SII-SWORD/CoKE huggingface dataset:
PTBP1, RNA recognition motif 1 (PTBP1_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of polypyrimidine tract-binding protein 1 (PTBP1).

PTBP1 (also known as PTB) is involved in numerous post-transcriptional steps in gene expression in both the nucleus and cytoplasm. It can act as a negative regulator of alternative splicing and as an activator of translation driven by IRESs (internal ribosome entry segments) . It contains four RNA recognition motifs (RRM). RRM1 and RRM2 are independent from each other and separated by flexible linkers. By contrast, there is an unusual and conserved interdomain interaction between RRM3 and RRM4. It is widely held that only RRMs 3 and 4 are involved in RNA binding and RRM2 mediates PTB homodimer formation. However, new evidence shows that the RRMs 1 and 2 also contribute substantially to RNA binding. Moreover, PTB may not always dimerize to repress splicing. It is a monomer in solution .
PTBP1, RNA recognition motif 3 (PTBP1_RRM3)
Type: Domain

This entry represents the RNA recognition motif 3 (RRM3) of polypyrimidine tract-binding protein 1 (PTBP1).
PTBP2, RNA recognition motif 1 (PTBP2_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of PTBP2, also known as nPTB, highly homologous to polypyrimidine tract binding protein (PTB) and perhaps specific to the vertebrates . Both PTB and PTBP2 are alternative splicing regulators . Unlike PTB, PTBP2 is enriched in the brain and in some neural cell lines . Interestingly, PTB directly suppresses expression of nPTB in nonneuronal cells by a mechanism that involves exon repression and mRNA silencing via nonsense-mediated decay (NMD) . PTBP2 contains four RNA recognition motifs (RRMs).
Emerin (Emerin)
Type: Family

Emerin is an inner nuclear membrane protein with roles in nuclear "lamina" structure, nuclear assembly, chromatin tethering, gene regulation, mitosis, development and signaling . Emerin is absent from the inner nuclear membrane in most patients with X-linked muscular dystrophy . BAF recruits emerin to chromatin and regulates higher-order chromatin structure during nuclear assembly . Emerin interacts with A-type lamins . It contains an N-terminal LEM domain followed by a poly-serine segment, a region rich in hydrophobic amino acids comprising the nuclear localization signal (NLS) followed by another poly-serine segment, and a C-terminal transmembrane region .
hnRNP-L, RNA recognition motif 1 (hnRNPL_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of hnRNP-L.

hnRNP-L is a subunit of the KMT3a (also known as HYPB or hSet2) complex required for histone H3 Lys-36 trimethylation activity and which is found only in higher eukaryotes . It plays both nuclear and cytoplasmic roles in pre-mRNA processing, mRNA export of intronless genes, internal ribosomal entry site-mediated translation, and chromatin modification . hnRNP-L is an RNA-binding protein with four RNA recognition motifs (RRMs) .
Ankyrin repeat and LEM domain-containing protein 2, LEM domain (LEM_ANKL2)
Type: Domain

Lem4 (also called ANKLE2) and C. elegans orthologue LEM-4L are required for BAF dephosphorylation. Lem4 coordinates BAF dephosphorylation by inhibiting kinase VRK-1 and by supporting PP2A dephosphorylation of BAF during mitotic exit .

Barrier-to-autointegration factor (BAF) is an essential protein that binds to dsDNA, chromatin, nuclear lamina proteins, histones and various transcription factors . Members of the vaccinia-related kinase (VRK) family of mitotic kinases phosphorylate BAF in mitosis and meiosis; this modification strongly reduces the affinity of BAF for chromatin and slightly weakens its affinity for LEM proteins. BAF dephosphorylation has been linked to mitotic exit and postmitotic NE formation .

ANKLE2 contains an N-terminal LEM domain and an ankyrin repeat region. The LEM domain is known to interact with BAF . The ankyrin repeats are unique motifs mediating protein-protein interactions.

