INSC_HUMAN
ID INSC_HUMAN Reviewed; 579 AA.
AC Q1MX18; A0PJX5; Q1MX19; Q3C1V6; Q4AC95; Q4AC96; Q4AC97; Q4AC98;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Protein inscuteable homolog;
GN Name=INSC;
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] (ISOFORMS 1 AND 2), FUNCTION, TISSUE
RP SPECIFICITY, AND INTERACTION WITH PARD3B; F2RL2; GPSM1 AND GPSM2.
RC TISSUE=Kidney, and Small intestine;
RX PubMed=16458856; DOI=10.1016/j.bbrc.2006.01.050;
RA Izaki T., Kamakura S., Kohjima M., Sumimoto H.;
RT "Two forms of human Inscuteable-related protein that links Par3 to the Pins
RT homologues LGN and AGS3.";
RL Biochem. Biophys. Res. Commun. 341:1001-1006(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 5).
RA Totoki Y., Yada T., Sakaki Y., Takeda T.;
RT "Identification of novel human genes predicted by combining multiple gene
RT finders.";
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
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 IDENTIFICATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12469229;
RA Katoh M., Katoh M.;
RT "Identification and characterization of human Inscuteable gene in silico.";
RL Int. J. Mol. Med. 11:111-116(2003).
RN [6] {ECO:0007744|PDB:3SF4}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 70-116 IN COMPLEX WITH GPSM2,
RP INTERACTION WITH GPSM2 AND GPSM1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP TRP-78; GLU-89 AND LYS-97.
RX PubMed=22074847; DOI=10.1073/pnas.1110951108;
RA Yuzawa S., Kamakura S., Iwakiri Y., Hayase J., Sumimoto H.;
RT "Structural basis for interaction between the conserved cell polarity
RT proteins Inscuteable and Leu-Gly-Asn repeat-enriched protein (LGN).";
RL Proc. Natl. Acad. Sci. U.S.A. 108:19210-19215(2011).
CC -!- FUNCTION: May function as an adapter linking the Par3 complex to the
CC GPSM1/GPSM2 complex (PubMed:16458856). Involved in spindle orientation
CC during mitosis. May regulate cell proliferation and differentiation in
CC the developing nervous system. May play a role in the asymmetric
CC division of fibroblasts and participate in the process of
CC stratification of the squamous epithelium (By similarity).
CC {ECO:0000250|UniProtKB:Q3HNM7, ECO:0000305|PubMed:16458856}.
CC -!- SUBUNIT: Interacts with ALS2CR19/PAR3B and F2RL2/PAR3
CC (PubMed:16458856). Interacts with GPSM1/AGS3 and GPSM2/LGN (via TPR
CC repeat region) (PubMed:16458856, PubMed:22074847). Identified in a
CC complex with GPSM2 and F2RL2 (PubMed:16458856).
CC {ECO:0000269|PubMed:16458856, ECO:0000269|PubMed:22074847}.
CC -!- INTERACTION:
CC Q1MX18; P55040: GEM; NbExp=3; IntAct=EBI-12081118, EBI-744104;
CC Q1MX18; O95872: GPANK1; NbExp=3; IntAct=EBI-12081118, EBI-751540;
CC Q1MX18; P81274: GPSM2; NbExp=3; IntAct=EBI-12081118, EBI-618655;
CC Q1MX18; Q9UBR4-2: LHX3; NbExp=3; IntAct=EBI-12081118, EBI-12039345;
CC Q1MX18; Q8IVT4: MGC50722; NbExp=3; IntAct=EBI-12081118, EBI-14086479;
CC Q1MX18; P0CG20: PRR35; NbExp=3; IntAct=EBI-12081118, EBI-11986293;
CC Q1MX18; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-12081118, EBI-6257312;
CC Q1MX18; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-12081118, EBI-358489;
CC Q1MX18; O60504: SORBS3; NbExp=3; IntAct=EBI-12081118, EBI-741237;
CC Q1MX18; Q9BXF9: TEKT3; NbExp=5; IntAct=EBI-12081118, EBI-8644516;
CC Q1MX18; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-12081118, EBI-9090990;
CC Q1MX18; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-12081118, EBI-11975223;
CC Q1MX18; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-12081118, EBI-6427977;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22074847}.
