SII-SWORD/CoKE huggingface dataset:
Ubiquinone biosynthesis protein Coq7, proteobacteria (COQ7_proteobact)
Type: Family

Coq7 (also known as Clk-1 and CAT5) is a di-iron carboxylate protein occuring in both prokaryotes and eukaryotes that is essential for ubiquinone biosynthesis . Coq7 is a membrane-bound protein that functions as a monooxygenase to hydroxylate demethoxyubiquinone (DMQ or 2-methoxy-5-methyl-6-polyprenyl-1,4-benzoquinone) in the penultimate step of ubiquinone biosynthesis . Biochemical studies indicate that NADH can serve directly as a reductant for catalytic activation of dioxygen and substrate oxidation by the enzyme, with no requirement for an additional reductase protein component . This direct reaction with NADH is so far unique amongst members of the di-iron carboxylate protein family.

This entry represents bacterial Coq7, mainly from beta and gammaproteobacteria.
Heterocyst frequency control protein PatD-like (PatD-like)
Type: Family

This entry represents PatD and its homologues, a protein identified in Anabaena sp. PCC 7120, that regulates heterocyst frequency in this organism, ensuring its optimal filament growth. The NtcA-regulated gene patD controls the ratio of heterocysts relative to vegetative cells on filaments. Such a regulation provides a mechanism through which carbon fixation by vegetative cells and nitrogen fixation by heterocysts are properly balanced to ensure optimal growth and keep a competitive edge for long-term survival .
Putative cytochrome C oxidase assembly protein (CytC_ox_assmbl_put)
Type: Family

This entry represents a proteobacterial family of small uncharacterised proteins, of about 40 amino acids in length. They contain a conserved region that is enriched of hydrophobic residues and it constitutes a probable transmembrane α-helix. Members of this family are regularly found encoded in the context of much larger cytochrome oxidase complex subunits, particularly in members of the Burkholderiales such as Bordetella pertussis and Burkholderia sp.
Small membrane protein YshB (YshB)
Type: Family

This entry represents YshB and its homologues which are small proteins of about 36 to 40 amino acids in length, found in gammaproteobacteria. YshB is a membrane-associated protein .
Pilus motility taxis protein HmpF (HmpF)
Type: Family

This family represents the cyanobacterial pilus motility taxis protein HmpF and its homologues, a protein that is part of the Hmp system. The chemotaxis-like Hmp system is essential for motility and the coordinated polar accumulation of PilA on cells in motile filaments, while the Ptx system controls positive phototaxis. A direct interaction between HmpF and the T4P system was found to activate pilus extension, thus the Hmp system facilitates coordinated polarity of HmpF to establish motility, and the Ptx system modulates HmpF localization to initiate reversals in response to changes in light intensity . The Hmp chemotaxis-like system of the filamentous cyanobacterium Nostoc punctiforme is capable of sensing light indirectly, possibly via alterations in proton motive force, and modulates direct interaction between HmpF, and Hfq, PilT1, and PilT2 to regulate the T4P motors .
TfpX/TfpZ-like, type IV pilin accessory protein (TfpX/TfpZ-like)
Type: Family

This entry represents TfpX/TfpZ family of type IV pilin accessory proteins. Type IV pili (TFP) are important colonisation factors, involved in biofilm formation and attachment to host cells. TFP are divided into five distinct phylogenetic groups. TfpZ and TfpX are homologous pilin accessory proteins identified in Pseudomonas aeruginosa that belong to group IV pilins . Member of this family is also FimB, a fimbrial assembly protein that is likely to regulate the fimbrial length .
Membrane protein SCO1431-like (SCO1431-like)
Type: Family

This entry represents proteins related to SCO1431 from Streptomyces coelicolor A3(2), which are small and extremely hydrophobic proteins that lack an N-terminal signal peptide. Toward the C terminus they are predicted to contain a single transmembrane helix that is sufficient for localization, suggesting a targeting pathway that is independent of the SRP (signal recognition particle) . Members of this family are restricted to the genus Streptomyces.
ABC-2 type transporter, transmembrane domain, bacterial-type (ABC2_TM_bact-type)
Type: Domain

