SII-SWORD/CoKE huggingface dataset:
Neutrophil cytosol factor 4, PX domain (PX_p40phox)
Type: Domain

The PX domain is a phosphoinositide binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p40phox contains an N-terminal PX domain, a central SH3 domain that binds p47phox, and a C-terminal PB1 domain that interacts with p67phox . It is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner . The PX domain is a phospholipid-binding module involved in the membrane targeting of proteins. The p40phox PX domain binds to PI3P, an abundant lipid in phagosomal membranes, playing an important role in the localization of NADPH oxidase . The PX domain of p40phox is also involved in protein-protein interaction.
mS27/PTCD2 (mS27/PTCD2)
Type: Family

Mammalian pentatricopeptide repeat domain (PPR) proteins are involved in regulation of mitochondrial RNA metabolism and translation and are required for mitochondrial function. The supernumerary mitochondrial ribosomal protein of the small subunit 27 (Small ribosomal subunit protein mS27 or MRPS27) is not required for mitochondrial RNA processing or the stability of the small ribosomal subunit. However, mS27 is required for mitochondrial protein synthesis .

Pentatricopeptide repeat-containing protein 2 (PTCD2) is a related mitochondrial PPR protein, although despite their similarity, they may not have the same function . PTCD2 has a role in mitochondrial RNA metabolism and downstream effects on mitochondrial translation . PTCD2 has been identified as a target for autoantibodies in neurodegenerative disease and is used as a biomarker for Alzheimer disease .
HuB, RNA recognition motif 3 (HuB_RRM3)
Type: Domain

This entry represents the RNA recognition motif 3 (RRM3) of HuB.

HuB (also known as ELAV-like protein 2 or Hel-N1) is one of the neuronal members of the Hu family . The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory. HuB is also expressed in gonads. It is up-regulated during neuronal differentiation of embryonic carcinoma P19 cells . Like other Hu proteins, HuB contains three RNA recognition motifs (RRMs). RRM1 and RRM2 may cooperate in binding to an AU-rich RNA element (ARE). RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions .
HuC, RNA recognition motif 3 (HuC_RRM3)
Type: Domain

This entry represents the RNA recognition motif 3 (RRM3) of HuC (also known as ELAV-like protein 3), one of the neuronal members of the Hu family. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory . Like other Hu proteins, HuC contains three RNA recognition motifs (RRMs). RRM1 and RRM2 may cooperate in binding to an AU-rich RNA element (ARE) . The AU-rich element binding of HuC can be inhibited by flavonoids. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions .
HuD, RNA recognition motif 3 (HuD_RRM3)
Type: Domain

This entry represents the RNA recognition motif 3 (RRM3) of HuD (also known as ELAV-like protein 4), one of the neuronal members of the Hu family. The neuronal Hu proteins play important roles in neuronal differentiation, plasticity and memory. HuD has been implicated in various aspects of neuronal function, such as the commitment and differentiation of neuronal precursors as well as synaptic remodeling in mature neurons . HuD also functions as an important regulator of mRNA expression in neurons by interacting with AU-rich RNA element (ARE) and stabilizing multiple transcripts . Moreover, HuD regulates the nuclear processing/stability of N-myc pre-mRNA in neuroblastoma cells . Like other Hu proteins, HuD contains three RNA recognition motifs (RRMs). RRM1 and RRM2 may cooperate in binding to an ARE. RRM3 may help to maintain the stability of the RNA-protein complex, and might also bind to poly(A) tails or be involved in protein-protein interactions .
Calcipressin-2, RNA recognition motif (RCAN2_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of RCAN2.

RCAN2 (regulator of calcineurin 2, also known as calcipressin-2) is encoded by a novel thyroid hormone-responsive gene ZAKI-4 that is abundantly expressed in human brain, heart and muscles . It Inhibits calcineurin-dependent transcriptional responses by binding to the catalytic domain of calcineurin A .
RNA exonuclease 1-like, exonuclease domain (REX1-like_exo)
Type: Domain

Proteins containing this domain are composed of RNA exonuclease 1 (REX1 or Rex1p), REX3 (or Rex3p), and similar eukaryotic proteins. In yeast, REX1 and REX3 are required for 5S rRNA and MRP (mitochondrial RNA processing) RNA maturation, respectively . They are DEDDh-type DnaQ-like 3'-5' exonucleases containing three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific Hx(4)D conserved pattern at ExoIII. These motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis .

REX1 is the major exonuclease from this family responsible for pre-tRNA trail trimming and may also be involved in nuclear CCA turnover . REX proteins function in the processing and maturation of many RNA species, similar to the function of Escherichia coli RNase T .
TNRC6A, RNA recognition motif (TNRC6A_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of the GW182 autoantigen, also termed trinucleotide repeat-containing gene 6A protein (TNRC6A).

Mammals have three GW182 paralogues, TNRC6A, TNRC6B and TNRC6C. They interact directly with Argonaute (Ago) proteins and function downstream as effectors mediating mRNA repression. They repress mRNAs by recruiting the CCR4-NOT complex to the mRNA. They contain the N-terminal effector domain (NED), the middle Q-rich region, and the C-terminal effector domain (CED) containing the poly(A) binding protein (PABP)-interacting motif 2 (PAM2) and the RNA-recognition motif (RRM) .
TNRC6B, RNA recognition motif (TNRC6B_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of trinucleotide repeat-containing gene 6B protein (TNRC6B). Similar to TNRC6A/C, TNRC6B is essential for efficient miRNA repression .

Mammals have three GW182 paralogues, TNRC6A, TNRC6B and TNRC6C. They interact directly with Argonaute (Ago) proteins and function downstream as effectors mediating mRNA repression. They repress mRNAs by recruiting the CCR4-NOT complex to the mRNA. They contain the N-terminal effector domain (NED), the middle Q-rich region, and the C-terminal effector domain (CED) containing the poly(A) binding protein (PABP)-interacting motif 2 (PAM2) and the RNA-recognition motif (RRM) .
TNRC6C, RNA recognition motif (TNRC6C_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of trinucleotide repeat-containing gene 6C protein (TNRC6C).

Mammals have three GW182 paralogues, TNRC6A, TNRC6B and TNRC6C. They interact directly with Argonaute (Ago) proteins and function downstream as effectors mediating mRNA repression. They repress mRNAs by recruiting the CCR4-NOT complex to the mRNA. They contain the N-terminal effector domain (NED), the middle Q-rich region, and the C-terminal effector domain (CED) containing the poly(A) binding protein (PABP)-interacting motif 2 (PAM2) and the RNA-recognition motif (RRM) .
Matrin-3, RNA recognition motif 1 (MATR3_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of Matrin 3.

Matrin 3 (MATR3 or P130) is an RNA- and DNA-binding nuclear matrix protein found to be associated with neural and muscular degenerative diseases. It contains a bipartite nuclear localization signal (NLS), two zinc finger domains and two RNA recognition motifs (RRM). It has been found to regulate alternative splicing and play a role in mRNA stabilization . It also functions as a co-factor for HIV-1 Rev in regulating post-transcriptional viral gene expression .
Matrin-3, RNA recognition motif 2 (MATR3_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of Matrin 3.

Matrin 3 (MATR3 or P130) is an RNA- and DNA-binding nuclear matrix protein found to be associated with neural and muscular degenerative diseases. It contains a bipartite nuclear localization signal (NLS), two zinc finger domains and two RNA recognition motifs (RRM). It has been found to regulate alternative splicing and play a role in mRNA stabilization . It also functions as a co-factor for HIV-1 Rev in regulating post-transcriptional viral gene expression .
ETP1, RNA recognition motif (ETP1_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of ETP1, the yeast homologue of BRCA1-associated protein (BRAP2) found in vertebrates. It may be involved in ethanol and salt-induced transcriptional activation of the NHA1 promoter and heat shock protein genes (HSP12 and HSP26), and participate in ethanol-induced turnover of the low-affinity hexose transporter Hxt3p . ETP1 contains an N-terminal RNA recognition motif (RRM), followed by a C3HC4-type ring finger domain and a UBP-type zinc finger.
BRAP2, RNA recognition motif (BRAP2_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of BRAP2, also known as BRCA1-associated protein, a novel cytoplasmic protein interacting with the two functional nuclear localisation signal (NLS) motifs of BRCA1, a nuclear protein linked to breast cancer. It also binds to the SV40 large T antigen NLS motif and the bipartite NLS motif found in mitosin . BRAP2 may serve as a cytoplasmic retention protein and play a role in the regulation of nuclear protein transport . It has been shown to act as a negative regulator of nuclear import of viral proteins . It contains an N-terminal RNA recognition motif (RRM), followed by a C3HC4-type ring finger domain and a UBP-type zinc finger.
F-BAR and double SH3 domains protein 2, F-BAR domain (FCHSD2_F-BAR_dom)
Type: Domain

