SII-SWORD/CoKE huggingface dataset:
Tubulin--tyrosine ligase-like protein 12, SET-like domain (SET_TTL12)
Type: Domain

This entry represents the SET-like domain found in Tubulin--tyrosine ligase-like protein 12 (TTL12) and related proteins in eukaryotes.

Tubulin tyrosine ligase-like 12 (TTLL2) is a member of the tubulin tyrosine ligase (TTL) group, although its precise function remains unclear. TTLL2 contains both SET-like and TTL-like domains, suggesting potential involvement in histone methylation and tubulin tyrosine ligase activities . However, it lacks catalytic activity related to tubulin or histone modification and is instead believed to play a regulatory role in these processes. TTL proteins more broadly are implicated in the negative regulation of tubulin post-translational modifications . The SET-like domain of TTLL2 is a divergent variant of the canonical SET domain; while it retains structural features of functional SET domains, it lacks the key residues necessary for histone lysine methyltransferase activity. Rather than enzymatic function, this domain is thought to exert non-catalytic effects, possibly influencing microtubule dynamics and stability .
SF0329-like (SF0329-like)
Type: Family

This family includes SF0329 (

) from Shigella flexneri and similar bacterial sequences. Full length homologues of SF0329 are found in hundreds of bacterial species. The function of these proteins is still unknown.
Major coat protein VP4 (SFV1_VP4)
Type: Family

This entry represents one of the two major coat proteins (VP4) of Sulfolobus filamentous virus 1 (SFV1), a membrane-enveloped filamentous virus that infects the hyperthermophilic acidophile Sulfolobus shibatae. VP4 forms a heterodimer with VP5 and wraps around A-form DNA. Despite having no detectable sequence similarity with VP5 or with coat proteins from other archaeal filamentous viruses, VP4 exhibits remarkable structural similarity to these proteins. The N-terminal portion of VP4 contains residues that project into the groove of the viral DNA .
Major coat protein VP5 (SFV1_VP5)
Type: Family

This entry represents one of the two major coat proteins (VP5) of Sulfolobus filamentous virus 1 (SFV1), a membrane-enveloped filamentous virus that infects the hyperthermophilic acidophile Sulfolobus shibatae. VP5 forms a heterodimer with VP4 and wraps around A-form DNA. Compared to VP4, VP5 has an insertion containing two beta-strands and a C-terminal extension containing two short helices that contacts subunits in adjacent helical turns. The N-terminal portion of VP5 contains 6-7 residues that project deeply into the hollow core of the viral DNA. Despite having no detectable sequence similarity with VP4 or with coat proteins from other archaeal filamentous viruses, VP5 exhibits remarkable structural similarity to these proteins.
SH3b_P2 domain (SH3b_P2_dom)
Type: Domain

This entry represents a bacterial SH3 domain. This domain is typically present in peptidoglycan-degrading enzymes from bacteriophages as a cell wall-binding domain. It is closely related to (

).
Shotokuvirus capsid protein (Shotoku_capsid)
Type: Family

This entry represents the capsid proteins from Shotokuviruses that are responsible for forming the icosahedral capsid of virions. Members of this family have the ability to self-assemble, which is a critical function in the construction of the protective shell that encases the viral genome. This structural role is essential for the stability and infectivity of the virus, as the capsid not only protects the viral genetic material from degradation but also plays a role in the recognition and attachment to host cells. The self-assembly property of these proteins is a key feature that facilitates the efficient packaging of viral components during the viral replication cycle.
Skunalikevirus tail terminator (Skunalike_TailTerm)
Type: Family

The Skunalikevirus tail terminator protein family is crucial for the assembly of viral tails. It functions by capping the rapidly elongating tail once it reaches its required length. This capping process is essential as it provides a stable interaction surface for the connector and tail tube proteins, ensuring proper tail assembly and structural integrity. This role is vital for the formation of functional viral particles, facilitating the correct attachment and assembly of other tail components.
Gp41 (Gp41)
Type: Family

This entry represents a family of proteins related to gene 41 protein from Bacillus phage SP01. Its specific function remains unknown. Members of this family are found in bacteriophages that infect Bacillus species.
SPT23/MGA2-like, DNA-binding domain (SPT23_MGA2_DBD)
Type: Domain

This entry represents the DNA-binding domain found in yeast SPT23 and MGA2 transcription factors. The specific function of this DNA-binding domain remains to be fully characterised .

