Ras-associating (RA) domain found in Ras-association domain-containing protein 1 (RASSF1); RASSF1 is a member of a family of six related RASSF1-6 proteins (the classical RASSF proteins). RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. With the exception of some minor splice variants (RASSF1F and RASSF1G), RASSF1 contains an RA domain and a C-terminal SARAH protein-protein interaction motif. The RA domain of the classical RASSF proteins has a beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases, and the SARAH domain mediates protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. RASSF1A and 1C are the most extensively studied RASSF1 with both localized to microtubules and involved in regulation of growth and migration.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25777684 134 LSQAEIEQKIKEYNAQINSNLFMSLNKDGSYTGFIKVQLKLVRPVSVPSSKKPPSLQDARRGPGRGTSVRRRTSFYLPKD 213
Cdd:cd17218   1 LSQAEIEQKIKEYNAQINSNLFMSLNKDGSYTGFIKVQLKLVRPVSVPANKKPSSIQDSRKGSGRSQPVKRRTSFYLPKD 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 25777684 214 AVKHLHVLSRTRAREVIEALLRKFLVVDDPRKFALFERAERHGQVYLRKLLDDEQPLRLRLLAGPSDKALSFVLKEN 290
Cdd:cd17218  81 TVKHLHISSKTRASEVIEALLKKFTVVDNPRKFALFERTEKDDQVYLRKLSDDEQPLYLRLLAGPNEKTLSFVLKEN 157

C-terminal SARAH domain found in Ras-association domain-containing protein 1 (RASSF1); RASSF1 is one of six related proteins, the classical RASSF proteins (RASSF1-6), that contain a conserved RalGDS/AF6 Ras association (RA) domain located towards the C-terminus. It acts as a potential tumor suppressor that is required for death receptor-dependent apoptosis. It mediates activation of STK3/MST2 and STK4/MST1 during Fas-induced apoptosis by preventing their dephosphorylation. 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. With the exception of some minor splice variants (RASSF1F and RASSF1G), RASSF1 contains an RA domain and a C-terminal SARAH (Salvador-RassF-Hippo) protein-protein interaction motif. The RA domain of the classical RASSF proteins has a beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases, and the SARAH domain mediates protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. This model corresponds to the SARAH domain of RASSF1.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 25777684 296 NWDAFSMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEALHAC 341
Cdd:cd21890   1 NWDAFSMPELQNFLRILQREEEEHVRQILQRYTRCREKMQEALASR 46

Ras-associating (RA) domain found in Ras-association domain-containing protein 1 (RASSF1); RASSF1 is a member of a family of six related RASSF1-6 proteins (the classical RASSF proteins). RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. With the exception of some minor splice variants (RASSF1F and RASSF1G), RASSF1 contains an RA domain and a C-terminal SARAH protein-protein interaction motif. The RA domain of the classical RASSF proteins has a beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases, and the SARAH domain mediates protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. RASSF1A and 1C are the most extensively studied RASSF1 with both localized to microtubules and involved in regulation of growth and migration.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25777684 134 LSQAEIEQKIKEYNAQINSNLFMSLNKDGSYTGFIKVQLKLVRPVSVPSSKKPPSLQDARRGPGRGTSVRRRTSFYLPKD 213
Cdd:cd17218   1 LSQAEIEQKIKEYNAQINSNLFMSLNKDGSYTGFIKVQLKLVRPVSVPANKKPSSIQDSRKGSGRSQPVKRRTSFYLPKD 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 25777684 214 AVKHLHVLSRTRAREVIEALLRKFLVVDDPRKFALFERAERHGQVYLRKLLDDEQPLRLRLLAGPSDKALSFVLKEN 290
Cdd:cd17218  81 TVKHLHISSKTRASEVIEALLKKFTVVDNPRKFALFERTEKDDQVYLRKLSDDEQPLYLRLLAGPNEKTLSFVLKEN 157

