Rap/ran-GAP;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112421013   625 YNNETAGPAFEEFLDLLGQRVRLKGFSKYRAQLDNKTDSTGTHSLYTTYKDYELMFHVSTLLPYMPNNRQQLLRKRHIGN 704
Cdd:pfam02145    1 LSNEEGSPAYEEFLNLLGWLVELKGFKGYRGGLDTKNNTTGEYSYYWADRGTEIMFHVSTLMPTTENDPQQLEKKRHIGN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112421013   705 DIVTIVFQEPGaLPFTPKSIRSHFQHVFVIVKVHNPCTENVCYSVGVSRSKDVPPFGPPIPKGVTFPKS--AVFRDFLLa 782
Cdd:pfam02145   81 DIVNIVFNESG-GPFDPSTIKSQFNHVFIVVQPNLPDTDNTLYRVSVVRKDDVPPFGPLLPDPKIFSKDnlPEFVRFLA- 158

                          170       180
                   ....*....|....*....|...
gi 112421013   783 kvINAENAAHKSEKFRAMATRTR 805
Cdd:pfam02145  159 --INAERAALKSSSFAERLRRIR 179

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 112421013  950 EMTLRRNGLGQLGFHVNFEGIVADVEPFGFAWKAGLRQGSRLVEICKVAVATLTHEQMIDLLRTSVTVKVVII 1022
Cdd:cd06745     1 ELTLRRNGLGQLGFHVNYEGFVTEVERFGFAWQAGLRQGSRLVEICKVPVATLTHEQMIDLLRTSVKVKVTVI 73

Rap/ran-GAP;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112421013   625 YNNETAGPAFEEFLDLLGQRVRLKGFSKYRAQLDNKTDSTGTHSLYTTYKDYELMFHVSTLLPYMPNNRQQLLRKRHIGN 704
Cdd:pfam02145    1 LSNEEGSPAYEEFLNLLGWLVELKGFKGYRGGLDTKNNTTGEYSYYWADRGTEIMFHVSTLMPTTENDPQQLEKKRHIGN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112421013   705 DIVTIVFQEPGaLPFTPKSIRSHFQHVFVIVKVHNPCTENVCYSVGVSRSKDVPPFGPPIPKGVTFPKS--AVFRDFLLa 782
Cdd:pfam02145   81 DIVNIVFNESG-GPFDPSTIKSQFNHVFIVVQPNLPDTDNTLYRVSVVRKDDVPPFGPLLPDPKIFSKDnlPEFVRFLA- 158

                          170       180
                   ....*....|....*....|...
gi 112421013   783 kvINAENAAHKSEKFRAMATRTR 805
Cdd:pfam02145  159 --INAERAALKSSSFAERLRRIR 179

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 112421013  950 EMTLRRNGLGQLGFHVNFEGIVADVEPFGFAWKAGLRQGSRLVEICKVAVATLTHEQMIDLLRTSVTVKVVII 1022
Cdd:cd06745     1 ELTLRRNGLGQLGFHVNYEGFVTEVERFGFAWQAGLRQGSRLVEICKVPVATLTHEQMIDLLRTSVKVKVTVI 73

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112421013   950 EMTLRRNGLGQLGF-------HVNFEGIVADVEPFGFAWKAGLRQGSRLVEICKVAVATLTHEQMIDLLRTSV-TVKVVI 1021
Cdd:pfam00595    1 QVTLEKDGRGGLGFslkggsdQGDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGSGgKVTLTI 80

                   .
gi 112421013  1022 I 1022
Cdd:pfam00595   81 L 81

Rap/ran-GAP;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112421013   625 YNNETAGPAFEEFLDLLGQRVRLKGFSKYRAQLDNKTDSTGTHSLYTTYKDYELMFHVSTLLPYMPNNRQQLLRKRHIGN 704
Cdd:pfam02145    1 LSNEEGSPAYEEFLNLLGWLVELKGFKGYRGGLDTKNNTTGEYSYYWADRGTEIMFHVSTLMPTTENDPQQLEKKRHIGN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112421013   705 DIVTIVFQEPGaLPFTPKSIRSHFQHVFVIVKVHNPCTENVCYSVGVSRSKDVPPFGPPIPKGVTFPKS--AVFRDFLLa 782
Cdd:pfam02145   81 DIVNIVFNESG-GPFDPSTIKSQFNHVFIVVQPNLPDTDNTLYRVSVVRKDDVPPFGPLLPDPKIFSKDnlPEFVRFLA- 158

                          170       180
                   ....*....|....*....|...
gi 112421013   783 kvINAENAAHKSEKFRAMATRTR 805
Cdd:pfam02145  159 --INAERAALKSSSFAERLRRIR 179

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 112421013  950 EMTLRRNGLGQLGFHVNFEGIVADVEPFGFAWKAGLRQGSRLVEICKVAVATLTHEQMIDLLRTSVTVKVVII 1022
Cdd:cd06745     1 ELTLRRNGLGQLGFHVNYEGFVTEVERFGFAWQAGLRQGSRLVEICKVPVATLTHEQMIDLLRTSVKVKVTVI 73

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 112421013  950 EMTLRRNGLGQLGFHV-----NFEGI-VADVEPFGFAWKAG-LRQGSRLVEICKVAVATLTHEQMIDLLRTS---VTVKV 1019
Cdd:cd00136     1 TVTLEKDPGGGLGFSIrggkdGGGGIfVSRVEPGGPAARDGrLRVGDRILEVNGVSLEGLTHEEAVELLKSAggeVTLTV 80

                  .
gi 112421013 1020 V 1020
Cdd:cd00136    81 R 81

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 112421013   950 EMTLRRNGLGQLGF-------HVNFEGIVADVEPFGFAWKAGLRQGSRLVEICKVAVATLTHEQMIDLLRTSV-TVKVVI 1021
Cdd:pfam00595    1 QVTLEKDGRGGLGFslkggsdQGDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGSGgKVTLTI 80

                   .
gi 112421013  1022 I 1022
Cdd:pfam00595   81 L 81

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 112421013  949 VEMTLRRNGLG-QLGFHVNfEGIVADVEPFGFAWKAGLRQGSRLVEICKVAVATLTHEQMIDLLRTSV 1015
Cdd:cd06793     3 TTVLIRRPDLKyQLGFSVQ-NGIICSLLRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVQLLSNSV 69

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 112421013  971 VADVEPFGFAWKAGLRQGSRLVEICKVAVATLTHEQMIDLLRTSV 1015
Cdd:cd23070    40 VSAVLEGGAADKAGVRKGDRILEVNGVNVEGATHKQVVDLIKSGG 84

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 112421013  951 MTLRRNGLGqLGFHVNFEGI--VADVEPFGFAWKAGLRQGSRLVEICKVAVATLTHEQMIDLLRTSVTVKV 1019
Cdd:cd23069     4 VVIQRDENG-YGLTVSGDNPvfVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLEVVKLIKSGSYVAL 73

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 112421013  950 EMTLRRNGLGQLGFHV--NFE---GI-VADVEPFGFAWKAGLRQGSRLVEICKVAVATLTHEQMIDLLRT--SVTVKV 1019
Cdd:cd06737     4 LVRLDRRGPESLGFSVrgGLEhgcGLfVSHVSPGSQADNKGLRVGDEIVRINGYSISQCTHEEVINLIKTkkTVSLKV 81