SII-SWORD/CoKE huggingface dataset:
Hemogen (Hemogen)
Type: Family

Hemogen (EDAG in human and RP59 in rat) regulates the proliferation and differentiation of hematopoietic cells and resists cell apoptosis through the activation of NF-kappa B . It may also have a role in spermatogenesis and in sex determination in chicken .
E3 ubiquitin-protein ligase MARCH-like (MARCH-like)
Type: Family

This entry includes human E3 ubiquitin-protein ligase MARCH proteins (MARCH1/2/3/4/5/8/9/11), and virus proteins (MIR1, MIR2, LAP and VIE1) that share homology with the MARCH proteins .
E3 ubiquitin-protein ligase BIG BROTHER (BB)
Type: Family

Protein BIG BROTHER is an E3 ubiquitin-protein ligase that limits organ size, and possibly seed size, in a dose-dependent manner. It may limit the duration of organ growth and ultimately organ size by actively degrading critical growth stimulators .
Membrane protein MLC1 (Membrane_MLC1)
Type: Family

MLC1 is a membrane protein, mainly expressed in brain astrocytes, that plays a role in astrocyte osmo-homeostasis . Mutations in the MLC1 gene are linked to a rare leukodystrophy known as megalencephalic leukoencephalopathy with subcortical cysts (MLC). Several studies suggest that MLC1 plays a role in the regulation of ion and water fluxes and cell volume, but its exact function is not known . It binds the beta-1 subunit of the Na,K-ATPase enzyme , and interacts with the calcium permeable channel TRPV4 and the vacuolar ATPase (V-ATPase) .
Coiled-coil domain-containing protein 39 (CCDC39)
Type: Family

CCDC39 is an axonemal protein with coiled-coil domains required for assembly of inner dynein arms and the dynein regulatory complex, a key regulator of motor activity in cilia . Mutations in CCDC39 are a cause of primary ciliary dyskinesia, a disorder caused by cilia and sperm dysmotility .
Thy-1 membrane glycoprotein (THY1)
Type: Family

Thy-1 membrane glycoprotein (also known as CD90) was identified as an activation-associated cell adhesion molecule on human dermal microvascular endothelial cells. Its cellular effects vary; however, it most often seems to affect cell-cell or cell-matrix interactions and cellular adhesion and migration . Thy-1 interacts with the leukocyte integrin Mac-1 and may play an important role in the regulation of leukocyte recruitment to sites of inflammation . It also plays an important role in normal retinal development .
Erlin1/2 (Erlin1/2)
Type: Family

This entry includes Erlin1/2 (also known as SPFH1/2) from animals and their homologues from plants. Mammalian Erlin1 and Erlin2 form a complex that mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs) such as ITPR1 . The Erlin1/2 complex may recruit RNF170 (an E3 ubiquitin-protein ligase) to activated IP(3) receptors where it mediates IP(3) receptor ubiquitination .

Interestingly, C. elegans erlin homologue, ERL-1, does not play an essential role in the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-triphosphate receptors (IP3Rs) .
Deleted in lung and esophageal cancer protein 1 (DLEC1)
Type: Family

Deleted in lung and esophageal cancer (DLEC1) is a tumour suppressor that is frequently silenced by promoter methylation in various kinds of cancer . However, in head and neck squamous cell carcinoma, DLEC1 is not silenced solely by promoter methylation . It has been shown to repress NF-kB signalling in prostate cancer .
Hydrocephalus-inducing-like (Hydin-like)
Type: Family

Hydrocephalus-inducing protein (Hydin) is required for ciliary motility . Hydin mutations have been shown to associate with primary ciliary dyskinesia in humans .
Ted1, metallophosphatase domain (Ted1_MPase_dom)
Type: Domain

Ted1 remodels the anchor of newly synthesized GPI-anchored proteins and acts together with Emp24 and Erv25 in cargo exit from the endoplasmic reticulum . This entry also includes an uncharacterised yeast protein C23A1.02c.

