Diacylglycerol kinase N-terminus; This domain is found at the N-terminus of diacylglycerol kinases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1090864009   5 QWVSLSSEEFDQLQKYSEYSSKKIKDVLAEFNEGGSLRQYDPHKPISYDVFKLFMRAYLEVDLPQPLSTHLFLAFSQKPR 84
Cdd:pfam14513   1 EWVSLSPEEFAQLQKYAEYSSKKLKDVLEEFNEDGVLAKYNPEEPIDYEGFKLFMKTYLEVDLPEDLCQHLFLSFQTKPS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1090864009  85 QETPDHPKEGASSSEPNVSDYNsdnaakadeacapdteskttktqapskeleaaaPWEDPGALASSSDAPVVYLKDVVCY 164
Cdd:pfam14513  81 QESPDSPKEGASSSVKAGFDKN---------------------------------PSSLPPAPSSPSASPVVYLKDVSCY 127

                  ....*...
gi 1090864009 165 LSLMETGR 172
Cdd:pfam14513 128 LSLLEGGR 135

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1090864009 252 LLVLLGMDDSgSKGDGRHAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGCVKTNSKA 325
Cdd:cd20846     1 LLVLLGMETN-VKDDGQHAWRLKHFKKPAYCNFCHTMLLGVRKQGLCCSFCKYTVHERCVSKDIASCISTYVKS 73

Diacylglycerol kinase accessory domain; Diacylglycerol (DAG) is a second messenger that acts as a protein kinase C activator. This domain is assumed to be an accessory domain: its function is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1090864009 536 IMNNYFSIGVDASIAHRFHMMREKHPEKFNSRMKNKLWYFEFGTSETFAATCKKLHDHIELECDGVEVDLSnIFLEGIAI 615
Cdd:pfam00609   1 VMNNYFSIGVDARIALGFHRLREEHPELFNSRLKNKLIYGVFGFKDMFQRSCKNLIEKVELEVDGKDLPLP-KSLEGIVV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1090864009 616 LNIPSMYGGTNLWGETKKNRaviresrksvtdpkeLKCCVQDLSDQLLEVVGLEGAMEMGQIYTGLKSAgRRLAQCSSVT 695
Cdd:pfam00609  80 LNIPSYAGGTDLWGNSKEDG---------------LGFAPQSVDDGLLEVVGLTGALHLGQVQVGLGSA-KRIAQGGPIR 143

                         170
                  ....*....|....*
gi 1090864009 696 IRTNKLLPMQVDGEP 710
Cdd:pfam00609 144 ITTKKKIPMQVDGEP 158

Diacylglycerol kinase catalytic domain (presumed); Diacylglycerol (DAG) is a second messenger that acts as a protein kinase C activator. DAG can be produced from the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by a phosphoinositide-specific phospholipase C and by the degradation of phosphatidylcholine (PC) by a phospholipase C or the concerted actions of phospholipase D and phosphatidate phosphohydrolase. This domain is presumed to be the catalytic domain. Bacterial homologues areknown.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1090864009  394 LVLVNPKSGGRQGERILRKFHYLLNPEQVFNLDNGGPTPGLNFFHDTPDF-RVLACGGDGTVGWILDCIDKANFTKH-PP 471
Cdd:smart00046   1 LVFVNPKSGGGKGEKLLRKFRLLLNPRQVFDLTKKGPAVALVIFRDVPDFnRVLVCGGDGTVGWVLNALDKRELPLPePP 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1090864009  472 VAVLPLGTGNDLARCLRWGGGYEGGSLTKILKEIEQSPLVMLDR 515
Cdd:smart00046  81 VAVLPLGTGNDLARSLGWGGGYDGEKLLKTLRDALESDTVKLDR 124

