INTU_MOUSE
ID INTU_MOUSE Reviewed; 942 AA.
AC Q059U7; Q80TG0; Q8BS60; Q8C9Y0;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2006, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Protein inturned;
DE AltName: Full=Inturned planar cell polarity effector homolog;
DE AltName: Full=PDZ domain-containing protein 6;
GN Name=Intu; Synonyms=Kiaa1284, Pdzd6;
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 [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-774 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
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 GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 122-942 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-678, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
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).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND SUBCELLULAR
RP LOCATION.
RX PubMed=20067783; DOI=10.1016/j.ydbio.2010.01.003;
RA Zeng H., Hoover A.N., Liu A.;
RT "PCP effector gene Inturned is an important regulator of cilia formation
RT and embryonic development in mammals.";
RL Dev. Biol. 339:418-428(2010).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21761479; DOI=10.1002/dvdy.22696;
RA Heydeck W., Liu A.;
RT "PCP effector proteins inturned and fuzzy play nonredundant roles in the
RT patterning but not convergent extension of mammalian neural tube.";
RL Dev. Dyn. 240:1938-1948(2011).
RN [9]
RP INTERACTION WITH CPLANE1; FUZ AND WDPCP.
RX PubMed=27158779; DOI=10.1038/ng.3558;
RA Toriyama M., Lee C., Taylor S.P., Duran I., Cohn D.H., Bruel A.L.,
RA Tabler J.M., Drew K., Kelly M.R., Kim S., Park T.J., Braun D.A.,
RA Pierquin G., Biver A., Wagner K., Malfroot A., Panigrahi I., Franco B.,
RA Al-Lami H.A., Yeung Y., Choi Y.J., Duffourd Y., Faivre L., Riviere J.B.,
RA Chen J., Liu K.J., Marcotte E.M., Hildebrandt F., Thauvin-Robinet C.,
RA Krakow D., Jackson P.K., Wallingford J.B.;
RT "The ciliopathy-associated CPLANE proteins direct basal body recruitment of
RT intraflagellar transport machinery.";
RL Nat. Genet. 48:648-656(2016).
CC -!- FUNCTION: Plays a key role in ciliogenesis and embryonic development.
CC Regulator of cilia formation by controlling the organization of the
CC apical actin cytoskeleton and the positioning of the basal bodies at
CC the apical cell surface, which in turn is essential for the normal
CC orientation of elongating ciliary microtubules. Plays a key role in
CC definition of cell polarity via its role in ciliogenesis but not via
CC conversion extension. Has an indirect effect on hedgehog signaling
CC (PubMed:20067783, PubMed:21761479). Proposed to function as core
CC component of the CPLANE (ciliogenesis and planar polarity effectors)
CC complex involved in the recruitment of peripheral IFT-A proteins to
CC basal bodies (By similarity). {ECO:0000250|UniProtKB:Q9ULD6,
CC ECO:0000269|PubMed:20067783, ECO:0000269|PubMed:21761479}.
CC -!- SUBUNIT: Interacts with CPLANE1. Interacts with FUZ and WDPCP; FUZ,
CC INTU and WDPCP probably form the core CPLANE (ciliogenesis and planar
CC polarity effectors) complex. {ECO:0000269|PubMed:27158779}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20067783}. Cell
CC surface {ECO:0000250|UniProtKB:Q2I0E5}. Cytoplasm, cytoskeleton, cilium
CC basal body {ECO:0000250|UniProtKB:Q2I0E5}. Note=Enriched at the apical
CC surface in ciliated cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q059U7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q059U7-2; Sequence=VSP_042603, VSP_042604, VSP_042605;
CC -!- TISSUE SPECIFICITY: Widely expressed in E8.5 and E9.5 wild type
CC embryos. Present in various adult organs (at protein level).
CC {ECO:0000269|PubMed:20067783}.
CC -!- DISRUPTION PHENOTYPE: Embryos die at midgestation. Embryos exhibit
CC multiple defects including neural tube closure defects, abnormal
CC dorsal/ventral patterning of the central nervous system and abnormal
CC anterior-posterior patterning of the limbs resulting in severe
CC polydactyly. Fewer and shorter cilia are present in mutant embryos. In
CC mice lacking both Intu and Fuz, the lack of convergent extension and
CC more severe patterning defects in Intu and Fuz mutants does not result
CC from a functional redundancy between these proteins.
CC {ECO:0000269|PubMed:20067783, ECO:0000269|PubMed:21761479}.
