Diacylglycerol kinase accessory 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 might either be an accessory domain or else contribute to the catalytic domain. Bacterial homologues are known.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997   741 QMSNYCGIGIDAELSLDFHQAREEEPGKFTSRLHNKGVYVRVGLQKI--SHSRSLHKQIRLQVERQEVELP-SIEGLIFI 817
Cdd:smart00045   1 VMNNYFSIGVDAHIALEFHNKREANPEKFNSRLKNKMWYFELGTKDLffRTCKDLHERIELECDGVDVDLPnSLEGIAVL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997   818 NIPSWGSGADLWG--SDSDTRFEKPRMDDGLLEVVGVTGVVHMGQVQGGLRSGIRIAQGSYFRVTLL--KATPVQVDGEP 893
Cdd:smart00045  81 NIPSYGGGTNLWGttDKEDLNFSKQSHDDGLLEVVGLTGAMHMAQIRQVGLAGRRIAQCSEVRITIKtsKTIPMQVDGEP 160

first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997 397 EVLKIYPGWLKVGVAYVSVRVTPKSTARSVVLEVLPLLGRQAESPESFQLVEVAMGCRHVQRTMLMDEQPLLDRLQdIRQ 476
Cdd:cd01783    1 GYIRVYPGWLKVGVAYKSIPVTKETTVEEVIKEALPKFGLQDEDPEDFRLVEVLMDKGVVERVMLRDECPWLILLD-IRK 79

                 ...
gi 767928997 477 GGL 479
Cdd:cd01783   80 ESL 82

first 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 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 767928997  60 GHSFRKVTLTKPTFCHLCSDFIWGL--AGFLCDVCNFMSHEKCLKHVRIPCTSVAP 113
Cdd:cd20803    1 GHSFRKKTFHKPTYCHHCTDLLWGLlnQGYQCEVCNFVSHERCLKTVVTPCSSIAP 56

second 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 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 767928997 117 RVPVAHCFGPRGLHKRKFCAVCRKVLE-APALHCEVCELHLHPDCVPFACSDCRQCH 172
Cdd:cd20804    1 KNPVAHCWSEPGHSKRKFCNVCRKRLEdSPAFRCEVCEYYVHSDCQDFAVSDCRECA 57

Diacylglycerol kinase accessory 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 might either be an accessory domain or else contribute to the catalytic domain. Bacterial homologues are known.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997   741 QMSNYCGIGIDAELSLDFHQAREEEPGKFTSRLHNKGVYVRVGLQKI--SHSRSLHKQIRLQVERQEVELP-SIEGLIFI 817
Cdd:smart00045   1 VMNNYFSIGVDAHIALEFHNKREANPEKFNSRLKNKMWYFELGTKDLffRTCKDLHERIELECDGVDVDLPnSLEGIAVL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997   818 NIPSWGSGADLWG--SDSDTRFEKPRMDDGLLEVVGVTGVVHMGQVQGGLRSGIRIAQGSYFRVTLL--KATPVQVDGEP 893
Cdd:smart00045  81 NIPSYGGGTNLWGttDKEDLNFSKQSHDDGLLEVVGLTGAMHMAQIRQVGLAGRRIAQCSEVRITIKtsKTIPMQVDGEP 160

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 767928997   590 LVFVNPKSGGLKGRDLLCSFRKLLNPHQVFDLTNGGPLPGLHLFSQVPCF-RVLVCGGDGTVGWVLGALEETRYRLacPE 668
Cdd:smart00046   1 LVFVNPKSGGGKGEKLLRKFRLLLNPRQVFDLTKKGPAVALVIFRDVPDFnRVLVCGGDGTVGWVLNALDKRELPL--PE 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 767928997   669 PSVAILPLGTGNDLGRVLRWGAGYSGEDPFSVLLSVDEADAVLMDR 714
Cdd:smart00046  79 PPVAVLPLGTGNDLARSLGWGGGYDGEKLLKTLRDALESDTVKLDR 124

