C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 360 LLVKIVKGDGI---RDAQNPYVVIEMDEPAQKNQTGTQRG-GKPFWDEHFLFELSPQSAEILFEVYDHPViaSDPPKFLG 435
Cdd:cd08678    1 LLVKNIKANGLseaAGSSNPYCVLEMDEPPQKYQSSTQKNtSNPFWDEHFLFELSPNSKELLFEVYDNGK--KSDSKFLG 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 221330438 436 LGLVGIDELAVGPASTQLLQLQPRPYETQPVSGAITVDFVFIEGAEIP 483
Cdd:cd08678   79 LAIVPFDELRKNPSGRQIFPLQGRPYEGDSVSGSITVEFLFMEPAELP 126

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain superfamily; The SMP domain is a lipid transport domain found in phospholipid transfer proteins such as synaptotagmin family proteins, tricalbin (TCB) family proteins, maintenance of mitochondrial morphology protein 1 (MMM1), mitochondrial distribution and morphology protein 12 (MDM12), mitochondrial distribution and morphology protein 34 (MDM34), PDZ domain-containing protein 8 (PDZD8), testis-expressed protein 2 (TEX2), meiotically up-regulated gene 190 protein (Mug190), C2 domain-containing protein 2 (C2CD2) and C2 domain-containing protein 2-like (C2CD2L). The SMP domain belongs to a superfamily of lipid/hydrophobic ligand-binding domains called TULIP (tubular lipid-binding proteins). It adopts a TULIP fold with two alpha helices and a highly curved antiparallel beta sheet forming a cornucopia-like structure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 147 WTSQVFRWLYSDLVIVNELLMSWVIAINDTLRKSveEHGVAVEVVRVLPDSPAPGLNNIFCncdENNPADMLIT---FDC 223
Cdd:cd21664    1 WLNSVLNWIYTQYCNTPELVEAWLKALNEQARRA--GSSVQVTFERIQSGSLPPKFTHVST---VAEPNDSLVVtcqVES 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 224 DAMpVLQVKTFRQKSGKVETSHYKVTVSRfrarmaipmnynsLKGEMRVEGY---PDVRIAMNSVG------AIKAMDQD 294
Cdd:cd21664   76 EGL-RFQVFATQQTAQSVKLSNCDVSVTK-------------LSGKLRCHGRtlgEELQISVSFEDrpdlklNIKPKNGS 141

                        170       180
                 ....*....|....*....|
gi 221330438 295 EQQLQTVISDILTTALRDTI 314
Cdd:cd21664  142 PTAEDSVDLDVVEEIVRNAI 161

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 360 LLVKIVKGDGI---RDAQNPYVVIEMDEPAQKNQTGTQRG-GKPFWDEHFLFELSPQSAEILFEVYDHPViaSDPPKFLG 435
Cdd:cd08678    1 LLVKNIKANGLseaAGSSNPYCVLEMDEPPQKYQSSTQKNtSNPFWDEHFLFELSPNSKELLFEVYDNGK--KSDSKFLG 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 221330438 436 LGLVGIDELAVGPASTQLLQLQPRPYETQPVSGAITVDFVFIEGAEIP 483
Cdd:cd08678   79 LAIVPFDELRKNPSGRQIFPLQGRPYEGDSVSGSITVEFLFMEPAELP 126

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438   359 RLLVKIVKGDGIRDAQ-----NPYVVIEMD-EPAQKNQTGTQRG-GKPFWDEHFLFELS-PQSAEILFEVYDHPVIASDp 430
Cdd:smart00239   1 TLTVKIISARNLPPKDkggksDPYVKVSLDgDPKEKKKTKVVKNtLNPVWNETFEFEVPpPELAELEIEVYDKDRFGRD- 79

                           90       100
                   ....*....|....*....|...
gi 221330438   431 pKFLGLGLVGIDELAVGPASTQL 453
Cdd:smart00239  80 -DFIGQVTIPLSDLLLGGRHEKL 101

