protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 1 (RASGRP1) and similar proteins; RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, functions as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. It 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. 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 7242201  540 FPHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECKKR 594
Cdd:cd20860   1 FPHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECKKR 55

C-terminal coiled-coil domain of RAS guanyl-releasing protein 1 (RasGRP1) and similar proteins; RasGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII), or Ras guanyl-releasing protein, acts as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor, specifically activating Ras through the exchange of bound GDP for GTP. This model corresponds to the C-terminal coiled-coil domain of RasGRP1, which mediates oligomerization.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 7242201  737 PELHLRLRTYQELEQEINTLKADNDALKIQLKYAQKKIESLQLGKSNHVLAQMDH 791
Cdd:cd22290   1 EERRLRKPTYQELEKENSNLKAENEALKIQLKDAQRRIEALRLELRKHVLDNLTH 55

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7242201  201 FDHLEPEELSEHLTYLEFKSFRRISFSDYQNYLVNSCVKE---NPTMERSIALCNGISQWVQLMVLSRPTPQLRAEVFIK 277
Cdd:cd00155   1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNihlSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7242201  278 FIHVAQKLHQLQNFNTLMAVIGGLCHSSISRLKETSSHVPHEINKVLGEMTELLSSCRNYDNYRRAYGECTH--FKIPIL 355
Cdd:cd00155  81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGPnpPCVPFL 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7242201  356 GVHLKDLISLYEAMPDYLEDGKVNVQKLLALYNHINELVQLQEMAPPLDANKDLVHLLTLSLDLYYTEDEIYELS 430
Cdd:cd00155 161 GVYLKDLTFLHEGNPDFLEGNLVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLELILNEDELYELS 235

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 1 (RASGRP1) and similar proteins; RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, functions as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. It 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. 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 7242201  540 FPHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECKKR 594
Cdd:cd20860   1 FPHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECKKR 55

C-terminal coiled-coil domain of RAS guanyl-releasing protein 1 (RasGRP1) and similar proteins; RasGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII), or Ras guanyl-releasing protein, acts as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor, specifically activating Ras through the exchange of bound GDP for GTP. This model corresponds to the C-terminal coiled-coil domain of RasGRP1, which mediates oligomerization.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 7242201  737 PELHLRLRTYQELEQEINTLKADNDALKIQLKYAQKKIESLQLGKSNHVLAQMDH 791
Cdd:cd22290   1 EERRLRKPTYQELEKENSNLKAENEALKIQLKDAQRRIEALRLELRKHVLDNLTH 55

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7242201   61 SLDDLIDSCIQSFDADgnlcrNNQLLQVMLTMHRIIISSAELLQKVMNLYKDAL----------EKNSPGVCLKICYFVR 130
Cdd:cd06224   1 TLEALIEHLTSTFDMP-----DPSFVSTFLLTYRSFTTPTELLEKLIERYEIAPpenleyndwdKKKSKPIRLRVLNVLR 75

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 7242201  131 YWITEFWIMFKMDASLTSTMEEFQDLVKANGEETHCHLIDTTQINSR 177
Cdd:cd06224  76 TWVENYPYDFFDDEELLELLEEFLNRLVQEGALLQELKKLLRKLLKL 122

RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this motif/domain N-terminal to the RasGef (Cdc25-like) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7242201     58 KGASLDDLIDSCIQSFDADgnlcrNNQLLQVMLTMHRIIISSAELLQKVMNLY-----------KDALEKNSPGVCLKIC 126
Cdd:pfam00618   3 KAGTLEKLVEYLTSTRIML-----DDSFLSTFLLTYRSFTTPAELLELLIERYnipppldlssdSYWISKKTLPIRIRVL 77

                          90       100
                  ....*....|....*....|....*..
gi 7242201    127 YFVRYWITEFWIMFKMDASLTSTMEEF 153
Cdd:pfam00618  78 SVLRHWVENYFSDFNDDPVLLSRLEKF 104

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 7242201    478 VFKNYDLDQDGYISQEEFEKIAASFPFSFCV-----------MDKDREGLISRDEITAYFM 527
Cdd:pfam13499   7 AFKLLDSDGDGYLDVEELKKLLRKLEEGEPLsdeeveelfkeFDLDKDGRISFEEFLELYS 67