SPT23 and MGA2 are involved in the regulation of OLE1 gene expression, which encodes a fatty acid desaturase essential for unsaturated fatty acid synthesis. SPT23 and MGA2 are activated through regulated ubiquitin/proteasome-dependent processing (RUP), releasing the N-terminal fragments that translocate to the nucleus to regulate transcription.
Capsid protein VP10 (SPV1_VP10)
Type: Family

This entry represents the VP10 capsid protein found in Sulfolobus polyhedral virus 1 (SPV1), a virus that infects hyperthermophilic acidophilic archaea. VP10 forms pentamers located at the 5-fold axes of the icosahedral virion. Despite having low sequence identity (~15%) with the major capsid protein VP4, VP10 shares a similar structural fold - a variation of the jelly-roll fold with additional beta-strands inserted next to the G-strand. VP10 pentamers act as adaptors for vertex complexes, anchoring them to the virion. The VP10 pentamers, along with VP4 hexamers, assemble into a T=43 icosahedral shell, which represents a capsid arrangement not previously described in viruses .
Major capsid protein VP4 (SPV1_VP4)
Type: Family

This entry represents the major capsid protein VP4 from Sulfolobus polyhedral virus 1 (SPV1), which infects hyperthermophilic acidophilic archaea. VP4 is the primary component of the icosahedral capsid of SPV1, forming hexamers that assemble into a T=43 surface lattice. The protein adopts a variation of the jelly-roll fold, with additional β-strands inserted next to the C-strand (C'). Unlike the classical jelly-roll fold, the axis of the β-barrel in SPV1 VP4 is tilted 30 degrees with respect to the normal to the capsid surface. VP4 shares limited sequence identity (~15%) but high structural similarity with VP10, which forms pentamers at the five-fold axes of the icosahedral capsid .
STEEP1 domain (STEEP1_dom)
Type: Domain

This domain is found towards the N-terminal end of human STING ER exit protein (STEEP1) and similar eukaryotic sequences. This domain adopts an all-β configuration.

STEEP1 is a molecular adapter that stimulates membrane curvature formation and subsequent endoplasmic reticulum exit site establishment by recruiting PI3K complex I, leading to COPII vesicle-mediated transport . STEEP interacts with STING and enables STING signaling by promoting ER exit .
Capsid assembly scaffolding protein, T4-phage (T4_SCAF)
Type: Family

This entry represents Capsid assembly scaffolding protein from Enterobacteria phage T4 (SCAF) and similar sequences mainly found in tailed bacteriophages. Members of this protein family are crucial for the assembly of icosahedral procapsids in bacteriophages. These proteins coassemble with capsid proteins to form the procapsid structure, positioning themselves within the external shell of the icosahedrally arranged capsid protein subunits. During the maturation process, the scaffolding proteins are cleaved by the viral protease and subsequently released, except for an internal peptide known as peptide VII, which remains incorporated into the mature phage head. This process is essential for the proper formation and function of the viral capsid.
Tape measure protein-like (T4_TMP)
Type: Family

This entry represents bacteriophage tape measure proteins (TMP) that serve as molecular rulers determining the length of phage tails . During tail assembly, the TMP acts as a template for tail tube polymerisation, with the protein being incorporated in an initially unfolded form. As the tail tube forms, the TMP extends, determining the final length of the tail structure. The tape measure protein is also involved in DNA transfer, possibly forming a channel through which phage DNA passes into the host cell during infection. In phage T4, the tape measure protein (gp29) is located in the central hub of the baseplate and extends through the tail tube.
Phage T4 Y03C-like (T4_Y03C-like)
Type: Family

This entry represents a family of small uncharacterised proteins found in bacteriophage T4, including the 10.3 kDa protein encoded in the Gp46-Gp47 intergenic region of T4 phage (Y03C). The function of this protein family remains unknown.
Bacteriophage T4 Y13H-like (T4_Y13H-like)
Type: Family

