Ras-associating (RA) domain 2 found in diacylgylcerol kinase theta (DAGK-theta) and similar proteins; DAGK phosphorylates the second messenger diacylglycerol to phosphatidic acid as part of a protein kinase C pathway. DAGK-theta is characterized as a type V DAGK that has three cysteine-rich domains (all other isoforms have two), a proline/glycine-rich domain at its N-terminal, and a proposed Ras-associating (RA) domain. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has a 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 in eukaryotes. There are ten mammalian isoforms of DAGK have been identified to date, these are organized into five categories based on the domain architecture. DAGK-theta also contains a pleckstrin homology (PH) domain. The subcellular localization and the activity of DAGK-theta are regulated in a complex (stimulation- and cell type-dependent) manner. This family corresponds to the second RA domain of DAGK-theta.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24649473  925 GHVRVYPGKLQCsmlEDPYVSVPVDNSTVIKDLIRDALDKFGLQDNQIQDYRCSEVLLDRGVTERILSWNERPWDIMKQL 1004
Cdd:cd01783    1 GYIRVYPGWLKV---GVAYKSIPVTKETTVEEVIKEALPKFGLQDEDPEDFRLVEVLMDKGVVERVMLRDECPWLILLDI 77

                         90
                 ....*....|....*...
gi 24649473 1005 GKDSIRQMELMRFYMQHK 1022
Cdd:cd01783   78 RKESLRQMRQTRFYLQQK 95

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 24649473  135 HHWREGNLPSTSKCAYCKKTCWSSECLTGYRCEWCGMTTHAGCRMYLPTECNFGILQPIYLPP 197
Cdd:cd20854    1 HHWREGNLPSNSKCEVCKKSCGSSECLAGMRCEWCGITAHASCYKSLPKECNFGRLRNIILPP 63

Ras-associating (RA) domain 1 found in diacylgylcerol kinase theta (DAGK-theta) and similar proteins; DAGK phosphorylates the second messenger diacylglycerol to phosphatidic acid as part of a protein kinase C pathway. DAGK-theta is characterized as a type V DAGK that has three cysteine-rich domains (all other isoforms have two), a proline/glycine-rich domain at its N-terminal, and a proposed Ras-associating (RA) domain. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has a 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 in eukaryotes. Ten mammalian isoforms of DAGK have been identified to date which are organized into five categories based on the domain architecture. DAGK-theta also contains a pleckstrin homology (PH) domain. The subcellular localization and the activity of DAGK-theta are regulated in a complex (stimulation- and cell type-dependent) manner. This family corresponds to the first RA domain of DAGK-theta.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24649473  833 EMIKVFDGNNSFRRQQYRVIIVQRTYTLEQLLTTALRAFHITRDPQAFYLTDLYAPAGMEDTPMLDPTPVLNLVHLEGKR 912
Cdd:cd17111    2 EIVKVFDGNASLKRNQFRLITVPRNASVEQVLEAALRAFHIPDDPENYYLTDAYESSLGDERELEDPGPLRNLVRREGKR 81

                         90
                 ....*....|
gi 24649473  913 PAIYLRFHDR 922
Cdd:cd17111   82 PAIFLRYKEK 91

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 24649473    1334 VMNNYFGIGIDADLCLDFHNAREENPNQFNSRLRNKGYYVKMGLRKIVGRKAvKDLQKELRLEVDGKIVELPPV-DGIII 1412
Cdd:smart00045    1 VMNNYFSIGVDAHIALEFHNKREANPEKFNSRLKNKMWYFELGTKDLFFRTC-KDLHERIELECDGVDVDLPNSlEGIAV 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24649473    1413 LNILSWGSGANPWG--PDKDDQFSTPNHYDGMLEVVGVTGVVHLGQIQSGIRTAMRIAQGGHIKIHLNTD--MPVQVDGE 1488
Cdd:smart00045   80 LNIPSYGGGTNLWGttDKEDLNFSKQSHDDGLLEVVGLTGAMHMAQIRQVGLAGRRIAQCSEVRITIKTSktIPMQVDGE 159

                    .
gi 24649473    1489 P 1489
Cdd:smart00045  160 P 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 24649473    1121 LVFVNVKSGGCQGLELISSFRKLLNPYQVFDLDNGGPLPGYVqpitvfvirplifdsiislyVFRQITNYK-ILVCGGDG 1199
Cdd:smart00046    1 LVFVNPKSGGGKGEKLLRKFRLLLNPRQVFDLTKKGPAVALV--------------------IFRDVPDFNrVLVCGGDG 60

