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Conserved domains on  [gi|1034657045|ref|XP_016868161|]
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cerebral cavernous malformations 2 protein isoform X8 [Homo sapiens]

Protein Classification

CCM2 family PTB domain-containing protein( domain architecture ID 10192175)

cerebral cavernous malformations 2 (CCM2) family PTB (phosphotyrosine-binding) domain-containing protein similar to PTB domain region of 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

CATH:  2.30.29.30
Gene Ontology:  GO:0005515
SCOP:  4002427

Graphical summary

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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 ...
29-200 8.96e-108

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: 309.43  E-value: 8.96e-108
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657045  29 ENEYLGQLTSIPGYLNPSSRTEILHFIDNAKRAHQLPGHLTQEHDAVLSLSAYNVKLAWRDGEDIILRVPIHDIAAVSYV 108
Cdd:cd13166    24 EVKYLGQLTSVPGSLDPSSRTELLQLLDTARRLGQLPLQLTPEQDAILSLSAYNVKLLWRDGEDLILRVPTHDIAAVSYV 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657045 109 RDDAAHLVVLKTAQDPGISPSQSLCAESSRGlsAGSLSESAVGPVEACCLVILAAESKVAAEELCCLLGQVFQVVYTEST 188
Cdd:cd13166   104 RDDSLHLVVLKTASEPGISPSQSLSAESSPT--SGSLSESGPVPVEYCNLVVLACENKAAAEELCSLLCQVFQIVYTEST 181
                         170
                  ....*....|..
gi 1034657045 189 IDFLDRAIFDGA 200
Cdd:cd13166   182 IDFLDRAIFDGA 193
 
Name Accession Description Interval E-value
PTB_CCM2 cd13166
Cerebral cavernous malformation 2 FERM domain C-lobe; CCM2 (also called malcavernin; C7orf22 ...
29-200 8.96e-108

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: 309.43  E-value: 8.96e-108
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657045  29 ENEYLGQLTSIPGYLNPSSRTEILHFIDNAKRAHQLPGHLTQEHDAVLSLSAYNVKLAWRDGEDIILRVPIHDIAAVSYV 108
Cdd:cd13166    24 EVKYLGQLTSVPGSLDPSSRTELLQLLDTARRLGQLPLQLTPEQDAILSLSAYNVKLLWRDGEDLILRVPTHDIAAVSYV 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657045 109 RDDAAHLVVLKTAQDPGISPSQSLCAESSRGlsAGSLSESAVGPVEACCLVILAAESKVAAEELCCLLGQVFQVVYTEST 188
Cdd:cd13166   104 RDDSLHLVVLKTASEPGISPSQSLSAESSPT--SGSLSESGPVPVEYCNLVVLACENKAAAEELCSLLCQVFQIVYTEST 181
                         170
                  ....*....|..
gi 1034657045 189 IDFLDRAIFDGA 200
Cdd:cd13166   182 IDFLDRAIFDGA 193
 
Name Accession Description Interval E-value
PTB_CCM2 cd13166
Cerebral cavernous malformation 2 FERM domain C-lobe; CCM2 (also called malcavernin; C7orf22 ...
29-200 8.96e-108

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: 309.43  E-value: 8.96e-108
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657045  29 ENEYLGQLTSIPGYLNPSSRTEILHFIDNAKRAHQLPGHLTQEHDAVLSLSAYNVKLAWRDGEDIILRVPIHDIAAVSYV 108
Cdd:cd13166    24 EVKYLGQLTSVPGSLDPSSRTELLQLLDTARRLGQLPLQLTPEQDAILSLSAYNVKLLWRDGEDLILRVPTHDIAAVSYV 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657045 109 RDDAAHLVVLKTAQDPGISPSQSLCAESSRGlsAGSLSESAVGPVEACCLVILAAESKVAAEELCCLLGQVFQVVYTEST 188
Cdd:cd13166   104 RDDSLHLVVLKTASEPGISPSQSLSAESSPT--SGSLSESGPVPVEYCNLVVLACENKAAAEELCSLLCQVFQIVYTEST 181
                         170
                  ....*....|..
gi 1034657045 189 IDFLDRAIFDGA 200
Cdd:cd13166   182 IDFLDRAIFDGA 193
PTB cd00934
Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are ...
32-180 1.12e-04

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: 40.96  E-value: 1.12e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657045  32 YLGQLTSIPGYLNPSSRTEILHFIDNAKRAHQLPGhltqehDAVLSLSAYNVKLAWRDGEDIILRVPIHDIAAVSYVRDD 111
Cdd:cd00934     7 YLGSVEVGSSRGVDVVEEALKALAAALKSSKRKPG------PVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPDN 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034657045 112 AAHLVVLktAQDPGISpsqslcaessrglsagslsesavgpvEACCLVILaAESKVAAEELCCLLGQVF 180
Cdd:cd00934    81 PNVFAFI--AGEEGGS--------------------------GFRCHVFQ-CEDEEEAEEILQAIGQAF 120
PTB_ICAP1 cd13163
Integrin beta-1-binding protein 1 Phosphotyrosine-binding (PTB) PH-like fold; ICAP1 (also ...
32-123 1.67e-04

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: 40.52  E-value: 1.67e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034657045  32 YLGQLTSIPGYLNP-SSRTEILHFIDNAKRAHQLPgHLTQEHDAVLSLSAYNVKLAWRDGEDIILRVPIHDIA-AVSYvr 109
Cdd:cd13163     7 YVGVIENLEGLSHSlEGPLDLINAIDVAQQDGKLP-FVAIEEEVILGLSKYGIKVTELNQPVVLKRHPLYSIIrMVCY-- 83
                          90
                  ....*....|....*..
gi 1034657045 110 DDA---AHLVVLKTAQD 123
Cdd:cd13163    84 DDGlggKSLLAVKTGDP 100
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options: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.
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