Protein kinase C-related kinase homology region 1 (HR1) domain that binds Rho family small GTPases; The HR1 domain, also called the ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. It is found in Rho effector proteins including PKC-related kinases such as vertebrate PRK1 (or PKN) and yeast PKC1 protein kinases C, as well as in rhophilins and Rho-associated kinase (ROCK). Rho family members function as molecular switches, cycling between inactive and active forms, controlling a variety of cellular processes. HR1 domains may occur in repeat arrangements (PKN contains three HR1 domains), separated by a short linker region.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958761131  95 PRAEQSRARLLEALHRQLEVELKVKQGAENMIHTCASGTPKERKLLAAAQQMLKDSQLKVALLRMKISGLEASG 168
Cdd:cd11632     1 EWATDPRARRLEALKRQLHVELKVKQGAENMIQTYSSGTSKERKLLATAQQMLQDSRTKIELLRMQIVKLEQSG 74

C2 domain; 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 1958761131 326 SEVLAVLKVDNRVVGQTGWGLVAEKSWDQAFSISLDRARELEIGVHWRDWRQLCGVAFLKLEEFLdnacHQLSLSLVPQG 405
Cdd:cd08687     9 SEVSAVLKLDNTVVGQTQWKPKSNQAWDQSFTLELERSRELEIAVYWRDWRSLCAVKFLKLEDER----HEVQLDMEPQL 84

                  ....*...
gi 1958761131 406 RLFAQVTF 413
Cdd:cd08687    85 CLVAELTF 92

EBNA-3B; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958761131 461 PPCSSPSTVSPPKGCPSAAaceTSSSASPSNFRPVKTLPGEDMKPPPKPPRLYLQEPAPGTPCTKRPHMDPRTGVAPPLA 540
Cdd:PHA03378  716 RPAAATGRARPPAAAPGRA---RPPAAAPGRARPPAAAPGRARPPAAAPGRARPPAAAPGAPTPQPPPQAPPAPQQRPRG 792

                          90       100
                  ....*....|....*....|
gi 1958761131 541 ALSTRCGDSLGPSSLAGTPP 560
Cdd:PHA03378  793 APTPQPPPQAGPTSMQLMPR 812

Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N3; PKN3, also called PKNbeta, is a serine/threonine protein kinase that is activated by the Rho family of small GTPases, preferentially by RhoC. Both PKN1 and RhoC show limited and barely detectable expression in normal tissues, but are both upregulated in cancer cells, particularly in late-stage malignancies. PKN3 has been implicated to play a role in the metastatic growth and invasiveness of cancer cells, downstream of the oncogenic phosphoinositide 3-kinase signaling network. PKN3 shares a common domain architecture with other PKNs, containing three HR1 domains, a C2 domain, and a kinase domain. In addition, PKN3 contains two proline-rich regions between its C2 and kinase domains, and has been shown to associate with SH3 domain containing proteins like GRAFs, GAP for RhoA, and Cdc42Hs. This model characterizes the second HR1 domain of PKN3. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; PKN3 binds Rho family GTPases, preferentially RhoC.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958761131  95 PRAEQSRARLLEALHRQLEVELKVKQGAENMIHTCASGTPKERKLLAAAQQMLKDSQLKVALLRMKISGLEASG 168
Cdd:cd11632     1 EWATDPRARRLEALKRQLHVELKVKQGAENMIQTYSSGTSKERKLLATAQQMLQDSRTKIELLRMQIVKLEQSG 74

C2 domain in Protein kinase C-like (PKN) proteins; PKN is a lipid-activated serine/threonine kinase. It is a member of the protein kinase C (PKC) superfamily, but lacks a C1 domain. There are at least 3 different isoforms of PKN (PRK1/PKNalpha/PAK1; PKNbeta, and PRK2/PAK2/PKNgamma). The C-terminal region contains the Ser/Thr type protein kinase domain, while the N-terminal region of PKN contains three antiparallel coiled-coil (ACC) finger domains which are relatively rich in charged residues and contain a leucine zipper-like sequence. These domains binds to the small GTPase RhoA. Following these domains is a C2-like domain. Its C-terminal part functions as an auto-inhibitory region. PKNs are not activated by classical PKC activators such as diacylglycerol, phorbol ester or Ca2+, but instead are activated by phospholipids and unsaturated fatty acids. 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 1958761131 326 SEVLAVLKVDNRVVGQTGWGLVAEKSWDQAFSISLDRARELEIGVHWRDWRQLCGVAFLKLEEFLdnacHQLSLSLVPQG 405
Cdd:cd08687     9 SEVSAVLKLDNTVVGQTQWKPKSNQAWDQSFTLELERSRELEIAVYWRDWRSLCAVKFLKLEDER----HEVQLDMEPQL 84

