SII-SWORD/CoKE huggingface dataset:
PGP phosphatase, mitochondrial/chloroplastic (PGP_Pase)
Type: Family

Mitochondrial phosphatidylglycerophosphatase (PGP phosphatase) (

) dephosphorylates phosphatidylglycerolphosphate to generate phosphatidylglycerol in cardiolipin biosynthesis. Cardiolipin is a unique dimeric phosphoglycerolipid predominantly present in mitochondrial membranes. The inverted phosphatase motif includes the highly conserved DKD triad . In Saccharomyces cerevisiae, Gep4 is required for the stability of respiratory chain supercomplexes and for growth at elevated temperature, in presence of ethidium bromide or in absence of prohibitins .

Chloroplastic phosphatidylglycerophosphate phosphatase is involved in the biosynthesis of phosphatidylglycerol (PG), a phosphoglycerolipid present in chloroplastic thylakoid membranes and has a photosynthetic function .
Troponin T (TNNT)
Type: Family

The troponin (Tn) complex regulates calcium-induced muscle contraction. Tn contains three subunits, Ca2+ binding (TnC), inhibitory (TnI), and tropomyosin binding (TnT), which is required for Ca(2+)-mediated activation of actomyosin ATPase activity . Three different troponin T genes that encode tissue-specific isoforms of subunit T have been found in mammals and birds, encoding cardiac (TNNT2), slow (TNNT1), and fast (TNNT3) skeletal muscle TnT isoforms .

Mutations of the TNNT1gene cause nemaline myopathy , while mutations of the TNNT2 gene cause familial hypertrophic cardiomyopathy , and mutations of the TNNT3 gene cause Arthrogryposis, distal, 2B2 (DA2B2) .
E3 ubiquitin-protein ligase Trim36, RING finger, HC subclass (Trim36_HC-RING)
Type: Domain

The tripartite motif-containing protein (Trim) family is defined by the presence of a common domain structure composed of a RING finger, a B-box, and a coiled-coil motif . Trim36 is a E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. It interacts with centromere protein-H, one of the kinetochore proteins and is involved in chromosome segregation and cell cycle regulation. This protein has been associated with anencephaly . It may play a role in the acrosome reaction and fertilisation .

This entry represents the HC-RING finger found at the N-terminal of Trim36.
Midline-1, B-box-type 2 zinc finger (MID1_Bbox2_Zfn)
Type: Domain

MID1 is associated with microtubules throughout the cell cycle, co-localising with cytoplasmic fibres in interphase and with the mitotic spindle and midbodies during mitosis and cytokinesis . It has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination .

This entry represents the B-box-type 2 (Bbox2) zinc finger of MID1, which is characterised by a CHC3H2 zinc-binding consensus motif .
Topless family (Topless_fam)
Type: Family

Protein Topless is a plant transcriptional co-repressor. It may repress the expression of root-promoting genes in the top half of the embryo to allow proper differentiation of the shoot pole during the transition stage of embryogenesis . This entry represents Topless and related proteins belonging to the same family.
Microtubule-associated protein 1A/1B light chain 3C (MAP1A/MAP1B_LC3C)
Type: Family

Autophagy-related protein LC3C (also known as microtubule-associated proteins 1A/1B light chain 3C) is a member of the ATG8 family, LC3 subfamily . It is an ubiquitin-like modifier that plays a crucial role in antibacterial autophagy (xenophagy) through the selective binding of CALCOCO2 . LC3C recruites all ATG8 family members to infecting bacteria such as Salmonella typhimurium .
Probable tubulin-tyrosine ligase (TTL)
Type: Family

This entry represents a group of probable tubulin-tyrosine ligases from fungi, including Pby1 from budding yeast . Tubulin--tyrosine ligase catalyses the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin .
Tubulin--tyrosine ligase-like protein 12 (TTLL12)
Type: Family

Tubulin tyrosine ligase-like 12 (TTLL2) is a member of the tubulin tyrosine ligase (TTL) group, although its precise function remains unclear. TTLL2 contains both SET-like and TTL-like domains, suggesting potential involvement in histone methylation and tubulin tyrosine ligase activities . However, it lacks catalytic activity related to tubulin or histone modification and is instead believed to play a regulatory role in these processes. TTL proteins more broadly are implicated in the negative regulation of tubulin post-translational modifications . The SET-like domain of TTLL2 is a divergent variant of the canonical SET domain; while it retains structural features of functional SET domains, it lacks the key residues necessary for histone lysine methyltransferase activity. Rather than enzymatic function, this domain is thought to exert non-catalytic effects, possibly influencing microtubule dynamics and stability .
Protein polyglycylase TTLL10 (TTLL10)
Type: Family

TTLL10 is a polyglycylase, which modifies both tubulin and non-tubulin proteins, generating side chains of glycine on the γ-carboxyl groups of specific glutamate residues of target proteins . It polyglycylates alpha tubulin and beta tubulin, but is not able to initiate glycylation and only has activity toward monoglycylated tubulin . It has the ability to polyglycylate non-tubulin proteins such as NAP1; in this case it can initiate glycylation and does not require preliminary monoglycylation by another glycylase .

