Guanine nucleotide exchange factor for Ras-like small GTPases;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287   148 FDHLEPIELAEHLTFLEHKSFRRISFTDYQSYVIHGCLENNP---TLERSIALFNGISKWVQLMVLSKPSAQQRAEVITK 224
Cdd:smart00147   1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPsplNLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287   225 FINVAQKLLQLKNFNTLMAVVGGLSHSSISRLKDTHSHLSSEVTKNWNEMTELVSSNGNYCNYRKAFADC-DGFKIPILG 303
Cdd:smart00147  81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCnLPPCIPFLG 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287   304 VHLKDLIAVHVIFPDWMEENKVNVVKMHQLSVTLSELVSLQNASHHLEPN-MDLINLLTLSLDLYHTEDDIYKLSLVLEP 382
Cdd:smart00147 161 VLLKDLTFIDEGNPDFLENGLVNFEKRRQIAEILREIRQLQSQPYNLRPNrSDIQSLLQQLLDHLDEEEELYQLSLKIEP 240

                   ..
gi 569000287   383 RN 384
Cdd:smart00147 241 RV 242

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 569000287  11 TLDELLSTCIEMFDDngdLNDSYLpRIVLLMHRWYLSSTELAGKLLCMYRNASGESCDE----------FRLKICYFMRY 80
Cdd:cd06224    1 TLEALIEHLTSTFDM---PDPSFV-STFLLTYRSFTTPTELLEKLIERYEIAPPENLEYndwdkkkskpIRLRVLNVLRT 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 569000287  81 WILKFPAEFNLDLGLIRMTEEFREVASQLGHEKHISLMDISSVPSY 126
Cdd:cd06224   77 WVENYPYDFFDDEELLELLEEFLNRLVQEGALLQELKKLLRKLLKL 122

Guanine nucleotide exchange factor for Ras-like small GTPases;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287   148 FDHLEPIELAEHLTFLEHKSFRRISFTDYQSYVIHGCLENNP---TLERSIALFNGISKWVQLMVLSKPSAQQRAEVITK 224
Cdd:smart00147   1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPsplNLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287   225 FINVAQKLLQLKNFNTLMAVVGGLSHSSISRLKDTHSHLSSEVTKNWNEMTELVSSNGNYCNYRKAFADC-DGFKIPILG 303
Cdd:smart00147  81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCnLPPCIPFLG 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287   304 VHLKDLIAVHVIFPDWMEENKVNVVKMHQLSVTLSELVSLQNASHHLEPN-MDLINLLTLSLDLYHTEDDIYKLSLVLEP 382
Cdd:smart00147 161 VLLKDLTFIDEGNPDFLENGLVNFEKRRQIAEILREIRQLQSQPYNLRPNrSDIQSLLQQLLDHLDEEEELYQLSLKIEP 240

                   ..
gi 569000287   383 RN 384
Cdd:smart00147 241 RV 242

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287  155 ELAEHLTFLEHKSFRRISFTDYQSYVI--HGCLENNPTLERSIALFNGISKWVQLMVLSKPSAQQRAEVITKFINVAQKL 232
Cdd:pfam00617   1 ELARQLTLIEFELFRKIKPRELLGSAWskKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287  233 LQLKNFNTLMAVVGGLSHSSISRLKDTHSHLSSEVTKNWNEMTELVSSNGNYCNYRKAFADCDGFKIPILGVHLKDLIAV 312
Cdd:pfam00617  81 RELNNFNSLMAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLMSPSRNFKNYREALSSASPPCIPFLGLYLTDLTFI 160

                         170
                  ....*....|....*....
gi 569000287  313 HVIFPDWMEENKVNVVKMH 331
Cdd:pfam00617 161 EEGNPDFLEGGLINFEKRR 179

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 569000287  11 TLDELLSTCIEMFDDngdLNDSYLpRIVLLMHRWYLSSTELAGKLLCMYRNASGESCDE----------FRLKICYFMRY 80
Cdd:cd06224    1 TLEALIEHLTSTFDM---PDPSFV-STFLLTYRSFTTPTELLEKLIERYEIAPPENLEYndwdkkkskpIRLRVLNVLRT 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 569000287  81 WILKFPAEFNLDLGLIRMTEEFREVASQLGHEKHISLMDISSVPSY 126
Cdd:cd06224   77 WVENYPYDFFDDEELLELLEEFLNRLVQEGALLQELKKLLRKLLKL 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 569000287   494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:smart00109   1 HKHVFRTFTKPTFCCVCRKSIWGSFKQGLRCSECKVKCHKKCADKVPKAC 50

