SII-SWORD/CoKE huggingface dataset:
G protein-coupled receptor 35, 7TM (GPR35_7tmA)
Type: Domain

This entry represents the seven transmembrane segments of G-protein coupled receptor 35 (GPR35) from animals. GPR35 shares closest homology with GPR55, and they belong to the class A G protein-coupled receptor superfamily, which all have a common structural architecture comprising of seven-transmembrane (TM) α-helices interconnected by three extracellular and three intracellular loops . A number of studies have suggested that GPR35 may play important physiological roles in hypertension, atherosclerosis, nociception, asthma, glucose homeostasis and diabetes, and inflammatory bowel disease. GPR35 is thought to be responsible for brachydactyly mental retardation syndrome, which is associated with a deletion comprising chromosome 2q37 in human , and is also implicated as a potential oncogene in stomach cancer. Several endogenous ligands for GPR35 have been identified including kynurenic acid , 2-oleoyl lysophosphatidic acid, and zaprinast.
Ran-binding protein Gid1/RanBPM/SPLA, SPRY domain (Gid1/RanBPM/SPLA_SPRY)
Type: Domain

This is the B30.2/SPRY domain found in Ran binding proteins (RanBPs), such as RanBP M homologue (AtRanBPM) from Arabidopsis , GID complex subunit 1 (Gid1), also known as vacuolar import and degradation protein 30, from Saccharomyces cerevisiae and dual specificity protein kinase splA (SPLA) from Dictyostelium discoideum.

The B30.2 domain was first identified as a protein domain encoded by an exon (named B30-2) in the Homo sapiens class I major histocompatibility complex region , whereas the SPRY domain was first identified in a Dictyostelium discoideum kinase splA and mammalian calcium-release channels ryanodine receptors . B30.2 domain consists of PRY and SPRY subdomains. The SPRY domains (after SPla and the RYanodine Receptor) are shorter at the N terminus than the B30.2 domains. The ~200-residue B30.2/SPRY (for B30.2 and/or SPRY) domain is present in a large number of proteins with diverse individual functions in different biological processes. The B30.2/SPRY domain in these proteins is likely to function through protein-protein interaction .
The N-terminal ~60 residues of B30.2/SPRY domains are poorly conserved and, as a consequence, a new domain name PRY was coined for a group of similar sequence segments N-terminal to the SPRY domains . The B30.2/SPRY domain contains three highly conserved motifs (LDP, WEVE and LDYE) . The B30.2/SPRY domain adopts a highly distorted, compact β-sandwich fold with two additional short β-helices at the N terminus. The β-sandwich of the B30.2/SPRY domain consists of two layers of β-sheets: sheet A composed of eight strands and sheet B composed of seven strands. All the β-strands are in antiparallel arrangement . The 5th β-strand corresponding to WEVE motif . Both the N- and C-terminal ends of the B30.2/SPRY domains in general are close to each other .
TopBP1, first BRCT domain (TopBP1_BRCT_1)
Type: Domain

The entry corresponds to the first BRCT domain found in TopBP1, which is a protein-protein binding module [3].

TopBP1, also known as DNA topoisomerase II-beta-binding protein 1, or DNA topoisomerase II-binding protein 1, functions in DNA replication and damage response, acting as a scaffold protein . It binds double-stranded DNA breaks and nicks as well as single-stranded DNA . It has been shown to activate the ATR-ATRIP complex . TopBP1 contains eight copies of BRCT domain which specifically recognise and bind phosphorylated proteins, bringing proteins together into functional combinations .
Autophagy-related protein 22 (Atg22)
Type: Family

Atg22 (also known as Aut4) protein functions as a vacuolar effluxer which mediates the efflux of amino acids resulting from autophagic degradation. The release of autophagic amino acids allows the maintenance of protein synthesis and viability during nitrogen starvation . Members of this family belong to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement .
NRT1/PTR family (NRT1/PTR)
Type: Family

The plant Nitrate transporter/Peptide transporter (NRT1/PTR) family (NPF) is related to the POT (proton-coupled oligopeptide transporter), Peptide transporter (PepT/PTR), or Solute Carrier 15 (SLC15) family in animals . In contrast to related animal and bacterial counterparts, the plant proteins transport a wide variety of substrates including nitrate, peptides, amino acids, dicarboxylates, glucosinolates, as well as the plant hormones indole-3-acetic acid (IAA) and abscisic acid (ABA). A study identified eight subfamilies within this family, named NPF1-NPF8 .

