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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368681  43 HTVVLSLPERVEPDRLLSDYIEKEVKYLGQLTSIPGYLNPSSRTEILHFIDNAKRAHQLPGHLTQEHDAVLSLSAYNVKL 122
Cdd:cd13166     1 SVPLYPPDYRVDPDVLLNDYIEKEVKYLGQLTSVPGSLDPSSRTELLQLLDTARRLGQLPLQLTPEQDAILSLSAYNVKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368681 123 AWRDGEDIILRVPIHDIAAVSYVRDDAAHLVVLKTAQDPGISPSQSLCAESSRGlsAGSLSESAVGPVEACCLVILAAES 202
Cdd:cd13166    81 LWRDGEDLILRVPTHDIAAVSYVRDDSLHLVVLKTASEPGISPSQSLSAESSPT--SGSLSESGPVPVEYCNLVVLACEN 158

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 2217368681 203 KVAAEELCCLLGQVFQVVYTESTIDFLDRAIFDGA 237
Cdd:cd13166   159 KAAAEELCSLLCQVFQIVYTESTIDFLDRAIFDGA 193

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368681  43 HTVVLSLPERVEPDRLLSDYIEKEVKYLGQLTSIPGYLNPSSRTEILHFIDNAKRAHQLPGHLTQEHDAVLSLSAYNVKL 122
Cdd:cd13166     1 SVPLYPPDYRVDPDVLLNDYIEKEVKYLGQLTSVPGSLDPSSRTELLQLLDTARRLGQLPLQLTPEQDAILSLSAYNVKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368681 123 AWRDGEDIILRVPIHDIAAVSYVRDDAAHLVVLKTAQDPGISPSQSLCAESSRGlsAGSLSESAVGPVEACCLVILAAES 202
Cdd:cd13166    81 LWRDGEDLILRVPTHDIAAVSYVRDDSLHLVVLKTASEPGISPSQSLSAESSPT--SGSLSESGPVPVEYCNLVVLACEN 158

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 2217368681 203 KVAAEELCCLLGQVFQVVYTESTIDFLDRAIFDGA 237
Cdd:cd13166   159 KAAAEELCSLLCQVFQIVYTESTIDFLDRAIFDGA 193

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368681  43 HTVVLSLPERVEPDRLLSDYIEKEVKYLGQLTSIPGYLNPSSRTEILHFIDNAKRAHQLPGHLTQEHDAVLSLSAYNVKL 122
Cdd:cd13166     1 SVPLYPPDYRVDPDVLLNDYIEKEVKYLGQLTSVPGSLDPSSRTELLQLLDTARRLGQLPLQLTPEQDAILSLSAYNVKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368681 123 AWRDGEDIILRVPIHDIAAVSYVRDDAAHLVVLKTAQDPGISPSQSLCAESSRGlsAGSLSESAVGPVEACCLVILAAES 202
Cdd:cd13166    81 LWRDGEDLILRVPTHDIAAVSYVRDDSLHLVVLKTASEPGISPSQSLSAESSPT--SGSLSESGPVPVEYCNLVVLACEN 158

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 2217368681 203 KVAAEELCCLLGQVFQVVYTESTIDFLDRAIFDGA 237
Cdd:cd13166   159 KAAAEELCSLLCQVFQIVYTESTIDFLDRAIFDGA 193

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217368681  64 EKEVKYLGQLTSIPGYLNP-SSRTEILHFIDNAKRAHQLPgHLTQEHDAVLSLSAYNVKLAWRDGEDIILRVPIHDIA-A 141
Cdd:cd13163     2 EFRVKYVGVIENLEGLSHSlEGPLDLINAIDVAQQDGKLP-FVAIEEEVILGLSKYGIKVTELNQPVVLKRHPLYSIIrM 80

                          90       100
                  ....*....|....*....|..
gi 2217368681 142 VSYvrDDA---AHLVVLKTAQD 160
Cdd:cd13163    81 VCY--DDGlggKSLLAVKTGDP 100