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Conserved domains on  [gi|1720365032|ref|XP_030101614|]
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protein KIBRA isoform X1 [Mus musculus]

Protein Classification

WWC family C2 domain-containing protein( domain architecture ID 10171457)

WWC family C2 domain-containing protein similar to Homo sapiens KIBRA/WWC1, which is a probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis

Gene Ontology:  GO:0019900|GO:0060090|GO:0035330|GO:0006355
PubMed:  8976547|9632630

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
C2_Kibra cd08680
C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador ...
 567-690 1.89e-60

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.


:

Pssm-ID: 176062  Cd Length: 124  Bit Score: 201.69  E-value: 1.89e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720365032  567 TRVQIALKYDEKNKQFAILIIQLSHLSALSLQQDQKVNIRVAILPCSESSTCLFRTRPLDSANTLVFNEAFWVSISYPAL 646
Cdd:cd08680      1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1720365032  647 HQKTLRVDVCTTDRSHTEECLGGAQISLAEVCRSGERSTRWYNL 690
Cdd:cd08680     81 YQKTLQVDVCSVGPDQQEECLGGAQISLADFESSEEMSTKWYNL 124
COG4913 super family cl25907
Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];
217-328 5.57e-04

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


The actual alignment was detected with superfamily member COG4913:

Pssm-ID: 443941 [Multi-domain]  Cd Length: 1089  Bit Score: 44.14  E-value: 5.57e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720365032  217 AKRRIANLKIQLAKLDSEAwpGVLDSERDRLI-LINEKEELLKEMRFISPRKWTQGEVEQLEMARRRLEKDLQAARDTQS 295
Cdd:COG4913    608 NRAKLAALEAELAELEEEL--AEAEERLEALEaELDALQERREALQRLAEYSWDEIDVASAEREIAELEAELERLDASSD 685

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1720365032  296 --KALTERLK-LNSKRNQLVRELEEATRQVATLHSQ 328
Cdd:COG4913    686 dlAALEEQLEeLEAELEELEEELDELKGEIGRLEKE 721
 
Name Accession Description Interval E-value
C2_Kibra cd08680
C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador ...
 567-690 1.89e-60

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.


Pssm-ID: 176062  Cd Length: 124  Bit Score: 201.69  E-value: 1.89e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720365032  567 TRVQIALKYDEKNKQFAILIIQLSHLSALSLQQDQKVNIRVAILPCSESSTCLFRTRPLDSANTLVFNEAFWVSISYPAL 646
Cdd:cd08680      1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1720365032  647 HQKTLRVDVCTTDRSHTEECLGGAQISLAEVCRSGERSTRWYNL 690
Cdd:cd08680     81 YQKTLQVDVCSVGPDQQEECLGGAQISLADFESSEEMSTKWYNL 124
C2 pfam00168
C2 domain;
620-690 4.26e-04

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 40.77  E-value: 4.26e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720365032  620 FRTRPLDsaNTL--VFNEAFWVSISYPalHQKTLRVDVCTTDRSHTEECLGGAQISLAEVCrSGERSTRWYNL 690
Cdd:pfam00168   37 KKTKVVK--NTLnpVWNETFTFSVPDP--ENAVLEIEVYDYDRFGRDDFIGEVRIPLSELD-SGEGLDGWYPL 104
COG4913 COG4913
Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];
217-328 5.57e-04

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


Pssm-ID: 443941 [Multi-domain]  Cd Length: 1089  Bit Score: 44.14  E-value: 5.57e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720365032  217 AKRRIANLKIQLAKLDSEAwpGVLDSERDRLI-LINEKEELLKEMRFISPRKWTQGEVEQLEMARRRLEKDLQAARDTQS 295
Cdd:COG4913    608 NRAKLAALEAELAELEEEL--AEAEERLEALEaELDALQERREALQRLAEYSWDEIDVASAEREIAELEAELERLDASSD 685

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1720365032  296 --KALTERLK-LNSKRNQLVRELEEATRQVATLHSQ 328
Cdd:COG4913    686 dlAALEEQLEeLEAELEELEEELDELKGEIGRLEKE 721
 
Name Accession Description Interval E-value
C2_Kibra cd08680
C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador ...
 567-690 1.89e-60

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.


