cerebral cavernous malformations 2 protein isoform 2 [Homo sapiens]
Protein Classification
cerebral cavernous malformations 2 family protein( domain architecture ID 10881498)
cerebral cavernous malformations 2 (CCM2) family protein is a PTB (phosphotyrosine-binding) domain-containing protein, similar to Homo sapiens CCM2, also called malcavernin, which is a component of the CCM signaling pathway that is a crucial regulator of heart and vessel formation and integrity
List of domain hits
| Name | Accession | Description | Interval | E-value | ||||
| PTB_CCM2 | cd13166 | Cerebral cavernous malformation 2 FERM domain C-lobe; CCM2 (also called malcavernin; C7orf22 ... |
43-237 | 2.03e-119 | ||||
Cerebral cavernous malformation 2 FERM domain C-lobe; CCM2 (also called malcavernin; C7orf22/chromosome 7 open reading frame 22; OSM) along with CCM1 and CCM3 constitutes a set of proteins which when mutated are responsible for cerebral cavernous malformations, an autosomal dominant neurovascular disease characterized by cerebral hemorrhages and vascular malformations in the central nervous system. CCM2 plays many functional roles. CCM2 functions as a scaffold involved in small GTPase Rac-dependent p38 mitogen-activated protein kinase (MAPK) activation when the cell is under hyperosmotic stress. It associates with CCM1 in the signalling cascades that regulate vascular integrity and participates in HEG1 (the transmembrane receptor heart of glass 1) mediated endothelial cell junctions. CCM proteins also inhibit the activation of small GTPase RhoA and its downstream effector Rho kinase (ROCK) to limit vascular permeability. CCM2 mediates TrkA-dependent cell death via its N-terminal PTB domain in pediatric neuroblastic tumours. CCM2 possesses an N-terminal PTB domain and a C-terminal Karet domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup. : Pssm-ID: 269987 Cd Length: 193 Bit Score: 346.41 E-value: 2.03e-119
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| CCM2_C | pfam16545 | Cerebral cavernous malformation protein, harmonin-homology; CCM2_HHD is a folded-helical ... |
287-381 | 1.04e-54 | ||||
Cerebral cavernous malformation protein, harmonin-homology; CCM2_HHD is a folded-helical region of a family of vertebral proteins, mutations in which cause cerebral cavernous malformations (CCMs). These malformations are congenital vascular anomalies of the central nervous system that can result in haemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. This domain is structurally homologous to the N-terminal domain of harmonin, so it is named the CCM2 harmonin-homology domain or CCM2_HHD. This protein is often called Malcavernin. : Pssm-ID: 435415 Cd Length: 95 Bit Score: 176.87 E-value: 1.04e-54
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| Name | Accession | Description | Interval | E-value | ||||
| PTB_CCM2 | cd13166 | Cerebral cavernous malformation 2 FERM domain C-lobe; CCM2 (also called malcavernin; C7orf22 ... |
43-237 | 2.03e-119 | ||||
Cerebral cavernous malformation 2 FERM domain C-lobe; CCM2 (also called malcavernin; C7orf22/chromosome 7 open reading frame 22; OSM) along with CCM1 and CCM3 constitutes a set of proteins which when mutated are responsible for cerebral cavernous malformations, an autosomal dominant neurovascular disease characterized by cerebral hemorrhages and vascular malformations in the central nervous system. CCM2 plays many functional roles. CCM2 functions as a scaffold involved in small GTPase Rac-dependent p38 mitogen-activated protein kinase (MAPK) activation when the cell is under hyperosmotic stress. It associates with CCM1 in the signalling cascades that regulate vascular integrity and participates in HEG1 (the transmembrane receptor heart of glass 1) mediated endothelial cell junctions. CCM proteins also inhibit the activation of small GTPase RhoA and its downstream effector Rho kinase (ROCK) to limit vascular permeability. CCM2 mediates TrkA-dependent cell death via its N-terminal PTB domain in pediatric neuroblastic tumours. CCM2 possesses an N-terminal PTB domain and a C-terminal Karet domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup. Pssm-ID: 269987 Cd Length: 193 Bit Score: 346.41 E-value: 2.03e-119
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| CCM2_C | pfam16545 | Cerebral cavernous malformation protein, harmonin-homology; CCM2_HHD is a folded-helical ... |
287-381 | 1.04e-54 | ||||
Cerebral cavernous malformation protein, harmonin-homology; CCM2_HHD is a folded-helical region of a family of vertebral proteins, mutations in which cause cerebral cavernous malformations (CCMs). These malformations are congenital vascular anomalies of the central nervous system that can result in haemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. This domain is structurally homologous to the N-terminal domain of harmonin, so it is named the CCM2 harmonin-homology domain or CCM2_HHD. This protein is often called Malcavernin. Pssm-ID: 435415 Cd Length: 95 Bit Score: 176.87 E-value: 1.04e-54
