Q9Y2I1 (NISCH_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 85.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Nischarin Alternative name(s): Imidazoline receptor 1 Short name=I-1 Short name=IR1 Imidazoline receptor antisera-selected protein Short name=hIRAS Imidazoline-1 receptor Short name=I1R Imidazoline-1 receptor candidate protein Short name=I-1 receptor candidate protein Short name=I1R candidate protein | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 1504 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| 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. Ref.1 Ref.2 Ref.11 Ref.12 Ref.13 |
| Subunit 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. Ref.10 Ref.13 |
| Subcellular location | 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. Ref.1 Ref.10 Ref.12 Ref.13 |
| Tissue specificity | Isoform 1, isoform 3 and isoform 4 are expressed in brain. Isoform 1 is expressed in endocrine tissues. Ref.2 Ref.9 |
| Domain | Both the presence of the PX domain and the coiled coil region are necessary for its endosomal targeting. |
| Sequence similarities | Contains 6 LRR (leucine-rich) repeats. Contains 1 PX (phox homology) domain. |
| Sequence caution | The sequence BAA76819.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. |
Ontologies
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q9Y2I1-1) Also known as: IRAS-1; IRAS-M; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q9Y2I1-2) The sequence of this isoform differs from the canonical sequence as follows: 1-511: Missing. | ||||||
| Isoform 3 (identifier: Q9Y2I1-3) Also known as: IRAS-L; The sequence of this isoform differs from the canonical sequence as follows: 511-583: IMFVQEEALA...PEVQVVPGSG → NRVCTLLLVE...CLLGEDSQLL 584-1504: Missing. | ||||||
| Isoform 4 (identifier: Q9Y2I1-4) Also known as: IRAS-S; The sequence of this isoform differs from the canonical sequence as follows: 512-515: MFVQ → LGDE 516-1504: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1504 | 1504 | Nischarin | PRO_0000348265 | ||||||||||||||||||||
Regions | ||||||||||||||||||||||||
| Domain | 11 – 121 | 111 | PX | |||||||||||||||||||||
| Repeat | 288 – 309 | 22 | LRR 1 | |||||||||||||||||||||
| Repeat | 311 – 332 | 22 | LRR 2 | |||||||||||||||||||||
| Repeat | 333 – 354 | 22 | LRR 3 | |||||||||||||||||||||
| Repeat | 356 – 377 | 22 | LRR 4 | |||||||||||||||||||||
| Repeat | 378 – 399 | 22 | LRR 5 | |||||||||||||||||||||
| Repeat | 403 – 424 | 22 | LRR 6 | |||||||||||||||||||||
| Region | 1 – 133 | 133 | Necessary for binding to phosphoinositide-3-P; not sufficient for targeting to endosomes | |||||||||||||||||||||
| Region | 120 – 695 | 576 | Necessary for homooligomerization and targeting to endosomes | |||||||||||||||||||||
| Region | 245 – 869 | 625 | Interaction with PAK1 By similarity | |||||||||||||||||||||
| Region | 660 – 869 | 210 | Interaction with LIMK By similarity | |||||||||||||||||||||
| Region | 709 – 807 | 99 | Interaction with ITGA5 By similarity | |||||||||||||||||||||
| Coiled coil | 634 – 695 | 62 | Potential | |||||||||||||||||||||
| Compositional bias | 629 – 691 | 63 | Glu-rich | |||||||||||||||||||||
| Compositional bias | 1048 – 1104 | 57 | Ala/Pro-rich | |||||||||||||||||||||
Amino acid modifications | ||||||||||||||||||||||||
| Modified residue | 1284 | 1 | Phosphoserine Ref.14 | |||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||
| Alternative sequence | 1 – 511 | 511 | Missing in isoform 2. | VSP_035131 | ||||||||||||||||||||
| Alternative sequence | 511 – 583 | 73 | IMFVQ…VPGSG → NRVCTLLLVEPHSPAWAPWL GWGWGRGASTCFQQGTQGGG QCLLQAGPRGGTHGRGAWPD ASCCLLGEDSQLL in isoform 3. | VSP_035132 | ||||||||||||||||||||
| Alternative sequence | 512 – 515 | 4 | MFVQ → LGDE in isoform 4. | VSP_035133 | ||||||||||||||||||||
