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Conserved domains on  [gi|2462515778|ref|XP_054195766|]
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rho guanine nucleotide exchange factor 11 isoform X12 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
RGS_PDZRhoGEF cd08753
Regulator of G protein signaling (RGS) domain found in the PDZ-Rho guanine nucleotide exchange ...
 330-474 1.19e-94

Regulator of G protein signaling (RGS) domain found in the PDZ-Rho guanine nucleotide exchange factor (RhoGEF) protein; The RGS domain is an essential part of the PDZ-RhoGEF (PDZ:Postsynaptic density 95, Disk large, Zona occludens-1; RhoGEF: Rho guanine nucleotide exchange factor; alias PRG) protein, a member of RhoGEFs subfamily of the RGS protein family. The RhoGEFs are peripheral membrane proteins that regulate essential cellular processes, including cell shape, cell migration, and cell cycle progression, as well as gene transcription by linking signals from heterotrimeric G-alpha12/13 protein-coupled receptors to Rho GTPase activation, leading to various cellular responses, such as actin reorganization and gene expression. RhoGEFs subfamily includes leukemia-associated RhoGEF protein (LARG), p115RhoGEF, PDZ-RhoGEF and its rat specific splice variant GTRAP48. The RGS domain of RhoGEFs has very little sequence similarity with the canonical RGS domain of the RGS proteins and is often refered to as RH (RGS Homology) domain. In contrast to p115RhoGEF and LARG, PDZ-RhoGEF cannot serve as a GTPase-activating protein (GAP), due to the mutation of sites in the RGS domain region that are crucial for GAP activity. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.


:

Pssm-ID: 188707  Cd Length: 145  Bit Score: 301.40  E-value: 1.19e-94
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  330 LIIGPEEDYDPGYFNNESDIIFQDLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFL 409
Cdd:cd08753      1 LIIGPEEDYDPGYFNNESDIIFQDLEKLKSRPAHLVVFLRYIFSQADPGPLLFYLCSEVYQQTSPKDSRSLGKDIWNIFL 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778  410 EKNAPLRVKIPEMLQAEIDSRLRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGEN 474
Cdd:cd08753     81 EKNAPLRVKIPEMLQAEIDLRLRNNEDPRGVLCEAQEAVMPEIQEQIQDYRSKRTLGLGSLYGEN 145
PH_PRG cd13391
PDZ Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; PRG (also called ...
 979-1121 2.71e-79

PDZ Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; PRG (also called RhoGEF11) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. RhoGEFs activate Rho GTPases regulating cytoskeletal structure, gene transcription, and cell migration. PRG contains an N-terminal PDZ domain, a regulators of G-protein signaling-like (RGSL) domain, a linker region, and a C-terminal Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. As is the case in p115-RhoGEF, it is thought that the PRG activated by relieving autoinhibition caused by the linker region. 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: 275426  Cd Length: 142  Bit Score: 257.65  E-value: 2.71e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  979 RLDATALERASNPLAAEFKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKTAVGSSDS 1058
Cdd:cd13391      1 RLDATALERASNPLAAEFKNLDLTTRRMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLVLKCHSKTAVGSSDS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515778 1059 KQTFSPVLKLNAVLIRSVATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELLEEAVRNA 1121
Cdd:cd13391     81 KQTFSPVLKLNSVLIRSVATDKRALFIICTSKLG-PQIYELVALTSSEKNTWMELLEEAVRNA 142
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 775-961 1.84e-52

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: 182.11  E-value: 1.84e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  775 RQEVINELFVTEASHLRTLRVLDLIFYQRMKKENL-MPREELARLFPNLPELIEIHNSWCEAMKKLREEGPIIKeisDLM 853
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSG---PRI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  854 LARFDGPAreELQQVAAQFCSYQSIALELIKTKQRKESRFQLFMQEAEShpQCRRLQLRDLIISEMQRLTKYPLLLESII 933
Cdd:cd00160     78 GDVFLKLA--PFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAES--ECGRLKLESLLLKPVQRLTKYPLLLKELL 153

                          170       180
                   ....*....|....*....|....*...
gi 2462515778  934 KHTEGGTSEHEKLCRARDQCREILKYVN 961
Cdd:cd00160    154 KHTPDGHEDREDLKKALEAIKEVASQVN 181
PDZ_ARHGEF11-12-like cd23069
PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density ...
 45-120 2.16e-44

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


:

Pssm-ID: 467282 [Multi-domain]  Cd Length: 76  Bit Score: 155.24  E-value: 2.16e-44
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462515778   45 QRCVIIQKDQHGFGFTVSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTLL 120
Cdd:cd23069      1 QRCVVIQRDENGYGLTVSGDNPVFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLEVVKLIKSGSYVALTLL 76
PHA03307 super family cl33723
transcriptional regulator ICP4; Provisional
 1239-1530 3.09e-05

transcriptional regulator ICP4; Provisional


The actual alignment was detected with superfamily member PHA03307:

Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 49.01  E-value: 3.09e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1239 DSALEDVENLRHLILWSLLPghTMETQAAQEPEDDlTPTPSVISVTSHPWDPGSPGQAPPGGEGDNTQLAGLEGERPEQE 1318
Cdd:PHA03307    75 PGTEAPANESRSTPTWSLST--LAPASPAREGSPT-PPGPSSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPGPPPAAS 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1319 DmglcSLEHLPPRTRNSGIWESPELDRNLAEDASSTEAaggykvvrkgncfyVSMPSGPPDSSTDHSEAPMSPPQPDS-L 1397
Cdd:PHA03307   152 P----PAAGASPAAVASDAASSRQAALPLSSPEETARA--------------PSSPPAEPPPSTPPAAASPRPPRRSSpI 213

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1398 PAGQTEPQPqLQGGNDDPRRPSRSPPSLALRDVGMIFHTIEQLTLKLNRLKDmeLAHRELLKSLGGESSGGTTPVGSFHT 1477
Cdd:PHA03307   214 SASASSPAP-APGRSAADDAGASSSDSSSSESSGCGWGPENECPLPRPAPIT--LPTRIWEASGWNGPSSRPGPASSSSS 290

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2462515778 1478 EAARWTDGSLSPPAKEPLASDSRNSHELGPCPEDGSDAPLEDSTADAAASPGP 1530
Cdd:PHA03307   291 PRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSP 343
 
Name Accession Description Interval E-value
RGS_PDZRhoGEF cd08753
Regulator of G protein signaling (RGS) domain found in the PDZ-Rho guanine nucleotide exchange ...
 330-474 1.19e-94

Regulator of G protein signaling (RGS) domain found in the PDZ-Rho guanine nucleotide exchange factor (RhoGEF) protein; The RGS domain is an essential part of the PDZ-RhoGEF (PDZ:Postsynaptic density 95, Disk large, Zona occludens-1; RhoGEF: Rho guanine nucleotide exchange factor; alias PRG) protein, a member of RhoGEFs subfamily of the RGS protein family. The RhoGEFs are peripheral membrane proteins that regulate essential cellular processes, including cell shape, cell migration, and cell cycle progression, as well as gene transcription by linking signals from heterotrimeric G-alpha12/13 protein-coupled receptors to Rho GTPase activation, leading to various cellular responses, such as actin reorganization and gene expression. RhoGEFs subfamily includes leukemia-associated RhoGEF protein (LARG), p115RhoGEF, PDZ-RhoGEF and its rat specific splice variant GTRAP48. The RGS domain of RhoGEFs has very little sequence similarity with the canonical RGS domain of the RGS proteins and is often refered to as RH (RGS Homology) domain. In contrast to p115RhoGEF and LARG, PDZ-RhoGEF cannot serve as a GTPase-activating protein (GAP), due to the mutation of sites in the RGS domain region that are crucial for GAP activity. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.


Pssm-ID: 188707  Cd Length: 145  Bit Score: 301.40  E-value: 1.19e-94
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  330 LIIGPEEDYDPGYFNNESDIIFQDLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFL 409
Cdd:cd08753      1 LIIGPEEDYDPGYFNNESDIIFQDLEKLKSRPAHLVVFLRYIFSQADPGPLLFYLCSEVYQQTSPKDSRSLGKDIWNIFL 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778  410 EKNAPLRVKIPEMLQAEIDSRLRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGEN 474
Cdd:cd08753     81 EKNAPLRVKIPEMLQAEIDLRLRNNEDPRGVLCEAQEAVMPEIQEQIQDYRSKRTLGLGSLYGEN 145
PH_PRG cd13391
PDZ Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; PRG (also called ...
 979-1121 2.71e-79

PDZ Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; PRG (also called RhoGEF11) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. RhoGEFs activate Rho GTPases regulating cytoskeletal structure, gene transcription, and cell migration. PRG contains an N-terminal PDZ domain, a regulators of G-protein signaling-like (RGSL) domain, a linker region, and a C-terminal Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. As is the case in p115-RhoGEF, it is thought that the PRG activated by relieving autoinhibition caused by the linker region. 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: 275426  Cd Length: 142  Bit Score: 257.65  E-value: 2.71e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  979 RLDATALERASNPLAAEFKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKTAVGSSDS 1058
Cdd:cd13391      1 RLDATALERASNPLAAEFKNLDLTTRRMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLVLKCHSKTAVGSSDS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515778 1059 KQTFSPVLKLNAVLIRSVATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELLEEAVRNA 1121
Cdd:cd13391     81 KQTFSPVLKLNSVLIRSVATDKRALFIICTSKLG-PQIYELVALTSSEKNTWMELLEEAVRNA 142
RGS-like pfam09128
Regulator of G protein signalling-like domain; Members of this family adopt a structure ...
 347-526 7.13e-78

Regulator of G protein signalling-like domain; Members of this family adopt a structure consisting of twelve helices that fold into a compact domain that contains the overall structural scaffold observed in other RGS proteins and three additional helical elements that pack closely to it. Helices 1-9 comprise the RGS (pfam00615) fold, in which helices 4-7 form a classic antiparallel bundle adjacent to the other helices. Like other RGS structures, helices 7 and 8 span the length of the folded domain and form essentially one continuous helix with a kink in the middle. Helices 10-12 form an apparently stable C-terminal extension of the structural domain, and although other RGS proteins lack this structure, these elements are intimately associated with the rest of the structural framework by hydrophobic interactions. Members of the family bind to active G-alpha proteins, promoting GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways.


Pssm-ID: 462687  Cd Length: 191  Bit Score: 255.50  E-value: 7.13e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  347 SDIIFQDLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFLEKNAPLRVKIPEMLQAE 426
Cdd:pfam09128    1 QCSCFQSLEQLKSRPAHLAVFLHHVVSQFDPSPLLCYLYADLYQQTNSKETRRVFLDIHNFFLEKNAPLRVPVPESVAAE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  427 ID---SRLRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGENDLLDLD-----GDPLRERQVAEKQLAALG 498
Cdd:pfam09128   81 LDrrrPELIPEDLHRRYIQTMQERAVPDIQRQLEDFRQKRSMGLTLAEGELSLLDAErdgdrGTLERERRVAEQILSKIE 160

                          170       180       190
                   ....*....|....*....|....*....|.
gi 2462515778  499 DIL---SKYEEDRSAPMDFALNTYMSHAGIR 526
Cdd:pfam09128  161 EILstsQTFDEERSATIQYVILTYMKHLGVR 191
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 775-961 1.84e-52

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: 182.11  E-value: 1.84e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  775 RQEVINELFVTEASHLRTLRVLDLIFYQRMKKENL-MPREELARLFPNLPELIEIHNSWCEAMKKLREEGPIIKeisDLM 853
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSG---PRI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  854 LARFDGPAreELQQVAAQFCSYQSIALELIKTKQRKESRFQLFMQEAEShpQCRRLQLRDLIISEMQRLTKYPLLLESII 933
Cdd:cd00160     78 GDVFLKLA--PFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAES--ECGRLKLESLLLKPVQRLTKYPLLLKELL 153

                          170       180
                   ....*....|....*....|....*...
gi 2462515778  934 KHTEGGTSEHEKLCRARDQCREILKYVN 961
Cdd:cd00160    154 KHTPDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 778-962 4.42e-52

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: 180.96  E-value: 4.42e-52
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   778 VINELFVTEASHLRTLRVLDLIFYQRMKKEN-LMPREELARLFPNLPELIEIHNSWCEAMKK-LREEGPIIKEISDLMLA 855
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFHRDFLDELEErIEEWDDSVERIGDVFLK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   856 RfdgparEELQQVAAQFCSYQSIALELIKtKQRKESRFQLFMQEAESHPQCRRLQLRDLIISEMQRLTKYPLLLESIIKH 935
Cdd:smart00325   81 L------EEFFKIYSEYCSNHPDALELLK-KLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKH 153

                           170       180
                    ....*....|....*....|....*..
gi 2462515778   936 TEGGTSEHEKLCRARDQCREILKYVNE 962
Cdd:smart00325  154 TPEDHEDREDLKKALKAIKELANQVNE 180
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 778-961 1.17e-47

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: 168.25  E-value: 1.17e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  778 VINELFVTEASHLRTLRVLDLIFYQRMKKENLMPREELARLFPNLPELIEIHNSwcEAMKKLREEGPIIKEISDLMLARF 857
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQ--LLLEELLKEWISIQRIGDIFLKFA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  858 DGpareelQQVAAQFCSYQSIALELIKTKQRKESRFQLFMQEAESHPQCRRLQLRDLIISEMQRLTKYPLLLESIIKHTE 937
Cdd:pfam00621   79 PG------FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTP 152

                          170       180
                   ....*....|....*....|....
gi 2462515778  938 GGTSEHEKLCRARDQCREILKYVN 961
Cdd:pfam00621  153 PDHPDYEDLKKALEAIKEVAKQIN 176
PDZ_ARHGEF11-12-like cd23069
PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density ...
 45-120 2.16e-44

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467282 [Multi-domain]  Cd Length: 76  Bit Score: 155.24  E-value: 2.16e-44
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462515778   45 QRCVIIQKDQHGFGFTVSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTLL 120
Cdd:cd23069      1 QRCVVIQRDENGYGLTVSGDNPVFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLEVVKLIKSGSYVALTLL 76
PH_16 pfam17838
PH domain;
990-1119 7.03e-44

PH domain;


Pssm-ID: 436083  Cd Length: 127  Bit Score: 155.64  E-value: 7.03e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  990 NPLAAEFKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSkTAVGSSDSKqTFSPVLKLN 1069
Cdd:pfam17838    1 HPLGEEFKKLDLTTRKLIHEGPLTWRNSKGKLVEVHALLLEDILVLLQEKDQKLVLACLS-TGSENVDQK-TQSPIISLK 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1070 AVLIRSVATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELLEEAVR 1119
Cdd:pfam17838   79 KLIVREVATDKKAFFLISTSPSD-PQMYELHASTKSERNTWTKLIQDAIE 127
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
 44-120 9.63e-19

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.


Pssm-ID: 214570 [Multi-domain]  Cd Length: 85  Bit Score: 82.04  E-value: 9.63e-19
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778    44 VQRCVIIQKDQHGFGFTVSGDRI----VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALT 118
Cdd:smart00228    1 EPRLVELEKGGGGLGFSLVGGKDegggVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKkAGGKVTLT 80


                    ..
gi 2462515778   119 LL 120
Cdd:smart00228   81 VL 82
RGS smart00315
Regulator of G protein signalling domain; RGS family members are GTPase-activating proteins ...
 353-457 9.23e-17

Regulator of G protein signalling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.


Pssm-ID: 214613  Cd Length: 118  Bit Score: 77.69  E-value: 9.23e-17
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   353 DLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQA-SPKDSRSLGKDIWNIFLEKNAPLRVKIPEMLQAEIDSRL 431
Cdd:smart00315    1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAeDDEERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                            90       100
                    ....*....|....*....|....*.
gi 2462515778   432 RNSEDARGVLCEAQEAAMPEIQEQIH 457
Cdd:smart00315   81 ESEEPPPDLFDEAQREVYELLEKDSF 106
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 756-1015 2.07e-15

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 82.25  E-value: 2.07e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  756 WQHTVGKDVVAGLTQREIDRQEVINELFVTEASHLRTLRVLDLIFYQRMKKENLMP---REELAR-LFPNLPELIEIHNS 831
Cdd:COG5422    466 WTLSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPenaRRNFIKhVFANINEIYAVNSK 545

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  832 WCEAMKKLREEGPIIKEISDLML---ARFDgpareelqqvaaQFCSY---QSIALELIKTKQRKESRFQLFMQEAESHPQ 905
Cdd:COG5422    546 LLKALTNRQCLSPIVNGIADIFLdyvPKFE------------PFIKYgasQPYAKYEFEREKSVNPNFARFDHEVERLDE 613

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  906 CRRLQLRDLIISEMQRLTKYPLLLESIIKHTEGGTSEHEKLCRARDQCREILKYVNEAVKQTENRHRLEGYQKRLDATAl 985
Cdd:COG5422    614 SRKLELDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFKP- 692

                          250       260       270
                   ....*....|....*....|....*....|
gi 2462515778  986 ERASNPLAAEFksldlttRKMIHEGPLTWR 1015
Cdd:COG5422    693 EYVNLGLNDEY-------RKIIFKGVLKRK 715
PDZ pfam00595
PDZ domain; PDZ domains are found in diverse signaling proteins.
 48-120 1.83e-14

PDZ domain; PDZ domains are found in diverse signaling proteins.