                  ....*...
gi 1958761131 406 RLFAQVTF 413
Cdd:cd08687    85 CLVAELTF 92

Hr1 repeat; The HR1 repeat was first described as a three times repeated homology region of the N-terminal non-catalytic part of protein kinase PRK1(PKN). The first two of these repeats were later shown to bind the small G protein rho known to activate PKN in its GTP-bound form. Similar rho-binding domains also occur in a number of other protein kinases and in the rho-binding proteins rhophilin and rhotekin. Recently, the structure of the N-terminal HR1 repeat complexed with RhoA has been determined by X-ray crystallography. It forms an antiparallel coiled-coil fold termed an ACC finger.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958761131 105 LEALHRQLEVELKVKQGAENMIHTCASgtPKERKLLAAAQQMLKDSQLKVALLRMKISGLEAS 167
Cdd:pfam02185   2 LQELRKKIEVEKKIKEGAENMLRLLQA--TKDRKVLAEAESELRESNRKIQLLREQLRELQAR 62

Rho effector or protein kinase C-related kinase homology region 1 homologues; Alpha-helical domain found in vertebrate PRK1 and yeast PKC1 protein kinases C. The HR1 in rhophilin bind RhoGTP; those in PRK1 bind RhoA and RhoB. Also called RBD - Rho-binding domain

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958761131  103 RLLEALHRQLEVELKVKQGAENMIHTcasgTPKERKLLAAAQQMLKDSQLKVALLRMKI 161
Cdd:smart00742   1 LRLEDLRRKIEKELKVKEGAENMRKL----TSNDRKVLSEAQSMLRESNQKLDLLKEEL 55

Hr1 repeat; The HR1 repeat was first described as a three times repeated homology region of the N-terminal non-catalytic part of protein kinase PRK1(PKN). The first two of these repeats were later shown to bind the small G protein rho known to activate PKN in its GTP-bound form. Similar rho-binding domains also occur in a number of other protein kinases and in the rho-binding proteins rhophilin and rhotekin. Recently, the structure of the N-terminal HR1 repeat complexed with RhoA has been determined by X-ray crystallography. It forms an antiparallel coiled-coil fold termed an ACC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1958761131 179 EELQHRLRIEAAVAAGAKNVVKLLggQRIQDRKALAEAQAQLQESSQK 226
Cdd:pfam02185   3 QELRKKIEVEKKIKEGAENMLRLL--QATKDRKVLAEAESELRESNRK 48

EBNA-3B; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958761131 461 PPCSSPSTVSPPKGCPSAAaceTSSSASPSNFRPVKTLPGEDMKPPPKPPRLYLQEPAPGTPCTKRPHMDPRTGVAPPLA 540
Cdd:PHA03378  716 RPAAATGRARPPAAAPGRA---RPPAAAPGRARPPAAAPGRARPPAAAPGRARPPAAAPGAPTPQPPPQAPPAPQQRPRG 792

                          90       100
                  ....*....|....*....|
gi 1958761131 541 ALSTRCGDSLGPSSLAGTPP 560
Cdd:PHA03378  793 APTPQPPPQAGPTSMQLMPR 812

Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N3; PKN3, also called PKNbeta, is a serine/threonine protein kinase that is activated by the Rho family of small GTPases, preferentially by RhoC. Both PKN1 and RhoC show limited and barely detectable expression in normal tissues, but are both upregulated in cancer cells, particularly in late-stage malignancies. PKN3 has been implicated to play a role in the metastatic growth and invasiveness of cancer cells, downstream of the oncogenic phosphoinositide 3-kinase signaling network. PKN3 shares a common domain architecture with other PKNs, containing three HR1 domains, a C2 domain, and a kinase domain. In addition, PKN3 contains two proline-rich regions between its C2 and kinase domains, and has been shown to associate with SH3 domain containing proteins like GRAFs, GAP for RhoA, and Cdc42Hs. This model characterizes the second HR1 domain of PKN3. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; PKN3 binds Rho family GTPases, preferentially RhoC.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958761131  95 PRAEQSRARLLEALHRQLEVELKVKQGAENMIHTCASGTPKERKLLAAAQQMLKDSQLKVALLRMKISGLEASG 168
Cdd:cd11632     1 EWATDPRARRLEALKRQLHVELKVKQGAENMIQTYSSGTSKERKLLATAQQMLQDSRTKIELLRMQIVKLEQSG 74

