SII-SWORD/CoKE huggingface dataset:
Structural accessory protein ORF7b, SARS-CoV-like (ORF7b_SARS-CoV-like)
Type: Family

This entry contains the ORF7b, also called NS7b, of Severe Acute Respiratory Syndrome coronaviruses (SARS-CoVs) and related betacoronaviruses identified in Chinese horseshoe bats, including bat SARS-like-CoV WIV1 and HKU3.

ORF7b/NS7b from betacoronavirus in the B lineage are not related to NS7b proteins from other betacoronavirus lineages. The SARS-CoV ORF7b protein is a 44 amino acid protein which is homologous to an accessory but structural component of SARS-CoV virion. While ORF7b is packaged into virions, it is not required for the virus budding process, as gene 7 deletion viruses replicate efficiently in vitro and in vivo. Moreover, ORF7b possesses a transmembrane helical domain (TMD), between 9-29 amino acid residues, is necessary for its Golgi complex localization, as replacing it with the TMD from the human endoprotease furin results in aberrant localization .
SF1 helicase-like, zinc-binding domain, ronidovirus (SF1_Hel-like_ZBD_rv)
Type: Domain

This entry represents the Cys/His rich zinc-binding domain (ZBD) of the helicase encoded on ORF1a and belongs to helicase superfamily 1 (SF1) from ronidovirus family including Gill-associated virus (GAV) . The ZBD has 3 zinc-finger (Znf1-3) motifs. Proteins containing this domain belong to a family of nindoviral replication helicases similar to SARS-NSP13 helicase, not included in this entry. The SARS-NSP13 ZBD is indispensable for helicase activity and interacts with SARS-Nsp12. SARS-Nsp12 can enhance the helicase activity of SARS-Nsp13 and can interact with SARS-Nsp13 on the third zinc finger motif of the ZBD .
SF1 helicase, ronidovirus (SF1_Hel_unc_rv-like)
Type: Domain

This entry represents an uncharacterised domain located between the Cys/His zinc-binding domain (ZBD) and the first helicase domain found in helicases from Gill-associated virus (GAV) and related viruses from ronidovirus family. It is thought to be a linker domain. They are related to the SF1 family of nidoviral replication helicases, similar to the Severe Acute Respiratory Syndrome coronavirus (SARS) non-structural protein 13 (SARS-NSP13) helicase (not included in this entry), which share a similar domain organisation. The location and orientation of this uncharacterised domain represented in this ronidovirus group resembles that of the 1B domain in SARS-NSP13 helicase .
NendoU domain, porcine torovirus-like (NendoU_PToV-like)
Type: Domain

Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end and are widely conserved among this order . This entry represents the NendoU domain from toroviruses including Breda virus 1, Berne virus, Porcine torovirus and related viruses. This domain is related to the NendoU domain found in Nsp15 from coronaviruses and Nsp11 from arteriviruses , which participate in the viral replication process and in the evasion of the host immune system.
Globin-sensor domain (Globin-sensor_dom)
Type: Domain

This domain is found at the N-terminal of globin-containing proteins mainly from bacteria, archaea and fungi . It is found in protoglobin, a single-domain globin of yet unknown biological function , which has specific loops and an amino-terminal extension which leads to the burying of the heme within the matrix of the protein. Protoglobin-specific apolar tunnels allow the access of O2, CO and NO to the haem distal site . This domain can also recognise cyanide (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).

Proteins containing this domain include protoglobins from the strictly anaerobic methanogen Methanosarcina acetivorans and from the obligate aerobic hyperthermophile Aeropyrum pernix . This domain is also found in the N-terminal regions of HemAT from the archaeon Halobacterium salinarum (HemAT-Hs) and from the Gram-positive bacterium Bacillus subtilis (HemAT-Bs) . It contains a myoglobin-like motif, displays characteristic heme-protein absorption spectra, and binds oxygen reversibly . This domain is present in Diguanylate cyclase DosC (also known as YddV) from E. coli which is coupled with a C-terminal diguanylate cyclase (DGC/GGDEF) domain, which likely functions as a c-di-GMP cyclase in the synthesis of the second messenger cyclic-di-GMP (c-di-GMP) .
NSP15, NendoU domain, coronavirus (NSP15_NendoU_CoV)
Type: Domain

Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. They are conserved among this order and a genetic marker of nidoviruses . A feature of these viruses' evolutionary relationship is the organisation and processing of the genome, which is translated in two large precursor polyproteins (pp1a and pp1ab) from the replicase gene, that are proteolytically processed by virus proteases into 13 to 16 nonstructural proteins (NSPs) .