This family also includes

, which is inactive .
Ovo-like (Ovo-like)
Type: Family

Protein ovo from Drosophila melanogaster is required for the survival and differentiation of female germline cells . Ovo plays a role in germline sex determination . It also has a somatic role regulating denticle formation and initiating cytoskeletal remodeling during epidermal differentiation . The different isoforms act antagonistically to each other having transcriptional repressor or activator activity .

Ovo-like proteins are members of the zinc finger protein family and serve as transcription factors to regulate gene expression in various differentiation processes . Three different OVOL genes (OVOL1-3) have been identified. Ovo-like 1 in involved in spermatogenesis in mice .
Dynactin subunit 6 (DCTN6)
Type: Family

Dynactin is a complex that binds to cytoplasmic dynein and is a required activator for cytoplasmic dynein-mediated vesicular transport. Dynactin localises to the cleavage furrow and to the midbodies of dividing cells, suggesting that it may function in cytokinesis . This entry represents the subunit6 (DCTN6) of the Dynactin complex. DCTN6 is critical for dynein-mediated early endosome movement but not for dynein-mediated nuclear distribution .
Bacterial Pleckstrin homology domain-related (Bacterial_PH-related)
Type: Domain

This domain is found in proteins with unknown function and appears to be related to bacterial Pleckstrin homology (PH) domain (

) . It was formerly known as DUF2679.
Structure-specific endonuclease subunit Slx4, ascomycetes (Slx4_ascomycetes)
Type: Family

The Slx4 protein is an endonuclease involved in processing DNA. In Saccharomyces cerevisiae, Slx4 forms complex with Slx1 that acts as a nuclease on branched DNA substrates, particularly simple-Y, 5'-flap, or replication fork structures by cleaving the strand bearing the 5' non-homologous arm at the branch junction and thus generating ligatable nicked products from 5'-flap or replication fork substrates . It is also involved in interstrand cross-link repair and in Rad1/Rad10-dependent processing of recombination intermediates.
UvrD-like helicase C-terminal domain (UvrD-like_helicase_C)
Type: Domain

This domain is found at the C terminus of a wide variety of helicase enzymes. This domain has an AAA-like structural fold.
Nse4/EID family (Nse4/EID)
Type: Family

Proteins in the NSE4/EID (Non-structural maintenance of chromosomes element 4/EP300-interacting inhibitor of differentiation 3) family are components of the Smc5/6 complex that is involved in repair of DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination and mediates sumoylation of shelterin complex (telosome) components . In human, it acts as a repressor of nuclear receptor-dependent transcription possibly by interfering with CREBBP-dependent coactivation. It may function as a coinhibitor of other CREBBP/EP300-dependent transcription factors .

Interestingly, there is a single NSE4 gene in most eukaryotes up to non-placental mammals while there are several NSE4/EID copies in placental mammals . In humans, there are two NSE4 proteins, NSE4a and NSE4b/EID3. They contain both N and C-terminal kleisin domains. Their N-terminal domain binds to SMC6 neck and bridges it to the SMC5 head and to the Nse3 (another SMC5-6 complex subunit) pocket , which seems to increased the stability of the ATP-free SMC5/6 complex.
Alpha/beta-hydrolase, catalytic domain (Alpha/beta-hydrolase_catalytic)
Type: Domain

This entry represents the C-terminal domain of a novel family of proteins with and alpha/beta hydrolase fold which may function as lipases . This domain includes the catalytic triad critical for hydrolysis (S, D, H) and the GXSXG sequence motif which is a characteristic of these enzymes .
Alpha/beta-hydrolase, N-terminal domain (Alpha/beta-hydrolase_N_dom)
Type: Domain

This is the N-terminal transmembrane domain of a family of α/β hydrolases which may function as lipases. The C-terminal domain

is the catalytic domain .
Syndecan/Neurexin domain (Syndecan/Neurexin_dom)
Type: Domain

Syndecans are multifunctional transmembrane heparan sulphate bearing cell surface receptors .

