SII-SWORD/CoKE huggingface dataset:
Calcium-responsive transcription factor (CaRF)
Type: Family

This entry represents calcium-responsive transcription factor (CaRF, also known as amyotrophic lateral sclerosis 2 chromosomal region candidate gene 8 protein) . CaRF acts as a transcriptional activator that mediates the calcium- and neuron-selective induction of BDNF exon III transcription. It binds to the consensus calcium-response element CaRE1 5'-CTATTTCGAG-3' sequence .
FANCI helical domain 1 (FANCI_HD1)
Type: Domain

FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) .

This is the helical domain 1 (HD1) of the Fanconi anemia complementation group I protein (FANCI).
Coiled-coil domain-containing protein 50, N-terminal (CCDC50_N)
Type: Domain

This entry represents the N-terminal domain of the coiled-coil domain-containing protein 50 (CCDC50). Human CCDC50 is overexpressed in mantle cell lymphoma and chronic lymphocytic leukemia. Its involvement in NFkappaB signalling pathways may have major effects on cell survival .
FANCI helical domain 2 (FANCI_HD2)
Type: Domain

FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) .

This is the helical domain 2 (HD2) of the Fanconi anemia complementation group I protein (FANCI).
FANCI solenoid 3 domain (FANCI_S3)
Type: Domain

FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) .

This is the solenoid 3 (S3) domain of the Fanconi anemia group I protein (FANCI).
FANCI solenoid 4 domain (FANCI_S4)
Type: Domain

FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) .

This is the solenoid 4 (S4) domain of the Fanconi anemia group I protein (FANCI).
FANCI solenoid 2 domain (FANCI_S2)
Type: Domain

FANCI and FANCD2 form a complex central to the Fanconi anemia (FA) pathway, which is essential for the repair of DNA interstrand cross-links. FANCI has four distinct alpha solenoid (α-α superhelical) segments (S1-S4). Two mostly helical segments intervene between solenoids 1 and 2 (HD1), and between solenoids 2 and 3 (HD2) .

This is the solenoid 2 (S2) domain of the Fanconi anemia group I protein (FANCI).
Regulatory factor X-associated protein, RFXANK-binding domain (RFXAP_RFXANK-bd)
Type: Domain

This C-terminal domain of Regulatory factor X-associated protein (RFXAP) binds to RFXANK , the ankyrin-repeat regulatory factor X protein. RFXAP is part of the RFX complex, mutants of either RFXAP or RFXANK protein fail to bind to each other. RFX5 binds only to the RFXANK-RFXAP scaffold and not to either protein alone, and neither the scaffold nor RFX5 alone can bind DNA. The binding of the RFXANK-RFXAP scaffold to RFX5 leads to a conformational change in the latter that exposes the DNA-binding domain of RFX5. The DNA-binding domain of RFX5 anchors the RFX complex to MHC class II X and S promoter boxes .
KRBA1 family repeat (KRBA1_rpt)
Type: Repeat

KRBA1 is a short repeating motif found in mammalian proteins. It is characterised by a highly conserved sequence of residues, SSPLxxLxxCLK. The function of the repeat, which can be present in up to seven copies, is unknown as is the function of the full length proteins.
Beclin-1, BH3 domain (BH3_dom)
Type: Domain

Beclin 1 is a tumour suppressor that coordinately regulates the autophagy and membrane trafficking involved in several physiological and pathological processes . The BH3 domain of Beclin 1 is bound to, and inhibited by Bcl-2 or Bcl-XL . This interaction enables Bcl-2 to function not only as an antiapoptotic protein, but also as an antiautophagy protein .
DNA ligase, OB-like domain (DNA_ligase_OB)
Type: Domain

This domain has an OB-like fold and it is found in DNA ligases . Proteins containing this domain are not in entry

.
Acyl-coenzyme A oxidase, N-terminal (Acyl-CoA_ox_N)
Type: Domain

Acyl-coenzyme A oxidase consists of three domains. An N-terminal α-helical domain, a middle domain

and a C-terminal catalytic domain

. This entry represents the N-terminal α-helical domain .
Integrator complex subunit 2 (INTS2)
Type: Family

This family of proteins are subunits of the integrator complex involved in snRNA transcription and processing .
Domain of unknown function DUF4474 (DUF4474)
Type: Domain

This domain is mainly found at the C terminus of uncharacterised proteins from Clostridia.
Equine arteritis virus, non-structural protein 1 (EAV_nsp1)
Type: Domain

The replicase polyproteins of the Nidoviruses such as, porcine arterivirus PRRSV, equine arterivirus EAV, human coronavirus 229E, and severe acute respiratory syndrome coronavirus (SARS-CoV), are predicted to be cleaved into 14 non-structural proteins (nsps) by the nsp4 main proteinase

and three accessory proteinases residing in nsp1-alpha, nsp1-beta and nsp2 .

