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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 824 STLVRVKKSAATLGIAIEGGANTRQPLPRIVTIQRGGSAHNCGQLKVGHVILEVNGLTLRGKEHREAARIIAEAFKTKDR 903
Cdd:cd06742    1 TLLVRIKKTKPTLGIAIEGGANTKQPLPRVINIQRGGSAHNCGGLKVGHVILEVNGTSLRGLEHREAARLIAEAFKNKSR 80

                         90
                 ....*....|.
gi 767956918 904 DYIDFLVTEFN 914
Cdd:cd06742   81 DYIEFLVTEFN 91

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 138 VRLVSLRRAKAHEGLGFSIRGGSEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKALKGSKKLVLS 217
Cdd:cd06740    1 VRQVTLKRSKSHEGLGFSIRGGAEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDVSFEKVTHAEAVKILRVSKKLVLS 80

                 ..
gi 767956918 218 VY 219
Cdd:cd06740   81 VR 82

second harmonin_N_like domain (repeat 2) of the long isoform of whirlin, and related domains; This subgroup contains the second of two harmonin_N_like domains found in the long isoform of whirlin, and related domains. Whirlin is a postsynaptic density-95/discs-large/ZO-1 (PDZ) domain-containing scaffold protein which binds various components of the Usher protein network of the inner ear and the retina: erythrocyte protein p55, usherin, VlGR1, and myosin XVa. The long isoform of whirlin contains two harmonin_N_like domains, and three PDZ protein-binding domains, PDZ1-3. The short whirlin isoform, derived from an alternative start ATG, lacks the first harmonin_N_like domain but has in common with the long isoform, this second harmonin_N_like domain (designated repeat 2, included in this subgroup) and PDZ3. This second harmonin_N_like domain is a putative protein-binding module based on its sequence similarity to the N-terminal domain of harmonin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 419 GNQTRVLLEEQARHLLNEQEHATMAYYLDEYRGGSVSVEALVMALFKLLNTHAKFSLLSEVRGTISPQDLERFDHLVLRR 498
Cdd:cd07357    1 SSQTAALVEEKARSLLNRSERATLSYYLAEYSSGHLTVDAFVLALFELLNTPEKFSLLSEIRELVAPEDLDRFDELVLRR 80

                 .
gi 767956918 499 E 499
Cdd:cd07357   81 E 81

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 824 STLVRVKKSAATLGIAIEGGANTRQPLPRIVTIQRGGSAHNCGQLKVGHVILEVNGLTLRGKEHREAARIIAEAFKTKDR 903
Cdd:cd06742    1 TLLVRIKKTKPTLGIAIEGGANTKQPLPRVINIQRGGSAHNCGGLKVGHVILEVNGTSLRGLEHREAARLIAEAFKNKSR 80

                         90
                 ....*....|.
gi 767956918 904 DYIDFLVTEFN 914
Cdd:cd06742   81 DYIEFLVTEFN 91

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 138 VRLVSLRRAKAHEGLGFSIRGGSEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKALKGSKKLVLS 217
Cdd:cd06740    1 VRQVTLKRSKSHEGLGFSIRGGAEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDVSFEKVTHAEAVKILRVSKKLVLS 80

                 ..
gi 767956918 218 VY 219
Cdd:cd06740   81 VR 82

second harmonin_N_like domain (repeat 2) of the long isoform of whirlin, and related domains; This subgroup contains the second of two harmonin_N_like domains found in the long isoform of whirlin, and related domains. Whirlin is a postsynaptic density-95/discs-large/ZO-1 (PDZ) domain-containing scaffold protein which binds various components of the Usher protein network of the inner ear and the retina: erythrocyte protein p55, usherin, VlGR1, and myosin XVa. The long isoform of whirlin contains two harmonin_N_like domains, and three PDZ protein-binding domains, PDZ1-3. The short whirlin isoform, derived from an alternative start ATG, lacks the first harmonin_N_like domain but has in common with the long isoform, this second harmonin_N_like domain (designated repeat 2, included in this subgroup) and PDZ3. This second harmonin_N_like domain is a putative protein-binding module based on its sequence similarity to the N-terminal domain of harmonin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 419 GNQTRVLLEEQARHLLNEQEHATMAYYLDEYRGGSVSVEALVMALFKLLNTHAKFSLLSEVRGTISPQDLERFDHLVLRR 498
Cdd:cd07357    1 SSQTAALVEEKARSLLNRSERATLSYYLAEYSSGHLTVDAFVLALFELLNTPEKFSLLSEIRELVAPEDLDRFDELVLRR 80

