SII-SWORD/CoKE huggingface dataset:
Mitofusin family (Mitofusin_fam)
Type: Family

The mitofusin family consists of the yeast transmembrane GTPase Fzo and mammalian homologues mitofusin-1 and mitofusin-2 . Fzo/mitofusins mediate mitochondrial fusion .

This entry also includes bacterial dynamin-like protein, including DynA from Bacillus subtilis, and dynamin-like protein from Nostoc punctiforme. DynA mediates lipid fusion in the absence and presence of GTP and affects several steps in cell division .
Golgin-45 (Golgin-45)
Type: Family

Golgin-45 is required for normal Golgi structure and for protein transport from the endoplasmic reticulum (ER) through the Golgi apparatus to the cell surface. It interacts with GORASP2 and with the GTP-bound form of RAB2, but not with other Golgi Rab proteins .
Sodium channel subunit beta-1/beta-3 (Na_channel_b1/b3)
Type: Family

The voltage-sensitive sodium channel consists of an ion conducting pore forming alpha-subunit regulated by one or more non-pore-forming beta subunits. There are five different beta-subunit proteins (beta-1, beta-1B, beta-2, beta-3, and beta-4) encoded by four genes (SCN1B-SCN4B; beta-1B is a splice variant of SCN1B) . Beta-subunits modulate the kinetics and voltage dependence of the alpha-subunits and they also affect the voltage-gated potassium channels. These subunits participate in nonconducting roles, including cell-cell and cell-matrix adhesion, directing neuronal proliferation, migration, and fasciculation, and modulating the effects of pharmacological compounds on voltage-gated sodium channels, playing important roles in development and disease .

Subunit beta-1 is crucial in the assembly, expression, and functional modulation of the sodium channel that can modulate multiple alpha subunit isoforms from brain, skeletal muscle, and heart . Both beta-1 and beta-3 associate with neurofascin through their extracellular immunoglobulin-like domains. This association may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons .
U4/U6 small nuclear ribonucleoprotein Prp3 (Prp3)
Type: Family

Prp3 (also known as PRP3) participates in pre-mRNA splicing . It may play a role in the assembly of the U4/U5/U6 tri-snRNP complex . Defects in PRPF3 are the cause of retinitis pigmentosa type 18 (RP18). RP leads to degeneration of retinal photoreceptor cells . In
Arabidposis thaliana
, protein RDM16 acts as a pre-mRNA splicing factor and functions in RNA-directed DNA methylation by influencing Pol V transcript levels .
U4/U6 small nuclear ribonucleoprotein Prp31 (Prp31)
Type: Family

Prp31 is a component of the U4/U6-U5 snRNP complex that is involved in pre-mRNA splicing . It is required for U4/U6.U5 tri-snRNP formation . Defects in PRPF31 are the cause of retinitis pigmentosa type 11 (RP11). RP leads to degeneration of retinal photoreceptor cells .
Tuberin/Ral GTPase-activating protein subunit alpha (Tuberin/Ral-act_asu)
Type: Family

The activity of GTPases is regulated by the opposing effects of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Tuberin (tuberous sclerosis 2 protein or Tsc2) is believed to be a tumor suppressor and is able to stimulate specific GTPases. It stimulates the intrinsic GTPase activity of the Ras-related protein Rap1A and Rab5 . In complex with Tsc1, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. It acts as a GTPase-activating protein (GAP) for the small GTPase RheB, a direct activator of the protein kinase activity of mTORC1 .
SWR1-complex protein 4/DNA methyltransferase 1-associated protein 1 (Swc4/Dmap1)
Type: Family

This entry consists of the SWR1-complex protein 4 (Swc4) from yeast, also known as EAF2, and its mammalian homologue DNA methyltransferase 1-associated protein 1 (Dmap1) . They are components of the NuA4 histone acetyltransferase (HAT) complex, which is highly conserved in eukaryotes. NuA4 acetylates the nucleosomal histones H4 and H2A and plays primary roles in transcription, DNA repair, and cell cycle control .