Pssm-ID: 395476 [Multi-domain]  Cd Length: 81  Bit Score: 70.00  E-value: 1.83e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQKD-QHGFGFTVSGDRI-----VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALTLL 120
Cdd:pfam00595    2 VTLEKDgRGGLGFSLKGGSDqgdpgIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKgSGGKVTLTIL 81
CtpA COG0793
C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, ...
 56-120 5.31e-10

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440556 [Multi-domain]  Cd Length: 341  Bit Score: 62.97  E-value: 5.31e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462515778   56 GFGFTVS-GDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI--KSGAYVALTLL 120
Cdd:COG0793     61 GLGAELGeEDGKVVVVSVIPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLLrgKAGTKVTLTIK 128
degP_htrA_DO TIGR02037
periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various ...
 67-120 1.07e-05

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]


Pssm-ID: 273938 [Multi-domain]  Cd Length: 428  Bit Score: 49.91  E-value: 1.07e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778   67 VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHL-EVVKLIKSGAYVALTLL 120
Cdd:TIGR02037  259 ALVAQVLPGSPAEKAGLKAGDVITSVNGKPISSFADLrRAIGTLKPGKKVTLGIL 313
PHA03307 PHA03307
transcriptional regulator ICP4; Provisional
 1239-1530 3.09e-05

transcriptional regulator ICP4; Provisional


Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 49.01  E-value: 3.09e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1239 DSALEDVENLRHLILWSLLPghTMETQAAQEPEDDlTPTPSVISVTSHPWDPGSPGQAPPGGEGDNTQLAGLEGERPEQE 1318
Cdd:PHA03307    75 PGTEAPANESRSTPTWSLST--LAPASPAREGSPT-PPGPSSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPGPPPAAS 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1319 DmglcSLEHLPPRTRNSGIWESPELDRNLAEDASSTEAaggykvvrkgncfyVSMPSGPPDSSTDHSEAPMSPPQPDS-L 1397
Cdd:PHA03307   152 P----PAAGASPAAVASDAASSRQAALPLSSPEETARA--------------PSSPPAEPPPSTPPAAASPRPPRRSSpI 213

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1398 PAGQTEPQPqLQGGNDDPRRPSRSPPSLALRDVGMIFHTIEQLTLKLNRLKDmeLAHRELLKSLGGESSGGTTPVGSFHT 1477
Cdd:PHA03307   214 SASASSPAP-APGRSAADDAGASSSDSSSSESSGCGWGPENECPLPRPAPIT--LPTRIWEASGWNGPSSRPGPASSSSS 290

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2462515778 1478 EAARWTDGSLSPPAKEPLASDSRNSHELGPCPEDGSDAPLEDSTADAAASPGP 1530
Cdd:PHA03307   291 PRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSP 343
PRK10779 PRK10779
sigma E protease regulator RseP;
63-98 8.58e-04

sigma E protease regulator RseP;


Pssm-ID: 182723 [Multi-domain]  Cd Length: 449  Bit Score: 43.52  E-value: 8.58e-04
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 2462515778   63 GDRI--VLVQsVRPGGAAMKAGVKEGDRIIKVNGTMVT 98
Cdd:PRK10779   218 GPQIepVLAE-VQPNSAASKAGLQAGDRIVKVDGQPLT 254
 
Name Accession Description Interval E-value
RGS_PDZRhoGEF cd08753
Regulator of G protein signaling (RGS) domain found in the PDZ-Rho guanine nucleotide exchange ...
 330-474 1.19e-94

Regulator of G protein signaling (RGS) domain found in the PDZ-Rho guanine nucleotide exchange factor (RhoGEF) protein; The RGS domain is an essential part of the PDZ-RhoGEF (PDZ:Postsynaptic density 95, Disk large, Zona occludens-1; RhoGEF: Rho guanine nucleotide exchange factor; alias PRG) protein, a member of RhoGEFs subfamily of the RGS protein family. The RhoGEFs are peripheral membrane proteins that regulate essential cellular processes, including cell shape, cell migration, and cell cycle progression, as well as gene transcription by linking signals from heterotrimeric G-alpha12/13 protein-coupled receptors to Rho GTPase activation, leading to various cellular responses, such as actin reorganization and gene expression. RhoGEFs subfamily includes leukemia-associated RhoGEF protein (LARG), p115RhoGEF, PDZ-RhoGEF and its rat specific splice variant GTRAP48. The RGS domain of RhoGEFs has very little sequence similarity with the canonical RGS domain of the RGS proteins and is often refered to as RH (RGS Homology) domain. In contrast to p115RhoGEF and LARG, PDZ-RhoGEF cannot serve as a GTPase-activating protein (GAP), due to the mutation of sites in the RGS domain region that are crucial for GAP activity. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.


Pssm-ID: 188707  Cd Length: 145  Bit Score: 301.40  E-value: 1.19e-94
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  330 LIIGPEEDYDPGYFNNESDIIFQDLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFL 409
Cdd:cd08753      1 LIIGPEEDYDPGYFNNESDIIFQDLEKLKSRPAHLVVFLRYIFSQADPGPLLFYLCSEVYQQTSPKDSRSLGKDIWNIFL 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778  410 EKNAPLRVKIPEMLQAEIDSRLRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGEN 474
Cdd:cd08753     81 EKNAPLRVKIPEMLQAEIDLRLRNNEDPRGVLCEAQEAVMPEIQEQIQDYRSKRTLGLGSLYGEN 145
PH_PRG cd13391
PDZ Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; PRG (also called ...
 979-1121 2.71e-79

PDZ Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; PRG (also called RhoGEF11) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. RhoGEFs activate Rho GTPases regulating cytoskeletal structure, gene transcription, and cell migration. PRG contains an N-terminal PDZ domain, a regulators of G-protein signaling-like (RGSL) domain, a linker region, and a C-terminal Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. As is the case in p115-RhoGEF, it is thought that the PRG activated by relieving autoinhibition caused by the linker region. 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: 275426  Cd Length: 142  Bit Score: 257.65  E-value: 2.71e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  979 RLDATALERASNPLAAEFKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKTAVGSSDS 1058
Cdd:cd13391      1 RLDATALERASNPLAAEFKNLDLTTRRMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLVLKCHSKTAVGSSDS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515778 1059 KQTFSPVLKLNAVLIRSVATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELLEEAVRNA 1121
Cdd:cd13391     81 KQTFSPVLKLNSVLIRSVATDKRALFIICTSKLG-PQIYELVALTSSEKNTWMELLEEAVRNA 142
RGS-like pfam09128
Regulator of G protein signalling-like domain; Members of this family adopt a structure ...
 347-526 7.13e-78

Regulator of G protein signalling-like domain; Members of this family adopt a structure consisting of twelve helices that fold into a compact domain that contains the overall structural scaffold observed in other RGS proteins and three additional helical elements that pack closely to it. Helices 1-9 comprise the RGS (pfam00615) fold, in which helices 4-7 form a classic antiparallel bundle adjacent to the other helices. Like other RGS structures, helices 7 and 8 span the length of the folded domain and form essentially one continuous helix with a kink in the middle. Helices 10-12 form an apparently stable C-terminal extension of the structural domain, and although other RGS proteins lack this structure, these elements are intimately associated with the rest of the structural framework by hydrophobic interactions. Members of the family bind to active G-alpha proteins, promoting GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways.


Pssm-ID: 462687  Cd Length: 191  Bit Score: 255.50  E-value: 7.13e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  347 SDIIFQDLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFLEKNAPLRVKIPEMLQAE 426
Cdd:pfam09128    1 QCSCFQSLEQLKSRPAHLAVFLHHVVSQFDPSPLLCYLYADLYQQTNSKETRRVFLDIHNFFLEKNAPLRVPVPESVAAE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  427 ID---SRLRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGENDLLDLD-----GDPLRERQVAEKQLAALG 498
Cdd:pfam09128   81 LDrrrPELIPEDLHRRYIQTMQERAVPDIQRQLEDFRQKRSMGLTLAEGELSLLDAErdgdrGTLERERRVAEQILSKIE 160

                          170       180       190
                   ....*....|....*....|....*....|.
gi 2462515778  499 DIL---SKYEEDRSAPMDFALNTYMSHAGIR 526
Cdd:pfam09128  161 EILstsQTFDEERSATIQYVILTYMKHLGVR 191
RGS_RhoGEF-like cd08736
Regulator of G protein signaling (RGS) domain found in the Rho guanine nucleotide exchange ...
 358-474 1.73e-57

Regulator of G protein signaling (RGS) domain found in the Rho guanine nucleotide exchange factor (RhoGEF) protein; The RGS domain found in the Rho guanine nucleotide exchange factor (RhoGEF) protein subfamily of the RGS domain containing protein family, which is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RhoGEFs link signals from heterotrimeric G-alpha12/13 protein-coupled receptors to Rho GTPase activation, leading to various cellular responses, such as actin reorganization and gene expression. The RGS domain of the RhoGEFs has very little sequence similarity with the canonical RGS domain of the RGS proteins and therefore is often refered to as the RH (RGS Homology) domain. The RGS-GEFs subfamily includes the leukemia-associated RhoGEF (LARG), p115RhoGEF, and PDZ-RhoGEF. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.


Pssm-ID: 188690  Cd Length: 120  Bit Score: 194.01  E-value: 1.73e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  358 KSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFLEKNAPLRVKIPEMLQAEIDSRLRNS--- 434
Cdd:cd08736      1 KSRPAHLAVFLHYVLSQFDPSPLLFYLITDLYKQGNPKDMRKWAYEIYSTFLEKNAPLKVKVPESLAAEIDKRLPNLide 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 2462515778  435 EDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGEN 474
Cdd:cd08736     81 EDLRRVFQEAQERAMPEIQEQLEDFRQKRTMGLGSLEGEL 120
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 775-961 1.84e-52

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: 182.11  E-value: 1.84e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  775 RQEVINELFVTEASHLRTLRVLDLIFYQRMKKENL-MPREELARLFPNLPELIEIHNSWCEAMKKLREEGPIIKeisDLM 853
Cdd:cd00160      1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLpLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSG---PRI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  854 LARFDGPAreELQQVAAQFCSYQSIALELIKTKQRKESRFQLFMQEAEShpQCRRLQLRDLIISEMQRLTKYPLLLESII 933
Cdd:cd00160     78 GDVFLKLA--PFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAES--ECGRLKLESLLLKPVQRLTKYPLLLKELL 153

                          170       180
                   ....*....|....*....|....*...
gi 2462515778  934 KHTEGGTSEHEKLCRARDQCREILKYVN 961
Cdd:cd00160    154 KHTPDGHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 778-962 4.42e-52

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: 180.96  E-value: 4.42e-52
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   778 VINELFVTEASHLRTLRVLDLIFYQRMKKEN-LMPREELARLFPNLPELIEIHNSWCEAMKK-LREEGPIIKEISDLMLA 855
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELkLLSPNELETLFGNIEEIYEFHRDFLDELEErIEEWDDSVERIGDVFLK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   856 RfdgparEELQQVAAQFCSYQSIALELIKtKQRKESRFQLFMQEAESHPQCRRLQLRDLIISEMQRLTKYPLLLESIIKH 935
Cdd:smart00325   81 L------EEFFKIYSEYCSNHPDALELLK-KLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKH 153

                           170       180
                    ....*....|....*....|....*..
gi 2462515778   936 TEGGTSEHEKLCRARDQCREILKYVNE 962
Cdd:smart00325  154 TPEDHEDREDLKKALKAIKELANQVNE 180
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 778-961 1.17e-47

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: 168.25  E-value: 1.17e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  778 VINELFVTEASHLRTLRVLDLIFYQRMKKENLMPREELARLFPNLPELIEIHNSwcEAMKKLREEGPIIKEISDLMLARF 857
Cdd:pfam00621    1 VIKELLQTERSYVRDLEILVEVFLPPNSKPLSESEEEIKTIFSNIEEIYELHRQ--LLLEELLKEWISIQRIGDIFLKFA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  858 DGpareelQQVAAQFCSYQSIALELIKTKQRKESRFQLFMQEAESHPQCRRLQLRDLIISEMQRLTKYPLLLESIIKHTE 937
Cdd:pfam00621   79 PG------FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTP 152

                          170       180
                   ....*....|....*....|....
gi 2462515778  938 GGTSEHEKLCRARDQCREILKYVN 961
Cdd:pfam00621  153 PDHPDYEDLKKALEAIKEVAKQIN 176
PH_LARG cd13390
Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; ...
 981-1114 1.38e-46

Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; LARG (also called RhoGEF12) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. RhoGEFs activate Rho GTPases regulating cytoskeletal structure, gene transcription, and cell migration. LARG contains a N-terminal extension, followed by Dbl homology (DH)-PH domains which bind and catalyze the exchange of GDP for GTP on RhoA in addition to a RGS domain. The active site of RhoA adopts two distinct GDP-excluding conformations among the four unique complexes in the asymmetric unit. The LARG PH domain also contains a potential protein-docking site. LARG forms a homotetramer via its DH domains. 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: 275425  Cd Length: 138  Bit Score: 163.62  E-value: 1.38e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  981 DATALERASNPLAAEFKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKTAVGSSDSKQ 1060
Cdd:cd13390      1 DLSSLKQSEYPMIDELRNLDLTKRKMIHEGPLTWKVNRDKTIDLYTLLLEDILVLLQKQDDRLVLRCHSKILASTADSKH 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2462515778 1061 TFSPVLKLNAVLIRSVATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELL 1114
Cdd:cd13390     81 TFSPVIKLNTVLVRQVATDNKAFFVISMSENG-AQIYELVAQTVSEKTVWQDLI 133
PDZ_ARHGEF11-12-like cd23069
PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density ...
 45-120 2.16e-44

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467282 [Multi-domain]  Cd Length: 76  Bit Score: 155.24  E-value: 2.16e-44
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462515778   45 QRCVIIQKDQHGFGFTVSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTLL 120
Cdd:cd23069      1 QRCVVIQRDENGYGLTVSGDNPVFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLEVVKLIKSGSYVALTLL 76
PH_16 pfam17838
PH domain;
990-1119 7.03e-44

PH domain;


Pssm-ID: 436083  Cd Length: 127  Bit Score: 155.64  E-value: 7.03e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  990 NPLAAEFKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSkTAVGSSDSKqTFSPVLKLN 1069
Cdd:pfam17838    1 HPLGEEFKKLDLTTRKLIHEGPLTWRNSKGKLVEVHALLLEDILVLLQEKDQKLVLACLS-TGSENVDQK-TQSPIISLK 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1070 AVLIRSVATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELLEEAVR 1119
Cdd:pfam17838   79 KLIVREVATDKKAFFLISTSPSD-PQMYELHASTKSERNTWTKLIQDAIE 127
PH_p115RhoGEF cd14679
Rho guanine nucleotide exchange factor Pleckstrin homology domain; p115RhoGEF (also called LSC, ...
 996-1118 7.04e-40

Rho guanine nucleotide exchange factor Pleckstrin homology domain; p115RhoGEF (also called LSC, GEF1 or LBCL2) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. In addition to the Dbl homology (DH)-PH domain, p115RhoGEF contains an N-terminal RGS (Regulator of G-protein signalling) domain. The DH-PH domains bind and catalyze the exchange of GDP for GTP on RhoA. 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: 275429  Cd Length: 125  Bit Score: 144.21  E-value: 7.04e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  996 FKSLDLTTRKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKTAVGSSDSKQTFSPVLKLNAVLIRS 1075
Cdd:cd14679      1 FKNIDITKKKLVHEGPLTWRVTKDKAIEVHVLLLDDLLVLLQKQDERLVLKCHSRTTTPTPDGKQMLSPIIKLNSAMTRE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2462515778 1076 VATDKRAFFIICTSKLGpPQIYELVALTSSDKNTWMELLEEAV 1118
Cdd:cd14679     81 VATDRKAFYVIFTWEQG-AQIYELVAQTVSERKNWCALISETA 122
PH_RhoGEF cd13329
Rho guanine nucleotide exchange factor Pleckstrin homology domain; RhoGEFs belongs to ...
 1006-1118 5.99e-37

Rho guanine nucleotide exchange factor Pleckstrin homology domain; RhoGEFs belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. The members here all contain Dbl homology (DH)-PH domains. In addition some members contain N-terminal C1 (Protein kinase C conserved region 1) domains, PDZ (also called DHR/Dlg homologous regions) domains, ANK (ankyrin) domains, and RGS (Regulator of G-protein signalling) domains or C-terminal ATP-synthase B subunit. The DH-PH domains bind and catalyze the exchange of GDP for GTP on RhoA. RhoGEF2/Rho guanine nucleotide exchange factor 2, p114RhoGEF/p114 Rho guanine nucleotide exchange factor, p115RhoGEF, p190RhoGEF, PRG/PDZ Rho guanine nucleotide exchange factor, RhoGEF 11, RhoGEF 12, RhoGEF 18, AKAP13/A-kinase anchoring protein 13, and LARG/Leukemia-associated Rho guanine nucleotide exchange factor are included in this CD. 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: 275411  Cd Length: 109  Bit Score: 135.08  E-value: 5.99e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1006 MIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSktaVGSSDSKQTFSPVLKLNAVLIRSVATDKRAFFI 1085
Cdd:cd13329      1 LIHEGPLTWKVARGKLIEVHVLLLEDLLVLLQKQDDKYLLKLHL---TGSFDSKDTKSPVIKLSTLLVREVATDKKAFFL 77

                           90       100       110
                   ....*....|....*....|....*....|...
gi 2462515778 1086 ICTSKLGpPQIYELVALTSSDKNTWMELLEEAV 1118
Cdd:cd13329     78 ISTSKNG-PQMYELVANSSSERKTWIKHISDAV 109
RGS_LARG cd08754
Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine ...
 331-531 9.11e-35

Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG); The RGS domain is an essential part of the leukemia-associated RhoGEF protein (LARG), a member of the RhoGEF (Rho guanine nucleotide exchange factor) subfamily of the RGS protein family. The RhoGEFs are peripheral membrane proteins that regulate essential cellular processes, including cell shape, cell migration, cell cycle progression of cells, and gene transcription by linking signals from heterotrimeric G-alpha12/13 protein-coupled receptors to Rho GTPase activation, leading to various cellular responses, such as actin reorganization and gene expression. The RhoGEF subfamily includes p115RhoGEF, LARG, PDZ-RhoGEF, and its rat specific splice variant GTRAP48. The RGS domain of RhoGEFs has very little sequence similarity with the canonical RGS domain of the RGS proteins and is often refered to as RH (RGS Homology) domain. In addition to being a G-alpha13 effector, the LARG protein also functions as a GTPase-activating protein (GAP) for G-alpha13. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.


Pssm-ID: 188708  Cd Length: 222  Bit Score: 133.20  E-value: 9.11e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  331 IIGPEEDYdpgyFNNESDII------FQDLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDI 404
Cdd:cd08754      2 IIGAEDDD----FPTESEQIngqcscFQNIELLKSRPAHLAVFLHHVVSQFDPAALLCYLYADLYKQTNSKETRRVFLEF 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  405 WNIFLEKNAPLRVKIPEMLQAEIDSR---LRNSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGENDLLDLDG 481
Cdd:cd08754     78 NQFFLDRAANLKVPVPDEVSLDLEKRrpeLIPEELHRHYIQTMQERVSPEVQRNLEDFRQKRSMGLTLAEGELTKLDAER 157

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2462515778  482 DPLR-----ERQVAEKQLAALGDIL---SKYEEDRSAPMDFALNTYMSHAGIRLREAR 531
Cdd:cd08754    158 FRDRntiekERACAEQIVAKIEEVLmtsQTPEEDKSSTIQYVILTYMKHLGVKVKEPR 215
RGS_GEF_like cd08756
Regulator of G protein signaling (RGS) domain found in the Rho guanine nucleotide exchange ...
 358-474 7.66e-30

Regulator of G protein signaling (RGS) domain found in the Rho guanine nucleotide exchange factor (RhoGEF) protein; The RGS domain found in the Rho guanine nucleotide exchange factor (RhoGEF) protein subfamily of the RGS domain containing protein family, which is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). The RhoGEFs are peripheral membrane proteins that regulate essential cellular processes, including cell shape, cell migration and cell cycle progression as well as gene transcription by linking signals from heterotrimeric G-alpha12/13 protein-coupled receptors to Rho GTPase activation, leading to various cellular responses, such as actin reorganization and gene expression. The RhoGEF subfamily includes the leukemia-associated RhoGEF protein (LARG), p115RhoGEF, PDZ-RhoGEF, and its rat specific splice variant GTRAP48. The RGS domain of RhoGEFs has very little sequence similarity with the canonical RGS domain of the RGS proteins and is often refered to as RH (RGS Homology) domain. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.


