SII-SWORD/CoKE huggingface dataset:
Rho GTPase-activating protein 1, RhoGAP domain (ARHGAP1_RhoGAP)
Type: Domain

This entry represents the C-terminal RhoGAP domain found in ARHGAP1 proteins in animals. ARHGAP1

, also known as RhoGAP-1 or p50RhoGAP, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain

, which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related Rho GTPase-activating protein 68F (RhoGAP68F) from fruit fly

.

Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signalling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude .
LIM/homeobox protein Lhx3, LIM domain 1 (Lhx3_LIM1)
Type: Domain

This entry represents the first LIM domain of human LIM/homeobox protein Lhx3 (Lhx3) and similar sequences specific to vertebrates. Lhx3 is a member of LHX protein family, which features two tandem N-terminal LIM domains and a C-terminal DNA binding homeodomain. Members of LHX family are found in the nucleus and act as transcription factors or cofactors. The lhx3 gene is expressed in the ventral spinal cord, the pons, the medulla oblongata, and the pineal gland of the developing nervous system during mouse embryogenesis, and transcripts are found in the emergent pituitary gland . Lhx3 functions in concert with other transcription factors to specify interneuron and motor neuron fates during development .

As in other LIM domains, this domain is 50-60 amino acids in size and shares two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes .
LIM/homeobox protein Lhx3/4-like, LIM domain 2 (Lhx3/4-like_LIM2)
Type: Domain

This entry represents the second LIM domain of human LIM/homeobox protein Lhx3 and Lhx4 and similar animal proteins. Lhx3 and Lhx4 belong to the LHX protein family, which features two tandem N-terminal LIM domains and a C-terminal DNA binding homeodomain. Members of LHX family are found in the nucleus and act as transcription factors or cofactors. The Lhx3 and Lhx4 LIM-homeodomain transcription factors play essential roles in pituitary gland and nervous system development .

As in other LIM domains, this domain family is 50-60 amino acids in size and shares two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes .
YlcG-like (YlcG-like)
Type: Family

This entry represents the family of YlcG (

) from the DLP12 prophage region of Eschichia coli K-12, and homologues from the Gifsy-1 and Gifsy-2 prophage regions of Salmonella enterica subsp. enterica serovar Typhimurium str. LT2. Members of this family are small, about 46 amino acids long. YlcG is known to be expressed. It is encoded immediately downstream of the Holliday junction resolvase RusA by the cryptic lambdoid prophage DLP12.
Divisome-associated membrane protein Blr (Blr-like)
Type: Family

This entry includes divisome-associated membrane protein Blr (

), a short membrane protein. It was shown that Blr mutations increased the sensitivity of bacteria to beta-lactam antibiotics or their resistance to cell envelope stress . Blr is an interacting partner of the essential cell division protein FtsL and it is a component of the cell division apparatus involved in the stabilization of the divisome under certain stress conditions .
Heterocyst commitment protein HetP-like (HetP-like)
Type: Family

This entry includes HetP (

) and related proteins. HetP and its homologues occur in heterocyst-forming members of the cyanobacteria, and play a role in commitment to development into heterocysts, which specialize in nitrogen fixation rather than photosynthesis .
Conjugal transfer protein TraX (TraX-like)
Type: Family

This entry represents the conjugal transfer protein TraX and related proteins found mainly in gammaproteobacteria.
Rhophilin-2, HR1 domain (Rhophilin-2_HR1)
Type: Domain

This entry represents the N-terminal HR1 (homology region 1) Rho-binding domain present in Rhophilin-2 (RHPN2) from vertebrates. Rhophilin-2 is a scaffolding protein that functions as an effector of the Rho family of small GTPases. It plays a role in regulating the organisation of the actin cytoskeleton. Rhophilin-2 contains an N-terminal HR1 (this entry), a central Bro1-like (

), and a C-terminal PDZ domain (

); all are protein-interacting domains. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; Rhophilin-2 has been shown to bind both RhoA and RhoB .
Solute carrier family 49 member 4-like (SLC49A4-like)
Type: Family

