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Conserved domains on  [gi|111154080|ref|NP_001036129|]
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pleckstrin homology domain-containing family G member 5 isoform a [Homo sapiens]

Protein Classification

pleckstrin homology domain-containing family G member 5( domain architecture ID 13018714)

pleckstrin homology domain-containing family G member 5 (PLEKHG5) functions as a guanine exchange factor (GEF) for RAB26 and thus regulates autophagy of synaptic vesicles in axon terminal of motoneurons

Gene Symbol:  PLEKHG5
Gene Ontology:  GO:0005085|GO:0051056|GO:0007266
PubMed:  11738596

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH_PLEKHG5_G6 cd13244
Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; ...
583-681 5.58e-51

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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: 270064  Cd Length: 100  Bit Score: 174.34  E-value: 5.58e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  583 RQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVK-KAERTRVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGA 661
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPVKrKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80
                          90       100
                  ....*....|....*....|
gi 111154080  662 YTFQASGQALCRGWVDTIYN 681
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIRK 100
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
340-527 3.13e-41

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: 149.37  E-value: 3.13e-41
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080    340 AVWELLHTEASYIRKLRVIINLFLCCLLnlQESGLLCEVEAERLFSNIPEIAQLHRRLWASvmapvLEKarRTRALLQPG 419
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLK--KELKLLSPNELETLFGNIEEIYEFHRDFLDE-----LEE--RIEEWDDSV 71
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080    420 DFL-KGFKMFGSLFKPYIRYCMEEEGCMEYMRGLlRDNDLFRAYITWAEKHPQCQRLKLSDMLAKPHQRLTKYPLLLKSV 498
Cdd:smart00325   72 ERIgDVFLKLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKEL 150
                           170       180       190
                    ....*....|....*....|....*....|
gi 111154080    499 LRKTE-EPRAKEAVVAMIGSVERFIHHVNA 527
Cdd:smart00325  151 LKHTPeDHEDREDLKKALKAIKELANQVNE 180
RBD_PLEKHG5 cd17068
Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 ...
74-147 4.28e-37

Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 (PLEKHG5) and similar proteins; PLEKHG5, is also termed PH domain-containing family G member 5, or guanine nucleotide exchange factor 720 (GEF720), Syx, or Tech, is a novel Dbl-like protein related to p115Rho-GEF. It functions as a Rho guanine nucleotide exchange factor directly activating RhoA in vivo and potentially involved in the control of neuronal cell differentiation. It also regulates the balance of the RhoA downstream effector Dia and ROCK activities to promote polarized-cancer-cell migration. Moreover, PLEKHG5 activates the nuclear factor kappaB (NFkappaB) signaling pathway. Mutations in the PLEKHG5 gene are relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and lower motor neuron disease (LMND).


:

Pssm-ID: 340588  Cd Length: 75  Bit Score: 133.47  E-value: 4.28e-37
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 111154080   74 KECFTLKFDLNVDIETEIVPAMKKKSLGEVLLPVFERKGIALGKVDIYLDQSNTPLSLTFEAYRFGGHYLRVKA 147
Cdd:cd17068     1 KECFTVKFDDDDDDDVEIVPAVKGKTLRDVLEPLLERRGLDLDRVNVFLDSSNTPLPLEFDTYFLGGHTLRVKA 74
 
Name Accession Description Interval E-value
PH_PLEKHG5_G6 cd13244
Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; ...
583-681 5.58e-51

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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: 270064  Cd Length: 100  Bit Score: 174.34  E-value: 5.58e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  583 RQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVK-KAERTRVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGA 661
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPVKrKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80
                          90       100
                  ....*....|....*....|
gi 111154080  662 YTFQASGQALCRGWVDTIYN 681
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIRK 100
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
340-527 3.13e-41