F-BAR proteins have been identified as important coordinators for membrane curvatures, which regulate cellular processes such as endocytosis, phagocytosis, adhesion and migration . They bind to cell membrane via a N-terminal F-BAR domain, which associates with membrane phospholipids . F-BAR and double SH3 domains protein 2 (FCHSD2), also known as carom, contains an N-terminal F-BAR domain and two SH3 domains at the C terminus . It may mediate receptor endocytosis and transport .

This entry represents the N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of FCHSD2.
Protocatechuate 4,5-dioxygenase beta chain (PCA_45_Dioxygenase_B)
Type: Family

Protocatechuate 4,5-dioxygenase (LigAB) catalyzes the oxidization and subsequent ring-opening of protocatechuate (or 3,4-dihydroxybenzoic acid, PCA), an intermediate in the breakdown of lignin and other compounds . Protocatechuate 4,5-dioxygenase is an aromatic ring opening dioxygenase belonging to the class III extradiol enzyme family, a group of enyzmes that cleaves aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon using a non-heme Fe(II) . LigAB is composed of two subunits, designated A and B, which form a tetramer composed of two copies of each subunit. The B subunit (LigB) is the catalytic subunit of LigAB .
3-O-Methylgallate 3,4-dioxygenase (3MGA_Dioxygenase)
Type: Family

3-O-Methylgallate dioxygenase (DesZ,

) catalyzes the oxidization and subsequent ring-opening of 3-O-methylgallate (3MGA) between carbons 2 and 3. 3-O-methylgallate dioxygenase is a key enzyme in the syringate degradation pathway, in which the syringate is first converted to 3-O-methylgallate by O-demethylase (DesA) . This enzyme is a member of the class III extradiol dioxygenase family, a group of enzymes which uses a non-heme Fe(II) to cleave aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon .
Gallate dioxygenase, N-terminal (Gallate_Doxase_N)
Type: Domain

Gallate Dioxygenase (galA/DesB) catalyzes the oxidization and subsequent ring-opening of gallate, an intermediate in the degradation of the aromatic compound, syringate . The reaction product of gallate dioxygenase is 4-oxalomesaconate. The amino acid sequence of the N-terminal and C-terminal regions of gallate dioxygenase exhibits homology with the sequence of PCA 4,5-dioxygenase B (catalytic) and A subunits, respectively . This entry represents the N-terminal domain, which is similar to the B subunit of PCA 4,5-dioxygenase (or LigAB). The enzyme is estimated to be a homodimer according to the Escherichia coli enzyme. LigAB-like enzymes are usually composed of two subunits, designated A and B, which form a tetramer composed of two copies of each subunit. In this group, the subunits A and B are fused to make a single polypeptide chain. The dimer interface may resemble the tetramer interface of classical LigAB enzymes . Gallate Dioxygenase belongs to the class III extradiol dioxygenase family, a group of enzymes which use a non-heme Fe(II) to cleave aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon .
Gallate dioxygenase, C-terminal (Gallate_dioxygenase_C)
Type: Domain

Gallate Dioxygenase (galA/DesB) catalyzes the oxidization and subsequent ring-opening of gallate, an intermediate in the degradation of the aromatic compound, syringate . The reaction product of gallate dioxygenase is 4-oxalomesaconate. The amino acid sequence of the N-terminal and C-terminal regions of gallate dioxygenase exhibits homology with the sequence of the PCA 4,5-dioxygenase B (catalytic) and A subunits, respectively . This entry represents the C-terminal domain, which is similar to the A subunit of PCA 4,5-dioxygenase (or LigAB). The enzyme is estimated to be a homodimer according to the Escherichia coli enzyme. Since enzymes in this subfamily have fused A and B subunits, the dimer interface may resemble the tetramer interface of classical LigAB enzymes . This enzyme belongs to the class III extradiol dioxygenase family, composed of enzymes which use a non-heme Fe(II) to cleave aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon .
PydA-like (PydA-like)
Type: Family

