Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N1; PKN1, also called PKNalpha or Protein-kinase C-related kinase 1 (PRK1), is a serine/threonine protein kinase that is activated by the Rho family of small GTPases, and by fatty acids such as arachidonic and linoleic acids. It is expressed ubiquitously and is the most abundant PKN isoform in neurons. PKN1 is implicated in a variety of functions including cytoskeletal reorganization, cardiac cell survival, cell adhesion, and glucose transport, among others. PKN1 contains three HR1 domains, a C2 domain, and a kinase domain. This model characterizes the second HR1 domain of PKN1. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; PKN1 binds the GTPases RhoA, RhoB, and RhoC, and can also interact weakly with Rac.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 63100313 121 SATNLSRVAGLEKQLAIELKVKQGAENMIQTYSNGSTKDRKLLLTAQQMLQDSKTKIDIIRMQLRRALQAGQLENQ 196
Cdd:cd11630   3 SAANQSRIAGLEKQLNIELKVKQGAENMIQTYANGSTKDRKLLQTAQQMLQDSKTKIDIIRMQIRKAMQADELENQ 78

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 63100313 389 SEVSTVLKLDNTVVGQTSWKPCGPNAWDQSFTLELERARELELAVFWRDQRGLCALKFLKLEDFldneRHEVQLDMEPQG 468
Cdd:cd08687   9 SEVSAVLKLDNTVVGQTQWKPKSNQAWDQSFTLELERSRELEIAVYWRDWRSLCAVKFLKLEDE----RHEVQLDMEPQL 84

                ....*...
gi 63100313 469 CLVAEVTF 476
Cdd:cd08687  85 CLVAELTF 92

Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N1; PKN1, also called PKNalpha or Protein-kinase C-related kinase 1 (PRK1), is a serine/threonine protein kinase that is activated by the Rho family of small GTPases, and by fatty acids such as arachidonic and linoleic acids. It is expressed ubiquitously and is the most abundant PKN isoform in neurons. PKN1 is implicated in a variety of functions including cytoskeletal reorganization, cardiac cell survival, cell adhesion, and glucose transport, among others. PKN1 contains three HR1 domains, a C2 domain, and a kinase domain. This model characterizes the second HR1 domain of PKN1. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; PKN1 binds the GTPases RhoA, RhoB, and RhoC, and can also interact weakly with Rac.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 63100313 121 SATNLSRVAGLEKQLAIELKVKQGAENMIQTYSNGSTKDRKLLLTAQQMLQDSKTKIDIIRMQLRRALQAGQLENQ 196
Cdd:cd11630   3 SAANQSRIAGLEKQLNIELKVKQGAENMIQTYANGSTKDRKLLQTAQQMLQDSKTKIDIIRMQIRKAMQADELENQ 78

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 63100313 389 SEVSTVLKLDNTVVGQTSWKPCGPNAWDQSFTLELERARELELAVFWRDQRGLCALKFLKLEDFldneRHEVQLDMEPQG 468
Cdd:cd08687   9 SEVSAVLKLDNTVVGQTQWKPKSNQAWDQSFTLELERSRELEIAVYWRDWRSLCAVKFLKLEDE----RHEVQLDMEPQL 84

                ....*...
gi 63100313 469 CLVAEVTF 476
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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 63100313   127 RVAGLEKQLAIELKVKQGAENMIQTYSNgsTKDRKLLLTAQQMLQDSKTKIDIIRMQLRRaLQAGQLENQ 196
Cdd:pfam02185   1 RLQELRKKIEVEKKIKEGAENMLRLLQA--TKDRKVLAEAESELRESNRKIQLLREQLRE-LQARHLPSD 67

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 63100313    213 LRIEELRHHFRVEHAVAEGAKNVLRLLSAakapDRKAVSEAQEKLTESNQKLGLLREALER 273
Cdd:smart00742   1 LRLEDLRRKIEKELKVKEGAENMRKLTSN----DRKVLSEAQSMLRESNQKLDLLKEELEK 57