C2 domain in Protein kinase C-like (PKN) proteins; PKN is a lipid-activated serine/threonine kinase. It is a member of the protein kinase C (PKC) superfamily, but lacks a C1 domain. There are at least 3 different isoforms of PKN (PRK1/PKNalpha/PAK1; PKNbeta, and PRK2/PAK2/PKNgamma). The C-terminal region contains the Ser/Thr type protein kinase domain, while the N-terminal region of PKN contains three antiparallel coiled-coil (ACC) finger domains which are relatively rich in charged residues and contain a leucine zipper-like sequence. These domains binds to the small GTPase RhoA. Following these domains is a C2-like domain. Its C-terminal part functions as an auto-inhibitory region. PKNs are not activated by classical PKC activators such as diacylglycerol, phorbol ester or Ca2+, but instead are activated by phospholipids and unsaturated fatty acids. 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 1958761131 326 SEVLAVLKVDNRVVGQTGWGLVAEKSWDQAFSISLDRARELEIGVHWRDWRQLCGVAFLKLEEFLdnacHQLSLSLVPQG 405
Cdd:cd08687     9 SEVSAVLKLDNTVVGQTQWKPKSNQAWDQSFTLELERSRELEIAVYWRDWRSLCAVKFLKLEDER----HEVQLDMEPQL 84

                  ....*...
gi 1958761131 406 RLFAQVTF 413
Cdd:cd08687    85 CLVAELTF 92

Third Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N3; PKN3, also called PKNbeta, is a serine/threonine protein kinase that is activated by the Rho family of small GTPases, preferentially by RhoC. Both PKN1 and RhoC show limited and barely detectable expression in normal tissues, but are both upregulated in cancer cells, particularly in late-stage malignancies. PKN3 has been implicated to play a role in the metastatic growth and invasiveness of cancer cells, downstream of the oncogenic phosphoinositide 3-kinase signaling network. PKN3 shares a common domain architecture with other PKNs, containing three HR1 domains, a C2 domain, and a kinase domain. In addition, PKN3 contains two proline-rich regions between its C2 and kinase domains, and has been shown to associate with SH3 domain containing proteins like GRAFs, GAP for RhoA, and Cdc42Hs. This model characterizes the third HR1 domain of PKN3. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; PKN3 binds Rho family GTPases, preferentially RhoC.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958761131 168 GSPEPGPDLLAEELQHRLRIEAAVAAGAKNVVKLLGGQRIQDRKALAEAQAQLQESSQK 226
Cdd:cd11637     1 GRPMSAPELRVEELRHHLRIEAAVAEGAKNVVKLLGGRRFQDRKILAEAQARLQESSQK 59

Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N2; PKN2, also called PKNgamma or Protein-kinase C-related kinase 2 (PRK2), is a serine/threonine protein kinase and an effector of the small GTPase Rho/Rac. It regulates G2/M cell cycle progression and the exit from cytokinesis. It also phosphorylates hepatitis C virus (HCV) RNA polymerase and thus, plays a role in HCV RNA replication. PKN2 shares a common domain architecture with other PKNs, containing three HR1 domains, a C2 domain, and a kinase domain. In addition, PKN2 contains a proline-rich region in between its C2 and kinase domains and has been shown to associate with SH3 domain containing proteins like NCK and Grb4. This model characterizes the second HR1 domain of PKN2. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; PKN2 specifically binds to RhoA GTPase in a GTP-dependent manner. The HR1 domains of PKN2, together with its C2 domain, also facilitate the recruitment of PKN2 to primordial junctions at nascent cell-cell contacts, where it promotes junctional maturation.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958761131  96 RAEQSRARLLEALHRQLEVELKVKQGAENMIHTCASGTPKERKLLAAAQQMLKDSQLKVALLRMKIsgLEAS 167
Cdd:cd11631     2 TRMSTNNNRLMALKKQLDIELKVKQGAENMIQMYSNGSSKDRKLLATAQQMLQDSKTKIEVIRMQI--LQAV 71

