SII-SWORD/CoKE huggingface dataset:
CLAVATA3/ESR (CLE)-related protein 1-4 (CLE1-4)
Type: Family

This entry includes CLAVATA3/ESR (CLE)-related proteins 1-4 (CLE1-4) from Arabidopsis and 33 from Medicago truncatula. They mimic host plant CLE extracellular signal peptides that regulate cell fat. CLE1 may play a role in the differentiation or division of feeding cells (syncytia) induced in plant roots during infection . CLE33 is a signaling peptide involved in the regulation of root colonization by arbuscular mycorrhizal (AM) fungi . It moves from root to shoot to function with the receptor kinase SUNN, in a signalling pathway that repress strigolactone biosynthetic genes and strigolactone content in the roots, and consequently reduces the promotion of further colonization by AM fungi .

The CLE proteins share a C-terminal CLE domain with CLV3, a small secreted polypeptide that is active as a ligand and has a function in shoot apical meristem maintenance . In general, the CLE-related proteins are C-terminally processed to generate an active CLE peptide . These small secreted peptide hormones then function in a variety of developmental and physiological processes . CLV3 and other A-type CLE peptides are involved in the suppression of stem cell development in root and shoot development, in contrast to the B-type CLE peptides, CLE41 and CLE44, in the case of Arabidopsis, which are not .
CLAVATA3/ESR (CLE)-related protein (CLAVATA3-CLE)
Type: Family

This entry includes CLAVATA3/ESR (CLE)-related proteins 5, 6, 7, 13 and 53. CLE13 control the nodule numbers by interacting with the SUPER NUMERIC NODULES (SUNN)-dependent auto-regulation of nodulation .

This entry also includes CLE-4B-2 from Globodera rostochiensis (Golden nematode worm). They mimics host plant CLE extracellular signal peptides that regulate cell fate .

The CLE proteins share a C-terminal CLE domain with CLV3, a small secreted polypeptide that is active as a ligand and has a function in shoot apical meristem maintenance . In general, the CLE-related proteins are C-terminally processed to generate an active CLE peptide . These small secreted peptide hormones then function in a variety of developmental and physiological processes . CLV3 and other A-type CLE peptides are involved in the suppression of stem cell development in root and shoot development, in contrast to the B-type CLE peptides, CLE41 and CLE44, in the case of Arabidopsis, which are not .
CLAVATA3/ESR (CLE)-related protein 9-13 (CLE9-13)
Type: Family

This entry includes CLAVATA3/ESR (CLE)-related protein 9-13 (CLE9-13) from Arabidopsis and FON2 SPARE1 (FOS1) form from rice. FOS1, a CLE-related protein, regulates floral meristem maintenance .

The CLE proteins share a C-terminal CLE domain with CLV3, a small secreted polypeptide that is active as a ligand and has a function in shoot apical meristem maintenance . In general, the CLE-related proteins are C-terminally processed to generate an active CLE peptide . These small secreted peptide hormones then function in a variety of developmental and physiological processes . CLV3 and other A-type CLE peptides are involved in the suppression of stem cell development in root and shoot development, in contrast to the B-type CLE peptides, CLE41 and CLE44, in the case of Arabidopsis, which are not .
Membrane-associated kinase regulator 2/5 (MAKR2/5)
Type: Family

This entry represents a group of plant proteins, including MAKR2 and MAKR5 from Arabidopsis. MAKR5 is a positive effector of CLE45 signaling .

MAKRs belong to the MEMBRANE-ASSOCIATED KINASE REGULATOR (MAKR) family, whose members contain putative kinase interacting motifs and membrane localization signals .
BKI1/Probable membrane-associated kinase regulator 1/3/4 (BKI1/MAKR1/3/4)
Type: Family

This entry represents a group of plant proteins, including BKI1 and MAKR1/3/4 from Arabidopsis. BKI1 interacts with BRI1, a leucine-rich repeat receptor serine/threonine kinase, and prevents the activation of BRI1 .

MAKRs belong to the MEMBRANE-ASSOCIATED KINASE REGULATOR (MAKR) family, whose members contain putative kinase interacting motifs and membrane localization signals .
Protein BIG GRAIN 1-like (BG1-like)
Type: Family

This entry represents a group of plant proteins, including BG1 (BIG GRAIN 1) and BIG1L from rice and BG1A-E from Arabidopsis. BG1 over-expressing plants exhibit increased grain size with both bigger length and width. BG1 functions in auxin pathway and positively regulates biomass, grain size and yield in rice .
Methyl-CpG-binding domain-containing protein 10/11 (MBD10/11)
Type: Family

This entry represents a group of methyl-CpG-binding domain-containing proteins from plants, including MBD10/11 from Arabidopsis.