C-terminal SARAH domain found in Ras-association domain-containing protein 1 (RASSF1); RASSF1 is one of six related proteins, the classical RASSF proteins (RASSF1-6), that contain a conserved RalGDS/AF6 Ras association (RA) domain located towards the C-terminus. It acts as a potential tumor suppressor that is required for death receptor-dependent apoptosis. It mediates activation of STK3/MST2 and STK4/MST1 during Fas-induced apoptosis by preventing their dephosphorylation. 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. With the exception of some minor splice variants (RASSF1F and RASSF1G), RASSF1 contains an RA domain and a C-terminal SARAH (Salvador-RassF-Hippo) protein-protein interaction motif. The RA domain of the classical RASSF proteins has a beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases, and the SARAH domain mediates protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. This model corresponds to the SARAH domain of RASSF1.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 25777684 296 NWDAFSMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEALHAC 341
Cdd:cd21890   1 NWDAFSMPELQNFLRILQREEEEHVRQILQRYTRCREKMQEALASR 46

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25777684   206 TSFYLPKDAVKHLHVLSRTRAREVIEALLRKFLVVDDPRKFALFERAERHGQVylRKLLDDEQPLRLRLLAGPSDKALSF 285
Cdd:pfam00788   9 TEDGKPGTTYKTILVSSSTTAEEVIEALLEKFGLEDDPRDYVLVEVLERGGGE--RRLPDDECPLQIQLQWPRDASDSRF 86

                  ....*.
gi 25777684   286 VLKEND 291
Cdd:pfam00788  87 LLRKRD 92

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 25777684    52 HRFQPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDC 105
Cdd:pfam00130   1 HHFVHRNFKQPTFCDHCGEFLWGLGKQGLKC----SWCKLNVHKRCHEKVPPEC 50

Ras-associating (RA) domain found in Ras-association domain-containing protein 1 (RASSF1); RASSF1 is a member of a family of six related RASSF1-6 proteins (the classical RASSF proteins). RASSF1 has eight transcripts (A-H) arising from alternative splicing and differential promoter usage. With the exception of some minor splice variants (RASSF1F and RASSF1G), RASSF1 contains an RA domain and a C-terminal SARAH protein-protein interaction motif. The RA domain of the classical RASSF proteins has a beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases, and the SARAH domain mediates protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. RASSF1A and 1C are the most extensively studied RASSF1 with both localized to microtubules and involved in regulation of growth and migration.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25777684 134 LSQAEIEQKIKEYNAQINSNLFMSLNKDGSYTGFIKVQLKLVRPVSVPSSKKPPSLQDARRGPGRGTSVRRRTSFYLPKD 213
Cdd:cd17218   1 LSQAEIEQKIKEYNAQINSNLFMSLNKDGSYTGFIKVQLKLVRPVSVPANKKPSSIQDSRKGSGRSQPVKRRTSFYLPKD 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 25777684 214 AVKHLHVLSRTRAREVIEALLRKFLVVDDPRKFALFERAERHGQVYLRKLLDDEQPLRLRLLAGPSDKALSFVLKEN 290
Cdd:cd17218  81 TVKHLHISSKTRASEVIEALLKKFTVVDNPRKFALFERTEKDDQVYLRKLSDDEQPLYLRLLAGPNEKTLSFVLKEN 157

Ras-associating (RA) domain of Ras-association domain family 5 (RASSF5); RASSF5, also called New ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is a member of a family of six related RASSF1-6 proteins (the classical RASSF proteins) and is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. All transcripts variants of RASSF5 contain the RA or SARAH domains. The RA domain of the classical RASSF proteins has a beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases, and the SARAH domain mediates protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25777684 135 SQAEIEQKIKEYNAQINSNLFMSLNKDGSYTGFIKVQLKLVRPVSVPSSKKPPSLQDArrGPGRGTSvrRRTSFYLPKDA 214
Cdd:cd17220   1 TVEEIKQKIESYNTKVKNCLGMKLSPDGTYTGFIKVHLKLRRPVTVPAGIRPQSIYEV--NPADTTD--KRTSFYLPLDA 76

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 25777684 215 VKHLHVLSRTRAREVIEALLRKFLVVDDPRKFALFERAERHGQVYLRKLLDDEQPLRLRLLAGPSDKALSFVLKEN 290
Cdd:cd17220  77 IKQLHISSTTTVSEVIQGLLKKFMVVDNPQKFALFKRMRKDGQVLFQKLPLTEYPLYLRLLAGPDTDVLSFVLKEN 152