Proteins containing the NendoU domain include NSP15 from coronaviruses and NSP11 from arteriviruses, both of which participate in the viral replication process and in the evasion of the host immune system. Although they are similar and conserved, they only share 27% identical residues and show structural differences . NSP11 has an N-terminal domain and a C-terminal NendoU catalytic domain. NSP11 functions as a dimer and Mg2 is dispensable for its activity. In Porcine reproductive and respiratory syndrome virus (PRRSV), NSP11 induces STAT2 degradation to inhibit interferon signaling. Mutagenesis studies revealed that the amino acid residue K59 located at the N-terminal domain of NSP11 is indispensable for inducing STAT2 reduction . This domain is not conserved in those nidovirus branches that replicate in invertebrate hosts (Mesoniviridae, Roniviridae), suggesting specific roles in vertebrate hosts.

The NendoU domain packs into two β-sheets which constitute the catalytic-site cleft located at one side of the domain. A group of small α-helices packed at the other side of the domain face the concave surface of the β-sheets. The active site, located in the shallow groove between the two β-sheets, carries the catalytic triad made of two histidines and a lysine .

This entry represents the C-terminal NendoU domain of NSP15. NSP15 is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. This domain exhibits endoribonuclease activity designated EndoU, highly conserved in all known CoVs and is part of the replicase-transcriptase complex that plays important roles in virus replication and transcription . NSP15 is a Uridylate-specific endoribonuclease that cleaves the 5'-polyuridines from negative-sense viral RNA, termed PUN RNA either upstream or downstream of uridylates, at GUU or GU to produce molecules with 2',3'-cyclic phosphate ends . PUN RNA is a CoV MDA5-dependent pathogen-associated molecular pattern (PAMP) .
PRDM8-like, PR/SET domain (PRDM8-like_PR/SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 8 (PRDM8). PRDM8 is a transcription factor that plays an essential role in the development of the mammalian retina .

This entry also includes the Zinc finger protein 488 from zebra fish which may have histone methyltransferase activity. It negatively regulates shh signaling activity in pMN progenitor cells which prevents their switch from motor neuron to oligodendrocyte precursor cell production and it also regulates oligodendrocyte formation . It was originally named prdm8 but the gene name was later changed to znf488 in recognition of the fact that it is an orthologue of mammalian ZNF488 as supported by synteny and phylogenetics. In non-mammalian gnathostomes, znf488 has an N-terminal SET domain and C-terminal zinc fingers similar to PRDM8.

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM10, PR/SET domain (PRDM10_PR/SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 10 (PRDM10). PRDM10 may be involved in transcriptional regulation .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM4, PR/SET domain (PRDM4_PR/SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 4 (PRDM4). PRDM4 may function as a transcription factor that recruits protein arginine methyltransferase 5 (PRMT5) to mediate histone arginine methylation and control neural stem cell proliferation and differentiation .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM11, PR/SET domain (PRDM11_PR/SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 11 (PRDM11). PRDM11 is a putative tumour suppressor that controls the expression of key oncogenes .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM12, PR/SET domain (PRDM12_PR/SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 12 (PRDM12). PRDM12 is essential for human pain perception . It is also a key regulator of sensory neuronal specification in Xenopus . It has been shown to initiate and maintain the expression of TrkA in developing nociceptors .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM13, PR/SET domain (PRDM13_PR/SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 13 (PRDM13). PRDM13 mediates the balance of inhibitory and excitatory neurons in somatosensory circuits . It is also required to achieve precise neuronal specification during mouse development . The duplication of PRMD13 causes North Carolina macular dystrophy .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM14, PR/SET domain (PRDM14_PR-SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 14 (PRDM14). PRDM14 acts on regulating epigenetic modifications in the cells, playing a key role in the regulation of cell pluripotency, epigenetic reprogramming, differentiation and development . Aberrant PRDM14 expression is associated with tumorigenesis, cell migration and cell chemotherapeutic drugs resistance .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM15, PR/SET domain (PRDM15_PR-SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 15 (PRDM15). PRDM15 plays an essential role as a chromatin factor that modulates the transcription of upstream regulators of WNT and MAPK-ERK signaling to safeguard naive pluripotency .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM16, PR/SET domain (PRDM16_PR-SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 16 (PRDM16, also known as MEL1). PRDM16 and PRDM3 share protein sequences similarities and have functions in hematopoietic and neuronal stem cells and in adipose tissue differentiation. They also act as oncoproteins (Mel1 and Evi1) involved in translocation-induced leukemia. PRDM3 and PRDM16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM3, PR/SET domain (PRDM3_PR-SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 3 (PRDM3, also known as MECOM or EVI-1). PRDM3 and PRDM16 share protein sequences similarities and have functions in hematopoietic and neuronal stem cells and in adipose tissue differentiation. They also act as oncoproteins (Mel1 and Evi1) involved in translocation-induced leukemia. PRDM3 and PRDM16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM17, PR/SET domain (PRDM17_PR-SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 17 (PRDM17, also known as ZNF408). Its function is not clear.