Cytosine methylation at symmetrical CpG and CpNpG sequences plays a key role in the epigenetic control of plant growth and development. In animals, the methylation signal is recognized by methyl-CpG-binding domain (MBD) proteins that specifically bind methylated CpG dinucleotides. In Arabidopsis thaliana 12 putative MBD proteins have been identified. However, the presence of an MBD motif does not necessarily point to methyl-CpG-binding activity. The Arabidopsis proteins AtMBD5, AtMBD6 and AtMBD7 have been proven to bind methyl CpG in vitro and to localize to highly methylated chromocentres in vivo, but none of the other Arabidopsis MBD-containing proteins show these properties, and therefore seem to be non-functional MBDs .
Late embryogenesis abundant protein 1/2/D7/Stress-induced protein KIN2 (LEA1/2/D7/KIN2)
Type: Family

This entry represents a group of proteins from plants, including the Late embryogenesis abundant proteins (LEAs), late embryonic proteins abundant in higher plant seed embryos LEA1/2 from Cicer arietinum (Chickpea) and LEAD7 from Gossypium hirsutum (Upland cotton) ; and Stress-induced protein KIN2 from Arabidopsis thaliana .
Transmembrane protein 178A/B (T178A/B)
Type: Family

In mice, Tmem178 is a negative regulator of osteoclast differentiation in basal and inflammatory conditions by regulating TNFSF11-induced Ca (2+) fluxes .
Mitochondrial escape protein 2 (Yme2_C)
Type: Family

Mitochondrial escape protein 2 (also known as RNA12) plays a role in maintaining the mitochondrial genome and in controlling mtDNA escape . It is also involved in the regulation of mtDNA nucleotide structure and number . Additionally, this protein have a dispensable role in the early maturation of pre-rRNA .
PILR alpha-associated neural protein (PIANP)
Type: Family

PIANP modulates gamma-secretase-mediated cleavage of E-Cadherin and therefore can affect junctional integrity and function . It has been shown to interact in vitro with the immune inhibitory receptor PILR-alpha, and may be involved in immune regulation .
R3H domain-containing protein 4 (R3HDM4)
Type: Family

The function of R3H domain-containing protein 4 is not known.
Protein FAM149 (FAM149)
Type: Family

This entry represents FAM149 proteins, including FAM149A and FAM149B1 from humans. Mutations of the FAM149B1 gene cause Joubert syndrome 36, which a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. FAM149B1 is involved in the localization of proteins to the cilium and cilium assembly .
Leucine-rich repeat-containing protein 42 (LRRC42)
Type: Family

The function of LRRC42 is not clear. It is significantly upregulated in the majority of lung cancers .
Transmembrane protein 42 (TMEM42)
Type: Family

The function of TMEM42 is not known.
Plastid-lipid-associated protein (PAP)
Type: Family

This entry includes a group of plastid-lipid-associated protein (PAP) from plants and Cyanobacteria (blue-green algae). The plant proteins in this entry are also known as plant fibrillins. Aarabidopsis PAP1 is involved in chloroplast stress-related jasmonate biosynthesis . PAP6, also known as FIBRILLIN4, is required for plastoglobule development and stress resistance in apple and Arabidopsis . FIBRILLIN5 has been shown to be involved in the plastoquinone-9 biosynthetic pathway in Arabidopsis and rice .
Bul1-like (Bul1-like)
Type: Family

This entry includes Bul1, Bul2, Bsc5 and YNR068C from Saccharomyces cerevisiae and homologues from fungi. They are adaptor proteins that facilitate the ligase-substrate interaction. Bul1 binds the ubiquitin ligase Rsp5, via an N-terminal PPSY motif . The complex containing Bul1 and Rsp5 is involved in intracellular trafficking of the general amino acid permease Gap1 , degradation of Rog1 in cooperation with Bul2 and GSK-3 , and mitochondrial inheritance . Bul2, which is homologous to Bul1, also interacts with Rsp5 .

