SII-SWORD/CoKE huggingface dataset:
Dual specificity protein phosphatase PPS1, dual specificity phosphatase domain (PPS1_DSP)
Type: Domain

This entry represents the catalytic dual specificity phosphatase domain found at the C-terminal of fungal proteins, including dual specificity protein phosphatase PPS1 from Saccharomyces cerevisiae, which has a role in the DNA synthesis phase of the cell cycle. As a dual specificity protein phosphatase, PPS1 functions as a protein-serine/threonine phosphatase (

) and a protein-tyrosine-phosphatase (

) .
Cis-biphenyl-2,3-dihydrodiol-2,3-dehydrogenase-like (BphB-like_SDR)
Type: Family

Cis-biphenyl-2,3-dihydrodiol-2,3-dehydrogenase (BphB) is a classical SDR of particular importance for its role in the degradation of biphenyl/polychlorinated biphenyls(PCBs); PCBs are a significant source of environmental contamination . This entry also includes Pseudomonas putida F1 cis-biphenyl-1,2-dihydrodiol-1,2-dehydrogenase (also known as cis-benzene glycol dehydrogenase, encoded by the bnzE gene), which participates in benzene metabolism. In addition, it includes Pseudomonas sp. C18 putative 1,2-dihydroxy-1,2-dihydronaphthalene dehydrogenase which participates in an upper naphthalene catabolic pathway.

SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns .
Transposase ISL3 (Transpos_ISL3)
Type: Family

This entry represents a group of proteins predominantly found in bacteria, that belong to the ISL3 family of transposases, including IS1557 from Mycobacterium tuberculosis and IS1001 from Bordetella parapertussis . Members of this protein family contain the DDE domain (

).
IS4 family transposase (Transpos_IS4)
Type: Family

This entry represents a group of proteins, from prokaryotes, belonging to the IS4 family of transposases. Most members of this protein family contain the domain (

).
Bone morphogenetic protein 2, TGF-beta-like domain (BMP2_TGF_beta-like)
Type: Domain

This entry represents the transforming growth factor beta (TGF-beta)-like domain found in bone morphogenetic protein 2 (BMP-2) and similar proteins from vertebrates. BMP-2, also termed BMP-2A, induces cartilage and bone formation. It stimulates the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A- ATF4 pathway .
DrmC-like (DrmC-like)
Type: Family

This entry represents uncharacterised bacterial phospholipase D-like proteins that are probably distantly related to DrmC. The latter is a phospholipase D (PLD) domain-containing protein and a component of DISARM (Defence Island System Associated with Restriction Modification) .
LIM/homeobox protein Lhx4, LIM domain 1 (LHX4_LIM1)
Type: Domain

This entry represents the first LIM domain of LIM/homeobox protein Lhx4 and similar proteins from vertebrates. LHX4 belongs to the LHX protein family, which features two tandem N-terminal LIM domains and a C-terminal DNA binding homeodomain. Members of LHX family are found in the nucleus and act as transcription factors or cofactors. LHX proteins are critical for the development of specialised cells in multiple tissue types, including the nervous system, skeletal muscle, the heart, the kidneys, and endocrine organs, such as the pituitary gland and the pancreas. LHX4 plays essential roles in pituitary gland and nervous system development. In mice, the lhx4 gene is expressed in the developing hindbrain, cerebral cortex, pituitary gland, and spinal cord . As in other LIM domains, this domain family is 50-60 amino acids in size and shares two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein .
Alkaline protease secretion ATP-binding protein AprD-like, 6TM domain (ABC_AprD-like_6TM)
Type: Domain

This entry represents the six-transmembrane helical domain (6-TMD) of the ABC subunit in the type 1 secretion systems (T1SS) such as AprD/PrtD, which is the integral membrane ATP-binding cassette component of the Dickeya dadantii (

formerly known as Erwinia chrysanthemi) metalloprotease secretion system (PrtDEF). T1SS are found in pathogenic Gram-negative bacteria (such as Escherichia coli, Vibrio cholerae or Bordetella pertussis) to export proteins (often proteases) across both inner and outer membranes to the extracellular medium. This is one of three proteins of the type I secretion apparatus. The Aquifex aeolicus PrtDEF of T1SS is composed of an inner-membrane ABC transporter (PrtD), a periplasmic membrane-fusion protein (PrtE), and an outer-membrane porin (PrtF). These three components assemble into complex spanning both membranes and provide a channel for the translocation of unfolded polypeptides .
B-4DMT transporter-like (B-4DMT-like)
Type: Family

