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Conserved domains on  [gi|153791628|ref|NP_001093325|]
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proto-oncogene DBL isoform a [Homo sapiens]

Protein Classification

SEC14 and RhoGEF domain-containing protein( domain architecture ID 11271239)

protein containing domains SEC14, SPEC, RhoGEF, and PH-like

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
740-871 2.37e-53

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd01227:

Pssm-ID: 473070 [Multi-domain]  Cd Length: 126  Bit Score: 182.01  E-value: 2.37e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 740 AINGYIGNLNELGKMIMQGGFSVWIGHKKGATKmkDLARFKPMQRHLFLYEKAIVFCKRRVESGEGsdryPSYSFKHCWK 819
Cdd:cd01227    1 AITGYDGNLGDLGKLLMQGSFNVWTEHKKGHTK--KLARFKPMQRHIFLYEKAVLFCKKRGENGEA----PSYSYKNSLN 74
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 153791628 820 MDEVGITEYVKGDNRKFEIWYGEKEEVYIVQASNVDVKMTWLKEIRNILLKQ 871
Cdd:cd01227   75 TTAVGLTENVKGDTKKFEIWLNGREEVFIIQAPTPEIKAAWVKAIRQVLLSQ 126
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
556-733 3.23e-49

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: 172.48  E-value: 3.23e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 556 KNHVLNELIQTERVYVRELYTVLLGYRAEMDNPEMfdlmpPLLRNKKDILFGNMAEIYEFHNdIFLSSLENC----AHAP 631
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELL-----PLSPEEVELLFGNIEEIYEFHR-IFLKSLEERveewDKSG 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 632 ERVGPCFLERKDDFQMYAKYCQNKPRSETIWRKY-SECAFFQECQRKLK---HRLRLDSYLLKPVQRITKYQLLLKELLK 707
Cdd:cd00160   75 PRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLkKFNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLK 154
                        170       180
                 ....*....|....*....|....*..
gi 153791628 708 YSKD-CEGSALLKKALDAMLDLLKSVN 733
Cdd:cd00160  155 HTPDgHEDREDLKKALEAIKEVASQVN 181
SEC14 smart00516
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ...
5-145 6.92e-23

Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


:

Pssm-ID: 214706 [Multi-domain]  Cd Length: 158  Bit Score: 96.21  E-value: 6.92e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628     5 AFLSGGRG--KDNAWIITFP--ENCNFRCIPEEVIAKVLTYLTSIARQNGSD---SRFTIILDRR-----LDTWSSLKIS 72
Cdd:smart00516   7 AYIPGGRGydKDGRPVLIERagRFDLKSVTLEELLRYLVYVLEKILQEEKKTggiEGFTVIFDLKglsmsNPDLSVLRKI 86
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 153791628    73 LQKISASFPGNLHLVLVLRPTSFLqRTFTDIGFWFSQEDFMLKLPVVMLSSVSDLLTYIDDKQLTPELGGTLQ 145
Cdd:smart00516  87 LKILQDHYPERLGKVYIINPPWFF-RVLWKIIKPFLDEKTREKIRFVGNDSKEELLEYIDKEQLPEELGGTLD 158
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
285-476 1.37e-08

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


:

Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 56.30  E-value: 1.37e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 285 QDFQQLVTEVEFLLNQQAELA---DVTGTIAQVKQKIKKLENLDENSQELLSKAQFVILHGHKLAANHHYALDLICQRCN 361
Cdd:cd00176    3 QQFLRDADELEAWLSEKEELLsstDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQERLE 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 362 ELRYLSDILVNEIKAKRIQLSRTFKMHKLLQQARQC---CDEGECLLANQEIDKfqSKEDAQKALQDIENFLEMaLPFIN 438
Cdd:cd00176   83 ELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLeqwLEEKEAALASEDLGK--DLESVEELLKKHKELEEE-LEAHE 159
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 153791628 439 YEPETLQYEFDVILSPELKVQMKTIQLKLENIRSIFEN 476
Cdd:cd00176  160 PRLKSLNELAEELLEEGHPDADEEIEEKLEELNERWEE 197
 
Name Accession Description Interval E-value
PH_Dbs cd01227
DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming ...
740-871 2.37e-53