Diacylglycerol kinase catalytic domain; Diacylglycerol (DAG) is a second messenger that acts as a protein kinase C activator. The catalytic domain is assumed from the finding of bacterial homologs. YegS is the Escherichia coli protein in this family whose crystal structure reveals an active site in the inter-domain cleft formed by four conserved sequence motifs, revealing a novel metal-binding site. The residues of this site are conserved across the family.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1090864009 392 PLLVLVNPKSGGRQGERILRKFHYLLNPEQV-FNLDN-GGPTPGLNFFHDTPD---FRVLACGGDGTVGWILDCIDKANf 466
Cdd:pfam00781   1 KLLVIVNPKSGGGKGKKLLRKVRPLLNKAGVeVELVLtEGPGDALELAREAAEdgyDRIVVAGGDGTVNEVLNGLAGLA- 79

                          90       100
                  ....*....|....*....|....*
gi 1090864009 467 tKHPPVAVLPLGTGNDLARCLRWGG 491
Cdd:pfam00781  80 -TRPPLGIIPLGTGNDFARALGIPG 103

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        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1090864009  269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGC 318
Cdd:smart00109   1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1090864009 176 KLEFMFRLYDSDENGLLDQAEMDQIVSQmlhvaqyLEWDPTElrPILKEMLQGMDYDKDGFVSLQEWING 245
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKS-------LGEGLSE--EEIDEMIREVDKDGDGKIDFEEFLEL 61

putative lipid kinase; Reviewed

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1090864009 445 VLACGGDGTVGWILDCIDKANFTKhpPVAVLPLGTGNDLARCLrwgggyegGSLTKILKEIEQ---SPLVMLD 514
Cdd:PRK13059   60 ILIAGGDGTVDNVVNAMKKLNIDL--PIGILPVGTANDFAKFL--------GMPTDIGEACEQilkSKPKKVD 122

Diacylglycerol kinase accessory domain; Diacylglycerol (DAG) is a second messenger that acts as a protein kinase C activator. This domain is assumed to be an accessory domain: its function is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1090864009 536 IMNNYFSIGVDASIAHRFHMMREKHPEKFNSRMKNKLWYFEFGTSETFAATCKKLHDHIELECDGVEVDLSnIFLEGIAI 615
Cdd:pfam00609   1 VMNNYFSIGVDARIALGFHRLREEHPELFNSRLKNKLIYGVFGFKDMFQRSCKNLIEKVELEVDGKDLPLP-KSLEGIVV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1090864009 616 LNIPSMYGGTNLWGETKKNRaviresrksvtdpkeLKCCVQDLSDQLLEVVGLEGAMEMGQIYTGLKSAgRRLAQCSSVT 695
Cdd:pfam00609  80 LNIPSYAGGTDLWGNSKEDG---------------LGFAPQSVDDGLLEVVGLTGALHLGQVQVGLGSA-KRIAQGGPIR 143

                         170
                  ....*....|....*
gi 1090864009 696 IRTNKLLPMQVDGEP 710
Cdd:pfam00609 144 ITTKKKIPMQVDGEP 158

Diacylglycerol kinase catalytic domain (presumed); Diacylglycerol (DAG) is a second messenger that acts as a protein kinase C activator. DAG can be produced from the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by a phosphoinositide-specific phospholipase C and by the degradation of phosphatidylcholine (PC) by a phospholipase C or the concerted actions of phospholipase D and phosphatidate phosphohydrolase. This domain is presumed to be the catalytic domain. Bacterial homologues areknown.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1090864009  394 LVLVNPKSGGRQGERILRKFHYLLNPEQVFNLDNGGPTPGLNFFHDTPDF-RVLACGGDGTVGWILDCIDKANFTKH-PP 471
Cdd:smart00046   1 LVFVNPKSGGGKGEKLLRKFRLLLNPRQVFDLTKKGPAVALVIFRDVPDFnRVLVCGGDGTVGWVLNALDKRELPLPePP 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1090864009  472 VAVLPLGTGNDLARCLRWGGGYEGGSLTKILKEIEQSPLVMLDR 515
Cdd:smart00046  81 VAVLPLGTGNDLARSLGWGGGYDGEKLLKTLRDALESDTVKLDR 124

