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 569005663 496 GFVHNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECRRR 551
Cdd:cd20861    1 GFIHNFAERTFLRPVACRHCKNLILGIYKQGLKCRACGVNCHKQCKDHLSIECRKR 56

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005663 407 LEEWTSVAKpkldqALVAEHIEKMVESVFRNFDVDGDGHISQEEFQIIRGNFPYLS-----AFGDLDQNQDGCISREEMI 481
Cdd:COG5126   52 REEFVAGME-----SLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGVSEeeadeLFARLDTDGDGKISFEEFV 126

                 ...
gi 569005663 482 SYF 484
Cdd:COG5126  127 AAV 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 569005663 150 FDHLEPMELAEHLTYLEYRSFCKILFQDYHSFVTHGCTVD---NPVLERFISLFNSVSQWVQLMILSKPTATQRALVITH 226
Cdd:cd00155    1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNihlSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005663 227 FVHVAERLLQLQNFNTLMAVVGGLSHSSISRLKETHSHVSPDTIKLWEGLTELVTATGNYSNYRRRLAAC--VGFRFPIL 304
Cdd:cd00155   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVgpNPPCVPFL 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569005663 305 GVHLKDLVALQLALPDWLDPGrtRLNGAKMRQLFCILEELAMVTSLRPPVQANPDLLSLLTVSLDQYQTEDELYQLSLQ 383
Cdd:cd00155  161 GVYLKDLTFLHEGNPDFLEGN--LVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLELILNEDELYELSLE 237

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 569005663 496 GFVHNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECRRR 551
Cdd:cd20861    1 GFIHNFAERTFLRPVACRHCKNLILGIYKQGLKCRACGVNCHKQCKDHLSIECRKR 56

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 569005663  12 TVEELLRGCIEAFDDSgkvrDPQLVRMFLMMHPWYIPSSQLASKLLHFYQ----------QSRKDNSNSLQMKTCHLVRY 81
Cdd:cd06224    1 TLEALIEHLTSTFDMP----DPSFVSTFLLTYRSFTTPTELLEKLIERYEiappenleynDWDKKKSKPIRLRVLNVLRT 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 569005663  82 WISAFPAEFDLNPELAEQIKELKALLDQEGNRRHSSLIDIES 123
Cdd:cd06224   77 WVENYPYDFFDDEELLELLEEFLNRLVQEGALLQELKKLLRK 118

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 569005663  499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECR 549
Cdd:pfam00130   1 HHFVHRNFKQPTFCDHCGEFLWGLGKQGLKCSWCKLNVHKRCHEKVPPECG 51

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 569005663 430 MVESVFRNFDVDGDGHISQEEF-QIIRGNFPYLS------AFGDLDQNQDGCISREEMI 481
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELkAALKSLGEGLSeeeideMIREVDKDGDGKIDFEEFL 59

XopAW family type III secretion system calcium-binding effector;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005663 410 WTSVAKPKLDQALVAEHIEKMvesvFRNFDVDGDGHISQEEFQIIrgnfpyLS-------------AFGDLDQNQDGCIS 476
Cdd:NF041410  12 YTSTSSSSTSSARSQQFQKQL----FAKLDSDGDGSVSQDELSSA------LSsksddgslidlseLFSDLDSDGDGSLS 81

                 ....
gi 569005663 477 REEM 480
Cdd:NF041410  82 SDEL 85

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 569005663   431 VESVFRNFDVDGDGHISQEEFQII 454
Cdd:smart00054   2 LKEAFRLFDKDGDGKIDFEEFKDL 25

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 569005663 150 FDHLEPMELAEHLTYLEYRSFCKILFQDYHSFVTHGCTVD---NPVLERFISLFNSVSQWVQLMILSKPTATQRALVITH 226
Cdd:cd00155    1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNihlSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005663 227 FVHVAERLLQLQNFNTLMAVVGGLSHSSISRLKETHSHVSPDTIKLWEGLTELVTATGNYSNYRRRLAAC--VGFRFPIL 304
Cdd:cd00155   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVgpNPPCVPFL 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569005663 305 GVHLKDLVALQLALPDWLDPGrtRLNGAKMRQLFCILEELAMVTSLRPPVQANPDLLSLLTVSLDQYQTEDELYQLSLQ 383
Cdd:cd00155  161 GVYLKDLTFLHEGNPDFLEGN--LVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLELILNEDELYELSLE 237