This entry represents NPF5, which includes Arabidopsis thaliana PTR3 (AtPTR3, now named AtNPF5.2), a wound-induced peptide transporter that is necessary for defense against virulent bacterial pathogens . NPF5 belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement .
Glucose-6-phosphate exchanger SLC37A1/ SLC37A2 (SLC37A1_2)
Type: Family

Solute carrier family 37 members 1 (SLC37A1) and 2 (SLC37A2) are also called sugar phosphate exchangers 1 (SPX1) and 2 (SPX2). SLC37A1 and SLC37A2 are ER-associated, Pi-linked antiporters that can transport glucose-6-phosphate (G6P) but are insensitive to chlorogenic acid, a competitive inhibitor of physiological ER G6P transport, unlike SLC37A4, the best characterised SLC37 family member and is the physiological G6P transporter (G6PT) . SLC37A1 and SLC37A2 belong to the Organophosphate:Pi antiporter (OPA)/SLC37 family, whose members are integral membrane proteins responsible for the transport of specific organophosphates or sugar phosphates across biological membranes with the simultaneous translocation of inorganic phosphate into the opposite direction .

The OPA/SLC37 family belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement .
Non-specific lipid-transfer protein-like (NsLTP-like)
Type: Domain

This domain is present in a subgroup of non-specific lipid-transfer proteins (nsLTPs), including MtN5 from Medicago truncatula, FIL1 from Antirrhinum majus, LIM3 from Lilium longiflorum and DIR1 from Arabidopsis. MtN5 is involved in root nodule development and is required for successful rhizobial symbiosis . FIL1 may be important in petal and stamen formation . The LIM3 gene is induced during the early prophase stage of meiosis in lily microsporocytes . DIR1 is required for systemic acquired resistance (SAR) long distance signalling .
RhlB-like, DEAD/DEAH-box helicase domain (DEAD/DEAH_RhlB)
Type: Domain

This is the ATP-binding domain of a group of DEAD-box RNA helicases which comprises a diverse family of proteins involved in ATP-dependent RNA unwinding, needed in a variety of cellular processes including splicing, ribosome biogenesis and RNA degradation .
USP48, Ubl domain (Ubl_USP48)
Type: Domain

This entry contains the ubiquitin-like domain of ubiquitin-specific peptidase 48 (USP48; MEROPS identifier C19.068).

In animals, USP48 is found in the nucleus, where it trims long Lys48-linked free and substrate-anchored ubiquitin chains, rather than completely disassembling them; a catalytic property only shared with ataxin-3 and otubain-1. USP48 ubiquitin-chain-trimming activity is regulated by casein-kinase-2-mediated phosphorylation in response to cytokine stimulation. USP48 controls the turnover of activated NF-kB/RelA in the nucleus together with the CSN and contributes to a timely control of immune responses . In plants, the gene name is USP26, which should not be confused with USP26 from mammals. USP26 deubiquitinates histone H2B and is required for heterochromatin silencing .

Ubiquitin carboxyl-terminal hydrolases (UCH) (

) are thiol proteases that recognise and hydrolyse the peptide bond at the C-terminal glycine of ubiquitin. These enzymes are involved in the processing of poly-ubiquitin precursors as well as that of ubiquinated proteins. The deubiquitinsing proteases can be split into 2 size ranges, 20-30kDa
(

) and 100-200kDa : the second class consist of large proteins (800 to 2000 residues) that belong to the peptidase family C19, and this group is currently represented by yeast UBP1 .
ZNRF4 /RNF13/RNF167, PA domain (ZNRF4/RNF13/RNF167_PA)
Type: Domain

This PA domain is found in ZNRF4 /RNF13/RNF167 from animals and RMR1-6 from Arabidopsis. These proteins contain a C3H2C3 RING finger and some of them are predicted to be membrane-anchored RING finger ubiquitin ligases . ZNRF4 is an ER-localized RING finger ubiquitin ligase and a regulator of calnexin stability and ER homeostasis . RNF13 is highly enriched in ER and serves as a critical mediator for facilitating ER stress-induced apoptosis through the activation of the IRE1alpha-TRAF2-JNK signaling pathway . RMR1 (also known as ReMembR-H2) is a sorting receptor involved in transport of storage proteins to protein storage vacuoles .