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| HHD_CCM2 | cd13516 | harmonin-homology domain (harmonin_N_like domain) of malcavernin (CCM2); CCM2 (also called ... |
282-377 | 1.54e-51 | ||||
harmonin-homology domain (harmonin_N_like domain) of malcavernin (CCM2); CCM2 (also called malcavernin; C7orf22/chromosome 7 open reading frame 22; OSM) along with CCM1 and CCM3 constitutes a set of proteins which when mutated are responsible for cerebral cavernous malformations, an autosomal dominant neurovascular disease characterized by cerebral hemorrhages and vascular malformations in the central nervous system. CCM2 plays many functional roles. CCM2 functions as a scaffold involved in small GTPase Rac-dependent p38 mitogen-activated protein kinase (MAPK) activation when the cell is under hyperosmotic stress. It associates with CCM1 in the signaling cascades that regulate vascular integrity and participates in HEG1 (the transmembrane receptor heart of glass 1) mediated endothelial cell junctions. CCM proteins also inhibit the activation of small GTPase RhoA and its downstream effector Rho kinase (ROCK) to limit vascular permeability. CCM2 mediates TrkA-dependent cell death via its N-terminal PTB domain in pediatric neuroblastic tumours. CCM2 possesses an N-terminal PTB domain. The C-terminal domain of malcavernin, which is represented here, appears similar to the N-terminal domain of the scaffolding protein harmonin. It has also been referred to as the Karet domain. Pssm-ID: 259825 Cd Length: 97 Bit Score: 168.59 E-value: 1.54e-51
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| Name | Accession | Description | Interval | E-value | ||||
| PTB_CCM2 | cd13166 | Cerebral cavernous malformation 2 FERM domain C-lobe; CCM2 (also called malcavernin; C7orf22 ... |
43-237 | 2.03e-119 | ||||
Cerebral cavernous malformation 2 FERM domain C-lobe; CCM2 (also called malcavernin; C7orf22/chromosome 7 open reading frame 22; OSM) along with CCM1 and CCM3 constitutes a set of proteins which when mutated are responsible for cerebral cavernous malformations, an autosomal dominant neurovascular disease characterized by cerebral hemorrhages and vascular malformations in the central nervous system. CCM2 plays many functional roles. CCM2 functions as a scaffold involved in small GTPase Rac-dependent p38 mitogen-activated protein kinase (MAPK) activation when the cell is under hyperosmotic stress. It associates with CCM1 in the signalling cascades that regulate vascular integrity and participates in HEG1 (the transmembrane receptor heart of glass 1) mediated endothelial cell junctions. CCM proteins also inhibit the activation of small GTPase RhoA and its downstream effector Rho kinase (ROCK) to limit vascular permeability. CCM2 mediates TrkA-dependent cell death via its N-terminal PTB domain in pediatric neuroblastic tumours. CCM2 possesses an N-terminal PTB domain and a C-terminal Karet domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup. Pssm-ID: 269987 Cd Length: 193 Bit Score: 346.41 E-value: 2.03e-119
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| CCM2_C | pfam16545 | Cerebral cavernous malformation protein, harmonin-homology; CCM2_HHD is a folded-helical ... |
287-381 | 1.04e-54 | ||||
Cerebral cavernous malformation protein, harmonin-homology; CCM2_HHD is a folded-helical region of a family of vertebral proteins, mutations in which cause cerebral cavernous malformations (CCMs). These malformations are congenital vascular anomalies of the central nervous system that can result in haemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. This domain is structurally homologous to the N-terminal domain of harmonin, so it is named the CCM2 harmonin-homology domain or CCM2_HHD. This protein is often called Malcavernin. Pssm-ID: 435415 Cd Length: 95 Bit Score: 176.87 E-value: 1.04e-54
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| HHD_CCM2 | cd13516 | harmonin-homology domain (harmonin_N_like domain) of malcavernin (CCM2); CCM2 (also called ... |
282-377 | 1.54e-51 | ||||
harmonin-homology domain (harmonin_N_like domain) of malcavernin (CCM2); CCM2 (also called malcavernin; C7orf22/chromosome 7 open reading frame 22; OSM) along with CCM1 and CCM3 constitutes a set of proteins which when mutated are responsible for cerebral cavernous malformations, an autosomal dominant neurovascular disease characterized by cerebral hemorrhages and vascular malformations in the central nervous system. CCM2 plays many functional roles. CCM2 functions as a scaffold involved in small GTPase Rac-dependent p38 mitogen-activated protein kinase (MAPK) activation when the cell is under hyperosmotic stress. It associates with CCM1 in the signaling cascades that regulate vascular integrity and participates in HEG1 (the transmembrane receptor heart of glass 1) mediated endothelial cell junctions. CCM proteins also inhibit the activation of small GTPase RhoA and its downstream effector Rho kinase (ROCK) to limit vascular permeability. CCM2 mediates TrkA-dependent cell death via its N-terminal PTB domain in pediatric neuroblastic tumours. CCM2 possesses an N-terminal PTB domain. The C-terminal domain of malcavernin, which is represented here, appears similar to the N-terminal domain of the scaffolding protein harmonin. It has also been referred to as the Karet domain. Pssm-ID: 259825 Cd Length: 97 Bit Score: 168.59 E-value: 1.54e-51