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 221330438  827 HTFIAKHLSGSGLqCSICMKSIpRRPGKQGYECRDCQLISHKQCHIRAPQACP 879
Cdd:pfam00130   1 HHFVHRNFKQPTF-CDHCGEFL-WGLGKQGLKCSWCKLNVHKRCHEKVPPECG 51

synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain found in C2 domain-containing protein 2-like (C2CD2L) and similar proteins; This family includes C2 domain-containing protein 2 (C2CD2) and C2CD2-like (C2CD2L). C2CD2 (also called transmembrane protein 24-like or TMEM24L), may be a lipid-binding protein that shows high sequence similarity with C2 domain-containing protein 2-like (C2CD2L; also called transmembrane protein 24 or TMEM24). C2CD2L is a lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum (ER) to the cell membrane. It is a Ca2+-regulated component of ER-plasma membrane contacts in mammalian neurons. This model corresponds to the SMP domain of C2CD2 and C2CD2L which binds glycerolipids with a preference for phosphatidylinositol (PI). The bound PI is then transferred to the plasma membrane (PM) where it is converted to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to replenish pools of this lipid hydrolyzed during glucose-stimulated signaling. PI(4,5)P2 is required for Ca2+-dependent exocytosis; hence, the SMP domain of TMEM24 is essential for sustaining the intracellular Ca2+ oscillations that trigger bursts of insulin granule release and subsequent insulin secretion.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 147 WTSQVFRWLYSDLVIVNELLMSWVIAINDTLRKSveEHGVAVEVVRVLPDSPAPGLNNIFCncdENNPADMLIT---FDC 223
Cdd:cd21664    1 WLNSVLNWIYTQYCNTPELVEAWLKALNEQARRA--GSSVQVTFERIQSGSLPPKFTHVST---VAEPNDSLVVtcqVES 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 224 DAMpVLQVKTFRQKSGKVETSHYKVTVSRfrarmaipmnynsLKGEMRVEGY---PDVRIAMNSVG------AIKAMDQD 294
Cdd:cd21664   76 EGL-RFQVFATQQTAQSVKLSNCDVSVTK-------------LSGKLRCHGRtlgEELQISVSFEDrpdlklNIKPKNGS 141

                        170       180
                 ....*....|....*....|
gi 221330438 295 EQQLQTVISDILTTALRDTI 314
Cdd:cd21664  142 PTAEDSVDLDVVEEIVRNAI 161

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 360 LLVKIVKGDGI---RDAQNPYVVIEMDEPAQKNQTGTQRG-GKPFWDEHFLFELSPQSAEILFEVYDHPViaSDPPKFLG 435
Cdd:cd08678    1 LLVKNIKANGLseaAGSSNPYCVLEMDEPPQKYQSSTQKNtSNPFWDEHFLFELSPNSKELLFEVYDNGK--KSDSKFLG 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 221330438 436 LGLVGIDELAVGPASTQLLQLQPRPYETQPVSGAITVDFVFIEGAEIP 483
Cdd:cd08678   79 LAIVPFDELRKNPSGRQIFPLQGRPYEGDSVSGSITVEFLFMEPAELP 126

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438   359 RLLVKIVKGDGIRDAQ-----NPYVVIEMD-EPAQKNQTGTQRG-GKPFWDEHFLFELS-PQSAEILFEVYDHPVIASDp 430
Cdd:smart00239   1 TLTVKIISARNLPPKDkggksDPYVKVSLDgDPKEKKKTKVVKNtLNPVWNETFEFEVPpPELAELEIEVYDKDRFGRD- 79

                           90       100
                   ....*....|....*....|...
gi 221330438   431 pKFLGLGLVGIDELAVGPASTQL 453
Cdd:smart00239  80 -DFIGQVTIPLSDLLLGGRHEKL 101

