Apx/Shroom domain ASD2; This region is found in the actin binding protein Shroom which mediates apical contriction in epithelial cells and is required for neural tube closure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883  1318 ELAREIVGKDKSLADILDPSVKIKTTMDLMEGIFPKDEHLLEEAQQRRKllpkipSPRSTEERKEEPSVPAAVSLATNST 1397
Cdd:pfam08687    1 ELVKELVPKDKSLADILDPKPSRKTTMDLMEGLFPEDTLRAMKPDLGEA------YKKAPSEEGSEEEASGTSSLSSCSA 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883  1398 YYSTSAPKAELLIKMKDL---QEQQEHEEDSGSDLDHDLSVKK-ELIESISRKLQVLREARESLLEDVQANTVLGAEVEA 1473
Cdd:pfam08687   75 YYTTSAPKAELLTKMKDLttlPSPDQPEEQGEEELDNDLQQKKvELIESLQRKLQVLREEQEALQEEIQANAALGAEVEA 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883  1474 IVKGVCKPSEFDKFRMFIGDLDKVVNLLLSLSGRLARVENALNNLDDGASPGDRQSLLEKQRVLIQQHEDAKELKENLDR 1553
Cdd:pfam08687  155 LVQEVCKPNELEKYRMFIGDLEKVVSLLLSLSGRLARVENALSSLDSDADAEERQSLLEKRRLLLRQLEDAKELKENLDR 234

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 578837883  1554 RERIVFDILANYLSEESLADYEHFVKMKSALIIEQRELEDKIHLGEEQLKCLLDSL 1609
Cdd:pfam08687  235 RERVVSGILARYLTAEQLQDYRHFVKMKAALLIEQRELDEKIKLGEEQLKALKESL 290

PDZ domain of shroom2, shroom3, shroom4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of shroom2, shroom3, shroom4, and related domains. Shroom family proteins shroom2 (also known as apical-like protein; protein APXL), shroom3 (also known as shroom-related protein), and shroom4 (also known as second homolog of apical protein) are essential regulators of cell morphology during animal development; they regulate cell architecture by directing the subcellular distribution and activation of Rho kinase (ROCK), which results in the localized activation of non-muscle myosin. The interaction between shroom and ROCK is mediated by the shroom domain 2 (SD2). 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 shroom2,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883   25 RLVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVGINDIGLSGFRQEAICLVKGSHKTLKLVV 104
Cdd:cd06750     1 QLIEVQLQGGAPWGFTLKGGLEHGEPLVISKIEEGGKAASVGKLQVGDEVVNINGVPLSGSRQEAIQLVKGSHKTLKLVV 80

                  ..
gi 578837883  105 KR 106
Cdd:cd06750    81 RR 82

Apx/Shroom domain ASD2; This region is found in the actin binding protein Shroom which mediates apical contriction in epithelial cells and is required for neural tube closure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883  1318 ELAREIVGKDKSLADILDPSVKIKTTMDLMEGIFPKDEHLLEEAQQRRKllpkipSPRSTEERKEEPSVPAAVSLATNST 1397
Cdd:pfam08687    1 ELVKELVPKDKSLADILDPKPSRKTTMDLMEGLFPEDTLRAMKPDLGEA------YKKAPSEEGSEEEASGTSSLSSCSA 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883  1398 YYSTSAPKAELLIKMKDL---QEQQEHEEDSGSDLDHDLSVKK-ELIESISRKLQVLREARESLLEDVQANTVLGAEVEA 1473
Cdd:pfam08687   75 YYTTSAPKAELLTKMKDLttlPSPDQPEEQGEEELDNDLQQKKvELIESLQRKLQVLREEQEALQEEIQANAALGAEVEA 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883  1474 IVKGVCKPSEFDKFRMFIGDLDKVVNLLLSLSGRLARVENALNNLDDGASPGDRQSLLEKQRVLIQQHEDAKELKENLDR 1553
Cdd:pfam08687  155 LVQEVCKPNELEKYRMFIGDLEKVVSLLLSLSGRLARVENALSSLDSDADAEERQSLLEKRRLLLRQLEDAKELKENLDR 234

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 578837883  1554 RERIVFDILANYLSEESLADYEHFVKMKSALIIEQRELEDKIHLGEEQLKCLLDSL 1609
Cdd:pfam08687  235 RERVVSGILARYLTAEQLQDYRHFVKMKAALLIEQRELDEKIKLGEEQLKALKESL 290