| Alternative sequence | 516 – 1504 | 989 | Missing in isoform 4. | VSP_035134 | ||||||||||||||||||||
| Alternative sequence | 584 – 1504 | 921 | Missing in isoform 3. | VSP_035135 | ||||||||||||||||||||
| Natural variant | 299 | 1 | V → I. Ref.1 Ref.2 Ref.3 Ref.4 Ref.7 Ref.8 Corresponds to variant rs9856575 [ dbSNP | Ensembl ]. | VAR_046130 | ||||||||||||||||||||
| Natural variant | 1056 | 1 | A → V. Ref.1 Ref.3 Ref.4 Ref.5 Ref.7 Ref.8 Ref.9 Corresponds to variant rs887515 [ dbSNP | Ensembl ]. | VAR_046131 | ||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||
| Mutagenesis | 49 | 1 | R → A: Inhibits targeting to endosomes. Ref.13 | |||||||||||||||||||||
| Mutagenesis | 50 | 1 | Y → A: Inhibits targeting to endosomes. Ref.13 | |||||||||||||||||||||
| Sequence conflict | 927 | 1 | M → I in AAH56900. Ref.8 | |||||||||||||||||||||
| Sequence conflict | 1023 | 1 | P → A in BAA76819. Ref.3 | |||||||||||||||||||||
| Sequence conflict | 1123 | 1 | S → P in AAH38102. Ref.8 | |||||||||||||||||||||
| Sequence conflict | 1382 | 1 | L → F in AAH54494. Ref.8 | |||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||
| Beta strand | 18 – 25 | 8 | ||||||||||||||||||||||
| Beta strand | 27 – 30 | 4 | ||||||||||||||||||||||
| Beta strand | 32 – 38 | 7 | ||||||||||||||||||||||
| Beta strand | 43 – 49 | 7 | ||||||||||||||||||||||
| Helix | 50 – 62 | 13 | ||||||||||||||||||||||
| Helix | 85 – 101 | 17 | ||||||||||||||||||||||
| Beta strand | 105 – 107 | 3 | ||||||||||||||||||||||
| Helix | 109 – 116 | 8 | ||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Imidazoline receptor antisera-selected (IRAS) cDNA: cloning and characterization." Piletz J.E., Ivanov T.R., Sharp J.D., Ernsberger P., Chang C.-H., Pickard R.T., Gold G., Roth B., Zhu H., Jones J.C., Baldwin J., Reis D.J. DNA Cell Biol. 19:319-329(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, VARIANTS ILE-299 AND VAL-1056. |
| [2] | "IRAS splice variants." Piletz J.E., Deleersnijder W., Roth B.L., Ernsberger P., Zhu H., Ziegler D. Ann. N. Y. Acad. Sci. 1009:419-426(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), FUNCTION, TISSUE SPECIFICITY, VARIANT ILE-299. |
| [3] | "Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:63-70(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS ILE-299 AND VAL-1056. Tissue: Brain. |
| [4] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS ILE-299 AND VAL-1056. Tissue: Brain. |
| [5] | "The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT VAL-1056. Tissue: Testis. |
| [6] | "The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. Gibbs R.A.Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS ILE-299 AND VAL-1056. |
| [8] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS ILE-299 AND VAL-1056. Tissue: Eye, PNS and Testis. |
| [9] | "Characterization of a partial cDNA clone detected by imidazoline receptor-selective antisera." Ivanov T.R., Jones J.C., Dontenwill M., Bousquet P., Piletz J.E. J. Auton. Nerv. Syst. 72:98-110(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 469-1063 (ISOFORM 1), TISSUE SPECIFICITY, VARIANT VAL-1056. Tissue: Hippocampus. |
| [10] | "Insulin receptor substrate 4 associates with the protein IRAS." Sano H., Liu S.C.H., Lane W.S., Piletz J.E., Lienhard G.E. J. Biol. Chem. 277:19439-19447(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRB2; IRS4 AND PIK3R1, SUBCELLULAR LOCATION. |
| [11] | "IRAS is an anti-apoptotic protein." Dontenwill M., Piletz J.E., Chen M., Baldwin J., Pascal G., Ronde P., Dupuy L., Greney H., Takeda K., Bousquetd P. Ann. N. Y. Acad. Sci. 1009:400-412(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [12] | "IRAS, the human homologue of Nischarin, prolongs survival of transfected PC12 cells." Dontenwill M., Pascal G., Piletz J.E., Chen M., Baldwin J., Ronde P., Dupuy L., Urosevic D., Greney H., Takeda K., Bousquet P. Cell Death Differ. 10:933-935(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION. |
| [13] | "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." Lim K.-P., Hong W. J. Biol. Chem. 279:54770-54782(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, INTERACTION WITH ITGA5, MUTAGENESIS OF ARG-49 AND TYR-50, SUBCELLULAR LOCATION. |
| [14] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1284, MASS SPECTROMETRY. Tissue: Leukemic T-cell. |
| [15] | "Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. |
| [16] | "Crystal structure of nischarin PX-domain." Structural genomics consortium (SGC) Submitted (OCT-2010) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 18-124. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | AF082516 mRNA. Translation: AAC33104.1. AB023192 mRNA. Translation: BAA76819.1. Different initiation. AK291398 mRNA. Translation: BAF84087.1. AL117432 mRNA. Translation: CAB55920.1. AC006208 Genomic DNA. No translation available. CH471055 Genomic DNA. Translation: EAW65229.1. BC038102 mRNA. Translation: AAH38102.1. BC054494 mRNA. Translation: AAH54494.1. BC056900 mRNA. Translation: AAH56900.1. AF058290 mRNA. Translation: AAC33321.1. | ||||||||||||
| IPI | IPI00032187. IPI00792206. IPI00795420. IPI00902963. | ||||||||||||
| PIR | T17230. | ||||||||||||
| RefSeq | NP_009115.2. NM_007184.3. | ||||||||||||
| UniGene | Hs.435290. | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||
| ProteinModelPortal | Q9Y2I1. | ||||||||||||
| SMR | Q9Y2I1. Positions 18-123, 289-468. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| IntAct | Q9Y2I1. 4 interactions. | ||||||||||||
| STRING | 9606.ENSP00000339958. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q9Y2I1. | ||||||||||||
Polymorphism databases | |||||||||||||
| DMDM | 296439287. | ||||||||||||
Proteomic databases | |||||||||||||
| PaxDb | Q9Y2I1. | ||||||||||||
| PRIDE | Q9Y2I1. | ||||||||||||
Protocols and materials databases | |||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000345716; ENSP00000339958; ENSG00000010322. ENST00000420808; ENSP00000392484; ENSG00000010322. ENST00000479054; ENSP00000418232; ENSG00000010322. | ||||||||||||
| GeneID | 11188. | ||||||||||||
| KEGG | hsa:11188. | ||||||||||||
| UCSC | uc003ded.4. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 11188. | ||||||||||||
| GeneCards | GC03P052489. | ||||||||||||
| HGNC | HGNC:18006. NISCH. | ||||||||||||
| HPA | HPA023189. | ||||||||||||
| neXtProt | NX_Q9Y2I1. | ||||||||||||
| PharmGKB | PA31635. | ||||||||||||
| HUGE | Search... | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| eggNOG | NOG269110. | ||||||||||||
| HOVERGEN | HBG108189. | ||||||||||||
| InParanoid | Q9Y2I1. | ||||||||||||
| OMA | TEFGFLM. | ||||||||||||
| OrthoDB | EOG4N5VW2. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | Q9Y2I1. | ||||||||||||
| Bgee | Q9Y2I1. | ||||||||||||
| CleanEx | HS_NISCH. | ||||||||||||
| Genevestigator | Q9Y2I1. | ||||||||||||
Family and domain databases | |||||||||||||
| Gene3D | 3.30.1520.10. 1 hit. | ||||||||||||
| InterPro | IPR001611. Leu-rich_rpt. IPR001683. Phox. [Graphical view] | ||||||||||||
| Pfam | PF00787. PX. 1 hit. [Graphical view] | ||||||||||||
| SMART | SM00312. PX. 1 hit. [Graphical view] | ||||||||||||
| SUPFAM | SSF64268. PX. 1 hit. | ||||||||||||
| PROSITE | PS51450. LRR. 6 hits. PS50195. PX. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other | |||||||||||||
| ChEMBL | CHEMBL3923. | ||||||||||||
| ChiTaRS | NISCH. human. | ||||||||||||
| GenomeRNAi | 11188. | ||||||||||||
| NextBio | 42587. | ||||||||||||
Entry information
| Entry name | NISCH_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9Y2I1 Secondary accession number(s): C9J245 Q9UFW3 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 3 Human chromosome 3: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with
