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Conserved domains on  [gi|2217298367|ref|XP_047287670|]
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son of sevenless homolog 2 isoform X2 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 821-1060 5.60e-75

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


:

Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 248.71  E-value: 5.60e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  821 LMTLHPIEIARQLTLLESDLYRKVQPSELVGSVWTKEDKEI-NSPNLLKMIRHTTNLTLWFEKCIVEAENFEERVAVLSR 899
Cdd:cd00155      1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNIhLSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  900 IIEILQVFQDLNNFNGVLEIVSAVNSVSVYRLDHTFEALQERKRKILDEAVEL--SQDHFKKYLVKLKSI--NPPCVPFF 975
Cdd:cd00155     81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELvdPSRNFKNYRKLLKSVgpNPPCVPFL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  976 GIYLTNILKTEEGNNDFLKKKgkdLINFSKRRKVAEITGEIQQYQNQPYCLRIEPDMRRFFENLNPmgsasEKEFTDYLF 1055
Cdd:cd00155    161 GVYLKDLTFLHEGNPDFLEGN---LVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLE-----LILNEDELY 232


                   ....*
gi 2217298367 1056 NKSLE 1060
Cdd:cd00155    233 ELSLE 237
PH_SOS cd01261
Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide ...
 484-590 7.27e-48

Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide exchange factor. SOS is thought to transmit signals from activated receptor tyrosine kinases to the Ras signaling pathway. SOS contains a histone domain, Dbl-homology (DH), a PH domain, Rem domain, Cdc25 domain, and a Grb2 binding domain. The SOS PH domain binds to phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidic acid (PA). SOS is dependent on Ras binding to the allosteric site via its histone domain for both a lower level of activity (Ras GDP) and maximal activity (Ras GTP). The DH domain blocks the allosteric Ras binding site in SOS. The PH domain is closely associated with the DH domain and the action of the DH-PH unit gates a reciprocal interaction between Ras and SOS. The C-terminal proline-rich domain of SOS binds to the adapter protein Grb2 which localizes the Sos protein to the plasma membrane and diminishes the negative effect of the C-terminal domain on the guanine nucleotide exchange activity of the CDC25-homology domain of SOS. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 269963  Cd Length: 109  Bit Score: 165.99  E-value: 7.27e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  484 QCCNEFIMEGPLTRIGA---KHERHIFLFDGLMISCKPNHGQTRLPGySSAEYRLKEKFVMRKIQICDKEDTCEHKHAFE 560
Cdd:cd01261      1 QCCNEFIMEGTLGKVGSgkrKTERHAFLFDGLLLLCKSNRRRTSTGG-PKPEYRLKEKFFIRKVEINDLEDTEELKNAFE 79

                           90       100       110
                   ....*....|....*....|....*....|
gi 2217298367  561 LVSKDENSIIFAAKSAEEKNNWMAALISLH 590
Cdd:cd01261     80 IVPRDQPSVILFAKSAEEKNNWMAALVMLN 109
HFD_SOS1_rpt1 cd22914
first histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; ...
 18-142 2.25e-40

first histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; SOS-1 is a guanine nucleotide exchange factor for Ras that binds to GRB2. It promotes the exchange of Ras-bound GDP by GTP. It is a catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac, by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity. SOS-1 contains tandem histone folds at the N-terminal region. The model corresponds to the first repeat.


:

Pssm-ID: 467039  Cd Length: 78  Bit Score: 143.55  E-value: 2.25e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   18 KWRGLLVSALRKmesrffarlgcsgailahcnlhlsgssdspasasrvagttgvchhaqVQEQVHPTLSANEESLYYIEE 97
Cdd:cd22914      1 KWRGLLVPALKK-----------------------------------------------VQKQVHPTLVAKEDALEYIEE 33

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 2217298367   98 LIFQLLNKLCMAQPRTVQDVEERVQKTFPHPIDKWAIADAQSAIE 142
Cdd:cd22914     34 LILQLLNMLCAAQPHSVQDVEERVQKTFPHPIDKWAIADAQAALE 78
RasGEFN smart00229
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine ...
 642-786 4.66e-40

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).


:

Pssm-ID: 214571  Cd Length: 127  Bit Score: 144.40  E-value: 4.66e-40
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   642 GIPIIKGGTVVKLIERLTYHMY-ADPNFVRTFLTTYRSFCKPQELLSLLIERFEIPEPEPTdadklaiekgeqpisadlk 720
Cdd:smart00229    1 DGGLIKGGTLEALIEHLTEAFDkADPSFVETFLLTYRSFITTQELLQLLLYRYNAIPPESW------------------- 61

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217298367   721 RFRKEYVQPVQLRILNVFRHWVEHHFYDFERDLELLERLESFISSVRGKAMKKWVESIAKIIRRKK 786
Cdd:smart00229   62 VEEKVNPRRVKNRVLNILRTWVENYWEDFEDDPKLISFLLEFLELVDDEKYPGLVTSLLNLLRRLS 127
HFD_SOS1_rpt2 cd22915
second histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; ...
 151-223 6.72e-37

second histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; SOS-1 is a guanine nucleotide exchange factor for Ras that binds to GRB2. It promotes the exchange of Ras-bound GDP by GTP. It is a catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac, by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity. SOS-1 contains tandem histone folds at the N-terminal region. The model corresponds to the second repeat.


:

Pssm-ID: 467040  Cd Length: 75  Bit Score: 133.52  E-value: 6.72e-37
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217298367  151 LLPVDKIHPSL-KEVLGYKVDYHVSLYIVAVLEYISADILKLAGNYVFNIRHYEISQQDIKVSMCADKVLMDMF 223
Cdd:cd22915      1 LFPVDKIHPLLkKDLLVYKVDPQVSLYLVAVLEYIAADILKLAGNYVRNIRHYEITSQDIKVAMCADKVLMDLF 74
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 246-433 8.87e-35

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


:

Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 131.27  E-value: 8.87e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  246 YYDLVRTEIAEERQYLRELNMIIKVFREAFLSDRKLFKPSDIEKIFSNISDIHELTVKLLGLIEDTVEMTDesSPHPLAG 325
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWD--KSGPRIG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  326 SCFEDLAEeqAFDPYETLSQDIlsPEFHEHFNKLMarpAVALHFQSIADGF-KEAVRYVLPRLMLVPVYHCWHYFELLKQ 404
Cdd:cd00160     79 DVFLKLAP--FFKIYSEYCSNH--PDALELLKKLK---KFNKFFQEFLEKAeSECGRLKLESLLLKPVQRLTKYPLLLKE 151

