synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in PDZ domain-containing protein 8 (PDZD8) and similar proteins; PDZ domain-containing protein 8 (PDZD8), also called Sarcoma antigen NY-SAR-84/NY-SAR-104, is a molecular tethering protein that connects endoplasmic reticulum (ER) and mitochondria membranes. PDZD8-dependent endoplasmic reticulum-mitochondria membrane tethering is essential for ER-mitochondria Ca(2+) transfer. In neurons, PDZD8 is involved in the regulation of dendritic Ca(2+) dynamics by regulating mitochondrial Ca(2+) uptake in neurons. It plays an indirect role in the regulation of cell morphology and cytoskeletal organization. PDZD8 is also a novel Gag-interacting factor that promotes retroviral infection. It may act as a novel moesin-interacting cytoskeletal regulatory protein that suppresses infection by herpes simplex virus type 1 (HSV1). This model corresponds to the SMP domain of PDZD8, which may be implicated in lipid transport.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403   93 ETCYFLNATILFLFRELRDTALTRRWVTKKIKVEFEELLQTKTAGRLLEGLSLRDVFLGETVPFIKTIRLVRPVVPSATG 172
Cdd:cd21674    1 ESCVWLNLLFQFLFQELRDTKRVRRWVTKKLNVEFEELLKTKTAGKFLESITVRDLSLGTSFPVIKNVTVINVKLSEDED 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403  173 epdgpegealpaaCPEELAFEAEVEYNGGFHLAIDVDLVFGKSAYLFVKLSRVVGRLRLVFTRVPFTHWFFSFVEDPLID 252
Cdd:cd21674   81 -------------VPEELDLALDLEYSGGFQLAIDVDLVFGKSAYLSIKVVKLSGRLRLQFSRLPYTHWSFSFYEEPIIE 147

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 29789403  253 FEVRSQFEGRPMPQLTSIIVNQLKKIIKRKHTLPNYKIRFKPFF 296
Cdd:cd21674  148 FDVESRFEGRQLPQLTSLIINQIRRVIRKKHTLPNYKIRYKPFF 191

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403     364 IKTVELIKGNlQSVGLTlrlVQSTDGYAGHVIIETVAPNSPAAIADLQRGDRLIAIGGVKIT--STLQVLKLIKQAGDRV 441
Cdd:smart00228    2 PRLVELEKGG-GGLGFS---LVGGKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEglTHLEAVDLLKKAGGKV 77

                    ....*..
gi 29789403     442 LVYYERP 448
Cdd:smart00228   78 TLTVLRG 84

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in PDZ domain-containing protein 8 (PDZD8) and similar proteins; PDZ domain-containing protein 8 (PDZD8), also called Sarcoma antigen NY-SAR-84/NY-SAR-104, is a molecular tethering protein that connects endoplasmic reticulum (ER) and mitochondria membranes. PDZD8-dependent endoplasmic reticulum-mitochondria membrane tethering is essential for ER-mitochondria Ca(2+) transfer. In neurons, PDZD8 is involved in the regulation of dendritic Ca(2+) dynamics by regulating mitochondrial Ca(2+) uptake in neurons. It plays an indirect role in the regulation of cell morphology and cytoskeletal organization. PDZD8 is also a novel Gag-interacting factor that promotes retroviral infection. It may act as a novel moesin-interacting cytoskeletal regulatory protein that suppresses infection by herpes simplex virus type 1 (HSV1). This model corresponds to the SMP domain of PDZD8, which may be implicated in lipid transport.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403   93 ETCYFLNATILFLFRELRDTALTRRWVTKKIKVEFEELLQTKTAGRLLEGLSLRDVFLGETVPFIKTIRLVRPVVPSATG 172
Cdd:cd21674    1 ESCVWLNLLFQFLFQELRDTKRVRRWVTKKLNVEFEELLKTKTAGKFLESITVRDLSLGTSFPVIKNVTVINVKLSEDED 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403  173 epdgpegealpaaCPEELAFEAEVEYNGGFHLAIDVDLVFGKSAYLFVKLSRVVGRLRLVFTRVPFTHWFFSFVEDPLID 252
Cdd:cd21674   81 -------------VPEELDLALDLEYSGGFQLAIDVDLVFGKSAYLSIKVVKLSGRLRLQFSRLPYTHWSFSFYEEPIIE 147

