SII-SWORD/CoKE huggingface dataset:
Myotubularin-related protein 14 (MTMR14)
Type: Family

Myotubularin-related protein 14 (MTMR14, also known as Jumpy) belongs to the myotubularin family, whose members are dual-specificity phosphatases that act primarily to dephosphorylate phosphoinositides (PIs). They act specifically on PI3P and PI3,5P2, dephosphorylating them to form PIP and PI5P, respectively . MTMR14 interacts with early autophagosomes and negatively regulates progression through the steps of autophagy . It has been linked to the a congenital muscle disorder known as myopathy, centronuclear, 1 (CNM1) .
MTMR14, PH-GRAM domain (MTMR14_PH-GRAM)
Type: Domain

Myotubularin-related protein 14 (MTMR14, also known as Jumpy) belongs to the myotubularin family, whose members are dual-specificity phosphatases that act primarily to dephosphorylate phosphoinositides (PIs). They act specifically on PI3P and PI3,5P2, dephosphorylating them to form PIP and PI5P, respectively . MTMR14 interacts with early autophagosomes and negatively regulates progression through the steps of autophagy . It has been linked to the a congenital muscle disorder known as myopathy, centronuclear, 1 (CNM1) .

MTMR14 contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain (SID), a coiled-coil region, and a C-terminal PDZ domain. This entry represents the PH-GRAM domain that binds to phosphoinositide lipid .
Listerin, zinc finger, RING-type (RING-CH-C4HC3_LTN1)
Type: Domain

Listerin, also known as RING finger protein 160 or zinc finger protein 294, is the mammalian homologue of yeast Ltn1. It is widely expressed in all tissues, but motor and sensory neurons and neuronal processes in the brainstem and spinal cord are primarily affected in the mutant. Listerin is required for embryonic development and plays an important role in neurodegeneration . It also functions as a critical E3 ligase involving quality control of nonstop proteins . It mediates ubiquitylation of aberrant proteins that become stalled on ribosomes during translation . Ltn1 works with several cofactors to form a large ribosomal subunit-associated quality control complex (RQC), which mediates the ubiquitylation and extraction of ribosome-stalled nascent polypeptide chains for proteasomal degradation. It appears to first associate with nascent chain-stalled 60S subunits together with two proteins of unknown function, Tae2 and Rqc1 .

Listerin contains a long stretch of HEAT (Huntingtin, Elongation factor 3, PR65/A subunit of protein phosphatase 2A, and TOR) or ARM (Armadillo) repeats in the N terminus and middle region, and a catalytic RING-CH finger, also known as vRING or RINGv, with an unusual arrangement of zinc-coordinating residues in the C terminus. Its cysteines and histidines are arranged in the sequence as C4HC3-type, rather than the C3H2C3-type in canonical RING-H2 finger .
CUE domain-containing protein 2, CUE domain (CUE_CUED2)
Type: Domain

CUEDC2 is a novel negative regulator of progesterone receptor (PR) and functions to promote the progesterone-induced PR degradation by the ubiquitin-proteasome pathway . It also acts as the regulator of JAK1/STAT3 signaling through inhibiting cytokine-induced phosphorylation of JAK1 and STAT3 and the subsequent STAT3 transcriptional activity . This entry represents the CUE domain found in CUEDC2.
Cadherin (Cadherin)
Type: Family

Cadherins are a group of transmembrane proteins that serve as the major adhesion molecules located within adherens junctions. They can regulate cell-cell adhesion through their extracellular domain and their cytosolic domains connect to the actin cytoskeleton by binding to catenins . These proteins preferentially interact with themselves in a homophilic manner in connecting cells; thus acting as both receptor and ligand. They may play an important role in the sorting of different cell types during morphogenesis, histogenesis and regeneration. They may also be involved in the regulation of tight and gap junctions, and in the control of intercellular spacing. Cadherins are evolutionary related to the desmogleins which are component of intercellular desmosome junctions involved in the interaction of plaque proteins.

