SII-SWORD/CoKE huggingface dataset:
PurR, sensor domain (PurR_sensor_dom)
Type: Domain

This entry represents the sensor domain found at the C-terminal in members of the PurR family. Dimerisation sites are present in the C-terminal domain, and binding of corepressors is cooperative . This domain is also present in ribose operon repressor proteins.

The purR gene encodes a transcriptional repressor of the HTH-type, which is responsible for controlling the syntehsis of enzymes involved in purine biosynthesis . PurR is dimeric and consists of an N-terminal domain for DNA binding and a C-terminal domain that is responsible for corepressor (hypoxanthine and guanine) binding.

The LacI/GalR family, which includes the LacL superfamily, represents one of the largest and most diverse groups of bacterial transcriptional regulators. These proteins play crucial roles in regulating various aspects of bacterial metabolism, particularly carbohydrate utilisation . Characterised by a conserved N-terminal helix-turn-helix (HTH) DNA-binding motif

and a C-terminal regulatory domain that binds effector molecules

, members of this family can function as both repressors and activators, though most act as repressors . They typically respond to specific effector molecules, often sugars or metabolites, which modulate their DNA-binding affinity and consequently their regulatory activity. This allows bacteria to fine-tune gene expression in response to environmental conditions and available carbon sources . Some well-characterised members of this family include:

LacI (lactose operon repressor) in Escherichia coli

GalR (galactose operon repressor) in Escherichia coli

PurR (purine biosynthesis repressor) in various bacteria

CcpA (catabolite control protein A) in Gram-positive bacteria

FruR (fructose repressor) in Enterobacteriaceae
SRB8, ARM-like domain (ARM_SRB8)
Type: Domain

This entry represents an ARM-like domain found in the Mediator of RNA polymerase II transcription subunit 12/SRB8 proteins from fungi. These proteins are components of the Mediator complex, which is a coactivator involved in the regulated transcription of nearly all RNA polymerase II- dependent genes . ARM-like domains typically form a right-handed superhelix of α-helices and are often involved in protein-protein interactions.
Transcription initiation factor TFIID subunit 2, Ig-like domain (Ig-like_TAF2)
Type: Domain

This entry represents the immunoglobulin-like (Ig-like) domain found in transcription factor TFIID subunit 2 (TAF2) from eukaryotes. This domain is inserted between subdomains 2 and 4 of the aminopeptidase-like region of TAF2 . The aminopeptidase-like region of TAF2 is involved in downstream promoter recognition and plays an important role in transcription initiation. The specific function of this Ig-like domain within the context of TAF2's role is not yet fully characterised.

In yeast, TAF2 functions as a component of the DNA-binding general transcription factor complex TFIID. Its binding to a promoter, whether or not it contains a TATA element, represents the initial step in pre-initiation complex (PIC) formation. TAF2 plays a crucial role in regulating gene expression by RNA polymerase II through various mechanisms, including interaction with transcription activators, recognition and selectivity of core promoters, interactions with TFIIA and TFIIB, chromatin modification via histone acetylation by TAF1, facilitation of DNA unwinding, and initiation of transcription. In mammals, the TAF2 basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription . It recognises and binds to promoters with or without a TATA box via its TBP subunit (TATA-box-binding protein), promoting the assembly of the PIC . The complex comprises TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12, and TAF13 . TAF2, in particular, forms a promoter DNA-binding subcomplex with TAF7 and TAF1 .
Talin-1/2, VBS2 domain (Talin1/2_VBS2)
Type: Domain

This entry represents the Talin VBS2 domain. Talin is an adaptor protein that activates integrin family of cell adhesion molecules and couples them to the actin cytoskeleton. The integrin activation is known to involve binding of the talin FERM domain to membrane proximal sequences in the cytoplasmic domain of the integrin beta-subunit. The domain represented by this entry folds into a four-helical up-and-down bundle and contains the VBS2 vinculin binding site . This domain interacts with the vinculin head and this interaction involves a major structural change in the talin fragment, including unfolding of one of its helices, making the VBS accessible to vinculin .
TANGO6, N-terminal domain (TANGO6_N)
Type: Domain

This domain is found in the Transport and Golgi organisation protein 6 homolog (TANGO6) and related proteins. It is predicted to fold into an array of α-helices.