This entry represents the metallophosphatase domain of Ted1. This domain is thought to allow for productive metal coordination.
PGAP5/Cdc1/Ted1 (PGAP5/Cdc1/Ted1)
Type: Family

This entry includes mammalian PGAP5 protein (also known as MPPE1) and budding yeast Ted1 and Cdc1 proteins. PGAP5 is involved in transport of GPI-anchored proteins from the ER to the Golgi . Ted1 is a GPI-glycan remodelase that acts together with Emp24 and Erv25 in cargo exit from the endoplasmic reticulum . Ted1 functions as the yeast orthologue of mammalian PGAP5 by removing a specific EtNP on GPI-glycan. By contrast, the other yeast PGAP5 homologue, Cdc1, seems not to be involved in GPI-AP trafficking . Instead, removes specifically the side-chain EtNP placed at the first mannose of the GPI-glycan, which is not important for trafficking but facilitates the integration of GPI-APs into the yeast cell wall .
Crossover junction endonuclease Mus81 (Mus81)
Type: Family

Budding yeast Mus81 complexes with Mms4 (EME1 or EME2 in humans) to form a structure-specific endonuclease that targets branched DNA structures with a 5'-end at the branch nick . Its typical substrates include 3'-flap structures, replication forks and nicked Holliday junctions .

Similar to MUS81-EME1, human MUS81-EME2 cleaves 3'-flaps, replication forks and nicked Holliday junctions, and exhibits limited endonuclease activity with intact Holliday junctions. However, MUS81-EME2 can also cleave a variety of DNA structures including D-loop recombination intermediates and nicked duplex .
Mms4/EME1/EME2 (Mms4/EME1/EME2)
Type: Family

This entry includes Mms4 from budding yeast, Eme1 from fission yeasts, and EME1/EME2 from animals. They interact with Mus81 to from a complex, which acts as a structure-specific endonuclease that targets branched DNA structures with a 5'-end at the branch nick . The typical substrates of this complex include 3'-flap structures, replication forks and nicked Holliday junctions .

Similar to MUS81-EME1, human MUS81-EME2 cleaves 3'-flaps, replication forks and nicked Holliday junctions, and exhibits limited endonuclease activity with intact Holliday junctions. However, MUS81-EME2 can also cleave a variety of DNA structures including D-loop recombination intermediates and nicked duplex .
DNA damage-binding protein 2 (DDB2)
Type: Family

DNA damage-binding protein 2 (DDB2) is required for DNA repair. It binds to DDB1 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair . It is also involved in the initiation of nucleotide excision repair via an ubiquitin ligase complex together with DDB1 and CUL4A (cullin 4A) .
Fanconi-associated nuclease 1-like (Fan1-like)
Type: Family

This entry includes a group of nucleases from bacteria and eukaryotes, including fanconi-associated nuclease 1 (Fan1) from eukaryotes.
DNA endonuclease RBBP8-like (RBBP8-like)
Type: Family

This entry includes DNA endonuclease RBBP8 from animals and protein gamma response 1 from plants . This entry also includes human RBBP8 N-terminal-like protein (RBBP8NL), whose function is not clear, and some uncharacterised fungal sequences.

RBBP8 is an endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in processing meiotic and mitotic double-strand breaks (DSBs) by ensuring both resection and intrachromosomal association of the broken ends .
Nectin-3, immunoglobulin variable domain 1 (Nectin-3_IgV_dom)
Type: Domain

Nectins are single-pass type I membrane glycoproteins belonging to the immunoglobulin superfamily. They are characterised by three Ig-like domains (a distal IgV domain and two IgC domains) in the ectodomain, followed by a transmembrane region and a cytoplasmic tail . Unlike cadherins, nectins are Ca2+-independent cell adhesion molecules that mediate not only homotypic but also heterotypic cell-cell adhesion . The cytoplasmic tail of nectins possesses a conserved afadin-binding motif, except for nectin-4 which binds the PDZ domain of afadin at its carboxyl terminus. Afadin connects nectins to F-actin and the actin cytoskeleton .

