Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family ...
987-1336
0e+00
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family represents the IQ motif containing GTPase activating protein 3 (IQGAP3), which associates with Ras GTP-binding proteins. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.
:
Pssm-ID: 213346 [Multi-domain] Cd Length: 350 Bit Score: 664.22 E-value: 0e+00
calponin homology (CH) domain superfamily; CH domains are actin filament (F-actin) binding motifs, which may be present as a single copy or in tandem repeats (which increase binding affinity). They either function as autonomous actin binding motifs or serve a regulatory function. CH domains are found in cytoskeletal and signal transduction proteins, including actin-binding proteins like spectrin, alpha-actinin, dystrophin, utrophin, and fimbrin, as well as proteins essential for regulation of cell shape (cortexillins), and signaling proteins (Vav).
The actual alignment was detected with superfamily member cd21276:
Pssm-ID: 469584 [Multi-domain] Cd Length: 152 Bit Score: 344.27 E-value: 9.77e-110
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family ...
987-1336
0e+00
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family represents the IQ motif containing GTPase activating protein 3 (IQGAP3), which associates with Ras GTP-binding proteins. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.
Pssm-ID: 213346 [Multi-domain] Cd Length: 350 Bit Score: 664.22 E-value: 0e+00
calponin homology (CH) domain found in Ras GTPase-activating-like protein IQGAP3; IQ motif ...
28-179
9.77e-110
calponin homology (CH) domain found in Ras GTPase-activating-like protein IQGAP3; IQ motif containing GTPase activating protein 3 (IQGAP3) associates with Ras GTP-binding proteins. It regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton. It belongs to the IQGAP family, which consists of multi-domain proteins having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP3 contains a single copy of the CH domain at the N-terminus.
Pssm-ID: 409125 [Multi-domain] Cd Length: 152 Bit Score: 344.27 E-value: 9.77e-110
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
1009-1220
3.39e-67
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position.
Pssm-ID: 459871 Cd Length: 207 Bit Score: 225.63 E-value: 3.39e-67
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
976-1329
6.34e-55
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position. Improved domain limits from structure.
Pssm-ID: 214617 Cd Length: 344 Bit Score: 195.60 E-value: 6.34e-55
RasGAP C-terminus; This domain can be found in the C terminus of the IQGAP family members, ...
1448-1555
2.76e-31
RasGAP C-terminus; This domain can be found in the C terminus of the IQGAP family members, including human IQGAP1/2/3, S. cerevisiae Iqg1 and S. pombe Rng2. Some members function in cytoskeletal remodelling. Human IQGAP1 is a scaffolding protein that can assemble multi-protein complexes involved in cell-cell interaction, cell adherence, and movement via actin/tubulin-based cytoskeletal reorganization. IQGAP1 is also a regulator of the MAPK and Wnt/beta-catenin signaling pathways.Iqg1 and Rng2 are required for actomyosin ring construction during cytokinesis.
Pssm-ID: 461071 Cd Length: 137 Bit Score: 119.96 E-value: 2.76e-31
Calponin homology (CH) domain; The CH domain is found in both cytoskeletal proteins and signal ...
34-147
1.76e-14
Calponin homology (CH) domain; The CH domain is found in both cytoskeletal proteins and signal transduction proteins. The CH domain is involved in actin binding in some members of the family. However in calponins there is evidence that the CH domain is not involved in its actin binding activity. Most member proteins have from two to four copies of the CH domain, however some proteins such as calponin have only a single copy.
Pssm-ID: 425596 [Multi-domain] Cd Length: 109 Bit Score: 71.16 E-value: 1.76e-14
Calponin homology domain; Actin binding domains present in duplicate at the N-termini of ...
38-145
3.99e-14
Calponin homology domain; Actin binding domains present in duplicate at the N-termini of spectrin-like proteins (including dystrophin, alpha-actinin). These domains cross-link actin filaments into bundles and networks. A calponin homology domain is predicted in yeasst Cdc24p.
