SII-SWORD/CoKE huggingface dataset:
Cyanobactin biosynthesis protein, PatB/AcyB/McaB family (PatB_AcyB_McaB)
Type: Family

Members of this protein family are small (~ 80 amino acids) and occur in biosynthesis clusters for cyanobactins, a type of ribosomal natural product, thiazole/oxazole-modified microcin (TOMM). The function of this protein family is unknown, and the recognised cyanobactin precursors (e.g., microcyclamides and patellamides) are encoded by a different protein. In this protein family, however, a core region of about 62 amino acids is followed by a hypervariable region of 5 to 23 amino acids, with hallmarks of possible cyclodehydratase modification sites. The hallmarks include Cys residues flanked by Gly, and variable length Ser-rich tripeptide repeats. Further, members of this family were shown dispensible for patellamide biosynthesis, and two may occur in a cluster. Therefore, this family may represent a precursor of another type of ribosomal natural product .
Plantazolicin (Plantazolicin)
Type: Family

Members of this protein family are precursors of TOMMs, that is, thizazole/oxazole-modified microcins. Members are about 42 residues in length, have a C-terminal region of extremely low complexity rich in Ser, and are often missed by ab initio gene callers. In the dimethylated form plantazolicin A, Bacillus amyloliquefaciens plantazolicin has the antibiotic activity of inhibiting growth of Gram-positive bacteria. The desmethyl form, plantazolicin B, has no antibiotic activity. The mode of action appears to be disruption of cell walls and lysis of cells. .
Archaetidylserine synthase (Archaetidylserine_synthase)
Type: Family

The activity CDP-2,3-di-O-geranylgeranyl-sn-glycerol:L-serine O-archaetidyltransferase (archaetidylserine synthase) was demonstrated experimentally in Methanothermobacter thermautotrophicus. Members represent an exception within the broader family of CDP-diacylglycerol-serine O-phosphatidyltransferases .
Sarcinarray family protein (Sarcinarray_fam)
Type: Family

Members of this protein family are exclusive to archaea, probably all of which have S-layer surface protein arrays. All member proteins have an N-terminal signal sequence. The majority of known members belong to codirectional tandem arrays in the genus Methanosarcina (nine in M. barkeri str. Fusaro). Nearly all members have an additional 50 residues, consisting of low-complexity sequence rich in E,N,Q,T,S, and P, followed by a variant (PAF) form of the PGF-CTERM putative archaeal surface glycoprotein sorting signal. The coined name, sarcinarray family protein, evokes the predicted archaeal surface layer localisation, the taxonomic bias of known members, and the tandem organisation of most members.
XrtJ-associated TM-motif-TM protein (Targ_of_XrtJ)
Type: Family

This entry represents essentially the full length, ~60 residues, of a two-gene paralogous family from Acidobacterium sp. MP5ACTX8, which are referred as to PExPT-CTERM proteins, the predicted target for protein sorting a cleavage by the exosortase XrtJ. Sequences consist of an N-terminal signal sequence ending in a GC motif, suggestive of the lipoprotein signal sequence, followed immediately by a C-terminal domain sequence with characteristics PEP-CTERM-like sequences, including a PExP motif and a transmembrane helix. Both members occur next to the novel exosortase variant, XrtJ, which contains a novel C-terminal domain . This highly unusual arrangement suggests that PExPT-CTERM proteins may be used as an adaptor molecule to assist in the proper sorting and anchoring of other proteins.
Exosortase J (Exosortase_J)
Type: Family

Exosortase J occurs as a three-member paralogous family in Acidobacterium sp. MP5ACTX8. It contains an N-terminal exosortase/archaeosortase domain and a novel C-terminal domain comprising about half of total protein length. The presumptive target, found as an adjacent gene for two of the three paralogs, consists of a possible lipoprotein signal peptide followed almost immediately by a C-terminal region with some PEP-CTERM-like characteristics .
Glycopeptide, sublancin family (Glycopep_SunS)
Type: Family

Members of this family, including sublancin, are post-ribosomal natural products (PRNP) with an S-linked glycosylation. Sublancin itself also has two disulfide bonds. Sublancin is a 37-amino acid antimicrobial peptide belonging to the glycocin family . A related gene cluster in Bacillus cereus E33L includes the four Cys involved in the disulfide cluster but lacks the region with the glycosylated Cys .

