breast cancer anti-estrogen resistance protein 1 isoform 3 [Rattus norvegicus]
Protein Classification
Serine_rich_BCAR1 and FAT-like_BCAR1_C domain-containing protein( domain architecture ID 10346136)
protein containing domains SH3, PHA03247, Serine_rich_BCAR1, and FAT-like_BCAR1_C
List of domain hits
| Name | Accession | Description | Interval | E-value | ||||||
| CAS_C | pfam12026 | Crk-Associated Substrate C-terminal domain; This is a C-terminal domain found in CAS family ... |
629-839 | 1.67e-100 | ||||||
Crk-Associated Substrate C-terminal domain; This is a C-terminal domain found in CAS family members. The CAS (Crk-Associated Substrate) protein family is a group of scaffolding proteins that play important modulatory roles in both normal and pathological cell growth regulation. They contain an N-terminal Src homology 3 (SH3) domain pfam00018 and a substrate domain (SD). The SD contains a large number of YxxP motifs, which when phosphorylated by Src-family kinases provide canonical binding sites for proteins containing SH2 domains such as Crk, Crk-L, CRKII presumed domain is functionally uncharacterized. : Pssm-ID: 463437 Cd Length: 202 Bit Score: 310.47 E-value: 1.67e-100
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| Serine_rich_BCAR1 | cd11552 | Serine rich Four helix bundle domain of CAS (Crk-Associated Substrate) scaffolding protein, ... |
429-585 | 3.19e-73 | ||||||
Serine rich Four helix bundle domain of CAS (Crk-Associated Substrate) scaffolding protein, Breast Cancer Anti-estrogen Resistance 1; a protein interaction module; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure containing protein interaction modules that enable their scaffolding function, including an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. CAS proteins associate with the 14-3-3 family; this interaction is regulated by integrin-mediated cell adhesion. The serine rich four helix bundle domain of BCAR1 has been shown to bind 14-3-3 in a phosphorylation-dependent manner. This domain is structurally similar to other helical bundles found in cell adhesion components such as alpha-catenin, vinculin, and FAK, and may bind other proteins in addition to the 14-3-3 family. : Pssm-ID: 211406 Cd Length: 157 Bit Score: 236.34 E-value: 3.19e-73
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| SH3 super family | cl17036 | Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ... |
1-41 | 2.18e-22 | ||||||
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction. The actual alignment was detected with superfamily member cd12001: Pssm-ID: 473055 Cd Length: 68 Bit Score: 91.26 E-value: 2.18e-22
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| Atrophin-1 super family | cl38111 | Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ... |
69-391 | 1.35e-03 | ||||||
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity. The actual alignment was detected with superfamily member pfam03154: Pssm-ID: 460830 [Multi-domain] Cd Length: 991 Bit Score: 42.45 E-value: 1.35e-03
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| Name | Accession | Description | Interval | E-value | ||||||
| CAS_C | pfam12026 | Crk-Associated Substrate C-terminal domain; This is a C-terminal domain found in CAS family ... |
629-839 | 1.67e-100 | ||||||
Crk-Associated Substrate C-terminal domain; This is a C-terminal domain found in CAS family members. The CAS (Crk-Associated Substrate) protein family is a group of scaffolding proteins that play important modulatory roles in both normal and pathological cell growth regulation. They contain an N-terminal Src homology 3 (SH3) domain pfam00018 and a substrate domain (SD). The SD contains a large number of YxxP motifs, which when phosphorylated by Src-family kinases provide canonical binding sites for proteins containing SH2 domains such as Crk, Crk-L, CRKII presumed domain is functionally uncharacterized. Pssm-ID: 463437 Cd Length: 202 Bit Score: 310.47 E-value: 1.67e-100
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| FAT-like_BCAR1_C | cd11569 | C-terminal FAT-like Four helix bundle domain, also called DUF3513, of CAS (Crk-Associated ... |
710-842 | 5.74e-90 | ||||||
C-terminal FAT-like Four helix bundle domain, also called DUF3513, of CAS (Crk-Associated Substrate) scaffolding protein, Breast Cancer Anti-estrogen Resistance 1; a protein interaction module; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure containing protein interaction modules that enable their scaffolding function, including an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain, which binds to the C-terminal domain of NSPs (novel SH2-containing proteins) to form multidomain signaling modules that mediate cell migration and invasion. Pssm-ID: 211410 Cd Length: 133 Bit Score: 279.95 E-value: 5.74e-90