Pssm-ID: 214479 [Multi-domain] Cd Length: 101 Bit Score: 69.65 E-value: 3.99e-14
calmodulin binding domain found in unconventional myosin-VI and similar proteins; Myosins, ...
793-933
2.02e-03
calmodulin binding domain found in unconventional myosin-VI and similar proteins; Myosins, which are actin-based motor molecules with ATPase activity, include unconventional myosins that serve in intracellular movements. Myosin-VI, also called unconventional myosin-6 (MYO6), is a reverse-direction motor protein that moves towards the minus-end of actin filaments. It is required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Myosin-VI appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. It modulates RNA polymerase II-dependent transcription. As part of the DISP (DOCK7-Induced Septin disPlacement) complex, Myosin-VI may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. Myosin-VI is encoded by gene MYO6, the human homolog of the gene responsible for deafness in Snell's waltzer mice. It is mutated in autosomal dominant non-syndromic hearing loss. This family also includes Drosophila melanogaster unconventional myosin VI Jaguar (Jar; also called myosin heavy chain 95F (Mhc95F), or 95F MHC), which is a motor protein necessary for the morphogenesis of epithelial tissues during Drosophila development. Jar is required for basal protein targeting and correct spindle orientation in mitotic neuroblasts. It contributes to synaptic transmission and development at the Drosophila neuromuscular junction. Together with CLIP-190 (CAP-Gly domain-containing/cytoplasmic linker protein 190), Jar may coordinate the interaction between the actin and microtubule cytoskeleton. Jar may link endocytic vesicles to microtubules and possibly be involved in transport in the early embryo and in the dynamic process of dorsal closure; its function is believed to change during the life cycle. This model corresponds to the calmodulin (CaM) binding domain (CBD), which consists of three subdomains: a unique insert (Insert 2 or Ins2), an IQ motif, and a proximal tail domain (PTD, also known as lever arm extension or LAE).
Pssm-ID: 409646 [Multi-domain] Cd Length: 149 Bit Score: 40.57 E-value: 2.02e-03
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family ...
987-1336
0e+00
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 3; This family represents the IQ motif containing GTPase activating protein 3 (IQGAP3), which associates with Ras GTP-binding proteins. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.
Pssm-ID: 213346 [Multi-domain] Cd Length: 350 Bit Score: 664.22 E-value: 0e+00
Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family ...
997-1327
2.07e-175
Ras-GTPase Activating Domain of IQ motif containing GTPase activating proteins; This family represents IQ motif containing GTPase activating protein (IQGAP) which associated with the Ras GTP-binding protein. A primary function of IQGAP proteins is to modulate cytoskeletal architecture. There are three known IQGAP family members: IQGAP1, IQGAP2 and IQGAP3. Human IQGAP1 and IQGAP2 share 62% identity. IQGAPs are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP is an essential regulator of cytoskeletal function. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity, the protein actually lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite of their similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3, only present in mammals, regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.
Pssm-ID: 213329 [Multi-domain] Cd Length: 331 Bit Score: 529.47 E-value: 2.07e-175
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 1; IQGAP1 is a ...
987-1351
5.18e-168
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 1; IQGAP1 is a homodimeric protein that is widely expressed among vertebrate cell types from early embryogenesis. Mammalian IQGAP1 protein is the best characterized member of the IQGAP family, and contains several protein-interacting domains. Human IQGAP1 is most similar to mouse Iqgap1 (94% identity) and has 62% identity to human IQGAP2. IQGAP1 binds and cross-links actin filaments in vitro and has been implicated in Ca2+/calmodulin signaling, E-cadherin-dependent cell adhesion, cell motility, and invasion. Yeast IQGAP homologs have a role in the recruitment of actin filaments, are components of the spindle pole body, and are required for actomyosin ring assembly and cytokinesis. Furthermore, IQGAP1 over-expression has also been detected in gastric and colorectal carcinomas and gastric cancer cell lines.