Bul3p, the product of two adjacent open reading frames (Bsc5 and YNR068C) separated by a stop codon that undergoes readthrough translation. BUL3 is involved in ubiquitin-mediated sorting of plasma membrane proteins and interacts with WW domains of Rsp5 in vitro .
Endoplasmic reticulum membrane-associated RNA degradation protein (ERMARD)
Type: Family

ERMARD (endoplasmic reticulum membrane-associated RNA degradation) is a multi-pass membrane protein that may play a role in neuronal migration during embryonic development .
CCR4-NOT transcription complex subunit 7/8/Pop2 (CNOT7/CNOT8/Pop2)
Type: Family

This entry includes subunits CNOT7 and CNOT8 of the CCR4-NOT complex required for RNA degradation. Both CNO7 and CNOT8 are 3'-5' poly(A) exoribonucleases removing the poly-A tail and have somewhat redundant activities . This entry also includes CNOT7/8 yeast homologue, Pop2, which is a nuclease subunit of the yeast Ccr4-Not complex .
Mediator of RNA polymerase II transcription subunit 33A/B (MED33A/B)
Type: Family

This entry represents a group of plant proteins, including MED33A/B (RFR1/REF4) from Arabidopsis. MED33A/B are components of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. They are required for phenylpropanoid homeostasis in Arabidopsis .
Protein IDA-like (IDA-like)
Type: Family

Mutations in IDA (INFLORESCENCE DEFICIENT IN ABSCISSION) block floral organ abscission in Arabidopsis thaliana . IDA signals through the leucine-rich repeat-receptor-like kinases (LRR-RLKs) HAESA (HAE), and HAESA-LIKE2 (HSL2) to control the fall of flowers after pollination .
Stomatal closure-related actin-binding protein (SCAB)
Type: Family

Stomatal closure-related actin-binding (SCAB) proteins bind, bundle and stabilise actin filaments and regulate stomatal movement . Homologues are known only from plants.
Low-molecular-weight cysteine-rich protein (LCR)
Type: Family

This entry represents a group of small, cysteine-rich plant proteins, also known as defensin-like proteins. They share sequence similarity to the PCP (pollen coat protein) family .
Dihydroxyacetone kinase phosphotransferase subunit DhaM (DhaM)
Type: Family

Several bacteria use glycerol dehydrogenase to transform glycerol into dihydroxyacetone (Dha), which is subsequently converted into Dha phosphate (Dha-P) by an ATP- or phosphoenolpyruvate (PEP)-dependent Dha kinase. Listeria innocua possesses two potential PEP-dependent Dha kinases. This entry includes the PEP-dependent dihydroxyacetone kinases 1 and 2, phosphoryl donor subunit DhaM from Listeria innocua serovar 6a . This entry also includes DhaM from Lactococcus lactis subsp. lactis. Its structure has been solved .
Zinc finger HIT domain-containing protein 2 (ZNHIT2)
Type: Family

The function of ZNHIT2 is not known. Homologues are known from animals, plants and fungi, and each contains a HIT-type zinc finger. The human gene (also known as C11orf5) is part of the FAUNA cluster, and is highly expressed in the testis, particularly the lumen of seminiferous tubules, suggesting it is highly expressed in germ cells of different developmental stages .
EF-hand domain pair protein CML-like (EF_hand_pair_protein_CML-like)
Type: Family

This entry includes a variety of proteins with two calcium-binding EF-hand domains including:

CML1-35: calcium-binding proteins from Arabidopsis .

Pollen allergens polcalcin Jun o 2 from juniper and Ole e 8 from olive
Pyridine nucleotide-disulphide oxidoreductase, N-terminal (DHPH_N)
Type: Domain

Proteins containing this domain include both class I and class II oxidoreductases and also NADH oxidases and peroxidases. This domain is actually a small NADH binding domain within a larger FAD binding domain .
H(2):CoB-CoM heterodisulfide,ferredoxin reductase subunit A-like (HdrA-like)
Type: Family

This entry represents a group of reductases, including HdrA1 from Archaea . HdrA1 is part of a complex that catalyzes the reversible reduction of CoM-S-S-CoB to the thiol-coenzymes H-S-CoM (coenzyme M) and H-S-CoB (coenzyme B) .
Protein FixC-like (FixC-like)
Type: Family

This entry includes protein FixC from bacteria. FixC is an integral membrane protein that shares similarity with the membrane-bound electron transfer flavoprotein ubiquinone oxidoreductase (ETF-QO) . It may be involved in electron transfer to nitrogenase in Rhodospirillum rubrum .
Coatomer subunit zeta (Coatomer_zeta)
Type: Family

Coatomer (COPI) is a cytosolic protein complex that coats Golgi-derived transport vesicles. It consists of seven subunits (alpha-, beta-, beta'-, gamma-, delta-, epsilon-, and zeta-COP) and is involved in retrograde transport between Golgi and ER . This entry includes the zeta subunit, which may be involved in regulating the coat assembly . This entry also includes TSET complex member tstD from Dictyostelium discoideum (Slime mold). TSET is a membrane trafficking complex .
Prenyltransferase (Prenyltransferase)
Type: Family

This entry includes various prenyltransferases, including:

4-hydroxybenzoate octaprenyltransferase (ubiA) catalyses the prenylation of para-hydroxybenzoate, a step in the biosynthesis of ubiquinone-8 .

mitochondrial 4-hydroxybenzoate polyprenyltransferase catalyses the prenylation of para-hydroxybenzoate, a step in the biosynthesis of coenzyme Q .