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 29789403  253 FEVRSQFEGRPMPQLTSIIVNQLKKIIKRKHTLPNYKIRFKPFF 296
Cdd:cd21674  148 FDVESRFEGRQLPQLTSLIINQIRRVIRKKHTLPNYKIRYKPFF 191

Phorbol esters/diacylglycerol binding domain (C1 domain); This domain is also known as the Protein kinase C conserved region 1 (C1) domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 29789403    841 HSFQDTQFQNPTWCDYCKKKVWTKA--ASQCMFCAYVCHKKCQEK 883
Cdd:pfam00130    1 HHFVHRNFKQPTFCDHCGEFLWGLGkqGLKCSWCKLNVHKRCHEK 45

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 29789403    395 IIETVAPNSPAAIADLQRGDRLIAIGGVKITSTLQVLKLIKQAGDRVLV 443
Cdd:pfam17820    1 VVTAVVPGSPAERAGLRVGDVILAVNGKPVRSLEDVARLLQGSAGESVT 49

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 29789403  366 TVELIKGNLQSVGLTLRlvqSTDGYAGHVIIETVAPNSPAAIA-DLQRGDRLIAIGGVKIT--STLQVLKLIKQAGDRV 441
Cdd:cd00136    1 TVTLEKDPGGGLGFSIR---GGKDGGGGIFVSRVEPGGPAARDgRLRVGDRILEVNGVSLEglTHEEAVELLKSAGGEV 76

EBNA-3A; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403   517 SLSHSPKRVPTTLSIKPL-GAISPVLNRKLAVGSHPLPPKIQskdgnkppplktseITDPAQVSKPTQGS-AFKPP--VP 592
Cdd:PHA03379  512 SLSQVPGVAFAPVMPQPMpVEPVPVPTVALERPVCPAPPLIA--------------MQGPGETSGIVRVReRWRPApwTP 577

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 29789403   593 PRPQAKVPLPSADAPNQAEPDVLVEKPEKVVPPPLVDKSAEKQ 635
Cdd:PHA03379  578 NPPRSPSQMSVRDRLARLRAEAQPYQASVEVQPPQLTQVSPQQ 620

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in PDZ domain-containing protein 8 (PDZD8) and similar proteins; PDZ domain-containing protein 8 (PDZD8), also called Sarcoma antigen NY-SAR-84/NY-SAR-104, is a molecular tethering protein that connects endoplasmic reticulum (ER) and mitochondria membranes. PDZD8-dependent endoplasmic reticulum-mitochondria membrane tethering is essential for ER-mitochondria Ca(2+) transfer. In neurons, PDZD8 is involved in the regulation of dendritic Ca(2+) dynamics by regulating mitochondrial Ca(2+) uptake in neurons. It plays an indirect role in the regulation of cell morphology and cytoskeletal organization. PDZD8 is also a novel Gag-interacting factor that promotes retroviral infection. It may act as a novel moesin-interacting cytoskeletal regulatory protein that suppresses infection by herpes simplex virus type 1 (HSV1). This model corresponds to the SMP domain of PDZD8, which may be implicated in lipid transport.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403   93 ETCYFLNATILFLFRELRDTALTRRWVTKKIKVEFEELLQTKTAGRLLEGLSLRDVFLGETVPFIKTIRLVRPVVPSATG 172
Cdd:cd21674    1 ESCVWLNLLFQFLFQELRDTKRVRRWVTKKLNVEFEELLKTKTAGKFLESITVRDLSLGTSFPVIKNVTVINVKLSEDED 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403  173 epdgpegealpaaCPEELAFEAEVEYNGGFHLAIDVDLVFGKSAYLFVKLSRVVGRLRLVFTRVPFTHWFFSFVEDPLID 252
Cdd:cd21674   81 -------------VPEELDLALDLEYSGGFQLAIDVDLVFGKSAYLSIKVVKLSGRLRLQFSRLPYTHWSFSFYEEPIIE 147

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 29789403  253 FEVRSQFEGRPMPQLTSIIVNQLKKIIKRKHTLPNYKIRFKPFF 296
Cdd:cd21674  148 FDVESRFEGRQLPQLTSLIINQIRRVIRKKHTLPNYKIRYKPFF 191

