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Aliases for NISCH Gene

Aliases for NISCH Gene

  • Nischarin 2 3
  • I-1 Receptor Candidate Protein 2 3 4
  • IRAS 3 4 6
  • Imidazoline Receptor Antisera Selected 2 3
  • Imidazoline Receptor 1 3 4
  • I1R Candidate Protein 3 4
  • KIAA0975 4 6
  • HIRAS 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
  • 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 rosacea and morphine dependence. Among its related pathways are Cell adhesion Integrin-mediated cell adhesion and migration and Hypothetical Network for Drug Addiction. GO annotations related to this gene include integrin binding and G-protein coupled amine receptor activity. 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

Genomic Location for NISCH Gene

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

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
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 Lys865, Lys942, Lys1009, Lys1290, Lys1299, and Lys1303
  • Modification sites at PhosphoSitePlus

Other Protein References for NISCH Gene

No data available for DME Specific Peptides for NISCH Gene

Domains 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 :
  • Q9Y2I1
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 --
GO:0005515 protein binding IPI 23386062
GO:0008227 G-protein coupled amine receptor activity IEA --
GO:0035091 phosphatidylinositol binding IEA --
GO:0042802 identical protein binding IPI 23386062
genes like me logo Genes that share ontologies with NISCH: view

miRNA for NISCH Gene

miRTarBase miRNAs that target NISCH

No data available for Enzyme Numbers (IUBMB) , Phenotypes , Animal Models , Transcription Factor Targeting 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
endosome 5
plasma membrane 5
cytosol 4
cytoskeleton 1

Gene Ontology (GO) - Cellular Components for NISCH Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005768 endosome --
GO:0005769 early endosome IEA --
GO:0005829 cytosol IDA 15028622
GO:0005886 plasma membrane IDA 15028622
GO:0016020 membrane IDA 19946888
genes like me logo Genes that share ontologies with NISCH: view

Pathways 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 --
GO:0007186 G-protein coupled receptor signaling pathway IEA --
GO:0008217 regulation of blood pressure IEA --
GO:0016601 Rac protein signal transduction IEA --
genes like me logo Genes that share ontologies with NISCH: view

Compounds for NISCH Gene

(4) Tocris Compounds for NISCH Gene

Compound Action Cas Number
AGN 192403 hydrochloride I1 selective ligand [1021868-90-5]
Cimetidine H2 antagonist, I1 agonist [51481-61-9]
Moxonidine hydrochloride I1 receptor and alpha2-adrenoceptor agonist (I1 > alpha2) [75536-04-8]
Rilmenidine hemifumarate alpha2 agonist. Also I1 ligand [207572-68-7]

(2) Drugbank Compounds for NISCH Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Agmatine
306-60-5 target agonist
Tizanidine
  • Tizanidina [INN-Spanish]
51322-75-9 target agonist

(33) Novoseek inferred chemical compound relationships for NISCH Gene

Compound -log(P) Hits PubMed IDs
rilmenidine 96 27
moxonidine 95.9 28
idazoxan 90.2 8
agmatine 88.4 21
efaroxan 87.5 2
genes like me logo Genes that share compounds with NISCH: view

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression 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 expressions with NISCH: view

No data available for mRNA differential expression in normal tissues 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 35
  • 87.64 (n)
  • 90.74 (a)
NISCH 36
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NISCH 35
  • 88.11 (n)
  • 90.79 (a)
NISCH 36
  • 90 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Nisch 16
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 36
  • 34 (a)
OneToOne
F13E9.1 37
  • 45 (a)
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

Selected 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 MAF
rs728408 -- 52,483,190(+) GCTTC(A/G)TGGGG intron-variant
rs758803 -- 52,481,517(+) GACGC(C/T)GCCTC intron-variant, utr-variant-5-prime
rs887514 -- 52,488,643(+) GGGCA(C/T)GGGTC intron-variant
rs887515 - 52,489,389(+) CCCAG(C/T)GGAAG reference, missense
rs929528 -- 52,471,429(+) CACCA(C/T)GCTGG intron-variant

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

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

MalaCards: The human disease database. (2) Diseases for NISCH Gene including...

Search for NISCH Gene in MalaCards »

(2) University of Copenhagen DISEASES for NISCH Gene

(18) Novoseek inferred disease relationships for NISCH Gene

Disease -log(P) Hits PubMed IDs
xerostomia 59.5 3
hypertension arterial 45 1
systemic hypertension 40.2 3
withdrawal syndrome 36.1 1
essential hypertension 31.4 1

Relevant External Links for NISCH

Genetic Association Database (GAD)
NISCH
Human Genome Epidemiology (HuGE) Navigator
NISCH
genes like me logo Genes that share disorders with NISCH: view

No data available for UniProtKB/Swiss-Prot 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
  2. IRAS, the human homologue of Nischarin, prolongs survival of transfected PC12 cells. (PMID: 12868002) Dontenwill M. … Bousquet P. (Cell Death Differ. 2003) 3 4 23
  3. IRAS splice variants. (PMID: 15028621) Piletz J.E. … Ziegler D. (Ann. N. Y. Acad. Sci. 2003) 3 4 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 4 23
  5. Insulin receptor substrate 4 associates with the protein IRAS. (PMID: 11912194) Sano H. … Lienhard G.E. (J. Biol. Chem. 2002) 2 3 4

Products for NISCH Gene

Sources for NISCH Gene

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