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 02-SEP-2026, entry version 170. 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 {ECO:0000312|HGNC:HGNC:29435}; Synonyms=KIAA0869, KIBRA; 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 SUBUNIT, INTERACTION WITH PRKCZ, AND PHOSPHORYLATION AT SER-975 AND RP 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 FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND INTERACTION WITH DLC1; PRKCZ; RP LATS1 AND LATS2. RX PubMed=24682284; DOI=10.1093/molbev/msu115; RA Wennmann D.O., Schmitz J., Wehr M.C., Krahn M.P., Koschmal N., RA Gromnitza S., Schulze U., Weide T., Chekuri A., Skryabin B.V., Gerke V., RA Pavenstadt H., Duning K., Kremerskothen J.; RT "Evolutionary and Molecular Facts Link the WWC Protein Family to Hippo RT Signaling."; RL Mol. Biol. Evol. 31:1710-1723(2014). RN [25] 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: Regulator of the Hippo signaling pathway, also known as the CC Salvador-Warts-Hippo (SWH) pathway (PubMed:24682284). Enhances CC phosphorylation of LATS1 and YAP1 and negatively regulates cell CC proliferation and organ growth due to a suppression of the CC transcriptional activity of YAP1, the major effector of the Hippo CC pathway (PubMed:24682284). Along with NF2 can synergistically induce CC the phosphorylation of LATS1 and LATS2 and function in the regulation CC of Hippo signaling pathway (PubMed:20159598). Acts as a transcriptional CC coactivator of ESR1 which plays an essential role in DYNLL1-mediated CC ESR1 transactivation (PubMed:16684779). Regulates collagen-stimulated CC activation of the ERK/MAPK cascade (PubMed:18190796). Modulates CC directional migration of podocytes (PubMed:18596123). Plays a role in CC cognition and memory performance (PubMed:18672031). Plays an important CC role in regulating AMPA-selective glutamate receptors (AMPARs) CC trafficking underlying synaptic plasticity and learning (By CC similarity). {ECO:0000250|UniProtKB:Q5SXA9, CC ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:18190796, CC ECO:0000269|PubMed:18596123, ECO:0000269|PubMed:18672031, CC ECO:0000269|PubMed:20159598, ECO:0000269|PubMed:24682284}. CC -!- SUBUNIT: Homodimer (PubMed:15081397, PubMed:18672031). Forms CC heterodimers with WWC2 and WWC3 (PubMed:24682284). Interacts with DDN. CC Interacts with DYNLL1 and histone H3. The interaction with DYNLL1 is CC mandatory for the recruitment and transactivation functions of ESR1 or CC DYNLL1 to the target chromatin and the interaction with histone H3 CC ensures proper regulatory interaction of WWC1-DYNLL1-ESR1 complexes CC with target chromatin. Interacts (via WW domains) with DDR1 (via PPxY CC motif) in a collagen-regulated manner. Interacts with PRKCZ (via the CC protein kinase domain). Forms a tripartite complex with DDR1 and PRKCZ, CC but 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. Interacts with CC DLC1 and PRKCZ (PubMed:24682284). Interacts (via WW domains) with LATS1 CC and LATS2 (PubMed:24682284). {ECO:0000269|PubMed:12559952, CC ECO:0000269|PubMed:15081397, ECO:0000269|PubMed:16684779, CC ECO:0000269|PubMed:17994011, ECO:0000269|PubMed:18190796, CC ECO:0000269|PubMed:18596123, ECO:0000269|PubMed:18672031, CC ECO:0000269|PubMed:20159599, ECO:0000269|PubMed:24682284}. CC -!- INTERACTION: CC Q8IX03-1; Q62824: Exoc4; Xeno; NbExp=3; IntAct=EBI-15812469, EBI-6959516; CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:18596123}. Nucleus {ECO:0000269|PubMed:16684779, CC ECO:0000269|PubMed:18190796}. Cell projection, ruffle membrane CC {ECO:0000269|PubMed:18190796}. Cytoplasm, cytosol CC {ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:18190796, CC ECO:0000269|PubMed:24682284}. Note=Colocalizes with PRKCZ in the CC 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_001161661.2. [Q8IX03-2] DR RefSeq; NP_001155134.1; NM_001161662.2. DR RefSeq; NP_056053.1; NM_015238.3. [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 