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 1972305184 318 IKVIKASRL--GREVSQPFVNVEMDEPAQKYSTTKGIN-ANPFWEETFDFDLTPATEEILFEIYEGNDKlhmnDDEGFLG 394
Cdd:cd08678     3 VKNIKANGLseAAGSSNPYCVLEMDEPPQKYQSSTQKNtSNPFWDEHFLFELSPNSKELLFEVYDNGKK----SDSKFLG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1972305184 395 LAIVNFEEIRRSGETVHSLKLQGRPYRKDAISGEITVQFDFFYDPNLL 442
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 1972305184  56 WSNEIVSWLYSNFHKVPAPMDAWIKSLNEAAKKVTSPTkcEVLFEGFGDHSdvlQPPKISNVRVEHGPRDHLTVRSnvHL 135
Cdd:cd21664     1 WLNSVLNWIYTQYCNTPELVEAWLKALNEQARRAGSSV--QVTFERIQSGS---LPPKFTHVSTVAEPNDSLVVTC--QV 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972305184 136 PCVKLRLV--SSQRTPERMIVSNYDVSIVDLRGEVECRMACIANQLYLMGCFSGRPEMDIEL--RNTDPNAQYQVSIPMV 211
Cdd:cd21664    74 ESEGLRFQvfATQQTAQSVKLSNCDVSVTKLSGKLRCHGRTLGEELQISVSFEDRPDLKLNIkpKNGSPTAEDSVDLDVV 153

                         170
                  ....*....|....*...
gi 1972305184 212 EESIRRCLLSAVTNINLS 229
Cdd:cd21664   154 EEIVRNAIASATTTFVLP 171

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 1972305184 318 IKVIKASRL--GREVSQPFVNVEMDEPAQKYSTTKGIN-ANPFWEETFDFDLTPATEEILFEIYEGNDKlhmnDDEGFLG 394
Cdd:cd08678     3 VKNIKANGLseAAGSSNPYCVLEMDEPPQKYQSSTQKNtSNPFWDEHFLFELSPNSKELLFEVYDNGKK----SDSKFLG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1972305184 395 LAIVNFEEIRRSGETVHSLKLQGRPYRKDAISGEITVQFDFFYDPNLL 442
Cdd:cd08678    79 LAIVPFDELRKNPSGRQIFPLQGRPYEGDSVSGSITVEFLFMEPAELP 126

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 1972305184  56 WSNEIVSWLYSNFHKVPAPMDAWIKSLNEAAKKVTSPTkcEVLFEGFGDHSdvlQPPKISNVRVEHGPRDHLTVRSnvHL 135
Cdd:cd21664     1 WLNSVLNWIYTQYCNTPELVEAWLKALNEQARRAGSSV--QVTFERIQSGS---LPPKFTHVSTVAEPNDSLVVTC--QV 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972305184 136 PCVKLRLV--SSQRTPERMIVSNYDVSIVDLRGEVECRMACIANQLYLMGCFSGRPEMDIEL--RNTDPNAQYQVSIPMV 211
Cdd:cd21664    74 ESEGLRFQvfATQQTAQSVKLSNCDVSVTKLSGKLRCHGRTLGEELQISVSFEDRPDLKLNIkpKNGSPTAEDSVDLDVV 153

                         170
                  ....*....|....*...
gi 1972305184 212 EESIRRCLLSAVTNINLS 229
Cdd:cd21664   154 EEIVRNAIASATTTFVLP 171

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 1972305184  315 KMRIKVIKASRL----GREVSQPFVNVEMD-EPAQKYST-TKGINANPFWEETFDFDLT-PATEEILFEIYegnDKLHMN 387
Cdd:smart00239   1 TLTVKIISARNLppkdKGGKSDPYVKVSLDgDPKEKKKTkVVKNTLNPVWNETFEFEVPpPELAELEIEVY---DKDRFG 77