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
                   ....*....|....*....|....*....|....*....|....*...
gi 63100313     46 IRKELKLKEGAENLRRATTDLGRSLGPVELLLRGSSRRLDLLHQQLQE 93
Cdd:smart00742  10 IEKELKVKEGAENMRKLTSNDRKVLSEAQSMLRESNQKLDLLKEELEK 57

Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of Protein Kinase N1; PKN1, also called PKNalpha or Protein-kinase C-related kinase 1 (PRK1), is a serine/threonine protein kinase that is activated by the Rho family of small GTPases, and by fatty acids such as arachidonic and linoleic acids. It is expressed ubiquitously and is the most abundant PKN isoform in neurons. PKN1 is implicated in a variety of functions including cytoskeletal reorganization, cardiac cell survival, cell adhesion, and glucose transport, among others. PKN1 contains three HR1 domains, a C2 domain, and a kinase domain. This model characterizes the second HR1 domain of PKN1. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; PKN1 binds the GTPases RhoA, RhoB, and RhoC, and can also interact weakly with Rac.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 63100313 121 SATNLSRVAGLEKQLAIELKVKQGAENMIQTYSNGSTKDRKLLLTAQQMLQDSKTKIDIIRMQLRRALQAGQLENQ 196
Cdd:cd11630   3 SAANQSRIAGLEKQLNIELKVKQGAENMIQTYANGSTKDRKLLQTAQQMLQDSKTKIDIIRMQIRKAMQADELENQ 78

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 63100313 389 SEVSTVLKLDNTVVGQTSWKPCGPNAWDQSFTLELERARELELAVFWRDQRGLCALKFLKLEDFldneRHEVQLDMEPQG 468
Cdd:cd08687   9 SEVSAVLKLDNTVVGQTQWKPKSNQAWDQSFTLELERSRELEIAVYWRDWRSLCAVKFLKLEDE----RHEVQLDMEPQL 84

                ....*...
gi 63100313 469 CLVAEVTF 476
Cdd:cd08687  85 CLVAELTF 92

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 63100313 119 TCSATNLSRVAGLEKQLAIELKVKQGAENMIQTYSNGSTKDRKLLLTAQQMLQDSKTKIDIIRMQLRRALQ 189
Cdd:cd11631   2 TRMSTNNNRLMALKKQLDIELKVKQGAENMIQMYSNGSSKDRKLLATAQQMLQDSKTKIEVIRMQILQAVQ 72

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 63100313 127 RVAGLEKQLAIELKVKQGAENMIQTYSNGSTKDRKLLLTAQQMLQDSKTKIDIIRMQLRRALQAG 191
Cdd:cd11632  10 RLEALKRQLHVELKVKQGAENMIQTYSSGTSKERKLLATAQQMLQDSRTKIELLRMQIVKLEQSG 74

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 63100313 208 LGAVELRIEELRHHFRVEHAVAEGAKNVLRLLSAAKAPDRKAVSEAQEKLTESNQKLGLLREALERRLGEL 278
Cdd:cd11637   4 MSAPELRVEELRHHLRIEAAVAEGAKNVVKLLGGRRFQDRKILAEAQARLQESSQKIDLLRLSLERCLAAL 74

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 63100313   127 RVAGLEKQLAIELKVKQGAENMIQTYSNgsTKDRKLLLTAQQMLQDSKTKIDIIRMQLRRaLQAGQLENQ 196
Cdd:pfam02185   1 RLQELRKKIEVEKKIKEGAENMLRLLQA--TKDRKVLAEAESELRESNRKIQLLREQLRE-LQARHLPSD 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 63100313 122 ATNLSRVAGLEKQLAIELKVKQGAENMIQTYSNGstKDRKLLLTAQQMLQDSKTKIDIIRMQLRRALQA 190
Cdd:cd00089   1 SKLQQRLEELRRKLEKELKIREGAENLLKLYSNP--KVKKDLAEVQLNLKESKEKIDLLKRQLERYNAL 67