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24649473    1200 TIGWVLQCLDNVGQDSECssPPCAIVPLGTGNDLARVLCWGSGYtGGEDPLNLLRDVIEAEEIRLDR 1266
Cdd:smart00046   61 TVGWVLNALDKRELPLPE--PPVAVLPLGTGNDLARSLGWGGGY-DGEKLLKTLRDALESDTVKLDR 124

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 24649473    5 GHSFVKKTFHKPTYCHHCSDLLWGLIQQGYICEVCNFIIHERCVSSVVTPCSGIAP 60
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 24649473   64 KNPVAHCWSEPTHHKRKFCTVCRKRLDETPAVHCLVCEYFAHIECQDFAVPDCTENA 120
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 24649473    923 DRGHVRVYPGKLQCSMledPYVSVPVDNSTVIKDLIRDALDKFGLQDNQiQDYRCSEVlLDRGVTERILSWNERPWDIMK 1002
Cdd:pfam00788    1 DDGVLKVYTEDGKPGT---TYKTILVSSSTTAEEVIEALLEKFGLEDDP-RDYVLVEV-LERGGGERRLPDDECPLQIQL 75

                           90       100
                   ....*....|....*....|..
gi 24649473   1003 QLGKDSIRqmelMRFYMQHKQD 1024
Cdd:pfam00788   76 QWPRDASD----SRFLLRKRDD 93

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 24649473    833 EMIKVFDGNNSFRRQqYRVIIVQRTYTLEQLLTTALRAFHITRDPQAFYLTDLYAPAGMEDTPMLDPTPVLNLVHL--EG 910
Cdd:pfam00788    3 GVLKVYTEDGKPGTT-YKTILVSSSTTAEEVIEALLEKFGLEDDPRDYVLVEVLERGGGERRLPDDECPLQIQLQWprDA 81

                           90
                   ....*....|..
gi 24649473    911 KRPAIYLRFHDR 922
Cdd:pfam00788   82 SDSRFLLRKRDD 93

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 24649473    135 HHWREGNLPSTSKCAYCKKTCWSSEcLTGYRCEWCGMTTHAGCRMYLPTEC 185
Cdd:pfam00130    1 HHFVHRNFKQPTFCDHCGEFLWGLG-KQGLKCSWCKLNVHKRCHEKVPPEC 50

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 24649473     135 HHWREGNLPSTSKCAYCKKTCWSSEcLTGYRCEWCGMTTHAGCRMYLPTEC 185
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIWGSF-KQGLRCSECKVKCHKKCADKVPKAC 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 24649473     923 DRGHVRVYPGklqcSMLEDPYVSVPVDNSTVIKDLIRDALDKFGLQDNQiQDYRCSEVLldRGVTERILSWNERPWDIMK 1002
Cdd:smart00314    1 DTFVLRVYVD----DLPGGTYKTLRVSSRTTARDVIQQLLEKFHLTDDP-EEYVLVEVL--PDGKERVLPDDENPLQLQK 73

                            90       100
                    ....*....|....*....|
gi 24649473    1003 QLGKDSirqmELMRFYMQHK 1022
Cdd:smart00314   74 LWPRRG----PNLRFVLRKR 89

putative lipid kinase; Reviewed

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24649473  1173 LIFDSIISLYVFrqitnykILVCGGDGTIGWVLQCLDNVGQDSecsspPCAIVPLGTGNDLARVlcwgsgytggedpLNL 1252
Cdd:PRK13059   48 NAFKDIDESYKY-------ILIAGGDGTVDNVVNAMKKLNIDL-----PIGILPVGTANDFAKF-------------LGM 102

                          90
                  ....*....|....*..
gi 24649473  1253 LRDVIEAEEIRLDRWTV 1269
Cdd:PRK13059  103 PTDIGEACEQILKSKPK 119

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 24649473    1334 VMNNYFGIGIDADLCLDFHNAREENPNQFNSRLRNKGYYVKMGLRKIVGRKAvKDLQKELRLEVDGKIVELPPV-DGIII 1412
Cdd:smart00045    1 VMNNYFSIGVDAHIALEFHNKREANPEKFNSRLKNKMWYFELGTKDLFFRTC-KDLHERIELECDGVDVDLPNSlEGIAV 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24649473    1413 LNILSWGSGANPWG--PDKDDQFSTPNHYDGMLEVVGVTGVVHLGQIQSGIRTAMRIAQGGHIKIHLNTD--MPVQVDGE 1488
Cdd:smart00045   80 LNIPSYGGGTNLWGttDKEDLNFSKQSHDDGLLEVVGLTGAMHMAQIRQVGLAGRRIAQCSEVRITIKTSktIPMQVDGE 159

