SII-SWORD/CoKE huggingface dataset:
TIA-1, RNA recognition motif 2 (TIA1_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of TIA-1.

TIA-1 is the 40kDa isoform of T-cell-restricted intracellular antigen-1 (TIA-1, also known as Cytotoxic granule associated RNA binding protein TIA1), a cytotoxic granule-associated RNA-binding protein mainly found in the granules of cytotoxic lymphocytes . TIA-1 regulate alternative pre-mRNA splicing by promoting the use of suboptimal 5' splice sites followed by uridine-rich intronic enhancer sequences. It can be phosphorylated by a serine/threonine kinase that is activated during Fas-mediated apoptosis, and functions as the granule component responsible for inducing apoptosis in cytolytic lymphocyte (CTL) targets . Under conditions of rapid oxygen decline and extreme hypoxia, TIA-1 can aggregate with TIAR and suppress the HIF-1alpha pathway . TIA-1 binds Zn, which is involved in formation and recruitment to stress granules .

TIA-1 is composed of three N-terminal highly homologous RNA recognition motifs (RRMs) and a glutamine-rich C-terminal auxiliary domain containing a lysosome-targeting motif. It interacts with RNAs containing short stretches of uridylates and its RRM2 can mediate the specific binding to uridylate-rich RNAs .
Laforin, CBM20 domain (CBM20_laforin)
Type: Domain

Laforin, encoded by the EPM2A gene, is a dual-specificity phosphatase that dephosphorylates complex carbohydrates. Mutations in the gene encoding laforin result in Lafora disease, a fatal autosomal recessive neurodegenerative disorder characterised by the presence of intracellular deposits of insoluble, abnormally branched, glycogen-like polymers, known as Lafora bodies, in neurons, muscle, liver, and other tissues. The molecular basis for the formation of these Lafora bodies is unknown. Laforin is one of the only phosphatases that contains a carbohydrate-binding module .

Laforin is a protein containing a dual-specificity protein phosphatase catalytic domain in the C terminus and a carbohydrate-binding domain in the N terminus .

The CBM20 domain is found in a large number of starch degrading enzymes including alpha-amylase, beta-amylase, glucoamylase, and CGTase (cyclodextrin glucanotransferase). CBM20 is also present in proteins that have a regulatory role in starch metabolism in plants (e.g. alpha-amylase) or glycogen metabolism in mammals (e.g. laforin). CBM20 folds as an antiparallel β-barrel structure with two starch binding sites. These two sites are thought to differ functionally with site 1 acting as the initial starch recognition site and site 2 involved in the specific recognition of appropriate regions of starch .
PGC-1alpha, RNA recognition motif (PPARGC1A_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha).

PGC-1alpha is the founding member of the PGC-1 family. It is a transcriptional coactivator involved in a wide range of biological processes, such as adipocyte differentiation, mitochondrial biogenesis and respiratory function. It interacts with receptors and transcription factors, such as estrogen-related receptor alpha and NRF-1 . Interestingly, PGC-1alpha and beta have an essential but complementary function in mitochondrial biogenesis and brown fat differentiation .
PGC-1-related coactivator, RNA recognition motif (PRC_RRM)
Type: Domain

This entry represents the RNA recognition motif of PGC-1-related coactivator (PRC).

PGC-1-related coactivator (PRC or PPRC1) was first identified as a transcriptional coactivator that shares structural and functional features with PGC-1alpha. It belongs to the PGC-1 family . Similar to other PGC-1 members, PRC has a function in growth-regulated mitochondrial biogenesis. Different from other PGC-1 family members, PRC mRNA is induced by serum growth factors in the absence of
de novo
protein synthesis, which place the PRC gene in a class of immediate early or primary response genes . In mice germ line, knock-out of PRC causes early embryonic lethality . PRC is also required for the induction of an inflammatory/stress response to multiple metabolic insults .
Beta-amylase, CBM20 domain (CBM20_beta_amylase)
Type: Domain

Beta-amylase has, in addition to its C-terminal CBM20 domain, an N-terminal catalytic domain belonging to glycosyl hydrolase family 14, which hydrolyzes the alpha-1,4-glucosidic bonds of starch, yielding beta-maltose from the nonreducing end of the substrate. Beta-amylase is found in both plants and microorganisms, however the plant members lack a C-terminal CBM20 domain and are not included in this group .
Glucoamylase, CBM20 domain (CBM20_glucoamylase)
Type: Domain

Glucoamylases are inverting, exo-acting starch hydrolases that hydrolyze starch and related polysaccharides by releasing the nonreducing end glucose. They are mainly active on alpha-1,4-glycosidic bonds but also have some activity towards 1,6-glycosidic bonds occurring in natural oligosaccharides. The ability of glucoamylases to cleave 1-6-glycosidic bonds is called "debranching activity" and is of importance in industrial applications, where complete degradation of starch to glucose is needed. Most glucoamylases are multidomain proteins containing an N-terminal catalytic domain, a C-terminal CBM20 domain, and a highly O-glycosylated linker region that connects the two .