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767928997 186 WREGNLPSGARCEVCRKTCGSSDVLAGVRCEWCGVQAHSLCSAALAPECGFGRLRSLVLPP 246
Cdd:cd20854    3 WREGNLPSNSKCEVCKKSCGSSECLAGMRCEWCGITAHASCYKSLPKECNFGRLRNIILPP 63

first 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 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 767928997  60 GHSFRKVTLTKPTFCHLCSDFIWGL--AGFLCDVCNFMSHEKCLKHVRIPCTSVAP 113
Cdd:cd20803    1 GHSFRKKTFHKPTYCHHCTDLLWGLlnQGYQCEVCNFVSHERCLKTVVTPCSSIAP 56

second 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 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 767928997 117 RVPVAHCFGPRGLHKRKFCAVCRKVLE-APALHCEVCELHLHPDCVPFACSDCRQCH 172
Cdd:cd20804    1 KNPVAHCWSEPGHSKRKFCNVCRKRLEdSPAFRCEVCEYYVHSDCQDFAVSDCRECA 57

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997  395 AQEVLKIYPGWLKVGVAYVSVRVTPKSTARSVVLEVLPLLGRqAESPESFQLVEVaMGCRHVQRTMLMDEQPLLDRLQDI 474
Cdd:pfam00788   1 DDGVLKVYTEDGKPGTTYKTILVSSSTTAEEVIEALLEKFGL-EDDPRDYVLVEV-LERGGGERRLPDDECPLQIQLQWP 78

                  ....
gi 767928997  475 RQGG 478
Cdd:pfam00788  79 RDAS 82

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997   395 AQEVLKIYPGWLkVGVAYVSVRVTPKSTARSVVLEVLPLLGRQAEsPESFQLVEVAmgCRHVQRTMLMDEQPLLDRLQDI 474
Cdd:smart00314   1 DTFVLRVYVDDL-PGGTYKTLRVSSRTTARDVIQQLLEKFHLTDD-PEEYVLVEVL--PDGKERVLPDDENPLQLQKLWP 76

                   ....*
gi 767928997   475 RQGGL 479
Cdd:smart00314  77 RRGPN 81

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 767928997   61 HSFRKVTLTKPTFCHLCSDFIWGLA--GFLCDVCNFMSHEKCLKHVRIPC 108
Cdd:pfam00130   1 HHFVHRNFKQPTFCDHCGEFLWGLGkqGLKCSWCKLNVHKRCHEKVPPEC 50

lipid kinase, YegS/Rv2252/BmrU family; The E. coli member of this family, YegS has been purified and shown to have phosphatidylglycerol kinase activity. The member from M. tuberculosis, Rv2252, has diacylglycerol kinase activity. BmrU from B. subtilis is in an operon with multidrug efflux transporter Bmr, but is uncharacterized. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997  640 RVLVCGGDGTVGWVLGALEETRYRlacpePSVAILPLGTGNDLGRVlrwgagysgedpFSVLLSVDEAdavlmdrwtilL 719
Cdd:TIGR00147  60 TVIAGGGDGTINEVVNALIQLDDI-----PALGILPLGTANDFARS------------LGIPEDLDKA-----------A 111

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997  720 DAHEAGsaendtaDAEPPKIVQMS------NYCGIGIDAELSLDFhqareeePGKFTSRLhNKGVYVRVGLQKISHSRSL 793
Cdd:TIGR00147 112 KLVIAG-------DARAIDMGQVNkqycfiNMAGGGFGTEITTET-------PEKLKAAL-GSLSYILSGLMRMDTLQPF 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997  794 HKQIRLQVERQEVElpsIEGLIFINIPSWGSGADLwGSDSDTRfekprmdDGLLEVVGVTG------VVHMGQVQGGLRS 867
Cdd:TIGR00147 177 RCEIRGEGEHWQGE---AVVFLVGNGRQAGGGQKL-APDASIN-------DGLLDLRIFTNdnllpaLVLTLMSDEGKHT 245

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 767928997  868 ---GIRIAQGSYFRVTLLKATPVQVDGEPWVQAPGHMIISAA 906
Cdd:TIGR00147 246 dnpNIIYGKASRIDIQTPHKITFNLDGEPLGGTPFHIEILPA 287