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 221330438 827 HTFIaKHLSGSGLQCSICMKSIpRRPGKQGYECRDCQLISHKQCHIRAPQAC 878
Cdd:cd00029    1 HRFV-PTTFSSPTFCDVCGKLI-WGLFKQGLKCSDCGLVCHKKCLDKAPSPC 50

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 221330438  827 HTFIAKHLSGSGLqCSICMKSIpRRPGKQGYECRDCQLISHKQCHIRAPQACP 879
Cdd:pfam00130   1 HHFVHRNFKQPTF-CDHCGEFL-WGLGKQGLKCSWCKLNVHKRCHEKVPPECG 51

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 221330438 815 RRKgtkLHIYNDHTFIAKHLSGSGLqCSICMKSIPRRPGKQGYECRDCQLISHKQCHIRAPQACP 879
Cdd:cd20835    1 RRR---VHQVNGHKFMATYLRQPTY-CSHCKDFIWGVIGKQGYQCQVCTCVVHKRCHQLVVTKCP 61

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 820 KLHIYNDHTFIAKHLsGSGLQCSICmKSIPRRPGKQGYECRDCQLISHKQCHIRAPQACP 879
Cdd:cd20834    1 KVHEVKGHEFIAKFF-RQPTFCSVC-KEFLWGFNKQGYQCRQCNAAVHKKCHDKILGKCP 58

protein kinase C conserved region 1 (C1 domain) found in the kinase suppressor of Ras (KSR) family; KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. KSR proteins contain a SAM-like domain, a zinc finger cysteine-rich domain (C1), and a pseudokinase domain. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 221330438 827 HTFIAKHLSGSglQCSICMKSIPRrpgkqGYECRDCQLISHKQCHIRAPQAC 878
Cdd:cd20812    3 HRFSKKLFMRQ--TCDYCHKQMFF-----GLKCKDCKYKCHKKCAKKAPPSC 47

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 221330438 825 NDHTFIAKHLSGSGLqCSICMKSIpRRPGKQGYECRDCQLISHKQCHIRAPQAC 878
Cdd:cd21095    1 NGHLFQAKRFNRRAY-CGQCSERI-WGLGRQGYKCINCKLLVHKRCHKLVPLTC 52

protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) iota 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-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. Members of this family contain C1 domain found in aPKC isoform iota. 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 221330438 825 NDHTFIAKHLSGSGlQCSICMKSIpRRPGKQGYECRDCQLISHKQCHIRAPQACPNP 881
Cdd:cd21094    1 NGHTFQAKRFNRRA-HCAICTDRI-WGLGRQGYKCINCKLLVHKKCHKLVTIECGRH 55

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 221330438 826 DHTFIAKHLSgsglQ---CSICMKSIpRRPGKQGYECRDCQLISHKQCHIRAPQACPN 880
Cdd:cd20792    1 GHKFVATFFK----QptfCSHCKDFI-WGLGKQGYQCQVCRFVVHKRCHEYVVFKCPG 53

protein kinase C conserved region 1 (C1 domain) found in tensin-2 and similar proteins; Tensin-2 (TNS2), also called C1 domain-containing phosphatase and tensin (C1-TEN), or tensin-like C1 domain-containing phosphatase (TENC1), is an essential component for the maintenance of glomerular basement membrane (GBM) structures. It regulates cell motility and proliferation. It may have phosphatase activity. TNS2 reduces AKT1 phosphorylation, lowers AKT1 kinase activity, and interferes with AKT1 signaling. It contains an N-terminal region with a zinc finger (C1 domain), a protein tyrosine phosphatase (PTP)-like domain and a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 822 HIYNDHTFIAKHlsgsglQCSICMKSIprrpGKQGYECRDCQLISHKQCHIRAPQACPNP 881
Cdd:cd20887    3 HSFKEKTFKKKR------ACAVCREPV----GGQGLVCRVCKVASHKKCEAKVTSACQPP 52

