SII-SWORD/CoKE huggingface dataset:
DNA-dependent protein kinase catalytic subunit, catalytic domain (DNA-PK_dom)
Type: Domain

This entry represents the catalytic domain of DNA-dependent protein kinase catalytic subunit (DNA-PKcs). The DNA-PK complex is composed of DNA-PKcs, the heterodimer Ku70/80, XRCC4, and ligase IV. The DNA-PK complex is involved in non-homologous end joining (NHEJ), a process of repairing double strand breaks (DSBs) by joining together two free DNA ends of little homology .
Phosphatidylinositol 3-kinase C2-gamma, catalytic domain (PI3-kinase_C2_gamma_cat)
Type: Domain

This entry represents the catalytic domain in PI3-kinase C2-gamma. It generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2). PI3K-C2gamma is expressed in the liver, breast, and prostate .

Phosphatidylinositol 3-kinase (PI3-kinases) can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3-kinases are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (p110alpha, beta, gamma or delta) and one of several regulatory subunits (p85alpha, beta or gamma). They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3-kinase homology domain of unknown function, and a C-terminal ATP-binding catalytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors .
Citron Rho-interacting kinase, catalytic domain (CRIK_dom)
Type: Domain

CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process . CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors . A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension .

CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs.
Serine/threonine-protein kinase Sgk3, catalytic domain (SGK3_dom)
Type: Domain

SGKs are serine/threonine-protein kinases involved in the regulation of transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three SGK isoforms: SGK1/2/3 . SGK3 regulates many transporters, ion channels, and receptors . It plays a critical role in hair follicle morphogenesis and hair cycling .
Microtubule-associated serine/threonine-protein kinase, catalytic domain (MAST)
Type: Domain

MAST (Microtubule-Associated Serine/Threonine) kinases are characterised by containing a serine/threonine kinase domain and a PDZ (postsynaptic density protein-95/discs large/zona occludens-1) domain . There are four mammalian MAST kinases, named MAST1-MAST4. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN . MAST1 links the dystrophin/utrophin network with microtubule filaments via the syntrophins . MAST1 localises in the DAPC/UAPC, which is found within the postsynaptic region of the neuromuscular junction (NMJ) and central synapses . The splice variant of its C-terminal affects its subcellular localisation within neurons . MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3 .
MSK2, N-terminal catalytic domain (MSK2_N_dom)
Type: Domain

MSK1/2 (Mitogen and Stress-induced Kinase, also known as RSKB) are partially redundant serine/threonine kinases that are phosphorylated downstream of MAPK (Erk and/or p38-mediated) and cAMP signal transduction pathways . They phosphorylate multiple substrates, including CREB and Histone H3 and regulate specific subsets of Immediate Early genes (IEG) . They are involved in limiting inflammation in innate immunity and is implicated in neurodegeneration and synaptic plasticity . MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90kDa ribosomal protein S6 kinases (RSKs) .

This entry represents the N-terminal catalytic domain of MSK2. MSK2 is also known as ribosomal protein S6 kinase alpha-4 (RPS6KA4).
Rhodopsin kinase, catalytic domain (GRK1_dom)
Type: Domain

Rhodopsin kinase (also known as G-protein-coupled Receptor Kinase 1, GRK1) is a retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade . Together with recoverin (a Ca2+-binding protein), GRK1 regulates cone phototransduction during photoreceptor light adaptation .

This entry represents the catalytic domain of GRK1.
A-kinase anchor protein 10, PKA-binding (AKB) domain (AKAP10_AKB_dom)
Type: Domain

A-kinase anchor proteins (AKAPs) coordinate the specificity of PKA signaling by facilitating the localization of the kinase to subcellular sites through their binding to regulatory (R) subunits of PKA. AKAP-10, also called PRKA10 or Dual-specific AKAP 2 (D-AKAP2), contains two regulator of G protein signaling (RGS)-like domains and a PKA-binding (AKB) domain .
Ferlin, second C2 domain (C2B_Ferlin)
Type: Domain

Ferlins are involved in vesicle fusion events . Ferlins and other proteins, such as synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1).

Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF .

C2 domains fold into an 8-standed β-sandwich that can adopt 2 structural arrangements: type I and type II, distinguished by a circular permutation involving their N- and C-terminal β strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins .

This entry represents the second C2 repeat of ferlins, C2B, which has a type-II topology.
Ferlin family (Ferlin)
Type: Family

Ferlins are involved in vesicle fusion events . Ferlins and other proteins, such as synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1).

Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF .
Ferlin, third C2 domain (C2C_Ferlin)
Type: Domain

Ferlins are involved in vesicle fusion events . Ferlins and other proteins, such as synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1).

Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF .

C2 domains fold into an 8-standed β-sandwich that can adopt 2 structural arrangements: type I and type II, distinguished by a circular permutation involving their N- and C-terminal β strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins .

This entry represents the third C2 repeat of ferlins, C2C, and has a type-II topology.
Ferlin, fourth C2 domain (C2D_Ferlin)
Type: Domain

Ferlins are involved in vesicle fusion events . Ferlins and other proteins, such as synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1).

Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF .

C2 domains fold into an 8-standed β-sandwich that can adopt 2 structural arrangements: type I and type II, distinguished by a circular permutation involving their N- and C-terminal β strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins .

This entry represents the fourth C2 repeat of ferlins, C2D, which has a type-II topology.
Ferlin, fifth C2 domain (C2E_Ferlin)
Type: Domain

This entry represents the fifth C2 repeat of ferlins, C2E, which has a type-II topology.

Ferlins are involved in vesicle fusion events . Ferlins and other proteins, such as synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1).

Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF .

C2 domains fold into an 8-standed β-sandwich that can adopt 2 structural arrangements: type I and type II, distinguished by a circular permutation involving their N- and C-terminal β strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins .
Ferlin, sixth C2 domain (C2F_Ferlin)
Type: Domain

This entry represents the sixth C2 repeat of ferlins, C2E, which has a type-II topology.

Ferlins are involved in vesicle fusion events . Ferlins and other proteins, such as synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1).

Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF .

C2 domains fold into an 8-standed β-sandwich that can adopt 2 structural arrangements: type I and type II, distinguished by a circular permutation involving their N- and C-terminal β strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins .
Ferlin, first C2 domain (C2A_Ferlin)
Type: Domain

Ferlins are involved in vesicle fusion events . Ferlins and other proteins, such as synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1).

Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF .

C2 domains fold into an 8-standed β-sandwich that can adopt 2 structural arrangements: type I and type II, distinguished by a circular permutation involving their N- and C-terminal β strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins .

This entry represents the first C2 repeat of ferlins, C2A, which has a type-II topology.
Microtubule-actin cross-linking factor 1-like (MCAF1-like)
Type: Family

This entry includes microtubule-actin cross-linking factor 1, isoforms 6/7 (MACF1), formerly known as KIAA0754, whose function is not clear.
Uncharacterized protein C21orf140-like (C21orf140-like)
Type: Family

The function of this family of proteins is not clear. The human protein in this entry is encoded by
C21orf140 gene.
Neuropeptide CCHamide 1/2 (CCHa1/2)
Type: Family

This entry includes neuropeptide CCHamide 1/2 (CCHa1/2) from insects. They are ligands for G protein-coupled receptors .
Mitochondrial inner membrane protease subunit 2 (IMP2)
Type: Family

This entry represents the mitochondrial inner membrane protease (IMP) subunit 2 (MEROPS identifier S26.012). IMP removes an N-terminal targeting signal from a protein synthesized in the mitochondrial matrix but destined for export across the membrane to the mitochondrial inter-membrane space. IMP is a hetero-oligomer containing two homologous subunits that are both serine endopeptidases (IMP1 and IMP2) plus SOM1 . IMP1 and IMP2 have overlapping specificities .
Meiosis-specific protein ASY3-like (ASY3-like)
Type: Family

This entry represents a group of plant meiosis-specific proteins, such as AtASY3 from Arabidopsis and PAIR3 from rice. They are coiled-coil domain proteins required for normal meiosis . PAIR3 is an axial element and part of the synaptonemal complex (SC) that forms between homologous chromosomes during meiosis . Members of this family are homologues of SYCP2 from vertebrates and fungal Red1/Red10 .
Synaptotagmin 7, C2A domain (C2A_Synaptotagmin-7)
Type: Domain

Synaptotagmin is a membrane-trafficking protein characterised by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains . Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and also functions as a vesicular Ca2+-sensor . It is distinguished from the other synaptotagmins by having over 12 splice forms .

Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10) . The general function of C2 domains in these is to mediate Ca2+-triggered binding of the protein to a membrane .

C2 domains fold into an 8-standed β-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal β strands. This entry represents the first C2 repeat, C2A, and has a type-I topology .
Extended synaptotagmin, C2A domain (Ext_Synaptotagmin_C2A)
Type: Domain

The extended-synaptotagmins derive their name from their partial domain structure similarity to the synaptotagmins, characterised by an N-terminal membrane anchor and cytosolically exposed C2 domains. Additionally they contain an SMP (synaptotagmin-like mitochondrial-lipid-binding protein) domain and multiple C2 domains (five in E-Syt1 and three in E-Syt2 and E-Syt3). However, the function of extended-synaptotagmins is different to that of synaptotagmins, which are involved in secretory vesicle tethering to the plasma membrane and exocytosis. The extended-synaptotagmins are located to the endoplasmic reticulum (ER), and tether this organelle to the plasma membrane via their C2 domains. They transport glycerolipids between the two bilayers via their lipid-harboring SMP domains. Ca2+ regulates their membrane tethering and lipid transport function .

C2 domains fold into an 8-standed β-sandwich that can adopt 2 structural arrangements: type I and type II, distinguished by a circular permutation involving their N- and C-terminal β strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This entry matches the first C2 repeat in extendend synaptotagmins (the first and the third in E-Syt1), with a type-I topology .
Thylakoid lumenal 17.9kDa protein (Thylakoid_lumenal_17.9)
Type: Family

This entry includes a group of plant proteins, including Arabidopsis 17.9kDa protein (AT4G24930), found in the thylakoid lumen .
Cadmium-induced protein AS8-like (AS8-like)
Type: Family

This entry represents a group of plant proteins, including cadmium-induced protein AS8 (AT4G19070) from Arabidopsis .
Photosystem I assembly factor PSA3 (PSA3)
Type: Family

PSI is a large protein-pigment complex located in the thylakoid membrane in plants and algae. PSA3 resides on the stromal face of the thylakoid membrane and cooperates with PYG7 (a PSI biogenesis factor) to promote the stable assembly of PSI .
Regulator of phospholipase D Srf1 (Srf1)
Type: Family

This entry includes budding yeast Srf1. It interacts with Spo14, yeast phospholipase D (PLD), and is essential for PLD catalytic activity in mitotic cells .
Protein Ecm13-like (Ecm13-like)
Type: Family

This entry includes budding yeast Ecm13 and its paralogue, YJR115W. The function of these proteins are not clear. Ecm13 has been found to be induced by treatment with 8-methoxypsoralen and UVA irradiation .
Uncharacterized protein C6orf141 (C6orf141)
Type: Family

The function of C6orf141 is not known.
Synaptotagmin 7, C2B domain (C2B_Synaptotagmin-7)
Type: Domain

Synaptotagmin is a membrane-trafficking protein characterised by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains . Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in the regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and also functions as a vesicular Ca2+-sensor . It is distinguished from the other synaptotagmins by having over 12 splice forms .

Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins, only 8 bind calcium (1-3, 5-7, 9, 10) . The general function of C2 domains in these is to mediate Ca2+-triggered binding of the protein to a membrane .

C2 domains fold into an 8-standed β-sandwich that can adopt 2 structural arrangements: type I and type II, distinguished by a circular permutation involving their N- and C-terminal β strands. This entry represents the second C2 repeat, C2B, and has a type-I topology .
FGD4, N-terminal PH domain (FDG4_N_PH)
Type: Domain

FGD4 (also known as FRABIN) is a member of the FGD family and is a small RhoGTPase Cdc42-guanine nucleotide exchange factor. It is associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance . FGD4 has been shown to regulate Schwann cell endocytosis . This entry represents the N-terminal PH domain of FGD4.

FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain .

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 polarised. 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 signalling 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 .