TANGO6 associates with COPI vesicles. Cytoplasmic TANGO6 tethers to COPI vesicle via a signal anchor and two transmembrane domains. Its N- and C-terminal cytoplasmic domains capture RNA polymerase II subunit B (RPB) 2 in the cis-Golgi during the G1 phase . TANGO6 is also observed in the nucleus where it enters via the COPI-SNARE-ER pathway . The nuclear entry of TANGO6 is assisted by KPNB1.
TELO2, ARM repeat domain (TELO2_ARM)
Type: Domain

This entry represents an ARM repeat domain found in TELO2 proteins that forms part of the TTT (TELO2-TTI1-TTI2) complex. Recent cryo-EM structures show that this domain adopts an elongated α-helical solenoid structure typical of ARM repeats . The domain mediates key interactions with TTI1 within the TTT complex, which functions as an adaptor complex for the R2TP chaperone system in the stabilisation of phosphatidylinositol 3-kinase-related protein kinases (PIKKs). The TELO2 ARM domain provides a binding platform for TTI1 while remaining flexibly connected to the C-terminal domain via an intrinsically disordered linker.

TELO2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling . In vitro the protein binds to telomeric DNA repeats.
Meiotically up-regulated Mug190 protein, third C2 domain (C2_Mug190_3rd)
Type: Domain

This entry represents the third C2 domain found in the meiotically up-regulated protein Mug190 (MU190) from Schizosaccharomyces pombe (

). C2 domains typically function as calcium-dependent membrane-targeting modules. This specific C2 domain is found as part of a multi-C2 domain protein that is expressed during meiosis, though its precise role in meiotic regulation remains to be determined. The domain appears to be specific to fungi, particularly found in ascomycetes.
Thrombomodulin-like domain (THBD)
Type: Domain

This domain is found in human Thrombomodulin (THBD) and similar animal proteins. THBD is an endothelial cell receptor that plays a critical role in regulating several physiological processes including hemostasis, coagulation, fibrinolysis, inflammation, and angiogenesis. This domain adopts a mainly β configuration.

This entry also includes Endoliasin, a cell surface glycoprotein that plays diverse roles in biological processes including angiogenesis, immune response modulation, and tissue remodeling. It enhances pericyte proliferation through positive modulation of PDGF receptor signaling and acts as a scaffold for factor X, facilitating coagulation activation via the TF-factor VIIa complex. Endoliasin interacts with the insulin receptor (INSR), inhibiting its autophosphorylation in response to insulin, while also regulating inflammatory responses in macrophages by promoting proinflammatory cytokine production. Notably, it exhibits differential effects on cell proliferation, negatively regulating T-cell proliferation while enhancing proliferation in stromal cells .
Transmembrane protein 225 domain (TM225_dom)
Type: Domain

This domain is found in human Transmembrane protein 225 (TM225), 225B (TM225B) and similar animal proteins. This domain is predicted to adopt an all-α configuration.

Transmembrane protein 225 (TM225) is specifically expressed in testis . It may be involved in the differentiation and function of spermatozoa through the regulation of PP1gamma2 activity .
TmcB/TmcC, TPR repeats (TPR_TmcB/C)
Type: Domain

This is a region of tetratricopeptide (TPR)-like repeats found in Tiny macrocysts protein B and C from Dictyostelium discoideum (TmcB and TmcC) and similar eukaryotic proteins. TmcB is a regulator of the cAMP signalling pathway specific to sexual development. It controls the levels of external cAMP by regulating the expression of phosphodiesterase PdsA and its inhibitor PdiA. Knockout mutants of tmcC gene were indistinguishable from the wild type cells with respect to the cAMP response, suggesting that this gene is relevant to other processes .
TNF receptor-like domain (TNFR_nem)
Type: Domain

This entry represents a TNF receptor-like domain found widely distributed throughout nematodes, including both Chromadorea and Enoplea. The domain appears in multiple copies in transmembrane proteins involved in cell adhesion and matrix interactions, such as MUP-4 and MUA-3 in C. elegans. The domain is found across multiple nematode clades including Trichinellida, Rhabditina, Tylenchina, Spirurina, and Dorylaimia.
Toc75-like, POTRA domain (POTRA1_3_Toc75)
Type: Domain

This entry represents the first and third POTRA domains of Toc75 from Arabidopsis thaliana and similar plant proteins. The first and third POTRA domains fold into one another, each containing the conserved core β-α-α-β-β fold seen in other POTRA domains .

Toc75 is an essential protein required for the import of protein precursors into chloroplasts. Toc75 has three POTRA domains, represented by

and

, which together adopt a bent L-shaped conformation.
Toc75-like, second POTRA domain (POTRA2_Toc75)
Type: Domain

This entry represents the second POTRA domain of Toc75 from Arabidopsis thaliana and similar plant proteins. The second POTRA domain contains a 40-residue insertion that folds into an elongated extra α-helix and loop, producing an overall β-α-α-β-β fold .