Structurally, these proteins consist of four separate domains:

A signal sequence;

An extracellular domain (ectodomain) of variable length whose sequence is not evolutionary conserved in the various forms of syndecans. The ectodomain contains the sites of attachment of the heparan sulphate glycosaminoglycan side chains;

A transmembrane region;

A highly conserved cytoplasmic domain of about 30 to 35 residues, which could interact with cytoskeletal proteins.

This entry represents the syndecans cytoplasmic domain . The domain is also found in neurexins, which are neuronal cell surface proteins that may be involved in cell recognition and cell adhesion.
S-adenosylmethionine synthase (AdoMet_synthase_2_family)
Type: Family

This family consists of several archaebacterial S-adenosylmethionine synthetase C (AdoMet synthetase or MAT) (

). S-Adenosylmethionine (AdoMet) occupies a central role in the metabolism of all cells. The biological roles of AdoMet include acting as the primary methyl group donor, as a precursor to the polyamines, and as a progenitor of a 5'-deoxyadenosyl radical. S-Adenosylmethionine synthetase catalyses the only known route of AdoMet biosynthesis. The synthetic process occurs in a unique reaction in which the complete triphosphate chain is displaced from ATP and a sulfonium ion formed. MATs from various organisms contain ~400-amino acid polypeptide chains .
Galactosyltransferase, C-terminal (Galactosyl_T_C)
Type: Domain

This is the C-terminal domain of a family of galactosyltransferases with three related galactosyltransferases activities, all three of which are possessed by one sequence in some cases: N-acetyllactosamine synthase (

), beta-N-acetylglucosaminyl-glycopeptide beta-1,4- galactosyltransferase (

), and lactose synthase (

). Note that N-acetyllactosamine synthase is a component of Lactose synthase along with alpha-lactalbumin; in the absence of alpha-lactalbumin (

) is the catalysed reaction . Proteins containing this domain include beta-1,4-galactosyltransferases and N-acetylgalactosaminyltransferases.
tRNase Z endonuclease (tRNase_Z_dom)
Type: Domain

This domain is found in the RNase Z enzymes, which are closely related structurally to the Lactamase B family members. tRNase Z (ribonuclease Z) is the endonuclease that is involved in tRNA 3'-end maturation through removal of the 3'-trailer sequences from tRNA precursors. The fission yeast Schizosaccharomyces pombe contains two candidate tRNase Zs encoded by two essential genes. The first, Trz1, is targeted to the nucleus and has an SV40 nuclear localisation signal at its N terminus, consisting of four consecutive arginine and lysine residues between residues 208 and 211 (KKRK) that is critical for the NLS function. The second, Trz2, is targeted to the mitochondria, with an N-terminal mitochondrial targeting signal within the first 38 residues .
CASTOR, ACT domain (CASTOR_ACT_dom)
Type: Domain

The ACT domain is a structural motif of 70-90 amino acids that functions in the control of metabolism, solute transport and signal transduction. They are thus found in a variety of different proteins in a variety of different arrangements . In mammalian phenylalanine hydroxylase the domain forms no contacts but promotes an allosteric effect despite the apparent lack of ligand binding .

This ACT domain is found in CASTOR proteins

and C-terminal in some aspartate kinases.
OTT_1508-like deaminase (OTT_1508_deam-like)
Type: Family

A member of the nucleic acid/nucleotide deaminase superfamily prototyped by OTT_1508 from the intracellular bacterial pathogen Orientia tsutsugamushi (. Members of this family are present in a wide phyletic range of bacteria,including several intracellular parasites and eukaryotes such as fungi, Leishmania, Selaginella, and some apicomplexa. In bacteria, these deaminases are predicted to function as toxins in bacterial polymorphic toxin systems . Versions in intracellular bacteria lack immunity proteins and are likely to be deployed against their eukaryotic hosts. Eukaryotic versions are predicted to function as nucleic acid (either DNA or RNA) deaminases. Among eukaryotes, some fungi show lineage-specific expansions of this family. Many fungal versions are fused to a distinct N-terminal globular domain. Various fungal versions are fused to domains involved in chromatin function. Apicomplexan versions are fused to tRNA guanine transglycosylase domain .
Pre-toxin TG domain (PT-TG_dom)
Type: Domain

PT-TG is a conserved region found in many bacterial toxin proteins. It could function as a linker that links N-terminal secretion-related domain and C-terminal toxin domain. It contains a TG motif .
Ubiquitin Mut7-C domain (Ub_Mut7C)
Type: Domain

This domain is a member of the ubiquitin superfamily and it is usually found at the N-terminal region of bacterial proteins with the Mut7-C domain

, suggestive of an RNA-binding role .
Replication termination factor 2, RING-finger (Rtf2_RING-finger)
Type: Domain

This entry represents the RING-finger domain of Replication termination factor 2 from Schizosaccharomyces pombe (Rtf2) and similar eukaryotic proteins. This RING finger-like structure forms only one functional Zn2+ ion-binding site .