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 221330438 840 QCSICMKSIpRRPGKQGYECRDCQLISHKQCHIRAPQACP 879
Cdd:cd20824   14 KCDYCGEKI-WGLSKKGLSCKDCGFNCHIKCELKVPPECP 52

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        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 221330438 827 HTFIAkHLSGSGLQCSICmKSIPRRPGKQGYECRDCQLISHKQCHIRAPQACPNPTVLSMELMASEE 893
Cdd:cd20843   12 HTFVI-HSYTRPTVCQFC-KKLLKGLFRQGLQCKDCKFNCHKRCATRVPNDCLGETLFNGDLVPMEA 76

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 360 LLVKIVKGDGIRDAQ-----NPYVVIEMDEPAQKNQTGTQRGGKPFWDEHFLFELS-PQSA---EILFEVYDHPVIASDp 430
Cdd:cd04049    3 LEVLLISAKGLQDTDflgkiDPYVIIQCRTQERKSKVAKGDGRNPEWNEKFKFTVEyPGWGgdtKLILRIMDKDNFSDD- 81

                         90       100       110
                 ....*....|....*....|....*....|...
gi 221330438 431 pKFLGLGLVGIDELAVGPASTQLLQLQPRPYET 463
Cdd:cd04049   82 -DFIGEATIHLKGLFEEGVEPGTAELVPAKYNV 113

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have type-II topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 376 PYVVIEMDEpAQKNQTGTQRGG-KPFWDEHFLFELSPQSAeILFEVYDHPVIASDPPKFLGLGLVGIDEL--AVGPASTQ 452
Cdd:cd08382   23 PFAVITVDG-GQTHSTDVAKKTlDPKWNEHFDLTVGPSSI-ITIQVFDQKKFKKKDQGFLGCVRIRANAVlpLKDTGYQR 100

                         90       100
                 ....*....|....*....|..
gi 221330438 453 LLQLQPRPYETQPVSGAITVDF 474
Cdd:cd08382  101 LDLRKLKKSDNLSVRGKIVVSL 122

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 353 HMVSGRRLLVKivkgdGIRDaqnPYVVIEMDEpAQKNQTGTQRGGKPFWDEHFLFELSPQ---SAEILFEVYDHPVIASD 429
Cdd:cd08383    5 RILEAKNLPSK-----GTRD---PYCTVSLDQ-VEVARTKTVEKLNPFWGEEFVFDDPPPdvtFFTLSFYNKDKRSKDRD 75

                         90       100
                 ....*....|....*....|....*....
gi 221330438 430 ppkfLGLGLVGIDELAVGPASTQLLQLQP 458
Cdd:cd08383   76 ----IVIGKVALSKLDLGQGKDEWFPLTP 100

protein kinase C conserved region 1 (C1 domain) found in tensin-1 (TNS1) variant and similar proteins; Tensin-1 (TNS1) plays a role in fibrillar adhesion formation. It may be involved in cell migration, cartilage development and in linking signal transduction pathways to the cytoskeleton. This model corresponds to the C1 domain found in TNS1 variant. Typical TNS1 does not contain 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 221330438 825 NDHTFIAKHLSGSGlQCSICMKSIPRrpgkQGYECRDCQLISHKQCHIRAPQACPNPT 882
Cdd:cd20888    4 HTHTFKVKTFKKVK-SCGICKQAITR----EGSTCRVCKLSCHKKCEAKVATPCVPAV 56