Toc75 is an essential protein required for the import of protein precursors into chloroplasts. Toc75 has three POTRA domains, represented by

and

, which together adopt a bent L-shaped conformation.
ZNF592-like, C2H2 zinc finger (Znf-C2H2_ZNF592)
Type: Domain

This C2H2 zinc finger domain is found in a group of zinc-finger proteins such as ZN532, ZN687, ZN592 and related proteins which are probably involved in transcriptional regulation. A missense mutation in ZNF592 was found associated with CAMOS (Cerebellar Ataxia with Mental retardation, Optic atrophy and Skin abnormalities) syndrome .
ZFAND2A/B-like, C2H2 zinc finger (Znf-C2H2_ZFAND2A/B)
Type: Domain

This C2H2 zinc finger is found in the stress-associated proteins AN1-type zinc finger protein 2A and 2B (ZFAND2A and ZFAND2B), and their plant homologues SAP11/13/16. The precise function of these proteins is unknown. The human ZFAND2A/AIRAP was identified as a stress-regulated survival factor implicated in the stabilization of the antiapoptotic protein cIAP2 in melanoma .
ZFAND1-like, ubiquitin-like domain (UBL_ZFAND1-like)
Type: Domain

This entry represents the ubiquitin-like domain (UBL) found in ZFAND1, CDC48-associated ubiquitin-like/zinc finger protein 1 and similar proteins. The domain adopts a β-grasp fold similar to ubiquitin and other UBLs, but contains an additional N-terminal helix. The UBL domain is the primary interaction site with p97/VCP and is essential for stress granule clearance. The domain shows low sequence identity with other UBLs despite structural similarity. Crystal and NMR structures reveal that the N-terminal helix adopts different conformations in solution versus crystal states .
YfjL-like, N-terminal domain (YfjL_N)
Type: Domain

This entry represents the N-terminal domain of the uncharacterised protein YfjL from Bacillus subtilis and similar sequences from Bacillota.
YxzE-like putative bacteriocin (YxzE)
Type: Family

This entry represents a putative bacteriocin family related to the YxzE protein found in B. subtilis. This entry contains both the leader peptide and the putative bacteriocin sequence.
WD repeat-containing protein 35, TPR repeats (TPR_WDR35)
Type: Repeat

This region of tetratricopeptide (TPR)-like repeats is found in human WD repeat-containing protein 35 (WDR35), a component of the IFT complex A (IFT-A), which is involved in ciliogenesis and ciliary protein trafficking. Members of this entry are mainly found in animals.
WDGH domain (WDGH)
Type: Domain

This domain is found in uncharacterised proteins from phages and bacteriophages. It is predicted to adopt an unique α/β structure composed of a central mixed four-stranded β-sheet and α-helices packed on one side of it. Members of this entry contain a highly conserved WDGH sequence motif after which it was named.
Volactin (Volactin)
Type: Family

This entry represents volcatin (

), an actin homologue that plays a role in disk-shape morphogenesis .
Up-regulator of cell proliferation-like domain (URGCP)
Type: Domain

This domain is found in the human URGCP. This domain is also found in human Interferon-induced very large GTPase 1 and caspase recruitment domain-containing protein 6. This domain is predicted to adopt an α-β structure.

URGCP, the up-regulator of cell proliferation, may be involved in cell cycle progression through the regulation of cyclin D1 expression. This protein is thought to play an important role in the development of gastric cancer .
TRPM-like domain (TRPM-like)
Type: Domain

This domain is found in human transient receptor potential cation channel subfamily M member 1-8 (TRPM 1-8) and similar proteins. This domain is found associated with [

] and adopts an all-α configuration. This entry also includes protein ced-11 of Caenorhabditis elegans, which plays a major role in programmed cell death .

Transient receptor potential cation channel subfamily M (TRPM) is a group of cation-permeable channels within the larger TRP superfamily. The TRPM subfamily consists of eight members: TRPM1-TRPM8. TRPMs have been involved in several physiological and pathological processes, including cellular proliferation, temperature sensing, vascular development, cancer progression, neurological diseases, endothelial dysfunction, inflammation, type II diabetes, and many other processes. TRPM channels possess a large cytosolic domain consisting of 732 and 1611 aa for each subunit, making them the largest members of the TRP superfamily .
Transmembrane protein PVRIG, immunoglobulin-like domain (Ig_PVRIG)
Type: Domain

This domain is found towards the N-terminal end of PVRIG and similar animal proteins.

