KIBRA_HUMAN
ID KIBRA_HUMAN Reviewed; 1113 AA.
AC Q8IX03; B4DK05; O94946; Q6MZX4; Q6Y2F8; Q7Z4G8; Q8WVM4; Q9BT29;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Protein KIBRA;
DE AltName: Full=HBeAg-binding protein 3;
DE AltName: Full=Kidney and brain protein;
DE Short=KIBRA;
DE AltName: Full=WW domain-containing protein 1;
GN Name=WWC1; Synonyms=KIAA0869;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH DDN, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=12559952; DOI=10.1016/s0006-291x(02)02945-5;
RA Kremerskothen J., Plaas C., Buether K., Finger I., Veltel S., Matanis T.,
RA Liedtke T., Barnekow A.;
RT "Characterization of KIBRA, a novel WW domain-containing protein.";
RL Biochem. Biophys. Res. Commun. 300:862-867(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 36-1113 (ISOFORM 2).
RC TISSUE=Fetal brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 225-1113 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 202-1113 (ISOFORM 1).
RC TISSUE=Liver;
RA Lu Y., Liu Y., Cheng J.;
RT "Screening and cloning of interaction protein 3 of HBeAg.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 782-1113 (ISOFORM 1).
RC TISSUE=Liver, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION, SUBUNIT, INTERACTION WITH PRKCZ, AND PHOSPHORYLATION AT SER-975
RP AND SER-978.
RX PubMed=15081397; DOI=10.1016/j.bbrc.2004.03.107;
RA Buether K., Plaas C., Barnekow A., Kremerskothen J.;
RT "KIBRA is a novel substrate for protein kinase Czeta.";
RL Biochem. Biophys. Res. Commun. 317:703-707(2004).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INTERACTION WITH
RP DYNLL1 AND HISTONE H3.
RX PubMed=16684779; DOI=10.1074/jbc.m600021200;
RA Rayala S.K., den Hollander P., Manavathi B., Talukder A.H., Song C.,
RA Peng S., Barnekow A., Kremerskothen J., Kumar R.;
RT "Essential role of KIBRA in co-activator function of dynein light chain 1
RT in mammalian cells.";
RL J. Biol. Chem. 281:19092-19099(2006).
RN [10]
RP POLYMORPHISM, AND INVOLVEMENT IN MEMRYQTL.
RX PubMed=17053149; DOI=10.1126/science.1129837;
RA Papassotiropoulos A., Stephan D.A., Huentelman M.J., Hoerndli F.J.,
RA Craig D.W., Pearson J.V., Huynh K.D., Brunner F., Corneveaux J.,
RA Osborne D., Wollmer M.A., Aerni A., Coluccia D., Hanggi J., Mondadori C.R.,
RA Buchmann A., Reiman E.M., Caselli R.J., Henke K., de Quervain D.J.;
RT "Common Kibra alleles are associated with human memory performance.";
RL Science 314:475-478(2006).
RN [11]
RP INTERACTION WITH SNX4.
RX PubMed=17994011; DOI=10.1038/ncb1656;
RA Traer C.J., Rutherford A.C., Palmer K.J., Wassmer T., Oakley J., Attar N.,
RA Carlton J.G., Kremerskothen J., Stephens D.J., Cullen P.J.;
RT "SNX4 coordinates endosomal sorting of TfnR with dynein-mediated transport
RT into the endocytic recycling compartment.";
RL Nat. Cell Biol. 9:1370-1380(2007).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SYNPO AND PATJ, AND TISSUE
RP SPECIFICITY.
RX PubMed=18596123; DOI=10.1681/asn.2007080916;
RA Duning K., Schurek E.M., Schlueter M., Bayer M., Reinhardt H.C., Schwab A.,
RA Schaefer L., Benzing T., Schermer B., Saleem M.A., Huber T.B., Bachmann S.,
RA Kremerskothen J., Weide T., Pavenstaedt H.;
RT "KIBRA modulates directional migration of podocytes.";
RL J. Am. Soc. Nephrol. 19:1891-1903(2008).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, INDUCTION, INTERACTION
RP WITH DDR1 AND PRKCZ, AND TISSUE SPECIFICITY.