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 569005663 496 GFVHNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECRRR 551
Cdd:cd20861    1 GFIHNFAERTFLRPVACRHCKNLILGIYKQGLKCRACGVNCHKQCKDHLSIECRKR 56

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 569005663     7 LDKGCTVEELLRGCIEAFDDsgkvRDPQLVRMFLMMHPWYIPSSQLASKLLHFYQ-------QSRKDNSNSLQMKTCHLV 79
Cdd:smart00229   4 LIKGGTLEALIEHLTEAFDK----ADPSFVETFLLTYRSFITTQELLQLLLYRYNaippeswVEEKVNPRRVKNRVLNIL 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 569005663    80 RYWISAFPAEFDLNPELAEQIKELKALLDQE-GNRRHSSLIDI 121
Cdd:smart00229  80 RTWVENYWEDFEDDPKLISFLLEFLELVDDEkYPGLVTSLLNL 122

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 569005663 496 GFVHNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECRR 550
Cdd:cd20862    5 GFIHNFQEMTYLKPTFCEHCAGFLWGIIKQGYKCKDCGVNCHKQCKDLLVLACRK 59

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 569005663  12 TVEELLRGCIEAFDDSgkvrDPQLVRMFLMMHPWYIPSSQLASKLLHFYQ----------QSRKDNSNSLQMKTCHLVRY 81
Cdd:cd06224    1 TLEALIEHLTSTFDMP----DPSFVSTFLLTYRSFTTPTELLEKLIERYEiappenleynDWDKKKSKPIRLRVLNVLRT 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 569005663  82 WISAFPAEFDLNPELAEQIKELKALLDQEGNRRHSSLIDIES 123
Cdd:cd06224   77 WVENYPYDFFDDEELLELLEEFLNRLVQEGALLQELKKLLRK 118

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 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECR 549
Cdd:cd20796    2 HTFVVHTYTKPTVCQHCKKLLKGLFRQGLQCKDCKFNCHKKCAEKVPKDCT 52

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECR 549
Cdd:cd20798    2 HTLAEHNYKKPTVCKVCDKLLVGLVRQGLKCRDCGVNVHKKCASLLPSNCR 52

protein kinase C conserved region 1 (C1 domain) found in Munc13-1 and similar proteins; Munc13-1, also called protein unc-13 homolog A (Unc13A), is a diacylglycerol (DAG) receptor that plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. It is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Loss of MUNC13-1 function causes microcephaly, cortical hyperexcitability, and fatal myasthenia. 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 569005663 492 GGRMGFVHNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECRRR 551
Cdd:cd20858    1 PISCTTPHNFEVWTATTPTYCYECEGLLWGIARQGMRCTECGVKCHEKCQDLLNADCLQR 60

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 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECRRR 551
Cdd:cd20807    1 HNFEVWTATTPTYCYECEGLLWGIARQGVRCTECGVKCHEKCKDLLNADCLQR 53

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 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECRR 550
Cdd:cd20828    6 HNFEPHSFVTPTNCDYCLQILWGIVKKGMKCSECGYNCHEKCQPQVPKQCSK 57

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVEC 548
Cdd:cd20842   35 HTFVIHSYTRPTVCQYCKKLLKGLFRQGLQCKDCKFNCHKRCAPKVPNNC 84

protein kinase C conserved region 1 (C1 domain) found in Munc13-2, Munc13-3 and similar proteins; Munc13-2, also called protein unc-13 homolog B (Unc13B), plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. It is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECRRRAQSVSLEGSA 561
Cdd:cd20859   20 HNFEVWTATTPTYCYECEGLLWGIARQGMRCSECGVKCHEKCQDLLNADCLQRAAEKSSKHGA 82

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569005663 494 RMGFVHNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECrrrAQSVSLEGSAPSP 564
Cdd:cd20844    1 RVKVPHTFAVHSYTRPTICQYCKRLLKGLFRQGMQCKDCRFNCHKRCASKVPRDC---LGEVTFNGEPASP 68

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005663 407 LEEWTSVAKpkldqALVAEHIEKMVESVFRNFDVDGDGHISQEEFQIIRGNFPYLS-----AFGDLDQNQDGCISREEMI 481
Cdd:COG5126   52 REEFVAGME-----SLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGVSEeeadeLFARLDTDGDGKISFEEFV 126

                 ...
gi 569005663 482 SYF 484
Cdd:COG5126  127 AAV 129

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 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQC 540
Cdd:cd20797    4 HVVEVEQYMTPTFCDYCGEMLTGLMKQGVKCKNCRCNFHKRC 45