Pssm-ID: 188710  Cd Length: 122  Bit Score: 115.18  E-value: 7.66e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  358 KSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFLEKNAPL-RVKIPEMLQAEIDSRLRNS-- 434
Cdd:cd08756      1 KTHPAHLAVFLNYLLSNSDPSSLFFYLITDLYKSGNIKDMRKWAYEIFSTFLVPNAPLlWPNIDESLIQEIDKILQNEqd 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2462515778  435 --EDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGEN 474
Cdd:cd08756     81 deEILRRVFLKAREKARDEINDQLADFRQKRTLGLGSIFGPN 122
RGS_p115RhoGEF cd08755
Regulator of G protein signaling (RGS) domain found in the Rho guanine nucleotide exchange ...
 357-530 5.80e-25

Regulator of G protein signaling (RGS) domain found in the Rho guanine nucleotide exchange factor (GEF), p115 RhoGEF; The RGS (Regulator of G-protein Signaling) domain is an essential part of the p115RhoGEF protein, a member of the RhoGEF (Rho guanine nucleotide exchange factor) subfamily of the RGS protein family. The RhoGEFs are peripheral membrane proteins that regulate essential cellular processes, including cell shape, cell migration, cell cycle progression of cells, and gene transcription by linking signals from heterotrimeric G-alpha12/13 protein-coupled receptors to Rho GTPase activation, leading to various cellular responses, such as actin reorganization and gene expression. The RhoGEF subfamily includes p115RhoGEF, LARG, PDZ-RhoGEF and its rat specific splice variant GTRAP48. The RGS domain of RhoGEFs has very little sequence similarity with the canonical RGS domain of the RGS proteins and is often refered to as RH (RGS Homology) domain. In addition to being a G-alpha13/12 effector, the p115RhoGEF protein also functions as a GTPase-activating protein (GAP) for G-alpha13. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.


Pssm-ID: 188709  Cd Length: 193  Bit Score: 103.82  E-value: 5.80e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  357 LKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSRSLGKDIWNIFLEKNAPLRVKIPEMLQAEIDsRLR---- 432
Cdd:cd08755      1 VKSRPAHLMVFLQHVMLQFDPAPLLCYLHADMLKNLNTKETKKHFGDFYNTFLEKGAVLKVSVPSNVAFELD-RTRpeli 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  433 NSEDARGVLCEAQEAAMPEIQEQIHDYRTKRTLGLGSLYGE------NDLLDLDGDPLRERQVAEKQLAALGDILSKY-- 504
Cdd:cd08755     80 NEEQQRRYVNEIQFAQSPAILRQLEDFRQKRMMGMTPNERElndlesHRPTDRIPMEAKEKAVAESLLEKLVEMNPTIvp 159

                          170       180
                   ....*....|....*....|....*.
gi 2462515778  505 EEDRSAPMDFALNTYMSHAGIRLREA 530
Cdd:cd08755    160 DEEKSNAIFGAIAYYMKHLGVKTKAF 185
PDZ_NHERF-like cd06768
PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related ...
 46-121 1.93e-20

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467249 [Multi-domain]  Cd Length: 80  Bit Score: 86.72  E-value: 1.93e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   46 RCVIIQKDQHGFGFTVSGDRIV---LVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALTLLG 121
Cdd:cd06768      1 RLCHLVKGPEGYGFNLHAEKGRpghFIREVDPGSPAERAGLKDGDRLVEVNGENVEGESHEQVVEKIKaSGNQVTLLVVD 80
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
 44-120 9.63e-19

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.


Pssm-ID: 214570 [Multi-domain]  Cd Length: 85  Bit Score: 82.04  E-value: 9.63e-19
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778    44 VQRCVIIQKDQHGFGFTVSGDRI----VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALT 118
Cdd:smart00228    1 EPRLVELEKGGGGLGFSLVGGKDegggVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKkAGGKVTLT 80


                    ..
gi 2462515778   119 LL 120
Cdd:smart00228   81 VL 82
PDZ_rhophilin-like cd06712
PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density ...
 46-111 1.28e-18

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This rhophilin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467196 [Multi-domain]  Cd Length: 78  Bit Score: 81.48  E-value: 1.28e-18
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462515778   46 RCVIIQKDQHGFGFTVSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06712      2 RTVHLTKEEGGFGFTLRGDSPVQVASVDPGSCAAEAGLKEGDYIVSVGGVDCKWSKHSEVVKLLKS 67
PDZ2_L-delphilin-like cd06744
PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 ...
 48-117 3.48e-18

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467226 [Multi-domain]  Cd Length: 75  Bit Score: 80.40  E-value: 3.48e-18
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462515778   48 VIIQKDQHGFGFTVSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVAL 117
Cdd:cd06744      2 VRVYRGNGSFGFTLRGHAPVYIESVDPGSAAERAGLKPGDRILFLNGLDVRNCSHDKVVSLLQgSGSMPTL 72
PDZ_SHANK1_3-like cd06746
PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and ...
 46-120 6.81e-17

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.


Pssm-ID: 467228 [Multi-domain]  Cd Length: 101  Bit Score: 77.63  E-value: 6.81e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   46 RCVIIQKDQHGFGFTVSG-------------DRIVLVQ---SVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI 109
Cdd:cd06746      7 RTVVLQKGDKGFGFVLRGakavgpileftptPAFPALQyleSVDPGGVADKAGLKKGDFLLEINGEDVVKASHEQVVNLI 86

                           90
                   ....*....|..
gi 2462515778  110 K-SGAYVALTLL 120
Cdd:cd06746     87 RqSGNTLVLKVV 98
RGS smart00315
Regulator of G protein signalling domain; RGS family members are GTPase-activating proteins ...
 353-457 9.23e-17

Regulator of G protein signalling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.


Pssm-ID: 214613  Cd Length: 118  Bit Score: 77.69  E-value: 9.23e-17
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   353 DLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQA-SPKDSRSLGKDIWNIFLEKNAPLRVKIPEMLQAEIDSRL 431
Cdd:smart00315    1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAeDDEERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                            90       100
                    ....*....|....*....|....*.
gi 2462515778   432 RNSEDARGVLCEAQEAAMPEIQEQIH 457
Cdd:smart00315   81 ESEEPPPDLFDEAQREVYELLEKDSF 106
PDZ_canonical cd00136
canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs ...
 48-120 1.10e-16

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467153 [Multi-domain]  Cd Length: 81  Bit Score: 76.04  E-value: 1.10e-16
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462515778   48 VIIQKD-QHGFGFTVSG----DRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKSgAYVALTLL 120
Cdd:cd00136      2 VTLEKDpGGGLGFSIRGgkdgGGGIFVSRVEPGGPAARDGrLRVGDRILEVNGVSLEGLTHEEAVELLKS-AGGEVTLT 79
PDZ_SNX27-like cd23070
PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density ...
 46-120 4.60e-16

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SNX27-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467283 [Multi-domain]  Cd Length: 93  Bit Score: 74.75  E-value: 4.60e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   46 RCVIIQKDQHGFGFTVSGD----------------RIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI 109
Cdd:cd23070      1 RVVTIVKSETGFGFNVRGQvseggqlrsingelyaPLQHVSAVLEGGAADKAGVRKGDRILEVNGVNVEGATHKQVVDLI 80

                           90
                   ....*....|..
gi 2462515778  110 KSGA-YVALTLL 120
Cdd:cd23070     81 KSGGdELTLTVI 92
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
 756-1015 2.07e-15

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


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 82.25  E-value: 2.07e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  756 WQHTVGKDVVAGLTQREIDRQEVINELFVTEASHLRTLRVLDLIFYQRMKKENLMP---REELAR-LFPNLPELIEIHNS 831
Cdd:COG5422    466 WTLSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPenaRRNFIKhVFANINEIYAVNSK 545

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  832 WCEAMKKLREEGPIIKEISDLML---ARFDgpareelqqvaaQFCSY---QSIALELIKTKQRKESRFQLFMQEAESHPQ 905
Cdd:COG5422    546 LLKALTNRQCLSPIVNGIADIFLdyvPKFE------------PFIKYgasQPYAKYEFEREKSVNPNFARFDHEVERLDE 613

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  906 CRRLQLRDLIISEMQRLTKYPLLLESIIKHTEGGTSEHEKLCRARDQCREILKYVNEAVKQTENRHRLEGYQKRLDATAl 985
Cdd:COG5422    614 SRKLELDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFKP- 692

                          250       260       270
                   ....*....|....*....|....*....|
gi 2462515778  986 ERASNPLAAEFksldlttRKMIHEGPLTWR 1015
Cdd:COG5422    693 EYVNLGLNDEY-------RKIIFKGVLKRK 715
RGS cd07440
Regulator of G protein signaling (RGS) domain superfamily; The RGS domain is an essential part ...
 358-454 7.16e-15

Regulator of G protein signaling (RGS) domain superfamily; The RGS domain is an essential part of the Regulator of G-protein Signaling (RGS) protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. While inactive, G-alpha-subunits bind GDP, which is released and replaced by GTP upon agonist activation. GTP binding leads to dissociation of the alpha-subunit and the beta-gamma-dimer, allowing them to interact with effectors molecules and propagate signaling cascades associated with cellular growth, survival, migration, and invasion. Deactivation of the G-protein signaling controlled by the RGS domain accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in the reassociation of the alpha-subunit with the beta-gamma-dimer and thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins are also involved in apoptosis and cell proliferation, as well as modulation of cardiac development. Several RGS proteins can fine-tune immune responses, while others play important roles in neuronal signals modulation. Some RGS proteins are principal elements needed for proper vision.


Pssm-ID: 188659 [Multi-domain]  Cd Length: 113  Bit Score: 72.04  E-value: 7.16e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778  358 KSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDS--RSLGKDIWNIFLEKNAPLRVKIPEMLQAEIDSRLRNSE 435
Cdd:cd07440      1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTSSDEelKSKAKEIYDKYISKDAPKEINIPESIREEIEENLEEPY 80

                           90
                   ....*....|....*....
gi 2462515778  436 DARGVLCEAQEAAMPEIQE 454
Cdd:cd07440     81 PDPDCFDEAQEHILNLLEK 99
PDZ pfam00595
PDZ domain; PDZ domains are found in diverse signaling proteins.
 48-120 1.83e-14

PDZ domain; PDZ domains are found in diverse signaling proteins.


Pssm-ID: 395476 [Multi-domain]  Cd Length: 81  Bit Score: 70.00  E-value: 1.83e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQKD-QHGFGFTVSGDRI-----VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALTLL 120
Cdd:pfam00595    2 VTLEKDgRGGLGFSLKGGSDqgdpgIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKgSGGKVTLTIL 81
PDZ_RGS12-like cd06710
PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 ...
 46-109 5.89e-14

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467194 [Multi-domain]  Cd Length: 76  Bit Score: 68.43  E-value: 5.89e-14
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462515778   46 RCVIIQKDQHGFGFTVSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI 109
Cdd:cd06710      1 RTVEIARGRAGYGFTISGQAPCVLSCVVRGSPADVAGLKAGDQILAVNGINVSKASHEDVVKLI 64
PDZ_RGS3-like cd06711
PDZ domain of regulator of G-protein signaling 3 (RGS3), and related domains; PDZ (PSD-95 ...
 48-120 1.93e-13

PDZ domain of regulator of G-protein signaling 3 (RGS3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS3, and related domains. RGS3 down-regulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. It downregulates G-protein-mediated release of inositol phosphates and activation of MAP kinases. In Eph/ephrin signaling, RGS3 binds via its PDZ domain to the cytoplasmic C terminus of Eph receptor tyrosine kinase EphB. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467195 [Multi-domain]  Cd Length: 77  Bit Score: 67.03  E-value: 1.93e-13
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515778   48 VIIQKDQHGFGFTVSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTLL 120
Cdd:cd06711      3 ITIQRGKDGFGFTICDDSPVRVQAVDPGGPAEQAGLQQGDTVLQINGQPVERSKCVELAHAIRNCPSEIILLV 75
PDZ_FRMPD1_3_4-like cd06769
PDZ domain of FERM and PDZ domain-containing protein 1 (FRMPD1), FRMPD3, FRMPD4, and related ...
 48-120 3.85e-11

PDZ domain of FERM and PDZ domain-containing protein 1 (FRMPD1), FRMPD3, FRMPD4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of FRMPD1, FRMPD3, FRMPD4, and related domains. FRMPD1 (also known as FERM domain-containing protein 2, FRMD2), inhibits the malignant phenotype of lung cancer by activating the Hippo pathway via interaction with WWC3; the FRMPD1 PDZ domain binds WWC3. FRMPD3 is a target gene of the neuron-specific transcription factor NPAS4 that is involved in synaptic plasticity. FRMPD4 (also known as PDZ domain-containing protein 10, PDZD10, PDZK10, PSD-95-interacting regulator of spine morphogenesis, and Preso) regulates dendritic spine morphogenesis, and mGluR1/5 signaling; the FRMPD4 PDZ domain binds PAK-interacting exchange factor-beta (betaPix). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This FRMPD1,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467250 [Multi-domain]  Cd Length: 75  Bit Score: 60.34  E-value: 3.85e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778   48 VIIQKD-QHGFGFTVSGDRIVLVQSVRPGGAAmKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKS-GAYVALTLL 120
Cdd:cd06769      2 VEIQRDaVLGFGFVAGSERPVVVRSVTPGGPS-EGKLLPGDQILKINNEPVEDLPRERVIDLIREcKDSIVLTVL 75
PDZ1_MAGI-1_3-like cd06731
PDZ domain 1 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, ...
 47-119 1.00e-10

PDZ domain 1 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467213 [Multi-domain]  Cd Length: 85  Bit Score: 59.53  E-value: 1.00e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   47 CVIIQKDQHGFGFTVSG----DRIVLVQSVRPGG-AAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKL---IKSGAYVALT 118
Cdd:cd06731      3 RTSLKKSARGFGFTIIGgdepDEFLQIKSVVPDGpAALDGKLRTGDVLVSVNDTCVLGYTHADVVKLfqsIPIGQSVNLE 82


                   .
gi 2462515778  119 L 119
Cdd:cd06731     83 V 83
PDZ2_GRIP1-2-like cd06681
PDZ domain 2 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 48-112 1.09e-10

PDZ domain 2 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467169 [Multi-domain]  Cd Length: 89  Bit Score: 59.55  E-value: 1.09e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462515778   48 VIIQKDQHGFGFTVSG--------DRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKSG 112
Cdd:cd06681      5 VTLEKEGNSFGFVIRGgahedrnkSRPLTVTHVRPGGPADREGtIKPGDRLLSVDGISLHGATHAEAMSILKQC 78
PDZ2_Par3-like cd23058
PDZ domain 2 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 ...
 46-111 1.98e-10

PDZ domain 2 of partitioning defective 3 (Par3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Par3 (or PAR3 or Par-3, also known as Atypical PKC isotype-specific-interacting protein, ASIP, Drosophila Bazooka) and related domains. Par3 is a scaffold protein involved in organizing cell polarity across animals. Par3 binds numerous molecules both for its recruitment to one pole of the cell and for downstream contributions to polarized cell function. It regulates cell polarity by targeting the Par complex proteins Par6 and atypical protein kinase C (aPKC) to specific cortical sites. Physical interactions between Par3 and the Par complex include Par3 PDZ domain 1 binding to the Par6 PDZ domain, Par3 PDZ domain 1 and PDZ domain 3 binding the Par6's PDZ-binding motif, and an interaction with an undefined region of aPKC that requires both Par3 PDZ2 and PDZ3. The PDZ domains of Par3 have also been implicated as potential phosphoinositide signaling integrators, since its second PDZ domain binds to phosphoinositides, and the third PDZ interacts with phosphoinositide phosphatase PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par3 family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467271 [Multi-domain]  Cd Length: 93  Bit Score: 58.81  E-value: 1.98e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462515778   46 RCVIIQKDQHGFGFTV-------SGDRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd23058      6 LHIQLKKGPEGLGFSItsrdnptGGSGPIYIKNILPKGAAIQDGrLKAGDRLLEVNGVDVTGKTQEEVVSLLRS 79
PDZ_MAST cd06705
PDZ domain of the microtubule-associated serine-threonine (MAST) protein kinase family; PDZ ...
 48-118 2.71e-10

PDZ domain of the microtubule-associated serine-threonine (MAST) protein kinase family; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST family kinases, including MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain; MAST family member MASTL is a shorter protein lacking the PDZ domain. The PDZ domain gives the MAST family the capacity to scaffold its own kinase activity. These kinases are implicated in the inhibition of neurite outgrowth and regeneration in cultured cells. Their binding partners include microtubules, beta2-syntrophin, TNF receptor-associated factor 6 (TRAF6), cAMP-regulated phosphoprotein (ARPP-16), and PTEN. This family also includes Caenorhabditis elegans KIN-4 MAST kinase, a key longevity factor acting through binding PTEN phosphatase, and Drosophila Drop out which regulates dynein-dependent transport during embryonic development. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAST-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467189 [Multi-domain]  Cd Length: 93  Bit Score: 58.41  E-value: 2.71e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQKDQHGFGFTVSGDRIV-----------LVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI-KSGAYV 115
Cdd:cd06705      5 IVIKKGPRGFGFTLRAIRVYigdsdvytvhhLVTAVEEGSPAYEAGLRPGDLITHVNGEPVQGLLHTQVVQLIlKGGNKV 84


                   ...
gi 2462515778  116 ALT 118
Cdd:cd06705     85 SIR 87
PDZ1_PTPN13_FRMPD2-like cd06694
PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13),FERM and PDZ ...
 48-126 3.47e-10

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13),FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467180 [Multi-domain]  Cd Length: 92  Bit Score: 58.18  E-value: 3.47e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQKD-QHGFGFTVSG-------DRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVaLT 118
Cdd:cd06694      5 VTLKKDpQKGLGFTIVGgensgslDLGIFVKSIIPGGPADKDGrIKPGDRIIAINGQSLEGKTHHAAVEIIQNAPDK-VE 83


                   ....*...
gi 2462515778  119 LLGSSPSS 126
Cdd:cd06694     84 LIISQPKS 91
CtpA COG0793
C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, ...
 56-120 5.31e-10

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440556 [Multi-domain]  Cd Length: 341  Bit Score: 62.97  E-value: 5.31e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462515778   56 GFGFTVS-GDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI--KSGAYVALTLL 120
Cdd:COG0793     61 GLGAELGeEDGKVVVVSVIPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLLrgKAGTKVTLTIK 128
PDZ4_MAGI-1_3-like cd06734
PDZ domain 4 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, ...
 48-120 5.35e-10

PDZ domain 4 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467216 [Multi-domain]  Cd Length: 84  Bit Score: 57.24  E-value: 5.35e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQ-KDQHGFGFTVSGDRIVLVQS----VRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALTLL 120
Cdd:cd06734      4 VTLTrRENEGFGFVIISSVNKKSGSkigrIIPGSPADRCGqLKVGDRILAVNGISILNLSHGDIVNLIKdSGLSVTLTIV 83
PH_ARHGEF2 cd13393
Rho guanine nucleotide exchange factor 2 Pleckstrin homology (PH) domain; ARHGEF2, also called ...
 1004-1119 7.72e-10

Rho guanine nucleotide exchange factor 2 Pleckstrin homology (PH) domain; ARHGEF2, also called GEF-H1, acts as guanine nucleotide exchange factor (GEF) for RhoA GTPases. It is thought to play a role in actin cytoskeleton reorganization in different tissues since its activation induces formation of actin stress fibers. ARHGEF2 contains a C1 domain followed by Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. 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: 275428  Cd Length: 116  Bit Score: 57.97  E-value: 7.72e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1004 RKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLKCHSKtavgssdskqtfSPVLKLNAVLIRSVATDKRAF 1083
Cdd:cd13393      2 RKLIHDGCLLWKTASGRFKDVQVLLMTDVLVFLQEKDQKYIFPTLDK------------PAVISLQNLIVRDIANQEKGM 69

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2462515778 1084 FIICTSklgPPQIYELVALTSSDKNTWMELLEEAVR 1119
Cdd:cd13393     70 FLISAA---PPEMYEVHAASRDDRNTWMRLIQQTVK 102
cpPDZ_CPP-like cd06782
circularly permuted PDZ domain of C-terminal processing peptidase (CPP), a serine protease, ...
 67-120 1.11e-09

circularly permuted PDZ domain of C-terminal processing peptidase (CPP), a serine protease, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CPP (also known as tail-specific protease, PRC protein, Protease Re, and Photosystem II D1 protein processing peptidase), and related domains. CPP belongs to the peptidase S41A family. It cleaves a C-terminal 11 residue peptide from the precursor form of penicillin-binding protein 3, and may have a role in protecting bacterium from thermal and osmotic stresses. In the plant chloroplast, the enzyme removes the C-terminal extension of the D1 polypeptide of photosystem II. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This CPP-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.