The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. It has been suggested that this domain forms a lid-like structure that covers the active site in active proteases, and is involved in protein recognition in vacuolar sorting receptors .
ABC transporter C family, six-transmembrane helical domain 1 (ABCC_6TM_D1)
Type: Domain

This entry represents the six-transmembrane domain 1 (TMD1) of the ABC transporters that belong to the ABCC subfamily . This TM subunit exhibits the type 3 ATP-binding cassette (ABC) exporter fold, which is characterised by 6 TM helices per subunit (domain), or a total of 12 TM helices for the complete transporter. The type 3 ABC exporters are found in both prokaryotes and eukaryotes, where they mediate the cellular secretion of toxic compounds, a various type of lipids and polypeptides .

ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily, which uses the hydrolysis of ATP to energise diverse biological systems. ABC transporters minimally consist of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These can be found on the same protein or on two different ones. Most ABC transporters function as a dimer and therefore are constituted of four domains, two ABC modules and two TMDs.

ABC transporters are involved in the export or import of a wide variety of substrates ranging from small ions to macromolecules. The major function of ABC import systems is to provide essential nutrients to bacteria. They are found only in prokaryotes and their four constitutive domains are usually encoded by independent polypeptides (two ABC proteins and two TMD proteins). Prokaryotic importers require additional extracytoplasmic binding proteins (one or more per systems) for function. In contrast, export systems are involved in the extrusion of noxious substances, the export of extracellular toxins and the targeting of membrane components. They are found in all living organisms and in general the TMD is fused to the ABC module in a variety of combinations. Some eukaryotic exporters encode the four domains on the same polypeptide chain .

The ATP-Binding Cassette (ABC) superfamily forms one of the largest of all protein families with a diversity of physiological functions . Several studies have shown that there is a correlation between the functional characterisation and the phylogenetic classification of the ABC cassette . More than 50 subfamilies have been described based on a phylogenetic and functional classification ; (for further information see
Transporter Classification Database
).
Trm3/ TARBP1, C-terminal (Trm3/TARBP1_C)
Type: Domain

This entry represents the C-terminal methyltransferase domain of TARBP1 and Trm3 .

Yeast tRNA (guanosine(18)-2'-O)-methyltransferase Trm3 catalyses the formation of 2'-O-methylguanosine at position 18 (Gm18) in various tRNAs . Trm3 is similar to C-terminal domain of TAR (HIV-1) RNA binding protein 1 (TARBP1), a protein binding to TAR, which functions as a RNA regulatory signal by forming a stable stem-loop structure to which transactivator protein Tat binds. The role of TARBP1 is believed to be to disengage RNA polymerase II from TAR during transcriptional elongation .
FANCM, DEAH-box helicase domain (FANCM_DEXDc)
Type: Domain

This entry represents the N-terminal domain of FANCM. It contains the ATP-binding region.

Fanconi anemia group M (FANCM) protein is a DNA-dependent ATPase component of the Fanconi anemia (FA) core complex . It is required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage . In complex with CENPS and CENPX, it binds double-stranded DNA (dsDNA), fork-structured DNA (fsDNA), and Holliday junction substrates. Its ATP-dependent DNA branch migration activity can process branched DNA structures such as a movable replication fork. This activity is strongly stimulated in the presence of CENPS and CENPX. In complex with FAAP24, it efficiently binds to single-strand DNA (ssDNA), splayed-arm DNA, and 3'-flap substrates . In vitro, on its own, it strongly binds ssDNA oligomers and weakly fsDNA, but does not bind to dsDNA . FANCM is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding .
SRC2/BAP, C2 domain (C2_SRC2/BAP)
Type: Domain

This is the C2 domain found in plant proteins, including SRC2 (Soybean genes Regulated by Cold 2) and BAP1/2 (BON1-associated protein 1/2), which are involved in defence responses . SRC2 is induced after pathogen infiltration and in cold conditions. Arabidopsis SRC2 homologue functions as a calcium-dependent activator of the NADPH oxidase AtRbohF, that mediates reactive oxygen species (ROS) production after cold induction. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding . BAP1/2 are negative regulators of cell death and defense responses, as they repress the activity of disease resistance (R) genes .
Ion transporter-like, CBS domain (Ion_transp-like_CBS)
Type: Domain