CC -!- SIMILARITY: Belongs to the inturned family. {ECO:0000305}.
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DR EMBL; AK040233; BAC30547.1; -; mRNA.
DR EMBL; AK035092; BAC28943.1; -; mRNA.
DR EMBL; AC146980; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC163023; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466530; EDL35133.1; -; Genomic_DNA.
DR EMBL; BC125523; AAI25524.1; -; mRNA.
DR EMBL; BC132387; AAI32388.1; -; mRNA.
DR EMBL; AK122485; BAC65767.1; -; mRNA.
DR CCDS; CCDS84619.1; -. [Q059U7-1]
DR RefSeq; NP_780724.3; NM_175515.5. [Q059U7-1]
DR PDB; 7Q3E; EM; 3.35 A; B=54-942.
DR PDBsum; 7Q3E; -.
DR AlphaFoldDB; Q059U7; -.
DR ComplexPortal; CPX-5026; CPLANE complex.
DR CORUM; Q059U7; -.
DR STRING; 10090.ENSMUSP00000088725; -.
DR iPTMnet; Q059U7; -.
DR PhosphoSitePlus; Q059U7; -.
DR jPOST; Q059U7; -.
DR MaxQB; Q059U7; -.
DR PaxDb; Q059U7; -.
DR PRIDE; Q059U7; -.
DR ProteomicsDB; 267145; -. [Q059U7-1]
DR ProteomicsDB; 267146; -. [Q059U7-2]
DR Antibodypedia; 26899; 82 antibodies from 17 providers.
DR DNASU; 380614; -.
DR Ensembl; ENSMUST00000061590; ENSMUSP00000054313; ENSMUSG00000060798. [Q059U7-2]
DR Ensembl; ENSMUST00000091186; ENSMUSP00000088725; ENSMUSG00000060798. [Q059U7-1]
DR GeneID; 380614; -.
DR KEGG; mmu:380614; -.
DR UCSC; uc033htd.1; mouse. [Q059U7-1]
DR CTD; 27152; -.
DR MGI; MGI:2443752; Intu.
DR VEuPathDB; HostDB:ENSMUSG00000060798; -.
DR eggNOG; ENOG502QQJQ; Eukaryota.
DR GeneTree; ENSGT00390000001301; -.
DR HOGENOM; CLU_104236_0_0_1; -.
DR InParanoid; Q059U7; -.
DR OMA; WKEINNV; -.
DR OrthoDB; 898612at2759; -.
DR PhylomeDB; Q059U7; -.
DR TreeFam; TF323932; -.
DR Reactome; R-MMU-5610787; Hedgehog 'off' state.
DR BioGRID-ORCS; 380614; 1 hit in 19 CRISPR screens.
DR ChiTaRS; Intu; mouse.
DR PRO; PR:Q059U7; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q059U7; protein.
DR Bgee; ENSMUSG00000060798; Expressed in ventricular zone and 69 other tissues.
DR ExpressionAtlas; Q059U7; baseline and differential.
DR Genevisible; Q059U7; MM.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005814; C:centriole; IDA:MGI.
DR GO; GO:0036064; C:ciliary basal body; ISO:MGI.
DR GO; GO:0035869; C:ciliary transition zone; IDA:MGI.
DR GO; GO:0005929; C:cilium; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031514; C:motile cilium; ISO:MGI.
DR GO; GO:0051301; P:cell division; IMP:MGI.
DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:MGI.
DR GO; GO:0001736; P:establishment of planar polarity; IC:ComplexPortal.
DR GO; GO:0031069; P:hair follicle morphogenesis; IMP:MGI.
DR GO; GO:0042073; P:intraciliary transport; IC:ComplexPortal.
DR GO; GO:0030216; P:keratinocyte differentiation; IMP:MGI.
DR GO; GO:0060173; P:limb development; IMP:UniProtKB.
DR GO; GO:0044458; P:motile cilium assembly; IMP:MGI.
DR GO; GO:0051782; P:negative regulation of cell division; IMP:MGI.
DR GO; GO:0010839; P:negative regulation of keratinocyte proliferation; IMP:MGI.
DR GO; GO:0007399; P:nervous system development; IMP:UniProtKB.
DR GO; GO:0021915; P:neural tube development; IMP:MGI.
DR GO; GO:1905515; P:non-motile cilium assembly; IMP:MGI.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IMP:MGI.
DR GO; GO:0033365; P:protein localization to organelle; IMP:MGI.
