SII-SWORD/CoKE huggingface dataset:
GRAF family (GRAF_fam)
Type: Family

Graf is an essential component of the CLIC (clathrin-independent carrier)/GEEC (GPI-anchored protein-enriched early endocytic compartment) endocytic pathway . It plays a critical role during development; it is essential for normal mushroom body (MB) development and, therefore, the formation of olfactory long-term memories . During embryo cellularization, it is required for maintaining and regulating the rate of actomyosin ring constriction .

OPHN1 is a RhoGAP involved in X-linked mental disabilities, epilepsy, rostral ventricular enlargement, and cerebellar hypoplasia. Affected individuals have morphological abnormalities of their brain with enlargement of the cerebral ventricles and cerebellar hypoplasia. OPHN1 negatively regulates RhoA, Cdc42, and Rac1 in neuronal and non-neuronal cells . GRAF1 sculpts the endocytic membranes of the CLIC/GEEC (clathrin-independent carriers/GPI-enriched early endosomal compartments) endocytic pathway. It strongly interacts with dynamin and inhibition of dynamin abolishes CLIC/GEEC endocytosis . Its mutations are linked to leukaemia. GRAF2, GRAF3 and oligophrenin are likely to play similar roles during clathrin-independent endocytic events .
COMM domain-containing protein 8 (COMMD8)
Type: Family

This entry represents COMM domain-containing protein 8 (COMMD8) and similar animal proteins. COMMD8 is a member of the COMMD family defined by the presence of a conserved and unique motif termed the COMM (copper metabolism gene MURR1) domain, which functions as an interface for protein-protein interactions .
DCC-interacting protein 13-alpha/beta, PH domain (PH_DP13A/B)
Type: Domain

This entry represents the PH domain of DP13A/B.

This entry includes DCC-interacting protein 13-alpha/beta from humans (DIP13A/B, also known as APPL1/2) and similar proteins predominantly found in vertebrates. DIP13A/B are multifunctional adapter proteins that bind to various membrane receptors, nuclear factors and signalling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism . DIP13B may also affect adult neurogenesis in hippocampus and olfactory system via regulating the sensitivity of glucocorticoid receptor .
DCC-interacting protein 13-alpha/beta, PTB domain (PTB_APPL)
Type: Domain

This entry represents the PTB domain of DPA13A/B. PTB domains have a common PH-like fold and are found in various eukaryotic signalling molecules.

This entry includes DCC-interacting protein 13-alpha/beta from humans (DIP13A/B, also known as APPL1/2) and similar proteins predominantly found in vertebrates. DIP13A/B are multifunctional adapter proteins that bind to various membrane receptors, nuclear factors and signalling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism . DIP13B may also affect adult neurogenesis in hippocampus and olfactory system via regulating the sensitivity of glucocorticoid receptor .
Ankyrin repeat and SAM domain-containing protein 3, SAM domain (ANKS3_SAM)
Type: Domain

This entry represents the SAM (sterile alpha motif) domain of ANKS3. This domain, which is located in the C-terminal region, is typical of signalling proteins.

This group of proteins includes Ankyrin repeat and SAM domain-containing protein 3 (ANKS3), which may be involved in vasopressin signalling in the kidney .
DCC-interacting protein 13-beta, BAR domain (BAR_APPL2)
Type: Domain

This entry represents the BAR domain of DCC-interacting protein 13-beta from humans (DIP13B, also known as APPL2) and similar proteins from vertebrates. DIP13B is a multifunctional adapter protein that bind to various membrane receptors, nuclear factors and signalling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism . DIP13B may affect adult neurogenesis in hippocampus and olfactory system via regulating the sensitivity of glucocorticoid receptor .
Pre-mRNA splicing factor component CDC5L/Cef1, second SANT/myb-like domain (SANT_CDC5L_II)
Type: Domain

This entry represents the second DNA-binding myb-like domain of CDC5/Cef1. The N-terminal myb-like domains are necessary for cell viability but not for PRP19/Prp19p association .

