KIBRA_DROME
ID KIBRA_DROME Reviewed; 1288 AA.
AC Q9VFG8; Q5BIC8;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Protein kibra;
GN Name=kibra; ORFNames=CG33967;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-992, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND INTERACTION WITH
RP HPO; SAV; MER AND EX.
RX PubMed=20159598; DOI=10.1016/j.devcel.2009.12.012;
RA Yu J., Zheng Y., Dong J., Klusza S., Deng W.-M., Pan D.;
RT "Kibra functions as a tumor suppressor protein that regulates Hippo
RT signaling in conjunction with Merlin and Expanded.";
RL Dev. Cell 18:288-299(2010).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND INTERACTION WITH
RP MER; EX AND WTS.
RX PubMed=20159599; DOI=10.1016/j.devcel.2009.12.011;
RA Genevet A., Wehr M.C., Brain R., Thompson B.J., Tapon N.;
RT "Kibra Is a regulator of the Salvador/Warts/Hippo signaling network.";
RL Dev. Cell 18:300-308(2010).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND INTERACTION WITH
RP MER.
RX PubMed=20159600; DOI=10.1016/j.devcel.2009.12.013;
RA Baumgartner R., Poernbacher I., Buser N., Hafen E., Stocker H.;
RT "The WW domain protein Kibra acts upstream of Hippo in Drosophila.";
RL Dev. Cell 18:309-316(2010).
CC -!- FUNCTION: Regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a
CC signaling pathway that plays a pivotal role in organ size control and
CC tumor suppression by restricting proliferation and promoting apoptosis.
CC The core of this pathway is composed of a kinase cascade wherein Hippo
CC (Hpo), in complex with its regulatory protein Salvador (Sav),
CC phosphorylates and activates Warts (Wts) in complex with its regulatory
CC protein Mats, which in turn phosphorylates and inactivates the Yorkie
CC (Yki) oncoprotein. Kibra acts synergistically along with Ex and Mer to
CC regulate the Hippo signaling pathway. {ECO:0000269|PubMed:20159598,
CC ECO:0000269|PubMed:20159599, ECO:0000269|PubMed:20159600}.
CC -!- SUBUNIT: Forms a complex with Mer and Ex. Interacts (via domain WW 1)
CC with Ex (via RXPPXY motif). Interacts with Mer, Sav, Hpo and Wts.
CC {ECO:0000269|PubMed:20159598, ECO:0000269|PubMed:20159599,
CC ECO:0000269|PubMed:20159600}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Apical cell membrane. Note=Localizes
CC at the apical cortex of epithelial cells and cytoplasmic, punctate.
CC -!- TISSUE SPECIFICITY: Expressed in ovarian posterior follicle cells and
CC wing disks (at protein level). {ECO:0000269|PubMed:20159599}.
CC -!- DISRUPTION PHENOTYPE: Homozygous embryonic lethality, oogenesis
CC defects, tissue overgrowth characterized by excessive cell
CC proliferation and diminished apoptosis. {ECO:0000269|PubMed:20159598,
CC ECO:0000269|PubMed:20159599, ECO:0000269|PubMed:20159600}.
CC -!- SIMILARITY: Belongs to the WWC family. KIBRA subfamily. {ECO:0000305}.
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DR EMBL; AE014297; AAF55090.2; -; Genomic_DNA.
DR EMBL; BT021296; AAX33444.1; -; mRNA.
DR RefSeq; NP_001034055.1; NM_001038966.2.
DR RefSeq; NP_001287329.1; NM_001300400.1.
DR AlphaFoldDB; Q9VFG8; -.
DR BioGRID; 66857; 27.
DR IntAct; Q9VFG8; 1.
DR STRING; 7227.FBpp0099467; -.
DR iPTMnet; Q9VFG8; -.
DR PaxDb; Q9VFG8; -.
DR PRIDE; Q9VFG8; -.
DR EnsemblMetazoa; FBtr0100008; FBpp0099467; FBgn0262127.
DR EnsemblMetazoa; FBtr0344383; FBpp0310756; FBgn0262127.
DR GeneID; 41783; -.
DR KEGG; dme:Dmel_CG33967; -.
DR UCSC; CG33967-RA; d. melanogaster.
DR CTD; 41783; -.
DR FlyBase; FBgn0262127; kibra.
DR VEuPathDB; VectorBase:FBgn0262127; -.
DR eggNOG; KOG0940; Eukaryota.
DR eggNOG; KOG3209; Eukaryota.
DR GeneTree; ENSGT00410000025556; -.
DR HOGENOM; CLU_005420_1_0_1; -.
DR InParanoid; Q9VFG8; -.
DR OMA; HHTHIPR; -.
DR OrthoDB; 364990at2759; -.
DR PhylomeDB; Q9VFG8; -.
DR Reactome; R-DME-2028269; Signaling by Hippo.
DR SignaLink; Q9VFG8; -.
DR BioGRID-ORCS; 41783; 0 hits in 3 CRISPR screens.
DR ChiTaRS; kibra; fly.
DR GenomeRNAi; 41783; -.
DR PRO; PR:Q9VFG8; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0262127; Expressed in oviduct (Drosophila) and 23 other tissues.
DR ExpressionAtlas; Q9VFG8; baseline and differential.
DR Genevisible; Q9VFG8; DM.