                          170       180       190
                   ....*....|....*....|....*....|
gi 2217298367  405 LKACSEE-QEDRECLNQAITALMNLQGSMD 433
Cdd:cd00160    152 LLKHTPDgHEDREDLKKALEAIKEVASQVN 181
 
Name Accession Description Interval E-value
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 821-1060 5.60e-75

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 248.71  E-value: 5.60e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  821 LMTLHPIEIARQLTLLESDLYRKVQPSELVGSVWTKEDKEI-NSPNLLKMIRHTTNLTLWFEKCIVEAENFEERVAVLSR 899
Cdd:cd00155      1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNIhLSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  900 IIEILQVFQDLNNFNGVLEIVSAVNSVSVYRLDHTFEALQERKRKILDEAVEL--SQDHFKKYLVKLKSI--NPPCVPFF 975
Cdd:cd00155     81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELvdPSRNFKNYRKLLKSVgpNPPCVPFL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  976 GIYLTNILKTEEGNNDFLKKKgkdLINFSKRRKVAEITGEIQQYQNQPYCLRIEPDMRRFFENLNPmgsasEKEFTDYLF 1055
Cdd:cd00155    161 GVYLKDLTFLHEGNPDFLEGN---LVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLE-----LILNEDELY 232


                   ....*
gi 2217298367 1056 NKSLE 1060
Cdd:cd00155    233 ELSLE 237
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
821-1065 1.64e-73

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 244.85  E-value: 1.64e-73
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   821 LMTLHPIEIARQLTLLESDLYRKVQPSELVGSVWTKEDKEINSP-NLLKMIRHTTNLTLWFEKCIVEAENFEERVAVLSR 899
Cdd:smart00147    1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPlNLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   900 IIEILQVFQDLNNFNGVLEIVSAVNSVSVYRLDHTFEALQERKRKILDEAVEL--SQDHFKKYLVKLKSIN-PPCVPFFG 976
Cdd:smart00147   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELlsPERNYKNYREALSSCNlPPCIPFLG 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   977 IYLTNILKTEEGNNDFLKKKgkdLINFSKRRKVAEITGEIQQYQNQPYCLRIEPDMRRFFENLNPMGSASEkeftDYLFN 1056
Cdd:smart00147  161 VLLKDLTFIDEGNPDFLENG---LVNFEKRRQIAEILREIRQLQSQPYNLRPNRSDIQSLLQQLLDHLDEE----EELYQ 233


                    ....*....
gi 2217298367  1057 KSLEIEPRN 1065
Cdd:smart00147  234 LSLKIEPRV 242
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 828-1007 3.01e-65

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.


Pssm-ID: 459872  Cd Length: 179  Bit Score: 218.62  E-value: 3.01e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  828 EIARQLTLLESDLYRKVQPSELVGSVWTKEDKEINSPNLLKMIRHTTNLTLWFEKCIVEAENFEERVAVLSRIIEILQVF 907
Cdd:pfam00617    1 ELARQLTLIEFELFRKIKPRELLGSAWSKKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  908 QDLNNFNGVLEIVSAVNSVSVYRLDHTFEALQERKRKILDEAVEL--SQDHFKKYLVKLKSINPPCVPFFGIYLTNILKT 985
Cdd:pfam00617   81 RELNNFNSLMAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLmsPSRNFKNYREALSSASPPCIPFLGLYLTDLTFI 160

                          170       180
                   ....*....|....*....|..
gi 2217298367  986 EEGNNDFLKKKgkdLINFSKRR 1007
Cdd:pfam00617  161 EEGNPDFLEGG---LINFEKRR 179
PH_SOS cd01261
Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide ...
 484-590 7.27e-48

Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide exchange factor. SOS is thought to transmit signals from activated receptor tyrosine kinases to the Ras signaling pathway. SOS contains a histone domain, Dbl-homology (DH), a PH domain, Rem domain, Cdc25 domain, and a Grb2 binding domain. The SOS PH domain binds to phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidic acid (PA). SOS is dependent on Ras binding to the allosteric site via its histone domain for both a lower level of activity (Ras GDP) and maximal activity (Ras GTP). The DH domain blocks the allosteric Ras binding site in SOS. The PH domain is closely associated with the DH domain and the action of the DH-PH unit gates a reciprocal interaction between Ras and SOS. The C-terminal proline-rich domain of SOS binds to the adapter protein Grb2 which localizes the Sos protein to the plasma membrane and diminishes the negative effect of the C-terminal domain on the guanine nucleotide exchange activity of the CDC25-homology domain of SOS. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269963  Cd Length: 109  Bit Score: 165.99  E-value: 7.27e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  484 QCCNEFIMEGPLTRIGA---KHERHIFLFDGLMISCKPNHGQTRLPGySSAEYRLKEKFVMRKIQICDKEDTCEHKHAFE 560
Cdd:cd01261      1 QCCNEFIMEGTLGKVGSgkrKTERHAFLFDGLLLLCKSNRRRTSTGG-PKPEYRLKEKFFIRKVEINDLEDTEELKNAFE 79

                           90       100       110
                   ....*....|....*....|....*....|
gi 2217298367  561 LVSKDENSIIFAAKSAEEKNNWMAALISLH 590
Cdd:cd01261     80 IVPRDQPSVILFAKSAEEKNNWMAALVMLN 109
HFD_SOS1_rpt1 cd22914
first histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; ...
 18-142 2.25e-40

first histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; SOS-1 is a guanine nucleotide exchange factor for Ras that binds to GRB2. It promotes the exchange of Ras-bound GDP by GTP. It is a catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac, by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity. SOS-1 contains tandem histone folds at the N-terminal region. The model corresponds to the first repeat.


Pssm-ID: 467039  Cd Length: 78  Bit Score: 143.55  E-value: 2.25e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   18 KWRGLLVSALRKmesrffarlgcsgailahcnlhlsgssdspasasrvagttgvchhaqVQEQVHPTLSANEESLYYIEE 97
Cdd:cd22914      1 KWRGLLVPALKK-----------------------------------------------VQKQVHPTLVAKEDALEYIEE 33

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 2217298367   98 LIFQLLNKLCMAQPRTVQDVEERVQKTFPHPIDKWAIADAQSAIE 142
Cdd:cd22914     34 LILQLLNMLCAAQPHSVQDVEERVQKTFPHPIDKWAIADAQAALE 78
RasGEFN smart00229
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine ...
 642-786 4.66e-40

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).