RX PubMed=18190796; DOI=10.1016/j.bbamcr.2007.12.007;
RA Hilton H.N., Stanford P.M., Harris J., Oakes S.R., Kaplan W., Daly R.J.,
RA Ormandy C.J.;
RT "KIBRA interacts with discoidin domain receptor 1 to modulate collagen-
RT induced signalling.";
RL Biochim. Biophys. Acta 1783:383-393(2008).
RN [14]
RP FUNCTION, SUBUNIT, TISSUE SPECIFICITY, AND DOMAIN C2.
RX PubMed=18672031; DOI=10.1016/j.neuroscience.2008.06.054;
RA Johannsen S., Duning K., Pavenstaedt H., Kremerskothen J., Boeckers T.M.;
RT "Temporal-spatial expression and novel biochemical properties of the
RT memory-related protein KIBRA.";
RL Neuroscience 155:1165-1173(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-912; THR-929 AND SER-931, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP FUNCTION.
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 [17]
RP INTERACTION WITH NF2.
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-947, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP POLYMORPHISM, AND INVOLVEMENT IN MEMRYQTL.
RX PubMed=23065961; DOI=10.1002/ajmg.b.32101;
RA Milnik A., Heck A., Vogler C., Heinze H.J., de Quervain D.J.,
RA Papassotiropoulos A.;
RT "Association of KIBRA with episodic and working memory: a meta-analysis.";
RL Am. J. Med. Genet. B Neuropsychiatr. Genet. 159B:958-969(2012).
RN [20]
RP PHOSPHORYLATION AT SER-542 AND SER-931 BY CDK1, AND DEPHOSPHORYLATION BY
RP CDC14B.
RX PubMed=22784093; DOI=10.1042/bj20120751;
RA Ji M., Yang S., Chen Y., Xiao L., Zhang L., Dong J.;
RT "Phospho-regulation of KIBRA by CDK1 and CDC14 phosphatase controls cell-
RT cycle progression.";
RL Biochem. J. 447:93-102(2012).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-535 AND THR-929, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP FUNCTION OF C2 DOMAIN, VARIANTS ILE-734 AND ALA-735, AND CHARACTERIZATION
RP OF VARIANTS ILE-734 AND ALA-735.
RX PubMed=23778582; DOI=10.1038/tp.2013.49;
RA Duning K., Wennmann D.O., Bokemeyer A., Reissner C., Wersching H.,
RA Thomas C., Buschert J., Guske K., Franzke V., Floel A., Lohmann H.,
RA Knecht S., Brand S.M., Poter M., Rescher U., Missler M., Seelheim P.,
RA Propper C., Boeckers T.M., Makuch L., Huganir R., Weide T., Brand E.,
RA Pavenstadt H., Kremerskothen J.;
RT "Common exonic missense variants in the C2 domain of the human KIBRA
RT protein modify lipid binding and cognitive performance.";
RL Transl. Psychiatry 3:E272-E272(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-899, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 638-785.
RG RIKEN structural genomics initiative (RSGI);
RT "Crystal structure of C2 domain of KIBRA protein.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling
CC pathway, a signaling pathway that plays a pivotal role in tumor
CC suppression by restricting proliferation and promoting apoptosis. Along
CC with NF2 can synergistically induce the phosphorylation of LATS1 and
CC LATS2 and can probably function in the regulation of the Hippo/SWH
CC (Sav/Wts/Hpo) signaling pathway. Acts as a transcriptional coactivator
CC of ESR1 which plays an essential role in DYNLL1-mediated ESR1
CC transactivation. Regulates collagen-stimulated activation of the
CC ERK/MAPK cascade. Modulates directional migration of podocytes. Acts as
CC a substrate for PRKCZ. Plays a role in cognition and memory
CC performance. {ECO:0000269|PubMed:15081397, ECO:0000269|PubMed:16684779,
CC ECO:0000269|PubMed:18190796, ECO:0000269|PubMed:18596123,
CC ECO:0000269|PubMed:18672031, ECO:0000269|PubMed:20159598,
CC ECO:0000269|PubMed:23778582}.