                    .
gi 24649473    1489 P 1489
Cdd:smart00045  160 P 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 24649473    1121 LVFVNVKSGGCQGLELISSFRKLLNPYQVFDLDNGGPLPGYVqpitvfvirplifdsiislyVFRQITNYK-ILVCGGDG 1199
Cdd:smart00046    1 LVFVNPKSGGGKGEKLLRKFRLLLNPRQVFDLTKKGPAVALV--------------------IFRDVPDFNrVLVCGGDG 60

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24649473    1200 TIGWVLQCLDNVGQDSECssPPCAIVPLGTGNDLARVLCWGSGYtGGEDPLNLLRDVIEAEEIRLDR 1266
Cdd:smart00046   61 TVGWVLNALDKRELPLPE--PPVAVLPLGTGNDLARSLGWGGGY-DGEKLLKTLRDALESDTVKLDR 124

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 24649473    5 GHSFVKKTFHKPTYCHHCSDLLWGLIQQGYICEVCNFIIHERCVSSVVTPCSGIAP 60
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 24649473   64 KNPVAHCWSEPTHHKRKFCTVCRKRLDETPAVHCLVCEYFAHIECQDFAVPDCTENA 120
Cdd:cd20804    1 KNPVAHCWSEPGHSKRKFCNVCRKRLEDSPAFRCEVCEYYVHSDCQDFAVSDCRECA 57

first protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) protein kinase C (cPKC), novel protein kinase C (nPKC), and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. nPKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs (aPKCs) only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. This family includes classical PKCs (cPKCs) and novel PKCs (nPKCs). There are four cPKC isoforms (named alpha, betaI, betaII, and gamma) and four nPKC isoforms (delta, epsilon, eta, and theta). Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 24649473    5 GHSFVKKTFHKPTYCHHCSDLLWGLIQQGYICEVCNFIIHERCVSSVVTPCSG 57
Cdd:cd20792    1 GHKFVATFFKQPTFCSHCKDFIWGLGKQGYQCQVCRFVVHKRCHEYVVFKCPG 53

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 24649473  135 HHWREGNLPSTSKCAYCKKTCWSSECLTGYRCEWCGMTTHAGCRMYLPTECNFG 188
Cdd:cd20852    1 HQWLEGNLPVSSKCAVCDKTCGSVLRLQDWRCLWCGATVHTACKDSLPTKCSLG 54

first protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) theta, delta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. Members of this family contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 24649473    5 GHSFVKKTFHKPTYCHHCSDLLWGLIQQGYICEVCNFIIHERCVSSVVTPCSGIA 59
Cdd:cd20834    7 GHEFIAKFFRQPTFCSVCKEFLWGFNKQGYQCRQCNAAVHKKCHDKILGKCPGSA 61

protein kinase C conserved region 1 (C1 domain) found in VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and as scaffold proteins, and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. 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 24649473    4 GGHSFVKKTFHKPTYCHHCSDLLWGLIQQGYICEVCNFIIHERCVSSvVTPCS 56
Cdd:cd20810    1 TGHSFELTTFKEPTTCSVCKKLLKGLFFQGYKCSVCGAAVHKECIAK-VKRCG 52

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 24649473    4 GGHSFVKKTFHKPTYCHHCSDLLWGLI-QQGYICEVCNFIIHERCVSSVVTPCSGI 58
Cdd:cd20835    8 NGHKFMATYLRQPTYCSHCKDFIWGVIgKQGYQCQVCTCVVHKRCHQLVVTKCPGN 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 24649473       6 HSFVKKTFHKPTYCHHCSDLLWGLIQQGYICEVCNFIIHERCVSSVVTPC 55
Cdd:smart00109    1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50

protein kinase C conserved region 1 (C1 domain) found in the Myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) family; MRCK is thought to be a coincidence detector of signaling by the small GTPase Cdc42 and phosphoinositides. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. MRCK has been shown to promote cytoskeletal reorganization, which affects many biological processes. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. MRCK consists of a serine/threonine kinase domain, a cysteine rich (C1) region, a PH domain and a p21 binding motif. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 24649473    6 HSFVKKTFHKPTYCHHCSDLLWGLIQQGYICEVCNFIIHERCVSSVVTPC 55
Cdd:cd20809    1 HKFIVRTFSTPTKCNHCTSLMVGLVRQGLVCEVCGYACHVSCADKAPQVC 50

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 24649473  135 HHWREGNLPSTSKCAYCKKTCWSSECLTGYRCEWCGMTTHAGCRMYLPTECNFGILQPIYLPP 197
Cdd:cd20853    1 HHWVRGNLPLCSVCCVCNEQCGNQPGLCDYRCCWCQRTVHDDCLAKLPKECDLGAFRNFIVPP 63

