Exchange Factor for ARF6 Pleckstrin homology (PH) domain; EFA6 (also called PSD/pleckstrin and Sec7 domain containing) is an guanine nucleotide exchange factor for ADP ribosylation factor 6 (ARF6), which is involved in membrane recycling. EFA6 has four structurally related polypeptides: EFA6A, EFA6B, EFA6C and EFA6D. It consists of a N-terminal proline rich region (PR), a SEC7 domain, a PH domain, a PR, a coiled-coil region, and a C-terminal PR. The EFA6 PH domain regulates its association with the plasma membrane. EFA6 activates Arf6 through its Sec7 catalytic domain and modulates this activity through its C-terminal domain, which rearranges the actin cytoskeleton in fibroblastic cell lines. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508 1250 TAVEYKKGYVMRKCCYDSSFKKTPFGKRSWKMFYCTLRDLVLYLHKDEHGFRKSQMSDNLHNAIRIHHALATKANDYTKK 1329
Cdd:cd13295     3 NAVEYKKGYLMRKCCADPDGKKTPFGKRGWKMFYATLKGLVLYLHKDEYGCKKALRYESLRNAISVHHSLATKATDYTKK 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 442620508 1330 QHVFRLQTADQAEYLFQTSDSKELQSWVETINYVCAAISAPPL 1372
Cdd:cd13295    83 PHVFRLRTADWREYLFQASDTKEMQSWIEAINLVAAAFSAPPL 125

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508    6 KVVLRRSEQhSGFGFSLLGTTGPPHVIY--DIVENSPAADCGAVEAGDVILKVNGTDVHRYTTKEVLKCLRLSEQLVTLE 83
Cdd:cd00136     1 TVTLEKDPG-GGLGFSIRGGKDGGGGIFvsRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGEVTLT 79

                  ..
gi 442620508   84 LK 85
Cdd:cd00136    80 VR 81

Exchange Factor for ARF6 Pleckstrin homology (PH) domain; EFA6 (also called PSD/pleckstrin and Sec7 domain containing) is an guanine nucleotide exchange factor for ADP ribosylation factor 6 (ARF6), which is involved in membrane recycling. EFA6 has four structurally related polypeptides: EFA6A, EFA6B, EFA6C and EFA6D. It consists of a N-terminal proline rich region (PR), a SEC7 domain, a PH domain, a PR, a coiled-coil region, and a C-terminal PR. The EFA6 PH domain regulates its association with the plasma membrane. EFA6 activates Arf6 through its Sec7 catalytic domain and modulates this activity through its C-terminal domain, which rearranges the actin cytoskeleton in fibroblastic cell lines. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508 1250 TAVEYKKGYVMRKCCYDSSFKKTPFGKRSWKMFYCTLRDLVLYLHKDEHGFRKSQMSDNLHNAIRIHHALATKANDYTKK 1329
Cdd:cd13295     3 NAVEYKKGYLMRKCCADPDGKKTPFGKRGWKMFYATLKGLVLYLHKDEYGCKKALRYESLRNAISVHHSLATKATDYTKK 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 442620508 1330 QHVFRLQTADQAEYLFQTSDSKELQSWVETINYVCAAISAPPL 1372
Cdd:cd13295    83 PHVFRLRTADWREYLFQASDTKEMQSWIEAINLVAAAFSAPPL 125

Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508  1254 YKKGYVMRKCCYDSSFKKTPFGKRSWKMFYCTLRDLVLYLHKDEHGFRKSQMSD--NLHNA----IRIHHALATKANDYT 1327
Cdd:pfam15410    1 YKKGIVMRKCCFESKGKKTPRGKRSWKMVYAVLKDLVLYLYKDEHPPESSQFEDkkSLKNApvgkIRLHHALATPAPDYT 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 442620508  1328 KKQHVFRLQTADQAEYLFQTSDSKELQSWVETINYVCA 1365
Cdd:pfam15410   81 KKSHVFRLQTADGAEYLFQTGSPKELQEWVDTLNYWAA 118

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for proper protein transport through the Golgi. The domain facilitates guanine nucleotide exchange on the small GTPases, ARFs (ADP ribosylation factors).