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM1, PR/SET domain (PRDM1_PR-SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 1 (PRDM1, also known as BLIMP-1). PRDM1 is a transcriptional repressor that is essential for cellular development. It is essential for the differentiation of B and T cells . In Caenorhabditis elegans, it regulates the spatiotemporal cell migration pattern . The degradation of PRDM1 by DRE-1/FBXO11-dependent mechanism regulates the C. elegans developmental timing and maturation .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM2, PR/SET domain (PRDM2_PR-SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 2 (PRDM2, also known as RIZ1). PRDM2 is S-adenosyl-L-methionine-dependent histone methyltransferase that specifically methylates 'Lys-9' of histone H3 .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM5, PR/SET domain (PRDM5_PR-SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 5 (PRDM5). PRDM5 is a sequence-specific DNA-binding transcription factor that represses transcription at least in part by recruitment of the histone methyltransferase EHMT2/G9A and histone deacetylases such as HDAC1 . Mutation of the PRDM5 gene has been linked to Brittle cornea syndrome 2 (BCS2) .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM6, PR/SET domain (PRDM6_PR-SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 6 (PRDM6, also known as PRISM). PRDM6 has been shown to co-localized with histone H4 and methylates H4-K20 . It has also been shown to act as a transcriptional repressor by interacting with class I histone deacetylases and the G9a histone methyltransferase . It promotes the transition from differentiated to proliferative smooth muscle by suppressing differentiation and maintaining the proliferative potential of vascular smooth muscle cells . It also plays a role in endothelial cells by inhibiting endothelial cell proliferation, survival and differentiation . Mutations in the PRDM6 gene have been linked to nonsyndromic patent ductus arteriosus (PDA), which is a common congenital heart defect (CHD) with both inherited and acquired causes .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
PRDM7/PRDM9, PR/SET domain (PRDM7_9_PR-SET)
Type: Domain

This entry represents the PR/SET domain found in PR domain zinc finger protein 7 and 9 (PRDM7/9). PRDM7 (also termed PR domain-containing protein 7) is a primate-specific histone methyltransferase that is the result of a recent gene duplication of PRDM9. It selectively catalyses the trimethylation of H3 lysine 4 (H3K4me3) . PRDM9 (also termed PR domain-containing protein 9) is a histone methyltransferase that specifically trimethylates 'Lys-4' of histone H3 (H3K4me3) during meiotic prophase and is essential for proper meiotic progression. It also efficiently mono-, di-, and trimethylates H3K36. Aberrant PRDM9 expression is associated with genome instability in cancer . PRDM9 has also been shown to be able to performs intramolecular automethylation on multiple lysine residues localised to a lysine-rich region on the post-SET domain .

The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains . They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes .
SMYD1, SET domain (SMYD1_SET)
Type: Domain

This entry represents the SET domain of SET and MYND domain-containing protein 1 (SMYD1). SMYD1 functions as a histone methyltransferase and regulates downstream gene transcription. It methylates histone H3 at 'Lys-4' (H3K4me), seems able to perform both mono-, di-, and trimethylation. SMYD1 plays a critical role in cardiomyocyte differentiation, cardiac morphogenesis and myofibril organisation, as well as in the regulation of endothelial cells (ECs) . It is expressed in vascular endothelial cells, it has been shown that knockdown of SMYD1 in endothelial cells impairs EC migration and tube formation .

The SMYD family consists of five members including SMYD1/2/3/4/5. They contain two highly conserved structural and functional domains, the SET and MYND domains. The SET domain is involved in lysine methylation, while the MYND domain is involved in protein-protein interaction. They are essential in several mammalian developmental pathways .
SMYD2, SET domain (SMYD2_SET)
Type: Domain

This entry represents the SET domain of SET and MYND domain-containing protein 2 (SMYD2). SMYD2 functions as a histone methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1 . It specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). It plays a role in myofilament organisation in both skeletal and cardiac muscles via Hsp90 methylation . SMYD2 overexpression is associated with tumour cell proliferation and a worse outcome in human papillomavirus-unrelated nonmultiple head and neck carcinomas . It regulates leukemia cell growth such that diminished SMYD2 expression upregulates SET7/9, thereby possibly shifting leukemia cells from growth to quiescence state associated with resistance to DNA damage associated with Acute Myeloid Leukemia (AML) .

The SMYD family consists of five members including SMYD1/2/3/4/5. They contain two highly conserved structural and functional domains, the SET and MYND domains. The SET domain is involved in lysine methylation, while the MYND domain is involved in protein-protein interaction. They are essential in several mammalian developmental pathways .