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

                           10        20
                   ....*....|....*....|....*...
gi 7242201     475 VDSVFKNYDLDQDGYISQEEFEKIAASF 502
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKDLLKAL 29

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7242201  201 FDHLEPEELSEHLTYLEFKSFRRISFSDYQNYLVNSCVKE---NPTMERSIALCNGISQWVQLMVLSRPTPQLRAEVFIK 277
Cdd:cd00155   1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNihlSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7242201  278 FIHVAQKLHQLQNFNTLMAVIGGLCHSSISRLKETSSHVPHEINKVLGEMTELLSSCRNYDNYRRAYGECTH--FKIPIL 355
Cdd:cd00155  81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGPnpPCVPFL 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7242201  356 GVHLKDLISLYEAMPDYLEDGKVNVQKLLALYNHINELVQLQEMAPPLDANKDLVHLLTLSLDLYYTEDEIYELS 430
Cdd:cd00155 161 GVYLKDLTFLHEGNPDFLEGNLVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLELILNEDELYELS 235

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 1 (RASGRP1) and similar proteins; RASGRP1, also called calcium and DAG-regulated guanine nucleotide exchange factor II (CalDAG-GEFII) or Ras guanyl-releasing protein, functions as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. It 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. 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 7242201  540 FPHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECKKR 594
Cdd:cd20860   1 FPHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECKKR 55

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 7242201  541 PHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECK 592
Cdd:cd20808   1 KHNFQETTYFKPTFCDHCTGLLWGLIKQGYKCKDCGINCHKHCKDLVVVECR 52

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7242201      54 GHLAKGASLDDLIDSCIQSFDADgnlcrNNQLLQVMLTMHRIIISSAELLQKVMNLYKDALE-------KNSPGVCLKIC 126
Cdd:smart00229   2 GGLIKGGTLEALIEHLTEAFDKA-----DPSFVETFLLTYRSFITTQELLQLLLYRYNAIPPeswveekVNPRRVKNRVL 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 7242201     127 YFVRYWITEFWIMFKMDASLTSTMEEFQDLVKAN-GEETHCHLIDTTQINS 176
Cdd:smart00229  77 NILRTWVENYWEDFEDDPKLISFLLEFLELVDDEkYPGLVTSLLNLLRRLS 127

protein kinase C conserved region 1 (C1 domain) found in the chimaerin family; Chimaerins are a family of phorbolester- and diacylglycerol-responsive GTPase activating proteins (GAPs) specific for the Rho-like GTPase Rac. Alpha1-chimerin (formerly known as N-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. Alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 7242201  541 PHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECKK 593
Cdd:cd20806   1 PHNFKVHTFKGPHWCDYCGNFMWGLIAQGVKCEDCGFNAHKQCSKLVPHDCQP 53

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 2 (RASGRP2) and similar proteins; RASGRP2, also called calcium and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), Cdc25-like protein (CDC25L), or F25B3.3 kinase-like protein, functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. It may also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. RASGRP2 is also 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. 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 7242201  539 GFPHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECKKR 594
Cdd:cd20861   1 GFIHNFAERTFLRPVACRHCKNLILGIYKQGLKCRACGVNCHKQCKDHLSIECRKR 56

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 7242201  542 HNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFEC 591
Cdd:cd20793   1 HKFKVHTYYSPTFCDHCGSLLYGLVRQGLKCKDCGMNVHHRCKENVPHLC 50

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7242201   61 SLDDLIDSCIQSFDADgnlcrNNQLLQVMLTMHRIIISSAELLQKVMNLYKDAL----------EKNSPGVCLKICYFVR 130
Cdd:cd06224   1 TLEALIEHLTSTFDMP-----DPSFVSTFLLTYRSFTTPTELLEKLIERYEIAPpenleyndwdKKKSKPIRLRVLNVLR 75

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 7242201  131 YWITEFWIMFKMDASLTSTMEEFQDLVKANGEETHCHLIDTTQINSR 177
Cdd:cd06224  76 TWVENYPYDFFDDEELLELLEEFLNRLVQEGALLQELKKLLRKLLKL 122