DR GO; GO:1902017; P:regulation of cilium assembly; IC:ComplexPortal.
DR GO; GO:0030278; P:regulation of ossification; IMP:MGI.
DR GO; GO:0008589; P:regulation of smoothened signaling pathway; IMP:UniProtKB.
DR GO; GO:0060021; P:roof of mouth development; ISO:MGI.
DR GO; GO:0007224; P:smoothened signaling pathway; IMP:MGI.
DR GO; GO:0021513; P:spinal cord dorsal/ventral patterning; IMP:MGI.
DR GO; GO:0043587; P:tongue morphogenesis; ISO:MGI.
DR GO; GO:0016192; P:vesicle-mediated transport; IEA:InterPro.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR043987; CCZ1/INTU/HSP4_longin_1.
DR InterPro; IPR043989; CCZ1/INTU/HSP4_longin_3.
DR InterPro; IPR043988; CCZ1/INTU_longin_2.
DR InterPro; IPR039151; INTU.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR PANTHER; PTHR21082; PTHR21082; 1.
DR Pfam; PF19031; Intu_longin_1; 1.
DR Pfam; PF19032; Intu_longin_2; 1.
DR Pfam; PF19033; Intu_longin_3; 1.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS50106; PDZ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell projection;
KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton;
KW Developmental protein; Phosphoprotein; Reference proteome.
FT CHAIN 1..942
FT /note="Protein inturned"
FT /id="PRO_0000416283"
FT DOMAIN 185..267
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 128..156
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 707..751
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 36..53
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 138..156
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 674
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:D4ACE5"
FT MOD_RES 678
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..49
FT /note="MAGLARGDSRGRPPELPGDLSSQEEEEEEGDSDAGASSLGSYSSASSDT ->
FT MFQGGGRTSIPKPAPRNLEDLDSVQRVLLHS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_042603"
FT VAR_SEQ 233..247
FT /note="DVLVAVNDVDVTSEN -> KCCSQLPSLFAEVHG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_042604"
FT VAR_SEQ 248..942
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_042605"
FT CONFLICT 538
FT /note="D -> H (in Ref. 1; BAC28943)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 942 AA; 104821 MW; C410DF463F0F457F CRC64;
MAGLARGDSR GRPPELPGDL SSQEEEEEEG DSDAGASSLG SYSSASSDTD VEPEWLDSVQ
KNGELFYLEL SEDEEESLLP ETQTANHVNH VRFSDKEVII EEDDSRERKK SEPKLRRFTK
ILKSKSLLPR RHHKKSSSNN GPVSILKHQS SQKTGVTVQQ RYKDVTVYIN PRKLTAIKAR
EQVKLLEVLV GIIHQTKRSW KRSAKQADGE RLVVHGLLPG GSAMKSGQVL VGDVLVAVND
VDVTSENIER VLSCIPGPMQ VKLTFENAYA VKRETAQPQK KKAQSSTQDL VKLLCGSEAD
AVQHSTLSIP HISMYLTLQL QSEAAREEQE ILYHYPVSEA SQKLKSVRGI FLTLCDMLES
VTGTQVTSSS LHLNGKQIHV AYLKESDKLL LIGLPAEEVP LPQLRNMIED VAQTLKFMYG
SLDSAFCQVE NAPRLDHFFS LFFERALRPG KLHLSGSPSA QQYAAASAVL LDNLPGVRWL
VLPQELKVEL DTALSDLEAA DFEELSEDYY DMRRLYTILG SSLFYKGYMV CSHLPKDDVI
EIAAYCRQHC LLPLAAKQRI GQLIIWREVF PRHHLQPPSD SDPEAFQEPE GRYFLLVVGL
RHYLLCVLLE AGGCASKATG NPGPDCIYVD QVRATLHQLE GVDSRIEEQL ATSPGPCLSC
ADWFLAAPRE KADSLTTSPI LSRLQGPSKT AASPTCRRTF FSDYSFKARK PSPSRIGGGR
EPTEGEESAG LSPHATPDAV RKQRESEGSD DNVALLKLAR KKSTLPNPFH LGTSKKELSE
KELEVYDIMK LTSGPENTLF HYVALETVQG IFITPTHEEV AQLGGSVHSQ LIKNFHQCCL
SIRAFFQQTL KEEKKKALSD GEHSEPTNSV SSLSPVKEHG VLFECSPENW TDQKKTPPVM
SYWVVGRLFL NPKPQELYVC FHDSVSEIAI EMAFKLFFGL TL