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287 402 EWASEVVPKPDPTIinkhiRKLVESVFRNYDHDHDGYISQEDFESIAANFPFLDS-----FCVLDKDQDGLISKDEMMAY 476
Cdd:COG5126   54 EFVAGMESLFEATV-----EPFARAAFDLLDTDGDGKISADEFRRLLTALGVSEEeadelFARLDTDGDGKISFEEFVAA 128

                 .
gi 569000287 477 F 477
Cdd:COG5126  129 V 129

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569000287  427 VFRNYDHDHDGYISQEDFESIAANF----PFLDS-----FCVLDKDQDGLISKDEMMAYFL 478
Cdd:pfam13499   7 AFKLLDSDGDGYLDVEELKKLLRKLeegePLSDEeveelFKEFDLDKDGRISFEEFLELYS 67

transaldolase;

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 569000287 418 KHIRKLVESVFRNYDHDHDGYISQEDFESIAANFpflDSfcvLDKDQDGLISKDEMMA 475
Cdd:PRK12309 330 EAFTHAAQEIFRLYDLDGDGFITREEWLGSDAVF---DA---LDLNHDGKITPEEMRA 381

Guanine nucleotide exchange factor for Ras-like small GTPases;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287   148 FDHLEPIELAEHLTFLEHKSFRRISFTDYQSYVIHGCLENNP---TLERSIALFNGISKWVQLMVLSKPSAQQRAEVITK 224
Cdd:smart00147   1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPsplNLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287   225 FINVAQKLLQLKNFNTLMAVVGGLSHSSISRLKDTHSHLSSEVTKNWNEMTELVSSNGNYCNYRKAFADC-DGFKIPILG 303
Cdd:smart00147  81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCnLPPCIPFLG 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287   304 VHLKDLIAVHVIFPDWMEENKVNVVKMHQLSVTLSELVSLQNASHHLEPN-MDLINLLTLSLDLYHTEDDIYKLSLVLEP 382
Cdd:smart00147 161 VLLKDLTFIDEGNPDFLENGLVNFEKRRQIAEILREIRQLQSQPYNLRPNrSDIQSLLQQLLDHLDEEEELYQLSLKIEP 240

                   ..
gi 569000287   383 RN 384
Cdd:smart00147 241 RV 242

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287  155 ELAEHLTFLEHKSFRRISFTDYQSYVI--HGCLENNPTLERSIALFNGISKWVQLMVLSKPSAQQRAEVITKFINVAQKL 232
Cdd:pfam00617   1 ELARQLTLIEFELFRKIKPRELLGSAWskKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000287  233 LQLKNFNTLMAVVGGLSHSSISRLKDTHSHLSSEVTKNWNEMTELVSSNGNYCNYRKAFADCDGFKIPILGVHLKDLIAV 312
Cdd:pfam00617  81 RELNNFNSLMAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLMSPSRNFKNYREALSSASPPCIPFLGLYLTDLTFI 160

                         170
                  ....*....|....*....
gi 569000287  313 HVIFPDWMEENKVNVVKMH 331
Cdd:pfam00617 161 EEGNPDFLEGGLINFEKRR 179

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 569000287 493 IHNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACR 544
Cdd:cd20808    1 KHNFQETTYFKPTFCDHCTGLLWGLIKQGYKCKDCGINCHKHCKDLVVVECR 52

protein kinase C conserved region 1 (C1 domain) found in RAS guanyl-releasing protein 4 (RASGRP4) and similar proteins; RASGRP4 functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. It 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 569000287 491 GFIHNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACRR 545
Cdd:cd20863    1 GFLHNFHETTFKKPTFCDSCSGFLWGVTKQGYRCQDCGINCHKHCKDQVDVECKK 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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:cd20792    2 HKFVATFFKQPTFCSHCKDFIWGLGKQGYQCQVCRFVVHKRCHEYVVFKC 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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:cd20837    1 HRFKVYNYMSPTFCDHCGSLLWGLFRQGLKCEECGMNVHHKCQKKVANLC 50

protein kinase C conserved region 1 (C1 domain) found in the myotubularin-related protein Sbf and similar proteins; This group includes Drosophila melanogaster SET domain binding factor (Sbf), the single homolog of human MTMR5/MTMR13, and similar proteins, that show high sequence similarity to vertebrate myotubularin-related proteins (MTMRs) which may function as guanine nucleotide exchange factors (GEFs). Sbf is a pseudophosphatase that coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. It also functions as a GEF that promotes Rab21 GTPase activation associated with PI(3)P endosomes. 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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACRR 545
Cdd:cd20827    2 HRFEKHNFTTPTYCDYCSSLLWGLVKTGMRCADCGYSCHEKCLEHVPKNCTK 53

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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:cd20806    2 HNFKVHTFKGPHWCDYCGNFMWGLIAQGVKCEDCGFNAHKQCSKLVPHDC 51