Structurally, cadherins comprise a number of domains: classically, these include a signal sequence; a propeptide of around 130 residues; a single transmembrane domain and five tandemly repeated extracellular cadherin domains, 4 of which are cadherin repeats, and the fifth contains 4 conserved cysteines and a C-terminal cytoplasmic domain . However, proteins are designated as members of the broadly defined cadherin family if they have one or more cadherin repeats. A cadherin repeat is an independently folding sequence of approximately 110 amino acids that contains motifs with the conserved sequences DRE, DXNDNAPXF, and DXD. Crystal structures have revealed that multiple cadherin domains form Ca2+-dependent rod-like structures with a conserved Ca2+-binding pocket at the domain-domain interface. Cadherins depend on calcium for their function: calcium ions bind to specific residues in each cadherin repeat to ensure its proper folding, to confer rigidity upon the extracellular domain and is essential for cadherin adhesive function and for protection against protease digestion.
Chemokine beta/gamma/delta (Chemokine_b/g/d)
Type: Family

The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family), or separated by an intervening residue (the CXC family), or have only one of the first two Cys residues (C chemokines), or contain both cysteines separated by three intervening residues (CX3C chemokines).

This entry includes beta-chemokines (CC chemokines), in addition to gamma (C chemokines) and delta-chemokines (CX3C chemokines). CC chemokines stimulate mainly monocytes, but also basophils, eosinophils, T-lymphocytes, and natural killer (NK) cells. C-C motif chemokine 2 (CCL2) stimulates chemotaxis of monocytes and several cellular events associated with chemotaxis. Two other chemokines structurally related to CCL2 are CCL8 (MCP-2) and CCL7 (MCP-3) .

The C chemokine subfamily is composed of two members, XC chemokine ligand 1 (XCL1), also known as lymphotactin or SCM-1 alpha, and XC chemokine ligand 2 (XCL2), also known as SCM-1 beta . The cognate receptor for these chemokines is XCR1 . The only CX3C chemokine identified to date is CX3C chemokine ligand 1 (CX3CL1), also known as fractalkine or neurotactin. With its unique CX3CR1 receptor , it is involved in adherence to the endothelium of the inflammatory monocyte population .
Vesicle-fusing ATPase (Vesicle-fus_ATPase)
Type: Family

This family of vesicle-fusing ATPases includes NSF, an essential protein in membrane fusion events. NSF plays the role of a chaperone by activating SNAP receptor proteins (SNAREs) so that they can participate in membrane fusion. For subsequent rounds of fusion, the SNARE complex must be disassembled, and NSF, in conjunction with SNAPs, utilises its intrinsic ATPase activity to provide a driving force that disassembles SNARE complexes .
N-alpha-acetyltransferase 80 (NAA80)
Type: Family

N-alpha-acetyltransferase 80 (NAA80, also known as Fus2) is a tumour suppressor . It has been shown to acetylate the N terminus of processed forms of beta- and gamma-actin. Actin N-terminal acetylation has been found to regulate cytoskeletal dynamics and motility .
Integrator complex subunit 14 (INTS14)
Type: Family

INTS14 is part of the integrator complex, a complex involved in the transcription of small nuclear RNAs (snRNA) and their 3'-box-dependent processing .
TBC1 domain family member 7 (TBC1D7)
Type: Family

TBC1D7 is part of the TSC1-TSC2-TBC1D7 complex that serves as a negative regulator of the mechanistic target of rapamycin complex 1 that controls cell growth in response to environmental cues . TBC1D7 helps to stabilize the TSC1-TSC2 complex through its direct interaction with TSC1. Homozygous inactivation of TBC1D7 causes intellectual disability and megaencephaly .
KxDL motif-containing protein 1-like (KXD1-like)
Type: Family

KXD1 is part of the BORC complex that may regulate lysosome positioning . This entry also includes CG10681 from fruit flies and KxDL motif-containing protein LO9-177 from rice. LO9-177 contributes to the promotion of leaf inclination and grain size by modulating cell elongation.
Nucleolar pre-ribosomal-associated protein 1 (URB1)
Type: Family

Nucleolar pre-ribosomal-associated protein 1 (Npa1) is required for ribosome biogenesis and operates in the same functional environment as Rsa3p and Dbp6p during early maturation of 60S ribosomal subunits . The protein partners of Npa1p include eight putative helicases as well as the novel Npa2p factor. Npa1p can also associate with a subset of H/ACA and C/D small nucleolar RNPs (snoRNPs) involved in the chemical modification of residues in the vicinity of the peptidyl transferase centre . The protein has also been referred to as Urb1.
PSME3-interacting protein (FAM192A)
Type: Family