CC -!- SUBUNIT: Homodimer. Interacts with DDN. Interacts with DYNLL1 and
CC histone H3. The interaction with DYNLL1 is mandatory for the
CC recruitment and transactivation functions of ESR1 or DYNLL1 to the
CC target chromatin and the interaction with histone H3 ensures proper
CC regulatory interaction of WWC1-DYNLL1-ESR1 complexes with target
CC chromatin. Interacts (via WW domains) with DDR1 (via PPxY motif) in a
CC collagen-regulated manner. Interacts with PRKCZ (via the protein kinase
CC domain). Forms a tripartite complex with DDR1 and PRKCZ, but
CC predominantly in the absence of collagen. Interacts (via the ADDV
CC motif) with PATJ (via PDZ domain 8). Interacts (via WW domains) with
CC SYNPO (via PPxY motifs). Interacts with NF2 and SNX4.
CC {ECO:0000269|PubMed:12559952, ECO:0000269|PubMed:15081397,
CC ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:17994011,
CC ECO:0000269|PubMed:18190796, ECO:0000269|PubMed:18596123,
CC ECO:0000269|PubMed:18672031, ECO:0000269|PubMed:20159599}.
CC -!- INTERACTION:
CC Q8IX03-1; Q62824: Exoc4; Xeno; NbExp=3; IntAct=EBI-15812469, EBI-6959516;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, perinuclear region.
CC Nucleus. Cell projection, ruffle membrane. Note=Colocalizes with PRKCZ
CC in the perinuclear region.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IX03-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IX03-2; Sequence=VSP_019448;
CC -!- TISSUE SPECIFICITY: Expressed in mammary epithelial cells and breast
CC cancer cell lines. Found in the luminal epithelium surrounding the
CC ducts in the normal breast. In the brain, expressed in somatodendritic
CC compartment of neurons in the cortex and hippocampus and in the
CC cerebellum it is found in the Purkinje cells and some granule cells (at
CC protein level). Detected in brain, heart, colon and kidney. In the
CC kidney, expressed in glomerular podocytes, in some tubules and in the
CC collecting duct. {ECO:0000269|PubMed:12559952,
CC ECO:0000269|PubMed:18190796, ECO:0000269|PubMed:18596123,
CC ECO:0000269|PubMed:18672031}.
CC -!- INDUCTION: Strongly up-regulated by progestin treatment.
CC {ECO:0000269|PubMed:18190796}.
CC -!- DOMAIN: The C2-domain mediates homodimerization. It is a calcium-
CC sensitive lipid-binding domain with preference for PI(3)P.
CC {ECO:0000269|PubMed:18672031}.
CC -!- PTM: Phosphorylation at Ser-542 and Ser-931 by CDK1 in response to
CC spindle damage stress regulates mitotic exit, these two sites are
CC dephosphorylated by CDC14B. {ECO:0000269|PubMed:15081397,
CC ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:18190796,
CC ECO:0000269|PubMed:22784093}.
CC -!- POLYMORPHISM: Genetic variations in WWC1 define the memory quantitative
CC trait locus (MEMRYQTL) [MIM:615602]. {ECO:0000269|PubMed:17053149,
CC ECO:0000269|PubMed:23065961}.
CC -!- SIMILARITY: Belongs to the WWC family. KIBRA subfamily. {ECO:0000305}.
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DR EMBL; AF506799; AAO15881.1; -; mRNA.
DR EMBL; AK296323; BAG59017.1; -; mRNA.
DR EMBL; AC020894; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026689; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX640827; CAE45903.1; -; mRNA.
DR EMBL; AB020676; BAA74892.1; -; mRNA.
DR EMBL; AF530058; AAQ09942.1; -; mRNA.
DR EMBL; AY189820; AAO73817.1; -; mRNA.
DR EMBL; BC004394; AAH04394.1; -; mRNA.
DR EMBL; BC017746; AAH17746.1; -; mRNA.
DR CCDS; CCDS4366.1; -. [Q8IX03-1]
DR CCDS; CCDS54945.1; -. [Q8IX03-2]
DR RefSeq; NP_001155133.1; NM_001161661.1. [Q8IX03-2]
DR RefSeq; NP_001155134.1; NM_001161662.1.