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) 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. 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: 269934 [Multi-domain]  Cd Length: 126  Bit Score: 182.01  E-value: 2.37e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 740 AINGYIGNLNELGKMIMQGGFSVWIGHKKGATKmkDLARFKPMQRHLFLYEKAIVFCKRRVESGEGsdryPSYSFKHCWK 819
Cdd:cd01227    1 AITGYDGNLGDLGKLLMQGSFNVWTEHKKGHTK--KLARFKPMQRHIFLYEKAVLFCKKRGENGEA----PSYSYKNSLN 74
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 153791628 820 MDEVGITEYVKGDNRKFEIWYGEKEEVYIVQASNVDVKMTWLKEIRNILLKQ 871
Cdd:cd01227   75 TTAVGLTENVKGDTKKFEIWLNGREEVFIIQAPTPEIKAAWVKAIRQVLLSQ 126
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
556-733 3.23e-49

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: 172.48  E-value: 3.23e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 556 KNHVLNELIQTERVYVRELYTVLLGYRAEMDNPEMfdlmpPLLRNKKDILFGNMAEIYEFHNdIFLSSLENC----AHAP 631
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELL-----PLSPEEVELLFGNIEEIYEFHR-IFLKSLEERveewDKSG 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 632 ERVGPCFLERKDDFQMYAKYCQNKPRSETIWRKY-SECAFFQECQRKLK---HRLRLDSYLLKPVQRITKYQLLLKELLK 707
Cdd:cd00160   75 PRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLkKFNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLK 154
                        170       180
                 ....*....|....*....|....*..
gi 153791628 708 YSKD-CEGSALLKKALDAMLDLLKSVN 733
Cdd:cd00160  155 HTPDgHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
559-734 1.02e-46

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: 165.17  E-value: 1.02e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628   559 VLNELIQTERVYVRELYTVLLGYRAEMDNPEMFdlmppLLRNKKDILFGNMAEIYEFHNdIFLSSLENC----AHAPERV 634
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKL-----LSPNELETLFGNIEEIYEFHR-DFLDELEERieewDDSVERI 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628   635 GPCFLERKDDFQMYAKYCQNKPRSETIWRKYSEC----AFFQECQRKLKH-RLRLDSYLLKPVQRITKYQLLLKELLKYS 709
Cdd:smart00325  75 GDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNprfqKFLKEIESSPQCrRLTLESLLLKPVQRLTKYPLLLKELLKHT 154
                          170       180
                   ....*....|....*....|....*.
gi 153791628   710 K-DCEGSALLKKALDAMLDLLKSVND 734
Cdd:smart00325 155 PeDHEDREDLKKALKAIKELANQVNE 180
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
559-733 1.01e-42

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: 153.61  E-value: 1.01e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628  559 VLNELIQTERVYVRELYTVLLGYraemdnpeMFDLMPPLLRNKKDI--LFGNMAEIYEFHNDIFLSSLENCAHAPERVGP 636
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVF--------LPPNSKPLSESEEEIktIFSNIEEIYELHRQLLLEELLKEWISIQRIGD 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628  637 CFLERKDDFQMYAKYCQNKPRSETIWRKYSE-----CAFFQECQ-RKLKHRLRLDSYLLKPVQRITKYQLLLKELLKYSK 710
Cdd:pfam00621  73 IFLKFAPGFKVYSTYCSNYPKALKLLKKLLKknpkfRAFLEELEaNPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTP 152
                         170       180
                  ....*....|....*....|....
gi 153791628  711 DC-EGSALLKKALDAMLDLLKSVN 733
Cdd:pfam00621 153 PDhPDYEDLKKALEAIKEVAKQIN 176
SEC14 smart00516
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ...
5-145 6.92e-23

Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


Pssm-ID: 214706 [Multi-domain]  Cd Length: 158  Bit Score: 96.21  E-value: 6.92e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628     5 AFLSGGRG--KDNAWIITFP--ENCNFRCIPEEVIAKVLTYLTSIARQNGSD---SRFTIILDRR-----LDTWSSLKIS 72
Cdd:smart00516   7 AYIPGGRGydKDGRPVLIERagRFDLKSVTLEELLRYLVYVLEKILQEEKKTggiEGFTVIFDLKglsmsNPDLSVLRKI 86
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 153791628    73 LQKISASFPGNLHLVLVLRPTSFLqRTFTDIGFWFSQEDFMLKLPVVMLSSVSDLLTYIDDKQLTPELGGTLQ 145
Cdd:smart00516  87 LKILQDHYPERLGKVYIINPPWFF-RVLWKIIKPFLDEKTREKIRFVGNDSKEELLEYIDKEQLPEELGGTLD 158
CRAL_TRIO_2 pfam13716
Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain ...
18-148 7.36e-16

Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain family. This family includes ECM25 that contains a divergent CRAL-TRIO domain identified by Gallego and colleagues.


