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 2130865312   765 VMNNYFGIGLDAKISLDFNNKRDEHPEKCRSRTKNMMWYGVLGTKELLHRTYKNLEQKVLLECDGRPIPLP-SLQGIAVL 843
Cdd:smart00045    1 VMNNYFSIGVDAHIALEFHNKREANPEKFNSRLKNKMWYFELGTKDLFFRTCKDLHERIELECDGVDVDLPnSLEGIAVL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312   844 NIPSYAGGTNFWGGT-KEDDTFAAPSFDDKILEVVAVFGSMQMAVSRVIKLQHHRIAQCRTVKISILGDEGVPVQVDGEA 922
Cdd:smart00045   81 NIPSYGGGTNLWGTTdKEDLNFSKQSHDDGLLEVVGLTGAMHMAQIRQVGLAGRRIAQCSEVRITIKTSKTIPMQVDGEP 160

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312  140 ALKTVQNREHFEPTQYSMDHFSGMHNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNCKWTTLA 219
Cdd:cd20847      1 ALKSVQNREHFESTQYSMDHFSGMHNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNCKWTTLA 80

                   ....*
gi 2130865312  220 SIGKD 224
Cdd:cd20847     81 SIGKD 85

second 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 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 2130865312  231 GIAMPHQWLEGNLPVSAKCTVCDKTCGSVLRLQDWRCLWCKAMVHTSCKESLQTKCPLGLC 291
Cdd:cd20893      1 GISMPHQWLEGNLPVSAKCTVCDKTCGSVLRLQDWRCLWCKAMVHTSCKELLLTKCPLGQC 61

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 2130865312   765 VMNNYFGIGLDAKISLDFNNKRDEHPEKCRSRTKNMMWYGVLGTKELLHRTYKNLEQKVLLECDGRPIPLP-SLQGIAVL 843
Cdd:smart00045    1 VMNNYFSIGVDAHIALEFHNKREANPEKFNSRLKNKMWYFELGTKDLFFRTCKDLHERIELECDGVDVDLPnSLEGIAVL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312   844 NIPSYAGGTNFWGGT-KEDDTFAAPSFDDKILEVVAVFGSMQMAVSRVIKLQHHRIAQCRTVKISILGDEGVPVQVDGEA 922
Cdd:smart00045   81 NIPSYGGGTNLWGTTdKEDLNFSKQSHDDGLLEVVGLTGAMHMAQIRQVGLAGRRIAQCSEVRITIKTSKTIPMQVDGEP 160

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312   55 IKEGMLTKQNNSFQRSKRRYFKLRGRTLYYAKTAKSIIFDEVDLTDASVAESSTKNVNNSFTVITPCRKLILCADNRKEM 134
Cdd:cd13274      1 IKEGPLLKQTSSFQRWKRRYFKLKGRKLYYAKDSKSLIFEEIDLSDASVAECSTKNVNNSFTVITPFRKLILCAESRKEM 80

                           90
                   ....*....|....*..
gi 2130865312  135 EEWIAALKTVQNREHFE 151
Cdd:cd13274     81 EEWISALKTVQQREFYE 97

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 2130865312   323 LVFVNSKSGDNQGVKFLRRFKQLLNPAQVFDLMNGGPHLGLRLFQKFDTF-RILVCGGDGSVGWVLSEIDSLNLHKQC-Q 400
Cdd:smart00046    1 LVFVNPKSGGGKGEKLLRKFRLLLNPRQVFDLTKKGPAVALVIFRDVPDFnRVLVCGGDGTVGWVLNALDKRELPLPEpP 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*
gi 2130865312   401 LGVLPLGTGNDLARVLGWGSACDDDTQLPqILEKLERASTKMLDR 445
Cdd:smart00046   81 VAVLPLGTGNDLARSLGWGGGYDGEKLLK-TLRDALESDTVKLDR 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 2130865312  321 PLLVFVNSKSGDNQGVKFLRRFKQLLNPAQV-FDLMN-GGPHLGLRLFQKFD---TFRILVCGGDGSVGWVLSEIDslNL 395
Cdd:pfam00781    1 KLLVIVNPKSGGGKGKKLLRKVRPLLNKAGVeVELVLtEGPGDALELAREAAedgYDRIVVAGGDGTVNEVLNGLA--GL 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 2130865312  396 HKQCQLGVLPLGTGNDLARVLGWGsacdddTQLPQILEKLERASTKMLD 444
Cdd:pfam00781   79 ATRPPLGIIPLGTGNDFARALGIP------GDPEEALEAILKGQTRPVD 121

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312    54 VIKEGMLTKQNNSFQRS-KRRYFKLRGRTLYYAKTAKSIIFDE----VDLTDASV---AESSTKNVNNSFTVITPCRK-L 124
Cdd:smart00233    1 VIKEGWLYKKSGGGKKSwKKRYFVLFNSTLLYYKSKKDKKSYKpkgsIDLSGCTVreaPDPDSSKKPHCFEIKTSDRKtL 80

