SII-SWORD/CoKE huggingface dataset:
QUIRKY-like, third C2 domain (C2C_MCTP_PRT_plant)
Type: Domain

This entry represents the third C2 domain, referred to as C2C, from QUIRKY and related proteins. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions .

This entry includes a group of plant proteins, such as QUIRKY and FTIP1/3/4/7 from Arabidopsis . These are Multiple C2 domain and Transmembrane region Proteins (MCTPs) which are involved in Ca2 signalling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2 but not phospholipids.

QUIRKY may contribute to plant organ organogenesis mediated by the receptor-like kinase STRUBBELIG and may play a role in Ca2-dependent signaling and membrane trafficking . It has been shown to be required for the appropriate spatial expression of several epidermal cell fate regulators . FTIP1 is involved in the export of FT from the phloem companion cells to the sieve elements through the plasmodesmata. It regulates flowering time under long days . FTIP3/4 play an essential role in mediating proliferation and differentiation of shoot stem cells . FTIP7 promotes nuclear translocation of the transcription factor OSH1 and reduces auxin levels at late stage of anther development, after meiosis of microspore mother cells. It is necessary for normal anther dehiscence and seed setting .
QUIRKY-like (QUIRKY-like)
Type: Family

This entry includes a group of plant proteins, such as QUIRKY and FTIP1/3/4/7 from Arabidopsis . These are Multiple C2 domain and Transmembrane region Proteins (MCTPs) which are involved in Ca2 signalling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2 but not phospholipids.

QUIRKY may contribute to plant organ organogenesis mediated by the receptor-like kinase STRUBBELIG and may play a role in Ca2-dependent signaling and membrane trafficking . It has been shown to be required for the appropriate spatial expression of several epidermal cell fate regulators . FTIP1 is involved in the export of FT from the phloem companion cells to the sieve elements through the plasmodesmata. It regulates flowering time under long days . FTIP3/4 play an essential role in mediating proliferation and differentiation of shoot stem cells . FTIP7 promotes nuclear translocation of the transcription factor OSH1 and reduces auxin levels at late stage of anther development, after meiosis of microspore mother cells. It is necessary for normal anther dehiscence and seed setting .
ERCC1-like, central domain (ERCC1-like_central_dom)
Type: Domain

This entry represents a domain located centrally in ERCC1, at the C-terminal of Rad10 and at the N-terminal of Swi10. In ERCC1, this domain interacts tightly with XPF and may be involved in binding to single-stranded DNA .

This group of proteins includes Rad10 from budding yeasts, Swi10 from fission yeasts and ERCC-1 from animals and plants. All proteins in this family for which functions are known are components in a multiprotein endonuclease complex (usually made up of Rad1 and Rad10 homologues). This complex is used primarily for nucleotide excision repair but also for some aspects of recombination repair.

In budding yeast, Rad10 works as a heterodimer with Rad1, and is involved in nucleotide excision repair of DNA damaged with UV light, bulky adducts or cross-linking agents. The complex forms an endonuclease which specifically degrades single-stranded DNA .

ERCC1 and XPF (xeroderma pigmentosum group F-complementing protein) are two structure-specific endonucleases of a class of seven containing an ERCC4 domain. Together they form an obligate complex that functions primarily in nucleotide excision repair (NER), a versatile pathway able to detect and remove a variety of DNA lesions induced by UV light and environmental carcinogens, and secondarily in DNA inter-strand cross-link repair and telomere maintenance. This domain in fact binds simultaneously to both XPF and single-stranded DNA; this ternary complex explains the important role of Ercc1 in targeting its catalytic XPF partner to the NER pre-incision complex .
rRNA methyltransferase 1, methyltransferase domain (MRM1_MeTrfase_dom)
Type: Domain

This entry represents the methyltransferase domain of MRM1.