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 25777684  49 GRGHRFQPAGPATHTWCDLCGDFIWGVVRKGLQCARlsadCKFTCHYRCRALVCLDCC 106
Cdd:cd20885   1 GEGHDFQPCSLTNPTWCDLCGDFIWGLYKQCLRCTH----CKYTCHLRCRDLVTLDCS 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 25777684  51 GHRFQPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDCC 106
Cdd:cd20820   1 GHRFVPLELEQPTWCDLCGSVILGLFRKCLRC----ANCKMTCHPRCRSLVCLTCR 52

C-terminal SARAH domain found in Ras-association domain proteins, RASSF1, RASSF3, and RASSF5; The RASSF subfamily of proteins shares a conserved RalGDS/AF6 Ras association (RA) domain which is located either at the C-terminus (RASSF1-6, the classical group) or at the N-terminus (RASSF7-10). Classical RASSF proteins interact either directly or indirectly with activated Ras. Ras proteins are small GTPases that are involved in cellular signal transduction. They seem to modulate some of the growth inhibitory responses mediated by Ras and may serve as tumor suppressor genes. RASSF1-6 contains a conserved SARAH (Salvador-RassF-Hippo) motif adjacent to the RA domain that functions in scaffolding and regulatory interactions. The RA domain of the classical RASSF proteins has a beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. This model corresponds to the SARAH domain of RASSF1, RASSF3, and RASSF5. It is a characteristic coiled-coil structure that is important in signal-transduction networks. The central function of the SARAH domain is the mediation of homo- and heterodimerization between SARAH domain-containing proteins.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 25777684 296 NWDAFSMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEALHA 340
Cdd:cd21885   1 LWEAFSLPELENFLKILDREEKEYIEQIREKYRIYRKKLQRRLDE 45

C-terminal SARAH domain found in Ras-association domain-containing protein 5 (RASSF5); RASSF5, also called New ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is one of six related proteins, the classical RASSF proteins (RASSF1-6), that contain a conserved RalGDS/AF6 Ras association (RA) domain located towards the C-terminus. It acts as a potential tumor suppressor that may be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. RASSF5 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. All transcript variants of RASSF5 contain the RA and SARAH (Salvador-RassF-Hippo) domains. The RA domain of the classical RASSF proteins has a beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. The RA domain mediates interactions with Ras and other small GTPases, and the SARAH domain mediates protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. This model corresponds to the SARAH domain of RASSF5, that mediates homo- and heterodimerization.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 25777684 293 GEVNWDAFSMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEAL 338
Cdd:cd21892   1 GEVEWDAFSVPELQNFLRILEKEEQDKIQQVQKKYAKFRQKLQDAL 46

Novel Ras effector 1 C-terminal SARAH (Sav/Rassf/Hpo) domain; The Nore1-SARAH, C-terminal, domain of Nore1, the tumour-suppressor, a novel Ras effector, has a characteriztic coiled-coil structure. It is a small helical module that is important in signal-transduction networks. The recombinant SARAH domain of Nore1 crystallizes as an anti-parallel homodimer with representative characteriztics of coiled coils. The central function of the SARAH domain seems to be the mediation of homo- and hetero-oligomerization between SARAH domain-containing proteins. Nore1 forms homo- and hetero complexes through its C-terminal SARAH (Sav/Rassf/Hpo) domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 25777684   299 AFSMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEAL 338
Cdd:pfam16517   1 AFSLPELENFLRILDEEEEREIQQIRRKYTALRQKLQQAL 40

protein kinase C conserved region 1 (C1 domain) found in Ras association domain-containing protein 5 (RASSF5) and similar proteins; RASSF5, also called new ras effector 1 (NORE1), or regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), is a member of a family of RAS effectors, of which there are currently 8 members (RASSF1-8), all containing a Ras-association (RA) domain of the Ral-GDS/AF6 type. It is expressed as three transcripts (A-C) via differential promoter usage and alternative splicing. RASSF5A is a pro-apoptotic Ras effector and functions as a Ras regulated tumor suppressor. RASSF5C is regulated by Ras related protein and modulates cellular adhesion. RASSF5 is a potential tumor suppressor that seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. It contains a C1 domain, which is descibed in this model. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 25777684  49 GRGHRFQPaGPATHTWCDLCGDFIwgvVRKGLQCArlsaDCKFTCHYRCRALVCLDC 105
Cdd:cd20886   1 GEGHRFEP-GALGPGWCDLCGRYI---LSQALRCT----NCKYTCHSECRDLVQLDC 49

