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Aliases for NISCH Gene

Aliases for NISCH Gene

  • Nischarin 2 3 5
  • I-1 Receptor Candidate Protein 2 3 4
  • Imidazoline Receptor Antisera Selected 2 3
  • Imidazoline Receptor 1 3 4
  • I1R Candidate Protein 3 4
  • HIRAS 3 4
  • IRAS 3 4
  • I-1 3 4
  • IR1 3 4
  • Imidazoline Receptor Antisera-Selected Protein 4
  • Imidazoline-1 Receptor Candidate Protein 4
  • Imidazoline Receptor Candidate 2
  • Imidazoline-1 Receptor 4
  • KIAA0975 4
  • I1R 4

External Ids for NISCH Gene

Previous GeneCards Identifiers for NISCH Gene

  • GC03P051581
  • GC03P051741
  • GC03P052345
  • GC03P052447
  • GC03P052464

Summaries for NISCH Gene

Entrez Gene Summary for NISCH Gene

  • This gene encodes a nonadrenergic imidazoline-1 receptor protein that localizes to the cytosol and anchors to the inner layer of the plasma membrane. The orthologous mouse protein has been shown to influence cytoskeletal organization and cell migration by binding to alpha-5-beta-1 integrin. In humans, this protein has been shown to bind to the adapter insulin receptor substrate 4 (IRS4) to mediate translocation of alpha-5 integrin from the cell membrane to endosomes. Expression of this protein was reduced in human breast cancers while its overexpression reduced tumor growth and metastasis; possibly by limiting the expression of alpha-5 integrin. In human cardiac tissue, this gene was found to affect cell growth and death while in neural tissue it affected neuronal growth and differentiation. Alternative splicing results in multiple transcript variants encoding differerent isoforms. Some isoforms lack the expected C-terminal domains of a functional imidazoline receptor. [provided by RefSeq, Jan 2013]

GeneCards Summary for NISCH Gene

NISCH (Nischarin) is a Protein Coding gene. Diseases associated with NISCH include silent myocardial infarction. Among its related pathways are Hypothetical Network for Drug Addiction and EPH-Ephrin signaling. GO annotations related to this gene include identical protein binding and phosphatidylinositol binding. An important paralog of this gene is STK11IP.

UniProtKB/Swiss-Prot for NISCH Gene

  • Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. Binds numerous imidazoline ligands that induces initiation of cell-signaling cascades triggering to cell survival, growth and migration. Its activation by the agonist rilmenidine induces an increase in phosphorylation of mitogen-activated protein kinases MAPK1 and MAPK3 in rostral ventrolateral medulla (RVLM) neurons that exhibited rilmenidine-evoked hypotension (By similarity). Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons (By similarity). Acts as a modulator of Rac-regulated signal transduction pathways (By similarity). Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity (By similarity). Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation (By similarity). Inhibits also LIMK1 kinase activity by reducing LIMK1 Tyr-508 phosphorylation (By similarity). Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells (By similarity). Inhibits lamellipodia formation, when overexpressed (By similarity). Plays a role in protection against apoptosis. Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3. When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures.

Gene Wiki entry for NISCH Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NISCH Gene

Genomics for NISCH Gene

Regulatory Elements for NISCH Gene

Promoters for NISCH Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around NISCH on UCSC Golden Path with GeneCards custom track

Genomic Location for NISCH Gene

Chromosome:
3
Start:
52,455,118 bp from pter
End:
52,493,072 bp from pter
Size:
37,955 bases
Orientation:
Plus strand

Genomic View for NISCH Gene

Genes around NISCH on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NISCH Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NISCH Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NISCH Gene

Proteins for NISCH Gene

  • Protein details for NISCH Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y2I1-NISCH_HUMAN
    Recommended name:
    Nischarin
    Protein Accession:
    Q9Y2I1
    Secondary Accessions:
    • C9J245
    • Q6PGP3
    • Q6PIB4
    • Q7L8M3
    • Q7Z2X6
    • Q9UES6
    • Q9UEU4
    • Q9UFW3