                           90       100
                   ....*....|....*....|....
gi 1972305184  388 DDEgFLGLAIVNFEEIRRSGETVH 411
Cdd:smart00239  78 RDD-FIGQVTIPLSDLLLGGRHEK 100

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 1972305184 725 HTFVAVKVKgcSGATCNVCQQRIRSsFSKQAYQCRDCKMVCHKTCHYKTDAFC 777
Cdd:pfam00130   1 HHFVHRNFK--QPTFCDHCGEFLWG-LGKQGLKCSWCKLNVHKRCHEKVPPEC 50

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 1972305184 318 IKVIKASRL--GREVSQPFVNVEMDEPAQKYSTTKGIN-ANPFWEETFDFDLTPATEEILFEIYEGNDKlhmnDDEGFLG 394
Cdd:cd08678     3 VKNIKANGLseAAGSSNPYCVLEMDEPPQKYQSSTQKNtSNPFWDEHFLFELSPNSKELLFEVYDNGKK----SDSKFLG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1972305184 395 LAIVNFEEIRRSGETVHSLKLQGRPYRKDAISGEITVQFDFFYDPNLL 442
Cdd:cd08678    79 LAIVPFDELRKNPSGRQIFPLQGRPYEGDSVSGSITVEFLFMEPAELP 126

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 1972305184  56 WSNEIVSWLYSNFHKVPAPMDAWIKSLNEAAKKVTSPTkcEVLFEGFGDHSdvlQPPKISNVRVEHGPRDHLTVRSnvHL 135
Cdd:cd21664     1 WLNSVLNWIYTQYCNTPELVEAWLKALNEQARRAGSSV--QVTFERIQSGS---LPPKFTHVSTVAEPNDSLVVTC--QV 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972305184 136 PCVKLRLV--SSQRTPERMIVSNYDVSIVDLRGEVECRMACIANQLYLMGCFSGRPEMDIEL--RNTDPNAQYQVSIPMV 211
Cdd:cd21664    74 ESEGLRFQvfATQQTAQSVKLSNCDVSVTKLSGKLRCHGRTLGEELQISVSFEDRPDLKLNIkpKNGSPTAEDSVDLDVV 153

                         170
                  ....*....|....*...
gi 1972305184 212 EESIRRCLLSAVTNINLS 229
Cdd:cd21664   154 EEIVRNAIASATTTFVLP 171

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 1972305184 725 HTFVAVKVKgcSGATCNVCQQRIRSSFsKQAYQCRDCKMVCHKTCHYKTDAFC 777
Cdd:cd00029     1 HRFVPTTFS--SPTFCDVCGKLIWGLF-KQGLKCSDCGLVCHKKCLDKAPSPC 50

C2 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972305184 314 NKMRIKVIKASRL----GREVSQPFVNVEMDEPAQKYST-TKGINANPFWEETFDFDLTPATEEIL-FEIYeGNDKLHMN 387
Cdd:pfam00168   1 GRLTVTVIEAKNLppkdGNGTSDPYVKVYLLDGKQKKKTkVVKNTLNPVWNETFTFSVPDPENAVLeIEVY-DYDRFGRD 79

                          90       100
                  ....*....|....*....|....*...
gi 1972305184 388 DdegFLGLAIVNFEEIRRSGETVHSLKL 415
Cdd:pfam00168  80 D---FIGEVRIPLSELDSGEGLDGWYPL 104

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 1972305184 717 KKLHIYNDHTFVAVKVKgcSGATCNVCQQRIRSSFSKQAYQCRDCKMVCHKTCHYKTDAFCT 778
Cdd:cd20835     2 RRVHQVNGHKFMATYLR--QPTYCSHCKDFIWGVIGKQGYQCQVCTCVVHKRCHQLVVTKCP 61

