protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 3 (RASGRP3) and similar proteins; 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. 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 1171342708 487 KMGPGFIHNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACRR 545
Cdd:cd20862     1 KMGPGFIHNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGVNCHKQCKDLLVLACRK 59

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1171342708 420 IRKLVESVFRNYDHDHDGYISQEDFESIAANFPFLDS-----FCVLDKDQDGLISKDEMMAYF 477
Cdd:COG5126    67 VEPFARAAFDLLDTDGDGKISADEFRRLLTALGVSEEeadelFARLDTDGDGKISFEEFVAAV 129

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 1171342708 148 FDHLEPIELAEHLTFLEHKSFRRISFTDYQSYVIHGCLEN---NPTLERSIALFNGISKWVQLMVLSKPTPQQRAEVITK 224
Cdd:cd00155     1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNihlSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1171342708 225 FINVAKKLLQLKNFNTLMAVVGGLSHSSISRLKETHSHLSSEVTKNWNEMTELVSSNGNYCNYRKAFADC--DGFKIPIL 302
Cdd:cd00155    81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVgpNPPCVPFL 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1171342708 303 GVHLKDLIAVHVIFPDWTEENKVNIVKMHQLSVTLSELVSLQNASHHLEPNMDLINLLTLSLDLYHTEDDIYKLSL 378
Cdd:cd00155   161 GVYLKDLTFLHEGNPDFLEGNLVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLELILNEDELYELSL 236

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 3 (RASGRP3) and similar proteins; 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. 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 1171342708 487 KMGPGFIHNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACRR 545
Cdd:cd20862     1 KMGPGFIHNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGVNCHKQCKDLLVLACRK 59

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 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACR 544
Cdd:pfam00130   1 HHFVHRNFKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEKVPPECG 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 1171342708  494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:smart00109   1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1171342708 420 IRKLVESVFRNYDHDHDGYISQEDFESIAANFPFLDS-----FCVLDKDQDGLISKDEMMAYF 477
Cdd:COG5126    67 VEPFARAAFDLLDTDGDGKISADEFRRLLTALGVSEEeadelFARLDTDGDGKISFEEFVAAV 129

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1171342708 424 VESVFRNYDHDHDGYISQEDFESI--AANFPFLDS-----FCVLDKDQDGLISKDEMMA 475
Cdd:cd00051     2 LREAFRLFDKDGDGTISADELKAAlkSLGEGLSEEeidemIREVDKDGDGKIDFEEFLE 60

XopAW family type III secretion system calcium-binding effector;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1171342708 408 MPKPDPTVINKHIRKLVESVFRNYDHDHDGYISQEDFES-IAANFPFLDS---FCVLDKDQDGLISKDEMMA 475
Cdd:NF041410   89 APPPPPPPDQAPSTELADDLLSALDTDGDGSISSDELSAgLTSAGSSADSsqlFSALDSDGDGSVSSDELAA 160

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 1171342708 148 FDHLEPIELAEHLTFLEHKSFRRISFTDYQSYVIHGCLEN---NPTLERSIALFNGISKWVQLMVLSKPTPQQRAEVITK 224
Cdd:cd00155     1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNihlSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1171342708 225 FINVAKKLLQLKNFNTLMAVVGGLSHSSISRLKETHSHLSSEVTKNWNEMTELVSSNGNYCNYRKAFADC--DGFKIPIL 302
Cdd:cd00155    81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVgpNPPCVPFL 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1171342708 303 GVHLKDLIAVHVIFPDWTEENKVNIVKMHQLSVTLSELVSLQNASHHLEPNMDLINLLTLSLDLYHTEDDIYKLSL 378
Cdd:cd00155   161 GVYLKDLTFLHEGNPDFLEGNLVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLELILNEDELYELSL 236

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 3 (RASGRP3) and similar proteins; 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. 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 1171342708 487 KMGPGFIHNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACRR 545
Cdd:cd20862     1 KMGPGFIHNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGVNCHKQCKDLLVLACRK 59

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 1171342708 492 FIHNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACRR 545
Cdd:cd20860     1 FPHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECKK 54

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 1171342708 491 GFIHNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACRR 545
Cdd:cd20861     1 GFIHNFAERTFLRPVACRHCKNLILGIYKQGLKCRACGVNCHKQCKDHLSIECRK 55

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 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:cd00029     1 HRFVPTTFSSPTFCDVCGKLIWGLFKQGLKCSDCGLVCHKKCLDKAPSPC 50

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 1171342708 494 HNFQeMTYLK-PTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:cd20792     2 HKFV-ATFFKqPTFCSHCKDFIWGLGKQGYQCQVCRFVVHKRCHEYVVFKC 51

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 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:cd20806     2 HNFKVHTFKGPHWCDYCGNFMWGLIAQGVKCEDCGFNAHKQCSKLVPHDC 51

second 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 domain. 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 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 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:cd20837     1 HRFKVYNYMSPTFCDHCGSLLWGLFRQGLKCEECGMNVHHKCQKKVANLC 50