CC Cytoplasm, cell cortex {ECO:0000269|PubMed:22074847}. Note=Uniformly
CC distributed in the cytoplasm during interphase. During metaphase,
CC detected in the cell cortex, adjacent to the mitotic spindle poles.
CC {ECO:0000269|PubMed:22074847}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=Long;
CC IsoId=Q1MX18-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=Q1MX18-2; Sequence=VSP_020947;
CC Name=3;
CC IsoId=Q1MX18-3; Sequence=VSP_020946, VSP_020948, VSP_020950;
CC Name=4;
CC IsoId=Q1MX18-4; Sequence=VSP_020947, VSP_020950;
CC Name=5;
CC IsoId=Q1MX18-5; Sequence=VSP_020947, VSP_020949;
CC Name=6;
CC IsoId=Q1MX18-6; Sequence=VSP_020947, VSP_054159;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in various tissues with
CC stronger expression in liver, kidney and small intestine. Isoform 2 is
CC abundantly expressed in small intestine and to a lower extent in lung
CC and pancreas. {ECO:0000269|PubMed:12469229,
CC ECO:0000269|PubMed:16458856}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal cochlea.
CC {ECO:0000269|PubMed:12469229}.
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DR EMBL; AB236158; BAE93463.1; -; mRNA.
DR EMBL; AB236159; BAE93464.1; -; mRNA.
DR EMBL; AB231744; BAE46891.1; -; mRNA.
DR EMBL; AB231745; BAE17133.1; -; mRNA.
DR EMBL; AB231746; BAE17134.1; -; mRNA.
DR EMBL; AB231747; BAE17135.1; -; mRNA.
DR EMBL; AB231748; BAE17136.1; -; mRNA.
DR EMBL; AC090744; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC127700; AAI27701.1; -; mRNA.
DR CCDS; CCDS41621.1; -. [Q1MX18-1]
DR CCDS; CCDS41622.1; -. [Q1MX18-2]
DR CCDS; CCDS60735.1; -. [Q1MX18-6]
DR CCDS; CCDS60736.1; -. [Q1MX18-4]
DR RefSeq; NP_001027024.3; NM_001031853.4. [Q1MX18-1]
DR RefSeq; NP_001036001.1; NM_001042536.2. [Q1MX18-2]
DR RefSeq; NP_001265242.1; NM_001278313.1. [Q1MX18-2]
DR RefSeq; NP_001265243.1; NM_001278314.1.
DR RefSeq; NP_001265244.1; NM_001278315.1. [Q1MX18-6]
DR RefSeq; NP_001265245.1; NM_001278316.1. [Q1MX18-4]
DR RefSeq; XP_006718290.1; XM_006718227.3. [Q1MX18-2]
DR RefSeq; XP_011518388.1; XM_011520086.1. [Q1MX18-6]
DR RefSeq; XP_016873186.1; XM_017017697.1. [Q1MX18-2]
DR PDB; 3SF4; X-ray; 2.60 A; D/E/F=70-116.
DR PDBsum; 3SF4; -.
DR AlphaFoldDB; Q1MX18; -.
DR SMR; Q1MX18; -.
DR BioGRID; 132426; 37.
DR CORUM; Q1MX18; -.
DR IntAct; Q1MX18; 13.
DR STRING; 9606.ENSP00000368872; -.
DR iPTMnet; Q1MX18; -.
DR PhosphoSitePlus; Q1MX18; -.
DR BioMuta; INSC; -.
DR DMDM; 116248172; -.
DR EPD; Q1MX18; -.
DR MassIVE; Q1MX18; -.
DR PaxDb; Q1MX18; -.
DR PeptideAtlas; Q1MX18; -.
DR PRIDE; Q1MX18; -.
DR ProteomicsDB; 61231; -. [Q1MX18-1]
DR ProteomicsDB; 61232; -. [Q1MX18-2]
DR ProteomicsDB; 61235; -. [Q1MX18-5]
DR ProteomicsDB; 69; -.
DR Antibodypedia; 48935; 190 antibodies from 22 providers.
DR DNASU; 387755; -.
DR Ensembl; ENST00000379554.7; ENSP00000368872.3; ENSG00000188487.12. [Q1MX18-1]
DR Ensembl; ENST00000379556.8; ENSP00000368874.3; ENSG00000188487.12. [Q1MX18-2]
DR Ensembl; ENST00000525218.1; ENSP00000436113.1; ENSG00000188487.12. [Q1MX18-4]
DR Ensembl; ENST00000528567.5; ENSP00000435022.1; ENSG00000188487.12. [Q1MX18-6]
DR Ensembl; ENST00000530161.5; ENSP00000436194.1; ENSG00000188487.12. [Q1MX18-2]
DR GeneID; 387755; -.
DR KEGG; hsa:387755; -.
DR MANE-Select; ENST00000379556.8; ENSP00000368874.3; NM_001042536.3; NP_001036001.1. [Q1MX18-2]
DR UCSC; uc001mly.5; human. [Q1MX18-1]
DR CTD; 387755; -.
DR GeneCards; INSC; -.
DR HGNC; HGNC:33116; INSC.
DR HPA; ENSG00000188487; Tissue enriched (parathyroid).
DR MIM; 610668; gene.
DR neXtProt; NX_Q1MX18; -.
DR OpenTargets; ENSG00000188487; -.
DR PharmGKB; PA162392191; -.
DR VEuPathDB; HostDB:ENSG00000188487; -.
DR eggNOG; ENOG502QRY2; Eukaryota.
DR GeneTree; ENSGT00390000001511; -.
DR InParanoid; Q1MX18; -.
DR OrthoDB; 569133at2759; -.
DR PhylomeDB; Q1MX18; -.
DR TreeFam; TF323559; -.
DR PathwayCommons; Q1MX18; -.
DR SignaLink; Q1MX18; -.
DR BioGRID-ORCS; 387755; 8 hits in 1070 CRISPR screens.
DR ChiTaRS; INSC; human.
DR GenomeRNAi; 387755; -.
DR Pharos; Q1MX18; Tbio.
DR PRO; PR:Q1MX18; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q1MX18; protein.
DR Bgee; ENSG00000188487; Expressed in tibia and 105 other tissues.
DR ExpressionAtlas; Q1MX18; baseline and differential.
DR Genevisible; Q1MX18; HS.
DR GO; GO:0045179; C:apical cortex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IMP:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0008093; F:cytoskeletal anchor activity; IBA:GO_Central.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IPI:UniProtKB.
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; IDA:UniProtKB.
DR Gene3D; 1.25.10.10; -; 1.
DR Gene3D; 6.20.200.10; -; 1.
DR IDEAL; IID00323; -.
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_0000252405"
FT REGION 74..89
FT /note="Important for interaction with GPSM2"
FT /evidence="ECO:0000269|PubMed:22074847"
FT MOTIF 576..579
FT /note="PDZ-binding"
FT VAR_SEQ 1..203
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_020946"
FT VAR_SEQ 1..47
FT /note="Missing (in isoform 2, isoform 4, isoform 5 and
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16458856, ECO:0000303|Ref.2"
FT /id="VSP_020947"
FT VAR_SEQ 204..238
FT /note="ENEHVLKSMKACVSETLSMLGQHFGQLLELALTRE -> MRREWEARMETHS
FT PIWQNLLMRLDNCLALRLQSPL (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_020948"
FT VAR_SEQ 239
FT /note="V -> VQVESHSVTRLECSGAISAQCNLRLPGSSDSPASAS (in
FT isoform 5)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_020949"
FT VAR_SEQ 278..319
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_020950"
FT VAR_SEQ 539..579
FT /note="ALRRLAGVCPEGLQDSDFQQLVQPRLVDSFLLCSNMEESFV -> MGIQLQV
FT KKTNISALLLWFLFWHIQGCSA (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054159"
FT VARIANT 333
FT /note="D -> N (in dbSNP:rs17507577)"
FT /id="VAR_051073"
FT VARIANT 450
FT /note="Q -> R (in dbSNP:rs7123855)"
FT /id="VAR_027852"
FT MUTAGEN 78
FT /note="W->A: Abolishes interaction with GPSM2."
FT /evidence="ECO:0000269|PubMed:22074847"
FT MUTAGEN 89
FT /note="E->R: Strongly reduces interaction with GPSM2.
FT Abolishes interaction with GPSM2 and GPSM1; when associated
FT with D-97."
FT /evidence="ECO:0000269|PubMed:22074847"
FT MUTAGEN 97
FT /note="K->D: Abolishes interaction with GPSM2 and GPSM1;
FT when associated with R-89."
FT /evidence="ECO:0000269|PubMed:22074847"
FT CONFLICT 212
FT /note="M -> T (in Ref. 2; BAE17134)"
FT /evidence="ECO:0000305"
FT CONFLICT 216
FT /note="V -> M (in Ref. 2; BAE17135)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="H -> R (in Ref. 2; BAE17133)"
FT /evidence="ECO:0000305"
FT CONFLICT 251
FT /note="N -> D (in Ref. 2; BAE17134)"
FT /evidence="ECO:0000305"
FT CONFLICT 513
FT /note="M -> T (in Ref. 2; BAE17135)"
FT /evidence="ECO:0000305"
FT CONFLICT 577..578
FT /note="SF -> GS (in Ref. 2; BAE17136)"
FT /evidence="ECO:0000305"
FT HELIX 73..82
FT /evidence="ECO:0007829|PDB:3SF4"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:3SF4"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:3SF4"
FT STRAND 109..112
FT /evidence="ECO:0007829|PDB:3SF4"
SQ SEQUENCE 579 AA; 63469 MW; 7CD8D19409FC3266 CRC64;
MRRPPGNGEA ASEGPGGWGL WGVQESRRLC CAGHDRCKQA LLQIGINMMA LPGGRHLDSV
TLPGQRLHLM QVDSVQRWME DLKLMTECEC MCVLQAKPIS LEEDAQGDLI LAGGPGPGDP
LQLLLKRGWV ISTELRRIGQ KLAQDRWARV HSMSVRLTCH ARSMVSEYSA VSRNSLKEMG
EIEKLLMEKC SELSAVTERC LQVENEHVLK SMKACVSETL SMLGQHFGQL LELALTREVQ
ALVRKIDASD NIYTTESTTG NLFSLTQEGA PLCRIIAKEG GVVALFKVCR QDSFRCLYPQ
ALRTLASICC VEEGVHQLEK VDGVLCLADI LTDNSHSEAT RAEAAAVVAQ VTSPHLPVTQ
HLSSFLESME EIVTALVKLC QEASSGEVFL LASAALANIT FFDTMACEML LQLNAIRVLL
EACSDKQRVD TPYTRDQIVT ILANMSVLEQ CASDIIQENG VQLIMGMLSE KPRSGTPAEV
AACERVQQKA AVTLARLSRD PDVAREAVRL SCMSRLIELC RSPSERNSSD AVLVACLAAL
RRLAGVCPEG LQDSDFQQLV QPRLVDSFLL CSNMEESFV