This entry represents the two nsp1 proteins that together act in a papain-like way to separate off the rest of the various functional domains of the polyprotein. Once inside the host cell, this nsp1 interferes with the regulation of interferon, thereby enabling the virus to replicate .
Mitochondrial apoptosis-inducing factor, C-terminal domain (AIF_C)
Type: Domain

This C-terminal domain appears to be a dimerisation domain of the mitochondrial apoptosis-inducing factor 1 protein. The domain also appears at the C terminus of FAD-dependent pyridine nucleotide-disulfide oxidoreductases. Apoptosis inducing factor (AIF) is a bifunctional mitochondrial flavoprotein critical for energy metabolism and induction of caspase-independent apoptosis . On reduction with NADH, AIF undergoes dimerisation and forms tight, long-lived FADH2-NAD charge-transfer complexes proposed to be functionally important .
ITPR-interacting domain (ITPR-bd)
Type: Domain

This domain entry includes the N terminus of the actin-interacting protein sperm-specific antigen 2 (SSFA2), also known as Ki-ras-induced actin-interacting protein (KRAP) . In this region are found the residues that interact with inositol 1,4,5-trisphosphate receptor (IP3R, also known as ITPR). SSFA2 was first localised as a membrane-bound form with extracellular regions, suggesting it might be involved in the regulation of filamentous actin and signals from the outside of the cells . It has now been shown to be critical for the proper subcellular localisation and function of IP3R. Inositol 1,4,5-trisphosphate receptor functions as the Ca2+ release channel on specialised endoplasmic reticulum membranes, so the subcellular localisation of IP3R is crucial for its proper function .

This entry also recognises a domain in Tespa1 and an uncharacterised coiled-coil protein CCDC129. Tespa1 (thymocyte-expressed positive selection-associated protein 1) is required for the development and maturation of T-cells . Tespa1 shows sequence homology to SSFA2 and physically associates with IP3R in T and B lymphocytes .
Sperm-specific antigen 2, C-terminal (SSFA2_C)
Type: Domain

This domain is found at the C terminus of the actin-interacting protein sperm-specific antigen 2 .
HAUS augmin-like complex subunit 4 (HAUS4)
Type: Family

HAUS4 is part of the HAUS augmin-like complex, which contributes to mitotic spindle assembly, maintenance of chromosome integrity and completion of cytokinesis .

Human augmin complex is composed of 8 subunits and interacts with the gamma-tubulin ring complex (gamma-TuRC) in centrosomes . This interaction affects MT generation during mitosis and is critical for chromosome segregation and cytokinesis in human cells .
Spindle pole component Bbp1, N-terminal (Bbp1_N)
Type: Domain

This N-terminal domain of Bbp1, a spindle pole body component, interacts directly, though transiently, with the polo-box domain of Cdc5. Full length Bbp1 localises at the cytoplasmic side of the central plaque periphery of the spindle pole body (SPB) and plays an important role in inserting a duplication plaque into the nuclear envelope and assembling a functional inner plaque . Although not a membrane protein itself, Bbp1 binds to Mps2 as well as to Spc29 and the half-bridge protein Kar1, thus providing a model for how the SPB core is tethered within the nuclear envelope and to the half-bridge .
Domain of unknown function DUF4472 (DUF4472)
Type: Domain

This domain is found in proteins from Metazoa. Some proteins also carry kinesin-motor domains at their N terminus (

).

Proteins containing this domain include the coiled-coil domain-containing protein 78 (CCDC78), which is a component of the deuterosome, a structure that promotes de novo centriole amplification in multiciliated cells that can generate more than 100 centrioles . CCDC78 does not have the kinesin-motor domain. Mutations in CCDC78 genes cause Myopathy, centronuclear, 4 (CNM4), which is a congenital muscle disorder characterised by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles .
Spindle pole body component Bbp1, C-terminal (Bbp1_C)
Type: Domain

This C-terminal domain of Bbp1, a spindle pole body component, carries coiled-coils that are necessary for the localisation of Bbp1 to the spindle pole body (SPB) . Although not a membrane protein itself, Bbp1 binds to Mps2 as well as to Spc29 and the half-bridge protein Kar1, thus providing a model for how the SPB core is tethered within the nuclear envelope and to the half-bridge .
Muscular LMNA-interacting protein (MLIP)
Type: Family

