SII-SWORD/CoKE huggingface dataset:
ARHGAP20-like, RhoGAP domain (ARHGAP20-like_RhoGAP)
Type: Domain

This entry represents the RhoGAP (GTPase-activator protein (GAP) for Rho-like small GTPases) domain of ARHGAP20-like proteins. ARHGAP20, also known as KIAA1391 and RA-RhoGAP, contains a RhoGAP, a RA, and a PH domain, and ANXL repeats. ARHGAP20 is thought to function in rearrangements of the cytoskeleton and cell signalling events that occur during spermatogenesis . It is activated by Rap1 and induces inactivation of Rho, which in turn leads to neurite outgrowth . Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signalling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude .

This entry also includes T-cell activation Rho GTPase-activating protein (TAGAP), a Rho GTPase-activating protein that plays an important regulatory role during T-cell activation . Single nucleotide polymorphisms (SNPs) in TAGAP have been associated with different autoimmune diseases, such as rheumatoid arthritis, celiac disease and Crohn's disease .
ARHGAP20, PH domain (ARHGAP20_PH)
Type: Domain

This entry represents the PH domain of ARHGAP20.

ARHGAP20 (also known as RARhoGAP/Rho GTPase-activating protein 20) is thought to function in rearrangements of the cytoskeleton and cell signalling events that occur during spermatogenesis . ARHGAP20 was also shown to be activated by Rap1 and to induce inactivation of Rho, resulting in the neurite outgrowth . Recent findings show that ARHGAP20, even although it is located in the middle of the MDR on 11q22-23, is expressed at higher levels in chronic lymphocytic leukemia patients with 11q22-23 and/or 13q14 deletions and its expression pattern suggests a functional link between cases with 11q22-23 and 13q14 deletions . ARHGAP20 contains a PH domain, a Ras-associating domain, a Rho-GAP domain, and ANXL repeats. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarised .
ARHGAP20, Ras-associating domain (ARHGAP20_RA)
Type: Domain

This entry represents the Ras-associating (RA) domain of ARHGAP20.

ARHGAP20 (also known as RARhoGAP/Rho GTPase-activating protein 20) is thought to function in rearrangements of the cytoskeleton and cell signalling events that occur during spermatogenesis . ARHGAP20 was also shown to be activated by Rap1 and to induce inactivation of Rho, resulting in the neurite outgrowth . Recent findings show that ARHGAP20, even although it is located in the middle of the MDR on 11q22-23, is expressed at higher levels in chronic lymphocytic leukemia patients with 11q22-23 and/or 13q14 deletions and its expression pattern suggests a functional link between cases with 11q22-23 and 13q14 deletions . ARHGAP20 contains a PH domain, a Ras-associating domain, a Rho-GAP domain, and ANXL repeats. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarised .
KHDC4, second type I KH domain (KHDC4_KH-I_second)
Type: Domain

KHDC4 (also known as Brings lots of money 7 (Blom7), or pre-mRNA splicing factor protein KHDC4), is an RNA-binding protein involved in pre-mRNA splicing. It interacts with the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome. KHDC4 binds preferentially RNA with A/C rich sequences and poly-C stretches. KHDC4 contains two type I K homology (KH) RNA-binding domains. This entry corresponds to the second one .
KHDC4, first type I KH domain (KHDC4_KH-I_first)
Type: Domain

KHDC4 (also known as Brings lots of money 7 (Blom7), or pre-mRNA splicing factor protein KHDC4), is an RNA-binding protein involved in pre-mRNA splicing. It interacts with the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome. KHDC4 binds preferentially RNA with A/C rich sequences and poly-C stretches. KHDC4 contains two type I K homology (KH) RNA-binding domains. This entry corresponds to the first one .
GPGG-motif containing membrane protein (GPGG_membr)
Type: Family

Members of this family are small highly conserved membrane proteins, most of which with a length of about 50 amino acid residues. These proteins are found exclusively in Actinobacteria and are predicted to contain two transmembrane helices.
Arylsulfatase K (ARSK)
Type: Family