This entry includes rRNA methyltransferase 1, mitochondrial (MRM1) from mammals and yeast, and similar proteins from eukaryotes, which are SpoU-type (class IV) methyltransferases . MRM1 from humans is a S-adenosyl-L-methionine-dependent 2'-O-ribose methyltransferase that catalyses the formation of 2'-O-methylguanosine at position 1145 (Gm1145) in the 16S mitochondrial large subunit ribosomal RNA (mtLSU rRNA), a universally conserved modification in the peptidyl transferase domain of the mtLSU rRNA .
Peroxiredoxin-like 1 (PRX-like1)
Type: Family

This family represents a group uncharacterised proteins that show sequence similarity to Peroxiredoxins (PRXs) . Members of this group contain a conserved cysteine that aligns to the first cysteine in the CXXC motif of TRX. This does not correspond to the peroxidatic cysteine found in PRXs, which aligns to the second cysteine in the CXXC motif of TRX. In addition, these proteins do not contain the other two conserved residues of the catalytic triad of PRX. PRXs confer a protective antioxidant role in cells through their peroxidase activity in which hydrogen peroxide, peroxynitrate, and organic hydroperoxides are reduced and detoxified using reducing equivalents derived from either thioredoxin, glutathione, trypanothione and AhpF.
Hydroxynitrile lyase-like, cupin domain (HNL-like_cupin)
Type: Domain

This entry includes archaeal, eukaryotic, and bacterial proteins homologous to hydroxynitrile lyase (also known as (R)-mandelonitrile lyase) from Granulicella tundricola (

GtHNL), a novel class of HNLs that does not show any sequence or structural similarity to any other HNL and does not contain conserved motifs typical of HNLs . HNLs comprise a diverse group of enzymes that vary in terms of their substrate specificity, enantioselectivity and the need for a cofactor. In plants, they catalyse the reversible cleavage of cyanohydrins, yielding HCN and aldehydes or ketones. Also included in this family is TM1010 from Thermotoga maritima, a protein of unknown function. Some but not all members of this family have N- or C-terminal carboxymuconolactone decarboxylase domains in addition to the cupin domain. Members of this family belong to the cupin superfamily with a conserved "jelly roll-like" β-barrel fold capable of homodimerisation .
HpaA-like, N-terminal cupin domain (Cupin_HpaA-like_N)
Type: Domain

This entry represents the N-terminal cupin domain of the AraC/XylS family of transcriptional regulators similar to Escherichia coli 4-hydroxyphenylacetate catabolism regulatory protein HpaA (

, also known as 4HPA). These proteins recognise aromatic effectors. Members of this group of proteins, which are predominantly found in proteobacteria, also contain a C-terminal AraC/XylS family helix-turn-helix (HTH) DNA-binding domain (

) and belong to the cupin superfamily with a conserved "jelly roll-like" β-barrel fold capable of homodimerization .
Transcription factor PIF1-like, basic helix-loop-helix domain (PIF1-like_bHLH)
Type: Domain

This entry represents the basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana phytochrome interacting factors (PIFs) and similar transcription factors from plants, including ALC, PIL1, SPATULA, and UNE10 .

PIFs (PIF1/3/4/5/6/7) have been shown to control light-regulated gene expression. They directly bind to the photoactivated phytochromes and are degraded in response to light signals . ALC, also termed protein ALCATRAZ, is required for the dehiscence of fruit, especially for the separation of the valve cells from the replum. It promotes the differentiation of a strip of labile non-lignified cells sandwiched between layers of lignified cells . PIL1 is involved in responses to transient and long-term shade. It is required for the light-mediated inhibition of hypocotyl elongation and necessary for rapid light-induced expression of the photomorphogenesis- and circadian-related gene APRR9. PIL1 seems to play a role in multiple PHYB responses, such as flowering transition and petiole elongation . SPATULA plays a role in floral organogenesis. It promotes the growth of carpel margins and of pollen tract tissues derived from them . UNE10 is required during the fertilization of ovules by pollen .
N-lysine methyltransferase KMT5A-like, SET domain (KMT5A-like_SET)
Type: Domain

This entry represents the SET domain of KMT5A.

This entry includes a group of animal proteins that belong to the class V-like SAM-binding methyltransferase superfamily and contain the SET domain usually flanked by other domains forming the so-called pre- and post-SET regions. The enzymes belonging to this class all N-methylate lysine in proteins. Most of them are histone methyltransferases (

), including human N-lysine methyltransferase KMT5A (also known as PR-Set7), which is a nucleosomal histone-lysine N-methyltransferase that specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). It plays a central role in the silencing of euchromatic genes .
Oligophrenin-1, BAR domain (OPHN1_BAR)
Type: Domain

This entry represents the BAR domain found at the N-terminal of OPHN1. This domain is normally associated with dimerisation, induction of membrane bending and curvature, and protein-protein interactions.