Pssm-ID: 176062  Cd Length: 124  Bit Score: 201.69  E-value: 1.89e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720365032  567 TRVQIALKYDEKNKQFAILIIQLSHLSALSLQQDQKVNIRVAILPCSESSTCLFRTRPLDSANTLVFNEAFWVSISYPAL 646
Cdd:cd08680      1 AQVQIGLRYDSGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPCSSSTSCLFRTKALEDQDKPVFNEVFRVPISSTKL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1720365032  647 HQKTLRVDVCTTDRSHTEECLGGAQISLAEVCRSGERSTRWYNL 690
Cdd:cd08680     81 YQKTLQVDVCSVGPDQQEECLGGAQISLADFESSEEMSTKWYNL 124
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 620-690 6.66e-06

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.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 45.91  E-value: 6.66e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720365032  620 FRTRPLDSANTLVFNEAFwvSISYPALHQKTLRVDVCTTDRSHTEECLGGAQISLAEVCRSGERSTRWYNL 690
Cdd:cd00030     34 FKTKVVKNTLNPVWNETF--EFPVLDPESDTLTVEVWDKDRFSKDDFLGEVEIPLSELLDSGKEGELWLPL 102
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 568-690 4.64e-05

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.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 44.19  E-value: 4.64e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720365032  568 RVQIALKYDEKNKQFAILIIQLSHLSALSlqqdqKVNI-----RVAILPCSESSTclfRTRPLDSANTL--VFNEAFWVS 640
Cdd:cd04030      4 RIQLTIRYSSQRQKLIVTVHKCRNLPPCD-----SSDIpdpyvRLYLLPDKSKST---RRKTSVKKDNLnpVFDETFEFP 75

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1720365032  641 ISYPALHQKTLRVDVCT--TDRSHTEECLGGAQISLAEVCRSgERSTRWYNL 690
Cdd:cd04030     76 VSLEELKRRTLDVAVKNskSFLSREKKLLGQVLIDLSDLDLS-KGFTQWYDL 126
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 568-690 1.05e-04

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). 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-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 43.01  E-value: 1.05e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720365032  568 RVQIALKYDEKNKQFAILIIQLSHLSALSLQQDQKVNIRVAILP-CSESSTclFRTRPLDSANTLVFNEAF-WVSISYPA 645
Cdd:cd04031      4 RIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPdRSEKSK--RRTKTVKKTLNPEWNQTFeYSNVRRET 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1720365032  646 LHQKTLRVDVCTTDRSHTEECLGGAQISLAEVCRSGErsTRWYNL 690
Cdd:cd04031     82 LKERTLEVTVWDYDRDGENDFLGEVVIDLADALLDDE--PHWYPL 124
C2 pfam00168
C2 domain;
620-690 4.26e-04

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 40.77  E-value: 4.26e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720365032  620 FRTRPLDsaNTL--VFNEAFWVSISYPalHQKTLRVDVCTTDRSHTEECLGGAQISLAEVCrSGERSTRWYNL 690
Cdd:pfam00168   37 KKTKVVK--NTLnpVWNETFTFSVPDP--ENAVLEIEVYDYDRFGRDDFIGEVRIPLSELD-SGEGLDGWYPL 104
COG4913 COG4913
Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];
217-328 5.57e-04

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


Pssm-ID: 443941 [Multi-domain]  Cd Length: 1089  Bit Score: 44.14  E-value: 5.57e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720365032  217 AKRRIANLKIQLAKLDSEAwpGVLDSERDRLI-LINEKEELLKEMRFISPRKWTQGEVEQLEMARRRLEKDLQAARDTQS 295
Cdd:COG4913    608 NRAKLAALEAELAELEEEL--AEAEERLEALEaELDALQERREALQRLAEYSWDEIDVASAEREIAELEAELERLDASSD 685

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1720365032  296 --KALTERLK-LNSKRNQLVRELEEATRQVATLHSQ 328
Cdd:COG4913    686 dlAALEEQLEeLEAELEELEEELDELKGEIGRLEKE 721
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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