ABC transporters are minimally constituted of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These regions can be found on the same protein (mostly in eukaryotes and bacterial exporters) or on two different ones (mostly bacterial importers) . But in a subgroup of exporters, the transmembrane region is encoded by a separated polypeptide, described as the ABC-2 type transport system integral membrane protein. A number of bacterial transport systems have been found to contain integral membrane components that have similar sequences : these systems fit the characteristics of ATP-binding cassette transporters . The proteins form homo- or hetero-oligomeric channels, allowing ATP-mediated transport. Hydropathy analysis of the proteins has revealed the presence of 6 possible transmembrane regions. This entry represents the transmembrane region of a subgroup of ABC-2 type transporters found mainly in bacteria.
Inorganic phosphate transporter PitA/PitB (Phos_trans_PitA_PitB)
Type: Family

PitA is a low-affinity transporter for inorganic phosphate . It imports phosphate complexed to divalent cations such as Mg(2) or Ca(2). Loss of PitA function can confer reduced sensitivity to high levels of Zn(2) . The PitB of Escherichia coli is a closely related PitA paralog .
P5B-type ATPase, N-terminal (P5A-ATPase_N)
Type: Domain

This entry represents the N-terminal extension domain from P5B-type ATPases, including ATP13A2 to ATP13A5 from human and its homologue from yeast, YPK9 . It contains three short hydrophobic α-helices that are conserved in P5B-ATPases . Human ATP13A2 (also known as PARK9) is a neuroprotective ATPase enriched in the brain that selectively imports spermine ions from lysosomes into the cytosol . Mutations in ATP13A2 cause a rare monogenic form of juvenile-onset Parkinson's disease named Kufor-Rakeb syndrome and other neurodegenerative diseases .
P5A-type ATPase (P5A-type_ATPase)
Type: Family

This entry represents P5A-type ATPases, which localises in the ER membrane and includes ATP13A1 from human and SPF1 from yeast .

SPF1 from yeast and ATP13A1 are ER translocases required to remove mitochondrial transmembrane proteins mistargeted to the endoplasmic reticulum . They were initially thought to mediate ion transport such as calcium or manganese but then it was reported that they specifically bind moderately hydrophobic transmembrane with short hydrophilic lumenal domains that misinsert into the endoplasmic reticulum .
P5B-type ATPase (P5B-type_ATPase)
Type: Family

This entry includes P5B-type ATPases which are vacuolar or lysosomal membrane-associated proteins, including ATP13A2-5 from human and YPK9 from yeast. Humans express four isoforms, ATP13A2 to ATP13A5 .

Human ATP13A2 (also known as PARK9), the most studied member of the P5B-type, plays a role in intracellular cation homeostasis and the maintenance of neuronal integrity. It confers cellular protection against Mn2 and Zn2 toxicity and mitochondrial stress . ATP13A2 modulates zinc levels in multi-vesicular bodies (MVBs) which, in turn, can regulate the biogenesis of exosomes and may play a neuroprotective role as dysfunction in MVBs are associated with detrimental effects, such as lysosomal dysfunction and impaired delivery of endocytosed proteins/autophagy cargo to the lysosome, central in Parkinson's disease pathogenesis . It is a neuroprotective ATPase enriched in the brain that selectively imports spermine ions from lysosomes into the cytosol . Mutations in ATP13A2 cause a rare monogenic form of juvenile-onset Parkinson's disease named Kufor-Rakeb syndrome and other neurodegenerative diseases .
TECRL, ubiquitin-like domain (TECRL_Ubl)
Type: Domain

This entry represents the Ubiquitin-like (Ubl) domain found in the trans-2,3-enoyl-CoA reductase-like (TECRL) protein, also known as steroid 5-alpha-reductase 2-like 2 protein (SRD5A2L2). TECRL is associated with life-threatening inherited arrhythmias displaying features of both long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) . In cardiomyocytes, TERCL deficiency results in malfunctioning of the mitochondria . TECRL contains an N-terminal Ubl domain, a common domain involved in protein-protein interactions, and a C-terminal catalytic domain .
RNF145, RING finger, H2 subclass (RNF145_RING-H2)
Type: Domain

This entry represents a RING finger domain present in the RNF145 protein, which is expressed in T lymphocytes, and its expression is altered in acute myelomonocytic and acute promyelocytic leukemias . RNF145 is a E3-ubiquitin ligase that mediates the degradation of different proteins, for example: HMG-CoA reductase and lipid hydrolase ADIPOR2 . RNF145 shows high sequence similarity with RNF139, an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. Like RNF139, RNF145 contains a C3H2C3-type RING-H2 finger .
BTB/POZ domain-containing protein 11, BACK domain (BTBD11_BACK)
Type: Domain

This entry represents the BTB and C-terminal Kelch (BACK) domain found in BTBD11. BTBD11, also known as ankyrin repeat and BTB/POZ domain-containing protein 3 (ABTB3), has been identified as an all-trans retinoic acid-responsive gene that may play a role in neural development .