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| Serine_rich_BCAR1 | cd11552 | Serine rich Four helix bundle domain of CAS (Crk-Associated Substrate) scaffolding protein, ... |
429-585 | 3.19e-73 | ||||||
Serine rich Four helix bundle domain of CAS (Crk-Associated Substrate) scaffolding protein, Breast Cancer Anti-estrogen Resistance 1; a protein interaction module; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure containing protein interaction modules that enable their scaffolding function, including an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. CAS proteins associate with the 14-3-3 family; this interaction is regulated by integrin-mediated cell adhesion. The serine rich four helix bundle domain of BCAR1 has been shown to bind 14-3-3 in a phosphorylation-dependent manner. This domain is structurally similar to other helical bundles found in cell adhesion components such as alpha-catenin, vinculin, and FAK, and may bind other proteins in addition to the 14-3-3 family. Pssm-ID: 211406 Cd Length: 157 Bit Score: 236.34 E-value: 3.19e-73
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| Serine_rich | pfam08824 | Serine rich protein interaction domain; This is a serine rich domain that is found in the ... |
429-583 | 2.06e-56 | ||||||
Serine rich protein interaction domain; This is a serine rich domain that is found in the docking protein p130(cas) (Crk-associated substrate). This domain folds into a four helix bundle which is associated with protein-protein interactions. Pssm-ID: 462610 Cd Length: 157 Bit Score: 190.86 E-value: 2.06e-56
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| SH3_BCAR1 | cd12001 | Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, ... |
1-41 | 2.18e-22 | ||||||
Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212934 Cd Length: 68 Bit Score: 91.26 E-value: 2.18e-22
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| Atrophin-1 | pfam03154 | Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ... |
69-391 | 1.35e-03 | ||||||
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity. Pssm-ID: 460830 [Multi-domain] Cd Length: 991 Bit Score: 42.45 E-value: 1.35e-03
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| Name | Accession | Description | Interval | E-value | ||||||
| CAS_C | pfam12026 | Crk-Associated Substrate C-terminal domain; This is a C-terminal domain found in CAS family ... |
629-839 | 1.67e-100 | ||||||
Crk-Associated Substrate C-terminal domain; This is a C-terminal domain found in CAS family members. The CAS (Crk-Associated Substrate) protein family is a group of scaffolding proteins that play important modulatory roles in both normal and pathological cell growth regulation. They contain an N-terminal Src homology 3 (SH3) domain pfam00018 and a substrate domain (SD). The SD contains a large number of YxxP motifs, which when phosphorylated by Src-family kinases provide canonical binding sites for proteins containing SH2 domains such as Crk, Crk-L, CRKII presumed domain is functionally uncharacterized. Pssm-ID: 463437 Cd Length: 202 Bit Score: 310.47 E-value: 1.67e-100
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| FAT-like_BCAR1_C | cd11569 | C-terminal FAT-like Four helix bundle domain, also called DUF3513, of CAS (Crk-Associated ... |
710-842 | 5.74e-90 | ||||||
C-terminal FAT-like Four helix bundle domain, also called DUF3513, of CAS (Crk-Associated Substrate) scaffolding protein, Breast Cancer Anti-estrogen Resistance 1; a protein interaction module; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure containing protein interaction modules that enable their scaffolding function, including an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain, which binds to the C-terminal domain of NSPs (novel SH2-containing proteins) to form multidomain signaling modules that mediate cell migration and invasion. Pssm-ID: 211410 Cd Length: 133 Bit Score: 279.95 E-value: 5.74e-90
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| Serine_rich_BCAR1 | cd11552 | Serine rich Four helix bundle domain of CAS (Crk-Associated Substrate) scaffolding protein, ... |
429-585 | 3.19e-73 | ||||||
Serine rich Four helix bundle domain of CAS (Crk-Associated Substrate) scaffolding protein, Breast Cancer Anti-estrogen Resistance 1; a protein interaction module; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure containing protein interaction modules that enable their scaffolding function, including an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. CAS proteins associate with the 14-3-3 family; this interaction is regulated by integrin-mediated cell adhesion. The serine rich four helix bundle domain of BCAR1 has been shown to bind 14-3-3 in a phosphorylation-dependent manner. This domain is structurally similar to other helical bundles found in cell adhesion components such as alpha-catenin, vinculin, and FAK, and may bind other proteins in addition to the 14-3-3 family. Pssm-ID: 211406 Cd Length: 157 Bit Score: 236.34 E-value: 3.19e-73