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: 149.37  E-value: 3.13e-41
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080    340 AVWELLHTEASYIRKLRVIINLFLCCLLnlQESGLLCEVEAERLFSNIPEIAQLHRRLWASvmapvLEKarRTRALLQPG 419
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLK--KELKLLSPNELETLFGNIEEIYEFHRDFLDE-----LEE--RIEEWDDSV 71
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080    420 DFL-KGFKMFGSLFKPYIRYCMEEEGCMEYMRGLlRDNDLFRAYITWAEKHPQCQRLKLSDMLAKPHQRLTKYPLLLKSV 498
Cdd:smart00325   72 ERIgDVFLKLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKEL 150
                           170       180       190
                    ....*....|....*....|....*....|
gi 111154080    499 LRKTE-EPRAKEAVVAMIGSVERFIHHVNA 527
Cdd:smart00325  151 LKHTPeDHEDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
337-526 2.33e-40

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: 147.06  E-value: 2.33e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  337 QQEAVWELLHTEASYIRKLRVIINLFLCCLLnlQESGLLCEVEAERLFSNIPEIAQLHRRLWASVMAPVLEKARRTRALl 416
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLD--KELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGPRI- 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  417 qpGDFLKGFKmfgSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKhpQCQRLKLSDMLAKPHQRLTKYPLLLK 496
Cdd:cd00160    78 --GDVFLKLA---PFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAES--ECGRLKLESLLLKPVQRLTKYPLLLK 150
                         170       180       190
                  ....*....|....*....|....*....|.
gi 111154080  497 SVLRKTEE-PRAKEAVVAMIGSVERFIHHVN 526
Cdd:cd00160   151 ELLKHTPDgHEDREDLKKALEAIKEVASQVN 181
RBD_PLEKHG5 cd17068
Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 ...
74-147 4.28e-37

Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 (PLEKHG5) and similar proteins; PLEKHG5, is also termed PH domain-containing family G member 5, or guanine nucleotide exchange factor 720 (GEF720), Syx, or Tech, is a novel Dbl-like protein related to p115Rho-GEF. It functions as a Rho guanine nucleotide exchange factor directly activating RhoA in vivo and potentially involved in the control of neuronal cell differentiation. It also regulates the balance of the RhoA downstream effector Dia and ROCK activities to promote polarized-cancer-cell migration. Moreover, PLEKHG5 activates the nuclear factor kappaB (NFkappaB) signaling pathway. Mutations in the PLEKHG5 gene are relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and lower motor neuron disease (LMND).


Pssm-ID: 340588  Cd Length: 75  Bit Score: 133.47  E-value: 4.28e-37
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 111154080   74 KECFTLKFDLNVDIETEIVPAMKKKSLGEVLLPVFERKGIALGKVDIYLDQSNTPLSLTFEAYRFGGHYLRVKA 147
Cdd:cd17068     1 KECFTVKFDDDDDDDVEIVPAVKGKTLRDVLEPLLERRGLDLDRVNVFLDSSNTPLPLEFDTYFLGGHTLRVKA 74
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
340-526 1.59e-34

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: 130.11  E-value: 1.59e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080   340 AVWELLHTEASYIRKLRVIINLFLCcllnlQESGLLCEVEAER--LFSNIPEIAQLHRRLWasvmapvLEKARRTRALLQ 417
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLP-----PNSKPLSESEEEIktIFSNIEEIYELHRQLL-------LEELLKEWISIQ 68
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080   418 P-GD-FLKgfkmFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKHPQCQRLKLSDMLAKPHQRLTKYPLLL 495
Cdd:pfam00621   69 RiGDiFLK----FAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLL 144
                          170       180       190
                   ....*....|....*....|....*....|..
gi 111154080   496 KSVLRKTEEPRA-KEAVVAMIGSVERFIHHVN 526
Cdd:pfam00621  145 KELLKHTPPDHPdYEDLKKALEAIKEVAKQIN 176
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
585-684 1.19e-06

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: 47.93  E-value: 1.19e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080    585 LLLEGSLRMKE--GKDSKMDVYCFLFTDLLLVTKAvKKAERTRVIRPPLLVDKIVCRELRD------PGSFLLIYLNEfh 656
Cdd:smart00233    1 VIKEGWLYKKSggGKKSWKKRYFVLFNSTLLYYKS-KKDKKSYKPKGSIDLSGCTVREAPDpdsskkPHCFEIKTSDR-- 77
                            90       100
                    ....*....|....*....|....*...
gi 111154080    657 savGAYTFQASGQALCRGWVDTIYNAQN 684
Cdd:smart00233   78 ---KTLLLQAESEEEREKWVEALRKAIA 102
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
328-617 2.08e-03

