PCPB) is produced by the exocrine pancreas and stored as a stable zymogen in the pancreatic granules until secretion into the digestive tract occurs where it is activated by trypsin . PCPB has been reported to be a good serum marker for the diagnosis of acute pancreatitis and graft rejection in pancreas transplant recipients .

The carboxypeptidase A family can be divided into four subfamilies: M14A (carboxypeptidase A or digestive), M14B (carboxypeptidase H or regulatory), M14C (gamma-D-glutamyl-L-diamino acid peptidase I) and M14D (AGTPBP-1/Nna1-like proteins) . Members of subfamily M14B have longer C-termini than those of subfamily M14A , and carboxypeptidase M (a member of the H family) is bound to the membrane by a glycosylphosphatidylinositol anchor, unlike the majority of the M14 family, which are soluble . The zinc ligands have been determined as two histidines and a glutamate, and the catalytic residue has been identified as a C-terminal glutamate, but these do not form the characteristic metalloprotease HEXXH motif . Members of the carboxypeptidase A family are synthesised as inactive molecules with propeptides that must be cleaved to activate the enzyme. Structural studies of carboxypeptidases A and B reveal the propeptide to exist as a globular domain, followed by an extended α-helix; this shields the catalytic site, without specifically binding to it, while the substrate-binding site is blocked by making specific contacts .
DNAJC17, RNA recognition motif (DNAJC17_RRM)
Type: Domain

The entry represents the RNA recognition motif (RRM) of eukaryotic DnaJ homologue subfamily C member 17 (DNAJC17) and similar proteins . DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, an important chaperonine family .
Ephrin-B ectodomain (Ephrin-B_Ecto)
Type: Domain

Ephrins and their receptors EphR play an important role in cell communication in normal physiology, as well as in disease pathogenesis . Binding of the ephrin (Eph) ligand to EphR requires cell-cell contact, since both molecules are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling, depending on Eph kinase activity) and ephrin-expressing cells (reverse signaling) . Eph signaling controls cell morphology, adhesion, migration and invasion. Ephrins can be subdivided into two groups, A and B, depending on their respective receptors EphA or EphB. The nine human EphA receptors bind to five GPI-linked ephrin-A ligands and the five EphB receptors bind to three transmembrane ephrin-B ligands . Interactions are promiscuous within each class, and some Eph receptors can also bind to ephrins of the other class.

Ephrin Bs have several conserved tyrosine phosphorylation sites in their cytoplasmic PDZ-like domain, which are important for signal transduction . All ephrin Bs contain a highly conserved receptor binding ectodomain described in this entry.
ALKBH8, RNA recognition motif (ALKBH8_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of ALKBH8 (Alkylated DNA repair protein alkB homologue 8), which plays a crucial role in the DNA damage survival pathway through a distinct mechanism involving the regulation of tRNA modification. It catalyzes the methylation of tRNA to yield 5-methylcarboxymethyl uridine (mcm5U) at the wobble position of the anticodon loop via its methyltransferase domain . It binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyluridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyl uridine and has a preference for tRNA(Gly) . It is essential in urothelial carcinoma cell survival mediated by NOX-1-dependent ROS signals .
Acinus, RNA recognition motif (Acinus_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of Acinus (called 'Apoptotic chromatin condensation inducer in the nucleus' or ACIN1). Acinus was first identified as a target of proteolytic cleavage during apoptosis and has been implicated in transcriptional control . Later, it was found to be part of the ASAP complex (consists of Acinus, RNPS1 and SAP18) that interacts with the exon-junction complex (EJC), a messenger ribonucleoprotein complex involved in post-transcriptional regulation. The ASAP complex serves as an auxiliary component of EJC deposited at splice junction on mRNAs . Acinus contains a P-loop motif and an RNA recognition motif (RRM).