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 1187953329  416 LVFVNPKSGGKQGQRVLWKFQYILNPRQVFNLLKDGPEIGLRLFKDVPDS-RILVCGGDGTVGWILETIDKANLPVL-PP 493
Cdd:smart00046   1 LVFVNPKSGGGKGEKLLRKFRLLLNPRQVFDLTKKGPAVALVIFRDVPDFnRVLVCGGDGTVGWVLNALDKRELPLPePP 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1187953329  494 VAVLPLGTGNDLARCLRWGGGYEGQNLAKILKDLEMSKVVHMDR 537
Cdd:smart00046  81 VAVLPLGTGNDLARSLGWGGGYDGEKLLKTLRDALESDTVKLDR 124

second protein kinase C conserved region 1 (C1 domain) found in diacylglycerol kinase alpha (DAG kinase alpha) and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase alpha, also called 80 kDa diacylglycerol kinase, or diglyceride kinase alpha (DGK-alpha), converts the second messenger diacylglycerol into phosphatidate upon cell stimulation, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity. 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 alpha contains 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1187953329 308 HVWVRGGCESGRCDRCQKKIRIYHSLTGLHCVWCHLEIHDDCLQAVGHECDCGLLRDHILPP 369
Cdd:cd20890     1 HVWVSGGCESSKCDKCQKKIKSFQSLTGLHCVWCHLKRHDECLSSVPSTCDCGPLRDHILPP 62

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 1187953329 152 KLEFTFKLYDTDRNGILDSSEvdkiilqMMRVAEYLDWDVSElrPILQEMMKEIDYDGSGSVSQAEWVRA 221
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADE-------LKAALKSLGEGLSE--EEIDEMIREVDKDGDGKIDFEEFLEL 61

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 1187953329 558 IINNYFSIGVDASIAHRFHIMREKYPEKFNSRMKNKLWYFEFATSESIFSTCKKLEESLTVEICGKPLDLSnLSLEGIAV 637
Cdd:pfam00609   1 VMNNYFSIGVDARIALGFHRLREEHPELFNSRLKNKLIYGVFGFKDMFQRSCKNLIEKVELEVDGKDLPLP-KSLEGIVV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187953329 638 LNIPSMHGGSNLWGDTRRPHgdiyginqalgatakvitdpdiLKTCVPDLSDKRLEVVGLEGAIEMGQIYTKLKNAgRRL 717
Cdd:pfam00609  80 LNIPSYAGGTDLWGNSKEDG----------------------LGFAPQSVDDGLLEVVGLTGALHLGQVQVGLGSA-KRI 136

                         170       180
                  ....*....|....*....|..
gi 1187953329 718 AKCSEITFHTTKTLPMQIDGEP 739
Cdd:pfam00609 137 AQGGPIRITTKKKIPMQVDGEP 158

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187953329  42 ERGLISPSDFAQLQKYMEYSTKKVSDVLKLF-EDGEMAKYVQGDAIGYEGFQQFLKIYLEVDnVPRHLSLALFQSFETGH 120
Cdd:pfam14513   1 EWVSLSPEEFAQLQKYAEYSSKKLKDVLEEFnEDGVLAKYNPEEPIDYEGFKLFMKTYLEVD-LPEDLCQHLFLSFQTKP 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1187953329 121 CLNETNVTK----------------------------DVVCLNDVSCYFSLLEGGR 148
Cdd:pfam14513  80 SQESPDSPKegasssvkagfdknpsslppapsspsasPVVYLKDVSCYLSLLEGGR 135