PIP30/FAM192A acts as a regulator of PA28-gamma, a nuclear activator of the 20S proteasome. PIP30 favours PA28-gamma interaction with the 20S proteasome while inhibiting its association with coilin, a central component of nuclear Cajal bodies .
Zinc finger CCHC domain-containing protein 4 (ZCCHC4)
Type: Family

ZCCHC4 is an rRNA N6-methyltransferase that specifically methylates the adenine in position 4220 of 28S rRNA . N6-methylation of adenine(4220) in 28S rRNA is required for translation .
RING finger protein 37 (Ubox5)
Type: Family

Proteins in this entry contain the U-box domain, which has been suggested to be a modified RING finger motif where the metal-coordinating cysteines and histidines have been replaced with other amino acids . RING finger protein 37 (RNF37, also known as Ubox5) belongs to the U box protein family, whose members are ubiquitin-protein ligases .
Small ribosomal subunit protein mS35, mitochondrial (Ribosomal_mS35_mt)
Type: Family

This entry represents a conserved region of approx. 125 residues of one of the small ribosomal subunit protein mS35 of the mitochondrial ribosome. In Saccharomyces cerevisiae (baker's yeast) it was known as mitochondrial ribosomal protein S24 whereas in humans was S35.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Cullin-associated NEDD8-dissociated protein 1/2 (CAND1/CAND2)
Type: Family

This entry includes cullin-associated NEDD8-dissociated proteins 1 (CAND1 also known as TIP120A) and 2 (CAND2); these proteins have a C-terminal TATA-binding protein interacting (TIP20) domain. CAND1 is required for the assembly of the SCF E3 ubiquitin ligase complex. The SCF ubiquitin E3 ligase consists of SKP1, CUL1 and F-box protein, and it regulates ubiquitin-dependent proteolysis. CAND1 binds to CUL1, preventing it from associating with the other components that form the ligase. Neddylation of CUL1 (or the presence of SKP1 and ATP) dissociates it from CAND1, allowing the ligase complex to form . CAND1 also interacts with CUL3, a component of the Cul3-dependent E3 ubiquitin ligase complex . CAND1 has been proposed to be an F-box protein exchange factor, and as substrates of the ligase complex are degraded by the proteasome and depleted, the ligase complex enters an intermediate, deneddylated state when CAND1 can bind, promoting dissociation of the substrate-recognition subunit and recruitment of a new substrate-recognition subunit . CAND2 is uncharacterised but is assumed to have similar roles to CAND1.
Pinin (Pinin)
Type: Family

Pinin (also known as memA and nuclear protein SDK3) is localised at the desmosomes and is implicated in anchoring intermediate filaments to the desmosomal plaque . It is also a transcriptional activator, binding to the the E-box 1 core sequence of the E-cadherin promoter gene . Pinin is also found in nuclear 'speckles' where it is also an auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs , and a component of the PSAP complex .
ER membrane protein complex subunit 2-like (EMC2-like)
Type: Family

ER membrane protein complex subunit 2 (EMC2, also known as tetratricopeptide repeat protein 35) is a tetratricopeptide repeat-containing protein, and a component of the ER membrane protein complex (EMC), which is required for efficient folding of proteins in the endoplasmic reticulum (ER) . This entry also includes TPR repeat protein Oca3 from the fission yeast Schizosaccharomyces pombe which may be involved in cell cycle regulation .
Intraflagellar transport protein 122/121 homolog (Ift122/121)
Type: Family

Intraflagellar transport protein 122 homolog (Ift122) and Intraflagellar transport protein 121 homolog (Ift121, also known as WD repeat-containing protein 35) are a multiple WD40-repeat containing proteins, required for ciliogenesis . They are components of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs) . Primary cilia are assembled and maintained by evolutionarily conserved intraflagellar transport (IFT) proteins that are involved in the coordinated movement of macromolecular cargo from the basal body to the cilium tip and back. Mice with mutant Ift122 lack cilia and have multiple developmental defects and the Sonic Hedgehog (Shh) signaling pathway is disrupted .
Palmitoyltransferase PFA4/ZDHHC16/ZDHHC20/ERF2-like (PFA4/ZDH16/20/ERF2-like)
Type: Family

This entry includes palmitoyltransferases such as PFA4, ZDHHC16, ZDHHC20, ERF2 from fungi and its homologues.

