Nischarin

Details

Name
Nischarin
Synonyms
  • hIRAS
  • I-1
  • I-1 receptor candidate protein
  • I1R
  • I1R candidate protein
  • Imidazoline receptor 1
  • Imidazoline receptor antisera-selected protein
  • Imidazoline-1 receptor
  • Imidazoline-1 receptor candidate protein
  • IR1
  • IRAS
  • KIAA0975
Gene Name
NISCH
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037248|Nischarin
MATARTFGPEREAEPAKEARVVGSELVDTYTVYIIQVTDGSHEWTVKHRYSDFHDLHEKL
VAERKIDKNLLPPKKIIGKNSRSLVEKREKDLEVYLQKLLAAFPGVTPRVLAHFLHFHFY
EINGITAALAEELFEKGEQLLGAGEVFAIGPLQLYAVTEQLQQGKPTCASGDAKTDLGHI
LDFTCRLKYLKVSGTEGPFGTSNIQEQLLPFDLSIFKSLHQVEISHCDAKHIRGLVASKP
TLATLSVRFSATSMKEVLVPEASEFDEWEPEGTTLEGPVTAVIPTWQALTTLDLSHNSVS
EIDESVKLIPKIEFLDLSHNGLLVVDNLQHLYNLVHLDLSYNKLSSLEGLHTKLGNIKTL
NLAGNLLESLSGLHKLYSLVNLDLRDNRIEQMEEVRSIGSLPCLEHVSLLNNPLSIIPDY
RTKVLAQFGERASEVCLDDTVTTEKELDTVEVLKAIQKAKEVKSKLSNPEKKGGEDSRLS
AAPCIRPSSSPPTVAPASASLPQPILSNQGIMFVQEEALASSLSSTDSLTPEHQPIAQGC
SDSLESIPAGQAASDDLRDVPGAVGGASPEHAEPEVQVVPGSGQIIFLPFTCIGYTATNQ
DFIQRLSTLIRQAIERQLPAWIEAANQREEGQGEQGEEEDEEEEEEEDVAENRYFEMGPP
DVEEEEGGGQGEEEEEEEEDEEAEEERLALEWALGADEDFLLEHIRILKVLWCFLIHVQG
SIRQFAACLVLTDFGIAVFEIPHQESRGSSQHILSSLRFVFCFPHGDLTEFGFLMPELCL
VLKVRHSENTLFIISDAANLHEFHADLRSCFAPQHMAMLCSPILYGSHTSLQEFLRQLLT
FYKVAGGCQERSQGCFPVYLVYSDKRMVQTAAGDYSGNIEWASCTLCSAVRRSCCAPSEA
VKSAAIPYWLLLTPQHLNVIKADFNPMPNRGTHNCRNRNSFKLSRVPLSTVLLDPTRSCT
QPRGAFADGHVLELLVGYRFVTAIFVLPHEKFHFLRVYNQLRASLQDLKTVVIAKTPGTG
GSPQGSFADGQPAERRASNDQRPQEVPAEALAPAPAEVPAPAPAAASASGPAKTPAPAEA
STSALVPEETPVEAPAPPPAEAPAQYPSEHLIQATSEENQIPSHLPACPSLRHVASLRGS
AIIELFHSSIAEVENEELRHLMWSSVVFYQTPGLEVTACVLLSTKAVYFVLHDGLRRYFS
EPLQDFWHQKNTDYNNSPFHISQCFVLKLSDLQSVNVGLFDQHFRLTGSTPMQVVTCLTR
DSYLTHCFLQHLMVVLSSLERTPSPEPVDKDFYSEFGNKTTGKMENYELIHSSRVKFTYP
SEEEIGDLTFTVAQKMAEPEKAPALSILLYVQAFQVGMPPPGCCRGPLRPKTLLLTSSEI
FLLDEDCVHYPLPEFAKEPPQRDRYRLDDGRRVRDLDRVLMGYQTYPQALTLVFDDVQGH
DLMGSVTLDHFGEVPGGPARASQGREVQWQVFVPSAESREKLISLLARQWEALCGRELPV
ELTG
Number of residues
1504
Molecular Weight
166627.105
Theoretical pI
4.8
GO Classification
Functions
identical protein binding / phosphatidylinositol binding
Processes
actin cytoskeleton organization / apoptotic process / G-protein coupled receptor signaling pathway / glucose metabolic process / negative regulation of cell migration / norepinephrine secretion / Rac protein signal transduction / regulation of blood pressure / regulation of synaptic transmission, GABAergic
Components
cytosol / early endosome / membrane / plasma membrane / recycling endosome
General Function