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain superfamily; The SMP domain is a lipid transport domain found in phospholipid transfer proteins such as synaptotagmin family proteins, tricalbin (TCB) family proteins, maintenance of mitochondrial morphology protein 1 (MMM1), mitochondrial distribution and morphology protein 12 (MDM12), mitochondrial distribution and morphology protein 34 (MDM34), PDZ domain-containing protein 8 (PDZD8), testis-expressed protein 2 (TEX2), meiotically up-regulated gene 190 protein (Mug190), C2 domain-containing protein 2 (C2CD2) and C2 domain-containing protein 2-like (C2CD2L). The SMP domain belongs to a superfamily of lipid/hydrophobic ligand-binding domains called TULIP (tubular lipid-binding proteins). It adopts a TULIP fold with two alpha helices and a highly curved antiparallel beta sheet forming a cornucopia-like structure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403  119 VTKKIKVEFEELLQTKTAGRLLEGLSLRDVFLGETVPFIKTIRLVRPVVPsatgepdgpegealpaacPEELAFEAEVEY 198
Cdd:cd21669    1 LEQLIRESLQELLEEVKKPSFIESLELTEFTLGSNPPRIKSVRVLDSPSS------------------DLQLVLDLDLEY 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403  199 NGGFHLAIDVDLV---FGKSAYLFVKLSRVVGRLRLVFTRVP----FTHWFFSFVEDPLIDFEVRSQFEGRPM--PQLTS 269
Cdd:cd21669   63 AGDFSVVLSAKLGgggLGLPVPVSVSDLSLEGRLRVRLTLLPefpyVGALSISFVEPPDIDFSIRPLGGVDLMelPGLSS 142

                        170
                 ....*....|....*...
gi 29789403  270 IIVNQLKKIIKRKHTLPN 287
Cdd:cd21669  143 WLEKLLTDALVELLVEPN 160

protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains. It contains the motif HX12CX2CXnCX2CX4HX2CX7C, where C and H are cysteine and histidine, respectively; X represents other residues; and n is either 13 or 14. C1 has a globular fold with two separate Zn(2+)-binding sites. It was originally discovered as lipid-binding modules in protein kinase C (PKC) isoforms. C1 domains that bind and respond to phorbol esters (PE) and diacylglycerol (DAG) are referred to as typical, and those that do not respond to PE and DAG are deemed atypical. A C1 domain may also be referred to as PKC or non-PKC C1, based on the parent protein's activity. Most C1 domain-containing non-PKC proteins act as lipid kinases and scaffolds, except PKD which acts as a protein kinase. PKC C1 domains play roles in membrane translocation and activation of the enzyme.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 29789403  841 HSFQDTQFQNPTWCDYCKKKVW--TKAASQCMFCAYVCHKKCQEKClaeTSVC 891
Cdd:cd00029    1 HRFVPTTFSSPTFCDVCGKLIWglFKQGLKCSDCGLVCHKKCLDKA---PSPC 50

first protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) protein kinase C (cPKC), novel protein kinase C (nPKC), and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. nPKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs (aPKCs) only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. This family includes classical PKCs (cPKCs) and novel PKCs (nPKCs). There are four cPKC isoforms (named alpha, betaI, betaII, and gamma) and four nPKC isoforms (delta, epsilon, eta, and theta). Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 29789403  841 HSFQDTQFQNPTWCDYCKKKVW--TKAASQCMFCAYVCHKKCQEK 883
Cdd:cd20792    2 HKFVATFFKQPTFCSHCKDFIWglGKQGYQCQVCRFVVHKRCHEY 46

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403     364 IKTVELIKGNlQSVGLTlrlVQSTDGYAGHVIIETVAPNSPAAIADLQRGDRLIAIGGVKIT--STLQVLKLIKQAGDRV 441
Cdd:smart00228    2 PRLVELEKGG-GGLGFS---LVGGKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEglTHLEAVDLLKKAGGKV 77

                    ....*..
gi 29789403     442 LVYYERP 448
Cdd:smart00228   78 TLTVLRG 84

protein kinase C conserved region 1 (C1 domain) found in unconventional myosin-IXa and similar proteins; Myosin-IXa, also called unconventional myosin-9a (Myo9a), is a single-headed, actin-dependent motor protein of the unconventional myosin IX class. It is expressed in several tissues and is enriched in the brain and testes. Myosin-IXa contains a Ras-associating (RA) domain, a motor domain, a protein kinase C conserved region 1 (C1), and a Rho GTPase activating domain (RhoGAP). Myosin-IXa binds the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) GluA2 subunit, and plays a key role in controlling the molecular structure and function of hippocampal synapses. Moreover, Myosin-IXa functions in epithelial cell morphology and differentiation, such that its knockout mice develop hydrocephalus and kidney dysfunction. Myosin-IXa regulates collective epithelial cell migration by targeting RhoGAP activity to cell-cell junctions. Myosin-IXa negatively regulates Rho GTPase signaling, and functions as a regulator of kidney tubule function. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 29789403  839 NKHSFQDTQFQNPTWCDYCKKKVW-TKAASQCMFCAYVCHKKCqekCLAETSVC 891
Cdd:cd20883    4 NGHIFKSTQYSIPTYCEYCSSLIWmMDRAYVCKLCRYACHKKC---CLKTTTKC 54

Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains); Some bind phorbol esters and diacylglycerol. Some bind RasGTP. Zinc-binding domains.

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*
gi 29789403     841 HSFQDTQFQNPTWCDYCKKKVWT--KAASQCMFCAYVCHKKCQEK 883
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIWGsfKQGLRCSECKVKCHKKCADK 45

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 29789403  366 TVELIKGNLQSVGLTLRlvqSTDGYAGHVIIETVAPNSPAAIA-DLQRGDRLIAIGGVKIT--STLQVLKLIKQAGDRV 441
Cdd:cd00136    1 TVTLEKDPGGGLGFSIR---GGKDGGGGIFVSRVEPGGPAARDgRLRVGDRILEVNGVSLEglTHEEAVELLKSAGGEV 76

circularly permuted PDZ domain of Synechocystis sp. PCC 6803 putative serine proteases HhoA, HhoB, and HtrA and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the cyanobacterial Synechocystis sp. PCC 6803 putative serine proteases HhoA, HhoB and HtrA, and related domains. These three proteases are functionally overlapping, and are involved in a number of key physiological responses, ranging from protection against light and heat stresses to phototaxis. HhoA assembles into trimers, mediated by its protease domain and further into a hexamer by a novel interaction between the PDZ domains of opposing trimers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This HhoA-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 29789403  366 TVELIKGNLQSVGLTLRlVQSTDGyaghVIIETVAPNSPAAIADLQRGDRLIAIGGVKITSTLQVLKLIKQAG 438
Cdd:cd10838   12 TPELAQQNNRNPNSPVR-IPEVDG----VLIMQVLPNSPAARAGLRRGDVIQAVDGQPVTTADDVQRIVEQAG 79

protein kinase C conserved region 1 (C1 domain) found in tensin-2 like (TNS2-like) proteins; The TNS2-like group includes TNS2, and variants of TNS1 and TNS3. Tensin-2 (TNS2), also called C1 domain-containing phosphatase and tensin (C1-TEN), or tensin-like C1 domain-containing phosphatase (TENC1), is an essential component for the maintenance of glomerular basement membrane (GBM) structures. It regulates cell motility and proliferation. It may have phosphatase activity. TNS2 reduces AKT1 phosphorylation, lowers AKT1 kinase activity and interferes with AKT1 signaling. Tensin-1 (TNS1) plays a role in fibrillar adhesion formation. It may be involved in cell migration, cartilage development and in linking signal transduction pathways to the cytoskeleton. Tensin-3 (TNS3), also called tensin-like SH2 domain-containing protein 1 (TENS1), or tumor endothelial marker 6 (TEM6), may play a role in actin remodeling. It is involved in the dissociation of the integrin-tensin-actin complex. Typical TNS1 and TNS3 do not contain C1 domains, but some isoforms/variants do. Members of this family contain an N-terminal region with a zinc finger (C1 domain), a protein tyrosine phosphatase (PTP)-like domain and a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 29789403  841 HSFQDTQFQNPTWCDYCKKKVWTKAaSQCMFCAYVCHKKCQEK 883
Cdd:cd20826    3 HSFKEKSFRKPRTCDVCKQIIWNEG-SSCRVCKYACHRKCEPK 44

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 29789403  365 KTVELIKGNlQSVGLTLRlvqSTDGYAGHvIIETVAPNSPAAIADLQRGDRLIAIGGVKITST--LQVLKLIKQAGDRV- 441
Cdd:cd06768    1 RLCHLVKGP-EGYGFNLH---AEKGRPGH-FIREVDPGSPAERAGLKDGDRLVEVNGENVEGEshEQVVEKIKASGNQVt 75