This entry also includes Lytic polysaccharide monooxygenases, such as 13A and AA13, which are starch-active polysaccharide monooxygenases that oxidizes the C1 position of starch substrates, but not in cellulose, chitin, polygalacturonan or esterified pectin, nor with Arabidopsis stem cell wall .

This entry represents the glucoamylase, starch-binding, C-terminal CBM20 (carbohydrate-binding module, family 20) domain.
IGF2BP1, RNA recognition motif 1 (IGF2BP1_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of IGF2BP1 (insulin-like growth factor 2 mRNA-binding protein 1 or IMP-1).

IGF2BP1 (also known as ZBP-1 or IMP1) is a multi-functional regulator of RNA metabolism that has been implicated in the control of aspects of localization, stability, and translation for many mRNAs . It is predominantly located in cytoplasm and was initially identified as a trans-acting factor that interacts with the zipcode in the 3'- untranslated region (UTR) of the beta-actin mRNA, which is important for its localization and translational regulation . IGF2BP1 also acts as human immunodeficiency virus type 1 (HIV-1) Gag-binding factor that interacts with HIV-1 Gag protein and blocks the formation of infectious HIV-1 particles . It has also been linked to tumour growth .
Starch-binding domain-containing protein 1, CBM20 domain (CBM20_genethonin_1)
Type: Domain

Starch-binding domain-containing protein 1 (STBD1), also known as Genethonin-1, is predicted to contain a hydrophobic N terminus, that allows it to associate with a cellular membrane structure, and a C-terminal CBM20 glycan binding domain. STBD1 is involved in glycogen metabolism by binding to glycogen and anchoring it to membranes, thereby affecting its cellular localization and its intracellular trafficking to lysosomes . It has also been reported to interact with a known autophagy protein GABARAPL1, a member of the Atg8 family .

The CBM20 domain of STBD1 is crucial for its stability and ability to interact with glycogen-associated proteins .
Glycerophosphocholine phosphodiesterase GPCPD1, CBM20 domain (CBM20_GPCPD1)
Type: Domain

Glycerophosphocholine phosphodiesterase GPCPD1, also known as Prei4 or GDE5, selectively hydrolyzes glycerophosphocholine. It has an inhibitory role in skeletal muscle differentiation that is independent of its phosphodiesterase activity .

This entry represents its N-terminal CBM20 (carbohydrate-binding module, family 20) domain.
DPE2, CBM20 domain 1 (CBM20_DPE2_1)
Type: Domain

DPE2 is a transglucosidase that is essential for the cytosolic metabolism of maltose in plant leaves at night. Maltose is an intermediate on the pathway from starch to sucrose and DPE2 is thought to metabolize the maltose that is exported from the chloroplast . DPE2 has two N-terminal CBM20 starch binding domains as well as a C-terminal amylomaltase (4-alpha-glucanotransferase) catalytic domain. DPE1, the plastid version of this enzyme, has a transglucosidase domain that is similar to that of DPE2 but lacks the N-terminal carbohydrate-binding domains .
DPE2, CBM20 domain 2 (CBM20_DPE2_2)
Type: Domain

DPE2 is a transglucosidase that is essential for the cytosolic metabolism of maltose in plant leaves at night. Maltose is an intermediate on the pathway from starch to sucrose and DPE2 is thought to metabolize the maltose that is exported from the chloroplast . DPE2 has two N-terminal CBM20 starch binding domains as well as a C-terminal amylomaltase (4-alpha-glucanotransferase) catalytic domain. DPE1, the plastid version of this enzyme, has a transglucosidase domain that is similar to that of DPE2 but lacks the N-terminal carbohydrate-binding domains .
IGF2BP1, RNA recognition motif 2 (IGF2BP1_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of IGF2BP1 (insulin-like growth factor 2 mRNA-binding protein 1 or IMP-1).