Oligophrenin-1 (OPHN1) is a GTPase activating protein (GAP) with activity towards RhoA, Rac, and Cdc42, that is expressed in developing spinal cord and in adult brain areas with high plasticity. It plays a role in regulating the actin cytoskeleton as well as morphology changes in axons and dendrites, and may also function in modulating neuronal connectivity. Mutations in the OPHN1 gene cause X-linked mental retardation associated with cerebellar hypoplasia, lateral ventricle enlargement and epilepsy . This protein also contains a Pleckstrin homology (PH) domain (

), and a Rho GAP domain (

) .
Zinc finger MYND domain-containing protein 11, PWWP domain (PWWP_BS69)
Type: Domain

This entry represents the PWWP domain of ZMY11, which specifically recognises DNA and histone methylated lysines.

Zinc finger MYND domain-containing protein 11 (ZMYND11 or ZMY11, also known as protein BS69) is a ubiquitously expressed nuclear protein acting as a transcriptional co-repressor in association with various transcription factors . This protein specifically recognises H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation . It is critical for the repression of a transcriptional program that is essential for tumour cell growth. It was originally identified as an adenovirus 5 E1A-binding protein that inhibits E1A transactivation, as well as c-Myb transcription . It also mediates repression, at least in part, through interaction with the co-repressor N-CoR . Moreover, it interacts with Toll-interleukin 1 receptor domain (TIR)-containing adaptor molecule-1 (TICAM-1, also named TRIF) to facilitate NF-kappaB activation and type I IFN induction. It associates with PIAS1, a SUMO E3 enzyme, and Ubc9, a SUMO E2 enzyme, and plays an inhibitory role in muscle and neuronal differentiation .

ZMY11 regulates Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1)/C-terminal activation region 2 (CTAR2)-mediated NF-kappaB activation by interfering with the complex formation between TNFR-associated death domain protein (TRADD) and LMP1/CTAR2 . It also cooperates with tumour necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) in the regulation of EBV-derived LMP1/CTAR1-induced NF-kappaB activation . Furthermore, ZMY11 is involved in the p53-p21Cip1-mediated senescence pathway .
Zinc finger MYND domain-containing protein 11 (ZMY11)
Type: Family

This entry represents ZMY11 and similar proteins from animals.

Zinc finger MYND domain-containing protein 11 (ZMYND11 or ZMY11, also known as protein BS69) is a ubiquitously expressed nuclear protein acting as a transcriptional co-repressor in association with various transcription factors . This protein specifically recognises H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation . It is critical for the repression of a transcriptional program that is essential for tumour cell growth. It was originally identified as an adenovirus 5 E1A-binding protein that inhibits E1A transactivation, as well as c-Myb transcription . It also mediates repression, at least in part, through interaction with the co-repressor N-CoR . Moreover, it interacts with Toll-interleukin 1 receptor domain (TIR)-containing adaptor molecule-1 (TICAM-1, also named TRIF) to facilitate NF-kappaB activation and type I IFN induction. It associates with PIAS1, a SUMO E3 enzyme, and Ubc9, a SUMO E2 enzyme, and plays an inhibitory role in muscle and neuronal differentiation .

ZMY11 regulates Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1)/C-terminal activation region 2 (CTAR2)-mediated NF-kappaB activation by interfering with the complex formation between TNFR-associated death domain protein (TRADD) and LMP1/CTAR2 . It also cooperates with tumour necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) in the regulation of EBV-derived LMP1/CTAR1-induced NF-kappaB activation . Furthermore, ZMY11 is involved in the p53-p21Cip1-mediated senescence pathway .
Signal peptide peptidase A-like, C-terminal (S49_SppA_C)
Type: Domain

This entry represents the C-terminal domain of Signal peptide peptidase A (SppA) from Escherichia coli and other members of the Peptidase S49 family (protease IV family, clan S in MEROPS) from cellular organisms.

Signal peptide peptidase A is involved in the cleavage of signal peptides after their removal from the precursor proteins by signal peptidases. This entry includes S49 family members with either a single domain (sometimes referred to as 36K type), such as Escherichia coli SohB peptidase and archaeal sprotease MJ0651, or an N-terminal domain in addition to the C-terminal protease domain that is conserved in all the S49 family members (sometimes referred to as 67K type), similar to E. coli and Arabidopsis thaliana SppA peptidases .