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 1187953329 414 PLLVFVNPKSGGKQGQRVLWKFQYILNPRQV-FNLLK-DGPEIGLRLFKDVPDS---RILVCGGDGTVGWILETIDKANL 488
Cdd:pfam00781   1 KLLVIVNPKSGGGKGKKLLRKVRPLLNKAGVeVELVLtEGPGDALELAREAAEDgydRIVVAGGDGTVNEVLNGLAGLAT 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1187953329 489 PvlPPVAVLPLGTGNDLARCLRWgggyeGQNLAKILKDLEMSKVVHMD 536
Cdd:pfam00781  81 R--PPLGIIPLGTGNDFARALGI-----PGDPEEALEAILKGQTRPVD 121

Phosphatidylglycerol kinase, diacylglycerol kinase family [Lipid transport and metabolism, General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187953329 415 LLVFVNPKSGGKQGQRVLWKFQYILNpRQVFNLL-------KDGPEIGLRLFKDVPDsRILVCGGDGTVGWILETIDKAN 487
Cdd:COG1597     5 ALLIVNPASGRGRAARLLERLVAALR-AAGLEVEvletespGDATELAREAAAEGAD-LVVAAGGDGTVNEVANGLAGTG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187953329 488 lpvlPPVAVLPLGTGNDLARCLRWgggyeGQNLAKILKDLEMSKVVHMDrwsveVIpqqteeKSDPVPFqiINNyFSIGV 567
Cdd:COG1597    83 ----PPLGILPLGTGNDFARALGI-----PLDPEAALEALLTGRTRRID-----LG------RVNGRYF--LNV-AGIGF 139

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187953329 568 DASIAHRfhimrekypekFNSRMKNKL-W--YFeFATSESIFSTcKKLEesLTVEICGKPLDLSNLSlegIAVLNIPSMH 644
Cdd:COG1597   140 DAEVVER-----------ANRALKRRLgKlaYV-LAALRALLRY-RPFR--LRIELDGEEIEGEALL---VAVGNGPYYG 201

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187953329 645 GGSNLWGDtrrphgdiyginqalgatakvitdpdilktcvPDLSDKRLEVVGLE--GAIEMGQIYTKLKNaGR------- 715
Cdd:COG1597   202 GGLRLAPD--------------------------------ASLDDGLLDVVVVRplSRLRLLRLLPRLLR-GRhlrhpgv 248

                         330       340       350
                  ....*....|....*....|....*....|....*...
gi 1187953329 716 RLAKCSEITFHTTKTLPMQIDGEP-WMQTPCTIKITHK 752
Cdd:COG1597   249 RYFRAREVEIESDRPLPVQLDGEPlGLATPLEFEVLPG 286

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 1187953329 152 KLEFTFKLYDTDRNGILDSSEvdkiilqMMRVAEYLDWDVSElrPILQEMMKEIDYDGSGSVSQAEWVRA 221
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADE-------LKAALKSLGEGLSE--EEIDEMIREVDKDGDGKIDFEEFLEL 61

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 1187953329  244 HMWRPKRFPRPVYCNLCESSI-GLGKQGLSCNLCKYTVHDQCAMKAL-PC 291
Cdd:smart00109   1 HKHVFRTFTKPTFCCVCRKSIwGSFKQGLRCSECKVKCHKKCADKVPkAC 50

putative lipid kinase; Reviewed

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187953329 420 NPKSGGKqgqRVLWKFQYILNPRQVFNLL------KDGPEIGLrLFKDVPDSR--ILVCGGDGTVGWILETIDKANLPVl 491
Cdd:PRK13059    9 NPYSGEN---AIISELDKVIRIHQEKGYLvvpyriSLEYDLKN-AFKDIDESYkyILIAGGDGTVDNVVNAMKKLNIDL- 83

                          90
                  ....*....|....*...
gi 1187953329 492 pPVAVLPLGTGNDLARCL 509
Cdd:PRK13059   84 -PIGILPVGTANDFAKFL 100

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 1187953329  306 QSHVWVRGGcESGRCDRCQKKIRIYHsLTGLHCVWCHLEIHDDCLQAVGHEC 357
Cdd:smart00109   1 HKHVFRTFT-KPTFCCVCRKSIWGSF-KQGLRCSECKVKCHKKCADKVPKAC 50

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.

