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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 118151040 787 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEYIAIQACK 849
Cdd:cd08713    1 LEKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQSKMASRAKKIFAEYIAIQSCK 63

Regulator of G protein signaling (RGS) domain found in the RGS3 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS3 protein. RGS3 is a member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes. RGS3 induces apoptosis when overexpressed and is involved in cell migration through interaction with the Ephrin receptor. RGS3 exits as several splice isoforms and interacts with neuroligin, estrogen receptor-alpha, and 14-3-3 outside of the GPCR pathways.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 118151040 787 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEYIAIQACK 849
Cdd:cd08713    1 LEKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQSKMASRAKKIFAEYIAIQSCK 63

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 118151040   786 SLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEYIAIQACKR 850
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAEDDEERIAKAREIYDKFLSPNAPKE 65

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040   18 QITIPRGKDG-FGFTI-----CCDSPVRVQAVDSGGPAERAGLQQLDTVLRLNERPVEHWKCVELAHEIRSCPSEIILLV 91
Cdd:pfam00595   1 QVTLEKDGRGgLGFSLkggsdQGDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTI 80

                  .
gi 118151040   92 W 92
Cdd:pfam00595  81 L 81

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 118151040  38 VRVQAVDSGGPAERAGLQQLDTVLRLNERPVEHWKcvELAHEIRSCP--SEIILLVWR 93
Cdd:COG0265  203 VLVARVEPGSPAAKAGLRPGDVILAVDGKPVTSAR--DLQRLLASLKpgDTVTLTVLR 258

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 118151040   38 VRVQAVDSGGPAERAGLQQLDTVLRLNERPVEHWKCVELAHEIRSCPSEIILLVWR 93
Cdd:TIGR02037 364 VVVTKVVSGSPAARAGLQPGDVILSVNQQPVSSVAELRKVLARAKKGGRVALLILR 419

Regulator of G protein signaling (RGS) domain found in the RGS3 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS3 protein. RGS3 is a member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes. RGS3 induces apoptosis when overexpressed and is involved in cell migration through interaction with the Ephrin receptor. RGS3 exits as several splice isoforms and interacts with neuroligin, estrogen receptor-alpha, and 14-3-3 outside of the GPCR pathways.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 118151040 787 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEYIAIQACK 849
Cdd:cd08713    1 LEKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQSKMASRAKKIFAEYIAIQSCK 63

Regulator of G protein signaling (RGS) domain found in the RGS5 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS5 protein. RGS5 is member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Two splice isoforms of RGS5 has been found: RGS5L (long) which is expressed in smooth muscle cells (pericytes) and heart and RGS5S (short) which is highly expressed in the ciliary body of the eye, kidney, brain, spleen, skeletal muscle, and small intestine. Outside of the GPCR pathway, RGS5 interacts with the 14-3-3 protein.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 118151040 787 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEYIAIQACK 849
Cdd:cd08717    1 LDKLLQNSYGLASFKSFLKSEFSEENIEFWEACEDYKKTKSPLKMATKAKKIYEEFIQTEAPK 63

Regulator of G protein signaling (RGS) domain found in the RGS2 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS2 protein. RGS2 is a member of R4/RGS subfamily of RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G- alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS2 plays important roles in the regulation of blood pressure and the pathogenesis of human hypertension, as well as in bone formation in osteoblasts. Outside of the GPCR pathway RGS2 interacts with calmodulin, beta- COP, tubulin, PKG1-alpha, and TRPV6.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 118151040 787 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEYIAIQACK 849
Cdd:cd08709    1 FDELLASKYGVAAFRAFLKSEFSEENIEFWLACEDFKKTKSPQKLTSKAKKIYTDFIEKEAPK 63

Regulator of G protein signaling (RGS) domain found in the RGS4 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS4 protein. RGS4 is a member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. RGS4 is expressed widely in brain including prefrontal cortex, striatum, locus coeruleus (LC), and hippocampus and has been implicated in regulation of opioid, cholinergic, and serotonergic signaling. Dysfunctions in RGS4 proteins are involved in etiology of Parkinson's disease, addiction, and schizophrenia. RGS4 also is up-regulated in the failing human heart. RGS4 interacts with many binding partners outside of GPCR pathways, including calmodulin, COP, Kir3, PIP, calcium/CaM, PA, ErbB3, and 14-3-3.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 118151040 787 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEYIAIQACK 849
Cdd:cd08714    1 LENLINHECGLAAFKAFLKSEYSEENIDFWVSCEDYKKTKSPSKLSPKARKIYEEFISVQATK 63