                 .
gi 767956918 499 E 499
Cdd:cd07357   81 E 81

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767956918   286 DGRSLGLTIRGGAEYGLGIYITGVDPGSEAEGSGLKVGDQILEVNGRSFLNILHDEAVRLLKSSR-HLILTVK 357
Cdd:smart00228  10 GGGGLGFSLVGGKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGgKVTLTVL 82

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918  279 KVNLVLGDGRSLGLTIRGGAEYGL-GIYITGVDPGSEAEGSGLKVGDQILEVNGRSFLNILHDEAVRLLKSSR-HLILTV 356
Cdd:pfam00595   1 QVTLEKDGRGGLGFSLKGGSDQGDpGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGSGgKVTLTI 80

                  .
gi 767956918  357 K 357
Cdd:pfam00595  81 L 81

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767956918 150 EGLGFSIRggSEHGvGIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKALKGSK--KLVLSVYSAG 222
Cdd:COG0793   60 GGLGAELG--EEDG-KVVVVSVIPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLLRGKAgtKVTLTIKRPG 131

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918  159 GSEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTH-AEAVKALKGSKKLVLSVYSAGRIPGGYVTnhIYTWV 237
Cdd:TIGR02037 252 GLEKQRGALVAQVLPGSPAEKAGLKAGDVITSVNGKPISSFADlRRAIGTLKPGKKVTLGILRKGKEKTITVT--LGASP 329

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918  238 DPQGRSISPPSGLpqphggalrqqegdrrsTLHLLQGGDEKKVNLVlGDGRslgltirggaeyglGIYITGVDPGSEAEG 317
Cdd:TIGR02037 330 EEQASSSNPFLGL-----------------TVANLSPEIRKELRLK-GDVK--------------GVVVTKVVSGSPAAR 377

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 767956918  318 SGLKVGDQILEVNGRSFLNI--LHDeAVRLLKSSRHLILTV 356
Cdd:TIGR02037 378 AGLQPGDVILSVNQQPVSSVaeLRK-VLARAKKGGRVALLI 417

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767956918  836 LGIAIEGGANTRQPLPRIVTIQRGGSAHnCGQLKVGHVILEVNGLTLRGKEHREAARIIAEA 897
Cdd:pfam00595  12 LGFSLKGGSDQGDPGIFVSEVLPGGAAE-AGGLKVGDRILSINGQDVENMTHEEAVLALKGS 72

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
                  ....*....|....*....|....*....|....*....|....
gi 767956918  289 SLGLTIRGGAeyglgiYITGVDPGSEAEGSGLKVGDQILEVNGR 332
Cdd:TIGR02037 250 SLGLEKQRGA------LVAQVLPGSPAEKAGLKAGDVITSVNGK 287

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 824 STLVRVKKSAATLGIAIEGGANTRQPLPRIVTIQRGGSAHNCGQLKVGHVILEVNGLTLRGKEHREAARIIAEAFKTKDR 903
Cdd:cd06742    1 TLLVRIKKTKPTLGIAIEGGANTKQPLPRVINIQRGGSAHNCGGLKVGHVILEVNGTSLRGLEHREAARLIAEAFKNKSR 80

                         90
                 ....*....|.
gi 767956918 904 DYIDFLVTEFN 914
Cdd:cd06742   81 DYIEFLVTEFN 91

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 138 VRLVSLRRAKAHEGLGFSIRGGSEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKALKGSKKLVLS 217
Cdd:cd06740    1 VRQVTLKRSKSHEGLGFSIRGGAEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDVSFEKVTHAEAVKILRVSKKLVLS 80

                 ..
gi 767956918 218 VY 219
Cdd:cd06740   81 VR 82

second harmonin_N_like domain (repeat 2) of the long isoform of whirlin, and related domains; This subgroup contains the second of two harmonin_N_like domains found in the long isoform of whirlin, and related domains. Whirlin is a postsynaptic density-95/discs-large/ZO-1 (PDZ) domain-containing scaffold protein which binds various components of the Usher protein network of the inner ear and the retina: erythrocyte protein p55, usherin, VlGR1, and myosin XVa. The long isoform of whirlin contains two harmonin_N_like domains, and three PDZ protein-binding domains, PDZ1-3. The short whirlin isoform, derived from an alternative start ATG, lacks the first harmonin_N_like domain but has in common with the long isoform, this second harmonin_N_like domain (designated repeat 2, included in this subgroup) and PDZ3. This second harmonin_N_like domain is a putative protein-binding module based on its sequence similarity to the N-terminal domain of harmonin.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 419 GNQTRVLLEEQARHLLNEQEHATMAYYLDEYRGGSVSVEALVMALFKLLNTHAKFSLLSEVRGTISPQDLERFDHLVLRR 498
Cdd:cd07357    1 SSQTAALVEEKARSLLNRSERATLSYYLAEYSSGHLTVDAFVLALFELLNTPEKFSLLSEIRELVAPEDLDRFDELVLRR 80