The BTB domain (Broad-Complex, Tramtrack and Bric a brac) is also known as the POZ domain (POxvirus and Zinc finger). It is a homodimerisation domain occurring at the N terminus of proteins containing multiple copies of either zinc fingers of the C2H2 type or Kelch repeats . Many BTB proteins are transcriptional regulators that are thought to act through the control of chromatin structure.

The structure of the BTB domain of the promyelocytic leukaemia zinc finger (PLZF) protein has been determined by X-ray crystallography and reveals a tightly intertwined dimer with an extensive hydrophobic interface . A surface-exposed groove lined with conserved amino acids is formed at the dimer interface, suggesting a peptide-binding site.
SHKBP1/KCTD3, BTB/POZ domain (SHKBP1_KCTD3_BTB_POZ)
Type: Domain

This entry represents the BTB/POZ domain present in two closely related human proteins: SH3KBP1 (also known as SETA-binding protein 1) and Potassium Channel Tetramerization Domain Containing protein 3 (KCTD3) which correspond to group D of KCTD family . SHKBP1 interacts with cathepsin B and participates in tumor necrosis factor (TNF)-induced apoptosis in ovarian cancer cells . KCTD3 has been associated with neurogenetic and neurodevelopmental disorders. It is an accessory subunit of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) as it interacts and increases its stability and cell surface expression . BTB/POZ domains, also known as tetramerization (T1) domains, are versatile protein-protein interaction domains that facilitates homodimerization or heterodimerization .
Calmin, second calponin homology domain (CLMN_CH_second)
Type: Domain

Calmin, also called calponin-like transmembrane domain protein, is a protein with calponin homology (CH) and transmembrane domains expressed in maturing spermatogenic cells . It may be involved in the development and/or maintenance of neuronal functions . Calmin contains two copies of the CH domain. This entry represents the second CH domain. CH domains are actin filament (F-actin) binding motifs .
Calmin, first calponin homology domain (CLMN_CH_first)
Type: Domain

Calmin, also called calponin-like transmembrane domain protein, is a protein with calponin homology (CH) and transmembrane domains expressed in maturing spermatogenic cells . It may be involved in the development and/or maintenance of neuronal functions . Calmin contains two copies of the CH domain. This entry represents the first CH domain. CH domains are actin filament (F-actin) binding motifs .
Fidgetin, ATPase domain (Fidgetin_ATPase)
Type: Domain

This entry represents the ATPase domain of Fidgetin (FIGN) and FIGNL2.

FIGN is an ATP-dependent microtubule severing protein that plays a key role in chromatin remodelling and centrosome organisation . This domain correspond to the meiotic clade of AAA ATPases that includes four families: Vps4, spastin, katanin and fidgetin. These ATPases regulate diverse cellular processes, including neuronal development, cell division, and ciliogenesis . Meiotic clade AAA ATPases function as hexamers that can cycle between the active assembly and inactive monomers/dimers in a regulated process, and they appear to disassemble their polymeric substrates by translocating subunits through the central pore of their hexameric ring .
G protein-coupled receptor 19, 7TM (GPR19_7tmA)
Type: Domain

This entry represents the seven transmembrane segments of G-protein coupled receptor 19 (GPR19).

GPR19 is an orphan receptor expressed predominantly in neuronal cells during mouse embryogenesis . Its mRNA is found frequently over-expressed in patients with small cell lung cancer . GPR19 is a member of the class A family of GPCRs, which represents a widespread protein family that includes the light-sensitive rhodopsin as well as receptors for biogenic amines, lipids, nucleotides, odorants, peptide hormones, and a variety of other ligands . A general feature of GPCR signalling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes .
Quinohemoprotein amine dehydrogenase subunit gamma (QHNDH_gamma)
Type: Family

This entry includes quinohemoprotein amine dehydrogenase (also known as QHNDH) subunit gamma. QHNDH catalyses the oxidative deamination of various aliphatic primary amines so that they can be assimilated as energy, carbon, and nitrogen sources. This enzyme is composed of three nonidentical subunits, designated alpha, beta, and gamma on the basis of their molecular sizes.