PFA4 from S. cerevisiae mediates the reversible addition of palmitate to target proteins, thereby regulating their membrane association and biological function. It palmitoylates several amino acid permeases and chitin synthase CHS3, which is required for its proper export from the ER . ZDHHC16 is a palmitoyl acyltransferase that mediates palmitoylation of proteins such as PLN and ZDHHC6 . In zebrafish, there are two ZDHHC16 homologues, ZDHHC16A and ZDHHC16B. They are involved in the proliferation of neural stem cells by regulating the FGF/ERK pathway .

Palmitoyltransferase ZDHHC20 can catalyse the addition of palmitate onto various protein substrates . It catalyses the palmitoylation of Cys residues in the cytoplasmic C-terminal of EGFR, and modulates the duration of EGFR signalling by modulating palmitoylation-dependent EGFR internalisation and degradation . ZDHHC20 can also utilise acyl-CoA with C14 and C18 fatty acid chains .

ERF2 from S. cerevisiae forms a complex with SHR5, palmitoyltransferase specific for Ras proteins. It palmitoylates RAS2, which is required for its proper plasma membrane localisation . In S. pombe it forms a complex with erf4 complex, a palmitoyltransferase with a major role in driving sexual development . It palmitoylates ras1, isp3 and rho3 .
Interphotoreceptor matrix proteoglycan (IMPG)
Type: Family

This entry includes interphotoreceptor matrix proteoglycans 1 and 2.

IMPG1, also known as SPACR, is a sialoprotein associated with photoreceptor cones and rods protein. It is a secreted glycoprotein containing a central mucin-like domain and an EGF-like domain in the C-terminal region. It also contains two SEA domains (after sea urchin sperm protein, enterokinase, and agrin), a highly conserved structure composed of four anti-parallel β sheets surrounded by α helices in an O-linked glycosylation-rich environment. IMPG1 has been linked to vitelliform macular dystrophies .

Interphotoreceptor matrix proteoglycan 2 (IMPG2, also known as SPACRCAN) is a interphotoreceptor matrix proteoglycan that binds to chondroitin sulfate and hyaluronan. It may be involved in organisation of the insoluble interphotoreceptor matrix . Mutations in the IMPG2 gene cause retinitis pigmentosa 56 (RP56) and vitelliform macular dystrophy 5 (VMD5) .
N-terminal EF-hand calcium binding protein 1/2/3 (NECAB1/2/3)
Type: Family

This entry includes N-terminal EF-hand calcium binding proteins 1, 2 and 3 (NECAB1, NECAB2 and NECAB3). They are expressed in the adult mouse hippocampus and dentate gyrus and in the rat/human spinal cord . NECAB2 has been shown to bind to the adenosine A(2A) receptor and the mGlu(5) receptor . NECAB3 has been shown to regulate HIF-1 (hypoxia inducible factor-1) activity via Mint3 in cancer cells .
Dickkopf related protein 1-4 (DKK1-4)
Type: Family

This entry includes Dickkopf-related proteins 1-4 (DKK1-4). The Dickkopf (Dkk) proteins are cysteine-rich secretory proteins and highly conserved inhibitors of the canonical Wnt signalling pathway, which play key roles in many essential biological processes .
Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma (PPP2R3C)
Type: Family

Protein phosphatase 2A (PP2A) forms several holoenzyme complexes. The core enzyme consists of a catalytic C subunit (PP2Ac) and a regulatory A subunit (PR65) that is associated with a regulatory B subunit. The regulatory B subunit can be classified as a member of the B, B' or B'' families .

PPP2R3C is a B'' family member and a regulatory B subunit of PP2A. It is also a subunit of the PP5/PPP2R3C complex. Both PP2A and PP5 are serine/threonine specific phosphatases. The PP5/PPP2R3C complex dephosphorylates P-glycoprotein/ABCB1 and down-regulates its expression and function . This entry also includes TONNEAU2/FASS from Arabidopsis. TONNEAU2 is the B'' subunit of protein phosphatase 2A that regulates interphase microtubule nucleation .
Carboxypeptidase Q (CPQ)
Type: Family

CPQ, also known as PGCP, is a carboxypeptidase and a member of peptidase family M28. CPQ is a secreted protein hydrolyzing the circulating peptides in the extracellular microenvironment . It has been shown to liberates I-thyroxine (T4) from thyroglobulin (Tg) . PGCP has been associated with pulmonary hypertension .
Protein furry/Tao3/Mor2 (Furry/Tao3/Mor2)
Type: Family

