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Search results 1 to 23 out of 23 for Apc

Category restricted to ProteinDomain (x)

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Category: ProteinDomain
Type Details Score
Protein Domain
Type: Family
Description: Adenomatous polyposis coli (APC) is a tumor suppressor protein that induces thedegradation of oncogenic beta-catenin and negatively regulates Wnt signalling []. It has roles in regulating cell migration, DNA replication/repair, mitosis and apoptosis [, ]. APC regulates cell-cell adhesion and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (GEF; Asef) [, ]. It acts as a mediator of ERBB2-dependent stabilisation of microtubules at the cell cortex []. It is required for the localisation of MACF1/ACF7 to the cell membrane and this localisation of MACF1/ACF7 is critical for its function in microtubule stabilisation []. APC mutations are particularly prevalent in colorectal cancer [].
Protein Domain
Type: Family
Description: This entry includes APC membrane recruitment protein 1/2/3 (Amer1/2/3). Amer1, also known as WTX, binds to the tumour suppressor adenomatous polyposis coli and acts as an inhibitor of Wnt signaling by inducing beta-catenin degradation []. Amer2 is a negative regulator of Wnt/beta-catenin signaling involved in neuroectodermal patterning [].WTX is a novel gene mutated in a proportion of Wilms' tumors and in patients suffering from sclerosing bone dysplasia [].
Protein Domain
Type: Family
Description: This entry consists of the suppressor APC domain-containing protein 1 and 2 (SAPCD1 and SAPCD2). SAPCD2 is expressed in many primary gastric carcinoma. It is expressed preferentially in M and G1 phases, compared to S and G2 phases [].
Protein Domain
Type: Domain
Description: This region of the APC family of proteins is known as the basic domain. It contains a high proportion of positively charged amino acids and interacts with microtubules [].
Protein Domain
Type: Domain
Description: Apc11 is one of the subunits of the anaphase-promoting complex or cyclosome (APC) []. The APC subunits are cullin family proteins with ubiquitin ligase activity []. Polyubiquitination marks proteins for degradation by the 26S proteasome and is carried out by a cascade of enzymes that includes ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). Apc11 acts as an E3 enzyme and is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiquitin to APC substrates in vivo. Apc11 contains a canonical RING-H2-finger domain, which includes one histidine and seven cysteine residues that coordinate two Zn2+ ions. In addition, it contains a third Zn2+-binding site and the third Zn2+ ion is not essential for its ligase activity []. In Saccharomyces cerevisiae this RING-H2 finger protein defines the minimal ubiquitin ligase activity of the APC, and the integrity of the RING-H2 finger is essential for budding yeast cell viability [].This entry represents the RING-H2 finger found in Apc11.
Protein Domain
Type: Family
Description: The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome [].All APC subunits are members of the cullin family proteins, which bind to a ring-finger subunit via a conserved cullin domain [].The APC can be divided in four parts, the third of which is a tetratricopeptide repeat arm (TPR) that contains multiple subunits, including Apc9 [].This entry represents Apc9, one of the subunits of the anaphase-promoting complex.
Protein Domain
Type: Domain
Description: This region at the C terminus of the APC proteins binds the microtubule-associating protein EB-1 []. At the C terminus of the alignment is also a PDZ-binding domain. A short motif in the middle of the region appears to be found in the APC2 proteins (e.g. ).
Protein Domain
Type: Repeat
Description: The 15 aa repeat is found in the APC protein family. It is involved in binding beta-catenin []along with the repeats. Many human cancer mutations map to the region around these motifs, and may be involved in disrupting their binding of beta-catenin.
Protein Domain
Type: Family
Description: Adenomatous polyposis coli (APC) is a tumor suppressor protein that induces thedegradation of oncogenic beta-catenin and negatively regulates Wnt signalling []. It has roles in regulating cell migration, DNA replication/repair, mitosis and apoptosis [, ]. APC regulates cell-cell adhesion and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (GEF; Asef) [, ]. It acts as a mediator of ERBB2-dependent stabilisation of microtubules at the cell cortex []. It is requiredfor the localisation of MACF1/ACF7 to the cell membrane and this localisation of MACF1/ACF7 is critical for its function in microtubule stabilisation []. APC mutations are particularly prevalent in colorectal cancer [].The adenomatous polyposis coli protein family also includes APC2 [, ]and APC-related protein 1 [].
Protein Domain
Type: Domain
Description: The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome [].This entry represents a domain found in the C terminus of APC subunit 2.
