C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. 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 1886102597  686 PQIHVGFLLDSASECLLVNVFQLKNFAELVMKEDCKIHIRVYFLPVSSGTLNSYCSKALEFQSPLIFNEIFRIPVHSSML 765
Cdd:cd08680      1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1886102597  766 TLKSLQLYVCSVSQQLQEELLGIAHINLADYDGSSEMQLRWYAL 809
Cdd:cd08680     81 YQKTLQVDVCSVGPDQQEECLGGAQISLADFESSEEMSTKWYNL 124

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.

                           10        20        30
                   ....*....|....*....|....*....|
gi 1886102597   68 LPLGWETVYDKQIGIYYMDHIKKLTQIEDP 97
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30

Type IV pilus assembly protein PilN [Cell motility, Extracellular structures];

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1886102597  318 LNWQYEEARKRVSTIQQQLAQLDKEswpgLGEADrdrlQLLKEKEALLQELQLI--IQQRRPV 378
Cdd:COG3166     43 LQGQIAQQQARNAALQQEIAKLDKQ----IAEIK----ELKKQKAELLARLQVIeqLQQSRPP 97

C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. 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 1886102597  686 PQIHVGFLLDSASECLLVNVFQLKNFAELVMKEDCKIHIRVYFLPVSSGTLNSYCSKALEFQSPLIFNEIFRIPVHSSML 765
Cdd:cd08680      1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1886102597  766 TLKSLQLYVCSVSQQLQEELLGIAHINLADYDGSSEMQLRWYAL 809
Cdd:cd08680     81 YQKTLQVDVCSVGPDQQEECLGGAQISLADFESSEEMSTKWYNL 124

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

                            10        20        30
                    ....*....|....*....|....*....|...
gi 1886102597    20 PLPAGWEEACDYDGRVFYIDHNTRQTSWIDPRD 52
Cdd:smart00456    1 PLPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.

                           10        20        30
                   ....*....|....*....|....*....|
gi 1886102597   68 LPLGWETVYDKQIGIYYMDHIKKLTQIEDP 97
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 1886102597   69 PLGWETVYDKQIGIYYMDHIKKLTQIEDPRE 99
Cdd:cd00201      1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1886102597  172 QIKAEIATHRDRLSRLKRELTQMKQELQYKEKGVETLQE-IDR---KMSSAHTTyklDEAQAIMSELRTIKKAICTGEKE 247
Cdd:COG1579     35 ELEDELAALEARLEAAKTELEDLEKEIKRLELEIEEVEArIKKyeeQLGNVRNN---KEYEALQKEIESLKRRISDLEDE 111

                   ....*
gi 1886102597  248 RWDLM 252
Cdd:COG1579    112 ILELM 116

C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. 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 1886102597  686 PQIHVGFLLDSASECLLVNVFQLKNFAELVMKEDCKIHIRVYFLPVSSGTLNSYCSKALEFQSPLIFNEIFRIPVHSSML 765
Cdd:cd08680      1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1886102597  766 TLKSLQLYVCSVSQQLQEELLGIAHINLADYDGSSEMQLRWYAL 809
Cdd:cd08680     81 YQKTLQVDVCSVGPDQQEECLGGAQISLADFESSEEMSTKWYNL 124

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

                            10        20        30
                    ....*....|....*....|....*....|...
gi 1886102597    20 PLPAGWEEACDYDGRVFYIDHNTRQTSWIDPRD 52
Cdd:smart00456    1 PLPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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 first C2 repeat, C2A, and has a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1886102597  695 DSASECLLVNVFQLKNFAEL-VMKEDCKIHIRVYFLP-----------VSSGTLNsycskalefqsPlIFNEIFRIPVHS 762
Cdd:cd08521     10 NYKTGSLEVHIKECRNLAYAdEKKKRSNPYVKVYLLPdkskqskrktsVKKNTTN-----------P-VFNETLKYHISK 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1886102597  763 SMLTLKSLQLYVCSVSQQLQEELLGIAHINLADYDGSSeMQLRWYAL 809
Cdd:cd08521     78 SQLETRTLQLSVWHHDRFGRNTFLGEVEIPLDSWDLDS-QQSEWYPL 123

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

                            10        20        30
                    ....*....|....*....|....*....|..
gi 1886102597    68 LPLGWETVYDKQIGIYYMDHIKKLTQIEDPRE 99
Cdd:smart00456    2 LPPGWEERKDPDGRPYYYNHETKETQWEKPRE 33

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 1886102597   69 PLGWETVYDKQIGIYYMDHIKKLTQIEDPRE 99
Cdd:cd00201      1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

Predicted nucleic acid-binding protein DR0291, contains C4-type Zn-ribbon domain [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1886102597  172 QIKAEIATHRDRLSRLKRELTQMKQELQYKEKGVETLQE-IDR---KMSSAHTTyklDEAQAIMSELRTIKKAICTGEKE 247
Cdd:COG1579     35 ELEDELAALEARLEAAKTELEDLEKEIKRLELEIEEVEArIKKyeeQLGNVRNN---KEYEALQKEIESLKRRISDLEDE 111

                   ....*
gi 1886102597  248 RWDLM 252
Cdd:COG1579    112 ILELM 116