This entry represents the LEM domain.
hnRNP-L, RNA recognition motif 2 (hnRNPL_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of hnRNP-L.

hnRNP-L is a subunit of the KMT3a (also known as HYPB or hSet2) complex required for histone H3 Lys-36 trimethylation activity and which is found only in higher eukaryotes . It plays both nuclear and cytoplasmic roles in pre-mRNA processing, mRNA export of intronless genes, internal ribosomal entry site-mediated translation, and chromatin modification . hnRNP-L is an RNA-binding protein with four RNA recognition motifs (RRMs) .
SR140, RNA recognition motif (SR140_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of SR140 (also known as U2SURP) which is a putative splicing factor mainly found in higher eukaryotes. Although it was initially identified as one of the 17S U2 snRNP-associated proteins, the molecular and physiological function of SR140 remains unclear . SR140 contains an N-terminal RNA recognition motif (RRM), a SWAP/SURP domain that is found in a number of pre-mRNA splicing factors in the middle region, and a C-terminal arginine/serine-rich domain (RS domain).

Proteins containing this domain also include Arabidopsis RRC1, which is a splicing factor which is required for phytochrome B (phyB) signal transduction .
Dual specificity protein phosphatase PHS1 (PHS1)
Type: Family

PHS1 is dual-specificity phophosphatase from plants. It specifically interacts with two MAPKs, MPK12 and MPK18. PHS1-MPK18 signalling probably regulates cortical microtubule functions . It is also a negative regulator of abscisic acid (ABA) signalling . Plant hormone ABA control numeros processes, such as dormancy and germination of seeds, senescence and resistance to abiotic stresses.
Tensin-like, SH2 domain (Tensin-like_SH2)
Type: Domain

This entry represents the SH2 domain found in tensin-like proteins. The tensins are a family of intracellular proteins that interact with receptor tyrosine kinases (RTKs), integrins, and actin. They are thought act as signaling bridges between the extracellular space and the cytoskeleton. There are four homologues: tensin1, tensin2 (TENC1, C1-TEN), tensin3 and tensin4 (cten), all of which contain a C-terminal tandem SH2-PTB domain pairing, as well as actin-binding regions that may localize them to focal adhesions. The isoforms of tensin2 and tensin3 contain N-terminal C1 domains, which are atypical and not expected to bind to phorbol esters. Tensins 1-3 contain a phosphatase (PTPase) and C2 domain pairing which resembles PTEN (phosphatase and tensin homologue deleted on chromosome 10) protein .

PTEN is a lipid phosphatase that dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to yield phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). As PtdIns(3,4,5)P3 is the product of phosphatidylinositol 3-kinase (PI3K) activity, PTEN is therefore a key negative regulator of the PI3K pathway . Because of their PTEN-like domains, the tensins may also possess phosphoinositide-binding or phosphatase capabilities. However, only tensin2 and tensin3 have the potential to be phosphatases since only their PTPase domains contain a cysteine residue that is essential for catalytic activity. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites .
YabN, N-terminal (YabN_N)
Type: Domain

Bacillus subtilis YabN is a fusion of an N-terminal TP-methylase and a C-terminal MazG-type nucleotide pyrophosphohydrolase domain. MazG-like NTP-PPases have been implicated in house-cleaning functions such as degrading abnormal (d)NTPs . TP-methylases use S-AdoMet (S-adenosyl-L-methionine or SAM) in the methylation of diverse substrates. Most members catalyze various methylation steps in cobalamin (vitamin B12) biosynthesis, other members like Diphthine synthase and Ribosomal RNA small subunit methyltransferase I (RsmI) act on other substrates (

). The specific function of YabN's TP-methylase domain is not known.
cGMP-dependent protein kinase, catalytic domain (STKc_cGK)
Type: Domain

Mammals have two cGMP-dependent protein kinase (cGK) isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic centre by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase .

cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm .
Methylene tetrahydromethanopterin dehydrogenase, NADP-binding domain (NAD-bd_H4MPT_DH)
Type: Domain

This entry represents the methylene tetrahydromethanopterin dehydrogenase (H4MPT DH) NADP binding domain. NADP-dependent H4MPT DH catalyses the dehydrogenation of methylene-H4MPT and methylene-tetrahydrofolate (H4F) with NADP+ as cofactor . H4F and H4MPT are both cofactors that carry the one-carbon units between the formyl and methyl oxidation level. H4F and H4MPT are structurally analogous to each other with respect to the pterin moiety, but each has distinct side chain. H4MPT is present only in anaerobic methanogenic archaea and aerobic methylotrophic proteobacteria. H4MPT seems to have evolved independently from H4F and functions as a distinct carrier in C1 metabolism .