The human transmembrane protein (PVRIG) is a cell surface receptor for NECTIN2. It may act as a coinhibitory receptor that suppresses T-cell receptor-mediated signals . It competes with CD226 to bind to CD112
USP32, N-terminal domain (USP32_N)
Type: Domain

This domain is found at the N-terminal of USP32 and related eukaryotic proteins. The domain represented by this entry has detectable similarity to EF-hand domains, and it is predicted to adopt similar structure. It lacks the Ca2+ coordinating residues.

Ubiquitin carboxyl-terminal hydrolase 32 (USP32) functions as a deubiquitinase that can remove conjugated ubiquitin from target proteins, such as RAB7A and LAMTOR1 . It acts as a positive regulator of the mTORC1 signalling by mediating deubiquitination of LAMTOR1. In Caenorhabditis elegans, USP cyk-3 (USP32 orthologue) is involved in the formation of a functional microtubule organising centre provided by the male pronucleus .
VG15 protein (VG15)
Type: Family

This entry represents the Gene 15 protein (VG15) from Mycobacterium phages D29 and L5 and related proteins from tailed bacteriophages. This family is probably distantly related to [

] and likely represents phage capsid proteins. Members of this family contain two pairs of highly conserved cysteine residues that may constitute a metal-binding site .
Endolysin-like domain (ELLD)
Type: Domain

This domain is found in a group of uncharacterised phage and bacterial proteins. It is related to domains that are members of the NlpC/P60 and Bacteriophage peptidoglycan hydrolase families of papain-like cysteine proteases, [

] and [

], respectively. This domain is probably catalytically active as it contains highly conserved cysteine and histidine residues. Some members of this entry are circularly permuted, and their N-terminal two β-strands occupy the position of the C-terminal strands in other members.
Vitelline envelope sperm lysin receptor, C-terminal domain (VERL_C)
Type: Domain

This entry represents the C-terminal domain of VERL and related proteins, which is related to the zona pellucida domain in animals [

].

VERL (Vitelline envelope sperm lysin receptor) is a giant unbranched glycoprotein comprising 30% of the vitelline envelope. It functions as a species-specific receptor for the sperm protein lysin; prevents fertilisation by sperm from other species .
UBP8/5-like, ubiquitin-like domain (Ubiquitin_UBP8/5)
Type: Domain

This domain is found in UBP5 and UBP8 from Arabidopsis thaliana and similar plant proteins. This domain is often found associated with [

].

Ubiquitin carboxyl-terminal hydrolases 5 and 8 (UBP5 and UBP8) recognise and hydrolyse the peptide bond at the C-terminal Gly of ubiquitin (

) . In Arabidopsis thaliana, UBP5 is involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins . In Oryza sativa subsp. japonica, UBP5 does not possess deubiquitinating enzyme activity in vitro .
ZNFX1 domain (ZNFX1)
Type: Domain

This domain is found in Znfx1 proteins in animals or hrr1 in fission yeast. This domain is often found associated with [

] and is predicted to adopt a mainly-β configuration.

Znfx1, or NFX1-type zinc finger-containing protein 1, are RNA-binding proteins involved in antiviral responses and immunity against certain bacteriaproteins . They act as double-stranded RNA sensors, recognising viral RNA and interacting with mitochondrial antiviral-signalling protein (MAVS) to initiate the type I interferon response .
Probable ubiquitin-like-specific protease 2A/B, PH domain (ULP2A/B_PH)
Type: Domain

This entry represents a pleckstrin homology (PH) domain found in the probable ubiquitin-like-specific protease 2A and 2B from Arabidopsis thaliana and similar plant proteins. These proteins contain a C-terminal Peptidase_C48 catalytic domain. The PH domain is found either before or after the peptidase domain in different proteins, suggesting it may have been subject to domain rearrangement during evolution.
Trematode, PH-like domain (PH_trem)
Type: Domain

This entry represents an uncharacterised family of PH-like domains found in trematode proteins.

