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Protein

Nischarin

Gene

Nisch

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

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. Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons. 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 (By similarity). Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3 (By similarity). When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures (By similarity).By similarity4 Publications

GO - Molecular functioni

GO - Biological processi

  • actin cytoskeleton organization Source: Ensembl
  • apoptotic process Source: UniProtKB-KW
  • glucose metabolic process Source: RGD
  • negative regulation of cell migration Source: Ensembl
  • norepinephrine secretion Source: RGD
  • Rac protein signal transduction Source: Ensembl
  • regulation of blood pressure Source: RGD
  • regulation of synaptic transmission, GABAergic Source: RGD

Keywordsi

Molecular functionReceptor
Biological processApoptosis

Names & Taxonomyi

Protein namesi
Recommended name:
Nischarin
Alternative name(s):
Imidazoline receptor 1
Short name:
I-1
Short name:
IR1
Imidazoline-1 receptor
Short name:
I1R
Gene namesi
Name:Nisch
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 16

Organism-specific databases

RGDi1306950 Nisch

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL5221

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003482671 – 1502NischarinAdd BLAST1502

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei542PhosphoserineBy similarity1
Modified residuei544PhosphoserineBy similarity1
Modified residuei547PhosphoserineBy similarity1
Modified residuei1280PhosphothreonineBy similarity1
Modified residuei1282PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ4G017
PRIDEiQ4G017

PTM databases

iPTMnetiQ4G017
PhosphoSitePlusiQ4G017

Expressioni

Gene expression databases

BgeeiENSRNOG00000018823
GenevisibleiQ4G017 RN

Interactioni

Subunit structurei

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. Interacts with LIMK1 (via PDZ and kinase domain); this interaction is direct. Interacts with LIMK2; this interaction depends on LIMK2 activity. Interacts with RAC1 (activated state) (By similarity). Interacts with STK11; this interaction may increase STK11 activity (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ4G017, 2 interactors
MINTiQ4G017
STRINGi10116.ENSRNOP00000032758

Chemistry databases

BindingDBiQ4G017

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 122PXPROSITE-ProRule annotationAdd BLAST111
Repeati289 – 310LRR 1Add BLAST22
Repeati312 – 333LRR 2Add BLAST22
Repeati334 – 355LRR 3Add BLAST22
Repeati357 – 378LRR 4Add BLAST22
Repeati379 – 400LRR 5Add BLAST22
Repeati404 – 425LRR 6Add BLAST22

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 134Necessary for binding to phosphoinositide-3-P; not sufficient for targeting to endosomesBy similarityAdd BLAST134
Regioni121 – 693Necessary for homooligomerization and targeting to endosomesBy similarityAdd BLAST573
Regioni246 – 867Interaction with PAK1By similarityAdd BLAST622
Regioni659 – 867Interaction with LIMKBy similarityAdd BLAST209
Regioni707 – 805Interaction with ITGA5By similarityAdd BLAST99

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili623 – 692Sequence analysisAdd BLAST70

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi630 – 689Glu-richAdd BLAST60
Compositional biasi1046 – 1102Ala/Pro-richAdd BLAST57

Domaini

Both the presence of the PX domain and the coiled coil region are necessary for its endosomal targeting.By similarity

Keywords - Domaini

Coiled coil, Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiENOG410IEQP Eukaryota
ENOG410XQUS LUCA
GeneTreeiENSGT00530000063625
HOGENOMiHOG000113789
HOVERGENiHBG108189
InParanoidiQ4G017
OMAiGKMENYE
OrthoDBiEOG091G0707

Family and domain databases

CDDicd06875 PX_IRAS, 1 hit
Gene3Di3.30.1520.10, 1 hit
3.80.10.10, 2 hits
InterProiView protein in InterPro
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR037904 Nischarin_PX
IPR001683 Phox
IPR036871 PX_dom_sf
PfamiView protein in Pfam
PF00787 PX, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 4 hits
SM00312 PX, 1 hit
SUPFAMiSSF64268 SSF64268, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 6 hits
PS50195 PX, 1 hit

Sequencei

Sequence statusi: Complete.