This entry represents human Arylsulfatase K (ARSK,

) and similar sequences from vertebrates. ARSK is a lysosomal sulfatase which exhibits an acidic pH optimum for catalytic activity against arylsulfate substrates. Other names for ARSK include arylsulfatase K and TSULF . Sulfatases catalyse the hydrolysis of sulfate esters from wide range of substrates, including steroids, carbohydrates and proteins. Sulfate esters may be formed from various alcohols and amines. The biological roles of sulfatase includes the cycling of sulfur in the environment, in the degradation of sulfated glycosaminoglycans and glycolipids in the lysosome, and in remodelling sulfated glycosaminoglycans in the extracellular space. The sulfatases are essential for human metabolism. At least eight human monogenic diseases are caused by the deficiency of individual sulfatases .
ASHR3-like, SET domain (ASHR3-like_SET)
Type: Domain

This entry represents the SET domain of a group of plant proteins, including Arabidopsis thaliana ASH1-related protein 3 (ASHR3, also termed protein SET DOMAIN GROUP 4 or protein stamen loss), ASH1 homolog 3 (ASHH3, also termed protein SET DOMAIN GROUP 7) and homolog 4 (ASHH4, also termed protein SET DOMAIN GROUP 24). They all function as histone-lysine N-methyltransferases (

) .
Adhesin competence regulator AdcR-like (AdcR-like)
Type: Family

This entry represents one of the unusual clades within the MarR family of transcription factors that bind Zn2 and regulate the response to zinc abundance or scarcity. This entry includes adhesin competence regulator AdcR (also known as ZitR in Lactococcus lactis

) that represses the transcription of a high-affinity zinc-specific uptake transporter, a group of surface antigen zinc-binding pneumococcal histidine triad proteins (PhtA, PhtB, PhtD, and PhtE), and an AdcA homologue (AdcAII). The Zn2-bound AdcR structure forms a mainly helical two-fold-symmetric dimer with two distinct metal-binding sites per protomer

.

AdcR differs from other members of the MarR family in two important ways: AdcR has a unique effector in Zn2, and co-repression mechanism induced by metal binding that is unprecedented in MarR family transcriptional regulators .
Aspartokinase 1, ACT domain 2 (AK1_ACT_2)
Type: Domain

This entry represents the second of two ACT domains located C-terminal to the catalytic domain of a monofunctional, lysine-sensitive, plant aspartate kinase 1 (AK1), which can be synergistically inhibited by S-adenosylmethionine (SAM). This isoenzyme is found in higher plants,
Arabidopsis thaliana
and
Zea mays
, and also in Chlorophyta. In its inactive state, Arabidopsis AK1 binds the effectors lysine and SAM (two molecules each) at the interface of two ACT1 domain subunits. The second ACT domain (ACT2), this entry, does not interact with an effector. Members of this entry belong to the superfamily of ACT regulatory domains .
Aspartokinase 1, ACT domain 1 (AK1_ACT_1)
Type: Domain

This entry represents the first of two ACT domains located C-terminal to the catalytic domain of a monofunctional, lysine-sensitive, plant aspartate kinase 1 (AK1), which can be synergistically inhibited by S-adenosylmethionine. This isoenzyme is found in higher plants,
Arabidopsis thaliana
(AT) and
Zea mays
, and also in Chlorophyta. Like the
Escherichia coli AKIII
(LysC), Arabidopsis AK1 binds two feedback allosteric inhibitor lysine molecules at the dimer interface located between the ACT1 domain of two subunits. A loop in common is involved in the binding of both Lys and S-adenosylmethionine providing an explanation for the synergistic inhibition by these effectors. Members of this entry belong to the superfamily of ACT regulatory domains .
Synaptotagmins 15/17, C2A domain (Synaptotagmin-15/17_C2A)
Type: Domain

Synaptotagmins (Syts) are membrane-trafficking proteins characterised by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. They have been widely studied for their role in the trafficking and exocytosis of secretory vesicles. All Syts contain two C2 domains separated by a short flexible linker. Previously, all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium .

Human synaptotagmin 15 (Syt-15) has 2 alternatively spliced forms that encode proteins with different C-terminal. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C-terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins, it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis.

Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. It is an unusual Syt isoform that lacks an N-terminal transmembrane domain, rather, it associates with membranes via a string of fatty-acylated cysteine residues near the N-terminal of the protein, and it does not bind calcium. In hippocampal neurons, it is localized to the Golgi complex, where it mediates the import of vesicles from the endoplasmic reticulum to support neurite outgrowth and facilitate axon regrowth after injury. There is a second pool of Syt-17 on early endosomes in neurites. These two pools control two crucial, independent membrane trafficking pathways in neurons and loss of this protein disrupts endocytic trafficking, resulting in the accumulation of excess postsynaptic AMPA receptors and defective synaptic plasticity. Function of Syt-17 seems to be one mechanism by which neurons have specialized their secretory and endosomal systems to support the demands of synaptic communication over sprawling neurite arbors .

This entry represents the first C2 domain, C2A found in Syt-15 and Syt-17.
Di-N-acetylchitobiase, catalytic domain (DIAC_cat)
Type: Domain

This entry represents the catalytic domain of human Di-N-acetylchitobiase (DIAC) and similar sequences from vertebrates. DIAC (also known as chitobiase) is a lysosomal glycosidase that hydrolyses the reducing-end N-acetylglucosamine from the chitobiose core of oligosaccharides during the ordered degradation of asparagine-linked glycoproteins in eukaryotes. DIAC can only do so if the asparagine that joins the oligosaccharide to protein is previously removed by a glycosylasparaginase. DIAC is therefore the final step in the lysosomal degradation of the protein/carbohydrate linkage component of asparagine-linked glycoproteins. The catalytic domain of DIAC is an eight-stranded α/β barrel fold similar to that of other family 18 glycosyl hydrolases such as hevamine and chitotriosidase .
Peptidase inhibitor R3HDML, CAP domain (R3HDML_CAP)
Type: Domain

This entry represents the CAP domain of Peptidase inhibitor R3HDML from Mus musculus, which has been described as a putative regulator of skeletal muscle development , and similar sequences from vertebrates. The R3HDML gene may be associated with clinical dimensions of schizophrenia .

The wider family of CAP domain containing proteins includes plant pathogenesis-related protein 1 (PR-1), cysteine-rich secretory proteins (CRISPs), and allergen 5 from vespid venom, among others. CAP superfamily proteins exhibit diverse roles encompassing various processes, such as modulating the production of the extracellular matrix and facilitating branching morphogenesis, potentially acting as either proteases or protease inhibitors. They are also implicated in regulating ion channels associated with fertility, exerting tumour-suppressive or pro-oncogenic effects in different tissues, including the prostate, and participating in cell-cell adhesion during fertilisation. .
Choice-of-anchor G domain (Choice_anch_G)
Type: Domain

Choice-of-anchor proteins belong to homologous families in which various branches carry C-terminal sorting signals known, or suspected, to be processed by transpeptidases as sortase, exosortase, archaeo sortase, rhombosortase, or the type 9 secretion system sorting enzyme. This entry include bacterial proteins, so-called choice-of-anchor G, sortase and exosortase targets, and are likely to be found on the cell surface.

This domain may occur as standalone or in combination with other domains.
BC1881-like (BC1881-like)
Type: Family

Members of this family are very small bacterial proteins (average length about 50 residues), including BC1881

from the phBC6A51 prophage region of the Bacillus cereus ATCC 14579 genome .
Rhophilin-2, BRO1 domain (RHPN2_BRO1)
Type: Domain

This entry represents the Bro1 domain of RhoA-binding protein Rhophilin-2, also known as RHPN2. Rhodophilin-2 belongs to the BRO1_Alix_like superfamily which also includes the Bro1-like domain of mammalian Alix (apoptosis-linked gene-2 interacting protein X), His-Domain type N23 protein tyrosine phosphatase (HD-PTP, also known as PTPN23), RhoA-binding protein Rhophilin-1, Brox, Bro1 and Rim20 (also known as PalA) from
Saccharomyces cerevisiae, Ustilago maydis
Rim23 (also known as PalC), and related domains.

