ID KIBRA_HUMAN Reviewed; 1113 AA. AC Q8IX03; O94946; Q6MZX4; Q6Y2F8; Q7Z4G8; Q8WVM4; Q9BT29; DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 05-OCT-2010, entry version 54. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH DDN, RP SUBCELLULAR 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., RA Matanis T., 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] 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., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 225-1113 (ISOFORM 2). RC TISSUE=Brain; RX MEDLINE=99156230; PubMed=10048485; DOI=10.1093/dnares/5.6.355; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XII. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 5:355-364(1998). RN [4] 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 [5] 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, SUBUNIT, INTERACTION WITH PRKCZ, AND PHOSPHORYLATION AT RP SER-975 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 [7] 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 RT chain 1 in mammalian cells."; RL J. Biol. Chem. 281:19092-19099(2006). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-922; THR-923 AND RP SER-927, AND MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=17924679; DOI=10.1021/pr070152u; RA Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa RT cells and high confident phosphopeptide identification by cross- RT validation of MS/MS and MS/MS/MS spectra."; RL J. Proteome Res. 6:4150-4162(2007). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SYNPO AND INADL, AND RP TISSUE SPECIFICITY. RX PubMed=18596123; DOI=10.1681/ASN.2007080916; RA Duning K., Schurek E.M., Schlueter M., Bayer M., Reinhardt H.C., RA Schwab A., Schaefer L., Benzing T., Schermer B., Saleem M.A., RA Huber T.B., Bachmann S., Kremerskothen J., Weide T., Pavenstaedt H.; RT "KIBRA modulates directional migration of podocytes."; RL J. Am. Soc. Nephrol. 19:1891-1903(2008). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, INDUCTION, RP INTERACTION 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., RA Daly R.J., Ormandy C.J.; RT "KIBRA interacts with discoidin domain receptor 1 to modulate RT collagen-induced signalling."; RL Biochim. Biophys. Acta 1783:383-393(2008). RN [11] 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., RA 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 [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-912; THR-929 AND RP SER-931, AND MASS SPECTROMETRY. 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 [13] 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 [14] 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 [15] 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) CC signaling pathway, a signaling pathway that plays a pivotal role CC in tumor suppression by restricting proliferation and promoting CC apoptosis. Along with NF2 can synergistically induce the CC phosphorylation of LATS1 and LATS2 and can probably function in CC the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. CC Acts as a transcriptional coactivator of ESR1 which plays an CC essential role in DYNLL1-mediated ESR1 transactivation. Regulates CC collagen-stimulated activation of the ERK/MAPK cascade. Modulates CC directional migration of podocytes. Acts as a substrate for PRKCZ CC and may be associated with memory performance. 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 CC proper regulatory interaction of WWC1-DYNLL1-ESR1 complexes with CC target chromatin. Interacts (via WW domains) with DDR1 (via PPxY CC motif) in a collagen-regulated manner. Interacts with PRKCZ (via CC the protein kinase domain). Forms a tripartite complex with DDR1 CC and PRKCZ, but predominantly in the absence of collagen. Interacts CC (via the ADDV motif) with INADL (via PDZ domain 8). Interacts (via CC WW domains) with SYNPO (via PPxY motifs). Interacts with NF2. CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, perinuclear region. CC Nucleus. Cell projection, ruffle membrane. Note=Co-localizes with CC PRKCZ 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, VSP_019449; CC -!