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 1803841344  122 ETCHFLNAIFLFLFRELRDTALVRNWVTKKIKVEFEELLQAKMTGKVLEGLSLRDVSLGNVLPVFKAVKLIRPVVCNEEG 201
Cdd:cd21674      1 ESCVWLNLLFQFLFQELRDTKRVRRWVTKKLNVEFEELLKTKTAGKFLESITVRDLSLGTSFPVIKNVTVINVKLSEDED 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1803841344  202 CPEELGFEVDLEYNGGFHLAIDADLVFGKSAYLFVKISRVIGKLKLVFTRLPFTHWSFSFMDDPVILFEVKSQFEGRPMP 281
Cdd:cd21674     81 VPEELDLALDLEYSGGFQLAIDVDLVFGKSAYLSIKVVKLSGRLRLQFSRLPYTHWSFSFYEEPIIEFDVESRFEGRQLP 160

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1803841344  282 QLTSIIVNQFKKVIKRKHTLPNYKIRYEPFF 312
Cdd:cd21674    161 QLTSLIINQIRRVIRKKHTLPNYKIRYKPFF 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 1803841344   380 IKTAELVKGnlqSVGLTLRLVQSKEEDAGhVVIETVTPNSPAAAADLQRGDRLLAIG--SVKITSTVQVLKLIRQAGDRV 457
Cdd:smart00228    2 PRLVELEKG---GGGLGFSLVGGKDEGGG-VVVSSVVPGSPAAKAGLRVGDVILEVNgtSVEGLTHLEAVDLLKKAGGKV 77

                    ....*..
gi 1803841344   458 LVFYERP 464
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 1803841344  122 ETCHFLNAIFLFLFRELRDTALVRNWVTKKIKVEFEELLQAKMTGKVLEGLSLRDVSLGNVLPVFKAVKLIRPVVCNEEG 201
Cdd:cd21674      1 ESCVWLNLLFQFLFQELRDTKRVRRWVTKKLNVEFEELLKTKTAGKFLESITVRDLSLGTSFPVIKNVTVINVKLSEDED 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1803841344  202 CPEELGFEVDLEYNGGFHLAIDADLVFGKSAYLFVKISRVIGKLKLVFTRLPFTHWSFSFMDDPVILFEVKSQFEGRPMP 281
Cdd:cd21674     81 VPEELDLALDLEYSGGFQLAIDVDLVFGKSAYLSIKVVKLSGRLRLQFSRLPYTHWSFSFYEEPIIEFDVESRFEGRQLP 160

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1803841344  282 QLTSIIVNQFKKVIKRKHTLPNYKIRYEPFF 312
Cdd:cd21674    161 QLTSLIINQIRRVIRKKHTLPNYKIRYKPFF 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 1803841344  853 HNFQDTQFQNPTWCDYCKKKVWTKA--ASQCMLCAYVCHKKCQEK 895
Cdd:pfam00130    1 HHFVHRNFKQPTFCDHCGEFLWGLGkqGLKCSWCKLNVHKRCHEK 45

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1803841344  411 VIETVTPNSPAAAADLQRGDRLLAIGSVKITSTVQVLKLIRQAGDRVLVF 460
Cdd:pfam17820    1 VVTAVVPGSPAERAGLRVGDVILAVNGKPVRSLEDVARLLQGSAGESVTL 50

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1803841344  411 VIETVTPNSPAAAADLQRGDRLLAIGSVKITSTVQVLKLIRQAGDRVLVF-YER 463
Cdd:COG0750    131 VVGEVVPGSPAAKAGLQPGDRIVAINGQPVTSWDDLVDIIRASPGKPLTLtVER 184

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1803841344  373 EEKSRSSIKTAELVKGNLQSvgLTLRLVQSKEEDAGHVVIEtVTPNSPAAAADLQRGDRLLAIGSVKITSTVQVLKLIRQ 452
Cdd:TIGR02037  330 EEQASSSNPFLGLTVANLSP--EIRKELRLKGDVKGVVVTK-VVSGSPAARAGLQPGDVILSVNQQPVSSVAELRKVLAR 406