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 1171342708    8 KAATLDELLCTCIEMFDDNgelDNSYLpRIVLLMHRWYLSSTELAEKLLCMYRNATGESCNE-------FRLKICYFMRY 80
Cdd:smart00229   6 KGGTLEALIEHLTEAFDKA---DPSFV-ETFLLTYRSFITTQELLQLLLYRYNAIPPESWVEekvnprrVKNRVLNILRT 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1171342708   81 WILKFPAEFNLDLGLIRMTEEFREVA-SQLGYEKHVSLIDI 120
Cdd:smart00229  82 WVENYWEDFEDDPKLISFLLEFLELVdDEKYPGLVTSLLNL 122

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 1171342708  494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:smart00109   1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50

protein kinase C conserved region 1 (C1 domain) found in uncharacterized proteins similar to myotubularin-related proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate myotubularin-related proteins (MTMRs), such as MTMR5 and MTMR13. MTMRs may function as guanine nucleotide exchange factors (GEFs). Vertebrate MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Members of this family contain these domains and have an additional 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 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACRR 545
Cdd:cd20828     6 HNFEPHSFVTPTNCDYCLQILWGIVKKGMKCSECGYNCHEKCQPQVPKQCSK 57

first protein kinase C conserved region 1 (C1 domain) found in the protein kinase D (PKD) family; 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 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
                  ....*....|....*....|....*....|....*....|..
gi 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQC 535
Cdd:cd20795     4 HSLFVHSYKSPTFCDFCGEMLFGLVRQGLKCEGCGLNFHKRC 45

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
                  ....*....|....*....|....*....|....*....|...
gi 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCK 536
Cdd:cd20838     3 HRFSVHNYKRPTFCDHCGSLLYGLYKQGLQCKVCKMNVHKRCQ 45

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1171342708 493 IHNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACR 544
Cdd:cd20856     5 VHNFKVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDCK 56

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
                  ....*....|....*....|....*....|....*....|....
gi 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKD 537
Cdd:cd20817     1 HSFQEHTFKKPTFCDVCKELLVGLSKQGLRCKNCKMNVHHKCQE 44

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 1171342708 494 HNFQeMTYLK-PTFCEHCAGFLWGII-KQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:cd20835    10 HKFM-ATYLRqPTYCSHCKDFIWGVIgKQGYQCQVCTCVVHKRCHQLVVTKC 60

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQC 535
Cdd:cd20797     4 HVVEVEQYMTPTFCDYCGEMLTGLMKQGVKCKNCRCNFHKRC 45

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 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:cd20809     1 HKFIVRTFSTPTKCNHCTSLMVGLVRQGLVCEVCGYACHVSCADKAPQVC 50

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
                  ....*....|....*....|....*....|....*....|..
gi 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQC 535
Cdd:cd20824     2 HNFKPHSFSIPTKCDYCGEKIWGLSKKGLSCKDCGFNCHIKC 43

first 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 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 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQC-KDLLVLACRR 545
Cdd:cd20829     1 HRLVDVYFVTPILCRHCKDYIWGKGKVGVRCEDCHACFHLVCaKYAAKHPCQR 53

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 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACRR 545
Cdd:cd20830     1 HRFVEQSFSTLQWCDKCGKFLFGLVHQGLQCQDCGLVCHRTCAATGLPKCEP 52

protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing protein 1 (RASSF1) and similar proteins; RASSF1 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. RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. RASSF1A and 1C are the most extensively studied RASSF1 with both localized to microtubules and involved in regulation of growth and migration. RASSF1 is a potential tumor suppressor that is required for death receptor-dependent apoptosis. 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 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACR 544
Cdd:cd20885     4 HDFQPCSLTNPTWCDLCGDFIWGLYKQCLRCTHCKYTCHLRCRDLVTLDCS 54

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1171342708 492 FIHnfqemTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQC 535
Cdd:cd20841    14 YVH-----SYKAPTFCDYCGEMLWGLVRQGLKCEGCGLNYHKRC 52

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACR 544
Cdd:cd20820     2 HRFVPLELEQPTWCDLCGSVILGLFRKCLRCANCKMTCHPRCRSLVCLTCR 52

protein kinase C conserved region 1 (C1 domain) found in male germ cell RacGap (MgcRacGAP) and similar proteins; MgcRacGAP, also called Rac GTPase-activating protein 1 (RACGAP1) or protein CYK4, plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling; and ii) after phosphorylation by aurora B, MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain an N-terminal C1 domain, and a C-terminal RhoGAP 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 1171342708 494 HNFQEMTYLKPTFCEHCA---GFLwgiiKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:cd20821     3 HRFVSKTVIKPETCVVCGkriKFG----KKALKCKDCRVVCHPDCKDKLPLPC 51

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
                  ....*....|....*....|....*....|....*....|..
gi 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQC 535
Cdd:cd20840    11 HALNVHSYRAPAFCDHCGEMLFGLVRQGLKCDGCGLNYHKRC 52

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 1171342708 494 HNFQEMTYLKPTFCEHCAGFLWgiikQGYKCKDCGANCHKQCKD 537
Cdd:cd20811     3 HNFVRKTFFTLAFCDVCRKLLF----QGFRCQTCGFKFHQRCSD 42