    Protein attributes for NISCH Gene

    Size:
    1504 amino acids
    Molecular mass:
    166629 Da
    Quaternary structure:
    • Homooligomer. Interacts with GRB2. Interacts with PIK3R1; probably associates with the PI3-kinase complex. Interacts with IRS4. Found in a complex with ITGA5 and PAK1. Found in a complex with LIMK1 and PAK1. Interacts with ITGA5 (via cytoplasmic domain); this interaction is direct. Interacts with PAK1 (via kinase domain); this interaction is direct and is increased upon activation of PAK1 (By similarity). Interacts with LIMK1 (via PDZ and kinase domain); this interaction is direct (By similarity). Interacts with LIMK2; this interaction depends on LIMK2 activity (By similarity). Interacts with RAC1 (activated state) (By similarity). Interacts with STK11; this interaction may increase STK11 activity.
    SequenceCaution:
    • Sequence=BAA76819.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for NISCH Gene

    Alternative splice isoforms for NISCH Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NISCH Gene

Proteomics data for NISCH Gene at MOPED

Post-translational modifications for NISCH Gene

  • Ubiquitination at Lys 865, Lys 942, Lys 1009, Lys 1290, Lys 1299, and Lys 1303
  • Modification sites at PhosphoSitePlus

Other Protein References for NISCH Gene

No data available for DME Specific Peptides for NISCH Gene

Domains & Families for NISCH Gene

Protein Domains for NISCH Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for NISCH Gene

Graphical View of Domain Structure for InterPro Entry

Q9Y2I1

UniProtKB/Swiss-Prot:

NISCH_HUMAN :
  • Both the presence of the PX domain and the coiled coil region are necessary for its endosomal targeting.
  • Contains 6 LRR (leucine-rich) repeats.
Domain:
  • Both the presence of the PX domain and the coiled coil region are necessary for its endosomal targeting.
  • Contains 1 PX (phox homology) domain.
Similarity:
  • Contains 6 LRR (leucine-rich) repeats.
genes like me logo Genes that share domains with NISCH: view

No data available for Gene Families for NISCH Gene

Function for NISCH Gene

Molecular function for NISCH Gene

UniProtKB/Swiss-Prot Function:
Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. Binds numerous imidazoline ligands that induces initiation of cell-signaling cascades triggering to cell survival, growth and migration. Its activation by the agonist rilmenidine induces an increase in phosphorylation of mitogen-activated protein kinases MAPK1 and MAPK3 in rostral ventrolateral medulla (RVLM) neurons that exhibited rilmenidine-evoked hypotension (By similarity). Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons (By similarity). Acts as a modulator of Rac-regulated signal transduction pathways (By similarity). Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity (By similarity). Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation (By similarity). Inhibits also LIMK1 kinase activity by reducing LIMK1 Tyr-508 phosphorylation (By similarity). Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells (By similarity). Inhibits lamellipodia formation, when overexpressed (By similarity). Plays a role in protection against apoptosis. Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3. When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures.

Gene Ontology (GO) - Molecular Function for NISCH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005178 integrin binding IEA --
genes like me logo Genes that share ontologies with NISCH: view
genes like me logo Genes that share phenotypes with NISCH: view

Animal Model Products

  • Taconic Biosciences Mouse Models for NISCH

miRNA for NISCH Gene

miRTarBase miRNAs that target NISCH

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for NISCH Gene

Localization for NISCH Gene

Subcellular locations from UniProtKB/Swiss-Prot for NISCH Gene

Cell membrane. Cytoplasm. Early endosome. Recycling endosome. Note=Enriched in the early/sorting and recycling endosomes. Colocalized in early/sorting endosomes with EEA1 and SNX2 and in recycling endosomes with transferrin receptor. Detected in the perinuclear region partially associated with punctate structures (By similarity). Colocalizes with PAK1 in cytoplasm, vesicular structures in the perinuclear area and membrane ruffles (By similarity). Colocalizes with RAC1 in the cytoplasm and vesicles structures (By similarity). Colocalized with MAPK1 and MAPK3 in RVLM neurons (By similarity). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NISCH Gene COMPARTMENTS Subcellular localization image for NISCH gene
Compartment Confidence
cytosol 5
endosome 5
plasma membrane 5
nucleus 2
chloroplast 1
extracellular 1
mitochondrion 1