Third Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N2; PKN2, also called PKNgamma or Protein-kinase C-related kinase 2 (PRK2), is a serine/threonine protein kinase and an effector of the small GTPase Rho/Rac. It regulates G2/M cell cycle progression and the exit from cytokinesis. It also phosphorylates hepatitis C virus (HCV) RNA polymerase and thus, plays a role in HCV RNA replication. PKN2 shares a common domain architecture with other PKNs, containing three HR1 domains, a C2 domain, and a kinase domain. In addition, PKN2 contains a proline-rich region in between its C2 and kinase domains and has been shown to associate with SH3 domain containing proteins like NCK and Grb4. This model characterizes the third HR1 domain of PKN2. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; PKN2 specifically binds to RhoA GTPase in a GTP-dependent manner. The HR1 domains of PKN2, together with its C2 domain, also facilitate the recruitment of PKN2 to primordial junctions at nascent cell-cell contacts, where it promotes junctional maturation.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958761131 175 DLLAEELQHRLRIEAAVAAGAKNVVKLLGGQRIQDRKALAEAQAQLQESSQK 226
Cdd:cd11635     8 ELRMEELRHHFRIESAVAEGAKNVMKLLGSGKVTDRKALSEAQARFNESSQK 59

Hr1 repeat; The HR1 repeat was first described as a three times repeated homology region of the N-terminal non-catalytic part of protein kinase PRK1(PKN). The first two of these repeats were later shown to bind the small G protein rho known to activate PKN in its GTP-bound form. Similar rho-binding domains also occur in a number of other protein kinases and in the rho-binding proteins rhophilin and rhotekin. Recently, the structure of the N-terminal HR1 repeat complexed with RhoA has been determined by X-ray crystallography. It forms an antiparallel coiled-coil fold termed an ACC finger.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958761131 105 LEALHRQLEVELKVKQGAENMIHTCASgtPKERKLLAAAQQMLKDSQLKVALLRMKISGLEAS 167
Cdd:pfam02185   2 LQELRKKIEVEKKIKEGAENMLRLLQA--TKDRKVLAEAESELRESNRKIQLLREQLRELQAR 62

Rho effector or protein kinase C-related kinase homology region 1 homologues; Alpha-helical domain found in vertebrate PRK1 and yeast PKC1 protein kinases C. The HR1 in rhophilin bind RhoGTP; those in PRK1 bind RhoA and RhoB. Also called RBD - Rho-binding domain

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958761131  103 RLLEALHRQLEVELKVKQGAENMIHTcasgTPKERKLLAAAQQMLKDSQLKVALLRMKI 161
Cdd:smart00742   1 LRLEDLRRKIEKELKVKEGAENMRKL----TSNDRKVLSEAQSMLRESNQKLDLLKEEL 55

Protein kinase C-related kinase homology region 1 (HR1) domain that binds Rho family small GTPases; The HR1 domain, also called the ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. It is found in Rho effector proteins including PKC-related kinases such as vertebrate PRK1 (or PKN) and yeast PKC1 protein kinases C, as well as in rhophilins and Rho-associated kinase (ROCK). Rho family members function as molecular switches, cycling between inactive and active forms, controlling a variety of cellular processes. HR1 domains may occur in repeat arrangements (PKN contains three HR1 domains), separated by a short linker region.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958761131 104 LLEALHRQLEVELKVKQGAENMIHTcaSGTPKERKLLAAAQQMLKDSQLKVALLRMKISGLEAS 167
Cdd:cd00089     6 RLEELRRKLEKELKIREGAENLLKL--YSNPKVKKDLAEVQLNLKESKEKIDLLKRQLERYNAL 67

Protein kinase C-related kinase homology region 1 (HR1) domain that binds Rho family small GTPases; The HR1 domain, also called the ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. It is found in Rho effector proteins including PKC-related kinases such as vertebrate PRK1 (or PKN) and yeast PKC1 protein kinases C, as well as in rhophilins and Rho-associated kinase (ROCK). Rho family members function as molecular switches, cycling between inactive and active forms, controlling a variety of cellular processes. HR1 domains may occur in repeat arrangements (PKN contains three HR1 domains), separated by a short linker region.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958761131  17 PEDEKEMIRRAIQKELKIKEGMENMRRVATD---RRHLGHVQQLLRASNRRLEQLHGELRELHAQV 79
Cdd:cd00089     3 LQQRLEELRRKLEKELKIREGAENLLKLYSNpkvKKDLAEVQLNLKESKEKIDLLKRQLERYNALV 68

Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Schizosaccharomyces pombe Ste20-like proteins; This group is composed of predominantly uncharacterized fungal proteins, which contain two known domains: HR1 at the N-terminal region and REM (Ras exchanger motif) at the C-terminal region. One member protein from Schizosaccharomyces pombe is named Ste16 while its gene is called ste20 (a target of rapamycin complex 2 subunit). It is a subunit in the protein kinase TOR complexes in fission yeast. The REM domain is usually found in nucleotide exchange factors for Ras-like small GTPases. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958761131 100 SRARLLEALHRQLEVELKVKQGAENMIHTCASGTPKERKLL-AAAQQMLKDSQLKVALLRMKI 161
Cdd:cd11627     2 VSEQRLEELRGKLEIETKIKDGAENLLQVLDSKNAKEKKDQrARVESELNSSNRKIAQLTSQL 64

Third Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N; PKN, also called Protein-kinase C-related kinase (PRK), is a serine/threonine protein kinase that can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytoskeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. In some vertebrates, there are three PKN isoforms from different genes (designated PKN1, PKN2, and PKN3), which show different enzymatic properties, tissue distribution, and varied functions. PKN proteins contain three HR1 domains, a C2 domain, and a kinase domain. This model characterizes the third HR1 domain of PKN. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958761131 100 SRARLLEALHRqLEVELKVKQGAENMIHTCASGTPKERKLLAAAQQMLKDSQLKVALLRM 159
Cdd:cd11625     7 LELRIEELRHH-LRVETAVVEGAKNVIKLLQNAKKDDKKALQEAQKSLSESSQKLDLLRL 65

Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N2; PKN2, also called PKNgamma or Protein-kinase C-related kinase 2 (PRK2), is a serine/threonine protein kinase and an effector of the small GTPase Rho/Rac. It regulates G2/M cell cycle progression and the exit from cytokinesis. It also phosphorylates hepatitis C virus (HCV) RNA polymerase and thus, plays a role in HCV RNA replication. PKN2 shares a common domain architecture with other PKNs, containing three HR1 domains, a C2 domain, and a kinase domain. In addition, PKN2 contains a proline-rich region in between its C2 and kinase domains and has been shown to associate with SH3 domain containing proteins like NCK and Grb4. This model characterizes the second HR1 domain of PKN2. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; PKN2 specifically binds to RhoA GTPase in a GTP-dependent manner. The HR1 domains of PKN2, together with its C2 domain, also facilitate the recruitment of PKN2 to primordial junctions at nascent cell-cell contacts, where it promotes junctional maturation.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1958761131 181 LQHRLRIEAAVAAGAKNVVKLLGGQRIQDRKALAEAQAQLQESSQK 226
Cdd:cd11631    14 LKKQLDIELKVKQGAENMIQMYSNGSSKDRKLLATAQQMLQDSKTK 59

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. 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-II topology.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958761131 352 WDQAFSISLDRARELEIGVHWRDWR-----QLCGVAFLKLE--EFLDNAC-HQLSLSLVPQGRLFAQVT 412
Cdd:cd04043    51 WDEEFELEVPAGEPLWISATVWDRSfvgkhDLCGRASLKLDpkRFGDDGLpREIWLDLDTQGRLLLRVS 119

EBNA-3B; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958761131 461 PPCSSPSTVSPPKGCPSAAaceTSSSASPSNFRPVKTLPGEDMKPPPKPPRLYLQEPAPGTPCTKRPHMDPRTGVAPPLA 540
Cdd:PHA03378  716 RPAAATGRARPPAAAPGRA---RPPAAAPGRARPPAAAPGRARPPAAAPGRARPPAAAPGAPTPQPPPQAPPAPQQRPRG 792

                          90       100
                  ....*....|....*....|
gi 1958761131 541 ALSTRCGDSLGPSSLAGTPP 560
Cdd:PHA03378  793 APTPQPPPQAGPTSMQLMPR 812