This entry represents the uncharacterised Y13H (cd.5) protein found in Enterobacteria phage T4. The protein is encoded in the cd-pseT intergenic region of the phage genome. The function of this small 8.7 kDa protein remains unknown. It may play a role in phage replication or host interaction.
Tail completion protein p143 (T5_p143)
Type: Family

This entry represents the tail completion protein p143 found in bacteriophage T5. Unlike typical tail completion proteins that are located at the head-tail joining region, p143 is found at the base of only one BHP pb3 monomer in the T5 tail tip. This protein appears to have a role in tail stability and may detach during the infection process. Cryo-EM structural studies have shown that this protein is absent from reconstructions of the tip after interaction with the bacterial receptor FhuA, suggesting a potential role in the infection mechanism.
Pleckstrin homology domain-containing family A member 4-7, TBCA domain (PKHA4-7_TBCA)
Type: Domain

This entry represents the tubulin chaperone cofactor A (TBCA) domain in Pleckstrin homology (PH) domain-containing proteins, mostly found in eukaryotes. The TBCA fold displays three α-helices forming an antiparallel bundle. Human TBCA functions as a molecular chaperone for beta-tubulin . PH domain-containing proteins, such as PKHA7, are crucial for the biogenesis and maintenance of zonula adherens, a type of cell-cell junction . The specific function of the TBCA domain in PH domain-containing proteins has not been elucidated yet.
Phage terminase small subunit (Terminase_7)
Type: Family

This entry represents a putative phage small terminase subunit. Predicted structures show similarity albeit weak to the structure of the HK97 terminase (

). Furthermore structure prediction suggests members of this family can form homomeric rings with high confidence as expected for small subunit terminases.
Transmembrane protein 218, N-terminal domain (TMEM218_N)
Type: Domain

This domain is found at the N-terminal end of human Transmembrane protein 218 (TMEM218), which may be involved in ciliary biogenesis or function .
NUA/TPR/MLP1-2-like domain (NUA/TPR/MLP1-2-like_dom)
Type: Domain

This domain is found in human Nucleoprotein TPR, Nuclear-pore anchor from Arabidopsis thaliana (NUA), yeast Protein MLP1/2 and similar eukaryotic proteins. This domain is often found associated with

and is predicted to adopt an all-α structure.

TPR is a component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope . NUA, a component of the nuclear pore complex, acts as a docking site for activities required for desumoylation and mRNA export. It is required for the proper expression or localisation of a subset of miRNAs . MLP1/2 are involved in the structural and functional organisation of perinuclear chromatin .
Anaphase-promoting complex subunit 2, TPR repeats (TPR_ANAPC2)
Type: Domain

This is a region of tetratricopeptide (TPR)-like repeats found in human Anaphase-promoting complex subunit 2 (ANAPC2) and similar eukaryotic sequences.

ANAPC2 is part of the catalytic component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle .

The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome .
DENND3-like, TPR repeats (TPR_DENND3)
Type: Domain

This is a region of tetratricopeptide (TPR)-like repeats found in human DENN domain-containing protein 3 (DENND3) and similar proteins from vertebrates.

DENND3 is a guanine nucleotide exchange factor (GEF) that promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form .
Dynein axonemal assembly factor 5, TPR repeats (TPR_DAAF5)
Type: Domain

This is a region of tetratricopeptide (TPR)-like repeats found towards the N-terminal end of human Dynein axonemal assembly factor 5 (DNAAF5) and similar eukaryotic proteins.

DAAF5 is a cytoplasmic protein involved in the delivery of the dynein machinery to the motile cilium. It is required for the assembly of the axonemal dynein inner and outer arms, two structures attached to the peripheral outer doublet A microtubule of the axoneme, that play a crucial role in cilium motility .
IFT121-like, TPR repeats (TPR_IFT121)
Type: Domain

This region of tetratricopeptide (TPR)-like repeats is found towards the C-terminal end of IFT121.

IFT121 (also known as WDR35) is a component of the IFT complex A (IFT-A), which is required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors that is involved in ciliogenesis and ciliary protein trafficking . This protein plays a role in cilia assembly and maintenance . IFT121 contains a zinc finger with rubredoxin-like fold . Knock-out IFT121 cells showed defective retrograde trafficking within cilia .
INTS8, TPR repeats (TPR_INTS8)
Type: Domain

This is a region of tetratricopeptide (TPR)-like repeats found towards the C-terminal end of human Integrator complex subunit 8 (INTS8).