Pssm-ID: 213335 Cd Length: 380 Bit Score: 512.28 E-value: 5.18e-168
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a ...
987-1327
6.63e-165
Ras-GTPase Activating Domain of IQ motif containing GTPase activating protein 2; IQGAP2 is a member of the IQGAP family that contains a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeat, a single WW domain, four IQ motifs which mediate interactions with calmodulin, and a Ras-GTPase-activating protein (GAP)-related domain that binds Rho family GTPases. IQGAP2 and IQGAP3 play important roles in the regulation of the cytoskeleton for axon outgrowth in hippocampal neurons and are thought to stay in a common regulatory pathway. The results of RNA interference studies indicated that IQGAP3 partially compensates functions of IQGAP2, but has lesser ability than IQGAP2 to promote axon outgrowth in hippocampal neuron. Moreover, IQGAP2 is required for the cadherin-mediated cell-to-cell adhesion in Xenopus laevis embryos.
Pssm-ID: 213333 [Multi-domain] Cd Length: 359 Bit Score: 502.99 E-value: 6.63e-165
calponin homology (CH) domain found in Ras GTPase-activating-like protein IQGAP3; IQ motif ...
28-179
9.77e-110
calponin homology (CH) domain found in Ras GTPase-activating-like protein IQGAP3; IQ motif containing GTPase activating protein 3 (IQGAP3) associates with Ras GTP-binding proteins. It regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton. It belongs to the IQGAP family, which consists of multi-domain proteins having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP3 contains a single copy of the CH domain at the N-terminus.
Pssm-ID: 409125 [Multi-domain] Cd Length: 152 Bit Score: 344.27 E-value: 9.77e-110
calponin homology (CH) domain found in Ras GTPase-activating-like protein IQGAP2; IQ motif ...
14-159
1.77e-81
calponin homology (CH) domain found in Ras GTPase-activating-like protein IQGAP2; IQ motif containing GTPase activating protein 2 (IQGAP2) is a member of the IQGAP family, which consists of multi-domain proteins having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP2 binds to activated Cdc42 and Rac1 but does not seem to stimulate their GTPase activity. It associates with calmodulin. IQGAP2 contains a single copy of the CH domain at the N-terminus.
Pssm-ID: 409124 [Multi-domain] Cd Length: 156 Bit Score: 264.57 E-value: 1.77e-81
calponin homology (CH) domain found in Ras GTPase-activating-like protein IQGAP1; IQ motif ...
27-179
2.88e-80
calponin homology (CH) domain found in Ras GTPase-activating-like protein IQGAP1; IQ motif containing GTPase activating protein 1 (IQGAP1), also called p195, is a homodimeric protein that is widely expressed among vertebrate cell types from early embryogenesis. It plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. It belongs to the IQGAP family, which consists of multi-domain proteins having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity. It lacks GAP activity. Both, IQGAP1 and IQGAP2, specifically bind to Cdc42 and Rac1, but not to RhoA. Despite similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP1 contains a single copy of the CH domain at the N-terminus.
Pssm-ID: 409123 [Multi-domain] Cd Length: 154 Bit Score: 261.08 E-value: 2.88e-80
calponin homology (CH) domain found in the IQ motif containing GTPase activating protein ...
28-153
4.02e-69
calponin homology (CH) domain found in the IQ motif containing GTPase activating protein family; Members of the IQ motif containing GTPase activating protein (IQGAP) family are associated with the Ras GTP-binding protein and act as essential regulators of cytoskeletal function. There are three known IQGAP family members: IQGAP1, IQGAP2, and IQGAP3. They are multi-domain molecules having a calponin-homology (CH) domain which binds F-actin, IQGAP-specific repeats, a single WW domain, four IQ motifs that mediate interactions with calmodulin, and a RasGAP related domain that binds active Rho family GTPases. IQGAP1 negatively regulates Ras family GTPases by stimulating their intrinsic GTPase activity. It lacks GAP activity. Both IQGAP1 and IQGAP2 specifically bind to Cdc42 and Rac1, but not to RhoA. Despite similarities to part of the sequence of RasGAP, neither IQGAP1 nor IQGAP2 interacts with Ras. IQGAP3 regulates the organization of the cytoskeleton under the regulation of Rac1 and Cdc42 in neuronal cells. The depletion of IQGAP3 is shown to impair neurite or axon outgrowth in neuronal cells with disorganized cytoskeleton.