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508   1062 SAIRLAKRLHSLDGFKKSDVSRHLSKNNDFSRAVADEYLKHFTFEKKSLDQALREFLQQFSLSGETQERERVLVHFSKRF 1141
Cdd:smart00222   36 DPQDVADFLSKNEGLNKKAIGDYLGEHDEFNRLVLHAFVDLFDFSAKDLDQALREFLESFRLPGEAQKIDRLLEAFSSRY 115

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 442620508   1142 LDCNPGTF--NSQDAVHTLTCAIMLLNTDLHGQNINRKMSCAEFVDNLADLNDGENFPKDVLKSLYQAIKTKPL 1213
Cdd:smart00222  116 CECNPGVFskANADAAYTLAYSLIMLNTDLHNPNVKKKMTLEDFIKNVRGSNDGEDLPREFLEELYDSIKNNEI 189

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508   1254 YKKGYVMrkccydssfKKTPFGKRSWKMFYCTLRDLVLYLHKDEhgfrKSQMSDNLHNAIRIHHALATKANDYT--KKQH 1331
Cdd:smart00233    2 IKEGWLY---------KKSGGGKKSWKKRYFVLFNSTLLYYKSK----KDKKSYKPKGSIDLSGCTVREAPDPDssKKPH 68

                            90       100       110
                    ....*....|....*....|....*....|....
gi 442620508   1332 VFRLQTADQAEYLFQTSDSKELQSWVETINYVCA 1365
Cdd:smart00233   69 CFEIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508      3 EELKVVLRRSEQhsGFGFSLLGTTGPPHVIY--DIVENSPAADCGaVEAGDVILKVNGTDVHRYTTKEVLKCLRLSEQLV 80
Cdd:smart00228    1 EPRLVELEKGGG--GLGFSLVGGKDEGGGVVvsSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKV 77

                    ....*...
gi 442620508     81 TLELKRDP 88
Cdd:smart00228   78 TLTVLRGG 85

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 442620508   16 SGFGFSLLGTTGPPhVIYDIVENSPAADCGaVEAGDVILKVNGTDVHRYTTKEVLKCLRLSE-QLVTLELKRDPKLKAR 93
Cdd:COG0793    60 GGLGAELGEEDGKV-VVVSVIPGSPAEKAG-IKPGDIILAIDGKSVAGLTLDDAVKLLRGKAgTKVTLTIKRPGEGEPI 136

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]

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 442620508    34 DIVENSPAADCGaVEAGDVILKVNGTDVHRYT------------TKEVLKCLRLSEQL-VTLELKRDPKLKA 92
Cdd:TIGR02037  263 QVLPGSPAEKAG-LKAGDVITSVNGKPISSFAdlrraigtlkpgKKVTLGILRKGKEKtITVTLGASPEEQA 333

Exchange Factor for ARF6 Pleckstrin homology (PH) domain; EFA6 (also called PSD/pleckstrin and Sec7 domain containing) is an guanine nucleotide exchange factor for ADP ribosylation factor 6 (ARF6), which is involved in membrane recycling. EFA6 has four structurally related polypeptides: EFA6A, EFA6B, EFA6C and EFA6D. It consists of a N-terminal proline rich region (PR), a SEC7 domain, a PH domain, a PR, a coiled-coil region, and a C-terminal PR. The EFA6 PH domain regulates its association with the plasma membrane. EFA6 activates Arf6 through its Sec7 catalytic domain and modulates this activity through its C-terminal domain, which rearranges the actin cytoskeleton in fibroblastic cell lines. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508 1250 TAVEYKKGYVMRKCCYDSSFKKTPFGKRSWKMFYCTLRDLVLYLHKDEHGFRKSQMSDNLHNAIRIHHALATKANDYTKK 1329
Cdd:cd13295     3 NAVEYKKGYLMRKCCADPDGKKTPFGKRGWKMFYATLKGLVLYLHKDEYGCKKALRYESLRNAISVHHSLATKATDYTKK 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 442620508 1330 QHVFRLQTADQAEYLFQTSDSKELQSWVETINYVCAAISAPPL 1372
Cdd:cd13295    83 PHVFRLRTADWREYLFQASDTKEMQSWIEAINLVAAAFSAPPL 125

Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508  1254 YKKGYVMRKCCYDSSFKKTPFGKRSWKMFYCTLRDLVLYLHKDEHGFRKSQMSD--NLHNA----IRIHHALATKANDYT 1327
Cdd:pfam15410    1 YKKGIVMRKCCFESKGKKTPRGKRSWKMVYAVLKDLVLYLYKDEHPPESSQFEDkkSLKNApvgkIRLHHALATPAPDYT 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 442620508  1328 KKQHVFRLQTADQAEYLFQTSDSKELQSWVETINYVCA 1365
Cdd:pfam15410   81 KKSHVFRLQTADGAEYLFQTGSPKELQEWVDTLNYWAA 118

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for proper protein transport through the Golgi. The domain facilitates guanine nucleotide exchange on the small GTPases, ARFs (ADP ribosylation factors).

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508   1062 SAIRLAKRLHSLDGFKKSDVSRHLSKNNDFSRAVADEYLKHFTFEKKSLDQALREFLQQFSLSGETQERERVLVHFSKRF 1141
Cdd:smart00222   36 DPQDVADFLSKNEGLNKKAIGDYLGEHDEFNRLVLHAFVDLFDFSAKDLDQALREFLESFRLPGEAQKIDRLLEAFSSRY 115

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 442620508   1142 LDCNPGTF--NSQDAVHTLTCAIMLLNTDLHGQNINRKMSCAEFVDNLADLNDGENFPKDVLKSLYQAIKTKPL 1213
Cdd:smart00222  116 CECNPGVFskANADAAYTLAYSLIMLNTDLHNPNVKKKMTLEDFIKNVRGSNDGEDLPREFLEELYDSIKNNEI 189

ARF guanine nucleotide exchange factor (ARF-GEF); Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508 1056 KAVDMPSAIrlAKRLHSLDGFKKSDVSRHLSKNNDFSRAVADEYLKHFTFEKKSLDQALREFLQQFSLSGETQERERVLV 1135
Cdd:PLN03076  643 KVGESPEEI--AAFLKDASGLNKTLIGDYLGEREDLSLKVMHAYVDSFDFQGMEFDEAIRAFLQGFRLPGEAQKIDRIME 720

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508 1136 HFSKRFLDCNPGTFNSQDAVHTLTCAIMLLNTDLHGQNINRKMSCAEFVDNLADLNDGENFPKDVLKSLYQAIKTKplEW 1215
Cdd:PLN03076  721 KFAERYCKCNPKAFSSADTAYVLAYSVIMLNTDAHNPMVKNKMSADDFIRNNRGIDDGKDLPEEFMRSLYERISKN--EI 798

                         170
                  ....*....|....*..
gi 442620508 1216 ALDEEAGDLQQQRANNS 1232
Cdd:PLN03076  799 KMKEDDLVPQQKQSANS 815

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508   1254 YKKGYVMrkccydssfKKTPFGKRSWKMFYCTLRDLVLYLHKDEhgfrKSQMSDNLHNAIRIHHALATKANDYT--KKQH 1331
Cdd:smart00233    2 IKEGWLY---------KKSGGGKKSWKKRYFVLFNSTLLYYKSK----KDKKSYKPKGSIDLSGCTVREAPDPDssKKPH 68

                            90       100       110
                    ....*....|....*....|....*....|....
gi 442620508   1332 VFRLQTADQAEYLFQTSDSKELQSWVETINYVCA 1365
Cdd:smart00233   69 CFEIKTSDRKTLLLQAESEEEREKWVEALRKAIA 102