Pssm-ID: 214571  Cd Length: 127  Bit Score: 144.40  E-value: 4.66e-40
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   642 GIPIIKGGTVVKLIERLTYHMY-ADPNFVRTFLTTYRSFCKPQELLSLLIERFEIPEPEPTdadklaiekgeqpisadlk 720
Cdd:smart00229    1 DGGLIKGGTLEALIEHLTEAFDkADPSFVETFLLTYRSFITTQELLQLLLYRYNAIPPESW------------------- 61

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217298367   721 RFRKEYVQPVQLRILNVFRHWVEHHFYDFERDLELLERLESFISSVRGKAMKKWVESIAKIIRRKK 786
Cdd:smart00229   62 VEEKVNPRRVKNRVLNILRTWVENYWEDFEDDPKLISFLLEFLELVDDEKYPGLVTSLLNLLRRLS 127
HFD_SOS1_rpt2 cd22915
second histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; ...
 151-223 6.72e-37

second histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; SOS-1 is a guanine nucleotide exchange factor for Ras that binds to GRB2. It promotes the exchange of Ras-bound GDP by GTP. It is a catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac, by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity. SOS-1 contains tandem histone folds at the N-terminal region. The model corresponds to the second repeat.


Pssm-ID: 467040  Cd Length: 75  Bit Score: 133.52  E-value: 6.72e-37
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217298367  151 LLPVDKIHPSL-KEVLGYKVDYHVSLYIVAVLEYISADILKLAGNYVFNIRHYEISQQDIKVSMCADKVLMDMF 223
Cdd:cd22915      1 LFPVDKIHPLLkKDLLVYKVDPQVSLYLVAVLEYIAADILKLAGNYVRNIRHYEITSQDIKVAMCADKVLMDLF 74
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 246-433 8.87e-35

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 131.27  E-value: 8.87e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  246 YYDLVRTEIAEERQYLRELNMIIKVFREAFLSDRKLFKPSDIEKIFSNISDIHELTVKLLGLIEDTVEMTDesSPHPLAG 325
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWD--KSGPRIG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  326 SCFEDLAEeqAFDPYETLSQDIlsPEFHEHFNKLMarpAVALHFQSIADGF-KEAVRYVLPRLMLVPVYHCWHYFELLKQ 404
Cdd:cd00160     79 DVFLKLAP--FFKIYSEYCSNH--PDALELLKKLK---KFNKFFQEFLEKAeSECGRLKLESLLLKPVQRLTKYPLLLKE 151

                          170       180       190
                   ....*....|....*....|....*....|
gi 2217298367  405 LKACSEE-QEDRECLNQAITALMNLQGSMD 433
Cdd:cd00160    152 LLKHTPDgHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 254-434 1.53e-34

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 130.88  E-value: 1.53e-34
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   254 IAEERQYLRELNMIIKVFREAFLSDRKLFKPSDIEKIFSNISDIHELTVKLLGLIEDTVEMTDesSPHPLAGSCFEDLAE 333
Cdd:smart00325    6 LQTERNYVRDLKLLVEVFLKPLKKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWD--DSVERIGDVFLKLEE 83

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   334 eqAFDPYETLSQDIlsPEFHEHFNKLMARPAVALHFQSIADGFKEAvRYVLPRLMLVPVYHCWHYFELLKQL-KACSEEQ 412
Cdd:smart00325   84 --FFKIYSEYCSNH--PDALELLKKLKKNPRFQKFLKEIESSPQCR-RLTLESLLLKPVQRLTKYPLLLKELlKHTPEDH 158

                           170       180
                    ....*....|....*....|..
gi 2217298367   413 EDRECLNQAITALMNLQGSMDR 434
Cdd:smart00325  159 EDREDLKKALKAIKELANQVNE 180
REM cd06224
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also ...
 650-784 2.34e-34

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.


Pssm-ID: 100121  Cd Length: 122  Bit Score: 127.91  E-value: 2.34e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  650 TVVKLIERLTYHM-YADPNFVRTFLTTYRSFCKPQELLSLLIERFEIPEPEPTDAdklaiekgeqpisadlKRFRKEYVQ 728
Cdd:cd06224      1 TLEALIEHLTSTFdMPDPSFVSTFLLTYRSFTTPTELLEKLIERYEIAPPENLEY----------------NDWDKKKSK 64

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2217298367  729 PVQLRILNVFRHWVEHHFYDFERDLELLERLESFISSVR--GKAMKKWVESIAKIIRR 784
Cdd:cd06224     65 PIRLRVLNVLRTWVENYPYDFFDDEELLELLEEFLNRLVqeGALLQELKKLLRKLLKL 122
RasGEF_N pfam00618
RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small ...
 645-762 3.19e-33

RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this motif/domain N-terminal to the RasGef (Cdc25-like) domain.


Pssm-ID: 459873  Cd Length: 104  Bit Score: 123.95  E-value: 3.19e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  645 IIKGGTVVKLIERLTYHMYA-DPNFVRTFLTTYRSFCKPQELLSLLIERFEIPEPEPTDADKLAIEKGEQPIsadlkrfr 723
Cdd:pfam00618    1 QVKAGTLEKLVEYLTSTRIMlDDSFLSTFLLTYRSFTTPAELLELLIERYNIPPPLDLSSDSYWISKKTLPI-------- 72

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2217298367  724 keyvqpvQLRILNVFRHWVEHHFYDFERDLELLERLESF 762
Cdd:pfam00618   73 -------RIRVLSVLRHWVENYFSDFNDDPVLLSRLEKF 104
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 257-433 1.99e-21

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 93.13  E-value: 1.99e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  257 ERQYLRELNMIIKVFREaFLSDRKLFKPSDIEKIFSNISDIHELTVKLLglIEdtvEMTDESSPHPLAGSCFEDLAEEqa 336
Cdd:pfam00621    9 ERSYVRDLEILVEVFLP-PNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LE---ELLKEWISIQRIGDIFLKFAPG-- 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  337 FDPYETLSQDIlsPEFHEHFNKLMARPAVALHFQSIADGFKEAVRYVLPRLMLVPVYHCWHYFELLKQL-KACSEEQEDR 415
Cdd:pfam00621   81 FKVYSTYCSNY--PKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELlKHTPPDHPDY 158

                          170
                   ....*....|....*...
gi 2217298367  416 ECLNQAITALMNLQGSMD 433
Cdd:pfam00621  159 EDLKKALEAIKEVAKQIN 176
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 489-591 4.60e-14