This entry includes protein furry (fry) from animals, Tao3 (also known as Pag1) from budding yeasts and Mor2 from fission yeasts. Protein furry is involved in the Trc/fry signaling pathway and plays a key role in maintaining the integrity of polarized cell extensions (arista) during morphogenesis . Tao3 is part of the the RAM signaling network involved in regulation of cellular morphogenesis . Mor2 is also involved in the cell morphogenesis .
Armadillo-like helical domain-containing protein 3-like (ARMD3-like)
Type: Family

This entry includes ARMD3 and related proteins. Their functions are not known.
Ubiquitin domain-containing protein 1/2 (UBTD1/2)
Type: Family

This entry represents a group of ubiquitin domain-containing proteins, including UBTD1 and UBTD2. UBTD1 regulates cellular senescence through a positive feedback loop with TP53 . UBTD1 and UBE2D (E2 ubiquitin conjugating enzyme) have been shown to form a stable, stoichiometric complex . UBTD2, also known as DC-UbP, interacts with deubiquitinating enzyme USP5 and the Ub-activating enzyme UbE1 .
Cytochrome oxidase assembly factor 4-like (Coa4-like)
Type: Family

Coa4 is a twin cx(9)c protein localized in the mitochondrial intermembrane space and associated with the inner membrane . It may function as a cytochrome oxidase assembly factor .
Protein FAM8A1 (FAM8A1)
Type: Family

The function of FAM8A1 is not known.
Uncharacterized protein KIAA0513 (KIAA0513)
Type: Family

The function of KIAA0513 is not known.
Coiled-coil domain-containing protein 78 (CCDC78)
Type: Family

CCDC78 is a component of the deuterosome, a structure that promotes de novo centriole amplification in multiciliated cells that can generate more than 100 centrioles . CCDC78 does not have the kinesin-motor domain. Mutations in CCDC78 genes cause centronuclear myopathy 4 (CNM4), which is a congenital muscle disorder characterised by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles .
Wings apart-like protein (WAPL)
Type: Family

Wings apart-like protein (WAPL) regulates heterochromatin structure . It is required to hold sister chromatids of meiotic heterochromatin together and is implicated in both heterochromatin pairing during female meiosis and the modulation of position-effect variegation (PEV) . hWAPL (

), the human homologue, is found to play a role in the development of cervical carcinogenesis, and is thought to have similar functions to Drosophila wapl protein . Malfunction of the hWAPL pathway is thought to activate an apoptotic pathway that consequently leads to cell death .
Leukocyte receptor cluster member 1-like (LENG1-like)
Type: Family

This entry includes leukocyte receptor cluster member 1-like (LENG1) and related proteins. Their functions are not known.
28kDa heat- and acid-stable phosphoprotein (HAP28)
Type: Family

The function of 28kDa heat- and acid-stable phosphoprotein (HAP28) is not known.
Transmembrane protein 131-like (TMEM131-like)
Type: Family

This entry includes TMEM131 and TMEM131L. In humans, TMEM131L may regulate immature single-positive thymocyte proliferation arrest by acting through mixed Wnt-dependent and -independent mechanisms .
RNA-binding protein 33 (RBM33)
Type: Family

The function of RNA-binding protein 33 (RBM33) is not known. Homologues are known only from vertebrates.
EF-hand calcium-binding domain-containing protein 10 (EFC10)
Type: Family

The function of EF-hand calcium-binding domain-containing protein 10 (EFC10) is not known.
CHD1 helical C-terminal domain containing protein 1-like (CHCT1-like)
Type: Family

This entry includes CHD1 helical C-terminal domain containing protein 1 (CHCT1, formerly known as C17orf64) and related proteins. CHCT1 may play a role in regulation of apoptosis .
mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase PCIF1-like (PCIF1-like)
Type: Family

PCIF1 is a cap-specific adenosine methyltransferase that catalyzes formation of N6,2'-O-dimethyladenosine cap (m6A(m)) by methylating the adenosine at the second transcribed position of capped mRNAs . It contains a WW domain that interacts with phosphorylated RNA polymerase II carboxy-terminal domain (CTD). The WW domain of PCIF1 can directly and preferentially bind to the phosphorylated CTD compared to the unphosphorylated CTD .