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 966949833  660 ARVQIALKYDEKNKQFAILIIQLSNLSALLQQQDQKVNIRVAVLPCSESTTCLFRTRPLDASDTLVFNEVFWVSMSYPAL 739
Cdd:cd08680     1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 966949833  740 HQKTLRVDVCTTDRSHLEECLGGAQISLAEVCRSGERSTRWYNL 783
Cdd:cd08680    81 YQKTLQVDVCSVGPDQQEECLGGAQISLADFESSEEMSTKWYNL 124

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 966949833   56 PLGWEEAYDPQVGDYFIDHNTKTTQIEDPR 85
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPR 30

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966949833   162 AEIATAKSRVNKLKREMVHLQHELqfkergFQTLKKIDKKMSDAQgsyKLDEAQAVL-RETKAIKKAITCGEKEKQDLIK 240
Cdd:TIGR02168  267 EKLEELRLEVSELEEEIEELQKEL------YALANEISRLEQQKQ---ILRERLANLeRQLEELEAQLEELESKLDELAE 337

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966949833   241 SLAMLKDGFrtdrgshsdlwssssslesssFPLPKQYLDVSSQTDISGSFSINSNNQLAEkvrLRLRYEEAKRRIANLKI 320
Cdd:TIGR02168  338 ELAELEEKL---------------------EELKEELESLEAELEELEAELEELESRLEE---LEEQLETLRSKVAQLEL 393

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966949833   321 QLAKLDSE---AWPGVLDSERDRLILINEKEELLKEMRfISPRKWTQGEVEQLEMARKRLEKDLQAARDTQSKALTERLK 397
Cdd:TIGR02168  394 QIASLNNEierLEARLERLEDRRERLQQEIEELLKKLE-EAELKELQAELEELEEELEELQEELERLEEALEELREELEE 472

                          250       260
                   ....*....|....*....|....*
gi 966949833   398 LNSKRNQLVRELEEATRQVATLHSQ 422
Cdd:TIGR02168  473 AEQALDAAERELAQLQARLDSLERL 497

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 966949833  660 ARVQIALKYDEKNKQFAILIIQLSNLSALLQQQDQKVNIRVAVLPCSESTTCLFRTRPLDASDTLVFNEVFWVSMSYPAL 739
Cdd:cd08680     1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 966949833  740 HQKTLRVDVCTTDRSHLEECLGGAQISLAEVCRSGERSTRWYNL 783
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 966949833     8 LPEGWEEARDFDGKVYYIDHTNRTTSWIDP 37
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 966949833   56 PLGWEEAYDPQVGDYFIDHNTKTTQIEDPR 85
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPR 30

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 966949833    55 LPLGWEEAYDPQVGDYFIDHNTKTTQIEDP 84
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966949833  311 AKRRIANLKIQLAKLDSEAwpGVLDSERDRLI-LINEKEELLKEMRFISPRKWTQGEVEQLEMARKRLEKDLQAARDTQS 389
Cdd:COG4913   608 NRAKLAALEAELAELEEEL--AEAEERLEALEaELDALQERREALQRLAEYSWDEIDVASAEREIAELEAELERLDASSD 685

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 966949833  390 --KALTERLK-LNSKRNQLVRELEEATRQVATLHSQ 422
Cdd:COG4913   686 dlAALEEQLEeLEAELEELEEELDELKGEIGRLEKE 721

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 966949833  660 ARVQIALKYDEKNKQFAILIIQLSNLSALLQQQDQKVNIRVAVLPCSESTTCLFRTRPLDASDTLVFNEVFWVSMSYPAL 739
Cdd:cd08680     1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 966949833  740 HQKTLRVDVCTTDRSHLEECLGGAQISLAEVCRSGERSTRWYNL 783
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 966949833     8 LPEGWEEARDFDGKVYYIDHTNRTTSWIDP 37
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 966949833   56 PLGWEEAYDPQVGDYFIDHNTKTTQIEDPR 85
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPR 30

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 966949833    55 LPLGWEEAYDPQVGDYFIDHNTKTTQIEDP 84
Cdd:pfam00397    1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. 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 third C2 repeat, C2C, and has a type-II topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966949833  658 GAARVQIALKYDEKNKQFAILIIQLSNLSALLQQQDQKVNIRVAVLPCSESTTclfRTRPLDASDTL--VFNEVFWVSMS 735
Cdd:cd04030     1 PLGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKST---RRKTSVKKDNLnpVFDETFEFPVS 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 966949833  736 YPALHQKTLRVDVCT--TDRSHLEECLGGAQISLAEVCRSgERSTRWYNL 783
Cdd:cd04030    78 LEELKRRTLDVAVKNskSFLSREKKLLGQVLIDLSDLDLS-KGFTQWYDL 126

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966949833  311 AKRRIANLKIQLAKLDSEAwpGVLDSERDRLI-LINEKEELLKEMRFISPRKWTQGEVEQLEMARKRLEKDLQAARDTQS 389
Cdd:COG4913   608 NRAKLAALEAELAELEEEL--AEAEERLEALEaELDALQERREALQRLAEYSWDEIDVASAEREIAELEAELERLDASSD 685

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 966949833  390 --KALTERLK-LNSKRNQLVRELEEATRQVATLHSQ 422
Cdd:COG4913   686 dlAALEEQLEeLEAELEELEEELDELKGEIGRLEKE 721

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966949833   162 AEIATAKSRVNKLKREMVHLQHELqfkergFQTLKKIDKKMSDAQgsyKLDEAQAVL-RETKAIKKAITCGEKEKQDLIK 240
Cdd:TIGR02168  267 EKLEELRLEVSELEEEIEELQKEL------YALANEISRLEQQKQ---ILRERLANLeRQLEELEAQLEELESKLDELAE 337

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966949833   241 SLAMLKDGFrtdrgshsdlwssssslesssFPLPKQYLDVSSQTDISGSFSINSNNQLAEkvrLRLRYEEAKRRIANLKI 320
Cdd:TIGR02168  338 ELAELEEKL---------------------EELKEELESLEAELEELEAELEELESRLEE---LEEQLETLRSKVAQLEL 393

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966949833   321 QLAKLDSE---AWPGVLDSERDRLILINEKEELLKEMRfISPRKWTQGEVEQLEMARKRLEKDLQAARDTQSKALTERLK 397
Cdd:TIGR02168  394 QIASLNNEierLEARLERLEDRRERLQQEIEELLKKLE-EAELKELQAELEELEEELEELQEELERLEEALEELREELEE 472

                          250       260
                   ....*....|....*....|....*
gi 966949833   398 LNSKRNQLVRELEEATRQVATLHSQ 422
Cdd:TIGR02168  473 AEQALDAAERELAQLQARLDSLERL 497