Pssm-ID: 409055 [Multi-domain] Cd Length: 118 Bit Score: 227.49 E-value: 4.02e-69
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the ...
1009-1220
3.39e-67
GTPase-activator protein for Ras-like GTPase; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position.
Pssm-ID: 459871 Cd Length: 207 Bit Score: 225.63 E-value: 3.39e-67
Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to ...
985-1319
1.31e-63
Ras-GTPase Activating Domain of GAPA; GAPA is an IQGAP-related protein and is predicted to bind to small GTPases, which are yet to be identified. IQGAP proteins are integral components of cytoskeletal regulation. Results from truncated GAPAs indicated that almost the entire region of GAPA homologous to IQGAP is required for cytokinesis in Dictyostelium. More members of the IQGAP family are emerging, and evidence suggests that there are both similarities and differences in their function.
Pssm-ID: 213334 Cd Length: 352 Bit Score: 221.07 E-value: 1.31e-63
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the ...
976-1329
6.34e-55
GTPase-activator protein for Ras-like GTPases; All alpha-helical domain that accelerates the GTPase activity of Ras, thereby "switching" it into an "off" position. Improved domain limits from structure.
Pssm-ID: 214617 Cd Length: 344 Bit Score: 195.60 E-value: 6.34e-55
Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is ...
1002-1255
1.34e-37
Ras GTPase Activating Domain; RasGAP functions as an enhancer of the hydrolysis of GTP that is bound to Ras-GTPases. Proteins having a RasGAP domain include p120GAP, IQGAP, Rab5-activating protein 6, and Neurofibromin, among others. Although the Rho (Ras homolog) GTPases are most closely related to members of the Ras family, RhoGAP and RasGAP exhibit no similarity at their amino acid sequence level. RasGTPases function as molecular switches in a large number of signaling pathways. They are in the on state when bound to GTP, and in the off state when bound to GDP. The RasGAP domain speeds up the hydrolysis of GTP in Ras-like proteins acting as a negative regulator.
Pssm-ID: 213328 Cd Length: 256 Bit Score: 142.63 E-value: 1.34e-37
Ras-GTPase Activating Domain of proteins related to IQGAPs; RasGAP: Ras-GTPase Activating ...
995-1329
9.12e-35
Ras-GTPase Activating Domain of proteins related to IQGAPs; RasGAP: Ras-GTPase Activating Domain. RasGAP functions as an enhancer of the hydrolysis of GTP that is bound to Ras-GTPases. Proteins having a RasGAP domain include p120GAP, IQGAP, Rab5-activating protein 6, and Neurofibromin. Although the Rho (Ras homolog) GTPases are most closely related to members of the Ras family, RhoGAP and RasGAP show no sequence homology at their amino acid level. RasGTPases function as molecular switches in a myriad of signaling pathways. When bound to GTP they are in the on state and when bound to GDP they are in the off state. The RasGap domain speeds up the hydrolysis of GTP in Ras-like proteins acting as a negative regulator.
Pssm-ID: 213345 [Multi-domain] Cd Length: 359 Bit Score: 137.46 E-value: 9.12e-35
RasGAP C-terminus; This domain can be found in the C terminus of the IQGAP family members, ...