Decaprenyl-phosphate phosphoribosyltransferase transfers a 5-phosphoribosyl residue from phosphoribose diphosphate to decaprenyl phosphateto form decaprenylphosphoryl-5-phosphoribose, a step in the biosynthesis of decaprenylphosphoryl arabinose, a precursor of a component required for mycobacterial cell wall biosynthesis .

4-hydroxybenzoate geranyltransferases 1 and 2 required for the biosynthesis of shikonin, a naphthoquinone secondary metabolite in plants .

4-hydroxybenzoate solanesyltransferase prenylates para-hydroxybenzoate during plastoquinone-9 biosynthesis .
HMG box-containing protein 1 (HBP1)
Type: Family

HMG box-containing protein 1 (HBP1) is a high mobility group (HMG) box transcription factor that negatively regulates the Wnt-beta-catenin pathway and is involved in histone H1(0) gene expression . It binds the transcription factor TCF4 and prevents it from binding to its target genes, including c-MYC and CYCLIN D . It acts as a tumour suppressor and an important effector in oncogene-induced premature senescence .
Synergin gamma (SYNRG)
Type: Family

Synergin gamma is an EH domain-containing protein that may link the adapter protein complex AP-1 to other proteins .
Dimethylallyltransferase (Dimethylallyltransferase)
Type: Family

This entry includes tRNA dimethylallyltransferases (IPTs) and adenylate dimethylallyltransferases (IZTs). IPT catalyses the first step in the modification of an adenosine near the anticodon to 2-methylthio-N6-isopentyladenosine . IZT transfers dimethylallyl groups to AMP as part of the biosynthesis of cytokinin phytohormones .
Transcription elongation factor SPT5 (SPT5)
Type: Family

Transcription elongation factor Spt5 is found in both eukaryotes and archaea. Spt5 forms a heterodimer with Spt4 and collaborates with other transcription factors to pause or promote RNA polymerase II transcription elongation . It has been demonstrated that Spt4, Spt5, and Spt6 play roles in transcription elongation in both yeast and humans, including a role in activation by Tat. It is known that Spt4, Spt5, and Spt6 are general transcription-elongation factors, controlling transcription both positively and negatively in important regulatory and developmental roles .
Large ribosomal subunit protein eL14 (Ribosomal_eL14)
Type: Family

This entry represents eL14, an eukaryote-specific ribosomal protein from the 60S ribosomal subunit, which is conserved in some but not all archaea. In yeast, eL14 assembles in the nucleolus at an early stage into pre-60S particles . Auto-antibodies to RPL14 in humans have been associated with systemic lupus erythematosus .
ELP3/YhcC (ELP3)
Type: Family

This entry includes proteins with a radical SAM domain and a radical SAM C-terminal extension domain. One such protein is elongator complex protein 3 (ELP3): the catalytic histone acetyltransferase subunit of the RNA polymerase II elongator complex, which is itself part of the RNA polymerase II (RNAPII) holoenzyme responsible for transcriptional elongation . A bacterial ELP3 homologue known as tRNA uridine(34) acetyltransferase, reflecting its role in mediating the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs is also included in this family . This entry also includes protein YhcC from
Escherichia coli
, which binds an [4Fe-4S] cluster, coordinated with three cysteines and an exchangeable S-adenosyl-L-methionine. YhcC cleaves S-adenosyl-L-methionine into methionine and 5'-deoxyadenosine . This entry also includes archaeosine synthase subunit beta (RaSEA) from archaea, it is a SAM enzyme which plays a role in the synthesis of archaeosine . Uncharacterised homologues are known from bacteria, archaea and eukaryotes.