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| FAT-like_CAS_C | cd11564 | C-terminal FAT-like Four helix bundle domain, also called DUF3513, of CAS (Crk-Associated ... |
715-840 | 2.00e-71 | ||||||
C-terminal FAT-like Four helix bundle domain, also called DUF3513, of CAS (Crk-Associated Substrate) scaffolding proteins; a protein interaction module; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure containing protein interaction modules that enable their scaffolding function, including an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The FAT-like C-terminal domain of CAS proteins binds to the C-terminal domain of NSPs (novel SH2-containing proteins) to form multidomain signaling modules that mediate cell migration and invasion. Pssm-ID: 211408 Cd Length: 126 Bit Score: 230.20 E-value: 2.00e-71
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| Serine_rich_CAS | cd11549 | Serine rich Four helix bundle domain of CAS (Crk-Associated Substrate) scaffolding proteins; a ... |
429-584 | 5.04e-58 | ||||||
Serine rich Four helix bundle domain of CAS (Crk-Associated Substrate) scaffolding proteins; a protein interaction module; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure containing protein interaction modules that enable their scaffolding function, including an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). CAS proteins associate with the 14-3-3 family; this interaction is regulated by integrin-mediated cell adhesion. The serine rich four helix bundle domain of BCAR1 has been shown to bind 14-3-3 in a phosphorylation-dependent manner. This domain is structurally similar to other helical bundles found in cell adhesion components such as alpha-catenin, vinculin, and FAK, and may bind other proteins in addition to the 14-3-3 family. Pssm-ID: 211403 Cd Length: 159 Bit Score: 195.12 E-value: 5.04e-58
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| Serine_rich | pfam08824 | Serine rich protein interaction domain; This is a serine rich domain that is found in the ... |
429-583 | 2.06e-56 | ||||||
Serine rich protein interaction domain; This is a serine rich domain that is found in the docking protein p130(cas) (Crk-associated substrate). This domain folds into a four helix bundle which is associated with protein-protein interactions. Pssm-ID: 462610 Cd Length: 157 Bit Score: 190.86 E-value: 2.06e-56
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| FAT-like_NEDD9_C | cd11570 | C-terminal FAT-like Four helix bundle domain, also called DUF3513, of CAS (Crk-Associated ... |
715-842 | 4.96e-55 | ||||||
C-terminal FAT-like Four helix bundle domain, also called DUF3513, of CAS (Crk-Associated Substrate) scaffolding protein, Neural precursor cell Expressed, Developmentally Down-regulated 9; a protein interaction module; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure containing protein interaction modules that enable their scaffolding function, including an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain, which binds to the C-terminal domain of NSPs (novel SH2-containing proteins) to form multidomain signaling modules that mediate cell migration and invasion. Pssm-ID: 211411 Cd Length: 128 Bit Score: 185.89 E-value: 4.96e-55
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| FAT-like_EFS_C | cd11571 | C-terminal FAT-like Four helix bundle domain, also called DUF3513, of CAS (Crk-Associated ... |
715-843 | 1.81e-43 | ||||||
C-terminal FAT-like Four helix bundle domain, also called DUF3513, of CAS (Crk-Associated Substrate) scaffolding protein, Embryonal Fyn-associated Substrate; a protein interaction module; EFS is also called HEFS, CASS3 (CAS scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure containing protein interaction modules that enable their scaffolding function, including an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain, which binds to the C-terminal domain of NSPs (novel SH2-containing proteins) to form multidomain signaling modules that mediate cell migration and invasion. Pssm-ID: 211412 Cd Length: 130 Bit Score: 153.46 E-value: 1.81e-43
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| FAT-like_CASS4_C | cd11568 | C-terminal FAT-like Four helix bundle domain, also called DUF3513, of CAS (Crk-Associated ... |
724-840 | 9.39e-29 | ||||||