Nectin-3 plays a role in cell-cell adhesion through heterophilic transinteractions with other nectins. Nectin-2 and nectin-3 are expressed in Sertoli cells and spermatids, respectively, and their transinteraction regulates the organization of the Sertoli cell-spermatid junctions that plays a critical role in spermatid development . Nectin-3 and nectin-2 also interact to promote lymphocyte transendothelial migration . Nectin-3 and nectin-1 interactions play a critical role in selective axo-dendritic adhesion .

This entry represents the first immunoglobulin variable (IgV) domain of Nectin-3.
Nectin-3/4, second Ig domain (IgC1_2_Nectin-3-4-like)
Type: Domain

Nectins are single-pass type I membrane glycoproteins belonging to the immunoglobulin superfamily. They are characterised by three Ig-like domains (a distal IgV domain and two IgC domains) in the ectodomain, followed by a transmembrane region and a cytoplasmic tail . Unlike cadherins, nectins are Ca2+-independent cell adhesion molecules that mediate not only homotypic but also heterotypic cell-cell adhesion . The cytoplasmic tail of nectins possesses a conserved afadin-binding motif, except for nectin-4 which binds the PDZ domain of afadin at its carboxyl terminus. Afadin connects nectins to F-actin and the actin cytoskeleton .

This entry represents the second Ig domain of nectin-3 and 4. Nectin-3 plays a role in cell-cell adhesion through heterophilic transinteractions with other nectins. Nectin-2 and nectin-3 are expressed in Sertoli cells and spermatids, respectively, and their transinteraction regulates the organization of the Sertoli cell-spermatid junctions that plays a critical role in spermatid development . Nectin-3 and nectin-1 interactions play a critical role in selective axo-dendritic adhesion . Nectin-4 seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions . It acts as a receptor for measles virus . Nectin 4 plays a significant role in cancer cell growth and invasion .
OX-2 membrane glycoprotein, immunoglobulin variable domain (CD200_Ig_V_dom)
Type: Domain

OX2/CD200 is a broadly distributed cell surface glycoprotein that interacts with a receptor (CD200R) predominantly expressed on myeloid lineage cells . It is involved in regulation of macrophage function . Interaction of CD200 with its receptor acts to suppress inflammatory responses . CD200 has been shown to play important roles in controlling autoimmunity, inflammation, the development and spread of cancer, hypersensitivity, and spontaneous fetal loss .

This entry also includes viral OX2 (vOX2). Viral OX2 is encoded by herpesvirurses and has significant homology with cellular OX2. Viral OX2 encodes a glycosylated cell surface protein which has been shown to target myeloid-lineage cells .

This entry represents the first immunoglobulin (Ig) variable (V) domain of CD200 and similar sequences from vertebrates and some viral species.
E3 ubiquitin-protein ligase BAH1 (BAH1)
Type: Family

BAH1 (also known as NLA in Arabidopsis) that function as a RING-type ubiquitin E3 ligase . It regulates the accumulation of salicylic acid and immune responses to Pseudomonas syringae DC3000, a bacterial pathogen . It acts as a negative regulator of resistance to the necrotrophic fungal pathogen Plectosphaerella cucumerina by modulating the accumulation of the phytoalexin camalexin and the salicylic acid- and jasmonate- dependent defense pathways .
Transmembrane protein 127 (TMEM127)
Type: Family

TMEM127 modulates mTOR function in the endolysosome. Its interaction with early endosomal GTPase Rab5 to inhibit mTOR signalling seems to be related with its tumour-suppressive properties .
BTG family (BTG)
Type: Family

The BTG/Tob family members contain an conserved N-terminal domain, known as APRO domain (AntiPROliferative) or BTG domain. In mammals, six family members have been identified: BTG1, BTG2/PC3/Tis21, BTG3/ANA, BTG4/PC3B, Tob1/Tob and Tob2. They interact with CAF1, a subunit of the CCR4-NOT complex. They display antiproliferative properties as their ectopic expression in a variety of cell lines reduced cell proliferation .
Fanconi anemia group B protein (FANCB)
Type: Family

FANCB (also known as FAAP95) is a component of the Fanconi anemia (FA) core complex . The FA core complex mediates FANCD2 ubiquitination, a key activation step in the FA DNA damage response pathway . The FANCB and the FA pathway also play a critical role in germ cell development and in the maintenance of hematopoietic stem cell function .