Q4G017-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAATLSFGP EREAEPAKEA RVVGSELVDT YTVYVIQVTD GNHEWTIKHR
60 70 80 90 100
YSDFHDLHEK LVAERKIDKT LLPPKKIIGK NSRSLVEKRE KDLEVYLQTL
110 120 130 140 150
LKTFPDVAPR VLAHFLHFHL YEINGVTAAL AEELFEKGEQ LLGAGEVFAI
160 170 180 190 200
RPLQLYAITE QLQQGKPTCA SGDAKTDLGH ILDFTCRLKY LKVSGTEGPF
210 220 230 240 250
GTSNIREQLL PFDLSIFKSL HQVEMSHCDA KHVRGLVTSK PTLATMSVRF
260 270 280 290 300
SAASMKEVLV PEASEFDEWE PEGTTLGGPV TAVIPTWQAL TTLDLSHNSI
310 320 330 340 350
SEIDESVKLI PKIEYLDLSH NGVLVVDNLQ HLYNLVHLDL SYNKLSSLEG
360 370 380 390 400
VHTKLGNVKT LNLAGNFLER LSGLHKLYSL VNLDLRDNRI EQLDEVKSIG
410 420 430 440 450
NLPCLEHVAL LNNPLSIIPD YRTKVLSQFG ERASEICLDD VATTEKELDT
460 470 480 490 500
VEVLKAIQKA KDVKSKLSST EKKVGEDFRL PTAPCIRPSS SPPTAVPTSA
510 520 530 540 550
SLPQPILSNQ GIMFVQEEAL ASSLSSTDSL PPDDRPIAQA CSNSMGSLPT
560 570 580 590 600
GQVAAEDLRD LPGAVGGVSP DHAEPEVQVV PGSGQIIFLP FTCIGYTATN
610 620 630 640 650
QDFIQRLSTL IRQAIERQLP AWIEAANQRE EAHGEQGEEE EEEEEEDVAE
660 670 680 690 700
SRYFEMGPPD AEEEEGSGQG EEDEEDEDEE AEEERLALEW ALGADEDFLL
710 720 730 740 750
EHIRILKVLW CFLIHVQGSI RQFAACLVLT DFGIAVFEIP HQESRGSSQH
760 770 780 790 800
ILSSLRFVFC FPHGDLTEFG FLMPELCLVL KVRHSENTLF IISDAANLHE
810 820 830 840 850
FHADLRSCFA PQHMAMLCSP ILYGSHTSLQ EFLRQLLTFY KVAGGSQERS
860 870 880 890 900
QGCFPVYLVY SDKRMVQTAA GDYSGNIEWA SCTLCSAVRR SCCAPSEAVK
910 920 930 940 950
SAAIPYWLLL TSQHLNVIKA DFNPMPSRGT HNCRNRNSFK LSRVPLSTVL
960 970 980 990 1000
LDPTRSCTQP RGAFADGHVL ELLVGYRFVT AIFVLPHEKF HFLRVYNQLR
1010 1020 1030 1040 1050
ASLKDLKTVV IAKNPSARPR TQGPLAGGQP AKSRVSAEQR LQETPAEAPA
1060 1070 1080 1090 1100
PAPAAAESAA EAPAAAEASA PAGAPAPAGA PAPAGAPAGA QAPAPAQAEV
1110 1120 1130 1140 1150
PAQYPSERLI QSTSEENQIP SHLPVCPSLQ HIARLRGRAI IDLFHSSIAE
1160 1170 1180 1190 1200
VENEELRHLL WSSVVFYQTP GLEVTACVLL STKAVYFILH DGLRRYFSEP
1210 1220 1230 1240 1250
LQDFWHQKNT DYNNSPFHIS QCFVLKLSDL QSVNVGLFDQ YFRLTGSSPT
1260 1270 1280 1290 1300
QVVTCLTRDS YLTHCFLQHL MLVLSSLERT PSPEPIDKDF YSEFGDKNTG
1310 1320 1330 1340 1350
KMENYELIHS SRVKFTYPSE EEVGDLTYVV AQKMADPAKN PALSILLYIQ
1360 1370 1380 1390 1400
AFQVITPQLG RGRGPLRPKT LLLTSAEIFL LDEDYIHYPL PEFAKEPPQR
1410 1420 1430 1440 1450
DRYRLDDGRR VRDLDRVLMG YNPYPQALTL VFDDTQGHDL MGSVTLDHFG
1460 1470 1480 1490 1500
EMPGGPGRAG QGREVQWQVF VPSAESREKL ISLLARQWEA LCGRELPVEL

TG
Length:1,502
Mass (Da):166,503
Last modified:September 2, 2008 - v2
Checksum:iE89025E32450ECF8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03100261 Genomic DNA No translation available.
BC098837 mRNA Translation: AAH98837.1
UniGeneiRn.96234

Genome annotation databases

EnsembliENSRNOT00000036910; ENSRNOP00000032758; ENSRNOG00000018823
UCSCiRGD:1306950 rat

Similar proteinsi

Entry informationi

Entry nameiNISCH_RAT
AccessioniPrimary (citable) accession number: Q4G017
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 2, 2008
Last sequence update: September 2, 2008
Last modified: May 23, 2018
This is version 83 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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