Amino acid DH-like NAD(P)-binding domains are members of the Rossmann fold superfamily and include glutamate, leucine, and phenylalanine DHs, methylene tetrahydrofolate DH, methylene-tetrahydromethanopterin DH, methylene-tetrahydropholate DH/cyclohydrolase, Shikimate DH-like proteins, malate oxidoreductases, and glutamyl tRNA reductase. Amino acid DHs catalyse the deamination of amino acids to keto acids with NAD(P)+ as a cofactor. The NAD(P)-binding Rossmann fold superfamily includes a wide variety of protein families including NAD(P)- binding domains of alcohol DHs, tyrosine-dependent oxidoreductases, glyceraldehyde-3-phosphate DH, lactate/malate DHs, formate/glycerate DHs, siroheme synthases, 6-phosphogluconate DH, amino acid DHs, repressor rex, NAD-binding potassium channel domain, CoA-binding, and ornithine cyclodeaminase-like domains. These domains have an α-β-α configuration. NAD binding involves numerous hydrogen and van der Waals contacts.
Protein kinase PknD, NHL repeat domain (NHL_PKND)
Type: Domain

PknD is a mycobacterial transmembrane protein with a cytosolic kinase domain and an extracellular sensor domain that contains NHL repeats . It plays a key role in the development of central nervous system tuberculosis, by mediating the invasion of host brain endothelia . The NHL (NCL-1, HT2A and LIN-41) repeat is found in multiple tandem copies, typically as 6 instances. It is about 40 residues long and resembles the WD repeat and other β-propeller structures .
Spt6, SH2 domain, C terminus (Spt6_SH2_C)
Type: Domain

This entry represents the C terminus of the SH2 domain found in Spt6.

Spt6 is an essential transcription elongation factor and histone chaperone that binds the C-terminal repeat domain (CTD) of RNA polymerase II . Spt6 contains a tandem SH2 domain with a novel structure and CTD-binding mode. The tandem SH2 domain binds to a serine 2-phosphorylated CTD peptide in vitro, whereas its N-terminal SH2 subdomain does not. CTD binding requires a positively charged crevice in the C-terminal SH2 subdomain, which lacks the canonical phospho-binding pocket of SH2 domains. The tandem SH2 domain is apparently required for transcription elongation in vivo as its deletion in cells is lethal in the presence of 6-azauracil. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites .
Spt6, SH2 domain, N terminus (Spt6_SH2_N)
Type: Domain

This entry represents the N terminus of the SH2 domain found in Spt6.

Spt6 is an essential transcription elongation factor and histone chaperone that binds the C-terminal repeat domain (CTD) of RNA polymerase II . Spt6 contains a tandem SH2 domain with a novel structure and CTD-binding mode. The tandem SH2 domain binds to a serine 2-phosphorylated CTD peptide in vitro, whereas its N-terminal SH2 subdomain does not. CTD binding requires a positively charged crevice in the C-terminal SH2 subdomain, which lacks the canonical phospho-binding pocket of SH2 domains. The tandem SH2 domain is apparently required for transcription elongation in vivo as its deletion in cells is lethal in the presence of 6-azauracil. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites .
PI3K p85 subunit, C-terminal SH2 domain (PI3kinase_P85_cSH2)
Type: Domain

This entry represents the C-terminal SH2 domain (cSH2) found in the PI3K p85 subunit.

Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. Class IA PI3Ks are heterodimers of a p110 catalytic (C) subunit and a p85-related regulatory (R) subunit . p110 is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. p85 is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are two inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are three inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110beta, and 3) p85 cSH2 domain with the kinase domain of p110beta .
PI3K p85 subunit, N-terminal SH2 domain (PI3kinase_P85_nSH2)
Type: Domain

This entry represents the N-terminal SH2 domain (nSH2) found in the PI3K p85 subunit.

Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. Class IA PI3Ks are heterodimers of a p110 catalytic (C) subunit and a p85-related regulatory (R) subunit . p110 is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. p85 is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are two inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are three inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110beta, and 3) p85 cSH2 domain with the kinase domain of p110beta .
PLC-gamma, C-terminal SH2 domain (PLC-gamma_C-SH2)
Type: Domain

This entry represents the C-terminal SH2 domain of phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma (PLC-gamma).

PLC-gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLC-gamma is composed of a pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases .
PLC-gamma, N-terminal SH2 domain (PLC-gamma_N-SH2)
Type: Domain

This entry represents the N-terminal SH2 domain of phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma (PLC-gamma).

