INSC_MOUSE
ID INSC_MOUSE Reviewed; 579 AA.
AC Q3HNM7; B2RTA5; Q8C7I7;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Protein inscuteable homolog;
DE AltName: Full=Minsc;
GN Name=Insc;
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 1-65 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Inner ear, and Liver tumor;
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 MRNA] (ISOFORM 2).
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 48-579 (ISOFORM 1), FUNCTION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, INTERACTION WITH F2RL2 AND GPSM2, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=CD-1; TISSUE=Epidermis;
RX PubMed=16094321; DOI=10.1038/nature03922;
RA Lechler T., Fuchs E.;
RT "Asymmetric cell divisions promote stratification and differentiation of
RT mammalian skin.";
RL Nature 437:275-280(2005).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=16301171; DOI=10.1016/j.neuron.2005.09.030;
RA Zigman M., Cayouette M., Charalambous C., Schleiffer A., Hoeller O.,
RA Dunican D., McCudden C.R., Firnberg N., Barres B.A., Siderovski D.P.,
RA Knoblich J.A.;
RT "Mammalian inscuteable regulates spindle orientation and cell fate in the
RT developing retina.";
RL Neuron 48:539-545(2005).
RN [5] {ECO:0007744|PDB:3RO3}
RP X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) OF 66-87 IN COMPLEX WITH GPSM2,
RP FUNCTION, INTERACTION WITH GPSM2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP SER-74; TRP-78; MET-79 AND LEU-82.
RX PubMed=21816348; DOI=10.1016/j.molcel.2011.07.011;
RA Zhu J., Wen W., Zheng Z., Shang Y., Wei Z., Xiao Z., Pan Z., Du Q.,
RA Wang W., Zhang M.;
RT "LGN/mInsc and LGN/NuMA complex structures suggest distinct functions in
RT asymmetric cell division for the Par3/mInsc/LGN and Galphai/LGN/NuMA
RT pathways.";
RL Mol. Cell 43:418-431(2011).
CC -!- FUNCTION: May function as an adapter linking the Par3 complex to the
CC GPSM1/GPSM2 complex. Involved in spindle orientation during mitosis
CC (PubMed:16301171, PubMed:21816348). May regulate cell proliferation and
CC differentiation in the developing nervous system (PubMed:16301171). May
CC play a role in the asymmetric division of fibroblasts and participate
CC in the process of stratification of the squamous epithelium
CC (PubMed:16094321). {ECO:0000269|PubMed:16094321,
CC ECO:0000269|PubMed:16301171, ECO:0000269|PubMed:21816348}.
CC -!- SUBUNIT: Interacts with ALS2CR19/PAR3B and GPSM1/AGS3 (By similarity).
CC Interacts with F2RL2/PAR3 (PubMed:16094321). Interacts with GPSM2/LGN
CC (via TPR repeat region) (PubMed:16094321, PubMed:21816348).
CC {ECO:0000250|UniProtKB:Q1MX18, ECO:0000269|PubMed:16094321,
CC ECO:0000269|PubMed:21816348}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16094321,
CC ECO:0000269|PubMed:16301171, ECO:0000269|PubMed:21816348}. Cytoplasm,
CC cell cortex {ECO:0000250|UniProtKB:Q1MX18}. Note=Uniformly distributed
CC in the cytoplasm during interphase. During metaphase, detected in the
CC cell cortex, adjacent to the mitotic spindle poles.
CC {ECO:0000250|UniProtKB:Q1MX18}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3HNM7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3HNM7-2; Sequence=VSP_020951;
CC -!- TISSUE SPECIFICITY: Expressed in brain, kidney, liver, testis and skin.
CC {ECO:0000269|PubMed:16094321, ECO:0000269|PubMed:16301171}.
CC -!- DEVELOPMENTAL STAGE: Expressed at 12.5 dpc in dorsal root and cranial
CC glanglia in the developing brain. Detected at 14.5 dpc in skin
CC epidermis (at protein level). First detected at 10.5 dpc in the dorsal
CC root glanglia and cranial glanglia. At 12.5 dpc expression appears in
CC retina, forebrain and outside of the nervous system. At 13.5 dpc a
CC strong expression is detected in the cortex. Expressed in embryonic,
CC newborn and adult skin. {ECO:0000269|PubMed:16094321}.
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DR EMBL; AK050143; BAC34091.1; -; mRNA.
DR EMBL; BY236076; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC139196; AAI39197.1; -; mRNA.
DR EMBL; BC139197; AAI39198.1; -; mRNA.
DR EMBL; DQ205645; ABA54267.1; -; mRNA.
DR RefSeq; NP_776128.2; NM_173767.3.
DR RefSeq; XP_006507722.1; XM_006507659.3. [Q3HNM7-1]
DR PDB; 3RO3; X-ray; 1.10 A; B=66-87.
DR PDBsum; 3RO3; -.
DR AlphaFoldDB; Q3HNM7; -.
DR SMR; Q3HNM7; -.
DR BioGRID; 231440; 3.
DR STRING; 10090.ENSMUSP00000112682; -.