This protein family represents human Solute carrier family 49 member 4 (also known as Disrupted in renal carcinoma protein 2, DIRC2) and similar proteins mainly found in vertebrates that belong to the Major Facilitator Superfamily (MFS) of transporters. DIRC2 was initially identified as a breakpoint-spanning gene in a chromosomal translocation associated with the development of renal cancer . It mediates H -dependent pyridoxine transport .
RNA-directed RNA polymerase L, OTU domain (L_OTU)
Type: Domain

This entry represents the N-terminal OTU (ovarian tumor) domain present in RNA-directed RNA polymerase L proteins mainly found in orthonairovirus. This protein, also known as protein L, large structural protein, replicase, transcriptase, or ubiquitin thioesterase, displays RNA-directed RNA polymerase (

), deubiquitinase (DUB)/ubiquitin thiolesterase (

), and deISGylating activities. It is a viral homologue of the ovarian tumor protease (vOTU), which has been implicated in the down-regulation of type I interferon immune response by removing post-translational modifying proteins ubiquitin (Ub) and the Ub-like interferon-simulated gene 15 (ISG15) from host cellular proteins. The attachment of Ub and ISG15 to cellular proteins mediates important innate antiviral responses, and their removal inhibits these antiviral pathways . Members of this group of proteins belong to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad .
UsfY-like (UsfY-like)
Type: Family

This entry includes UsfY from Mycobacterium and related proteins. The usfY gene is tightly linked with the anti-sigma B factor rsbW (usfX) . The function of UsfY is unknown.
YrbN-like (YrbN-like)
Type: Family

This entry represents YrbN, a small protein of only 26 amino acids. Homologues of YrbN are found in gammaproteobacteria. It is known to be expressed in E. coli .
Conjugal transfer protein TraP-like (TraP-like)
Type: Family

This entry represents the conjugal transfer protein TraP from IncI1 plasmids and homologues .
Syp1-like, mu-homology domain (Syp1-like_MHD)
Type: Domain

This entry represents the mu-homology domain (MHD) present in the endocytic adaptor Suppressor of yeast profilin deletion from Saccharomyces cerevisiae (Syp1) and similar fungal proteins. Syp1 is a yeast protein with multiple biological functions. It was originally identified as a suppressor of a yeast profiling deletion and later as a suppressor of arf3delta (Arf3 is the yeast homologue of Arf6, a mammalian regulator of endocytosis). Syp1 can bind to septins and physically link with cell polarity factors. It also directly binds to the endocytic adaptor/scaffold protein Ede1, and plays a role in endocytosis. Further studies show that Syp1 is itself an endocytic adaptor protein contributing to stress responses. Its mu-homology domain at the C-terminal binds to the cargo protein Mid2, a transmembrane stress sensor protein, and mediates Mid2 internalisation. In addition, Syp1 contains an EFC/F-BAR domain which can induce membrane tubulation .
Low-complexity tail membrane protein-like (LCTMP-like)
Type: Family

This entry represents Low-complexity tail membrane proteins (LCTMP) found mainly in cyanobacteria. Members of this family appear typically as an unusual gene pair with members of

. The members tend to have tail-to-tail overlapping regions, where the tail region from this protein is long, low-complexity, and typically rich in Asp, Glu, Asn, Gln, Ser, and Thr. The function of this pair of convergently-transcribed overlapping proteins is unknown.
Stress response membrane protein YncL (YncL)
Type: Family

This entry represents the small stress response protein YncL from E.coli and related proteins from gammaproteobacteria. YncL is overexpressed under heat shock . The function of this protein is unknown.
Byr1-like, catalytic domain (Byr1-like_cat)
Type: Domain

This entry represents the protein kinase (PK) catalytic domain present in Protein kinase byr1 from Schizosaccharomyces pombe, Dual specificity protein kinase FUZ7 from Ustilago maydis, Serine/threonine-protein kinase STE7 from Saccharomyces cerevisiae
and similar fungal proteins. PKs catalyse the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by Byr2 . The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast . FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U.maydis . STE7 is thought to be phosphorylated by the Ste11 protein kinase and to phosphorylate the FUS3 and or KSS1 kinases .
HrpB, DEXH-box helicase domain (HrpB_DEXH)
Type: Domain

This entry represents the DEAD-box helicase domain found in HrpB proteins. HrpB is part of the HrpB-HrpA two-partner secretion (TPS) system, a secretion pathway important to the secretion of large virulence-associated proteins . HrpB belongs to the DEAD-like helicase superfamily, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding . This domain contains the ATP-binding region .
BH0509-like (BH0509-like)
Type: Family