Pssm-ID: 463965 [Multi-domain]  Cd Length: 140  Bit Score: 75.44  E-value: 7.36e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628   18 IITFPENCNFRC-IPEEVIAKVLTYLTSIARQNGSDSRFTIILDRRLDT------WSSLKISLQKISASFPGNLHLVLVL 90
Cdd:pfam13716   4 VLVFISKLLPSRpASLDDLDRLLFYLLKTLSEKLKGKPFVVVVDHTGVTsenfpsLSFLKKAYDLLPRAFKKNLKAVYVV 83
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 153791628   91 RPTSFLQRTFTDIGFWFSQEDFMLKlpVVMLSSVSDLLTYIDDKQLTPELGGTLQYCH 148
Cdd:pfam13716  84 HPSTFLRTFLKTLGSLLGSKKLRKK--VHYVSSLSELWEGIDREQLPTELPGVLSYDE 139
SEC14 cd00170
Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory ...
4-143 1.13e-08

Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory proteins, such as S. cerevisiae phosphatidylinositol transfer protein (Sec14p), and in lipid regulated proteins such as RhoGAPs, RhoGEFs and neurofibromin (NF1). SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


Pssm-ID: 469559 [Multi-domain]  Cd Length: 156  Bit Score: 55.03  E-value: 1.13e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628   4 IAFLSGGRGKDNAWIITF-PENCNFRCIPEEVIAKVLTYLTSIARQNG--SDSRFTIILDRR------LDTWSSLKISLQ 74
Cdd:cd00170   10 GIGYLGGRDKEGRPVLVFrAGWDPPKLLDLEELLRYLVYLLEKALRELeeQVEGFVVIIDLKgfslsnLSDLSLLKKLLK 89
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 153791628  75 KISASFPGNLHLVLVLRPTSFLqRTFTDIGFWFSQEDFMLKLpVVMLSSVSDLLTYIDDKQLTPELGGT 143
Cdd:cd00170   90 ILQDHYPERLKKIYIVNAPWIF-SALWKIVKPFLSEKTRKKI-VFLGSDLEELLEYIDPDQLPKELGGT 156
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
285-476 1.37e-08

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 56.30  E-value: 1.37e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 285 QDFQQLVTEVEFLLNQQAELA---DVTGTIAQVKQKIKKLENLDENSQELLSKAQFVILHGHKLAANHHYALDLICQRCN 361
Cdd:cd00176    3 QQFLRDADELEAWLSEKEELLsstDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQERLE 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 362 ELRYLSDILVNEIKAKRIQLSRTFKMHKLLQQARQC---CDEGECLLANQEIDKfqSKEDAQKALQDIENFLEMaLPFIN 438
Cdd:cd00176   83 ELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLeqwLEEKEAALASEDLGK--DLESVEELLKKHKELEEE-LEAHE 159
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 153791628 439 YEPETLQYEFDVILSPELKVQMKTIQLKLENIRSIFEN 476
Cdd:cd00176  160 PRLKSLNELAEELLEEGHPDADEEIEEKLEELNERWEE 197
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
771-868 1.75e-07

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: 50.24  E-value: 1.75e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628   771 TKMKDLARFKPMQRHLFLYEKAIVFCKRRvesgegsDRYPSYSFKHCWKMDEVGITEYVKGDNRK----FEIWYGEKeEV 846
Cdd:smart00233   8 YKKSGGGKKSWKKRYFVLFNSTLLYYKSK-------KDKKSYKPKGSIDLSGCTVREAPDPDSSKkphcFEIKTSDR-KT 79
                           90       100
                   ....*....|....*....|..
gi 153791628   847 YIVQASNVDVKMTWLKEIRNIL 868
Cdd:smart00233  80 LLLQAESEEEREKWVEALRKAI 101
SPEC smart00150
Spectrin repeats;
281-381 1.30e-05