Pssm-ID: 467623 [Multi-domain]  Cd Length: 88  Bit Score: 56.34  E-value: 1.11e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462515778   67 VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI--KSGAYVALTLL 120
Cdd:cd06782     16 LVVVSPIPGGPAEKAGIKPGDVIVAVDGESVRGMSLDEVVKLLrgPKGTKVKLTIR 71
PH_p190RhoGEF cd14680
Rho guanine nucleotide exchange factor Pleckstrin homology domain; p190RhoGEF (also called ...
 1006-1118 1.90e-09

Rho guanine nucleotide exchange factor Pleckstrin homology domain; p190RhoGEF (also called RIP2 or ARHGEF28) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. In addition to the Dbl homology (DH)-PH domain, p190RhoGEF contains an N-terminal C1 (Protein kinase C conserved region 1) domain. The DH-PH domains bind and catalyze the exchange of GDP for GTP on RhoA. 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: 275430  Cd Length: 101  Bit Score: 56.55  E-value: 1.90e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1006 MIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLkchsktavGSSDSKqtfSPVLKLNAVLIRSVATDKRAFFI 1085
Cdd:cd14680      1 LLHEGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIF--------AAVDQK---PPVICLQKLIVREVANEERGMFL 69

                           90       100       110
                   ....*....|....*....|....*....|...
gi 2462515778 1086 ICTSKLGpPQIYELVALTSSDKNTWMELLEEAV 1118
Cdd:cd14680     70 ISASSAG-PEMYEIHTSSKEERNNWMRLIQEAV 101
PH_ARHGEF18 cd15794
Rho guanine nucleotide exchange factor 18 Pleckstrin homology (PH) domain; ARHGEF18, also ...
 1004-1118 1.94e-09

Rho guanine nucleotide exchange factor 18 Pleckstrin homology (PH) domain; ARHGEF18, also called p114RhoGEF, is a key regulator of RhoA-Rock2 signaling that is crucial for maintenance of polarity in the vertebrate retinal epithelium, and consequently is essential for cellular differentiation, morphology and eventually organ function. ARHGEF18 contains Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. 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: 275437  Cd Length: 119  Bit Score: 56.84  E-value: 1.94e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1004 RKMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLkchsktavGSSDSKqtfSPVLKLNAVLIRSVATDKRAF 1083
Cdd:cd15794      2 RQLLLEGMLYWKAASGRLKDILALLLTDVLLLLQEKDQKYVF--------ASVDSK---PPVISLQKLIVREVANEEKAM 70

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2462515778 1084 FIICTSKLGpPQIYELVALTSSDKNTWMELLEEAV 1118
Cdd:cd15794     71 FLISASLNG-PEMYEIHTNSKEDRNTWMAHIRRAV 104
PDZ_DEPTOR-like cd23067
PDZ domain of DEP domain-containing mTOR-interacting protein (DEPTOR), and related domains; ...
 50-112 2.75e-09

PDZ domain of DEP domain-containing mTOR-interacting protein (DEPTOR), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of DEPTOR, and related domains. DEPTOR (also known as DEP domain-containing protein 6, DEP6) is a regulatory protein of mTOR signaling; it is a negative regulator of both the mTORC1 and mTORC2 signaling pathways. DEPTOR's PDZ domain binds to mTOR's FAT domain to suppress mTOR's kinase activity. The DEPTOR PDZ domain also binds lysine-specific demethylase 4A (KDM4A), leucine-rich repeat containing 4 (LRRC4), p38gamma, and major intrinsically disordered Notch2-binding receptor 1 (MINAR1, also known as Ubtor). DEPTOR also interacts with salt-inducible kinase 3 (SIK3). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This DEPTOR-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467280 [Multi-domain]  Cd Length: 75  Bit Score: 55.12  E-value: 2.75e-09
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515778   50 IQKDQHGFGFTVSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSG 112
Cdd:cd23067      4 IVGDAVGWGFVVRGSKPCHIQAVDPSGPAAAAGMKVCQFIVSVNGLNVLHMDHRTVSNLILTG 66
PDZ7_PDZD2-PDZ4_hPro-IL-16-like cd06763
PDZ domain 7 of PDZ domain containing 2 (PDZD2), PDZ domain 4 of human pro-interleukin-16 ...
 45-111 7.97e-09

PDZ domain 7 of PDZ domain containing 2 (PDZD2), PDZ domain 4 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of PDZD2, also known as KIAA0300, PIN-1, PAPIN, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family include the PDZ domain of the secreted mature form of human interleukin-16 (IL-16); this is the fourth PDZ domain (PDZ4) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16). Precursor IL-16 is cleaved to produce pro-IL-16 and C-terminal mature IL-16. Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467244 [Multi-domain]  Cd Length: 86  Bit Score: 54.16  E-value: 7.97e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778   45 QRCVIIQKDQHGFGFT-------VSGDRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06763      1 AVTVELEKGSAGLGFSleggkgsPLGDRPLTIKRIFKGGAAEQSGvLQVGDEILQINGTSLQGLTRFEAWNIIKS 75
cpPDZ_Deg_HtrA-like cd06779
permuted PDZ domain of Deg/high-temperature requirement factor A (HtrA) family of housekeeping ...
 67-120 8.06e-09

permuted PDZ domain of Deg/high-temperature requirement factor A (HtrA) family of housekeeping serine proteases and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Deg/HtrA-type serine proteases that participate in folding and degradation of aberrant proteins, and in processing and maturation of native proteins. Typically, these proteases have an N-terminal serine protease domain and at least one C-terminal PDZ domain that recognizes substrates, and in some cases activates the protease function. An exception is yeast Nma11p which has two protease domains and four PDZ domains; its N-terminal half is comprised of a protease domain, followed by two PDZ domains, and its C-terminal half has a similar domain arrangement. HtrA-type proteases include the human HtrA1-4 and MBTPS2, tricorn protease, DegS, DegP and C-terminal processing peptidase, cyanobacterial serine proteases Hhoa, HhoB, and HtrA, and yeast Nma11p. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-termini of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This Deg/HtrA family PDZ domain is a circularly permuted PDZ domain which places beta-strand A at the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.


Pssm-ID: 467621 [Multi-domain]  Cd Length: 91  Bit Score: 54.22  E-value: 8.06e-09
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778   67 VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHL-EVVKLIKSGAYVALTLL 120
Cdd:cd06779     27 VLVAEVIPGSPAAKAGLKEGDVILSVNGKPVTSFNDLrAALDTKKPGDSLNLTIL 81
PDZ3_MAGI-1_3-like cd06733
PDZ domain 3 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, ...
 48-119 1.44e-08

PDZ domain 3 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467215 [Multi-domain]  Cd Length: 85  Bit Score: 53.38  E-value: 1.44e-08
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gi 2462515778   48 VIIQKDQHGFGFTVSG----DRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKSGA---YVALTL 119
Cdd:cd06733      4 VFLRRQETGFGFRILGgteeGSQVSIGAIVPGGAADLDGrLRTGDELLSVDGVNVVGASHHKVVDLMGNAArngQVNLTV 83
PDZ1_Scribble-like cd06704
PDZ domain 1 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 ...
 50-120 1.52e-08

PDZ domain 1 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467188 [Multi-domain]  Cd Length: 87  Bit Score: 53.44  E-value: 1.52e-08
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gi 2462515778   50 IQKDQHGFGFTVSG----------DRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALT 118
Cdd:cd06704      5 IERQTGGLGISIAGgkgstpykgdDEGIFISRVTEGGPAAKAGVRVGDKLLEVNGVDLVDADHHEAVEALKnSGNTVTMV 84


                   ..
gi 2462515778  119 LL 120
Cdd:cd06704     85 VL 86
PDZ_6 pfam17820
PDZ domain; This entry represents the PDZ domain from a wide variety of proteins.
 68-120 1.56e-08

PDZ domain; This entry represents the PDZ domain from a wide variety of proteins.


Pssm-ID: 436067 [Multi-domain]  Cd Length: 54  Bit Score: 52.15  E-value: 1.56e-08
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                   ....*....|....*....|....*....|....*....|....*....|...
gi 2462515778   68 LVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSShlEVVKLIKSGAYVALTLL 120
Cdd:pfam17820    1 VVTAVVPGSPAERAGLRVGDVILAVNGKPVRSLE--DVARLLQGSAGESVTLT 51
PDZ3_Scribble-like cd06702
PDZ domain 3 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 ...
 54-118 1.96e-08

PDZ domain 3 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467186 [Multi-domain]  Cd Length: 89  Bit Score: 53.03  E-value: 1.96e-08
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gi 2462515778   54 QHGFGFTVSGdriVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVK-LIKSGAYVALT 118
Cdd:cd06702     24 SHPFGVDEPG---IFISKVIPDGAAAKSGLRIGDRILSVNGKDLRHATHQEAVSaLLSPGQEIKLL 86
PDZ_syntrophin-like cd06801
PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), ...
 46-118 2.35e-08

PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of syntrophins (including alpha-1-syntrophin, beta-1-syntrophin, beta-2-syntrophin, gamma-1-syntrophin, and gamma-2-syntrophin), and related domains. Syntrophins play a role in recruiting various signaling molecules into signaling complexes and help provide appropriate spatiotemporal regulation of signaling pathways. They function in cytoskeletal organization and maintenance; as components of the dystrophin-glycoprotein complex (DGC), they help maintain structural integrity of skeletal muscle fibers. They link voltage-gated sodium channels to the actin cytoskeleton and the extracellular matrix, and control the localization and activity of the actin reorganizing proteins such as PI3K, PI(3,4)P2 and TAPP1. Through association with various cytoskeletal proteins within the cells, they are involved in processes such as regulation of focal adhesions, myogenesis, calcium homeostasis, and cell migration. They also have roles in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This syntrophin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467262 [Multi-domain]  Cd Length: 83  Bit Score: 52.58  E-value: 2.35e-08
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gi 2462515778   46 RCVIIQK-DQHGFGFTVSGDR----IVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALT 118
Cdd:cd06801      1 RTVRVVKqDVGGLGISIKGGAehkmPILISKIFKGQAADQTGqLFVGDAILSVNGENLEDATHDEAVQALKnAGDEVTLT 80
PDZ2_harmonin cd06738
PDZ domain 2 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic ...
 56-120 3.82e-08

PDZ domain 2 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467220 [Multi-domain]  Cd Length: 82  Bit Score: 51.94  E-value: 3.82e-08
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gi 2462515778   56 GFGFTVSGDRI----VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTLL 120
Cdd:cd06738     14 GLGCSISSGPTqkpgIFISNVKPGSLAEEVGLEVGDQIVEVNGTSFTNVDHKEAVMALKSSRHLTITVR 82
PDZ_tamalin_CYTIP-like cd06713
PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ ...
 45-111 4.19e-08

PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of tamalin, cytohesin-1-interacting protein, and related domains. Tamalin (trafficking regulator and scaffold protein tamalin, also known as general receptor for phosphoinositides 1-associated scaffold protein, GRASP) functions to link receptors, including group 1 metabotropic glutamate receptors (mGluRs), to neuronal proteins. The tamalin PDZ domain binds the C-terminal domains of group I mGluRs; it also binds potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2), neurotrophin-3 (NT3) TrkCT1-truncated receptor, SAP90/PSD-95-associated protein, and tamalin itself. CYTIP (cytohesin-1-interacting protein, also known as Pleckstrin homology Sec7 and coiled-coil domain-binding protein) sequesters cytohesin-1 in the cytoplasm, limiting its interaction with beta2 integrins; cytohesin-1 binds the CYTIP coiled coil domain. The CYTIP PDZ domain can bind the C-terminal peptide of protocadherin alpha-1 (PCDHA1), indicating a possible interaction between the two. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This tamalin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467197 [Multi-domain]  Cd Length: 91  Bit Score: 52.24  E-value: 4.19e-08
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gi 2462515778   45 QRCVIIQKDQHG-FGFTV-----------SGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06713      3 RRTIILEKQDNEtFGFEIqtyglhhknsnEVEMCTYVCRVHEDSPAYLAGLTAGDVILSVNGVSVEGASHQEIVELIRS 81
DegQ COG0265
Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational ...
 67-120 4.29e-08

Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440035 [Multi-domain]  Cd Length: 274  Bit Score: 56.31  E-value: 4.29e-08
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gi 2462515778   67 VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLE-VVKLIKSGAYVALTLL 120
Cdd:COG0265    203 VLVARVEPGSPAAKAGLRPGDVILAVDGKPVTSARDLQrLLASLKPGDTVTLTVL 257
PDZ1_harmonin cd06737
PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic ...
 54-117 9.08e-08

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467219 [Multi-domain]  Cd Length: 85  Bit Score: 51.10  E-value: 9.08e-08
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gi 2462515778   54 QHGFGFTVSGDRI----VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVAL 117
Cdd:cd06737     12 PESLGFSVRGGLEhgcgLFVSHVSPGSQADNKGLRVGDEIVRINGYSISQCTHEEVINLIKTKKTVSL 79
PDZ3_PTPN13_FRMPD2-like cd06695
PDZ domain 3 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), FERM and PDZ ...
 48-119 2.07e-07

PDZ domain 3 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467181 [Multi-domain]  Cd Length: 90  Bit Score: 50.34  E-value: 2.07e-07
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gi 2462515778   48 VIIQKDQHGFGFTVSGDR----------IVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYV 115
Cdd:cd06695      4 VKLTKGSSGLGFSFLGGEnnspedpfsgLVRIKKLFPGQPAAESGlIQEGDVILAVNGEPLKGLSYQEVLSLLRgAPPEV 83


                   ....
gi 2462515778  116 ALTL 119
Cdd:cd06695     84 TLLL 87
PDZ2-PTPN13_FRMPD2-like cd06792
PDZ domain 2 of tyrosine kinase PTPN13, FERM and PDZ domain-containing protein 2 (FRMPD2), and ...
 48-110 2.60e-07

PDZ domain 2 of tyrosine kinase PTPN13, FERM and PDZ domain-containing protein 2 (FRMPD2), and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of human PTPN13, and related domains. PTPN13, also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1), negatively regulates FAS-mediated apoptosis and NGFR-mediated pro-apoptotic signaling, and may also regulate phosphoinositide 3-kinase (PI3K) signaling. It contains 5 PDZ domains; interaction partners of its second PDZ domain (PDZ2) include the Fas receptor (TNFRSF6) and thyroid receptor-interacting protein 6 (TRIP6). The second PDZ (PDZ2) domain, but not PDZ1 or PDZ3, of FRMPD2 binds to GluN2A and GluN2B, two subunits of N-methyl-d-aspartic acid (NMDA) receptors. Other binding partners of the FRMPDZ2 PDZ2 domain include NOD2, and catenin family members, delta catenin (CTNND2), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) and p0071 (also known as plakophilin 4; PKP4). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467254 [Multi-domain]  Cd Length: 87  Bit Score: 49.90  E-value: 2.60e-07
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gi 2462515778   48 VIIQKDQHGFGFTVSG-----DRI--VLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIK 110
Cdd:cd06792      5 VELSKKDGSLGISVTGgintsVRHggIYVKSLVPGGAAEQDGrIQKGDRLLEVNGVSLEGVTHKQAVECLK 75
PDZ6_PDZD2-PDZ3_hPro-IL-16-like cd06762
PDZ domain 6 of PDZ domain containing 2 (PDZD2), PDZ domain 3 of human pro-interleukin-16 ...
 48-111 2.98e-07

PDZ domain 6 of PDZ domain containing 2 (PDZD2), PDZ domain 3 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 6 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family also includes the third PDZ domain (PDZ3) of human pro-interleukin-16 (isoform 1, also known as nPro-IL-16). Precursor IL-16 is cleaved to produce pro-IL-16 and C-terminal mature IL-16. Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ6 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467243 [Multi-domain]  Cd Length: 86  Bit Score: 49.57  E-value: 2.98e-07
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gi 2462515778   48 VIIQKDQ-HGFGFTVSG-----DRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06762      4 VVLHKEEgSGLGFSLAGgsdleNKSITVHRVFPSGLAAQEGtIQKGDRILSINGKSLKGVTHGDALSVLKQ 74
PDZ7_GRIP1-2-like cd06685
PDZ domain 7 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 48-109 4.65e-07

PDZ domain 7 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467173 [Multi-domain]  Cd Length: 85  Bit Score: 49.18  E-value: 4.65e-07
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gi 2462515778   48 VIIQKDQHG--FGFTVSG---DRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI 109
Cdd:cd06685      6 VTLYKDSDTedFGFSVSDglyEKGVYVNAIRPGGPADLSGLQPYDRILQVNHVRTRDFDCCLVVPLI 72
PDZ3_LNX1_2-like cd06679
PDZ domain 3 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ ...
 46-113 4.80e-07

PDZ domain 3 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2) and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467167 [Multi-domain]  Cd Length: 88  Bit Score: 49.17  E-value: 4.80e-07
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gi 2462515778   46 RCVIIQKDQH-GFGFTVSG-------DRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKSGA 113
Cdd:cd06679      1 KTVTIKKEPSeSLGISVAGgrgsrrgDLPIYVTNVQPDGCLGRDGrIKKGDVLLSINGISLTNLSHSEAVAVLKASA 77
PDZ2_MAGI-1_3-like cd06732
PDZ domain 2 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, ...
 48-118 5.08e-07

PDZ domain 2 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467214 [Multi-domain]  Cd Length: 82  Bit Score: 48.70  E-value: 5.08e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQKDQHGFGFTVSGdrivlvqsvRPGGAAMK--------AGVKEGDRIIKVNGTMVTNSSHLEVVKLIKS---GAYVA 116
Cdd:cd06732      6 VPIVKGPMGFGFTIAD---------SPQGQRVKqildpqrcRGLQEGDLIVEINGQNVQNLSHAQVVDVLKEcpkGSEVT 76


                   ..
gi 2462515778  117 LT 118
Cdd:cd06732     77 LL 78
PDZ_ARHGAP21_23-like cd06756
PDZ domain of ARHGAP21 and ARHGAP23, and related domains; PDZ (PSD-95 (Postsynaptic density ...
 46-110 5.39e-07

PDZ domain of ARHGAP21 and ARHGAP23, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGAP21, ARHGAP23, and related domains. This subfamily includes the GAPs (GTPase activating proteins): ARHGAP21 (Rho GTPase-activating protein 21; also known as Rho GTPase-activating protein 10, Rho-type GTPase-activating protein 21) and ARHGAP23 (Rho GTPase-activating protein 23; also known as Rho-type GTPase-activating protein 23). GAPs deactivate Rho GTPases by accelerating GTP hydrolysis. ARHGAP21/23 interact with a planar cell polarity (PCP) protein Pk1 to regulate a lateral signaling pathway in migrating cells. The ARHGAP21 PDZ domain binds claudin-2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGAP21-23-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467238 [Multi-domain]  Cd Length: 109  Bit Score: 49.76  E-value: 5.39e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   46 RCVIIQKDQHGFGFTV--------------------SGDR------------IVLVQSVRPGGAAMKAGVKEGDRIIKVN 93
Cdd:cd06756      2 KTVTLQRTSQGFGFTLrhfivyppesavheslkdeeNGNRggkqrsrlepmdTIFVKQVKEGGPAHQAGLCTGDRIVKVN 81

                           90
                   ....*....|....*..
gi 2462515778   94 GTMVTNSSHLEVVKLIK 110
Cdd:cd06756     82 GESVIGKTYSQVIALIQ 98
cpPDZ1_DegP-like cd10839
circularly permuted first PDZ domain (PDZ1) of Escherichia coli periplasmic serine ...
 67-120 5.67e-07

circularly permuted first PDZ domain (PDZ1) of Escherichia coli periplasmic serine endoprotease DegP and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Escherichia coli DegP (also known as heat shock protein DegP and Protease Do) and related domains. DegP belongs to the HtrA family of housekeeping proteases. It acts as a protease, degrading transiently denatured and unfolded or misfolded proteins which accumulate in the periplasm following heat shock or other stress conditions, and as a molecular chaperone at low temperatures. DegP has two PDZ domains in addition to the protease domain; its PDZ1 domain is responsible for identifying the distinct substrate sequences that affect degradation (degron) of the substrate sequence, and its PDZ2 domain is responsible for combining with other DegP monomers to form a stable oligomer structure. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This DegP family PDZ domain 1 is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.


