CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-023659
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Nischarin 
Protein Synonyms/Alias
 Imidazoline receptor 1; I-1; IR1; Imidazoline receptor antisera-selected protein; hIRAS; Imidazoline-1 receptor; I1R; Imidazoline-1 receptor candidate protein; I-1 receptor candidate protein; I1R candidate protein 
Gene Name
 NISCH 
Gene Synonyms/Alias
 IRAS; KIAA0975 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
498RASLQDLKTVVIAKTubiquitination[1, 2]
504LKTVVIAKTPGTGGSubiquitination[1]
779PSPEPVDKDFYSEFGubiquitination[1, 2]
788FYSEFGNKTTGKMENubiquitination[1]
792FGNKTTGKMENYELIubiquitination[1, 2]
805LIHSSRVKFTYPSEEubiquitination[1]
Reference
 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789
Functional Description
 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. 
Sequence Annotation
 DOMAIN 11 121 PX.
 REPEAT 288 309 LRR 1.
 REPEAT 311 332 LRR 2.
 REPEAT 333 354 LRR 3.
 REPEAT 356 377 LRR 4.
 REPEAT 378 399 LRR 5.
 REPEAT 403 424 LRR 6.
 REGION 2 133 Necessary for binding to
 REGION 120 695 Necessary for homooligomerization and
 REGION 245 869 Interaction with PAK1 (By similarity).
 REGION 660 869 Interaction with LIMK (By similarity).
 REGION 709 807 Interaction with ITGA5 (By similarity).
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 1284 1284 Phosphoserine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Apoptosis; Cell membrane; Coiled coil; Complete proteome; Cytoplasm; Endosome; Leucine-rich repeat; Membrane; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1504 AA 
Protein Sequence
MFVQEEALAS SLSSTDSLTP EHQPIAQGCS DSLESIPAGQ AASDDLRDVP GAVGGASPEH 60
AEPEVQVVPG SGQIIFLPFT CIGYTATNQD FIQRLSTLIR QAIERQLPAW IEAANQREEG 120
QGEQGEEEDE EEEEEEDVAE NRYFEMGPPD VEEEEGGGQG EEEEEEEEDE EAEEERLALE 180
WALGADEDFL LEHIRILKVL WCFLIHVQGS IRQFAACLVL TDFGIAVFEI PHQESRGSSQ 240
HILSSLRFVF CFPHGDLTEF GFLMPELCLV LKVRHSENTL FIISDAANLH EFHADLRSCF 300
APQHMAMLCS PILYGSHTSL QEFLRQLLTF YKVAGGCQER SQGCFPVYLV YSDKRMVQTA 360
AGDYSGNIEW ASCTLCSAVR RSCCAPSEAV KSAAIPYWLL LTPQHLNVIK ADFNPMPNRG 420
THNCRNRNSF KLSRVPLSTV LLDPTRSCTQ PRGAFADGHV LELLVGYRFV TAIFVLPHEK 480
FHFLRVYNQL RASLQDLKTV VIAKTPGTGG SPQGSFADGQ PAERRASNDQ RPQEVPAEAL 540
APAPAEVPAP APAAASASGP AKTPAPAEAS TSALVPEETP VEAPAPPPAE APAQYPSEHL 600
IQATSEENQI PSHLPACPSL RHVASLRGSA IIELFHSSIA EVENEELRHL MWSSVVFYQT 660
PGLEVTACVL LSTKAVYFVL HDGLRRYFSE PLQDFWHQKN TDYNNSPFHI SQCFVLKLSD 720
LQSVNVGLFD QHFRLTGSTP MQVVTCLTRD SYLTHCFLQH LMVVLSSLER TPSPEPVDKD 780
FYSEFGNKTT GKMENYELIH SSRVKFTYPS EEEIGDLTFT VAQKMAEPEK APALSILLYV 840
QAFQVGMPPP GCCRGPLRPK TLLLTSSEIF LLDEDCVHYP LPEFAKEPPQ RDRYRLDDGR 900
RVRDLDRVLM GYQTYPQALT LVFDDVQGHD LMGSVTLDHF GEVPGGPARA SQGREVQWQV 960
FVPSAESREK LISLLARQWE ALCGRELPVE LTG 993 
Gene Ontology
 GO:0005829; C:cytosol; IDA:BHF-UCL.
 GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
 GO:0005886; C:plasma membrane; IDA:BHF-UCL.
 GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
 GO:0008227; F:G-protein coupled amine receptor activity; IEA:Compara.
 GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
 GO:0030036; P:actin cytoskeleton organization; IEA:Compara.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0006006; P:glucose metabolic process; IEA:Compara.
 GO:0030336; P:negative regulation of cell migration; IEA:Compara.
 GO:0048243; P:norepinephrine secretion; IEA:Compara.
 GO:0016601; P:Rac protein signal transduction; IEA:Compara.
 GO:0008217; P:regulation of blood pressure; IEA:Compara.
 GO:0032228; P:regulation of synaptic transmission, GABAergic; IEA:Compara. 
Interpro
 IPR001611; Leu-rich_rpt.
 IPR001683; Phox. 
Pfam
 PF00787; PX 
SMART
 SM00312; PX 
PROSITE
 PS51450; LRR
 PS50195; PX 
PRINTS