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 45.01  E-value: 1.30e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628   281 WKFEQDFQQL---VTEVEFLLNQQaelaDVTGTIAQVKQKIKKLENLDENSQELLSKAQFVILHGHKLAANHHYALDLIC 357
Cdd:smart00150   1 QQFLRDADELeawLEEKEQLLASE----DLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIE 76
                           90       100
                   ....*....|....*....|....
gi 153791628   358 QRCNELRYLSDILVNEIKAKRIQL 381
Cdd:smart00150  77 ERLEELNERWEELKELAEERRQKL 100
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
535-797 1.30e-04

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 46.04  E-value: 1.30e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628  535 QEKRS---SGPSSSLDNGNSLDVLKNHVLNELIQTERVYVRELYTVLLGYraeMDNPEMFDLMPPllRNKKDIL---FGN 608
Cdd:COG5422   461 EEKNLwtlSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTW---IKPLEESNIIPE--NARRNFIkhvFAN 535
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628  609 MAEIYEFhNDIFLSSL---ENCAHAPERVGPCFLERKDDFQMYAKYCQNKP----RSETiwRKYSECAFF------QECQ 675
Cdd:COG5422   536 INEIYAV-NSKLLKALtnrQCLSPIVNGIADIFLDYVPKFEPFIKYGASQPyakyEFER--EKSVNPNFArfdhevERLD 612
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628  676 RKLKHRLrlDSYLLKPVQRITKYQLLLKELLKYSK-DCEGSALLKKALDAMLDLLKSVN--------------DSMHQIA 740
Cdd:COG5422   613 ESRKLEL--DGYLTKPTTRLARYPLLLEEVLKFTDpDNPDTEDIPKVIDMLREFLSRLNfesgkaenrgdlfhLNQQLLF 690
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 153791628  741 INGYI--GNLNELGKMIMQGGFSVWIGHKKGATKMKDLarfkpmqrHLFLYEKAIVFCK 797
Cdd:COG5422   691 KPEYVnlGLNDEYRKIIFKGVLKRKAKSKTDGSLRGDI--------QFFLLDNMLLFCK 741
PH pfam00169
PH domain; PH stands for pleckstrin homology.
783-868 5.49e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 40.24  E-value: 5.49e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628  783 QRHLFLYEKAIVFCKRRvESGEGSDRYPSYSFKHCwKMDEVGITEYVKGDNrKFEIWYGEK--EEVYIVQASNVDVKMTW 860
Cdd:pfam00169  20 KRYFVLFDGSLLYYKDD-KSGKSKEPKGSISLSGC-EVVEVVASDSPKRKF-CFELRTGERtgKRTYLLQAESEEERKDW 96

                  ....*...
gi 153791628  861 LKEIRNIL 868
Cdd:pfam00169  97 IKAIQSAI 104
 
Name Accession Description Interval E-value
PH_Dbs cd01227
DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming ...
740-871 2.37e-53

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) 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. 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: 269934 [Multi-domain]  Cd Length: 126  Bit Score: 182.01  E-value: 2.37e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 740 AINGYIGNLNELGKMIMQGGFSVWIGHKKGATKmkDLARFKPMQRHLFLYEKAIVFCKRRVESGEGsdryPSYSFKHCWK 819
Cdd:cd01227    1 AITGYDGNLGDLGKLLMQGSFNVWTEHKKGHTK--KLARFKPMQRHIFLYEKAVLFCKKRGENGEA----PSYSYKNSLN 74
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 153791628 820 MDEVGITEYVKGDNRKFEIWYGEKEEVYIVQASNVDVKMTWLKEIRNILLKQ 871
Cdd:cd01227   75 TTAVGLTENVKGDTKKFEIWLNGREEVFIIQAPTPEIKAAWVKAIRQVLLSQ 126
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
556-733 3.23e-49

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: 172.48  E-value: 3.23e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 556 KNHVLNELIQTERVYVRELYTVLLGYRAEMDNPEMfdlmpPLLRNKKDILFGNMAEIYEFHNdIFLSSLENC----AHAP 631
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELL-----PLSPEEVELLFGNIEEIYEFHR-IFLKSLEERveewDKSG 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 632 ERVGPCFLERKDDFQMYAKYCQNKPRSETIWRKY-SECAFFQECQRKLK---HRLRLDSYLLKPVQRITKYQLLLKELLK 707
Cdd:cd00160   75 PRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLkKFNKFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLK 154
                        170       180
                 ....*....|....*....|....*..
gi 153791628 708 YSKD-CEGSALLKKALDAMLDLLKSVN 733
Cdd:cd00160  155 HTPDgHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
559-734 1.02e-46

