KIBRA_MOUSE
ID KIBRA_MOUSE Reviewed; 1104 AA.
AC Q5SXA9; Q571D0; Q8K1Y3; Q8VD17; Q922W3;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Protein KIBRA;
DE AltName: Full=Kidney and brain protein;
DE Short=KIBRA;
DE AltName: Full=WW domain-containing protein 1;
GN Name=Wwc1; Synonyms=Kiaa0869;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129/SvEv;
RA Kremerskothen J.;
RT "Protein-coding sequence of KIBRA from Mus musculus.";
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 141-1104.
RC TISSUE=Pancreatic islet;
RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Seino S., Nishimura M.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT fractionated libraries.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 146-1104.
RC STRAIN=FVB/N; TISSUE=Mammary gland, Mammary tumor, and Salivary gland;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-887 AND SER-891, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-141; SER-919 AND SER-939, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 and may be associated with memory performance (By
CC similarity). Regulates collagen-stimulated activation of the ERK/MAPK
CC cascade. {ECO:0000250, ECO:0000269|PubMed:18190796}.
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 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18190796}.
CC Cytoplasm, perinuclear region {ECO:0000250}. Nucleus {ECO:0000250}.
CC Cell projection, ruffle membrane {ECO:0000250}. Note=Colocalizes with
CC PRKCZ in the perinuclear region. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Mammary epithelium. {ECO:0000269|PubMed:18190796}.
CC -!- DEVELOPMENTAL STAGE: Expressed in mammary tissue throughout development
CC (at protein level). Strongly up-regulated during pregnancy, falls
CC during lactation and is again up-regulated during involution of the
CC gland at weaning. {ECO:0000269|PubMed:18190796}.
CC -!- DOMAIN: The C2-domain mediates homodimerization. {ECO:0000250}.
CC -!- PTM: Phosphorylation at Ser-542 and Ser-923 by CDK1 in response to
CC spindle damage stress regulates mitotic exit, these two sites are
CC dephosphorylated by CDC14B. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the WWC family. KIBRA subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH06733.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH37006.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; DQ256090; ABB51169.1; -; mRNA.
DR EMBL; AL596084; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL645912; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK220259; BAD90184.1; -; mRNA.
DR EMBL; BC006733; AAH06733.1; ALT_INIT; mRNA.
DR EMBL; BC017638; AAH17638.1; -; mRNA.
DR EMBL; BC037006; AAH37006.1; ALT_INIT; mRNA.
DR CCDS; CCDS24545.1; -.
DR RefSeq; NP_740749.1; NM_170779.1.
DR PDB; 6J68; X-ray; 2.50 A; A/B=5-132.
DR PDB; 6J69; X-ray; 2.75 A; A=5-132.
DR PDB; 6JJW; X-ray; 2.40 A; A=5-132.
DR PDB; 6JJX; X-ray; 2.00 A; A/B=5-132.
DR PDB; 6JJY; X-ray; 2.30 A; A=5-132.
DR PDBsum; 6J68; -.
DR PDBsum; 6J69; -.
DR PDBsum; 6JJW; -.
DR PDBsum; 6JJX; -.
DR PDBsum; 6JJY; -.
DR AlphaFoldDB; Q5SXA9; -.
DR SMR; Q5SXA9; -.
DR BioGRID; 229255; 4.
DR STRING; 10090.ENSMUSP00000018993; -.
DR iPTMnet; Q5SXA9; -.
DR PhosphoSitePlus; Q5SXA9; -.
DR jPOST; Q5SXA9; -.
DR MaxQB; Q5SXA9; -.
DR PaxDb; Q5SXA9; -.
DR PRIDE; Q5SXA9; -.
DR ProteomicsDB; 269299; -.
DR Antibodypedia; 48675; 222 antibodies from 25 providers.
DR DNASU; 211652; -.
DR Ensembl; ENSMUST00000018993; ENSMUSP00000018993; ENSMUSG00000018849.
DR GeneID; 211652; -.
DR KEGG; mmu:211652; -.
DR UCSC; uc007ili.1; mouse.
DR CTD; 23286; -.
DR MGI; MGI:2388637; Wwc1.
DR VEuPathDB; HostDB:ENSMUSG00000018849; -.
DR eggNOG; KOG3209; Eukaryota.
DR GeneTree; ENSGT00410000025556; -.
DR HOGENOM; CLU_005420_0_0_1; -.
DR InParanoid; Q5SXA9; -.
DR OMA; HHTHIPR; -.
DR OrthoDB; 364990at2759; -.
DR PhylomeDB; Q5SXA9; -.
DR TreeFam; TF324040; -.
DR Reactome; R-MMU-2028269; Signaling by Hippo.
DR BioGRID-ORCS; 211652; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Wwc1; mouse.
DR PRO; PR:Q5SXA9; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q5SXA9; protein.
DR Bgee; ENSMUSG00000018849; Expressed in vestibular membrane of cochlear duct and 218 other tissues.
DR Genevisible; Q5SXA9; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0032587; C:ruffle membrane; ISS:UniProtKB.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0060090; F:molecular adaptor activity; ISO:MGI.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:MGI.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0035331; P:negative regulation of hippo signaling; ISO:MGI.
DR GO; GO:0046621; P:negative regulation of organ growth; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0035330; P:regulation of hippo signaling; ISO:MGI.
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; PF00168; C2; 1.