C-terminal FAT-like Four helix bundle domain, also called DUF3513, of CAS (Crk-Associated Substrate) scaffolding protein family member 4; a protein interaction module; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure containing protein interaction modules that enable their scaffolding function, including an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain, which binds to the C-terminal domain of NSPs (novel SH2-containing proteins) to form multidomain signaling modules that mediate cell migration and invasion. Pssm-ID: 211409 Cd Length: 123 Bit Score: 111.48 E-value: 9.39e-29
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| Serine_rich_NEDD9 | cd11550 | Serine rich Four helix bundle domain of CAS (Crk-Associated Substrate) scaffolding protein, ... |
429-583 | 1.06e-27 | ||||||
Serine rich Four helix bundle domain of CAS (Crk-Associated Substrate) scaffolding protein, Neural precursor cell Expressed, Developmentally Down-regulated 9; a protein interaction module; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure containing protein interaction modules that enable their scaffolding function, including an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. CAS proteins associate with the 14-3-3 family; this interaction is regulated by integrin-mediated cell adhesion. The serine rich four helix bundle domain of BCAR1, another CAS protein, has been shown to bind 14-3-3 in a phosphorylation-dependent manner. This domain is structurally similar to other helical bundles found in cell adhesion components such as alpha-catenin, vinculin, and FAK, and may bind other proteins in addition to the 14-3-3 family. Pssm-ID: 211404 Cd Length: 162 Bit Score: 109.95 E-value: 1.06e-27
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| SH3_BCAR1 | cd12001 | Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, ... |
1-41 | 2.18e-22 | ||||||
Src homology 3 domain of the CAS (Crk-Associated Substrate) scaffolding protein family member, Breast Cancer Anti-estrogen Resistance 1; BCAR1, also called p130cas or CASS1, is the founding member of the CAS family of scaffolding proteins and was originally identified through its ability to associate with Crk. The name BCAR1 was designated because the human gene was identified in a screen for genes that promote resistance to tamoxifen. It is widely expressed and its deletion is lethal in mice. It plays a role in regulating cell motility, survival, proliferation, transformation, cancer progression, and bacterial pathogenesis. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212934 Cd Length: 68 Bit Score: 91.26 E-value: 2.18e-22
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| Serine_rich_CASS4 | cd11551 | Serine rich Four helix bundle domain of CAS (Crk-Associated Substrate) scaffolding protein ... |
429-582 | 2.05e-20 | ||||||
Serine rich Four helix bundle domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; a protein interaction module; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure containing protein interaction modules that enable their scaffolding function, including an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. CAS proteins associate with the 14-3-3 family; this interaction is regulated by integrin-mediated cell adhesion. The serine rich four helix bundle domain of BCAR1, another CAS protein, has been shown to bind 14-3-3 in a phosphorylation-dependent manner. This domain is structurally similar to other helical bundles found in cell adhesion components such as alpha-catenin, vinculin, and FAK, and may bind other proteins in addition to the 14-3-3 family. Pssm-ID: 211405 Cd Length: 159 Bit Score: 88.75 E-value: 2.05e-20
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| SH3_CAS | cd11844 | Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins ... |
1-33 | 2.80e-17 | ||||||
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding proteins; CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes including migration, chemotaxis, apoptosis, differentiation, and progenitor cell function. They mediate the signaling of integrins at focal adhesions where they localize, and thus, regulate cell invasion and survival. Over-expression of these proteins is implicated in poor prognosis, increased metastasis, and resistance to chemotherapeutics in many cancers such as breast, lung, melanoma, and glioblastoma. CAS proteins have also been linked to the pathogenesis of inflammatory disorders, Alzheimer's, Parkinson's, and developmental defects. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Vertebrates contain four CAS proteins: BCAR1 (or p130Cas), NEDD9 (or HEF1), EFS (or SIN), and CASS4 (or HEPL). The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212778 Cd Length: 56 Bit Score: 76.23 E-value: 2.80e-17
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| SH3_NEDD9 | cd12002 | Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, ... |
1-34 | 9.87e-17 | ||||||