Sublancin is a small bacteriocin active against Gram-positive bacteria. Sublancin was thought to be a lantibiotic but was later shown to be an S-linked glycopeptide . Glycosylation is essential for its antimicrobial activity. Sublancin is biosynthesised as a precursor peptide bearing an N-terminal leader peptide, and a C-terminal core peptide that is converted into the mature peptide . Sublancin comprises two α helices and a well-defined inter-helical loop . Sublancin inhibits B.cereus spore outgrowth, after the germination stage, approximately 1000-fold better than it inhibits exponential growth of the same cells and inhibits B.subtilis strain ATCC6633 and B. megaterium strain 14581 .
Arginine N-methyltransferase 2-like domain (RMT2_dom)
Type: Domain

This domain is found in arginine N-methyltransferase 2, a delta-N-monomethylarginine transferase which monomethylates 'Arg-67' of ribosomal protein L12 . The domain is also found in guanidinoacetate N-methyltransferase (GAMT), defects in which cause GAMT deficiency, an autosomal recessive disorder .
CCGSCS motif protein (CCGSCS)
Type: Family

This protein family, with average protein length about 58 residues, occurs in several marine bacteria, such as Shewanella benthica KT99, Marinobacter sp. ELB17, and Photobacterium profundum 3TCK. The striking feature is a C-terminal motif CCGSCS, which (perhaps coincidentally) resembles conserved core motif [LC]CGSC shared by two methanobactin precursors

.
Nif11-class peptide radical SAM maturase 3 (rSAM_nif11_3)
Type: Family

Members of this protein family are peptide-modifying radical SAM enzymes, with a C-terminal additional 4Fe-4S cluster binding domain like many other peptide-modifying radical SAM enzymes. This form occurs primarily in the genera Cyanothece and Nostoc.
CRISPR-associated protein Csx17, subtype Dpsyc (Cas_Csx17)
Type: Family

Members of this protein family are found exclusively in CRISPR-associated (cas) type I system gene clusters of the Dpsyc subtype. Markers for that type include a variant form of cas3 and the GSU0054-like protein family. This family occurs in less than half of known Dpsyc clusters.
Cys-Xaa-Xaa-Xaa repeat radical SAM target protein (Syntroph_Cxxx)
Type: Family

This entry represents a paralogous family, in Syntrophus aciditrophicus SB, of peptides with a conserved N-terminal region followed by ten to seventeen direct repeats of the sequence CXXX.
Archaeosortase family protein ArtE (Archaeo_ArtE)
Type: Family

This protein family is related to the predicted protein-sorting transpeptidase Exosortase (EpsH), with the Cys, Arg, and His putative active site residues preserved, but it is strictly archaeal and is not associated with any known PEP-CTERM-like target sequence. The immediate gene neighbourhood in most genomes suggests RNA (methylase, cyclase) and cofactor (thiamine pyrophosphate) metabolism. The function is unknown. It is designated archaeosortase family protein ArtE .
Uncharacterised protein AF_0576 (CHP_AF_0576)
Type: Family

This entry represents an uncharacterised small archaeal protein.
Sporadically distributed protein CHP04141 (CHP04141)
Type: Family

This entry represents a sporadically distributed conserved hypothetical protein in which complete members average over 500 amino acids in length, although matching sequences frequently are truncated or broken into tandem ORFs. Regular co-clustering with known markers of mobility (integrases, transposases, phage proteins, restriction enzymes, etc.) suggests this family also is part of the mobilome. The function is unknown.
Exosortase C, VPDSG-CTERM-specific (Exosort_VPDSG)
Type: Family