                            90       100
                    ....*....|....*....|..
gi 2130865312   125 ILCADNRKEMEEWIAALKTVQN 146
Cdd:smart00233   81 LLQAESEEEREKWVEALRKAIA 102

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 2130865312   236 HQWLEGNLPVSAKCTVCDKTCGSVlRLQDWRCLWCKAMVHTSCKESLQTKC 286
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIWGS-FKQGLRCSECKVKCHKKCADKVPKAC 50

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312   54 VIKEGMLTKQNNSFQRS-KRRYFKLRGRTLYY--------AKTAKSIIfDEVDLTDASVAESSTKNVNNSFTVITPC--- 121
Cdd:pfam00169    1 VVKEGWLLKKGGGKKKSwKKRYFVLFDGSLLYykddksgkSKEPKGSI-SLSGCEVVEVVASDSPKRKFCFELRTGErtg 79

                           90       100
                   ....*....|....*....|..
gi 2130865312  122 -RKLILCADNRKEMEEWIAALK 142
Cdd:pfam00169   80 kRTYLLQAESEEERKDWIKAIQ 101

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312  768 NYFGIGLDAKISLDFNNKRdehpekcrSRTKNMMWYGVLGTKELlhRTYKNLEqkVLLECDGRPIPLPSLQgIAVLNIPS 847
Cdd:COG1597    133 NVAGIGFDAEVVERANRAL--------KRRLGKLAYVLAALRAL--LRYRPFR--LRIELDGEEIEGEALL-VAVGNGPY 199

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312  848 YAGGTNFwggtkeddtFAAPSFDDKILEVVAV----FGSMQMAVSRVIK---LQHHRIAQCRTVKISILGDEGVPVQVDG 920
Cdd:COG1597    200 YGGGLRL---------APDASLDDGLLDVVVVrplsRLRLLRLLPRLLRgrhLRHPGVRYFRAREVEIESDRPLPVQLDG 270

                          170
                   ....*....|....*.
gi 2130865312  921 EA-WIQPPGYIRIIHK 935
Cdd:COG1597    271 EPlGLATPLEFEVLPG 286

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
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2130865312  367 QKFDTFRILVCGGDGSVGWVLSEIDSLNlhKQCQLGVLPLGTGNDLARVLG 417
Cdd:TIGR00147   54 RKFGVDTVIAGGGDGTINEVVNALIQLD--DIPALGILPLGTANDFARSLG 102

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 2130865312   765 VMNNYFGIGLDAKISLDFNNKRDEHPEKCRSRTKNMMWYGVLGTKELLHRTYKNLEQKVLLECDGRPIPLP-SLQGIAVL 843
Cdd:smart00045    1 VMNNYFSIGVDAHIALEFHNKREANPEKFNSRLKNKMWYFELGTKDLFFRTCKDLHERIELECDGVDVDLPnSLEGIAVL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312   844 NIPSYAGGTNFWGGT-KEDDTFAAPSFDDKILEVVAVFGSMQMAVSRVIKLQHHRIAQCRTVKISILGDEGVPVQVDGEA 922
Cdd:smart00045   81 NIPSYGGGTNLWGTTdKEDLNFSKQSHDDGLLEVVGLTGAMHMAQIRQVGLAGRRIAQCSEVRITIKTSKTIPMQVDGEP 160

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312   55 IKEGMLTKQNNSFQRSKRRYFKLRGRTLYYAKTAKSIIFDEVDLTDASVAESSTKNVNNSFTVITPCRKLILCADNRKEM 134
Cdd:cd13274      1 IKEGPLLKQTSSFQRWKRRYFKLKGRKLYYAKDSKSLIFEEIDLSDASVAECSTKNVNNSFTVITPFRKLILCAESRKEM 80

                           90
                   ....*....|....*..
gi 2130865312  135 EEWIAALKTVQNREHFE 151
Cdd:cd13274     81 EEWISALKTVQQREFYE 97

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 2130865312   323 LVFVNSKSGDNQGVKFLRRFKQLLNPAQVFDLMNGGPHLGLRLFQKFDTF-RILVCGGDGSVGWVLSEIDSLNLHKQC-Q 400
Cdd:smart00046    1 LVFVNPKSGGGKGEKLLRKFRLLLNPRQVFDLTKKGPAVALVIFRDVPDFnRVLVCGGDGTVGWVLNALDKRELPLPEpP 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*
gi 2130865312   401 LGVLPLGTGNDLARVLGWGSACDDDTQLPqILEKLERASTKMLDR 445
Cdd:smart00046   81 VAVLPLGTGNDLARSLGWGGGYDGEKLLK-TLRDALESDTVKLDR 124

second 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 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 2130865312  231 GIAMPHQWLEGNLPVSAKCTVCDKTCGSVLRLQDWRCLWCKAMVHTSCKESLQTKCPLGLC 291
Cdd:cd20893      1 GISMPHQWLEGNLPVSAKCTVCDKTCGSVLRLQDWRCLWCKAMVHTSCKELLLTKCPLGQC 61