Rhophilin-2, binds both GDP- and GTP-bound RhoA. Bro1-like domains are boomerang-shaped, and part of the domain is a tetratricopeptide repeat (TPR)-like structure. In addition to this Bro1-like domain, Rhophilin-2 contains an N-terminal Rho-binding domain and a C-terminal PDZ (PS.D.-95, Disc-large, ZO-1) domain. Roles for Rhophilin-2 may include limiting stress fibre formation or increasing the turnover of F-actin in the absence of high levels of RhoA signalling activity. Rhophilin-2 lacks the V-shaped (V) domain found in many members of the BRO1_Alix_like superfamily .
NDxxF-motif containing lipoprotein (NDxxF_lipo)
Type: Family

Members of this family are lipoproteins, about 200 amino acid residues long, found mainly in order Bacillales. These proteins contain several highly conserved motifs, one of which is NDxxF-motif that this family was named after.
MARCHF9, RING-CH finger C4HC3-type (MARCHF9_RING_CH-C4HC3)
Type: Domain

This entry represents the C4HC3-type RING-CH finger of MARCHF9.

MARCH4 and MARCH9 belong to the family of MARCH E3 ligases. They downregulate major histocompatibility complex-I (MHC-I). In the presence of MARCH4 or MARCH9, MHC-I can be ubiquitinated and rapidly internalised by endocytosis, whereas MHC-I molecules lacking lysines in their cytoplasmic tail are resistant to downregulation. Moreover, MARCH4 and MARCH9, but not other MARCH proteins, can associate with Mult1 and prevent Mult1 expression at the cell surface in a lysine-dependent manner that can be reversed by heat shocking the cells. MARCHF4 appears to be mainly expressed in the brain. MARCHF9 controls the expression of the critical cell adhesion molecule ICAM-1 . Both MARCH4 and MARCH9 contain an N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, followed by two transmembrane regions .
MARCHF4, RING-CH finger C4HC3-type (MARCHF4_RING_CH-C4HC3)
Type: Domain

This entry represents the C4HC3-type RING-CH finger of MARCHF4.

MARCH4 and MARCH9 belong to the family of MARCH E3 ligases. They downregulate major histocompatibility complex-I (MHC-I). In the presence of MARCH4 or MARCH9, MHC-I can be ubiquitinated and rapidly internalised by endocytosis, whereas MHC-I molecules lacking lysines in their cytoplasmic tail are resistant to downregulation. Moreover, MARCH4 and MARCH9, but not other MARCH proteins, can associate with Mult1 and prevent Mult1 expression at the cell surface in a lysine-dependent manner that can be reversed by heat shocking the cells. MARCHF4 appears to be mainly expressed in the brain. MARCHF9 controls the expression of the critical cell adhesion molecule ICAM-1 . Both MARCH4 and MARCH9 contain an N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, followed by two transmembrane regions .
MARCHF11, RING-CH finger C4HC3-type (MARCHF11_RING_CH-C4HC3)
Type: Domain

This entry represents the C4HC3-type RING-CH finger of MARCHF11.

MARCHF11, also known as membrane-associated RING finger protein 11, or membrane-associated RING-CH protein XI (MARCH-XI), is a transmembrane RING-finger ubiquitin ligase that is predominantly expressed in developing spermatids in a stage-specific manner and is localised to trans-Golgi network (TGN) vesicles and multivesicular bodies (MVBs). It mediates selective protein sorting via the TGN-MVB transport pathway through its ubiquitin ligase activity . SAMT family proteins have been identified as substrates of MARCHF11 in mouse spermatids, suggesting that MARCHF11 plays a role in mammalian spermatogenesis . Moreover, MARCHF11 targets CD4 for ubiquitination. It also forms complexes with the adaptor protein complex-1 and with fucose-containing glycoproteins including ubiquitinated forms. MARCHF11 contains an N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, and two transmembrane regions. In addition, it harbours a proline-rich region, a tyrosine-based motif, and a PDZ binding motif.
Phage-related CD1375-like (CD1375-like)
Type: Family

Members of this family are small proteins found typically in prophage regions of Gram-positive bacteria.
Testis-specific serine/threonine kinase 4, catalytic domain (TSSK4_cat)
Type: Domain

Testis-specific serine/threonine-protein kinases (TSSKs) are almost exclusively expressed post meiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis . There are five mammalian TSSK proteins which show differences in their localisation and timing of expression . This entry represents the catalytic domain of TSSK4, also called TSSK5, which is expressed in testis from haploid round spermatids to mature spermatozoa. It mediates its autophosphorylation at Thr-197 in the T-loop region which is essential to its kinase activity . It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation . Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis .
SPJ_0845-like, N-terminal domain (SPJ_0845-like_N)
Type: Domain

