CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-023658
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
843RQLLTFYKVAGGCQEubiquitination[1, 2]
865VYLVYSDKRMVQTAAubiquitination[2, 3]
902CAPSEAVKSAAIPYWubiquitination[2, 4]
942CRNRNSFKLSRVPLSubiquitination[2, 3]
1009RASLQDLKTVVIAKTubiquitination[2, 3, 5, 6, 7]
1015LKTVVIAKTPGTGGSubiquitination[6, 7]
1290PSPEPVDKDFYSEFGubiquitination[2, 5, 6, 7]
1299FYSEFGNKTTGKMENubiquitination[2, 3, 6, 7]
1303FGNKTTGKMENYELIubiquitination[2, 3, 5, 6, 7]
1316LIHSSRVKFTYPSEEubiquitination[6, 7]
1481PSAESREKLISLLARubiquitination[2]
Reference
 [1] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [4] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [6] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [7] 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] 
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
MATARTFGPE REAEPAKEAR VVGSELVDTY TVYIIQVTDG SHEWTVKHRY SDFHDLHEKL 60
VAERKIDKNL LPPKKIIGKN SRSLVEKREK DLEVYLQKLL AAFPGVTPRV LAHFLHFHFY 120
EINGITAALA EELFEKGEQL LGAGEVFAIG PLQLYAVTEQ LQQGKPTCAS GDAKTDLGHI 180
LDFTCRLKYL KVSGTEGPFG TSNIQEQLLP FDLSIFKSLH QVEISHCDAK HIRGLVASKP 240
TLATLSVRFS ATSMKEVLVP EASEFDEWEP EGTTLEGPVT AVIPTWQALT TLDLSHNSVS 300
EIDESVKLIP KIEFLDLSHN GLLVVDNLQH LYNLVHLDLS YNKLSSLEGL HTKLGNIKTL 360
NLAGNLLESL SGLHKLYSLV NLDLRDNRIE QMEEVRSIGS LPCLEHVSLL NNPLSIIPDY 420
RTKVLAQFGE RASEVCLDDT VTTEKELDTV EVLKAIQKAK EVKSKLSNPE KKGGEDSRLS 480
AAPCIRPSSS PPTVAPASAS LPQPILSNQG IMFVQEEALA SSLSSTDSLT PEHQPIAQGC 540
SDSLESIPAG QAASDDLRDV PGAVGGASPE HAEPEVQVVP GSGQIIFLPF TCIGYTATNQ 600
DFIQRLSTLI RQAIERQLPA WIEAANQREE GQGEQGEEED EEEEEEEDVA ENRYFEMGPP 660
DVEEEEGGGQ GEEEEEEEED EEAEEERLAL EWALGADEDF LLEHIRILKV LWCFLIHVQG 720
SIRQFAACLV LTDFGIAVFE IPHQESRGSS QHILSSLRFV FCFPHGDLTE FGFLMPELCL 780
VLKVRHSENT LFIISDAANL HEFHADLRSC FAPQHMAMLC SPILYGSHTS LQEFLRQLLT 840
FYKVAGGCQE RSQGCFPVYL VYSDKRMVQT AAGDYSGNIE WASCTLCSAV RRSCCAPSEA 900
VKSAAIPYWL LLTPQHLNVI KADFNPMPNR GTHNCRNRNS FKLSRVPLST VLLDPTRSCT 960
QPRGAFADGH VLELLVGYRF VTAIFVLPHE KFHFLRVYNQ LRASLQDLKT VVIAKTPGTG 1020
GSPQGSFADG QPAERRASND QRPQEVPAEA LAPAPAEVPA PAPAAASASG PAKTPAPAEA 1080
STSALVPEET PVEAPAPPPA EAPAQYPSEH LIQATSEENQ IPSHLPACPS LRHVASLRGS 1140
AIIELFHSSI AEVENEELRH LMWSSVVFYQ TPGLEVTACV LLSTKAVYFV LHDGLRRYFS 1200
EPLQDFWHQK NTDYNNSPFH ISQCFVLKLS DLQSVNVGLF DQHFRLTGST PMQVVTCLTR 1260
DSYLTHCFLQ HLMVVLSSLE RTPSPEPVDK DFYSEFGNKT TGKMENYELI HSSRVKFTYP 1320
SEEEIGDLTF TVAQKMAEPE KAPALSILLY VQAFQVGMPP PGCCRGPLRP KTLLLTSSEI 1380
FLLDEDCVHY PLPEFAKEPP QRDRYRLDDG RRVRDLDRVL MGYQTYPQAL TLVFDDVQGH 1440
DLMGSVTLDH FGEVPGGPAR ASQGREVQWQ VFVPSAESRE KLISLLARQW EALCGRELPV 1500
ELTG 1504 
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