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
                  ....*....|....*....|....*....|....*....|
gi 1972305184 739 TCNVCQQRIRSsfskQAYQCRDCKMVCHKTCHYKTDAFCT 778
Cdd:cd20826    15 TCDVCKQIIWN----EGSSCRVCKYACHRKCEPKVTAACS 50

protein kinase C conserved region 1 (C1 domain) found in the atypical protein kinase C (aPKC) 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. 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. 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 one 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 1972305184 723 NDHTFVAVKVKgcSGATCNVCQQRIRSsFSKQAYQCRDCKMVCHKTCHYKTDAFCTQ 779
Cdd:cd20794     1 NGHLFQAKRFN--RRAVCAYCSDRIWG-LGRQGYKCINCKLLVHKKCHKLVKVACGQ 54

protein kinase C conserved region 1 (C1 domain) found in the unconventional myosin-IX family; Myosins IX (Myo9) is a class of unique motor proteins with a common structure of an N-terminal extension preceding a myosin head homologous to the Ras-association (RA) domain, a head (motor) domain, a neck with IQ motifs that bind light chains, and a C-terminal tail containing cysteine-rich zinc binding (C1) and Rho-GTPase activating protein (RhoGAP) domains. There are two genes for myosins IX in humans, IXa and IXb, that are different in their expression and localization. IXa is expressed abundantly in brain and testis, and IXb is expressed abundantly in tissues of the immune system. 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 1972305184 722 YNDHTFVAVKVkgcSGAT-CNVCQQRIRSSfsKQAYQCRDCKMVCHKTCHYKTDAFCTQS 780
Cdd:cd20818     1 HNGHKFATVQF---NIPTyCEVCNSFIWLM--EKGLVCQVCKFTCHKKCYSKITAPCKGN 55

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 1972305184 722 YNDHTFVAVKVKGCsgATCNVCQqriRSSFSKQAYQCRDCKMVCHK 767
Cdd:cd20815     1 KNTHQFVPVSFSNS--TKCDVCS---KPLTNKPALQCENCSVNVHD 41

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1972305184 725 HTFVAVKVkgCSGATCNVCQQRIRSsFSKQAYQCRDCKMVCHKTCHYKTDAFCTQ 779
Cdd:cd20824     2 HNFKPHSF--SIPTKCDYCGEKIWG-LSKKGLSCKDCGFNCHIKCELKVPPECPG 53

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 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-II topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972305184 313 PNKMRIKVI------KASRLGREVSQPFVNVEM----DEPAQKYSTtKGINAN---PFWEETFDFDLT-PATEEILFEIY 378
Cdd:cd00275     1 PLTLTIKIIsgqqlpKPKGDKGSIVDPYVEVEIhglpADDSAKFKT-KVVKNNgfnPVWNETFEFDVTvPELAFLRFVVY 79

                          90       100
                  ....*....|....*....|....*..
gi 1972305184 379 EGNdklhMNDDEgFLGLAIVNFEEIRR 405
Cdd:cd00275    80 DED----SGDDD-FLGQACLPLDSLRQ 101

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1972305184 715 KGKKLHIYNDHTFVAVKvkgcsgaTCNVCQQRIrssfSKQAYQCRDCKMVCHKTCHYKTDAFCT 778
Cdd:cd20888     1 EAPHTHTFKVKTFKKVK-------SCGICKQAI----TREGSTCRVCKLSCHKKCEAKVATPCV 53

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 1972305184 739 TCNVCQQRIRSSFsKQAYQCRDCKMVCHKTC 769
Cdd:cd20810    15 TCSVCKKLLKGLF-FQGYKCSVCGAAVHKEC 44

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
                  ....*....|....*....|....*....|....*....|....*
gi 1972305184 725 HTFVAVKVKGCSgaTCNVCQQRIRSSFsKQAYQCRDCKMVCHKTC 769
Cdd:cd20820     2 HRFVPLELEQPT--WCDLCGSVILGLF-RKCLRCANCKMTCHPRC 43