Muscular LMNA-interacting protein (MLIP) is a muscle-enriched A-type Lamin-interacting protein, an innovation of amniotes, and is expressed ubiquitously and most abundantly in heart, skeletal, and smooth muscle. MLIP interacts directly and co-localises with lamin A and C in the nuclear envelope. MLIP also co-localises with promyelocytic leukemia (PML) bodies within the nucleus. PML, like MLIP, is only found in amniotes, suggesting that a functional link between the nuclear envelope and PML bodies may exist through MLIP .
PEHE domain (PEHE_dom)
Type: Domain

This domain was first identified in drosophila MSL1 (male-specific lethal 1) . In drosophila it binds to the histone acetyltransferase males-absent on the first protein (MOF) and to protein male-specific lethal-3 (MSL3) . This domain can also be found in KAT8 regulatory NSL complex subunit 1 (KANSL1 or NSL1), which is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription .
BBS2, GAE domain (BBS2_GAE_dom)
Type: Domain

This entry represents the gamma-adaptin ear (GAE) domain of BBS2.

BBSome complex member BBS2 (BBS2) is one of the BBS proteins that form the BBSome complex found in vertebrates and nematodes, including humans, mice, and Caenorhabditis elegans. The BBSome complex is required for ciliogenesis, as well as the assembly and movement of intraflagellar transport proteins along the ciliary membrane.

Bardet-Biedl syndrome (BBS) is a heterogeneous genetic disorder characterised by many features, including retinal degeneration, obesity, cognitive impairment, polydactyly, renal abnormalities, and hypogenitalism. The BBSome is a complex of 8 subunits that lies at the base of the flagellar microtubule structure. The precise function of the all the individual components in cilia formation is unclear, however they function to promote loading of cargo to the ciliary axoneme . The primary cilium, a slim microtubule-based organelle that projects from the surface of vertebrate cells has crucial roles in vertebrate development and human genetic diseases. Cilia are required for the response to developmental signals, and evidence is accumulating that the primary cilium is specialised for Hedgehog (Hh) signal transduction. Formation of cilia, in turn, is regulated by other signalling pathways, possibly including the planar cell polarity pathway. The connections between cilia and developmental signalling have begun to clarify the basis of human diseases associated with ciliary dysfunction .

BBS2 is one of the three Bardet-Biedl syndrome subunits that is required for leptin receptor signalling in the hypothalamus , and BBS2 and 4 are also required for the localisation of somatostatin receptor 3 and melanin-concentrating hormone receptor 1 into neuronal cilia .
Protein phosphatase 1 binding domain (PP1-bd)
Type: Domain

This domain contains a protein phosphatase 1 (PP1) binding site .
Phage-encoded virulence factor (PAGK)
Type: Family

PAGK represents a new group of virulence factors that is translocated into the host cytoplasm via bacterial outer membrane vesicles (OMV). Members are small proteins composed of 70 amino acids. In Salmonella they are secreted independently of the SPI-2 type-III secretion system, T3SS. The OMV functions as a vehicle for transferring virulence determinants to the cytoplasm of the infected host cell. OMVs are released from the cell envelopes of Gram-negative bacteria and comprise a variety of outer membrane and periplasmic constituents, including proteins, phospholipids, lipopolysaccharides, and DNA .
Protein of unknown function DUF4594 (DUF4594)
Type: Family

This entry represents a group of eukaryotic proteins that are typically between 170 and 183 amino acids in length. In humans, the gene encoding this protein lies in the position, chromosome 15 open reading frame 52.
Inhibitory synaptic factor 2 (INSYN2)
Type: Family

This entry includes inhibitory synaptic factor 2A/B (INSYN2A/B). INSYN2A is part of the complex that mediates postsynaptic inhibition . The function of INSYN2B is not clear.
Tumour suppressing sub-chromosomal transferable candidate 4 (TSSC4)
Type: Family

The TSSC4 (for tumor-suppressing STF cDNA 4) gene is located in the centre of a 1 Mb gene cluster which contains several imprinted genes; however in humans the TSSC4 gene is not imprinted . This same cluster is associated with the Beckwith-Wiedermann syndrome . Proteins in the TSSC4 family are found in eukaryotes, and contain a conserved YSL sequence motif.
Protein FAM219 (FAM219)
Type: Family

This entry represents a group of eukaryotic proteins that are typically between 144 and 191 amino acids in length. There are two conserved sequence motifs: QLL and LDE.
Protein FAM222 (FAM222)
Type: Family