This entry represents a family of uncharacterised proteins that are restricted to firmicutes. The family is named after BH0509 (

) from Halalkalibacterium halodurans. The proteins are small and are predicted to fold into a three helical bundle.
Phenylalanyl--tRNA ligase operon leader peptide PheM (PheM)
Type: Family

This entry represents the phenylalanyl--tRNA ligase operon leader peptide from E.coli (

) and related species. The pheST operon codes for the two subunits of phenylalanyl-tRNA synthetase. The nucleotide sequence of the control regions of the operon indicates the presence of several open reading frames one of which, the leader peptide, is translated efficiently . The leader peptide is essential for attenuation control .
Measles virus hemagglutinin-like, C-terminal receptor-binding head domain (MV-h_C)
Type: Domain

The hemagglutinin (H) of measles virus plays several roles during viral infection; it participates in virus attachment to host cells via binding to a proteinaceous receptor and it has a stimulating effect on membrane fusion during the entry of the virus into the host cell by interacting with the fusion protein F . This entry represents the C-terminal receptor-binding head domain of measles hemagglutinin and of other Morbilliviruses. This entry doesn't include the stalk region. Receptors for measles virus have been identified as the signaling lymphocyte activation molecule (SLAM, in particular its distal ectodomain), CD46, and nectin-4 in epithelial cells .
Lhx1/5, LIM domain 1 (Lhx1/5_LIM1)
Type: Domain

This entry represents the first LIM domain of Lhx1 (also known as Lim1) and Lhx5. Lhx1 and Lhx5 are closely related members of LHX protein family, which features two tandem N-terminal LIM domains and a C-terminal DNA binding homeodomain {

}. Members of LHX family are found in the nucleus and act as transcription factors or cofactors. LHX proteins are critical for the development of specialized cells in multiple tissue types, including the nervous system, skeletal muscle, the heart, the kidneys, and endocrine organs, such as the pituitary gland and the pancreas. Lhx1 is required for regulating the vertebrate head organizer, the nervous system, and female reproductive tract development. During embryogenesis in the mouse, Lhx1 is expressed early in mesodermal tissue, then later during urogenital, kidney, liver, and nervous system development. In the adult, expression is restricted to the kidney and brain. A mouse embryos with Lhx1 gene knockout cannot grow normal anterior head structures, kidneys, and gonads, but with normally developed trunk and tail morphology. In the developing nervous system, Lhx1 is required to direct the trajectories of motor axons in the limb. Lhx1 null female mice lack the oviducts and uterus . Lhx5 protein may play complementary or overlapping roles with Lhx1. The expression of Lhx5 in the anterior portion of the mouse neural tube suggests a role in patterning of the forebrain {

}.

All LIM domains are 50-60 amino acids in size and share two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes .
Lhx1/5, LIM domain 2 (Lhx1/5_LIM2)
Type: Domain

This entry represents the second LIM domain of Lhx1 (also known as Lim1) and Lhx5. Lhx1 and Lhx5 are closely related members of LHX protein family, which features two tandem N-terminal LIM domains and a C-terminal DNA binding homeodomain {

}. Members of LHX family are found in the nucleus and act as transcription factors or cofactors. LHX proteins are critical for the development of specialized cells in multiple tissue types, including the nervous system, skeletal muscle, the heart, the kidneys, and endocrine organs, such as the pituitary gland and the pancreas. Lhx1 is required for regulating the vertebrate head organizer, the nervous system, and female reproductive tract development. During embryogenesis in the mouse, Lhx1 is expressed early in mesodermal tissue, then later during urogenital, kidney, liver, and nervous system development. In the adult, expression is restricted to the kidney and brain. A mouse embryos with Lhx1 gene knockout cannot grow normal anterior head structures, kidneys, and gonads, but with normally developed trunk and tail morphology. In the developing nervous system, Lhx1 is required to direct the trajectories of motor axons in the limb. Lhx1 null female mice lack the oviducts and uterus . Lhx5 protein may play complementary or overlapping roles with Lhx1. The expression of Lhx5 in the anterior portion of the mouse neural tube suggests a role in patterning of the forebrain {

}.