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: 165.17  E-value: 1.02e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628   559 VLNELIQTERVYVRELYTVLLGYRAEMDNPEMFdlmppLLRNKKDILFGNMAEIYEFHNdIFLSSLENC----AHAPERV 634
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKL-----LSPNELETLFGNIEEIYEFHR-DFLDELEERieewDDSVERI 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628   635 GPCFLERKDDFQMYAKYCQNKPRSETIWRKYSEC----AFFQECQRKLKH-RLRLDSYLLKPVQRITKYQLLLKELLKYS 709
Cdd:smart00325  75 GDVFLKLEEFFKIYSEYCSNHPDALELLKKLKKNprfqKFLKEIESSPQCrRLTLESLLLKPVQRLTKYPLLLKELLKHT 154
                          170       180
                   ....*....|....*....|....*.
gi 153791628   710 K-DCEGSALLKKALDAMLDLLKSVND 734
Cdd:smart00325 155 PeDHEDREDLKKALKAIKELANQVNE 180
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
559-733 1.01e-42

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: 153.61  E-value: 1.01e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628  559 VLNELIQTERVYVRELYTVLLGYraemdnpeMFDLMPPLLRNKKDI--LFGNMAEIYEFHNDIFLSSLENCAHAPERVGP 636
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVF--------LPPNSKPLSESEEEIktIFSNIEEIYELHRQLLLEELLKEWISIQRIGD 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628  637 CFLERKDDFQMYAKYCQNKPRSETIWRKYSE-----CAFFQECQ-RKLKHRLRLDSYLLKPVQRITKYQLLLKELLKYSK 710
Cdd:pfam00621  73 IFLKFAPGFKVYSTYCSNYPKALKLLKKLLKknpkfRAFLEELEaNPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTP 152
                         170       180
                  ....*....|....*....|....
gi 153791628  711 DC-EGSALLKKALDAMLDLLKSVN 733
Cdd:pfam00621 153 PDhPDYEDLKKALEAIKEVAKQIN 176
PH_puratrophin-1 cd13242
Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell ...
747-871 7.93e-25

Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. 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: 270062  Cd Length: 136  Bit Score: 100.83  E-value: 7.93e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 747 NLNELGKMIMQGGFSVWIGHKKGatkmkdlarfkpmQRHLFLYEKAIVFCKRRVESGeGSDrypSYSFKHCWKMDEVGIT 826
Cdd:cd13242   22 NLKEQGQLLRQDEFLVWQGRKKC-------------LRHVFLFEDLILFSKPKKTPG-GKD---VYIYKHSIKTSDIGLT 84
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 153791628 827 EYVKGDNRKFEIWYGEKE--EVYIVQASNVDVKMTWLKEIRNILLKQ 871
Cdd:cd13242   85 ENVGDSGLKFEIWFRRRKarDTYILQATSPEIKQAWTSDIAKLLWKQ 131
SEC14 smart00516
Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain ...
5-145 6.92e-23

Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p); Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) and in RhoGAPs, RhoGEFs and the RasGAP, neurofibromin (NF1). Lipid-binding domain. The SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


Pssm-ID: 214706 [Multi-domain]  Cd Length: 158  Bit Score: 96.21  E-value: 6.92e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628     5 AFLSGGRG--KDNAWIITFP--ENCNFRCIPEEVIAKVLTYLTSIARQNGSD---SRFTIILDRR-----LDTWSSLKIS 72
Cdd:smart00516   7 AYIPGGRGydKDGRPVLIERagRFDLKSVTLEELLRYLVYVLEKILQEEKKTggiEGFTVIFDLKglsmsNPDLSVLRKI 86
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 153791628    73 LQKISASFPGNLHLVLVLRPTSFLqRTFTDIGFWFSQEDFMLKLPVVMLSSVSDLLTYIDDKQLTPELGGTLQ 145
Cdd:smart00516  87 LKILQDHYPERLGKVYIINPPWFF-RVLWKIIKPFLDEKTREKIRFVGNDSKEELLEYIDKEQLPEELGGTLD 158
PH_Obscurin cd13239
Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; ...
741-867 2.95e-20