PDZ domain of shroom2, shroom3, shroom4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of shroom2, shroom3, shroom4, and related domains. Shroom family proteins shroom2 (also known as apical-like protein; protein APXL), shroom3 (also known as shroom-related protein), and shroom4 (also known as second homolog of apical protein) are essential regulators of cell morphology during animal development; they regulate cell architecture by directing the subcellular distribution and activation of Rho kinase (ROCK), which results in the localized activation of non-muscle myosin. The interaction between shroom and ROCK is mediated by the shroom domain 2 (SD2). 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 shroom2,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883   25 RLVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVGINDIGLSGFRQEAICLVKGSHKTLKLVV 104
Cdd:cd06750     1 QLIEVQLQGGAPWGFTLKGGLEHGEPLVISKIEEGGKAASVGKLQVGDEVVNINGVPLSGSRQEAIQLVKGSHKTLKLVV 80

                  ..
gi 578837883  105 KR 106
Cdd:cd06750    81 RR 82

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883    26 LVEVQLSGGAPWGFTLKGGREHGE-PLVITKIEEGSkAAAVDKLLAGDEIVGINDIGLSGFRQE-AICLVKGSHKTLKLV 103
Cdd:pfam00595    1 QVTLEKDGRGGLGFSLKGGSDQGDpGIFVSEVLPGG-AAEAGGLKVGDRILSINGQDVENMTHEeAVLALKGSGGKVTLT 79

                   ..
gi 578837883   104 VK 105
Cdd:pfam00595   80 IL 81

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883  1480 KPSEFDKFRMFIGDLDKVVNLLLSLSGRLARVENALNNLDDGASPGDRQ-SLLEKQRVLI-QQHEDAKELKENLDRRERI 1557
Cdd:TIGR02169  669 SRSEPAELQRLRERLEGLKRELSSLQSELRRIENRLDELSQELSDASRKiGEIEKEIEQLeQEEEKLKERLEELEEDLSS 748

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 578837883  1558 VFDILANYlsEESLADYEHfvkmksaliiEQRELEDKIHLGEEQLKCLLDSLQPER 1613
Cdd:TIGR02169  749 LEQEIENV--KSELKELEA----------RIEELEEDLHKLEEALNDLEARLSHSR 792

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578837883   37 WGFTLKGGREHGEPLVITKIEEGSKAAAVDkLLAGDEIVGINDIGLSGFrQEAICLVKGS-HKTLKLVVKR 106
Cdd:COG0750   116 AVLFMTVGVPVLTPPVVGEVVPGSPAAKAG-LQPGDRIVAINGQPVTSW-DDLVDIIRASpGKPLTLTVER 184

Apx/Shroom domain ASD2; This region is found in the actin binding protein Shroom which mediates apical contriction in epithelial cells and is required for neural tube closure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883  1318 ELAREIVGKDKSLADILDPSVKIKTTMDLMEGIFPKDEHLLEEAQQRRKllpkipSPRSTEERKEEPSVPAAVSLATNST 1397
Cdd:pfam08687    1 ELVKELVPKDKSLADILDPKPSRKTTMDLMEGLFPEDTLRAMKPDLGEA------YKKAPSEEGSEEEASGTSSLSSCSA 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883  1398 YYSTSAPKAELLIKMKDL---QEQQEHEEDSGSDLDHDLSVKK-ELIESISRKLQVLREARESLLEDVQANTVLGAEVEA 1473
Cdd:pfam08687   75 YYTTSAPKAELLTKMKDLttlPSPDQPEEQGEEELDNDLQQKKvELIESLQRKLQVLREEQEALQEEIQANAALGAEVEA 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883  1474 IVKGVCKPSEFDKFRMFIGDLDKVVNLLLSLSGRLARVENALNNLDDGASPGDRQSLLEKQRVLIQQHEDAKELKENLDR 1553
Cdd:pfam08687  155 LVQEVCKPNELEKYRMFIGDLEKVVSLLLSLSGRLARVENALSSLDSDADAEERQSLLEKRRLLLRQLEDAKELKENLDR 234

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 578837883  1554 RERIVFDILANYLSEESLADYEHFVKMKSALIIEQRELEDKIHLGEEQLKCLLDSL 1609
Cdd:pfam08687  235 RERVVSGILARYLTAEQLQDYRHFVKMKAALLIEQRELDEKIKLGEEQLKALKESL 290

PDZ domain of shroom2, shroom3, shroom4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of shroom2, shroom3, shroom4, and related domains. Shroom family proteins shroom2 (also known as apical-like protein; protein APXL), shroom3 (also known as shroom-related protein), and shroom4 (also known as second homolog of apical protein) are essential regulators of cell morphology during animal development; they regulate cell architecture by directing the subcellular distribution and activation of Rho kinase (ROCK), which results in the localized activation of non-muscle myosin. The interaction between shroom and ROCK is mediated by the shroom domain 2 (SD2). 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 shroom2,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883   25 RLVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVGINDIGLSGFRQEAICLVKGSHKTLKLVV 104
Cdd:cd06750     1 QLIEVQLQGGAPWGFTLKGGLEHGEPLVISKIEEGGKAASVGKLQVGDEVVNINGVPLSGSRQEAIQLVKGSHKTLKLVV 80