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 42.19  E-value: 2.08e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  328 EKLTRRQCHQQEAVWELLHTEASYIRKLRVIinlFLCCLLNLQESGLLCEVEAERL----FSNIPEIAQLHRRLwasvma 403
Cdd:COG5422   476 ESLPKQEIKRQEAIYEVIYTERDFVKDLEYL---RDTWIKPLEESNIIPENARRNFikhvFANINEIYAVNSKL------ 546
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  404 pvlEKARRTRALLQP-----GDFlkgFKMFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKHPQCQRLKLS 478
Cdd:COG5422   547 ---LKALTNRQCLSPivngiADI---FLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLELD 620
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  479 DMLAKPHQRLTKYPLLLKSVLRKTEEPRA-KEAVVAMIGSVERFIhhvnacmrqrqerqrlaavvSRIDayevVESSSDE 557
Cdd:COG5422   621 GYLTKPTTRLARYPLLLEEVLKFTDPDNPdTEDIPKVIDMLREFL--------------------SRLN----FESGKAE 676
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111154080  558 VDKLLKEFLHLDLTAPIPGASPE--ETRQLLLEGSLRMKE-GKDS---KMDVYCFLFTDLLLVTKA 617
Cdd:COG5422   677 NRGDLFHLNQQLLFKPEYVNLGLndEYRKIIFKGVLKRKAkSKTDgslRGDIQFFLLDNMLLFCKA 742
 
Name Accession Description Interval E-value
PH_PLEKHG5_G6 cd13244
Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; ...
583-681 5.58e-51

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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: 270064  Cd Length: 100  Bit Score: 174.34  E-value: 5.58e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  583 RQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVK-KAERTRVIRPPLLVDKIVCRELRDPGSFLLIYLNEFHSAVGA 661
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPVKrKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80
                          90       100
                  ....*....|....*....|
gi 111154080  662 YTFQASGQALCRGWVDTIYN 681
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIRK 100
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
340-527 3.13e-41

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: 149.37  E-value: 3.13e-41
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080    340 AVWELLHTEASYIRKLRVIINLFLCCLLnlQESGLLCEVEAERLFSNIPEIAQLHRRLWASvmapvLEKarRTRALLQPG 419
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLK--KELKLLSPNELETLFGNIEEIYEFHRDFLDE-----LEE--RIEEWDDSV 71
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080    420 DFL-KGFKMFGSLFKPYIRYCMEEEGCMEYMRGLlRDNDLFRAYITWAEKHPQCQRLKLSDMLAKPHQRLTKYPLLLKSV 498
Cdd:smart00325   72 ERIgDVFLKLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKEL 150
                           170       180       190
                    ....*....|....*....|....*....|
gi 111154080    499 LRKTE-EPRAKEAVVAMIGSVERFIHHVNA 527
Cdd:smart00325  151 LKHTPeDHEDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
337-526 2.33e-40

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: 147.06  E-value: 2.33e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  337 QQEAVWELLHTEASYIRKLRVIINLFLCCLLnlQESGLLCEVEAERLFSNIPEIAQLHRRLWASVMAPVLEKARRTRALl 416
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLD--KELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGPRI- 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  417 qpGDFLKGFKmfgSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKhpQCQRLKLSDMLAKPHQRLTKYPLLLK 496
Cdd:cd00160    78 --GDVFLKLA---PFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAES--ECGRLKLESLLLKPVQRLTKYPLLLK 150
                         170       180       190
                  ....*....|....*....|....*....|.
gi 111154080  497 SVLRKTEE-PRAKEAVVAMIGSVERFIHHVN 526
Cdd:cd00160   151 ELLKHTPDgHEDREDLKKALEAIKEVASQVN 181
RBD_PLEKHG5 cd17068
Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 ...
74-147 4.28e-37

Ras-binding domain (RBD) found in pleckstrin homology (PH) and RhoGEF domain containing G5 (PLEKHG5) and similar proteins; PLEKHG5, is also termed PH domain-containing family G member 5, or guanine nucleotide exchange factor 720 (GEF720), Syx, or Tech, is a novel Dbl-like protein related to p115Rho-GEF. It functions as a Rho guanine nucleotide exchange factor directly activating RhoA in vivo and potentially involved in the control of neuronal cell differentiation. It also regulates the balance of the RhoA downstream effector Dia and ROCK activities to promote polarized-cancer-cell migration. Moreover, PLEKHG5 activates the nuclear factor kappaB (NFkappaB) signaling pathway. Mutations in the PLEKHG5 gene are relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and lower motor neuron disease (LMND).