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 767928997  296 GKQTLKIFDGDDAVRRsQFRLVTVSRLAGAEEVLEAALRAHHIPEDPGHLELC 348
Cdd:pfam00788   1 DDGVLKVYTEDGKPGT-TYKTILVSSSTTAEEVIEALLEKFGLEDDPRDYVLV 52

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 767928997  122 HCFGPRGLHKRKFCAVCRK---VLEAPALHCEVCELHLHPDCVPFACSDCR 169
Cdd:pfam00130   1 HHFVHRNFKQPTFCDHCGEflwGLGKQGLKCSWCKLNVHKRCHEKVPPECG 51

Diacylglycerol kinase accessory 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 might either be an accessory domain or else contribute to the catalytic domain. Bacterial homologues are known.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997   741 QMSNYCGIGIDAELSLDFHQAREEEPGKFTSRLHNKGVYVRVGLQKI--SHSRSLHKQIRLQVERQEVELP-SIEGLIFI 817
Cdd:smart00045   1 VMNNYFSIGVDAHIALEFHNKREANPEKFNSRLKNKMWYFELGTKDLffRTCKDLHERIELECDGVDVDLPnSLEGIAVL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997   818 NIPSWGSGADLWG--SDSDTRFEKPRMDDGLLEVVGVTGVVHMGQVQGGLRSGIRIAQGSYFRVTLL--KATPVQVDGEP 893
Cdd:smart00045  81 NIPSYGGGTNLWGttDKEDLNFSKQSHDDGLLEVVGLTGAMHMAQIRQVGLAGRRIAQCSEVRITIKtsKTIPMQVDGEP 160

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 767928997   590 LVFVNPKSGGLKGRDLLCSFRKLLNPHQVFDLTNGGPLPGLHLFSQVPCF-RVLVCGGDGTVGWVLGALEETRYRLacPE 668
Cdd:smart00046   1 LVFVNPKSGGGKGEKLLRKFRLLLNPRQVFDLTKKGPAVALVIFRDVPDFnRVLVCGGDGTVGWVLNALDKRELPL--PE 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 767928997   669 PSVAILPLGTGNDLGRVLRWGAGYSGEDPFSVLLSVDEADAVLMDR 714
Cdd:smart00046  79 PPVAVLPLGTGNDLARSLGWGGGYDGEKLLKTLRDALESDTVKLDR 124

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767928997 186 WREGNLPSGARCEVCRKTCGSSDVLAGVRCEWCGVQAHSLCSAALAPECGFGRLRSLVLPP 246
Cdd:cd20854    3 WREGNLPSNSKCEVCKKSCGSSECLAGMRCEWCGITAHASCYKSLPKECNFGRLRNIILPP 63

first 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 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 767928997  60 GHSFRKVTLTKPTFCHLCSDFIWGL--AGFLCDVCNFMSHEKCLKHVRIPCTSVAP 113
Cdd:cd20803    1 GHSFRKKTFHKPTYCHHCTDLLWGLlnQGYQCEVCNFVSHERCLKTVVTPCSSIAP 56

second 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 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 767928997 117 RVPVAHCFGPRGLHKRKFCAVCRKVLE-APALHCEVCELHLHPDCVPFACSDCRQCH 172
Cdd:cd20804    1 KNPVAHCWSEPGHSKRKFCNVCRKRLEdSPAFRCEVCEYYVHSDCQDFAVSDCRECA 57

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997  395 AQEVLKIYPGWLKVGVAYVSVRVTPKSTARSVVLEVLPLLGRqAESPESFQLVEVaMGCRHVQRTMLMDEQPLLDRLQDI 474
Cdd:pfam00788   1 DDGVLKVYTEDGKPGTTYKTILVSSSTTAEEVIEALLEKFGL-EDDPRDYVLVEV-LERGGGERRLPDDECPLQIQLQWP 78