                           10        20
                   ....*....|....*....|....
gi 1187953329  198 LQEMMKEIDYDGSGSVSQAEWVRA 221
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKDL 25

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 1187953329 558 IINNYFSIGVDASIAHRFHIMREKYPEKFNSRMKNKLWYFEFATSESIFSTCKKLEESLTVEICGKPLDLSnLSLEGIAV 637
Cdd:pfam00609   1 VMNNYFSIGVDARIALGFHRLREEHPELFNSRLKNKLIYGVFGFKDMFQRSCKNLIEKVELEVDGKDLPLP-KSLEGIVV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187953329 638 LNIPSMHGGSNLWGDTRRPHgdiyginqalgatakvitdpdiLKTCVPDLSDKRLEVVGLEGAIEMGQIYTKLKNAgRRL 717
Cdd:pfam00609  80 LNIPSYAGGTDLWGNSKEDG----------------------LGFAPQSVDDGLLEVVGLTGALHLGQVQVGLGSA-KRI 136

                         170       180
                  ....*....|....*....|..
gi 1187953329 718 AKCSEITFHTTKTLPMQIDGEP 739
Cdd:pfam00609 137 AQGGPIRITTKKKIPMQVDGEP 158

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187953329  42 ERGLISPSDFAQLQKYMEYSTKKVSDVLKLF-EDGEMAKYVQGDAIGYEGFQQFLKIYLEVDnVPRHLSLALFQSFETGH 120
Cdd:pfam14513   1 EWVSLSPEEFAQLQKYAEYSSKKLKDVLEEFnEDGVLAKYNPEEPIDYEGFKLFMKTYLEVD-LPEDLCQHLFLSFQTKP 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1187953329 121 CLNETNVTK----------------------------DVVCLNDVSCYFSLLEGGR 148
Cdd:pfam14513  80 SQESPDSPKegasssvkagfdknpsslppapsspsasPVVYLKDVSCYLSLLEGGR 135

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 1187953329 414 PLLVFVNPKSGGKQGQRVLWKFQYILNPRQV-FNLLK-DGPEIGLRLFKDVPDS---RILVCGGDGTVGWILETIDKANL 488
Cdd:pfam00781   1 KLLVIVNPKSGGGKGKKLLRKVRPLLNKAGVeVELVLtEGPGDALELAREAAEDgydRIVVAGGDGTVNEVLNGLAGLAT 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1187953329 489 PvlPPVAVLPLGTGNDLARCLRWgggyeGQNLAKILKDLEMSKVVHMD 536
Cdd:pfam00781  81 R--PPLGIIPLGTGNDFARALGI-----PGDPEEALEAILKGQTRPVD 121

second 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 second 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
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1187953329 308 HVWVRGGCEsGRCDRCQKKIRIYHSLTGLHCVWCHLEIHDDCLQAVGHECDCG 360
Cdd:cd20851     1 HHWVEGNCP-GKCDKCHKSIKSYQGLTGLHCVWCHITLHNKCASHVKPECDLG 52

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 1187953329 237 TLKDDGQHMWRPKRFPRPVYCNLCESS-IGLGKQGLSCNLCKYTVHDQCAMKALPCEVSTYAKSRK 301
Cdd:cd20845     1 NVKDDGQHVWRLKHFNKPAYCNLCLNMlVGLGKQGLCCSFCKYTVHERCVQRAPASCIKTYVKSKK 66

second 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 second 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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1187953329 308 HVWVRGGCESgRCDRCQKKIRIYHSLTGLHCVWCHLEIHDDCLQAVGHECDCGLLRDH 365
Cdd:cd20891     3 HFWVEGNCPT-KCDKCHKTIKCYQGLTGLHCVWCQITLHNKCASHVKPECDCGPLKDH 59