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 69.50  E-value: 4.60e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   489 FIMEGPLTRIGAK-----HERHIFLFDGLMISCKPNHGQTRlpgyssaeYRLKEKFVMRKIQI--CDKEDTCEHKHAFEL 561
Cdd:smart00233    1 VIKEGWLYKKSGGgkkswKKRYFVLFNSTLLYYKSKKDKKS--------YKPKGSIDLSGCTVreAPDPDSSKKPHCFEI 72

                            90       100       110
                    ....*....|....*....|....*....|
gi 2217298367   562 VSKDENSIIFAAKSAEEKNNWMAALISLHY 591
Cdd:smart00233   73 KTSDRKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 490-591 1.26e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 59.88  E-value: 1.26e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  490 IMEGPLTRIGAK-----HERHIFLFDGLMISCKPnhgqtrlpGYSSAEYRLKEKFVMRKIQICD--KEDTCEHKHAFELV 562
Cdd:pfam00169    2 VKEGWLLKKGGGkkkswKKRYFVLFDGSLLYYKD--------DKSGKSKEPKGSISLSGCEVVEvvASDSPKRKFCFELR 73

                           90       100       110
                   ....*....|....*....|....*....|..
gi 2217298367  563 SKD---ENSIIFAAKSAEEKNNWMAALISLHY 591
Cdd:pfam00169   74 TGErtgKRTYLLQAESEEERKDWIKAIQSAIR 105
H2A smart00414
Histone 2A;
144-194 1.43e-04

Histone 2A;


Pssm-ID: 197711  Cd Length: 106  Bit Score: 42.32  E-value: 1.43e-04
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 2217298367   144 RKRRNPLLLPVDKIHPSLKE-VLGYKVDYHVSLYIVAVLEYISADILKLAGN 194
Cdd:smart00414    2 RSARAGLQFPVGRIHRLLRKgTYAKRVGAGAPVYLAAVLEYLTAEVLELAGN 53
HTA1 COG5262
Histone H2A [Chromatin structure and dynamics];
131-219 3.65e-04

Histone H2A [Chromatin structure and dynamics];


Pssm-ID: 227587 [Multi-domain]  Cd Length: 132  Bit Score: 42.16  E-value: 3.65e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  131 KWAIADAQSAIEKRKRRNPLLLPVDKIHPSLKEVLG-YKVDYHVSLYIVAVLEYISADILKLAGNYVFNIRHYEISQQDI 209
Cdd:COG5262      6 KGGKAADARVSQSRSAKAGLIFPVGRVKRLLKKGNYrMRIGAGAPVYLAAVLEYLAAEILELAGNAARDNKKKRIIPRHL 85

                           90
                   ....*....|
gi 2217298367  210 KVSMCADKVL 219
Cdd:COG5262     86 QLAIRNDEEL 95
PTZ00017 PTZ00017
histone H2A; Provisional
 144-194 5.43e-04

histone H2A; Provisional


Pssm-ID: 185399  Cd Length: 134  Bit Score: 41.65  E-value: 5.43e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2217298367  144 RKRRNPLLLPVDKIHPSLKE-VLGYKVDYHVSLYIVAVLEYISADILKLAGN 194
Cdd:PTZ00017    20 RSAKAGLQFPVGRVHRYLKKgRYAKRVGAGAPVYLAAVLEYLTAEVLELAGN 71
 
Name Accession Description Interval E-value
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 821-1060 5.60e-75

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 248.71  E-value: 5.60e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  821 LMTLHPIEIARQLTLLESDLYRKVQPSELVGSVWTKEDKEI-NSPNLLKMIRHTTNLTLWFEKCIVEAENFEERVAVLSR 899
Cdd:cd00155      1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNIhLSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  900 IIEILQVFQDLNNFNGVLEIVSAVNSVSVYRLDHTFEALQERKRKILDEAVEL--SQDHFKKYLVKLKSI--NPPCVPFF 975
Cdd:cd00155     81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELvdPSRNFKNYRKLLKSVgpNPPCVPFL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  976 GIYLTNILKTEEGNNDFLKKKgkdLINFSKRRKVAEITGEIQQYQNQPYCLRIEPDMRRFFENLNPmgsasEKEFTDYLF 1055
Cdd:cd00155    161 GVYLKDLTFLHEGNPDFLEGN---LVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLE-----LILNEDELY 232


                   ....*
gi 2217298367 1056 NKSLE 1060
Cdd:cd00155    233 ELSLE 237
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
821-1065 1.64e-73

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 244.85  E-value: 1.64e-73
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   821 LMTLHPIEIARQLTLLESDLYRKVQPSELVGSVWTKEDKEINSP-NLLKMIRHTTNLTLWFEKCIVEAENFEERVAVLSR 899
Cdd:smart00147    1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPlNLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   900 IIEILQVFQDLNNFNGVLEIVSAVNSVSVYRLDHTFEALQERKRKILDEAVEL--SQDHFKKYLVKLKSIN-PPCVPFFG 976
Cdd:smart00147   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELlsPERNYKNYREALSSCNlPPCIPFLG 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   977 IYLTNILKTEEGNNDFLKKKgkdLINFSKRRKVAEITGEIQQYQNQPYCLRIEPDMRRFFENLNPMGSASEkeftDYLFN 1056
Cdd:smart00147  161 VLLKDLTFIDEGNPDFLENG---LVNFEKRRQIAEILREIRQLQSQPYNLRPNRSDIQSLLQQLLDHLDEE----EELYQ 233


                    ....*....
gi 2217298367  1057 KSLEIEPRN 1065
Cdd:smart00147  234 LSLKIEPRV 242
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 828-1007 3.01e-65

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.


Pssm-ID: 459872  Cd Length: 179  Bit Score: 218.62  E-value: 3.01e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  828 EIARQLTLLESDLYRKVQPSELVGSVWTKEDKEINSPNLLKMIRHTTNLTLWFEKCIVEAENFEERVAVLSRIIEILQVF 907
Cdd:pfam00617    1 ELARQLTLIEFELFRKIKPRELLGSAWSKKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  908 QDLNNFNGVLEIVSAVNSVSVYRLDHTFEALQERKRKILDEAVEL--SQDHFKKYLVKLKSINPPCVPFFGIYLTNILKT 985
Cdd:pfam00617   81 RELNNFNSLMAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLmsPSRNFKNYREALSSASPPCIPFLGLYLTDLTFI 160

                          170       180
                   ....*....|....*....|..
gi 2217298367  986 EEGNNDFLKKKgkdLINFSKRR 1007
Cdd:pfam00617  161 EEGNPDFLEGG---LINFEKRR 179
PH_SOS cd01261
Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide ...
 484-590 7.27e-48

Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide exchange factor. SOS is thought to transmit signals from activated receptor tyrosine kinases to the Ras signaling pathway. SOS contains a histone domain, Dbl-homology (DH), a PH domain, Rem domain, Cdc25 domain, and a Grb2 binding domain. The SOS PH domain binds to phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidic acid (PA). SOS is dependent on Ras binding to the allosteric site via its histone domain for both a lower level of activity (Ras GDP) and maximal activity (Ras GTP). The DH domain blocks the allosteric Ras binding site in SOS. The PH domain is closely associated with the DH domain and the action of the DH-PH unit gates a reciprocal interaction between Ras and SOS. The C-terminal proline-rich domain of SOS binds to the adapter protein Grb2 which localizes the Sos protein to the plasma membrane and diminishes the negative effect of the C-terminal domain on the guanine nucleotide exchange activity of the CDC25-homology domain of SOS. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269963  Cd Length: 109  Bit Score: 165.99  E-value: 7.27e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  484 QCCNEFIMEGPLTRIGA---KHERHIFLFDGLMISCKPNHGQTRLPGySSAEYRLKEKFVMRKIQICDKEDTCEHKHAFE 560
Cdd:cd01261      1 QCCNEFIMEGTLGKVGSgkrKTERHAFLFDGLLLLCKSNRRRTSTGG-PKPEYRLKEKFFIRKVEINDLEDTEELKNAFE 79

                           90       100       110
                   ....*....|....*....|....*....|
gi 2217298367  561 LVSKDENSIIFAAKSAEEKNNWMAALISLH 590
Cdd:cd01261     80 IVPRDQPSVILFAKSAEEKNNWMAALVMLN 109
HFD_SOS1_rpt1 cd22914
first histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; ...
 18-142 2.25e-40

first histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; SOS-1 is a guanine nucleotide exchange factor for Ras that binds to GRB2. It promotes the exchange of Ras-bound GDP by GTP. It is a catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac, by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity. SOS-1 contains tandem histone folds at the N-terminal region. The model corresponds to the first repeat.


Pssm-ID: 467039  Cd Length: 78  Bit Score: 143.55  E-value: 2.25e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   18 KWRGLLVSALRKmesrffarlgcsgailahcnlhlsgssdspasasrvagttgvchhaqVQEQVHPTLSANEESLYYIEE 97
Cdd:cd22914      1 KWRGLLVPALKK-----------------------------------------------VQKQVHPTLVAKEDALEYIEE 33

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 2217298367   98 LIFQLLNKLCMAQPRTVQDVEERVQKTFPHPIDKWAIADAQSAIE 142
Cdd:cd22914     34 LILQLLNMLCAAQPHSVQDVEERVQKTFPHPIDKWAIADAQAALE 78
RasGEFN smart00229
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine ...
 642-786 4.66e-40

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).


Pssm-ID: 214571  Cd Length: 127  Bit Score: 144.40  E-value: 4.66e-40
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   642 GIPIIKGGTVVKLIERLTYHMY-ADPNFVRTFLTTYRSFCKPQELLSLLIERFEIPEPEPTdadklaiekgeqpisadlk 720
Cdd:smart00229    1 DGGLIKGGTLEALIEHLTEAFDkADPSFVETFLLTYRSFITTQELLQLLLYRYNAIPPESW------------------- 61

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217298367   721 RFRKEYVQPVQLRILNVFRHWVEHHFYDFERDLELLERLESFISSVRGKAMKKWVESIAKIIRRKK 786
Cdd:smart00229   62 VEEKVNPRRVKNRVLNILRTWVENYWEDFEDDPKLISFLLEFLELVDDEKYPGLVTSLLNLLRRLS 127
HFD_SOS1_rpt2 cd22915
second histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; ...
 151-223 6.72e-37

second histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; SOS-1 is a guanine nucleotide exchange factor for Ras that binds to GRB2. It promotes the exchange of Ras-bound GDP by GTP. It is a catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac, by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity. SOS-1 contains tandem histone folds at the N-terminal region. The model corresponds to the second repeat.


Pssm-ID: 467040  Cd Length: 75  Bit Score: 133.52  E-value: 6.72e-37
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2217298367  151 LLPVDKIHPSL-KEVLGYKVDYHVSLYIVAVLEYISADILKLAGNYVFNIRHYEISQQDIKVSMCADKVLMDMF 223
Cdd:cd22915      1 LFPVDKIHPLLkKDLLVYKVDPQVSLYLVAVLEYIAADILKLAGNYVRNIRHYEITSQDIKVAMCADKVLMDLF 74
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 246-433 8.87e-35

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 131.27  E-value: 8.87e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  246 YYDLVRTEIAEERQYLRELNMIIKVFREAFLSDRKLFKPSDIEKIFSNISDIHELTVKLLGLIEDTVEMTDesSPHPLAG 325
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWD--KSGPRIG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  326 SCFEDLAEeqAFDPYETLSQDIlsPEFHEHFNKLMarpAVALHFQSIADGF-KEAVRYVLPRLMLVPVYHCWHYFELLKQ 404
Cdd:cd00160     79 DVFLKLAP--FFKIYSEYCSNH--PDALELLKKLK---KFNKFFQEFLEKAeSECGRLKLESLLLKPVQRLTKYPLLLKE 151

                          170       180       190
                   ....*....|....*....|....*....|
gi 2217298367  405 LKACSEE-QEDRECLNQAITALMNLQGSMD 433
Cdd:cd00160    152 LLKHTPDgHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 254-434 1.53e-34

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 130.88  E-value: 1.53e-34
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   254 IAEERQYLRELNMIIKVFREAFLSDRKLFKPSDIEKIFSNISDIHELTVKLLGLIEDTVEMTDesSPHPLAGSCFEDLAE 333
Cdd:smart00325    6 LQTERNYVRDLKLLVEVFLKPLKKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWD--DSVERIGDVFLKLEE 83

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   334 eqAFDPYETLSQDIlsPEFHEHFNKLMARPAVALHFQSIADGFKEAvRYVLPRLMLVPVYHCWHYFELLKQL-KACSEEQ 412
Cdd:smart00325   84 --FFKIYSEYCSNH--PDALELLKKLKKNPRFQKFLKEIESSPQCR-RLTLESLLLKPVQRLTKYPLLLKELlKHTPEDH 158

                           170       180
                    ....*....|....*....|..
gi 2217298367   413 EDRECLNQAITALMNLQGSMDR 434
Cdd:smart00325  159 EDREDLKKALKAIKELANQVNE 180
REM cd06224
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also ...
 650-784 2.34e-34

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.