                           90
                   ....*....|...
gi 1803841344  453 A--GDRVLVFYER 463
Cdd:TIGR02037  407 AkkGGRVALLILR 419

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 1803841344  122 ETCHFLNAIFLFLFRELRDTALVRNWVTKKIKVEFEELLQAKMTGKVLEGLSLRDVSLGNVLPVFKAVKLIRPVVCNEEG 201
Cdd:cd21674      1 ESCVWLNLLFQFLFQELRDTKRVRRWVTKKLNVEFEELLKTKTAGKFLESITVRDLSLGTSFPVIKNVTVINVKLSEDED 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1803841344  202 CPEELGFEVDLEYNGGFHLAIDADLVFGKSAYLFVKISRVIGKLKLVFTRLPFTHWSFSFMDDPVILFEVKSQFEGRPMP 281
Cdd:cd21674     81 VPEELDLALDLEYSGGFQLAIDVDLVFGKSAYLSIKVVKLSGRLRLQFSRLPYTHWSFSFYEEPIIEFDVESRFEGRQLP 160

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1803841344  282 QLTSIIVNQFKKVIKRKHTLPNYKIRYEPFF 312
Cdd:cd21674    161 QLTSLIINQIRRVIRKKHTLPNYKIRYKPFF 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 1803841344  148 VTKKIKVEFEELLQAKMTGKVLEGLSLRDVSLGNVLPVFKAVKLIRPVVcneegCPEELGFEVDLEYNGGFHLAIDADLV 227
Cdd:cd21669      1 LEQLIRESLQELLEEVKKPSFIESLELTEFTLGSNPPRIKSVRVLDSPS-----SDLQLVLDLDLEYAGDFSVVLSAKLG 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1803841344  228 ---FGKSAYLFVKISRVIGKLKLVFTRLP----FTHWSFSFMDDPVILFEVKSQFEGRPM--PQLTSIIVNQFKKVIKRK 298
Cdd:cd21669     76 gggLGLPVPVSVSDLSLEGRLRVRLTLLPefpyVGALSISFVEPPDIDFSIRPLGGVDLMelPGLSSWLEKLLTDALVEL 155

                   ....*
gi 1803841344  299 HTLPN 303
Cdd:cd21669    156 LVEPN 160

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in maintenance of mitochondrial morphology protein 1 (Mmm1) and similar proteins; Maintenance of mitochondrial morphology protein 1 (Mmm1), also called mitochondrial outer membrane protein Mmm1, or yeast mitochondrial escape protein 6 (YME6), is a mitochondrial outer membrane protein essential for establishing and maintaining the structure of mitochondria and maintenance of mtDNA nucleoids. It is a component of the ER-mitochondrion encounter structure/ mitochondrial distribution and morphology (ERMES/Mdm) complex, which serves as a molecular tether to connect the endoplasmic reticulum and mitochondria. Components of this complex are involved in the control of mitochondrial shape and protein biogenesis, and function in nonvesicular lipid trafficking between the ER and mitochondria. The Mdm12-Mmm1 subcomplex functions in the major beta-barrel assembly pathway that is responsible for biogenesis of all outer membrane beta-barrel proteins, and acts in a late step after the SAM complex. The Mdm10-Mdm12-Mmm1 subcomplex further acts in the TOM40-specific pathway after the action of the Mdm12-Mmm1 complex. This model corresponds to the SMP domain of Mmm1, which may be implicated in lipid transport.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1803841344  122 ETCHFLNAIFLFLFRELRDTALVRNWVTKKIkvefEELLQAKMTGKVLEGLSLRDVSLGNVLPVFKAVKlIRPvvCNEEG 201
Cdd:cd21671     19 ESLDWLNVLLAQILAQYRSDAEGDDNLLRKL----EEALNGERKPSFLDPIKVTDLDLGDDFPRFSNAR-IRP--SDDSG 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1803841344  202 CPEelgFEVDLEYNGGFHLAIDADLVFG----KSAYL----FVKISRVIGKLKLVF--TRLPFTHWSFSFMDDPVILFEV 271
Cdd:cd21671     92 GLR---AEIDIDYSDTISLGIDTSLLLNypkpRFASLpvslSVSLVRFSGTLTIELpsPSSPGPTLSFSLLPDFRLDLKV 168

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1803841344  272 KSQFEGRPM----PQLTSIIVNQFKKVIKRKHTLPNYK 305
Cdd:cd21671    169 SSLIGSRAKlqdvPKLHSLIESRLRRWFADRCVEPNFW 206

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
                   ....*....|....*....|....*....|....*....|....*.
gi 1803841344  853 HNFQDTQFQNPTWCDYCKKKVW--TKAASQCMLCAYVCHKKCQEKC 896
Cdd:cd00029      1 HRFVPTTFSSPTFCDVCGKLIWglFKQGLKCSDCGLVCHKKCLDKA 46