The subunits of the NuA4 complex are shared by the ATP-dependent chromatin-remodeling SWR1 complex in yeast and its human orthologue, Snf 2-related CREB-binding protein (CBP) activator protein (SRCAP) complex. The mammalian NuA4 complex includes the SRCAP complex, and thus combines the functions of the yeast NuA4 and Swr1 complexes . The SWR1/SRCAP complex mediates the ATP-dependent exchange of histone H2A for the H2A variant HZT1 leading to transcriptional regulation of selected genes by chromatin remodeling .
Pyruvate dehydrogenase E1 component subunit beta, mitochondrial-type (PDHB_mito-type)
Type: Family

Proteins in this family are E1 beta subunit (also known as PDB1 or PDHB) of the pyruvate dehydrogenase (PDH) complex. This PDH complex catalyses the overall conversion of pyruvate to acetyl-CoA and CO2. It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3) . In mitochondria the E1 enzyme exists as a heterotetramer of two E1 alpha subunits and two E1 beta subunits, with thiamine pyrophosphate as a cofactor . Some bacteria also have E1 alpha and E1 beta subunits, found as a heterodimer of an alpha and a beta chain .

Defects in PDHB are the cause of pyruvate dehydrogenase E1-beta deficiency (PDHBD), an enzymatic defect causing primary lactic acidosis in children .
Transcription factor NFYB/HAP3 (Transc_fact_NFYB/HAP3)
Type: Family

The eukaryotic transcription factors NF-Y, also known as CCAAT-binding factors (CBF) or heme activator protein (HAP), bind to a CCAAT element in the promoters of a wide variety of genes, to regulate its expression. They consists of three distinct subunits: NF-YA (also known as CBF-B or HAP2), NF-YB (CBF-A or HAP3) and NF-YC (CBF-C or HAP5). The NF-YB subunit consists of three regions, an N-terminal A domain, a central conserved B domain, and a C-terminal C domain. The B domain is highly conserved and the most important part of the NF-YB subunit, as it is required for the interaction with NF-YA and NF-YC to form the heterotrimeric complex and contain the evolutionarily-conserved DNA binding domain . There is only a gene encoding NF-YB in yeast and animals, but in plants there are gene families encoding this subunit, for example in Arabidopsis there are at least 10 NF-YB genes .

This entry represents CBF-A or NF-YB from vertebrates and HAP3 from yeast. The Kluyveromyces lactis HAP3 protein has been predicted to contain a 4-cysteine zinc finger, which is thought to be present in similar HAP3 and CBF subunit A proteins, in which the third cysteine is replaced by a serine .
Matrix Gla protein (MGP)
Type: Family

Matrix Gla protein associates with the organic matrix of bone and cartilage. It is thought to act as an inhibitor of calcification . Defects in MGP are the cause of Keutel syndrome (KS). KS is an autosomal recessive disorder characterised by abnormal cartilage calcification, peripheral pulmonary stenosis neural hearing loss and midfacial hypoplasia .
Smc2, ATP-binding cassette domain (Smc2_ABC)
Type: Domain

Structural maintenance of chromosomes protein 2 (Smc2) is a central component of the condensin complex, which is required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases .

Amino-acid sequence homology of SMC proteins between species is largely confined to the amino- and carboxy-terminal globular domains. The amino-terminal domain contains a 'Walker A' nucleotide-binding domain (GxxGxGKS/T, in the single-letter amino-acid code), which by mutational studies has been shown to be essential in several proteins. The carboxy-terminal domain contains a sequence (the DA-box) that resembles a 'Walker B' motif, and a motif with homology to the signature sequence of the ATP-binding cassette (ABC) family of ATPases .
SWR1-complex protein 5/Craniofacial development protein 1/2 (Swc5/CFDP1/2)
Type: Family

This family includes SWR1-complex protein 5 (Swc5) from fungi, craniofacial development protein 1 (CFDP1) and 2 (CFDP2) from animals and some uncharacterised protein from plants.

Swc5 is a component of the SWR1 complex which mediates the ATP-dependent exchange of histone H2A for the H2A variant HZT1 leading to transcriptional regulation of selected genes by chromatin remodeling. It is involved in chromosome stability .