FA is a recessive genetic disorder characterised by congenital abnormalities, progressive bone marrow failure and cancer susceptibility . Eight proteins (FANCA, B, C, E, F, G, L and M) encoded by the FA causative genes have been demonstrated to form the FA nuclear core complex.
Protein LONGIFOLIA 1/2 (LNG1/2)
Type: Family

This entry includes protein LONGIFOLIA 1/2 (LNG1/2) from Arabidopsis. They regulate leaf morphology by positively promoting longitudinal polar cell elongation independently of ROT3 .
Microtubule-associated protein Jupiter (JUPITER)
Type: Family

This entry includes microtubule-associated protein Jupiter from fruit flies and Jupiter microtubule associated homologues 1 and 2 from mammals, also known as hematological and neurological expressed 1 (HN1) and hematological and neurological expressed 1-like (HN1L) respectively.

Jupiter binds to all microtubule populations . HN1/HN1L may be involved in embryo development . HN1 is a regulator of GSK3beta-dependent interactions of beta-catenin and E-cadherin .
Stabilizer of axonemal microtubules 1/2 (SAXO1/2)
Type: Family

Stabilizer of axonemal microtubules 1/2 (SAXO1/2) may play a role in the regulation of cilium length. Human SAXO1 binds specifically to centriole and cilium microtubules. It stabilizes microtubules at low temperature .
MT-associated protein TORTIFOLIA1/SINE1-2 (TORTIFOLIA1/SINE1-2)
Type: Family

This entry includes a group of plant microtubule-associated proteins, including TORTIFOLIA1/SPIRAL2 and SPIRAL2-like (SP2L) from Arabidopsis. They regulate the orientation of cortical microtubules and the direction of organ growth . TORTIFOLIA1-like protein 1 (also known as SPIRAL2) may regulate katanin-based microtubule (MT) severing . During virus infection, it may stabilize MT crossovers to support the formation and intercellular spread of the viral RNA complexes .

This entry also includes SINE 1 and 2, paralogous KASH proteins that function during stomatal dynamics induced by light-dark transitions and abscisic acid (ABA), which requires F-actin reorganisation . KASH proteins are outer nuclear membrane proteins part of the linker of nucleoskeleton and cytoskeleton (LINC) complexes and interact in the nuclear envelope lumen with inner nuclear membrane SUN proteins that
connect the nucleus and cytoskeleton. SINE2 influences actin depolymerisation and SINE1 actin repolymerisation .
Spc105/Spc7 (Spc105/Spc7)
Type: Family

This entry includes Spc105 from budding yeasts and Spc7 from fission yeasts. Spc7 is a component of the NMS (Ndc80-MIND-Spc7) super complex which has a role in kinetochore function during late meiotic prophase and throughout the mitotic cell cycle . Spc105 and Kre28 forms a kinetochore complex, which is required for kinetochore binding by a discrete subset of kMAPs (BIM1, BIK1 and SLK19) and motors (CIN8, KAR3) .
Spindle and kinetochore-associated protein 3 (SKA3)
Type: Family

The Ska complex is an essential mitotic component required for accurate cell division in human cells. It is an important kinetochore component involved in the formation of kinetochore-microtubule interactions, and together with the Ndc80 complex couples chromosome movement to microtubule depolymerization . The complex is composed of three subunits: Ska1, Ska2, and Ska3.