1448-1555
2.76e-31
RasGAP C-terminus; This domain can be found in the C terminus of the IQGAP family members, including human IQGAP1/2/3, S. cerevisiae Iqg1 and S. pombe Rng2. Some members function in cytoskeletal remodelling. Human IQGAP1 is a scaffolding protein that can assemble multi-protein complexes involved in cell-cell interaction, cell adherence, and movement via actin/tubulin-based cytoskeletal reorganization. IQGAP1 is also a regulator of the MAPK and Wnt/beta-catenin signaling pathways.Iqg1 and Rng2 are required for actomyosin ring construction during cytokinesis.
Pssm-ID: 461071 Cd Length: 137 Bit Score: 119.96 E-value: 2.76e-31
calponin homology (CH) domain superfamily; CH domains are actin filament (F-actin) binding motifs, which may be present as a single copy or in tandem repeats (which increase binding affinity). They either function as autonomous actin binding motifs or serve a regulatory function. CH domains are found in cytoskeletal and signal transduction proteins, including actin-binding proteins like spectrin, alpha-actinin, dystrophin, utrophin, and fimbrin, as well as proteins essential for regulation of cell shape (cortexillins), and signaling proteins (Vav).
Pssm-ID: 409031 [Multi-domain] Cd Length: 103 Bit Score: 108.97 E-value: 6.91e-28
Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins ...
986-1329
8.42e-25
Ras-GTPase Activating Domain of proteins similar to neurofibromin; Neurofibromin-like proteins include the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2, the closest homolog of neurofibromin, which is responsible for the human autosomal dominant disease neurofibromatosis type I (NF1). The RasGAP Ira1/2 proteins are negative regulators of the Ras-cAMP signaling pathway and conserved from yeast to human. In yeast Ras proteins are activated by GEFs, and inhibited by two GAPs, Ira1 and Ira2. Ras proteins activate the cAMP/protein kinase A (PKA) pathway, which controls metabolism, stress resistance, growth, and meiosis. Recent studies showed that the kelch proteins Gpb1 and Gpb2 inhibit Ras activity via association with Ira1 and Ira2. Gpb1/2 bind to a conserved C-terminal domain of Ira1/2, and loss of Gpb1/2 results in a destabilization of Ira1 and Ira2, leading to elevated levels of Ras2-GTP and uninhibited cAMP-PKA signaling. Since the Gpb1/2 binding domain on Ira1/2 is conserved in the human neurofibromin protein, the studies suggest that an analogous signaling mechanism may contribute to the neoplastic development of NF1.
Pssm-ID: 213341 Cd Length: 317 Bit Score: 106.98 E-value: 8.42e-25
calponin homology (CH) domain found in Drosophila melanogaster muscle-specific protein 20 ...
39-145
2.63e-17
calponin homology (CH) domain found in Drosophila melanogaster muscle-specific protein 20 (dMP20) and similar domains; This subfamily contains Drosophila melanogaster muscle-specific protein 20 (dMP20), Echinococcus granulosus myophilin, Dictyostelium discoideum Rac guanine nucleotide exchange factor B (also called Trix), and similar proteins. dMP20 is present only in the synchronous muscles of D. melanogaster. It may be involved in the system linking the nerve impulse with the contraction or the relaxation process. Trix is involved in the regulation of the late steps of the endocytic pathway. dMP20 contains a single copy of the CH domain, while Trix (triple CH-domain array exchange factor) contains three, two type 3 CH domains which are included in this model, and one type 1 CH domain that is not included in this subfamily, but is part of the superfamily. CH domains are actin filament (F-actin) binding motifs.
Pssm-ID: 409056 [Multi-domain] Cd Length: 107 Bit Score: 78.89 E-value: 2.63e-17
Calponin homology (CH) domain; The CH domain is found in both cytoskeletal proteins and signal ...
34-147
1.76e-14
Calponin homology (CH) domain; The CH domain is found in both cytoskeletal proteins and signal transduction proteins. The CH domain is involved in actin binding in some members of the family. However in calponins there is evidence that the CH domain is not involved in its actin binding activity. Most member proteins have from two to four copies of the CH domain, however some proteins such as calponin have only a single copy.