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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 24649473  135 HHWREGNLPSTSKCAYCKKTCWSSECLTGYRCEWCGMTTHAGCRMYLPTECNFG 188
Cdd:cd20893    6 HQWLEGNLPVSAKCTVCDKTCGSVLRLQDWRCLWCKAMVHTSCKELLLTKCPLG 59

protein kinase C conserved region 1 (C1 domain) found in the RAS guanyl-releasing protein (RASGRP) family; The RASGRP family includes RASGRP1-4. They function as cation-, usually calcium-, and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, activates the Erk/MAP kinase cascade and regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. RASGRP1 also regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways. RASGRP2, also called calcium and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Cdc25-like protein (CDC25L), or F25B3.3 kinase-like protein, specifically activates Rap and may also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. RASGRP2 is involved in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation, as well as in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. RASGRP3, also called calcium and DAG-regulated guanine nucleotide exchange factor III (CalDAG-GEFIII), or guanine nucleotide exchange factor for Rap1, is a guanine nucleotide-exchange factor activating H-Ras, R-Ras and Ras-associated protein-1/2. It functions as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. RASGRP4 may function in mast cell differentiation. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 24649473    6 HSFVKKTFHKPTYCHHCSDLLWGLIQQGYICEVCNFIIHERCVSSVVTPCS 56
Cdd:cd20808    2 HNFQETTYFKPTFCDHCTGLLWGLIKQGYKCKDCGINCHKHCKDLVVVECR 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 24649473      6 HSFVKKTFHKPTYCHHCSDLLWGLIQQGYICEVCNFIIHERCVSSVVTPC 55
Cdd:pfam00130    1 HHFVHRNFKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEKVPPEC 50

protein kinase C conserved region 1 (C1 domain) found in the Raf (Rapidly Accelerated Fibrosarcoma) kinase family; Raf kinases are serine/threonine kinases (STKs) that catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. They act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain (C1), and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 24649473    6 HSFVKKTFHKPTYCHHCSDLLWgliqQGYICEVCNFIIHERCVSSVVTPCS 56
Cdd:cd20811    3 HNFVRKTFFTLAFCDVCRKLLF----QGFRCQTCGFKFHQRCSDQVPALCE 49

second protein kinase C conserved region 1 (C1 domain) found in classical (or conventional) protein kinase C (cPKC), novel protein kinase C (nPKC), and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. nPKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs (aPKCs) only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. This family includes classical PKCs (cPKCs) and novel PKCs (nPKCs). There are four cPKC isoforms (named alpha, betaI, betaII, and gamma) and four nPKC isoforms (delta, epsilon, eta, and theta). Members of this family contain two copies of 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 24649473    6 HSFVKKTFHKPTYCHHCSDLLWGLIQQGYICEVCNFIIHERCVSSVVTPC 55
Cdd:cd20793    1 HKFKVHTYYSPTFCDHCGSLLYGLVRQGLKCKDCGMNVHHRCKENVPHLC 50

protein kinase C conserved region 1 (C1 domain) found in the SH3 and cysteine-rich domain-containing protein (Stac) family; Stac proteins are putative adaptor proteins that are important for neuronal function. There are three mammalian members (Stac1, Stac2 and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. Stac proteins contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 24649473    6 HSFVKKTFHKPTYCHHCSDLLWGLIQQGYICEVCNFIIHERCVSSvVTPCSG 57
Cdd:cd20817    1 HSFQEHTFKKPTFCDVCKELLVGLSKQGLRCKNCKMNVHHKCQEG-VPDCSG 51

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 24649473  135 HHWREGNlpSTSKCAYCKKTCWSSECLTGYRCEWCGMTTHAGCRMYLPTECNFG 188
Cdd:cd20851    1 HHWVEGN--CPGKCDKCHKSIKSYQGLTGLHCVWCHITLHNKCASHVKPECDLG 52

second protein kinase C conserved region 1 (C1 domain) found in uncharacterized phosphatidylinositol 3-kinase regulatory subunit-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate phosphatidylinositol 3-kinase regulatory subunits (PIK3Rs), which bind to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulate their kinase activity. Unlike typical PIK3Rs, members of this family have two C1 domains. This model corresponds to the 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 24649473    6 HSFVKKTFHKPTYCHHCSDLLWGLIQQGYICEVCNFIIHERCVSSVVTPCSG 57
Cdd:cd20830    1 HRFVEQSFSTLQWCDKCGKFLFGLVHQGLQCQDCGLVCHRTCAATGLPKCEP 52