ELP3 is required for the complex integrity and for the association of the complex with nascent RNA transcript . ELP3 is thought to act as a highly conserved histone acetyltransferase (HAT) capable of acetylating core histones in vitro, however, it is clearly a multi-domain protein. The HAT activity is thought to be present only in the C-terminal GNAT domain (histone acyltransferase domain) . Studies suggest that both the histone acetyltransferase and radical S-adenosylmethionine domains are essential for function, although the exact role of the Radical SAM domain is still unclear . The radical SAM domain is important for the structural integrity of the protein complex, as in yeast (previously demonstrated) . However, an alternative may be that ELP3 binds ands cleave SAM, as seen in the archaea M. jannaschii. It has also been shown in previous studies that the mouse ELP3 does not require the histone acyltransferase domain for zygotic paternal genome demethylation .
Cohesin subunit Scc3/SA (Cohesin_Scc3/SA)
Type: Family

Proteins in this family are subunits of the cohesin complex - a protein complex required for sister chromatid cohesion in eukaryotes, including subunits SA-1, SA-2, SA-3 from chordates, Scc3 from S. cerevisiae and Psc3 from S. pombe . They contain a STAG domain and a stromalin conservative domain (SCD). The SCD domain is also found in human STAG3-like proteins and meiotic recombination protein Rec11 from S. pombe . The structure of Scc3 has been revealed .
AIP/AIPL1/TTC9 (AIP/AIPL1/TTC9)
Type: Family

Proteins in this entry have an N-terminal FKBP-type peptidyl-prolyl cis-trans isomerase domain followed by a C-terminal tetratricopeptide repeat-containing domain. Included in this entry are: aryl-hydrocarbon-interacting protein-like 1 (AIPL1), which is associated with inherited blindness and interacts with cell cycle regulator protein NUB1 ; and AH receptor-interacting protein (AIP), which interacts with the tyrosine kinase receptor RET , and mutations in AIP are associated with familial isolated pituitary adenomas .

This entry also matches Tetratricopeptide repeat protein 9 (TTC9). TTC9 contains tetratricopeptide repeat (TPR) domains constituted of the 34 amino acid consensus motif present in various number of tandem repeats . This entry includes TTC9B/C whose function is still unknown.
GRB/APBB1IP (GRB/APBB1IP)
Type: Family

Proteins in this entry consist of a Ras-associated (RA) domain, a PH domain, a family-specific BPS region, and a C-terminal SH2 domain. Grb7, Grb10 and Grb14 are paralogues that are also present in this entry . These adapter proteins bind a variety of receptor tyrosine kinases, including the insulin and insulin-like growth factor-1 (IGF1) receptors. Grb10 and Grb14 are important tissue-specific negative regulators of insulin and IGF1 signaling based and may contribute to type 2 (non-insulin-dependent) diabetes in humans. RA-PH function as a single structural unit and is dimerized via a helical extension of the PH domain. The PH domain here are proposed to bind phosphoinositides non-cannonically and are unlikely to bind an activated GTPase .
APBB1IP, PH domain (PH_APBB1IP)
Type: Domain

Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP) consists of a Ras-associated (RA) domain, a PH domain, a family-specific BPS region, and a C-terminal SH2 domain. Grb7, Grb10 and Grb14 are paralogues that are also present in this entry . These adapter proteins bind a variety of receptor tyrosine kinases, including the insulin and insulin-like growth factor-1 (IGF1) receptors. Grb10 and Grb14 are important tissue-specific negative regulators of insulin and IGF1 signaling based and may contribute to type 2 (non-insulin-dependent) diabetes in humans. RA-PH function as a single structural unit and is dimerized via a helical extension of the PH domain. The PH domain here are proposed to bind phosphoinositides non-cannonically and are unlikely to bind an activated GTPase . The tandem RA-PH domains are present in a second adapter-protein family, MRL proteins,
Caenorhabditis elegans
protein MIG-1012, the mammalian proteins RIAM and lamellipodin and the
Drosophila melanogaster
protein Pico12, all of which are Ena/VASP-binding proteins involved in actin-cytoskeleton rearrangement.

PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane . A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.
Dolichyldiphosphatase, PAP2 domain (Dolichyldiphosphatase_PAP2)
Type: Domain

Dolichyldiphosphatase is a membrane-associated protein located in the endoplasmic reticulum and hydrolyzes dolichyl pyrophosphate, as well as dolichylmonophosphate at a low rate . The enzyme is necessary for maintaining proper levels of dolichol-linked oligosaccharides and protein N-glycosylation, and might play a role in re-utilization of the glycosyl carrier lipid for additional rounds of lipid intermediate biosynthesis after its release during protein N-glycosylation reactions .
TRAF family member-associated NF-kappa-B activator (TANK)
Type: Family

TANK-binding kinase 1 (TBK1) and inducible IkappaB-kinase (IKK) are central regulators of type-I interferon induction. TANK (TRAF family member-associated NF-kappa-B activator) is a adaptor protein that connects IKK complexes with IKK epsilon and TBK1 kinases . It negatively regulates NF-kappaB activation by DNA damage via inhibiting ubiquitination of TRAF6 . It is also a negative regulator of osteoclastogenesis and bone formation .