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1090864009 264 KGDGRHAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGCVKTNSKA 325
Cdd:cd20799     1 KDDGQHVWRLKHFNKPAYCNVCENMLVGLRKQGLCCTFCKYTVHERCVSRAPASCIRTYVKS 62

first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase beta (DAG kinase beta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase beta, also called 90 kDa diacylglycerol kinase, or diglyceride kinase beta (DGK-beta), exhibits high phosphorylation activity for long-chain diacylglycerols. It is classified as a type I DAG kinase (DGK), containing EF-hand structures that bind Ca(2+) and a recoverin homology domain, in addition to C1 and catalytic domains that are present in all DGKs. As a type I DGK, it is regulated by calcium binding. DAG kinase beta contains two copies of the C1 domain. This model corresponds to the first one. DGK-beta contains 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1090864009 264 KGDGRHAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGCVKTNSKAKR 327
Cdd:cd20845     3 KDDGQHVWRLKHFNKPAYCNLCLNMLVGLGKQGLCCSFCKYTVHERCVQRAPASCIKTYVKSKK 66

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        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1090864009  269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGC 318
Cdd:smart00109   1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50

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 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGCVKT 321
Cdd:cd20834     8 HEFIAKFFRQPTFCSVCKEFLWGFNKQGYQCRQCNAAVHKKCHDKILGKCPGS 60

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 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGC 318
Cdd:cd20792     2 HKFVATFFKQPTFCSHCKDFIWGLGKQGYQCQVCRFVVHKRCHEYVVFKC 51

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1090864009 176 KLEFMFRLYDSDENGLLDQAEMDQIVSQmlhvaqyLEWDPTElrPILKEMLQGMDYDKDGFVSLQEWING 245
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKS-------LGEGLSE--EEIDEMIREVDKDGDGKIDFEEFLEL 61

first protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group 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 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGCV 319
Cdd:cd20797     4 HVVEVEQYMTPTFCDYCGEMLTGLMKQGVKCKNCRCNFHKRCANAPRNNCA 54

second 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 domain. 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 C1 domain. 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGC 318
Cdd:cd20838     3 HRFSVHNYKRPTFCDHCGSLLYGLYKQGLQCKVCKMNVHKRCQKNVANNC 52

first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase eta (DAG kinase eta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase eta, also called diglyceride kinase eta (DGK-eta), plays a key role in promoting cell growth. It is classified as a type II DAG kinase (DGK), containing pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. The diacylglycerol kinase eta gene, DGKH, is a replicated risk gene of bipolar disorder (BPD). DAG kinase eta contains 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 1090864009 267 GRHAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGC 318
Cdd:cd20848    28 GMHNWYACSHARPTFCNVCRESLSGVTSHGLSCEVCKFKAHKRCAVRATNNC 79

first protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase delta (DAG kinase delta) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase delta, also called 130 kDa diacylglycerol kinase, or diglyceride kinase delta (DGK-delta), is a residential lipid kinase in the endoplasmic reticulum. It promotes lipogenesis and is involved in triglyceride biosynthesis. It is classified as a type II DAG kinase (DGK), containing pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. DAG kinase delta contains 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 1090864009 267 GRHAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGC 318
Cdd:cd20847    23 GMHNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNC 74

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 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRC 310
Cdd:cd20833     3 HKFIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCSFVVHKRC 44

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 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGCV 319
Cdd:cd20844     6 HTFAVHSYTRPTICQYCKRLLKGLFRQGMQCKDCRFNCHKRCASKVPRDCL 56

protein kinase C conserved region 1 (C1 domain) found in Schizosaccharomyces pombe protein BZZ1 and similar proteins; BZZ1 is a syndapin-like F-BAR protein that plays a role in endocytosis and trafficking to the vacuole. It functions with type I myosins to restore polarity of the actin cytoskeleton after NaCl stress. BZZ1 contains an N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs), a central coiled-coil, and two C-terminal SH3 domains. Schizosaccharomyces pombe BZZ1 also harbors a C1 domain, but Saccharomyces cerevisiae BZZ1 doesn't have any. 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 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSK 313
Cdd:cd20824     2 HNFKPHSFSIPTKCDYCGEKIWGLSKKGLSCKDCGFNCHIKCELK 46

protein kinase C conserved region 1 (C1 domain) found in the myotubularin-related protein Sbf and similar proteins; This group includes Drosophila melanogaster SET domain binding factor (Sbf), the single homolog of human MTMR5/MTMR13, and similar proteins, that show high sequence similarity to vertebrate myotubularin-related proteins (MTMRs) which may function as guanine nucleotide exchange factors (GEFs). Sbf is a pseudophosphatase that coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. It also functions as a GEF that promotes Rab21 GTPase activation associated with PI(3)P endosomes. 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.