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 7242201  541 PHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFEC 591
Cdd:cd20796   1 PHTFVVHTYTKPTVCQHCKKLLKGLFRQGLQCKDCKFNCHKKCAEKVPKDC 51

protein kinase C conserved region 1 (C1 domain) found in the Munc13 family; The Munc13 gene family encodes a family of neuron-specific, synaptic molecules that bind to syntaxin, an essential mediator of neurotransmitter release. Munc13-1 is a component of presynaptic active zones in which it acts as an essential synaptic vesicle priming protein. Munc13-2 is essential for normal release probability at hippocampal mossy fiber synapses. Munc13-3 is almost exclusively expressed in the cerebellum. It acts as a tumor suppressor and plays a critical role in the formation of release sites with calcium channel nanodomains. 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 7242201  542 HNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECKKR 594
Cdd:cd20807   1 HNFEVWTATTPTYCYECEGLLWGIARQGVRCTECGVKCHEKCKDLLNADCLQR 53

second protein kinase C conserved region 1 (C1 domain) found in novel protein kinase C (nPKC) epsilon, eta, and similar proteins; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. Members of this family contain two copies of C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 7242201  541 PHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFEC 591
Cdd:cd20838   2 PHRFSVHNYKRPTFCDHCGSLLYGLYKQGLQCKVCKMNVHKRCQKNVANNC 52

protein kinase C conserved region 1 (C1 domain) found in uncharacterized Rho guanine nucleotide exchange factor (ARHGEF)-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate Rho guanine nucleotide exchange factors ARHGEF11 and ARHGEF12, which may play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Unlike typical ARHGEF11 and ARHGEF12, members of this family contain a C1 domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 7242201  542 HNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFEC 591
Cdd:cd20832   2 HQFVLQHYYQVTFCNHCSGLLWGIGYQGYQCSDCEFNIHKQCIEVIEESC 51

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 7242201     542 HNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFEC 591
Cdd:smart00109   1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50

protein kinase C conserved region 1 (C1 domain) found in beta-chimaerin and similar proteins; Beta-chimaerin, also called beta-chimerin (BCH) or Rho GTPase-activating protein 3 (ARHGAP3), is a GTPase-activating protein (GAP) for p21-rac. Insufficient expression of beta-2 chimaerin is expected to lead to higher Rac activity and could therefore play a role in the progression from low-grade to high-grade tumors. Beta-chimaerin contains a functional SH2 domain that can bind to phosphotyrosine motifs within receptors, a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 7242201  542 HNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECKKRIK 596
Cdd:cd20857   6 HNFKVHTFRGPHWCEYCANFMWGLIAQGVRCSDCGLNVHKQCSKHVPNDCQPDLK 60

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.

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                ....*....|....*....|....*....|....*....|..
gi 7242201  542 HNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQC 583
Cdd:cd20810   3 HSFELTTFKEPTTCSVCKKLLKGLFFQGYKCSVCGAAVHKEC 44

protein kinase C conserved region 1 (C1 domain) found in alpha-chimaerin and similar proteins; Alpha-chimaerin, also called A-chimaerin, N-chimaerin (CHN), alpha-chimerin, N-chimerin (NC), or Rho GTPase-activating protein 2 (ARHGAP2), is a GTPase-activating protein (GAP) for p21-rac and a phorbol ester receptor. It is involved in the assembly of neuronal locomotor circuits as a direct effector of EPHA4 in axon guidance. Alpha-chimaerin contains a functional SH2 domain that can bind to phosphotyrosine motifs within receptors, a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 7242201  542 HNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECK 592
Cdd:cd20856   6 HNFKVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDCK 56

second protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group contain two copies of the C1 domain. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 7242201  541 PHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFEC 591
Cdd:cd20798   1 PHTLAEHNYKKPTVCKVCDKLLVGLVRQGLKCRDCGVNVHKKCASLLPSNC 51

first protein kinase C conserved region 1 (C1 domain) found in Caenorhabditis elegans serine/threonine-protein kinase DKF-1 and similar proteins; DKF-1 converts transient diacylglycerol (DAG) signals into prolonged physiological effects, independently of PKC. It plays a role in the regulation of growth and neuromuscular control of movement. It is involved in immune response to Staphylococcus aureus bacterium by activating transcription factor hlh-30 downstream of phospholipase plc-1. Members of this group contain two copies of the C1 domain. This model corresponds to the first one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                ....*....|....*....|....*....|....*....|...
gi 7242201  541 PHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQC 583
Cdd:cd20797   3 PHVVEVEQYMTPTFCDYCGEMLTGLMKQGVKCKNCRCNFHKRC 45