Phosphatidylinositol binding
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0021702|Nischarin (NISCH)
ATGGCGACCGCGCGCACCTTCGGGCCCGAGCGGGAAGCCGAGCCGGCCAAGGAAGCGCGC
GTCGTGGGCTCGGAGCTTGTGGACACTTATACGGTTTACATCATCCAGGTCACTGATGGC
AGCCATGAGTGGACAGTAAAGCACCGCTACAGCGACTTCCATGACCTGCATGAAAAGCTC
GTTGCAGAGAGAAAGATTGATAAAAATCTGCTTCCGCCCAAAAAGATAATTGGGAAAAAC
TCAAGAAGCTTGGTGGAGAAGAGGGAGAAGGATCTGGAGGTCTACCTCCAGAAGCTCCTG
GCTGCCTTCCCTGGCGTGACCCCCAGAGTACTGGCCCACTTCTTGCATTTTCACTTCTAT
GAGATAAATGGCATCACCGCGGCACTGGCTGAAGAGCTCTTTGAGAAAGGAGAACAGCTC
CTGGGGGCCGGCGAGGTCTTTGCCATTGGACCCCTGCAGCTGTATGCCGTCACGGAGCAG
CTGCAGCAGGGAAAGCCCACGTGCGCCAGTGGGGATGCCAAGACCGACCTCGGGCACATC
CTGGACTTCACCTGTCGCCTTAAGTACCTTAAGGTTTCTGGCACAGAAGGACCTTTTGGG
ACCAGCAACATTCAGGAGCAGCTCCTGCCGTTCGACCTATCAATATTCAAGTCCCTGCAT
CAGGTGGAGATAAGTCACTGTGATGCTAAGCACATCAGAGGGCTGGTCGCATCGAAGCCC
ACCTTAGCCACGCTGAGTGTCCGCTTCTCAGCAACCTCGATGAAGGAAGTCCTTGTTCCT
GAAGCCTCAGAATTTGATGAGTGGGAGCCTGAAGGCACAACCCTAGAAGGCCCTGTGACT
GCCGTCATCCCCACTTGGCAGGCATTGACCACGCTTGACCTGAGCCACAACAGCATCTCC
GAGATCGACGAGTCTGTGAAACTGATCCCAAAGATTGAGTTCCTGGACCTGAGTCACAAT
GGATTGCTGGTTGTGGACAATCTGCAGCACCTGTATAACCTTGTGCATCTGGACCTGTCC
TACAACAAGCTCTCCTCCTTGGAAGGGCTTCACACCAAGCTGGGGAACATCAAGACCTTA
AACCTGGCAGGCAACCTCCTAGAGAGTCTGAGTGGCCTGCACAAGCTCTACTCACTGGTC
AACCTGGATCTCCGGGACAACAGGATCGAACAGATGGAGGAGGTCCGGAGCATAGGCAGC
CTCCCGTGTCTGGAGCACGTGTCTCTGCTGAACAACCCTCTGAGCATCATCCCCGACTAC
CGGACCAAGGTGCTGGCTCAGTTCGGAGAGAGGGCCTCAGAGGTCTGTCTGGATGACACA
GTGACCACAGAGAAGGAGCTGGACACTGTGGAAGTGCTGAAAGCAATTCAGAAAGCCAAG
GAGGTCAAGTCCAAACTGAGCAACCCAGAGAAGAAGGGTGGTGAAGACTCCCGGCTCTCA
GCTGCCCCCTGCATCAGACCCAGCAGCTCCCCTCCCACTGTGGCTCCCGCATCTGCCTCC
CTGCCCCAGCCCATCCTCTCTAACCAAGGTAATCGTGTATGTATCTTGCTTCTAGTGGAG
CCACACAGCCCTGCCTGGGCCCCCTGGCTGGGCTGGGGTTGGGGGAGAGGTGCCAGCACC
TGCTTCCAACAGGGTCAGACACAGGGAGGGCAGTGCCTTCTGCAGGCTGGTCCTCGCGGG
GGGACACATGGCAGGGGTGCCTGGCCTGATGCCAGCTGTTGCTTGCTTGGTGAGGACTCC
CAATTGCTCTGA
Chromosome Location
3
Locus
3p21.1
External Identifiers
ResourceLink
UniProtKB IDQ9Y2I1
UniProtKB Entry NameNISCH_HUMAN
GenBank Protein ID3462807
GenBank Gene IDAF082516
HGNC IDHGNC:18006
General References
  1. Piletz JE, Ivanov TR, Sharp JD, Ernsberger P, Chang CH, Pickard RT, Gold G, Roth B, Zhu H, Jones JC, Baldwin J, Reis DJ: Imidazoline receptor antisera-selected (IRAS) cDNA: cloning and characterization. DNA Cell Biol. 2000 Jun;19(6):319-29. [PubMed:10882231]
  2. Piletz JE, Deleersnijder W, Roth BL, Ernsberger P, Zhu H, Ziegler D: IRAS splice variants. Ann N Y Acad Sci. 2003 Dec;1009:419-26. [PubMed:15028621]