                 ...
gi 29789403  442 -LV 443
Cdd:cd06768   76 lLV 78

first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) epsilon, eta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 29789403  839 NKHSFQDTQFQNPTWCDYCKKKVW---TKAASQCMFCAYVCHKKCQE----KC 884
Cdd:cd20835    8 NGHKFMATYLRQPTYCSHCKDFIWgviGKQGYQCQVCTCVVHKRCHQlvvtKC 60

protein kinase C conserved region 1 (C1 domain) found in the RAS guanyl-releasing protein (RASGRP) family; The RASGRP family includes RASGRP1-4. They function as cation-, usually calcium-, and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, activates the Erk/MAP kinase cascade and regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. RASGRP1 also regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways. RASGRP2, also called calcium and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Cdc25-like protein (CDC25L), or F25B3.3 kinase-like protein, specifically activates Rap and may also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. RASGRP2 is involved in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation, as well as in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. RASGRP3, also called calcium and DAG-regulated guanine nucleotide exchange factor III (CalDAG-GEFIII), or guanine nucleotide exchange factor for Rap1, is a guanine nucleotide-exchange factor activating H-Ras, R-Ras and Ras-associated protein-1/2. It functions as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. RASGRP4 may function in mast cell differentiation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 29789403  840 KHSFQDTQFQNPTWCDYCKKKVW--TKAASQCMFCAYVCHKKCQEKCLAE 887
Cdd:cd20808    1 KHNFQETTYFKPTFCDHCTGLLWglIKQGYKCKDCGINCHKHCKDLVVVE 50

first protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) protein kinase C (cPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 29789403  839 NKHSFQDTQFQNPTWCDYCKKKVW--TKAASQCMFCAYVCHKKCQE 882
Cdd:cd20833    1 KDHKFIARFFKQPTFCSHCTDFIWgfGKQGFQCQVCSFVVHKRCHE 46

circularly permuted PDZ domains of Escherichia coli Regulator of sigma-E protease (RseP) and related domains; Permuted PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ResP (also known as Site-2 protease RseP, and YaeL), and related domains. RseP is involved in the regulation of an extracytoplasmic stress response through the cleavage of membrane-spanning anti-stress-response transcription factor (anti-sigmE) protein RseA; it cleaves the peptide bond between the critical alanine and cysteine in the transmembrane region of RseA, releasing the cytoplasmic domain of RseA with its associated sigmaE. RseP contains two tandem-arranged periplasmic PDZ domains (PDZ-N/PDZ1 and PDZ-C/PDZ2) which act to negatively regulate protease action on intact RseA; they serve as a size-exclusion filter which prevents the access of an intact RseA into the active site of RseP. PDZ domains usually bind in sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This RseP family PDZ domain is a circularly permuted PDZ domain which places both beta-strands A and B at the C-terminus. Another permutation exists in the PDZ superfamily which places beta-strand A at the C-terminus.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 29789403  394 VIIETVAPNSPAAIADLQRGDRLIAIGGVKITSTLQVLKLIKQ-AGDRVLVYYER 447
Cdd:cd23081    1 PVVGEVVANSPAAEAGLKPGDRILKIDGQKVRTWEDIVRIVREnPGKPLTLKIER 55

first protein kinase C conserved region 1 (C1 domain) found in uncharacterized phosphatidylinositol 3-kinase regulatory subunit-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate phosphatidylinositol 3-kinase regulatory subunits (PIK3Rs), which bind to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulate their kinase activity. Unlike typical PIK3Rs, members of this family have two C1 domains. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 29789403  841 HSFQDTQFQNPTWCDYCKKKVWT--KAASQCMFCAYVCHKKCQEkcLAETSVC 891
Cdd:cd20829    1 HRLVDVYFVTPILCRHCKDYIWGkgKVGVRCEDCHACFHLVCAK--YAAKHPC 51

second protein kinase C conserved region 1 (C1 domain) found in the family of protein kinase D (PKD); PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs contain N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 29789403  841 HSFQDTQFQNPTWCDYCKKKVWT--KAASQCMFCAYVCHKKCQEK----CLAE 887
Cdd:cd20796    2 HTFVVHTYTKPTVCQHCKKLLKGlfRQGLQCKDCKFNCHKKCAEKvpkdCTGE 54

PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Drosophila melanogaster Zasp52 and related domains. Drosophila melanogaster Zasp52 (also known as Z band alternatively spliced PDZ-motif protein or Zasp) colocalizes with integrins at myotendinous junctions and with alpha-actinin at Z-disks and is required for muscle attachment as well as Z-disk assembly and maintenance. The Zasp52 actin-binding site includes the extended PDZ domain and the ZM region. The Zasp52-PDZ domain is required for myofibril assembly. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Zasp52-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 29789403  394 VIIETVAPNSPAAIADLQRGDRLIAIGGVkITSTL---QVLKLIKQAGDRVLVYYER 447
Cdd:cd23068   27 LSIQKVNPGSPADKAGLRRGDVILRINGT-DTSNLthkQAQDLIKRAGNDLQLTVQR 82

Predicted metalloprotease, contains C-terminal PDZ domain [General function prediction only];

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403  374 LQSVGLTLRLVQSTDGYA----------GHVIIETVAPNSPAAIADLQRGDRLIAIGGVKITSTlQVLKLIK--QAGDRV 441
Cdd:COG3975  466 LAPFGLKLVYEDAPSLKPslglrvsadgGGLVVTSVLWGSPAYKAGLSAGDELLAIDGLRVTAD-NLDDALAayKPGDPI 544

                 ....*.
gi 29789403  442 LVYYER 447
Cdd:COG3975  545 ELLVFR 550

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. 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 rhophilin-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 29789403  365 KTVELIKGNlQSVGLTLRlvqstdGYAGhVIIETVAPNSPAAIADLQRGDRLIAIGG--VKITSTLQVLKLIKQAGDRVL 442
Cdd:cd06712    2 RTVHLTKEE-GGFGFTLR------GDSP-VQVASVDPGSCAAEAGLKEGDYIVSVGGvdCKWSKHSEVVKLLKSAGEEGL 73

second protein kinase C conserved region 1 (C1 domain) found in uncharacterized phosphatidylinositol 3-kinase regulatory subunit-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate phosphatidylinositol 3-kinase regulatory subunits (PIK3Rs), which bind to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulate their kinase activity. Unlike typical PIK3Rs, members of this family have two C1 domains. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                 ....*....|....*....|....*....|....*....|..
gi 29789403  841 HSFQDTQFQNPTWCDYCKKKVW--TKAASQCMFCAYVCHKKC 880
Cdd:cd20830    1 HRFVEQSFSTLQWCDKCGKFLFglVHQGLQCQDCGLVCHRTC 42

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D (PKD) and similar proteins; PKD is also called PKD1, PRKD1, protein kinase C mu type (nPKC-mu), PRKCM, serine/threonine-protein kinase D1, or nPKC-D1. It is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. PKD contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 29789403  841 HSFQDTQFQNPTWCDYCKK--KVWTKAASQCMFCAYVCHKKCQEK----CLAETSVCG 892
Cdd:cd20842   35 HTFVIHSYTRPTVCQYCKKllKGLFRQGLQCKDCKFNCHKRCAPKvpnnCLGEVAING 92

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 29789403  366 TVELIKGNlQSVGLTLRlvqstdgyaGH--VIIETVAPNSPAAIADLQRGDRLIAIGG--VKITSTLQVLKLIKQAG 438
Cdd:cd06744    1 TVRVYRGN-GSFGFTLR---------GHapVYIESVDPGSAAERAGLKPGDRILFLNGldVRNCSHDKVVSLLQGSG 67

protein kinase C conserved region 1 (C1 domain) found in the 190 kDa guanine nucleotide exchange factor (p190RhoGEF)-like family; The p190RhoGEF-like protein family includes p190RhoGEF, Rho guanine nucleotide exchange factor 2 (ARHGEF2), A-kinase anchor protein 13 (AKAP-13) and similar proteins. p190RhoGEF is a brain-enriched, RhoA-specific guanine nucleotide exchange factor that regulates signaling pathways downstream of integrins and growth factor receptors. It is involved in axonal branching, synapse formation and dendritic morphogenesis, as well as in focal adhesion formation, cell motility and B-lymphocytes activation. ARHGEF2 acts as a guanine nucleotide exchange factor (GEF) that activates Rho-GTPases by promoting the exchange of GDP for GTP. It is thought to play a role in actin cytoskeleton reorganization in different tissues since its activation induces formation of actin stress fibers. AKAP-13 is a scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. It activates RhoA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor. It may also activate other Rho family members. AKAP-13 plays a role in cell growth, cell development and actin fiber formation. Members of this family share a common domain architecture containing C1, RhoGEF or Dbl-homologous (DH), and Pleckstrin Homology (PH) domains. Some members may contain additional domains such as the DUF5401 domain. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 29789403  839 NKHSFQDTQFQNPTWCDYCKKKVWTKAASQCMFCAYVCHKK-CQE 882
Cdd:cd20815    2 NTHQFVPVSFSNSTKCDVCSKPLTNKPALQCENCSVNVHDSsCKD 46