DR GO; GO:0106037; C:apicomedial cortex; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0098592; C:cytoplasmic side of apical plasma membrane; IDA:FlyBase.
DR GO; GO:0036375; C:Kibra-Ex-Mer complex; IDA:UniProtKB.
DR GO; GO:0019900; F:kinase binding; IBA:GO_Central.
DR GO; GO:0060090; F:molecular adaptor activity; IBA:GO_Central.
DR GO; GO:0007298; P:border follicle cell migration; IMP:FlyBase.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0001745; P:compound eye morphogenesis; IGI:FlyBase.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; IMP:FlyBase.
DR GO; GO:0046621; P:negative regulation of organ growth; IMP:FlyBase.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:FlyBase.
DR GO; GO:0035332; P:positive regulation of hippo signaling; IDA:FlyBase.
DR GO; GO:0045463; P:R8 cell development; IGI:FlyBase.
DR GO; GO:0045464; P:R8 cell fate specification; IMP:FlyBase.
DR GO; GO:0035330; P:regulation of hippo signaling; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR CDD; cd08680; C2_Kibra; 1.
DR CDD; cd00201; WW; 2.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037771; C2_WWC.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00397; WW; 2.
DR SMART; SM00239; C2; 1.
DR SMART; SM00456; WW; 2.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51045; SSF51045; 2.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 2.
PE 1: Evidence at protein level;
KW Cell membrane; Coiled coil; Cytoplasm; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation.
FT CHAIN 1..1288
FT /note="Protein kibra"
FT /id="PRO_0000392971"
FT DOMAIN 54..87
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 101..134
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 691..811
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 541..560
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 841..869
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 890..912
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 942..975
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1224..1269
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 201..229
FT /evidence="ECO:0000255"
FT COILED 335..463
FT /evidence="ECO:0000255"
FT COILED 1049..1076
FT /evidence="ECO:0000255"
FT COMPBIAS 14..38
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 39..53
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 843..869
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 895..912
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 992
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 230
FT /note="Y -> C (in Ref. 3; AAX33444)"
FT /evidence="ECO:0000305"
FT CONFLICT 743
FT /note="T -> A (in Ref. 3; AAX33444)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1288 AA; 144350 MW; C450A07D640D6492 CRC64;
MPNLQQTASQ SQHHLHPHHL RPQQQQQQHH HHHQQQQQQQ HTHHQQQQQH HSDFPLPDGW
DIAKDFDGKT YYIDHINKKT TWLDPRDCYT KPQTFEDCVG DELPMGWEES YDPNIGPYYI
NHLAQSTQLE DPRQEWKTVQ EQMLSDYLSA AQDQLENKRE MFDVKQQRLL WAQEEYNHLK
LAASRSSLCS SSSSMSRHDP ELLRADLMLA RERVHQLKQE LTHITNDISY TERGMNTLYS
VGEKINAREN GCYDIAEVHA IREEMLKVHK SLVSGEKVRE ELMRSLVQIK NELGRQQISE
ENSDLASPFD RVCVASQTDL CGSSGENLNG GARFAEMAKT KWQYAEWRKH IKKLQQQLAD
HVERIEPGQL ESDKDRILLI QEKEKLLNDL NSISLKSRSE EEKRVIHQTR HKLEEDLKEA
YEANNTCVAN RLRFHEEKQL LLDKLQEALK STKLLEERLK SFSSESTFSI SSGSSLGSLS
TASSKSALSF TDIYIDPFAV DSPIDVVDLR RRSQRLFQQH QQQRLHPVHP VLQQQQSAEV
TLSPRSSLSM ETPPASPMKY NAGADQTPQA LKEEPTYANA LPAPPAYTAP PPVPISGVRA
RPYDLDSTVL DCMMLEAKLQ KLNMGTPLNL AVAPLSPISE KPSLLDLPQE MLSRSSSTSN
TRSVSAAVSN ESVAGDSGVF EASRAHLPRK ELAQVQIGLK YLKQEGVLVV SLERANNLLA
LWTASADNSQ VYLRAALLPN SLTSIRTKAL GDFQKPVFND TFAVPITLDK LLTKSLQVTV
VTMTGQKEEI IGTVQISMAE FNPEDSTLKW YNVLSSKFIP SFESLDIPST SAAAAAAAVA
ASNAPNPGNN REESSDESTI TSSQTSTLTR NQAPCMELQE QMAAELLGLG PLNEPECSDD
DDDDEEEELD DKQLVSDVGL MNSSSMLHAY LQNMKQEFAD KETNTDRAYL PEKSRGQSQL
MDDRPVKRSQ TFTPSEAFSK NRYNCRLNRS DSDSAMHCGV APHTFQRGAA ERRSLRFHSK
APKSVTKLHH THIPRTSLDL ELDLQAQHSK LYFLNDQIAK LQNLKEVLQK ACENKDPLVA
AWAIENEEFQ RLVARADPAK CPEERQLQKL LMKTAKEIHK LRKTKVPKGC PDLVSFKEKI
TFFTRKGLSV PELPSEFTLP EANPIEEEEE EEDENEFYNS AETAIAINTA LVASSNRNKN
LSEHPHRATS GAVPKIPAPV VTPAATPAAT PAATPAATSA ATPAATPVVS PAAQPDAKPA
DAPIPVASND AEQQRFDYVV DRNYGVEV