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1972305184 712 LMRKGKKLHIYNDHTFVAVKVkgcsgatCNVCQQRIRSSFsKQAYQCRDCKMVCHKTCHYKTDAFC 777
Cdd:cd20842    27 LLSKVKVPHTFVIHSYTRPTV-------CQYCKKLLKGLF-RQGLQCKDCKFNCHKRCAPKVPNNC 84

protein kinase C conserved region 1 (C1 domain) found in citron Rho-interacting kinase (CRIK) and similar proteins; CRIK, also called serine/threonine-protein kinase 21, is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger (C1 domain), and a pleckstrin homology (PH) domain, in addition to other motifs. 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
                  ....*....|....*....|....*....|.
gi 1972305184 740 CNVCQQRIrsSFSKQAYQCRDCKMVCHKTCH 770
Cdd:cd20814    18 CAVCLDGV--PFGRQASKCSECGIVCHPKCS 46

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
                  ....*....|....*....|....*....|....*....|....*...
gi 1972305184 723 NDHTFVAVKVKgcSGATCNVCQQRIRSsFSKQAYQCRDCKMVCHKTCH 770
Cdd:cd21095     1 NGHLFQAKRFN--RRAYCGQCSERIWG-LGRQGYKCINCKLLVHKRCH 45

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
                  ....*....|....*....|....*....|....*....|.
gi 1972305184 740 CNVCQQrIRSSFSKQAYQCRDCKMVCHKTCHYKTDAFCTQS 780
Cdd:cd20798    15 CKVCDK-LLVGLVRQGLKCRDCGVNVHKKCASLLPSNCRLS 54

DNL zinc finger; The domain is named after a short C-terminal motif of D(N/H)L. This domain is a novel zinc-finger protein essential for protein import into mitochondria.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1972305184 739 TCNVCQQRIRSSFSKQAY-------QCRDCK 762
Cdd:pfam05180   5 TCKVCNTRSTKTFSKQAYhkgvviiQCPGCK 35

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. 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 1972305184 316 MRIKVIKASRLGRE----VSQPFVNVEM------DEPAQKYSTTKGINANPFWEETFDFDLTPATEEILFEIYEGNdKLH 385
Cdd:cd04033     2 LRVKVLAGIDLAKKdifgASDPYVKISLydpdgnGEIDSVQTKTIKKTLNPKWNEEFFFRVNPREHRLLFEVFDEN-RLT 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1972305184 386 MNDDEGFLGLAIVN--FEEIRRSGETVHSLKLQGRPYRKDAISGEITVQFDF 435
Cdd:cd04033    81 RDDFLGQVEVPLNNlpTETPGNERRYTFKDYLLRPRSSKSRVKGHLRLYMAY 132

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
                  ....*....|....*....|....*....|....*...
gi 1972305184 740 CNVCQQRIRSSFsKQAYQCRDCKMVCHKTCHYKTDAFC 777
Cdd:cd20844    19 CQYCKRLLKGLF-RQGMQCKDCRFNCHKRCASKVPRDC 55

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1972305184 720 HIYNDHTFvavKVKGCsgatCNVCQQRIRSsfskQAYQCRDCKMVCHKTCHYKTDAFC 777
Cdd:cd20887     3 HSFKEKTF---KKKRA----CAVCREPVGG----QGLVCRVCKVASHKKCEAKVTSAC 49

protein kinase C conserved region 1 (C1 domain) found in uncharacterized Rho guanine nucleotide exchange factor (ARHGEF)-like proteins; The family includes a group of uncharacterized proteins that show high sequence similarity to vertebrate Rho guanine nucleotide exchange factors ARHGEF11 and ARHGEF12, which may play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Unlike typical ARHGEF11 and ARHGEF12, members of this family contain a 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
                  ....*....|....*....|....*....|
gi 1972305184 740 CNVCQqRIRSSFSKQAYQCRDCKMVCHKTC 769
Cdd:cd20832    15 CNHCS-GLLWGIGYQGYQCSDCEFNIHKQC 43