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| harmonin_N_like | cd07347 | N-terminal protein-binding module of harmonin and similar domains, also known as HHD (harmonin ... |
295-371 | 3.01e-20 | ||||
N-terminal protein-binding module of harmonin and similar domains, also known as HHD (harmonin homology domain); This domain is found in harmonin, and similar proteins such as delphilin, and whirlin. These are postsynaptic density-95/discs-large/ZO-1 (PDZ) domain-containing scaffold proteins. Harmonin and whirlin are organizers of the Usher protein network of the inner ear and the retina, delphilin is found at the cerebellar parallel fiber-Purkinje cell synapses. This domain is also found in CCM2 (also called malcavernin; C7orf22/chromosome 7 open reading frame 22; OSM). CCM2 along with CCM1 and CCM3 constitutes a set of proteins which when mutated are responsible for cerebral cavernous malformations, an autosomal dominant neurovascular disease characterized by cerebral hemorrhages and vascular malformations in the central nervous system. CCM2 plays many functional roles. CCM2 functions as a scaffold involved in small GTPase Rac-dependent p38 mitogen-activated protein kinase (MAPK) activation when the cell is under hyperosmotic stress. It associates with CCM1 in the signaling cascades that regulate vascular integrity and participates in HEG1 (the transmembrane receptor heart of glass 1) mediated endothelial cell junctions. CCM proteins also inhibit the activation of small GTPase RhoA and its downstream effector Rho kinase (ROCK) to limit vascular permeability. CCM2 mediates TrkA-dependent cell death via its N-terminal PTB domain in pediatric neuroblastic tumours; the C-terminal domain of malcavernin represented here has also been refered to as the Karet domain. Harmonin contains a single copy of this domain at its N-terminus which binds specifically to a short internal peptide fragment of the cadherin 23 cytoplasmic domain (a component of the Usher protein network). Whirlin contains two copies of this domain; the first of these has been assayed for interaction with the cytoplasmic domain of cadherin 23 and no interaction could be detected. Pssm-ID: 259818 Cd Length: 78 Bit Score: 84.56 E-value: 3.01e-20
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| HN_RTEL1 | cd13932 | harmonin_N_like domain of regulator of telomere elongation helicase 1 (also known as RTEL); ... |
287-372 | 7.17e-09 | ||||
harmonin_N_like domain of regulator of telomere elongation helicase 1 (also known as RTEL); Mouse Rtel is an essential protein required for the maintenance of both telomeric and genomic stability. RTEL1 appears to maintain genome stability by suppressing homologous recombination (HR). In vitro, purified human and insect RTEL1 have been shown to promote the disassembly of D loop recombination intermediates, in a reaction dependent upon ATP hydrolysis. Human RTEL1 is implicated in the etiology of Dyskeratosis congenital (DC, is an inherited bone marrow failure and cancer predisposition syndrome). Point mutations in its helicase domains, and truncations which result in loss of its C-terminus have been discovered in DC families. RTEL1 is also a candidate gene influencing glioma susceptibility. The C-terminal domain of RTEL1, represented here, appears similar to the N-terminal domain of the scaffolding protein harmonin. Pssm-ID: 259826 [Multi-domain] Cd Length: 99 Bit Score: 53.05 E-value: 7.17e-09
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| PTB | cd00934 | Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are ... |
66-217 | 7.39e-06 | ||||
Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to bind peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. Pssm-ID: 269911 Cd Length: 120 Bit Score: 45.19 E-value: 7.39e-06
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| PTB_ICAP1 | cd13163 | Integrin beta-1-binding protein 1 Phosphotyrosine-binding (PTB) PH-like fold; ICAP1 (also ... |
64-160 | 1.03e-05 | ||||
Integrin beta-1-binding protein 1 Phosphotyrosine-binding (PTB) PH-like fold; ICAP1 (also called Integrin cytoplasmic domain-associated protein 1) binds specifically to the beta1 integrin subunit cytoplasmic domain and the cerebral cavernous malformation (CCM) protein CCM1. It regulates beta1 integrin-dependent cell migration by affecting the pattern of focal adhesion formation. ICAP1 recruits CCM1 to the cell membrane and activates CCM1 by changing its conformation. Since CCM1 plays role in cardiovascular development, it is hypothesized ICAP1 is involved in vascular differentiation. ICAP-1 has an N-terminal domain that rich in serine and threonine and a C-terminal PTB domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup. Pssm-ID: 269985 Cd Length: 129 Bit Score: 44.75 E-value: 1.03e-05
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