Integrator complex subunit 8 (INTS8) is a component of the multiprotein complex Integrator, which is responsible for the endonucleolytic cleavage in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing .

The Integrator is an RNA polymerase II complex which contains at least 12 novel subunits and core RNAPII subunits. Two of the Integrator subunits share similarity with subunits of the cleavage and polyadenylation specificity factor (CPSF) complex. Integrator has been shown to be recruited to the U1 and U2 snRNA genes, and to mediate the snRNAs' 3' end processing. The Integrator complex is evolutionarily conserved in metazoans, and directly interacts with the C-terminal domain of the RNA polymerase II largest subunit .
LAA1-like, C-terminal TPR repeats (TPR_LAA1-like_C)
Type: Domain

This is a region of tetratricopeptide (TPR)-like repeats found at the C-terminal end of AP-1 accessory protein LAA1 from Saccharomyces cerevisiae and similar sequences mainly found in fungi. LAA1 is involved in localisation of clathrin adapter protein complex-1 (AP-1) and subsequent AP-1-mediated clathrin-coated vesicle cargo loading . Pof6 interactor protein 1 from Schizosaccharomyces pombe (Sip1), which is required for endocytosis and also involved in cytokinesis and cell division .
NAA35-like, TPR repeats (TPR_NAA35)
Type: Domain

This is a region of tetratricopeptide (TPR)-like repeats found at the C-terminal end of human N-alpha-acetyltransferase 35, NatC auxiliary subunit (NAA35) and similar sequences.

In budding yeasts, NatC N(alpha)-terminal acetyltransferases contain Mak10, Mak31 and Mak3 subunits. All three subunits are associated with each other to form the active complex . Naa35, also known as MAK10, catalyses acetylation of the N-terminal Met of the L-A virus Gag protein. MAK10 has a role in the propagation of L-A and M viruses, perhaps in the viral assembly. It is apparently directly needed for optimum respiration . The N-terminal acetylation protects proteins from ubiquitination and degradation by the N-end rule pathway . In humans, Naa35 is involved in regulation of apoptosis and proliferation of smooth muscle cells .
NAA35-like, N-terminal (NAA35-like_N)
Type: Domain

This entry represents the N-terminal region of human N-alpha-acetyltransferase 35, NatC auxiliary subunit (NAA35) and similar sequences.

In budding yeasts, NatC N(alpha)-terminal acetyltransferases contain Mak10, Mak31 and Mak3 subunits. All three subunits are associated with each other to form the active complex . Naa35, also known as MAK10, catalyses acetylation of the N-terminal Met of the L-A virus Gag protein. MAK10 has a role in the propagation of L-A and M viruses, perhaps in the viral assembly. It is apparently directly needed for optimum respiration . The N-terminal acetylation protects proteins from ubiquitination and degradation by the N-end rule pathway . In humans, Naa35 is involved in regulation of apoptosis and proliferation of smooth muscle cells .
PATROL1-like, C-terminal (PATROL1_C)
Type: Domain

This region is found towards the C-terminal end of Protein unc-13 homolog from Arabidopsis thaliana (PATROL1), which is essential for stomatal opening in response to low concentration of carbon dioxide and light .
26S proteasome non-ATPase regulatory subunit 3, N-terminal TPR repeats (TPR_PSMD3_N)
Type: Domain

This region of tetratricopeptide (TPR)-like repeats is found at the N-terminal of human 26S proteasome non-ATPase regulatory subunit 3 (PSMD3) and similar eukaryotic sequences. PSMD3 is a component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins .

Intracellular proteins, including short-lived proteins such as cyclin, Mos, Myc, p53, NF-kappaB, and IkappaB, are degraded by the ubiquitin-proteasome system. The 26S proteasome is a self-compartmentalising protease responsible for the regulated degradation of intracellular proteins in eukaryotes . This giant intracellular protease is formed by several subunits arranged into two 19S polar caps, where protein recognition and ATP-dependent unfolding occur, flanking a 20S central barrel-shaped structure with an inner proteolytic chamber. This overall structure is highly conserved among eukaryotes and is essential for cell viability. Proteins targeted to the 26S proteasome are conjugated with a polyubiquitin chain by an enzymatic cascade before delivery to the 26S proteasome for degradation into oligopeptides.

