SII-SWORD/CoKE huggingface dataset:
TFIIIC subunit GTF3C6-like (GTF3C6-like)
Type: Family

This entry includes TFIIIC subunit GTF3C6 (also known as TFIIIC35) from animals. Human TFIIIC35 does not contain the phosphoglycerate mutase domain of its yeast counterpart. TFIIIC is required for transcription of tRNA and 5 S RNA genes by RNA polymerase III .
SH3 domain and tetratricopeptide repeat-containing protein SH3TC1/SH3TC2 (SH3TC1/SH3TC2)
Type: Family

This entry includes SH3TC1 and SH3TC2. SH3TC2 is an effector of Rab11 in Schwann cells . Mutations of the SH3TC2 gene cause Charcot-Marie-Tooth disease 4C (CMT4C), a recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterised by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms . The function of SH3TC1 is not clear.
UBXN6, PUB domain (UBXN6_PUB)
Type: Domain

This entry represents the PUB domain found in p97 adaptor protein UBXD6 (also called UBXD1) . It functions as a p97 (also known as valosin-containing protein or VCP) adaptor by interacting with the D1 and/or D2 ATPase domains. The type II AAA ATPase p97 is involved in a variety of cellular processes such as the deglycosylation of ERAD substrates, membrane fusion, transcription factor activation and cell cycle regulation through differential binding to specific adaptor proteins .
Large ribosomal subunit protein mL53, fungi (Ribosomal_mL53_fung)
Type: Family

This entry represents the large ribosomal subunit protein mL53 (also known as MRPL44) from fungi. It is a component of the mitochondrial ribosome (mitoribosome), a dedicated translation machinery responsible for the synthesis of mitochondrial genome-encoded proteins, including at least some of the essential transmembrane subunits of the mitochondrial respiratory chain .
tRNA-splicing endonuclease subunit Sen15, fungi (Sen15_fungi)
Type: Family

This entry includes Sen15 from fungi.

The Sen15 subunit of the tRNA intron-splicing endonuclease is one of the two structural subunits of this heterotetrameric enzyme. Residues 36-157 of this subunit possess a novel homodimeric fold. Each monomer consists of three α-helices and a mixed antiparallel/parallel β-sheet. Two monomers of Sen15 fold with two monomers of Sen34, one of the two catalytic subunits, to form an alpha2-beta2 tetramer as part of the functional endonuclease assembly .
Zinc finger CW-type PWWP domain protein ZCWPW1/ZCWPW2 (ZCWPW1/ZCWPW2)
Type: Family

The function of ZCWPW1 and ZCWPW2 is not clear. It has been suggested than when mutated, ZCWPW1 plays a role in late onset Alzheimer's disease .
MISP/MISP3-like (MISP/MISP3-like)
Type: Family

This entry includes MISP/MISP3 from animals. MISP is an actin-binding protein that functions in spindle orientation probably by linking the astral microtubules (MTs) to the actin cytoskeleton . It has been shown to regulate IQGAP1 and Cdc42 to ensure proper mitotic progression and correct spindle orientation . The function of MISP3 is not clear.
TRIM47, PRY/SPRY domain (TRIM47_SPRY_PRY)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of TRIM47 (also known as GOA). TRIM47 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is highly expressed in kidney tubular cells, but lowly expressed in most tissue. It is overexpressed in astrocytoma tumor cells and plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis; astrocytoma, also known as cerebral astrocytoma, is a malignant glioma that arises from astrocytes . Genome wide studies on white matter lesions have identified a novel locus on chromosome 17q25 harboring several genes such as TRIM47 and TRIM65 which pinpoints to possible novel mechanisms leading to these lesions .
Syntaxin 11, SNARE motif (Syntaxin11_SNARE)
Type: Domain

This entry represents the SNARE motif found in Syntaxin 11.

Syntaxin-11 (STX11) belongs to the syntaxin family, which is a group of the membrane integrated proteins participating in exocytosis. Syntaxins are associated with various intracellular membrane compartments and have been implicated in various physiological processes such as axonal growth and cell division .

STX11 is associated with SNAP-23 on late endosomes and the trans-Golgi network . Mutations in STX11 gene cause familial hemophagocytic lymphohistiocytosis 4 (FHL4), a rare disorder characterised by immune dysregulation with hypercytokinemia, defective function of natural killer cell, and massive infiltration of several organs by activated lymphocytes and macrophages .
Tetraspanin-32, extracellular domain (PHEMX_LEL)
Type: Domain

This entry represents the extracellular domain or large extracellular loop (LEL) of Tetraspanin-32 (also known as PHEMX or TSSC6). This domain spans the extracellular domain between the 3rd and 4th trans-membrane segment. Phemx (pan hematopoietic expression) may play a role in hematopoietic cell function .

Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. Tetraspanins are involved in diverse processes and their various functions may relate to their ability to act as molecular facilitators. Tetraspanins associate laterally with one another and cluster dynamically with numerous parnter domains in membrane microdomains, forming a network of multimolecular complexes, the "tetraspanin web" .
Synaptotagmin-l, FYVE-related domain (SYTL5_FYVE)
Type: Domain

Synaptotagmin-like protein 5 (SYTL5 or Slp5) is a novel Rab27A-specific effector that is highly expressed in placenta and liver. Slp5 specifically interacted with the GTP-bound form of Rab27A and is involved in Rab27A-dependent membrane trafficking in specific tissues. Slp5 contains an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains. The Slp homology domain (SHD) consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of Slp5 are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif .

This entry represents the FYVE-related domain found in SYTL5.
TRIM10, RING-HC finger (TRIM10_RING-HC)
Type: Domain

TRIM10 (also known as HERF1) is a hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells . TRIM10 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.
Tyrosine-protein kinase ITK/TSK, catalytic domain (ITK_PTKc)
Type: Domain

PTKs catalyse the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region .

Itk is expressed in T-cells and mast cells, and is important in their development and differentiation . Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signalling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization . It also plays a role in the downstream signalling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4
. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses .
PDZD7, Harmonin N-like domain (PDZD7_HN-like)
Type: Domain

Human PDZ domain-containing protein 7 (PDZD7) is a scaffolding protein which associates with the Usher Syndrome protein network, and localizes to the stereocilia Ankle-link. Usher syndrome is the leading cause of genetic deaf-blindness. PDZD7 has a role as in Usher syndrome type 2 (and not in USH1) in humans. Whirlin, Usherin and GRP98 are other USH2 proteins. The latter two form the ankle links and whirlin is thought to be a scaffold for protein interactions at these links. PDZD7, whirlin, and harmonin (an USH1 protein) have a similar domain composition . The domain represented here is a putative protein-binding module based on its sequence similarity to the N-terminal domain of harmonin . Cooperative effects of mutations in PDZD7 and Usherin, and in PDZD7 and GPR98, result in a digenic USH2 phenotype .
M3K14, catalytic domain (M3K14_STKc)
Type: Domain

STKs catalyse the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K14 (also known as NIK) phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others . NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription .
Protein ANKUB1 (ANKUB1)
Type: Family

The function of ANKUB1 (ankyrin repeat and ubiquitin domain-containing 1) is not clear.
DOMON domain-containing protein FRRS1L (FRRS1L)
Type: Family

Ferric Chelate Reductase 1 Like protein (FRRS1L) interacts with both GluA1 and GluA2 subunits of AMPA receptors (AMPARs). It plays an important role in the regulation of excitatory synaptic strength . Mutations in the FRRS1L gene cause epileptic encephalopathy, early infantile, 37 (EIEE37), a form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterised by refractory seizures, neurodevelopmental impairment, and poor prognosis .
Heat shock protein beta-8, alpha-crystallin domain (ACD) (HspB8_ACD)
Type: Domain

This entry represents the alpha-crystallin domain (ACD) found in mammalian 21.6kDa small heat shock protein (sHsp) HspB8, also known as Hsp22 in humans . sHsps are molecular chaperones that suppress protein aggregation and protect against cell stress, and are generally active as large oligomers consisting of multiple subunits . A chaperone complex formed of HspB8 and Bag3 stimulates the degradation of protein complexes by macroautophagy . HspB8 also forms complexes with Hsp27 (HspB1), MKBP (HspB2), HspB3, alphaB-crystallin (HspB5), Hsp20 (HspB6), and cvHsp (HspB7). These latter interactions may depend on phosphorylation of the respective partner sHsp. HspB8 may participate in the regulation of cell proliferation, cardiac hypertrophy, apoptosis, and carcinogenesis .

Point mutations in HspB8 have been correlated with the development of several congenital neurological diseases, including Charcot Marie tooth disease and distal motor neuropathy type II .
CDK5 regulatory subunit-associated protein 2 (CDK5RAP2)
Type: Family

CDK5 regulatory subunit-associated protein 2 (CDK5RAP2) is a centrosomal protein that regulates centrosomal maturation by recruitment of a gamma-tubulin ring complex (gamma-TuRC) onto centrosomes . It interacts directly with EB1, a prototypic member of microtubule plus-end tracking proteins. The CDK5RAP2-EB1 complex regulates microtubule dynamics and stability . CDK5RAP2 also interacts with Cep169, a microtubule plus-end-tracking centrosomal protein; this interaction regulates stability of microtubules . Mutations in the CDK5RAP2 gene cause microcephaly 3, primary, autosomal recessive (MCPH3) .
Myb/SANT-like DNA-binding domain-containing protein 2 (MSANTD2)
Type: Family