This CBS domain is found associated with CorC_HlyC domain and/or CNNM domain, domains that are related to metal ion transport. This domain consists of a CBS pair which is thought to play a regulatory role, although its exact function is not clear. This domain is found in highly conserved proteins that either have unknown function or are predicted to be hemolysins, exotoxins involved in lysis of red blood cells in vitro .
Exonuclease 1-like, PIN-like domain (PIN-like_EXO1)
Type: Domain

This is the PIN domain found in animal exonuclease-1 (EXO1) and its paralogue from yeasts, Din7. EXO1 is a 5'-3'-exonuclease that functions in DNA mismatch repair (MMR), double-strand break repair, replication, recombination and telomere integrity . It also possesses a flap-endonuclease activity , being a member of the Flap endonuclease-like (FEN-like) family, which are structure-specific endonucleases capable of cleaving single-stranded DNA or RNA at the bifurcated end of a base-paired duplex. DIN7 is involved in mitochondrial DNA repair and replication .

PIN domains belong to a large nuclease superfamily, which share a common core fold consisting of a three-layered α/β/α core motif with a central, parallel five-stranded β-sheet. Its active site, possess invariant acidic amino acid residues and binds one or more divalent metal ions .
HELLS, N-terminal (HELLS_N)
Type: Domain

HELLS (helicase, lymphoid specific, also known as Lsh or SMARCA6) is a major epigenetic regulator crucial for normal heterochromatin structure and function . HELLS is part of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding . This domain contains the ATP-binding region.
Isw1/2, N-terminal (Isw1/2_DEXHc)
Type: Domain

Nucleosome remodelling is an energy-dependent process that alters histone-DNA interactions within nucleosomes, thereby rendering nucleosomal DNA accessible to regulatory factors. The ATPases involved belong to the SWI2/SNF2 subfamily of DEAD/H-helicases, which contain a conserved ATPase domain characterised by seven motifs. Proteins within this family differ with regard to domain organisation, their associated proteins and the remodelling complex in which they reside.

The ATPase ISWI is a member of this family. ISWI can be divided into two regions: an N-terminal region that contains the SWI2/SNF2 ATPase domain, and a C-terminal region that is responsible for substrate recognition. The C-terminal region contains 12 α-helices and can be divided into three domains and a spacer region: a HAND domain (named because its 4-helical structure resembles an open hand), a SANT domain (c-Myb DNA-binding like), a spacer helix, and a SLIDE domain (SANT-like but with several insertions).

This entry represents the N-terminal domain of Isw1/2.
SMARCA1, N-terminal (SMARCA1_N)
Type: Domain

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 1 (SMARCA1, also called SNF2L) is a component of NURF (nucleosome-remodeling factor) and CERF (CECR2-containing-remodeling factor) complexes which promote the perturbation of chromatin structure in an ATP-dependent manner . SMARCA1 is a member of the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding . This domain contains the ATP-binding region.
DHX15, DEXH-box helicase domain (DHX15_DEXHc)
Type: Domain

DEAH-box helicase 15 (DHX15) is a pre-mRNA processing factor involved in disassembly of spliceosomes after the release of mature mRNA . DHX15 belongs to the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding .

This entry represents the DEXH-box helicase domain of DHX15. This domain contains the ATP-binding region.
IAA-amino acid hydrolase ILR1-like (ILR1-like_Hyd)
Type: Family

In higher plants, the growth regulator indole-3-acetic acid (IAA or auxin) is found both free and conjugated via amide bonding to a variety of amino acids and peptides, and via an ester linkage to carbohydrates. IAA-Asp conjugates are involved in homeostatic control, protection, storing and subsequent use of free IAA. IAA-Asp is also found in some plants as a unique intermediate for entering into IAA non-decarboxylative oxidative pathway. IAA amidohydrolases, which belong to the M20 family of peptidases, cleave the amide bond between the auxin and the conjugated amino acid to regulate IAA levels .

IAA-amino acid hydrolase ILR1 (IAA-LEUCINE RESISTANT 1) from Arabidopsis hydrolyses certain amino acid conjugates of IAA, including IAA-Phe, IAA-Leu and IAA-Tyr, although it can also use IAA-Ala, IAA-Gly, IAA-Met and IAA-Glu as substrates with lower efficiency, having no activity with IAA-Ile, IAA-1-O-beta-D-glucose or IAA-myo-inositol . ILL4, also known as IAR3, hydrolyses IAA-Ala, IAA-Asn, IAA-Cys, IAA-Glu, IAA-Met, IAA-Ser and IAA-Gly and has a lower efficiency with IAA-Phe, IAA-Leu and IAA-Val and no activity with IAA-Ile . ILL4 also hydrolyses amino acid conjugates of jasmonic acid and 12-hydroxy jasmonic acid .