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.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2130865312  231 GIAMPHQWLEGNLPVSAKCTVCDKTCGSVLRLQDWRCLWCKAMVHTSCKESLQTKCPLGLCK 292
Cdd:cd20894      1 GIAMPHQWLEGNLPVSAKCSVCDKTCGSVLRLQDWRCLWCKAMVHTACKDQYPRKCPLGQCR 62

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 2130865312  321 PLLVFVNSKSGDNQGVKFLRRFKQLLNPAQV-FDLMN-GGPHLGLRLFQKFD---TFRILVCGGDGSVGWVLSEIDslNL 395
Cdd:pfam00781    1 KLLVIVNPKSGGGKGKKLLRKVRPLLNKAGVeVELVLtEGPGDALELAREAAedgYDRIVVAGGDGTVNEVLNGLA--GL 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 2130865312  396 HKQCQLGVLPLGTGNDLARVLGWGsacdddTQLPQILEKLERASTKMLD 444
Cdd:pfam00781   79 ATRPPLGIIPLGTGNDFARALGIP------GDPEEALEAILKGQTRPVD 121

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 2130865312  236 HQWLEGNLPVSAKCTVCDKTCGSVLRLQDWRCLWCKAMVHTSCKESLQTKCPLGLCKVSVIPP 298
Cdd:cd20853      1 HHWVRGNLPLCSVCCVCNEQCGNQPGLCDYRCCWCQRTVHDDCLAKLPKECDLGAFRNFIVPP 63

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 2130865312   164 HNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNC 213
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312   56 KEGMLTKQNNSFQRS-KRRYFKLRGRTLYYAKTAKSIIF---DEVDLTD-ASVAESSTKNVNNSFTVITP-CRKLILCAD 129
Cdd:cd00821      1 KEGYLLKRGGGGLKSwKKRWFVLFEGVLLYYKSKKDSSYkpkGSIPLSGiLEVEEVSPKERPHCFELVTPdGRTYYLQAD 80

                           90
                   ....*....|..
gi 2130865312  130 NRKEMEEWIAAL 141
Cdd:cd00821     81 SEEERQEWLKAL 92

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 2130865312  164 HNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNC 213
Cdd:cd00029      1 HRFVPTTFSSPTFCDVCGKLIWGLFKQGLKCSDCGLVCHKKCLDKAPSPC 50

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and similar proteins; PKD2, also called PRKD2, HSPC187, or serine/threonine-protein kinase D2 (nPKC-D2), is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. PKD2 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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2130865312  164 HNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNCKWTTLASIGKDIIEDE 229
Cdd:cd20843     12 HTFVIHSYTRPTVCQFCKKLLKGLFRQGLQCKDCKFNCHKRCATRVPNDCLGETLFNGDLVPMEAA 77

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312  322 LLVFVNSKSGDNQGVKFLRRFKQLLN----PAQVFDLMNGGPhlGLRLFQK-----FDtfRILVCGGDGSVGWVLSEIds 392
Cdd:COG1597      5 ALLIVNPASGRGRAARLLERLVAALRaaglEVEVLETESPGD--ATELAREaaaegAD--LVVAAGGDGTVNEVANGL-- 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2130865312  393 lnLHKQCQLGVLPLGTGNDLARVLGWgsacddDTQLPQILEKLERASTKMLD 444
Cdd:COG1597     79 --AGTGPPLGILPLGTGNDFARALGI------PLDPEAALEALLTGRTRRID 122

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2130865312  164 HNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNC 213
Cdd:cd20842     35 HTFVIHSYTRPTVCQYCKKLLKGLFRQGLQCKDCKFNCHKRCAPKVPNNC 84

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312   50 RQKTVIKEGMLTKQNNSFQRSKRRYFKLRGRTLYYAKTAKSIIF--DEVDLTDASVAESSTKNVNN--SFTVITPCRKLI 125
Cdd:cd13215     17 RSGAVIKSGYLSKRSKRTLRYTRYWFVLKGDTLSWYNSSTDLYFpaGTIDLRYATSIELSKSNGEAttSFKIVTNSRTYK 96

                           90       100
                   ....*....|....*....|
gi 2130865312  126 LCADNRKEMEEWIAALKTVQ 145
Cdd:cd13215     97 FKADSETSADEWVKALKKQI 116