Pssm-ID: 425596 [Multi-domain] Cd Length: 109 Bit Score: 71.16 E-value: 1.76e-14
Calponin homology domain; Actin binding domains present in duplicate at the N-termini of ...
38-145
3.99e-14
Calponin homology domain; Actin binding domains present in duplicate at the N-termini of spectrin-like proteins (including dystrophin, alpha-actinin). These domains cross-link actin filaments into bundles and networks. A calponin homology domain is predicted in yeasst Cdc24p.
Pssm-ID: 214479 [Multi-domain] Cd Length: 101 Bit Score: 69.65 E-value: 3.99e-14
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the ...
1120-1301
7.86e-14
Ras-GTPase Activating Domain of neurofibromin; Neurofibromin is the product of the neurofibromatosis type 1 gene (NF1) and shares a region of similarity with catalytic domain of the mammalian p120RasGAP protein and an extended similarity with the Saccharomyces cerevisiae RasGAP proteins Ira1 and Ira2. Neurofibromin has been shown to function as a GAP (GTPase-activating protein) which inhibits low molecular weight G proteins such as Ras by stimulating their intrinsic GTPase activity. NF1 is a common genetic disorder characterized by various symptoms ranging from predisposition for the development of tumors to learning disability or mental retardation. Loss of neurofibromin activity can be correlated to the increase in Ras-GTP concentration in neurofibromas of NF1 of patients, supporting the notion that unregulated Ras signaling may contribute to their development.
Pssm-ID: 213332 [Multi-domain] Cd Length: 332 Bit Score: 74.67 E-value: 7.86e-14
calponin homology (CH) domain found in Saccharomyces cerevisiae transgelin (SCP1) and similar ...
38-146
1.98e-13
calponin homology (CH) domain found in Saccharomyces cerevisiae transgelin (SCP1) and similar proteins; The family includes transgelins from Saccharomyces cerevisiae and Schizosaccharomyces pombe, which are also called SCP1 and STG1, respectively. Transgelin, also called calponin homolog 1, has actin-binding and actin-bundling activity. It stabilizes actin filaments against disassembly. Transgelin contains a single copy of the CH domain. CH domains are actin filament (F-actin) binding motifs.
Pssm-ID: 409059 [Multi-domain] Cd Length: 101 Bit Score: 67.78 E-value: 1.98e-13
calponin homology (CH) domain found in LIM domain only protein 7 and similar proteins; This ...
37-143
2.07e-10
calponin homology (CH) domain found in LIM domain only protein 7 and similar proteins; This family includes LIM domain only protein 7 (LMO-7) and LIM and calponin homology domains-containing protein 1 (LIMCH1), and similar proteins. LMO-7, also called F-box only protein 20, or LOMP, is a transcription regulator for expression of many Emery-Dreifuss muscular dystrophy (EDMD)-relevant genes. It binds to alpha-actinin and AF6/afadin at adherens junctions for epithelial cell-cell adhesion. LIMCH1 acts as an actin stress fiber-associated protein that activates the non-muscle myosin IIa complex by promoting the phosphorylation of its regulatory subunit MRLC/MYL9. It positively regulates actin stress fiber assembly and stabilizes focal adhesions, and therefore negatively regulates cell spreading and cell migration. Members of this family contain a single copy of the CH domain at the N-terminus. CH domains are actin filament (F-actin) binding motifs.
Pssm-ID: 409057 [Multi-domain] Cd Length: 119 Bit Score: 59.66 E-value: 2.07e-10
calponin homology (CH) domain found in Arabidopsis thaliana Kinesin-like KIN-14 protein family; ...