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 25777684  52 HRFQPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDC 105
Cdd:cd00029   1 HRFVPTTFSSPTFCDVCGKLIWGLFKQGLKC----SDCGLVCHKKCLDKAPSPC 50

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 25777684  52 HRFQPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDC 105
Cdd:cd20793   1 HKFKVHTYYSPTFCDHCGSLLYGLVRQGLKC----KDCGMNVHHRCKENVPHLC 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 25777684  52 HRFQPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDC 105
Cdd:cd20827   2 HRFEKHNFTTPTYCDYCSSLLWGLVKTGMRC----ADCGYSCHEKCLEHVPKNC 51

Ras-associating (RA) domain found in Ras-association domain-containing protein 6 (RASSF6); RASSF6 is a member of a family of six related classical RASSF1-6 proteins and is expressed as four transcripts via alternative splicing. All transcripts variant of RASSF6 contain the RA and SARAH domains. The RA domain of the classical RASSF protein family has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. RA domains mediate interactions with Ras and other small GTPases, SARAH domains mediate protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis. RASSF6 is ubiquitiated and degraded by interacting with MDM2 to stabilize P53 and regulates apoptosis and cell cycle. RASSF6 is a tumor suppressor protein and is epigenetically silenced in childhood leukemia and neuroblastomas. Overexpression of RASSF6 causes apoptosis in HeLa cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25777684 205 RTSFYLPK-DAVKHLHVLSRTRAREVIEALLRKFLVVDDPRKFALFeraERHGQVYLRKLLDDEQPLRLRLLAGPSDKAL 283
Cdd:cd17223   3 KTSVFTPAfGSETKVRINSNMTTQEVIKQLLQKFKIENSPNEFALY---IIHATGEKKRLKNTDFPLWERLLQGPSGKIA 79

                ....*...
gi 25777684 284 SFVLKEND 291
Cdd:cd17223  80 KMFLMDKD 87

C-terminal SARAH domain found in scaffold protein salvador (Sav), Ras-association domain proteins, and mammalian STE20-like protein kinases (MST); The SARAH (Salvador-RassF-Hippo) domain family includes scaffold protein salvador (Sav), Ras-association domain proteins (RASSF1-6), and mammalian STE20-like protein kinase (MST) subfamily members (MST1-2 and Hippo). Sav is a scaffold protein mainly found in metazoans. Drosophila melanogaster Sav, also called Shar-pei (SHRP), promotes both cell cycle exit and apoptosis in Drosophila. It plays a key role in the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. Human protein salvador homolog 1, also called 45 kDa WW domain protein (WW45), acts as a mammalian sterile 20-like kinase 1 (MST1)-binding protein required to enhance MST1-mediated apoptosis. It is a regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling pathway. Classical RASSF proteins interact either directly or indirectly with activated Ras. Ras proteins are small GTPases that are involved in cellular signal transduction. They seem to modulate some of the growth inhibitory responses mediated by Ras and may serve as tumor suppressor genes. RASSF1-6 contains a conserved SARAH motif adjacent to the RA domain that functions in scaffolding and regulatory interactions. MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 and MST2 are STE20 family stress-activated, pro-apoptotic serine/threonine-protein kinases which, following caspase-cleavage, enter the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. They are key components of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. Hippo (Hpo), also called STE20-like kinase MST (dMST), is the Drosophila homolog of STE20-like protein kinases, MST1 and MST2. It is a STE20 family serine/threonine-protein kinase that functions as a tumor suppressor by restricting cell proliferation and promotes apoptosis in conjunction with salvador and warts. Hpo also plays a key role in the Hippo/SWH signaling pathway. This model corresponds to the C-terminal SARAH domain, a characteristic coiled-coil structure. It is a small helical module that is important in signal-transduction networks. The central function of the SARAH domain seems to be the mediation of homo- and heterodimerization between SARAH domain-containing proteins.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 25777684 297 WDAFSMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEALHA 340
Cdd:cd21883   2 LKNFSLPELQMFLKMLDPEEEREIEQLVKKYTAYRQAILDALEE 45