Pssm-ID: 467630 [Multi-domain]  Cd Length: 91  Bit Score: 49.02  E-value: 5.67e-07
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                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778   67 VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLE-VVKLIKSGAYVALTLL 120
Cdd:cd10839     27 ALVAQVLPDSPAAKAGLKAGDVILSLNGKPITSSADLRnRVATTKPGTKVELKIL 81
PDZ2_PDZD2-like cd06758
PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 ...
 50-113 6.19e-07

PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains, and is expressed at exceptionally high levels in the pancreas and certain cancer tissues such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467239 [Multi-domain]  Cd Length: 88  Bit Score: 48.89  E-value: 6.19e-07
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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462515778   50 IQKDQHGFGFTVSG-------DRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKSGA 113
Cdd:cd06758      7 LLKEKGGLGIQITGgkgskrgDIGIFVAGVEEGGSADRDGrLKKGDELLMINGQSLIGLSHQEAVAILRSSA 78
PDZ5_DrPTPN13-like cd23060
PDZ domain 5 of Danio rerio tyrosine-protein phosphatase non-receptor type 13 (Ptpn13) and ...
 56-119 7.50e-07

PDZ domain 5 of Danio rerio tyrosine-protein phosphatase non-receptor type 13 (Ptpn13) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of Danio rerio Ptpn13, and related domains. Protein-tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosyl residues in proteins that are phosphorylated by protein tyrosine kinases (PTKs). Danio rerio Ptpn13 is a classical non-receptor-like PTP. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467273 [Multi-domain]  Cd Length: 80  Bit Score: 48.12  E-value: 7.50e-07
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gi 2462515778   56 GFGFT-VSGD--RIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLI-KSGAYVALTL 119
Cdd:cd23060     11 GLGFSlVGGEggSGIFVKSISPGGVADRDGrLQVGDRLLQVNGESVIGLSHSKAVNILrKAKGTVQLTV 79
PDZ1_ZO1-like cd06727
PDZ domain 1 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ ...
 48-119 7.81e-07

PDZ domain 1 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins, and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467209 [Multi-domain]  Cd Length: 87  Bit Score: 48.42  E-value: 7.81e-07
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gi 2462515778   48 VIIQKDQ-HGFGFTVSGDR----------IVLVQSVRPGGAAMkAGVKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYV 115
Cdd:cd06727      3 VTLHRAPgFGFGIAVSGGRdnphfqsgdtSIVISDVLKGGPAE-GKLQENDRVVSVNGVSMENVEHSFAVQILRkCGKTA 81


                   ....
gi 2462515778  116 ALTL 119
Cdd:cd06727     82 NITV 85
RseP COG0750
Membrane-associated protease RseP, regulator of RpoE activity [Posttranslational modification, ...
 59-119 8.34e-07

Membrane-associated protease RseP, regulator of RpoE activity [Posttranslational modification, protein turnover, chaperones, Transcription];


Pssm-ID: 440513 [Multi-domain]  Cd Length: 349  Bit Score: 52.78  E-value: 8.34e-07
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gi 2462515778   59 FTVSGDRIVL---VQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSShlEVVKLIKSGAYVALTL 119
Cdd:COG0750    119 FMTVGVPVLTppvVGEVVPGSPAAKAGLQPGDRIVAINGQPVTSWD--DLVDIIRASPGKPLTL 180
cpPDZ_HtrA-like cd06785
circularly permuted PDZ domain of high-temperature requirement factor A (HtrA) family serine ...
 67-118 1.02e-06

circularly permuted PDZ domain of high-temperature requirement factor A (HtrA) family serine proteases and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of HtrA family serine proteases including human HtrA1, HtrA2 (mitochondrial), HtrA3, and HtrA4, and related domains. These proteases are key enzymes associated with pregnancy. Their diverse biological functions include cell growth proliferation, migration and apoptosis. They are also implicated in disorders including Alzheimer's, Parkinson's, arthritis and cancer. HtrA1 (also known as high-temperature requirement A serine peptidase 1, L56, and serine protease 11) substrates include extracellular matrix proteins, proteoglycans, and insulin-like growth factor (IGF)-binding proteins. HtrA1 also inhibits signaling by members of the transforming growth factor beta (TGF-beta) family. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This HtrA-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.


Pssm-ID: 467624 [Multi-domain]  Cd Length: 98  Bit Score: 48.26  E-value: 1.02e-06
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gi 2462515778   67 VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSShlEVVKLIKSGAYVALT 118
Cdd:cd06785     33 VYVHKVIPGSPAQRAGLKDGDVIISINGKPVKSSS--DVYEAVKSGSSLLVV 82
PDZ5_MUPP1-like cd06669
PDZ domain 5 of multi-PDZ-domain protein 1 (MUPP1), PATJ (protein-associated tight junction) ...
 48-111 1.23e-06

PDZ domain 5 of multi-PDZ-domain protein 1 (MUPP1), PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ5 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467157 [Multi-domain]  Cd Length: 98  Bit Score: 48.38  E-value: 1.23e-06
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gi 2462515778   48 VIIQKDQHGFGFTV--------SGDRIVLVQSVRPGGAAMKAGVKE-GDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06669     11 IELEKGDRGLGFSIldyqdpldPSETVIVIRSLVPGGVAEQDGRLLpGDRLVFVNDVSLENASLDEAVQALKS 83
PDZ2_PDZD7-like cd10834
PDZ domain 2 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related ...
 52-119 1.31e-06

PDZ domain 2 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the second PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467270 [Multi-domain]  Cd Length: 85  Bit Score: 47.77  E-value: 1.31e-06
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gi 2462515778   52 KDQHGFGFTVSGDRI----VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTL 119
Cdd:cd10834     10 SDDYCLGFNIRGGSEyglgIYVSKVDPGGLAEQNGIKVGDQILAVNGVSFEDITHSKAVEVLKSQTHLMLTI 81
PDZ9_MUPP1-like cd10817
PDZ domain 9 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 ...
 48-119 1.55e-06

PDZ domain 9 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 9 of MUPP1. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ9 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ9 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467263 [Multi-domain]  Cd Length: 79  Bit Score: 47.34  E-value: 1.55e-06
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gi 2462515778   48 VIIQKDQHGFGFTVSGDRI---VLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKSG-AYVALTL 119
Cdd:cd10817      2 VELPKDQGGLGIAISEEDTengIVIKSLTEGGPAAKDGrLKVGDQILAVDDESVVGCPYEKAISLLKTAkGTVKLTV 78
PDZ_Lin-7-like cd06796
PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), ...
 46-111 2.03e-06

PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Lin-7 (also known as LIN-7 or LIN7), and related domains. Lin-7 targets and organize protein complexes to epithelial and synaptic plasma membranes. There are three mammalian Lin-7 homologs: Lin-7A (protein lin-7 homolog A, also known as mammalian lin-seven protein 1 (MALS-1), vertebrate lin-7 homolog 1 (Veli-1), tax interaction protein 33); Lin-7B (also known as MALS-2, Veli-2); and Lin-7C (also known as MALS-3, Veli-3). Lin-7 is involved in localization of the Let-23 growth factor receptor to the basolateral membrane of epithelial cells, in tight junction localization of insulin receptor substrate p53 (IRSp53), in retaining gamma-aminobutyric (GABA) transporter (BGT-1) at the basolateral surface of epithelial cells, and in regulating recruitment of neurotransmitter receptors to the postsynaptic density (PSD). The Lin7 PDZ domain binds Let-23, BGT and beta-catenin, and NMDA (N-methyl-D-aspartate) receptor NR2B. Lin-7 also binds to the PDZ binding motif located in the C-terminal tail of Rhotekin, an effector protein for small GTPase Rho. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Lin-7-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467258 [Multi-domain]  Cd Length: 86  Bit Score: 47.43  E-value: 2.03e-06
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gi 2462515778   46 RCVIIQKDQHGFGFTVSGDR----IVLVQSVRPGGAAMK-AGVKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06796      3 RVVELPKTEEGLGFNVMGGKeqnsPIYISRIIPGGVADRhGGLKRGDQLLSVNGVSVEGEHHEKAVELLKA 73
PDZ_MAST2 cd23074
PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 2; PDZ (PSD-95 ...
 48-118 2.22e-06

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 2; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST2 (also known as microtubule-associated serine/threonine kinase-205 kD, MAST205) , and related domains. MAST2 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain. MAST2 may function to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Binding partners of MAST2 include beta2-syntrophin, TNF receptor-associated factor 6 (TRAF6), cAMP-regulated phosphoprotein (ARPP-16), Na+/H+ exchanger NHE3 (SLC9A3) and PTEN. MAST2 is also associated with microtubules of the spermatid manchette. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAST2 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467287 [Multi-domain]  Cd Length: 93  Bit Score: 47.31  E-value: 2.22e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQKDQHGFGFTVSGDRIVL-----------VQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI-KSGAYV 115
Cdd:cd23074      5 IIIHRAGKKYGFTLRAIRVYMgdsdvytvhhmVWHVEDGGPASEAGLRQGDLITHVNGEPVHGLVHTEVVELIlKSGNKV 84


                   ...
gi 2462515778  116 ALT 118
Cdd:cd23074     85 SIS 87
PDZ1_INAD-like cd23063
PDZ domain 1 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 ...
 48-110 2.47e-06

PDZ domain 1 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This INAD-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467276 [Multi-domain]  Cd Length: 87  Bit Score: 47.12  E-value: 2.47e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778   48 VIIQKD-QHGFGFTVSGDRI----------VLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIK 110
Cdd:cd23063      2 VVIEKTeKKSFGICIVRGEVkvspntkttgIFIKGIIPDSPAHKCGrLKVGDRILSVNGNDVRNSTEQAAIDLIK 76
PDZ_MAST3 cd23075
PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 3 (MAST3); PDZ ...
 48-117 2.74e-06

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 3 (MAST3); PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST3, and related domains. MAST3 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain. MAST3 plays a critical role in regulating the immune response of inflammatory bowel disease (IBD), and is involved in the process of cytoskeleton organization, intracellular signal transduction and peptidyl-serine phosphorylation. MAST3 also promotes the proliferation and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis. Binding partners of MAST3 include cAMP-regulated phosphoprotein (ARPP-16) and the tumor suppressor PTEN. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAST3 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467288 [Multi-domain]  Cd Length: 94  Bit Score: 47.33  E-value: 2.74e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQKDQHGFGFTVSGDRIVL-----------VQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVK-LIKSGAYV 115
Cdd:cd23075      5 IIIHSSGKKYGFTLRAIRVYMgdsdvytvhhmVWSVEDGSPAQEAGLRAGDLITHINGESVLGLVHMDVVElLLKSGNKV 84


                   ..
gi 2462515778  116 AL 117
Cdd:cd23075     85 SL 86
PDZ_SYNJ2BP-like cd06709
PDZ domain of synaptojanin-2-binding protein (SYNJ2BP), and related domains; PDZ (PSD-95 ...
 56-118 2.78e-06

PDZ domain of synaptojanin-2-binding protein (SYNJ2BP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNJ2BP, and related domains. SYNJ2BP (also known as mitochondrial outer membrane protein 25, OMP25) regulates endocytosis of activin type 2 receptor kinases through the Ral/RALBP1-dependent pathway and may be involved in suppression of activin-induced signal transduction. Binding partners of the SYNJ2BP PDZ domain include activin type II receptors (ActR-II), and SYNJ2. SYNJ2BP interacts with the PDZ binding motif of the Notch Delta-like ligand 1 (DLL1) and DLL4, promoting Delta-Notch signaling, and inhibiting sprouting angiogenesis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SYNJ2BP-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467193 [Multi-domain]  Cd Length: 86  Bit Score: 46.90  E-value: 2.78e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462515778   56 GFGFTV---------SGDRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALT 118
Cdd:cd06709     11 GLGFNIvggtdqpyiPNDSGIYVAKIKEDGAAAIDGrLQEGDKILEINGQSLENLTHQDAVELFRnAGEDVKLK 84
PDZ2_FL-whirlin cd06741
PDZ domain 2 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 ...
 54-119 3.34e-06

PDZ domain 2 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467223 [Multi-domain]  Cd Length: 84  Bit Score: 46.49  E-value: 3.34e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462515778   54 QHGFGFTVSGdrivlvqsVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTL 119
Cdd:cd06741     23 EYGLGIYVTG--------VDPGSVAENAGLKVGDQILEVNGRSFLDITHDEAVKILKSSKHLIMTV 80
PDZ12_MUPP1-like cd06675
PDZ domain 12 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 10 of protein-associated tight ...
 63-110 3.35e-06

PDZ domain 12 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 10 of protein-associated tight junction (PATJ, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 12 of MUPP1, PDZ domain 10 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like PDZ12 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467163 [Multi-domain]  Cd Length: 86  Bit Score: 46.59  E-value: 3.35e-06
                           10        20        30        40
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gi 2462515778   63 GDRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIK 110
Cdd:cd06675     26 GDVPVFIAMIQPNGVAAQTGkLKVGDRIVSINGQSTDGLTHSEAVNLLK 74
PDZ4_PTPN13-like cd06696
PDZ domain 4 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), and related ...
 48-111 3.74e-06

PDZ domain 4 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)] and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467182 [Multi-domain]  Cd Length: 85  Bit Score: 46.53  E-value: 3.74e-06
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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778   48 VIIQKDQHG-FGFTVSGdrivlvqSVRPGGAAMKAGVKE----------GDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06696      6 VTLTKSEKGsLGFTVTK-------GKDDNGCYIHDIVQDpaksdgrlrpGDRLIMVNGVDVTNMSHTEAVSLLRA 73
PDZ3_PDZD2-PDZ1_hPro-IL-16-like cd06759
PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 of human pro-interleukin-16 ...
 56-111 5.35e-06

PDZ domain 3 of PDZ domain containing 2 (PDZD2), PDZ domain 1 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family also includes the first PDZ domain (PDZ1) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16; 1332 amino-acid protein). Precursor IL-16 is cleaved to produce pro-IL-16 and mature IL-16 (derived from the C-terminal 121 AA). Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467240 [Multi-domain]  Cd Length: 87  Bit Score: 46.11  E-value: 5.35e-06
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gi 2462515778   56 GFGFTVSGDRI-------VLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06759     13 GLGFSIVGGRDsprgpmgIYVKTIFPGGAAAEDGrLKEGDEILEVNGESLQGLTHQEAIQKFKQ 76
RGS pfam00615
Regulator of G protein signaling domain; RGS family members are GTPase-activating proteins for ...
 353-459 5.86e-06

Regulator of G protein signaling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.