Protein Domain
Type: Family
Description: The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome [].This entry represents APC subunit 2, which is a distant member of the cullin protein family that functions as a scaffold in SCF assembly [].
Protein Domain
Type: Family
Description: This entry includes human TMEM9/TMEM9B and their homologues. TMEM9 is a transmembrane protein that binds to and facilitates the assembly of lysosomal proton-transporting V-type ATPase (v-ATPase), resulting in enhanced lysosomal acidification and trafficking []. It acts as a Wnt signaling amplifier that hyperactivates Wnt signaling for liver regeneration and tumorigenesis via lysosomal degradation of APC []. TMEM9B has been shown to regulate the activity of inflammatory signaling pathways [].
Protein Domain
Type: Domain
Description: Apc4 is one of the larger of the subunits of the anaphase-promoting complex (APC) or cyclosome. The anaphase-promoting complex is a multiprotein subunit E3 ubiquitin ligase complex that controls segregation ofchromosomes and exit from mitosis in eukaryotes [, ]. Results in Caenorhabditis elegans show that the primary essential role of the spindle assembly checkpoint is not in the chromosome segregation process itself but rather in delaying anaphase onset until all chromosomes are properly attached to the spindle. The APC is likely to be required for all metaphase-to-anaphase transitions in a multicellular organism [].This entry represents the long domain downstream of the WD40 repeat/s that are present on the Apc4 subunits.
Protein Domain
Type: Domain
Description: This entry represents a tyrosine-rich domain found in Sam68, also known as KH domain-containing, RNA-binding, signal transduction-associated protein. Sam68 regulates TCF-1 alternative splicing. It is a crucial binding-partner of the APC-Arm domain that forms a superhelix with a positively charged groove, the surface-residues of which groove form numerous interactions with this domain to fix it in a bent conformation. APC-Arm is the armadillo repeat domain of the tumour-suppressor protein adenomatous polyposis coli or APC. APC plays plays important roles in Wnt signalling and other cellular processes [].
Protein Domain
Type: Domain
Description: This entry represents a domain found in Apc5 (anaphase-promoting complex subunit 5).Apc5 is a subunit of the anaphase-promoting complex/cyclosome (APC/C) which is a multisubunit ubiquitin ligase that mediates the proteolysis of cell cycle proteins in mitosis and G1. Tetratricopeptide repeat protein 19 is a mitochondrial protein required for formation of the mitochondrial complex III [].Apc5, although it does not harbour a classical RNA binding domain, Apc5 binds the poly(A) binding protein (PABP), which directly binds the internal ribosome entry site (IRES) of growth factor 2 mRNA. PABP was found to enhance IRES-mediated translation, whereas Apc5 over-expression counteracted this effect. In addition to its association with the APC/C complex, Apc5 binds much heavier complexes and co-sediments with the ribosomal fraction [, ]. The N terminus of Afi1 serves to stabilise the union between Apc4 and Apc5, both of which lie towards the bottom-front of the APC []. This region of the Apc5 member proteins carries a TPR-like motif.
Protein Domain
Type: Family
Description: The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome [].One of the subunits of the APC that is required for its ubiquitination activity is Doc1/Apc10, a protein composed of a Doc1 homology domain that has been identified in a number of diverse putative E3 ubiquitin ligases []. The Doc1 homology domain forms a β-sandwich structure that is related in architecture to the galactose-binding domain of galactose oxidase, the coagulation factor C2 domain and a domain of XRCC1. This group represents a subgroup of subunit 10.
Protein Domain
Type: Family
Description: This entry consists of several lipoproteins mainly from Mycobacterium species, collectively known as the LppX/LprAFG family. Proteins in this entry include:LprG () from Mycobacterium tuberculosis: an immunogenic 27kDa membrane-associated lipoprotein []. Expression of the LprG protein is essential for the growth of M. tuberculosis in immunocompetent mice []. Purification of LprG showed that it inhibits MHC-II antigen processing in primary human macrophages, providing a mechanism to avoid the host MHC-II-restricted CD4+ T cell response which is considered essential for control of M. tuberculosis infection []. LppX: a lipoprotein required for the translocation of complex lipids to the outer membrane of Mycobacterium tuberculosis. Its structure consists of a U-shaped β-half-barrel with a large hydrophobic cavity []. LprF: a membrane lipoprotein involved in the kdp signal transduction pathway, thought to be the primary response to osmotic stress [].lprA: a lipoprotein agonist of TLR2 that regulates innate immunity and APC function [].