This entry represents the N-terminal domain of uncharacterised proteins found exclusively in Lactobacillales.
SCO0930-like (SCO0930-like)
Type: Family

Members of this family are full-length bacterial homologues of the putative lipoprotein SCO0930 from Streptomyces coelicolor (

) . These proteins contain an N-terminal lipoprotein attachment site and four copies of the lipoprotein repeat (

).
tRNA methyltransferase 10 homolog B, TRM10-type domain (Trm10_B_MTase_dom)
Type: Domain

This entry represents the methyltransferase TRM10-type domain of eukaryotic tRNA m1G9 methyltransferase Trm10 homolog B (Trm10B), which catalyses the N(1) methylation of guanine at position 9 (m(1)G9) of tRNA, which might play a role in the stabilisation of tRNA and in translation termination efficiency . Trm10 is a member of the SPOUT (SpoU-TrmD) methyltransferase (MTase) superfamily, a large class of S-adenosyl-L-methionine (AdoMet or SAM)-dependent RNA MTases which are structurally characterised by a deep trefoil knot .
Non-structural protein 13, helicase domain, alphacoronavirus (Nsp13_helicase_alphaCoV)
Type: Domain

This entry represents the helicase domain of non-structural protein 13 (Nsp13) from alphacoronavirus, including Porcine epidemic diarrhoea (PED) virus and Human coronavirus (CoV) NL63. Helicases catalyse NTP-dependent unwinding of nucleic acid duplexes into single strands and are classified based on the arrangement of conserved motifs into six superfamilies. CoV Nsp13 is a member of the helicase superfamily 1 (SF1); SF1 and SF2 helicases do not form toroidal structures, while SF3-6 helicases do. Nsp13 is a component of the viral RNA synthesis replication and transcription complex (RTC). It is a multidomain protein containing a Cys/His rich zinc-binding domain (CH/ZBD), a stalk domain, a 1B domain involved in nucleic acid substrate binding, and a SF1 helicase core .
Zinc finger CCHC domain-containing protein 17, S1 domain (ZCCHC17_S1)
Type: Domain

This entry represents the S1 domain of metazoan ZCCHC17 (also known as pNO40) family. ZCCHC17 is a nucleolar protein with an N-terminal S1 RNA binding domain , a CCHC type zinc finger, and clusters of basic amino acids representing a potential nucleolar targeting signal. This protein was identified through a yeast two-hybrid interaction screen of a human kidney cDNA library using the pinin (pnn) protein as bait . ZCCHC17 is thought to play a role in ribosome maturation and/or biogenesis and has been identified as a regulator of synaptic gene expression in Alzheimer's disease .

The S1 domain was originally identified in ribosomal protein S1 but is found in a large number of RNA-associated proteins. The structure of the S1 RNA-binding domain from the Escherichia coli polynucleotide phosphorylase has been determined using NMR methods and consists of a five-stranded antiparallel β barrel. Conserved residues on one face of the barrel and adjacent loops form the putative RNA-binding site .
TagK-like, C-terminal domain (TagK-like_C)
Type: Domain

This entry represents a presumed domain found at the C-terminal of TagK-like proteins, mainly from Enterobacterales and Burkholderiales. Members of this entry are involved in type VI secretion system (T6SS) and were initially identified in Gram-negative proteobacterium Burkholderia pseudomallei .
Tau-Tubulin Kinase 2, catalytic domain (TTBK2_STKc)
Type: Domain

Tau-Tubulin Kinases (TTBKs) are neuron-specific kinases that phosphorylate the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration . Mutations in TTBK2 is associated with the development of spinocerebellar ataxia type 11, belonging to a group of neurodegenerative disorders characterised by progressive incoordination, dysarthria and impairment of eye movements . Brain tissues of SCA11 patients show the presence of neurofibrillary tangles and tau deposition in the brain, similar to Alzheimer's disease (AD) patients .

This entry represents the kinase domain of TTBK2.
Tau-tubulin kinase homolog Asator-like, catalytic domain (TTBK_Asator-like_STKc)
Type: Domain

STKs (serine/threonine-protein kinases) catalyse the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. The Drosophila TTBK homologue, Asator, is an essential protein that localises to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function .

This entry represents the catalytic domain of Asator and similar proteins from lower eukaryotes.