Pssm-ID: 340588  Cd Length: 75  Bit Score: 133.47  E-value: 4.28e-37
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 111154080   74 KECFTLKFDLNVDIETEIVPAMKKKSLGEVLLPVFERKGIALGKVDIYLDQSNTPLSLTFEAYRFGGHYLRVKA 147
Cdd:cd17068     1 KECFTVKFDDDDDDDVEIVPAVKGKTLRDVLEPLLERRGLDLDRVNVFLDSSNTPLPLEFDTYFLGGHTLRVKA 74
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
340-526 1.59e-34

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: 130.11  E-value: 1.59e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080   340 AVWELLHTEASYIRKLRVIINLFLCcllnlQESGLLCEVEAER--LFSNIPEIAQLHRRLWasvmapvLEKARRTRALLQ 417
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLP-----PNSKPLSESEEEIktIFSNIEEIYELHRQLL-------LEELLKEWISIQ 68
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080   418 P-GD-FLKgfkmFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKHPQCQRLKLSDMLAKPHQRLTKYPLLL 495
Cdd:pfam00621   69 RiGDiFLK----FAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLL 144
                          170       180       190
                   ....*....|....*....|....*....|..
gi 111154080   496 KSVLRKTEEPRA-KEAVVAMIGSVERFIHHVN 526
Cdd:pfam00621  145 KELLKHTPPDHPdYEDLKKALEAIKEVAKQIN 176
RBD cd01760
Ras-binding domain (RBD), structurally similar to a beta-grasp ubiquitin-like fold; The RBD of ...
75-147 6.81e-23

Ras-binding domain (RBD), structurally similar to a beta-grasp ubiquitin-like fold; The RBD of the serine/threonine kinase Raf is structurally similar to the beta-grasp fold of ubiquitin, a common structure involved in protein-protein interactions. Ubiquitin (Ub) is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. A Raf-like RBD is also present in Regulator of G protein Signaling (RGS12 and RGS14) members of GTPase activating proteins.


Pssm-ID: 340461  Cd Length: 71  Bit Score: 92.85  E-value: 6.81e-23
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 111154080   75 ECFTLKFdlnVDIETEIVPAMKK-KSLGEVLLPVFERKGIALGKVDIYLDQSNTPLSLTFEAYRFGGHYLRVKA 147
Cdd:cd01760     1 NTFRLFL---PNNETSVVVAVKPgKSLHEVLMPVLERHGLQLECVDVFLLGEKAPLDLNTDASSLIGQELRLDF 71
PH_PLEKHG7 cd13245
Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; ...
584-679 6.69e-11

Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; PLEKHG7 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG7 is proposed to functions as a guanine nucleotide exchange factor (GEF) and is involved in the regulation of Rho protein signal transduction. 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: 270065  Cd Length: 128  Bit Score: 60.75  E-value: 6.69e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  584 QLLLEGSLRMKE-GKdsKMDVYCFLFTDLLLVTK----AVKK-----------AERTRVI---------RPPLLVDKIVC 638
Cdd:cd13245     1 QLLHEGPLTLIEsGK--TLDVYLFLFDDMLLITKmkknLKKKkssdsensmpsLELTPLIkeggsytvyKQPIPLDRLCL 78
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 111154080  639 RELrDP---------GSFLLIYLNEFHSAVGAYTFQASGQALCRGWVDTI 679
Cdd:cd13245    79 HDV-DPneatanglkHAFVLVHLNRYQQVIGVYTLQASSENTKQTWMSKL 127
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
585-684 1.19e-06