The site-specific replication barrier RTS1 terminates replication forks that are moving in the cen2-distal direction while allowing forks moving in the cen2-proximal direction to pass through the region. Rtf2 was thought to stabilise the replication fork stalled at the RTS1 element by preventing replication restart until completion of DNA synthesis by a converging replication fork initiated at a flanking origin . However, this protein has been later reported to be associated with mRNA processing and splicing factors, and essential for the correct splicing of the rtf1 transcript, necessary for a functional Rtf1 protein (Replication Termination Factor 1) and thus for RTS activity . Its human homologue has been reported essential for the ability of cells to manage replication stress .
Centromere protein P (CENP-P)
Type: Family

CENP-P is a component of the CENPA-CAD (nucleosome distal) complex. The centromere, which is the basic element of chromosome inheritance, is epigenetically determined in mammals. CENP-A, the centromere-specific histone H3 variant, assembles an array of nucleosomes and it is this that seems to be the prime candidate for specifying centromere identity. CENP-A nucleosomes directly recruit a proximal CENP-A nucleosome associated complex (NAC) comprised of CENP-M, CENP-N and CENP-T, CENP-U(50), CENP-C and CENP-H. Assembly of the CENP-A NAC at centromeres is dependent on CENP-M, CENP-N and CENP-T. Additionally, there are seven other subunits which make up the CENP-A-nucleosome distal (CAD) centromere, CENP-K, CENP-L, CENP-O, CENP-P, CENP-Q, CENP-R and CENP-S, also assembling on the CENP-A NAC . Fta7 is the equivalent component of the fission yeast Sim4 complex .
Multi-ubiquitin domain (Multi-ubiquitin_dom)
Type: Domain

This entry represents a ubiquitin-like domain that is often present in multiple tandem copies in the same polypeptide. Proteins in this entry are associated in gene neighbourhoods, or on occasions fused to, bacterial homologues of components of ubiquitin-dependent modification system such as the E1, E2 and JAB metallopeptidase enzymes and a distinct metal-binding domain . The E2/UBC fold domain appears to be inactive. The JAB domain in these operons is usually fused to the E1 domain .
Toxin/Nuclease, N-terminal (Toxin/Nuc_N)
Type: Domain

This is a conserved short region that is found in many bacterial polymorphic toxin proteins . It is often located before C-terminal nuclease domains .
Transposase, Helix-turn-helix domain (Transposase_HTH_dom)
Type: Domain

This domain is the probable DNA-binding region of transposase enzymes, necessary for efficient DNA transposition. Most of the members derive from the IS superfamily IS5 and rather fewer from IS4.
Harbinger transposase-derived nuclease domain (HARBI1_dom)
Type: Domain

This domain is found in proteins that are related to

and are probably endonucleases of the DDE superfamily. Proteins containing this domain include the putative nuclease HARBI1. HARBI1 is a transposase-derived protein that may have nuclease activity potential. It does not have transposase activity .
CRISPR-associated protein Cas8a1/Csx13, Myxan subtype, C-terminal (CRISPR-assoc_Csx13_C)
Type: Domain

Members of the Myxococcus xanthus subtype of the Cas8a1/Csx13 family are found among cas (CRISPR-Associated) genes close to CRISPR repeats in Leptospira interrogans (a spirochete), Myxococcus xanthus (a delta-proteobacterium), and Lyngbya sp. PCC 8106 (a cyanobacterium). They are found with other cas genes in Anabaena variabilis ATCC 29413. In Myxococcus xanthus Cas8a1 is also known as DevT (developmental protein T) where stimulates synthesis of a signal transduction protein required for fruiting body morphogenesis (formation of fruiting bodies within the rod-shaped cells under starvation conditions that differentiate into spherical spores) .