Pssm-ID: 100121  Cd Length: 122  Bit Score: 127.91  E-value: 2.34e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  650 TVVKLIERLTYHM-YADPNFVRTFLTTYRSFCKPQELLSLLIERFEIPEPEPTDAdklaiekgeqpisadlKRFRKEYVQ 728
Cdd:cd06224      1 TLEALIEHLTSTFdMPDPSFVSTFLLTYRSFTTPTELLEKLIERYEIAPPENLEY----------------NDWDKKKSK 64

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2217298367  729 PVQLRILNVFRHWVEHHFYDFERDLELLERLESFISSVR--GKAMKKWVESIAKIIRR 784
Cdd:cd06224     65 PIRLRVLNVLRTWVENYPYDFFDDEELLELLEEFLNRLVqeGALLQELKKLLRKLLKL 122
RasGEF_N pfam00618
RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small ...
 645-762 3.19e-33

RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this motif/domain N-terminal to the RasGef (Cdc25-like) domain.


Pssm-ID: 459873  Cd Length: 104  Bit Score: 123.95  E-value: 3.19e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  645 IIKGGTVVKLIERLTYHMYA-DPNFVRTFLTTYRSFCKPQELLSLLIERFEIPEPEPTDADKLAIEKGEQPIsadlkrfr 723
Cdd:pfam00618    1 QVKAGTLEKLVEYLTSTRIMlDDSFLSTFLLTYRSFTTPAELLELLIERYNIPPPLDLSSDSYWISKKTLPI-------- 72

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2217298367  724 keyvqpvQLRILNVFRHWVEHHFYDFERDLELLERLESF 762
Cdd:pfam00618   73 -------RIRVLSVLRHWVENYFSDFNDDPVLLSRLEKF 104
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 257-433 1.99e-21

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 93.13  E-value: 1.99e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  257 ERQYLRELNMIIKVFREaFLSDRKLFKPSDIEKIFSNISDIHELTVKLLglIEdtvEMTDESSPHPLAGSCFEDLAEEqa 336
Cdd:pfam00621    9 ERSYVRDLEILVEVFLP-PNSKPLSESEEEIKTIFSNIEEIYELHRQLL--LE---ELLKEWISIQRIGDIFLKFAPG-- 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  337 FDPYETLSQDIlsPEFHEHFNKLMARPAVALHFQSIADGFKEAVRYVLPRLMLVPVYHCWHYFELLKQL-KACSEEQEDR 415
Cdd:pfam00621   81 FKVYSTYCSNY--PKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELlKHTPPDHPDY 158

                          170
                   ....*....|....*...
gi 2217298367  416 ECLNQAITALMNLQGSMD 433
Cdd:pfam00621  159 EDLKKALEAIKEVAKQIN 176
PH_Collybistin_ASEF cd01224
Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; ...
 464-587 1.73e-17

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269931  Cd Length: 138  Bit Score: 80.38  E-value: 1.73e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  464 IKKMNEIQKNIDGWEGKDIGQCCNEFIMEGPLTRIGAKH--ERHIFLFDGLMISCKPNHGQTRLPGYssaeyrlKEKFVM 541
Cdd:cd01224      4 LEKLAAWQSTVEGWEGEDLSDRSSELIHSGELTKISAGRaqERTFFLFDHQLVYCKKDLLRRKNYIY-------KGRIDT 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2217298367  542 RKIQICDKEDTCEH------KHAFELVSKDEN-SIIFAAKSAEEKNNWMAALI 587
Cdd:cd01224     77 DNMEIEDLPDGKDDesgvtvKNAWKIYNASKNkWYVLCAKSAEEKQRWLEAFA 129
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 489-591 4.60e-14

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 69.50  E-value: 4.60e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367   489 FIMEGPLTRIGAK-----HERHIFLFDGLMISCKPNHGQTRlpgyssaeYRLKEKFVMRKIQI--CDKEDTCEHKHAFEL 561
Cdd:smart00233    1 VIKEGWLYKKSGGgkkswKKRYFVLFNSTLLYYKSKKDKKS--------YKPKGSIDLSGCTVreAPDPDSSKKPHCFEI 72

                            90       100       110
                    ....*....|....*....|....*....|
gi 2217298367   562 VSKDENSIIFAAKSAEEKNNWMAALISLHY 591
Cdd:smart00233   73 KTSDRKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 490-591 1.26e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 59.88  E-value: 1.26e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  490 IMEGPLTRIGAK-----HERHIFLFDGLMISCKPnhgqtrlpGYSSAEYRLKEKFVMRKIQICD--KEDTCEHKHAFELV 562
Cdd:pfam00169    2 VKEGWLLKKGGGkkkswKKRYFVLFDGSLLYYKD--------DKSGKSKEPKGSISLSGCEVVEvvASDSPKRKFCFELR 73

                           90       100       110
                   ....*....|....*....|....*....|..
gi 2217298367  563 SKD---ENSIIFAAKSAEEKNNWMAALISLHY 591
Cdd:pfam00169   74 TGErtgKRTYLLQAESEEERKDWIKAIQSAIR 105
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 491-586 1.13e-09

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 56.40  E-value: 1.13e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  491 MEGPLTRIGAK-----HERHIFLFDGLMISCKPNHGQTrlpgyssaeYRLKEKFVMRKIQICDKEDTCEHKHAFELVSKD 565
Cdd:cd00821      1 KEGYLLKRGGGglkswKKRWFVLFEGVLLYYKSKKDSS---------YKPKGSIPLSGILEVEEVSPKERPHCFELVTPD 71

                           90       100
                   ....*....|....*....|.
gi 2217298367  566 ENSIIFAAKSAEEKNNWMAAL 586
Cdd:cd00821     72 GRTYYLQADSEEERQEWLKAL 92
PH1_FGD1-4_like cd13388
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, ...
 490-586 2.26e-08

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. They play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275423  Cd Length: 94  Bit Score: 52.71  E-value: 2.26e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  490 IMEGPLTRIGAK----HERHIFLFDGLMISCKPnhgQTRLPGyssAEYRLKEKFVMRKIQICDKeDTCEHKHAFElVSKD 565
Cdd:cd13388      2 IKEGKILKISARngdtQERYLFLFNDMLLYCSP---RLRLIG---QKYKVRARFDVDGMQVLEG-DNLETPHTFY-VRGK 73

                           90       100
                   ....*....|....*....|.
gi 2217298367  566 ENSIIFAAKSAEEKNNWMAAL 586
Cdd:cd13388     74 QRSLELQASTQEEKAEWVDAI 94
PH1_FDG_family cd13328
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal ...
 492-586 2.31e-07