No data available for Gene Ontology (GO) - Cellular Components for NISCH Gene

Pathways & Interactions for NISCH Gene

genes like me logo Genes that share pathways with NISCH: view

Pathways by source for NISCH Gene

1 BioSystems pathway for NISCH Gene
1 GeneGo (Thomson Reuters) pathway for NISCH Gene

Gene Ontology (GO) - Biological Process for NISCH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006006 glucose metabolic process IEA --
GO:0006915 apoptotic process IEA --
genes like me logo Genes that share ontologies with NISCH: view

No data available for SIGNOR curated interactions for NISCH Gene

Drugs & Compounds for NISCH Gene

(27) Drugs for NISCH Gene - From: Novoseek, DrugBank, ApexBio, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Tizanidine Approved Pharma Target, agonist 18
Cimetidine Approved Pharma Inhibition, Inhibitor H2 receptor antagonist, H2 antagonist, I1 agonist 67
agmatine Experimental, Investigational Pharma Activator, Target, agonist 0
Moxonidine hydrochloride Pharma α2AR/I1R agonist, I1 receptor and alpha2-adrenoceptor agonist (I1 > alpha2) 0
Moxonidine Pharma I1R/α2AR agonist 13

(12) Additional Compounds for NISCH Gene - From: Novoseek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
AGN 192403 hydrochloride
1021868-90-5
Clonidine hydrochloride
4205-91-8
Rilmenidine hemifumarate
207572-68-7
genes like me logo Genes that share compounds with NISCH: view

Drug Products

Transcripts for NISCH Gene

Unigene Clusters for NISCH Gene

Nischarin:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for NISCH Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11a · 11b · 11c ^ 12a · 12b ^ 13a · 13b ^ 14a · 14b · 14c ^ 15 ^ 16a · 16b · 16c · 16d ^
SP1: - - - - - -
SP2: - - -
SP3:
SP4: - - -
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12: - -
SP13:
SP14:
SP15:
SP16:
SP17:
SP18:

ExUns: 17a · 17b · 17c ^ 18 ^ 19a · 19b · 19c · 19d ^ 20 ^ 21a · 21b · 21c ^ 22a · 22b ^ 23a · 23b ^ 24a · 24b · 24c ^ 25 ^ 26 ^ 27 ^ 28a · 28b · 28c · 28d ·
SP1:
SP2: - - - - - -
SP3: - - - -
SP4:
SP5: - -
SP6:
SP7:
SP8:
SP9: - - - - - -
SP10: - - - -
SP11: - -
SP12:
SP13:
SP14:
SP15: - -
SP16:
SP17:
SP18:

ExUns: 28e ^ 29
SP1:
SP2:
SP3: -
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:
SP15:
SP16:
SP17:
SP18:

Relevant External Links for NISCH Gene

GeneLoc Exon Structure for
NISCH
ECgene alternative splicing isoforms for
NISCH

Expression for NISCH Gene

mRNA expression in normal human tissues for NISCH Gene

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for NISCH Gene



SOURCE GeneReport for Unigene cluster for NISCH Gene Hs.435290

mRNA Expression by UniProt/SwissProt for NISCH Gene

Q9Y2I1-NISCH_HUMAN
Tissue specificity: Isoform 1, isoform 3 and isoform 4 are expressed in brain. Isoform 1 is expressed in endocrine tissues.
genes like me logo Genes that share expression patterns with NISCH: view

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues and Protein tissue co-expression partners for NISCH Gene

Orthologs for NISCH Gene

This gene was present in the common ancestor of animals.