All LIM domains are 50-60 amino acids in size and share two characteristic zinc finger motifs. The two zinc fingers contain eight conserved residues, mostly cysteines and histidines, which coordinately bond to two zinc atoms. LIM domains function as adaptors or scaffolds to support the assembly of multimeric protein complexes .
CAXIP2, GIY-YIG domain (GIY-YIG_AtGrxS16)
Type: Domain

This entry represents the GIY-YIG domain of CAX-interacting protein-2 (CXIP2), also known as CAXIP1-like and AtGRXS16 (bifunctional monothiol glutaredoxin-S16) from Arabidopsis . CAXIP1 (AtGRXS14) is a novel PICOT (Protein Kinase C-interacting Cousin of Thioredoxin) domain-containing Arabidopsis protein that activates H /Ca2 exchanger CAX1, and its homologue CAX4, but not CAX2 or CAX3 . The GIY-YIG domain has significant similarity to the N-terminal catalytic domains of GIY-YIG family of intron-encoded homing endonuclease I-TevI and catalytic GIY-YIG domain of nucleotide excision repair endonuclease UvrC.
DHX8 helicase, S1 domain (S1_DHX8_helicase)
Type: Domain

This entry represents the S1 domain found in human ATP-dependent RNA helicase DHX8 (also known as HRH1) and its homologues, such as PRP22 from yeast. DHX8 is a DEAH (Asp-Glu-Ala-His) box polypeptide. The DEAH-box RNA helicases are thought to play key roles in pre-mRNA splicing and DHX8 facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome .
Dihydroorotate dehydrogenase class I, catalytic (Dihydroorotate_DH_I)
Type: Domain

This entry represents a domain found in class I dihydroorotate and dihydropyrimidine dehydrogenases. Dihydroorotate dehydrogenases included in this entry catalyse the conversion of dihydroorotate to orotate using fumarate and NAD as electron acceptor but not quinone. Dihydropyrimidine dehydrogenases catalyse the conversion of 5,6-dihydrouracil to uracil and are involved in pyrimidine base degradation .

Dihydroorotate dehydrogenase (

) (DHOdehase) catalyses the fourth step in the
de novo
biosynthesis of pyrimidine, the conversion of dihydroorotate into orotate. DHOdehase is a ubiquitous FAD flavoprotein. In bacteria (gene pyrD), DHOdease is located on the inner side of the cytosolic membrane. In some yeasts, such as in Saccharomyces cerevisiae (gene URA1, subfamily 2), it is a cytosolic protein while in other eukaryotes it is found in the mitochondria .
Phenylacetate--CoA ligase PaaK, proteobacteria/actinomycetes (PA_CoA_lig_proteobact_actino)
Type: Family

This entry represents Phenylacetate-coenzyme A ligase (PaaK) found mainly in proteobacteria and actinomycetes.

Phenylacetate-CoA ligase (PA-CoA ligase) catalyses the first step in aromatic catabolism of phenylacetic acid (PA) into phenylacetyl-CoA (PA-CoA) . Often located in a conserved gene cluster with enzymes involved in phenylacetic acid activation (paaG/H/I/J), phenylacetate-CoA ligase has been found among the proteobacteria as well as in Gram-positive prokaryotes . In the B-subclass proteobacterium Azoarcus evansii, phenylacetate-CoA ligase has been shown to be induced under aerobic and anaerobic growth conditions. It remains unclear however, whether this induction is due to the same enzyme or to another isoenzyme restricted to specific anaerobic growth conditions .
Forkhead box protein N1/4 (FOXN1_4)
Type: Family

This family includes Forkhead box protein N41 and N4.

Forkhead box protein N1 (FOXN1) acts as a transcriptional regulator which regulates the development, differentiation, and function of thymic epithelial cells (TECs) , both in the prenatal and postnatal thymus . Loss of function of this transcription factor leads to the human counterpart of the nude mouse characterised by athymia with severe T cell immunodeficiency, congenital alopecia, and nail dystrophy . It has been reported that FOXN1 duplication leads to congenital hypertrichosis . It is also an important factor in controlling the skin wound healing process, as it actively participates in re-epithelialization and is responsible for scar formation .