This entry includes cell division cycle 5-like protein (CDC5L) from human and its orthologues from yeast, Cef1, DNA-binding proteins involved in cell cycle control. They function in pre-mRNA splicing as components of the PRP19-CDC5L complex (Prp19p-Cef1 in yeast) , which constitutes an integral part of the spliceosome and is required for activating pre-mRNA splicing. CDC5L is a DNA-binding protein The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR) .
Kinesin-like protein KIF11-like, kinesin motor domain (KIF11-like_kin_motor_dom)
Type: Domain

This entry represents the kinesin motor domain of KIF11 and similar eukaryotic spindle pole proteins.

This entry includes a group of kinesin-like proteins, including human Eg5/KIF11, its orthologue from Drosophila Klp61F, BimC from Emericella nidulans and CIN8 from Saccharomyces cerevisiae. These are spindle pole proteins, which participate in spindle assembly and chromosome segregation during cell division, required for spindle body separation .
Pre-mRNA splicing factor component CDC5L/Cef1 (CDC5L/Cef1)
Type: Family

This entry includes cell division cycle 5-like protein (CDC5L) from human and its orthologues from yeast, Cef1, DNA-binding proteins involved in cell cycle control. They function in pre-mRNA splicing as components of the PRP19-CDC5L complex (Prp19p-Cef1 in yeast) , which constitutes an integral part of the spliceosome and is required for activating pre-mRNA splicing. CDC5L is a DNA-binding protein The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR) .
BRCA1-associated protein, RING finger, H2 subclass (RING-H2_BRAP2)
Type: Domain

This entry represents the RING finger, H2 subclass found in BRAP2 and it homologues.

This entry includes human BRCA1-associated protein (BRAP/BRAP2, also known as impedes mitogenic signal propagation (IMP), RING finger protein 52, or renal carcinoma antigen NY-REN-63) and its homologues from yeast ETP1. BRAP2 is a cytoplasmic protein interacting with the two functional nuclear localization signal (NLS) motifs of BRCA1, a nuclear protein linked to breast cancer. It also binds to the SV40 large T antigen NLS motif and the bipartite NLS motif found in mitosin. BRAP2 serves as a cytoplasmic retention protein and plays a role in the regulation of nuclear protein transport .

These proteins contain an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C3H2C3-type RING-H2 finger and a UBP-type zinc finger.
Insulin gene enhancer protein ISL-1/2-like, LIM domain1 (ISL1/2-like_LIM1)
Type: Domain

This entry represents the first LIM domain of ISL-1/2, which show two tandem N-terminal LIM domains and a C-terminal DNA binding homeodomain (

).

This group of proteins includes the DNA-binding transcriptional activators insulin gene enhancer proteins ISL-1/2 (also known as Islet-1/2) and its homologues from animals . ISL1 recognises and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes . The early expression of ISL-1 in the developing hypothalamus determines the fate specification of melanocortinergic neurons and is essential for hypothalamic Pomc expression. It is required for melanocortin-induced satiety and normal adiposity throughout the entire lifespan . ISL2 is a transcriptional factor that may define subclasses of motoneurons that segregate into columns in the spinal cord and select distinct axon pathways.
Ajuba-like, LIM domain 1 (Ajuba-like_LIM1)
Type: Domain

This entry represents the first LIM domain of Ajuba-like proteins. This domain shares two characteristic zinc finger motifs that contain eight conserved residues each, mostly cysteines and histidines, which coordinately bond to two zinc atoms.

Ajuba-like LIM domain-containing protein family includes three highly homologous proteins Ajuba, LIMD1, and WTIP, adapter or scaffold proteins that participate in the assembly of numerous protein complexes and are involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, mitosis, cell-cell adhesion, cell differentiation, proliferation and migration . They bind to Ago1/2, RCK, Dcp2, and eIF4E in vivo, being required for miRNA-mediated gene silencing. These three proteins bind to the mRNA 5' m(7)GTP cap-protein complex . Members of this family negatively regulates the Hippo signalling pathway . WTIP, the Wt1-interacting protein, was originally identified as an interaction partner of the Wilms tumour protein 1 (WT1). WTIP is involved in kidney and neural crest development. It interacts with the receptor tyrosine kinase Ror2 and inhibits canonical Wnt signaling.