This entry includes ILR1 and ILR1-like proteins (ILL) from Arabidopsis thaliana and Oryza sativa.
RF2-like transcription factor, bZIP domain (bZIP_RF2)
Type: Domain

This is the bZIP domain found in plant transcription factors with similarity to Oryza sativa RF2a and RF2b, which are important for plant development. RF2a and b interact, as homodimers or heterodimers, with each other, and activate transcription from the RTBV (rice tungro bacilliform virus) promoter, which is regulated by sequence-specific DNA-binding proteins that bind to the essential cis element BoxII. They show differences in binding affinities to BoxII, expression patterns in different rice organs, and subcellular localisation. Transgenic rice with increased RF2a and RF2b display increased resistance to rice tungro disease (RTD) with no impact on plant development .

bZIP domains from Arabidopsis have been classified into 11 groups (groups A-I and S), the ones included in this entry belong to group I such as VIP1 or PosF21 (also known as bZIP transcription factor 59) .

bZIP factors act in networks of homo and heterodimers in the regulation of a diverse set of cellular processes. The bZIP structural motif contains a basic region and a leucine zipper, composed of α helices with leucine residues 7 amino acids apart, which stabilize dimerization with a parallel leucine zipper domain. Dimerization of leucine zippers creates a pair of the adjacent basic regions that bind DNA and undergo conformational change. Dimerization occurs in a specific and predictable manner resulting in hundreds of dimers having unique effects on transcription .
Trafficking protein particle complex subunit 2-like (TRAPPC2L)
Type: Family

The function of TRAPPC2L (trafficking protein particle complex subunit 2-like) is not known, but evidence suggests that it is part of the TRAPP II complex required for distinct tethering events at Golgi membranes, playing a role in vesicular transport from endoplasmic reticulum to Golgi . Mutations in the TRAPPC2L gene cause an autosomal recessive disease characterised by encephalopathy with episodic rhabdomyolysis .
DHX8/ Prp22, DEXH-box helicase domain (DHX8/Prp22_DEXHc)
Type: Domain

This entry represents the ATP-binding domain found in DHX8 from animals and Prp22 from yeasts.

DHX8 and its homologue, Prp22, act late in the splicing of pre-mRNA and mediates the release of the spliced mRNA from spliceosomes . They belong to the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding .
Ded1/Dbp1, DEAD-box helicase domain (Ded1/Dbp1_DEADc)
Type: Domain

This entry represents the DEAD/DEAH box helicase domain found in Ded1 and its paralog, Dbp1, from yeasts, which contains the ATP-binding region. Ded1 and Dbp1 are ATP-dependent DEAD-box RNA helicases involved in eIF4F-dependent 48S translation preinitiation complex (PIC) assembly . This entry also includes Drosophila melanogaster Vasa, which is essential for development .
DDX52/Rok1, DEAD-box helicase domain (DDX52/Rok1_DEADc)
Type: Domain

This entry represents the DEAD-box helicase domain found in DDX52 from animals and Rok1 from yeasts. This domain contains the ATP-binding region. Rok1 is an RNA helicase involved in pre-rRNA processing and in control of cell cycle progression . In humans, DDX52 is ubiquitously expressed in testis, endometrium, and other tissues . DDX52 from Drosophila has been identified as part of a translational control module, also containing pths/DDX47 and ath/DHX33, which coordinates germline stem cell differentiation with ribosome biogenesis during oogenesis. This module allows for coregulation of ribosomal proteins and non1/GTPBP4, a p53 repressor, preventing p53 stabilization, cell cycle arrest and loss of stem cell differentiation .
DDX47/Rrp3, DEAD-box helicase domain (DDX47/Rrp3_DEADc)
Type: Domain

This entry represents the DEAD-box helicase domain found in DDX47 from animals and Rrp3 from yeasts. This domain contains the ATP-binding region. Rrp3 is involved in rRNA processing . DDX47 (also called E4-DEAD box protein) can shuttle between the nucleus and the cytoplasm, and has an RNA-independent ATPase activity . DDX47 is involved in ribosome biogenesis .