PLC-gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLC-gamma is composed of a pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases .
CSK-like, SH2 domain (Csk-like_SH2)
Type: Domain

This entry represents the SH2 domain found in CSK and CHK.

Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism .

CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs .
Vav, SH2 domain, invertebrate (Vav_SH2_invertebrate)
Type: Domain

Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases . Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, two SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. This entry represents the SH2 domain which mediates a high affinity interaction with tyrosine phosphorylated proteins .
Growth factor receptor-bound protein 7, SH2 domain (Grb7_SH2)
Type: Domain

Grb7 (growth factor receptor bound protein 7) is an adapter protein mediating signal transduction from multiple cell surface receptors to diverse downstream pathways . It contains a Ras-associating (RA) domain, a pleckstrin-homology (PH) domain, a family-specific BPS (between PH and SH2) region and a C-terminal SH2 domain .

This entry represents the C-terminal SH2 domain of Grb7. It is responsible for the binding of this protein to the epidermal growth factor receptor (EGFR, erbB1) via the SH2 domain .
TRIM39, PRY/SPRY domain (PRY/SPRY_TRIM39)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of TRIM39, an E3 ubiquitin-protein ligase .

Tripartite motif 39 (TRIM39), also known as Ring finger protein 23 (RNF23), has been shown to stabilize modulator of apoptosis 1 (MOAP-1) by suppressing its polyubiquitylation by the anaphase promoting complex . It also stabilizes p21, thus regulating cell cycle progression and the balance between cytostasis and apoptosis after DNA damage. TRIM39 interacts with p21, preventing binding to Cdt2, ubiquitylation by Cdt2 E3 ligase, and degradation .
Grb14, SH2 domain (Grb14_SH2)
Type: Domain

This entry represents the SH2 domain of Grb14.

The Grb7 (growth factor receptor-bound 7) family includes Grb7, Grb10, and Grb14. These are adapter proteins mediating signal transduction from multiple cell surface receptors to diverse downstream pathways. They are composed of an N-terminal proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a PIR (phosphorylated insulin receptor interacting region) domain (also known as the family-specific BPS region), and a C-terminal SH2 domain .

Grb14 binds to various receptor tyrosine kinases (RTKs) under ligand induction. This interaction involves the SH2 and PIR domains .
Grb10, SH2 (Grb10_SH2)
Type: Domain

This entry represents the SH2 domain of Grb10.

The Grb7 (growth factor receptor-bound 7) family includes Grb7, Grb10, and Grb14. These are adapter proteins mediating signal transduction from multiple cell surface receptors to diverse downstream pathways. They are composed of an N-terminal proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a PIR (phosphorylated insulin receptor interacting region) domain (also known as the family-specific BPS region), and a C-terminal SH2 domain .

Grb10 inhibits insulin receptor kinase activity and mediates insulin-stimulated degradation of the insulin receptor . It binds to the regulatory kinase loop of the insulin receptor (IR) via its SH2 and BPS domains . Grb10 is directly phosphorylated by mTORC1 and may participate in a feedback inhibition of the phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated, mitogen-activated protein kinase (ERK-MAPK) pathways .
SHE, SH2 domain (SHE_SH2)
Type: Domain

This entry represents the SH2 domain found in SHE.

SHE (SH2 domain-containing adapter protein E) is expressed in heart, lung, brain, and skeletal muscle .
SHF, SH2 domain (SHF_SH2)
Type: Domain

This entry represents the SH2 domain of SHF.

SHF (SH2 domain-containing adapter protein F) is an adapter protein which may play a role in the regulation of apoptosis in response to PDGF . It contains four putative tyrosine phosphorylation sites and an SH2 domain.
SHB, SH2 domain (SHB_SH2)
Type: Domain

This entry represents the SH2 domain of SHB.

SHB (SH2 domain-containing adapter protein B) functions as an adapter protein which regulates several signal transduction cascades by linking activated receptors to downstream signaling components . It transmits signals from receptor tyrosine kinases regulating diverse processes such as apoptosis and differentiation . It regulates normal oocyte and follicle development and is required for appropriate hematopoietic and vascular differentiation in embryos .
SHD, SH2 domain (SHD_SH2)
Type: Domain

This entry represents the SH2 domain of SHD.

SHD (SH2 domain-containing adapter protein D) is thought to act as an adapter protein in the central nervous system. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a proline-rich region and a C-terminal SH2 domain .