Unlike the eukaryotic functional homologues that are proposed to be aspartic proteases, site-directed mutagenesis and sequence analysis have shown that members in this subfamily, mostly bacterial, are serine proteases. The predicted active site serine for members in this entry occurs in a transmembrane domain. Mutagenesis studies also suggest that the catalytic centre comprises a Ser-Lys dyad (both residues absolutely conserved within bacteria, chloroplast and mitochondrial signal peptidase family members) and not the usual Ser-His-Asp catalytic triad found in the majority of serine proteases. Interestingly, the single membrane spanning E. coli SppA carries out catalysis using a Ser-Lys dyad with the serine located in the C-terminal protease domain and the lysine in the N-terminal domain. The N- and C-terminal halves of SppA in E. coli are tandem repeats .
Vertnin-like, ovarian tumor domain (VRTN_OTU_dom)
Type: Domain

This entry represents the OTU (ovarian tumour) domain of Vertnin and similar proteins predominantly found in animals. Vertnin and some subfamily members do not possess the conserved catalytic residues and may not have deubiquitinase activity.

Vertnin is reported to be a maternal factor involved in dorsoventral patterning in zebrafish. It is rapidly transported to the animal pole region after fertilisation and binds to a bmp2b regulatory region to prevent its transcription . In mammals, it is associated with variations in vertebral number .
RNA-binding protein Nova-1/2, type I K Homology domain 3 (KH-I_NOVA_rpt3)
Type: Domain

This entry represents the third type I K homology (KH) RNA-binding domain found in Nova-1 and Nova-2.

This group of proteins includes related neuronal RNA-binding proteins, such as Nova-1 and Nova-2. Nova-1 may regulate RNA splicing or metabolism in a specific subset of developing neurons. It interacts with RNA containing repeats of the YCAY sequence. It is a brain-enriched splicing factor regulating neuronal alternative splicing. Nova-1 is involved in neurological disorders and carcinogenesis. Nova-2 is a neuronal RNA-binding protein expressed in a broader central nervous system (CNS) distribution than Nova-1. It functions in neuronal RNA metabolism. NOVA family proteins contain three K-homology (KH) RNA-binding domains .
RNA-binding protein Nova-1/2, type I K Homology domain 1 (KH-I_NOVA_rpt1)
Type: Domain

This entry represents the first type I K homology (KH) RNA-binding domain found in Nova-1 and Nova-2.

This group of proteins includes related neuronal RNA-binding proteins, such as Nova-1 and Nova-2. Nova-1 may regulate RNA splicing or metabolism in a specific subset of developing neurons. It interacts with RNA containing repeats of the YCAY sequence. It is a brain-enriched splicing factor regulating neuronal alternative splicing. Nova-1 is involved in neurological disorders and carcinogenesis. Nova-2 is a neuronal RNA-binding protein expressed in a broader central nervous system (CNS) distribution than Nova-1. It functions in neuronal RNA metabolism. NOVA family proteins contain three K-homology (KH) RNA-binding domains .
RNA-binding protein Nova-1/2, type I K Homology domain 2 (KH-I_NOVA_rpt2)
Type: Domain

This entry represents the second type I K homology (KH) RNA-binding domain found in Nova-1 and Nova-2.

This group of proteins includes related neuronal RNA-binding proteins, such as Nova-1 and Nova-2. Nova-1 may regulate RNA splicing or metabolism in a specific subset of developing neurons. It interacts with RNA containing repeats of the YCAY sequence. It is a brain-enriched splicing factor regulating neuronal alternative splicing. Nova-1 is involved in neurological disorders and carcinogenesis. Nova-2 is a neuronal RNA-binding protein expressed in a broader central nervous system (CNS) distribution than Nova-1. It functions in neuronal RNA metabolism. NOVA family proteins contain three K-homology (KH) RNA-binding domains .
DENN domain-containing protein 5A/B, PLAT/LH2 domain (PLAT_RAB6IP1)
Type: Domain

This entry represents the PLAT/LH2 domain of DENN domain-containing proteins 5A/B (DEN5A/B) and similar animal proteins that belong to the RAB6 interacting protein 1 (Rab6IP1) family. PLAT/LH2 domains consist of an eight stranded β-barrel. In RabIP1, this domain may participate in lipid-mediated modulation of Rab6IP1's function via its generally proposed function of mediating interaction with lipids or membrane bound proteins .