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972305184 331 SQPFVNVEM---DEPAQKYST-TKGINANPFWEETFDFDLTPATEE--ILFEIYEGnDKLHMNDdegFLG 394
Cdd:cd04026    34 SDPYVKLKLipdPKNETKQKTkTIKKTLNPVWNETFTFDLKPADKDrrLSIEVWDW-DRTTRND---FMG 99

protein kinase C conserved region 1 (C1 domain) found in the SH3 and cysteine-rich domain-containing protein (Stac) family; Stac proteins are putative adaptor proteins that are important for neuronal function. There are three mammalian members (Stac1, Stac2 and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C-terminus. Stac1 and Stac2 have been found to be expressed differently in mature dorsal root ganglia (DRG) neurons. Stac1 is mainly expressed in peptidergic neurons while Stac2 is found in a subset of nonpeptidergic and all trkB+ neurons. Stac proteins contain a cysteine-rich C1 domain and one or two SH3 domains at the C-terminus. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1972305184 720 HIYNDHTFVAVKVkgcsgatCNVCQQRIRSsFSKQAYQCRDCKMVCHKTC 769
Cdd:cd20817     1 HSFQEHTFKKPTF-------CDVCKELLVG-LSKQGLRCKNCKMNVHHKC 42

first protein kinase C conserved region 1 (C1 domain) found in type II diacylglycerol kinases; Diacylglycerol (DAG) kinase (EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol to form phosphatidic acid. Type II DAG kinases (DGKs) contain pleckstrin homology (PH) and sterile alpha motifs (SAM) domains, in addition to C1 and catalytic domains that are present in all DGKs. The SAM domain mediates oligomerization of type II DGKs. Three DGK isozymes (delta, eta and kappa) are classified as type II. DAG kinase delta, also called 130 kDa DAG kinase, or diglyceride kinase delta (DGK-delta), is a residential lipid kinase in the endoplasmic reticulum. It promotes lipogenesis and is involved in triglyceride biosynthesis. DAG kinase eta, also called diglyceride kinase eta (DGK-eta), plays a key role in promoting cell growth. The DAG kinase eta gene, DGKH, is a replicated risk gene of bipolar disorder (BPD). DAG kinase kappa is also called diglyceride kinase kappa (DGK-kappa) or 142 kDa DAG kinase. 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
                  ....*....|....*....|....*....|
gi 1972305184 740 CNVCQQRIrSSFSKQAYQCRDCKMVCHKTC 769
Cdd:cd20800    18 CNVCREAL-SGVTSHGLSCEVCKFKAHKRC 46

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        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1972305184 732 VKGCSGATCNVCQQRIRSSFSKQAYQCRDCKMVCHKTCHYKTDAFC 777
Cdd:cd20851     4 VEGNCPGKCDKCHKSIKSYQGLTGLHCVWCHITLHNKCASHVKPEC 49

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses 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. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972305184 315 KMRIKVIKASRLGRE----VSQPFVNVEMDEPAQKYSTTKGiNANPFWEETFDFDLTPATEEIL-FEIYEGnDKLHMNDd 389
Cdd:cd04025     1 RLRCHVLEARDLAPKdrngTSDPFVRVFYNGQTLETSVVKK-SCYPRWNEVFEFELMEGADSPLsVEVWDW-DLVSKND- 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1972305184 390 egFLGLAIVNFEEIRRSGETVHSLKLQGRPYRKDAISGEI 429
Cdd:cd04025    78 --FLGKVVFSIQTLQQAKQEEGWFRLLPDPRAEEESGGNL 115

protein kinase C conserved region 1 (C1 domain) found in VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. Its function has been implicated in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1972305184 720 HIYNDHTFVAVkvkgcsgATCNVCQQRIRSSFSkQAYQCRDCKMVCHKTC 769
Cdd:cd20869     9 HDFKMHTFERV-------TSCKVCQMLLRGTFY-QGYLCSKCGAGAHKEC 50