Regulator of G protein signaling (RGS) domain found in the RGS20 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS20 protein (also known as RGSZ1), a member of the RZ subfamily of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling is controlled by the RGS domain, which accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP resulting in reassociation of the alpha-subunit with the beta-gamma-dimer and inhibition of downstream activity. As a major G-protein regulator, the RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The RZ subfamily of RGS proteins include RGS17, RGS19 (former GAIP), and the splice variant of RGS20, Ret-RGS. RGS20 is expressed exclusively in brain, with the highest concentrations in the temporal lobe and the caudate nucleus and may play a role in signaling regulation in these brain regions. RGS20 acts as a GAP of both G-alpha-z and G-alpha-I and controls signaling in the mu opioid receptor pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040 752 RRRNESPGAQPTGKTDkVMKSFKPTSEEALKWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKM 831
Cdd:cd08746   20 RNRRTSYEFRAEGIPN-CEESPKPTLEEVCAWGQSFDKLMLTPAGRNAFREFLRTEFSEENMLFWMACEELKKEANKSVI 98

                         90
                 ....*....|....*...
gi 118151040 832 AAKAKKIFAEYIAIQACK 849
Cdd:cd08746   99 EEKARIIYEDYISILSPK 116

Regulator of G protein signaling (RGS) domain found in the RGS21 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part RGS21 protein, a member of RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, apoptosis, and cell proliferation, as well as modulation of cardiac development. RGS21 is a member of the R4/RGS subfamily and its mRNA was detected only in sensory taste cells that express sweet taste receptors and the taste G-alpha subunit, gustducin, suggesting a potential role in regulating taste transduction.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040 790 LLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEYIAIQACK 849
Cdd:cd08723    1 LLANQAGLDAFRTFLKSEFSEENVEFWLACEDFKKTKSSTEIALKAQMIYSEFIQADAPK 60

Regulator of G protein signaling (RGS) domain found in the RGS18 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS18 protein. RGS18 is a member of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS18 is a member of the R4/RGS subfamily and is expressed predominantly in osteoclasts where it acts as a negative regulator of the acidosis-induced osteoclastogenic OGR1/NFAT signaling pathway. RANKL (receptor activator of nuclear factor B ligand) stimulates osteoclastogenesis by inhibiting expression of RGS18.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 118151040 787 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEYIAIQACK 849
Cdd:cd08712    1 FDKLLSHKDGLEAFTRFLKTEFSEENIEFWIACEDYKKSKTPQQIHLKAKAIYEKFIQTDAPK 63

Regulator of G protein signaling (RGS) domain found in the RGS19 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS19 protein (also known as GAIP), a member of the RZ subfamily of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling is controlled by RGS domains, which accelerate GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, resulting in a reassociation of the alpha-subunit with the beta-gamma-dimer and an inhibition of downstream activity. As a major G-protein regulator, the RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The RZ subfamily of RGS proteins includes RGS17, RGS20, and its splice variant Ret-RGS. RGS19 participates in regulation of dopamine receptor D2R and D3R, as well as beta-adrenergic receptors .

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 118151040 783 WGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEYIAIQACK 849
Cdd:cd08745    1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELKAEANKHVIDEKARLIYEDYISILSPK 67

Regulator of G protein signaling (RGS) domain found in the RGS13 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS13 protein. RGS13 is member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS13 is predominantly expressed in T and B lymphocytes and in mast cells, and plays a role in adaptive immune responses. RGS13 also found in Rgs13, which is also expressed in dendritic cells and in neuroendocrine cells of the thymus, gastrointestinal, and respiratory tracts. Outside of the GPCR pathway, RGS5 interacts with the PIP3 protein.