LIMD1 was reported to inhibit cell growth and metastases; it has been described that LIMD1 functions as tumour suppressor to block lung tumour cell line in vitro and in vivo . The inhibition may be mediated through an interaction with the protein barrier-to-autointegration (BAF), a component of SWI/SNF chromatin-remodeling protein; or through the interaction with retinoblastoma protein (pRB), resulting in inhibition of E2F-mediated transcription, and expression of the majority of genes with E2F1-responsive elements. Recently, LIMD1 was shown to interact with the p62/sequestosome protein and influence IL-1 and RANKL signalling by facilitating the assembly of a p62/TRAF6/a-PKC multi-protein complex.

Members of the family contain three tandem C-terminal LIM domains and a proline-rich N-terminal region.
Threonine-tRNA ligase, class IIa, anticodon-binding domain (ThrRS_anticodon)
Type: Domain

This entry represents the ThrRS Threonyl-anticodon binding domain, which is responsible for specificity in tRNA-binding, so that the activated amino acid is transferred to a ribose 3' OH group of the appropriate tRNA only .

Threonine-tRNA ligase (also known as Threonyl-tRNA synthetase) (

) exists as a monomer and belongs to class IIa. The enzyme from Escherichia coli represses the translation of its own mRNA. The crystal structure of the complex between tRNA(Thr) and ThrRS show structural features that reveal novel strategies for providing specificity in tRNA selection. These include an amino-terminal domain containing a novel protein fold that makes minor groove contacts with the tRNA acceptor stem. The enzyme induces a large deformation of the anticodon loop, resulting in an interaction between two adjacent anticodon bases, which accounts for their prominent role in tRNA identity and translational regulation. A zinc ion found in the active site is implicated in amino acid recognition/discrimination . The zinc ion may act to ensure that only amino acids that possess a hydroxyl group attached to the β-position are activated .
Ajuba-like, LIM domain 2 (Ajuba-like_LIM2)
Type: Domain

This entry represents the second LIM domain of Ajuba-like proteins. This domain shares two characteristic zinc finger motifs that contain eight conserved residues each, mostly cysteines and histidines, which coordinately bond to two zinc atoms.

Ajuba-like LIM domain-containing protein family includes three highly homologous proteins Ajuba, LIMD1, and WTIP, adapter or scaffold proteins that participate in the assembly of numerous protein complexes and are involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, mitosis, cell-cell adhesion, cell differentiation, proliferation and migration . They bind to Ago1/2, RCK, Dcp2, and eIF4E in vivo, being required for miRNA-mediated gene silencing. These three proteins bind to the mRNA 5' m(7)GTP cap-protein complex . Members of this family negatively regulates the Hippo signalling pathway . WTIP, the Wt1-interacting protein, was originally identified as an interaction partner of the Wilms tumour protein 1 (WT1). WTIP is involved in kidney and neural crest development. It interacts with the receptor tyrosine kinase Ror2 and inhibits canonical Wnt signaling.

LIMD1 was reported to inhibit cell growth and metastases; it has been described that LIMD1 functions as tumour suppressor to block lung tumour cell line in vitro and in vivo . The inhibition may be mediated through an interaction with the protein barrier-to-autointegration (BAF), a component of SWI/SNF chromatin-remodeling protein; or through the interaction with retinoblastoma protein (pRB), resulting in inhibition of E2F-mediated transcription, and expression of the majority of genes with E2F1-responsive elements. Recently, LIMD1 was shown to interact with the p62/sequestosome protein and influence IL-1 and RANKL signalling by facilitating the assembly of a p62/TRAF6/a-PKC multi-protein complex.

Members of the family contain three tandem C-terminal LIM domains and a proline-rich N-terminal region.
Ajuba-like, LIM domain 3 (Ajuba-like_LIM3)
Type: Domain

This entry represents the third LIM domain of Ajuba-like proteins. This domain shares two characteristic zinc finger motifs that contain eight conserved residues each, mostly cysteines and histidines, which coordinately bond to two zinc atoms.