Trematodes are a class of flatworms. They are obligate internal parasites with a complex life cycle requiring at least two hosts .
Connectase MJ0548-like, C-terminal domain (MJ0548_C)
Type: Domain

This domain is found at the C-terminal end of Connectase MJ0548 from Methanocaldococcus jannaschii and similar archaeal sequences. This protein is a sequence-specific protein ligase. MJ0548 is a distant, monomeric proteasome homologue which connects proteins in a sequence-specific manner. It shows a mainly β structure and one α-helix .
Pre-tape measure protein (Pre_tape_measure)
Type: Family

This entry represents a conserved region found in bacteriophage pre-tape measure proteins, located just upstream of the tape measure protein. The region is typically around 140-160 amino acids in length. In some phages, the pre-tape measure protein is produced by a programmed translational frameshift .
Prospore membrane adapter protein SPO71, PH domain (PH_SPO71)
Type: Domain

This domain is found in the budding yeast prospore membrane adapter protein SPO71, including its orthologue Mug56 from fission yeasts. The domain represented by this entry has weak sequence similarity to PH domains, and it is predicted to adopt a similar structure. SPO71 is predicted to contain a tandem of three PH domains. This domain is the first in the tandem.

SPO71 is involved in the recruitment of the lipid transfer protein VPS13 to the prospore membrane during sporulation . It plays an important role in the prospore membrane development . MUG56 is required for meiosis .
Protein kinase SIK1/2/3, UBA domain (UBA_SIK1/2/3)
Type: Domain

This domain is found in the human Serine/threonine-protein kinase (salt-inducible kinase) SIK1, SIK2, SIK3 and related proteins, including Sperm motility kinase Y. The domain represented by this entry has a significant sequence similarity to UBA domains, and it is predicted to adopt a similar structure consisting of a three-helical bundle.

Salt-inducible kinases (SIKs) are serine/threonine protein kinases that regulate gene expression in response to extracellular cues, particularly those that increase intracellular cAMP levels . The characterised salt-inducible kinases (SIKs) are SIK1, SIK2, and SIK3.

SIK1 is a regulator of p53-dependent anoikis. Inactivation of SIK1 compromised p53 function in anoikis and allowed cells to grow in an anchorage-independent manner .

SIK2 was identified as key upstream regulators of Carbohydrate-responsive element-binding protein (ChREBP) activity. SIK2 inhibits p300 HAT activity by direct phosphorylation, which results in decreased ChREBP-mediated lipogenesis in hepatocytes .

SIK3 is a positive regulator of mTOR signaling that functions by triggering the degradation of DEPTOR, an mTOR inhibitor. This protein is involved in the dynamic regulation of mTOR signaling in chondrocyte differentiation during skeletogenesis .
Zinc finger, Tenuivirus (Znf_Tenuivirus)
Type: Domain

This entry represents a zinc finger domain found in proteins from tenuivirus, such as P3, which is a plant virus.
Type VI secretion system effector TseH-like (TseH)
Type: Domain

This domain is found in the Type VI secretion system effector TseH and related bacterial proteins. TseH structure is significantly similar to papain-like proteases, including the conserved active site architecture (

). This domain is standalone or combined with [

].

V. cholerae T6SS effector TseH is a PAAR-dependent species-specific effector. It is highly toxic to Aeromonas and Edwardsiella species, bacteria that V. cholerae encounters in natural environments or common hosts .
Type I Thoeris inhibitor Tad3 (Tad3)
Type: Family

This entry represents the Tad3 family of phage proteins that inhibit the bacterial Type I Thoeris defence system. Tad3 forms a homodimer that binds two ThsB proteins, blocking their active sites by inserting a conserved serine residue (S48) that forms a hydrogen bond with the ThsB catalytic residue E85. This prevents the production of the immune signalling molecule gcADPR. The structure has been solved in complex with ThsB at 1.8A resolution (

) The protein contains N-terminal helices that mediate homodimer formation and C-terminal regions that make extensive contacts with ThsB . This entry also includes a group of uncharacterised prokaryotic proteins.
Myxosortase MrtX (CAAX_MXAN_2755)
Type: Family

Members of this family, such as the founding protein (MrtX, MXAN_2755) from Myxococcus xanthus (

), are restricted to the taxonomic order Myxococcales, within the Deltaproteobacteria. The N-terminal region is a domain unique to this family. The C-terminal domain is a CPBP family (Rce1-like) intramembrane glutamic endoprotease domain (

), related to eukaryotic CAAX endopeptidases, which cleave at the site of a prenylated Cys residue in a C-terminal motif involved in protein sorting.

MrtX is responsible for the C-terminal cleavage and cell surface anchoring of TraA, a prototypic cell surface receptor MrtX . Thus, this family represents a group of sorting enzymes that enable cell surface localisation of MYXO-CTERM proteins and is involved in protein sorting in prokaryotes .