Ska3 was the last subunit of the complex identified . Ska3 accumulates on kinetochores in prometaphase after nuclear envelope breakdown. During mitosis, it is required for the maintenance of chromosome cohesion and may play an important role in silencing the spindle checkpoint .
Protein CURVATURE THYLAKOID 1 (CURT1)
Type: Family

CURVATURE THYLAKOID 1 (CURT1) protein family is conserved in plants and cyanobacteria. There are four Arabidopsis CURT1 proteins, CURT1A, B, C, and D. They can modify thylakoid architecture by inducing membrane curvature .
Di19 (Di19)
Type: Family

This entry represents Di19 proteins.

Protein dehydration-induced19 (Di19) increases the sensitivity of plants to environmental stress, such as salinity, drought, osmotic stress and cold. The protein is also induced by an increased supply of stress-related hormones such as abscisic acid ABA and ethylene . Di19 has been found to be strongly expressed in both the roots and leaves of Arabidopsis thaliana during progressive drought . It is phosphorylated by AtCPK11 in a Ca(2+)-dependent manner
Aryl hydrocarbon receptor, basic helix-loop-helix domain (AHR_bHLH)
Type: Domain

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the biological and toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dioxin-like compounds (DLC), as well as some drugs and endogenous tryptophan metabolites . Without ligands, AHR is part of the Hsp90/XAP2 (heat shock protein 90/hepatitis B virus X-associated protein) multi-chaperone protein complex. Upon ligand binding, the receptor dissociates from the chaperone complex and translocates into the nucleus where it heterodimerises with ARNT (AHR nuclear translocator). The respective heterodimeric complex then modulates the cell's transcriptional activity by binding to specific xenobiotic response elements (XREs) in the promoters of AHR target genes .

This entry represents the basic helix-loop-helix (bHLH) domain of AHR.
ATR-interacting protein (ATRIP)
Type: Family

The function of the ATR-ATRIP (ATR-interacting protein) protein kinase complex is crucial for the cellular response to replication stress and DNA damage. ATRIP is a regulatory partner of ATR. The binding of ATRIP to replication protein A-coated ssDNA at sites of DNA damage drives ATR activation and enables the ATR-ATRIP complex to stimulate phosphorylation of substrates, such as Rad17 or Chk1, and the initiation of checkpoint signalling . ATRIP deacetylation by SIRT2 promotes ATR-ATRIP binding to RPA-ssDNA .
Centrosomal protein POC5 (POC5)
Type: Family

POC5 is a centrin-binding protein required for assembly of full-length centrioles. POC5 is not required for the initiation of procentriole assembly, but is essential for building the distal half of centrioles .
Transmembrane protein 88 (TMEM88)
Type: Family

There are two TMEM88 isoforms: TMEM88A/CRA-a, which inhibits the canonical Wnt/beta-catenin pathway through interactions with Dishevelled (Dvl) proteins and regulates the development of myocardial cells, and TMEM88A/CRA-b, which lacks the VWV motif and therefore likely does not interact with Dvl proteins .
SSNA1 family (SSNA1_fam)
Type: Family

Sjoegren syndrome nuclear autoantigen 1 (SSNA1/NA14) is a major specific target for autoantibodies in Sjögren's Syndrome, a highly prevalent autoimmune disease . SSNA1 is a microtubule-binding protein which stabilizes dynamic microtubules by slowing growth and shrinkage at both plus and minus ends and serves as a sensor of microtubule damage, protecting microtubules from the microtubule-severing enzyme SPAST . SSNA1 can assemble into large fibrils, a structure that is important for its interaction with spastin as well as for microtubule dynamics . It is also a binding partner for the G-protein coupled receptor TPRA40, which regulates early mouse embryogenesis .
BRI3-binding protein (BRI3BP)
Type: Family

BRI3-binding protein (BRI3BP) is a mitochondria protein and a binding partner for HCCR-1, which is overexpressed in various human tumours and appears to serve as a negative regulator of the p53 gene . BRI3BP may also be involved in the structural dynamics of the ER and affects mitochondrial viability. It possesses a pro-apoptotic property and can potentiate drug-induced apoptosis .
Protein C19orf12 (C19orf12)
Type: Family