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        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1803841344  853 HNFQDTQFQNPTWCDYCKKKVW--TKAASQCMLCAYVCHKKCQEKCLTETP 901
Cdd:cd20792      2 HKFVATFFKQPTFCSHCKDFIWglGKQGYQCQVCRFVVHKRCHEYVVFKCP 52

protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing protein 1 (RASSF1) and similar proteins; RASSF1 is a member 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 with both localized to microtubules and involved in regulation of growth and migration. RASSF1 is a potential tumor suppressor that is required for death receptor-dependent apoptosis. It contains 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 1803841344  853 HNFQDTQFQNPTWCDYCKKKVWT--KAASQCMLCAYVCHKKCQE 894
Cdd:cd20885      4 HDFQPCSLTNPTWCDLCGDFIWGlyKQCLRCTHCKYTCHLRCRD 47

first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) theta, delta, 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-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. 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 1803841344  853 HNFQDTQFQNPTWCDYCKKKVW--TKAASQCMLCAYVCHKKCQEKCLTETP 901
Cdd:cd20834      8 HEFIAKFFRQPTFCSVCKEFLWgfNKQGYQCRQCNAAVHKKCHDKILGKCP 58

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 1803841344   853 HNFQDTQFQNPTWCDYCKKKVWT--KAASQCMLCAYVCHKKCQEK 895
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIWGsfKQGLRCSECKVKCHKKCADK 45

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 1803841344  851 NKHNFQDTQFQNPTWCDYCKKKVW---TKAASQCMLCAYVCHKKCQEKCLTETP 901
Cdd:cd20835      8 NGHKFMATYLRQPTYCSHCKDFIWgviGKQGYQCQVCTCVVHKRCHQLVVTKCP 61

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 1803841344  853 HNFQDTQFQNPTWCDYCKKKVWTKAaSQCMLCAYVCHKKCQEK 895
Cdd:cd20826      3 HSFKEKSFRKPRTCDVCKQIIWNEG-SSCRVCKYACHRKCEPK 44

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 1803841344  852 KHNFQDTQFQNPTWCDYCKKKVW--TKAASQCMLCAYVCHKKCQEKCLTE 899
Cdd:cd20808      1 KHNFQETTYFKPTFCDHCTGLLWglIKQGYKCKDCGINCHKHCKDLVVVE 50

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 4 (RASGRP4) and similar proteins; RASGRP4 functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. It 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
                   ....*....|....*....|....*....|....*....|....*.
gi 1803841344  851 NKHNFQDTQFQNPTWCDYCKKKVW--TKAASQCMLCAYVCHKKCQE 894
Cdd:cd20863      2 FLHNFHETTFKKPTFCDSCSGFLWgvTKQGYRCQDCGINCHKHCKD 47

protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are a family of phorbolester- and diacylglycerol-responsive GTPase activating proteins (GAPs) specific for the Rho-like GTPase Rac. Alpha1-chimerin (formerly known as N-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. Alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. 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
                   ....*....|....*....|....*....|....*....|....*
gi 1803841344  853 HNFQDTQFQNPTWCDYCKKKVWTKAAS--QCMLCAYVCHKKCQEK 895
Cdd:cd20806      2 HNFKVHTFKGPHWCDYCGNFMWGLIAQgvKCEDCGFNAHKQCSKL 46

protein kinase C conserved region 1 (C1 domain) found in uncharacterized proteins similar to myotubularin-related proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate myotubularin-related proteins (MTMRs), such as MTMR5 and MTMR13. MTMRs may function as guanine nucleotide exchange factors (GEFs). Vertebrate MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Members of this family contain these domains and have an additional C1 domain. 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
                   ....*....|....*....|....*....|....*....|...
gi 1803841344  853 HNFQDTQFQNPTWCDYCKKKVW--TKAASQCMLCAYVCHKKCQ 893
Cdd:cd20828      6 HNFEPHSFVTPTNCDYCLQILWgiVKKGMKCSECGYNCHEKCQ 48

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 1803841344  382 TAELVKGNLQSVGLTLRlvqSKEEDAGHVVIETVTPNSPAAAA-DLQRGDRLLAIG--SVKITSTVQVLKLIRQAGDRV 457
Cdd:cd00136      1 TVTLEKDPGGGLGFSIR---GGKDGGGGIFVSRVEPGGPAARDgRLRVGDRILEVNgvSLEGLTHEEAVELLKSAGGEV 76