                 .
gi 767956918 499 E 499
Cdd:cd07357   81 E 81

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 138 VRLVSLRRAKAHEGLGFSIRGGSEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKALKGSKKLVLS 217
Cdd:cd10834    1 RRIVHLYTTSDDYCLGFNIRGGSEYGLGIYVSKVDPGGLAEQNGIKVGDQILAVNGVSFEDITHSKAVEVLKSQTHLMLT 80

                 ....*
gi 767956918 218 VYSAG 222
Cdd:cd10834   81 IKEVG 85

N-terminal protein-binding module of harmonin and similar domains, also known as HHD (harmonin homology domain); This domain is found in harmonin, and similar proteins such as delphilin, and whirlin. These are postsynaptic density-95/discs-large/ZO-1 (PDZ) domain-containing scaffold proteins. Harmonin and whirlin are organizers of the Usher protein network of the inner ear and the retina, delphilin is found at the cerebellar parallel fiber-Purkinje cell synapses. This domain is also found in CCM2 (also called malcavernin; C7orf22/chromosome 7 open reading frame 22; OSM). CCM2 along with CCM1 and CCM3 constitutes a set of proteins which when mutated are responsible for cerebral cavernous malformations, an autosomal dominant neurovascular disease characterized by cerebral hemorrhages and vascular malformations in the central nervous system. CCM2 plays many functional roles. CCM2 functions as a scaffold involved in small GTPase Rac-dependent p38 mitogen-activated protein kinase (MAPK) activation when the cell is under hyperosmotic stress. It associates with CCM1 in the signaling cascades that regulate vascular integrity and participates in HEG1 (the transmembrane receptor heart of glass 1) mediated endothelial cell junctions. CCM proteins also inhibit the activation of small GTPase RhoA and its downstream effector Rho kinase (ROCK) to limit vascular permeability. CCM2 mediates TrkA-dependent cell death via its N-terminal PTB domain in pediatric neuroblastic tumours; the C-terminal domain of malcavernin represented here has also been refered to as the Karet domain. Harmonin contains a single copy of this domain at its N-terminus which binds specifically to a short internal peptide fragment of the cadherin 23 cytoplasmic domain (a component of the Usher protein network). Whirlin contains two copies of this domain; the first of these has been assayed for interaction with the cytoplasmic domain of cadherin 23 and no interaction could be detected.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767956918 419 GNQTRVLLEEQARHLLNEQEHATMAYYLDEYRGGSvSVEALVMALFKLLNTHAKFSLLSEVRGTISPQDLERFDHLVLR 497
Cdd:cd07347    1 RRELARLFSEQADQLLTDQERAYVTQALSEYRKGR-SVEALVADLFPVLDTPAKLSLLQGLRSLIPPKDQQRFDELVAQ 78

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767956918 287 GRSLGLTIRGGAEYGLGIYITGVDPGSEAEGSGLKVGDQILEVNGRSFLNILHDEAVRLLKSSRHLILTVK 357
Cdd:cd06752   10 GEQLGFNIRGGKASGLGIFISKVIPDSDAHRLGLKEGDQILSVNGVDFEDIEHSEAVKVLKTAREIQMRVR 80

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 138 VRLVSLRRAKaHEGLGFSIRGGSEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKALKGSKKLVLS 217
Cdd:cd06741    1 ERKVNLVVED-GQSLGLMIRGGAEYGLGIYVTGVDPGSVAENAGLKVGDQILEVNGRSFLDITHDEAVKILKSSKHLIMT 79

                 ....*
gi 767956918 218 VYSAG 222
Cdd:cd06741   80 VKDVG 84

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 138 VRLVSLRRAKAhEGLGFSIRGGSEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKALKGSKKLVLS 217
Cdd:cd06737    2 LRLVRLDRRGP-ESLGFSVRGGLEHGCGLFVSHVSPGSQADNKGLRVGDEIVRINGYSISQCTHEEVINLIKTKKTVSLK 80

                 ....*
gi 767956918 218 VYSAG 222
Cdd:cd06737   81 VRHVG 85

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767956918 290 LGLTIRGGAEYGLGIYITGVDPGSEAEGSGLKVGDQILEVNGRSFLNILHDEAVRLLKSSRHLILTVK 357
Cdd:cd06755   14 LHFSLLGGSEKGFGIFVSKVEKGSKAAEAGLKRGDQILEVNGQNFENITLKKALEILRNNTHLSITVK 81