This entry represents a family of uncharacterised bacterial proteins found exclusively in Actinomycetes. These proteins are predicted to contain four transmembrane regions. They are classified as a new transporter family (9.B.148) by TCDB.
IS5 family transposase (Transpos_IS5)
Type: Family

This entry represents a group of proteins from prokaryotes belonging to the IS5 family of transposases.
IS1380 family transposase (Transpos_IS1380)
Type: Family

This entry represents a group of proteins from prokaryotes belonging to the IS1380 family of transposases. Most members of this protein family contain the transposase DDE domain (

).
Transporter suffix domain-like (Transp_suffix-like)
Type: Domain

This entry represents a domain found in uncharacterised proteins, mainly from bacteria, that are predicted to be associated with membrane. This domain spans a highly hydrophobic region about 70 amino acids long that often occurs as a standalone domain of small membrane proteins, but rarely occurs as a C-terminal suffix domain for RND efflux transporter permease subunit proteins.
Lysine-sensitive aspartokinase 3, ACT2 domain (LysC_ACT_2)
Type: Domain

This entry represents the second of two ACT domains located C-terminal to the catalytic domain of the lysine-sensitive aspartokinase isoenzyme AKIII LysC, a monofunctional class enzyme found in bacteria (Escherichia coli (EC) LysC). Aspartokinase is the first enzyme in the aspartate metabolic pathway and catalyzes the conversion of aspartate and ATP to aspartylphosphate and ADP. The E. coli LysC binds two feedback allosteric inhibitor lysine molecules at the dimer interface located between the ACT1 domain of two subunits. The second ACT domain (ACT2), is not involved in the binding of heterotrophic effectors .
Sensor histidine kinase YcbM-like, ATPase domain (YcbM-like_HATPase)
Type: Domain

This entry represents the histidine kinase-like ATPase (HATPase) domain of various two-component sensor histidine kinase (HKs) such as Sensor histidine kinase YcbM from Bacillus subtilis, a HK of the two-component system YcbM-YcbL. Proteins having this HATPase domain also contain a histidine kinase dimerisation and phosphoacceptor domain (HisKA) .
Polyferredoxin EFR1-like (EFR1-like)
Type: Family

This entry represents a group of prokaryotic proteins, including Polyferredoxin from Clostridium acetobutylicum (EFR1,

), which has a C-terminal ferrodoxin domain, with eight conserved Cys residues in two CxxCxxCxxxCP motifs, each of which binds a 4Fe-4S cluster . The N-terminal region resembles flavodoxin domains.
Sensor histidine kinase YpdA-like, ATPase domain (YpdA-like_HATPase)
Type: Domain

This entry represents the histidine kinase-like ATPase (HATPase) domain of various two-component sensor histidine kinase (HKs) such as Escherichia coli YpdA, a HK of the two-component system (TCS) YpdA-YpdB that is involved in a nutrient sensing regulatory network with YehU-YehT. Proteins having this HATPase domain also contain a histidine kinase domain (His-kinase) .
Pleckstrin homology domain-containing family F member 2, FYVE domain (PLEKHF2_FYVE)
Type: Domain

This entry represents the FYVE domain present in human Pleckstrin homology domain-containing family F member 2 (PLEKHF2) and similar sequences from vertebrates. PLEKHF2, also termed Phafin-2 ,or endoplasmic reticulum-associated apoptosis-involved protein containing PH and FYVE domains (EAPF), is a ubiquitously expressed endoplasmic reticulum-associated protein that facilitates tumour necrosis factor alpha (TNF-alpha)-triggered cellular apoptosis through endoplasmic reticulum (ER)-mitochondrial apoptotic pathway. It is an endosomal phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) effector, as well as an interactor of the endosomal-tethering protein EEA1. It regulates endosome fusion upstream of Rab5. PKHF2 also functions as a novel regulator of endocytic epidermal growth factor receptor (EGFR) degradation through a role in endosomal fusion .
PolX, PHP domain (PolX_PHP)
Type: Domain