36-145
1.95e-08
calponin homology (CH) domain found in Arabidopsis thaliana Kinesin-like KIN-14 protein family; Kinesins are microtubule-dependent molecular motors that play important roles in intracellular transport and in cell division. This family includes a group of kinesin-like proteins belonging to KIN-14 protein family. They all contain a single copy of the CH domain at the N-terminus. CH domains are actin filament (F-actin) binding motifs.
Pssm-ID: 409052 [Multi-domain] Cd Length: 112 Bit Score: 53.96 E-value: 1.95e-08
Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras ...
1005-1192
1.33e-06
Ras-GTPase Activating Domain of GAP1 and similar proteins; The GAP1 family of Ras GTPase-activating proteins includes GAP1(m) (or RASA2), GAP1_IP4BP (or RASA3), Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), and Ras GTPase activating-like proteins (RASAL) or RASAL1. The members are characterized by a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin homology domain that is associated with a Bruton's tyrosine kinase motif. While this domain structure is conserved, a small change in the function of each individual domain and the interaction between domains has a marked effect on the regulation of each protein.
Pssm-ID: 213330 Cd Length: 269 Bit Score: 51.87 E-value: 1.33e-06
Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like ...
1048-1192
2.51e-06
Ras-GTPase Activating Domain of RASAL1 and similar proteins; Ras GTPase activating-like protein (RASAL) or RASAL1 is a member of the GAP1 family, and a Ca2+ sensor responding in-phase to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. It contains a conserved domain structure comprising N-terminal tandem C2 domains, a highly conserved central RasGAP domain, and a C-terminal pleckstrin-homology domain that is associated with a Bruton's tyrosine kinase motif. RASAL, like Ca2+ -promoted Ras inactivator (CAPRI, or RASAL4), is a cytosolic protein that undergoes a rapid translocation to the plasma membrane in response to receptor-mediated elevation in the concentration of intracellular free Ca2+, a translocation that activates its ability to function as a RasGAP. However, unlike RASAL4, RASAL undergoes an oscillatory translocation to the plasma membrane that occurs in synchrony with repetitive Ca2+ spikes.
Pssm-ID: 213337 Cd Length: 287 Bit Score: 50.97 E-value: 2.51e-06
Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates ...
1119-1325
4.75e-05
Ras-GTPase Activating Domain of p120; p120GAP is a negative regulator of Ras that stimulates hydrolysis of bound GTP to GDP. Once the Ras regulator p120GAP, a member of the GAP protein family, is recruited to the membrane, it is transiently immobilized to interact with Ras-GTP. The down-regulation of Ras by p120GAP is a critical step in the regulation of many cellular processes, which is disrupted in approximately 30% of human cancers. p120GAP contains SH2, SH3, PH, calcium- and lipid-binding domains, suggesting its involvement in a complex network of cellular interactions in vivo.
Pssm-ID: 213340 Cd Length: 328 Bit Score: 47.48 E-value: 4.75e-05
Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is ...
954-1217
8.63e-05
Ras-GTPase Activating Domain of Rab5-activating protein 6; Rab5-activating protein 6 (RAP6) is an endosomal protein with a role in the regulation of receptor-mediated endocytosis. RAP6 contains a Vps9 domain, which is involved in the activation of Rab5, and a Ras GAP domain (RGD). Rab5 is a small GTPase required for the control of the endocytic route, and its activity is regulated by guanine nucleotide exchange factor, such as Rabex5, and GAPs, such as RN-tre. Human Rap6 protein is localized on the plasma membrane and on the endosome. RAP6 binds to Rab5 and Ras through the Vps9 and RGD domains, respectively.
Pssm-ID: 213331 Cd Length: 365 Bit Score: 46.57 E-value: 8.63e-05
calponin homology (CH) domain found in VAV proteins; VAV proteins function both as cytoplasmic ...
54-146
4.71e-04
calponin homology (CH) domain found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as scaffold proteins, and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the CH domain, an actin-binding domain which is present as a single copy in VAV proteins.
Pssm-ID: 409050 Cd Length: 117 Bit Score: 41.47 E-value: 4.71e-04
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras ...