This family is composed of Rhizobium sp. PydA (

) and similar proteins. PydA is required for the degradation of 3-hydroxy-4-pyridone (HP), an intermediate in the Leucaena toxin mimosine degradation pathway . It is a member of the class III extradiol dioxygenase family, a group of enzymes that use a non-heme Fe(II) to cleave aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon .
PhnC-like (PhnC-like)
Type: Family

This family is composed of Burkholderia sp. PhnC and similar proteins. PhnC is one of nine protein products encoded by the phn locus. These proteins are involved in the polycyclic aromatic hydrocarbon (PAH) catabolic pathway . PhnC is a member of the class III extradiol dioxygenase family, a group os enzymes which use a non-heme Fe(II) to cleave aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon .
2-aminophenol 1,6-dioxygenase, beta subunit (2A5CPDO_B)
Type: Family

2-amino-5-chlorophenol 1,6-dioxygenase (2A5CPDO), catalyzes the oxidization and subsequent ring-opening of 2-amino-5-chlorophenol, which is an intermediate during p-chloronitrobenzene degradation . This enzyme is a member of the class III extradiol dioxygenase family, a group of enzymes which use a non-heme Fe(II) to cleave aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon. The active 2A5CPDO enzyme is probably a heterotetramer, composed of two alpha and two beta subunits. The alpha and beta subunits share significant sequence similarity and may have evolved by gene duplication. This entry describes the beta subunit, which contains a putative metal binding site with two conserved histidines; these residues are equivalent to two out of three Fe(II) binding residues present in the catalytic subunit dioxygenase LigB . The alpha subunit does not contain these potential metal binding residues. The 2A5CPDO beta subunit may be the catalytic subunit of the enzyme.
2-aminobiphenyl-2,3-diol-1,2-dioxygenase, beta subunit (CarBb)
Type: Family

CarBb is the B subunit of 2-aminophenol 1,6-dioxygenase (CarB), which catalyzes the oxidization and subsequent ring-opening of 2-aminophenyl-2,3-diol. It is a key enzyme in the carbazole degradation pathway isolated from bacterial strains with carbazole degradation ability. The enzyme is a heterotetramer composed of two A and two B subunits. CarB belongs to the class III extradiol dioxygenase family, a group of enzymes which use a non-heme Fe(II) to cleave aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon. Although the enzyme was originally isolated as a meta-cleavage enzyme for 2'-aminobiphenyl-2,3-diol involved in carbazole degradation, it has also shown high specificity for 2,3-dihydroxybiphenyl .
2-aminobiphenyl-2,3-diol 1,2-dioxygenase, A subunit (CarBa)
Type: Family

CarBa is the A subunit of 2-aminobiphenyl-2,3-diol 1,2-dioxygenase, which catalyzes the oxidization and subsequent ring-opening of 2-aminophenyl-2,3-diol. It is a key enzyme in the carbazole degradation pathway isolated from bacterial strains with carbazole degradation ability. The enzyme is a heterotetramer composed of two A and two B subunits. CarB belongs to the class III extradiol dioxygenase family, composed of enzymes which use a non-heme Fe(II) to cleave aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon. Although the enzyme was originally isolated as a meta-cleavage enzyme for 2'-aminobiphenyl-2,3-diol involved in carbazole degradation, the enzyme has also shown high specificity for 2,3-dihydroxybiphenyl .
La-related protein 7, La domain (LARP7_La)
Type: Domain

LARP7 is a component of the 7SK snRNP, a key factor in the regulation of RNA polymerase II transcription. 7SK functionality is dependent on the presence of LARP7, which is thought to stabilize the 7SK RNA by interacting with its 3' end. The release of 7SK RNA from P-TEFb/HEXIM/7SK complexes activates the cyclin-dependent kinase P-TEFb, which in turn phosphorylates the C-terminal domain of RNA pol II and mediates a transition into productive transcription elongation .

LARP7 belongs to a group of factors that share an N-terminal La-like domain followed by one or two RNA-recognition motifs (RRM) . This entry represents the La-like domain.
Regulator of G-protein signalling 2, regulator of G protein signaling domain (RGS2_RGS)
Type: Domain

RGS2 is a member of B/R4 subfamily of RGS family, a diverse group of multifunctional proteins that regulate cellular signalling events downstream of G-protein coupled receptors (GPCRs) . Signaling is initiated when GPCRs bind to their ligands, triggering the replacement of
GDP bound to the G-alpha subunits of heterotrimeric G proteins with GTP. RGSs inhibit signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. This activity defines them as GTPase activating proteins (GAPs).