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 442620508    7 VVLRRSEQhSGFGFSLLGTTGP--PHVIYDIVENSPAADCGAVEAGDVILKVNGTDVHRYTTKEVLKCLRLSEQLVTL 82
Cdd:cd06734     4 VTLTRREN-EGFGFVIISSVNKksGSKIGRIIPGSPADRCGQLKVGDRILAVNGISILNLSHGDIVNLIKDSGLSVTL 80

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508      3 EELKVVLRRSEQhsGFGFSLLGTTGPPHVIY--DIVENSPAADCGaVEAGDVILKVNGTDVHRYTTKEVLKCLRLSEQLV 80
Cdd:smart00228    1 EPRLVELEKGGG--GLGFSLVGGKDEGGGVVvsSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKV 77

                    ....*...
gi 442620508     81 TLELKRDP 88
Cdd:smart00228   78 TLTVLRGG 85

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508 1255 KKGYVMrkccydssfKKTPFGKRSWKMFYCTLRDLVLYLHKDehgfrKSQMSDNLHNAIRIHHALATKANDYTKKQHVFR 1334
Cdd:cd00821     1 KEGYLL---------KRGGGGLKSWKKRWFVLFEGVLLYYKS-----KKDSSYKPKGSIPLSGILEVEEVSPKERPHCFE 66

                          90       100
                  ....*....|....*....|....*.
gi 442620508 1335 LQTADQAEYLFQTSDSKELQSWVETI 1360
Cdd:cd00821    67 LVTPDGRTYYLQADSEEERQEWLKAL 92

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 442620508    7 VVLRRSEQhsGFGFSLLGTTGPP-HVIYDIVENSPAADCGaVEAGDVILKVNGTDVHRYTTKEVLKCLRLSEQLVTL 82
Cdd:cd06768     3 CHLVKGPE--GYGFNLHAEKGRPgHFIREVDPGSPAERAG-LKDGDRLVEVNGENVEGESHEQVVEKIKASGNQVTL 76

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.

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gi 442620508    6 KVVLRRSEQHSgFGFSLLGTT---GPPHV-----IYDIVENSPAADCGAVEAGDVILKVNGTDVHRYTTKEVLKCLRLSE 77
Cdd:cd23063     1 MVVIEKTEKKS-FGICIVRGEvkvSPNTKttgifIKGIIPDSPAHKCGRLKVGDRILSVNGNDVRNSTEQAAIDLIKEAD 79

                  ....*...
gi 442620508   78 QLVTLELK 85
Cdd:cd23063    80 FKIVLEIQ 87

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.

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gi 442620508   31 VIYDIVENSPAADCGaVEAGDVILKVNGTDVHRYTTKEVLKCLRLSEQ-LVTLELKRD 87
Cdd:cd06782    17 VVVSPIPGGPAEKAG-IKPGDVIVAVDGESVRGMSLDEVVKLLRGPKGtKVKLTIRRG 73

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

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                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 442620508    31 VIYDIVENSPAADCGaVEAGDVILKVNGTDVHryTTKEVLKCLRLSE-QLVTLELKR 86
Cdd:pfam17820    1 VVTAVVPGSPAERAG-LRVGDVILAVNGKPVR--SLEDVARLLQGSAgESVTLTVRR 54

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508    3 EELKVVLRrSEQHSGFGFSLLG------TTGPPHVIYDIVENSPAADCGAVEAGDVILKVNGTDVHRYTTKEVLKCLRLS 76
Cdd:cd06686     6 ETTEVILR-GDPLKGFGIQLQGgvfateTLSSPPLISFIEPDSPAERCGVLQVGDRVLSINGIPTEDRTLEEANQLLRDS 84

                          90
                  ....*....|.
gi 442620508   77 EQLVTLELKRD 87
Cdd:cd06686    85 ASKVTLEIEFD 95

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.