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 25777684  52 HRFQPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDCC 106
Cdd:cd20806   2 HNFKVHTFKGPHWCDYCGNFMWGLIAQGVKC----EDCGFNAHKQCSKLVPHDCQ 52

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 25777684  52 HRFQPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDC 105
Cdd:cd20828   6 HNFEPHSFVTPTNCDYCLQILWGIVKKGMKC----SECGYNCHEKCQPQVPKQC 55

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
                   ....*....|....*....|....*....|....*....|...
gi 25777684     63 TWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDC 105
Cdd:smart00109  12 TFCCVCRKSIWGSFKQGLRC----SECKVKCHKKCADKVPKAC 50

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 25777684  50 RGHRFQPAGPATHTWCDLCGDFIWGVVRKGLQCARlsadCKFTCHYRCRALVCLDCCG 107
Cdd:cd20833   1 KDHKFIARFFKQPTFCSHCTDFIWGFGKQGFQCQV----CSFVVHKRCHEFVTFSCPG 54

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 25777684  52 HRFQPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRC---RALVCL 103
Cdd:cd20830   1 HRFVEQSFSTLQWCDKCGKFLFGLVHQGLQC----QDCGLVCHRTCaatGLPKCE 51

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
                ....*....|....*....|....*....|....*....|....*....|....
gi 25777684  63 TWCDLCGDFIWGVVRKGLQCArlsaDCKFTCHYRCRALVCLDCCGPRDLGWEPA 116
Cdd:cd20844  17 TICQYCKRLLKGLFRQGMQCK----DCRFNCHKRCASKVPRDCLGEVTFNGEPA 66

second protein kinase C conserved region 1 (C1 domain) found in protein kinase D2 (PKD2) and similar proteins; PKD2, also called PRKD2, HSPC187, or serine/threonine-protein kinase D2 (nPKC-D2), is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. PKD2 contains N-terminal tandem cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. This model corresponds to the second C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 25777684  63 TWCDLCGDFIWGVVRKGLQCArlsaDCKFTCHYRCRALVCLDCCG 107
Cdd:cd20843  23 TVCQFCKKLLKGLFRQGLQCK----DCKFNCHKRCATRVPNDCLG 63

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
                ....*....|....*....|....*....|....*....|....*..
gi 25777684  52 HRFQPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCR 98
Cdd:cd20809   1 HKFIVRTFSTPTKCNHCTSLMVGLVRQGLVC----EVCGYACHVSCA 43

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 25777684  51 GHRFQPAGPATHTWCDLCGDFIWGVVRK-GLQCARlsadCKFTCHYRCRALVCLDCCG 107
Cdd:cd20835   9 GHKFMATYLRQPTYCSHCKDFIWGVIGKqGYQCQV----CTCVVHKRCHQLVVTKCPG 62

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
                ....*....|....*....|....*....|....*....|....*.
gi 25777684  52 HRFQPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRC 97
Cdd:cd20829   1 HRLVDVYFVTPILCRHCKDYIWGKGKVGVRC----EDCHACFHLVC 42