The bacterial/archaeal X-family DNA polymerases (PolXs) have a PHP domain at their C-terminal, represented in this entry. The bacterial/archaeal PolX core domain and PHP domain interact with each other and together are involved in metal dependent 3'-5' exonuclease activity. PolX is found in all kingdoms, however bacterial PolXs have a completely different domain structure from eukaryotic PolXs. Bacterial PolX has an extended conformation in contrast to the common closed 'right hand' conformation for DNA polymerases. This extended conformation is stabilized by the PHP domain. The PHP domain of PolX is structurally homologous to other members of the PHP family that has a distorted (β/α)7 barrel fold with a trinuclear metal site on the C-terminal side of the barrel .
Long-chain-fatty-acid--AMP ligase FadD32 (FAAL_FadD32)
Type: Family

This entry represents the long-chain-fatty-acid--AMP ligase FadD32, also called FAAL32, from Actinomycetes. FadD32 is a marker enzyme for the biosynthesis of the type of mycolic acids, the very large 'eumycolic acids'. It catalyses the activation of long-chain fatty acids as acyl-adenylates (acyl-AMP), which are then transferred to the phosphopantetheine arm of the polyketide synthase Pks13 for further chain extension .

FadD32 was identified as one of the best genetically and chemically validated new TB drug targets . The 4,6-diaryl-5,7-dimethyl coumarins can directly inhibit the acyl-acyl carrier protein synthetase activity of FadD32 .
Synaptic vesicle 2-related protein-like, major facilitator superfamily domain (SVOP-like_MFS_dom)
Type: Domain

This entry represents the major facilitator superfamily domain of Synaptic vesicle 2-related protein (SVOP), a transporter-like nucleotide binding protein that localises to neurotransmitter-containing vesicles in the brain. Like Synaptic vesicle 2 (SV2), SVOP is expressed in all brain regions, with highest levels in cerebellum, hindbrain and pineal gland . Studies with knockout mice suggest that SVOP may perform a subtle function that is not necessary for survival under normal conditions, since mice lacking SVOP are viable, fertile, and phenotypically normal . SVOP shares structural similarity to the solute carrier family 22 (SLC22), a large family of organic cation and anion transporters . This family belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement .
Lysine-specific demethylase 5A, second PHD finger (KDM5A_PHD2)
Type: Domain

This entry corresponds to the second PHD finger of KDM5A from animals.
KDM5A (also termed Histone demethylase JARID1A, or Retinoblastoma-binding protein 2 (RBBP-2 or RBP2)) was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation . It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK, and BMAL1 . KDM5A functions as a trimethylated histone H3 lysine 4 (H3K4me3) demethylase that belongs to the JARID subfamily within the JmjC proteins . It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC . KDM5A contains the catalytic JmjC domain, JmjN, the AT-rich DNA-interacting domain (ARID, also known as BRIGHT), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers .
Extracellular endonuclease ExeM-like (ExeM-like)
Type: Family

This entry represents Extracellular endonuclease ExeM from Shewanella oneidensis (

) and similar bacterial proteins. ExeM, which is crucial for normal biofilm formation, is a sugar-unspecific endonuclease, which requires Ca2 and Mg2 /Mn2 as co-factors for full activity .
Lysine-specific demethylase 5A, third PHD-finger (KDM5A_PHD3)
Type: Domain

This entry represents the third PHD finger of KDM5A from chordates.
KDM5A (also termed Histone demethylase JARID1A, or Retinoblastoma-binding protein 2 (RBBP-2 or RBP2)) was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation . It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK, and BMAL1 . KDM5A functions as a trimethylated histone H3 lysine 4 (H3K4me3) demethylase that belongs to the JARID subfamily within the JmjC proteins . It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC . KDM5A contains the catalytic JmjC domain, JmjN, the AT-rich DNA-interacting domain (ARID, also known as BRIGHT), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers .
Lysine-specific demethylase 5A, first PHD-finger (KDM5A_PHD1)
Type: Domain