Pssm-ID: 459870  Cd Length: 117  Bit Score: 46.84  E-value: 5.86e-06
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gi 2462515778  353 DLEKLKSRPAHLGVFLRYIFSQADPSPLLFYLCAEVYQQASPKDSR-SLGKDIWNIFLEKNAPLRVKIPEMLQAEIDSRL 431
Cdd:pfam00615    1 SFDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKADPDEERlKKAKEIYNEFLAPGSPKEINLDSDLREEIRENL 80

                           90       100
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gi 2462515778  432 RNSEDargvlceaqEAAMPEIQEQIHDY 459
Cdd:pfam00615   81 EKEPT---------RDLFDEAQAEVYEL 99
PDZ1_GRIP1-2-like cd06687
PDZ domain 1 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 49-117 6.31e-06

PDZ domain 1 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467175 [Multi-domain]  Cd Length: 83  Bit Score: 45.86  E-value: 6.31e-06
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gi 2462515778   49 IIQKDQHGFGFTVSG----DRIVLVQSVRPGGAAMKAGVKE-GDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVAL 117
Cdd:cd06687      5 LIKKEGSTLGLTVSGgidkDGKPRVSNLRPGGIAARSDQLNvGDYIKSVNGIRTTKLRHDEIISLLKnVGERVVL 79
PDZ_MAST1 cd23073
PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 1; PDZ (PSD-95 ...
 48-118 7.32e-06

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 1; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST family kinase MAST1, and related domains. MAST1 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain; MAST family member MASTL is a shorter protein lacking the PDZ domain. MAST1 functions as a scaffold protein to link the dystrophin/utrophin network with microfilaments via syntrophin, and it has been identified as a main driver of cisplatin resistance in human cancers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAST1 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467286 [Multi-domain]  Cd Length: 95  Bit Score: 46.17  E-value: 7.32e-06
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gi 2462515778   48 VIIQKDQHGFGFTVSGDRIVL-----------VQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI-KSGAYV 115
Cdd:cd23073      5 ITIQRSGKKYGFTLRAIRVYMgdsdvysvhhiVWHVEEGGPAQEAGLCAGDLITHVNGEPVHGMVHPEVVELIlKSGNKV 84


                   ...
gi 2462515778  116 ALT 118
Cdd:cd23073     85 AVT 87
PDZ1_PTPN13-like cd23072
PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), and related ...
 46-124 7.88e-06

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467285 [Multi-domain]  Cd Length: 92  Bit Score: 45.94  E-value: 7.88e-06
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gi 2462515778   46 RCVIIQKD-QHGFGFTVSG-------DRIVLVQSVRPGGAA-MKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKsGAYVA 116
Cdd:cd23072      3 TLVNLKKDaKYGLGFQIVGgeksgrlDLGIFISSITPGGPAdLDGRLKPGDRLISVNDVSLEGLSHDAAVEILQ-NAPED 81


                   ....*...
gi 2462515778  117 LTLLGSSP 124
Cdd:cd23072     82 VTLVVSQP 89
PDZ1_L-delphilin-like cd06743
PDZ domain 1 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 ...
 57-129 7.95e-06

PDZ domain 1 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467225 [Multi-domain]  Cd Length: 76  Bit Score: 45.35  E-value: 7.95e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515778   57 FGFTVSGDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSgayvaltlLGSSPSSMGI 129
Cdd:cd06743     11 FGFSIGGSGPCYILSVEEGSSAHAAGLQPGDQILELDGQDVSSLSCEAIIALARR--------CPSVPPSLGV 75
PDZ_2 pfam13180
PDZ domain;
64-104 8.53e-06

PDZ domain;


Pssm-ID: 433015 [Multi-domain]  Cd Length: 74  Bit Score: 44.96  E-value: 8.53e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2462515778   64 DRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLE 104
Cdd:pfam13180    5 EGGVVVVSVKSSGPAAKAGLKAGDVILSIDGRKINDLTDLE 45
PDZ13_MUPP1-like cd06676
PDZ domain 13 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 ...
 48-120 8.88e-06

PDZ domain 13 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 13 of MUPP1. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ13 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ13 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467164 [Multi-domain]  Cd Length: 83  Bit Score: 45.41  E-value: 8.88e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQKDQHGFGFTV-------SGDRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALT 118
Cdd:cd06676      2 ITLERGSDGLGFSIvggfgspHGDLPIYVKTVFEKGAAAEDGrLKRGDQILAVNGESLEGVTHEEAVNILKkTKGTVTLT 81


                   ..
gi 2462515778  119 LL 120
Cdd:cd06676     82 VL 83
PDZ_MAST4 cd23076
PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 4 (MAST4); PDZ ...
 48-118 8.95e-06

PDZ domain of microtubule-associated serine-threonine (MAST) protein kinase 4 (MAST4); PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MAST4, and related domains. MAST4 belongs to the MAST family kinases, which include MAST1-4. These MAST proteins contain a DUF1908 domain, a serine/threonine kinase domain, a AGC-kinase C-terminal domain, and a PDZ domain. MAST4 is a component of the AICD-MAST4-FOXO1-RTKN2 neuroprotective pathway; MAST4 phosphorylation of forkhead box protein O1 (FOXO1) regulates rhotekin 2 (RTKN2) expression. As this pathway is repressed in Alzheimer's Disease (AD), MAST4 may play a role in preventing AD pathogenesis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAST4 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467289 [Multi-domain]  Cd Length: 95  Bit Score: 45.79  E-value: 8.95e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQKDQHGFGFTVSGDRIV-----------LVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVK-LIKSGAYV 115
Cdd:cd23076      5 IVIHSSGKNYGFTIRAIRVYvgdsdiytvhhIVWNVEEGSPACQAGLKAGDLITHINGEPVHGLVHTEVIElLLKSGNKV 84


                   ...
gi 2462515778  116 ALT 118
Cdd:cd23076     85 SIT 87
PDZ_PDZD11-like cd06752
PDZ domain of PDZ domain-containing protein 11, and related domains; PDZ (PSD-95 (Postsynaptic ...
 46-119 9.05e-06

PDZ domain of PDZ domain-containing protein 11, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZD11, and related domains. PDZD11 (also known as ATPase-interacting PDZ protein, plasma membrane calcium ATPase-interacting single-PDZ protein, PMCA-interacting single-PDZ protein, PISP) is involved in the dynamic assembly of apical junctions (AJs). It is recruited by PLEKHA7 to AJs to promote the efficient junctional recruitment and stabilization of nectins, and the efficient early phases of assembly of AJs in epithelial cells. The PDZD11 PDZ domain binds nectin-1 and nectin-3. PDZD11 also binds to a PDZ binding motif located in the C-terminal tail of the human sodium-dependent multivitamin transporter, to the cytoplasmic tail of the Menkes copper ATPase ATP7A, and to the cytoplasmic tail of all plasma membrane Ca2+-ATPase b-splice variants. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD11-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467234 [Multi-domain]  Cd Length: 83  Bit Score: 45.38  E-value: 9.05e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462515778   46 RCVIIQKDQ-HGFGFTVSGDRI----VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTL 119
Cdd:cd06752      1 RTVVLKRPPgEQLGFNIRGGKAsglgIFISKVIPDSDAHRLGLKEGDQILSVNGVDFEDIEHSEAVKVLKTAREIQMRV 79
PDZ2_Scribble-like cd06703
PDZ domain 2 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 ...
 52-113 9.16e-06

PDZ domain 2 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467187 [Multi-domain]  Cd Length: 92  Bit Score: 45.71  E-value: 9.16e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515778   52 KDQHGFGFTVSG----------DRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKSGA 113
Cdd:cd06703      9 RDGKGLGFSIAGgkgstpfrdgDEGIFISRITEGGAADRDGkLQVGDRVLSINGVDVTEARHDQAVALLTSSS 81
PDZ1_FRMPD2-like cd23071
PDZ domain 1 of FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ ...
 47-111 9.75e-06

PDZ domain 1 of FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of FRMPD2 (also known as PDZ domain-containing protein 4, and related domains. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467284 [Multi-domain]  Cd Length: 92  Bit Score: 45.56  E-value: 9.75e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462515778   47 CVIIQKD-QHGFGFTVSG-------DRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd23071      4 CVTLKRDpKRGFGFVIVGgentgklDLGIFIASIIPGGPAEKDGrIKPGGRLISLNNISLEGVTFNTAVKILQN 77
PDZ_nNOS-like cd06708
PDZ domain of neuronal nitric oxide synthase (nNOS), and related domains; PDZ (PSD-95 ...
 48-147 1.06e-05

PDZ domain of neuronal nitric oxide synthase (nNOS), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of nNOS, and related domains. nNOS produces a key signaling molecule, nitric oxide (NO), which has diverse functions throughout the body and acts as a neurotransmitter and intracellular signaling molecule in the central and peripheral nervous system. nNOS is concentrated at synaptic junctions in the brain and motor endplates in skeletal muscle. The PDZ domain of neuronal nitric oxide synthase (nNOS) interacts with the PDZ domain of alpha1-syntrophin (in muscle cells) and with the second PDZ domain of Disks large homolog 4 (Dlg4, also known as PSD-95), and nitric oxide synthase 1 adaptor protein NOS1AP in neurons. Dlg4 binds NMDA receptors, and nNOS, forming a complex in neurons. NOS1AP competes with Dgl4 for the nNOS PDZ domain and prevents the coupling of nNos activation with NMDA receptor-mediated calcium influx. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This nNOS-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467192 [Multi-domain]  Cd Length: 110  Bit Score: 45.83  E-value: 1.06e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQKDQHGFGFTVSGDRI---VLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSH---LEVVKLIKSGAYVALTLL 120
Cdd:cd06708      6 RLFKRKVGGLGFLVKQRVCkppVIISDLIRGGAAEQSGlVQVGDIILAVNGRPLVDVSYesaLEVLRSIPSETPVVLILR 85

                           90       100
                   ....*....|....*....|....*...
gi 2462515778  121 GSSpssmGISG-LQQDPSPAGAPRITSV 147
Cdd:cd06708     86 GPE----GFTThLETTFTGDGTPKTVRV 109
degP_htrA_DO TIGR02037
periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various ...
 67-120 1.07e-05

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]


Pssm-ID: 273938 [Multi-domain]  Cd Length: 428  Bit Score: 49.91  E-value: 1.07e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778   67 VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHL-EVVKLIKSGAYVALTLL 120
Cdd:TIGR02037  259 ALVAQVLPGSPAEKAGLKAGDVITSVNGKPISSFADLrRAIGTLKPGKKVTLGIL 313
PDZ_PDLIM-like cd06753
PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density ...
 57-111 1.45e-05

PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZ-LIM family proteins including PDLIM1-7, and related domains. PDZ-LIM family proteins (also known as Zasp PDZ domain proteins) are involved in the rearrangement of the actin cytoskeleton; they mediate association with the cytoskeleton through alpha-actinin as well as with other proteins involved in signal transduction pathways. Members of this family include PDLIM1 (also known as C-terminal LIM domain protein 1, elfin, LIM domain protein CLP-36), PDLIM2 (also known as PDZ-LIM protein mystique), PDLIM3 (also known as actinin-associated LIM protein, alpha-actinin-2-associated LIM protein, ALP), PDLIM4 (also known as LIM protein RIL, Reversion-induced LIM protein), PDLIM5 (also known as enigma homolog, ENH, enigma-like PDZ and LIM domains protein), PDLIM6 (also known as LIM domain-binding protein 3, ZASP, Cypher, Oracle), and PDLIM7 (also known as PDZ and LIM domain protein 7, LIM mineralization protein, LMP; protein enigma). PDLIM1 has been shown to negatively regulate NF-kappaB-mediated signaling in the cytoplasm. PDLIM7 negatively regulates p53 through binding murine double minute 2 (MDM2). The PDZ domains of PDZ-LIM family proteins PDLIM1, 2, 3, 5, 6, 7 have been shown to bind actin. Other PDZ-LIM family PDZ domain binding partners include thyroid receptor interacting protein-6 (PDLIM4-PDZ), the LIM domain of PDLIM4 (PDLIM4-PDZ), tropomyosin (PDLIM7-PDZ), myotilin and calsarcin 1 (PDLIM6-PDZ), and proteins from the myotilin and FATZ (calsarcin/myozenin) families (PDLIM1, 3, 4, 6 PDZ domains). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDLIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467235 [Multi-domain]  Cd Length: 79  Bit Score: 44.44  E-value: 1.45e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462515778   57 FGFTVSGDRIV---LVQS-VRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06753     10 WGFRLQGGKDFnqpLTISrVTPGGKAAQANLRPGDVILAINGESTEGMTHLEAQNKIKA 68
PDZ_ZASP52-like cd23068
PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), ...
 69-119 1.59e-05

PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Drosophila melanogaster Zasp52 and related domains. Drosophila melanogaster Zasp52 (also known as Z band alternatively spliced PDZ-motif protein or Zasp) colocalizes with integrins at myotendinous junctions and with alpha-actinin at Z-disks and is required for muscle attachment as well as Z-disk assembly and maintenance. The Zasp52 actin-binding site includes the extended PDZ domain and the ZM region. The Zasp52-PDZ domain is required for myofibril assembly. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Zasp52-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467281 [Multi-domain]  Cd Length: 82  Bit Score: 44.44  E-value: 1.59e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2462515778   69 VQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALTL 119
Cdd:cd23068     29 IQKVNPGSPADKAGLRRGDVILRINGTDTSNLTHKQAQDLIKrAGNDLQLTV 80
PDZ_TAX1BP3-like cd10822
PDZ domain of tax1-binding protein 3 (TAX1BP3), and related domains; PDZ (PSD-95 (Postsynaptic ...
 50-110 1.61e-05

PDZ domain of tax1-binding protein 3 (TAX1BP3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of TAX1BP3, and related domains. TAX1BP3 (also known as glutaminase-interacting protein 3, tax interaction protein 1, TIP-1, tax-interacting protein 1) may regulate a number of protein-protein interactions by competing for PDZ domain binding sites. TAX1BP3 binds beta-catenin and may act as an inhibitor of the Wnt signaling pathway. It competes with LIN7A (also known as Lin-7A or LIN-7A) for inward rectifier potassium channel 4 (KCNJ4) binding, and thereby promotes KCNJ4 internalization. It may play a role in the Rho signaling pathway, and in the activation of CDC42 by the viral protein HPV16 E6. Binding partners of the TAX1BP3 PDZ domain include beta-catenin, KCNJ4, glutaminase liver isoform (GLS2), rho guanine nucleotide exchange factor 16 (ARHGEF16), rhotekin, and CDK5 regulatory subunit-associated protein 3 (also known as LAPZ). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This TAX1BP3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467265 [Multi-domain]  Cd Length: 94  Bit Score: 45.02  E-value: 1.61e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462515778   50 IQKD--QHGFGFTVSGdriVLVQSVRPGGAAMKAGVKEGDRIIKVNG---TMVTnssHLEVVKLIK 110
Cdd:cd10822     23 IDQDpsKNPFSYTDKG---IYVTRVSEGGPAEKAGLQVGDKILQVNGwdmTMVT---HKQAVKRLT 82
PH_ARHGEF2_18_like cd15789
rho guanine nucleotide exchange factor; RhoGEFs belongs to regulator of G-protein signaling ...
 1056-1118 1.63e-05

rho guanine nucleotide exchange factor; RhoGEFs belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. The members here all contain Dbl homology (DH)-PH domains. In addition some members contain N-terminal C1 (Protein kinase C conserved region 1) domains, PDZ (also called DHR/Dlg homologous regions) domains, ANK (ankyrin) domains, and RGS (Regulator of G-protein signalling) domains or C-terminal ATP-synthase B subunit. The DH-PH domains bind and catalyze the exchange of GDP for GTP on RhoA. RhoGEF2/Rho guanine nucleotide exchange factor 2, p114RhoGEF/p114 Rho guanine nucleotide exchange factor, p115RhoGEF, p190RhoGEF, PRG/PDZ Rho guanine nucleotide exchange factor, RhoGEF 11, RhoGEF 12, RhoGEF 18, AKAP13/A-kinase anchoring protein 13, and LARG/Leukemia-associated Rho guanine nucleotide exchange factor are included in this CD. 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: 275432  Cd Length: 102  Bit Score: 45.14  E-value: 1.63e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462515778 1056 SDSKQTFS------PVLKLNAVLIRSVATDKRAFFIICTSKLGPPQIYELVALTSSDKNTWMELLEEAV 1118
Cdd:cd15789     34 KDQKYVFVspdnkaGVVSLQKLLVREKAGQEKRMFLISASPDGMPEMYELKVQKPKDKNTWIQTIRQAV 102
cpPDZ2_DegP-like cd23084
circularly permuted second PDZ domain (PDZ2) of Escherichia coli periplasmic serine ...
 58-120 2.55e-05

circularly permuted second PDZ domain (PDZ2) of Escherichia coli periplasmic serine endoprotease DegP and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Escherichia coli DegP (also known as heat shock protein DegP and Protease Do), and related domains. DegP belongs to the HtrA family of housekeeping proteases. It acts as a protease, degrading transiently denatured and unfolded or misfolded proteins which accumulate in the periplasm following heat shock or other stress conditions, and as a molecular chaperone at low temperatures. DegP has two PDZ domains in addition to the protease domain; its PDZ1 domain is responsible for the identifying the distinct substrate sequences that affect degradation (degron) of the substrate sequence, and its PDZ2 domain is responsible for the combining with other DegP monomers to form a stable oligomer structure. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This DegP family PDZ domain 2 is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.


Pssm-ID: 467631 [Multi-domain]  Cd Length: 83  Bit Score: 44.16  E-value: 2.55e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462515778   58 GFTVS------GDRIVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVkLIKSGAYVALTLL 120
Cdd:cd23084      5 GATVSnvtdedGGKGVVVTEVDPGSPAAQSGLKKGDVIIGVNRQPVKSIAELRKV-LKSKPSAVLLQIK 72
degP_htrA_DO TIGR02037
periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various ...
 67-120 2.75e-05

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]


Pssm-ID: 273938 [Multi-domain]  Cd Length: 428  Bit Score: 48.37  E-value: 2.75e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778   67 VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHL-EVVKLIKSGAYVALTLL 120
Cdd:TIGR02037  364 VVVTKVVSGSPAARAGLQPGDVILSVNQQPVSSVAELrKVLARAKKGGRVALLIL 418
PHA03307 PHA03307
transcriptional regulator ICP4; Provisional
 1239-1530 3.09e-05

transcriptional regulator ICP4; Provisional


Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 49.01  E-value: 3.09e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1239 DSALEDVENLRHLILWSLLPghTMETQAAQEPEDDlTPTPSVISVTSHPWDPGSPGQAPPGGEGDNTQLAGLEGERPEQE 1318
Cdd:PHA03307    75 PGTEAPANESRSTPTWSLST--LAPASPAREGSPT-PPGPSSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPGPPPAAS 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1319 DmglcSLEHLPPRTRNSGIWESPELDRNLAEDASSTEAaggykvvrkgncfyVSMPSGPPDSSTDHSEAPMSPPQPDS-L 1397
Cdd:PHA03307   152 P----PAAGASPAAVASDAASSRQAALPLSSPEETARA--------------PSSPPAEPPPSTPPAAASPRPPRRSSpI 213

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1398 PAGQTEPQPqLQGGNDDPRRPSRSPPSLALRDVGMIFHTIEQLTLKLNRLKDmeLAHRELLKSLGGESSGGTTPVGSFHT 1477
Cdd:PHA03307   214 SASASSPAP-APGRSAADDAGASSSDSSSSESSGCGWGPENECPLPRPAPIT--LPTRIWEASGWNGPSSRPGPASSSSS 290

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2462515778 1478 EAARWTDGSLSPPAKEPLASDSRNSHELGPCPEDGSDAPLEDSTADAAASPGP 1530
Cdd:PHA03307   291 PRERSPSPSPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSP 343
cpPDZ_AtDEGP1-like cd00990
circularly permuted PDZ domain of Arabidopsis thaliana DEGP1, and related domains; PDZ (PSD-95 ...
 67-103 3.59e-05

circularly permuted PDZ domain of Arabidopsis thaliana DEGP1, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Arabidopsis thaliana DEGP1 (also known as protease Do-like 1, chloroplastic, protein DEGRADATION OF PERIPLASMIC PROTEINS 1, DEGP PROTEASE 1 and DEG1), and related domains. DEGP1 is a serine protease that is required at high temperature and may be involved in the degradation of damaged proteins. This family also includes Arabidopsis protease DEGP8/Do-like 8 (chloroplastic), a probable serine protease. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This AtDEGP-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.