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 25777684  50 RGHRFQPAGPATHTWCDLCGDFIWGVVRKGLQCARlsadCKFTCHYRC 97
Cdd:cd20797   2 RPHVVEVEQYMTPTFCDYCGEMLTGLMKQGVKCKN----CRCNFHKRC 45

first protein kinase C conserved region 1 (C1 domain) found in Saccharomyces cerevisiae protein kinase C-like 1 (ScPKC1) and similar proteins; ScPKC1 is required for cell growth and for the G2 to M transition of the cell division cycle. It mediates a protein kinase cascade, activating BCK1 which itself activates MKK1/MKK2. The family also includes Schizosaccharomyces pombe PKC1 and PKC2, which are involved in the control of cell shape and act as targets of the inhibitor staurosporine. 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
                ....*....|....*....|....*....|....*....|....*...
gi 25777684  50 RGHRFQPAGPATHTWCDLCGDFIwgvVRKGLQCArlsaDCKFTCHYRC 97
Cdd:cd20822   1 RGHKFVQKQFYQIMRCAVCGEFL---VNAGYQCE----DCKYTCHKKC 41

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
                ....*....|....*....|....*....|....*....|..
gi 25777684  64 WCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDC 105
Cdd:cd20856  18 WCEYCANFMWGLIAQGVKC----ADCGLNVHKQCSKMVPNDC 55

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
                ....*....|....*....|....*....|....*....|....*
gi 25777684  63 TWCDLCGDFIWGVVRKGLQCArlsaDCKFTCHYRCRALVCLDCCG 107
Cdd:cd20842  46 TVCQYCKKLLKGLFRQGLQCK----DCKFNCHKRCAPKVPNNCLG 86

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        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 25777684  52 HRFQPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDC 105
Cdd:cd20836   1 HKFKVHTYSSPTFCDHCGSLLYGLIHQGMKC----DTCDMNVHKRCVKNVPSLC 50

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
                ....*....|....*....|....*....|....*....|....*....|....
gi 25777684  52 HRFQPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDC 105
Cdd:cd20859  20 HNFEVWTATTPTYCYECEGLLWGIARQGMRC----SECGVKCHEKCQDLLNADC 69

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 25777684  51 GHRFQPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDC 105
Cdd:cd21095   2 GHLFQAKRFNRRAYCGQCSERIWGLGRQGYKC----INCKLLVHKRCHKLVPLTC 52

second protein kinase C conserved region 1 (C1 domain) found in Saccharomyces cerevisiae protein kinase C-like 1 (ScPKC1) and similar proteins; ScPKC1 is required for cell growth and for the G2 to M transition of the cell division cycle. It mediates a protein kinase cascade, activating BCK1 which itself activates MKK1/MKK2. The family also includes Schizosaccharomyces pombe PKC1 and PKC2, which are involved in the control of cell shape and act as targets of the inhibitor staurosporine. 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 25777684  52 HRFQPAGPATHTWCDLCGDFIWGVVRKGLQCArlsaDCKFTCHYRCRALVcLDCCG 107
Cdd:cd20823   5 HRFEPFTNLGANWCCHCGQMLPLGRKQIRKCT----ECGKTAHAQCAHLV-PNFCG 55

first 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 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 25777684  64 WCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDCCGPR 109
Cdd:cd20839  20 FCDHCGEMLWGLVRQGLKC----EGCGLNYHKRCAFKIPNNCSGVR 61

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 25777684 213 DAVKHLHVLSRTRAREVIEALLRKFLVVD-DPRKFALFERAERHGQVYlRKLLDDEQPLRLRL 274
Cdd:cd01783  14 VAYKSIPVTKETTVEEVIKEALPKFGLQDeDPEDFRLVEVLMDKGVVE-RVMLRDECPWLILL 75

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        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 25777684  51 GHRF--QPAGPATHTWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRALVCLDC 105
Cdd:cd20819   5 GHHFvlQKSKSSSKQYCDKCCGIIWGLLQTWYRC----TDCGYRCHSKCLNSITRTC 57

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 25777684  52 HRFQPAGPATHTWCDLCGDFIWGVVRKGLQCArlsaDCKFTCHYRCRALVCLDC 105
Cdd:cd20798   2 HTLAEHNYKKPTVCKVCDKLLVGLVRQGLKCR----DCGVNVHKKCASLLPSNC 51

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
                ....*....|....*....|....*....|....*..
gi 25777684  63 TWCDLCGDFIWGVVRKGLQCarlsADCKFTCHYRCRA 99
Cdd:cd20817  12 TFCDVCKELLVGLSKQGLRC----KNCKMNVHHKCQE 44