protein kinase C conserved region 1 (C1 domain) found in 190 kDa guanine nucleotide exchange factor (p190RhoGEF) and similar proteins; p190RhoGEF, also called Rho guanine nucleotide exchange factor (RGNEF), Rho guanine nucleotide exchange factor 28 (ARHGEF28), or RIP2, is a brain-enriched, RhoA-specific guanine nucleotide exchange factor that regulates signaling pathways downstream of integrins and growth factor receptors. It is involved in axonal branching, synapse formation and dendritic morphogenesis, as well as in focal adhesion formation, cell motility and B-lymphocytes activation. In addition to the Dbl homology (DH)-PH domain, p190RhoGEF contains an N-terminal C1 (Protein kinase C conserved region 1) 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 221330438 825 NDHTFIAKHLSGSgLQCSICMKSIPrrpGKQGYECRDCQLISHKQCHIRAPqAC 878
Cdd:cd20876    6 NGHQFVTGSFSGP-TLCVVCDKPVT---GKELLQCSNCTVNVHKGCKESAP-PC 54

protein kinase C conserved region 1 (C1 domain) found in the 190 kDa guanine nucleotide exchange factor (p190RhoGEF)-like family; The p190RhoGEF-like protein family includes p190RhoGEF, Rho guanine nucleotide exchange factor 2 (ARHGEF2), A-kinase anchor protein 13 (AKAP-13) and similar proteins. p190RhoGEF is a brain-enriched, RhoA-specific guanine nucleotide exchange factor that regulates signaling pathways downstream of integrins and growth factor receptors. It is involved in axonal branching, synapse formation and dendritic morphogenesis, as well as in focal adhesion formation, cell motility and B-lymphocytes activation. ARHGEF2 acts as a guanine nucleotide exchange factor (GEF) that activates Rho-GTPases by promoting the exchange of GDP for GTP. It is thought to play a role in actin cytoskeleton reorganization in different tissues since its activation induces formation of actin stress fibers. AKAP-13 is a scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. It activates RhoA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor. It may also activate other Rho family members. AKAP-13 plays a role in cell growth, cell development and actin fiber formation. Members of this family share a common domain architecture containing C1, RhoGEF or Dbl-homologous (DH), and Pleckstrin Homology (PH) domains. Some members may contain additional domains such as the DUF5401 domain. This model describes the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 221330438 824 YNDHTFIAKHLSGSgLQCSICMKSIprrPGKQGYECRDCQLISHK 868
Cdd:cd20815    1 KNTHQFVPVSFSNS-TKCDVCSKPL---TNKPALQCENCSVNVHD 41

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 221330438 822 HIYNDHTFIAKHLsgsglqCSICMKSIpRRPGKQGYECRDCQLISHKQCHIRAPQAC 878
Cdd:cd20808    2 HNFQETTYFKPTF------CDHCTGLL-WGLIKQGYKCKDCGINCHKHCKDLVVVEC 51

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
                 ....*....|....*....|....*....|
gi 221330438 841 CSICMKSIpRRPGKQGYECRDCQLISHKQC 870
Cdd:cd20810   16 CSVCKKLL-KGLFFQGYKCSVCGAAVHKEC 44

protein kinase C conserved region 1 (C1 domain) found in tensin-2 like (TNS2-like) proteins; The TNS2-like group includes TNS2, and variants of TNS1 and TNS3. Tensin-2 (TNS2), also called C1 domain-containing phosphatase and tensin (C1-TEN), or tensin-like C1 domain-containing phosphatase (TENC1), is an essential component for the maintenance of glomerular basement membrane (GBM) structures. It regulates cell motility and proliferation. It may have phosphatase activity. TNS2 reduces AKT1 phosphorylation, lowers AKT1 kinase activity and interferes with AKT1 signaling. Tensin-1 (TNS1) plays a role in fibrillar adhesion formation. It may be involved in cell migration, cartilage development and in linking signal transduction pathways to the cytoskeleton. Tensin-3 (TNS3), also called tensin-like SH2 domain-containing protein 1 (TENS1), or tumor endothelial marker 6 (TEM6), may play a role in actin remodeling. It is involved in the dissociation of the integrin-tensin-actin complex. Typical TNS1 and TNS3 do not contain C1 domains, but some isoforms/variants do. Members of this family contain an N-terminal region with a zinc finger (C1 domain), a protein tyrosine phosphatase (PTP)-like domain and a protein kinase 2 (C2) domain, and a C-terminal region with SH2 and pTyr binding (PTB) domains. This model corresponds to C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 221330438 826 DHTFIAKHLSGSGlQCSICMKSIPRrpgkQGYECRDCQLISHKQCHIRAPQAC 878
Cdd:cd20826    2 SHSFKEKSFRKPR-TCDVCKQIIWN----EGSSCRVCKYACHRKCEPKVTAAC 49