DR iPTMnet; Q3HNM7; -.
DR PhosphoSitePlus; Q3HNM7; -.
DR MaxQB; Q3HNM7; -.
DR PaxDb; Q3HNM7; -.
DR PRIDE; Q3HNM7; -.
DR ProteomicsDB; 269318; -. [Q3HNM7-1]
DR ProteomicsDB; 269319; -. [Q3HNM7-2]
DR Ensembl; ENSMUST00000161800; ENSMUSP00000125061; ENSMUSG00000048782. [Q3HNM7-1]
DR GeneID; 233752; -.
DR KEGG; mmu:233752; -.
DR UCSC; uc009jii.2; mouse. [Q3HNM7-1]
DR CTD; 387755; -.
DR MGI; MGI:1917942; Insc.
DR eggNOG; ENOG502QRY2; Eukaryota.
DR GeneTree; ENSGT00390000001511; -.
DR InParanoid; Q3HNM7; -.
DR OrthoDB; 569133at2759; -.
DR PhylomeDB; Q3HNM7; -.
DR BioGRID-ORCS; 233752; 2 hits in 57 CRISPR screens.
DR ChiTaRS; Insc; mouse.
DR PRO; PR:Q3HNM7; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q3HNM7; protein.
DR GO; GO:0045179; C:apical cortex; IBA:GO_Central.
DR GO; GO:0005938; C:cell cortex; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0008093; F:cytoskeletal anchor activity; IBA:GO_Central.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:MGI.
DR GO; GO:0045176; P:apical protein localization; IBA:GO_Central.
DR GO; GO:0008356; P:asymmetric cell division; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0009786; P:regulation of asymmetric cell division; IBA:GO_Central.
DR GO; GO:0031647; P:regulation of protein stability; ISO:MGI.
DR Gene3D; 1.25.10.10; -; 1.
DR Gene3D; 6.20.200.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR045789; Insc_C.
DR InterPro; IPR031938; INSC_LBD.
DR InterPro; IPR038205; INSC_LBD_sf.
DR InterPro; IPR039921; Inscuteable.
DR PANTHER; PTHR21386; PTHR21386; 1.
DR Pfam; PF19427; Insc_C; 1.
DR Pfam; PF16748; INSC_LBD; 1.
DR SMART; SM00185; ARM; 3.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Developmental protein;
KW Differentiation; Neurogenesis; Reference proteome.
FT CHAIN 1..579
FT /note="Protein inscuteable homolog"
FT /id="PRO_0000252406"
FT REGION 74..89
FT /note="Important for interaction with GPSM2"
FT /evidence="ECO:0000269|PubMed:21816348"
FT MOTIF 576..579
FT /note="PDZ-binding"
FT VAR_SEQ 1..186
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_020951"
FT MUTAGEN 74
FT /note="S->E: Abolishes interaction with GPSM2."
FT /evidence="ECO:0000269|PubMed:21816348"
FT MUTAGEN 78
FT /note="W->E: Abolishes interaction with GPSM2."
FT /evidence="ECO:0000269|PubMed:21816348"
FT MUTAGEN 79
FT /note="M->E: Abolishes interaction with GPSM2."
FT /evidence="ECO:0000269|PubMed:21816348"
FT MUTAGEN 82
FT /note="L->E: Abolishes interaction with GPSM2."
FT /evidence="ECO:0000269|PubMed:21816348"
FT CONFLICT 560
FT /note="V -> L (in Ref. 3; ABA54267)"
FT /evidence="ECO:0000305"
FT HELIX 73..82
FT /evidence="ECO:0007829|PDB:3RO3"
SQ SEQUENCE 579 AA; 63615 MW; BE18903D7D66C830 CRC64;
MRRPPGDGDS TGEGPGNWGL WGAQESRRLC CVGPDRCGQA LLQIGINMMA LPGGRHLDSV
PLQEQRLHFM QVDSVQRWME DLKLMTECEC MCVLQAKPIS LEEDTQGDLI LAGGPGPGDP
LQLLLKRGWV ISTELRRIGQ KLAQDRWARV HSMSVRLTCH ARSMVSEYST ISRTASQEMG
QAEKLLMEKC SELSAVTERC LQVENEHVLK SMKACVSETL SLLGEHFGQL LELALTREVQ
ALVRKIDTSD NIYITESTTG NLFGLTQEGA PLCRIIAKEG GVVALFKVCR QDSFRCLYPQ
ALRTLASICC VEEGVHQLEK VDGILCLADI LTDESHSEAT RAEAAAVVAQ VTSPHLSFTQ
HLTSFLENME EIVTALIKLC QEASSGEVFL LASAALANIT FFDKMACEML LQLNAIRVLL
EACGDKQRVD TPYTRDQIVT ILANMSVLEQ CGSDIIQENG VQLIMGMLSE KPRSGTPAEV
AACERVQQKA AVTLARLCRD PDVAQEAVRL SCMSRLIELC RSPSERNSSD AVLVACLAAL
RRLAGVCPEG LQDSDFQQLV QPRLVDSFLL CSNMEESFV