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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1803841344  853 HNFQDTQFQNPTWCDYCKKKVWT--KAASQCMLCAYVCHKKC 892
Cdd:cd20829      1 HRLVDVYFVTPILCRHCKDYIWGkgKVGVRCEDCHACFHLVC 42

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
                   ....*....|....*....|....*....|....*....|....*...
gi 1803841344  412 IETVTPNSPAAAADLQRGDRLLAIGSVKIT--STVQVLKLIRQAGDRV 457
Cdd:cd23068     29 IQKVNPGSPADKAGLRRGDVILRINGTDTSnlTHKQAQDLIKRAGNDL 76

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.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1803841344  853 HNFQDTQFQNPTWCDYCKKKVWT--KAASQCMLCAYVCHKKCQEKCLTEtpfCVG 905
Cdd:cd20796      2 HTFVVHTYTKPTVCQHCKKLLKGlfRQGLQCKDCKFNCHKKCAEKVPKD---CTG 53

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        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1803841344  852 KHNFQDTQFQNPTWCDYCKKKVW--TKAASQCMLCAYVCHKKCQEK-CLT 898
Cdd:cd20820      1 GHRFVPLELEQPTWCDLCGSVILglFRKCLRCANCKMTCHPRCRSLvCLT 50

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1803841344  385 LVKGNLQSVGLTLRLVQSKeeDAGHVVIETVTPNSPAAAADLQRGDRLLAIGSVKIT--STVQVLKLIRQAGDRV 457
Cdd:pfam00595    4 LEKDGRGGLGFSLKGGSDQ--GDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVEnmTHEEAVLALKGSGGKV 76

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
                   ....*....|....*....|....*....|....*....|....*.
gi 1803841344  851 NKHNFQDTQFQNPTWCDYCKKKVW-TKAASQCMLCAYVCHKKCQEK 895
Cdd:cd20818      2 NGHKFATVQFNIPTYCEVCNSFIWlMEKGLVCQVCKFTCHKKCYSK 47

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1803841344  144 VRNWVTKKIKVEFEELLQAKMTGKvLEGLSLRDVSLGNVLPVFKAVKlirpvvCNEEGC-PEELGFEVDLEYNGgfhlai 222
Cdd:cd21670     17 INEYVEKLLKEKIEPSIRALLPGP-LKSFRFEKIDLGDKPPRIGGVK------VYTDNVdRDEIILDLDISYDG------ 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1803841344  223 DADLVFGKSAYLFVKISRVI--GKLKLVFT----RLPFT-HWSFSFMDDPVILFEVKSQFEGRPMPQLTSIIVNQFKKVI 295
Cdd:cd21670     84 DADIEVSVGTGIKAGIKDIQlrGTLRIVLKpllsELPLVgGVQIFFLNPPEIDFDLTGLANLLDIPGLSNLLRKIIVDQI 163

                   ....*...
gi 1803841344  296 KRKHTLPN 303
Cdd:cd21670    164 ASFLVLPN 171

PDZ domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1803841344  410 VVIETVTPNSPAAAADLQRGDRLLAIGSVKITSTVQVLKLIR--QAGDRVLVFYERP 464
Cdd:pfam13180    8 VVVVSVKSSGPAAKAGLKAGDVILSIDGRKINDLTDLESALYghKPGDTVTLQVYRD 64

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 1803841344  851 NKHNFQDTQFQNPTWCDYCKKKVWTKAASQCMLCAYVCHKK-CQE 894
Cdd:cd20815      2 NTHQFVPVSFSNSTKCDVCSKPLTNKPALQCENCSVNVHDSsCKD 46

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 3 (RASGRP3) and similar proteins; 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. 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 1803841344  853 HNFQDTQFQNPTWCDYCKKKVW--TKAASQCMLCAYVCHKKCQE 894
Cdd:cd20862      8 HNFQEMTYLKPTFCEHCAGFLWgiIKQGYKCKDCGVNCHKQCKD 51

circularly permuted PDZ domain of DegS serine endoprotease; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Escherichia coli DegS and related domains. DegS (also known as Site-1 protease DegS, S1P protease DegS, and Site-1-type intramembrane protease) participates in the activation of the sigma(E) extracytoplasmic stress response. Initially, there is an accumulation of misfolded membrane proteins (OMPs) in the periplasm which bind by their YXF motif to the DegS PDZ domain, activating DegS-catalyzed cleavage of the RseA periplasmic domain and making RseA a substrate for cleavage by another membrane protease RseP. 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 DegS family 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
                   ....*....|....*....|....*....|....*....|....*
gi 1803841344  410 VVIETVTPNSPAAAADLQRGDRLLAIGSVKITSTVQVLKLIRQAG 454
Cdd:cd06777     27 ALVKGVSPDSPAAKAGIQVGDIILQFDNKPVISVLELMDLVAEIR 71