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 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVEC 548
Cdd:cd20792    2 HKFVATFFKQPTFCSHCKDFIWGLGKQGYQCQVCRFVVHKRCHEYVVFKC 51

second protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) protein kinase C (cPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. 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 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKE 542
Cdd:cd20836    1 HKFKVHTYSSPTFCDHCGSLLYGLIHQGMKCDTCDMNVHKRCVK 44

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 569005663 430 MVESVFRNFDVDGDGHISQEEF-QIIRGNFPYLS------AFGDLDQNQDGCISREEMI 481
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELkAALKSLGEGLSeeeideMIREVDKDGDGKIDFEEFL 59

protein kinase C conserved region 1 (C1 domain) found in SH3 and cysteine-rich domain-containing protein 2 (Stac2) and similar proteins; Stac2, also called 24b2/Stac2, or Src homology 3 and cysteine-rich domain-containing protein 2, plays a redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity. It slows down the inactivation rate of the calcium channel CACNA1C. Stac2 contains a cysteine-rich C1 domain and one SH3 domain 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 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLS 545
Cdd:cd20881    6 HSFQEHVFKKPSPCELCHQMIVGNSKQGLRCKMCKVSVHLWCSEEVS 52

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
                 ....*....|....*....|....*....|....*....|..
gi 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQC 540
Cdd:cd20810    3 HSFELTTFKEPTTCSVCKKLLKGLFFQGYKCSVCGAAVHKEC 44

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 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECR 549
Cdd:cd20885    4 HDFQPCSLTNPTWCDLCGDFIWGLYKQCLRCTHCKYTCHLRCRDLVTLDCS 54

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 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVECR 549
Cdd:cd20820    2 HRFVPLELEQPTWCDLCGSVILGLFRKCLRCANCKMTCHPRCRSLVCLTCR 52

protein kinase C conserved region 1 (C1 domain) found in VAV2 protein; VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42. It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others. It has been reported to associate with Nek3. 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
                 ....*....|....*....|....*....|....*....|....
gi 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKE 542
Cdd:cd20868    6 HNFQMYTFDKTTNCKACKMLLRGTFYQGYYCSKCGAGAHKECLE 49

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569005663  428 EKMVESVFRNFDVDGDGHISQEEF----QIIRGNFPYLSA-----FGDLDQNQDGCISREEMISYFL 485
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELkkllRKLEEGEPLSDEeveelFKEFDLDKDGRISFEEFLELYS 67

first protein kinase C conserved region 1 (C1 domain) found in the classical (or conventional) protein kinase C (cPKC) family; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domains. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. 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 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVEC 548
Cdd:cd20833    3 HKFIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCSFVVHKRCHEFVTFSC 52

protein kinase C conserved region 1 (C1 domain) found in the GEM-interacting protein (GMIP)-like family; The GMIP-like family includes GMIP, Rho GTPase-activating protein 29 (ARHGAP29) and Rho GTPase-activating protein 45 (ARHGAP45). GMIP is a RhoA-specific GTPase-activating protein that acts as a key factor in saltatory neuronal migration. It associates with the Rab27a effector JFC1 and modulates vesicular transport and exocytosis. ARHGAP29, also called PTPL1-associated RhoGAP protein 1 (PARG1) or Rho-type GTPase-activating protein 29, is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. It has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. ARHGAP29 may act as a specific effector of RAP2A to regulate Rho. In concert with RASIP1, ARHGAP29 suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis. ARHGAP45, also called minor histocompatibility antigen HA-1 (mHag HA-1), is a Rac-GAP (GTPase-Activating Protein) in endothelial cells. It acts as a novel regulator of endothelial integrity. ARHGAP45 contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, it also contains N-terminally a BAR-domin which can play an autoinhibitory effect on this RhoGAP activity. Members of this family contain a zinc-binding 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 569005663 499 HNFQESNSlrPVACRHCKALIlgiYKQGLKCRACGVNCHKQCKERLSVEC 548
Cdd:cd20816    3 HRFRRLRT--PSKCRECDSYV---YFNGAECEECGLACHKKCLETLAIQC 47

protein kinase C conserved region 1 (C1 domain) found in VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. Its function has been implicated in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and plays a role in regulating androgen receptor transcriptional activity. 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 569005663 499 HNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQCKERLSVeCRR 550
Cdd:cd20869    9 HDFKMHTFERVTSCKVCQMLLRGTFYQGYLCSKCGAGAHKECLGRLDS-CGR 59