The function of Myb/SANT-like DNA-binding domain-containing protein 2 (MSANTD2) is not clear.
Zinc finger CCHC domain-containing protein 2 (ZCCHC2)
Type: Family

The function of ZCCHC2 (Zinc finger CCHC domain-containing protein 2) is not clear.
Neurite extension and migration factor (Nexmif)
Type: Family

Nexmif (Neurite extension and migration factor), also known as KIAA2022, regulates neurite outgrowth via N-Cadherin and delta-Catenin signalling . Mutations of the KIAA2022 gene cause mental retardation, X-linked 98 (MRX98) .
WD repeat-containing protein 73 (Wdr73)
Type: Family

WDR73 (WD repeat-containing protein 73) contains six WD40 repeats that form a six-bladed propeller structure. It is expressed in brain and kidney, localizing to spindle poles during mitosis. Mutations of the WDR73 gene cause Galloway-Mowat syndrome, a rare autosomal-recessive condition characterised by nephrotic syndrome associated with microcephaly and neurological impairment .
Chromobox protein homolog 2 (CBX2)
Type: Family

Chromobox protein homolog 2 (CBX2) is a polycomb protein, responsible for polycomb-repressive complex 1 (PRC1) targeting to chromatin via recognition of the repressive mark H3K27me3 . CBX2 is required during sex determination to stabilize the testis fate by blocking the upregulation of bivalent ovary pathway genes . It is overexpressed in breast cancer and plays an essential role in tumour progression .
Glutaredoxin domain-containing cysteine-rich protein 1 (GRXCR1)
Type: Family

Glutaredoxin domain-containing cysteine-rich protein 1 (GRXCR1) contains a region of similarity to glutaredoxin proteins and a cysteine-rich region at its C terminus. It may be involved in regulation of actin filament architecture in hair cell stereocilia . Mutations of the GRXCR1 gene cause deafness, autosomal recessive, 25 (DFNB25) .

This entry also includes the orthologues from Drosophila CG31559 and CG12206 which are predicted to enable protein-disulfide reductase activity. CG31559 is possibly expressed in embryonic/larval system and CG12206 is expressed in embryonic/larval posterior spiracle, epithelium, and larval foregut atrium.
EF-hand calcium-binding domain-containing protein 9 (EFCAB9)
Type: Family

EF-hand calcium-binding domain-containing protein 9 (EFCAB9) is a pH-dependent Ca2 sensor modulating the channel activity and the domain organization of CatSper, a sperm-specific, pH-sensitive calcium channel essential for hyperactivated motility and male fertility .
Talin rod domain-containing protein 1 (TLNRD1)
Type: Family

Talin rod domain-containing protein 1 (TLNRD1), also known as mesoderm development candidate 1, is an actin-binding protein that may have an oncogenic function and regulates cell proliferation, migration and invasion in cancer cells .
MAP3K7 C-terminal-like protein (Map3k7cl)
Type: Family

The function of MAP3K7 C-terminal-like (Map3k7cl) is not clear.
Otoraplin (OTOR)
Type: Family

Otoraplin, also known as MIAL (MIA-like), is specifically expressed in the cochlea and the vestibule of the inner ear and may contribute to inner ear dysfunction in humans . It is a member of the MIA family.

MIA (melanoma inhibitory activity) family members include MIA, MIAL, MIA2, and MIA3 (also called TANGO). MIA was found to be strongly expressed and secreted by malignant melanomas. It contains a domain that adopts a Src Homology 3 (SH3) domain-like fold; however, it contains an additional antiparallel β sheet and two disulfide bonds compared to classical SH3 domains. Unlike classical SH3 domains, MIA does not bind proline-rich ligands .
Ankyrin repeat domain-containing protein 22 (ANR22)
Type: Family

The function of Ankyrin repeat domain-containing protein 22 (ANR22) is not clear.
Transcription factor 19 (TCF19)
Type: Family

Transcription factor 19 (TCF19) contains a PHD and a Forkhead-associated (FHA) domain. It is a transcription factor that interacts with histone H3K4Me3 and controls gluconeogenic gene expression via the nucleosome-remodeling-deacetylase complex .
Probable G-protein coupled receptor 82 (GPR82)
Type: Family

The function of Probable G-protein coupled receptor 82 (GPR82) is not clear. GPR82 is a member of the rhodopsin-like, class A GPCRs, which is 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. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) α-helices interconnected by three extracellular and three intracellular loops. 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 .
Proline-rich protein 3 (PRR3)
Type: Family