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: 47.93  E-value: 1.19e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080    585 LLLEGSLRMKE--GKDSKMDVYCFLFTDLLLVTKAvKKAERTRVIRPPLLVDKIVCRELRD------PGSFLLIYLNEfh 656
Cdd:smart00233    1 VIKEGWLYKKSggGKKSWKKRYFVLFNSTLLYYKS-KKDKKSYKPKGSIDLSGCTVREAPDpdsskkPHCFEIKTSDR-- 77
                            90       100
                    ....*....|....*....|....*...
gi 111154080    657 savGAYTFQASGQALCRGWVDTIYNAQN 684
Cdd:smart00233   78 ---KTLLLQAESEEEREKWVEALRKAIA 102
PH_Net1 cd13224
Neuroepithelial cell transforming 1 Pleckstrin homology (PH) domain; Net1 (also called ArhGEF8) ...
580-685 2.05e-05

Neuroepithelial cell transforming 1 Pleckstrin homology (PH) domain; Net1 (also called ArhGEF8) is part of the family of Rho guanine nucleotide exchange factors. Members of this family activate Rho proteins by catalyzing the exchange of GDP for GTP. The protein encoded by this gene interacts with RhoA within the cell nucleus and may play a role in repairing DNA damage after ionizing radiation. Net1 binds to caspase activation and recruitment domain (CARD)- and membrane-associated guanylate kinase-like domain-containing (CARMA) proteins and regulates nuclear factor kB activation. Net1 contains a RhoGEF domain N-terminal to a single 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: 270044  Cd Length: 135  Bit Score: 45.28  E-value: 2.05e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  580 EETRQLLLEGSLRMKEGKDskmdVYCFLFTDLLLVTKAVKKAERT--RVIRPPLLVDKIVCRELRD-----PGSFLLIYL 652
Cdd:cd13224    15 ENSKALLCHGELRNKSGHK----LYVFLFQDILVLTRPVTRNERQsfQVYRQPIPVQELVLEDLQDgdvrmGGSFRGAFS 90
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 111154080  653 N----------EFH--SAVGAYTFQASGQALCRGWVDTIYNAQNQ 685
Cdd:cd13224    91 NsekaknifrvRFLdpSPGQSHTLQANDVFHKQQWLNCIRTAISP 135
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
587-679 2.40e-05

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: 43.69  E-value: 2.40e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  587 LEGSLRMKEGKDSK--MDVYCFLFTDLLLVTKAVKKA--ERTRVIRPPLLVDKIVCRELRDPGSFLLIylnefHSAVGAY 662
Cdd:cd00821     1 KEGYLLKRGGGGLKswKKRWFVLFEGVLLYYKSKKDSsyKPKGSIPLSGILEVEEVSPKERPHCFELV-----TPDGRTY 75
                          90
                  ....*....|....*..
gi 111154080  663 TFQASGQALCRGWVDTI 679
Cdd:cd00821    76 YLQADSEEERQEWLKAL 92
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
583-691 2.57e-04

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: 41.87  E-value: 2.57e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  583 RQLLLEGSLrMKEGKDSKMDVYCFLFTDLLLVTKAVKKAERTRVIRPPLLVDKIVCRELRDPgsflliYLNEFH--SAVG 660
Cdd:cd13389    12 RKLIKEGEL-MKVSRKEMQPRYFFLFNDCLLYTTPVQSSGMLKLNNELPLSGMKVKLPEDEE------YSNEFQiiSTKR 84
                          90       100       110
                  ....*....|....*....|....*....|.
gi 111154080  661 AYTFQASGQALCRGWVDTIYNAQNQLQQLRA 691
Cdd:cd13389    85 SFTLIASSEEERDEWVKALSRAIEEHTKKQR 115
PH_PLEKHG1_G2_G3 cd13243
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ...
585-679 4.71e-04

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: 41.57  E-value: 4.71e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  585 LLLEGSLRMKEGKDskmDVYCFLFTDLLLVTKavKKAERTRVIRppllvDKIVCREL-------RDPGSFLLIYLNEFHS 657
Cdd:cd13243    52 LVLEGTFRMAGAKN---ERLLFLFDKMLLITK--KREDGILQYK-----THIMCSNLmlsesipKEPLSFQVLPFDNPKL 121
                          90       100
                  ....*....|....*....|..
gi 111154080  658 avgAYTFQASGQALCRGWVDTI 679
Cdd:cd13243   122 ---QYTLQAKNQEQKRLWTQEI 140
PH_RARhoGAP cd13319
RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called ...
583-622 1.50e-03

RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called Rho GTPase-activating protein 20 and ARHGAP20 ) is thought to function in rearrangements of the cytoskeleton and cell signaling events that occur during spermatogenesis. RARhoGAP was also shown to be activated by Rap1 and to induce inactivation of Rho, resulting in the neurite outgrowth. Recent findings show that ARHGAP20, even although it is located in the middle of the MDR on 11q22-23, is expressed at higher levels in chronic lymphocytic leukemia patients with 11q22-23 and/or 13q14 deletions and its expression pattern suggests a functional link between cases with 11q22-23 and 13q14 deletions. The mechanism needs to be further studied. RARhoGAP contains a PH domain, a Ras-associating domain, a Rho-GAP domain, and ANXL repeats. 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: 270129  Cd Length: 97  Bit Score: 38.76  E-value: 1.50e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 111154080  583 RQLLLEGSLRMKEGKDSKmDVYCFLFTDLLLVTKAVKKAE 622
Cdd:cd13319     1 RTFLLEGPVQLTRGLQTQ-ERHLFLFSDVLVVAKPKSKNS 39
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
328-617 2.08e-03

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 42.19  E-value: 2.08e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  328 EKLTRRQCHQQEAVWELLHTEASYIRKLRVIinlFLCCLLNLQESGLLCEVEAERL----FSNIPEIAQLHRRLwasvma 403
Cdd:COG5422   476 ESLPKQEIKRQEAIYEVIYTERDFVKDLEYL---RDTWIKPLEESNIIPENARRNFikhvFANINEIYAVNSKL------ 546
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  404 pvlEKARRTRALLQP-----GDFlkgFKMFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKHPQCQRLKLS 478
Cdd:COG5422   547 ---LKALTNRQCLSPivngiADI---FLDYVPKFEPFIKYGASQPYAKYEFEREKSVNPNFARFDHEVERLDESRKLELD 620
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111154080  479 DMLAKPHQRLTKYPLLLKSVLRKTEEPRA-KEAVVAMIGSVERFIhhvnacmrqrqerqrlaavvSRIDayevVESSSDE 557
Cdd:COG5422   621 GYLTKPTTRLARYPLLLEEVLKFTDPDNPdTEDIPKVIDMLREFL--------------------SRLN----FESGKAE 676
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 111154080  558 VDKLLKEFLHLDLTAPIPGASPE--ETRQLLLEGSLRMKE-GKDS---KMDVYCFLFTDLLLVTKA 617
Cdd:COG5422   677 NRGDLFHLNQQLLFKPEYVNLGLndEYRKIIFKGVLKRKAkSKTDgslRGDIQFFLLDNMLLFCKA 742
PH_ephexin cd01221
Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine ...
573-622 3.82e-03

Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine nucleotide exchange factor) plays a role in the homeostatic modulation of presynaptic neurotransmitter release. Specific functions are still unknown for Ephexin-2 (also called RhoGEF19) and Ephexin-3 (also called Rho guanine nucleotide exchange factor 5/RhoGEF5, Transforming immortalized mammary oncogene/p60 TIM, and NGEF/neuronalGEF). Ephexin-4 (also called RhoGEF16) acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. This in turn results in the activation of RhoG which recruits ELMO2 and Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. Ephexin-5 is the specific GEF for RhoA activation and the regulation of vascular smooth muscle contractility. It interacts with EPHA4 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. The members of the Ephexin family contains a RhoGEF (DH) followed by a PH domain and an SH3 domain. The ephexin PH domain is believed to act with the DH domain in mediating protein-protein interactions. 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: 269929  Cd Length: 131  Bit Score: 38.39  E-value: 3.82e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 111154080  573 PIPGASPEetRQLLLEGSLRMKEGKD---------SKMDVYCFLFTDLLLVTKavKKAE 622
Cdd:cd01221     4 AFPLISSS--RWLVKRGELTELVEDGgsltfrkkfSKTPVYLFLFNDLLLITK--KKSE 58
 
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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