IGF2BP1 (also known as ZBP-1 or IMP1) is a multi-functional regulator of RNA metabolism that has been implicated in the control of aspects of localization, stability, and translation for many mRNAs . It is predominantly located in cytoplasm and was initially identified as a trans-acting factor that interacts with the zipcode in the 3'- untranslated region (UTR) of the beta-actin mRNA, which is important for its localization and translational regulation . IGF2BP1 also acts as human immunodeficiency virus type 1 (HIV-1) Gag-binding factor that interacts with HIV-1 Gag protein and blocks the formation of infectious HIV-1 particles . It has also been linked to tumour growth .
IGF2BP2, RNA recognition motif 1 (IGF2BP2_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of IGF2BP2.

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2, also known as IMP-2) is a ubiquitously expressed RNA-binding protein that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs) . It is involved in the stimulation of insulin action and has a role in metabolic homeostasis . SNPs in IGF2BP2 gene are implicated in susceptibility to type 2 diabetes . IGF2BP2 also plays an important role in cellular motility; it regulates the expression of PINCH-2, an important mediator of cell adhesion and motility, and MURF-3, a microtubule-stabilizing protein, through direct binding to their mRNAs . IGF2BP2 may be involved in the regulation of mRNA stability through the interaction with the AU-rich element-binding factor AUF1 .
hnRNP A1, RNA recognition motif 1 (hnRNPA1_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1).

hnRNP A1 is an abundant eukaryotic nuclear RNA-binding protein that may modulate splice site selection in pre-mRNA splicing . hnRNP A1 has been characterised as a splicing silencer, often acting in opposition to an activating hnRNP H. It silences exons when bound to exonic elements in the alternatively spliced transcripts of c-src, HIV, GRIN1, and beta-tropomyosin. hnRNP A1 can shuttle between the nucleus and the cytoplasm . Thus, it may be involved in transport of cellular RNAs, including the packaging of pre-mRNA into hnRNP particles and transport of poly A+ mRNA from the nucleus to the cytoplasm .

The cytoplasmic hnRNP A1 has high affinity with AU-rich elements, whereas the nuclear hnRNP A1 has high affinity with a polypyrimidine stretch bordered by AG at the 3' ends of introns. hnRNP A1 is also involved in the replication of an RNA virus, such as mouse hepatitis virus (MHV), through an interaction with the transcription-regulatory region of viral RNA. Moreover, hnRNP A1, together with the scaffold protein septin 6, serves as host proteins to form a complex with NS5b and viral RNA, and further play important roles in the replication of Hepatitis C virus (HCV) .

hnRNP A1 contains two RNA recognition motifs (RRMs) , followed by a long glycine-rich region at the C terminus. The RRMs of hnRNP A1 play an important role in silencing the exon and the glycine-rich domain is responsible for protein-protein interactions.
hnRNPAB, RNA recognition motif 1 (hnRNPAB_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of hnRNP A/B, which is a RNA-binding protein that is involved in mRNA processing . hnRNP A/B has also been identified as an APOBEC1-binding protein that interacts with apolipoprotein B (apoB) mRNA transcripts around the editing site and thus plays an important role in apoB mRNA editing . hnRNP A/B contains two RNA recognition motifs (RRMs), followed by a long C-terminal glycine-rich domain that contains a potential ATP/GTP binding loop.
hnRNP DL, RNA recognition motif 1 (hnRPDL_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of hnRNP DL (or hnRNP D-like, also known as JKTBP), which is a dual functional protein that possesses DNA- and RNA-binding properties . It has been implicated in mRNA biogenesis at the transcriptional and post-transcriptional levels . hnRNP DL binds single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) in a non-sequence-specific manner, and interacts with poly(G) and poly(A) tenaciously . It contains two putative two RNA recognition motifs (RRMs) and a glycine- and tyrosine-rich C terminus.
Phosphoglucan water dikinase, CB20 domain (CBM20_water_dikinase)
Type: Domain

This domain is found in the chloroplast-encoded phosphoglucan water dikinase (PWD), one of two enzymes involved in the phosphorylation of plant starches leading to starch turnover. PWD/GWD3 primarily catalyses phosphorylation at the C-3 position of the glucose unit of preferably pre-phosphorylated amylopectin . In addition to the CBM20 domain, phosphoglucan water dikinase contains a C-terminal pyruvate binding domain .
Maltogenic alpha-amylase, CBM20 domain (CBM20_novamyl)
Type: Domain

This is the C-terminal CBM20 (carbohydrate-binding module, family 20) domain of novamyl (also known as acarviose transferase, ATase, maltogenic alpha-amylase, glucan 1,4-alpha-maltohydrolase, and AcbD). Novamyl has a five-domain structure similar to that of cyclodextrin glucanotransferase (CGTase). It has a substrate-binding surface with an open groove which can accommodate both cyclodextrins and linear substrates .
Dual specificity mitogen-activated protein kinase kinase 5, PB1 domain (PB1_MAP2K5)
Type: Domain

Mitogen-activated protein kinase kinase 5 (MAP2K5, alias MEK5) is a member of the ERK5 pathway, involved in angiogenesis and development . ERK5 is a MAPK activated in response to various stimuli through a three-tier cascade constituting MEK5 and MEKK2/3. MEK5 phosphorylates the activation loop of ERK5 at Thr218 and Tyr220 leading to its activation . The PB1 domain of MEK5 interacts with the PB1 domains of other members of the kinase cascade, MEKK2 and MEKK3 .