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins; PKD3 is also called PRKD3, PRKCN, serine/threonine-protein kinase D3 (nPKC-D3), protein kinase C nu type (nPKC-nu), or protein kinase EPK2. It converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. It is involved in the regulation of the cell cycle by modulating microtubule nucleation and dynamics. PKD3 acts as a key mediator in several cancer development signaling pathways. PKD3 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.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1803841344  853 HNFQDTQFQNPTWCDYCKK--KVWTKAASQCMLCAYVCHKKCQEK----CLTETPF 902
Cdd:cd20844      6 HTFAVHSYTRPTICQYCKRllKGLFRQGMQCKDCRFNCHKRCASKvprdCLGEVTF 61

protein kinase C conserved region 1 (C1 domain) found in the kinase suppressor of Ras (KSR) family; KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. KSR proteins contain a SAM-like domain, a zinc finger cysteine-rich domain (C1), and a pseudokinase 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 1803841344  852 KHNFQDTQFQNPTwCDYCKKKVWTkaASQCMLCAYVCHKKCQEK 895
Cdd:cd20812      2 KHRFSKKLFMRQT-CDYCHKQMFF--GLKCKDCKYKCHKKCAKK 42

protein kinase C conserved region 1 (C1 domain) found in the Rho-associated coiled-coil containing protein kinase (ROCK) family; ROCK is a serine/threonine protein kinase, catalyzing the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. It is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD), a pleckstrin homology (PH) domain and a C1 domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. 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 1803841344  853 HNFQDTQFQNPTWCDYCKKKVW----TKAASQCMLCAYVCHK 890
Cdd:cd20813      8 HEFVEITFHMPTTCDVCHKPLWhlfkPPPALECKRCRMKIHK 49

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        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1803841344  397 LRLVQSKEEDAGHVVIETVTPNSPAAAADLQRGDRLLAIGSVKITSTVQVLKLIRQ--AGDRVLVFYERP 464
Cdd:cd06779     14 LLAKELGLPVNRGVLVAEVIPGSPAAKAGLKEGDVILSVNGKPVTSFNDLRAALDTkkPGDSLNLTILRD 83

PDZ domain of Ras-associating and dilute domain-containing protein (Radil) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Radil (also known as protein KIAA1849) and related domains. Radil is required for cell adhesion and migration of neural crest precursors during development. Radil is a component of a Rasip1-Radil-ARHGAP29 complex at endothelial cell-cell junctions. Rap1, via its effectors Radil and Rasip1 and their binding partner ArhGAP29, controls the endothelial barrier by decreasing Rho-mediated radial tension on cell-cell junctions. ArhGAP29 binds the Radil PDZ domain. The Radil PDZ domain also binds kinesin family protein 14 (KIF14); KIF14 negatively regulates Rap1-mediated inside-out integrin activation by tethering Radil on microtubules. 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 Radil-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 1803841344  382 TAELVKGNLqsvGLTLRLVQSKE---EDAGhVVIETVTPNSPAAAAD-LQRGDRLLAigsVKITSTV-----QVLKLIRQ 452
Cdd:cd06690      5 VVELERGPK---GLGLGLIDGLHtplRSPG-IYIRTLVPDSPAARDGrLRLGDRILA---VNGTSLVgadyqSAMDLIRT 77

                   ....*
gi 1803841344  453 AGDRV 457
Cdd:cd06690     78 SGDKL 82

protein kinase C conserved region 1 (C1 domain) found in tensin-1 (TNS1) variant and similar proteins; 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. This model corresponds to the C1 domain found in TNS1 variant. Typical TNS1 does not contain 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 1803841344  851 NKHNFQDTQFQNPTWCDYCKKKVwTKAASQCMLCAYVCHKKCQEKCLT 898
Cdd:cd20888      4 HTHTFKVKTFKKVKSCGICKQAI-TREGSTCRVCKLSCHKKCEAKVAT 50

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
                   ....*....|....*....|....*....|....*....|....*...
gi 1803841344  412 IETVTPNSPAAAADLQRGDRLLAIGSVKITSTV--QVLKLIRQAGDRV 457
Cdd:cd06746     46 LESVDPGGVADKAGLKKGDFLLEINGEDVVKASheQVVNLIRQSGNTL 93