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 2088747460  727 PQIHVGLLRDSGSECLLVHVLQLKNPAGLAVKEDCKVHIRVYLPPLDSGTPNTYCSKALEFQVPLVFNEVFRIPVHSSAL 806
Cdd:cd08680      1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2088747460  807 TLKSLQLYVCSVTPQLQEELLGIAQINLADYDSLSEMQLRWHSV 850
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 2088747460  109 LPLGWETVYDKQIGVYYMDHINKLTQIEDP 138
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30

Tho complex subunit 7; The Tho complex is involved in transcription elongation and mRNA export from the nucleus.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088747460  127 DHINK---LTQIEDPREQwrREQERMLKEYLIVAQEALNAKKEIYQIKQQ------RFELAQEEYQQLHKMCEDDSRSYA 197
Cdd:pfam05615    1 DELIKrrlLNDGLGLGEE--RPLKRLTKRFLKLCNSLDSTPEEIQALREDllldlaAFELSIEKSQLLAEANERERENYE 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2088747460  198 SsfsgystntkyDPHQIKAEIASRRDRLSRLKRELTQMKQELQYKEK 244
Cdd:pfam05615   79 A-----------EKEEIEEEIEAVREEIEELKERLEEAKRTRKNREE 114

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 2088747460  727 PQIHVGLLRDSGSECLLVHVLQLKNPAGLAVKEDCKVHIRVYLPPLDSGTPNTYCSKALEFQVPLVFNEVFRIPVHSSAL 806
Cdd:cd08680      1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2088747460  807 TLKSLQLYVCSVTPQLQEELLGIAQINLADYDSLSEMQLRWHSV 850
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 2088747460    61 PLPAGWEEARDYDGRVFYIDHNTRQTSWIDPRD 93
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 2088747460  109 LPLGWETVYDKQIGVYYMDHINKLTQIEDP 138
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 2088747460  110 PLGWETVYDKQIGVYYMDHINKLTQIEDPRE 140
Cdd:cd00201      1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

Tho complex subunit 7; The Tho complex is involved in transcription elongation and mRNA export from the nucleus.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088747460  127 DHINK---LTQIEDPREQwrREQERMLKEYLIVAQEALNAKKEIYQIKQQ------RFELAQEEYQQLHKMCEDDSRSYA 197
Cdd:pfam05615    1 DELIKrrlLNDGLGLGEE--RPLKRLTKRFLKLCNSLDSTPEEIQALREDllldlaAFELSIEKSQLLAEANERERENYE 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2088747460  198 SsfsgystntkyDPHQIKAEIASRRDRLSRLKRELTQMKQELQYKEK 244
Cdd:pfam05615   79 A-----------EKEEIEEEIEAVREEIEELKERLEEAKRTRKNREE 114

N-terminal C2 in EEIG1 and EHBP1 proteins; This version of the C2 domain was initally identified in the vertebrate estrogen early-induced gene 1 (EEIG1), and its Drosophila ortholog required for uptake of dsRNA via the endocytotic machinery to induce RNAi silencing. It is also in C.elegans ortholog Sym-3 (SYnthetic lethal with Mec-3) and the mammalian protein EHBP1 (EH domain Binding Protein-1) that regulates endocytotic recycling and two plant proteins, RPG that regulates Rhizobium-directed polar growth and PMI1 (Plastid Movement Impaired 1) that is essential for intracellular movement of chloroplasts in response to blue light.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088747460  756 AVKEDCKVHI-RVYLPPLDSGT-------PNTYCSKALEFQVPL-----VFNEVFRIPV------HSSALTLKSLQLYVC 816
Cdd:pfam10358    4 KPKFQFVLTIhELQNLPLVGGElfvkwrrGDKKGSSGTTEKALVnngraIFNEEFSIPVtlfldkKGGKYEEKLLEFSVY 83

                           90       100
                   ....*....|....*....|....*.
gi 2088747460  817 SVTPQLQEELLGIAQINLADYDSLSE 842
Cdd:pfam10358   84 KVTKKGKKKVLGKASIDLAEYANLKK 109

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 2088747460  727 PQIHVGLLRDSGSECLLVHVLQLKNPAGLAVKEDCKVHIRVYLPPLDSGTPNTYCSKALEFQVPLVFNEVFRIPVHSSAL 806
Cdd:cd08680      1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2088747460  807 TLKSLQLYVCSVTPQLQEELLGIAQINLADYDSLSEMQLRWHSV 850
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 2088747460    61 PLPAGWEEARDYDGRVFYIDHNTRQTSWIDPRD 93
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 2088747460  109 LPLGWETVYDKQIGVYYMDHINKLTQIEDP 138
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 2088747460  110 PLGWETVYDKQIGVYYMDHINKLTQIEDPRE 140
Cdd:cd00201      1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

Tho complex subunit 7; The Tho complex is involved in transcription elongation and mRNA export from the nucleus.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088747460  127 DHINK---LTQIEDPREQwrREQERMLKEYLIVAQEALNAKKEIYQIKQQ------RFELAQEEYQQLHKMCEDDSRSYA 197
Cdd:pfam05615    1 DELIKrrlLNDGLGLGEE--RPLKRLTKRFLKLCNSLDSTPEEIQALREDllldlaAFELSIEKSQLLAEANERERENYE 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2088747460  198 SsfsgystntkyDPHQIKAEIASRRDRLSRLKRELTQMKQELQYKEK 244
Cdd:pfam05615   79 A-----------EKEEIEEEIEAVREEIEELKERLEEAKRTRKNREE 114

Phosphatidylinositol 3-kinase regulatory subunit P85 inter-SH2 domain; This domain is found between the two SH2 domains in phosphatidylinositol 3-kinase regulatory subunit P85. It forms a complex with the adaptor-binding domain of phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088747460  145 EQERMLKEYlivaQEALNAKKEIYQIKQQrfelAQEEYQQLHKMCEDDSRSYASsfsgYSTntKYDPHQIKAEIASRRDR 224
Cdd:pfam16454   28 EKSREYDRL----YEEYNKTSQEIQMKRQ----ALEAFNEAIKMFEEQIKLQER----FSK--EAQPHEIERLLENYELL 93

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2088747460  225 LSRLKrELTQMKQELQYK-EKGVETLQEIDRKMSS 258
Cdd:pfam16454   94 KSRLK-ELHDSKEQLEEDlKTQKEYNRELEREMNS 127

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088747460  216 AEIASRRDRLSRLKRELTQMKQELQYKEKGVET----LQEIDRKMSSTHTSYKLDEAQ--AIMSELRTIKKAICTGEKER 289
Cdd:COG4942     20 DAAAEAEAELEQLQQEIAELEKELAALKKEEKAllkqLAALERRIAALARRIRALEQElaALEAELAELEKEIAELRAEL 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2088747460  290 RDLMHSLAKLTDS-FKNscsvtdslvdfphhvgvpgdagvpqqfcdaGSQTDIIGEFVFDDKTRLVDRVRLNWQYEEARK 368
Cdd:COG4942    100 EAQKEELAELLRAlYRL------------------------------GRQPPLALLLSPEDFLDAVRRLQYLKYLAPARR 149

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2088747460  369 -RVANIQQQLARLDNESwpSTAEADRDRLQ-LIKEKEALLQELQLIIAQRRSA 419
Cdd:COG4942    150 eQAEELRADLAELAALR--AELEAERAELEaLLAELEEERAALEALKAERQKL 200