                         10        20        30        40        50        60
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gi 118151040 788 EKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEYIAIQA 847
Cdd:cd08716    2 ENLMATKYGPIIYATYLKTEHSDENIEFWLACETYKKIASQRKRISMARKLFASYIQPQA 61

Regulator of G protein signaling (RGS) domain found in the RGS10 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS10 protein. RGS10 is a member of the RA/RGS subfamily of RGS proteins family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS10 belong to the R12 RGS subfamily, which includes RGS12 and RGS14, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS10 exists in 2 splice isoforms. RGS10A is specifically expressed in osteoclasts and is a key component in the RANKL signaling mechanism for osteoclast differentiation, whereas RGS10B expressed in brain and in immune tissues and has been implicated in diverse processes including: promoting of dopaminergic neuron survival via regulation of the microglial inflammatory response, modulation of presynaptic and postsynaptic G-protein signalling, as well as a possible role in regulation of gene expression.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 118151040 787 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEYIAIQA 847
Cdd:cd08741    1 LENLLEDPEGVKRFREFLKKEFSEENVLFWLACEDFKKMQDKTQMQEKAKEIYMTFLSSKA 61

Regulator of G protein signaling (RGS) domain found in the RGS14 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS14 protein. RGS14 is a member of the RA/RGS subfamily of RGS proteins family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS14 belong to the R12 RGS subfamily, which includes RGS10 and RGS12, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS14 binds and regulates the subcellular localization and activities of H-Ras and Raf kinases in cells and thereby integrates G protein and Ras/Raf signaling pathways.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 118151040 783 WGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQ--SKMAAKAKKIFAEYIAIQA 847
Cdd:cd08743    7 WAVSFERLLQDPLGVEYFTEFLKKEFSAENVNFWKACERFQQIPASdtQQLAQEARKIYNEFLSSSS 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 118151040  19 ITIPRGK-DGFGFTIC----CDSPVRVQAVDSGGPAERAG-LQQLDTVLRLNERPVEHWKCVELAHEIRSCPSEIILLV 91
Cdd:cd00136    2 VTLEKDPgGGLGFSIRggkdGGGGIFVSRVEPGGPAARDGrLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGEVTLTV 80

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 118151040  16 YRQITIPRGKDGFGFTICCDSPVRVQAVDSGGPAERAGLQQLDTVLRLNERPVEHWKCVELAHEIRS 82
Cdd:cd23069    1 QRCVVIQRDENGYGLTVSGDNPVFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLEVVKLIKS 67

Regulator of G protein signaling (RGS) domain found in the RGS9 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS9 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Other members of the R7 subfamily (Neuronal RGS) include: RGS6, RGS7, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. RGS9 forms constitutive complexes with G-beta-5 subunit and controls such fundamental functions as vision and behavior. RGS9 exists in two splice isoforms: RGS9-1 which regulates phototransduction in rods and cones and RGS9-2 which regulates dopamine and opioid signaling in the basal ganglia. In addition, RGS9 was found to bind many other proteins outside of G protein signaling pathways including: mu-opioid receptor, beta-arrestin, alpha-actinin-2, NMDAR, polycystin, spinophilin, and guanylyl cyclase, among others.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 118151040 782 KWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFkKVKSQSKMAAKAKKIFAEYIA 844
Cdd:cd08739    4 RWAFNFSELIRDPKGRQSFQLFLKKEFSGENLGFWEACEDL-KYGDQSKVKEKAEEIYKLFLA 65

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040  17 RQITIPRGKDGFGFTICCDSPVR---VQAVDSGGPAERAGLQQLDTVLRLNERPVE---HWKCVELaheIRSCPSEIILL 90
Cdd:cd06768    1 RLCHLVKGPEGYGFNLHAEKGRPghfIREVDPGSPAERAGLKDGDRLVEVNGENVEgesHEQVVEK---IKASGNQVTLL 77

                 .
gi 118151040  91 V 91
Cdd:cd06768   78 V 78

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 118151040  18 QITIPRgkD---GFGFTICCDSPVRVQAVDSGGPAErAGLQQLDTVLRLNERPVEHWKCVELAHEIRSCPSEIILLV 91
Cdd:cd06769    1 TVEIQR--DavlGFGFVAGSERPVVVRSVTPGGPSE-GKLLPGDQILKINNEPVEDLPRERVIDLIRECKDSIVLTV 74