Protein Domain
Type: Family
Description: This entry includes Axin-1 and Axin-2 from vertebrates and related proteins from invertebrates. Axin is a central component of the canonical Wnt signaling pathway that interacts with the adenomatous polyposis coli protein APC and the kinase GSK3beta to downregulate the effector beta-catenin []. Axin-1 (axis inhibition protein 1) is a scaffold protein that is involved in many signalling pathways, including the Wnt, transforming growth factor-beta, MAP kinase pathways, as well as p53 activation cascades [, ]. It controls many biological processes ranging from sugar intake, cell proliferation, and organ development to cell death [].Mutations in Axin-1 gene cause hepatocellular carcinoma (HCC), a primary malignant neoplasm of epithelial liver cells [], and caudal duplication anomaly (CADUA), a condition characterised by the occurrence of duplications of different organs in the caudal region [].Like its mammalian counterpart, Drosophila Axin homologue, Daxin, acts as a negative regulator of wg/Wnt signaling []. In C. elegans AXL-1 functions redundantly with its ortholog, PRY-1, in negatively regulating BAR-1/beta-catenin signaling in the developing vulva and the Q neuroblast lineage. AXL-1 also functions independently of PRY-1 in negatively regulating canonical Wnt signaling during excretory cell development [].
Protein Domain
Type: Domain
Description: The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome [].One of the subunits of the APC that is required for ubiquitination activity is APC10, a one-domain protein homologous to a sequence element, termed the DOC domain, found in several hypothetical proteins that may also mediate ubiquitination reactions, because they contain combinations of either RING finger (see ), cullin (see ) or HECT (see ) domains [, , ].The DOC domain consists of a β-sandwich, in which a five-stranded antiparallel β-sheet is packed on top of a three stranded antiparallel β-sheet, exhibiting a 'jellyroll' fold [, ].Proteins known to contain a DOC domain include:Eucaryotic Doc1/Apc10.Mammalian protein associated with the transcription factor Myc (PAM).Mouse runty-jerky-sterile (RJS) protein.Human HERC2, the ortholog of RJS.
Protein Domain
Type: Family
Description: This entry includes cell division cycle-associated protein 3 (CDCA3; also known as trigger of mitotic entry protein 1 or TOME-1), which is required for entry into mitosis. The protein is found at high levels during the G2 and M phases of mitosis, but declines rapidly during the G2 phase. Entry into mitosis requires the relocalization to the nucleus and activation of cyclin-dependent kinase 1 (cdk1) by association with cyclin B, and exit from mitosis occurs when cyclin B is degraded and the kinase activity decreases. Anaphase promoting complex (APC) is an E3 ligase active during anaphase and G1, and is required for the degradation of cyclin B. CDCA3 is a cytosolic protein and a substrate of APC. It associates with Skp-1 and is required for the degradation of the cdk1 inhibitor wee1, a tyrosine kinase. Degradation of CDCA3 leads to an accumulation of wee1 during interphase []. The CDCA3 protein contains an F-box-like region and a KEN box; the latter is required for association with the APC complex.
Protein Domain
Type: Family
Description: GABA permease (gabP) catalyses the translocation of 4-aminobutyrate (GABA) across the plasma membrane, with homologues expressed in Gram-negative and Gram-positive organisms. This permease is a highly hydrophobic transmembrane protein consisting of 12 transmembrane domains with hydrophilic N- and C-terminal ends []. Induced by nitrogen-limited culture conditions in both Escherichia coli and Bacillus subtilis, gabP is an energy dependent transport system stimulated by membrane potential and has been observed adjacent and distant from other GABA degradation proteins [, ]. GabP is highly homologous to amino acid permeases from B. subtilis, E. coli, as well as to other members of the amino acid permease family (). A member of the APC (amine-polyamine-choline) transporter superfamily, GABA permease possesses a "consensus amphiphatic region"(CAR) found to be evolutionarily conserved within this transport family []. This amphiphatic region is located between helix 8 and cytoplasmic loop 8-9, forming a potential channel domain and suggested to play a significant role in ligand recognition and translocation []. Unique to GABA permeases, a conserved cysteine residue (CYS-300, E. coli) located at the beginning of the amphiphatic domain, has been determined to be critical for catalytic specificity [].