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                  ....*....|....*....|....*....|....*....|....*
gi 1090864009 276 FKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGCVK 320
Cdd:cd20827     9 FTTPTYCDYCSSLLWGLVKTGMRCADCGYSCHEKCLEHVPKNCTK 53

protein kinase C conserved region 1 (C1 domain) found in the SH3 and cysteine-rich domain-containing protein (Stac) family; Stac proteins are putative adaptor proteins that are important for neuronal function. There are three mammalian members (Stac1, Stac2 and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. Stac proteins contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. 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.

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                  ....*....|....*....|....*....|....*
gi 1090864009 276 FKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRC 310
Cdd:cd20817     8 FKKPTFCDVCKELLVGLSKQGLRCKNCKMNVHHKC 42

protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase alpha (MRCK alpha) and similar proteins; MRCK alpha, also called Cdc42-binding protein kinase alpha, DMPK-like alpha, or myotonic dystrophy protein kinase-like alpha, is a serine/threonine-protein kinase expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK alpha is an important downstream effector of Cdc42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. 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 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGC 318
Cdd:cd20864     3 HQFVVKSFTTPTKCNQCTSLMVGLIRQGCTCEVCGFSCHVTCADKAPSVC 52

protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. Members of this family contain one 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 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGC 318
Cdd:cd20794     3 HLFQAKRFNRRAVCAYCSDRIWGLGRQGYKCINCKLLVHKKCHKLVKVAC 52

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.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGCVK 320
Cdd:cd20806     2 HNFKVHTFKGPHWCDYCGNFMWGLIAQGVKCEDCGFNAHKQCSKLVPHDCQP 53

EF-hand domain pair;

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1090864009 175 DKLEFMFRLYDSDENGLLDQAEMDQIVsQMLHVAQylEWDPTELRPILKEmlqgMDYDKDGFVSLQE 241
Cdd:pfam13499   2 EKLKEAFKLLDSDGDGYLDVEELKKLL-RKLEEGE--PLSDEEVEELFKE----FDLDKDGRISFEE 61

first 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 first 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 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGC 318
Cdd:cd20841    11 HTLYVHSYKAPTFCDYCGEMLWGLVRQGLKCEGCGLNYHKRCAFKIPNNC 60

second protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group contain two copies of the C1 domain. 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 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCVSKTIHGCV 319
Cdd:cd20798     2 HTLAEHNYKKPTVCKVCDKLLVGLVRQGLKCRDCGVNVHKKCASLLPSNCR 52

first protein kinase C conserved region 1 (C1 domain) found in Saccharomyces cerevisiae protein kinase C-like 1 (ScPKC1) and similar proteins; ScPKC1 is required for cell growth and for the G2 to M transition of the cell division cycle. It mediates a protein kinase cascade, activating BCK1 which itself activates MKK1/MKK2. The family also includes Schizosaccharomyces pombe PKC1 and PKC2, which are involved in the control of cell shape and act as targets of the inhibitor staurosporine. 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.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQglcCIYCKYTVHQRCVSKTIHGC 318
Cdd:cd20822     3 HKFVQKQFYQIMRCAVCGEFLVNAGYQ---CEDCKYTCHKKCYEKVVTKC 49

protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) zeta type; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. Members of this family contain C1 domain found in aPKC isoform zeta. 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 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRC 310
Cdd:cd21095     3 HLFQAKRFNRRAYCGQCSERIWGLGRQGYKCINCKLLVHKRC 44

second 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 domain. 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 C1 domain. 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1090864009 269 HAWTLKHFKKPTYCNFCRAMLMGVGKQGLCCIYCKYTVHQRCV 311
Cdd:cd20836     1 HKFKVHTYSSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKRCV 43