Ajuba-like LIM domain-containing protein family includes three highly homologous proteins Ajuba, LIMD1, and WTIP, adapter or scaffold proteins that participate in the assembly of numerous protein complexes and are involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, mitosis, cell-cell adhesion, cell differentiation, proliferation and migration . They bind to Ago1/2, RCK, Dcp2, and eIF4E in vivo, being required for miRNA-mediated gene silencing. These three proteins bind to the mRNA 5' m(7)GTP cap-protein complex . Members of this family negatively regulates the Hippo signalling pathway . WTIP, the Wt1-interacting protein, was originally identified as an interaction partner of the Wilms tumour protein 1 (WT1). WTIP is involved in kidney and neural crest development. It interacts with the receptor tyrosine kinase Ror2 and inhibits canonical Wnt signaling.

LIMD1 was reported to inhibit cell growth and metastases; it has been described that LIMD1 functions as tumour suppressor to block lung tumour cell line in vitro and in vivo . The inhibition may be mediated through an interaction with the protein barrier-to-autointegration (BAF), a component of SWI/SNF chromatin-remodeling protein; or through the interaction with retinoblastoma protein (pRB), resulting in inhibition of E2F-mediated transcription, and expression of the majority of genes with E2F1-responsive elements. Recently, LIMD1 was shown to interact with the p62/sequestosome protein and influence IL-1 and RANKL signalling by facilitating the assembly of a p62/TRAF6/a-PKC multi-protein complex.

Members of the family contain three tandem C-terminal LIM domains and a proline-rich N-terminal region.
TP53-binding protein 1-like, first BRCT domain (BRCT_p53bp1-like_rpt1)
Type: Domain

This entry represents the BRCT domain of TP53BP1 and its orthologues. It corresponds to the first BRCT domain of TP53BP1 and hsr-9.

This entry includes TP53-binding protein 1 (TP53BP1, also known as p53BP1 or 53BP1) and its orthologues, such as DNA repair protein RAD9 from S.cerevisiae and Crb2 from S.pombe . TP53BP1 is a double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis . TP53BP1 and its homologue from C.elegans hsr-9 contain two tandem BRCT domains, while the fungal orthologues contain one BRCT domain . Crb2, is a checkpoint mediator required for the cellular response to DNA damage .
TP53-binding protein 1-like, second BRCT domain (BRCT_p53bp1-like_rpt2)
Type: Domain

This entry represents the second BRCT domain of TP53-binding protein 1 (TP53BP1, also known as p53BP1 or 53BP1) and its homologue from C.elegans .

TP53BP1 is a double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis .
Protein-tyrosine phosphatase non-receptor type-12, catalytic domain (PTN12_cat)
Type: Domain

This entry represents the catalytic domain of PTN12 .

Tyrosine-protein phosphatase non-receptor type 12 (PTPN12) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (

) catalyse the dephosphorylation of phosphotyrosine peptides. PTPN12 is characterised as a tumour suppressor and a pivotal regulator of EGFR/HER2 signalling. It regulates various physiological processes, including cell migration, immune response, and neuronal activity, by dephosphorylating multiple substrates including HER2, FAK, PYK2, PSTPIP, WASP, p130Cas, paxillin, Shc, catenin, c-Abl, ArgBP2, p190RhoGAP, RhoGDI, cell adhesion kinase beta, and Rho GTPase .
TP53-binding protein 1-like (TP53BP1-like)
Type: Family

This entry includes TP53-binding protein 1 (TP53BP1, also known as p53BP1 or 53BP1) and its orthologues, such as DNA repair protein RAD9 from S.cerevisiae and Crb2 from S.pombe . TP53BP1 is a double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis . TP53BP1 and its homologue from C.elegans hsr-9 contain two tandem BRCT domains, while the fungal orthologues contain one BRCT domain . Crb2, is a checkpoint mediator required for the cellular response to DNA damage .
Tyrosine-protein phosphatase non-receptor type 22, catalytic domain (PTN22_cat)
Type: Domain

This entry represents the catalytic domain of PTN22.