This entry corresponds to the first PHD finger of KDM5A from chordates.
KDM5A (also termed Histone demethylase JARID1A, or Retinoblastoma-binding protein 2 (RBBP-2 or RBP2)) was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation . It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK, and BMAL1 . KDM5A functions as a trimethylated histone H3 lysine 4 (H3K4me3) demethylase that belongs to the JARID subfamily within the JmjC proteins . It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC . KDM5A contains the catalytic JmjC domain, JmjN, the AT-rich DNA-interacting domain (ARID, also known as BRIGHT), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers .
Lysine-specific demethylase 5A, ARID domain (KDM5A_ARID)
Type: Domain

This entry represents the ARID domain of KDM5A from chordates.
KDM5A (also termed Histone demethylase JARID1A, or Retinoblastoma-binding protein 2 (RBBP-2 or RBP2)) was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation . It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK, and BMAL1 . KDM5A functions as a trimethylated histone H3 lysine 4 (H3K4me3) demethylase that belongs to the JARID subfamily within the JmjC proteins . It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC . KDM5A contains the catalytic JmjC domain, JmjN, the AT-rich DNA-interacting domain (ARID, also known as BRIGHT), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers .
Heme-binding protein, predicted (Heme_bind_FMP)
Type: Family

This entry represents a group of uncharacterised proteins from bacteria and fungi, that are predicted to contain a barrel-like heme-binding domain, related to the C-terminal domain of THAP4.
Antitoxin VapB2-like (Anti_VapB2-like)
Type: Family

This entry represents VapB from enteric bacteria and related proteins that are part of the VapBC toxin-antitoxin system. Toxin-antitoxin (TA) systems are common in prokaryotes and allow cells to rapidly adapt to changing environmental conditions through release of active regulators of metabolism. For enteric vapBC TA, the VapC toxins specifically cleave tRNA(fMet) and thus down-regulate protein synthesis. VapB contains an N-terminal DNA-binding SpoVT-AbrB domain (

) and inhibits VapC by binding to the VapC PIN domain via its C-terminal domain.

The structure of VapBC complex was determined (

), revealing a large globular hetero-octameric assembly with SpoVT/AbrB-type DNA-binding domains of VapB at each end . VapBC is the first example of a TA system containing an SpoVT/AbrB-type DNA-binding domain. The DNA-binding motif in VapBC forms through homodimerization of the antitoxin, and it may therefore be one of the main determinants for whether TA complexes form tetramers or octamers.

This entry also includes VapB2 from Haemophilus influenzae (

) , and from Rickettsia felis (

) . It seems unrelated to proteins called VapB in Mycobacterium tuberculosis (

).
UBL3-like, ubiquitin-like domain, metazoan (UBL3_Ubl_met)
Type: Domain

This entry represents the ubiquitin-like domain of UBL3 (Ubiquitin-like protein 3) from metazoan. UBL3, also termed membrane-anchored ubiquitin-fold protein (MUB), or protein HCG-1, belongs to a newly described MUB protein family with structural homology with ubiquitin. UBL3 has been described a regulator of protein sorting to small extracellular vesicles . UBL3 also regulates sorting of MHC II and CD86 in human dendritic cells (DCs) and macrophages . UBL3 proteins have a β-grasp ubiquitin-like (Ubl) domain with longer N- and C-termini and extended loops. The Ubl domain contains a C-terminal CAAX-box, a canonical motif for protein prenylation, which is modified through protein lipidation with a hydrophobic membrane anchor. The lipidation and membrane localisation inhibit attachment of MUBs to target proteins .
Lysine-specific demethylase 5B, first PHD-finger (KDM5B_PHD1)
Type: Domain