Forkhead box protein N4 (FOXN4) acts as a transcription factor essential for neural and some non-neural tissue development, such as retina and lung, respectively . During development of the central nervous system, FOXN4 is required in specifying the amacrine and horizontal cell fates from multipotent retinal progenitors, while suppressing alternative photoreceptor cell fates . In non-neural tissues, it plays an essential role in specifying the atrioventricular canal and is indirectly required for patterning the distal airway during lung development . FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.
Glycosyltransferase 61, catalytic domain (Glyco_transf_61_cat)
Type: Domain

This entry represents the catalytic domain of glycosyltransferase 61 members .

Glycosyltransferase 61 family members are further processed into a mature form. Proteins in this family includes O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2 (POMGnT2, also known as EOGTL) and EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT) .

This entry also includes plant beta-(1,2)-xylosyltransferase .
E3 ubiquitin-protein ligase complex SLX5-SLX8 subunit SLX8 (SLX8)
Type: Family

This entry includes E3 ubiquitin-protein ligase complex SLX5-SLX8 subunit SLX8 from budding yeast, which mediates ubiquitination and subsequent desumoylation/degradation of sumoylated proteins and proteins containing SUMO-like domains. It acts as a critical suppressor of gross chromosomal rearrangements (GCRs) during normal cell cycle progression. It is also involved in stabilising, restarting or resolving transiently stalled replication forks. It prevents accumulation of DNA damage during cell cycle progression .

This entry also includes uncharacterised plant sequences.
CNK1-3, SAM domain (CNK1-3_SAM)
Type: Domain

This entry represents the SAM domain of connector enhancer of kinase suppressor of ras (CNK). CNK proteins are multidomain scaffold proteins containing a few protein-protein interaction domains and are required for connecting Rho and Ras signaling pathways. In Drosophila, the SAM domain of CNK is known to interact with the SAM domain of the Aveugle protein, forming a heterodimer . Mutation of the SAM domain in human CNK1 abolishes the ability to cooperate with the Ras effector, supporting the idea that this interaction is necessary for proper Ras signal transduction .
DPY30/SDC1, dimerization/docking domain (DPY30_SDC1_DD)
Type: Domain

This entry represents the dimerization/docking domain (DD) of DPY-30 from animals and its homologues SDC1 from yeast.

Protein dpy-30 homologue (DPY30) is a component of the MLL1/MLL complex which trimethylates histone H3 at 'Lys-4' as a specific tag for epigenetic transcriptional activation . DPY30 is also a component in MLL2/3 and MLL4/WBP7 methyltransferase-containing complexes and the SET1 complex . DPY30 is found in the nucleus and the trans-Golgi network where it interacts with ARFGEF1 implying a role in endosomal trafficking . This entry also includes C. elegans dpy-30, which is an essential component of the C. elegans dosage compensation machinery that reduces X chromosome transcript levels in hermaphrodites (XX) .
DPY30 domain-containing protein-like, dimerization/docking domain (DYDC-like_DD)
Type: Domain

The DYDC-like family includes DYDC1 and DYDC2 proteins. DYDC1 plays a crucial role during acrosome biogenesis. RSP2 is a calmodulin binding spoke stalk protein required for motility in Chlamydomonas reinhardtii. It binds calmodulin in a calcium-dependent manner. Members of this entry contain an N-terminal domain that shows high sequence similarity to the dimerization/docking (D/D) domain of protein DPY-30/SDC1 .
Dickkopf-like protein 1 (DKKL1)
Type: Family

This entry represents the human Dickkopf-like protein 1 (DKKL1, also known as soggy-1 (SGY-1),

) and related mammalian proteins. DKKL1 is an acrosomal protein that affects in vitro fertilisation by facilitating sperm penetration of the zona pellucida .
Large ribosomal subunit protein eL6, conserved site (Ribosomal_eL6_CS)
Type: Conserved_site

This entry represents a conserved site found in the centre of large ribosomal subunit proteins eL6 from eukaryotes, including mammalian eL6 (which was previously known as L6 and TAX-responsive enhancer element binding protein 107 ; Saccharomyces cerevisiae (Baker's yeast) ribosomal proteins eL6A/B (also known as YL16A/YL16B); and Mesembryanthemum crystallinum (Common ice plant) eL6 (also known as YL16-like). These proteins have 175 (yeast) to 287 (mammalian) amino acids.