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        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2130865312  163 MHNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNC 213
Cdd:cd20824      1 PHNFKPHSFSIPTKCDYCGEKIWGLSKKGLSCKDCGFNCHIKCELKVPPEC 51

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
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2130865312  162 GMHNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNCKWTTLAS 220
Cdd:cd20845      6 GQHVWRLKHFNKPAYCNLCLNMLVGLGKQGLCCSFCKYTVHERCVQRAPASCIKTYVKS 64

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312   55 IKEGMLTK----QNNSFqrsKRRYFKLRGRTLYYAKT-----AKSIIF----DEVDLTDASVAESSTKNVNNSFTVITPC 121
Cdd:cd01251      3 LKEGYLEKtgpkQTDGF---RKRWFTLDDRRLMYFKDpldafPKGEIFigskEEGYSVREGLPPGIKGHWGFGFTLVTPD 79

                           90       100
                   ....*....|....*....|....*.
gi 2130865312  122 RKLILCADNRKEMEEWIAALKTVQNR 147
Cdd:cd01251     80 RTFLLSAETEEERREWITAIQKVLER 105

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312   50 RQKTVIKEGMLTKQNNSFQRS-KRRYFKLRGRTLYYAKTAKsiifDE-----VDLTDASVAE-SSTKNVN--NSFTVITP 120
Cdd:cd13248      3 PNAPVVMSGWLHKQGGSGLKNwRKRWFVLKDNCLYYYKDPE----EEkalgsILLPSYTISPaPPSDEISrkFAFKAEHA 78

                           90       100
                   ....*....|....*....|..
gi 2130865312  121 -CRKLILCADNRKEMEEWIAAL 141
Cdd:cd13248     79 nMRTYYFAADTAEEMEQWMNAM 100

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312   54 VIKEGMLTKQNNSFQRSKRRYFKLRGRTL-YY-----AKTAKSIIFDEVdLTDASVAESSTKNVnnsFTVITPCRKLILC 127
Cdd:cd13298      6 VLKSGYLLKRSRKTKNWKKRWVVLRPCQLsYYkdekeYKLRRVINLSEL-LAVAPLKDKKRKNV---FGIYTPSKNLHFR 81

                           90       100
                   ....*....|....*....|.
gi 2130865312  128 ADNRKEMEEWIAALKTVQNRE 148
Cdd:cd13298     82 ATSEKDANEWVEALREEFRLD 102

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 2130865312  164 HNWYACSHARPTYCNVCREALSGVTSHGLSCEVCKFKAHKRCAVRATNNC 213
Cdd:cd20796      2 HTFVVHTYTKPTVCQHCKKLLKGLFRQGLQCKDCKFNCHKKCAEKVPKDC 51

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 2130865312  164 HNWYACSHARPTYCNVCREALSGVTShgLSCEVCKFKAHKRCAVRATNNCK 214
Cdd:cd20804      6 HCWSEPGHSKRKFCNVCRKRLEDSPA--FRCEVCEYYVHSDCQDFAVSDCR 54

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312   56 KEGMLTKQNNSFQRSKRRYFKLRGRTLYYAKTAKSII---FDEVDLTDasVAESSTKNVNNSFTVITPCRKLILCADNRK 132
Cdd:cd13282      1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIrkpQGQIALDG--SCEIARAEGAQTFEIVTEKRTYYLTADSEN 78

                           90
                   ....*....|....*
gi 2130865312  133 EMEEWIAALKTVQNR 147
Cdd:cd13282     79 DLDEWIRVIQNVLRR 93

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 2130865312  236 HQWLEGNLPvsAKCTVCDKTCGSVLRLQDWRCLWCKAMVHTSCKESLQTKCPLG 289
Cdd:cd20851      1 HHWVEGNCP--GKCDKCHKSIKSYQGLTGLHCVWCHITLHNKCASHVKPECDLG 52

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312  768 NYFGIGLDAKISLDFNNKRdehpekcrSRTKNMMWYGVLGTKELlhRTYKNLEqkVLLECDGRPIPLPSLQgIAVLNIPS 847
Cdd:COG1597    133 NVAGIGFDAEVVERANRAL--------KRRLGKLAYVLAALRAL--LRYRPFR--LRIELDGEEIEGEALL-VAVGNGPY 199

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130865312  848 YAGGTNFwggtkeddtFAAPSFDDKILEVVAV----FGSMQMAVSRVIK---LQHHRIAQCRTVKISILGDEGVPVQVDG 920
Cdd:COG1597    200 YGGGLRL---------APDASLDDGLLDVVVVrplsRLRLLRLLPRLLRgrhLRHPGVRYFRAREVEIESDRPLPVQLDG 270

                          170
                   ....*....|....*.
gi 2130865312  921 EA-WIQPPGYIRIIHK 935
Cdd:COG1597    271 EPlGLATPLEFEVLPG 286