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Protein

Nischarin

Gene

Nisch

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Apoptosis

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 16

Organism-specific databases

RGDi1306950. Nisch.

Subcellular locationi

  • Cell membrane By similarity
  • Cytoplasm By similarity
  • Early endosome By similarity
  • Recycling endosome By similarity

  • Note: Enriched in the early/sorting and recycling endosomes. Colocalized in early/sorting endosomes with EEA1 and SNX2 and in recycling endosomes with transferrin receptor. Detected in the perinuclear region partially associated with punctate structures. Colocalizes with PAK1 in cytoplasm, vesicular structures in the perinuclear area and membrane ruffles. Colocalizes with RAC1 in the cytoplasm and vesicles structures (By similarity). Colocalized with MAPK1 and MAPK3 in RVLM neurons.By similarity2 Publications

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL5221.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 15021502NischarinPRO_0000348267Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei542 – 5421PhosphoserineBy similarity
Modified residuei544 – 5441PhosphoserineBy similarity
Modified residuei547 – 5471PhosphoserineBy similarity
Modified residuei1280 – 12801PhosphothreonineBy similarity
Modified residuei1282 – 12821PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ4G017.
PRIDEiQ4G017.

PTM databases

iPTMnetiQ4G017.
PhosphoSiteiQ4G017.

Expressioni

Gene expression databases

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

Protein-protein interaction databases

IntActiQ4G017. 2 interactions.
STRINGi10116.ENSRNOP00000032758.

Chemistry

BindingDBiQ4G017.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini12 – 122111PXPROSITE-ProRule annotationAdd
BLAST
Repeati289 – 31022LRR 1Add
BLAST
Repeati312 – 33322LRR 2Add
BLAST
Repeati334 – 35522LRR 3Add
BLAST
Repeati357 – 37822LRR 4Add
BLAST
Repeati379 – 40022LRR 5Add
BLAST
Repeati404 – 42522LRR 6Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 134134Necessary for binding to phosphoinositide-3-P; not sufficient for targeting to endosomesBy similarityAdd
BLAST
Regioni121 – 693573Necessary for homooligomerization and targeting to endosomesBy similarityAdd
BLAST
Regioni246 – 867622Interaction with PAK1By similarityAdd
BLAST
Regioni659 – 867209Interaction with LIMKBy similarityAdd
BLAST
Regioni707 – 80599Interaction with ITGA5By similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili623 – 69270Sequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi630 – 68960Glu-richAdd
BLAST
Compositional biasi1046 – 110257Ala/Pro-richAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 6 LRR (leucine-rich) repeats.Curated
Contains 1 PX (phox homology) domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiENOG410IEQP. Eukaryota.
ENOG410XQUS. LUCA.
GeneTreeiENSGT00530000063625.
HOGENOMiHOG000113789.
HOVERGENiHBG108189.
InParanoidiQ4G017.
OMAiYSGNIEW.
OrthoDBiEOG70ZZMH.

Family and domain databases

Gene3Di3.30.1520.10. 1 hit.
3.80.10.10. 3 hits.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR001683. Phox.
[Graphical view]
PfamiPF00787. PX. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 4 hits.
SM00312. PX. 1 hit.
[Graphical view]
SUPFAMiSSF64268. SSF64268. 1 hit.
PROSITEiPS51450. LRR. 6 hits.
PS50195. PX. 1 hit.
[Graphical view]

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.

Cross-referencesi

Sequence databases

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

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ4G017. 2 interactions.
STRINGi10116.ENSRNOP00000032758.

Chemistry

BindingDBiQ4G017.
ChEMBLiCHEMBL5221.

PTM databases

iPTMnetiQ4G017.
PhosphoSiteiQ4G017.

Proteomic databases

PaxDbiQ4G017.
PRIDEiQ4G017.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000036910; ENSRNOP00000032758; ENSRNOG00000018823.
UCSCiRGD:1306950. rat.

Organism-specific databases

RGDi1306950. Nisch.

Phylogenomic databases

eggNOGiENOG410IEQP. Eukaryota.
ENOG410XQUS. LUCA.
GeneTreeiENSGT00530000063625.
HOGENOMiHOG000113789.
HOVERGENiHBG108189.
InParanoidiQ4G017.
OMAiYSGNIEW.
OrthoDBiEOG70ZZMH.

Miscellaneous databases

PROiQ4G017.

Gene expression databases

GenevisibleiQ4G017. RN.

Family and domain databases

Gene3Di3.30.1520.10. 1 hit.
3.80.10.10. 3 hits.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR001683. Phox.
[Graphical view]
PfamiPF00787. PX. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 4 hits.
SM00312. PX. 1 hit.
[Graphical view]
SUPFAMiSSF64268. SSF64268. 1 hit.
PROSITEiPS51450. LRR. 6 hits.
PS50195. PX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
    Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M.
    , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
    Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Brown Norway.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1287-1502.
    Tissue: Spleen.
  3. "Imidazoline I(1) receptor-induced activation of phosphatidylcholine-specific phospholipase C elicits mitogen-activated protein kinase phosphorylation in PC12 cells."
    Zhang J., El-Mas M.M., Abdel-Rahman A.A.
    Eur. J. Pharmacol. 415:117-125(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  4. "Mitogen-activated protein kinase phosphorylation in the rostral ventrolateral medulla plays a key role in imidazoline (I1)-receptor-mediated hypotension."
    Zhang J., Abdel-Rahman A.A.
    J. Pharmacol. Exp. Ther. 314:945-952(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  5. "Identification of IRAS/Nischarin as an I1-imidazoline receptor in PC12 rat pheochromocytoma cells."
    Sun Z., Chang C.-H., Ernsberger P.
    J. Neurochem. 101:99-108(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Inhibition of nischarin expression attenuates rilmenidine-evoked hypotension and phosphorylated extracellular signal-regulated kinase 1/2 production in the rostral ventrolateral medulla of rats."
    Zhang J., Abdel-Rahman A.A.
    J. Pharmacol. Exp. Ther. 324:72-78(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiNISCH_RAT
AccessioniPrimary (citable) accession number: Q4G017
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 2, 2008
Last sequence update: September 2, 2008
Last modified: June 8, 2016
This is version 72 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.