second protein kinase C conserved region 1 (C1 domain) found in the diacylglycerol kinase family; The diacylglycerol kinase (DGK, EC 2.7.1.107) family of enzymes plays critical roles in lipid signaling pathways by converting diacylglycerol to phosphatidic acid, thereby downregulating signaling by the former and upregulating signaling by the latter second messenger. Ten DGK family isozymes have been identified to date, which possess different interaction motifs imparting distinct temporal and spatial control of DGK activity to each isozyme. They have been classified into five types (I-V), according to domain architecture and some common features. All DGK isozymes, except for DGKtheta, contain two copies of the C1 domain. This model corresponds to the second one. DGKtheta harbors three C1 domains. Its third C1 domain is included here. 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 1187953329 308 HVWVRGGCESG-RCDRCQKKIRIYHSLTGLHCVWCHLEIHDDCLQAVGH-ECDCG 360
Cdd:cd20805     1 HHWVEGNLPSGaKCSVCGKKCGSSFGLAGYRCSWCKRTVHSECIDKLGPeECDLG 55

first protein kinase C conserved region 1 (C1 domain) found in type II diacylglycerol kinases; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. Type II DAG kinases (DGKs) contain 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. Three DGK isozymes (delta, eta and kappa) are classified as type II. DAG kinase delta, also called 130 kDa DAG 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. DAG kinase eta, also called diglyceride kinase eta (DGK-eta), plays a key role in promoting cell growth. The DAG kinase eta gene, DGKH, is a replicated risk gene of bipolar disorder (BPD). DAG kinase kappa is also called diglyceride kinase kappa (DGK-kappa) or 142 kDa DAG kinase. 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1187953329 240 DDGQHMWRPKRFPRPVYCNLCESSI-GLGKQGLSCNLCKYTVHDQCAMKAL-PCEVSTYA 297
Cdd:cd20800     1 LSGSHNWYACSHARPTYCNVCREALsGVTSHGLSCEVCKFKAHKRCAVKAPnNCKWTTLA 60

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        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1187953329 308 HVWVRGG-CESGRCDRCQKKIRiYHSLTGLHCVWCHLEIHDDCLQAVGHECDCG 360
Cdd:pfam00130   1 HHFVHRNfKQPTFCDHCGEFLW-GLGKQGLKCSWCKLNVHKRCHEKVPPECGCD 53

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 1187953329  244 HMWRPKRFPRPVYCNLCESSI-GLGKQGLSCNLCKYTVHDQCAMKAL-PC 291
Cdd:smart00109   1 HKHVFRTFTKPTFCCVCRKSIwGSFKQGLRCSECKVKCHKKCADKVPkAC 50

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1187953329 242 GQHMWRPKRFPRPVYCNLCESSI-GLGKQGLSCNLCKYTVHDQCAMKAL-PCEVSTYAKSRKD 302
Cdd:cd20847    23 GMHNWYACSHARPTYCNVCREALsGVTSHGLSCEVCKFKAHKRCAVRATnNCKWTTLASIGKD 85

second protein kinase C conserved region 1 (C1 domain) found in type III diacylglycerol kinase, DAG kinase epsilon, and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase epsilon, also called diglyceride kinase epsilon (DGK-epsilon), is the only isoform classified as type III; it possesses a hydrophobic domain in addition to C1 and catalytic domains that are present in all DGKs, and shows selectivity for acyl chains. It is highly selective for arachidonate-containing species of DAG. It may terminate signals transmitted through arachidonoyl-DAG or may contribute to the synthesis of phospholipids with defined fatty acid composition. DAG kinase epsilon contains 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1187953329 308 HVWVRGGCE-SGRCDRCQKKIRIYHSLTGLHCVWCHLEIHDDCLQAVGHECDCGLLRDHILPP 369
Cdd:cd20853     1 HHWVRGNLPlCSVCCVCNEQCGNQPGLCDYRCCWCQRTVHDDCLAKLPKECDLGAFRNFIVPP 63

