Nischarin

NameNischarin
SynonymshIRAS 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 NameNISCH
OrganismHuman
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 residues1504
Molecular Weight166627.105
Theoretical pI4.8
GO Classification
Functions
    phosphatidylinositol binding
identical protein binding
Processes
    negative regulation of cell migration
regulation of blood pressure
regulation of synaptic transmission, GABAergic
glucose metabolic process
Rac protein signal transduction
actin cytoskeleton organization
norepinephrine secretion
apoptotic process
G-protein coupled receptor signaling pathway
Components
    recycling endosome
membrane
plasma membrane
early endosome
cytosol
General FunctionPhosphatidylinositol binding
Specific FunctionActs 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.
Transmembrane Regions
GenBank Protein ID3462807
UniProtKB IDQ9Y2I1
UniProtKB Entry NameNISCH_HUMAN
Cellular LocationCell 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
GenBank Gene IDAF082516
GeneCard IDNone
GenAtlas ID
HGNC IDHGNC:18006
Chromosome Location3
Locus3p21.1
References
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  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.[15028621 ]
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  9. 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.[12868002 ]
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  14. 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.[23572524 ]
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