Pssm-ID: 467618 [Multi-domain]  Cd Length: 102  Bit Score: 44.11  E-value: 3.59e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2462515778   67 VLVQSVRPGGAAMKAGVKE-----------GDRIIKVNGTMVTNSSHL 103
Cdd:cd00990     25 VLVLDVPPGGPAAKAGLRGtkrdefgrivlGDVIVAVDGKPVKNESDL 72
PDZ8_MUPP1-PDZ7_PATJ-PDZ2_INAD-like cd06672
PDZ domain 8 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 7 of protein-associated tight ...
 50-111 4.41e-05

PDZ domain 8 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 7 of protein-associated tight junction (PATJ), PDZ domain 2 of Drosophila melanogaster inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 8 of MUPP1, PDZ domain 7 of PATJ, and PDZ domain 2 of Drosophila melanogaster INAD, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ8 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467160 [Multi-domain]  Cd Length: 84  Bit Score: 43.44  E-value: 4.41e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462515778   50 IQKDQHGFGFTVSGDR-----IVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06672      6 LEKGSSGLGLSLAGNKdrsrmSVFVVGIDPDGAAGKDGrIQVGDELLEINGQVLYGRSHLNASAIIKS 73
PDZ2_Dlg1-2-4-like cd06724
PDZ domain 2 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg) ...
 56-111 5.55e-05

PDZ domain 2 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Dlg1, human Dlg1,2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197 or SAP-97), Dlg2 (also known as channel-associated protein of synapse-110, postsynaptic density protein 93, or PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95, synapse-associated protein 90, or SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling. It regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord, and it also interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467207 [Multi-domain]  Cd Length: 85  Bit Score: 43.03  E-value: 5.55e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462515778   56 GFGFTVSG---------DRIVLVQSVRPGGAAMKAGVKE-GDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06724     10 GLGFSIAGgvgnqhipgDNGIYVTKIIEGGAAQKDGRLQvGDKLLAVNDVSLEEVTHEEAVAALKN 75
PDZ2_ZO1-like_ds cd06728
PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form ...
 56-109 5.75e-05

PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form domain-swapping dimers; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins , and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467210 [Multi-domain]  Cd Length: 79  Bit Score: 42.98  E-value: 5.75e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778   56 GFGFTVsGDRIvLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLI 109
Cdd:cd06728     13 EYGLRL-GSRI-FVKEITPDSLAAKDGnLQEGDIILKINGTPVENLSLSEAKKLI 65
cpPDZ_BsHtra-like cd06781
circularly permuted PDZ domain of Bacillus subtilis HtrA-type serine proteases HtrA, HtrB, and ...
 67-103 6.70e-05

circularly permuted PDZ domain of Bacillus subtilis HtrA-type serine proteases HtrA, HtrB, and YyxA and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Bacillus subtilis HtrA/YkdA, HtrB/YvtA and YyxA/YycK, and related domains. HtrA-type serine proteases participate in folding and degradation of aberrant proteins, and in processing and maturation of native proteins. HtrA, HtrB, and YyxA have a single transmembrane domain at the N-terminus and a PDZ domain at the C-terminus. Expression of htrA and htrB genes is induced both by heat shock and by secretion stress (by a common) mechanism; yyxA is neither heat shock nor secretion stress inducible. HtrA and HtrB may have overlapping cellular functions; YyxA may have a cellular function distinct from the other two proteases or have the same function but under different conditions. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This BsHtrA-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.


Pssm-ID: 467622 [Multi-domain]  Cd Length: 98  Bit Score: 43.39  E-value: 6.70e-05
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2462515778   67 VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHL 103
Cdd:cd06781     32 VYVAQVQSNSPAEKAGLKKGDVITKLDGKKVESSSDL 68
COG3975 COG3975
Predicted metalloprotease, contains C-terminal PDZ domain [General function prediction only];
57-119 7.65e-05

Predicted metalloprotease, contains C-terminal PDZ domain [General function prediction only];


Pssm-ID: 443174 [Multi-domain]  Cd Length: 591  Bit Score: 47.12  E-value: 7.65e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462515778   57 FGFTVSGDR-IVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTL 119
Cdd:COG3975    485 LGLRVSADGgGLVVTSVLWGSPAYKAGLSAGDELLAIDGLRVTADNLDDALAAYKPGDPIELLV 548
PDZ5_MAGI-1_3-like cd06735
PDZ domain 5 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, ...
 48-120 8.35e-05

PDZ domain 5 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5, and belongs to this MAGI1,2,3-like family. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ5 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467217 [Multi-domain]  Cd Length: 84  Bit Score: 42.57  E-value: 8.35e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462515778   48 VIIQKDQHGFGFTVSGDRIVL-----VQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTLL 120
Cdd:cd06735      4 VELERGPKGFGFSIRGGREYNnmplyVLRLAEDGPAQRDGrLRVGDQILEINGESTQGMTHAQAIELIRSGGSVVRLLL 82
PDZ_PTPN3-4-like cd06706
PDZ domain of tyrosine-protein phosphatase non-receptor type 3 (PTPN3), tyrosine-protein ...
 50-111 8.60e-05

PDZ domain of tyrosine-protein phosphatase non-receptor type 3 (PTPN3), tyrosine-protein phosphatase non-receptor type 4 (PTNP4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PTPN3, PTPN4 and related domains. PTPN3 (also known as protein-tyrosine phosphatase H1, PTP-H1) has a tumor-suppressive or a tumor-promoting role in many cancers. It serves as a specific phosphatase for the MAP kinase p38gamma; the two interact via their PDZ domains and cooperate to promote Ras-induced oncogenesis. Interaction partners of the PTPN3 PDZ domain include p38gamma and human papillomavirus E6 oncoprotein. PTPN4 (also known as protein-tyrosine phosphatase MEG1) plays a role in immunity, learning, synaptic plasticity or cell homeostasis. p38gamma is also an interaction partner of the PTPN4 PDZ domain: PTPN4 regulates neuronal cell homeostasis by protecting neurons against apoptosis; binding of the C terminus of p38gamma to the PDZ domain of PTPN4, antagonizes the catalytic autoinhibition of PTPN4, leading to cell apoptosis. Other interaction partners of the PTPN4 PDZ domain include glutamate receptor subunit GluN2A, and RABV strain G protein, among others. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467190 [Multi-domain]  Cd Length: 90  Bit Score: 42.68  E-value: 8.60e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462515778   50 IQKDQHG-FGFTVSG----DRIVLVQSVRPGGAAMKA--GVKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06706      8 MKPDENGrFGFNVKGgvdqKMPVIVSRVAPGTPADLCipRLNEGDQVLLINGRDISEHTHDQVVMFIKA 76
PDZ1-PDZRN4-like cd06715
PDZ domain 1 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related ...
 48-111 8.62e-05

PDZ domain 1 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZRN4-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467199 [Multi-domain]  Cd Length: 92  Bit Score: 42.76  E-value: 8.62e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462515778   48 VIIQKDQHGFGFTVSGDR-------------IVLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06715      5 VVLHRENGSLGFNIIGGRpcennqegsssegIYVSKIVENGPAADEGGLQVHDRIIEVNGKDLSKATHEEAVEAFRT 81
PDZ_RapGEF2_RapGEF6-like cd06755
PDZ domain of Rap guanine nucleotide exchange factor 2 and Rap guanine nucleotide exchange ...
 67-119 1.17e-04

PDZ domain of Rap guanine nucleotide exchange factor 2 and Rap guanine nucleotide exchange factor 6, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Rap guanine nucleotide exchange factor 2 (RapGEF2, also named RA-GEF-1, PDZ-GEF1, CNrasGEF and nRapGEP) and Rap guanine nucleotide exchange factor 6 (RapGEF6, also named RA-GEF-2 and PDZ-GEF2). RapGEF2 and RapGEF6 constitute a subfamily of guanine nucleotide exchange factors (GEFs) for RAP small GTPases that is characterized by the possession of the PDZ and Ras/Rap-associating domains. They activate Rap small GTPases, by catalyzing the release of GDP from the inactive GDP-bound forms, thereby accelerating GTP loading to yield the active GTP-bound forms. The PDZ domain of RapGEF6 (also known as PDZ-GEF2) binds junctional adhesion molecule A (JAM-A). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RapGEF2 and RapGEF6 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467237 [Multi-domain]  Cd Length: 83  Bit Score: 42.25  E-value: 1.17e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2462515778   67 VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTL 119
Cdd:cd06755     28 IFVSKVEKGSKAAEAGLKRGDQILEVNGQNFENITLKKALEILRNNTHLSITV 80
PDZ3_Dlg1-2-4-like cd06795
PDZ domain 3 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg) ...
 46-119 1.39e-04

PDZ domain 3 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila Dlg1, human Dlg1, 2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197; SAP-97), Dlg2 (also known as channel-associated protein of synapse-110; postsynaptic density protein 93, PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95; synapse-associated protein 90, SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling, regulating surface expression of NMDA receptors in dorsal horn neurons of the spinal cord; it interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. The Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development; postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467257 [Multi-domain]  Cd Length: 91  Bit Score: 42.34  E-value: 1.39e-04
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gi 2462515778   46 RCVIIQKDQHGFGFT-VSGD--RIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVALTL 119
Cdd:cd06795      3 RKIVLHKGSTGLGFNiVGGEdgEGIFISFILAGGPADLSGeLRRGDQILSVNGVDLRNATHEQAAAALKnAGQTVTIIA 81
PDZ3_MUPP1-like cd06791
PDZ domain 3 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) ...
 52-119 1.59e-04

PDZ domain 3 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467253 [Multi-domain]  Cd Length: 89  Bit Score: 41.83  E-value: 1.59e-04
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gi 2462515778   52 KDQHGFGFTVSGDRI---------VLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKS-GAYVALTL 119
Cdd:cd06791      9 KDEQGLGITIAGYVGekasgelsgIFVKSIIPGSAADQDGrIQVNDQIIAVDGVNLQGFTNQEAVEVLRNtGQVVHLTL 87
PDZ_densin_erbin-like cd06749
PDZ domain of densin, erbin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95) ...
 47-111 1.78e-04

PDZ domain of densin, erbin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of densin, erbin, and related domains. Densin (also known as leucine-rich repeat-containing protein 7, LRRC7, densin-180, protein LAP1) and erbin (also known as densin-180-like protein, Erbb2-interacting protein, protein LAP2) belong to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that play roles in the maintenance of cell shape and apical-basal polarity. Densin and erbin are components of the excitatory postsynaptic compartment and are regulators of dendritic morphology and postsynaptic structure. The densin PDZ domain binds CaV1.3 alpha1 subunit, delta-catenin, and MAGUIN-1. Binding partners of the erbin PDZ domain include ErbB receptor tyrosine kinase ErbB2, HTLV-1 Tax1, Cav1.3 Ca2+channels, and constituents of the cadherin:catenin cell adhesion complex, in particular delta-catenin, p0071 and ARVCF. The erbin PDZ domain binds Smad3, a transductor of the TGFbeta pathway, possibly by a novel interface of binding. Erbin and two other LAP proteins (scribble and lano) redundantly regulate epithelial polarity and apical adhesion complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This densin and erbin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467231 [Multi-domain]  Cd Length: 87  Bit Score: 41.93  E-value: 1.78e-04
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gi 2462515778   47 CVIIQKDQhGFGFTVSG------------DRIVLVQSVRPGGAAMKAgVKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06749      2 RVRIEKNP-GLGFSISGgigsqgnpfrpdDDGIFVTKVQPDGPASKL-LQPGDKILEVNGYDFVNIEHGQAVSLLKS 76
PDZ_SYNPO2-like cd10820
PDZ domain of synaptopodin 2 (SYNPO2), synaptopodin 2-like protein (SYNPO2L), and related ...
 69-113 1.91e-04

PDZ domain of synaptopodin 2 (SYNPO2), synaptopodin 2-like protein (SYNPO2L), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNPO2, SYNPO2L, and related domains. SYNPO2 (also known as genethonin-2, myopodin) is a cytoskeleton adaptor protein. It participates in chaperone-assisted selective autophagy (CASA), a mechanism for the disposal of misfolded and damaged proteins and provides a link between the CASA chaperone complex and a membrane-tethering and fusion machinery that generates autophagosome membranes. The SYNPO2 PPxY motif binds CASA cochaperone BCL2-associated athanogene 3 (BAG3) and the SYNPO2 PDZ domain binds vacuolar protein sorting 18 homolog (VPS18). There are three isoforms of SYNPO2, which possess an amino-terminal PDZ domain (SYNPO2a, b, c); the short isoform SYNPO2d, lacks the PDZ domain. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SYNPO2-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467264 [Multi-domain]  Cd Length: 78  Bit Score: 41.53  E-value: 1.91e-04
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gi 2462515778   69 VQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGA 113
Cdd:cd10820     26 VAKIRKKSKAALAGLCEGDELLSINGKPCADLSHSEAMDLIDSSG 70
PDZ1_FL-whirlin cd06740
PDZ domain 1 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 ...
 52-113 1.93e-04

PDZ domain 1 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467222 [Multi-domain]  Cd Length: 82  Bit Score: 41.58  E-value: 1.93e-04
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gi 2462515778   52 KDQHGFGFTVSGDRI----VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGA 113
Cdd:cd06740     10 KSHEGLGFSIRGGAEhgvgIYVSLVEPGSLAEKEGLRVGDQILRVNDVSFEKVTHAEAVKILRVSK 75
PDZ_MPP5-like cd06798
PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related ...
 46-111 1.95e-04

PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP5, Drosophila Stardust, and related domains. MPP5 (also known as MAGUK p55 subfamily member 1, protein associated with Lin-7 1 or PALS1) and Drosophila Stardust are membrane-associated guanylate kinase (MAGUK)-like proteins that serve as signaling and scaffolding proteins, linking different proteins critical to the formation and maintenance of tight junctions (TJ) and apical-basal polarity. Apical-basal polarity determinants cluster in complexes; in particular, the Crumbs complex (Crb, MPP5, and PATJ) and the PAR/aPKC-complex (PAR-3, PAR-6, aPKC) determine the apical plasma membrane domain. Within the Crumbs complex, Crb is stabilized in the plasma membrane by MPP5, which in turn recruits PATJ and Lin-7 to the complex. MPP5 also links the Crumbs complex with the PAR/aPKC-complex. The Drosophila homolog of the Crumbs complex is the (CRB)-Stardust (Sdt)-Discs Lost (Dlt) complex. MPP5 also acts as an interaction partner for SARS-CoV envelope protein E, which results in delayed formation of TJs and dysregulation of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP5-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467259 [Multi-domain]  Cd Length: 79  Bit Score: 41.56  E-value: 1.95e-04
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gi 2462515778   46 RCVIIQKDQHGFGFTV--SGDRIVLVQSVRpGGAAMKAGV-KEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06798      1 KIVRIEKTREPLGATVrnEGDSVIISRIVK-GGAAEKSGLlHEGDEILEINGIEIRGKDVNEVCDLLAD 68
cpPDZ_EcRseP-like cd23081
circularly permuted PDZ domains of Escherichia coli Regulator of sigma-E protease (RseP) and ...
 69-119 2.13e-04

circularly permuted PDZ domains of Escherichia coli Regulator of sigma-E protease (RseP) and related domains; Permuted PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ResP (also known as Site-2 protease RseP, and YaeL), and related domains. RseP is involved in the regulation of an extracytoplasmic stress response through the cleavage of membrane-spanning anti-stress-response transcription factor (anti-sigmE) protein RseA; it cleaves the peptide bond between the critical alanine and cysteine in the transmembrane region of RseA, releasing the cytoplasmic domain of RseA with its associated sigmaE. RseP contains two tandem-arranged periplasmic PDZ domains (PDZ-N/PDZ1 and PDZ-C/PDZ2) which act to negatively regulate protease action on intact RseA; they serve as a size-exclusion filter which prevents the access of an intact RseA into the active site of RseP. PDZ domains usually bind in sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This RseP family PDZ domain is a circularly permuted PDZ domain which places both beta-strands A and B at the C-terminus. Another permutation exists in the PDZ superfamily which places beta-strand A at the C-terminus.


Pssm-ID: 467638 [Multi-domain]  Cd Length: 83  Bit Score: 41.41  E-value: 2.13e-04
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gi 2462515778   69 VQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSShlEVVKLIKSGAYVALTL 119
Cdd:cd23081      3 VGEVVANSPAAEAGLKPGDRILKIDGQKVRTWE--DIVRIVRENPGKPLTL 51
PDZ10_MUPP1-PDZ8_PATJ-like cd06673
PDZ domain 10 of multi-PDZ-domain protein 1 (MUPP1), domain 8 of PATJ (protein-associated ...
 45-106 2.34e-04

PDZ domain 10 of multi-PDZ-domain protein 1 (MUPP1), domain 8 of PATJ (protein-associated tight junction) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 10 of MUPP1, PDZ domain 8 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ10 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467161 [Multi-domain]  Cd Length: 86  Bit Score: 41.51  E-value: 2.34e-04
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gi 2462515778   45 QRCVI-IQKDQHGFGFTVSG--DRI---VLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVV 106
Cdd:cd06673      2 RETTIeINKGKKGLGLSIVGgsDTLlgaIIIHEVYEDGAAAKDGrLWAGDQILEVNGEDLRKATHDEAI 70
PDZ7_MUPP1-PD6_PATJ-like cd06671
PDZ domain 7 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 6 of PATJ (protein-associated ...
 46-110 2.73e-04

PDZ domain 7 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 6 of PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of MUPP1 and PDZ domain 6 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ7 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467159 [Multi-domain]  Cd Length: 96  Bit Score: 41.54  E-value: 2.73e-04
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gi 2462515778   46 RCVIIQKD-QHGFGFTVSGDRI-------------VLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIK 110
Cdd:cd06671      3 RRVELWREpGKSLGISIVGGRVmgsrlsngeeirgIFIKHVLEDSPAGRNGtLKTGDRILEVNGVDLRNATHEEAVEAIR 82
cpPDZ2_EcRseP-like cd23083
circularly permuted PDZ domain 2 (PDZ-C) of Escherichia coli Regulator of sigma-E protease ...
 72-111 2.84e-04

circularly permuted PDZ domain 2 (PDZ-C) of Escherichia coli Regulator of sigma-E protease (RseP) and related domains; Permuted PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ResP (also known as Site-2 protease RseP, and YaeL) and related domains. RseP is involved in the regulation of an extracytoplasmic stress response through the cleavage of membrane-spanning anti-stress-response transcription factor (anti-sigmaE) protein RseA; it cleaves the peptide bond between the critical alanine and cysteine in the transmembrane region of RseA, releasing the cytoplasmic domain of RseA with it associated sigmaE. RseP contains two tandem-arranged periplasmic PDZ domains (PDZ-N/PDZ1 and PDZ-C/PDZ2) which act to negatively regulate protease action on intact RseA; they serve as a size-exclusion filter which prevents the access of an intact RseA into the active site of RseP. PDZ domains usually bind in sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This RseP family PDZ domain is a circularly permuted PDZ domain which places both beta-strands A and B at the C-terminus. Another permutation exists in the PDZ superfamily which places beta-strand A at the C-terminus.


Pssm-ID: 467640 [Multi-domain]  Cd Length: 85  Bit Score: 40.96  E-value: 2.84e-04
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gi 2462515778   72 VRPGGAAMKAGVKEGDRIIKVNGTMVTnsSHLEVVKLIKS 111
Cdd:cd23083      6 VQPNSAAEKAGLQAGDRIVKVDGQPLT--QWQTFVMAVRD 43
PDZ2_DLG5-like cd06765
PDZ domain 2 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density ...
 67-124 4.55e-04

PDZ domain 2 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PSZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467246 [Multi-domain]  Cd Length: 77  Bit Score: 40.41  E-value: 4.55e-04
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gi 2462515778   67 VLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKS-GAYVALTLLGSSP 124
Cdd:cd06765     18 VFISRIVPGSPAAKEGsLTVGDRIIAINGIALDNKSLSECEALLRScRDSLSLSLMKVFP 77
PDZ2_APBA1_3-like cd06793
PDZ domain 2 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, ...
 58-111 5.01e-04

PDZ domain 2 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking, and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2) which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins, APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 PDZ1 and PDZ2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This APBA1,3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467255 [Multi-domain]  Cd Length: 78  Bit Score: 40.08  E-value: 5.01e-04
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gi 2462515778   58 GFTVSGDRIVlvqSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06793     17 GFSVQNGIIC---SLLRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVQLLSN 67
PDZ_MYO18-like cd06747
PDZ domain of MYO18A protein, and related domains; PDZ (PSD-95 (Postsynaptic density protein ...
 48-118 5.34e-04

PDZ domain of MYO18A protein, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MYO18 protein and related domains. MYO18 (also known as myosin XVIIIA, KIAA0216, MysPDZ), a member of the myosin superfamily, is involved in regulating cell protrusion and migration, and Golgi trafficking and morphology, and is required for myoblast adhesion and muscle integrity. The MYO18A/MRCK/LRAP35a complex regulates actomyosin retrograde flow in cell protrusion and migration; the PtdIns(4)P/GOLPH3/MYO18A/F-actin complex is a hub for signals that regulate Golgi trafficking function. The MYO18A PDZ domain binds p190Rho-guanine nucleotide exchange factor (p190RhoGEF), Golgin45, and leucine repeat adaptor protein 1 (Lurap1, also known as Lrap35a). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MYO18-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.