AlphaFoldDB; Q8IX03; -. DR SMR; Q8IX03; -. DR BioGRID; 116884; 101. DR CORUM; Q8IX03; -. DR DIP; DIP-35287N; -. DR FunCoup; Q8IX03; 1318. DR IntAct; Q8IX03; 79. DR MINT; Q8IX03; -. DR NDEx; IQUERY-CP-WWC1; 2 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000427772; -. DR CarbonylDB; Q8IX03; -. DR GlyGen; Q8IX03; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q8IX03; -. DR PhosphoSitePlus; Q8IX03; -. DR BioMuta; WWC1; -. DR DMDM; 74714457; -. DR jPOST; Q8IX03; -. DR MassIVE; Q8IX03; -. DR PaxDb; 9606-ENSP00000427772; -. DR PeptideAtlas; Q8IX03; -. DR ProteomicsDB; 70950; -. [Q8IX03-1] DR ProteomicsDB; 70951; -. [Q8IX03-2] DR Pumba; Q8IX03; -. DR Antibodypedia; 48675; 219 antibodies from 27 providers. DR DNASU; 23286; -. DR Ensembl; ENST00000265293.9; ENSP00000265293.4; ENSG00000113645.16. [Q8IX03-1] DR Ensembl; ENST00000521089.5; ENSP00000427772.1; ENSG00000113645.16. [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 AGR; HGNC:29435; -. DR ClinPGx; PA143485670; -. 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 OpenTargets; ENSG00000113645; -. DR VEuPathDB; HostDB:ENSG00000113645; -. DR eggNOG; KOG3209; Eukaryota. DR GeneTree; ENSGT00410000025556; -. DR HOGENOM; CLU_005420_0_0_1; -. DR InParanoid; Q8IX03; -. DR OMA; QVTVVSM; -. DR OrthoDB; 2020426at2759; -. DR PAN-GO; Q8IX03; 7 GO annotations based on evolutionary models. DR PhylomeDB; Q8IX03; -. 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 Agora; ENSG00000113645; -. DR BioGRID-ORCS; 23286; 13 hits in 1139 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 180 other cell types or tissues. DR ExpressionAtlas; Q8IX03; baseline and differential. 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: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:0035591; F:signaling adaptor activity; IDA:UniProt. 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:0035329; P:hippo signaling; IDA:UniProt. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB. 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:0006355; P:regulation of DNA-templated transcription; IBA:GO_Central. DR GO; GO:0035330; P:regulation of hippo signaling; IMP:UniProtKB. DR CDD; cd08680; C2_Kibra; 1. DR CDD; cd00201; WW; 2. DR FunFam; 2.20.70.10:FF:000001; Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1; 1. DR FunFam; 2.60.40.150:FF:000084; Protein KIBRA isoform 1; 1. DR FunFam; 2.20.70.10:FF:000041; WW and C2 domain containing 1; 1. DR Gene3D; 2.20.70.10; -; 2. DR Gene3D; 2.60.40.150; C2 domain; 1. DR IDEAL; IID00850; -. 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 InterPro; IPR051105; WWC/KIBRA_Hippo_Reg. DR InterPro; IPR057747; WWC1_hairpin. DR PANTHER; PTHR14791; BOMB/KIRA PROTEINS; 1. DR PANTHER; PTHR14791:SF22; PROTEIN KIBRA; 1. DR Pfam; PF00168; C2; 1. DR Pfam; PF00397; WW; 2. DR Pfam; PF25802; WWC1; 1. DR SMART; SM00456; WW; 2. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF51045; WW domain; 2. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS01159; WW_DOMAIN_1; 1. DR PROSITE; PS50020; WW_DOMAIN_2; 2. DR PDBsum; 2Z0U; -. DR PDBsum; 6FB4; -. DR PDBsum; 6FD0; -. DR PDBsum; 6FJC; -. DR PDBsum; 6FJD; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Cell membrane; KW Cell projection; Coiled coil; Cytoplasm; Membrane; Nucleus; Phosphoprotein; KW Proteomics identification; Reference proteome; Repeat; Repressor; KW 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 REGION 956..975 FT /note="Interaction with PRKCZ" FT /evidence="ECO:0000269|PubMed:24682284" 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 522..532 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 533..542 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 847..870 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 924..938 FT /note="Polar 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 HELIX 715..717 FT /evidence="ECO:0007829|PDB:6FB4" 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 //