The PB1s are dimerization/oligomerization domains present in adaptor and scaffold proteins as well as kinases and serve to organize platforms that ensure specificity and fidelity during cellular signalling . The interaction between two PB1 domain depends on the type of PB1. There are three types of PB1 domains: type I which contains an OPCA motif, acidic aminoacid cluster, type II which contains a basic cluster, and type I/II which contains both an OPCA motif and a basic cluster. The Map2k5 protein contains a type I PB1 domain .
Nbr1, PB1 domain (PB1_Nbr1)
Type: Domain

The PB1 domain is an essential part of Nbr1 (next to BRCA1) protein, a scaffold protein mediating specific protein-protein interaction with both titin protein kinase and with another scaffold protein p62 .

A canonical PB1-PB1 interaction, which involves heterodimerization of two PB1 domain, is required for the formation of macromolecular signaling complexes ensuring specificity and fidelity during cellular signaling. The interaction between two PB1 domain depends on the type of PB1. There are three types of PB1 domains: type I which contains an OPCA motif, acidic aminoacid cluster, type II which contains a basic cluster, and type I/II which contains both an OPCA motif and a basic cluster . The Nbr1 protein contains a type I PB1 domain.

Nbr1 (next to BRCA1) is an ubiquitin-binding autophagy adapter that participates in different processes including host defense or intracellular homeostasis . Nbr1-like molecules contain an N-terminal PB1 domain, one (animals, plants) or more (fungi) ZZ domains, an FW domain, and a C-terminal UBA domain .
Neutrophil cytosol factor P40, PB1 domain (PB1_P40)
Type: Domain

The PB1 domain is essential part of the p40 adaptor protein, also known as neutrophil cytosol factor 4 (Ncf-4), which plays an important role in activating phagocyte NADPH oxidase during phagocytosis. During activation of the phagocyte NADPH oxidase, the cytoplasmic Phox complex, consisting of p47(phox), p67(phox) and p40(phox), translocates and associates with the membrane-spanning flavocytochrome b(558) . p40(phox) and p47(phox) cooperate in executing the carrier function directing the cytoplasmic ternary Phox complex to phagosomes. p40(phox) and p67(phox) subunits form a complex via association of their PB1 domains .

The PB1 domain of p40 represents a type I PB1 domain which interacts with the PB1 domain of oxidase activator p67 which belong to type II PB1 domain. The interaction between two PB1 domain depends on the type of PB1. There are three types of PB1 domains: type I which contains an OPCA motif, acidic aminoacid cluster, type II which contains a basic cluster, and type I/II which contains both an OPCA motif and a basic cluster. The PB1 domain of p40 represents a type I PB1 domain which interacts with the PB1 domain of oxidase activator p67 which belong to type II PB1 domain. A canonical PB1-PB1 interaction involves heterodimerization of two PB1 domain. Interactions of PB1 domains with other protein domains have been described as noncanonical PB1-interactions .
RBM12, RNA recognition motif 5 (RBM12_RRM5)
Type: Domain

This entry represents the RNA recognition motif 5 (RRM5) of RNA-binding protein 12 (RBM12).

RBM12 is ubiquitously expressed. It contains five distinct RNA binding motifs (RRMs), two proline-rich regions, and several putative transmembrane domains. The biological role of RBM12 remains unclear .
RBM12, RNA recognition motif 3 (RBM12_RRM3)
Type: Domain

This entry represents the RNA recognition motif 3 (RRM3) of RNA-binding protein 12 (RBM12).

RBM12 is ubiquitously expressed. It contains five distinct RNA binding motifs (RRMs), two proline-rich regions, and several putative transmembrane domains. The biological role of RBM12 remains unclear .
RBM12, RNA recognition motif 4 (RBM12_RRM4)
Type: Domain

This entry represents the RNA recognition motif 4 (RRM4) of RNA-binding protein 12 (RBM12).