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 360 LLVKIVKGDGIRD-----AQNPYVVIEMDePAQKNQTG--TQRGGKPFWDEHFLF-----ELSPQSAEILFEVYDHPVIA 427
Cdd:cd04051    2 LEITIISAEDLKNvnlfgKMKVYAVVWID-PSHKQSTPvdRDGGTNPTWNETLRFplderLLQQGRLALTIEVYCERPSL 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 221330438 428 SDppKFLGLGLVGIDELAVGPAS---TQLLQLQ 457
Cdd:cd04051   81 GD--KLIGEVRVPLKDLLDGASPageLRFLSYQ 111

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 221330438 362 VKIVKGDGIRD-----AQNPYVVIeMDEpAQKNQTGTQRGGK-PFWDEHFLFELSPQSAEILFEVYDHPVIASDppkFLG 435
Cdd:cd04046    7 VHVHSAEGLSKqdsggGADPYVII-KCE-GESVRSPVQKDTLsPEFDTQAIFYRKKPRSPIKIQVWNSNLLCDE---FLG 81

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 221330438 436 LGLVGIDELAVGPASTQLLQLQPRPyETQPVSGAITVD 473
Cdd:cd04046   82 QATLSADPNDSQTLRTLPLRKRGRD-AAGEVPGTISVK 118

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 221330438 827 HTFIAkHLSGSGLQCSICmKSIPRRPGKQGYECRDCQLISHKQCHIRAPQAC 878
Cdd:cd20844    6 HTFAV-HSYTRPTICQYC-KRLLKGLFRQGMQCKDCRFNCHKRCASKVPRDC 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        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 221330438 827 HTFIAkHLSGSGLQCSICmKSIPRRPGKQGYECRDCQLISHKQCHIRAPQAC 878
Cdd:cd20842   35 HTFVI-HSYTRPTVCQYC-KKLLKGLFRQGLQCKDCKFNCHKRCAPKVPNNC 84

second protein kinase C conserved region 1 (C1 domain) found in type I diacylglycerol kinases; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. Type I DAG kinases (DGKs) contain EF-hand structures that bind Ca(2+) and recoverin homology domains, in addition to C1 and catalytic domains that are present in all DGKs. Type I DGKs, regulated by calcium binding, include three DGK isozymes (alpha, beta and gamma). DAG kinase alpha, also called 80 kDa DAG kinase, or diglyceride kinase alpha (DGK-alpha), is active upon cell stimulation, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity. DAG kinase beta, also called 90 kDa DAG kinase, or diglyceride kinase beta (DGK-beta), exhibits high phosphorylation activity for long-chain diacylglycerols. DAG kinase gamma, also called diglyceride kinase gamma (DGK-gamma), reverses the normal flow of glycerolipid biosynthesis by phosphorylating diacylglycerol back to phosphatidic acid. Members of this family contain two copies of the C1 domain. This model corresponds to the second one. DGK-alpha contains atypical C1 domains, while DGK-beta and DGK-gamma contain typical C1 domains that bind DAG and phorbol esters. 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 221330438 841 CSICMKSIPRRPGKQGYECRDCQLISHKQCHIRAPQAC 878
Cdd:cd20851   12 CDKCHKSIKSYQGLTGLHCVWCHITLHNKCASHVKPEC 49