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.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 7242201  542 HNFQETTYLKPTFCDNCAGFLWGVI-KQGYRCKDCGMNCHKQCKDLVVFEC 591
Cdd:cd20835  10 HKFMATYLRQPTYCSHCKDFIWGVIgKQGYQCQVCTCVVHKRCHQLVVTKC 60

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.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 7242201  541 PHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFEC 591
Cdd:cd20843  11 PHTFVIHSYTRPTVCQFCKKLLKGLFRQGLQCKDCKFNCHKRCATRVPNDC 61

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.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 7242201  541 PHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFEC 591
Cdd:cd20803   1 GHSFRKKTFHKPTYCHHCTDLLWGLLNQGYQCEVCNFVSHERCLKTVVTPC 51

protein kinase C conserved region 1 (C1 domain) found in the Ras association domain-containing protein 1 (RASSF1)-like family; The RASSF1-like family includes RASSF1 and RASSF5. RASSF1 and RASSF5 are members of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. RASSF1A and 1C are the most extensively studied RASSF1; both are localized to microtubules and involved in the regulation of growth and migration. RASSF1 is a potential tumor suppressor that is required for death receptor-dependent apoptosis. RASSF5, also called new ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. RASSF5A is a pro-apoptotic Ras effector and functions as a Ras regulated tumor suppressor. RASSF5C is regulated by Ras related protein and modulates cellular adhesion. RASSF5 is a potential tumor suppressor that seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. RASSF1 and RASSF5 contain a C1 domain, which is descibed in this model. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                ....*....|....*....|....*....|....*....|....*....|
gi 7242201  542 HNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFEC 591
Cdd:cd20820   2 HRFVPLELEQPTWCDLCGSVILGLFRKCLRCANCKMTCHPRCRSLVCLTC 51

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.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 7242201  541 PHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFEC 591
Cdd:cd20842  34 PHTFVIHSYTRPTVCQYCKKLLKGLFRQGLQCKDCKFNCHKRCAPKVPNNC 84

first protein kinase C conserved region 1 (C1 domain) found in protein kinase D3 (PKD3) and similar proteins; PKD3 is also called PRKD3, PRKCN, serine/threonine-protein kinase D3 (nPKC-D3), protein kinase C nu type (nPKC-nu), or protein kinase EPK2. It converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. It is involved in the regulation of the cell cycle by modulating microtubule nucleation and dynamics. PKD3 acts as a key mediator in several cancer development signaling pathways. PKD3 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

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                ....*....|....*....|....*....|....*....|....*....|....*..
gi 7242201  541 PHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFEC---KKR 594
Cdd:cd20841  10 PHTLYVHSYKAPTFCDYCGEMLWGLVRQGLKCEGCGLNYHKRCAFKIPNNCsgvRKR 66

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
                ....*....|....*....|....*....|....*....|....*...
gi 7242201  540 FPHNFQETTYLKPTFCDNCAGFLWgvikQGYRCKDCGMNCHKQCKDLV 587
Cdd:cd20811   1 ISHNFVRKTFFTLAFCDVCRKLLF----QGFRCQTCGFKFHQRCSDQV 44

first 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 first C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7242201  541 PHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFEC----KKRIKSPAI 600
Cdd:cd20840  10 PHALNVHSYRAPAFCDHCGEMLFGLVRQGLKCDGCGLNYHKRCAFSIPNNCsgarKRRLSSTSL 73

protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing protein 5 (RASSF5) and similar proteins; RASSF5, also called new ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is a member of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. It is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. RASSF5A is a pro-apoptotic Ras effector and functions as a Ras regulated tumor suppressor. RASSF5C is regulated by Ras related protein and modulates cellular adhesion. RASSF5 is a potential tumor suppressor that seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. It contains a C1 domain, which is descibed in this model. 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 7242201  539 GFPHNFQETTyLKPTFCDNCAGFlwgVIKQGYRCKDCGMNCHKQCKDLVVFEC 591
Cdd:cd20886   1 GEGHRFEPGA-LGPGWCDLCGRY---ILSQALRCTNCKYTCHSECRDLVQLDC 49