The gamma subunit, the smallest of the three, is buried inside the alpha subunit and it has a particularly unusual structure consisting mostly of featureless coils with a covalently bound quinone cofactor, cysteine tryptophylquinone (CTQ), derived from Trp and Cys residues, and three intra peptidyl thioether cross-links formed between Cys and Glu or Asp residues . These structural features of the gamma
subunit clearly indicate that it must undergo multiple posttranslational modifications before it can form an active QHNDH complex with the alpha
and beta subunits .
GPR180/TMEM145 (GPR180/TMEM145)
Type: Family

This entry includes GPR180 (also known as intimal thickness-related receptor, ITR) and TMEM145 . In vivo analyses of this gene revealed that expression of GPR180 protein increased with intimal thickening induced by cuff placement around murine femoral artery. Furthermore, GPR180-knockout mice were found to be resistant to this experimental intimal thickening . GPR180 was first thought to be an orphan Rhodopsin-like GPCR (G protein-coupled receptor) given structural similarities to GPCR transmembrane region, however, it was then confirmed not to signal as a a GPCR . This protein is associated with TGF-beta signalling as it regulates the activity of the TGF-beta receptor complex through SMAD3 phosphorylation. Furthermore, GPR180 is also required for the action of Collagen triple helix repeat containing 1 (CTHRC1) to regulate brown and beige adipocyte activity and glucose homeostasis .

GPR180 and TMEME145 are homologous to TMEM181 and Wntless (WLS), which have been described as GOST proteins (for GOLD domain seven-transmembrane helix proteins) together with TMEM87A/B, GPR107, and GPR108, given they share the same domain architecture consisting of a GOLD domain atop of a membrane-spanning seven-transmembrane helix domain .
Peptidase inhibitor 15, CAP domain (PI15_CAP)
Type: Domain

This entry represents the CAP domain of peptidase inhibitor 15 (PI15) protein, also known as cysteine-rich secretory protein 8 (CRISP-8), or SugarCrisp. It is a serine protease inhibitor which displays weak inhibitory activity against trypsin and may play a role in facial patterning during embryonic development . The PI15 gene is a candidate gene for abdominal aortic internal elastic lamina ruptures in the rat .

The cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP) superfamily proteins are found in a wide range of organisms, including prokaryotes and non-vertebrate eukaryotes , The nine subfamilies of the mammalian CAP superfamily include: the human glioma pathogenesis-related 1 (GLIPR1), Golgi associated pathogenesis related-1 (GAPR1) proteins, peptidase inhibitor 15 (PI15), peptidase inhibitor 16 (PI16), cysteine-rich secretory proteins (CRISPs), CRISP LCCL domain containing 1 (CRISPLD1), CRISP LCCL domain containing 2 (CRISPLD2), mannose receptor like and the R3H domain containing like proteins. Members are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility; as tumour suppressor or pro-oncogenic genes in tissues including the prostate; and in cell-cell adhesion during fertilisation. The overall protein structural conservation within the CAP superfamily results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters the target specificity and, thus, the biological consequences . The Ca2-chelating function would fit with the various signalling processes (e.g. the CRISP proteins) that members of this family are involved in, and also the sequence and structural evidence of a conserved pocket containing two histidines and a glutamate. It also may explain how

blocks the Ca2 transporting ryanodine receptors.
Bone morphogenetic protein 4, TGF-beta-like domain (BMP4_TGF_beta-like)
Type: Domain

This entry represents the TGF-beta-like domain found at the C-terminal of Bone morphogenetic protein 4 (BMP4). BMP4 induces cartilage and bone formation. It also acts in mesoderm induction, tooth development, limb formation and fracture repair. It regulates a plethora of developmental processes, including the dorsal-ventral axis and neural patterning .
Ovarian tumor domain-containing protein 1, OTU domain (OTUD1_OTU)
Type: Domain

This entry represents the OTU domain of the OTU domain-containing protein 1 (OTUD1), also known as DUBA-7 in humans.