Through in silico analysis, the PEP-CTERM/exosortase system was described. This entry describes the exosortase subtype specific for the VPDSG-CTERM variant of PEP-CTERM. Systems are found, so far, in Verrucomicrobiae bacterium DG1235 and bacterium Ellin514 (Pedosphaera parvula). This system may coexist with other system variants .
CXC domain (CXC_dom)
Type: Domain

Polycomb group (Pc-G) proteins ensure the stable inheritance of expression patterns through cell division and regulate the control of cell proliferation. The Enhancer of zeste (E(z))-type of Pc-G proteins includes:

Drosophila melanogaster Enhancer of zeste E(z).

Mammalian ENX-1 and ENX-2.

Arabidopsis thaliana CURLY LEAF (CLF), a transcriptional repressor of floral homeotic gene AGAMOUS.

Arabidopsis thaliana CLF-like.

Arabidopsis thaliana MEDEA (MEA), a suppressor of endosperm development.

Arabidopsis thaliana EZA1.

These proteins contain a SET domain at the C terminus. Unique to them is the presence of a CXC domain, an ~65-residue cys-rich region preceding the SET domain. The spacing of 17 cyteines is conserved. The CXC domain contains three units of C-X(6)-C-X(3)-C-X-C motif, although the most C- terminal unit is reverse-oriented. Because of its evolutionary conservation, the CXC domain is likely to be involved in an important function of E(z)- related proteins . The CXC domain shows some similarity to the CRC domain found in the tesmin/ TSO1 protein family .
mRNA cap 0/1 methyltransferase (mRNA_cap_0/1_MeTrfase)
Type: Domain

This entry represents the mRNA cap 0/1 methyltransferase domain found at the N-terminal of non-structural protein 5 (NS5). NS5 is one of the fourteen chains of genome poplyprotein from Flavivirus. NS5 has three activities: The N-terminal domain catalyses both guanine N-7 and ribose 2'-OH methylations during viral cap formation , and the C-terminal functions as a RNA-directed RNA polymerase .
Exosortase D, VPLPA-CTERM-specific (ExosortD_VPLPA)
Type: Family

This entry describes a variant sub class, exosortase D, of protein sorting enzyme, specific for the VPLPA-CTERM variant of the PEP-CTERM protein sorting signal .
Cyanoexosortase B (Cyanoexo_CrtB)
Type: Family

This entry represents a cyanobacterial-restricted form of exosortase, associated with a PEP-CTERM domain subclass (see

). This is one of two such cyanoexosortases, the other being

.
Cys-rich peptide (Cys-rich_pep)
Type: Family

Members of this small peptide family occur strictly in a subset of archaeal methanogens. Members have four invariant Cys residues in two Cys-Xaa-Xaa-Cys-Gly motifs and may have other Cys residues as well. At least two members occur next to family

radical SAM enzymes predicted to act in peptide or protein modification.
Ribonucleoside-diphosphate reductase subunit beta (RNR_NrdF-like)
Type: Family

Ribonucleotide reductase (also known as ribonucleoside-diphosphate reductase) catalyses the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides providing the precursors necessary for DNA synthesis. Three main classes of ribonucleotide reductases (RNR) have been discovered that depend on different metal cofactors for the catalytic activity: class I enzymes contain a diiron-oxygen cluster, class II a cobalt containing cobalamin cofactor (vitamin B12), and class III an 4Fe-4S iron-sulfur cluster coupled to S-adenosylmethionine (SAM) .