DR RefSeq; NP_056053.1; NM_015238.2. [Q8IX03-1]
DR PDB; 2Z0U; X-ray; 2.20 A; A/B=638-785.
DR PDB; 6FB4; X-ray; 2.42 A; A/B=658-785.
DR PDB; 6FD0; X-ray; 2.64 A; A/B=658-785.
DR PDB; 6FJC; X-ray; 2.60 A; A/B=658-785.
DR PDB; 6FJD; X-ray; 2.90 A; A/B=658-785.
DR PDBsum; 2Z0U; -.
DR PDBsum; 6FB4; -.
DR PDBsum; 6FD0; -.
DR PDBsum; 6FJC; -.
DR PDBsum; 6FJD; -.
DR AlphaFoldDB; Q8IX03; -.
DR SMR; Q8IX03; -.
DR BioGRID; 116884; 89.
DR CORUM; Q8IX03; -.
DR DIP; DIP-35287N; -.
DR IntAct; Q8IX03; 50.
DR MINT; Q8IX03; -.
DR STRING; 9606.ENSP00000427772; -.
DR CarbonylDB; Q8IX03; -.
DR iPTMnet; Q8IX03; -.
DR PhosphoSitePlus; Q8IX03; -.
DR BioMuta; WWC1; -.
DR DMDM; 74714457; -.
DR EPD; Q8IX03; -.
DR jPOST; Q8IX03; -.
DR MassIVE; Q8IX03; -.
DR MaxQB; Q8IX03; -.
DR PaxDb; Q8IX03; -.
DR PeptideAtlas; Q8IX03; -.
DR PRIDE; Q8IX03; -.
DR ProteomicsDB; 70950; -. [Q8IX03-1]
DR ProteomicsDB; 70951; -. [Q8IX03-2]
DR Antibodypedia; 48675; 222 antibodies from 25 providers.
DR DNASU; 23286; -.
DR Ensembl; ENST00000265293.9; ENSP00000265293.4; ENSG00000113645.15. [Q8IX03-1]
DR Ensembl; ENST00000521089.5; ENSP00000427772.1; ENSG00000113645.15. [Q8IX03-2]
DR GeneID; 23286; -.
DR KEGG; hsa:23286; -.
DR MANE-Select; ENST00000265293.9; ENSP00000265293.4; NM_015238.3; NP_056053.1.
DR UCSC; uc003lzu.4; human. [Q8IX03-1]
DR CTD; 23286; -.
DR DisGeNET; 23286; -.
DR GeneCards; WWC1; -.
DR HGNC; HGNC:29435; WWC1.
DR HPA; ENSG00000113645; Tissue enhanced (salivary).
DR MalaCards; WWC1; -.
DR MIM; 610533; gene.
DR MIM; 615602; phenotype.
DR neXtProt; NX_Q8IX03; -.
DR OpenTargets; ENSG00000113645; -.
DR PharmGKB; PA143485670; -.
DR VEuPathDB; HostDB:ENSG00000113645; -.
DR eggNOG; KOG3209; Eukaryota.
DR GeneTree; ENSGT00410000025556; -.
DR HOGENOM; CLU_005420_0_0_1; -.
DR InParanoid; Q8IX03; -.
DR OMA; HHTHIPR; -.
DR OrthoDB; 364990at2759; -.
DR PhylomeDB; Q8IX03; -.
DR TreeFam; TF324040; -.
DR PathwayCommons; Q8IX03; -.
DR Reactome; R-HSA-2028269; Signaling by Hippo.
DR Reactome; R-HSA-9013508; NOTCH3 Intracellular Domain Regulates Transcription.
DR SignaLink; Q8IX03; -.
DR SIGNOR; Q8IX03; -.
DR BioGRID-ORCS; 23286; 10 hits in 1061 CRISPR screens.
DR ChiTaRS; WWC1; human.
DR EvolutionaryTrace; Q8IX03; -.
DR GeneWiki; WWC1; -.
DR GenomeRNAi; 23286; -.
DR Pharos; Q8IX03; Tbio.
DR PRO; PR:Q8IX03; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q8IX03; protein.