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.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1187953329 244 HMWRPKRFPRPVYCNLCESSI-GLGKQGLSCNLCKYTVHDQCAMKAL 289
Cdd:cd20834     8 HEFIAKFFRQPTFCSVCKEFLwGFNKQGYQCRQCNAAVHKKCHDKIL 54

third protein kinase C conserved region 1 (C1 domain) found in type V diacylglycerol kinase, DAG kinase theta, and similar proteins; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. DAG kinase theta, also called diglyceride kinase theta (DGK-theta), is the only isoform classified as type V; it contains a pleckstrin homology (PH)-like domain and an additional C1 domain, compared to other DGKs. It may regulate the activity of protein kinase C by controlling the balance between the two signaling lipids, diacylglycerol and phosphatidic acid. DAG kinase theta contains three copies of the C1 domain. This model corresponds to the third 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 1187953329 308 HVWVRGGCESG-RCDRCQKKIRIYHSLTGLHCVWCHLEIHDDCLQAVGHECDCGLLRDHILPP 369
Cdd:cd20854     1 HHWREGNLPSNsKCEVCKKSCGSSECLAGMRCEWCGITAHASCYKSLPKECNFGRLRNIILPP 63

protein kinase C conserved region 1 (C1 domain) found in the Myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) family; MRCK is thought to be a coincidence detector of signaling by the small GTPase Cdc42 and phosphoinositides. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. MRCK has been shown to promote cytoskeletal reorganization, which affects many biological processes. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. MRCK consists of a serine/threonine kinase domain, a cysteine rich (C1) region, a PH domain and a p21 binding motif. 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.

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                  ....*....|....*....|....*....|....*....|....*...
gi 1187953329 244 HMWRPKRFPRPVYCNLCES-SIGLGKQGLSCNLCKYTVHDQCAMKALP 290
Cdd:cd20809     1 HKFIVRTFSTPTKCNHCTSlMVGLVRQGLVCEVCGYACHVSCADKAPQ 48

EF-hand domain pair;

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1187953329 150 EDKLEFTFKLYDTDRNGILDSSEVDKIILQMMRvaeyldwDVSELRPILQEMMKEIDYDGSGSVSQAE 217
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLEE-------GEPLSDEEVEELFKEFDLDKDGRISFEE 61

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 1187953329 244 HMWRPKRFPRPVYCNLCESSI-GLGKQGLSCNLCKYTVHDQC 284
Cdd:cd21095     3 HLFQAKRFNRRAYCGQCSERIwGLGRQGYKCINCKLLVHKRC 44

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.

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                  ....*....|....*....|....*....|....*....|..
gi 1187953329 244 HMWRPKRFPRPVYCNLCESSI-GLGKQGLSCNLCKYTVHDQC 284
Cdd:cd20833     3 HKFIARFFKQPTFCSHCTDFIwGFGKQGFQCQVCSFVVHKRC 44

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 1187953329 244 HMWRPKRFPRPVYCNLCES-SIGLGKQGLSCNLCKYTVHDQCAMKA 288
Cdd:cd20864     3 HQFVVKSFTTPTKCNQCTSlMVGLIRQGCTCEVCGFSCHVTCADKA 48

protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) iota 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-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 C1 domain found in aPKC isoform iota. 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 1187953329 244 HMWRPKRFPRPVYCNLCESSI-GLGKQGLSCNLCKYTVHDQC 284
Cdd:cd21094     3 HTFQAKRFNRRAHCAICTDRIwGLGRQGYKCINCKLLVHKKC 44

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.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1187953329 244 HMWRPKRFPRPVYCNLCESSIGlgKQGLSCNLCKYTVHDQC-AMKALPCEVS 294
Cdd:cd20826     3 HSFKEKSFRKPRTCDVCKQIIW--NEGSSCRVCKYACHRKCePKVTAACSPS 52