Pssm-ID: 467229 [Multi-domain]  Cd Length: 90  Bit Score: 40.37  E-value: 5.34e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQKDQHG-FGFTV---------SGDRIVLVQSV---RPGGAA--MKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI-KS 111
Cdd:cd06747      2 ITLKRQPTGdFGFSLrrgtivergPDDGQELKRTVhfaEPGAGTknLATGLLPGDRLIEVNGVNVENASRDEIIEMIrKS 81


                   ....*..
gi 2462515778  112 GAYVALT 118
Cdd:cd06747     82 GDTVTLK 88
Peptidase_M50 pfam02163
Peptidase family M50;
67-125 6.82e-04

Peptidase family M50;


Pssm-ID: 426630 [Multi-domain]  Cd Length: 291  Bit Score: 43.63  E-value: 6.82e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462515778   67 VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTLLGSSPS 125
Cdd:pfam02163   95 PVIGGVAPGSPAAKAGLKPGDVILSINGKKITSWQDLVEALAKSPGKPITLTVERGGQT 153
PDZ3_PDZD7-like cd06751
PDZ domain 3 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related ...
 48-114 7.22e-04

PDZ domain 3 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of the Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa and can also form homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the third PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467233 [Multi-domain]  Cd Length: 89  Bit Score: 40.11  E-value: 7.22e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462515778   48 VIIQKDQHGFGFTVSGDR------IVLVQSVRPGGAAMKAGV-KEGDRIIKVNGTMVTNSSHLEVVKLIKSgAY 114
Cdd:cd06751      4 VELSKMKQSLGISISGGIeskvqpVVKIEKIFPGGAAALSGNlKAGYELVSVDGESLQQVTHQQAVDIIRR-AY 76
PH_AKAP13 cd13392
A-kinase anchoring protein 13 Pleckstrin homology (PH) domain; The Rho-specific GEF activity ...
 1006-1118 8.17e-04

A-kinase anchoring protein 13 Pleckstrin homology (PH) domain; The Rho-specific GEF activity of AKAP13 (also called Brx-1, AKAP-Lbc, and proto-Lbc) mediates signaling downstream of G-protein coupled receptors and Toll-like receptor 2. It plays a role in cell growth, cell development and actin fiber formation. Protein kinase A (PKA) binds and phosphorylates AKAP13, regulating its Rho-GEF activity. Alternative splicing of this gene in humans has at least 3 transcript variants encoding different isoforms (i.e. proto-/onco-Lymphoid blast crisis, Lbc and breast cancer nuclear receptor-binding auxiliary protein, Brx) containing a dbl oncogene homology (DH) domain and PH domain which are required for full transforming activity. The DH domain is associated with guanine nucleotide exchange activation while the PH domain has multiple functions including determine protein sub-cellular localisation via phosphoinositide interactions, while others bind protein partners. Other ligands include protein kinase C which is bound by the PH domain of AKAP13, serving to activate protein kinase D and mobilize a cardiac hypertrophy signaling pathway. 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: 275427  Cd Length: 103  Bit Score: 40.28  E-value: 8.17e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778 1006 MIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLLLkchsktavGSSDSKQTfspVLKLNAVLIRSVATDKRAFFI 1085
Cdd:cd13392      1 LVRDGPVSLKNTAGRLKEVQAVLLSDVLVFLQEKDQKYVF--------ASLDQKST---VISLKKLIVREVAHEEKGLFL 69

                           90       100       110
                   ....*....|....*....|....*....|...
gi 2462515778 1086 IcTSKLGPPQIYELVALTSSDKNTWMELLEEAV 1118
Cdd:cd13392     70 I-SMGIADPEMVEVHASSKEERNSWMQIIQDTI 101
PRK10779 PRK10779
sigma E protease regulator RseP;
63-98 8.58e-04

sigma E protease regulator RseP;


Pssm-ID: 182723 [Multi-domain]  Cd Length: 449  Bit Score: 43.52  E-value: 8.58e-04
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 2462515778   63 GDRI--VLVQsVRPGGAAMKAGVKEGDRIIKVNGTMVT 98
Cdd:PRK10779   218 GPQIepVLAE-VQPNSAASKAGLQAGDRIVKVDGQPLT 254
PDZ4_Scribble-like cd06701
PDZ domain 4 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 ...
 45-111 8.75e-04

PDZ domain 4 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Scribble-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467185 [Multi-domain]  Cd Length: 98  Bit Score: 40.29  E-value: 8.75e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   45 QRCVIIQKDQHGFGFTVSG-------------DRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIK 110
Cdd:cd06701      5 QELTIVKEPGEKLGISIRGgakghagnpldptDEGIFISKINPDGAAARDGrLKVGQRILEVNGQSLLGATHQEAVRILR 84


                   .
gi 2462515778  111 S 111
Cdd:cd06701     85 S 85
cpPDZ_HhoA-like cd10838
circularly permuted PDZ domain of Synechocystis sp. PCC 6803 putative serine proteases HhoA, ...
 62-120 9.22e-04

circularly permuted PDZ domain of Synechocystis sp. PCC 6803 putative serine proteases HhoA, HhoB, and HtrA and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the cyanobacterial Synechocystis sp. PCC 6803 putative serine proteases HhoA, HhoB and HtrA, and related domains. These three proteases are functionally overlapping, and are involved in a number of key physiological responses, ranging from protection against light and heat stresses to phototaxis. HhoA assembles into trimers, mediated by its protease domain and further into a hexamer by a novel interaction between the PDZ domains of opposing trimers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This HhoA-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.


Pssm-ID: 467629 [Multi-domain]  Cd Length: 104  Bit Score: 40.38  E-value: 9.22e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778   62 SGDRI-----VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHL-EVVKLIKSGAYVALTLL 120
Cdd:cd10838     25 SPVRIpevdgVLIMQVLPNSPAARAGLRRGDVIQAVDGQPVTTADDVqRIVEQAGVGEELELTVL 89
PDZ5_PDZD2-like cd06761
PDZ domain 5 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 ...
 67-121 1.09e-03

PDZ domain 5 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ5 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467242 [Multi-domain]  Cd Length: 85  Bit Score: 39.40  E-value: 1.09e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2462515778   67 VLVQSVRPGGAAMKAGVKE---GDRIIKVNGTMVTNSSHLEVVKLIKSgAYVALTLLG 121
Cdd:cd06761     27 VLVTGLRPGGAAERESMGKltaGDEIVSINGTPVSAMSYQETCHLMQN-LPKSLTLEV 83
PDZ3_ZO1-like_domain cd06729
PDZ domain 3 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ ...
 69-95 1.18e-03

PDZ domain 3 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins , and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467211 [Multi-domain]  Cd Length: 82  Bit Score: 39.09  E-value: 1.18e-03
                           10        20
                   ....*....|....*....|....*..
gi 2462515778   69 VQSVRPGGAAMKAGVKEGDRIIKVNGT 95
Cdd:cd06729     27 VAGVQEGSPAEKQGLQEGDQILKVNGV 53
PDZ3_FL-whirlin-like cd06742
PDZ domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short isoform of ...
 48-123 1.24e-03

PDZ domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short isoform of whirlin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short isoform of whirlin, and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 complex. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This whirlin family PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467224 [Multi-domain]  Cd Length: 91  Bit Score: 39.65  E-value: 1.24e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQKDQHGFGFTVSGD--------RIVLVQsvrPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLI------KSG 112
Cdd:cd06742      4 VRIKKTKPTLGIAIEGGantkqplpRVINIQ---RGGSAHNCGgLKVGHVILEVNGTSLRGLEHREAARLIaeafknKSR 80

                           90
                   ....*....|.
gi 2462515778  113 AYVALTLLGSS 123
Cdd:cd06742     81 DYIEFLVTEFN 91
SdrC COG3480
Predicted secreted protein YlbL, contains PDZ domain [Signal transduction mechanisms];
67-120 1.31e-03

Predicted secreted protein YlbL, contains PDZ domain [Signal transduction mechanisms];


Pssm-ID: 442703 [Multi-domain]  Cd Length: 344  Bit Score: 42.87  E-value: 1.31e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462515778   67 VLVQSVRPGGAAmkAGV-KEGDRIIKVNGTMVTNSSHL-EVVKLIKSGAYVALTLL 120
Cdd:COG3480    140 VYVASVLEGSPA--DGVlQPGDVITAVDGKPVTTAEDLrDALAAKKPGDTVTLTVT 193
PDZ4_GRIP1-2-like cd06686
PDZ domain 4 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related ...
 48-119 1.66e-03

PDZ domain 4 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467174 [Multi-domain]  Cd Length: 99  Bit Score: 39.25  E-value: 1.66e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   48 VIIQKD-QHGFGFTVSGDRIV--------LVQSVRPGGAAMKAGV-KEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVA 116
Cdd:cd06686     10 VILRGDpLKGFGIQLQGGVFAtetlssppLISFIEPDSPAERCGVlQVGDRVLSINGIPTEDRTLEEANQLLRdSASKVT 89


                   ...
gi 2462515778  117 LTL 119
Cdd:cd06686     90 LEI 92
PDZ4_LNX1_2-like cd06680
PDZ domain 4 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ ...
 63-111 1.94e-03

PDZ domain 4 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2)and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467168 [Multi-domain]  Cd Length: 89  Bit Score: 38.87  E-value: 1.94e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2462515778   63 GDRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06680     26 GNQPFFVKSIVPGTPAYNDGrLKCGDIILAVNGVSTVGMSHAALVPLLKE 75
PDZ4_MUPP1-like cd06668
PDZ domain 4 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) ...
 52-111 2.23e-03

PDZ domain 4 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467156 [Multi-domain]  Cd Length: 88  Bit Score: 38.82  E-value: 2.23e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462515778   52 KDQHGFGFTVSGDRIVLV------QSVRPGGAAMKAGV-KEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06668     11 SESSGLGISLEGTVDVEVrghhyiRSILPEGPVGRNGKlFSGDELLEVNGIQLLGLSHKEVVSILKE 77
PDZ_SIPA1-like cd06745
PDZ domain of signal-induced proliferation-associated protein 1 (SIPA1), and related domains; ...
 58-120 2.47e-03

PDZ domain of signal-induced proliferation-associated protein 1 (SIPA1), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SIPA1, and related domains. The Rap-GTPase activating protein SIPA1 (also known as GTPase-activating protein Spa-1, p130 SPA1) is a metastasis promoter; a polymorphism in a region of the Sipa1 gene encoding the PDZ domain is associated with metastasis. The SIPA1 PDZ domain binds ribosomal RNA processing 1 homolog B (Rrp1b). SIPA1 also forms a complex with water channel aquaporin-2 (AQP2) and plays a role in trafficking of AQP2, targeted positioning of which strictly regulates body water homeostasis; the SIPA1 PDZ domain binds AQP2. Rrp1b or AQP2 binding inhibits the RapGAP activity of SIPA1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SIPA1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.


Pssm-ID: 467227 [Multi-domain]  Cd Length: 73  Bit Score: 38.03  E-value: 2.47e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515778   58 GFTVSGDRIVlvQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTLL 120
Cdd:cd06745     13 GFHVNYEGFV--TEVERFGFAWQAGLRQGSRLVEICKVPVATLTHEQMIDLLRTSVKVKVTVI 73
PDZ2-PDZRN4-like cd06716
PDZ domain 2 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related ...
 57-111 2.92e-03

PDZ domain 2 of PDZ domain-containing RING finger protein 4 (PDZRN4), PDZRN3-B, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PDZRN4, PDZRN3-B, and related domains. PDZRN4 (also known as ligand of numb protein X 4, and SEMACAP3-like protein) contains an N-terminal RING domain and two tandem repeat PDZ domains. It is involved in the progression of cancer, including human liver cancer and breast cancer, and may contribute to the tumorigenesis of rectal adenocarcinoma. Danio rerio PDZRN3-B may participate in neurogenesis: the first PDZ domain of Danio rerio Pdzrn3 interacts with Kidins220 (Kinase D-interacting substrate 220 kD, also named Ankyrin Repeat-Rich Membrane Spanning), a crucial mediator of signal transduction in neural tissues. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZRN4-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467200 [Multi-domain]  Cd Length: 88  Bit Score: 38.41  E-value: 2.92e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462515778   57 FGFTV------SGDRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSShlEVVKLIKS 111
Cdd:cd06716     17 LGLTLcyrtddEEDTGIYVSEVDPNSIAAKDGrIREGDQILQINGVDVQNRE--EAIALLSE 76
PDZ2_MUPP1-like cd06667
PDZ domain 2 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) ...
 53-117 3.90e-03

PDZ domain 2 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of MUPP1 and PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467155 [Multi-domain]  Cd Length: 80  Bit Score: 37.65  E-value: 3.90e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462515778   53 DQHGFGFTVSGDRI--VLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIK-SGAYVAL 117
Cdd:cd06667      8 DGSGLGFGIVGGKStgVVVKTILPGGVADRDGrLRSGDHILQIGDTNLRGMGSEQVAQVLRqCGSHVRL 76
PDZ6_MUPP1-like cd06670
PDZ domain 6 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 ...
 46-101 4.28e-03

PDZ domain 6 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 6 of multi-PDZ-domain protein 1 (MUPP1). MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ6 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ6 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F


Pssm-ID: 467158 [Multi-domain]  Cd Length: 87  Bit Score: 38.00  E-value: 4.28e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   46 RCVIIQKDQHGFGFTVSGDRIV---LVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSS 101
Cdd:cd06670      5 RTITIVKGNSSLGITVSADKDGngcIVKSIIHGGAVSRDGrISVGDFIVSINNESLRNVT 64
PDZ1_Dlg1-2-4-like cd06723
PDZ domain 1 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg) ...
 56-117 5.50e-03

PDZ domain 1 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Dlg1, human Dlg1,2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197 or SAP-97), Dlg2 (also known as channel-associated protein of synapse-110, postsynaptic density protein 93, or PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95, synapse-associated protein 90, or SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling. It regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord, and it also interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467206 [Multi-domain]  Cd Length: 89  Bit Score: 37.68  E-value: 5.50e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462515778   56 GFGFTVSG---------DRIVLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKS-GAYVAL 117
Cdd:cd06723     12 GLGFSIAGgtdnphigdDPSIYITKIIPGGAAAADGrLRVNDIILRVNDVDVRNVTHSVAVEALKEaGSIVRL 84
PDZ_GOPC-like cd06800
PDZ domain of Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC), and ...
 46-109 6.58e-03

PDZ domain of Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of GOPC and related domains. GOPC, also known as PIST (PDZ domain protein interacting specifically with TC10), FIG (fused in glioblastoma), and CAL (CFTR-associated ligand), regulates the trafficking of a wide array of proteins, including small GTPases, receptors, and cell surface molecules such as cadherin 23 and CFTR. It may regulate CFTR chloride currents and acid-sensing ASIC3 currents by modulating cell surface expression of both channels, and may play a role in autophagy. Interaction partners of the GOPC PDZ domains include: FZD5, FZD8, ASIC3, CFTR, MUC3, ARFRP1, Ggamma13, neuroligin, and Stargazin. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GOPC-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467261 [Multi-domain]  Cd Length: 83  Bit Score: 37.35  E-value: 6.58e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462515778   46 RCVIIQKDQH-GFGFTVSGDR----IVLVQSVRPGGAAMK-AGVKEGDRIIKVNGTMVTNSSHLEVVKLI 109
Cdd:cd06800      1 RKVLLSKEPHeGLGISITGGKehgvPILISEIHEGQPADRcGGLYVGDAILSVNGIDLRDAKHKEAVTIL 70
PDZ_Radil-like cd06690
PDZ domain of Ras-associating and dilute domain-containing protein (Radil) and related domains; ...
 67-112 7.24e-03

PDZ domain of Ras-associating and dilute domain-containing protein (Radil) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Radil (also known as protein KIAA1849) and related domains. Radil is required for cell adhesion and migration of neural crest precursors during development. Radil is a component of a Rasip1-Radil-ARHGAP29 complex at endothelial cell-cell junctions. Rap1, via its effectors Radil and Rasip1 and their binding partner ArhGAP29, controls the endothelial barrier by decreasing Rho-mediated radial tension on cell-cell junctions. ArhGAP29 binds the Radil PDZ domain. The Radil PDZ domain also binds kinesin family protein 14 (KIF14); KIF14 negatively regulates Rap1-mediated inside-out integrin activation by tethering Radil on microtubules. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Radil-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467177 [Multi-domain]  Cd Length: 88  Bit Score: 37.27  E-value: 7.24e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2462515778   67 VLVQSVRPGGAAMKAG-VKEGDRIIKVNGTMVTNSSHLEVVKLIKSG 112
Cdd:cd06690     32 IYIRTLVPDSPAARDGrLRLGDRILAVNGTSLVGADYQSAMDLIRTS 78
PDZ_GIPC cd06707
PDZ domain of GIPC family proteins; GIPC1/GIPC (GAIP/RGS19-interacting protein), GIPC2, and ...
 50-111 8.97e-03

PDZ domain of GIPC family proteins; GIPC1/GIPC (GAIP/RGS19-interacting protein), GIPC2, and GIPC3 (also known as C19orf64) constitute the GIPC family. These proteins contain an N-terminal GIPC-homology 1 (GH1) domain, a central PDZ domain, and a C-terminal GH2 domain. GIPC proteins function as adaptor molecules that assemble RTKs, GPCRs, integrins, transmembrane proteins and cytoplasmic signaling regulators as cargoes of MYO6-dependent endocytic transport. Mutations in the Gipc1 and Gipc2 genes have been linked to cancer, while mutations in the Gipc3 gene cause nonsyndromic hearing loss. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GIPC family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467191 [Multi-domain]  Cd Length: 89  Bit Score: 36.82  E-value: 8.97e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462515778   50 IQKDQHGFGFTVS--GDRIVLVQSVRPGG-AAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLIKS 111
Cdd:cd06707      9 VTKSEDALGLTITdnGAGYAFIKRIKEGSiMDKVPAICVGDHIEKINGESLVGCRHYEVARMLKE 73
PDZ1_PDZD7-like cd10833
PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related ...
 48-109 9.09e-03

PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the first PDZ domain of the canonical isoform of PDZD7- isoform 1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD7-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.


Pssm-ID: 467269 [Multi-domain]  Cd Length: 84  Bit Score: 37.03  E-value: 9.09e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462515778   48 VIIQKDQHG-FGFTVSGDRI----VLVQSVRPGGAAMKAGVKEGDRIIKVNGTMVTNSSHLEVVKLI 109
Cdd:cd10833      4 VTVEKSPDGsLGFSVRGGSEhglgIFVSKVEEGSAAERAGLCVGDKITEVNGVSLENITMSSAVKVL 70
 
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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