OTUD1 is a deubiquitinating enzyme/ubiquitinyl hydrolase

, that specifically hydrolyzes 'Lys-63'-linked polyubiquitin to monoubiquitin; this specificity is facilitated by the C-terminal Ub-interacting motif (UIM) of OTUD1 . It interacts and promotes the deubiquitination of myeloid cell leukaemia 1 (MCL1), a pro-survival Bcl-2 family protein that plays important roles in cell survival, proliferation, differentiation and tumorigenesis . OTUD1 also deubiquitinates IFN regulatory factor 3 (IRF3) and attenuates its function; IRF3 is critical for the transcription of type I IFNs in defending virus and promoting inflammatory responses . Loss-of-function mutations of OTUD1 associated with multiple autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ulcerative colitis (UC) and Hashimoto's thyroiditis (HT) . OTUD1 belongs to the OTU family of cysteine proteases .
PTS N-acetylgalactosamine transporter subunit IIC, AgaW-like (PTS_IIC_GalNAc_AgaW-like)
Type: Family

This entry represents PTS N-acetylgalactosamine transporter subunit IIC AgaW and related proteins. This subunit is a component of GalNAc-specific phosphotransferase system (PTS). N-acetylgalactosamine is degraded through individual PTS transporters and pathways that resemble those for GlcNAc .
G protein-coupled receptor 174, 7TM (GPR174_7tmA)
Type: Domain

This entry represents the seven transmembrane segments of G-protein coupled receptor 174 (GPR174).

GPR174 has been identified as a lysophosphatidylserine receptor that enhances intracellular cAMP formation . It is involved in the immune response and has been linked to autoimmune diseases . GPR174 is a member of the class A family of GPCRs, which represents a widespread protein family that includes the light-sensitive rhodopsin as well as receptors for biogenic amines, lipids, nucleotides, odorants, peptide hormones, and a variety of other ligands . A general feature of GPCR signalling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes .
Probable RNA-binding protein 46, RNA recognition motif 3 (RBM46_RRM3)
Type: Domain

This entry represents the RNA recognition motif 3 (RRM3) of RBM46, predominantly found in mammals.

RNA-binding motif protein 46 (RBM46), also known as cancer/testis antigen 68 (CT68), is a germ cell-specific RNA-binding protein that is essential for spermatogenesis and male fertility. It is involved in the regulation of gene expression during meiosis . It has been shown to bind to and stabilise Cdx2 mRNA in early mouse embryos . RBM46 contains two well-defined and one degenerated RNA recognition motifs (RRMs) and a C-terminal double-stranded RNA binding motif (DSRM) .
STM4013-like hydrolase (STM4013-like)
Type: Family

Members of this family are sulfatase-like metal-dependent hydrolases, of unknown function, regularly found in a conserved gene neighbourhood that also includes two uncharacterised radical SAM proteins.
Small membrane protein YoaK (YoaK-like)
Type: Family

This entry represents YoaK, a small protein (about 32 amino acids) mainly found in gammaproteobacteria. It associates with the inner membrane .
SP_0191-like (SP_0191-like)
Type: Family

This is a family of uncharacterised proteins found exclusively in Streptococcus, including a lipoprotein from Streptococcus pneumoniae (

), whose structure is known and consists of six-stranded antiparallel β-sheet packed on one side with helices (

). Most members of this family have an N-terminal lipoprotein lipid attachment site.
Reactive chlorine resistance periplasmic protein RclB (RclB-like)
Type: Family

This entry represents RclB and its homologues, found in gammaproteobacteria. RclB is an ~80 amino acid long periplasmic protein. It is anticipated that this protein is part of a membrane-associated complex responsible for reducing cellular components specifically oxidized by reactive chlorine species (RCS) .
YdaE-like (YdaE-like)
Type: Family

Members of this family include YdaE from the Rac prophage region of Escherichia coli K-12, a homologue from the Gifsy-1 prophage region of Salmonella enterica LT2, and related proteins from other closely related species. The presence of four conserved Cys residues has led to annotations as a zinc-binding protein or metallothionein, but the actual function is unclear. Their predicted structure resembles treble clef (TC) zinc fingers topology.