- TISSUE SPECIFICITY: Expressed in mammary epithelial cells and CC breast cancer cell lines. Found in the luminal epithelium CC surrounding the ducts in the normal breast. In the brain, CC expressed in somatodendritic compartment of neurons in the cortex CC and hippocampus and in the cerebellum it is found in the Purkinje CC cells and some granule cells (at protein level). Detected in CC brain, heart, colon and kidney. In the kidney, expressed in CC glomerular podocytes, in some tubules and in the collecting duct. CC -!- INDUCTION: Strongly up-regulated by progestin treatment. CC -!- DOMAIN: The C2-domain mediates homodimerization. CC -!- SIMILARITY: Belongs to the WWC family. KIBRA subfamily. CC -!- SIMILARITY: Contains 1 C2 domain. CC -!- SIMILARITY: Contains 2 WW domains. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF506799; AAO15881.1; -; mRNA. 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 IPI; IPI00217340; -. DR IPI; IPI00761080; -. DR RefSeq; NP_001155134.1; -. DR RefSeq; NP_056053.1; -. DR UniGene; Hs.484047; -. DR PDB; 2Z0U; X-ray; 2.20 A; A/B=638-785. DR PDBsum; 2Z0U; -. DR ProteinModelPortal; Q8IX03; -. DR SMR; Q8IX03; 4-85. DR DIP; DIP-35287N; -. DR IntAct; Q8IX03; 6. DR MINT; MINT-1405937; -. DR STRING; Q8IX03; -. DR PhosphoSite; Q8IX03; -. DR PRIDE; Q8IX03; -. DR Ensembl; ENST00000265293; ENSP00000265293; ENSG00000113645. DR GeneID; 23286; -. DR UCSC; uc003lzu.1; human. DR UCSC; uc003lzv.1; human. DR CTD; 23286; -. DR GeneCards; GC05P167652; -. DR H-InvDB; HIX0021481; -. DR HGNC; HGNC:29435; WWC1. DR MIM; 610533; gene. DR eggNOG; prNOG14919; -. DR HOVERGEN; HBG058082; -. DR OrthoDB; EOG9Z91FP; -. DR PhylomeDB; Q8IX03; -. DR NextBio; 45094; -. DR ArrayExpress; Q8IX03; -. DR Bgee; Q8IX03; -. DR CleanEx; HS_WWC1; -. DR Genevestigator; Q8IX03; -. 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:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0016477; P:cell migration; IDA:UniProtKB. DR GO; GO:0043410; P:positive regulation of MAPKKK cascade; IDA:UniProtKB. DR GO; GO:0035330; P:regulation of hippo signaling cascade; IMP:UniProtKB. DR GO; GO:0006350; P:transcription; IEA:UniProtKB-KW. DR InterPro; IPR008973; C2_Ca/lipid-bd_dom_CaLB. DR InterPro; IPR001202; WW_Rsp5_WWP. DR Pfam; PF00397; WW; 2. DR SMART; SM00456; WW; 2. DR SUPFAM; SSF49562; C2_CaLB; 1. DR SUPFAM; SSF51045; WW_Rsp5_WWP; 2. DR PROSITE; PS50004; C2; FALSE_NEG. 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; Complete proteome; Cytoplasm; Membrane; KW Nucleus; Phosphoprotein; Polymorphism; Repeat; Transcription; KW Transcription regulation. FT CHAIN 1 1113 Protein KIBRA. FT /FTId=PRO_0000242153. FT DOMAIN 6 39 WW 1. FT DOMAIN 53 86 WW 2. FT DOMAIN 655 783 C2. FT REGION 839 1113 Interaction with histone H3. FT REGION 953 996 Interaction with PRKCZ. FT COILED 107 193 Potential. FT COILED 293 431 Potential. FT COILED 1001 1032 Potential. FT MOTIF 1111 1113 ADDV motif. FT COMPBIAS 261 265 Poly-Ser. FT COMPBIAS 819 873 Glu-rich. FT MOD_RES 899 899 Phosphoserine (By similarity). FT MOD_RES 912 912 Phosphothreonine. FT MOD_RES 922 922 Phosphoserine. FT MOD_RES 923 923 Phosphothreonine. FT MOD_RES 927 927 Phosphoserine. FT MOD_RES 929 929 Phosphothreonine. FT MOD_RES 931 931 Phosphoserine. FT MOD_RES 975 975 Phosphoserine; by PKC/PRKCZ. FT MOD_RES 978 978 Phosphoserine; by PKC/PRKCZ. FT VAR_SEQ 974 974 S -> SPPPQPS (in isoform 2). FT /FTId=VSP_019448. FT VAR_SEQ 1051 1051 Missing (in isoform 2). FT /FTId=VSP_019449. FT VARIANT 250 250 R -> C (in dbSNP:rs17551608). FT /FTId=VAR_026844. FT VARIANT 734 734 M -> I (in dbSNP:rs3822660). FT /FTId=VAR_053449. FT VARIANT 735 735 S -> A (in dbSNP:rs3822659). FT /FTId=VAR_053450. FT CONFLICT 561 561 F -> L (in Ref. 2; CAE45903). FT CONFLICT 759 759 C -> R (in Ref. 2; CAE45903). FT CONFLICT 811 811 T -> TVSWDQ (in Ref. 4; AAO73817). FT CONFLICT 834 834 S -> N (in Ref. 2; CAE45903). FT CONFLICT 865 865 Missing (in Ref. 4; AAO73817). FT CONFLICT 1064 1065 DK -> AR (in Ref. 4; AAO73817). FT STRAND 660 669 FT TURN 670 673 FT STRAND 674 683 FT HELIX 685 687 FT STRAND 694 704 FT HELIX 708 711 FT STRAND 712 714 FT STRAND 722 733 FT HELIX 736 741 FT STRAND 743 751 FT STRAND 757 759 FT STRAND 764 766 FT STRAND 777 783 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 //