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 139 RLVSLRRAKAHEgLGFSIRGGSEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKALKGSKKLVLSV 218
Cdd:cd06752    1 RTVVLKRPPGEQ-LGFNIRGGKASGLGIFISKVIPDSDAHRLGLKEGDQILSVNGVDFEDIEHSEAVKVLKTAREIQMRV 79

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767956918 151 GLGFSIRGGSEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKALKGSKKLVLSV 218
Cdd:cd06738   14 GLGCSISSGPTQKPGIFISNVKPGSLAEEVGLEVGDQIVEVNGTSFTNVDHKEAVMALKSSRHLTITV 81

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 767956918   137 EVRLVSLRraKAHEGLGFSIRGGSEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKALKGSK-KLV 215
Cdd:smart00228   1 EPRLVELE--KGGGGLGFSLVGGKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGgKVT 78

                   ....*..
gi 767956918   216 LSVYSAG 222
Cdd:smart00228  79 LTVLRGG 85

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767956918   286 DGRSLGLTIRGGAEYGLGIYITGVDPGSEAEGSGLKVGDQILEVNGRSFLNILHDEAVRLLKSSR-HLILTVK 357
Cdd:smart00228  10 GGGGLGFSLVGGKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGgKVTLTVL 82

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767956918 139 RLVSLRRAKaHEGLGFSIRGGSEHGVGIYVSLVEPGSLAEK-EGLRVGDQILRVNDKSLARVTHAEAVKAL 208
Cdd:cd06800    1 RKVLLSKEP-HEGLGISITGGKEHGVPILISEIHEGQPADRcGGLYVGDAILSVNGIDLRDAKHKEAVTIL 70

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767956918 152 LGFSIRGGSEH-----GV---GIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKAL-KGSKKLVLSV 218
Cdd:cd06702   12 LGLSIVGGSDHsshpfGVdepGIFISKVIPDGAAAKSGLRIGDRILSVNGKDLRHATHQEAVSALlSPGQEIKLLV 87

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 278 KKVNLVLGDGRSLGLTIRGGAEYGLGIYITGVDPGSEAEGSG-LKVGDQILEVNGRSFLNILHDEAVRLLKSS-RHLILT 355
Cdd:cd06801    1 RTVRVVKQDVGGLGISIKGGAEHKMPILISKIFKGQAADQTGqLFVGDAILSVNGENLEDATHDEAVQALKNAgDEVTLT 80

                 ..
gi 767956918 356 VK 357
Cdd:cd06801   81 VK 82

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 287 GRSLGLTIRGGAEygLGIYITGVDPGSEAEGSGLKVGDQILEVNGRSFLNILHDEAVRLL 346
Cdd:cd06729   10 GGSVGLRLAGGND--VGIFVAGVQEGSPAEKQGLQEGDQILKVNGVDFRNLTREEAVLFL 67

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767956918 137 EVRLVslrraKAHEGLGFSIRGG--SEH---GVGIYVSLVEPGSLAEKEG-LRVGDQILRVNDKSLARVTHAEAVKALKG 210
Cdd:cd06724    1 EIKLV-----KGPKGLGFSIAGGvgNQHipgDNGIYVTKIIEGGAAQKDGrLQVGDKLLAVNDVSLEEVTHEEAVAALKN 75

                 ....*
gi 767956918 211 SKKLV 215
Cdd:cd06724   76 TSDVV 80

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.

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gi 767956918 825 TLVRVKKSAATLGIAIEGGANTRQPLpRIVTIQRGGSAHNCGQLKVGHVILEVNGLTLRGKEHREAARIIAEAFKT 900
Cdd:cd00136    1 TVTLEKDPGGGLGFSIRGGKDGGGGI-FVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGE 75

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.

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gi 767956918 141 VSLRRAKAHEGLGFSIRGGSEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKALKGS-KKLVLSVY 219
Cdd:cd23068    2 IRLRRDDSNTPWGFRLQGGADFGQPLSIQKVNPGSPADKAGLRRGDVILRINGTDTSNLTHKQAQDLIKRAgNDLQLTVQ 81

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.

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gi 767956918 151 GLGFSIRGG------SEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKALKGSKKLVLSV 218
Cdd:cd06704   11 GLGISIAGGkgstpyKGDDEGIFISRVTEGGPAAKAGVRVGDKLLEVNGVDLVDADHHEAVEALKNSGNTVTMV 84