protein kinase C conserved region 1 (C1 domain) found in the unconventional myosin-IX family; Myosins IX (Myo9) is a class of unique motor proteins with a common structure of an N-terminal extension preceding a myosin head homologous to the Ras-association (RA) domain, a head (motor) domain, a neck with IQ motifs that bind light chains, and a C-terminal tail containing cysteine-rich zinc binding (C1) and Rho-GTPase activating protein (RhoGAP) domains. There are two genes for myosins IX in humans, IXa and IXb, that are different in their expression and localization. IXa is expressed abundantly in brain and testis, and IXb is expressed abundantly in tissues of the immune system. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 29789403  839 NKHSFQDTQFQNPTWCDYCKKKVW-TKAASQCMFCAYVCHKKCQEKClaeTSVCGAT 894
Cdd:cd20818    2 NGHKFATVQFNIPTYCEVCNSFIWlMEKGLVCQVCKFTCHKKCYSKI---TAPCKGN 55

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain of the extended synaptotagmin (E-Syt) family; The extended synaptotagmin (E-Syt) family includes a group of Ca2+-regulated intrinsic membrane proteins, such as E-Syt1, E-Syt2 and E-Syt3. They are composed of an N-terminal endoplasmic reticulum (ER)-membrane anchor, a central SMP-domain, and five (E-Syt1) or three C-terminal cytoplasmic C2-domains (E-Syt2 and E-Syt3). The ER-membrane anchor and C2 domains are required for tethering, while the SMP domain is a lipid-binding domain that links the ER with other lipid bilayer-membranes within the cell. This model corresponds to the SMP domain, which has a beta-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerizes to form an approximately 90-Angstrom-long cylinder traversed by a channel lined entirely with hydrophobic residues. The following two C2 domains then form arched structures flexibly linked to the SMP domain.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403  116 RRWVTKKIKVEFEELLQtKTAGRLLEGLSLRDVFLGETVPFIKTIRlvrpVVPSATGepdgpegealpaacPEELAFEAE 195
Cdd:cd21670   18 NEYVEKLLKEKIEPSIR-ALLPGPLKSFRFEKIDLGDKPPRIGGVK----VYTDNVD--------------RDEIILDLD 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29789403  196 VEYNGgfhlaiDVDLVFGKSAYLFVKLSRV--VGRLRLVFT----RVPFthwF----FSFVEDPLIDFEvrsqFEG---- 261
Cdd:cd21670   79 ISYDG------DADIEVSVGTGIKAGIKDIqlRGTLRIVLKpllsELPL---VggvqIFFLNPPEIDFD----LTGlanl 145

                        170       180       190
                 ....*....|....*....|....*....|..
gi 29789403  262 RPMPQLTSIIVNQLKKIIKRKHTLPNyKIRFK 293
Cdd:cd21670  146 LDIPGLSNLLRKIIVDQIASFLVLPN-RITIP 176

protein kinase C conserved region 1 (C1 domain) found in the Ras association domain-containing protein 1 (RASSF1)-like family; The RASSF1-like family includes RASSF1 and RASSF5. RASSF1 and RASSF5 are members of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. RASSF1A and 1C are the most extensively studied RASSF1; both are localized to microtubules and involved in the regulation of growth and migration. RASSF1 is a potential tumor suppressor that is required for death receptor-dependent apoptosis. RASSF5, also called new ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. RASSF5A is a pro-apoptotic Ras effector and functions as a Ras regulated tumor suppressor. RASSF5C is regulated by Ras related protein and modulates cellular adhesion. RASSF5 is a potential tumor suppressor that seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. RASSF1 and RASSF5 contain a C1 domain, which is descibed in this model. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 29789403  840 KHSFQDTQFQNPTWCDYCKKKVW--TKAASQCMFCAYVCHKKCQE 882
Cdd:cd20820    1 GHRFVPLELEQPTWCDLCGSVILglFRKCLRCANCKMTCHPRCRS 45