DR Bgee; ENSG00000113645; Expressed in ventricular zone and 178 other tissues.
DR ExpressionAtlas; Q8IX03; baseline and differential.
DR Genevisible; Q8IX03; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB.
DR GO; GO:0019900; F:kinase binding; IPI:BHF-UCL.
DR GO; GO:0060090; F:molecular adaptor activity; IDA:BHF-UCL.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0016477; P:cell migration; IDA:UniProtKB.
DR GO; GO:0030010; P:establishment of cell polarity; TAS:BHF-UCL.
DR GO; GO:0035331; P:negative regulation of hippo signaling; IDA:BHF-UCL.
DR GO; GO:0046621; P:negative regulation of organ growth; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0035330; P:regulation of hippo signaling; IMP:UniProtKB.
DR GO; GO:0032386; P:regulation of intracellular transport; TAS:BHF-UCL.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
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; PF00397; WW; 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 3D-structure; Activator; Alternative splicing; Cell membrane;
KW Cell projection; Coiled coil; Cytoplasm; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation.
FT CHAIN 1..1113
FT /note="Protein KIBRA"
FT /id="PRO_0000242153"
FT DOMAIN 6..39
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 53..86
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 658..781
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 429..448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 522..547
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 825..975
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 839..1113
FT /note="Interaction with histone H3"
FT REGION 953..996
FT /note="Interaction with PRKCZ"
FT COILED 107..193
FT /evidence="ECO:0000255"
FT COILED 293..431
FT /evidence="ECO:0000255"
FT COILED 1001..1032
FT /evidence="ECO:0000255"
FT MOTIF 1111..1113
FT /note="ADDV motif"
FT COMPBIAS 523..546
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 850..871
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 916..957
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 959..975
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 141
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5SXA9"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 542
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:22784093"
FT MOD_RES 899
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 912
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 927
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5SXA9"
FT MOD_RES 929
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 931
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:22784093,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 947
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 975
FT /note="Phosphoserine; by PKC/PRKCZ"
FT /evidence="ECO:0000269|PubMed:15081397"
FT MOD_RES 978
FT /note="Phosphoserine; by PKC/PRKCZ"
FT /evidence="ECO:0000269|PubMed:15081397"
FT VAR_SEQ 974
FT /note="S -> SPPPQPS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10048485,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:17974005"
FT /id="VSP_019448"
FT VARIANT 250
FT /note="R -> C (in dbSNP:rs17551608)"
FT /id="VAR_026844"