Class I RNRs can be further divided into two subclasses, Ia and Ib. Class Ia exists in eukaryotes, prokaryotes, viruses, and bacteriophages, while Ib has only been found in prokaryotes. Class I RNRs are tetrameric enzymes (alpha2beta2). The small beta2-homodimer is called R2 in class Ia, encoded by nrdB, and R2F for the class Ib, encoded by nrdF .
PIP-CTERM protein sorting domain (PIP_CTERM)
Type: Domain

Proteins closely related to MJ_1469.1 from Methanocaldococcus jannaschii DSM 2661 are designated archaeosortase D (ArtD). ArtD appears to be a dedicated protein-sorting enzyme with a single target, a PKD domain

repeat protein encoded by adjacent gene. This model describes the C-terminal putative protein-sorting region structurally similar to PEP-CTERM and found only on these methanogen PKD domain proteins .
Putative ATP-grasp target RiPP (GRASP_targ)
Type: Domain

A RiPP is a ribosomally produced, post-translationally modified peptide. Proteins in this entry regularly occur next to ATP-grasp enzymes related to those of microviridin maturation and next to a methyltransferase.
SPASM domain peptide maturase, GRASP-with-SPASM system (GRASP-with-SPASM)
Type: Family

A 4Fe-4S-binding C-terminal domain is shared by radical SAM maturases for Subtilosin A (S), PQQ (P), Anaerobic sulfatases (AS), and mycofactocin (M), hence SPASM. Radical SAM proteins with SPASM tend to be peptide maturases. All members of this family, like some members of the quasi-rSAM family, lack the 4Fe-4S cluster of the radical SAM domain in the N-terminal region. Members of this family occur with an ATP-GRASP family protein, known as a possible maturase from microviridin biosynthetic clusters. Systems occur in Microscilla marina ATCC 23134, Kordia algicida OT-1, Sphingobacterium spiritivorum ATCC 33300, etc.
Grasp-with-spasm leader A domain (Grasp_w_spasm_A)
Type: Domain

This entry represent the leader peptide domain, ending in a Gly-Gly cleavage motif, for a post-ribosomal natural product (PRNP) precursor. The corresponding modification enzymes include an ATP-GRASP enzyme and a SPASM-domain protein, related to the C-terminal region of numerous peptide-modification radical SAM enzymes.
Peptide S-glycosyltransferase, SunS family (S_glycosyl_SunS)
Type: Family

Members of this family include SunS, the S-glycosyltransferase that transfers a sugar (substrate is variable in reconstitution assays) onto the precursor of the glycopeptide sublancin, which once was thought to be a lantibiotic .
Dendrin (Dendrin)
Type: Family

Dendrin is a cytosolic protein that is expressed in the brain , where it interacts with alpha-actinin, possibly modulating the structure of the actin cytoskeleton . Dendrin is also expressed in the kidney . It may have a role in apoptosis of kidney glomerular podocytes .
Limbin/EvC complex member EVC (Limbin/EVC)
Type: Family

EVC is a protein mutated in the human chondroectodermal dysplasia Ellis-van Creveld syndrome. Limbin or EVC2 interacts with AVC . They act as positive mediators of Hedgehog signaling and play a critical role in bone formation and skeletal development .
Histone RNA stem-loop-binding protein SLBP1/SLBP2 (SLBP1/SLBP2)
Type: Family

This family consists of the histone stem-loop-binding protein (SLBP1) and the Xenopus Oocyte-specific histone RNA stem-loop-binding protein 2 (SLBP2). They both bind to the 3' end of histone mRNA in frog oocytes. However, their functions are different. SLBP1 participates in histone pre-mRNA processing in the nucleus, while oocyte specific SLBP2 doesn't support the histone pre-mRNA processing and locates in the cytoplasm .