first protein kinase C conserved region 1 (C1 domain) found in type I diacylglycerol kinases; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. Type I DAG kinases (DGKs) contain EF-hand structures that bind Ca(2+) and recoverin homology domains, in addition to C1 and catalytic domains that are present in all DGKs. Type I DGKs, regulated by calcium binding, include three DGK isozymes (alpha, beta and gamma). DAG kinase alpha, also called 80 kDa DAG kinase, or diglyceride kinase alpha (DGK-alpha), is active upon cell stimulation, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity. DAG kinase beta, also called 90 kDa DAG kinase, or diglyceride kinase beta (DGK-beta), exhibits high phosphorylation activity for long-chain diacylglycerols. DAG kinase gamma, also called diglyceride kinase gamma (DGK-gamma), reverses the normal flow of glycerolipid biosynthesis by phosphorylating diacylglycerol back to phosphatidic acid. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. DGK-alpha contains atypical C1 domains, while DGK-beta and DGK-gamma contain typical C1 domains that bind DAG and phorbol esters. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 29789403  838 ENKHSFQDTQFQNPTWCDYCKKKV--WTKAASQCMFCAYVCHKKCQEKCLA 886
Cdd:cd20799    3 DGQHVWRLKHFNKPAYCNVCENMLvgLRKQGLCCTFCKYTVHERCVSRAPA 53

permuted PDZ domain of Deg/high-temperature requirement factor A (HtrA) family of housekeeping serine proteases and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Deg/HtrA-type serine proteases that participate in folding and degradation of aberrant proteins, and in processing and maturation of native proteins. Typically, these proteases have an N-terminal serine protease domain and at least one C-terminal PDZ domain that recognizes substrates, and in some cases activates the protease function. An exception is yeast Nma11p which has two protease domains and four PDZ domains; its N-terminal half is comprised of a protease domain, followed by two PDZ domains, and its C-terminal half has a similar domain arrangement. HtrA-type proteases include the human HtrA1-4 and MBTPS2, tricorn protease, DegS, DegP and C-terminal processing peptidase, cyanobacterial serine proteases Hhoa, HhoB, and HtrA, and yeast Nma11p. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-termini of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This Deg/HtrA family PDZ domain is a circularly permuted PDZ domain which places beta-strand A at the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 29789403  393 HVIIETVAPNSPAAIADLQRGDRLIAIGGVKITSTLQVLKLI--KQAGDRVLVYYERP 448
Cdd:cd06779   26 GVLVAEVIPGSPAAKAGLKEGDVILSVNGKPVTSFNDLRAALdtKKPGDSLNLTILRD 83

PDZ domain 2 of tyrosine kinase PTPN13, FERM and PDZ domain-containing protein 2 (FRMPD2), and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of human PTPN13, and related domains. PTPN13, also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1), negatively regulates FAS-mediated apoptosis and NGFR-mediated pro-apoptotic signaling, and may also regulate phosphoinositide 3-kinase (PI3K) signaling. It contains 5 PDZ domains; interaction partners of its second PDZ domain (PDZ2) include the Fas receptor (TNFRSF6) and thyroid receptor-interacting protein 6 (TRIP6). The second PDZ (PDZ2) domain, but not PDZ1 or PDZ3, of FRMPD2 binds to GluN2A and GluN2B, two subunits of N-methyl-d-aspartic acid (NMDA) receptors. Other binding partners of the FRMPDZ2 PDZ2 domain include NOD2, and catenin family members, delta catenin (CTNND2), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) and p0071 (also known as plakophilin 4; PKP4). 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 PTPN13-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

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gi 29789403  366 TVELIKGNlQSVGLTLRLVQSTDGYAGHVIIETVAPNSPAA-IADLQRGDRLIAIGGVKIT--STLQVLKLIKQAGDRVL 442
Cdd:cd06792    4 EVELSKKD-GSLGISVTGGINTSVRHGGIYVKSLVPGGAAEqDGRIQKGDRLLEVNGVSLEgvTHKQAVECLKNAGQVVT 82

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gi 29789403  443 VYYER 447
Cdd:cd06792   83 LVLER 87