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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACRR 545
Cdd:cd20828    6 HNFEPHSFVTPTNCDYCLQILWGIVKKGMKCSECGYNCHEKCQPQVPKQCSK 57

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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCK 536
Cdd:cd20838    3 HRFSVHNYKRPTFCDHCGSLLYGLYKQGLQCKVCKMNVHKRCQ 45

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
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 569000287 489 GPGFIHNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACR 544
Cdd:cd20858    3 SCTTPHNFEVWTATTPTYCYECEGLLWGIARQGMRCTECGVKCHEKCQDLLNADCL 58

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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACR 544
Cdd:cd20798    2 HTLAEHNYKKPTVCKVCDKLLVGLVRQGLKCRDCGVNVHKKCASLLPSNCR 52

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 569000287 493 IHNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACR 544
Cdd:cd20856    5 VHNFKVHTFRGPHWCEYCANFMWGLIAQGVKCADCGLNVHKQCSKMVPNDCK 56

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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQC 535
Cdd:cd20810    3 HSFELTTFKEPTTCSVCKKLLKGLFFQGYKCSVCGAAVHKEC 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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGII-KQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:cd20835   10 HKFMATYLRQPTYCSHCKDFIWGVIgKQGYQCQVCTCVVHKRCHQLVVTKC 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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQC 535
Cdd:cd20797    4 HVVEVEQYMTPTFCDYCGEMLTGLMKQGVKCKNCRCNFHKRC 45

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:cd20834    8 HEFIAKFFRQPTFCSVCKEFLWGFNKQGYQCRQCNAAVHKKCHDKILGKC 57

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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQC 535
Cdd:cd20824    2 HNFKPHSFSIPTKCDYCGEKIWGLSKKGLSCKDCGFNCHIKC 43

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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLAC 543
Cdd:cd20833    3 HKFIARFFKQPTFCSHCTDFIWGFGKQGFQCQVCSFVVHKRCHEFVTFSC 52

second protein kinase C conserved region 1 (C1 domain) found in uncharacterized phosphatidylinositol 3-kinase regulatory subunit-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate phosphatidylinositol 3-kinase regulatory subunits (PIK3Rs), which bind to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulate their kinase activity. Unlike typical PIK3Rs, members of this family have two C1 domains. This model corresponds to the second one. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACRR 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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACR 544
Cdd:cd20885    4 HDFQPCSLTNPTWCDLCGDFIWGLYKQCLRCTHCKYTCHLRCRDLVTLDCS 54

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
                 ....*....|....*....|....*....|....*....|..
gi 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQC 535
Cdd:cd20844    6 HTFAVHSYTRPTICQYCKRLLKGLFRQGMQCKDCRFNCHKRC 47

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 569000287 492 FIHNFQemnylKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQC 535
Cdd:cd20841   14 YVHSYK-----APTFCDYCGEMLWGLVRQGLKCEGCGLNYHKRC 52

protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) zeta type; PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. Members of this family contain C1 domain found in aPKC isoform zeta. 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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDLLVLACRR 545
Cdd:cd21095    3 HLFQAKRFNRRAYCGQCSERIWGLGRQGYKCINCKLLVHKRCHKLVPLTCKR 54

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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQC 535
Cdd:cd20840   11 HALNVHSYRAPAFCDHCGEMLFGLVRQGLKCDGCGLNYHKRC 52

protein kinase C conserved region 1 (C1 domain) found in myotonic dystrophy kinase-related Cdc42-binding kinase beta (MRCK beta) and similar proteins; MRCK beta, also called Cdc42-binding protein kinase beta (Cdc42BP-beta), DMPK-like beta, or myotonic dystrophy protein kinase-like beta, is a serine/threonine-protein kinase expressed ubiquitously in many tissues. MRCK beta is an important downstream effector of Cdc42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. 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 569000287 494 HNFQEMNYLKPTFCEHCAGFLWGIIKQGYKCKDCGANCHKQCKD 537
Cdd:cd20865    1 HQLSIKSFSSPTQCSHCTSLMVGLVRQGYACEVCSFACHVSCKD 44

protein kinase C conserved region 1 (C1 domain) found in differentially expressed in FDCP 8 (DEF-8) and similar proteins; DEF-8 positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts. It is involved in bone resorption. DEF-8 contains a protein kinase C conserved region 1 (C1) domain followed by a putative zinc-RING and/or ribbon. 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 569000287 494 HNFQEMNYLKPT--FCEHCAGFLWGIIKQGYKCKDCGANCHKQCKDL 538
Cdd:cd20819    6 HHFVLQKSKSSSkqYCDKCCGIIWGLLQTWYRCTDCGYRCHSKCLNS 52