This entry corresponds to the C-terminal domain of the proteins; the N-terminal domain is described by

. In Lyngbya sp., the protein is split into two tandem genes, and this entry corresponds to the downstream gene in these species.
Protein of unknown function DUF4653 (DUF4653)
Type: Family

This family of proteins is found in eukaryotes. Proteins in this family are typically between 93 and 229 amino acids in length.
Protein of unknown function DUF4642 (DUF4642)
Type: Family

This family of proteins is found in eukaryotes. Proteins in this family are typically between 115 and 196 amino acids in length.
Protein of unknown function DUF4562 (DUF4562)
Type: Family

This family of proteins is found in eukaryotes and is functionally uncharacterised. Members of the family contain a conserved HRYQNPW sequence motif. This family includes the human protein SPMIP2 (

) that is also known as sperm-associated microtubule inner protein 2.
CSC1/OSCA1-like, cytosolic domain (CSC1/OSCA1-like_cyt)
Type: Domain

This is the cytosolic domain of integral membrane proteins, such as plant OSCA1, yeast PHM7 and CSC1-like protein 1 (also known as TRANSMEMBRANE PROTEIN 63A),

. Fold recognition programs consistently and with high significance predict this domain to be distantly homologous to RNA binding proteins from the RRM clan .

CSC1, OSCA1 and PHM7 are mechanosensitive calcium-permeable ion channels consisting of an N-terminal transmembrane domain (RSN1_TM), a cytosolic domain and a 7TM region at the C-terminal. Fold recognition programs consistently and with high significance predict this domain to be distantly homologous to RNA binding proteins from the RRM clan . Human CSC1-like protein 1 is involved myelin development .
Membrane-anchored junction protein (MAJIN)
Type: Family

Membrane-anchored junction protein (MAJIN) is a meiosis-specific telomere-associated protein involved in meiotic telomere attachment to the nucleus inner membrane, a crucial step for homologous pairing and synapsis. It is a component of the MAJIN-TERB1-TERB2 complex, which promotes telomere cap exchange by mediating attachment of telomeric DNA to the inner nuclear membrane and replacement of the protective cap of telomeric chromosomes: in early meiosis, the MAJIN-TERB1-TERB2 complex associates with telomeric DNA and the shelterin/telosome complex. During prophase, the complex matures and promotes release of the shelterin/telosome complex from telomeric DNA. In the complex, MAJIN acts as the anchoring subunit to the nucleus inner membrane. MAJIN shows DNA-binding activity, possibly for the stabilization of telomere attachment on the nucleus inner membrane .
Costars domain (Costars_dom)
Type: Domain

This domain is found both alone (in the costars family of proteins) and at the C terminus of actin-binding Rho-activating protein (ABRA). It binds to actin, and in muscle regulates the actin cytoskeleton and cell motility . It has a winged helix-like fold consisting of three α-helices and four antiparallel β strands. Unlike typical winged helix proteins it does not bind to DNA, but contains a hydrophobic groove which may be responsible for interaction with other proteins .
Sperm acrosome-associated protein 9 (SPACA9)
Type: Family

This family of proteins found in eukaryotes represents sperm acrosome-associated protein 9 (SPACA9, previously known as C9orf9 or MAST).

Sperm acrosome-associated protein 9 has been suggested to form a complex with calcium-binding proteins calreticulin and caldendrin localized to the acrosome. Despite this, no known protein interaction motifs have been identified in MAST .
Guanine nucleotide exchange factor C9orf72 (C9orf72)
Type: Family

The entry includes Guanine nucleotide exchange factor C9orf72 protein, a component of the C9orf72-SMCR8 complex, which has guanine nucleotide exchange factor activity and regulates autophagy . The C9orf72 protein is proposed to be a catalytic component for the exchange of GDP to GTP and promoting autophagosome maturation by converting inactive GDP-bound RAB8A and RAB39B into their active forms . Defects in the C9orf72 gene are the cause of frontotemporal dementia and/or amyotrophic lateral sclerosis (FTDALS) which is an autosomal dominant neurodegenerative disorder. The disorder is caused by a large expansion of a GGGGCC hexanucleotide within the first C9orf72 intron located between the first and the second non-coding exons. The expansion leads to the loss of transcription of one of the two transcripts encoding isoform 1 and to the formation of nuclear RNA foci . This family is found in eukaryotes.

C9orf72 contains the DENN domain, which forms a heart-shaped structure (

), with the N-terminal residues forming one lobe and the C-terminal residues forming the second one. The tripartite DENN (after differentially expressed in neoplastic versus normal cells) domain is found in several proteins that share common structural features and have been shown to be guanine nucleotide exchange factors (GEFs) for Rab GTPases, which are regulators of practically all membrane trafficking events in eukaryotes .