This entry represents the first PHD finger of KDM5B which recognizes unmodified H3K4 during the demethylation of histone H3K4me2/3 .
KDM5B (also termed Cancer/testis antigen 31 (CT31), Histone demethylase JARID1B, PLU-1, or retinoblastoma-binding protein 2 homolog 1 (RBP2-H1 or RBBP2H1A)) is a member of the JARID subfamily within the JmjC proteins. It has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of pregnant females and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis . KDM5B acts as a histone demethylase that catalyses the removal of trimethylation of lysine 4 on histone H3 (H3K4me3) , induced by polychlorinated biphenyls (PCBs) . It also mediates demethylation of H3K4me2 and H3K4me1. Moreover, KDM5B functions as a negative regulator of hematopoietic stem cell (HSC) self-renewal and progenitor cell activity . KDM5B has also been shown to interact with the DNA binding transcription factors BF-1 and PAX9, as well as TIEG1/KLF10 (transforming growth factor-beta inducible early gene-1/Kruppel-like transcription factor 10), and possibly function as a transcriptional corepressor. KDM5B contains the catalytic JmjC domain, JmjN, an AT-rich interacting domain (ARID, also known as BRIGHT), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers .
Lysine-specific demethylase 5B, third PHD-finger (KDM5B_PHD3)
Type: Domain

This entry represents the third PHD finger of KDM5B.
KDM5B (also termed Cancer/testis antigen 31 (CT31), Histone demethylase JARID1B, PLU-1, or retinoblastoma-binding protein 2 homolog 1 (RBP2-H1 or RBBP2H1A)) is a member of the JARID subfamily within the JmjC proteins. It has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of pregnant females and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis . KDM5B acts as a histone demethylase that catalyses the removal of trimethylation of lysine 4 on histone H3 (H3K4me3) , induced by polychlorinated biphenyls (PCBs) . It also mediates demethylation of H3K4me2 and H3K4me1. Moreover, KDM5B functions as a negative regulator of hematopoietic stem cell (HSC) self-renewal and progenitor cell activity . KDM5B has also been shown to interact with the DNA binding transcription factors BF-1 and PAX9, as well as TIEG1/KLF10 (transforming growth factor-beta inducible early gene-1/Kruppel-like transcription factor 10), and possibly function as a transcriptional corepressor. KDM5B contains the catalytic JmjC domain, JmjN, an AT-rich interacting domain (ARID, also known as BRIGHT), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers .
Lysine-specific demethylase 5B, ARID domain (KDM5B_ARID)
Type: Domain

This entry represents the ARID DNA-binding domain of KDM5B.
KDM5B (also termed Cancer/testis antigen 31 (CT31), Histone demethylase JARID1B, PLU-1, or retinoblastoma-binding protein 2 homolog 1 (RBP2-H1 or RBBP2H1A)) is a member of the JARID subfamily within the JmjC proteins. It has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of pregnant females and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis . KDM5B acts as a histone demethylase that catalyses the removal of trimethylation of lysine 4 on histone H3 (H3K4me3) , induced by polychlorinated biphenyls (PCBs) . It also mediates demethylation of H3K4me2 and H3K4me1. Moreover, KDM5B functions as a negative regulator of hematopoietic stem cell (HSC) self-renewal and progenitor cell activity . KDM5B has also been shown to interact with the DNA binding transcription factors BF-1 and PAX9, as well as TIEG1/KLF10 (transforming growth factor-beta inducible early gene-1/Kruppel-like transcription factor 10), and possibly function as a transcriptional corepressor. KDM5B contains the catalytic JmjC domain, JmjN, an AT-rich interacting domain (ARID, also known as BRIGHT), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers .
Penicillin-binding protein 2B (PBP2B)
Type: Family

This family includes penicillin-binding protein 2B (PBP2B) found in Streptococcus. PBP2B from Streptococcus pneumoniae is a monofunctional (class B) high-molecular-weight PBP which catalyses the transpeptidation between adjacent stem peptides of peptidoglycan . PBP2B is essential for peripheral peptidoglycan synthesis in this organism .

Extensive use of β-lactam antibiotics over the past 4 decades has led to the selection of pathogenic streptococci resistant to their action. PBP2B was identified as one of the primary resistance determinants for these antibiotics .
Differentially expressed in FDCP 8, C conserved region 1 (DEF8_C1)
Type: Domain

Differentially expressed in FDCP 8 (DEF-8) positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts. It is involved in bone resorption . DEF-8 contains a protein kinase C conserved region 1 (C1) domain followed by a RUBICON domain.

This entry represents the C1 domain of DEF-8 from mammals and its homologues. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2)-binding sites .