Orthologs for NISCH Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NISCH 35
  • 99.07 (n)
  • 98.94 (a)
NISCH 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia NISCH 36
  • 87 (a)
OneToOne
NISCH 35
  • 87.64 (n)
  • 90.74 (a)
dog
(Canis familiaris)
Mammalia NISCH 35
  • 88.11 (n)
  • 90.79 (a)
NISCH 36
  • 90 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Nisch 36
  • 84 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NISCH 36
  • 60 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NISCH 36
  • 59 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nisch 35
  • 85.24 (n)
  • 89.43 (a)
chicken
(Gallus gallus)
Aves NISCH 36
  • 60 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NISCH 36
  • 56 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii nisch 36
  • 48 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP011394 35
  • 45.95 (n)
  • 36.04 (a)
fruit fly
(Drosophila melanogaster)
Insecta CG11807 35
  • 47.95 (n)
  • 40.6 (a)
CG11807 36
  • 35 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea F13E9.1 37
  • 45 (a)
F13E9.1 36
  • 34 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 43 (a)
OneToOne
Species with no ortholog for NISCH:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for NISCH Gene

ENSEMBL:
Gene Tree for NISCH (if available)
TreeFam:
Gene Tree for NISCH (if available)

Paralogs for NISCH Gene

Paralogs for NISCH Gene

(1) SIMAP similar genes for NISCH Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with NISCH: view

Variants for NISCH Gene

Sequence variations from dbSNP and Humsavar for NISCH Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type
rs9856575 - 52,476,576(+) ACAGC(A/G)TCTCC reference, missense, utr-variant-5-prime
rs887515 - 52,489,389(+) CCCAG(C/G/T)GGAAG reference, missense
rs887514 -- 52,488,643(+) GGGCA(C/T)GGGTC intron-variant
rs1011062 -- 52,472,887(-) GACTT(C/T)TCTTT intron-variant
rs2240897 -- 52,492,519(+) CTGAC(A/G/T)CCTAC utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for NISCH Gene

Variant ID Type Subtype PubMed ID
nsv876789 CNV Loss 21882294
nsv834697 CNV Loss 17160897
dgv5137n71 CNV Loss 21882294
nsv876794 CNV Loss 21882294
nsv3819 CNV Insertion 18451855

Variation tolerance for NISCH Gene

Residual Variation Intolerance Score: 1.13% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.64; 56.78% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for NISCH Gene

HapMap Linkage Disequilibrium report
NISCH
Human Gene Mutation Database (HGMD)
NISCH

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NISCH Gene

Disorders for NISCH Gene

MalaCards: The human disease database

(1) MalaCards diseases for NISCH Gene - From: DISEASES

Disorder Aliases PubMed IDs
silent myocardial infarction
- elite association - COSMIC cancer census association via MalaCards
Search NISCH in MalaCards View complete list of genes associated with diseases

Relevant External Links for NISCH

Genetic Association Database (GAD)
NISCH
Human Genome Epidemiology (HuGE) Navigator
NISCH
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NISCH
genes like me logo Genes that share disorders with NISCH: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NISCH Gene

Publications for NISCH Gene

  1. Imidazoline receptor antisera-selected (IRAS) cDNA: cloning and characterization. (PMID: 10882231) Piletz J.E. … Reis D.J. (DNA Cell Biol. 2000) 2 3 4 23 67
  2. [Imidazoline receptor]. (PMID: 18561481) Tanabe M. (Nippon Yakurigaku Zasshi 2008) 3 23
  3. Involvement of phosphatidylcholine-selective phospholipase C in activation of mitogen-activated protein kinase pathways in imidazoline receptor antisera-selected protein. (PMID: 16598778) Li F. … Li J. (J. Cell. Biochem. 2006) 3 23
  4. Human Nischarin/imidazoline receptor antisera-selected protein is targeted to the endosomes by a combined action of a PX domain and a coiled-coil region. (PMID: 15475348) Lim K.-P. … Hong W. (J. Biol. Chem. 2004) 3 23
  5. IRAS, the human homologue of Nischarin, prolongs survival of transfected PC12 cells. (PMID: 12868002) Dontenwill M. … Bousquet P. (Cell Death Differ. 2003) 3 23

Products for NISCH Gene

Sources for NISCH Gene

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