                  ..
gi 578837883  105 KR 106
Cdd:cd06750    81 RR 82

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883   29 VQLSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAAVdKLLAGDEIVGINDI---GLSgfRQEAICLVKGSHKTLKLVVK 105
Cdd:cd10820     2 VTLTGGAPWGFRLQGGSEQKKPLQVAKIRKKSKAALA-GLCEGDELLSINGKpcaDLS--HSEAMDLIDSSGDTLQLLIK 78

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 578837883   26 LVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVGINDIGLSGF-RQEAICLVKGSHKTLKLVV 104
Cdd:cd00136     1 TVTLEKDPGGGLGFSIRGGKDGGGGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLtHEEAVELLKSAGGEVTLTV 80

                  .
gi 578837883  105 K 105
Cdd:cd00136    81 R 81

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883    26 LVEVQLSGGAPWGFTLKGGREHGE-PLVITKIEEGSkAAAVDKLLAGDEIVGINDIGLSGFRQE-AICLVKGSHKTLKLV 103
Cdd:pfam00595    1 QVTLEKDGRGGLGFSLKGGSDQGDpGIFVSEVLPGG-AAEAGGLKVGDRILSINGQDVENMTHEeAVLALKGSGGKVTLT 79

                   ..
gi 578837883   104 VK 105
Cdd:pfam00595   80 IL 81

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 578837883   25 RLVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVGINDIGLSGFR-QEAICLVKGSHKTLKLV 103
Cdd:cd06801     1 RTVRVVKQDVGGLGISIKGGAEHKMPILISKIFKGQAADQTGQLFVGDAILSVNGENLEDAThDEAVQALKNAGDEVTLT 80

                  ..
gi 578837883  104 VK 105
Cdd:cd06801    81 VK 82

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 578837883   38 GFTLKGGREHGEPLVITKIEEGSkAAAVDKLLAGDEIVGINDIGLSGFRQEAICLVKGSHKTLKLVVKR 106
Cdd:cd10833    15 GFSVRGGSEHGLGIFVSKVEEGS-AAERAGLCVGDKITEVNGVSLENITMSSAVKVLTGSNRLRMVVRR 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
                  ....*....|....*....|....*....|....*....|....*
gi 578837883   38 GFTLKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVGINDIGL 82
Cdd:cd06800    14 GISITGGKEHGVPILISEIHEGQPADRCGGLYVGDAILSVNGIDL 58

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 578837883   37 WGFTLKGGREHGEPLVITKIEEGSKAaavDK--LLAGDEIVGINDIGLSGF-RQEAICLVKGShKTLKLVVK 105
Cdd:cd06740    15 LGFSIRGGAEHGVGIYVSLVEPGSLA---EKegLRVGDQILRVNDVSFEKVtHAEAVKILRVS-KKLVLSVR 82

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 578837883   25 RLVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGSkAAAVDKLLAGDEIVGINDIGLSGF-RQEAICLVKgSHKTLKLV 103
Cdd:cd06741     2 RKVNLVVEDGQSLGLMIRGGAEYGLGIYVTGVDPGS-VAENAGLKVGDQILEVNGRSFLDItHDEAVKILK-SSKHLIMT 79

                  ...
gi 578837883  104 VKR 106
Cdd:cd06741    80 VKD 82

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578837883   38 GFTLKGGREHG------EPLVITKIEEGSKAAAVDKLLAGDEIVGINDIGLSGFRQ-EAICLVKGSHKTLKLVVKRRS 108
Cdd:cd06703    15 GFSIAGGKGSTpfrdgdEGIFISRITEGGAADRDGKLQVGDRVLSINGVDVTEARHdQAVALLTSSSPTITLVVEREA 92

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 578837883   25 RLVEVQ-LSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAAVDkLLAGDEIVGINdiglsGFRQEAICLVK 94
Cdd:cd06755     1 RTVTLTrPSRESPLHFSLLGGSEKGFGIFVSKVEKGSKAAEAG-LKRGDQILEVN-----GQNFENITLKK 65

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883   33 GGAPWGFTLKGGREH----GEP-LVITKIEEGSKAAAVDKLLAGDEIVGINDIGLSGF-RQEAICLVKGSHKTLKLVVKR 106
Cdd:cd06723     9 GNSGLGFSIAGGTDNphigDDPsIYITKIIPGGAAAADGRLRVNDIILRVNDVDVRNVtHSVAVEALKEAGSIVRLYVKR 88