  3. Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: 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. DNA Res. 1999 Feb 26;6(1):63-70. [PubMed:10231032]
  4. 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, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  5. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005]
  6. Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Chen R, Chen Z, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang J, Wang J, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA: The DNA sequence, annotation and analysis of human chromosome 3. Nature. 2006 Apr 27;440(7088):1194-8. [PubMed:16641997]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  8. Ivanov TR, Jones JC, Dontenwill M, Bousquet P, Piletz JE: Characterization of a partial cDNA clone detected by imidazoline receptor-selective antisera. J Auton Nerv Syst. 1998 Oct 15;72(2-3):98-110. [PubMed:9851558]
  9. Sano H, Liu SC, Lane WS, Piletz JE, Lienhard GE: Insulin receptor substrate 4 associates with the protein IRAS. J Biol Chem. 2002 May 31;277(22):19439-47. Epub 2002 Mar 23. [PubMed:11912194]
  10. Dontenwill M, Piletz JE, Chen M, Baldwin J, Pascal G, Ronde P, Dupuy L, Greney H, Takeda K, Bousquetd P: IRAS is an anti-apoptotic protein. Ann N Y Acad Sci. 2003 Dec;1009:400-12. [PubMed:15028619]
  11. Dontenwill M, Pascal G, Piletz JE, Chen M, Baldwin J, Ronde P, Dupuy L, Urosevic D, Greney H, Takeda K, Bousquet P: IRAS, the human homologue of Nischarin, prolongs survival of transfected PC12 cells. Cell Death Differ. 2003 Aug;10(8):933-5. [PubMed:12868002]
  12. Lim KP, Hong W: 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. J Biol Chem. 2004 Dec 24;279(52):54770-82. Epub 2004 Oct 8. [PubMed:15475348]
  13. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330]
  14. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332]
  15. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  16. Jain P, Baranwal S, Dong S, Struckhoff AP, Worthylake RA, Alahari SK: Integrin-binding protein nischarin interacts with tumor suppressor liver kinase B1 (LKB1) to regulate cell migration of breast epithelial cells. J Biol Chem. 2013 May 31;288(22):15495-509. doi: 10.1074/jbc.M112.418103. Epub 2013 Apr 9. [PubMed:23572524]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00697Tizanidineapproved, investigationalnoagonistDetails
DB08838Agmatineexperimental, investigationalyesagonistDetails
DB09242Moxonidineapproved, investigationalyesagonistDetails