C19orf12 codes for a transmembrane glycine zipper-containing mitochondrial protein of unknown function. Mutations of C19orf12 cause inability to respond to oxidative stress and increased mitochondrial Ca2+ . Mutations in C19orf12 have been identified in patients affected by Neurodegeneration with Brain Iron Accumulation (NBIA), a condition characterised by iron accumulation in the basal ganglia . Transgenic flies with impaired C19orf12 homologues also show the neurodegenerative phenotype . This family also includes protein Nazo from Drosophila melanogaster, an orthologue of human C190rf12 which functions as an antiviral effector protein expressed downstream of Sting and Rel (Relish) signalling in response to viral infection .
Conserved oligomeric Golgi complex subunit 1 (COG1)
Type: Family

The conserved oligomeric Golgi complex (COG) is a peripheral membrane protein complex involved in intra-Golgi protein trafficking. The complex is composed of eight subunits that are located in two lobes; Lobe A contains COG1-4, and Lobe B is composed of COG5-8. COG1 and COG8 are required for the stable association between two COG subcomplexes .
Arginine and glutamate-rich protein 1 (ARGLU1)
Type: Family

The arginine and glutamate-rich 1 (ARGLU1) family of proteins is found in metazoa and plants. In mammals, ARGLU1 cooperates with MED1 to regulate estrogen receptor-mediated gene transcription .
Small kinetochore-associated protein (SKAP)
Type: Family

Small kinetochore associated protein (SKAP) cooperates with kinetochore and mitotic spindle proteins to regulate the metaphase-to-anaphase transition . Its interaction with astrin in the kinetochore is important for normal spindle architecture and chromosome alignment . It interacts with MIS13 to orchestrate accurate interaction between kinetochore and dynamic spindle microtubules . It also interacts with mitotic motor CENP-E to orchestrate accurate chromosome segregation in mitosis . SKAP may also promote UV-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19 .
NMDA receptor synaptonuclear signalling and neuronal migration factor (NSMF)
Type: Family

NSMF/NELF/Jacob is a synaptic and a nuclear protein with two putative zinc fingers. The activation of NMDA receptors induces the NELF recruitment to neuronal nuclei, resulting in a rapid stripping of synaptic contacts. In brain NELF binds to importin-alpha through its bipartite nuclear localization signal (NLS) region. It also binds caldendrin, a neuronal Ca2+ sensor (NCS) protein, in a Ca2+-dependent manner. Caldendrin binding can mask the bipartite NLS of Jacob in competition with Importin-alpha and thereby prevent its nuclear trafficking .
CGG triplet repeat-binding protein 1 (Cggbp1)
Type: Family

CGG triplet repeat-binding protein 1 (CGGBP1) is a repetitive DNA-binding transcription regulator with target sites at CpG-rich sequences such as CGG repeats and Alu-SINEs and L1-LINEs . CGGBP1 mitigates cytosine methylation at repetitive DNA sequences . It also functions in DNA damage/repair and telomere metabolism . There are indications that it may be involved in mRNA metabolism . CGGBP1 ensures CTCF occupancy preferentially on repeats over canonical CTCF motifs, being a regulator of CTCF and its binding sites in interspersed repeats .

CGGBP1/p20 is known to bind to nonmethylated 5'-d(CGG)(n)-3' trinucleotide repeats in the in the promoter of the fragile X messenger ribonucleoprotein 1 (FMR1/FMRP) gene , although it seems not to have a direct effect on FMR1 transcription .
Protein BRICK1 (BRICK1)
Type: Family

Protein BRICK1 (Brk1) is part of the WAVE/SCAR complex, which links upstream Rho-GTPase signalling to the activation of the Arp2/3-complex and mediates actin nucleation . Brk1 is the only subunit for which a major pool is not associated with the WAVE/SCAR complex . This free pool of Brk1 is composed of an homotrimer and is a critical precursor for the assembly of the WAVE/SCAR complex . Brk1 is required for embryonic development and cell transformation .