                  .
gi 578837883  107 R 107
Cdd:cd06723    89 R 89

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 578837883   38 GFTLKGGREHGEPLVITKIEEGSKAA-AVDKLLAGDEIVGINDIGLSGFRQE 88
Cdd:cd06706    17 GFNVKGGVDQKMPVIVSRVAPGTPADlCIPRLNEGDQVLLINGRDISEHTHD 68

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883   25 RLVEVQlSGGAPWGFTLKGGRehgePLVITKIEEGSKAAAVDkLLAGDEIVGINDIGLSGFRQE-AICLVKGSHKTLKLV 103
Cdd:cd06710     1 RTVEIA-RGRAGYGFTISGQA----PCVLSCVVRGSPADVAG-LKAGDQILAVNGINVSKASHEdVVKLIGKCTGVLRLV 74

                  .
gi 578837883  104 V 104
Cdd:cd06710    75 I 75

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 578837883   38 GFTLKGGREHGEPLVITKIEEGSKAAAVDKLLAGDEIVGINDIGLSGF 85
Cdd:cd06731    14 GFTIIGGDEPDEFLQIKSVVPDGPAALDGKLRTGDVLVSVNDTCVLGY 61

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883  1480 KPSEFDKFRMFIGDLDKVVNLLLSLSGRLARVENALNNLDDGASPGDRQ-SLLEKQRVLI-QQHEDAKELKENLDRRERI 1557
Cdd:TIGR02169  669 SRSEPAELQRLRERLEGLKRELSSLQSELRRIENRLDELSQELSDASRKiGEIEKEIEQLeQEEEKLKERLEELEEDLSS 748

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 578837883  1558 VFDILANYlsEESLADYEHfvkmksaliiEQRELEDKIHLGEEQLKCLLDSLQPER 1613
Cdd:TIGR02169  749 LEQEIENV--KSELKELEA----------RIEELEEDLHKLEEALNDLEARLSHSR 792

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883  933 SVELRRQAGDPGEP----REELPSAVRAEEGQSTPRqADAQCREGSPGSQQHPPSQKAPNPPTFSELSHCRGAPE----- 1003
Cdd:PHA03247 2567 SVPPPRPAPRPSEPavtsRARRPDAPPQSARPRAPV-DDRGDPRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPhpppt 2645

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883 1004 LPREGRGRAGTLPRDYRYSEESTPADLGPRAQSPgsPLHARGQDSWPVSSALLS--------KRPAPQRPPPPKREPRRY 1075
Cdd:PHA03247 2646 VPPPERPRDDPAPGRVSRPRRARRLGRAAQASSP--PQRPRRRAARPTVGSLTSladpppppPTPEPAPHALVSATPLPP 2723

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883 1076 RATDGAPADAPVGVLGRPFPTPSPASLDVYVARLSLSHSPSVFSSAQPQDTPKATVCERGSQHVSGDASRPLPEALLPPK 1155
Cdd:PHA03247 2724 GPAAARQASPALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWD 2803

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883 1156 QQH----LRLQTATMETSRSPSPQFAP-----QKLTDKPPLLIQDEDSTRIERVMDNNTTVKMVPIKIVHSESQPEKESR 1226
Cdd:PHA03247 2804 PADppaaVLAPAAALPPAASPAGPLPPptsaqPTAPPPPPGPPPPSLPLGGSVAPGGDVRRRPPSRSPAAKPAAPARPPV 2883

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 578837883 1227 QSLACPA-EPPALPHGLEKDQIKTLSTSEQFYSrfclyTRQGAEPEAPHRAQPAEPQPLGTQVPPEKDRCTSPPG 1300
Cdd:PHA03247 2884 RRLARPAvSRSTESFALPPDQPERPPQPQAPPP-----PQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAG 2953

DNA double-strand break repair ATPase Rad50;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883 1308 EKTVEDLKSE--ELaREIVGKDKSLADILDPSVKIKTTMDLMEGIFPKDEHLLEEAQQRRK-LLPKIPSPRSTEERKEEp 1384
Cdd:PRK03918  265 EERIEELKKEieEL-EEKVKELKELKEKAEEYIKLSEFYEEYLDELREIEKRLSRLEEEINgIEERIKELEEKEERLEE- 342

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578837883 1385 svpaavslatnstyysTSAPKAELLIKMKDLQEQQEHEEDSGSDLDHDLSVKKEL----IESISRKLQVLREARESLLED 1460
Cdd:PRK03918  343 ----------------LKKKLKELEKRLEELEERHELYEEAKAKKEELERLKKRLtgltPEKLEKELEELEKAKEEIEEE 406