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gi 442620508    7 VVLRRSeqHSGFGFSLLGTTGPPHV-----IY--DIVENSPAADCGAVEAGDVILKVNGTDVHRYTTKEVLKCLRLSEQL 79
Cdd:cd06723     4 ITLERG--NSGLGFSIAGGTDNPHIgddpsIYitKIIPGGAAAADGRLRVNDIILRVNDVDVRNVTHSVAVEALKEAGSI 81

                  ....*..
gi 442620508   80 VTLELKR 86
Cdd:cd06723    82 VRLYVKR 88

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442620508    6 KVVLRRsEQHSGFGFSLLGTT--GPPHVIYDIVENSPAADCGAVEAGDVILKVNGTDVHRYTTKEVLKCLRLSEQLVTLE 83
Cdd:cd06800     2 KVLLSK-EPHEGLGISITGGKehGVPILISEIHEGQPADRCGGLYVGDAILSVNGIDLRDAKHKEAVTILSQQRGEITLE 80

                  .
gi 442620508   84 L 84
Cdd:cd06800    81 V 81

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.

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gi 442620508    5 LKVVLRRSEQHSGFGFSLlgttGPPHVIYDIVENSPAADCGAVEAGDVILKVNGTDVHRYTTKEVLKCLRLSEQLVTLEL 84
Cdd:cd06728     1 LKVTLTKSRKNDEYGLRL----GSRIFVKEITPDSLAAKDGNLQEGDIILKINGTPVENLSLSEAKKLIEKSKDKLQLVV 76

                  ...
gi 442620508   85 KRD 87
Cdd:cd06728    77 LRD 79

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.

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gi 442620508    6 KVVLRRSEqhSGFGFSLLGTT-GPPHVIYDIVENSPAADCGAVEAGDVILKVNGTDVHRYTTKEVLKCLRLSEQLVTLEL 84
Cdd:cd06795     4 KIVLHKGS--TGLGFNIVGGEdGEGIFISFILAGGPADLSGELRRGDQILSVNGVDLRNATHEQAAAALKNAGQTVTIIA 81

                  ....
gi 442620508   85 KRDP 88
Cdd:cd06795    82 QYKP 85

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

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gi 442620508    7 VVLRRseQHSGFGFSLLGTTgpPHVIYDIVENSPAADCGaVEAGDVILKVNGTDVHRYTTKEVLKCLRLSEQLVTLEL 84
Cdd:cd06744     2 VRVYR--GNGSFGFTLRGHA--PVYIESVDPGSAAERAG-LKPGDRILFLNGLDVRNCSHDKVVSLLQGSGSMPTLVV 74

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.

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gi 442620508    3 EELKVVLRRsEQHSgFGFSLLG--------TTGPPHVIY--DIVENSPAADCGAVEAGDVILKVNGTDVHRYTTKEVLKC 72
Cdd:cd06715     1 KPFTVVLHR-ENGS-LGFNIIGgrpcennqEGSSSEGIYvsKIVENGPAADEGGLQVHDRIIEVNGKDLSKATHEEAVEA 78

                          90
                  ....*....|....
gi 442620508   73 LRLSEQLVTLELKR 86
Cdd:cd06715    79 FRTAKEPIVVQVLR 92

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.

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gi 442620508   16 SGFGFSLLGTTGPPH---VIYDIVENSPAADCGAVEAGDVILKVNGTDVHRYTTKEVLKCLRLSEQLVTLELKR 86
Cdd:cd06673    13 KGLGLSIVGGSDTLLgaiIIHEVYEDGAAAKDGRLWAGDQILEVNGEDLRKATHDEAINVLRQTPQKVRLLVYR 86

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.

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gi 442620508    6 KVVLRRSEQHSGFGFSLLGttGPPHV--IY-DIVENSPAADCGAVEAGDVILKVNGTDVHRYTTKEVLKCLRLSEQLV 80
Cdd:cd06740     3 QVTLKRSKSHEGLGFSIRG--GAEHGvgIYvSLVEPGSLAEKEGLRVGDQILRVNDVSFEKVTHAEAVKILRVSKKLV 78