Tyrosine-protein phosphatase non-receptor type 22 (PTPN22) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (

) catalyse the dephosphorylation of phosphotyrosine peptides. PTPN22 is expressed in hematopoietic cells and it functions as a key regulator of immune homeostasis by inhibiting T-cell receptor signalling through the direct dephosphorylation of Src family kinases (Lck and Fyn), ITAMs of the TCRz/CD3 complex, and other signalling molecules . Mutations in the PTPN22 gene are associated with multiple connective tissue and autoimmune diseases including type 1 diabetes mellitus, rheumatoid arthritis, and systemic lupus erythematosus .

PTPN22 contains an N-terminal catalytic PTP domain and four proline-rich regions at the C-terminal.
Tyrosine-protein phosphatase non-receptor type 18, catalytic domain (PTN18_cat)
Type: Domain

This entry represents the catalytic domain of PTN18 and similar proteins from vertebrates. This domain blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation .

Tyrosine-protein phosphatase non-receptor type 18 (PTPN18) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (

) catalyse the dephosphorylation of phosphotyrosine peptides. PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination states. The C-terminal PEST domain promotes K48-linked HER2 ubiquitination and its destruction via the proteasome pathway .
QUIRKY-like, fourth C2 domain (C2D_MCTP_PRT_plant)
Type: Domain

This entry represents the fourth C2 domain, referred to as C2D, from QUIRKY and related proteins. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions .

This entry includes a group of plant proteins, such as QUIRKY and FTIP1/3/4/7 from Arabidopsis . These are Multiple C2 domain and Transmembrane region Proteins (MCTPs) which are involved in Ca2 signalling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2 but not phospholipids.

QUIRKY may contribute to plant organ organogenesis mediated by the receptor-like kinase STRUBBELIG and may play a role in Ca2-dependent signaling and membrane trafficking . It has been shown to be required for the appropriate spatial expression of several epidermal cell fate regulators . FTIP1 is involved in the export of FT from the phloem companion cells to the sieve elements through the plasmodesmata. It regulates flowering time under long days . FTIP3/4 play an essential role in mediating proliferation and differentiation of shoot stem cells . FTIP7 promotes nuclear translocation of the transcription factor OSH1 and reduces auxin levels at late stage of anther development, after meiosis of microspore mother cells. It is necessary for normal anther dehiscence and seed setting .
Tyrosine-protein kinase BAZ1B, PHD finger (BAZ1B_PHD)
Type: Domain

This entry represents the plant homeodomain (PHD) finger of BAZ1B .

BAZ1B (also known as Williams-Beuren syndrome transcription factor, WSTF) is a multifunctional protein implicated in several nuclear processes, including replication, transcription, and the DNA damage response. It is a component of the WICH complex (WSTF-ISWI ATP-dependent chromatin-remodelling complex). It has intrinsic tyrosine kinase activity by means of a domain that shares no sequence homology to any known kinase fold. It has been shown to phosphorylate Tyr 142 of H2A . It is involved in chromatin assembly, RNA polymerase I and III gene regulation, vitamin D metabolism, and DNA repair .
QUIRKY-like, second C2 domain (C2B_MCTP_PRT_plant)
Type: Domain

This entry represents the second C2 domain, referred to as C2B, from QUIRKY and related proteins. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions .

This entry includes a group of plant proteins, such as QUIRKY and FTIP1/3/4/7 from Arabidopsis . These are Multiple C2 domain and Transmembrane region Proteins (MCTPs) which are involved in Ca2 signalling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2 but not phospholipids.

QUIRKY may contribute to plant organ organogenesis mediated by the receptor-like kinase STRUBBELIG and may play a role in Ca2-dependent signaling and membrane trafficking . It has been shown to be required for the appropriate spatial expression of several epidermal cell fate regulators . FTIP1 is involved in the export of FT from the phloem companion cells to the sieve elements through the plasmodesmata. It regulates flowering time under long days . FTIP3/4 play an essential role in mediating proliferation and differentiation of shoot stem cells . FTIP7 promotes nuclear translocation of the transcription factor OSH1 and reduces auxin levels at late stage of anther development, after meiosis of microspore mother cells. It is necessary for normal anther dehiscence and seed setting .