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: 87.60  E-value: 2.95e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 741 INGYIGNLNELGKMIMQGGFSVWighkKGATKMKDLARfkPMQRHLFLYEKAIVFCKRRVESGEGSDrypSYSFKHCWKM 820
Cdd:cd13239    2 IENYPAPLQALGEPIRQGHFTVW----EEAPEVKTSSR--GHHRHVFLFKNCVVICKPKRDSRTDTV---TYVFKNKMKL 72
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 153791628 821 DEVGITEYVKGDNRKFEIWYGEKEEV--YIVQASNVDVKMTWLKEIRNI 867
Cdd:cd13239   73 SDIDVKDTVEGDDRSFGLWHEHRGSVrkYTLQARSAIIKSSWLKDLRDL 121
CRAL_TRIO_2 pfam13716
Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain ...
18-148 7.36e-16

Divergent CRAL/TRIO domain; This family includes divergent members of the CRAL-TRIO domain family. This family includes ECM25 that contains a divergent CRAL-TRIO domain identified by Gallego and colleagues.


Pssm-ID: 463965 [Multi-domain]  Cd Length: 140  Bit Score: 75.44  E-value: 7.36e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628   18 IITFPENCNFRC-IPEEVIAKVLTYLTSIARQNGSDSRFTIILDRRLDT------WSSLKISLQKISASFPGNLHLVLVL 90
Cdd:pfam13716   4 VLVFISKLLPSRpASLDDLDRLLFYLLKTLSEKLKGKPFVVVVDHTGVTsenfpsLSFLKKAYDLLPRAFKKNLKAVYVV 83
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 153791628   91 RPTSFLQRTFTDIGFWFSQEDFMLKlpVVMLSSVSDLLTYIDDKQLTPELGGTLQYCH 148
Cdd:pfam13716  84 HPSTFLRTFLKTLGSLLGSKKLRKK--VHYVSSLSELWEGIDREQLPTELPGVLSYDE 139
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
743-876 9.82e-16

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: 74.99  E-value: 9.82e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 743 GYIGNLNELGKMIMQGGFSVwighkkgaTKMKDLARFKPMQRHLFLYEKAIVFC-----KRRVESgegsdryPSYSFKHC 817
Cdd:cd13241    6 GFDGKITAQGKLLLQGTLLV--------SEPSAGLLQKGKERRVFLFEQIIIFSeilgkKTQFSN-------PGYIYKNH 70
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 153791628 818 WKMDEVGITEYVKGDNRKFEIW---YGEKEEVYIVQASNVDVKMTWLKEIRNILLKQQELLT 876
Cdd:cd13241   71 IKVNKMSLEENVDGDPLRFALKsrdPNNPSETFILQAASPEVRQEWVDTINQILDTQRDFLK 132
PH1_Kalirin_Trio_like cd13240
Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; ...
743-868 9.64e-15

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. 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.


Pssm-ID: 270060  Cd Length: 123  Bit Score: 71.65  E-value: 9.64e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 743 GYIGNLNELGKMIMQGGFSVWighkkgatKMKDLARfKPMQRHLFLYEKAIVFCKRrVESGEGSDRYpsySFKHCWKMDE 822
Cdd:cd13240    4 GCDEDLDSLGEVILQDSFQVW--------DPKQLIR-KGRERHVFLFELCLVFSKE-VKDSNGKSKY---IYKSRLMTSE 70
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 153791628 823 VGITEYVKGDNRKFEIWYGE---KEEVYIVQASNVDVKMTWLKEIRNIL 868
Cdd:cd13240   71 IGVTEHIEGDPCKFALWTGRvptSDNKIVLKASSLEVKQTWVKKLREVI 119
SEC14 cd00170
Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory ...
4-143 1.13e-08

Sec14p-like lipid-binding domain; Sec14p-like lipid-binding domains are found in secretory proteins, such as S. cerevisiae phosphatidylinositol transfer protein (Sec14p), and in lipid regulated proteins such as RhoGAPs, RhoGEFs and neurofibromin (NF1). SEC14 domain of Dbl is known to associate with G protein beta/gamma subunits.