RBM12 is ubiquitously expressed. It contains five distinct RNA binding motifs (RRMs), two proline-rich regions, and several putative transmembrane domains. The biological role of RBM12 remains unclear .
TFG, PB1 domain (PB1_TFG)
Type: Domain

This is the PB1 domain found in TFG protein (TRK-fused gene), an oncogenic gene product first identified as a fusion partner to nerve growth factor tyrosine kinase receptor TrkA/NTRK1 and subsequently found as an oncogenic fusion gene in various cancers . TFG is localised at endoplasmic reticulum (ER) exit sites and modulates ER export . It may function at the ER/ERGIC interface to locally concentrate COPII-coated transport carriers and link exit sites on the ER to ERGIC membranes . It is also a an inhibitory regulator of the ubiquitin-proteasome system .

The PB1 domain is a modular domain mediating specific protein-protein interaction in many critical cell processes, such as osteoclastogenesis, angiogenesis, early cardiovascular development and cell polarity. A canonical PB1-PB1 interaction, which involves heterodimerization of two PB1 domains, is required for the formation of macromolecular signaling complexes ensuring specificity and fidelity during cellular signaling. The interaction between two PB1 domain depends on the type of PB1. There are three types of PB1 domains: type I which contains an OPCA motif, acidic aminoacid cluster, type II which contains a basic cluster, and type I/II which contains both an OPCA motif and a basic cluster . The PB1 domain of TFG represent a type I/II domain.
RBM12B, RNA recognition motif 3 (RBM12B_RRM3)
Type: Domain

This entry represents the RNA recognition motif 3 (RRM3) of RBM12B which contains five distinct RNA binding motifs (RRMs). Its biological role remains unclear.
RBM26, RNA recognition motif 1 (RBM26_RRM1)
Type: Domain

This subgroup corresponds to the RNA recognition motif 1 (RRM1) of RBM26, also known as cutaneous T-cell lymphoma (CTCL) tumor antigen se70-2, which represents a cutaneous lymphoma (CL)-associated antigen . It contains two RNA recognition motifs (RRMs). The RRMs may play some functional roles in RNA-binding or protein-protein interactions.
Fungal Mei2-like, RNA recognition motif 3 (Fungal_Mei2-like_RRM3)
Type: Domain

This entry represents the RNA recognition motif 3 (RRM3) of fungal Mei2-like proteins. The Mei2 protein is an essential component of the switch from mitotic to meiotic growth in the fission yeast Schizosaccharomyces pombe . It is an RNA-binding protein that contains three RNA recognition motifs (RRMs). In the nucleus, S. pombe Mei2 stimulates meiosis upon binding a specific non-coding RNA through its C-terminal RRM motif (RRM3) .
Fungal Mei2-like, RNA recognition motif 2 (Fungal_Mei2-like_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of fungal Mei2-like proteins. The Mei2 protein is an essential component of the switch from mitotic to meiotic growth in the fission yeast Schizosaccharomyces pombe . It is an RNA-binding protein that contains three RNA recognition motifs (RRMs). In the nucleus, S. pombe Mei2 stimulates meiosis upon binding a specific non-coding RNA through its C-terminal RRM motif (RRM3) .
Sequestosome-1, PB1 domain (PB1_p62)
Type: Domain

The PB1 domain is an essential part of p62 scaffold protein (alias sequestosome 1, SQSTM) involved in cell signaling, receptor internalization, and protein turnover . It binds ubiquitinated substrates and aid their aggregation and degradation by macroautophagy .
Partitioning defective protein 6, PB1 domain (PB1_Par6)
Type: Domain

PAR-6 is essential for asymmetric division of the Caenorhabditis elegans zygote and for cell polarization in the Drosophila embryo . Mammalian Par6 binds to Par3 and aPKC, as well as to the small GTPase Cdc42, to form a complex which is a major cell polarity regulator . This complex has been implicated in the formation of tight junctions (TJ) in mammalian epithelial cells. Whereas only one par-6 gene exists in Drosophila and C. elegans, a family of four is present in mammals, designated as Par6A-D , although no full-length clone of Par6D has yet been identified. Par6 isoforms A-C localize differently when expressed in MDCK epithelial cells and have distinct effects on TJ formation .

Par6 contains an N-terminal PB1 domain, a C-terminal PDZ domain and a semi-CRIB motif immediately preceding the PDZ domain. The PB1 domain of Par6 forms a hetero-dimer with the PB1 domain of aPKC .
EWS, RNA recognition motif (EWS_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of EWS.

RNA-binding protein EWS (also known as EWSR1) participates in transcriptional regulation and RNA processing. It is structurally and functionally related to FUS (TLS) protein . EWSR1 gene rearrangements are often observed in myoepithelial tumours .