1048-1328
6.44e-04
Ras-GTPase Activating Domain of DAB2IP and similar proteins; The DAB2IP family of Ras GTPase-activating proteins includes DAB2IP, nGAP, and Syn GAP. Disabled 2 interactive protein, (DAB2IP; also known as ASK-interacting protein 1 (AIP1)), is a member of the GTPase-activating proteins, down-regulates Ras-mediated signal pathways, and mediates TNF-induced activation of ASK1-JNK signaling pathways. The mechanism by which TNF signaling is coupled to DAB2IP is not known.
Pssm-ID: 213338 Cd Length: 324 Bit Score: 43.73 E-value: 6.44e-04
calponin homology (CH) domain found in transgelin-2; Transgelin-2, also called epididymis ...
32-138
1.80e-03
calponin homology (CH) domain found in transgelin-2; Transgelin-2, also called epididymis tissue protein Li 7e, or SM22-alpha homolog, acts as an actin-binding protein that induces actin gelation and regulates the actin cytoskeleton. It may participate in the development and progression of multiple cancers. It contains a single copy of the CH domain. CH domains are actin filament (F-actin) binding motifs.
Pssm-ID: 409129 [Multi-domain] Cd Length: 137 Bit Score: 40.25 E-value: 1.80e-03
calmodulin binding domain found in unconventional myosin-VI and similar proteins; Myosins, ...
793-933
2.02e-03
calmodulin binding domain found in unconventional myosin-VI and similar proteins; Myosins, which are actin-based motor molecules with ATPase activity, include unconventional myosins that serve in intracellular movements. Myosin-VI, also called unconventional myosin-6 (MYO6), is a reverse-direction motor protein that moves towards the minus-end of actin filaments. It is required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Myosin-VI appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. It modulates RNA polymerase II-dependent transcription. As part of the DISP (DOCK7-Induced Septin disPlacement) complex, Myosin-VI may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. Myosin-VI is encoded by gene MYO6, the human homolog of the gene responsible for deafness in Snell's waltzer mice. It is mutated in autosomal dominant non-syndromic hearing loss. This family also includes Drosophila melanogaster unconventional myosin VI Jaguar (Jar; also called myosin heavy chain 95F (Mhc95F), or 95F MHC), which is a motor protein necessary for the morphogenesis of epithelial tissues during Drosophila development. Jar is required for basal protein targeting and correct spindle orientation in mitotic neuroblasts. It contributes to synaptic transmission and development at the Drosophila neuromuscular junction. Together with CLIP-190 (CAP-Gly domain-containing/cytoplasmic linker protein 190), Jar may coordinate the interaction between the actin and microtubule cytoskeleton. Jar may link endocytic vesicles to microtubules and possibly be involved in transport in the early embryo and in the dynamic process of dorsal closure; its function is believed to change during the life cycle. This model corresponds to the calmodulin (CaM) binding domain (CBD), which consists of three subdomains: a unique insert (Insert 2 or Ins2), an IQ motif, and a proximal tail domain (PTD, also known as lever arm extension or LAE).
Pssm-ID: 409646 [Multi-domain] Cd Length: 149 Bit Score: 40.57 E-value: 2.02e-03
calponin homology (CH) domain found in VAV1 protein; VAV1 is expressed predominantly in the ...
57-146
5.79e-03
calponin homology (CH) domain found in VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the CH domain, an actin-binding domain which is present as a single copy in VAV1 protein.
Pssm-ID: 409111 Cd Length: 120 Bit Score: 38.38 E-value: 5.79e-03
Database: CDSEARCH/cdd Low complexity filter: no Composition Based Adjustment: yes E-value threshold: 0.01
References:
Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
of the residues that compose this conserved feature have been mapped to the query sequence.
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(labeled illustration) Standard Display shows only the best scoring domain model from each source, in each hit category listed below for each region on the query sequence.
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