Gene duplication of the ancestral bnct (bucentaur) gene leads to the h-type bnct (cfdp1) gene and the p97bcnt (cfdp2) gene. Cfdp2 is rumiant-specific, containing a region derived from the endonuclease domain of a retrotransposable element RTE-1 not found in human and mouse . For this reason bcnt has been used as a model for molecular evolution . CFDP1, also known as Cp27, may play a role during embryogenesis .
TNF receptor-associated factor 3, C3HC3D-type RING zinc finger (TRAF3_RING-HC)
Type: Domain

Tumor necrosis factor (TNF) receptor associated factor 3 (TRAF3) is a highly versatile regulator that positively controls type I interferon production, but negatively regulates mitogen-activated protein (MAP) kinase activation and non-canonical nuclear factor-kB signalling . It is a critical regulator of both innate and adaptive immune responses . TRAF3 plays a role in the regulation of B-cell survival , in the regulation of antiviral responses , and in T-cell dependent immune responses . It is required for normal antibody isotype switching from IgM to IgG . Differences in the ubiquitination of TRAF3 are the key to the selective production of type I interferons versus proinflammatory cytokines .

This entry represents the modified C3HC3D-type (HC subclass) RING zinc finger of TRAF3.
TNF receptor-associated factor 5, C3HC3D-type RING-HC finger (TRAF5_C3HC3D_RING-HC_finger)
Type: Domain

TNF receptor-associated factor 5 (TRAF5) is an adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. TRAF5 mediates activation of NF-kappa-B and probably JNK . TRAF5 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger (this entry), several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain .
TNF receptor-associated factor 2, C3HC3D-type RING zinc finger (TRAF2_RING-HC)
Type: Domain

TNF receptor-associated factor 2 (TRAF2) regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis .

TRAF2 is heavily regulated by ubiquitin signals. It has E3 ubiquitin-protein ligase activity and promotes K63-linked ubiquitination of target proteins. Alternatively, TRAF2 may be required for recruiting other E3 ligases, such as A20, to help processing and turnover. Furthermore, TRAF2 is regulated by both K63 and K48 type ubiquitin chains. K63 linkage may be mediated by TRAF2 auto-ubiquitination, and is required for TRAF2 activation. c-IAPl and Siah2 are known E3 ligases that can K48-ubiquitinate TRAF2 to target it for proteasome-dependent degradation . TRAF2 contains a RING finger domain, five zinc finger domains, and a TRAF domain.

This entry represents the modified C3HC3D-type (HC subclass) RING zinc finger of TRAF2 .
TNF receptor-associated factor 6, C3HC3D-type RING zinc finger (TRAF6_RING-HC)
Type: Domain

TNF receptor-associated factor 6 (TRAF6) regulates a diverse array of processes, including adaptive immunity, innate immunity, bone metabolism and tissue development. It is a unique member of the TRAF family of adaptor proteins in that it is involved in both the TNF receptor superfamily and the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily signal transduction pathways . TRAF6 possesses ubiquitin ligase activity that controls the activation of IKK and NF-kappaB . TRAF6 contains a RING finger domain, five zinc finger domains, and a TRAF domain.

This entry represents the modified C3HC3D-type (HC subclass) RING zinc finger of TRAF6 .
Like-Sm (LSM) domain containing protein, LSm4/SmD1/SmD3 (LSm4/Sm_D1/D3)
Type: Family

This entry represents a group of LSM domain containing proteins functioning in RNA processing, including U6 snRNA-associated Sm-like protein LSm4 and small nuclear ribonucleoproteins Sm D1 and D3.

LSm4 is a component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. It binds specifically to the 3'-terminal U-tract of U6 snRNA .
Periodic tryptophan protein 2 (PWP2)
Type: Family

Periodic tryptophan protein 2 (also known as UTP1) is involved in nucleolar processing of pre-18S ribosomal RNA . In budding yeast, it is a component of the ribosomal small subunit (SSU) processome composed of at least 40 protein subunits and snoRNA U3 .
AP-3 complex subunit sigma (APS3)
Type: Family

APS3 is part of the AP-3 complex, an adaptor-related complex which is essential for the compartmentalization of the endocytic pathway .
In Saccharomyces cerevisiae, the AP-3 complex is associated with the Golgi region as well as more peripheral structures . It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to the vacuole . It is required for the transport via the ALP pathway, which directs the transport of the cargo proteins Pho8 and Vam3 to the vacuole .
AP-2 complex subunit sigma (APS2)
Type: Family

Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 complex subunit sigma (APS2, also known as AP17) is a component of the adaptor protein complex which links clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration . The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif .
Nuclear cap-binding protein subunit 2 (NCBP2)
Type: Family

Nuclear cap-binding protein subunit 2 (NCBP2, also known as CBC2 and CBP20) forms the CBC complex with the nuclear cap-binding protein subunit 1 (

). The CBC complex binds co-transcriptionally to the 5' cap of pre-mRNAs and is involved in maturation, export and degradation of nuclear mRNAs . In humans, the CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus and plays a central role in nonsense-mediated mRNA decay (NMD) . During cell proliferation, the CBC complex is involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2, thereby being required for miRNA-mediated RNA interference .
Nuclear cap-binding protein subunit 1 (CBP80)
Type: Family

Nuclear cap-binding protein subunit 1 (also known as CBP80 or STO1) forms the CBC complex with the nuclear cap-binding protein subunit 2 (

). CBC complex binds co-transcriptionally to the 5' cap of pre-mRNAs and is involved in maturation, export and degradation of nuclear mRNAs . In humans, the CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus and plays a central role in nonsense-mediated mRNA decay (NMD) . During cell proliferation, the CBC complex is involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2, thereby being required for miRNA-mediated RNA interference .
Condensin complex subunit 3 (CND3)
Type: Family

Condensin complex subunit 3 (also known as NCAPG or YCG1) is a regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerase .
Cx9C motif-containing protein 4 (CMC4)
Type: Family

Proteins in this family adopt a coiled coil structure, with two antiparallel α-helices that are tightly strapped together by two disulfide bridges at each end. The protein sequence shows a cysteine motif, required for the stabilisation of the coiled-coil-like structure. Additional inter-helix hydrophobic contacts impart stability to this scaffold .

The precise function of this family is, as yet, unknown . Cx9C motif-containing protein 4 (CMC4, also known as Mature T-cell proliferation 1 neighbor protein or Mature T-cell proliferation-1 type A) is found in mitochondria. Mature-T-Cell Proliferation is the first gene unequivocally identified in the group of uncommon leukemias with a mature phenotype .
Nucleolar complex protein 4 (Noc4)
Type: Family

In Saccharomyces cerevisiae, Noc4 is involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly. It forms a complex with Nop14p that mediates maturation and nuclear export of 40S ribosomal subunits .
Equilibrative nucleobase transporter 1 (SLC43A3)
Type: Family

This family includes Equilibrative nucleobase transporter 1 (also known as Solute carrier family 43 member 3), a sodium-independent purine-selective nucleobase transporter which mediates the equilibrative transport of extracellular purine nucleobases such as adenine, guanine and hypoxanthine .
Adaptin medium chain homologue Apm2, N-terminal domain (Apm2_N)
Type: Domain

Adaptin medium chain homolog APM2 from Saccharomyces cerevisiae is homologous to the medium chain of mammalian clathrin-associated protein complex (AP)

. It may be involved in a nonclathrin-mediated vesicular transport process .

This entry represents the N-terminal longin domain of APM2.
Cystatin (Cystatin)
Type: Family

This entry represents the type1, type2 and cystatin-like proteins.

Cystatins are cysteine proteinase inhibitors belonging to MEROPS inhibitor family I25, clan IH . They mainly inhibit peptidases belonging to peptidase families C1 (papain family) and C13 (legumain family). The cystatin family includes:

The Type 1 cystatins, which are intracellular cystatins that are present in the cytosol of many cell types, but can also appear in body fluids at significant concentrations. They are single-chain polypeptides of about 100 residues, which have neither disulphide bonds nor carbohydrate side chains.

The Type 2 cystatins, which are mainly extracellular secreted polypeptides synthesised with a 19-28 residue signal peptide. They are broadly distributed and found in most body fluids.

The Type 3 cystatins, which are multidomain proteins. The mammalian representatives of this group are the kininogens. There are three different kininogens in mammals: H- (high molecular mass,

) and L- (low molecular mass) kininogen which are found in a number of species, and T-kininogen that is found only in rat.