Pssm-ID: 469559 [Multi-domain]  Cd Length: 156  Bit Score: 55.03  E-value: 1.13e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628   4 IAFLSGGRGKDNAWIITF-PENCNFRCIPEEVIAKVLTYLTSIARQNG--SDSRFTIILDRR------LDTWSSLKISLQ 74
Cdd:cd00170   10 GIGYLGGRDKEGRPVLVFrAGWDPPKLLDLEELLRYLVYLLEKALRELeeQVEGFVVIIDLKgfslsnLSDLSLLKKLLK 89
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 153791628  75 KISASFPGNLHLVLVLRPTSFLqRTFTDIGFWFSQEDFMLKLpVVMLSSVSDLLTYIDDKQLTPELGGT 143
Cdd:cd00170   90 ILQDHYPERLKKIYIVNAPWIF-SALWKIVKPFLSEKTRKKI-VFLGSDLEELLEYIDPDQLPKELGGT 156
SPEC cd00176
Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members ...
285-476 1.37e-08

Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; the repeats are independent folding units; tandem repeats are found in differing numbers and arrange in an antiparallel manner to form dimers; the repeats are defined by a characteristic tryptophan (W) residue in helix A and a leucine (L) at the carboxyl end of helix C and separated by a linker of 5 residues; two copies of the repeat are present here


Pssm-ID: 238103 [Multi-domain]  Cd Length: 213  Bit Score: 56.30  E-value: 1.37e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 285 QDFQQLVTEVEFLLNQQAELA---DVTGTIAQVKQKIKKLENLDENSQELLSKAQFVILHGHKLAANHHYALDLICQRCN 361
Cdd:cd00176    3 QQFLRDADELEAWLSEKEELLsstDYGDDLESVEALLKKHEALEAELAAHEERVEALNELGEQLIEEGHPDAEEIQERLE 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 362 ELRYLSDILVNEIKAKRIQLSRTFKMHKLLQQARQC---CDEGECLLANQEIDKfqSKEDAQKALQDIENFLEMaLPFIN 438
Cdd:cd00176   83 ELNQRWEELRELAEERRQRLEEALDLQQFFRDADDLeqwLEEKEAALASEDLGK--DLESVEELLKKHKELEEE-LEAHE 159
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 153791628 439 YEPETLQYEFDVILSPELKVQMKTIQLKLENIRSIFEN 476
Cdd:cd00176  160 PRLKSLNELAEELLEEGHPDADEEIEEKLEELNERWEE 197
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
771-868 1.75e-07

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: 50.24  E-value: 1.75e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628   771 TKMKDLARFKPMQRHLFLYEKAIVFCKRRvesgegsDRYPSYSFKHCWKMDEVGITEYVKGDNRK----FEIWYGEKeEV 846
Cdd:smart00233   8 YKKSGGGKKSWKKRYFVLFNSTLLYYKSK-------KDKKSYKPKGSIDLSGCTVREAPDPDSSKkphcFEIKTSDR-KT 79
                           90       100
                   ....*....|....*....|..
gi 153791628   847 YIVQASNVDVKMTWLKEIRNIL 868
Cdd:smart00233  80 LLLQAESEEEREKWVEALRKAI 101
SPEC smart00150
Spectrin repeats;
281-381 1.30e-05

Spectrin repeats;


Pssm-ID: 197544 [Multi-domain]  Cd Length: 101  Bit Score: 45.01  E-value: 1.30e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628   281 WKFEQDFQQL---VTEVEFLLNQQaelaDVTGTIAQVKQKIKKLENLDENSQELLSKAQFVILHGHKLAANHHYALDLIC 357
Cdd:smart00150   1 QQFLRDADELeawLEEKEQLLASE----DLGKDLESVEALLKKHEAFEAELEAHEERVEALNELGEQLIEEGHPDAEEIE 76
                           90       100
                   ....*....|....*....|....
gi 153791628   358 QRCNELRYLSDILVNEIKAKRIQL 381
Cdd:smart00150  77 ERLEELNERWEELKELAEERRQKL 100
PH_unc89 cd13325
unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest ...
746-866 1.11e-04

unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest isoform is composed of 53 immunoglobulin (Ig) domains, 2 Fn3 domains, a triplet of SH3, DH and PH domains at its N-terminus, and 2 protein kinase domains (PK1 and PK2) at its C-terminus. unc-89 mutants display disorganization of muscle A-bands, and usually lack M-lines. The COOH-terminal region of obscurin, the human homolog of unc89, interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin, a protein that connects the Z line to the M line in the sarcomere and contributes to the contraction of striated muscle. obscurin is also thought to be involved in Ca2+/calmodulin via its IQ domains, as well as G protein-coupled signal transduction in the sarcomere via its RhoGEF/DH domain. The DH-PH region of OBSCN and unc89, the C. elegans homolog, has exchange activity for RhoA and Rho-1 respectively, but not for the small GTPases homologous to Cdc42 or Rac. 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: 270134  Cd Length: 114  Bit Score: 42.72  E-value: 1.11e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 746 GNLNELGKMIMQGGFSVWIGhkkgatkmkdlaRFKPMQRHLFLYEKAIVFCK-RRVesgeGSDRyPSYSFKHCWKMDEVG 824
Cdd:cd13325    1 GNIHKLGRLLRHDWFTVTDG------------EGKAKERYLFLFKSRILITKvRRI----SEDR-SVFILKDIIRLPEVN 63
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 153791628 825 ITEYvKGDNRKFEIWYGEKE---EVYIVQASNVDVKMTWLKEIRN 866
Cdd:cd13325   64 VKQH-PDDERTFELQPKLPAfgiLPIDFKAHKDEIKDYWLNEIEE 107
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
535-797 1.30e-04