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 63100313    126 SRVAGLEKQLAIELKVKQGAENMIQTYSNgstkDRKLLLTAQQMLQDSKTKIDIIRMQLRR 186
Cdd:smart00742   1 LRLEDLRRKIEKELKVKEGAENMRKLTSN----DRKVLSEAQSMLRESNQKLDLLKEELEK 57

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
                ....*....|....*....|....*....|....*....|....*....|....*
gi 63100313  46 IRKELKLKEGAENLRRATTDLG--RSLGPVELLLRGSSRRLDLLHQQLQELHAHV 98
Cdd:cd00089  14 LEKELKIREGAENLLKLYSNPKvkKDLAEVQLNLKESKEKIDLLKRQLERYNALV 68

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 63100313    46 IRKELKLKEGAENLRR---ATTDLgRSLGPVELLLRGSSRRLDLLHQQLQELHAHVVLPD 102
Cdd:pfam02185   9 IEVEKKIKEGAENMLRllqATKDR-KVLAEAESELRESNRKIQLLREQLRELQARHLPSD 67

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 63100313 122 ATNLSRVAGLEKQLAIELKVKQGAENMIQTYSNGSTKDRKLL-LTAQQMLQDSKTKIDIIRMQLRRALQ 189
Cdd:cd11627   1 LVSEQRLEELRGKLEIETKIKDGAENLLQVLDSKNAKEKKDQrARVESELNSSNRKIAQLTSQLEEEIQ 69

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. 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-II topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 63100313 395 LKLDNTVVGQTSWKP--CGPnAWDQSFTLELERARELELAVFWRDQRGL------CALKFlklEDFLDNERH--EVQLDM 464
Cdd:cd04014  41 IDVDDTHIGKTSTKPktNSP-VWNEEFTTEVHNGRNLELTVFHDAAIGPddfvanCTISF---EDLIQRGSGsfDLWVDL 116

                ....
gi 63100313 465 EPQG 468
Cdd:cd04014 117 EPQG 120

Second Protein kinase C-related kinase homology region 1 (HR1) Rho-binding domain of fungal Protein Kinase C-like proteins; This subfamily is composed of fungal PKC-like proteins including Pkc1p from Saccharomyces cerevisiae, and Pck1p and Pck2p from Schizosaccharomyces pombe. The yeast PKC-like proteins play a critical role in regulating cell wall biosynthesis and maintaining cell wall integrity. They contain two HR1 domains, C2 and C1 domains, and a kinase domain. This model characterizes the second HR1 domain. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family. The HR1 domains of Pck1p and Pck2p interact with GTP-bound Rho1p and Rho2p.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 63100313 206 PDLGA-VELRIEELRHHFRVEHAVAEGAKNVLRLLSAAkaPDRKAVSEAQEKLTESNQKLGLLREALER 273
Cdd:cd11620   1 PLTGAkIQRMLQQLEFKLQVEKQYKEGIEKMARLYQAE--GDKRSIADAENKRVESEQKIQLLKKALKR 67

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 63100313 118 PTCSATNLsRVAGLEKQLAIELKVKQGAENMIQTYSNGSTKDRKLLLTAQQMLQDSKTKIDIIRMQLRRAL 188
Cdd:cd11635   2 PVISPLEL-RMEELRHHFRIESAVAEGAKNVMKLLGSGKVTDRKALSEAQARFNESSQKLDLLKYSLEQRL 71

First 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 first 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 63100313 131 LEKQLAIELKVKQGAENMIQtysngSTKDRKLLLTAQQMLQDSKTKIDiirmQLRRALQA 190
Cdd:cd11622  11 IRREIRKELKIKEGAENLRK-----ATTDKKSLAHVESILKKSNRKLE----DLHQELQE 61

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.

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gi 63100313 212 ELRIEELRHHFRVEHAVAEGAKNVLRLLSAAKAPDRK-AVSEAQEKLTESNQKLGLLREALER 273
Cdd:cd11627   4 EQRLEELRGKLEIETKIKDGAENLLQVLDSKNAKEKKdQRARVESELNSSNRKIAQLTSQLEE 66