Protein Domain
Type: Family
Description: Upon vascular injury, flowing blood is exposed to cells expressing tissue factor (TF) on their surfaces and FVII/FVIIa binds to its receptor/cofactor TF and is rapidly activated to FVIIa and the activity of bound FVIIa is dramatically enhanced. The TF/FVIIa complex activates zymogens factor X (FX) and factor IX (FIX). The FXa, in the absence of activated cofactor factor Va (FVa) generates only trace amounts of thrombin. Although insufficient to initiate fibrin polymerisation alone, these small amounts of thrombin, however, back activate factors V (FV), VIII (FVIII), and XI(FXI). FVIII and FV function as membrane-bound cofactors for proteinases FIXa and FXa, respectively increasing the Vmax of the reaction complexes dramatically. Amplification of the pro-coagulant response consequently occurs through formation of the tenase complex FIXa/FVIIIa and the thrombinase complex FXa/FVa that generate sufficient amounts of thrombin to mediate sustained haemostasis.In addition to its function in cleaving soluble fibrinogen to form insoluble fibrin monomers, thrombin can also activate an anticoagulant pathway. Thrombomodulin (TM), a receptor present on the endothelial cell surface, binds thrombin and alters thrombin's substrate specificity through an allosteric mechanism. Bound to TM, thrombin can no longer efficiently proteolyse its pro-coagulant substrates FV, FVIII and fibrinogen. The thrombin-TM complex proteolytically activates its substrate protein C (PC) to activated protein C (APC). In complex with its cofactor protein S (PS), APC rapidly inactivates pro-coagulant factors FVa and FVIIIa by further proteolysis in a negative feedback loop. Activation of protein C by thrombin bound to thrombomodulin is enhanced by endothelial protein C receptor (EPCR). The EPCR is an N-glycosylated type I membrane protein and mutations in this EPCR gene have been associated with venous thromboembolism and myocardial infarction, as well as with late foetal loss during pregnancy.
Protein Domain
Type: Family
Description: T cell-dependent immune processes require cell-surface interactions thatmediate the initiation, modulation and the ultimate course of the response.The specificity of T cell recognition is determined by the engagement of theT cell receptor (TCR) on T cells with cognate peptide-MHC complexes presented by antigen presenting cells (APCs). Additional signals arerequired to sustain and enhance T cell activity, the most important of whichis provided by the engagement of CD28 on T cells with its ligands B7-1(CD80) and B7-2 (CD86). By contrast, the interaction of B7 isoformswith cytotoxic T lymphocyte-associated molecule-4 CTLA-4, a CD28 homologue receptor on T cells (31% identity), provides inhibitory signals requiredfor down-regulation of the response, while it may also prevent T cell activation by weak TCR signals[, , , , ].Unlike CD28, which is not expressed on resting T cells, CTLA-4 is not detected on the cell surface until 24 hours after activation. In fact, Tcell activation leads to both increased CTLA4 gene expression andtrafficking of CTLA4 protein to the cell surface. In addition, CTLA-4exhibits an affinity for the B7 isoforms that is 10 to 100 times that forCD28. Covalent dimerisation of CTLA4 is required for its high bindingavidity, but each monomeric subunit also contains a binding site for CD80and CD86. It is likely that CTLA-4 directly competes with CD28 for bindingB7 and also directs the assembly of inhibitory signalling complexes thatlead to quiescence or anergy. Thus the balance between the opposing signals elicited by CD28 and CTLA-4 is central to the regulation of T cellresponsiveness and homeostasis. One mechanism by which CTLA-4 may performthis function is by regulating cell-cycle progression; by contrast with CD28, which down-regulates the cell-cycle inhibitor p27kip1, CTLA-4 prevents this degradation[, , ].Sequence comparison between human CTLA-4 and CD28 proteins suggests they arehomologous, with the highest of degree of similarity being in the juxta-membrane and cytoplasmic regions. In addition, the cytoplasmic domainsof human and murine CTLA-4 are identical, suggesting that this region hasimportant functional properties [].Typically, activation of T cells by TCR-engaging peptide-MHC is dramatically enhanced by interaction of the CD28 co-stimulatory receptor with its ligands CD80 (B7-1) and CD86 (B7-2) on the APC surface. Interestingly, CTLA-4 is transported from intracellular stores toward the region of the cell surface receiving activation signals. This suggests that binding of CD28 to its ligand may occur primarily at the centre of the mature immunological synapse, and that CTLA-4 may be transported to this site under certain circumstancesto block or reverse this effect.