RGS2 blocks Gq-alpha mediated signalling . It lacks Gs-alpha GAP activity, but can directly inhibit the activity of several adenylyl cyclase isoforms . RGS2 is involved in the regulation of multiple G-protein linked signaling pathways. It plays a crucial role in the pathogenesis of cardiovascular diseases .

This entry represents the regulator of G protein signaling (RGS) domain found in RGS2. RGS shows an all-α structure .
Regulator of G-protein signalling 8, RGS domain (RGS_RGS8)
Type: Domain

The RGS (Regulator of G-protein Signalling) domain is an essential part of the RGS8 protein.

RGS8 is a member of R4 subfamily of RGS family, a diverse group of multifunctional proteins that regulate cellular signalling events downstream of G-protein coupled receptors (GPCRs) . Signalling is initiated when GPCRs bind to their ligands, triggering the replacement of GDP bound to the G-alpha subunits of heterotrimeric G proteins with GTP. RGSs inhibit signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. This activity defines them as GTPase activating proteins (GAPs).

RGS8 is involved in G-protein-gated potassium channels regulation and is predominantly expressed in the brain . In the hematopoietic system, it is selectively expressed in natural killer (NK) cells .
Regulator of G-protein signalling 3, RGS domain (RGS_RGS3)
Type: Domain

RGS3 is a member of R4 subfamily of RGS family, a diverse group of multifunctional proteins that regulate cellular signalling events downstream of G-protein coupled receptors (GPCRs) . Signalling is initiated when GPCRs bind to their ligands, triggering the replacement of
GDP bound to the G-alpha subunits of heterotrimeric G proteins with GTP. RGSs inhibit signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. This activity defines them as GTPase activating proteins (GAPs).

Regulator of G protein signaling 3 (RGS3) contains a membrane-targeting C2 domain, one PDZ domain, and an RGS (Regulator of G-protein Signalling) domain. RGS3 has been identified to inhibit Galpha-q and Galpha-i-mediated signaling by acting as a GTPase-activating protein . RGS3 exits as several splice isoforms . A short form, RGS3S, induced apoptosis when overexpressed , whereas PDZ-RGS3 has been linked to cell migration through interaction with Ephrin receptors . RGS3 interacts with neuroligin, estrogen receptor-alpha, and 14-3-3 outside of the GPCR pathways .

This entry represents the RGS domain of RGS3.
Regulator of G-protein signalling 4, RGS domain (RGS_RGS4)
Type: Domain

RGS4 is a member of R4 subfamily of RGS family, a diverse group of multifunctional proteins that regulate cellular signalling events downstream of G-protein coupled receptors (GPCRs) . Signalling is initiated when GPCRs bind to their ligands, triggering the replacement of
GDP bound to the G-alpha subunits of heterotrimeric G proteins with GTP. RGSs inhibit signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. This activity defines them as GTPase activating proteins (GAPs).

RGS4 is expressed widely in brain and has been implicated in regulation of opioid, cholinergic, and serotonergic signaling . Dysfunctions in RGS4 proteins are involved in etiology of Parkinson's disease, addiction, and schizophrenia . RGS4 also is up-regulated in the failing human heart . RGS4 interacts with many binding partners outside of GPCR pathways, including PIP, calcium/CaM, PA and 14-3-3 .

The RGS (Regulator of G-protein Signalling) domain is an essential part of the RGS4 protein.
Regulator of G-protein signalling 5, RGS domain (RGS_RGS5)
Type: Domain

The RGS (Regulator of G-protein Signalling) domain is an essential part of the RGS5 protein.

RGS5 is a member of R4 subfamily of RGS family, a diverse group of multifunctional proteins that regulate cellular signalling events downstream of G-protein coupled receptors (GPCRs) . Signalling is initiated when GPCRs bind to their ligands, triggering the replacement of GDP bound to the G-alpha subunits of heterotrimeric G proteins with GTP. RGSs inhibit signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. This activity defines them as GTPase activating proteins (GAPs).

RGS5 may have a role in pericyte (peri-endothelial cell) and vascular smooth muscle cell development and function . It is also expressed is the heart, where it is upregulated by beta-adrenergic mediated induction .