The function of Proline-rich protein 3 (PRR3) is not clear.
C-type lectin domain family 7 member A (CLEC7A)
Type: Family

C-type lectin domain family 7 member A (CLEC7A), also known as Dectin-1, is a beta-glucan receptor that binds beta-1,3 and beta-1,6 glucans and collaborates with with TLR2 to activate a macrophage's proinflammatory response to a mycobacterial infection . It is a type II transmembrane protein of the C-type lectin family with single carbohydrate recognition domains (CRDs) in their extracellular region . Its cytoplasmic tail contains an immunoreceptor tyrosine based activation motif (ITAM) that signals in part through the spleen tyrosine kinase and in collaboration with Toll-like receptors. It plays an important role in the host defense against fungal infection .
Sterile alpha motif domain-containing protein 3 (SAMD3)
Type: Family

The function of Sterile alpha motif domain-containing protein 3 (SAMD3) is not clear.
SAMD3, SAM domain (SAMD3_SAM)
Type: Domain

The function of Sterile alpha motif domain-containing protein 3 (SAMD3) is not clear. The SAM (sterile alpha motif) domain of SAMD3 is a putative protein-protein interaction domain. SAM is a widespread domain in signaling and regulatory proteins. In many cases SAM mediates dimerization/oligomerization .
MORN repeat-containing protein 5 (Morn5)
Type: Family

The function of MORN repeat-containing protein 5 (Morn5) is not clear.
Dynein regulatory complex protein 10 (DRC10)
Type: Family

Dynein regulatory complex protein 10 (DRC10), also known as IQCD, is a component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes . It interacts with mammalian homologue of C. elegans uncoordinated gene 13 (Munc13) in spermatozoa and may participate in acrosome exocytosis . I
Nuclear speckle splicing regulatory protein 1 (Nsrp1)
Type: Family

Nuclear speckles are subnuclear storage sites containing pre-mRNA splicing machinery. Nuclear speckle splicing regulatory protein 1 (Nsrp1), also known as NSRP70, is a nuclear speckle-related protein that mediates alternative splice site selection, targeting several pre-mRNAs . It contains an N-terminal coiled-coil domain that is critical not only for self-oligomerization but also for splicing activity. It interacts physically with two SR (serine/arginine) proteins, SRSF1 and SRSF2, and reverses their splicing activity in terms of CD44 exon v5 as exon exclusion .
Serine/threonine-protein kinase LMTK1, catalytic domain (LMTK1_c)
Type: Domain

PTKs catalyse the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. LMTK1, also called
Apoptosis-associated tyrosine kinase (AATK) or AATYK, is a cytoplasmic (or nonreceptor) kinase containing a long C-terminal region. The expression of LMTK1 is upregulated during growth arrest and apoptosis in myeloid cells . LMTK1 has been implicated in neural differentiation , and is a regulator of the Na-K-2Cl cotransporter, a membrane protein involved in cell proliferation and survival, epithelial transport, and blood pressure control .
RIbeta, dimerization/docking domain (RIbeta_DD)
Type: Domain

This entry represents the dimerization/docking (D/D) domain of RIbeta, the Type I beta Regulatory subunit of cAMP-dependent protein kinase. RIbeta is expressed highly in the brain and is associated with hippocampal function. The R subunit contains an N-terminal dimerisation/docking (D/D) domain, a linker with an inhibitory sequence, and two c-AMP binding domains. The D/D domain dimerises to form a four-helix bundle that serves as a docking site for A-kinase-anchoring proteins (AKAPs), which facilitates the localisation of PKA to specific sites in the cell .

cAMP-dependent protein kinase (PKA) is a serine/threonine kinase (STK), catalysing the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. There are two classes of R subunits, RI and RII; each exists as two isoforms (alpha and beta) from distinct genes. These functionally non-redundant R isoforms allow for specificity in PKA signalling. RI subunits are pseudo-substrates as they do not contain a phosphorylation site in their inhibitory site unlike RII subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis .
EphB1 , SAM domain (EphB1_SAM)
Type: Domain

This entry represents the SAM (sterile alpha motif) domain of the EphB1 receptors. This domain, located in the cytoplasmic region of EphB1, is a potential C-terminal protein-protein interaction domain. In human vascular endothelial cells, it appears to mediate cell-cell initiated signal transduction via the binding of the adaptor protein GRB10 (growth factor) through its SH2 domain to a conserved tyrosine that is phosphorylated . EphB1 receptors play a role in neurogenesis, in particular in regulation of proliferation and migration of neural progenitors in the hippocampus and in corneal neovascularization ; they are involved in converting the crossed retinal projection to ipsilateral retinal projection . They may be potential targets in angiogenesis-related disorders .