SLBP1 binds the 5' side of the stem-loop structure of replication-dependent histone pre-mRNAs and contributes to efficient 3'-end processing by stabilising the complex between histone pre-mRNA and U7 small nuclear ribonucleoprotein (snRNP), via the histone downstream element (HDE) . It plays an important role in targeting mature histone mRNA from the nucleus to the cytoplasm and to the translation machinery. It stabilises mature histone mRNA and could be involved in cell-cycle regulation of histone gene expression .
Meiosis-specific nuclear structural protein 1 (MNS1)
Type: Family

MNS1 is a skeletal protein involved in organisation of the nuclear or perinuclear architecture and may affect the nuclear morphology during meiotic prophase in spermatocytes .
Solute carrier family 35 member F3/F4 (Solute_c_fam_35_mem_F3/F4)
Type: Family

This entry consists of solute transporters including solute carrier family 35 members F3 and F4 (SLC35F3/F4). SLC35F3 has been identified as a thiamine transporter .
GDP-L-galactose/GDP-D-glucose phosphorylase (GDPGP)
Type: Family

GDP-D-glucose phosphorylase 1 (GDPGP1) is a specific and highly efficient GDP-D-glucose phosphorylase regulating the levels of GDP-D-glucose in cells . This family also includes the GDP-L-galactose phosphorylases VTC2 and VTC2L (VTC5) from Arabidopsis, which use preferentially GDP-L-galactose and GDP-D-glucose as substrates and are part of the Smirnoff-Wheeler pathway for ascorbate biosynthesis in plants. They act as a phosphorylase rather than as transferases .

This entry also includes uncharacterised proteins from bacteria.
Piercer of microtubule wall 1/2 (PIRC1/2)
Type: Family

This family represents piercer of microtubule wall 1/2 (PIRC1/2), which are microtubule inner proteins involved in the attachment of outer dynein arms (ODAs) to dynein-decorated doublet microtubules (DMTs) in cilia axoneme . In mice, PIRC1 has been shown to function at the initial step of left-right asymmetry specification of the visceral organs .
Transmembrane protein 164 (TMEM164)
Type: Family

This entry represents the transmembrane protein 164 (TMEM164) which is a positive regulator of ferroptosis. It selectively mediates ATG5-dependent autophagosome formation during ferroptosis, rather than during starvation, and regulates the degradation of ferritin, GPX4 and lipid droplets to increase iron accumulation and lipid peroxidation, thereby promoting ferroptotic cell death .
Transmembrane protein 183 (TMEM183)
Type: Family

Proteins in this family include TMEM183, TMEM183A and TMEM183B. The function of this family is unknown.
Peroxisomal membrane protein 11C, metazoa (PEX11C_met)
Type: Family

This family consists of peroxisomal biogenesis factor 11C (PEX11C) proteins from Metazoa . They belong to the PEX11 protein family.
Parathyroid hormone-responsive B1 (PTHB1)
Type: Family

Parathyroid hormone-responsive B1 (PTHB1, also known as BBS9 in human) is part of the BBSome complex. The BBSome complex (contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9 and BBIP10) is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localises to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane .
RGS7BP/RGS9BP family (RGS7BP/RGS9BP)
Type: Family

This family consists of regulator of G-protein signalling 7-binding protein (RGS7BP) and regulator of G-protein signalling 9-binding protein (RGS9BP). They interact with regulation of G-protein signalling (RGS) proteins and Gbeta5 to form complexes that act to regulate G-proteins .

RGS7BP is expressed neuronally and interacts with R7 family of RGS proteins (RGS6, RGS7, RGS9 and RGS11). RGS9BP interacts with RGS9 and is involved in the regulation of G-protein signalling in the phototransduction, participating in the recovery phase of visual transduction .
THAP domain-containing protein 1/10 (THAP1/10)
Type: Family

The THAP domain is a C2CH module with zinc-dependent sequence-specific DNA-binding activity . Several THAP domain-containing proteins have been described. Human THAP1 is a transcription regulator that regulates endothelial cell proliferation and G1/S cell-cycle progression . It specifically binds the 5'-[AT]NTNN[GT]GGCA[AGT]-3' core DNA sequence and acts by modulating expression of pRB-E2F cell-cycle target genes, including RRM1. It is a component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. It may also have pro-apoptopic activity by potentiating both serum-withdrawal and TNF-induced apoptosis .
THAP domain-containing protein 7 (THAP7)
Type: Family