This entry includes DENN domain-containing proteins 5A/B (DEN5A/B) from humans and similar animal proteins that belong to the RAB6 interacting protein 1 (Rab6IP1) family. DEN5A/B are guanine nucleotide exchange factors (GEFs) which may activate RAB6A and RAB39A and/or RAB39B. They promote the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form . DEN5A is involved in the negative regulation of neurite outgrowth .
DENN domain-containing protein 5A/B (DEN5A/B)
Type: Family

This entry includes DENN domain-containing proteins 5A/B (DEN5A/B) from humans and similar animal proteins that belong to the RAB6 interacting protein 1 (Rab6IP1) family. DEN5A/B are guanine nucleotide exchange factors (GEFs) which may activate RAB6A and RAB39A and/or RAB39B. They promote the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form . DEN5A is involved in the negative regulation of neurite outgrowth .
Polycomb protein SCMH1, first MBT repeat (MBT_SCMH1_rpt1)
Type: Repeat

This entry represents the first MBT repeat of SCMH1 and similar proteins specific to vertebrates. MTB repeats are protein modules that recognise methylated lysine residues on histones. Unlike other MTB repeats, this repeat does not contain a semi-aromatic cage and may not bind methylated lysine residues.

Sex comb on midleg homologue 1 (SCMH1) is the mammal homologue of Drosophila Sex comb on midleg (Scm). It is a component of PRC1 (Polycomb repressive complex 1), which acts as an E3 ubiquitin ligase, both for histone H2A to silence transcription and for geminin to regulate its stability. SCMH1 provides the complex with an interaction domain for geminin. It contains two MBT (malignant brain tumor) repeats .
Polycomb protein SCMH1, second MBT repeat (MBT_SCMH1_rpt2)
Type: Repeat

This entry represents the second MBT repeat of SCMH1 and similar proteins specific to vertebrates. MTB repeats are protein modules that recognise methylated lysine residues on histones. This repeat contains a semi-aromatic cage to accommodate methylated lysine residues and show specificity towards the lower methylation states of lysines.

Sex comb on midleg homologue 1 (SCMH1) is the mammal homologue of Drosophila Sex comb on midleg (Scm). It is a component of PRC1 (Polycomb repressive complex 1), which acts as an E3 ubiquitin ligase, both for histone H2A to silence transcription and for geminin to regulate its stability. SCMH1 provides the complex with an interaction domain for geminin. It contains two MBT (malignant brain tumor) repeats .
Phospholemman (PLM)
Type: Family

This entry represents phospholemman (PLM), also known as FXYD domain-containing ion transport regulator 1 (FXYD1), and similar proteins from vertebrates. PLM associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na out of the cell and K into the cell. It is a plasma membrane substrate for several kinases, including protein kinase A, protein kinase C, NIMA kinase, and myotonic dystrophy kinase. It is thought to form an ion channel or regulate ion channel activity. Transcript variants with different 5' UTR sequences have been described in the literature .
Sodium/potassium-transporting ATPase subunit gamma (ATNG)
Type: Family

This entry represents Sodium/potassium-transporting ATPase subunit gamma (ATNG), also known as FXYD domain-containing ion transport regulator 2 (FXYD2), and similar proteins from vertebrates. ATNG is the regulatory subunit of the sodium/potassium-transporting ATPase (Na,K-ATPase). Na,K-ATPase is a heteromeric complex consisting of a large alpha-subunit, which is responsible for ATP hydrolysis, ion transport, and CTS binding, and a beta-subunit, acting as a chaperone. Although the Na,K-ATPase does not depend on the gamma subunit to be functional, it is thought that the gamma subunit modulates the enzyme's activity by inducing ion channel activity. Mutations in this gene have been associated with renal hypomagnesaemia .
FXYD domain-containing ion transport regulator 4 (FXYD4)
Type: Family

This entry represents FXYD domain-containing ion transport regulator 4 (FXYD4, also known as CHIF) and similar proteins from vertebrates. FXYD4 evokes K conductance in oocytes and is localized in the distal parts of the nephron and in the colon. CHIF, a putative K channel regulator, is regulated by aldosterone in the colon and by K intake in the kidney .