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 46.04  E-value: 1.30e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628  535 QEKRS---SGPSSSLDNGNSLDVLKNHVLNELIQTERVYVRELYTVLLGYraeMDNPEMFDLMPPllRNKKDIL---FGN 608
Cdd:COG5422   461 EEKNLwtlSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTW---IKPLEESNIIPE--NARRNFIkhvFAN 535
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628  609 MAEIYEFhNDIFLSSL---ENCAHAPERVGPCFLERKDDFQMYAKYCQNKP----RSETiwRKYSECAFF------QECQ 675
Cdd:COG5422   536 INEIYAV-NSKLLKALtnrQCLSPIVNGIADIFLDYVPKFEPFIKYGASQPyakyEFER--EKSVNPNFArfdhevERLD 612
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628  676 RKLKHRLrlDSYLLKPVQRITKYQLLLKELLKYSK-DCEGSALLKKALDAMLDLLKSVN--------------DSMHQIA 740
Cdd:COG5422   613 ESRKLEL--DGYLTKPTTRLARYPLLLEEVLKFTDpDNPDTEDIPKVIDMLREFLSRLNfesgkaenrgdlfhLNQQLLF 690
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 153791628  741 INGYI--GNLNELGKMIMQGGFSVWIGHKKGATKMKDLarfkpmqrHLFLYEKAIVFCK 797
Cdd:COG5422   691 KPEYVnlGLNDEYRKIIFKGVLKRKAKSKTDGSLRGDI--------QFFLLDNMLLFCK 741
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
771-864 4.94e-04

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: 40.22  E-value: 4.94e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 771 TKMKDLARFKPMQRHLFLYEKAIVFCKrrvesgegSDRYPSYSFKHCWKMDE-VGITEYVKGD-NRKFEIWYgEKEEVYI 848
Cdd:cd00821    6 LKRGGGGLKSWKKRWFVLFEGVLLYYK--------SKKDSSYKPKGSIPLSGiLEVEEVSPKErPHCFELVT-PDGRTYY 76
                         90
                 ....*....|....*.
gi 153791628 849 VQASNVDVKMTWLKEI 864
Cdd:cd00821   77 LQADSEEERQEWLKAL 92
PH pfam00169
PH domain; PH stands for pleckstrin homology.
783-868 5.49e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 40.24  E-value: 5.49e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628  783 QRHLFLYEKAIVFCKRRvESGEGSDRYPSYSFKHCwKMDEVGITEYVKGDNrKFEIWYGEK--EEVYIVQASNVDVKMTW 860
Cdd:pfam00169  20 KRYFVLFDGSLLYYKDD-KSGKSKEPKGSISLSGC-EVVEVVASDSPKRKF-CFELRTGERtgKRTYLLQAESEEERKDW 96

                  ....*...
gi 153791628  861 LKEIRNIL 868
Cdd:pfam00169  97 IKAIQSAI 104
PH_PLEKHG1_G2_G3 cd13243
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ...
783-870 1.54e-03

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: 40.03  E-value: 1.54e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 153791628 783 QRHLFLYEKAIVFCKRRVESGegsdrypsYSFKHCWKMDEVGITEYVKGDNRKFEIW-YGEKEEVYIVQASNVDVKMTWL 861
Cdd:cd13243   66 ERLLFLFDKMLLITKKREDGI--------LQYKTHIMCSNLMLSESIPKEPLSFQVLpFDNPKLQYTLQAKNQEQKRLWT 137

                 ....*....
gi 153791628 862 KEIRNILLK 870
Cdd:cd13243  138 QEIKRLILE 146
 
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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