The THAP domain is a C2CH module with zinc-dependent sequence-specific DNA-binding activity . Several THAP domain-containing proteins have been described. THAP7 is a chromatin-associated, histone tail-binding protein that represses transcription via recruitment of histone deacetylase 3 (HDAC3) and nuclear hormone receptor corepressors (NCoR) .
THAP domain-containing protein 3 (THAP3)
Type: Family

The THAP domain is a C2CH module with zinc-dependent sequence-specific DNA-binding activity . Several THAP domain-containing proteins have been described. THAP3 is a component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of the cell cycle-specific gene RRM1 .
THAP domain-containing protein 2 (THAP2)
Type: Family

The THAP domain is a C2CH module with zinc-dependent sequence-specific DNA-binding activity . Several THAP domain-containing proteins have been described. This entry represents THAP domain-containing protein 2 (THAP2) and similar animal proteins.
Paraneoplastic antigen Ma (PNMA)
Type: Family

The paraneoplastic Ma antigens (PNMA) have been identified using sera from patients with paraneoplastic neurological syndromes . This entry includes paraneoplastic antigen PNMA1 , PNMA2 , PNMA3 , PNMA4 (also known as modulator of apoptosis 1 or MOAP-1) and some paraneoplastic antigen-like proteins (PNMA5 and PNMA6). PNMA4/MOAP-1 has a role in death receptor-dependent apoptosis , and it also plays a role in autophagy as it promotes phagophore closure via association with ATG8 proteins .

Zinc finger CCHC domain-containing protein 12 (ZCCHC12, also known as Sizn1 in mouse), also a member of this entry, is a transcriptional coactivator in the bone morphogenetic protein (BMP)-signaling pathway. It positively modulates BMP signaling by interacting with SMAD1 and associating with CBP in the transcription complex. It contributes to the BMP-induced enhancement of cholinergic-neuron-specific gene expression . This protein may be a potential molecular marker of papillary thyroid carcinoma .
Lymphocyte antigen 6 complex locus protein G6d/G6f (LY6G6d/LY6G6f)
Type: Family

This entry includes lymphocyte antigen 6 complex locus protein G6d and G6f, which are encoded in the MHC (major histocompatibility complex). Human and mouse G6d was found to be GPI-anchored cell surface proteins, highly expressed at the leading edges of cells, on filopodia, which are normally involved in cell adhesion and migration. The human G6f protein may play a role in the downstream signal transduction pathways involving GRB2 and GRB7, including the Ras-MAP kinase pathway .
Coiled-coil domain-containing protein 8 (CCDC8)
Type: Family

Coiled-coil domain-containing protein 8 (CCDC8) is a widely expressed protein . It is phosphorylated upon DNA damage, probably by ATM or ATR . It is a core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer . CCDC8 is also required for localization of CUL7 to the centrosome .

Defects in CCDC8 are the cause of 3M syndrome type 3 (3M3), a disorder characterised by poor postnatal growth and distinctive facial features, including triangular facies, frontal bossing, fleshy tipped nose, and fleshy lips. Other features may include skeletal anomalies and prominent heels .
Phosphoenolpyruvate synthase regulatory protein (PSRP)
Type: Family

This entry represents a famiy of bifunctional serine/threonine kinase/phosphorylases involved in the regulation of the phosphoenolpyruvate synthase (PEPS) by catalysing its phosphorylation/dephosphorylation .
Ribosome biogenesis protein BRX1 (BRX1)
Type: Family

This family consists of BRX1 and homologues. In yeast, BRX1 is part of a complex that also includes RPF1, RPF2 and SSF1 or SSF2. It is required for biogenesis of the 60S ribosomal subunit .