Regulator of G protein signaling (RGS) domain found in the RGS12 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS12 protein. RGS12 is a member of the RA/RGS subfamily of RGS proteins family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS12 belong to the R12 RGS subfamily, which includes RGS10 and RGS14, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS12 exist in multiple splice variants: RGS12s (short) contains the core RGS/RBD/GoLoco domains, while RGS12L (long) has additional N-terminal PDZ and PTB domains. RGS12 splice variants show distinct expression patterns, suggesting that they have discrete functions during mouse embryogenesis. RGS12 also may play a critical role in coordinating Ras-dependent signals that are required for promoting and maintaining neuronal differentiation.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 118151040 787 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSK--MAAKAKKIFAEYIAIQA 847
Cdd:cd08742    1 FERLLQDPVGVRYFSEFLRKEFSEENILFWQACEYFNHVPAHDKkeLSYRAREIFSKFLCSKA 63

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 118151040  28 FGFTICCDSPVRVQAVDSGGPAERAGLQQLDTVLRLNERPVEHWKC---VELAHEIRSCPSEI 87
Cdd:cd06743   11 FGFSIGGSGPCYILSVEEGSSAHAAGLQPGDQILELDGQDVSSLSCeaiIALARRCPSVPPSL 73

Regulator of G protein signaling (RGS) domain found in the RGS7 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS7 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Other members of the R7 subfamily (Neuronal RGS) include: RGS6, RGS9, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. R7 RGS proteins are key modulators of the pharmacological effects of drugs involved in the development of tolerance and addiction. In addition, RGS7 was found to bind a component of the synaptic fusion complex, snapin, and some other proteins outside of G protein signaling pathways.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 118151040 782 KWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKvKSQSKMAAKAKKIFAEYIAIQA 847
Cdd:cd08738    4 RWGFGMDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKK-RPIREVPSRVQEIWQEFLAPGA 68

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040  19 ITIPRGKDGFGFTIccdSPVRV--------------QAVDSGGPAERAGLQQLDTVLRLNERPVEHWKCVELAHEIRSCP 84
Cdd:cd06705    5 IVIKKGPRGFGFTL---RAIRVyigdsdvytvhhlvTAVEEGSPAYEAGLRPGDLITHVNGEPVQGLLHTQVVQLILKGG 81

                         90
                 ....*....|....*
gi 118151040  85 SEIILlvwRMVPQVK 99
Cdd:cd06705   82 NKVSI---RATPLEK 93

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040  19 ITIPRGKDGFGFTIcCDSPV--RV-QAVDSggpaER-AGLQQLDTVLRLNERPVEHWKCVELAHEIRSCP--SEIILLVW 92
Cdd:cd06732    6 VPIVKGPMGFGFTI-ADSPQgqRVkQILDP----QRcRGLQEGDLIVEINGQNVQNLSHAQVVDVLKECPkgSEVTLLVQ 80

                 .
gi 118151040  93 R 93
Cdd:cd06732   81 R 81

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040  17 RQITIPRGKDGFGFTI---CCDSPVR-------------VQAVDSGGPAERAGLQQLDTVLRLNERPV---EHWKCVELa 77
Cdd:cd06746    7 RTVVLQKGDKGFGFVLrgaKAVGPILeftptpafpalqyLESVDPGGVADKAGLKKGDFLLEINGEDVvkaSHEQVVNL- 85

                         90
                 ....*....|....
gi 118151040  78 heIRSCPSEIILLV 91
Cdd:cd06746   86 --IRQSGNTLVLKV 97

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040  411 PGEKGKGLGAKDPSPSkDPSPGQEPLPGQelPPKEDSSSGQKPSADPESTPSKDSS---------SCKEPPVRQECSPSK 481
Cdd:PHA03307  284 PASSSSSPRERSPSPS-PSSPGSGPAPSS--PRASSSSSSSRESSSSSTSSSSESSrgaavspgpSPSRSPSPSRPPPPA 360

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040  482 DSPPGQEHPAAAVFSPCQDLSAGRESSPGQGPLISKDLPALQEAPAQDLLPHQDLPPGQGPLASEPLAEET--TSSGDPP 559
Cdd:PHA03307  361 DPSSPRKRPRPSRAPSSPAASAGRPTRRRARAAVAGRARRRDATGRFPAGRPRPSPLDAGAASGAFYARYPllTPSGEPW 440

                  ....*..
gi 118151040  560 AATGNPP 566
Cdd:PHA03307  441 PGSPPPP 447

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040  17 RQITIPRGKDGFGFTiccdspVR----------------------VQAVDSGGPAERAGLQQLDTVLRLNERPVE---HW 71
Cdd:cd23070    1 RVVTIVKSETGFGFN------VRgqvseggqlrsingelyaplqhVSAVLEGGAADKAGVRKGDRILEVNGVNVEgatHK 74