This entry represents a group of eukaryotic proteins that are typically between 411 and 562 amino acids in length.
FAM21/CAPZIP domain (FAM21/CAPZIP)
Type: Domain

This domain is found on WASH complex subunits FAM21 and CAP-ZIP proteins . Proteins containing this domain are eukaryotic proteins that are typically between 305 and 1321 amino acids in length. The exact function of this domain is not known.
ECSIT, C-terminal domain (ECIST_C)
Type: Domain

Activation of NF-kappaB as a consequence of signalling through the Toll and IL-1 receptors is a major element of innate immune responses. ECSIT (Evolutionarily conserved signaling intermediate in Toll pathway) plays an important role in signalling to NF-kappaB, functioning as an adapter protein of the Toll-like and IL-1 receptor signalling pathway and an intermediary in the signalling pathways between TRAF-6 and MEKK-1 . It is part of the MCIA (mitochondrial complex I intermediate assembly) complex, involved in the assembly of mitochondrial complex I .

This entry represents the C-terminal domain of ECSIT, which is missing in isoform 2. This domain may be distantly homologous to the pleckstrin homology domain.
Coiled-coil domain-containing protein 14 (CCDC14)
Type: Family

This coiled-coil domain-containing protein 14 (CCDC14) is an eukaryotic protein that is typically between 301 and 912 amino acids in length.
Histone RNA hairpin-binding protein, RNA-binding domain (SLBP_RNA_bind)
Type: Domain

This entry represents the RNA-binding domain of histone RNA hairpin-binding protein, also known as SLBP . Proteins containing this domain include SLBP1 and SLBP2 from Xenopus laevis.

SLBP1 binds the 5' side of the stem-loop structure of replication-dependent histone pre-mRNAs and contributes to efficient 3'-end processing by stabilising the complex between histone pre-mRNA and U7 small nuclear ribonucleoprotein (snRNP), via the histone downstream element (HDE) . It plays an important role in targeting mature histone mRNA from the nucleus to the cytoplasm and to the translation machinery. It stabilises mature histone mRNA and could be involved in cell-cycle regulation of histone gene expression .
Maltose transport system permease protein MalF, P2 domain (MalF_P2)
Type: Domain

The maltose transport system is composed of a periplasmic maltose-binding protein (MBP), two integral membrane proteins, MalF and MalG, and two copies of the cytoplasmic ATP-binding cassette MalK . The structures of the two transmembrane (TM) subunits, MalF and MalG, are composed of eight and six TM helices, respectively. The TM helices of MalF and MalG assemble into two crescent shaped structures with their concave surfaces facing each other and enclosing the maltose. MalF consists of four periplasmic domains. This entry represents the second periplasmic loop of MalF (P2), which binds to MalE and is involved in activation of the MalFGK2-E complex by inducing structural changes in maltose-bound MalE . P2 is also responsible for substrate recognition .
Ubiquitin carboxyl-terminal hydrolase, C-terminal (USP_C)
Type: Domain

This domain is found in the C-terminal of the ubiquitin carboxyl-terminal hydrolases (USPs) . The structure from C-terminal USP7 revealed that it can positively regulate deubiquitinating activity .
Raptor, N-terminal CASPase-like domain (Raptor_N)
Type: Domain

Human Raptor is involved in the control of the mammalian target of rapamycin complex 1 (mTORC1) activity which regulates cell growth and survival, and autophagy in response to nutrient and hormonal signals. It functions as a scaffold for recruiting mTORC1 substrates .

All Raptor orthologs contain a unique conserved region in their N-terminal half (raptor N-terminal conserved, also called the RNC domain) followed by three HEAT (huntingtin, elongation factor 3, A subunit of protein phosphatase 2A and TOR1) repeats and seven WD-40 repeats near the C terminus .
Nucleotidyltransferase-like domain (NTF-like)
Type: Domain

Structural comparisons with PDB:1kny indicate that this N-terminal domain resembles a nucleotidyltransferase fold.
Domain of unknown function DUF4443 (DUF4443)
Type: Domain

This domain is a putative gyrase domain mainly found in archaeal proteins.
GAD domain (GAD_dom)
Type: Domain

This domain is found in the glutamyl-tRNA amidotransferase subunit E and some aspartyl tRNA ligases . The function of this domain is not yet known.
Photoreceptor cilium actin regulator (PCARE)
Type: Family

This entry represents PCARE encoded by the C2ORF71 gene . Mutations of C2ORF71 has been associated with autosomal recessive (AR) retinitis pigmentosa (RP) in humans and with visual defects in zebrafish . The function of this family of proteins is unknown, but it is predominately expressed in the photoreceptors and is likely to be important in the development and function of the retina.
Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter, C-terminal domain (NYAP_C)
Type: Domain