Unclassified cystatins. These are cystatin-like proteins found in a range of organisms: plant phytocystatins, fetuin in mammals, insect cystatins and a puff adder venom cystatin which inhibits metalloproteases of the MEROPS peptidase family M12 (astacin/adamalysin). Also a number of the cystatins-like proteins have been shown to be devoid of inhibitory activity.

All true cystatins inhibit cysteine peptidases of the papain family (MEROPS peptidase family C1), and some also inhibit legumain family enzymes (MEROPS peptidase family C13). These peptidases play key roles in physiological processes, such as intracellular protein degradation (cathepsins B, H and L), are pivotal in the remodelling of bone (cathepsin K), and may be important in the control of antigen presentation (cathepsin S, mammalian legumain). Moreover, the activities of such peptidases are increased in pathophysiological conditions, such as cancer metastasis and inflammation. Additionally, such peptidases are essential for several pathogenic parasites and bacteria. Thus in animals cystatins not only have capacity to regulate normal body processes and perhaps cause disease when down-regulated, but in other organisms may also participate in defence against biotic and abiotic stress.
Semaphorin (Semaphorin)
Type: Family

Semaphorins are a family of cell surface and soluble proteins originally identified as axon guidance factors, but are now recognised to to be involved in a wide range of functions, including neural connectivity, angiogenesis, immunoregulation, and cancer . Some semaphorins have an important role in the immune response, some regulate immune cell activation or differentiation, while others regulate the trafficking of immune cells . Semaphorins signal through two major receptor families, plexins and neuropilins (Nrps). All semaphorins have a Sema domain, characterised by a seven-blade β propeller structure, which contains sites for semaphorin dimerisation and receptor binding.

Semaphorins are grouped into eight classes based on their structural domains, with classes 3-7 comprising the vertebrate semaphorins .
Protein phosphatase Slingshot homologue 1, dual specificity phosphatase domain (DSP_SSH1)
Type: Domain

Slingshot homologue 1 (SSH1) is a dual specificity protein phosphatase which regulates actin filament dynamics. It dephosphorylates and activates the actin binding/depolymerising factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly . SSH1 links NOD1 signaling to actin remodeling, facilitating the changes that leads to NF-kappaB activation and innate immune responses . There are at least two human SSH1 isoforms reported: hSSH-1L (long) and hSSH-1S (short). As SSH family phosphatases, they contain an N-terminal, SSH family-specific non-catalytic (SSH-N) domain, followed by a short domain with similarity to the C-terminal domain of the chromatin-associated protein DEK, and a dual specificity phosphatase catalytic domain. They also contain C-terminal tails, differing in the lengths of the tail.
Prefoldin subunit 2 (PFD2)
Type: Family

This entry represents prefoldin subunit 2 (PFD2, also known as Gim4 in budding yeasts). PFD2 is part of the prefoldin heterohexamer complex (consists of two PFD-alpha type and four PFD-beta type subunits) that binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it . It binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for non-native proteins .
RuvB-like (RuvB-like)
Type: Family

This entry represents RuvB-like proteins, including RuvB-like 1 and 2 (Rvb1 and Rvb2).
Calcium-binding protein CAB45, EF-hand (CAB45_EFh)
Type: Domain

Calcium-binding protein CAB45 contains EF-hand domains and may regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment .

This entry represents the EF-hand, calcium binding motif of CAB45.
Reticulocalbin-1 (Rcn1)
Type: Family

Reticulocalbin-1 contains EF-hand domains and may regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment . It belongs to the CREC family.
Vacuolar membrane-associated protein Iml1 (IML1)
Type: Family

Proteins in this family contain a DEP domain, which is a globular domain of about 80 residues. This entry includes GTPase-activating proteins (GAPs), such as Iml1 from fungi and GATOR complex protein DEPDC5 from mammals. In Saccharomyces cerevisiae, Iml1 is a GAP subunit of both the SEA (Seh1-associated) and Iml1 complexes (Iml1-Npr2-Npr3). SEA complex is associated dynamically with the vacuole and is involved in autophagy . Iml1 complex is required for non-nitrogen-starvation (NNS)-induced autophagy . In mammals, DEPDC5 is a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway .