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INSC INSC spindle orientation adaptor protein [ Homo sapiens (human) ]

Gene ID: 387755, updated on 7-Apr-2024

Summary

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Official Symbol
INSCprovided by HGNC
Official Full Name
INSC spindle orientation adaptor proteinprovided by HGNC
Primary source
HGNC:HGNC:33116
See related
Ensembl:ENSG00000188487 MIM:610668; AllianceGenome:HGNC:33116
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary
In Drosophila, neuroblasts divide asymmetrically into another neuroblast at the apical side and a smaller ganglion mother cell on the basal side. Cell polarization is precisely regulated by 2 apically localized multiprotein signaling complexes that are tethered by Inscuteable, which regulates their apical localization (Izaki et al., 2006 [PubMed 16458856]).[supplied by OMIM, Mar 2008]
Expression
Low expression observed in reference dataset See more
Orthologs
mouse all
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Genomic context

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Location:
11p15.2
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (15111416..15269676)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (15207776..15366083)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (15133970..15268754)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 7615 Neighboring gene olfactory receptor family 7 subfamily E member 41 pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:15096041-15096542 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3176 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3177 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4478 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:15135643-15136176 Neighboring gene calcitonin related polypeptide beta Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:15196965-15197488 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:15197489-15198010 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3178 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:15260043-15260544 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:15260545-15261044 Neighboring gene NANOG hESC enhancer GRCh37_chr11:15363023-15363618 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:15454895-15455061 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:15467942-15469141 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:15581971-15582472 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr11:15583102-15584301 Neighboring gene VISTA enhancer hs692 Neighboring gene uncharacterized LOC105376568 Neighboring gene long intergenic non-protein coding RNA 2751 Neighboring gene MPRA-validated peak1210 silencer Neighboring gene NANOG hESC enhancer GRCh37_chr11:15610492-15610993 Neighboring gene NANOG hESC enhancer GRCh37_chr11:15643853-15644482 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3179 Neighboring gene uncharacterized LOC105376567 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr11:15732871-15733685

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Genome-wide association study identified INSC gene associated with Trail Making Test Part A and Alzheimer's disease related cognitive phenotypes. Wang K, et al. Prog Neuropsychopharmacol Biol Psychiatry, 2021 Dec 20. PMID 34224794
  2. Identification and characterization of human Inscuteable gene in silico. Katoh M, et al. Int J Mol Med, 2003 Jan. PMID 12469229
  3. On the inscrutable role of Inscuteable: structural basis and functional implications for the competitive binding of NuMA and Inscuteable to LGN. Mapelli M, et al. Open Biol, 2012 Aug. PMID 22977735, Free PMC Article
  4. Distribution of activator of G-protein signaling 3 within the aggresomal pathway: role of specific residues in the tetratricopeptide repeat domain and differential regulation by the AGS3 binding partners Gi(alpha) and mammalian inscuteable. Vural A, et al. Mol Cell Biol, 2010 Mar. PMID 20065032, Free PMC Article
  5. Insc:LGN tetramers promote asymmetric divisions of mammary stem cells. Culurgioni S, et al. Nat Commun, 2018 Mar 9. PMID 29523789, Free PMC Article

See all (17) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Genome-wide association study identified INSC gene associated with Trail Making Test Part A and Alzheimer's disease related cognitive phenotypes.
    Title: Genome-wide association study identified INSC gene associated with Trail Making Test Part A and Alzheimer's disease related cognitive phenotypes.
  2. In mammary stem cells, the asymmetric domain of Insc bound to LGN:Galphai(GDP) suffices to drive asymmetric fate, and reverts aberrant symmetric divisions induced by p53 loss.
    Title: Insc:LGN tetramers promote asymmetric divisions of mammary stem cells.
  3. Studies indicate that the Inscuteable (Insc)and NuMA are mutually exclusive interactors of LGN.
    Title: On the inscrutable role of Inscuteable: structural basis and functional implications for the competitive binding of NuMA and Inscuteable to LGN.
  4. mInsc-LGN interaction is vital for stabilization of LGN and for intracellular localization of mInsc.
    Title: Structural basis for interaction between the conserved cell polarity proteins Inscuteable and Leu-Gly-Asn repeat-enriched protein (LGN).
  5. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
  6. These data present AGS3, G-proteins, and mInsc as candidate proteins involved in regulating cellular stress associated with protein-processing pathologies.
    Title: Distribution of activator of G-protein signaling 3 within the aggresomal pathway: role of specific residues in the tetratricopeptide repeat domain and differential regulation by the AGS3 binding partners Gi(alpha) and mammalian inscuteable.
  7. cloning of two distinct cDNAs from Insc gene, which is differentially expressed from alternative first exons;Insc proteins bind to the Pins homologues LGN and AGS3, and also to Par3 and Par3beta
    Title: Two forms of human Inscuteable-related protein that links Par3 to the Pins homologues LGN and AGS3.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide search for loci interacting with known prostate cancer risk-associated genetic variants.
EBI GWAS Catalog
Common variation near ROBO2 is associated with expressive vocabulary in infancy.
EBI GWAS Catalog
Genome wide association study of age at menarche in the Japanese population.
EBI GWAS Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables cytoskeletal anchor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein domain specific binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-macromolecule adaptor activity IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in apical protein localization IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in asymmetric cell division IEA
Inferred from Electronic Annotation
more info
  
involved_in cell differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in establishment of mitotic spindle orientation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in nervous system development IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of asymmetric cell division IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of protein stability IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in apical cortex IBA
Inferred from Biological aspect of Ancestor
more info
  
colocalizes_with cell cortex IMP
Inferred from Mutant Phenotype
more info
 PubMed 
located_in plasma membrane IMP
Inferred from Mutant Phenotype
more info
 PubMed 
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of protein-containing complex IMP
Inferred from Mutant Phenotype
more info
 PubMed 

General protein information

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Preferred Names
protein inscuteable homolog
Names
inscuteable homolog
inscuteable spindle orientation adaptor protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001031853.5 → NP_001027024.3  protein inscuteable homolog isoform a

    See identical proteins and their annotated locations for NP_001027024.3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a).
    Source sequence(s)
    AB236159, DY654442
    Consensus CDS
    CCDS41621.1
    UniProtKB/Swiss-Prot
    A0PJX5, Q1MX18, Q1MX19, Q3C1V6, Q4AC95, Q4AC96, Q4AC97, Q4AC98
    UniProtKB/TrEMBL
    A0A0A0MSI1
    Related
    ENSP00000368872.3, ENST00000379554.7
    Conserved Domains (2) summary
    cd00020
    Location:454 → 562
    ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
    pfam16748
    Location:70 → 113
    INSC_LBD; Inscuteable LGN-binding domain

  2. NM_001042536.3 → NP_001036001.1  protein inscuteable homolog isoform b

    See identical proteins and their annotated locations for NP_001036001.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) has an alternate exon at the 5' end, which results in a downstream start codon, compared to variant 1. The resulting isoform (b) has a shorter N-terminus, compared to isoform a. Variants 2 and 3 encode the same isoform b.
    Source sequence(s)
    AB236158, AC090744, BU147420, DY654442
    Consensus CDS
    CCDS41622.1
    UniProtKB/TrEMBL
    A0A0A0MSI1
    Related
    ENSP00000368874.3, ENST00000379556.8
    Conserved Domains (2) summary
    cd00020
    Location:407 → 515
    ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
    pfam16748
    Location:23 → 66
    INSC_LBD; Inscuteable LGN-binding domain

  3. NM_001278313.2 → NP_001265242.1  protein inscuteable homolog isoform b

    See identical proteins and their annotated locations for NP_001265242.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) lacks an exon at the 5' end but has an alternate segment, which results in a downstream start codon, compared to variant 1. The resulting isoform (b) has a shorter N-terminus, compared to isoform a. Variants 2 and 3 encode the same isoform b.
    Source sequence(s)
    AB231745, AB236158, BC127700, DY654442
    Consensus CDS
    CCDS41622.1
    UniProtKB/TrEMBL
    A0A0A0MSI1
    Related
    ENSP00000436194.1, ENST00000530161.5
    Conserved Domains (2) summary
    cd00020
    Location:407 → 515
    ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
    pfam16748
    Location:23 → 66
    INSC_LBD; Inscuteable LGN-binding domain

  4. NM_001278314.2 → NP_001265243.1  protein inscuteable homolog isoform c

    Status: VALIDATED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and has multiple coding region differences, compared to variant 1. The resulting isoform (c) is shorter at the N-terminus and has an additional internal segment, compared to isoform a.
    Source sequence(s)
    AB236158, AC090744, BC127700, DY654442
    UniProtKB/TrEMBL
    A0A0A0MSI1
    Related
    ENSP00000389161.2, ENST00000424273.5
    Conserved Domains (2) summary
    cd00020
    Location:442 → 550
    ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
    pfam16748
    Location:23 → 66
    INSC_LBD; Inscuteable LGN-binding domain

  5. NM_001278315.2 → NP_001265244.1  protein inscuteable homolog isoform d

    See identical proteins and their annotated locations for NP_001265244.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR and has multiple coding region differences, compared to variant 1. The resulting isoform (d) is shorter at the N-terminus and has a distinct C-terminus, compared to isoform a.
    Source sequence(s)
    AB236158, BC127700, DY654442
    Consensus CDS
    CCDS60735.1
    UniProtKB/TrEMBL
    A0A0A0MSI1
    Related
    ENSP00000435022.1, ENST00000528567.5
    Conserved Domains (1) summary
    pfam16748
    Location:23 → 66
    INSC_LBD; Inscuteable LGN-binding domain

  6. NM_001278316.2 → NP_001265245.1  protein inscuteable homolog isoform e

    Status: VALIDATED

    Description
    Transcript Variant: This variant (6) differs in the 5' UTR and has multiple coding region differences, compared to variant 1. The resulting isoform (e) is shorter at the N-terminus and lacks an internal segment, compared to isoform a.
    Source sequence(s)
    AB236158, BC117561, BC127700, DY654442
    Consensus CDS
    CCDS60736.1
    UniProtKB/TrEMBL
    A0A0A0MSI1
    Related
    ENSP00000436113.1, ENST00000525218.1
    Conserved Domains (2) summary
    cd00020
    Location:365 → 473
    ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
    pfam16748
    Location:23 → 66
    INSC_LBD; Inscuteable LGN-binding domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    15111416..15269676
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006718227.3 → XP_006718290.1  protein inscuteable homolog isoform X1

    See identical proteins and their annotated locations for XP_006718290.1

    UniProtKB/TrEMBL
    A0A0A0MSI1
    Conserved Domains (2) summary
    cd00020
    Location:407 → 515
    ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
    pfam16748
    Location:23 → 66
    INSC_LBD; Inscuteable LGN-binding domain

  2. XM_017017698.2 → XP_016873187.1  protein inscuteable homolog isoform X4

    UniProtKB/TrEMBL
    A0A0A0MSI1

  3. XM_017017697.2 → XP_016873186.1  protein inscuteable homolog isoform X1

    UniProtKB/TrEMBL
    A0A0A0MSI1
    Conserved Domains (2) summary
    cd00020
    Location:407 → 515
    ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
    pfam16748
    Location:23 → 66
    INSC_LBD; Inscuteable LGN-binding domain

  4. XM_011520086.2 → XP_011518388.1  protein inscuteable homolog isoform X3

    See identical proteins and their annotated locations for XP_011518388.1

    UniProtKB/TrEMBL
    A0A0A0MSI1
    Conserved Domains (1) summary
    pfam16748
    Location:23 → 66
    INSC_LBD; Inscuteable LGN-binding domain

  5. XM_011520085.2 → XP_011518387.1  protein inscuteable homolog isoform X2

    UniProtKB/TrEMBL
    A0A0A0MSI1
    Conserved Domains (1) summary
    pfam16748
    Location:23 → 66
    INSC_LBD; Inscuteable LGN-binding domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    15207776..15366083
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054368732.1 → XP_054224707.1  protein inscuteable homolog isoform X1

  2. XM_054368736.1 → XP_054224711.1  protein inscuteable homolog isoform X4

  3. XM_054368733.1 → XP_054224708.1  protein inscuteable homolog isoform X1

  4. XM_054368735.1 → XP_054224710.1  protein inscuteable homolog isoform X3

  5. XM_054368734.1 → XP_054224709.1  protein inscuteable homolog isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q1MX18.1 GenPept UniProtKB/Swiss-Prot:Q1MX18

Gene LinkOut

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