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; Cell membrane; Cell projection; Coiled coil;
KW Cytoplasm; Membrane; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Transcription; Transcription regulation.
FT CHAIN 1..1104
FT /note="Protein KIBRA"
FT /id="PRO_0000242154"
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 659..782
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 429..449
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 509..547
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 822..949
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 836..1104
FT /note="Interaction with histone H3"
FT /evidence="ECO:0000250"
FT REGION 945..988
FT /note="Interaction with PRKCZ"
FT /evidence="ECO:0000250"
FT COILED 107..193
FT /evidence="ECO:0000255"
FT COILED 994..1024
FT /evidence="ECO:0000255"
FT MOTIF 1102..1104
FT /note="ADDV motif"
FT COMPBIAS 520..546
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 842..863
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 864..880
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 912..949
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 141
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IX03"
FT MOD_RES 542
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q8IX03"
FT MOD_RES 887
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 891
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 919
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 921
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8IX03"
FT MOD_RES 923
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q8IX03"
FT MOD_RES 939
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 967
FT /note="Phosphoserine; by PKC/PRKCZ"
FT /evidence="ECO:0000250|UniProtKB:Q8IX03"
FT MOD_RES 970
FT /note="Phosphoserine; by PKC/PRKCZ"
FT /evidence="ECO:0000250|UniProtKB:Q8IX03"
FT CONFLICT 141..145
FT /note="SQVSL -> AGLPV (in Ref. 3; BAD90184)"
FT /evidence="ECO:0000305"
FT CONFLICT 348
FT /note="E -> K (in Ref. 4; AAH06733)"
FT /evidence="ECO:0000305"
FT STRAND 12..16
FT /evidence="ECO:0007829|PDB:6JJX"
FT STRAND 22..26
FT /evidence="ECO:0007829|PDB:6JJX"
FT TURN 27..30
FT /evidence="ECO:0007829|PDB:6JJX"
FT STRAND 31..35
FT /evidence="ECO:0007829|PDB:6JJX"
FT HELIX 39..42
FT /evidence="ECO:0007829|PDB:6JJX"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:6JJY"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:6JJX"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:6JJX"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:6JJX"
FT TURN 74..77
FT /evidence="ECO:0007829|PDB:6JJX"
FT STRAND 78..82
FT /evidence="ECO:0007829|PDB:6JJX"
FT HELIX 84..116
FT /evidence="ECO:0007829|PDB:6JJX"
FT TURN 117..119
FT /evidence="ECO:0007829|PDB:6JJX"
FT HELIX 122..128
FT /evidence="ECO:0007829|PDB:6JJX"
SQ SEQUENCE 1104 AA; 124110 MW; D827EFD9AAB19FBA CRC64;
MPRPELPLPE GWEEARDFDG KVYYIDHRNR TTSWIDPRDR YTKPLTFADC ISDELPLGWE
EAYDPQVGDY FIDHNTKTTQ IEDPRVQWRR EQEHMLKDYL VVAQEALSAQ KEIYQVKQQR
LELAQQEYQQ LHAVWEHKLG SQVSLVSGSS SSSKYDPEIL KAEIATAKSR VNKLKREMVH
LQHELQFKER GFQTLKKIDE RMSDAQGGYK LDEAQAVLRE TKAIKKAITC GEKEKQDLIK
SLAMLKDGFR TDRGSHSDLW SSSSSLESSS FPMPKQFLDV SSQTDISGSF STSSNNQLAE
KVRLRLRYEE AKRRIANLKI QLAKLDSEAW PGVLDSERDR LILINEKEEL LKEMRFISPR
KWTQGEVEQL EMARRRLEKD LQAARDTQSK ALTERLKLNS KRNQLVRELE EATRQVATLH
SQLKSLSSSM QSLSSGSSPG SLTSSRGSLA ASSLDSSTSA SFTDLYYDPF EQLDSELQSK
VELLFLEGAT GFRPSGCITT IHEDEVAKTQ KAEGGSRLQA LRSLSGTPRS MTSLSPRSSL
SSPSPPCSPL ITDPLLTGDA FLAPLEFEDT ELSTTLCELN LGGSGTQERY RLEEPGPEGK
PLGQAASVAP GCGLKVACVS AAVSDESVAG DSGVYEASAQ RPGTSEAAAF DSDESEAVGA
TRVQIALKYD EKNKQFAILI IQLSHLSALS LQQDQKVNIR VAILPCSESS TCLFRTRPLD
SANTLVFNEA FWVSISYPAL HQKTLRVDVC TTDRSHTEEC LGGAQISLAE VCRSGERSTR
WYNLLSYKYL KKQCREPQPT EAPGPDHVDA VSALLEQTAV ELEKRQEGRS SSQTLEGSWT
YEEEASENEA VAEEEEEGEE DVFTEKVSPE AEECPALKVD RETNTDSVAP SPTVVRPKDR
RVGAPSTGPF LRGNTIIRSK TFSPGPQSQY VCRLNRSDSD SSTLSKKPPF VRNSLERRSV
RMKRPSSVKS LRTERLIRTS LDLELDLQAT RTWHSQLTQE ISVLKELKEH LEQAKNHGEK
ELPQWLREDE RFRLLLRMLE KKVDRGEHKS ELQADKMMRA AAKDVHRLRG QSCKEPPEVQ
SFREKMAFFT RPRMNIPALS ADDV