FT VARIANT 734
FT /note="M -> I (associated with Ala-735; affects KIBRA
FT lipid-binding specificity showing stronger interactions
FT with PI(4)P and PI(5)P; dbSNP:rs3822660)"
FT /evidence="ECO:0000269|PubMed:23778582"
FT /id="VAR_053449"
FT VARIANT 735
FT /note="S -> A (associated with Ile-734; affects KIBRA
FT lipid-binding specificity showing stronger interactions
FT with PI(4)P and PI(5)P; dbSNP:rs3822659)"
FT /evidence="ECO:0000269|PubMed:23778582"
FT /id="VAR_053450"
FT CONFLICT 561
FT /note="F -> L (in Ref. 4; CAE45903)"
FT /evidence="ECO:0000305"
FT CONFLICT 759
FT /note="C -> R (in Ref. 4; CAE45903)"
FT /evidence="ECO:0000305"
FT CONFLICT 811
FT /note="T -> TVSWDQ (in Ref. 6; AAO73817)"
FT /evidence="ECO:0000305"
FT CONFLICT 834
FT /note="S -> N (in Ref. 4; CAE45903)"
FT /evidence="ECO:0000305"
FT CONFLICT 865
FT /note="Missing (in Ref. 6; AAO73817)"
FT /evidence="ECO:0000305"
FT CONFLICT 1051
FT /note="Missing (in Ref. 4; CAE45903 and 5; BAA74892)"
FT /evidence="ECO:0000305"
FT CONFLICT 1064..1065
FT /note="DK -> AR (in Ref. 6; AAO73817)"
FT /evidence="ECO:0000305"
FT STRAND 660..669
FT /evidence="ECO:0007829|PDB:2Z0U"
FT TURN 670..673
FT /evidence="ECO:0007829|PDB:2Z0U"
FT STRAND 674..683
FT /evidence="ECO:0007829|PDB:2Z0U"
FT HELIX 685..687
FT /evidence="ECO:0007829|PDB:2Z0U"
FT STRAND 691..693
FT /evidence="ECO:0007829|PDB:6FB4"
FT STRAND 694..704
FT /evidence="ECO:0007829|PDB:2Z0U"
FT HELIX 708..711
FT /evidence="ECO:0007829|PDB:2Z0U"
FT STRAND 712..714
FT /evidence="ECO:0007829|PDB:2Z0U"
FT STRAND 722..733
FT /evidence="ECO:0007829|PDB:2Z0U"
FT HELIX 736..741
FT /evidence="ECO:0007829|PDB:2Z0U"
FT STRAND 743..751
FT /evidence="ECO:0007829|PDB:2Z0U"
FT TURN 753..755
FT /evidence="ECO:0007829|PDB:6FD0"
FT STRAND 757..766
FT /evidence="ECO:0007829|PDB:2Z0U"
FT STRAND 772..775
FT /evidence="ECO:0007829|PDB:6FB4"
FT STRAND 777..784
FT /evidence="ECO:0007829|PDB:2Z0U"
SQ SEQUENCE 1113 AA; 125301 MW; 9010B9C127129165 CRC64;
MPRPELPLPE GWEEARDFDG KVYYIDHTNR TTSWIDPRDR YTKPLTFADC ISDELPLGWE
EAYDPQVGDY FIDHNTKTTQ IEDPRVQWRR EQEHMLKDYL VVAQEALSAQ KEIYQVKQQR
LELAQQEYQQ LHAVWEHKLG SQVSLVSGSS SSSKYDPEIL KAEIATAKSR VNKLKREMVH
LQHELQFKER GFQTLKKIDK KMSDAQGSYK LDEAQAVLRE TKAIKKAITC GEKEKQDLIK
SLAMLKDGFR TDRGSHSDLW SSSSSLESSS FPLPKQYLDV SSQTDISGSF GINSNNQLAE
KVRLRLRYEE AKRRIANLKI QLAKLDSEAW PGVLDSERDR LILINEKEEL LKEMRFISPR
KWTQGEVEQL EMARKRLEKD LQAARDTQSK ALTERLKLNS KRNQLVRELE EATRQVATLH
SQLKSLSSSM QSLSSGSSPG SLTSSRGSLV ASSLDSSTSA SFTDLYYDPF EQLDSELQSK
VEFLLLEGAT GFRPSGCITT IHEDEVAKTQ KAEGGGRLQA LRSLSGTPKS MTSLSPRSSL
SSPSPPCSPL MADPLLAGDA FLNSLEFEDP ELSATLCELS LGNSAQERYR LEEPGTEGKQ
LGQAVNTAQG CGLKVACVSA AVSDESVAGD SGVYEASVQR LGASEAAAFD SDESEAVGAT
RIQIALKYDE KNKQFAILII QLSNLSALLQ QQDQKVNIRV AVLPCSESTT CLFRTRPLDA
SDTLVFNEVF WVSMSYPALH QKTLRVDVCT TDRSHLEECL GGAQISLAEV CRSGERSTRW
YNLLSYKYLK KQSRELKPVG VMAPASGPAS TDAVSALLEQ TAVELEKRQE GRSSTQTLED
SWRYEETSEN EAVAEEEEEE VEEEEGEEDV FTEKASPDMD GYPALKVDKE TNTETPAPSP
TVVRPKDRRV GTPSQGPFLR GSTIIRSKTF SPGPQSQYVC RLNRSDSDSS TLSKKPPFVR
NSLERRSVRM KRPSSVKSLR SERLIRTSLD LELDLQATRT WHSQLTQEIS VLKELKEQLE
QAKSHGEKEL PQWLREDERF RLLLRMLEKR QMDRAEHKGE LQTDKMMRAA AKDVHRLRGQ
SCKEPPEVQS FREKMAFFTR PRMNIPALSA DDV