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275410  Cd Length: 92  Bit Score: 50.18  E-value: 2.31e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  492 EGPLTRIGAKH----ERHIFLFDGLMISCKPnhgQTRLPGyssAEYRLKEKFVMRKIQICDKEDTcEHKHAFeLVSKDEN 567
Cdd:cd13328      2 EGQILKLSAKNgtpqPRYLFLFNDMLLYCVP---KLSLVG---QKFSVRNRLDVAGMKVREPVNE-NYPHTF-KISGKER 73

                           90
                   ....*....|....*....
gi 2217298367  568 SIIFAAKSAEEKNNWMAAL 586
Cdd:cd13328     74 SLELQASSAEEKDEWIQAI 92
PH_PLEKHG1_G2_G3 cd13243
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ...
 456-583 3.02e-07

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270063 [Multi-domain]  Cd Length: 147  Bit Score: 51.20  E-value: 3.02e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  456 QLRSKHLAIKKMNEIQKNIDGWEGKDIgQCCNEFIMEGPLTRIGAKHERHIFLFDGLMISCKPNHGqtrlpgyssAEYRL 535
Cdd:cd13243     20 DMKRKHEHAVRVQEIQSLLDGWEGPEL-TTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITKKRED---------GILQY 89

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2217298367  536 KEKFVMRKIQIC---DKEDTcehkhAFELVSKDE--NSIIFAAKSAEEKNNWM 583
Cdd:cd13243     90 KTHIMCSNLMLSesiPKEPL-----SFQVLPFDNpkLQYTLQAKNQEQKRLWT 137
HFD_H2A cd00074
histone-fold domain found in histone H2A and similar proteins; Histone H2A is the core ...
 142-223 3.19e-07

histone-fold domain found in histone H2A and similar proteins; Histone H2A is the core component of the nucleosome, which wraps and compacts DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.


Pssm-ID: 467020  Cd Length: 89  Bit Score: 49.45  E-value: 3.19e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  142 EKRKRRNPLLLPVDKIHPSLKEvlgYKVDYHVS----LYIVAVLEYISADILKLAGNYVFNIRHYEISQQDIKVSMCADK 217
Cdd:cd00074      1 QSRSKRAGLQFPVGRIHRLLKK---GTYAKRVGagapVYLAAVLEYLTAEILELAGNAARDNKKKRITPRHIQLAIRNDE 77


                   ....*.
gi 2217298367  218 VLMDMF 223
Cdd:cd00074     78 ELNKLF 83
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
 489-586 5.01e-06

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269927 [Multi-domain]  Cd Length: 123  Bit Score: 47.25  E-value: 5.01e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  489 FIMEGPLT---RIGAKhERHIFLFDGLMI--SCKPNHGQtrlpgyssaeYRLKEKFVMRKIQICDKEDTCEHKHAFELVS 563
Cdd:cd01218     30 LVGEGVLTkvcRKKPK-PRQFFLFNDILVygSIVINKKK----------YNKQRIIPLEDVKIEDLEDTGELKNGWQIIS 98

                           90       100
                   ....*....|....*....|...
gi 2217298367  564 KDENSIIFAAkSAEEKNNWMAAL 586
Cdd:cd01218     99 PKKSFVVYAA-TATEKSEWMDHI 120
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
 488-586 5.22e-06

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275424  Cd Length: 124  Bit Score: 46.88  E-value: 5.22e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  488 EFIMEGPLTRIGAK--HERHIFLFDGLMISCKPNHgqtrlpgySSAEYRLKEKFVMRKIQICDKEDTcEHKHAFELVSkD 565
Cdd:cd13389     13 KLIKEGELMKVSRKemQPRYFFLFNDCLLYTTPVQ--------SSGMLKLNNELPLSGMKVKLPEDE-EYSNEFQIIS-T 82

                           90       100
                   ....*....|....*....|.
gi 2217298367  566 ENSIIFAAKSAEEKNNWMAAL 586
Cdd:cd13389     83 KRSFTLIASSEEERDEWVKAL 103
PH_Vav cd01223
Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) ...
 500-586 7.34e-06

Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) for Rho/Rac proteins. They control processes including T cell activation, phagocytosis, and migration of cells. The Vav subgroup of Dbl GEFs consists of three family members (Vav1, Vav2, and Vav3) in mammals. Vav1 is preferentially expressed in the hematopoietic system, while Vav2 and Vav3 are described by broader expression patterns. Mammalian Vav proteins consist of a calponin homology (CH) domain, an acidic region, a catalytic Dbl homology (DH) domain, a PH domain, a zinc finger cysteine rich domain (C1/CRD), and an SH2 domain, flanked by two SH3 domains. In invertebrates such as Drosophila and C. elegans, Vav is missing the N-terminal SH3 domain. The DH domain is involved in RhoGTPase recognition and selectivity and stimulates the reorganization of the switch regions for GDP/GTP exchange. The PH domain is implicated in directing membrane localization, allosteric regulation of guanine nucleotide exchange activity, and as a phospholipid- dependent regulator of GEF activity. Vavs bind RhoGTPases including Rac1, RhoA, RhoG, and Cdc42, while other members of the GEF family are specific for a single RhoGTPase. This promiscuity is thought to be a result of its CRD. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269930  Cd Length: 127  Bit Score: 46.86  E-value: 7.34e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  500 AKHERHIFLFDGLMISCKPNHGQTrlpgyssaeYRLKE-----KFVMRKIQICDK-EDTCEHKHAFELVSKDE-NSIIFA 572
Cdd:cd01223     34 KKKDRYAFLFDKVLLICKSLRGDQ---------YEYKEiinlsEYRIEDDPSRRTlKRDKRWSYQFLLVHKQGkTAYTLY 104

                           90
                   ....*....|....
gi 2217298367  573 AKSAEEKNNWMAAL 586
Cdd:cd01223    105 AKTEELKKKWMEAI 118
H2A smart00414
Histone 2A;
144-194 1.43e-04

Histone 2A;


Pssm-ID: 197711  Cd Length: 106  Bit Score: 42.32  E-value: 1.43e-04
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 2217298367   144 RKRRNPLLLPVDKIHPSLKE-VLGYKVDYHVSLYIVAVLEYISADILKLAGN 194
Cdd:smart00414    2 RSARAGLQFPVGRIHRLLRKgTYAKRVGAGAPVYLAAVLEYLTAEVLELAGN 53
PH1_FGD2 cd13386
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 2, N-terminal Pleckstrin ...
 489-585 3.41e-04