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Neural precursor cell Expressed, Developmentally Down-regulated 9; NEDD9 is also called human enhancer of filamentation 1 (HEF1) or CAS-L (Crk-associated substrate in lymphocyte). It was first described as a gene predominantly expressed in early embryonic brain, and was also isolated from a screen of human proteins that regulate filamentous budding in yeast, and as a tyrosine phosphorylated protein in lymphocytes. It promotes metastasis in different solid tumors. NEDD9 localizes in focal adhesions and associates with FAK and Abl kinase. It also interacts with SMAD3 and the proteasomal machinery which allows its rapid turnover; these interactions are not shared by other CAS proteins. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212935 Cd Length: 57 Bit Score: 75.02 E-value: 9.87e-17
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| SH3_EFS | cd12003 | Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, ... |
1-34 | 1.94e-13 | ||||||
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate; EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212936 Cd Length: 62 Bit Score: 65.68 E-value: 1.94e-13
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| SH3_CASS4 | cd12000 | Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; ... |
1-33 | 1.66e-09 | ||||||
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member 4; CASS4, also called HEPL (HEF1-EFS-p130Cas-like), localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading. It is most abundant in blood cells and lung tissue, and is also found in high levels in leukemia and ovarian cell lines. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212933 Cd Length: 57 Bit Score: 54.50 E-value: 1.66e-09
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| SH3_DNMBP_C2_like | cd11800 | Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and ... |
1-31 | 4.97e-05 | ||||||
Second C-terminal Src homology 3 domain of Dynamin Binding Protein, also called Tuba, and similar domains; DNMBP or Tuba is a cdc42-specific guanine nucleotide exchange factor (GEF) that contains four N-terminal SH3 domains, a central RhoGEF [or Dbl homology (DH)] domain followed by a Bin/Amphiphysin/Rvs (BAR) domain, and two C-terminal SH3 domains. It provides a functional link between dynamin, Rho GTPase signaling, and actin dynamics. It plays an important role in regulating cell junction configuration. The C-terminal SH3 domains of DNMBP bind to N-WASP and Ena/VASP proteins, which are key regulatory proteins of the actin cytoskeleton. Also included in this subfamily is the second C-terminal SH3 domain of Rho guanine nucleotide exchange factor 37 (ARHGEF37), whose function is still unknown. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212734 [Multi-domain] Cd Length: 57 Bit Score: 41.59 E-value: 4.97e-05
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| SH3_iASPP | cd11952 | Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called ... |
1-29 | 1.07e-04 | ||||||
Src Homology 3 (SH3) domain of Inhibitor of ASPP protein (iASPP); iASPP, also called RelA-associated inhibitor (RAI), is an oncoprotein that inhibits the apoptotic transactivation potential of p53. It is upregulated in human breast cancers expressing wild-type p53, in acute leukemias regardless of the p53 mutation status, as well as in ovarian cancer where it is associated with poor patient outcome and chemoresistance. iASPP is also a binding partner and negative regulator of p65RelA, which promotes cell proliferation and inhibits apoptosis; p65RelA has the opposite effect on cell growth compared to the p53 family. It contains a proline-rich region, four ankyrin (ANK) repeats, and an SH3 domain at its C-terminal half. The SH3 domain and the ANK repeats of iASPP contribute to the p53 binding site; they bind to the DNA binding domain of p53. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212885 [Multi-domain] Cd Length: 56 Bit Score: 40.68 E-value: 1.07e-04
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| SH3_p47phox_like | cd11856 | Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ... |
1-32 | 5.65e-04 | ||||||
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies. Pssm-ID: 212790 [Multi-domain] Cd Length: 53 Bit Score: 38.39 E-value: 5.65e-04
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| Atrophin-1 | pfam03154 | Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ... |
69-391 | 1.35e-03 | ||||||
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity. Pssm-ID: 460830 [Multi-domain] Cd Length: 991 Bit Score: 42.45 E-value: 1.35e-03
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| Atrophin-1 | pfam03154 | Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ... |
67-320 | 7.10e-03 | ||||||
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity. Pssm-ID: 460830 [Multi-domain] Cd Length: 991 Bit Score: 40.14 E-value: 7.10e-03
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