The 26S proteasome can be divided into two subcomplexes: the 19S regulatory particle (RP) and the 20S core particle (CP) . The 19S component is divided into a "base" subunit containing six ATPases (Rpt proteins) and two non-ATPases (Rpn1, Rpn2), and a "lid" subunit composed of eight stoichiometric proteins (Rpn3, Rpn5, Rpn6, Rpn7, Rpn8, Rpn9, Rpn11, Rpn12) . Additional non-essential and species specific proteins may also be present. The 19S unit performs several essential functions including binding the specific protein substrates, unfolding them, cleaving the attached ubiquitin chains, opening the 20S subunit, and driving the unfolded polypeptide into the proteolytic chamber for degradation. The 26s proteasome and 19S regulator are of medical interest due to their involvement in burn rehabilitation .
Zinc finger protein Rlf/292/654, TPR repeats (TPR_Rlf/292/654)
Type: Domain

This region of tetratricopeptide (TPR)-like repeats is found in human Zinc finger protein Rlf/292/654 and similar proteins. These proteins may be involved in transcriptional regulation.
E3 ubiquitin-protein ligase RNF123/RKP, TPR repeat (TPR_RNF123/RKP)
Type: Domain

This is a region of tetratricopeptide (TPR)-like repeats found in human E3 ubiquitin-protein ligase RNF123 and similar eukaryotic proteins including E3 ubiquitin-protein ligase RKP	from plants.

RNF123 is the catalytic subunit of the KPC complex and functions as an E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasome-mediated degradation of CDKN1B, a cyclin-dependent kinase inhibitor involved in the G0-G1 transition of the cell cycle . In addition to its E3 ligase activity, RNF123 also acts as an inhibitor of innate antiviral signalling mediated by DDX58 and IFIH1, functioning independently of its ligase activity .

RKP is an E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of KRP1 and KRP2 .
PBCV-1 P7, disulphide-bonded domain (PBCV1_P7)
Type: Domain

This entry represents a small disulphide-bonded subdomain in multiple copies of the P7 protein of Paramecium bursaria chlorella virus 1 (PBCV-1). In the viral capsid, P7 is situated at the conjunction of capsomers b, c, and e, glueing these three capsomers together within the pentasymmetron. This subdomain plays a crucial role in stabilising the viral capsid structure of PBCV-1, a large dsDNA-containing virus that infects certain chlorella-like green algae .
RPAP1/MINIYO-like, TPR repeats (TPR_RPAP1/MINIYO-like)
Type: Domain

This region of tetratricopeptide (TPR)-like repeats is found in human RNA polymerase II-associated protein 1 (RPAP1), Transcriptional elongation regulator MINIYO from Arabidopsis thaliana and similar eukaryotic proteins. RPAP1 is required for interaction of the RNA polymerase II complex with acetylated histone H3 . MINIYO is a positive regulator of transcriptional elongation that is essential for cells to initiate differentiation. It interacts with RNA polymerase II and the Elongator complex and is required to sustain global levels of transcriptional elongation activity, specifically in differentiating tissues .
SYO1-like, TPR repeats (TPR_SYO1)
Type: Domain

This is a region of tetratricopeptide (TPR)-like repeats found in Synchronised import protein 1 from Saccharomyces cerevisiae (SYO1), human HEAT repeat-containing protein 3 (HEATR3) and similar eukaryotic proteins.

SYO1 and HEATR3 are involved in ribosome biogenesis and nuclear import, functioning as adaptor proteins that facilitate the transport of ribosomal components into the nucleus. Specifically, SYO1 acts as a nuclear import adaptor that recruits the functionally and topologically linked ribosomal proteins RPL5 and RPL11 . HEATR3 also contributes to ribosome biogenesis by mediating the nuclear import of the 60S ribosomal protein RPL5, also known as large ribosomal subunit protein uL18 . These proteins are essential for the proper assembly of the ribosome, ensuring the coordinated delivery of RPL5 and RPL11 to the nascent 5S rRNA within the nucleus. In addition to their roles in ribosome assembly, they are critical for erythrocyte maturation, highlighting their broader importance in cellular development and function.