                         90       100
                 ....*....|....*....|
gi 118151040  72 KCVELaheIRSCPSEIILLV 91
Cdd:cd23070   75 QVVDL---IKSGGDELTLTV 91

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 118151040  38 VRVQAVDSGGPAERAGLQQLDTVLRLNERPVEHWKcvELAHEIRSCP--SEIILLVWR 93
Cdd:COG0265  203 VLVARVEPGSPAAKAGLRPGDVILAVDGKPVTSAR--DLQRLLASLKpgDTVTLTVLR 258

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040  36 SPVRVQAVDSGGPAERAGLQQLDTVLRLNERPVEHWKcvELAHEIRSCP-SEIILLVWR--------MVPQVKPGPDGGV 106
Cdd:COG0750  128 TPPVVGEVVPGSPAAKAGLQPGDRIVAINGQPVTSWD--DLVDIIRASPgKPLTLTVERdgeeltltVTPRLVEEDGVGR 205

                 .
gi 118151040 107 L 107
Cdd:COG0750  206 I 206

104 kDa microneme/rhoptry antigen; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040 411 PGEKGKGLGAKDPSP-SKDPSPGQEPLPGQElppkedSSSGQKPSADPESTPSKDSSSCKEPpvrqECSPSKDSPPGQEH 489
Cdd:PTZ00449 524 PGDKEGEEGEHEDSKeSDEPKEGGKPGETKE------GEVGKKPGPAKEHKPSKIPTLSKKP----EFPKDPKHPKDPEE 593

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040 490 PAaavfSPCQDLSAGRESSPGQGPLI-SKDLPALQEAPAQDLLPHQDLPPgQGPlaSEPLAEETTSSGDPPAATGNPPVA 568
Cdd:PTZ00449 594 PK----KPKRPRSAQRPTRPKSPKLPeLLDIPKSPKRPESPKSPKRPPPP-QRP--SSPERPEGPKIIKSPKPPKSPKPP 666

                        170       180
                 ....*....|....*....|
gi 118151040 569 SKPNFvipEVRLDSTYSQKA 588
Cdd:PTZ00449 667 FDPKF---KEKFYDDYLDAA 683

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040  387 QQQLATPSPDSKMFEGSEADEKEMPgekgkglgakdpsPSKDPSPGQEPLPGQELPPKEDSSSGQKPSADPESTPSKDSS 466
Cdd:pfam03154 322 QQRIHTPPSQSQLQSQQPPREQPLP-------------PAPLSMPHIKPPPTTPIPQLPNPQSHKHPPHLSGPSPFQMNS 388

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040  467 SCKEPPVRQECSPSKDSPPGQEHPaaavfSPCQDLSAGRE--SSPGQGPLI--SKDLPA----------LQEAPAQDLLP 532
Cdd:pfam03154 389 NLPPPPALKPLSSLSTHHPPSAHP-----PPLQLMPQSQQlpPPPAQPPVLtqSQSLPPpaashpptsgLHQVPSQSPFP 463

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 118151040  533 HQDLPPGQGPLASEPLAEETTSsgdPPAATGNPPVASKP 571
Cdd:pfam03154 464 QHPFVPGGPPPITPPSGPPTST---SSAMPGIQPPSSAS 499

DNA polymerase III subunit gamma/tau;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040 385 AKQQQLATPSPDSKMFEgSEADEKEMPGEKGKGLGAKDPSPSKDPSPGQEPLPGQELPPkedsssgqkPSADPESTPSkd 464
Cdd:PRK12323 415 AARAVAAAPARRSPAPE-ALAAARQASARGPGGAPAPAPAPAAAPAAAARPAAAGPRPV---------AAAAAAAPAR-- 482

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 118151040 465 sssckEPPVRQECSPSKDSPPGQEHPAA-AVFSPCQDLSA--GRESSPGQGPLI---SKDLPALQEAPAQDLLPHQDLPP 538
Cdd:PRK12323 483 -----AAPAAAPAPADDDPPPWEELPPEfASPAPAQPDAApaGWVAESIPDPATadpDDAFETLAPAPAAAPAPRAAAAT 557