                  ....
gi 767928997  475 RQGG 478
Cdd:pfam00788  79 RDAS 82

Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in various functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997 398 VLKIYPGWLKVGVAYVSVRVTPKSTARSVVLEVLPLLGRqAESPESFQLVEVAMGcRHVQRTMLMDEQPLLDRLQDIRQG 477
Cdd:cd17043    1 VLKVYDDDLAPGSAYKSILVSSTTTAREVVQLLLEKYGL-EEDPEDYSLYEVSEK-QETERVLHDDECPLLIQLEWGPQG 78

second 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 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 767928997 186 WREGNLPSGARCEVCRKTCGSSDVLAGVRCEWCGVQAHSLCSAALAPECGFG 237
Cdd:cd20852    3 WLEGNLPVSSKCAVCDKTCGSVLRLQDWRCLWCGATVHTACKDSLPTKCSLG 54

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 767928997  61 HSFRKVTLTKPTFCHLCSDFIWGLA--GFLCDVCNFMSHEKCLKHVRIPC 108
Cdd:cd00029    1 HRFVPTTFSSPTFCDVCGKLIWGLFkqGLKCSDCGLVCHKKCLDKAPSPC 50

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767928997   395 AQEVLKIYPGWLkVGVAYVSVRVTPKSTARSVVLEVLPLLGRQAEsPESFQLVEVAmgCRHVQRTMLMDEQPLLDRLQDI 474
Cdd:smart00314   1 DTFVLRVYVDDL-PGGTYKTLRVSSRTTARDVIQQLLEKFHLTDD-PEEYVLVEVL--PDGKERVLPDDENPLQLQKLWP 76

                   ....*
gi 767928997   475 RQGGL 479
Cdd:smart00314  77 RRGPN 81

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767928997  60 GHSFRKVTLTKPTFCHLCSDFIWGLA--GFLCDVCNFMSHEKCLKHVRIPC 108
Cdd:cd20794    2 GHLFQAKRFNRRAVCAYCSDRIWGLGrqGYKCINCKLLVHKKCHKLVKVAC 52

second 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 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 767928997 186 WREGNLPSGARCEVCRKTCGSSDVLAGVRCEWCGVQAHSLCSAALAPECGFGRLR 240
Cdd:cd20894    8 WLEGNLPVSAKCSVCDKTCGSVLRLQDWRCLWCKAMVHTACKDQYPRKCPLGQCR 62

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 767928997  60 GHSFRKVTLTKPTFCHLCSDFIWGL---AGFLCDVCNFMSHEKCLKHVRIPCTSV 111
Cdd:cd20835    9 GHKFMATYLRQPTYCSHCKDFIWGVigkQGYQCQVCTCVVHKRCHQLVVTKCPGN 63

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767928997  60 GHSFRKVTLTKPTFCHLCSDFIWGL-AGFLCDVCNFMSHEKCLKHVRIPCT 109
Cdd:cd20818    3 GHKFATVQFNIPTYCEVCNSFIWLMeKGLVCQVCKFTCHKKCYSKITAPCK 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
                   ....*....|....*....|....*....|....*....|....*....
gi 767928997   186 WREGNLPSGARCEVCRKTCGSSDvLAGVRCEWCGVQAHSLCSAALAPEC 234
Cdd:smart00109   3 HVFRTFTKPTFCCVCRKSIWGSF-KQGLRCSECKVKCHKKCADKVPKAC 50

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 767928997 186 WREGNLPsgARCEVCRKTCGSSDVLAGVRCEWCGVQAHSLCSAALAPECGFG 237
Cdd:cd20851    3 WVEGNCP--GKCDKCHKSIKSYQGLTGLHCVWCHITLHNKCASHVKPECDLG 52

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 767928997 186 WREGNLPSGaRCEVCRKTCGSSDVLAGVRCEWCGVQAHSLCSAALAPECGFGRLRSLVLPP 246
Cdd:cd20890    3 WVSGGCESS-KCDKCQKKIKSFQSLTGLHCVWCHLKRHDECLSSVPSTCDCGPLRDHILPP 62

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 767928997  61 HSFRKVTLTKPTFCHLCSDFIWGLA--GFLCDVCNFMSHEKCLKHVRIPCT 109
Cdd:cd20796    2 HTFVVHTYTKPTVCQHCKKLLKGLFrqGLQCKDCKFNCHKKCAEKVPKDCT 52