This entry represents the C-terminal domain of the neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 1 (NYAP1). NYAP1 belongs to the neuronal tyrosine-phosphorylated adaptor for the PI 3-kinase (NYAP) family, which consists of NYAP1, NYAP2, NAP3/Myosin16. NYAPs activate PI3K in PI3K pathway, which is a fundamental pathway for various cellular events in neurons. They also interact with components of the WAVE1 complex, which mediates actin cytoskeleton remodeling through Arp2/3 complex.
It was suggested that NYAPs connect PI3K activation to WAVE1 signalling in neurons .
Cylicin, N-terminal (Cylicin_N)
Type: Domain

This entry represents the N-terminal of cylicin proteins. Cylicins are proteins of the sperm head cytoskeleton and may play a role in spermatid differentiation .
Proline-rich protein 19 (Pro-rich_19)
Type: Family

This family includes proline-rich protein 19. Its function is not clear.
Family of FAM53 (FAM53)
Type: Family

This entry represents a group of eukaryotic proteins that bind to a transcriptional regulator and modulate cell proliferation . They are known to be highly important in neural tube development .
Spermatogenesis-associated protein 7 (SPATA7)
Type: Family

This entry represents the spermatogenesis-associated protein 7 (SPATA7, also known as HSD3). It was first identified in human spermatocytes. Later on, it was also found expressed in multiple layers of the mature mouse retina . Mutations in SPATA7 cause Leber congenital amaurosis 3 (LCA3), which is a severe dystrophy of the retina, typically becoming evident in the first years of life . Mutations in SPATA7 also cause autosomal recessive retinitis pigmentosa (ARRP), which is a retinal dystrophy belonging to the group of pigmentary retinopathies .
Cilia-and flagella-associated protein 96 (CFAP96)
Type: Family

This family (previously DUF4586) represents Cilia-and flagella-associated protein 96 (CFAP96, also known as C4orf47). CFAP96 is an axonemal microtubule-associated protein (MAP). The EM structure of sperm DMTs shows that CFAP96 binds to tubulin and, similarly to other axonemal wedge-MAPs, binds deeper into the inter-protofilament cleft making extensive contacts with flanking protofilaments .
FAM181 (FAM181)
Type: Family

This entry includes transcriptional regulators FAM181A and FAM181B, which interact with TEAD transcription factors that require partner interactions to execute their activity .
Serine/arginine repetitive matrix protein, C-terminal (SRRM_C)
Type: Domain

This domain is found near to the C terminus of Serine/arginine repetitive matrix proteins 3 and 4.
Sperm microtubule inner protein 9 (SPMIP9)
Type: Family

This entry represents homologs of Sperm microtubule inner protein 9 (SPMIP9 also known as TEX37, TSC21) . SPMIP9 is a microtubule-associated protein (MIP) that is found only in mammalian sperm. The EM structure of sperm DMTs shows that SPMIP9 is part of the tektin bundle making contacts with TECT3-1 and DUSP21 .
Fusion protein IQCJ-SCHIP1, N-terminal (IQCJ-SCHIP1_N)
Type: Domain

IQCJ-SCHIP1 is a fusion protein bridging two adjacent genes that encode distinct proteins, IQCJ, a novel IQ motif containing protein and SCHIP1, a schwannomin interacting protein. Its unique calmodulin-binding IQ motif at the N terminus is not shared with its shorter isoform SCHIP1, suggesting a distinctive function for this protein. It is localised to cytoplasm and actin-rich regions, and in differentiated PC12 cells is seen in neurite extension . IQCJ-SCHIP1 may play a role in action potential conduction in myelinated cells through the organisation of molecular complexes at nodes of Ranvier and axon initial segments .
Protein of unknown function DUF4575 (DUF4575)
Type: Family

This family of uncharacterised proteins is found in eukaryotes.
ALK and LTK ligand 1/2 (ALKL1/2)
Type: Family

This entry includes ALK and LTK ligand 1 and 2 (ALKL1/2, also known as FAM150A and FAM150B, respectively) from vertebrates. ALKL1/2 are activating ligands for the receptor anaplastic lymphoma kinase (ALK) and the receptor leukocyte tyrosine kinase (LTK) . However, ALKL1 does not act as a potent physiological ligand for ALK, in contrast to ALKL2 . Monomeric ALKAL1 binds to LTK, leading to LTK homodimerization and activation . It is not yet clear if ALKL2 activates ALK as a homodimer or a monomer .