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 2, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275421  Cd Length: 108  Bit Score: 41.44  E-value: 3.41e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  489 FIMEGPLTRIGAKH----ERHIFLFDGLMISCKPNHGQTRlpgyssAEYRLKEKFVMRKIQICDKEDTcEHKHAFeLVSK 564
Cdd:cd13386      1 LLKEGPVLKISFRNnnpkERYLFLFNNMLLYCVPKVIQVG------AKFQVHMRIDVDGMKVRELNDA-EFPHSF-LVSG 72

                           90       100
                   ....*....|....*....|.
gi 2217298367  565 DENSIIFAAKSAEEKNNWMAA 585
Cdd:cd13386     73 KQRTLELQARSQEEMEAWIQA 93
HTA1 COG5262
Histone H2A [Chromatin structure and dynamics];
131-219 3.65e-04

Histone H2A [Chromatin structure and dynamics];


Pssm-ID: 227587 [Multi-domain]  Cd Length: 132  Bit Score: 42.16  E-value: 3.65e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  131 KWAIADAQSAIEKRKRRNPLLLPVDKIHPSLKEVLG-YKVDYHVSLYIVAVLEYISADILKLAGNYVFNIRHYEISQQDI 209
Cdd:COG5262      6 KGGKAADARVSQSRSAKAGLIFPVGRVKRLLKKGNYrMRIGAGAPVYLAAVLEYLAAEILELAGNAARDNKKKRIIPRHL 85

                           90
                   ....*....|
gi 2217298367  210 KVSMCADKVL 219
Cdd:COG5262     86 QLAIRNDEEL 95
PH1_FGD3 cd13387
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin ...
 489-583 4.44e-04

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275422  Cd Length: 108  Bit Score: 41.11  E-value: 4.44e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  489 FIMEGPLTRIGAKH----ERHIFLFDGLMISCKPnhgQTRLPGyssAEYRLKEKFVMRKIQICD--KEDTcehKHAFELV 562
Cdd:cd13387      1 LIKEGHIQKLSAKNgtaqDRYLYLFNSMVLYCVP---KLRLMG---QKFSVREKIDIAGMQVQEivKQNV---PHTFTIT 71

                           90       100
                   ....*....|....*....|.
gi 2217298367  563 SKdENSIIFAAKSAEEKNNWM 583
Cdd:cd13387     72 GK-KRSLELQARTEEEKKEWI 91
PTZ00017 PTZ00017
histone H2A; Provisional
 144-194 5.43e-04

histone H2A; Provisional


Pssm-ID: 185399  Cd Length: 134  Bit Score: 41.65  E-value: 5.43e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2217298367  144 RKRRNPLLLPVDKIHPSLKE-VLGYKVDYHVSLYIVAVLEYISADILKLAGN 194
Cdd:PTZ00017    20 RSAKAGLQFPVGRVHRYLKKgRYAKRVGAGAPVYLAAVLEYLTAEVLELAGN 71
PLN00154 PLN00154
histone H2A; Provisional
 144-219 5.88e-04

histone H2A; Provisional


Pssm-ID: 177756  Cd Length: 136  Bit Score: 41.47  E-value: 5.88e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2217298367  144 RKRRNPLLLPVDKIHPSLKEVL--GYKVDYHVSLYIVAVLEYISADILKLAGNYVFNIRHYEISQQDIKVSMCADKVL 219
Cdd:PLN00154    31 RSSRAGLQFPVGRIHRQLKQRVsaHGRVGATAAVYTAAILEYLTAEVLELAGNASKDLKVKRITPRHLQLAIRGDEEL 108
PH1_FDG4 cd15791
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin ...
 489-586 1.64e-03

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275434  Cd Length: 94  Bit Score: 39.21  E-value: 1.64e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  489 FIMEGPLTRIGAKH----ERHIFLFDGLMISCKPnhgQTRLPGyssAEYRLKEKFVMRKIQICDKEDTcEHKHAFElVSK 564
Cdd:cd15791      1 LIKEGQILKLAARNtsaqERYLFLFNNMLLYCVP---KFSLVG---SKYTVRTRIGIDGMKVVETQNE-DYPHTFQ-VSG 72

                           90       100
                   ....*....|....*....|..
gi 2217298367  565 DENSIIFAAKSAEEKNNWMAAL 586
Cdd:cd15791     73 KERTLELQASSEQDKEEWIKAL 94
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
 503-601 3.06e-03

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270061  Cd Length: 140  Bit Score: 39.55  E-value: 3.06e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  503 ERHIFLFDGLMISCKPNHGQTrlpGYSSAEYRLKEKFVMRKIQICDKEDTCEHKhaFELVSKDEN----SIIFAAKSAEE 578
Cdd:cd13241     38 ERRVFLFEQIIIFSEILGKKT---QFSNPGYIYKNHIKVNKMSLEENVDGDPLR--FALKSRDPNnpseTFILQAASPEV 112

                           90       100
                   ....*....|....*....|...
gi 2217298367  579 KNNWMaalislhyrSTLDRMLDS 601
Cdd:cd13241    113 RQEWV---------DTINQILDT 126
PH_Obscurin cd13239
Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; ...
 502-593 3.39e-03

Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270059  Cd Length: 125  Bit Score: 39.06  E-value: 3.39e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  502 HERHIFLFDGLMISCKPNhgqtRLPGYSSAEYRLKEKFVMRKIQICDKEDTCEhkHAFELVSKDENS---IIFAAKSAEE 578
Cdd:cd13239     37 HHRHVFLFKNCVVICKPK----RDSRTDTVTYVFKNKMKLSDIDVKDTVEGDD--RSFGLWHEHRGSvrkYTLQARSAII 110

                           90
                   ....*....|....*
gi 2217298367  579 KNNWMAALISLHYRS 593
Cdd:cd13239    111 KSSWLKDLRDLQQRL 125
PH1_FARP1-like cd01220
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
 488-586 8.62e-03

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269928  Cd Length: 109  Bit Score: 37.29  E-value: 8.62e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217298367  488 EFIMEGPLTRIGAK--HERHIFLF-DGLMISCKpnhGQTrlpgySSAEYRLKEKFVMRKIQICDKEDTCEHKHAFELVSK 564
Cdd:cd01220      7 EFIREGCLQKLSKKglQQRMFFLFsDVLLYTSR---SPT-----PSLQFKVHGQLPLRGLMVEESEPEWGVAHCFTIYGG 78

                           90       100
                   ....*....|....*....|..
gi 2217298367  565 DEnSIIFAAKSAEEKNNWMAAL 586
Cdd:cd01220     79 NR-ALTVAASSEEEKERWLEDL 99
 
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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